Angioneurotic edema; Welts; Allergic reaction - angioedema; Hives - angioedema ... symptoms may include: Abdominal cramping Breathing difficulty Swollen eyes and mouth Swollen lining of the eyes ( chemosis )
Angioedema may be an overlooked common disease. Angioedema comprises the idiopathic, the allergic, pseudo allergic, the physical form as well as the hereditary form. Diagnosis is simple when symptoms are classical (lips, eyes and tongue) but might be missed if symptoms are nonspecific such as dizziness or dyspnoea. However, the most striking observation reviewing the literature is the absence of original research on angioedema considering the high prevalence of the disease. From a patient and physician perspective more information and research on angioedema is needed.
Busse, Paula J; Smith, Tukisa
Angioedema is frequently categorized into histamine- or bradykinin-mediated disease. It is critical to determine the underlying mediator of symptoms as it directs treatment. Histaminergic angioedema is the most frequent cause of angioedema. It is classified as either acute (lasting 6 weeks). It is further classified into angioedema presenting with or without urticaria. Some patients with acute angioedema may have disease that becomes chronic. Mast cells and basophils are central to the underlying pathophysiology of histamine-mediated angioedema. The underlying treatments of histamine-mediated angioedema are antihistamines, corticosteroids, and epinephrine. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available Hereditary angioedema — a rare disease caused by a congenital deficiency of C1-inhibitor. Clinical manifestations of the disease — recurrent episodes of angioedema, which manifest in childhood or adolescence, more often localized in the subcutaneous tissue (limbs, face, trunk, genitals or submucosa (intestine, larynx. Swellings of the larynx are potentially harmful to the patient’s life. Early detection enables to carry out timely appropriate treatment and prevention of angioedema. The paper presents a case of hereditary angioedema with manifestation in early childhood. The case study demonstrates the complexity of diagnosis and treatment of hereditary angioedema.
Pattanaik, Debendra; Lieberman, Jay Adam
The aims of this study are to update the clinician on current understanding of angioedema as it presents in the pediatric population and to review proper diagnostic techniques and treatment modalities for various types of angioedema. Angioedema is still best classified by whether it is likely histaminergic or kinin-mediated. New guidelines have been published around the world to help diagnose and treat both forms (urticaria/angioedema and hereditary angioedema). The vast majority of the studies on treatment have been conducted in the adult population; however, there are data available in the pediatric population. In the realm of hereditary angioedema, there are multiple new therapies that have been studied in the pediatric population (down to 2 years in some studies) in recent years and offer the clinician options for treatment. Angioedema (whether occurring with or without urticaria) is common in the pediatric population. The majority of the recent studies has been conducted in hereditary angioedema, and now, the clinician should have various options to treat all forms of angioedema. Many treatment options, especially for hereditary angioedema, are further being examined specifically in the pediatric population.
... disease; HAE- Hereditary angioedema; Kallikrein inhibitor-HAE: bradykinin receptor antagonist-HAE; C1-inhibitors-HAE; Hives-HAE ... aunt, uncle, or grandparent. Dental procedures, sickness (including colds and the flu), and surgery may trigger HAE ...
Peterson, M P; Bygum, A
We report a 64-year-old man who suffered from recurrent visible swelling attacks since the age of 20 as well as episodes with severe upper airway edema, resulting in 4 emergency tracheotomies. Eventually after 44 years he was diagnosed with hereditary angioedema (HAE) type II. The aims of this re......We report a 64-year-old man who suffered from recurrent visible swelling attacks since the age of 20 as well as episodes with severe upper airway edema, resulting in 4 emergency tracheotomies. Eventually after 44 years he was diagnosed with hereditary angioedema (HAE) type II. The aims...
Abdel-Karim, Omar; Dizdarevic, Adis; Bygum, Anette
of life. Most studies have been conducted in adults. We report a 13-year-old boy who quickly learned self-administration, which resulted in reduced frequency and severity of attacks. The aim of this report is to emphasize that children should be considered for self-administration training......Hereditary angioedema is an inherited disease that causes periodic swelling attacks, which can be life threatening and have a major effect on a patient's life. Studies have shown that home therapy for angioedema reduces disease severity, leads to faster relief of symptoms, and improves quality...
... Allergy Library ▸ Understanding Hereditary Angioedema Share | Understanding Hereditary Angioedema This article has been reviewed by Thanai Pongdee, MD, FAAAAI Hereditary Angioedema (HAE) is a rare genetic condition. People with ...
Bracho, Francisco A
Hereditary angioedema is an autosomal-dominant deficiency of C1 inhibitor--a serpin inhibitor of kallikrein, C1r, C1s, factor XII, and plasmin. Quantitative or qualitative deficiency of C1 inhibitor leads to the generation of vasoactive mediators, most likely bradykinin. The clinical syndrome is repeated bouts of nonpruritic, nonpitting edema of the face, larynx, extermities, and intestinal viscera. Recently, investigators, physicians, and industry have demonstrated a renewed interest in the biology and treatment of hereditary angioedema. Investigators have generated a C1INH-/- mouse model that has demonstrated the importance of the contact activation system for hereditary angioedema-related vascular permeability. An interactive database of mutations is available electronically. Investigators have continued exploration into mRNA/protein levels. The proceedings of a recent workshop have been impressive in the scope and depth. Clinicians have produced consensus documents and expert reviews. The pharmaceutical industry has initiated clinical trails with novel agents. Hereditary angioedema is often misdiagnosed and poorly treated. Diagnosis requires careful medical and family history and the measurement of functional C1 inhibitor and C4 levels. Attenuated androgens, anti-fibrinolytics, and C1 inhibitor concentrates are used for long-term and preprocedure prophylaxis, but have significant drawbacks. C1 inhibitor concentrates and fresh frozen plasma are available for acute intervention. The mainstays of supportive care are airway monitoring, pain relief, hydration, and control of nausea. New agents such as recombinant C1 inhibitor, kallikrein inhibitors, and bradykinin inhibitors may offer safer and more tolerable treatments.
Angioedema and urticaria often constitute a challenge in daily clinical practice. They may either co- -occur or present as independent conditions. They are characterized by a complex pathomechanism, and their symptoms may be triggered by diverse factors. These differences are crucial for developing a successful treatment regimen. Both conditions may have an allergic origin (immunoglobulin [Ig] E and non-IgE-related), usually induced by histamine, or a nonallergic one, such as bradykinin-mediated angioedema in patients with C1 inhibitor (C1-INH) deficiency or angioedema induced by certain drugs (eg, angiotensin-converting enzyme inhibitors). Currently, we distinguish 5 types of nonallergic angioedema: hereditary angioedema (HAE) due to C1-INH deficiency, acquired angioedema (AAE), and angioedema induced by the renin-angiotensin-aldosterone system, all of which are mediated by bradykinin, as well as pseudoallergic angioedema and idiopathic angioedema. Bradykinin-mediated angioedema (eg, laryngeal angioedema) may be life-threatening because of resistance to corticosteroids and antihistamine drugs. C1-INH concentrates are the drugs of choice in the treatment of HAE and AAE. In recent years, some new drugs have been introduced in the treatment of bradykinin-mediated angioedema, such as bradykinin B2-receptor antagonist, icatibant, and kallikrein inhibitor, ecallantide, which allow to improve treatment outcomes.
Kjaer, Line; Bygum, Anette
Hereditary angioedema (HAE) is a rare inherited disease that is often difficult to diagnose. We report a case of a 9-year-old boy with a spontaneous mutation causing HAE, diagnosed after a life-threatening episode of angioedema of the head and upper respiratory tract after a 5-year history...
Urticaria, also known as hives, and angioedema, where the swelling occurs below the skin instead of on the skin, are extremely common but there is a misconception that the most likely cause is an allergic reaction. Chronic urticaria in particular is rarely due to allergy. Equally for angioedema, many will consider the exceptionally rare hereditary angioedema (HAE), but in fact other medical causes are the most likely, in particular the use of angiotensin-converting enzyme inhibitor (ACE-I) drugs. Approximately 3-5% of patients receiving ACE-I will develop angioedema at some time in the course of their treatment.1 Stress is a major contributor to both chronic urticaria and recurrent angioedema. Treatment needs to focus on the use of long-acting, non-sedating, antihistamines. Corticosteroids may be used acutely but not long term.
Full Text Available Angioedema is a serious adverse drug reaction that can rarely be associated with trifluoperazine treatment. We present the case of a 44-year-old male with an established diagnosis of schizoaffective disorder, for which trifluoperazine therapy was considered. He presented to the emergency department with bilateral lower limb oedematous painful erythematous swelling that eased off completely when trifluoperazine was stopped. The possibility of allergic reaction, such as angioedema, should always be kept in mind by psychiatrists and mental health professionals when prescribing trifluoperazine antipsychotic.
Full Text Available Angioedema is an abrupt swelling of the skin, mucous membrane, or both including respiratory and gastrointestinal tracts. This study aimed to report an experience of angioedema in a university hospital with respect to etiologies, clinical features, treatment, and outcome. One hundred and five patients were enrolled. About half had angioedema without urticaria. The common sites of involvement were periorbital area and lips. Forty five patients (49% had systemic symptoms. The most common cause of angioedema was allergic angioedema. Nonsteroidal anti-inflammatory drug-induced angioedema and idiopathic angioedema were detected in 20% and 18%, respectively. Among patients with allergic angioedema, 41.7% were caused by food, 39.6% by drugs. Thirty seven patients (39% had recurrent attacks of angioedema. Mean standard deviation (SD number of attacks in patients with recurrent angioedema was 3.9 (2.7 (ranging from 2 to 10 times. Patients who had older age and multiple sites of skin involvement had tendency to have systemic symptoms.
Boccon-Gibod, I; Bouillet, L
Angiœdema (AE) is the clinical expression of urticaria (U) which occurs when urticaria is located within the subcutis. It is a syndrome characterized by a sudden and limited subcutaneous and/or submucous swelling. The updated classification of urticaria distinguishes acute and chronic urticaria. Chronic urticaria is spontaneous (CSU) or inducible (CIU). Angioedema in chronic urticaria is rarely allergic, but most of the time caused by a non-specific histamine release from activated mast-cell (non IgE mediated reaction). Angioedemas are recurrent, concomitant or not with wheals. They appear skin-coloured, sometimes slightly rosy, non-inflammatory, and more painful than itchy. They are transient, ephemeral, migrant, last most of the time a few hours (Angioedema can be elicited or worsened by physical factors (cold urticaria, exercise, heat, solar, vibratory, aquagenic, delayed pressure urticaria…) and /or drugs (as aspirin, nonsteroid anti-inflammatory drugs, morphine, antibiotics…). The treatment of histaminergic angioedemas of chronic urticaria is based on modern second generation antihistamines (anti H1). In allergic acute urticaria only, additional treatment for anaphylaxis can be used if needed (grade 2 to 4). In chronic urticaria, steroids should be avoided : they can make symptoms worse and long-lasting because of corticosteroid dependence. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Martins, Sandrina; Salgado, Miguel; Raposo, Filipa; Pinto, Diana; Martinho, Isabel; Araújo, Ana Rita
Introduction: Hereditary angioedema (HA) is a rare cause of recurrent angioedema caused by a default in the gene that encodes the C1 esterase inhibitor (C1-INH). The oedema involves predominantly the face, limbs and genital and gastrointestinal tract. The involvement of the larynx, although less frequent, is the most severe clinical expression of HA and is potentially fatal. Case report: Clinical report of an eight-year-old female with multiple episodes of angioedema. The...
Full Text Available Abstract Women with hereditary angioedema (HAE are more likely to be symptomatic that men. Hormonal factors (puberty, contraception, pregnancy,.... play a significant role in the precipitation or worsening of the condition in women. So, combined contraceptive pills are not indicated and progestogen pill must be preferred. During pregnancy, attack rate can increase (38-48% of women. C1Inhibitor concentrate and tranexamic acid can be used during pregnancy. Attenuated androgens for long term prophylaxis are effective but side effects appear more often in female patients. These side effects are dose dependant and can be attenuated by titrating the dose down the lowest effective level.
Gill, Parwinder; Betschel, Stephen D
The clinical evaluation of angioedema is reliant on obtaining a thorough patient and family history with an assessment of risk factors and presenting symptoms unique to each subtype. It is important to distinguish between angioedema with and without urticaria as a primary step in the evaluation; thereafter, laboratory parameters and investigations allow for subsequent stratification. There is a significant disease burden associated with angioedema and thus it is essential for health care practitioners to establish a prompt and accurate diagnosis, and a comprehensive care plan that addresses the patient's physical and mental well-being alike. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.
Baram, Michael; Kommuri, Anand; Sellers, Subhashini A; Cohn, John R
Angiotensin-converting enzyme inhibitors (ACEI) are commonly prescribed for blood pressure control and renal protection. ACEI angioedema is a common problem in patients who are taking ACEI, although, in most cases, the disorder is self-limited, and spontaneous episodes of apparently unprovoked angioedema stop with the discontinuation of the medication. In a subset of patients, hospitalization and even intubation are required for airway protection. The diagnosis is made clinically. There are no laboratory studies that establish the diagnosis. However, such investigations help exclude alternative diagnoses as the cause for the patient's presentation. Conventional treatment with regimens used to control allergic angioedema is ineffective in this condition. The mechanism of ACEI-induced angioedema is thought to be related to its effect on the kallikrein-kinin system. Kallikrein is a protease that converts high-molecular-weight kininogens into kinins, primarily bradykinin. Medications recently developed, primarily icatibant and ecallantide, to control hereditary angioedema, a disorder also associated with kallikrein-kinin activation, have been used to treat ACEI angioedema with some success. The efficacy of these agents and their optimal use remains to be established by randomized and placebo controlled trials. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Andersen, Michelle Fog; Bygum, Anette
Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does...... however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack...... of hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting....
Knecht, Stephanie E; Dunn, Steven P; Macaulay, Tracy E
Angiotensin inhibitors have been extensively evaluated in clinical trials and have demonstrated significant reductions in morbidity and mortality following myocardial infarction and stroke, as well as in patients with heart failure or who are at risk of cardiovascular disease. Further, both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are frequently prescribed for the treatment of hypertension and to preserve renal function in patients with diabetes mellitus and chronic kidney disease. Angioedema is a known, but rare, adverse effect of ACEIs and ARBs. Therefore, it is important for clinicians to have a thorough understanding of risks and benefits of prescribing these medications, particularly in patients with a history of angioedema. This review describes the literature evaluating the incidence and cross-reactivity of angioedema with ACEIs and ARBs in order to provide guidance for clinical decision making. © The Author(s) 2014.
Full Text Available Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life- threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines. Drug-induced angioedema, like other cutaneous drug reactions, has been reported to be most frequently elicited by beta-lactam antibiotics and nonsteroidal anti-inflammatory drugs, although reliable data from epidemiologic studies are scarce. Recent reports suggested an increasing role of angiotensin-converting enzyme inhibitors (ACEIs in the causation of life- threatening angioedema. ACEI-related angioedema is never accompanied by urticaria and occurs via a kinin- dependent mechanism. ACEI-related angioedema not only can start years after beginning the treatment, but it can then recur irregularly while under that treatment. Furthermore, allergy tests are unreliable for the diagnosis of ACEI-related angioedema, and so the relationship between angioedema and ACEIs is often missed and consequently quite underestimated. Accordingly, better understanding of the kinin-dependent mechanism, which is particular to angioedema, is necessary for the appropriate management of drug-induced angioedema.
Yazıcı, Selçuk; Nacaroglu, Hikmet Tekin; Bahçeci Erdem, Semiha; Karaman, Sait; Can, Demet
We present a 13-year-old male childallergic to three different plants (Salvia officinalis, Mentha piperita and Origanum onites L.) of Lamiaceae family. The patient developed angioedema 20-30 minutes after eating chicken meat with cheddar cheese. There was no history of allergy. Oral food challenge (OFC) with both cheddar cheese and chicken meat was negative. Skin tests for inhalant allergens were negative. 3 weeks later, the patient was admitted with angioedema after drinking sage tea. OFC with sage was applied and angioedema was observed. It was recognized that the first trigger, chicken meat with cheddar cheese, included oregano (Origanum onites L.). OFC for oregano was positive. Prick to prick test for Lamiaceae herbs (oregano, sage, mint) was performed. A positive reaction was observed only to mint. OFC was repeated with fresh mint and angioedema developed after 16 hours. Diagnose of Lamiaceae allergy is complicated and cross-sensitivity is common. Skin prick test (prick to prick)revealed a positive response only to mint but not to oregano and sage. Commercial radioallergosorbent (RAST) tests are available only for a few members of the family. Finally, thediagnose is based mainly on OFC. Spices from Lamiaceae group should be considered as potential triggers of allergic reactions.
Carr, Tara F; Saltoun, Carol A
Urticaria, also known as hives, may affect up to 20% of the population at some time in their lives. Urticaria is characterized by extreme pruritus and described as erythematous, raised, circumscribed lesions with central pallor that blanch with pressure. The pathogenesis of urticaria involves mast cell activation, with subsequent release of histamine and other vasoactive mediators, leading to increased vascular permeability of postcapillary venules and development of edema, erythema, and pruritus. Urticaria is closely associated with angioedema in 40% of individuals; ∼10% of patients experience angioedema without urticaria. Urticarial lesions often are generalized with multiple lesions in no specific distribution; angioedema tends to be localized, commonly affecting the face (periorbital and perioral regions), tongue, uvula, soft palate or larynx, extremities, and genitalia. Urticaria is subdivided into acute and chronic urticaria based on duration of symptoms. Acute urticaria lasts products, medications (aspirin, nonsteroidal anti-inflammatory drugs, and antibiotics), or insect stings. Urticaria lasting >6 weeks is designated as chronic urticaria, and an etiology is seldom identified and thus considered idiopathic. Chronic urticaria may have an autoimmune basis. There is a well-documented association between autoimmune hypothyroidism (Hashimoto's disease) and urticaria and angioedema with higher incidence of antithyroid (antithyroglobulin and antiperoxidase) antibodies in these usually euthyroid patients. Furthermore, studies have revealed a circulating IgG antibody directed against the IgE receptor (F(Cε)RIα) or IgE in 40-60% of patients with chronic urticaria. Histamine 1-receptor antagonists (antihistamines) are initial therapy.
Ertoy Karagol, Hacer I; Yilmaz, Ozlem; Bakirtas, Arzu; Topal, Erdem; Demirsoy, Mehmet S; Turktas, Ipek
There has been no separate study investigating angioedema without urticaria (Aw/oU) exclusively in children so far. The purpose of this study was to investigate the frequency, clinical presentation, etiology, management and follow-up of Aw/oU in children. This is a prospective study that included all consecutive patients with a history of Aw/oU referred to our clinic between January 2011 and May 2012. A standard diagnostic and therapeutic algorithm was applied to all patients. The frequency of Aw/oU was found to be 1.6% during the study period. An etiological factor could be found in only 45 patients (49%). The causes of Aw/oU were infection (21%), allergy (14%), thyroid autoimmunity (TA)-related (8%) and nonsteroid anti-inflammatory drug hypersensitivity (6%), and idiopathic angioedema (51%). There was no hereditary type I, II or acquired type of angioedema or rare syndromes associated with Aw/oU. The median follow-up was 16 months (range: 12-30 months). Antihistamine prophylaxis was initiated at therapeutic doses in 20 patients with frequently recurrent angioedema due to idiopathic and euthyroid TA-related Aw/oU for 3 months. These patients responded to antihistamine prophylaxis for 3 months. Four patients relapsed after cessation of prophylaxis at the end of 3 months. Antihistamine prophylaxis was prolonged to 6 months in three patients and to 9 months in one patient. Angioedema without urticaria in children is a rare condition and no etiology can be identified in half of them. Antihistamine treatment alone is sufficient, and prognosis is good in recurrent non hereditary cases in a short-term follow-up period. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Wu, Maddalena Alessandra; Perego, Francesca; Zanichelli, Andrea; Cicardi, Marco
Due to marked heterogeneity of clinical presentations, comprehensive knowledge of angioedema phenotypes is crucial for correct diagnosis and choosing the appropriate therapeutic approach. One of the ways to a meaningful clinical distinction can be made between forms of angioedema occurring "with or without wheals." Angioedema with wheals (rash) is a hallmark of urticaria, either acute or chronic, spontaneous or inducible. Angioedema without wheals may still be manifested in about 10 % of patients with urticaria, but it may also occur as a separate entity. Several classifications of angioedema as part of urticaria were published over time, while a latest one, released in 2014 (HAWK group consensus, see below), provided a classification of all forms of "angioedema without wheals" distinct from urticaria, which will be the focus of the present review. At this time, the HAWK consensus classification is the best in terms of covering the pathophysiology, mediators involved, angioedema triggers, and clinical expression. According to this classification, three types of hereditary angioedema (genetic C1-INH deficiency, normal C1-INH with factor XII mutations, and unknown origin) and four types of acquired angioedema (C1-INH deficiency, related to ACE inhibitors intake, idiopathic histaminergic, and idiopathic non-histaminergic) are presented. We will review the distinctive clinical features of each phenotype in details.
Cicardi, M; Suffritti, C; Perego, F; Caccia, S
Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. In the present review, we discuss nonallergic angioedema without wheals, which can be divided into 3 acquired and 4 hereditary forms. Histamine is the mediator in acquired angioedema of unknown etiology (idiopathic histaminergic acquired angioedema), whereas in other forms the main mediator is bradykinin. Angioedema can be caused by C1-inhibitor deficiency (C1-INH-hereditary angioedema and C1-INH-acquired angioedema), mutations in coagulation factor XII (FXII-hereditary angioedema), and treatment with angiotensin-converting enzyme inhibitors (ACEI-acquired angioedema). Etiology remains unclear in acquired angioedema (idiopathic nonhistaminergic acquired angioedema) and in 1 type of hereditary angioedema (hereditary angioedema of unknown origin). Several treatments are licensed for hereditary C1-INH deficiency. Plasma-derived and recombinant C1-INHs, the bradykinin receptor blocker icatibant, and the plasma kallikrein inhibitor ecallantide have been approved for on-demand treatment to reverse angioedema symptoms. Attenuated androgen and plasma-derived C1-INH are approved for prophylaxis.
Eli, Magen; Joseph, Mishal; Kuznik, Boris; Menachem, Schlesinger
Chronic idiopathic angioedema (CIA) is defined as three or more episodes of angioedema in a period of > 6 months without a clear etiology. In the study, we tried to explore clinical and laboratory characteristics of patients with CIA unaccompanied by urticaria. We retrospectively reviewed clinical and laboratory characteristics of 1238 patients with chronic urticaria and/or angioedema referred to our allergy clinic. Eight hundred and forty-one (67.9%) subjects had chronic urticaria without angioedema (CU Group), 323 (26.1%) had both urticaria and angioedema (CU + CA group), and 74 (5.9%) had chronic angioedema without urticaria (CA). In 29 (39.2%) cases of CA, no etiologic factor of angioedema was discovered, thus the patients were defined as having chronic idiopathic angioedema (CIA Group). Twenty-two (75.8%) subjects had antihistamine-responsive CIA and seven (24.1%) had antihistamine-unresponsive CIA. There were no statistically significant differences in clinical (except of urticarial eruptions) and laboratory characteristics between CU, CA + CU, and CIA groups. Antihistamine responsive and antihistamine-unresponsive CIA groups had no distinguishable clinical or laboratory features. We suppose that CIA, at least its antihistamine-responsive form, represents a rare form of chronic spontaneous urticaria. The reasons why in CIA there are no other clinical signs of mast cell/basophil activation, such as pruritus, urticarial, and dermatographism, are largely unknown and have to be elucidated in future studies. © 2014 The International Society of Dermatology.
Bouillet, Laurence; Longhurst, Hilary; Boccon-Gibod, Isabelle
OBJECTIVE: Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The course of angioedema may be very variable in different women. STUDY DESIGN: Within the PREHAEAT...... project launched by the European Union, data on 150 postpubertal women with hereditary angioedema were collected in 8 countries, using a patient-based questionnaire. RESULTS: Puberty worsened the disease for 62%. Combined oral contraceptives worsened the disease for 79%, whereas progestogen-only pills......-sensitive phenotype for some patients. CONCLUSION: The course of angioedema in women with C1 inhibitor deficiency is affected by physiologic hormonal changes; consequently, physicians should take these into account when advising on management....
Shroba, Jodi; Hanson, Jill; Portnoy, Jay
Idiopathic angioedema is defined as localized swelling of the cutaneous and mucosal tissue that occurs in episodes without a clear etiology. It can be problematic to treat when the underlying pathophysiology is not well understood. To identify successful treatments of idiopathic angioedema reported in the literature. A literature search was performed using PubMed. Published case reports and articles discussing treatment of idiopathic angioedema were used in the formulation of this review. In addition, 2 case reports are provided. Although there are no approved treatments for idiopathic angioedema, several medications used for the treatment of hereditary angioedema, such as bradykinin receptor antagonists (icatibant), kallikrein inhibitors (ecallantide), and C1 inhibitors, were successful in 10 patients. Anti-IgE monoclonal antibody (omalizumab) proved successful in 5 patients. The most widely used and successful medication was tranexamic acid (154 patients). Despite an unknown etiology, this article highlights viable treatment options for idiopathic angioedema. More clinical trials and better markers identifying the cause of angioedema are needed. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Hofman, Zonne L M; Relan, Anurag; Zeerleeder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C. Erik
Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to
Hofman, Zonne L. M.; Relan, Anurag; Zeerleder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C. Erik
Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to
A. Calvo Gómez-Rodulfo; J.E. García López; J.D. Herrero-Morín; G. Rodríguez García; F. González Guerra
Introducción: El angioedema hereditario es una patología de origen genético causada por la alteración del gen que codifica la proteína inhibidora de la C1 esterasa activada (C1-INH). La prevalencia de esta entidad es baja, lo que dificulta su diagnóstico y manejo adecuado.
Caso clínico: Se presenta el caso de una paciente con episodios repetidos de edema subcutáneo localizado en las extremidades desde los tres años de vida, añadiendo disfagia y disfonía a partir de la pu...
Speck, Aimee L; Killen, Paul D; Greenhawt, Matthew J
Angioedema is swelling of the deep layers of the dermis and subcutaneous tissue due to an increase in vascular permeability. Angioedema sometimes occurs concomitantly with urticaria and represents an allergic disease. In other cases, angioedema is not associated with an allergic condition. We present the case of a 31-year-old woman with new-onset angioedema in the setting of her first pregnancy. After detailed history, physical examination, and laboratory evaluation, a cause for her angioedema was found that had not been considered previously and had significant implications for future management, particularly in light of her current pregnancy. Because allergists are commonly called on to evaluate and treat angioedema, we should be aware of the many disease processes that can present with this symptom and be well-versed in the workup of new-onset angioedema.
Cicardi, M; Aberer, W; Banerji, A
Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have...... angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired...... and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema....
Felder, Sarah; Curtis, R Mason; Ball, Ian; Borici-Mazi, Rozita
Angioedema is a transient, localized swelling caused by two distinct mechanisms, mediated by histamine and bradykinin, respectively, although a proportion of cases remain idiopathic. Studies that characterize undifferentiated angioedema presenting in emergency departments (EDs) are limited. This study investigates the presentation patterns of undifferentiated angioedema in the ED based on the presumed mechanism of swelling. Medical records from all ED visits to two tertiary care hospitals from July 2007 to March 2012 were electronically reviewed. Records with documented visible swelling on general inspection and/or fiberoptic laryngoscopy and a diagnostic code for anaphylactic shock, angioneurotic edema, allergy unspecified, defects in the complement system, or unspecified drug adverse effects were included. Demographic, clinical, and outcome data were collected via a standardized form. Data were analyzed descriptively, including frequencies and percentages for categorical data and means and SDs for continuous data. Predictors for admission were identified using multivariate logistic regression models. ED records from 527 visits for angioedema by 455 patients were included in the study. Annual rate of angioedema was 1 per 1000 ED visits. Urticaria was associated with peripheral (p = 0.008) and lip angioedema (p = 0.001), and the absence of urticaria correlated with tongue angioedema (p = 0.001) and trended toward correlation with pharyngeal angioedema (p = 0.056). Significant predictors of admission included nonsteroidal anti-inflammatory drug-induced angioedema (odds ratio [OR], 15.3), epinephrine treatment (OR, 8.34), hypotension (OR, 15.7), multiple-site angioedema (OR, 4.25), and pharyngeal (OR, 1.23) and tongue angioedema (OR, 4.62). Concomitant urticaria was associated with a significant longer stay in the ED (p angioedema, need for airway management, length of ED visit, and recurrence. A detailed drug and family history, screening blood work for C1 esterase
Kim, Susan J; Brooks, Jordan C; Sheikh, Javed; Kaplan, Michael S; Goldberg, Bruce J
Hospital admission data indicate that the angioedema incidence has increased during the past several decades. Little is known about mortality trends. To count the number of deaths associated with angioedema in the United States, investigate correlations with age, sex, race, and other contributory causes, and analyze trends from 1979 to 2010. All US death certificates in which angioedema was listed as an underlying or contributing cause of death during 1979 to 2010 were analyzed. Age-adjusted mortality rates were analyzed by age, sex, and race. Other conditions designated as the underlying cause of death were investigated. From 1979 to 2010, there were 5,758 deaths in which angioedema was listed as a contributing cause. The age-adjusted death rate for hereditary angioedema decreased from 0.28 (95% confidence interval [CI] 0.25-0.32) to 0.06 (95% CI 0.05-0.08) per million persons per year. Conversely, mortality for angioedema increased from 0.24 (95% CI 0.21-0.27) to 0.34 (95% CI 0.31-0.37) per million. Blacks constituted 55% of angioedema deaths that were associated with use of angiotensin-converting enzyme inhibitors. On death certificates that listed hereditary angioedema as the underlying cause of death, cancer (frequently lymphoma or leukemia) was the second most commonly listed cause. Angioedema-associated deaths were very rare from 1979 to 2010. Hereditary angioedema deaths became even more so, whereas nonhereditary angioedema deaths increased. Risks associated with angiotensin-converting enzyme inhibitors were higher in blacks. Lack of specific coding for acquired angioedema most likely explains the observed association between cancer and hereditary angioedema. In the future, more granular coding systems may help distinguish hereditary from acquired angioedema. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Salas-Lozano, Nereo Guillermo; Meza-Cardona, Javier; González-Fernández, Coty; Pineda-Figueroa, Laura; de Ariño-Suárez, Mauricio
Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance characterized by sudden attacks of peripheral swelling. Patients also commonly have episodic swelling of the wall of hollow viscera, including the bowel. We present a 33-year-old previously healthy male with a complaint of acute-onset intense abdominal pain localized in the epigastrium. Pain irradiated to the right lower quadrant and was associated with five episodes of vomiting. Computed tomography showed thickening of the duodenal wall with liquid in the subphrenic space. Complementary laboratory tests showed low C4 complement levels (5.5 mg/dl) and 30% complement C1 inhibitor activity. Hereditary angioedema is caused by a deficiency (type I) or dysfunction (type II) in complement C1 inhibitor. Abdominal associated with angioedema may manifest as severe acute-onset abdominal pain or as moderately severe chronic recurrent abdominal pain. Two medications are currently FDA-approved for the treatment of these patients.
Full Text Available Angioedema is the swelling of the mucosal membranes as a variant of urticaria induced by hereditary C1 esterase inhibitor enzyme deficiency, certain foods, or drugs. Herein, we report the case of a 23-year-old woman, with mild-moderate acne presenting with widespread facial angioedema on the 2nd day of systemic isotretinoin treatment. The patient had taken no drugs other than isotretinoin in the preceding days and had no known food allergy. Her angioedema was resolved after the isotretinoin was discontinued. We want to draw the attention of dermatologists to this rare adverse allergic effect of isotretinoin which is frequently used in the treatment of acne vulgaris.
Cicardi, M; Aberer, W; Banerji, A; Bas, M; Bernstein, J A; Bork, K; Caballero, T; Farkas, H; Grumach, A; Kaplan, A P; Riedl, M A; Triggiani, M; Zanichelli, A; Zuraw, B
Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
The bradykinin B2 receptor antagonist icatibant is effective in angiotensin-converting enzyme inhibitor-induced angioedema. The drug is not approved officially for this indication and has to be administered in an emergency situation off-label. Corticosteroids or antihistamines do not seem to work in this condition. The effectiveness of C1-esterase-inhibitor in angiotensin-converting enzyme-induced angioedema must be verified in a double-blind study. Copyright Â© 2016 Elsevier Inc. All rights reserved.
C1-inhibitor (C1-INH) deficiency is a rare blood disorder resulting in angioedema attacks that are debilitating and may be life-threatening. Prophylaxis and therapy of events has changed since our first Canadian Consensus Conference on the diagnosis, therapy and management of HAE. We have formed the Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'Angioédème Héréditaire (RCAH) - http://www.haecanada.com to advance care of patients with this disorder in Canada. We here present a review of management of HAE in Canada. PMID:20667123
Farkas, Henriette; Veszeli, Nóra; Kajdácsi, Erika; Cervenak, László; Varga, Lilian
Angioedema, as a distinct disease entity, often becomes a clinical challenge for physicians, because it may cause a life-threatening condition, whereas prompt and accurate laboratory diagnostics may not be available. Although the bedside diagnosis needs to be established based on clinical symptoms and signs, family history, and the therapeutic response, later, laboratory tests are available. Currently, only for five out of the nine different types of angioedema can be diagnosed by laboratory testing, and these occur only in a minority of the patient population. Hereditary angioedema with C1-inhibitor (C1-INH) deficiency type I can be diagnosed by the low C1-INH function and concentration, whereas in type II, C1-INH function is low, but its concentration is normal or even elevated. C1q concentration is normal in both forms. Acquired angioedema with C1-INH deficiency type I is characterized by the low C1-INH function and concentration; however, C1q concentration is also low, and autoantibodies against C1-INH cannot be detected. Complement profile of acquired angioedema with C1-INH deficiency type II is similar to that of type I, but in this form, autoantibodies against C1-INH are present. Hereditary angioedema due to a mutation of the coagulation factor XII can be diagnosed exclusively by mutation analysis of FXII gene. Diagnostic metrics are not available for idiopathic histaminergic acquired angioedema, idiopathic non-histaminergic acquired angioedema, acquired angioedema related to angiotensin-converting enzyme inhibitor, and hereditary angioedema of unknown origin; these angioedemas can be diagnosed by medical and family history, clinical symptoms, and therapeutic response and by excluding the forms previously described. Several potential biomarkers of angioedema are used to date only in research. In the future, they could be utilized into the clinical practice to improve the differential diagnosis, therapy, as well as the prognosis of angioedema.
Defendi, F; Charignon, D; Ghannam, A; Ponard, D; Drouet, C
Kinin-mediated angioedema results from accumulation of kinins, vasoactive and vasopermeant peptides, on the vascular endothelium. The disease is characterized by sudden episodes of swelling in the subcutaneous and submucosal tissues; the edema may occur spontaneously or it may be precipitated by triggering factors such as physical or emotional stress, or certain medicines. The characterization of kinin formation and catabolism systems helps improve knowledge of the aetiopathogenic mechanisms involved and provides the basis for classification of kinin-mediated angioedema conditions; thus, we may distinguish between angioedema with C1 inhibitor deficiency, whether inherited or acquired, and angioedema with normal C1 inhibitor activity, associated with increased kinin-forming activity or deficiency in kinin catabolism enzymes. In support of the clinical diagnosis, the physician may request laboratory investigation for a functional and molecular definition of the disease. Laboratory diagnosis is based on the characterization of: (1) kinin production control by C1 inhibitor investigation (function, antigen levels and circulating species); (2) kinin production (kininogenase activity, kininogen cleavage species); and (3) kinin catabolism enzymes (aminopeptidase P, carboxypeptidase N, angiotensin-I converting enzyme and dipeptidyl peptidase IV). An abnormal biological phenotype is supported by examination of susceptibility genes (SERPING1, F12 and XPNPEP2) and mutation segregation in the families. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Bygum, Anette; Aygören-Pürsün, Emel; Beusterien, Kathleen
The objective of the Hereditary Angioedema Burden of Illness Study in Europe was to assess the real-world experience of HAE from the patient perspective. Based on open-ended qualitative interviews with 30 patients from Spain, Germany and Denmark, 5 key themes emerged characterizing the impact...
Rasmussen, Eva Rye; Pallesen, Kristine A U; Bygum, Anette
We report a case of acute dystonia of the face, jaw and tongue caused by metoclopramide and mimicking angioedema. The patient had attacks for several years before the correct diagnosis was made and we present the first ever published video footage of an attack. This adverse drug reaction is known...
Madsen, Flemming; Attermann, Jorn; Linneberg, Allan
The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...
Madsen, Flemming; Attermann, Jørn; Linneberg, Allan
The prevalence of non-hereditary angioedema was investigated in a general population sample (n¿=¿7,931) and in a sample of Danish patients (n¿=¿7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...
Bork, Konrad; Wulff, Karin; Witzke, Günther; Stanger, Christian; Lohse, Peter; Hardt, Jochen
In women with sporadic recurrent angioedema with an unknown cause who are unresponsive to antihistamines and have normal C1 inhibitor activity and a negative family history of angioedema, it is unclear whether they have idiopathic angioedema or hereditary angioedema with normal C1 inhibitor, and what impact exogenous estrogens have on their angioedema. A cohort of 147 women was analyzed for F12 exon 9 mutations and for the influence of oral contraceptives, hormonal replacement therapy, and pregnancy on their angioedema. A total of 142 women had idiopathic angioedema unresponsive to antihistamines. Five women had an F12 mutation and thereby hereditary angioedema with F12 mutations. Among the women with idiopathic angioedema, 63 had never taken estrogens. There was no estrogen impact in 42 women, a moderate impact in 15 women, and a severe impact in 22 women. The type and dose of estrogens did not differ in women with and without an estrogen impact. In 5 women, idiopathic angioedema disappeared after desogestrel use. Among the 5 women with hereditary angioedema with F12 mutations, angioedema symptoms occurred during 4 pregnancies, whereas no symptoms occurred during any of the 58 pregnancies in women with idiopathic angioedema. Women with recurrent angioedema unresponsive to antihistamines may have idiopathic angioedema or, more rarely, hereditary angioedema with F12 mutations. Both conditions may be provoked or aggravated by exogenous estrogens. In idiopathic angioedema, treatment with progestins may be helpful. Copyright © 2013. Published by Elsevier Inc.
Rasmussen, Eva Rye; Mey, Kristianna; Bygum, Anette
Angioedema is a sudden localised and often asymmetric swelling of the skin or mucous membranes caused by transient increased endothelial permeability causing plasma extravasation. In the last decades the incidence of severe angioedema involving the upper airways and even fatal outcome due....... The diagnosis is often delayed and traditional treatment usually ineffective. Complement C1 inhibitor concentrate and bradykinin receptor antagonists, normally used to treat patients with hereditary angioedema, have shown good results when used in patients with bradykinin-mediated angioedema. This review...
Cosatti, Micaela; Fernández Romero, Diego S; Juri, María Cecilia; Malbrán, Alejandro
The use of fillers for cosmetic purposes is becoming increasingly frequent. Although initially considered inert, these products produce adverse reactions around the injection site. We present 5 cases of women with a history of filler injections who presented a hard and persistent angioedema followed by local subcutaneous nodules. They were referred to the allergist for suspected allergy related angioedema without response to usual antihistamine treatment. The angioedema episodes initiated 27.6 months (range 1 to 48) after the fillers treatment. The patients underwent exacerbations and remissions of angioedema, partially relieved with oral steroids and, in 2 cases, local triamcinolone injections. Mean time from onset of symptoms to remission of angioedema was 8.75 months (range 1 to 24). Until October 2009 four patients continued into remission after 24.5 months (range 7 to 36) free of symptoms. One patient continued with exacerbations 11 months after the initial symptoms. Fillers may cause angioedema as an adverse event and should be considered in the differential diagnosis of persistent angioedema. They are only sensitive to steroid treatment and in some steroid dependent cases they respond to ciclosporin. The frequency of angioedema after filler injections among patients with angioedema in the Unit of Asthma Allergy and Clinical Immunology was 0.5%.
Krizova, Adriana; Gardner, Taylor; Little, D'Arcy L; Arcieri-Piersanti, V; Pollanen, Michael S
Angioedema is an episodic swelling of the deep dermis, subcutis, and/or submucosal tissue due to an increase in local vascular permeability. Swelling may involve skin, respiratory, and gastrointestinal tracts. The most commonly involved areas are the periorbital region and the lips. Here we report a case of a fatal laryngeal obstruction due to angioedema likely caused by an angiotensin-converting-enzyme inhibitor. The decedent, a 58-year-old man, was witnessed developing sudden facial swelling and acute respiratory difficulties quickly followed by unresponsiveness. His past medical history suggested that this was his second episode of angioedema without urticaria. Postmortem examination revealed a complete laryngeal obstruction in the absence of infection, neoplasm, or autoimmune disease. Postmortem computed tomography of the head and neck showed a complete obstruction of the upper airway. Based on the current understanding of the pathophysiology of different types of angioedema, we will suggest a workup of angioedema without urticaria in the forensic setting and offer readers resources they can use in their practice.
Hofman, Zonne L M; Relan, Anurag; Zeerleder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C Erik
Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to the formation of bradykinin (BK), which increases local vasopermeability and mediates angioedema on interaction with BK receptor 2 on the endothelium. However, several observations in patients with HAE are difficult to explain from a pathogenic model claiming a local activation process at the site of the angioedema attack. Therefore we postulate an alternative model for angioedema attacks in patients with HAE, which assumes a systemic, fluid-phase activation of the contact system to generate BK and its breakdown products. Interaction of these peptides with endothelial receptors that are locally expressed in the affected tissues rather than with receptors constitutively expressed by the endothelium throughout the whole body explains that such a systemic activation process results in local manifestations of an attack. In particular, BK receptor 1, which is induced on the endothelium by inflammatory stimuli, such as kinins and cytokines, meets the specifications of the involved receptor. The pathogenic model discussed here also provides an explanation for why angioedema can occur at multiple sites during an attack and why HAE attacks respond well to modest increases of circulating C1INH activity levels because inhibition of fluid-phase Factor XIIa and kallikrein requires lower C1INH levels than inhibition of activator-bound factors. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Acute allergic angioedema is an abrupt-onset, unpredictable inflammatory reaction of the skin and mucous membranes. A 60-years-old female patient presented to our emergency department with dispne and edema in her mouth and lips. It was learned from the history that her symptoms were begun 15 minutes after eating a pear. 40 mg methylprednisolone and 50 mg diphenhydramine were administered intravenously.
Acute allergic angioedema is an abrupt-onset, unpredictable inflammatory reaction of the skin and mucous membranes. A 35-year-old female patient presented to our emergency department with redness on the cheeks and edema in her mouth and eyelids. It was learned from the history that her symptoms were begun 15 minutes after eating a pomegranate. 40 mg methylprednisolone and 50 mg diphenhydramine were administered intravenously.
Full Text Available Acute allergic angioedema is an abrupt-onset, unpredictable inflammatory reaction of the skin and mucous membranes. A 35-year-old female patient presented to our emergency department with redness on the cheeks and edema in her mouth and eyelids. It was learned from the history that her symptoms were begun 15 minutes after eating a pomegranate. 40 mg methylprednisolone and 50 mg diphenhydramine were administered intravenously.
Acute allergic angioedema is an abrupt-onset, unpredictable inflammatory reaction of the skin and mucous membranes. A 60-years-old female patient presented to our emergency department with dispne and edema in her mouth and lips. It was learned from the history that her symptoms were begun 15 minutes after eating a pear. 40 mg methylprednisolone and 50 mg diphenhydramine were administered intravenously.
Francisca Muñoz Peralta
Full Text Available El angioedema hereditario es una enfermedad rara, de gran heterogeneidad en los síntomas, manifestándose con edema a nivel cutáneo, mucosa gastrointestinal y de laringe/faringe. Aunque existen tres variedades, el tipo I es el más frecuente y es provocado por una deficiencia en la síntesis del complemento C1 inhibidor. La gravedad de la clínica, junto a la baja prevalencia de la enfermedad y la necesidad de un tratamiento específico, hacen que el diagnóstico y tratamiento de dicha patología sea aún una asignatura pendiente para el médico de familia en atención primaria. Presentamos el caso de un adolescente varón con déficit de α-1 antitripsina desde los seis meses de edad, con aparición de angioedemas en piernas y brazos a los 11 años, diagnosticado de angioedema hereditario tipo I un año después. El diagnóstico definitivo de la enfermedad permitió instaurar un tratamiento adecuado a su patología, que consiste en la prevención de brotes que puedan comprometer la vida del paciente y, en el caso de que aparezcan, en la administración del complemento C1 inhibidor.
Hudey, Stephanie N; Westermann-Clark, Emma; Lockey, Richard F
Medication-induced angioedema is a bradykinin-mediated process that results from increased production or decreased degradation of bradykinin. These reactions are documented for several cardiac medications including blockers of the renin-angiotensin-aldosterone system (RAAS). Other cardiovascular and diabetes medications further increase the risk of medication-induced angioedema, particularly with concomitant use of RAAS inhibitors. Dipeptidyl peptidase IV inhibitors are a class of oral diabetic agents that affect bradykinin and substance P degradation and therefore can lead to angioedema. Neprilysin inhibitors are a separate class of cardiac medications, which includes sacubitril, and can lead to drug-induced angioedema especially when used in combination with RAAS inhibitors. This article discusses the proposed mechanisms by which these medications cause angioedema and how medication-induced angioedema differs from mast cell-mediated angioedema. It also details how to recognize medication-induced angioedema and the treatment options available. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Lucerna, Alan R; Espinosa, James; Darlington, Anne M
It is rare for angioedema to be misidentified by the experienced clinician or for it to mimic another disease process. As an Emergency Physician, it is important to recognize and treat angioedema immediately. Of equal importance is the recognition and initiation of treatment of facial cellulitis. A case report follows that illustrates methicillin-resistant Staphylococcus aureus (MRSA) lip infection mimicking angioedema. Here, we describe a case of a 21-year-old man who presented with a swollen lower lip, initially diagnosed as angioedema. Further investigation revealed the cause of his lip swelling was actually a MRSA abscess and surrounding cellulitis, an unusual presentation for lip infection, which we discuss below. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Misidentifying MRSA lip infection for angioedema, with a delay in proper treatment, could result in serious morbidity or mortality. Copyright © 2015 Elsevier Inc. All rights reserved.
Bertazzoni, G; Spina, M T; Scarpellini, M G; Buccelletti, F; De Simone, M; Gregori, M; Valeriano, V; Pugliese, F R; Ruggieri, M P; Magnanti, M; Susi, B; Minetola, L; Zulli, L; D'Ambrogio, F
Acute angioedema represents a cause of admission to the emergency department requiring rapid diagnosis and appropriate management to prevent airway obstruction. Several drugs, including angiotensin-converting enzyme inhibitors (ACE-I), nonsteroidal anti-inflammatory drugs (NSAIDs) and oral antidiabetics, have been reported to induce angioedema. The aim of this prospective observational study conducted in a setting of routine emergency care was to evaluate the incidence and extent of drug-induced non-histaminergic angioedema in this specific clinical setting, and to identify the class of drugs possibly associated with angioedema. Patients admitted to seven different emergency departments (EDs) in Rome with the diagnosis of angioedema and urticaria were enrolled during a 6-month period. Of the 120,000 patients admitted at the EDs, 447 (0.37 %) were coded as having angioedema and 655 (0.5 %) as having urticaria. After accurate clinical review, 62 cases were defined as drug-induced, non-histaminergic angioedema. NSAIDs were the most frequent drugs (taken by 22 out of 62 patients) associated with the angioedema attack. Of the remaining patients, 15 received antibiotic treatment and 10 antihypertensive treatment. In addition, we observed in our series some cases of angioedema associated with drugs (such as antiasthmatics, antidiarrheal and antiepileptics) of which there are few descriptions in the literature. The present data, which add much needed information to the existing limited literature on drug-induced angioedema in the clinical emergency department setting, will provide more appropriate diagnosis and management of this potentially life-threatening adverse event.
Sergio Duarte Dortas Junior; Solange Oliveira Rodrigues Valle; Soloni Afra Pires Levy; Rosangela P. Tortora; Augusto Tiaqui Abe; Gisele Viana Pires; José Angelo de Souza Papi; Alfeu Tavares França
Hereditary Angioedema is a dominantly inherited disease. Routine screening of autoantibodies (AAB) is not recommended for individuals with Hereditary Angioedema; however, prevalence of these antibodies in Hereditary Angioedema patients is not well documented. We aim to determine the prevalence of AAB so that individuals at risk of developing autoimmune diseases can be identified. Fifteen patients with Hereditary Angioedema attended at Clementino Fraga Filho University Hospital accepted to par...
Full Text Available Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom the disease goes undetected and who are therefore incorrectly treated is 25-40%. In addition to edema of the glottis, hereditary angioedema often results in edema of the gastrointestinal tract, which can be incapacitating. Patients with hereditary angioedema may undergo unnecessary surgical interventions because the digestive tract can be the primary or only organ system involved, thus mimicking acute surgical abdomen. It is estimated that patients with hereditary angioedema experience some degree of disability 20-100 days per year. The Experts in Clinical Immunology and Allergy of the "Associação Brasileira de Alergia e Imunopatologia -ASBAI" developed these guidelines for the diagnosis, therapy, and management of hereditary angioedema.
Bezalel, Shira; Mahlab-Guri, Keren; Asher, Ilan; Werner, Ben; Sthoeger, Zev Moshe
Angiotensin-converting enzyme inhibitors (ACE-I) are widely used, effective, and well-tolerated antihypertensive agents. The mechanisms by which those agents act can cause side effects such as decreased blood pressure, hyperkalemia, and impaired renal function. ACE-I can induce cough in 5%-35% and angioedema in up to 0.7% of treated patients. Because cough and angioedema are considered class adverse effects, switching treatment to other ACE-I agents is not recommended. Angioedema due to ACE-I has a low fatality rate, although deaths have been reported when the angioedema involves the airways. Here, we review the role of bradykinin in the development of angioedema in patients treated with ACE-I, as well as the incidence, risk factors, clinical presentation, and available treatments for ACE-I-induced angioedema. We also discuss the risk for recurrence of angioedema after switching from ACE-I to angiotensin receptor blockers treatment. Copyright © 2015 Elsevier Inc. All rights reserved.
Pedrosa, Maria; Prieto-García, Alicia; Sala-Cunill, Anna
Angioedema refers to a localized, transient swelling of the deep skin layers or the upper respiratory or gastrointestinal mucosa. It develops as a result of mainly two different vasoactive peptides, histamine or bradykinin. Pathophysiology, as well as treatment, is different in each case; nevertheless, the resulting signs and symptoms may be similar and difficult to distinguish. Angioedema may occur at any location. When the affected area involves the upper respiratory tract, both forms of angioedema can lead to an imminent upper airway obstruction and a life-threatening emergency. Emergency physicians must have a basic understanding of the pathophysiology underlying this process. Angioedema evaluation in the emergency department (ED) should aim to distinguish between histamine- and bradykinin-induced angioedema, in order to provide appropriate treatment to patients. However, diagnostic methods are not available at the ED setting, neither to confirm one mechanism or the other, nor to identify a cause. For this reason, the management of angioedema should rely on clinical data depending on the particular features of the episode and the patient in each case. The history-taking should be addressed to identify a possible etiology or triggering agent, recording complete information for an ulterior diagnostic study in the outpatient clinic. It is mandatory quickly to recognize and treat a potential life-threatening upper airway obstruction or anaphylaxis. This review focuses on the underlying mechanisms and management of histamine- and bradykinin-induced angioedema at the emergency department and provides an update on the currently available treatments.
Angioedema is a sudden, transient swelling of well-demarcated areas of the dermis, subcutaneous tissue, mucosa, and submucosal tissues that can occur with or without urticaria. Up to 25% of people in the US will experience an episode of urticaria or angioedema during their lifetime, and many will present to the emergency department with an acute attack. Most cases of angioedema are attributable to the vasoactive mediators histamine and bradykinin. Histamine-mediated (allergic) angioedema occurs through a type I hypersensitivity reaction, whereas bradykinin-mediated (non-allergic) angioedema is iatrogenic or hereditary in origin. Although their clinical presentations bear similarities, the treatment algorithm for histamine-mediated angioedema differs significantly from that for bradykinin-mediated angioedema. Corticosteroids, and epinephrine are effective in the management of histamine-mediated angioedema but are ineffective in the management of bradykinin-mediated angioedema. Recent advancements in the understanding of angioedema have yielded pharmacologic treatment options for hereditary angioedema, a rare hereditary form of bradykinin-mediated angioedema. These novel therapies include a kallikrein inhibitor (ecallantide) and a bradykinin β2 receptor antagonist (icatibant). The physician’s ability to distinguish between these types of angioedema is critical in optimizing outcomes in the acute care setting with appropriate treatment. This article reviews the pathophysiologic mechanisms, clinical presentations, and diagnostic laboratory evaluation of angioedema, along with acute management strategies for attacks. PMID:23131076
Caballero, Teresa; Aygören-Pürsün, Emel; Bygum, Anette
Hereditary angioedema (HAE) is a rare but potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The broad range of consequences of HAE on patients? lives is not well understood. The study objective was to comprehensively characterize the burden of illness......, traveling, and passing HAE to their children. Based on Hospital Anxiety and Depression Scale scores, 38 and 14% had clinically meaningful anxiety and depression, respectively. Despite standard of care, HAE patients still have frequent and painful attacks. Patients experience substantial impairment...
Experiences from a Danish patient cohort with hereditary angioedema are reported with focus on home therapy and burden of illness. Eighty patients have been prospectively followed over 11 years, having experienced a total of 7,809 attacks over 469 patient years. More than half of the patients...... stopped long-term prophylaxis with danazol or tranexamic acid and changed treatment regimen to on-demand treatment with C1 inhibitor concentrate or icatibant. At least 10% of the attacks remained un-treated. More than half of the patients felt that hereditary angioedema had a significant psychological...... therapy has profoundly improved the lives of hereditary angioedema patients....
Lewis, Lawrence M
Angioedema (AE) is characterized by nonpitting edema of the dermis and subcutaneous layers. The most common sites of involvement are the tongue, lips, face, and throat; however, swelling can also occur in the extremities, genitalia, and viscera. Life-threatening airway swelling can also occur. AE may be allergic or nonallergic. The overall lifetime incidence of AE is reported to be as high as 15%. This article summarizes the etiology, pathophysiology, and current treatment of several forms of nonallergic AE (including hereditary, acquired, and idiopathic AE) and focuses on angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE), which is responsible for 30%-40% of all AE seen in United States emergency departments. Although the triggers, which are primary biologic mechanisms, and treatments for ACEi-AE may differ from those of the hereditary and acquired forms of AE, the clinical effects of ACEi-AE are mediated through a shared pathway, the kallikrein-kinin system. Thus, although current therapeutic options for ACEi-AE are limited, recent advances in the treatment of hereditary AE (HAE) appear promising for improving the outcomes of patients with ACEi-AE. New HAE medications that correct imbalances in the kallikrein-kinin system may prove safe and efficacious in the treatment of ACEi-AE. Copyright © 2013 Elsevier Inc. All rights reserved.
Micaela A. Cosatti
Full Text Available En los últimos años se ha incrementado la utilización de sustancias de relleno facial con fines estéticos. Estos productos, originalmente considerados inertes, se asocian con diversos efectos adversos localizados alrededor del sitio de la aplicación. Describimos a 5 mujeres con antecedentes de inyecciones de sustancia de relleno facial que presentaron como síntoma inicial angioedema facial duro y persistente seguido por la aparición de nódulos subcutáneos. Todas las pacientes fueron derivadas al servicio de alergia por sospecha de angioedema de causa alérgica sin respuesta al tratamiento con antihistamínicos. El angioedema inició 27.6 meses (1 a 48 luego de la inyección del producto, y las pacientes evolucionaron con brotes y remisiones que fueron tratados con corticoides orales y en 2 oportunidades con inyecciones locales. El tiempo medio desde el inicio de los síntomas hasta la remisión del angioedema fue 8.75 meses (1 a 24. A octubre de 2009 cuatro pacientes se mantuvieron en remisión persistente, luego de un seguimiento clínico de 24.5 meses (7 a 36. Una paciente continúa con exacerbaciones luego de 11 meses de iniciados los síntomas. Las sustancias de relleno facial pueden producir angioedema como evento adverso y deben ser consideradas en el diagnóstico diferencial del angioedema persistente. Sólo responden al tratamiento con esteroides y en algunos casos esteroides dependientes, con ciclosporina. La frecuencia de angioedema por rellenos faciales entre pacientes con angioedema asistidos en la Unidad de Asma, Alergia e Inmunología Clínica fue del 0.5%.The use of fillers for cosmetic purposes is becoming increasingly frequent. Although initially considered inert, these products produce adverse reactions around the injection site. We present 5 cases of women with a history of filler injections who presented a hard and persistent angioedema followed by local subcutaneous nodules . They were referred to the allergist for
Full Text Available Angioedema secondary to C1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. A genetic defect of C1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless edema, but edema of the genital area, gastrointestinal and laryngeal tracts have also been reported. In lupus patients, angioedema may be the result of an acquired type of C1 inhibitor deficiency, most probably due to antibody formation directed against the C1 inhibitor molecule. Herein we report a new case of lupus nephritis that developed angioedema and a rapid course of disease progression with acute renal failure and alveolar hemorrhage without response to high dose steroid and plasmapheresis.
Full Text Available Angioedema can cause potentially life-threatening airway obstruction. This case report describes an exceedingly rare episode of ticagrelor-induced hypersensitivity reaction, manifesting as angioedema with periorbital and likely respiratory involvement. The heart team should be vigilant for this precarious condition which may require emergent airway management. Desensitization protocols and alternative regimens (e.g., clopidogrel, prasugrel, and addition of an adjunctive anticoagulant should be considered when there is an absolute indication for antiplatelet therapy.
Seecheran, Rajeev; Seecheran, Valmiki; Persad, Sangeeta; Lalla, Sasha; Seecheran, Naveen Anand
Angioedema can cause potentially life-threatening airway obstruction. This case report describes an exceedingly rare episode of ticagrelor-induced hypersensitivity reaction, manifesting as angioedema with periorbital and likely respiratory involvement. The heart team should be vigilant for this precarious condition which may require emergent airway management. Desensitization protocols and alternative regimens (e.g., clopidogrel, prasugrel, and addition of an adjunctive anticoagulant) should be considered when there is an absolute indication for antiplatelet therapy.
MacBeth, Lisa S; Volcheck, Gerald W; Sprung, Juraj; Weingarten, Toby N
Two types of bradykinin-mediated angioedema, hereditary angioedema (HAE) and acquired angioedema (AAE), result from deficiency or dysfunction of C1 esterase inhibitor, leading to an overproduction of bradykinin, which can lead to vascular permeability and life-threatening angioedema of the airway. The objective of this study was to review perioperative outcomes in a series of patients with HAE and AAE and to review current knowledge about anesthetic complications in patients with HAE or AAE. Medical records were retrospectively reviewed for perioperative complications in patients with HAE or AAE who underwent general anesthesia from January 1, 2000, to December 31, 2014, at our institution. Twenty-four patients (13 with HAE, 10 with AAE, and 1 with unspecified angioedema) underwent 38 instances of general anesthesia with airway manipulation. All except 4 received prophylactic therapy. One patient, a 67-year-old woman who was pretreated with stanozolol and fresh frozen plasma required reintubation after postoperative airway edema developed. Life-threatening episodes of angioedema of the airway occur infrequently, but they can occur in patients who received pretreatment and in patients who have previously undergone anesthesia uneventfully. Anesthesiologists must be ready to emergently manage a difficult airway and must be familiar with recommendations provided in consensus guidelines for the treatment of HAE and AAE patients. Copyright © 2016 Elsevier Inc. All rights reserved.
Winters, Michael E; Rosenbaum, Steven; Vilke, Gary M; Almazroua, Faisal Y
Angiotensin-converting-enzyme inhibitors (ACEI) are one of the most prescribed medications worldwide. Angioedema is a well-recognized adverse effect of this class of medications, with a reported incidence of ACEI angioedema of up to 1.0%. Of importance to note, ACEI angioedema is a class effect and is not dose dependent. The primary goal of this literature search was to determine the appropriate Emergency Department management of patients with ACEI angioedema. A MEDLINE literature search from January 1990 to August 2012 and limited to human studies written in English for articles with keywords of ACEI angioedema. Guideline statements and non-systematic reviews were excluded. Studies identified then underwent a structured review from which results could be evaluated. Five hundred sixty-two papers on ACEI angioedema were screened and 27 appropriate articles were rigorously reviewed in detail and recommendations given. The literature search did not support any specific treatment protocol with a high level of evidence due to the limited--and limitations of the--available studies. Copyright © 2013 Elsevier Inc. All rights reserved.
Floccard, B; Crozon, J; Rimmelé, T; Vulliez, A; Coppere, B; Chamouard, V; Boccon-Gibod, I; Bouillet, L; Allaouchiche, B
Present the clinical signs of bradykinin-mediated angioedema, a disease little known to intensive care anaesthesiologists, and develop their scientific basis with recent data on management in emergency and perioperative care. International recommendations and recent general reviews. Data collection was performed using the Medline database with the keyword: angioedema. Research studies published during the last 10 years were reviewed. Relevant clinical information was extracted and discussed. Angioedema is a clinical syndrome characterized by episodes of transitory recurrent submucosal and subcutaneous oedema, called attacks. During an attack, the oedema may be localized at the level of the skin and/or ENT and digestive tract mucosa. This syndrome is not due to an allergic reaction. It is related to a C1 complement inhibitor deficiency or an increase in factor XII resulting in the excessive release of bradykinin, which leads to capillary permeability. There are hereditary and acquired forms, notably associated with the use of ACE inhibitors and sartans. This rare disease should be recognized by anaesthesiologists and intensive care and emergency physicians because, in the absence of specific treatment, it can be life-threatening due to the appearance of laryngeal oedema. In addition, there is a risk that the patient may have an attack during the perioperatory period, due to surgical trauma. International recommendations exist, and there are new molecules available in France. For moderate attacks, treatment is based on tranexamic acid. For hereditary forms, according to the localization and gravity of the attacks, emergency treatment is based on the use of Icatibant, a bradykinin B2 receptor inhibitor, and C1 inhibitor concentrate. For pregnant women and acquired forms, C1 inhibitor concentrate is the treatment of reference. Antalgic and perfusion treatments should not be neglected, and should be modified as a function of clinical signs. High-risk situations
Maurer, M; Sofen, H; Ortiz, B; Kianifard, F; Gabriel, S; Bernstein, J A
Approximately 50% of patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report hives and angioedema; some experience hives/angioedema only. Assess omalizumab's effect on angioedema and quality of life (QoL) in subgroups with refractory CIU/CSU: those with and without angioedema. Patients received omalizumab (75, 150 or 300 mg) or placebo every 4 weeks for 12/24 weeks. Angioedema and QoL were assessed [Urticaria Patient Daily Diary and Dermatology Quality of Life Index (DLQI)]. Subgroups were based on the presence/absence of baseline angioedema 7 days prior to randomization. Patients with baseline angioedema randomized to omalizumab 300 mg had a greater reduction in mean weekly incidence of angioedema and mean number of days/week with angioedema vs. placebo at 12 and 24 weeks. A 3.3- to 4.5-point greater mean reduction in DLQI score was achieved with omalizumab 300 mg treatment vs. placebo, above the minimal clinically important difference threshold. Results with lower doses vs. placebo were variable. Compared with placebo, omalizumab 300 mg treatment over 12-24 weeks resulted in marked reduction in incidence and number of days/week with angioedema accompanied by clinically relevant improvement in QoL. © 2016 European Academy of Dermatology and Venereology.
Malbrán, Eloisa; Fernández Romero, Diego; Juri, Maria Cecilia; Larrauri, Blas J; Malbrán, Alejandro
We describe the diagnostic epidemiology, the clinical course, the family history and the response to treatment of patients with angioedema without wheals (AWW) at an Allergy and Immunology Clinical Center. We reviewed the case records of all patients at our office from January 1997 to April 2013. We recorded sex, age, age at onset of symptoms, family history of angioedema, number of visits to the office, type of angioedema, and response to treatment from those patients with angioedema without wheals. We classified angioedema according to its pathophysiology. We also describe those patients with angioedema mimics. From a total of 17,823 new patients, 303 had a presumptive diagnosis of angioedema without wheals. Twenty-three patients had an angioedema mimic. Forty percent were male and 60% were female. Average age at first visit was 40.6. Average number of visits was 2.4. Fifty-seven patients referred a family history. We attributed idiopathic angioedema to 55.7% of patients, 24.3% were drug related, 15.7% were due to C1 inhibitor deficiency, 2.1% were drug related+idiopathic angioedema, 1.4% were type III and 0.7% had exercise-induced angioedema. Ninety six percent of 53 evaluable idiopathic angioedema patients referred a benefit with anti-histamine therapy. AWW was a rare cause of consultation. Most of our patients had anti H1 responsive idiopathic angioedema and none had allergic angioedema. Women cases prevailed over men's. Family history and average age of onset of symptoms were different among the different types of angioedema.
Davis Alvin E
Full Text Available Abstract Hereditary angioedema is a serious medical condition caused by a deficiency of C1-inhibitor. The condition is the result of a defect in the gene controlling the synthesis of C1-inhibitor, which regulates the activity of a number of plasma cascade systems. Although the prevalence of hereditary angioedema is low – between 1:10,000 to 1:50,000 – the condition can result in considerable pain, debilitation, reduced quality of life, and even death in those afflicted. Hereditary angioedema presents clinically as cutaneous swelling of the extremities, face, genitals, and trunk, or painful swelling of the gastrointestinal mucosa. Angioedema of the upper airways is extremely serious and has resulted in death by asphyxiation. Subnormal levels of C1-inhibitor are associated with the inappropriate activation of a number of pathways – including, in particular, the complement and contact systems, and to some extent, the fibrinolysis and coagulation systems. Current findings indicate bradykinin, a product of contact system activation, as the primary mediator of angioedema in patients with C1-inhibitor deficiency. However, other systems may play a role in bradykinin's rapid and excessive generation by depleting available levels of C1-inhibitor. There are currently no effective therapies in the United States to treat acute attacks of hereditary angioedema, and currently available agents used to treat hereditary angioedema prophylactically are suboptimal. Five new agents are, however, in Phase III development. Three of these agents replace C1-inhibitor, directly addressing the underlying cause of hereditary angioedema and re-establishing regulatory control of all pathways and proteases involved in its pathogenesis. These agents include a nano-filtered C1-inhibitor replacement therapy, a pasteurized C1-inhibitor, and a recombinant C1-inhibitor isolated from the milk of transgenic rabbits. All C1-inhibitors are being investigated for acute angioedema
Bas, M; Greve, J; Strassen, U; Khosravani, F; Hoffmann, T K; Kojda, G
During the last years, two new cardiovascular drug classes, namely inhibitors of DPP IV or neprilysin, have been developed. In both cases, there is clinical evidence for their potential to induce angioedema as known already from blockers of the renin-angiotensin-aldosterone system (RAAS). The majority of angioedema induced by DPP IV inhibitors occurs during concomitant treatment with ACEi and is therefore likely mediated by overactivation of bradykinin type 2 receptors (B2). In striking contrast, the molecular pathways causing angioedema induced by neprilysin inhibitors, that is, sacubitril, are unclear, although a contribution of bradykinin appears likely. Nevertheless, there is no clinical evidence suggesting that inhibition of B2 might relieve the symptoms and/or prevent invasive treatment including coniotomy or tracheotomy in angioedema caused by these drugs. Therefore, the risk of angioedema should always be considered, especially in ambulatory care situations where patients have no rapid access to intensive care. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Gandhi, Jimit; Jones, Rachel; Teubner, David; Gabb, Genevieve
Angiotensin-converting enzyme (ACE) inhibitors are a commonly used class of medications that are generally well tolerated. However, angioedema, a rare but potentially life-threatening adverse effect, may occur. A retrospective audit was performed on patients who presented with angioedema to two emergency departments in Adelaide, Australia. Case notes of patients presenting with angioedema who were using an ACE inhibitor were reviewed. This study examined the clinical features of presentation, treatment and outcomes of the patients. A total of 164 patients were identified as having angioedema across the two emergency departments. Fifty-one (31%; 95% CI = 24-39) were found to be on an ACE inhibitor. The two main presenting symptoms were soft tissue swelling in the head and neck (98%), and respiratory distress (33%), both of which usually developed after several hours. Patients were commonly treated with steroids (70%), antihistamines (65%) and adrenaline (35%). Two patients developed airway obstruction. A substantial proportion of emergency department encounters with angioedema in South Australia are from patients who also use an ACE inhibitor. It is important that general practitioners are aware of this problem, to enable rapid recognition and appropriate patient education when prescribing these medications.
Andersen, Michelle Fog; Longhurst, Hilary J; Rasmussen, Eva Rye
BACKGROUND: Angioedema is a vascular reaction involving the lower dermis, subcutis and/or submucosal tissue and causing a temporary localized swelling in any part of the body. For many health care professionals, the diagnosis presents an ongoing challenge; several disorders may manifest with subc......BACKGROUND: Angioedema is a vascular reaction involving the lower dermis, subcutis and/or submucosal tissue and causing a temporary localized swelling in any part of the body. For many health care professionals, the diagnosis presents an ongoing challenge; several disorders may manifest...... with subcutaneous or submucosal swelling and falsely be assumed to be angioedema. The clinicians at the emergency department and in the immunology/allergy clinics must be skilled at recognizing the features of angioedema and its differential diagnosis. METHODS: The review is based on a literature search...... with specific indexing terms in PubMed, a review of bibliographies and the authors' clinical experience. RESULTS: The most essential diseases that mimic angioedema, the so-called pseudoangioedemas, will each be discussed and illustrated by clinical photos, pointing out key features that help clarify...
Rasmussen, Eva Rye; von Buchwald, Christian; Wadelius, Mia
Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study...... Design. Cohort study. Methods. This was a retrospective cohort study of 105 patients with angiotensin converting enzyme-inhibitor induced angioedema in the period 1995-2014. Results. The cohort consisted of 67 females and 38 males (F : M ratio 1.8), with a mean age of 63 [range 26-86] years. Female...... gender was associated with a significantly higher risk of angiotensin converting enzyme-inhibitor induced angioedema. 6.7% had a positive family history of angioedema. Diabetes seemed to be a protective factor with regard to angioedema. 95% experienced angioedema of the head and neck. 4.7% needed...
Sergio Duarte Dortas Junior
Full Text Available Hereditary Angioedema is a dominantly inherited disease. Routine screening of autoantibodies (AAB is not recommended for individuals with Hereditary Angioedema; however, prevalence of these antibodies in Hereditary Angioedema patients is not well documented. We aim to determine the prevalence of AAB so that individuals at risk of developing autoimmune diseases can be identified. Fifteen patients with Hereditary Angioedema attended at Clementino Fraga Filho University Hospital accepted to participate in this study. Prevalence of AAB was 40%. Our data indicate high prevalence of AAB in patients with Hereditary Angioedema. Large-scale studies should be considered to determine the significance of these AAB in the follow-up care of patients with Hereditary Angioedema.O Angioedema Hereditário é uma doença autossômica dominante. A pesquisa de rotina para autoanticorpos não é recomendada para pacientes com Angioedema Hereditário; entretanto, a prevalência desses anticorpos em pacientes com Angioedema Hereditário não está bem documentada. Objetivamos determinar a prevalência de autoanticorpos para identificar indivíduos sob risco de desenvolver doenças autoimunes. Quinze pacientes com Angioedema Hereditário atendidos no Hospital Universitário Clementino Fraga Filho aceitaram participar do estudo. A prevalência de autoanticorpos foi de 40%. Nossos dados indicam alta prevalência de autoanticorpos em pacientes com Angioedema Hereditário. Estudos de maior escala deveriam ser considerados para determinar a significância desses autoanticorpos no acompanhamento clínico de pacientes com Angioedema Hereditário.
Banerji, Aleena; Blumenthal, Kimberly G; Lai, Kenneth H; Zhou, Li
Angiotensin-converting enzyme inhibitors (ACEIs) are a common cause of drug-induced angioedema in the United States. Most epidemiologic ACEI angioedema data are from large multicenter clinical trials. The objective of this study was to identify the incidence of and risk factors for ACEI angioedema using a large integrated electronic health record (EHR). We conducted a retrospective cohort study of all ACEI prescriptions in the outpatient setting of a large academic center between January 1, 2000, and September 30, 2008. We determined frequency, timing, and risk factors for ACEI angioedema within 5 years of prescription. All data were derived from EHR sources, with angioedema defined by EHR reactions of angioedema, swelling, edema, or lip, eye, face, tongue, throat or mouth swelling. Among 134,945 patients prescribed an ACEI, 0.7% (n = 888) developed angioedema during the subsequent 5 years. Sex was similar but patients who developed ACEI angioedema were younger (61.5 vs 62.7 years, P = .007). Patients with ACEI angioedema were more likely to have a history of nonsteroidal anti-inflammatory drug allergy compared with patients who did not develop angioedema (7.1% vs 4.2%, P angioedema within 1 month of prescription and a 0.23% incidence during the first year. Incidence of angioedema was relatively constant annually over the subsequent 4 years (0.10% to 0.12%). The incidence of ACEI angioedema within a large EHR is consistent with large clinical trial data. We observed a persistent and relatively constant annual risk; however, angioedema risk factors and underlying genetic and pathophysiological mechanisms require further study. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Full Text Available Hereditary angioedema is a rare autosomal dominant disorder caused by reduced activity of the C1 esterase inhibitor. Patients with hereditary angioedema are clinically characterized by recurrent episodes of swelling of the extremities, face, trunk, airways and abdominal organs. Attacks may occur either spontaneously or following trauma, stress, surgery, infections and hormonal fluctuations. The most common cause of death is asphyxia related to laryngeal edema. Giving C1 esterase inhibitor is the most effective method of treatment. Also fresh frozen plasma, androgen steroids, quinine pathway inhibitors, antifibrinolytics and bradykinin receptor antagonists can be used as treatment. In this paper, the anesthetic management of a patient with hereditary angioedema undergoing inguinal hernia repair surgery is reported.
Full Text Available Hereditary angioedema (HAE caused by a deficiency of C1 esterase inhibitor enzyme (C1-INH is a very rare, autosomal dominantly inherited genetic disorder, characterized by recurrent peripheral angioedema, painful abdominal attacks and episodes of laryngeal edema. Abdominal attacks are frequent symptoms in adult HAE patients, occurring in more than 90% of the cases. Angioedema in the bowel or abdomen can occur in the absence of cutaneous manifestations and may be easily misdiagnosed unless the clinician has a high degree of awareness to include HAE in the differential diagnosis. Misdiagnosis is associated with inadequate treatments, including unnecessary surgical procedures. Any patient who presents recurrent episodes of swelling should be evaluated for HAE caused by C1-INH deficiency. New therapies could save lives and dramatically improve their quality of life.
Sezer, Özgür; Aydin, Ali Attila; Bilge, Sedat; Arslan, Fatih; Arslan, Hasan
Lingual hematoma is a severe situation, which is rare and endangers the airway. It can develop due to trauma, vascular abnormalities, and coagulopathy. Due to its sudden development, it can be clinically confused with angioedema. In patients who applied to the doctor with complaints of a swollen tongue, lingual hematoma can be confused with angioedema, in particular, at the beginning if the symptoms occurred after drug use. It should especially be considered that dystonia in the jaw can present as drug-induced hyperkinetic movement disorder. Early recognition of this rare clinical condition and taking precautions for providing airway patency are essential. In this case report, we will discuss mimicking angioedema and caused by a bite due to dystonia and separation of the tongue from the base of the mouth developing concurrently with lingual hematoma. PMID:29326495
Andre, Pierre; Fléchet, Marie Laure
Hyaluronic acid injections are becoming popular in aesthetic dermatology, and, sometimes, misplacements and very rarely adverse events have been reported. Hyaluronidase, an enzyme that hydrolyzes hyaluronic acid, is used to treat overcorrection or granulomatous reactions. Allergic reactions are well known except for how frequent they occur. This paper aims to confirm the efficacy of hyaluronidase injections to dissolve hyaluronic acid, but insists on the risk of hypersensitivity with animal-derived products. A case of angioedema due to ovine hyaluronidase is reported, and treatment is discussed. Hyaluronidase is highly effective, but skin test must be done before injection to avoid risk of angioedema and/or Quincke's edema.
Longhurst, H J; Zanichelli, A; Caballero, T; Bouillet, L; Aberer, W; Maurer, M; Fain, O; Fabien, V; Andresen, I
Icatibant is used to treat acute hereditary angioedema with C1 inhibitor deficiency types I/II (C1-INH-HAE types I/II) and has shown promise in angioedema due to acquired C1 inhibitor deficiency (C1-INH-AAE). Data from the Icatibant Outcome Survey (IOS) were analysed to evaluate the effectiveness of icatibant in the treatment of patients with C1-INH-AAE and compare disease characteristics with those with C1-INH-HAE types I/II. Key medical history (including prior occurrence of attacks) was recorded upon IOS enrolment. Thereafter, data were recorded retrospectively at approximately 6-month intervals during patient follow-up visits. In the icatibant-treated population, 16 patients with C1-INH-AAE had 287 attacks and 415 patients with C1-INH-HAE types I/II had 2245 attacks. Patients with C1-INH-AAE versus C1-INH-HAE types I/II were more often male (69 versus 42%; P = 0·035) and had a significantly later mean (95% confidence interval) age of symptom onset [57·9 (51·33-64·53) versus 14·0 (12·70-15·26) years]. Time from symptom onset to diagnosis was significantly shorter in patients with C1-INH-AAE versus C1-INH-HAE types I/II (mean 12·3 months versus 118·1 months; P = 0·006). Patients with C1-INH-AAE showed a trend for higher occurrence of attacks involving the face (35 versus 21% of attacks; P = 0·064). Overall, angioedema attacks were more severe in patients with C1-INH-HAE types I/II versus C1-INH-AAE (61 versus 40% of attacks were classified as severe to very severe; P < 0·001). Median total attack duration was 5·0 h and 9·0 h for patients with C1-INH-AAE versus C1-INH-HAE types I/II, respectively. © 2016 British Society for Immunology.
Hereditary or acquired deficiency, or functional impairment, of the C1 esterase enzyme should be also considered, especially if there is a family history of swelling, airway compromise or surgical complications indicating possible hereditary angioedema. .... Depression, functional and sleep impairment are common and it.
consecutive days.16 Common side effects include: nausea, vomiting while rare side effects include: rash, alopecia, urticaria and angioedema. Adverse effects appear to occur more frequently when higher doses are used.17. A compiled information from Food and Drug administration (FDA) and Facts Med users submissions.
Urticaria (i.e., pruritic, raised wheals) and angioedema (i.e., deep mucocutaneous swelling) occur in up to 25 percent of the U.S. population. Vasoactive mediators released from mast cells and basophils produce the classic wheal and flare reaction. Diagnosis can be challenging, especially if symptoms are chronic or ...
ACE inhibitors are often prescribed in the treatment of hypertension, heart failure and kidney disease. These drugs are on the Essential Drugs List, and are therefore used at primary to tertiary health care levels in South Africa. Angioedema is considered a rare, but potentially fatal side-effect of this agent, with a reported ...
Background: Angiotensin converting enzyme (ACE) inhibitor related angioneurotic edema or simply angioedema is a rare but common condition not well noticed in health facilities especially in developing countries. The complication can be life threatening with serious morbidity and mortality if not promptly diagnosed from ...
Urticaria and angioedema are characterized by pruritic hives and sometimes swelling of deeper mucocutaneous layers. Urticaria is caused by release of histamine and other mediators from mast cells. A cut-off of six weeks distinguishes acute and chronic forms, as these seem to differ regarding etiological and response ...
Children are at a higher risk of developing adverse drug reactions as they seldom express their own drug therapy experiences. Factors that have been implicated include polypharmacy ... Cutaneous drug allergy is a common manifestation of adverse drug reactions. Keywords: Angioedema, Mebendazole, Co-trimoxazole, ...
Reshef, Avner; Kidon, Mona; Leibovich, Iris
The term "swelling" has been used in the old scriptures to illustrate a change of normal figure and, as such, an expression of illness. It should be noted that in ancient times, human diseases were very often regarded a punishment from God. Hence, it is not surprising that one of the oldest tests for infidelity involved swelling as an inflicted punishment. The great Greek physician Hippocrates (377-460 BC), considered one of the most outstanding figures in the history of medicine and "Father of the Western Medicine," already used the term oídēma to describe swelling of organs. It took many centuries later until the first description of angioedema as a distinct medical entity was minted by Quinke in 1882. The historical progression in angioedema research has been characterized by intermittent "leaps" in interest and scientific achievements. As an example, it took 75 years from the accurate description of hereditary angioedema (HAE) by Osler (1888), until a group of researchers headed by Donaldson (1963) disclosed the central role of C1 inhibitor in angioedema pathophysiology. What followed was a result of a collective effort by many researchers and scientific groups who were able to elucidate the intricate connections between the implicated biochemical pathways. Still, scientific progress was hardly translated into effective therapy, and another 45 years had to elapse until the renewed interest in HAE was boosted by studies on the efficacy and safety of novel therapies about 10 years ago. In the twenty-first century, HAE ceased to be an "orphan disease" and its future is far more optimistic. It is better managed now by specialized angioedema centers, harmonized clinical guidelines, educational programs, laboratory services, and continued basic and clinical research. Patient associations worldwide are offering support and guidance, and governments and healthcare systems are gradually addressing patient and family needs.
Cicardi, Marco; Banerji, Aleena; Bracho, Francisco; Malbrán, Alejandro; Rosenkranz, Bernd; Riedl, Marc; Bork, Konrad; Lumry, William; Aberer, Werner; Bier, Henning; Bas, Murat; Greve, Jens; Hoffmann, Thomas K; Farkas, Henriette; Reshef, Avner; Ritchie, Bruce; Yang, William; Grabbe, Jürgen; Kivity, Shmuel; Kreuz, Wolfhart; Levy, Robyn J; Luger, Thomas; Obtulowicz, Krystyna; Schmid-Grendelmeier, Peter; Bull, Christian; Sitkauskiene, Brigita; Smith, William B; Toubi, Elias; Werner, Sonja; Anné, Suresh; Björkander, Janne; Bouillet, Laurence; Cillari, Enrico; Hurewitz, David; Jacobson, Kraig W; Katelaris, Constance H; Maurer, Marcus; Merk, Hans; Bernstein, Jonathan A; Feighery, Conleth; Floccard, Bernard; Gleich, Gerald; Hébert, Jacques; Kaatz, Martin; Keith, Paul; Kirkpatrick, Charles H; Langton, David; Martin, Ludovic; Pichler, Christiane; Resnick, David; Wombolt, Duane; Fernández Romero, Diego S; Zanichelli, Andrea; Arcoleo, Francesco; Knolle, Jochen; Kravec, Irina; Dong, Liying; Zimmermann, Jens; Rosen, Kimberly; Fan, Wing-Tze
Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
Hahn, J; Bas, M; Hoffmann, T K; Greve, J
The incidence of bradykinin-induced angioedema is considerably lower than that of histamine-induced forms; however, the same is true for the clinician's knowledge of this condition. Bradykinin-induced angioedemas include hereditary angioedema (HAE), as well as acquired forms induced by drugs or antibody formation, e.g., during the course of oncologic disease. Drug-induced forms affect almost exclusively the head and neck region, and are thus important for the otorhinolaryngologist. Clear differentiation between histamine-induced angioedema (e. g., connected to allergy/urticaria) and bradykinin-induced angioedema is essential for selection of the specific treatment and may be lifesaving. Antihistamines and cortisone derivatives have no relevant effect in bradykinin induced-angioedema, whereas blood-derived C1 esterase inhibitor and bradykinin receptor 2 antagonists represent effective therapeutic options--both for acute and prophylactic treatment.
Bowen, Tom; Cicardi, Marco; Farkas, Henriette
ABSTRACT: BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007...... International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. OBJECTIVE: To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010). METHODS: The Canadian Hereditary Angioedema Network (CHAEN...... approach. The Consensus document was reviewed at the meeting and then circulated for review. RESULTS: This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. CONCLUSIONS: Consensus approach is only...
Loftus, Patricia A; Tan, Melin; Patel, Gunj; Lin, Juan; Helman, Sam; Badhey, Arvind; Du, Eugenie; Smith, Richard V; Fried, Marvin P; Ow, Thomas J
To evaluate the etiology and risk factors for severe manifestation and recurrent episodes of angioedema; to evaluate efficacy of short-term and long-term management strategies for angioedema among a high-risk population. Institutional review board-approved retrospective review of a large, urban population. Data from 875 adult patients treated from January 2008 to December 2013 with the diagnosis of angioedema were obtained using the Clinical Looking Glass utility and review of medical records. Demographic and clinicopathologic risk factors were recorded. The major outcomes evaluated were hospital admission, need for airway intervention, and recurrent episodes of angioedema following the first presentation. Initial treatment strategy and follow-up recommendations were also recorded. The most common cause of angioedema was angiotensin converting enzyme inhibitor (ACEi)-induced (496 [56.6%]). Significant risk factors for severe cases of angioedema included older age, Hispanic race, ACEi-induced angioedema type, American Society of Anesthesiologists class III or above, coexistent cardiopulmonary disease, and a positive smoking history. A total of 17.2% of patients experienced recurrent attacks of angioedema; of those patients, 25.9% were still taking an ACEi at subsequent presentation. Risk factors for recurrent episodes included older age, idiopathic angioedema type, and coexistent cardiopulmonary disease. Only 54.1% of patients who experienced ACEi-induced angioedema had electronic medical record documentation of these allergies. Knowledge of risk factors for severe and recurrent episodes of angioedema and improved education for both healthcare providers and patients, specifically related to ACEi use and allergy documentation, may significantly decrease the burden and morbidity of angioedema among high risk populations. 2b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.
Soo Hoo, Guy W; Lin, Henry K; Junaid, Imran; Klaustermeyer, William B
The purpose of this study was to review consecutive cases of angiotensin-converting enzyme (ACE) inhibitor angioedema admitted to an intensive care unit. Fifty subjects with ACE-inhibitor angioedema admitted from 1998-2011 were reviewed. All 50 subjects were men, 62.8 ± 8.4 years of age, 76% African Americans. Fifteen (30%) required ventilatory support and 2 (4%) required tracheostomy. Over half (56%) had taken ACE inhibitors for over a year. Logistic regression identified dyspnea and tongue involvement with the need for ventilatory support (P angioedema. Angioedema can occur even after extended use. Dyspnea and tongue involvement identified patients requiring ventilatory support. Published by Elsevier Inc.
Stone, Cosby; Brown, Nancy J
Nonsteroidal antiinflammatory agents, β-lactam antibiotics, non-β lactam antibiotics, and angiotensin-converting enzyme inhibitors are the most common classes of drugs that cause angioedema. Drug-induced angioedema is known to occur via mechanisms mediated by histamine, bradykinin, or leukotriene, and an understanding of these mechanisms is crucial in guiding therapeutic decisions. Nonallergic angioedema occurs in patients with genetic variants that affect metabolism or synthesis of bradykinin, substance P, prostaglandins, or leukotrienes, or when patients are taking drugs that have synergistic mechanisms. The mainstay in treatment of nonallergic drug-induced angioedema is cessation of the offending agents. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available El angioedema hereditario (HAE es una enfermedad rara, autosómica dominante, caracterizada por episodios que comprometen la piel, el tracto gastrointestinal y la laringe. Tiene una mortalidad histórica por asfixia del 15 al 50%. Es producida por la deficiencia funcional del C1 inhibidor. La identificación de la bradiquinina como mediador principal ha estimulado el desarrollo de nuevos medicamentos para tratar la enfermedad. El tratamiento del HAE se establece en consensos internacionales. El desarrollo de guías para el tratamiento de la enfermedad permite ordenar el uso de procedimientos diagnósticos y drogas. Describimos aquí algunas características farmacológicas de los medicamentos utilizados en el tratamiento del HAE en la Argentina: el concentrado plasmático de C1 inhibidor, el antagonista de la bradiquinina, icatibant, el andrógeno atenuado danazol y los agentes anti-fibrinolíticos ácidos épsilon aminocaproico (EACA y tranexámico. Asimismo, se describe su forma de uso y del control de los eventos adversos más frecuentes, así como las recomendaciones del último consenso internacional, aplicables para conformar una primera guía de tratamiento del HAE en la Argentina.Hereditary angioedema (HAE is a rare autosomal dominant disease, characterized by episodes of edema involving the skin, gastrointestinal tract and larynx. HAE has a historical asphyxia mortality of 15% to 50%. It is the consequence of functional C1 inhibitor deficiency. The identification of bradykinin as the principal mediator of the disease has lead to the development of new drugs for its treatment. HAE management and treatment are agreed by international consensus decision. A therapeutic guide for the treatment of the disease is important to improve diagnosis and treatment. We here describe the pharmacology of drugs available for the treatment of HAE in Argentina: plasma derived C1 Inhibitor, the bradykinin antagonist: icatibant, the attenuated androgen
Bork, Konrad; Bygum, Anette; Hardt, Jochen
BACKGROUND: Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Treatment with androgens prevents attacks for those with this condition. OBJECTIVE: To examine....... In the other patients, hereditary angioedema ran a mild course. The frequency of acute attacks during danazol treatment was reduced to 16.2%, and the attacks were considerably milder than before treatment. Laryngeal edema was reduced to 4.8%. Adverse effects (weight gain, virilization, menstrual irregularities......, headache, depression, and/or liver adenomas) occurred in 93 of the 118 patients and led to discontinuation of danazol therapy in 30 patients. CONCLUSIONS: Danazol is highly beneficial in patients with frequent and severe attacks of HAE. Because the risk of adverse effects is high, close monitoring...
Baliga, Mohan; Ramanathan, Arvind; Bhambar, Rohan S
C1-esterase inhibitor deficiency results in episodes of non-allergic edema of parts of the body. Edema of the face may be triggered by dental therapy. We report a case of C1-esterase inhibitor deficiency which was detected in a 42-year-old woman. The patient was completely unaware that she had this disorder or of any related family history, and the patient developed an intense facial angioedema after pulp extirpation of lower premolar tooth. In this case, the diagnosis of angioedema due to C1-esterase inhibitor deficiency was established at a later stage. The differing causes of C1-esterase inhibitor deficiency are briefly discussed and the treatment modalities outlined.
Lumry, William Raymond
This review will discuss the cost burden of hereditary angioedema on patients, healthcare systems, and society. The impact of availability of and access to novel and specific therapies on morbidity, mortality, and the overall burden of disease will be explored along with potential changes in treatment paradigms to improve effectiveness and reduce cost of treatment. The prevalence of orphan diseases, legislative incentives to encourage development of orphan disease therapies and the impact of orphan disease treatment on healthcare payment systems will be discussed.
Karagol, Hacer Ilbilge Ertoy; Yilmaz, Ozlem; Topal, Erdem; Bideci, Aysun; Bakirtas, Arzu
The association between thyroid autoimmunity (TA) and idiopathic isolated angioedema (or angioedema without urticaria) has not been evaluated in either children or in adults up until now. We, therefore, aimed to investigate underlying or concomitant TA and/or autoimmune thyroid disease in children diagnosed with recurrent idiopathic angioedema. Children who were consecutively diagnosed with recurrent idiopathic histaminergic acquired angioedema (IH-AAE) between January 2011 and January 2014 constituted the case group. A standard diagnostic and therapeutic algorithm was applied to all the patients with recurrent IH-AAE. Thyroid autoantibodies and thyroid function tests were measured in all the patients with recurrent IH-AAE and in healthy control groups. Prophylaxis with an antihistamine was started for patients with frequently recurrent IH-AAE. Eighty consecutive children with recurrent IH-AAE (49 boys; median age, 8.3 years) and 80 healthy children (39 boys; median, 8 years) were enrolled in this prospective, case-control study (p > 0.05 for age and sex). The IH-AAE group was significantly different than the control group with respect to TA (13.7% versus 2.5%, respectively; p = 0.009) but was similar with respect to autoimmune thyroid disease (3.7% versus 0%, respectively; p = 0.2). The median follow-up of the recurrent IH-AAE group was 34 months (range, 12-45 months). Patients with recurrent IH-AAE with and those without TA were not different with respect to either the need or the duration of antihistamine prophylaxis (p > 0.05 for both). Recurrent IH-AAE may be related to or associated with TA and/or autoimmune thyroid diseases in some children. However, exploring to see whether this association is a causal link or just an epiphenomenon deserves further investigation and longer follow-ups.
Pichler, W J; Lehner, R; Späth, P J
Two male patients with hypogonadism and four female patients who received an anti-androgen as contraceptive (cyproteronacetate) and who had recurrent angioedema are described. In one male patient, augmentation of the plasma androgen level resulted in disappearance of symptoms. In the four female patients, recurrent angioedema and urticaria developed after initiation of the anti-androgen treatment. Cessation of cyproteronacetate and a change to another contraceptive resulted in complete resolution of the previously frequent angioedematous attacks. The women are still symptom free after more than 60 patient's months. These cases suggest that an androgen deficit due to either hypogonadism or to anti-androgen treatment may be another cause of angioedema. One of the two male patients was untreated and presented with 40% normal value of C1-INH. Androgen therapy normalized C1-INH concentration in this male patient. Functional C1-INH in the same patient, studied before and after the beginning of androgen therapy, clearly increased when assessed by inhibition of amidolytic activity of C1-esterase. The other male patient with hypogonadism had already been under androgen treatment for 4 years and had C1-INH levels in the normal range. In the female patients, complement profiles were normal before and after cessation of anti-androgen contraception; however, the C1-INH plasma levels were higher after cessation of anti-androgen anticonception. These results indicate an effect of androgen deficit on the level of C1-INH in circulating plasma but do not prove a role of C1-INH in angioedema associated with diminished androgen plasma levels.
Witschi, A; Krähenbühl, L; Frei, E; Saltzman, J; Späth, P J; Müller, U R
A 21-year-old man with a history of hereditary angioedema presented with protracted abdominal pain which failed to respond to infusion of C1 inhibitor concentrate. Evaluation by CT scan revealed extensive colorectal intussusception requiring surgical intervention. Under replacement therapy with C1 inhibitor concentrate, both the operation under general anesthesia and the postoperative phase were uneventful. The intraoperative examination suggested initiation of intussusception by local mucosal edema in the transverse colon.
Full Text Available Abstract Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor (C1-INH is a rare, life-threatening disorder. It is characterized by attacks of angioedema involving the skin and/or the mucosa of the upper airways, as well as the intestinal mucosa. In approximately 50 per cent of cases, clinical manifestations may appear during childhood. The complex management of HAE in pediatric patients is in many respects different from the management of adults. Establishing the diagnosis early, preferably before the onset of clinical symptoms, is essential in cases with a positive family history. Complement studies usually afford accurate diagnosis, whereas molecular genetics tests may prove helpful in uncertain cases. Appropriate therapy, supported by counselling, suitable modification of lifestyle, and avoidance of triggering factors (which primarily include mechanical trauma, mental stress and airway infections in children may spare the patient unnecessary surgery and may prevent mortality. Prompt control of edematous attacks, short-term prophylaxis and intermittent therapy are recommended as the primary means for the management of pediatric cases. Medicinal products currently used for the treatment of children with hereditary angioedema include antifibrinolytics, attenuated androgens, and C1-INH replacement therapy. Current guidelines favour antifibrinolytics for long-term prophylaxis because of their favorable safety profile but efficacy may be lacking. Attenuated androgens administered in the lowest effective dose are another option. C1-INH replacement therapy is also an effective and safe agent for children. Regular monitoring and follow-up of patients are necessary.
Stelmach, Iwona; Sztafińska, Anna; Lechańka, Joanna; Balcerak, Joanna; Jerzyńska, Joanna
Urticaria is a heterogeneous group of disorders, with various clinical manifestations and intensity of symptoms. Urticaria can be induced with a wide variety of environmental stimuli, such as cold, pressure, vibration, sunlight, exercise, temperature changes, heat, and water. In a select group of patients, exercise can induce a spectrum of urticaria symptoms, ranging from cutaneous pruritus and warmth, generalised urticaria, angioedema, and the appearance of such additional manifestations as collapse, upper respiratory distress, and anaphylaxis. Specific provocation tests should be carried out on an individual basis to investigate the suspected cause and proper diagnosis. Modification of activities and behaviour is the mainstay of treatment in patients with physical urticaria. The aim of this study was to emphasise that primary care paediatricians should be able to recognise physical urticaria, supply a patient with rescue medications, and refer him/her to a specialist. In the article, the authors present a 13-year-old girl with typical urticaria lesions and angioedema after exercise. According to the history, physical examination, and provocation test, exercise-induced urticaria and angioedema were diagnosed.
Urticaria and angioedema are common clinical conditions representing a major concern for physicians and patients alike. The World Allergy Organization (WAO), recognizing the importance of these diseases, has contributed to previous guidelines for the diagnosis and management of urticaria. The Scientific and Clinical Issues Council of WAO proposed the development of this global Position Paper to further enhance the clinical management of these disorders through the participation of renowned experts from all WAO regions of the world. Sections on definition and classification, prevalence, etiology and pathogenesis, diagnosis, treatment, and prognosis are based on the best scientific evidence presently available. Additional sections devoted to urticaria and angioedema in children and pregnant women, quality of life and patient-reported outcomes, and physical urticarias have been incorporated into this document. It is expected that this article will supplement recent international guidelines with the contribution of an expert panel designated by the WAO, increasing awareness of the importance of urticaria and angioedema in medical practice and will become a useful source of information for optimum patient management worldwide. PMID:23282382
Full Text Available Introdução: O Angioedema hereditário (AEH é uma causa rara de angioedema recorrente, resultante de um defeito a nível do gene que codifica o inibidor do C1 esterase (C1 -INH. O edema envolve predominantemente os tecidos da face, membros, trato gastrointestinal e área genital. O envolvimento da laringe, apesar de menos frequente, constitui a expressão clínica mais grave, sendo potencialmente fatal. Caso clínico: Descreve -se o caso clínico de uma criança do sexo feminino de oito anos de idade referenciada à consulta de pediatria por episódios recorrentes de angioedema. O estudo efetuado revelou tratar -se de um caso de AEH. Discussão: O diagnóstico, estabelecido com base no quadro clínico, estudo do complemento e história familiar, é de importância fundamental considerando que o AEH é potencialmente fatal e exige uma terapêutica específica.
Relan, Anurag; Bakhtiari, Kamran; van Amersfoort, Edwin S.; Meijers, Joost C. M.; Hack, C. Erik
Background: Recombinant human C1-inhibitor (rhC1INH; Ruconest (R)) has been developed for treatment of acute angioedema attacks in patients with hereditary angioedema (HAE) due to heterozygous deficiency of C1INH. Previous reports suggest that administration of plasma-derived C1INH products may be
Mahmoudpour, Seyed Hamidreza; Leusink, Maarten; van der Putten, Lisa; Terreehorst, Ingrid; Asselbergs, Folkert W.; de Boer, Anthonius; Maitland-van der Zee, Anke H.
Angioedema and cough are the two most important adverse effects of ACE inhibitors (ACEIs). Evidence exists that ACEI-related angioedema/cough is partly genetically determined and several genes have been identified to play a role in the development of ACEI-related adverse effects. This study was
Zegers, I.H.A.; Aaldering, K.N.; Nieuwhof, C.M.; Schouten, H.C.
INTRODUCTION: Acquired angioedema is a rare disorder causing recurrent life-threatening angioedema, due to decreased activity of C1 esterase inhibitor. CASE REPORT: A 57-year-old man presented to our hospital with recurrent swelling of the hands, lips, tongue, scrotum and throat. Lab examination
Atalay, Eray; Özdemir, Mehmet Tamer; Çiğsar, Gülşen; Omurca, Ferhat; Aslan, Nurullah; Yildiz, Mehmet; Gey, Zehra Bahar
Angioedema is an asymmetric non-pitting oedema on face, lips, tongue and mucous membranes; any delay in diagnosis and treatment can be fatal. Treatment with lisinopril as an angiotensin converting enzyme (ACE) inhibitor, can be a reason of angioedema. Here we report a case who developed oral-facial edema four years after using lisinopril/hydrochlorothiazide. Laryngeal oedema is a main cause of death in angioedema. The treatment of choice in angioedema including fresh frozen plasma, C1 inhibitor concentrations and BRK-2 antagonists (bradykinin B2 receptor antagonists) were used. In this case; a 77 years old female patient suffering from hypertension was considered. This patient was suffering two days from swelling on her face and neck. Non- allergic angioedema was distinguished in five major forms; acquired (AAO), hereditary (HAE), renin-angiotensin-aldosterone system (RAAS) blocker-dependent, pseudoallergic angioedema (PAS) and an idiopathic angioedema (IAO). She was admitted to our clinic with the diagnosis of hereditary angioedema. Patient had skin edema and life threatening laryngeal edema. In emergency department treatment was started using intravenous methylprednisolone, diphenydramine as well as inhaled and subcutaneous epinephrine simultaneously. Despite the initial treatment, the patient died due to the insufficient respiration and cardiac arrest. The patient has no history of kidney disease.
von Buchwald, Christian; Prasad, Sumangali Chandra; Kamaleswaran, Shailajah; Ajgeiy, Kawa Khaled; Authried, Georg; Pallesen, Kristine Appel U.
Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study Design. Cohort study. Methods. This was a retrospective cohort study of 105 patients with angiotensin converting enzyme-inhibitor induced angioedema in the period 1995–2014. Results. The cohort consisted of 67 females and 38 males (F : M ratio 1.8), with a mean age of 63 [range 26–86] years. Female gender was associated with a significantly higher risk of angiotensin converting enzyme-inhibitor induced angioedema. 6.7% had a positive family history of angioedema. Diabetes seemed to be a protective factor with regard to angioedema. 95% experienced angioedema of the head and neck. 4.7% needed intubation or tracheostomy. 74 admissions took place during the study period with a total of 143 days spent in the hospital. The diagnosis codes most often used for this condition were “DT783 Quincke's oedema” and “DT78.4 Allergy unspecified”. Complement C1 inhibitor was normal in all tested patients. Conclusion. Female gender predisposes to angiotensin converting enzyme-inhibitor induced angioedema, whereas diabetes seems to be a protective factor. PMID:28286522
van den Elzen, M.T.
The occurrence of wheals, angioedema or both for at least 6 weeks is diagnosed as chronic spontaneous urticaria in (inter) national guidelines - after excluding other illnesses. The underlying mechanism of angioedema without wheals is not entirely known. The objective of this thesis is to increase
Scott, Susanne Irene; Andersen, Michelle Fog; Aagaard, Lise
Introduction Angioedema is a potentially fatal adverse drug reaction of some medications, as swellings of the upper airways can cause death by asphyxiation. Angiotensin converting enzyme-inhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl...
Wagenaar-Bos, Ineke G A; Drouet, Christian; Aygören-Pursun, Emel
Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor C1 esterase inhibitor (C1-Inh). In addition ...
Stipić Marković, Asja; Rožmanić, Vojko; Anić, Branimir; Aberle, Neda; Račić, Goran; Novak, Srđan; Sunara, Davor; Grdinić, Boris; Karadža-Lapić, Ljerka; Ražov Radas, Melanija; Karanović, Boris; Kvenić, Barbara
Hereditary angioedema (HAE) is a rare but potentially fatal genetic disorder with nonpitting, nonerythematous, and not pruritic swelling which can affect the hands, feet, face, genitals and visceral mucosa. The type, frequency, and severity of the attacks vary between patients, and over the lifetime of an individual patient. Efforts in Croatian counties have identified approximately 100 patients (but there must be more undiagnosed patients). The first global guideline for the management of HA...
Caballero, Teresa; Prior, Nieves
Burden of illness studies and evaluation of health-related quality of life using validated questionnaires have become an important task in the comprehensive management of angioedema conditions, mainly angioedema associated with chronic spontaneous urticaria and hereditary angioedema caused by C1-inhibitor deficiency. A review of the principal tools and studies is presented. Both diseases present a higher proportion of psychiatric disorders, impair work and studies productivity, and produce high direct and indirect costs. These assessments also have been useful to evaluate the positive impact of new drugs and interventions. More studies are desirable, especially in other types of angioedema disorders, such as hereditary angioedema with normal C1 inhibitor. Copyright © 2017 Elsevier Inc. All rights reserved.
Mansi, Marta; Wu, Maddalena Alessandra; Zanichelli, Andrea; Cicardi, Marco
The definition of angioedema is an edema of subcutaneous and submucosal tissues due to increased vascular permeability and fluid extravasation. It can affect different areas, including extremities, genitals, upper airways and intestinal mucosa. The symptoms are disabling and this condition can be fatal if it involves the larynx. We can distinguish different forms of angioedema (hereditary and acquired) with different pathogenetic mechanisms, therefore responding to different treatments. Bradykinin-mediated angioedema (such as hereditary angioedema due to C1-inhibitor deficiency) does not respond to the standard therapy used for histamine-mediated angioedema. These forms should be immediately recognized and specific treatment should be used. In addition, when a patient manifests hypotension not responding to fluid replacement and associated with diffuse edema, hypoalbuminemia and hemoconcentration, we should consider the diagnosis of idiopathic systemic capillary leak syndrome, a very rare but fatal condition.
Dermendzhiev, Svetlan M; Simeonova, Radostina; Murdjeva, Marianna A
Systemic allergic reactions, which include angioedema, are very common in clinical practice. There is great diversity in the etiological factors known to trigger angioedema, and in the pathogenetic mechanisms defining this condition. Beside the broad spectrum of immuno-allergic reactions involved in the angioedemic pathogenesis, this condition is known to also develop on the background of other disorders. These disorders may be of different etiology and have different pathogenesis (either non-immune or immune) but have one common feature referred to as "serological overlap". From research and clinical perspective, it is interesting to explore the combination of some rare neurological diseases, such as myopathies and in particular muscular dystrophies with systemic allergic reactions such as angioedema, urticaria and others. It is known that progressive muscular dystrophies (PMD) are hereditary diseases with different types of inheritance--X-chromosome recessive, X-chromosome dominant, autosomal dominant and others. In some forms, such as Duchenne muscular dystrophy (DMD), an increased expression of perforin in muscle is found which is evidence for involvement of the cellular immune response in the pathogenesis of myopathy. It is in this sense that it is interesting to explore and discuss a clinical case diagnosed as a facioscapulohumeral form of PMD, which also manifests angioedema with urticaria. We present a 41-year-old male hospitalized in the Division of Occupational Diseases and Allergology at St. George University Hospital in Plovdiv who suffered two incidents of massive angioedema on the face, back and chest, accompanied by an itchy urticarial rash. In 1985, after hospitalization to the Clinic of Neurology, he was diagnosed with PMD of facioscapulohumeral type. The medical history could not reveal any of the most common etiologic factors such as drugs, food, insects and other allergens that may be associated with the systemic allergic reactions. The
[Prophylactic use of icatibant before tracheal intubation of a patient with hereditary angioedema type III. (A literature review of perioperative management of patients with hereditary angioedema type III)].
Iturri Clavero, F; González Uriarte, A; Tamayo Medel, G; Gamboa Setién, P M
Type III hereditary angioedema is a rare familial disorder that has recently been described as a separate condition. Triggers for episodes of angioedema include surgery, dental procedures, and tracheal intubation maneuvers. Since episodes affecting the upper airway are potentially life-threatening, prophylactic treatment is recommended in these situations. The use of icatibant (Firazyr(®)), for prevention of angioedema prior to tracheal intubation, is reported in a patient with type iii hereditary angioedema. A literature review on the anesthetic management of this condition was conducted. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.
Straka, Brittany; Nian, Hui; Sloan, Chantel; Byrd, James Brian; Woodard-Grice, Alencia; Yu, Chang; Stone, Elizabeth; Steven, Gary; Hartert, Tina; Teo, Koon K; Pare, Guillaume; McCarty, Catherine A; Brown, Nancy J
The incidence of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema is increased in patients with seasonal allergies. We tested the hypothesis that patients with ACE inhibitor-associated angioedema present during months when pollen counts are increased. Cohort analysis examined the month of presentation of ACE inhibitor-associated angioedema and pollen counts in the ambulatory and hospital setting. Patients with ACE inhibitor-associated angioedema were ascertained through (1) an observational study of patients presenting to Vanderbilt University Medical Center, (2) patients presenting to the Marshfield Clinic and participating in the Marshfield Clinic Personalized Medicine Research Project, and (3) patients enrolled in The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). Measurements include date of presentation of ACE inhibitor-associated angioedema, population exposure to ACE inhibitor by date, and local pollen counts by date. At Vanderbilt, the rate of angioedema was significantly associated with tree pollen months (P = .01 from χ(2) test). When separate analyses were conducted in patients with a history of seasonal allergies and patients without, the rate of ACE inhibitor-associated angioedema was increased during tree pollen months only in patients with a history of seasonal allergies (P = .002). In Marshfield, the rate of angioedema was significantly associated with ragweed pollen months (P = .025). In ONTARGET, a positive trend was observed between the ACE inhibitor-associated angioedema rate and grass season, although it was not statistically significant (P = .057). Patients with ACE inhibitor-associated angioedema are more likely to present with this adverse drug event during months when pollen counts are increased. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Background Hereditary angioedema (HAE) due to C1 inhibitor deficiency is a rare but serious and potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The study objective was to characterize direct and indirect resource utilization associated with HAE from the patient perspective in Europe. Methods The study was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE via a cross-sectional survey of HAE patients, including direct and indirect resource utilization during and between attacks for patients and their caregivers over the past 6 months. A regression model examined predictors of medical resource utilization. Results Overall, 164 patients had an attack in the past 6 months and were included in the analysis. The most significant predictor of medical resource utilization was the severity of the last attack (OR 2.6; p < 0.001). Among patients who sought medical care during the last attack (23%), more than half utilized the emergency department. The last attack prevented patients from their normal activities an average of 4–12 hours. Patient and caregiver absenteeism increased with attack severity and frequency. Among patients who were working or in school (n = 120), 72 provided work/school absenteeism data, resulting in an estimated 20 days missing from work/school on average per year; 51% (n = 84) indicated that HAE has hindered their career/educational advancement. Conclusion HAE poses a considerable burden on patients and their families in terms of direct medical costs and indirect costs related to lost productivity. This burden is substantial at the time of attacks and in between attacks. PMID:24996814
Andersen, Michelle Fog; Longhurst, Hilary J; Rasmussen, Eva Rye; Bygum, Anette
Angioedema is a vascular reaction involving the lower dermis, subcutis and/or submucosal tissue and causing a temporary localized swelling in any part of the body. For many health care professionals, the diagnosis presents an ongoing challenge; several disorders may manifest with subcutaneous or submucosal swelling and falsely be assumed to be angioedema. The clinicians at the emergency department and in the immunology/allergy clinics must be skilled at recognizing the features of angioedema and its differential diagnosis. The review is based on a literature search with specific indexing terms in PubMed, a review of bibliographies and the authors' clinical experience. The most essential diseases that mimic angioedema, the so-called pseudoangioedemas, will each be discussed and illustrated by clinical photos, pointing out key features that help clarify the diagnoses and differentiate these from classic angioedema. A variety of dermatologic conditions can cause swelling that resembles angioedema, some with a potentially fatal outcome if misdiagnosed. Knowledge of pseudoangioedema is fundamental in the emergency setting when handling patients with edema and should be kept in mind when assessing an atypical angioedema case. © 2016 S. Karger AG, Basel.
James, Christine; Bernstein, Jonathan A
Angioedema, a sudden, self-limited swelling of localized areas of any part of the body that may or may not be associated with urticaria, is thought to be the result of a mast-cell mediated process versus a bradykinin etiology. Understanding the mechanism is key in determining the proper treatment. Areas Covered: Clinical presentation of varying angioedema types may be similar; however, the appropriate treatment algorithm is dependent upon clinicians' knowledge of the underlying pathophysiology and classification of angioedema. Literature review of recent guidelines, available medications, and alternative therapies was completed to provide an overview of options. There are no formal guidelines for treatment of acute or chronic histamine-mediated angioedema, and therefore, algorithms for the treatment of acute and chronic urticaria should be followed until such information becomes available. Differentiating histamine-mediated versus bradykinin mediated angioedema is essential, as treatments and treatment responses are quite different. Further research is needed to better understand idiopathic angioedema that is unresponsive to H1/H2 antagonists, LTMAs, or medications designed to treat bradykinin-mediated angioedema.
Owens, Ryan E; Oliphant, Carrie S
Incorporation of neprilysin inhibition into heart failure pharmacotherapy regimens has recently been recommended by U.S. guidelines, based on results from the PARADIGM-HF trial comparing sacubitril/valsartan to enalapril. While most of the discussion has focused on efficacy, a closer examination of the safety results, particularly the incidence of angioedema during the run-in and double-blind periods, is also warranted. Although no major safety concerns were identified, an angioedema risk comparable to enalapril was found, primarily in the black population. Therefore, despite combination with an angiotensin receptor blocker, which historically has a lower incidence of angioedema, the addition of neprilysin inhibition yields an angioedema risk profile comparable to angiotensin converting enzyme (ACE) inhibitors. Clinicians should recognize this safety risk when prescribing sacubitril/valsartan and remain vigilant in counseling patients regarding the signs and symptoms of angioedema. As recommended by the guidelines, avoiding sacubitril/valsartan use concurrently or within 36 hours of the last dose of an ACE inhibitor or in patients with a history of angioedema is also crucial to minimize angioedema risk and prevent patient harm. © Copyright 2017 by the American Board of Family Medicine.
Pare, Guillaume; Kubo, Michiaki; Byrd, James B.; McCarty, Catherine A.; Woodard-Grice, Alencia; Teo, Koon K.; Anand, Sonia S.; Zuvich, Rebecca L.; Bradford, Yuki; Ross, Stephanie; Nakamura, Yusuke; Ritchie, Marylyn; Brown, Nancy J.
Objective The objective of this study was to identify genetic variants associated with angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. Participants and methods We carried out a genome-wide association study in 175 individuals with ACE inhibitor-associated angioedema and 489 ACE inhibitor-exposed controls from Nashville (Tennessee) and Marshfield (Wisconsin). We tested for replication in 19 cases and 57 controls who participated in Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). Results There were no genome-wide significant associations of any single-nucleotide polymorphism (SNP) with angioedema. Sixteen SNPs in African Americans and 41 SNPs in European Americans were associated moderately with angioedema (Pangioedema in the Nashville/Marshfield sample and ONTARGET. In a candidate gene analysis, rs989692 in the gene encoding neprilysin (MME), an enzyme that degrades bradykinin and substance P, was significantly associated with angioedema in ONTARGET and Nashville/Marshfield African Americans. Conclusion Unlike other serious adverse drug effects, ACE inhibitor-associated angioedema is not associated with a variant with a large effect size. Variants in MME and genes involved in immune regulation may be associated with ACE inhibitor-associated angioedema. PMID:23838604
Strassen, Ulrich; Bas, Murat; Hoffmann, Thomas K; Knopf, Andreas; Greve, Jens
Angiotensin II receptor antagonists have been proposed as a replacement therapy after the occurrence of either an angiotensin converting enzyme (ACE) inhibitor-induced angioedema or cough. However, recent studies indicate that angioedema is associated with elevated bradykinin levels in a small fraction of patients treated with angiotensin-II-receptor blockers, suggesting a common pathophysiological mechanism. To date, a standard treatment for angiotensin II receptor blocker-induced angioedema does not exist. We present a case series of patients admitted to our hospital due to angioedema induced by an angiotensin II receptor blocker. The patients were either treated with either icatibant (n = 3) or prednisolone-21-hydrogen succinate/clemastine (n = 5). Both patient groups were compared with an untreated patient cohort (n = 3). All patients were previously diagnosed with essential hypertonia. Icatibant was an effective therapy for angiotensin II receptor blocker-induced angioedema. Full symptom recovery was achieved after 5 to 7 hours, whereas symptom remission occurred within 27 to 52 and 24 to 54 hours in patients treated with Solu-Decortin prednisolone/clemastine and untreated patients, respectively. The recovery time for icatibant was similar to that described in previous studies regarding the therapeutic efficacy of icatibant for the treatment of hereditary angioedema and patients suffering from angiotensin converting enzyme inhibitor-induced angioedema. Icatibant is a safe and effective substance for the treatment of angiotensin II receptor blocker-induced angioedema. Although the pathophysiology of angiotensin II receptor blocker-induced angioedema remains unclear, it appears to be associated with the bradykinin pathway. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.
William Raymond Lumry
Full Text Available This review will discuss the cost burden of hereditary angioedema on patients, healthcare systems, and society. The impact of availability of and access to novel and specific therapies on morbidity, mortality, and the overall burden of disease will be explored along with potential changes in treatment paradigms to improve effectiveness and reduce cost of treatment. The prevalence of orphan diseases, legislative incentives to encourage development of orphan disease therapies and the impact of orphan disease treatment on healthcare payment systems will be discussed.
Misra, Lopa; Khurmi, Narjeet; Trentman, Terrence L
Angioedema is a rare condition which manifests as sudden localised, non-pitting swelling of certain body parts including skin and mucous membranes. It is vital that anaesthesiologists understand this condition, as it may present suddenly in the perioperative period with airway compromise. To identify literature for this review, the authors searched the PubMed, Medline, Embase, Scopus and Web of Science databases for English language articles covering a 10-year period, 2006 through 2016. Angioedema can be either mast-cell mediated or bradykinin-induced. Older therapies for histaminergic symptoms are well known to anaesthesiologists (e.g., adrenaline, anti-histamines and steroids), whereas older therapies for bradykinin-induced symptoms include plasma and attenuated androgens. New classes of drugs for bradykinin-induced symptoms are now available, including anti-bradykinin, plasma kallikrein inhibitor and C1 esterase inhibitors. These can be used prophylactically or as rescue medications. Anaesthesiologists are in a unique position to coordinate perioperative care for this complex group of patients. PMID:27601734
Full Text Available En el mundo, el angioedema hereditario (HAE afecta a 1 de cada 50 000 personas. Produce episodios de angioedema cutáneo, abdominal y laríngeos que generan gran incapacidad. La mortalidad por la enfermedad oscila entre 15 y 50%. Aunque en Argentina un concentrado plasmático de C1 inhibidor (pdC1INH ha estado aprobado y disponible por décadas para el tratamiento del ataque agudo, solo 15 (26% de 58 pacientes había recibido pdC1INH alguna vez hasta el año 2008, y solo 2(3.4% lo usaban regularmente. Luego de la aprobación de los nuevos medicamentos para HAE, incluido el icatibant en Argentina y de la publicación de las guías terapéuticas, 42 (82% de 51 pacientes del grupo original tienen pdC1INH para tratar el próximo ataque. Sin embargo, 16 (18% de estos pacientes continúan sin acceso a la medicación y otros 15 (35.7% acceden a través de otro enfermo en forma espuria. Solo 12 (28.6% de los pacientes con el medicamento puede auto tratarse en su domicilio. La mejora en el acceso a la medicación es importante pero debe extenderse a todos los afectados y facilitarse el auto-tratamiento.
Full Text Available Angioedema is a rare condition which manifests as sudden localised, non-pitting swelling of certain body parts including skin and mucous membranes. It is vital that anaesthesiologists understand this condition, as it may present suddenly in the perioperative period with airway compromise. To identify literature for this review, the authors searched the PubMed, Medline, Embase, Scopus and Web of Science databases for English language articles covering a 10-year period, 2006 through 2016. Angioedema can be either mast-cell mediated or bradykinin-induced. Older therapies for histaminergic symptoms are well known to anaesthesiologists (e.g., adrenaline, anti-histamines and steroids, whereas older therapies for bradykinin-induced symptoms include plasma and attenuated androgens. New classes of drugs for bradykinin-induced symptoms are now available, including anti-bradykinin, plasma kallikrein inhibitor and C1 esterase inhibitors. These can be used prophylactically or as rescue medications. Anaesthesiologists are in a unique position to coordinate perioperative care for this complex group of patients.
Bygum, Anette; Busse, Paula; Caballero, Teresa
Hereditary angioedema (HAE) is a group of rare, potentially life-threatening, and frequently debilitating diseases characterized by recurrent, and often with an unpredictable onset, of swelling attacks. HAE is heterogeneous, with considerable differences between its subtypes, patients, and even...
Full Text Available Abdominal angioedema is a less recognized type of angioedema, which can occur in patients with hereditary angioedema (HAE. The clinical signs may range from subtle, diffuse abdominal pain and nausea, to overt peritonitis. We describe two cases of abdominal angioedema in patients with known HAE that were diagnosed in the emergency department by point-of-care (POC ultrasound. In each case, the patient presented with isolated abdominal complaints and no signs of oropharyngeal edema. Findings on POC ultrasound included intraperitoneal free fluid and bowel wall edema. Both patients recovered uneventfully after receiving treatment. Because it can be performed rapidly, requires no ionizing radiation,and can rule out alternative diagnoses, POC ultrasound holds promise as a valuable tool in the evaluation and management of patients with HAE. [West J Emerg Med. 2014;15(7:-0.
Guarneri, Fabrizio; Guarneri, Claudio; Marini, Herbert Ryan
Vibratory angioedema is a rare form of physical urticaria, hereditary or acquired, which occurs at body sites exposed to vibrations. Pathogenic mechanisms of disease are not completely clear and, consequently, current pharmacological treatment is sometimes unsatisfactory. We report the case of a horn player affected by acquired vibratory angioedema, relapsing after prolonged use of the instrument and resistant to systemic antihistamines and corticosteroids, which successfully responded to therapy with low doses of amitriptyline and bromazepam. A neuroinflammatory mechanism can be likely implicated in the pathogenesis of vibratory angioedema, in line with many different cutaneous/mucosal diseases involving a complex interplay of homeostatic/allostatic systems. Furthermore, in mucosal diseases, such as vibratory angioedema, physical/psychological stressors have a relevant role. In such cases, because of the complex interplay between nervous and immune system, the pharmacological activity of benzodiazepines and typical antidepressants may downregulate neuroinflammation. © 2014 Wiley Periodicals, Inc.
Krause, Karoline; Metz, Martin; Zuberbier, Torsten; Maurer, Marcus; Magerl, Markus
The bradykinin B2 receptor antagonist icatibant has recently become available for treating hereditary angioedema. Our observations demonstrate icatibant to be effective and safe for the treatment of both, abdominal and cutaneous attacks in a practice setting beyond clinical studies.
Seo, Nieun; Chung, Yong Eun; Lim, Joon Seok; Song, Mi Kyung; Kim, Myeong-Jin; Kim, Ki Whang
Bowel angioedema is an acute adverse reaction to iodinated contrast media (CM) that involves the gastrointestinal tract. We aimed to investigate the incidence and predisposing factors of iodinated CM-associated bowel angioedema during computed tomography (CT) examinations. This study was approved by our institutional review board, and informed consent was waived due to its retrospective design. From July 2013 to July 2015, adult patients with a history of adverse reactions to iodinated CM during CT (group A, n = 427) and patients without adverse reactions matched for age and sex with the propensity-score matching method (group B, n = 427) were studied. Contrast media-associated bowel angioedema was determined when bowel wall thickness increased after contrast enhancement compared with the precontrast scan. Potential predisposing factors including patient demographics, symptoms and time of adverse reactions, and CM-related factors were compared between patients with and without angioedema in group A. In addition, the incidence of bowel angioedema was compared between groups A and B. The incidence of CM-associated bowel angioedema in group A was 3.3% (14/427) in the per-patient analysis and 2.6% (15/578) in the per-examination analysis. The CM-associated bowel angioedema involved the distal duodenum and/or proximal jejunum and showed long-segmental circumferential bowel wall thickening on CT. None of the studied predisposing factors was different between patients with and without bowel angioedema (P > 0.05). The incidence of CM-associated bowel angioedema in group B was 1.9% (8/427) and 1.7% (8/458) for per-patient and per-examination analyses, respectively, and these rates were not significantly different between groups A and B (P = 0.346 and P = 0.370, respectively). The incidence of CM-associated bowel angioedema during CT was 1.7% to 3.3%, and none of the studied predisposing factors was associated with bowel angioedema.
Full Text Available Ravdeep Kaur, Aerik Anthony Williams, Catherine Baker Swift, Jason W Caldwell Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, NC, USA Abstract: Acquired angioedema is often associated with significant morbidity. An underlying lymphatic malignancy, autoimmune disorder, adenocarcinoma, or other malignancy may be present. Screening for these disorders should occur in all patients with acquired angioedema as treatment may result in resolution of angioedema. Keywords: complement, C1-INH deficiency, ecallantide, hemopathy
Aberer, W; Maurer, M; Reshef, A
Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self-administered ica......Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self...
Fok, J S; Katelaris, C H; Brown, A F; Smith, W B
Angioedema occurs in up to 2% of those taking angiotensin-converting enzyme (ACE) inhibitors. Upper airway angioedema may potentially require endotracheal intubation or cricothyrotomy, and is usually unresponsive to adrenaline. The bradykinin receptor antagonist icatibant is proven to be effective in the treatment of acute attacks of hereditary angioedema, and has also been reported effective in the treatment of angioedema associated with ACE inhibitors. To describe the use of icatibant for ACE inhibitor-associated airway angioedema. We treated 13 consecutive emergency department (ED) patients, who had not improved with adrenaline and/or corticosteroids, with icatibant 30 mg subcutaneously for ACE inhibitor-associated upper respiratory tract angioedema according to an agreed protocol. Four patients were intubated in the ED either before or after receiving icatibant; three of these were extubated within 24 h of treatment. Eight patients received early icatibant and did not require intubation. The time from onset of airway angioedema to ED presentation ranged from 1 h to 3 days (median 4 h); from ED presentation to receiving icatibant, from 30 minutes to 3 days (median 3 h); and to onset of symptom improvement after icatibant, 15 minutes to 7 h (median 2 h). One patient received a second dose of icatibant. All patients improved after receiving icatibant, consistent with its bradykinin receptor blocking mechanism. Icatibant rapidly reversed symptoms, and appeared to avert the need for intubation or expedite extubation. Timely use of icatibant in ACE inhibitor-associated angioedema may avert the need for invasive airway procedures and intensive care unit admission. © 2015 Royal Australasian College of Physicians.
PRKAČIN, INGRID; BAN, ANA; CAVRIĆ, GORDANA; BARTOLEK HAMP, DUBRAVKA
Hereditary angioedema (HAE) is rare autosomal dominant disease, characterised by spontaneous and recurrent swellings in various parts of the body. The main inflammatory factor in HAE is bradykinin (a key mediator of non-allergic angioedema) and it is responsible for capillary leak. C1 esterase inhibitor (C1-INH) is a protease inhibitor that blocks the activation of the classic complement pathway, but there are also many others biochemical pathways, including kinin. Type I HAE is defi...
R. Mason Curtis
Full Text Available Introduction: Upper airway angioedema is a life-threatening emergency department (ED presentation with increasing incidence. Angiotensin-converting enzyme inhibitor induced angioedema (AAE is a non-mast cell mediated etiology of angioedema. Accurate diagnosis by clinical examination can optimize patient management and reduce morbidity from inappropriate treatment with epinephrine. The aim of this study is to describe the incidence of angioedema subtypes and the management of AAE. We evaluate the appropriateness of treatments and highlight preventable iatrogenic morbidity. Methods: We conducted a retrospective chart review of consecutive angioedema patients presenting to two tertiary care EDs between July 2007 and March 2012. Results: Of 1,702 medical records screened, 527 were included. The cause of angioedema was identified in 48.8% (n=257 of cases. The most common identifiable etiology was AAE (33.1%, n=85, with a 60.0% male predominance. The most common AAE management strategies included diphenhydramine (63.5%, n=54, corticosteroids (50.6%, n=43 and ranitidine (31.8%, n=27. Epinephrine was administered in 21.2% (n=18 of AAE patients, five of whom received repeated doses. Four AAE patients required admission (4.7% and one required endotracheal intubation. Epinephrine induced morbidity in two patients, causing myocardial ischemia or dysrhythmia shortly after administration. Conclusion: AAE is the most common identifiable etiology of angioedema and can be accurately diagnosed by physical examination. It is easily confused with anaphylaxis and mismanaged with antihistamines, corticosteroids and epinephrine. There is little physiologic rationale for epinephrine use in AAE and much risk. Improved clinical differentiation of mast cell and non-mast cell mediated angioedema can optimize patient management.
Pahs, Lesley; Droege, Chris; Kneale, Hilary; Pancioli, Arthur
Orolingual angioedema is a rare adverse effect of tissue plasminogen activator (tPA), with an incidence of 1% to 5%. There are currently no published reports describing resolution of tPA-induced orolingual angioedema with complement inhibitor therapy. A 72-year-old man receiving home angiotensin-converting enzyme inhibitor therapy presented to the emergency department with newly developed orolingual angioedema after treatment with tPA for acute ischemic stroke. Therapy was initiated with intravenous methylprednisolone 125 mg, famotidine 20 mg, and diphenhydramine 50 mg, without significant improvement. Because of increased concern for airway protection, plasma-derived C1 esterase inhibitor was administered. Concerns about progressive and airway-threatening orolingual angioedema subsided 2 hours after administration, and invasive airway maneuvers were avoided. Orolingual angioedema is an infrequent, severe adverse effect of tPA for treatment of acute ischemic stroke. Complement inhibitors may be an additional therapeutic option for patients presenting with orolingual angioedema with potential airway compromise that is refractory to standard anaphylactic therapies. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
Bork, Konrad; Witzke, Günther
To evaluate whether activated partial thromboplastin time (APTT) could be used in the laboratory diagnosis of hereditary or acquired angioedema (HAE or AAE) with and without C1 inhibitor (C1-INH) deficiency. In a prospective investigation, APTT and other coagulation parameters were determined in 149 adult patients with various types of angioedema and in 26 healthy participants (HP). Mean APTT was significantly shortened in HAE-C1-INH type I (p angioedema, 4/30 (13.3%) patients with nonhistaminergic angioedema and in 2/26 (7.7%) HP. Thus, a shortened APTT was obtained in 8-9 times more patients with angioedema due to C1-INH deficiency when compared to patients with various forms of angioedema with normal C1-INH and also to HP. A shortened APTT may help to diagnose HAE-C1-INH and AAE-C1-INH when determination of C1-INH is not yet available. © 2016 S. Karger AG, Basel.
Brook, Christopher D; Devaiah, Anand K; Davis, Elizabeth M
Angioedema of the upper aerodigestive tract can lead to significant airway obstruction. To date no articles have delineated risk factors for progression after initial evaluation. This article presents the results of a retrospective study of patients with angioedema at a single institution. Patients included were consecutive otolaryngology consultations for angioedema in the emergency department (ED) from 1999 to 2003. All patients were evaluated by an otolaryngologist and underwent fiber-optic laryngoscopy, which was repeated serially depending on findings. Data was collected on demographics, comorbidities, intubation, disposition, and progression of angioedema. A total of 177 patients were included in the study: 32 (18%) patients required intubation; 25 (14%) on initial presentation and 7 (4%) who progressed from an initially stable airway to requiring intervention after reevaluation. Analysis of variance (ANOVA) demonstrated a statistically significant variance between location of edema and rate of intubation, with higher rates in the pharynx and larynx vs the lip and face. Patients who required intubation after progression between serial evaluations were statistically more likely to have edema that involved deeper portions of the aerodigestive tract. Patients who required intubation were statistically more likely to be older (average age 61.8 vs 55.1 years, p = 0.03). In this large series of patients managed for aerodigestive angioedema we demonstrate risk factors associated with airway intervention, and risk factors associated with clinical progression on serial examination to airway intervention. In addition, we demonstrate a successful management algorithm for patients with aerodigestive angioedema. © 2014 ARS-AAOA, LLC.
Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010). Methods The Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'angioédème héréditaire (RCAH) http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring) held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. Results This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. Conclusions Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management. PMID:20667127
Sánchez, María Dulfary; Cuervo, Julián; Rave, Deisi; Clemen, Gustavo; Yepes-Núñez, Juan José; Ortiz-Reyes, Blanca; Sus, Sara; Cardona, Ricardo
Hereditary angioedema is an autosomal dominant primary immunodeficiency caused by a deficiency of the C1 inhibitor protein and characterized by recurrent episodes of subcutaneous and mucosal edema. Unpredictable and frequent crisis of angioedema affect the quality of life of individuals suffering this kind of disorder. To analyze the clinical characteristics of a family with an index case of hereditary angioedema and to determine the impact of this disease on their quality of life. Twenty six members of the family were included in the trial; 25 of them were analyzed for C4 complement and antigenic and functional C1 inhibitor blood levels. Two instruments (SF-365 and KIDSCREEN-27) were used to evaluate adult health quality and children and teenagers quality of life, respectively. Eighty three percent (83%) of individuals reporting symptoms of the condition exhibited serological criteria of hereditary angioedema type I: low levels of both C4 complement and quantitative (antigenic) and qualitative (functional) C1 inhibitor. In relation to patients' psychological and emotional performance, their quality of life was significantly affected by the symptoms of hereditary angioedema. This study provides evidence of the first family in Valle de Aburrá (Colombia) characterized as having hereditary angioedema type I. Despite the use of a generic instrument, the negative impact on the quality of life of individuals suffering this disease was also confirmed.
Full Text Available Abstract Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010. Methods The Canadian Hereditary Angioedema Network (CHAEN/Réseau Canadien d'angioédème héréditaire (RCAH http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. Results This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. Conclusions Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.
Powell, R J; Leech, S C; Till, S; Huber, P A J; Nasser, S M; Clark, A T
This guidance for the management of patients with chronic urticaria and angioedema has been prepared by the Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is aimed at both adult physicians and paediatricians practising in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a Web-based system. Their comments and suggestions were carefully considered by the Standards of Care Committee. Where evidence was lacking, a consensus was reached by the experts on the committee. Included in this management guideline are clinical classification, aetiology, diagnosis, investigations, treatment guidance with special sections on children with urticaria and the use of antihistamines in women who are pregnant or breastfeeding. Finally, we have made recommendations for potential areas of future research. © 2015 John Wiley & Sons Ltd.
Frías Iniesta, Jesús
El angioedema hereditario (AEH) es una enfermedad transmitida con un patrón autosómico dominante, caracterizada por la presencia de angioedema recurrente y ocasionada por un defecto de la enzima conocida como inhibidor de C1. El principal mediador involucrado en el desarrollo del angioedema es la bradicinina
Hereditary angioedema (HAE) is a rare genetic disease characterized by long-term recurrent attacks of subcutaneous or submucosal edema in different parts of the body. A comprehensive review of the literature on burden of illness for patients with HAE is presented. A Boolean search was performed using MEDLINE and EMBASE databases and the Internet. Articles discussing aspects of the burden of illness in HAE were selected. Topics focused on the course of the disease, nature of attacks, treatment, quality of life, and costs. Hereditary angioedema is associated with a significant and multifaceted disease burden. Diagnosis is often delayed for years, with patients receiving ineffective treatment and unnecessary medical procedures before diagnosis. HAE attacks are painful, unpredictable, and debilitating and often require emergency medical attention. Attacks can affect a patient's daily activities, including work or schooling. Depression and anxiety are prevalent in patients with HAE. Recent advances in treatment provide patients with effective and well-tolerated prophylactic and on-demand therapeutic options. However, end points specific to HAE that better measure the impact of treatment on disease burden are lacking. Furthermore, there is a notable paucity of literature directed toward physicians who are instrumental in diagnosing and treating patients with HAE (eg, emergency department). More publications are broadening the understanding of HAE. However, important gaps remain. Effective management of HAE requires a more comprehensive understanding of the disease burden so that disease management can be individualized to meet specific patient needs. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Busse, Paula; Christiansen, Sandra C.; Li, Henry; Lumry, William; Davis-Lorton, Mark; Bernstein, Jonathan A.; Frank, Michael; Castaldo, Anthony; Long, Janet F.; Zuraw, Bruce L.; Riedl, Marc
Hereditary angioedema (HAE) is a chronic disease with a high burden of disease that is poorly understood and often misdiagnosed. Availability of treatments, including C1 esterase inhibitor (C1INH) replacement, ecallantide, and icatibant, marks a significant advance for HAE patients. We aimed to better understand the current state of HAE care, from a patient perspective, after the introduction of several novel therapies. One session of the United States Hereditary Angioedema Association 2013 patient summit was devoted to data collection for this study. Patients attending the summit were self-selected, and HAE diagnosis was self-reported. Survey questions assessed patient characteristics, burden of disease, and treatment. Participant responses were captured using an audience response system. We surveyed 149 (80%) type I and II HAE (HAE-C1INH) and 37 (20%) HAE with normal C1INH (HAE-nlC1INH) patients. HAE-C1INH (72%) and HAE-nlCINH patients (76%) equally reported that HAE had a significant impact on quality of life (QOL). A third of HAE-C1INH patients were diagnosed within one year of their first HAE attack, but another third reported a delay of more than 10 years. Most HAE-C1INH (88%) and HAE-nlC1INH (76%) patients had on-demand treatment available. HAE-C1INH patients frequently had an individual treatment plan (76%) compared with 50% of HAE-nlC1INH patients. Most HAE-C1INH patients went to the emergency department (ED) or were hospitalized less than once every six months (80%). Our findings show that HAE management is improving with good access to on-demand and prophylactic treatment options. However, HAE patients still have a significant burden of disease and continued research and educational efforts are needed. PMID:25976438
Full Text Available M Aamir Ali, Marie L Borum Division of Gastroenterology and Liver Diseases, George Washington University, Washington, DC, USA Abstract: Up to 93% of patients with hereditary angioedema (HAE experience recurrent abdominal pain. Many of these patients, who often present to emergency departments, primary care physicians, general surgeons, or gastroenterologists, are misdiagnosed for years and undergo unnecessary testing and surgical procedures. Making the diagnosis of HAE can be challenging because symptoms and attack locations are often inconsistent from one episode to the next. Abdominal attacks are common and can occur without other attack locations. An early, accurate diagnosis is central to managing HAE. Unexplained abdominal pain, particularly when accompanied by swelling of the face and extremities, suggests the diagnosis of HAE. A family history and radiologic imaging demonstrating edematous bowel also support an HAE diagnosis. Once HAE is suspected, C4 and C1 esterase inhibitor (C1-INH laboratory studies are usually diagnostic. Patients with HAE may benefit from recently approved specific treatments, including plasma-derived C1-INH or recombinant C1-INH, a bradykinin B2-receptor antagonist, or a kallikrein inhibitor as first-line therapy and solvent/detergent-treated or fresh frozen plasma as second-line therapy for acute episodes. Short-term or long-term prophylaxis with nanofiltered C1-INH or attenuated androgens will prevent or reduce the frequency and severity of episodes. Gastroenterologists can play a critical role in identifying and treating patients with HAE, and should have a high index of suspicion when encountering patients with recurrent, unexplained bouts of abdominal pain. Given the high rate of abdominal attacks in HAE, it is important for gastroenterologists to appropriately diagnose and promptly recognize and treat HAE, or refer patients with HAE to an allergist. Keywords: hereditary angioedema, abdominal pain, diagnosis
Zazzali, James L; Kaplan, Allen; Maurer, Marcus; Raimundo, Karina; Trzaskoma, Benjamin; Solari, Paul G; Antonova, Evgeniya; Mendelson, Meryl; Rosén, Karin E
Angioedema, present in some patients with chronic idiopathic/spontaneous urticaria (CIU/CSU), may have a negative effect on patient quality of life. To describe patient-reported angioedema and its management in the pivotal omalizumab studies (ASTERIA I, ASTERIA II, GLACIAL). Enrolled patients with CIU/CSU remained symptomatic despite treatment with histamine 1 (H 1 )-antihistamines at licensed doses (ASTERIA I, ASTERIA II) or H 1 -antihistamines at up to 4 times the approved dose plus H 2 -antihistamines and/or a leukotriene receptor antagonist (GLACIAL). All studies administered omalizumab (75, 150, or 300 mg in ASTERIA I and ASTERIA II; 300 mg in GLACIAL) or placebo subcutaneously every 4 weeks for at least 12 weeks. Urticaria Patient Daily Diary entries were completed by patients and summarized. At baseline, angioedema prevalence was higher in GLACIAL (53.1%) than in ASTERIA I (47.5%) or ASTERIA II (40.7%). The mean proportion of angioedema-free days during weeks 4 to 12 was greater for patients treated with 300 mg of omalizumab than placebo in ASTERIA I (96.1% vs 88.2%, P angioedema was managed by low-intensity interventions (doing nothing or taking medication). Treatment with 300 mg of omalizumab was efficacious in reducing patient-reported angioedema. Low-intensity interventions were generally used to manage angioedema episodes. clinicaltrials.gov Identifiers: NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Scalese, Michael J; Reinaker, Travis S
The published evidence on pharmacologic approaches to the management of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema is reviewed. Angioedema is a serious, potentially life-threatening adverse effect of ACEI use. Although the underlying mechanism is not fully understood, excess bradykinin produced through a complex interplay between the kallikrein-kinin and renin-angiotensin-aldosterone systems is thought to play a major role. The nonallergic nature of the reaction renders traditional therapies (corticosteroids and antihistamines) ineffective because those agents do not modify the proposed pathophysiology. Fresh frozen plasma (FFP) provides kinase II, a protein that breaks down bradykinin. Case reports support FFP as a treatment for ACEI-induced angioedema, but no formal evaluations have been completed to date. Both ecallantide and complement 1 esterase (C1) inhibitor concentrate reduce bradykinin production through upstream inhibition of kallikrein. C1 inhibitor concentrate has been used successfully to manage ACEI-induced angioedema in a few reported cases, but robust supportive studies are lacking. Conversely, ecallantide has been evaluated in multiple randomized trials but has not been shown to offer advantages over traditional therapies. The use of icatibant, a direct antagonist of bradykinin B2 receptors, was reported to be beneficial in several case reports and in a small Phase II study, safely and rapidly reducing symptoms of ACEI-induced angioedema. An ongoing Phase III trial (NCT01919801) will better define the role of icatibant in the management of ACEI-induced angioedema. FFP, C1 inhibitor, and icatibant appear to be safe and effective therapeutic options for the management of ACEI-induced angioedema, whereas it appears ecallantide should be avoided. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
Gang, Cheng; Lindsell, Christopher J.; Moellman, Joseph; Sublett, Wesley; Hart, Kim; Collins, Sean
Angiotensin-converting enzyme inhibitor (ACE-I)–induced angioedema can be life-threatening without emergent intervention. The putative mediator is believed to be bradykinin, similar to hereditary angioedema, so these patients respond poorly to corticosteroids and antihistamines. This study was designed to determine characteristics and clinical outcomes of patients presenting to an emergency department (ED) with ACE-I angioedema. This was a retrospective chart review of 100 patients presenting to the ED from 2007 to 2008 with an ICD-9 code of 995.1 (angioedema) or 995.2 (drug-induced angioedema). Two hundred fifty-two patients with these ICD-9 codes were identified and placed in random order, and the first 100 meeting inclusion criteria were included. Statistical analysis was primarily descriptive. All 100 patients had an ICD-9 code of 995.1 (angioedema). Patients presented in every month, with spring months (April–June) having the most presentations (32%). The median age was 59 years, 75% were African American, and 66% were admitted to the hospital. Two patients (2%) required endotracheal intubation. Lisinopril was the most commonly prescribed ACE-I (84%). The most common symptom was moderate lip and tongue swelling (89%) followed by mild difficulty breathing (12%). Tongue swelling was significantly associated with admission. Time from symptom onset to ED presentation was not associated with need for admission. Concomitant medications did not differ between admitted and discharged patients. ACE-I angioedema is associated with significant morbidity and health care use because many patients require hospitalization, suggesting an unmet need for novel therapies targeted to treat this condition. PMID:23676576
Zegers, I H A; Aaldering, K N A; Nieuwhof, C M G; Schouten, H C
Acquired angioedema is a rare disorder causing recurrent life-threatening angioedema, due to decreased activity of C1 esterase inhibitor. A 57-year-old man presented to our hospital with recurrent swelling of the hands, lips, tongue, scrotum and throat. Lab examination showed the presence of an IgM kappa monoclonal antibody. Additional analysis showed that in the IgM fraction autoantibody activity against C1 esterase inhibitor was present. This confirmed the diagnosis of acquired angioedema in the presence of lymphoplasmacytic lymphoma. Despite standard therapy, there was an increase in the episodes of laryngeal oedema. Therefore it was decided to perform a non-myeloablative allogeneic haematopoietic stem cell transplantation, with his HLA-identical brother as donor. The post-transplantation course was without complications. Five years following alloSCT he is in complete remission without symptoms and with increased C1 esterase inhibitor activity. In this case all other known treatment options for severe acquired angioedema failed. This is the first case describing treatment of severe acquired angioedema, caused by lymphoplasmacytic lymphoma, with an alloSCT.
Javaud, Nicolas; Floccard, Bernard; Gontier, Florian; Lapostolle, Frédéric; Boccon-Gibod, Isabelle; Martin, Ludovic; Amarger, Stéphanie; Boumedienne, Abdalia; Boubaya, Marouane; Asfar, Pierre; Coppere, Brigitte; Ollivier, Yann; Bouillet, Laurence; Adnet, Frédéric; Fain, Olivier
Bradykinin-mediated angioedema is characterized by transient attacks of localized edema of subcutaneous or submucosal tissues and can be life-threatening when involving the upper airways. The aim of this study was to determine the features of acute attacks that might be associated with admission to an ICU. We carried out a retrospective, multicenter, observational study in consecutive patients attending one of six reference centers in France for acute bradykinin-mediated angioedema attacks. Patients had been hospitalized for an acute episode at least once previously. Acute attacks requiring ICU admission were compared with acute attacks that had not required ICU admission. Overall, 118 acute attacks in 31 patients were analyzed (10 patients with hereditary angioedema, 19 patients with angiotensin-converting enzyme inhibitor-induced angioedema, and two patients with acquired C1-inhibitor deficiency angioedema). In multivariate analysis, upper airway involvement, corticosteroid, and C1-inhibitor concentrate administration were associated with ICU admission. Seven episodes (18%) needed airway protection. The evolution was favorable in 38 of 39 attacks warranting ICU admission: patients were able to get out of the service (mean ICU stay 4±5 days). One death was observed by asphyxiation because of laryngeal swelling. Upper airway involvement is an independent risk factor for ICU admission. Corticosteroid use, which is an ineffective treatment, and C1-inhibitor concentrate use are factors for ICU admission. The presence of upper airway involvement should be a warning signal that the attack may be severe.
Nakamura, Rintaro; Nihei, Shun-Ichi; Arai, Hideaki; Nagata, Keiji; Isa, Yasuki; Harayama, Nobuya; Aibara, Keiji; Kamochi, Msayuki
Although angiotensin-converting enzyme (ACE) inhibitors are widely used as the first choice drug for treating hypertension, we have only a superficial understanding of their relationship to angioedema. We report a case of life-threatening angioedema. The case was a 60-year-old man who had been taking an ACE inhibitor for hypertension for 11 years. He visited his home doctor for dyspnea, and tongue and neck swelling. He was transported to our hospital because of the possibility of airway obstruction. On admission, his tongue and neck swelling became more severe. We performed an intubation using an endoscope and started airway management. We also stopped his ACE inhibitor. The severe tongue and neck swelling improved gradually and he was extubated on day 3. On the fifth day he was discharged. We diagnosed angioedema caused by an ACE inhibitor. Although the risk of airway obstruction with ACE inhibitors is acknowledged, we have only a superficial understanding of how prolonged ACE inhibitor treatment induces angioedema. So we should consider angioedema in cases of taking ACE inhibitors, especially in cases of prolonged treatment.
Ismail, Sharif; Cheng, Leo; Grigoriadou, Sofia; Laffan, James; Menon, Manoj
Acute angioedema attacks are conventionally treated with antihistamines and steroids, in line with a presumed mechanism of disease involving overwhelming mast-cell degranulation. This approach overlooks a small but important minority of cases in which attacks are bradykinin driven and exhibit poor responsiveness to steroid or anti-histamine therapy. These patients may have a family history of angioedema (hereditary angioedema), or a past medical history including B-cell lymphoproliferative disorders or autoimmune disease (acquired angioedema). Rather than steroid therapy, they respond to administration of a bradykinin inhibitor, or more commonly, a C1 esterase inhibitor substitute, to control acute symptoms and reduce the probability of invasive airway insertion. In the long-term, they require C1 esterase inhibitor sparing therapy and a treat-the-cause approach to reduce the risk of recurrent attacks. We present here a case of a middle-aged woman who presented with recurrent angioedema of initially uncertain aetiology. © 2015 Royal College of Physicians.
Full Text Available Aasia Ghazi, J Andrew GrantUniversity of Texas Medical Branch, Division of Allergy and Clinical Immunology, Galveston, TX, USAAbstract: Hereditary angioedema (HAE is an autosomal dominant, potentially life-threatening condition, manifesting as recurrent and self-limiting episodes of facial, laryngeal, genital, or peripheral swelling with abdominal pain secondary to intra-abdominal edema. The estimated prevalence of HAE in the general population is one individual per 50,000, with reported ranges from 1:10,000 to 1:150,000, without major sex or ethnic differences. Various treatment options for acute attacks and prophylaxis of HAE are authorized and available in the market, including plasma-derived (Berinert®, Cinryze®, and Cetor® and recombinant (Rhucin® and Ruconest™ C1 inhibitors, kallikrein inhibitor-ecallantide (Kalbitor®, and bradykinin B2 receptor antagonist-icatibant (Firazyr®. Some of these drugs are used only to treat HAE attacks, whereas others are only approved for prophylactic therapies and all of them have improved disease outcomes due to their different mechanisms of action. Bradykinin and its binding to B2 receptor have been demonstrated to be responsible for most of the symptoms of HAE. Thus icatibant (Firazyr®, a bradykinin B2 receptor antagonist, has proven to be an effective and more targeted treatment option and has been approved for the treatment of acute attacks of HAE. Rapid and stable relief from symptoms of cutaneous, abdominal, or laryngeal HAE attacks has been demonstrated by 30 mg of icatibant in Phase III clinical trials. Self-resolving mild to moderate local site reactions after subcutaneous injection of icatibant were observed. Icatibant is a new, safe, and effective treatment for acute attacks of HAE. HAE has been reported to result in enormous humanistic burden to patients, affecting both physical and mental health, with a negative impact on education, career, and work productivity, and with substantial
Javaud, Nicolas; Achamlal, Jallal; Reuter, Paul-George; Lapostolle, Frédéric; Lekouara, Akim; Youssef, Mustapha; Hamza, Lilia; Karami, Ahmed; Adnet, Frédéric; Fain, Olivier
Abstract The number of cases of acquired angioedema related to angiotensin converting enzyme inhibitors induced (ACEI-AAE) is on the increase, with a potential concomitant increase in life-threatening attacks of laryngeal edema. Our objective was to determine the main characteristics of ACEI-AAE attacks and, in doing so, the factors associated with likelihood of hospital admission from the emergency department (ED) after a visit for an attack. A prospective, multicenter, observational study (April 2012–December 2014) was conducted in EDs of 4 French hospitals in collaboration with emergency services (SAMU 93) and a reference center for bradykinin-mediated angioedema. For each patient presenting with an attack, emergency physicians collected demographic and clinical presentation data, treatments, and clinical course. They recorded time intervals from symptom onset to ED arrival and to treatment decision, from ED arrival to specific treatment with plasma-derived C1-inhibitor (C1-INH) or icatibant, and from specific treatment to onset of symptom relief. Attacks requiring hospital admission were compared with those not requiring admission. Sixty-two eligible patients with ACEI-AAE (56% men, median age 63 years) were included. Symptom relief occurred significantly earlier in patients receiving specific treatment than in untreated patients (0.5 [0.5–1.0] versus 3.9 [2.5–7.0] hours; P < 0.0001). Even though icatibant was injected more promptly than plasma-derived C1-INH, there, however, was no significant difference in median time to onset of symptom relief between the 2 drugs (0.5 [0.5–1.3] versus 0.5 [0.4–1.0] hours for C1-INH and icatibant, respectively, P = 0.49). Of the 62 patients, 27 (44%) were admitted to hospital from the ED. In multivariate analysis, laryngeal involvement and progressive swelling at ED arrival were independently associated with admission (Odds ratio [95% confidence interval] = 6.2 [1.3–28.2] and 5.9 [1.3–26
Zanichelli, Andrea; Longhurst, Hilary J; Maurer, Marcus
BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) causes swelling in the skin and upper airways and pain in the abdomen because of mucosal swelling. C1-INH-HAE is frequently misdiagnosed, leading to delays in diagnosis, inadequate treatment, and unnecessary procedures...... being diagnosed as having C1-INH-HAE. RESULTS: In January 2016, a total of 418 of 633 IOS patients with C1-INH-HAE type I or II had provided misdiagnosis data. Of these, 185 of 418 (44.3%) received 1 or more prior misdiagnoses. The most common misdiagnoses were allergic angioedema (103 of 185...... patients without (1.7 years; P angioedema or appendicitis. Misdiagnosis results in marked delays in receiving the correct...
Mutnuri, Sangeeta; Khan, Adnan; Variyam, Easwaran P
Cough and upper airway angioedema are well-recognized adverse reactions of angiotensin-converting enzyme inhibitor (ACEI) therapy. Visceral angioedema is an infrequent and often unrecognized complication of ACEI therapy. We describe a patient in whom the diagnosis was delayed for > 2 years. A 60-year-old woman with hypertension on treatment with enalapril presented with complaints of abdominal pain and diarrhea for 2 days. Physical examination was significant for diffuse abdominal tenderness and hypotension. Laboratory data were normal except for leukocytosis and elevated creatinine. Computed tomography (CT) of the abdomen showed diffuse small bowel wall thickening. ACEI-induced visceral angioedema was considered, enalapril was discontinued and supportive care was provided. Patient's symptoms and CT appearance improved 48 and 72 hours, respectively, after stopping enalapril. She remained symptom-free 1 year after discharge.
Csuka, Dorottya; Munthe-Fog, Lea; Hein, Estrid
BACKGROUND: The activation of plasma enzyme systems is insufficiently controlled in hereditary angioedema due to the deficiency of C1-inhibitor (C1-INH) (HAE-C1-INH). Recently, it was suggested that the ficolin-lectin pathway (ficolin-LP) might play a more dominant role than the mannose-binding l......BACKGROUND: The activation of plasma enzyme systems is insufficiently controlled in hereditary angioedema due to the deficiency of C1-inhibitor (C1-INH) (HAE-C1-INH). Recently, it was suggested that the ficolin-lectin pathway (ficolin-LP) might play a more dominant role than the mannose......: There is a marked heterogeneity of the pathomechanism and development of hereditary angioedema attacks in different patients. Our results suggest that the activation of the ficolin-LP may deplete the innately low level of C1-INH and thus, it may contribute to the uncontrolled activation of plasma cascade systems...
Roberto Rheingantz da Cunha Filho
Full Text Available Angioedema may be caused by nonsteroidal antiinflammatory drugs, angiotensin- converting enzyme inhibitors, radiocontrast media, antibiotics, sea food etc. It can involve an allergic (IgE-mediated or non-allergic hypersensitivity reaction, both with a similar clinical presentation. While angioedema due to isotretionin has been described previously, this is the first description of angiodema due to acitretin. We report two uncommon cases of palpebral and labial angiodema due to retinoids, by acitretin and oral isotretinoin respectively: a 48-year-old man with psoriasis and a 24-year-old woman with severe acne resistant to antibiotics and topical drugs. In both cases the reaction persisted through-out treatment with these drugs, but resolved quickly after discontinuation. Reintroduction of the drugs brought on angioedema againAngioedema pode ser causado por diversos fármacos como : antiinflamatórios não-esteroidais, inibidores da ECA, contrastes, antibióticos e frutos do mar, entre outras causas. Pode ser uma reação alérgica, mediada por IgE, ou não-alérgica, com apresentações clínicas semelhantes. Angioedema por isotretinoína já foi relatado, mas não por acitretina. Relatamos dois casos, uma com angioedema palpebral e um labial, por acitretina e isotretinoína, respectivamente: um paciente de 48 anos com psoríase e uma paciente de 24 anos com acne resistente à terapia convencional. Em ambos casos a afecção persistiu durante o tratamento, resolveu com a interrupção e recidivou com reexposição
Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen
OBJECTIVE: To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact...... conceptually with the EuroQol 5-Dimensions (EQ-5D) domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey...
Gornowicz-Porowska, Justyna; Dmochowski, Marian; Pietkiewicz, Pawel; Bowszyc-Dmochowska, Monika
We describe a 39-year-old woman with an apparent captopril-induced, contact mucosal-dominant pemphigus vulgaris and angioedema, who took captopril during a bout of arterial hypertension. This exposure suggests that captopril and pathophysiology of angioedema stimulated the development of pemphigus vulgaris, which was diagnosed using the novel, indirect immunofluorescence BIOCHIP mosaic, with the modification to detect serum IgG4 autoantibodies. We discuss the patient, who experienced a chain of events leading to the active stage of pemphigus vulgaris, and review concepts of pemphigus vulgaris inducible by drugs and pathological immunity.
Miranda, Amanda Rodrigues; de Ue, Ana Paula Fusel; Sabbag, Dominique Vilarinho; Furlani, Wellington de Jesus; de Souza, Patr?cia Karla; Rotta, Osmar
In this article, three cases of hereditary angioedema (HAE) type III (estrogen-dependent or with normal C1 inhibitor) are reported. The HAE was initially described in women of the same family in association with high-leveled estrogenic conditions such as the use of oral contraceptives and pregnancy. There is no change in the C1 inhibitor as happens in other types of hereditary angioedema, and mutations are observed in the encoding gene of the XII factor of coagulation in several patients. The...
Full Text Available Abstract Hereditary angioedema is a rare disorder with a genetic background involving mutations in the genes encoding C1-INH and of factor XII. Its etiology is unknown in a proportion of cases. Recurrent edema formation may involve the subcutis and the submucosa - the latter can produce obstruction in the upper airways and thereby lead to life-threatening asphyxia. This is the reason for the high, 30-to 50-per-cent mortality of undiagnosed or improperly managed cases. Airway obstruction can be prevented through early diagnosis, meaningful patient information, timely recognition of initial symptoms, state-of-the-art emergency therapy, and close monitoring of the patient. Prophylaxis can substantially mitigate the risk of upper airway edema and also improve the patients' quality of life. Notwithstanding the foregoing, any form of upper airway edema should be regarded as a potentially life-threatening condition. None of the currently available prophylactic modalities is capable of preventing UAE with absolute certainty.
Hofman, Zonne L M; Relan, Anurag; Hack, C Erik
Hereditary angioedema (HAE) patients experience recurrent local swelling in various parts of the body including painful swelling of the intestine and life-threatening laryngeal oedema. Most HAE literature is about attacks located in one anatomical site, though it is mentioned that HAE attacks may also involve multiple anatomical sites simultaneously. A detailed description of such multi-location attacks is currently lacking. This study investigated the occurrence, severity and clinical course of HAE attacks with multiple anatomical locations. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. Visual analog scale scores filled out by the patients for various symptoms at various locations and investigator symptoms scores during the attack were analysed. Data of 219 eligible attacks in 119 patients was analysed. Thirty-three patients (28%) had symptoms at multiple locations in anatomically unrelated regions at the same time during their first attack. Up to five simultaneously affected locations were reported. The observation that severe HAE attacks often affect multiple sites in the body suggests that HAE symptoms result from a systemic rather than from a local process as is currently believed.
Full Text Available El angioedema hereditario (HAE es una enfermedad rara, autosómica dominante, caracterizada por episodios que comprometen la piel, el tracto gastrointestinal y la laringe. Tiene una mortalidad histórica por asfixia del 15 al 50%. Es producida por la deficiencia funcional del C1 inhibidor. La identificación de la bradiquinina como mediador principal ha estimulado el desarrollo de nuevos medicamentos para tratar la enfermedad. El tratamiento del HAE se establece en consensos internacionales. El desarrollo de guías para el tratamiento de la enfermedad permite ordenar el uso de procedimientos diagnósticos y drogas. Describimos aquí algunas características farmacológicas de los medicamentos utilizados en el tratamiento del HAE en la Argentina: el concentrado plasmático de C1 inhibidor, el antagonista de la bradiquinina, icatibant, el andrógeno atenuado danazol y los agentes anti-fibrinolíticos ácidos épsilon aminocaproico (EACA y tranexámico. Asimismo, se describe su forma de uso y del control de los eventos adversos más frecuentes, así como las recomendaciones del último consenso internacional, aplicables para conformar una primera guía de tratamiento del HAE en la Argentina.
Aberer, Werner; Bouillet, Laurence; Caballero, Teresa; Maurer, Marcus; Fabien, Vincent; Zanichelli, Andrea
Objective To characterize the management and outcomes of life-threatening laryngeal attacks of hereditary angioedema (HAE) treated with icatibant in the observational Icatibant Outcome Survey (NCT01034969) registry. Methods This retrospective analysis was based on data from patients with HAE type I/II who received healthcare professional-administered or self-administered icatibant to treat laryngeal attacks between September 2008 and May 2013. Results Twenty centers in seven countries contributed data. Overall, 42 patients with HAE experienced 67 icatibant-treated laryngeal attacks. Icatibant was self-administered for 62.3% of attacks (healthcare professional-administered, 37.7%). One icatibant injection was used for 87.9% of attacks, with rescue or concomitant medication used for 9.0%. The median time to treatment was 2.0 h (n=31 attacks) and the median time to resolution was 6.0 h (n=35 attacks). Conclusions This analysis describes successful use of icatibant for the treatment of laryngeal HAE attacks in a real-world setting. PMID:27116379
Åbom, Anne; Bygum, Anette; Koch, Claus
, that C1-INH-HAE may potentially be overlooked, if screening is performed only by measurement of C4. It has been suggested that measurement of C4 activation products is better suited to avoid false negative results. Our aim was to investigate whether total antigenic C4 or non-functional C4c is a better......Objectives: Low complement factor C4 is usually considered a valuable screening tool for patients with the potentially life-threatening hereditary angioedema with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE). However, there are patients with C1-INH-HAE presenting with normal C4 levels. This means...... measure of the increased C4 activation in C1-INH-HAE patients. Design and methods: Two different monoclonal antibodies (mAb) to human C4 were produced: one had specificity for the β-chain of C4 and would thus react with both functional and non-functional C4, and the other was developed against the factor...
Full Text Available We present a case of a 27-year-old man with recurrent episodes of angioedema since he was 19, who responded well to treatment with medical grade cannabis. Initially, he responded to steroids and antihistamines, but several attempts to withdraw treatment resulted in recurrence. In the last few months before prescribing cannabis, the frequency and severity of the attacks worsened and included several presyncope events, associated with scrotal and neck swelling. No predisposing factors were identified, and extensive workup was negative. The patient reported that he was periodically using cannabis socially and that during these periods he was free of attacks. Recent data suggest that cannabis derivatives are involved in the control of mast cell activation. Consequently, we decided to try a course of inhaled cannabis as modulators of immune cell functions. The use of inhaled cannabis resulted in a complete response, and he has been free of symptoms for 2 years. An attempt to withhold the inhaled cannabis led to a recurrent attack within a week, and resuming cannabis maintained the remission, suggesting a cause and effect relationship.
Duke, Jon D; Ryan, Patrick B; Suchard, Marc A; Hripcsak, George; Jin, Peng; Reich, Christian; Schwalm, Marie-Sophie; Khoma, Yuriy; Wu, Yonghui; Xu, Hua; Shah, Nigam H; Banda, Juan M; Schuemie, Martijn J
Recent adverse event reports have raised the question of increased angioedema risk associated with exposure to levetiracetam. To help address this question, the Observational Health Data Sciences and Informatics research network conducted a retrospective observational new-user cohort study of seizure patients exposed to levetiracetam (n = 276,665) across 10 databases. With phenytoin users (n = 74,682) as a comparator group, propensity score-matching was conducted and hazard ratios computed for angioedema events by per-protocol and intent-to-treat analyses. Angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per-protocol and 248 vs. 435 in intent-to-treat). No significant increase in angioedema risk with levetiracetam was seen in any individual database (hazard ratios ranging from 0.43 to 1.31). Meta-analysis showed a summary hazard ratio of 0.72 (95% confidence interval [CI] 0.39-1.31) and 0.64 (95% CI 0.52-0.79) for the per-protocol and intent-to-treat analyses, respectively. The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin, which does not currently carry a labeled warning for angioedema. Further studies are warranted to evaluate angioedema risk across all antiepileptic drugs. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Moriya, Maki; Aihara, Michiko; Hirota, Rie; Hirata, Yuko; Ikinaga, Naoko; Takamura, Naoko; Kunimi, Yuko; Uchida, Takahisa; Ikezawa, Zenro
The pathogenesis of urticaria and angioedema induced by non-steroidal anti-inflammatory drugs (NSAIDs) is still obscure. We analyzed the clinical characteristics of patients with NSAIDs-induced urticaria and angioedema without asthma in Japan. We retrospectively collected the cases of NSAIDs-induced urticaria and angioedema from Japanese medical journals in 2000-2009. Seventy-six patients were analyzed. The male/female ratio was 1:2.5 and the mean age was 38.1 years. Urticaria was most frequent clinical manifestation in 3 groups; urticaria alone, urticaria and angioedema, and angioedema alone. Time interval from drug administration to onset was 5 minutes to 48 hours by aspirin at a dose of 25-1000 mg. Skin prick test was performed with aspirin in 33 patients, and the results were negative in all patients. Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, and celecoxib, a new selective COX-2 inhibitor, were administered safely in 4 of 6 patients and in 2 of 3 patients with NSAIDs-induced urticaria, respectively. These drugs were administered safely in all administered patients with NSAIDs-induced angioedema. Tiaramidehydrochroride (a basic COX-1 inhibitor) was safely used in 23 administered patients with NSAIDs-induced angioedema. Leukotriene receptor antagonists were effective in 2 of 5 patients administered, but aggravated symptoms in the others. Diversity of NSAIDs-induced urticaria and angioedema was shown in this study. Pathogenesis of NSAIDs-induced urticaria and angioedema without asthma seems to be different from that of NSAIDs-induced asthma.
Bartal, Carmi; Zeldetz, Vladimir; Stavi, Vered; Barski, Leonid
Angioedema is a localized, sudden, transient, and often recurrent swelling of the deeper layers of the skin or mucosa with no epidermal component. It is caused by vasoactive substances that produce a transient increase in endothelial permeability. Angioedema involving the laryngeal components is a life-threatening situation for the patient,and it is a challenge for the emergency medicine physician to rapidly achieve a safety airway. Most cases of laryngeal angioedema are induced by histamine release; but 10% are bradykinin induced, which does not respond to the conventional algorithm of treating allergic induced angioedema. We present a case report of an angiotensin converting enzyme (ACE) inhibitor–induced laryngeal angioedema alleviated only after treatment with the new bradykinin receptor inhibitor medication icatibant which was licensed only for use in hereditary angioedema. We reviewed the literature for the use of icatibant in acquired drug-induced angioedema; and because of the similar pathogenesis between the hereditary angioedema and the ACE inhibitor–induced angioedema,we propose an algorithm for careful use of icatibantin life-threatening angioedema in the emergency department.
Savino, Michael R; Mittal, Pardeep K; Miller, Frank H
Angioedema is a condition in which an increase in vascular permeability leads to the swelling of body tissues. There are both hereditary and acquired forms of the disease, with the latter often associated with the administration of angiotensin-converting enzyme inhibitor medication. Involvement of the intestinal tract is a rare manifestation of angioedema, and can present with abdominal pain, nausea, and vomiting. It is critical for radiologists to be aware of this entity, as they may have the only opportunity to make the diagnosis. We present three cases of intestinal angioedema diagnosed on MRI with discussion of the imaging findings. Copyright © 2017 Elsevier Inc. All rights reserved.
Conceição, Luís; Martinho, Hélder; Azenha, Marta
O angioedema hereditário é uma entidade rara, com transmissão autossómica dominante, causada por deficiência no inibidor de C1. Esta condiciona uma ativação descontrolada da via clássica do complemento e da cascata das cininas, sendo responsável por episódios de angioedema com possível comprometimento da via aérea. Os autores descrevem um caso clínico de um doente com 36 anos com angioedema hereditário tipo I proposto para colecistectomia electiva sob anestesia geral, tendo sido tomadas algum...
Csuka, Dorottya; Munthe-Fog, Lea; Skjoedt, Mikkel-Ole
Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) causes disturbances in the complement system. However, the influence of HAE-C1-INH on the lectin pathway of complement is unresolved. Thus, we studied the main initiator molecules, enzymes and regulators in the lectin pathway...
Bygum, A; Fagerberg, C R; Ponard, D
Hereditary angioedema (HAE), type I and II, is an autosomal dominant disease with deficiency of functional C1 inhibitor protein causing episodic swellings of skin, mucosa and viscera. HAE is a genetically heterogeneous disease with more than 200 different mutations in the SERPING1 gene. A genotype...
Aabom, Anne; Andersen, Klaus E; Fagerberg, Christina
BACKGROUND: With a potentially early onset, hereditary angioedema (HAE) requires special knowledge also in infancy and early childhood. In children from families with HAE, the diagnosis should be confirmed or refuted early, which can be difficult. Studies of childhood HAE and the diagnostic...
Joseph, Kusumam; Bains, Sonia; Tholanikunnel, Baby G
BACKGROUND: Hereditary angioedema types I and II are caused by a functional deficiency of C1 inhibitor (C1-INH) leading to overproduction of bradykinin. The current functional diagnostic assays employ inhibition of activated C1s, however, an alternative, more physiologic method, is desirable...
Rasmussen, Eva R; Valente de Freitas, Priscila; Bygum, Anette
Erythema marginatum is a characteristic skin rash seen in patients with hereditary angioedema (HAE); however, it can be confused with urticaria, leading to delay in correct diagnosis. The aim of this study was to clarify how often erythema marginatum is misinterpreted as urticaria, potentially...
Full Text Available Angiotensin-converting enzyme (ACE inhibitors are the leading cause of a drug-induced angioedema. This occurrence is frequently underdiagnosed, but its relapse can be life-threatening. The authors’ intention in reporting this clinical case is to sound a warning about reviewing attitudes and surveillance to try to improve patient perioperative safety.
Choi, Goda; Soeters, Maarten R.; Farkas, Henriette; Varga, Lilian; Obtulowicz, Krystyna; Bilo, Barbara; Porebski, Greg; Hack, C. Erik; Verdonk, Rene; Nuijens, Jan; Levi, Marcel
BACKGROUND: Patients with hereditary C1-inhibitor deficiency have recurrent attacks of angioedema, preferably treated with C1-inhibitor concentrate. A recombinant human C1-inhibitor (rHuC1INH) was developed, derived from milk from transgenic rabbits. This study was undertaken to investigate the
Busse, Paula; Bygum, Anette; Edelman, Jonathan
BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products, typ...
Kozel, M. M.; Mekkes, J. R.; Bossuyt, P. M.; Bos, J. D.
OBJECTIVE: To assess the value of extensive laboratory screening for the identification of causes in patients with chronic urticaria and/or angioedema. DESIGN: In a prospective study involving 220 patients, 2 diagnostic strategies were compared: the combination of detailed history taking and limited
Fouche, Andrew S; Saunders, Erika F H; Craig, Timothy
Hereditary angioedema (HAE) is characterized by edematous swelling attacks of the face, extremities, abdomen, genitalia, and upper airway. The potential for laryngeal swelling makes the disease life-threatening, and the swelling elsewhere contributes to the significant burden of illness. The increased risk for mental health disorders in HAE is due to the burden of disease and possibly associated activation of the immune system. To determine the prevalence of depression and anxiety in HAE patients and the most high-yield features of depression to target in a clinical encounter. Depression and anxiety symptoms were evaluated using the 29 items of the Hamilton Depression Rating Scale along with the 14-item Hamilton Anxiety Rating Scale. The sample size was 26 participants with a diagnosis of type 1 or 2 HAE drawn from a cohort of 60 adult patients. In addition, a literature search was performed regarding how immune modulation affects depression and anxiety. A total of 39% of participants were identified as experiencing depression of mild (50%), moderate (40%), or severe (10%) levels. Fifteen percent of participants displayed prominent anxiety, half of whom had mild anxiety, 25% moderate anxiety, and 25% severe anxiety. The literature on inflammation and depression suggests a possible link between HAE and depression. Our data and the literature support that depression and anxiety symptoms are common in patients with HAE and may be secondary to chronic disease burden, associated pathophysiologic features, or both. Treatment that addresses the psychosocial and mental health of HAE patients is critical for best practice. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Perricone, C; Agmon-Levin, N; Shoenfeld, N; de Carolis, C; Guarino, M D; Gigliucci, G; Milana, I; Novelli, L; Valesini, G; Perricone, R; Shoenfeld, Y
Hereditary angioedema (HAE) is an autosomal-dominant disorder resulting from C1-inhibitor (C1INH) deficiency. Smell impairments were found in patients affected with systemic lupus erythematosus, that, similarly to HAE, is characterized by the activation of the classical complement pathway with C4 consumption. In this study, we aimed at evaluating the sense of smell in patients with HAE. Thirty patients with HAE and 30 healthy age- and sex-matched controls were evaluated for olfactory functions using the 3-stages Sniffin'-Sticks kit (threshold, discrimination, and identification [TDI]). TDI scores were analyzed according to complement levels (C1INH, C3, C4 and CH50), Beck depression inventory (BDI-II) and danazol treatment. A significant decrease in olfactory function was observed in patients affected with HAE compared with controls in total TDI score (P < 0.001), and in the discrimination (P < 0.001) and identification scores (P = 0.012). Anosmia was present only in patients with HAE (3.3%) who also exhibited more frequently hyposmia (53.3%vs 3.3%, P < 0.0001). Complement levels were reduced in patients with HAE. C4 serum levels showed positive correlation with total TDI score (P < 0.001), and with discrimination (P = 0.002) and identification (P = 0.011) scores. CH50 complement levels showed positive correlation with total TDI score (P < 0.001), and with threshold (P = 0.002) and discrimination (P = 0.011) scores. Sex, age, danazol treatment, BDI-II scores were not different between the patients and controls and did not influence TDI scores significantly. Evidence for an impaired sense of smell was found in patients with HAE. The reduction in olfactory function in these cases seems to correlate with complement C4 and CH50 levels. Immune and genetic mechanisms might play a role in this defect. © 2010 John Wiley & Sons A/S.
Maddalena A Wu
Full Text Available Attacks of Hereditary Angioedema due to C1-inhibitor deficiency (C1-INH-HAEare often triggered by stressful events/hormonal changes.Our study evaluates the relationship between autonomic nervous system (ANS and contact/complement system activation.Twenty-three HAE patients (6 males, mean age 47.5±11.4 years during remission and 24 healthy controls (8 males, mean age 45.3±10.6 years were studied. ECG, beat-by-beat blood pressure, respiratory activity were continuously recorded during rest (10' and 75-degrees-head-up tilt (10'. C1-INH, C4, cleaved high molecular weight kininogen (cHK were assessed; in 16 patients and 11 controls plasma catecholamines were also evaluated. Spectral analysis of heart rate variability allowed extraction of low-(LF and high-(HF frequency components, markers of sympathetic and vagal modulation respectively.HAE patients showed higher mean systolic arterial pressure (SAP than controls during both rest and tilt. Tilt induced a significant increase in SAP and its variability only in controls. Although sympathetic modulation (LFnu increased significantly with tilt in both groups, LF/HF ratio, index of sympathovagal balance, increased significantly only in controls. At rest HAE patients showed higher noradrenaline values (301.4±132.9 pg/ml vs 210.5±89.6pg/ml, p = 0.05. Moreover, in patients tilt was associated with a significant increase in cHK, marker of contact system activation (49.5 ± 7.5% after T vs 47.1 ± 7.8% at R, p = 0.01.Our data are consistent with altered ANS modulation in HAE patients, i.e. increased sympathetic activation at rest and blunted response to orthostatic challenge. Tilt test-induced increased HK cleavage suggests a link between stress and bradykinin production.
Henao, Maria Paula; Kraschnewski, Jennifer L; Kelbel, Theodore; Craig, Timothy J
Hereditary angioedema (HAE) is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a deficiency of C1 esterase inhibitor (C1-INH) that leads to the overproduction of bradykinin, causing an abrupt increase in vascular permeability. A less-understood and less-common form of the disease presents with normal C1-INH levels. Symptoms of angioedema may be confused initially with mast cell-mediated angioedema, such as allergic reactions, and may perplex physicians when epinephrine, antihistamine, or glucocorticoid therapies do not provide relief. Similarly, abdominal attacks may lead to unnecessary surgeries or opiate dependence. All affected individuals are at risk for a life-threatening episode of laryngeal angioedema, which continues to be a source of fatalities due to asphyxiation. Unfortunately, the diagnosis is delayed on average by almost a decade due to a misunderstanding of symptoms and general lack of awareness of the disease. Once physicians suspect HAE, however, diagnostic methods are reliable and available at most laboratories, and include testing for C4, C1-INH protein, and C1-INH functional levels. In patients with HAE, management consists of acute treatment of an attack as well as possible short- or long-term prophylaxis. Plasma-derived C1-INH, ecallantide, icatibant, and recombinant human C1-INH are new treatments that have been shown to be safe and effective in the treatment of HAE attacks. The current understanding of HAE has greatly improved in recent decades, leading to growing awareness, new treatments, improved management strategies, and better outcomes for patients. PMID:27194914
Kamil, Rebecca J; Jerschow, Elina; Loftus, Patricia A; Tan, Melin; Fried, Marvin P; Smith, Richard V; Foster, David; Ow, Thomas J
Black race is a risk factor for angioedema. The primary aim was to examine the relationship between race-ethnicity and risk factors for angioedema. Using a retrospective case-control study design, data was extracted with the Clinical Looking Glass utility, a data collection and management tool that captures data from electronic medical record systems within the Montefiore Healthcare System. Cases were emergency department (ED) visits with primary or secondary International Classification of Diseases, Ninth Revision, code diagnoses of angioedema in adults aged ≥ 18 years from January 2008 to December 2013 at three Montefiore centers in Bronx, New York. Controls were a random sampling of adult ED visits during the same period. In primary analyses, angiotensin-converting enzyme inhibitor (ACE-I) and black race were evaluated for synergy. The influence of different risk factors in the development of angioedema was evaluated using logistic regression models. Finally, race-ethnicity was further explored by evaluating for effect modification by stratification of models by race-ethnicity categories. There were 1,247 cases and 6,500 controls randomly selected from a larger control pool. ACE-I use (odds ratio [OR] 3.70, 95% confidence interval [CI] 2.98, 4.60), hypertension (OR 1.88, 95% CI 1.55, 2.29), and black race (OR 2.25, 95% CI 1.86, 2.72) were the strongest risk factors. ACE-I use and black race were not synergistic (OR 1.10, 95% CI 0.80, 1.51). Race-ethnicity was an effect modifier for certain risk factors. Race-ethnicity acts as an effect modifier for particular angioedema risk factors. The two strongest risk factors, ACE-I use and black race, were not synergistic. 3b. Laryngoscope, 126:1823-1830, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.
Greve, Jens; Bas, Murat; Hoffmann, Thomas K; Schuler, Patrick J; Weller, Patrick; Kojda, Georg; Strassen, Ulrich
The study objective was to generate pilot data to evaluate the effectiveness and safety of C1-esterase-inhibitor concentrate (C1-INH) compared to standard treatment in patients with angiotensin-converting enzyme inhibitor (ACEi)-induced angioedema affecting the upper aerodigestive tract. Proof-of-concept case series with historical control. Adult patients with angioedema in the upper aerodigestive tract presenting to the emergency department were included. After establishing the diagnosis of ACEi-induced angioedema based on patient history and thorough clinical examination, all patients were administered 1,000 international units (IU) of C1-INH intravenously. A historical control group consisting of adult patients with ACEi-induced angioedema who had been treated with intravenous corticosteroids and antihistamines at the same institution over the past 8 years was used for comparison. The most important parameters assessed were the time to complete resolution of symptoms and the need for intubation or tracheotomy. Ten patients were included in the C1-INH group and 47 in the corticosteroid/antihistamine group. The time to complete resolution of symptoms was considerably longer in the historical control group (33.1 ± 19.4 hours) than in the C1-INH group (10.1 ± 3.0 hours). No intubation or tracheotomy was needed in the C1-INH group (0/10 patients), whereas three out of the 47 historical controls required tracheotomy and two were intubated (5/47). The results suggest a role for C1-INH as an effective and safe therapeutic option in patients with ACEi-induced angioedema, which needs to be confirmed by further larger and double-blinded studies. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.
Caballero, T.; Baeza, M. L.; Cabañas, R.; Campos, A.; Cimbollek, S.; Gómez-Traseira, C.; González-Quevedo, T.; Guilarte, M.; Jurado-Palomo, J.; Larco, J. I.; López-Serrano, M. C.; López-Trascasa, M.; Marcos, C.; Muñoz- Caro, J. M.; Pedrosa, M.
Background: There are no previous Spanish guidelines or consensus statements on bradykinin-induced angioedema. Aim: To draft a consensus statement on the management and treatment of angioedema mediated by bradykinin in light of currently available scientifi c evidence and the experience of experts. This statement will serve as a guideline to health professionals. Methods: The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema, a working group of the Spanish...
Wadelius, M; Marshall, S E; Islander, G; Nordang, L; Karawajczyk, M; Yue, Q-Y; Terreehorst, I; Baranova, E V; Hugosson, S; Sköldefors, K; Pirmohamed, M; Maitland-van der Zee, A-H; Alfirevic, A; Hallberg, P; Palmer, C N A
Angioedema is a potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. To study the genetic etiology of this rare adverse event, international consortia and multicenter recruitment of patients are needed. To reduce patient heterogeneity, we have standardized the phenotype. In brief, it comprises swelling in the head and neck region that first occurs during treatment. It should not coincide with urticaria or have another likely cause such as hereditary angioedema. PMID:24960520
Hallberg, Pär; Nagy, Julia; Karawajczyk, Malgorzata; Nordang, Leif; Islander, Gunilla; Norling, Pia; Johansson, Hans-Erik; Kämpe, Mary; Hugosson, Svante; Yue, Qun-Ying; Wadelius, Mia
Angioedema is a rare and serious adverse drug reaction (ADR) to angiotensin-converting enzyme (ACE) inhibitor treatment. Dry cough is a common side effect of ACE inhibitors and has been identified as a possible risk factor for angioedema. We compared characteristics between patients with ACE inhibitor-induced angioedema and cough with the aim of identifying risk factors that differ between these adverse events. Data on patients with angioedema or cough induced by ACE inhibitors were collected from the Swedish database of spontaneously reported ADRs or from collaborating clinicians. Wilcoxon rank sum test, Fisher's exact test, and odds ratios (ORs) with 95% CIs were used to test for between-group differences. The significance threshold was set to P angioedema and 121 with cough only. Smoking and concomitant selective calcium channel blocker treatment were more frequent among patients with angioedema than cough: OR = 4.3, 95% CI = 2.1-8.9, P = 2.2 × 10 -5 , and OR = 3.7, 95% CI = 2.0-7.0, P = 1.7 × 10 -5 . Angioedema cases were seen more often in male patients (OR = 2.2, 95% CI = 1.4-3.6, P = 1.3 × 10 -4 ) and had longer time to onset and higher doses than those with cough ( P = 3.2 × 10 -10 and P = 2.6 × 10 -4 ). A multiple model containing the variables smoking, concurrent calcium channel blocker treatment, male sex, and time to onset accounted for 26% of the variance between the groups. Smoking, comedication with selective calcium channel blockers, male sex, and longer treatment time were associated with ACE inhibitor-induced angioedema rather than cough.
Venditto, Chelsea; Jager, Zachary; LoGiudice, John; Matloub, Hani
Compartment syndrome of the upper extremity is a surgical emergency that, when left untreated, can have dire consequences. Its causes are numerous, one of which is the uncommon entity hereditary angioedema, an autosomal dominant disease resulting in edema in a variety of potential locations, including the extremities. This is only the second time hereditary angioedema has been mentioned in the literature as a cause of compartment syndrome. We present a case of hereditary angioedema leading to hand and forearm compartment syndrome in a 13-year-old pediatric patient. Diagnosis of hereditary angioedema was made by our Rheumatology colleagues with physical exam and a thorough history, and confirmed by laboratory studies. Our patient presented with compartment syndrome of the hand and forearm and underwent hand and volar forearm fasciotomies. She was subsequently worked up for hereditary angioedema with laboratory results confirming the diagnosis. She was discharged after a 5-day hospitalization with prophylactic C1-inhibitor therapy. Hereditary angioedema is a rare but known cause of compartment syndrome of the upper extremity, and must be considered when patients present with compartment syndrome of unknown etiology. This disease can be diagnosed by laboratory studies and symptoms can be controlled with medical therapy.
Longhurst, Hilary; Bygum, Anette
Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disorder characterized by intermittent and unpredictable episodes of swelling which cause disfigurement, disability, pain, or, in case of laryngeal swelling, risk of death. Historical factors, including the intermittent nature of the disorder, the lack of awareness of this ultra-rare condition amongst medical personnel, lack of specialist centers, and limited treatment options have contributed to under-diagnosis and under-treatment of the condition. Incorrect treatment of attacks has been common, even when medical help is sought. This has lead to reduced health-seeking behavior and alternative coping strategies, sometimes even denial, in many families, while a minority of HAE-affected patients have become serial emergency room attenders with chronic pain and ongoing requirement for opiate-based painkillers. Both strategies have incurred not only physical but also psychological and economic consequences.In the last 10 years, new and effective acute therapies have been made available, some of which have also provided short-term and long-term prophylaxis options, together with a better understanding of older prophylactic drugs. Improved awareness of HAE amongst the general public, family members, and physicians has reduced the long delay in diagnosis and increased the number of patients receiving effective and up-to-date therapies to improve the physical impact of the disorder.Data on the impact of treatment on the psychological outcomes is scarce, but the limited information available suggests that access to specialist advice and treatment leads to psychological as well as physical improvement.HAE also has profound effects on individual and family economic output, directly via absenteeism from school or work and indirectly via lost opportunities. Economic improvements associated with better treatments are offset by the high cost of new acute treatments, resulting in difficult pharmaco
Zeerleder, Sacha; Levi, Marcel
Uncontrolled generation of bradykinin (BK) due to insufficient levels of protease inhibitors controlling contact phase (CP) activation, increased activity of CP proteins, and/or inadequate degradation of BK into inactive peptides increases vascular permeability via BK-receptor 2 (BKR2) and results in subcutaneous and submucosal edema formation. Hereditary and acquired angioedema due to C1-inhibitor deficiency (C1-INH-HAE and -AAE) are diseases characterized by serious and potentially fatal attacks of subcutaneous and submucosal edemas of upper airways, facial structures, abdomen, and extremities, due to inadequate control of BK generation. A decreased activity of C1-inhibitor is the hallmark of C1-INH-HAE (types 1 and 2) due to a mutation in the C1-inhibitor gene, whereas the deficiency in C1-inhibitor in C1-INH-AAE is the result of autoimmune phenomena. In HAE with normal C1-inhibitor, a significant percentage of patients have an increased activity of factor XIIa due to a FXII mutation (FXII-HAE). Treatment of C1-inhibitor-dependent angioedema focuses on restoring control of BK generation by inhibition of CP proteases by correcting the balance between CP inhibitors and BK breakdown or by inhibition of BK-mediated effects at the BKR2 on endothelial cells. This review will address the pathophysiology, clinical picture, diagnosis and available treatment in C1-inhibitor-dependent angioedema focusing on BK-release and its regulation. Key Messages Inadequate control of bradykinin formation results in the formation of characteristic subcutaneous and submucosal edemas of the skin, upper airways, facial structures, abdomen and extremities as seen in hereditary and acquired C1-inhibitor-dependent angioedema. Diagnosis of hereditary and acquired C1-inhibitor-dependent angioedema may be troublesome as illustrated by the fact that there is a significant delay in diagnosis; a certain grade of suspicion is therefore crucial for quick diagnosis. Submucosal edema formation in
Hassan A Farhat
Full Text Available Angioedema is a rare but potentially life threatening condition commonly associated with angiotensin-converting enzyme inhibitors (ACEIs. The incidence is approximately 0.1- 0.2% and may occur within the first week to several years of taking an ACEI. We present a case of a 37-year-old African-American male who was uneventfully taking a drug combination of quinapril and hydrochlorothiazide. When his medication was changed to lisinopril he developed an acute swelling of his lower lip and chin on fifth dose. The angioedema subsided within 24 hours after discontinuation of lisinopril. Therefore, this suggests that future treatment with ACEIs, as well as angiotensin receptor blockers (ARBs, is not recommended in this type of patient.
Visy, Beáta; Füst, George; Bygum, Anette
BACKGROUND: Helicobacter pylori infection is considered among the causative factors of urticaria and angioedema. Having conducted a study on 65 patients, Hungarian authors reported in 2001 that successful eradication of H. pylori is followed by a significant reduction in the number of attacks...... in patients with hereditary angioedema (HAE). The present study aimed to reinvestigate the relationship between H. pylori infection and the attack rate in the framework of an international collaborative study. MATERIALS AND METHODS: Within the framework of the PREHAEAT project launched by the European Union......, further 152 patients were studied in seven collaborating centers, and participants of the earlier study were followed up in order to detect any relationship between H. pylori infection and the occurrence of attacks in patients suffered from HAE. RESULTS: The proportion of patients experiencing frequent...
Khoury, Paneez; Herold, Jacqueline; Alpaugh, Alexandra; Dinerman, Ellen; Holland-Thomas, Nicole; Stoddard, Jennifer; Gurprasad, Shakuntala; Maric, Irina; Simakova, Olga; Schwartz, Lawrence B; Fong, Juelia; Lee, Chyi-Chia Richard; Xi, Liqiang; Wang, Zengfeng; Raffeld, Mark; Klion, Amy D
Episodic angioedema with eosinophilia (Gleich syndrome) is a rare disorder characterized by episodes of angioedema and eosinophilia that occur at monthly intervals and resolve spontaneously without therapy. Despite the striking periodicity of this disorder, its similarity to other cyclic hematopoietic disorders with multilineage involvement has not been assessed. To characterize the involvement of cell lineages in the etiology and pathogenesis of episodic angioedema with eosinophilia, four subjects were evaluated by blood counts and other analyses over the course of 1-2 months. Surface marker expression was assessed on T cells by flow cytometry and clonality by polymerase chain reaction. Intracellular cytokine evaluation, bone marrow and skin biopsies were performed during different parts of the cycle. Cycling of multiple cell lineages, including neutrophils, lymphocytes and eosinophils, was observed in the four subjects with the disorder with a periodicity of 25-35 days. An aberrant CD3(-)CD4(+) T-cell population was detected in all four subjects, and T-cell receptor rearrangement studies showed a clonal pattern in three subjects. A peak of type II cytokines was detected in the serum of subjects prior to the onset of symptoms and eosinophil cycling and corresponded to ex-vivo type II cytokines detected intracellularly in CD3(+)CD4(+)CD154(+) T cells. Although the etiology of episodic angioedema with eosinophilia is not yet known, multiple lineages, including lymphocytes, neutrophils and mast cells, are involved and may be related to disease pathogenesis. Whether these cells act directly or promote eosinophilia and eosinophil activation remains to be elucidated. All subjects gave informed consent and were evaluated under an Institutional Review Board-approved protocol (NCT00001406). Copyright© Ferrata Storti Foundation.
Wu, Maddalena Alessandra; Castelli, Roberto
Several clinical and biological features of lymphoproliferative diseases have been associated with an increased risk of developing autoimmune manifestations. Acquired deficiency of C1-inhibitor (C1-INH) (AAE) is a rare syndrome clinically similar to hereditary angioedema (HAE) characterized by local increase in vascular permeability (angioedema) of the skin and the gastrointestinal and oro-pharyngo-laryngeal mucosa. Bradykinin, a potent vasoactive peptide, released from high molecular weight kininogen when it is cleaved by plasma kallikrein (a serine protease controlled by C1-INH), is the mediator of symptoms. In total 46% of AAE patients carry an underlying hematological disorder including monoclonal gammopathy of uncertain significance (MGUS) or B cell malignancies. However, 74% of AAE patients have anti-C1-INH autoantibodies without hematological, clinical or instrumental evidence of lymphoproliferative disease. Unlike HAE patients, AAE patients usually have late-onset symptoms, do not have a family history of angioedema and present variable response to treatment due to the hypercatabolism of C1-INH. Experiments show that C1-INH and/or the classical complement pathway were consumed by the neoplastic lymphatic tissues and/or anti-C1-INH neutralizing autoantibodies. Therapy of AAE follows two directions: 1) prevention/reversal of the symptoms of angioedema; and 2) treatment of the associated disease. Different forms of B cell disorders coexist and/or evolve into each other in AAE and seem to be dominated by an altered control of B cell proliferation, thus AAE represents an example of the strict link between autoimmunity and lymphoproliferation.
Boccon‐Gibod, I.; Mansard, C.; Dumestre Perard, C.; Pralong, P.; Chatain, C.; Deroux, A.; Bouillet, L.
Summary Idiopathic histaminergic acquired angioedema (IH‐AAE) is a common cause of recurrent angioedema without wheals. It is a mast cell‐mediated disease thought to belong to the same clinical entity as chronic urticaria (CU). The objective of this study was to describe the clinical and epidemiological characteristics of IH‐AAE patients. From 2014 to 2015, 534 patients were seen at our national reference centre for angioedema and/or urticaria. Among them, we identified 31 patients with idiopathic histaminergic acquired angioedema without wheals (IH‐AAE). Thirty‐one patients (15 men and 16 women) with a mean age of 50 years met the criteria for IH‐AAE. The average delay in diagnosis was 6·3 years. A history of allergy was found in 12 patients (38·7%), nine suffering from allergic rhinitis. The mean duration of attacks was 28·1 h. The AE attack was located in the upper respiratory tract in 54·8% of cases (17 patients). A lingual location was found in 29% of patients. Men were more likely than women to have an upper airway involvement. No intubations or admissions to intensive care units were reported. The dosage of anti‐histamines to control the symptoms was onefold the recommended dose in 51·6% of patients (16 patients), twofold in 32% (10 patients) and three–fourfold in 16·1% (five patients). IH‐AAE is characterized by an important delay in diagnosis, a frequent involvement of the upper airway and a benign course during attacks. As in CU, a trial of up to fourfold dose of H1‐anti‐histamines may be necessary to control symptoms. PMID:26969870
Faisant, C; Boccon-Gibod, I; Mansard, C; Dumestre Perard, C; Pralong, P; Chatain, C; Deroux, A; Bouillet, L
Idiopathic histaminergic acquired angioedema (IH-AAE) is a common cause of recurrent angioedema without wheals. It is a mast cell-mediated disease thought to belong to the same clinical entity as chronic urticaria (CU). The objective of this study was to describe the clinical and epidemiological characteristics of IH-AAE patients. From 2014 to 2015, 534 patients were seen at our national reference centre for angioedema and/or urticaria. Among them, we identified 31 patients with idiopathic histaminergic acquired angioedema without wheals (IH-AAE). Thirty-one patients (15 men and 16 women) with a mean age of 50 years met the criteria for IH-AAE. The average delay in diagnosis was 6·3 years. A history of allergy was found in 12 patients (38·7%), nine suffering from allergic rhinitis. The mean duration of attacks was 28·1 h. The AE attack was located in the upper respiratory tract in 54·8% of cases (17 patients). A lingual location was found in 29% of patients. Men were more likely than women to have an upper airway involvement. No intubations or admissions to intensive care units were reported. The dosage of anti-histamines to control the symptoms was onefold the recommended dose in 51·6% of patients (16 patients), twofold in 32% (10 patients) and three-fourfold in 16·1% (five patients). IH-AAE is characterized by an important delay in diagnosis, a frequent involvement of the upper airway and a benign course during attacks. As in CU, a trial of up to fourfold dose of H1-anti-histamines may be necessary to control symptoms. © 2016 British Society for Immunology.
Botey, J; Navarro, C; Aulesa, C; Marín, A; Eseverri, J L
From the report of Hirschberg, only 3 years after aspirin synthesis, there have been numerous works dedicated to showing the different types of adverse reactions found following aspirin administration. However, there are few publications on the process of urticaria and/or acute angioedema induced by ASA and few reported cases were found in children. Thus, we present 6 atopic children with urticaria and/or angioedema related with ASA. A carefully detailed history, oral provocation with ASA, oral provocation with other NSAI and HBDT with ASA were done to all of them. The oral provocation with ASA was positive in 5 of the 6 cases. The provocations with the rest of the NSAI and tartrazine and sodium benzoate were negative in all of the patients. The HBDT was positive in 5 of the cases. In conclusion, we insist that aspirin intolerance is not infrequent in infancy and it is not rare to see urticaria and or angioedema, in spite of the fact that asthmatics, atopics or non atopics, usually present as bronchospasm. We also believe that the HBDT can be a method of diagnosis used in these cases.
Chan, Norman J; Soliman, Ahmed M S
This study aimed to determine the duration of use, presentation, and management of angiotensin converting enzyme (ACE) inhibitor-related angioedema patients at an urban academic medical center. Retrospective chart review. Eighty-eight patients who presented with ACE inhibitor-related angioedema between January 1, 2012, and December 31, 2012, were identified. They presented anywhere from 1 day to 20 years after starting an ACE inhibitor. About half the patients (50.7%) presented after taking an ACE inhibitor for at least 1 year. Fifty-five patients were female (62.5%). Twenty-eight patients (31.8%) had an airway intervention with 27 intubated and 1 requiring cricothyroidotomy. Six patients were intubated after more than 1 flexible laryngoscopy. The percentage of patients with involvement of the face, lips, tongue, floor of mouth, soft palate/uvula, and larynx were 12.5%, 60.2%, 39.7%, 6.8%, 17.0%, and 29.5%, respectively. Sixty-eight percent of patients with laryngeal edema were intubated. The majority of patients were treated with a corticosteroid and H1 and H2 receptor antagonists. Angioedema can occur at any time after starting ACE inhibitor use, with nearly half occurring after 1 year of use. Laryngeal involvement occurred in a minority of patients, but most of these patients were felt to require airway protection. © The Author(s) 2014.
Full Text Available A case report of fosinopril-induced angioedema of the intestine with a chronic course accompanied by multiple acute exacerbations is described. Angiotensin-converting enzyme (ACE inhibitor-induced angioedema of the intestine (AIAI occurs in a minority of patients taking an ACE inhibitor. The clinical presentation encompasses acute abdominal symptoms, pronounced bowel edema and ascites with occasional facial and/or oropharyngeal swelling. AIAI is diagnosed based on the temporal relationship between the symptomatic presentation and drug use, absence of alternative diagnoses including other causes of angioedema, and the prompt resolution of symptoms upon discontinuation of the ACE inhibitor. Prompt radiological investigation (abdominal computerized tomography and/or ultrasound is critical in making an early diagnosis and in preventing unnecessary surgical intervention. There is a female predominance of AIAI, which may reflect the interaction of estradiol with the various pathways involved in the pathophysiology of AIAI. Management of AIAI consists mainly of conservative measures and discontinuation of the ACE inhibitor. Angiotensin II receptor antagonists should not be considered as appropriate alternatives. Awareness and knowledge of AIAI are important because of the increasing use of ACE inhibitors, current delays in making the diagnosis, obvious management strategies once the diagnosis is made and the dysutility of alternative diagnoses, which may lead to considerable morbidity. AIAI must be considered in patients taking ACE inhibitors who develop gastrointestinal complaints irrespective of the duration of the therapy.
Bork, K; Davis-Lorton, M
Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a rare, autosomal-dominant disease. HAE-C1-INH is characterized by recurrent attacks of marked, diffuse, nonpitting and nonpruritic skin swellings, painful abdominal attacks, and laryngeal edema. The extremities and the gastrointestinal tract are most commonly affected. Swelling of the upper respiratory mucosa poses the greatest risk because death from asphyxiation can result from laryngealedema. HAE-C1-INH attacks are variable, unpredictable, and may be induced by a variety of stimuli, including stress or physical trauma. Because the clinical presentation of HAE-C1-INH is similar to other types of angioedema, the condition may be a challenge to diagnose. Accurate identification of HAE-C1-INH is critical in order to avoid asphyxiation by laryngeal edema and to improve the burden of disease. Based on an understanding of the underlying pathophysiology of IHAE-C1-INH, drugs targeted specifically to the disease, such as C1-inhibitor therapy, bradykinin B2-receptor antagonists, and kallikrein-inhibitors, have become available for both treatment and prevention of angioedema attacks. This article reviews the clinical features, differential diagnosis, and current approaches to management of HAE-C1-INH.
Nettis, E; Colanardi, M C; Ferrannini, A; Tursi, A
Tartrazine has been frequently linked to several diseases. However, a cause-and-effect role for tartrazine in these illnesses, especially in urticaria, has not always been established. The aim of this study is to determine the incidence of intolerance to tartrazine among subjects who experienced an acute episode of urticaria/angioedema following the ingestion of a meal or a product containing this substance. This was a retrospective study based on analysis of data of patients reported to have experienced episodes of urticaria and/or angioedema after ingesting meals or products containing tartrazine. At the first visit to the outpatients clinic, a careful anamnesis had been taken. Patients had then been submitted to the following diagnostic tests: IgE tests to common inhalant allergens and food allergens and a double-blind placebo-controlled challenge with tartrazine. A total of 102 subjects were enrolled in the study: 19 (18.6%) showed at least one relevant positive reaction to an IgE test for food allergy. Only one subject (1%) had reactions after ingestion of 5 mg of tartrazine, given on day 5. She did not have adverse reactions to placebo. This study shows that the percentage of acute urticaria and/or angioedema induced by tartrazine is very low (1%). In view of our results, we suggest that all physicians with patients who have suffered adverse reactions that could be attributed to tartrazine should also carefully evaluate other possible causes.
Urnoski, Eric; Grillo, Angelo; Rosini, Jamie M
Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema is a rare, albeit serious emergency that can result in airway compromise and potentially death if not treated promptly. Currently, there are no agents approved by the Food and Drug Administration to target ACE inhibitor angioedema and to prevent intubation. C1 inhibitors are approved for hereditary angioedema but may show promise in alleviating inflammation associated with ACE inhibitor angioedema. A 41-year-old man presented to the emergency department with swelling of his lips a few days after starting lisinopril for hypertension. Despite receiving diphenhydramine, ranitidine, and methylprednisolone, the swelling progressed to the patient's tongue. A C1 inhibitor was ordered in an effort to prevent intubation. Before the arrival of the medication, the patient was intubated emergently for airway protection. After receipt of the C1 inhibitor, the swelling dramatically improved, and the patient was successfully extubated after less than 18 hours from presentation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case illustrates a potential role for C1 inhibitors in the emergency setting for treating drug-induced angioedema, which may prevent or minimize mechanical ventilation time. Copyright © 2015 Elsevier Inc. All rights reserved.
Full Text Available Objective: To elucidate the progression of angioedema of the head and neck with routine management and to assess the utility of serial physical exams and fiberoptic laryngoscopy in its management. Methods: This study was a prospective observational research. From 2013 to 2014, a prospective observational study was conducted at a tertiary referral center. Forty patient were approached, 7 refused, 33 (18â90 years old were enrolled. Patients presented with angioedema involving the head and neck over a 12 month period were asked to participate in the study. Physical examination and fiberoptic laryngoscopy were performed at presentation and then repeated at least 1Â h later. Results: Thirty-three patients with head and neck angioedema from any cause were enrolled (mean age 58, range 23â89 years. The upper lip was the most commonly involved site (58%. On reevaluation, 82% of patients reported subjective improvement in symptoms. The association between subjective improvement and the physical exam, including fiberoptic laryngoscopy findings, was statistically significant (PÂ <Â 0.001. Conclusion: In stable patients with angioedema of any head and neck subsite, self-reported symptoms are associated with clinical stability or improvement as assessed by physical signs and fiberoptic laryngoscopy. Patients' symptoms may be an appropriate surrogate to monitor clinical status without the need for routine serial physical examinations or fiberoptic laryngoscopy, though further study is needed. Keywords: Angioedema, Physical examination, Fiberoptic laryngoscopy
Aygören-Pürsün, E; Martinez Saguer, I; Kreuz, W; Klingebiel, T; Schwabe, D
Background Hereditary angioedema (HAE), caused by deficiency in C1-inhibitor (C1-INH), leads to unpredictable edema of subcutaneous tissues with potentially fatal complications. As surgery can be a trigger for edema episodes, current guidelines recommend preoperative prophylaxis with C1-INH or attenuated androgens in patients with HAE undergoing surgery. However, the risk of an HAE attack in patients without prophylaxis has not been quantified. Objectives This analysis examined rates of perioperative edema in patients with HAE not receiving prophylaxis. Methods This was a retrospective analysis of records of randomly selected patients with HAE type I or II treated at the Frankfurt Comprehensive Care Centre. These were examined for information about surgical procedures and the presence of perioperative angioedema. Results A total of 331 patients were included; 247 underwent 700 invasive procedures. Of these procedures, 335 were conducted in 144 patients who had not received prophylaxis at the time of surgery. Categories representing significant numbers of procedures were abdominal (n = 113), ENT (n = 71), and gynecological (n = 58) procedures. The rate of documented angioedema without prophylaxis across all procedures was 5.7%; in 24.8% of procedures, the presence of perioperative angioedema could not be excluded, leading to a maximum potential risk of 30.5%. Predictors of perioperative angioedema could not be identified. Conclusion The risk of perioperative angioedema in patients with HAE type I or II without prophylaxis undergoing surgical procedures ranged from 5.7% to 30.5% (CI 3.5–35.7%). The unpredictability of HAE episodes supports current international treatment recommendations to consider short-term prophylaxis for all HAE patients undergoing surgery. PMID:23968383
Driver, Brian E; McGill, John W
Angioedema is an uncommon but important cause of airway obstruction. Emergency airway management of angioedema is difficult. We seek to describe the course and outcomes of emergency airway management for severe angioedema in our institution. We performed a retrospective, observational study of all intubations for angioedema performed in an urban academic emergency department (ED) between November 2007 and June 2015. We performed a structured review of video recordings of each intubation. We identified the methods of airway management, the success of each method, and the outcomes and complications of the effort. We identified 52 patients with angioedema who were intubated in the ED; 7 were excluded because of missing videos, leaving 45 patients in the analysis. Median time from arrival to the ED to the first intubation attempt was 33 minutes (interquartile range 17 to 79 minutes). Nasotracheal intubation was the most common first method (33/45; 73%), followed by video laryngoscopy (7/45; 16%). Two patients required attempts at more invasive airway procedures (retrograde intubation and cricothyrotomy). The intubating laryngeal mask airway was used as a rescue method 5 times after failure of multiple methods, with successful oxygenation, ventilation, and intubation through the laryngeal mask airway in all 5 patients. All patients were successfully intubated. In this series of ED patients who were intubated because of angioedema, emergency physicians used a range of methods to successfully manage the airway. These observations provide key lessons for the emergency airway management of these critical patients. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
Weller, K; Magerl, M; Peveling-Oberhag, A; Martus, P; Staubach, P; Maurer, M
The Angioedema Quality of Life Questionnaire (AE-QoL) has recently been developed and validated as the first specific patient-reported outcome tool to assess quality of life (QoL) impairment in recurrent angioedema patients. As of yet, its sensitivity to change and minimal clinically important difference (MCID) have not been established. Recurrent angioedema patients with chronic spontaneous urticaria or hereditary angioedema were repeatedly asked to complete the AE-QoL along with the SF-12 and other anchors for QoL impairment and disease activity during routine care visits. The sensitivity to change of AE-QoL was determined by correlating changes in its scores over time with changes in the applied anchors. In addition, the MCID was determined using anchor-based and distributional criterion-based approaches. Two hundred and seventy-eight patients contributed data sets for analysis. Baseline AE-QoL values were found to correlate well with SF-12 results as well as all other applied anchors for angioedema-related QoL impairment and disease activity. In addition, AE-QoL score changes over time correlated significantly with changes in the above anchors, thus demonstrating its sensitivity to change. The MCID of the AE-QoL total score was found to be six points. The AE-QoL is a valuable tool to assess changes of QoL impairment in recurrent angioedema patients over time, including changes due to treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Mansi, M; Zanichelli, A; Coerezza, A; Suffritti, C; Wu, M A; Vacchini, R; Stieber, C; Cichon, S; Cicardi, M
The first classification of angioedema without wheals was recently reported and comprises different forms of the disease distinguished by aetiology, mediator of oedema and inheritance. In total, 1725 consecutive patients with angioedema without wheals were examined at our centre between 1993 and 2012. We excluded from the analysis 667 patients because of incomplete data or because angioedema was related to a specific factor. According to the new classification of angioedema, the 1058 patients included in this analysis were diagnosed with hereditary (HAE; n = 377) or acquired angioedema (AAE; n = 681). The former group included HAE with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE; n = 353) and HAE with normal C1-INH levels (n = 24), of which six had a factor XII mutation (FXII-HAE) and 18 had disease of unknown origin (U-HAE). The AAE group included disease with C1-INH deficiency (C1-INH-AAE; n = 49), AAE related to angiotensin-converting enzyme inhibitor treatment (n = 183), idiopathic histaminergic (IH-AAE; n = 379) and idiopathic nonhistaminergic angioedema (InH-AAE; n = 70). We compared hereditary and AAE with uncertain aetiopathogenesis: the FXII-HAE and U-HAE groups pooled (FXII/U-HAE) versus InH-AAE. The median age at onset of FXII/U-HAE and InH-AAE was 26 and 38 years, respectively. In addition, 56% of patients with FXII/U-HAE and 81% of those with InH-AAE reported more than five attacks per year (median duration of 48 h). The location of angioedema in patients with FXII/U-HAE versus those with InH-AAE was the following: face, 70% versus 86%; tongue, oral cavity or larynx, 55% versus 68%; limbs, 70% versus 56%; and gastrointestinal mucosa, 50% versus 20%. Prophylaxis with tranexamic acid was effective in all six patients with U-HAE and in 37 of 38 with InH-AAE who were started on this treatment. Our findings in this cohort of patients with angioedema provide new information on the clinical characteristics, diagnosis and treatment of this
Full Text Available Emel Aygören-Pürsün,1 Anette Bygum,2 Kathleen Beusterien,3 Emily Hautamaki,4 Zlatko Sisic,5 Henrik B Boysen,6 Teresa Caballero7 1Angioedema Centre, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt, Germany; 2Hereditary Angioedema Centre Denmark, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark; 3Outcomes Research Strategies in Health, Washington, DC, 4Patient Reported Outcomes, Oxford Outcomes Inc., an ICON plc company, Bethesda, MD, USA; 5ViroPharma Incorporated, Chatsworth House, Maidenhead, UK; 6HAEi – Hereditary Angioedema International Patient Organization for C1 Inhibitor Deficiencies, Skanderborg, Denmark; 7Allergy Department, Hospital La Paz Institute for Health Research (IdiPaz, Biomedical Research Network on Rare Diseases U754 (CIBERER, University Hospital La Paz, Madrid, Spain Objective: To estimate health status utility (preference weights for hereditary angioedema (HAE during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe survey. Utility measures quantitatively describe the net impact of a condition on a patient’s life; a score of 0.0 reflects death and 1.0 reflects full health.Study design and methods: The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks.Results: Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation
Hahn, Janina; Trainotti, Susanne; Hoffmann, Thomas K; Greve, Jens
BACKGROUND Bradykinin is an underestimated mediator of angioedema. One subgroup of bradykinin induced angioedema is angioedema triggered by treatment with angiotensin converting enzyme (ACE) inhibitors. Due to its localization in the head and neck region and its unpredictable course, it is a possibly life-threatening condition. There is not an officially approved treatment for ACE inhibitor induced angioedema. CASE REPORT We present a case of an 83-year-old woman, who presented to our ENT department because of acute swelling of the tongue. On admission, there was no pharyngeal or laryngeal edema and no dyspnea. Treatment with glucocorticoids and antihistamines had no response. The patient had ramipril as regular medication, so we assumed ACE inhibitor induced angioedema and treated consequently with C1-inhibitor (human) 1,500 IU. Nevertheless, swelling was progressive and required intubation. Even after the second specific treatment with icatibant, her angioedema subsided extremely slowly. The patient also had regular treatment with saxagliptin, a dipeptidyl peptidase 4 inhibitor, so we assumed that the simultaneous inhibition of two bradykinin degrading enzymes led to a treatment-refractory course of angioedema. CONCLUSIONS General awareness for bradykinin induced angioedema due to regular medication is limited. Our case demonstrated the importance of improving awareness and knowledge about this side effect. We need a better understanding of the pathomechanism to aid in more precise clinical diagnosis. Securing the patient's airway as well as administration of an officially approved therapy is of utmost importance. As the number of patients simultaneously treated with antihypertensive and antidiabetic drugs is likely to increase, the incidence of bradykinin mediated drug induced angioedema is likely to increase as well.
Staubach, P; Metz, M; Chapman-Rothe, N; Sieder, C; Bräutigam, M; Canvin, J; Maurer, M
Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied. The primary objective was to evaluate the efficacy of omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives. X-ACT was a phase III, randomized, double-blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to omalizumab 300 mg or placebo (every 4 weeks up to week 24) (ClinicalTrials.gov number: NCT01723072). Of the 91 patients randomized to omalizumab (n = 44) or placebo (n = 47) at baseline, 68 completed the 28-week treatment phase (omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU-Q2oL scores at week 28 (P omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57-63 days with omalizumab and Omalizumab significantly improved angioedema-specific QoL (P omalizumab. Omalizumab was an effective treatment option for patients with moderate-to-severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Varga, L; Széplaki, G; Laki, J
) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured...... by standard laboratory methods. MBL-2 genotypes were determined by polymerase chain reaction. Besides the complement alterations (low CP and C1INH activity, low C4-, C1INH concentrations), which characterize HAE, the level of MASP-2 was also lower (P = 0.0001) in patients compared with controls. Depressed LP...
Bygum, Anette; Aygören-Pürsün, Emel; Caballero, Teresa
ABSTRACT: BACKGROUND: Hereditary angioedema (HAE) is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation...... of HAE-I or HAE-II. Data collection includes: (i) a survey on individuals' health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale); and (ii) one-on-one interviews to collect...
Kirankumar N Kulkarni
Full Text Available We report the clinical details and imaging findings of a case of transient angioedema of the small bowel following intravenous administration of non-ionic iodinated contrast material in a 17 year old female with no predisposing risk factors. Findings included long segment, symmetric, circumferential, low-density, bowel wall thickening involving the duodenum, jejunum, and most of the ileum on computed tomography scan obtained at 7 min following intravenous contrast material injection. This entity is self-limiting with a favourable clinical outcome and requires no specific treatment but only aggressive clinical monitoring.
Tukenmez Demirci, Gulsen; Kivanc Altunay, Ilknur; Atis, Guldehan; Kucukunal, Asli
Active sensitization to paraphenylendiamine (PPD) and related compounds from temporary black henna tattoos has become an epidemic in the recent years. Hair dyes also include PPD like black henna tatoos which cause allergic contact dermatitis. Skin lesions of allergic contact dermatitis from PPD are mostly seen as an exudative erythema, an erythema multiforme-like eruption or a bullous contact dermatitis. We, herein, report a 27 year-old woman with an angioedema-like reaction occurring after the first exposure to hair dye who was unaware of being previously sensitized to PPD from black henna tattoo.
Faisant, Charles; Du Thanh, Aurélie; Mansard, Catherine; Deroux, Alban; Boccon-Gibod, Isabelle; Bouillet, Laurence
Idiopathic non-histaminergic acquired angioedema (InH-AAE) is a rare disease characterized by AE resistant to antihistamines and a chronic course. We report five new cases of InH-AAE (two women and three men) with a rapid and dramatic response to the anti-immunoglobulin-E antibody omalizumab. In our literature review, we found 13 other relevant cases with a good response to this treatment. Overall, in 6 out of 18 patients, the doses of omalizumab required to prevent recurrences of attacks were higher than the licensed dose for chronic urticaria. No significant adverse effects have been reported.
Pino Rivero, V; Rodríguez Carmona, M; Iglesias González, R J; del Castillo Beneyto, F
Vegetal or animal food can produce hipersensibility reactions IgE mediated of diverse intensity. We report the case of a 54 years old woman without previous allergic antecedents who after eating frozen fish had to go to Emergencies due to angioedema especially in face and oropharynx. The ENT exploration by fibroscopia descarted laryngeal edema but the patient showed initially respiratory symptoms so she was treated with SC adrenalina and then steroids during her admission. The diagnosis of alimentary alergia would be confirmed after by Allergology with cutaneous test prick type.
Full Text Available Angioedema related to a deficiency in the C1-inhibitor protein is characterized by its lack of response to therapies including antihistamine, steroids, and epinephrine. In the case of laryngeal edema, mortality rate is approximately 30 percent. The first case of the acquired form of angioedema related to a deficiency in C1-inhibitor was published in 1972. In our paper, we present a case of an acquired form of angioedema of the oropharyngeal region secondary to the simultaneous occurrence of two causative factors: neutralization of C1-inhibitor by an autoantibody and the use of an angiotensin convertin enzyme inhibitor.
Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette
Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor...... concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema...
Farkas, H; Martinez-Saguer, I; Bork, K
BACKGROUND: The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagn...
Bygum, Anette; Andersen, Klaus Ejner; Mikkelsen, Carsten Sauer
Hereditary angioedema (HAE) is often debilitating with a serious effect on quality of life (QOL). Treatment of acute HAE attacks is usually with C1 esterase inhibitor (C1-INH) concentrates; however, treatment can be delayed by patients' travel time for attending emergency units. We assessed...
de Lange, Jan; de Ruiter, M.H.T.; Smeele, L. E.
Abstract An 80-year-old woman who was medically compromised had recurrent diffuse unilateral swelling of the tongue and the floor of the mouth. The clinical working diagnosis of angioedema as a result of the use of ACE-inhibitors (lisinopril) was made. In consultation with the cardiologist in charge
Wadelius, M.; Marshall, S. E.; Islander, G.; Nordang, L.; Karawajczyk, M.; Yue, Q.-Y.; Terreehorst, I.; Baranova, E. V.; Hugosson, S.; Sköldefors, K.; Pirmohamed, M.; Maitland-van der Zee, A.-H.; Alfirevic, A.; Hallberg, P.; Palmer, C. N. A.
Angioedema is a potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. To study the genetic etiology of this rare adverse event, international consortia and multicenter recruitment of patients are needed. To reduce patient
Vilson Furlanetto Junior
Full Text Available O angioedema adquirido é causado por diferentes medicamentos e doenças linfoproliferativas, e tem sido raramente relacionado com a presença de doenças autoimunes. Descrevemos aqui uma paciente de 47 anos com lúpus eritematoso sistêmico (LES com envolvimento cutâneo importante que desenvolveu angioedema recorrente localizado em face incluindo lábios e pálpebras, membros superiores e tórax, não acompanhado de urticária e com dosagem do inibidor de C1 esterase reduzida. A utilização de antimaláricos, glicocorticoides e pulsoterapia com metilprednisolona associada ao uso de azatioprina não determinou melhora. A paciente utilizou também danazol sem sucesso, e apresentou resposta clínica somente após ter sido submetida a múltiplas sessões de plasmaferese, ocorrendo inclusive resolução de extenso angioedema na mucosa do trato gastrointestinal.Acquired angioedema is caused by different drugs and lymphoproliferative diseases, and rarely it has also been related to the presence of auto-immune disorders. We report the case of a 47 year old female with systemic lupus erythematosus (SLE and severe cutaneous involvement who developed recurrent localized angioedema of the face, including lips and eye lids, upper limbs, and thorax, not associated with urticaria, and with reduced levels of C1 esterase inhibitor. Treatment with antimalarials, glucocorticoids, and pulse therapy with methylprednisolone associated with azathioprine did not improve her condition. The patient was also unsuccessfully treated with danazol, and she only showed clinical response after several sessions of plasmapheresis, including resolution of the extensive edema of the gastrointestinal tract.
Tarbox, James A; Gutta, Ravi C; Radojicic, Cristine; Lang, David M
Laboratory tests are routinely ordered to identify or rule out a cause in patients with chronic urticaria/angioedema (CUA). The results of these tests are usually within normal limits or unremarkable. To investigate the proportion of abnormal test results in patients with CUA leading to a change in management and in outcomes of care. Retrospective analysis of a random sample of adult patients with CUA from 2001-2009. Cases totaled 356: 166 with urticaria and angioedema (AE), 187 with urticaria, and 3 with only AE. Patients were predominately women (69.1%) and white (75.6%), with a mean age of 48 ± 15 years. Abnormalities were commonly seen in complete blood counts (34%) and in complete metabolic panels (9.4%). Among the 1,872 tests that were ordered, results of 319 (17%) were abnormal. Of 356 patients, 30 underwent further testing because of abnormalities in laboratory work. This represented 30 of 1,872 tests (1.60%). Only 1 patient benefited from a subsequent change in management. Laboratory testing in CUA patients referred for an Allergy and Immunology evaluation rarely lead to changes in management resulting in improved outcomes of care. Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Deroux, Alban; Vilgrain, Isabelle; Dumestre-Pérard, Chantal; Boccon-Gibod, Isabelle; Bouillet, Laurence
Bradykinin-mediated angioedema (AE) is a rare disease characterised by recurrent angioedema linked to acquired (e.g. angiotensin converting enzyme inhibitor induced AE) or hereditary disorders (e.g. AE type I or II). As the clinical picture can be misleading, diagnosis of this disease is sometimes difficult. A bradykinin-mediated AE attack may be a therapeutic emergency which requires access to effective, but expensive, treatments. Their prescription must therefore be justified. No specific marker of acute bradykinin-mediated AE attacks has yet been identified to facilitate the therapeutic decision but it has been sought in many studies. This article reviews the literature on this type of biomarker, comparing candidate bradykinin-mediated AE markers to candidate markers of mast cell activation. The most interesting biomarkers are those linked to endothelial stress (VE cadherin, E-selectin, endothelin-1, von Willebrand factor and its activity) which is significantly increased during an AE attack. All these markers must now be validated by prospective studies to determine their specificity and utility in diagnosis.
Salehi, Nooshin; Choi, Eric D; Garrison, Roger C
BACKGROUND Miller Fisher Syndrome is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia, and is considered to be a variant of Guillain-Barre Syndrome. Miller Fisher Syndrome is observed in approximately 1-5% of all Guillain-Barre cases in Western countries. Patients with Miller Fisher Syndrome usually have good recovery without residual deficits. Venous thromboembolism is a common complication of Guillain-Barre Syndrome and has also been reported in Miller Fisher Syndrome, but it has generally been reported in the presence of at least one prothrombotic risk factor such as immobility. A direct correlation between venous thromboembolism and Miller Fisher Syndrome or Guillain-Barre Syndrome has not been previously described. CASE REPORT We report the case of a 32-year-old Hispanic male who presented with acute, severe thromboembolic disease and concurrently demonstrated characteristic clinical features of Miller Fisher Syndrome including ophthalmoplegia, ataxia, and areflexia. Past medical and family history were negative for thromboembolic disease, and subsequent hypercoagulability workup was unremarkable. During the course of hospitalization, the patient also developed angioedema. CONCLUSIONS We describe a possible association between Miller Fisher Syndrome, thromboembolic disease, and angioedema.
Full Text Available Henriette Farkas, Lilian Varga3rd Department of Internal Medicine, Semmelweis University, Budapest, HungaryAbstract: Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor protein is a rare disease, characterized by paroxysms of edema formation in the subcutis and in the submucosa. Edema can cause obstruction of the upper airway, which may lead to suffocation. Prompt elimination of edema is necessary to save patients from this life-threatening condition. Essentially, these edematous attacks are related to the activation of the kinin-kallikrein system and the consequent release of bradykinin. Ecallantide (known as DX-88 previously, a potent and specific inhibitor of plasma kallikrein is an innovative medicinal product. This is the only agent approved recently by the FDA for all localizations of edematous HAE attacks. Its advantages include no risk of viral contamination, high selectivity, very rapid onset of action, good tolerability, and straightforward subcutaneous administration. Owing to the risk of anaphylaxis, ecallantide should be administered by a health care professional. A postmarketing survey to improve risk-assessment and risk-minimization has been launched. The results of these studies may lead to the approval of ecallantide for self-administration.Keywords: hereditary angioedema, C1-inhibitor deficiency, treatment, bradykinin, kallikrein inhibitor, subcutaneous administration
Mayorga, Álvaro José; Ayestas-Moreno, Gerardo José
Hereditary angioedema is a disease which manifests itself with episodes of spontaneous edema on skin, mucosal and airway. Treatment includes acute and prophylactic approach to minimize the attacks and severity. In many parts of the world, androgen derivatives, antifibrinolytic and fresh frozen plasma are the therapies available for prophylaxis. 16 years old teenager of without history of immune decease, has in the course of 1-year repetitive episodes of painless, non-pruritic angioedema, does not respond to antihistamine therapy, corticosteroids or adrenaline; fresh frozen plasma is applied in 1 occasion exacerbating episode with severity. The diagnosis is delayed because of the unavailability of the study in the country, so it is shipped abroad confirming the deficit of C1 Inhibitor (7.1 μg/mL). Initiating prophylactic therapy with Danazol, with subsequent episodes decreased. The delay diagnosis involves considerable risk in these patients; the importance of long-term prophylactic treatment is ratified in the use of androgens, being as an available option in developing countries.
Win, Thet Su Zin; Chaiyakunapruk, Nathorn; Suwankesawong, Wimon; Dilokthornsakul, Piyameth; Nathisuwan, Surakit
Renin-angiotensin-aldosterone system (RAS) blockers are commonly used for cardiovascular diseases. Currently, little information exists for the Asian population on angioedema, a rare yet serious adverse event. This study aimed to describe characteristics of RAS blockers-associated angioedema (RASBA) in Thai patients. A retrospective study using the national pharmacovigilance database of Thailand was undertaken. Cases indicating the presence of angioedema with RAS blockers uses from 1984-2011 were identified. Patient demographics, co-morbidities, concomitant drugs, information for the RAS blockers and angioedema were obtained as well as causality assessment and quality of reports. A total of 895 cases were identified. Mean age was 59.9+12.8 years and 66.5% being female. Most angioedema events (48.6%) occurred during the first week of treatment. Angiotensin converting enzyme inhibitors (87.7%) were the most commonly implicated agents followed by angiotensin receptor blockers (10.5%), aldosterone antagonist (2.1%) and direct renin inhibitor (0.2%). Out of the 895 cases incorporated in this study, 165 (18.4%) were classified as serious events and resulted in hospitalization. The overall case fatality rate was 0.4%. Respiratory disturbance occurred in 46 cases (5.1%). Patients with respiratory complications tended to be younger (53.4+13.9 vs 60.3+12.7 years old; p=0.002) and with higher frequency of allergy history (26.1% vs 14.7%; p=0.032) compared to those without respiratory complications. Based on multivariate logistic regression, the adjusted OR for history of allergy was 2.23 (95%CI: 1.04 - 4.78, p = 0.041). RASBA in Thai population occurred mostly in elderly female patients and often led to hospitalization. Since large number of patients is regularly exposed to RAS-blockers, a nationwide attempt to raise awareness of clinicians when prescribing RAS-blockers is prudent.
Diego S. Fernández Romero
Full Text Available El angioedema hereditario (AEH es una enfermedad rara, autosómica dominante, caracterizada por episodios de angioedema que comprometen la piel, el tracto gastrointestinal y la laringe. Analizamos las características epidemiológicas y clínicas en una serie de 58 pacientes, 53 (91% con diagnóstico de AEH tipo I y 5 (9% con tipo II. La edad media al inicio fue de 10.8 ± 9.5 años (0.1 a 59 y de 25.8 ± 16.2 años (2 a 77 en el momento del diagnóstico, con un retraso diagnóstico de 15.3 ± 14.3 años. El promedio de ataques en los 6 meses previos a la consulta fue de 7.4 ± 7.6 (0 a 40. Cincuenta y cuatro (93% presentaron ataques cutáneos, 50 (86% abdominales, 24 (41% laríngeos y 24 (41% cutáneos y abdominales combinados. Veintisiete (46.5% nunca utilizaron medicación preventiva para la enfermedad y 17 (29% recibieron danazol en diferentes dosis por diferentes periodos de tiempo. Durante los ataques, 15 (26% pacientes recibieron C1 inhibidor endovenoso alguna vez, 7 (12% recibieron plasma fresco y 40 (69% tratamiento sintomático. Ansiedad o situaciones de estrés y traumatismos fueron los desencadenantes más frecuentes. Identificamos a 6 (10% pacientes como primera mutación y a 52 (90% con historia familiar previa. Analizamos 20 troncos familiares identificando 205 individuos en riesgo de heredar la enfermedad, 109 (53% de ellos con síntomas o diagnóstico AEH. El total de individuos con síntomas de AEH fue de 145, de los cuales 19 (13% murieron por asfixia. Disminuir el retraso diagnóstico y ofrecer una terapéutica adecuada son desafíos a afrontar en el AEH.Hereditary angioedema (HAE is a rare autosomal dominant disease, characterized by episodes of edema typically involving the skin, gastrointestinal tract and larynx. We here describe the epidemiologic and clinical characteristic of a series of 58 patients with diagnosis of HAE, 53 (91% type I and 5 (9% type II. The mean age at first symptom was 10.8 ± 9.5 years and the mean
Full Text Available A 50-year-old man was admitted to our emergency department due to new episode of palpitation. He had history of angioplasty of right coronary artery (RCA with drug eluting stent 2 years ago. His electrocardiogram revealed atrial fibrillation (AF. Intravenous amiodarone 150 mg during 10 minutes and then 1 mg/min infusion were started to achieve rate control and pharmacologic conversion to sinus rhythm. After 60 minutes of starting amiodarone infusion, he developed swelling of the skin around his mouth and eyes, and also mucosa of the mouth, eyes and tongue. To conclude, angioedema should be considered a rare side effect of amiodarone which is used broadly in cardiovascular field.
Kelly W Burak
Full Text Available A case of C1 inhibitor deficiency presenting as localized edema of the small intestine is described. A 16-year-old, previously healthy woman presented with recurrent attacks of abdominal pain and vomiting following minor abdominal trauma. Investigations including computed tomography scan and barium studies confirmed localized edema of the jejunum. At laparoscopy, Crohn’s disease was suspected; however, a subsequent enteroscopy was normal. Complement levels revealed a low C4 level, and C1 inhibitor deficiency was later confirmed. Attacks of abdominal pain began after starting oral contraceptives and have not returned since stopping the birth control pill. This rare cause of abdominal pain is examined, and C1 inhibitor deficiency and angioedema are reviewed.
Aberer, Werner; Maurer, Marcus; Bouillet, Laurence
BACKGROUND: Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long......-term prophylaxis (LTP), breakthrough attacks are known to occur. We used data from the Icatibant Outcome Survey (IOS) to evaluate the characteristics of breakthrough attacks and the effectiveness of icatibant as a treatment option. METHODS: Data on LTP use, attacks, and treatments were recorded. Attack...... characteristics, treatment characteristics, and outcomes (time to treatment, time to resolution, and duration of attack) were compared for attacks that occurred with versus without LTP. RESULTS: Data on 3228 icatibant-treated attacks from 448 patients with C1-INH-HAE were analyzed; 30.1% of attacks occurred while...
Kessel, Aharon; Farkas, Henriette; Kivity, Shmuel; Veszeli, Nóra; Kőhalmi, Kinga V; Engel-Yeger, Batya
The severe life-threatening characteristics of hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) can affect anxiety levels among pediatric patients. This emotional burden together with the physical restrictions of C1-INH-HAE may decrease children's health-related quality of life (HRQoL). (i) To compare anxiety state and trait between children with C1-INH-HAE and healthy controls; (ii) to examine the relationship between the level of anxiety of children with C1-INH-HAE, their disease activity/affected sites and their HRQoL; and (iii) to predict the HRQoL of children with C1-INH-HAE based on their anxiety level and disease activity/affected sites METHODS: Thirty-three children with C1-INH-HAE (aged 5-18 years) and 52 healthy controls were recruited from Israel and Hungary. All children completed the State-Trait Anxiety Inventory for Children (STAIC), the Pediatric Quality of Life Inventory (Peds-QL) demographic questionnaire and a disease activity and site questionnaire . Disease activity was defined as the number of attacks in last year. Both anxiety state and trait were significantly higher among children with C1-INH-HAE as compared to the controls (44.74±10.56 vs 38.76±10.67, Panxiety state (F 56,2 =4.69, P=.001) and trait (F 56,2 =9.06, Panxiety trait was correlated with the number of angioedema-affected sites (r=.52, P=.003). The presence of HAE attacks and higher anxiety trait predicted a lower HRQoL in children with C1-INH-HAE. C1-INH-HAE children have higher anxiety trait and state, which correlate with reduced HRQoL domains. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Farkas, H.; Martinez?Saguer, I.; Bork, K.; Bowen, T.; Craig, T.; Frank, M.; Germenis, A. E.; Grumach, A. S.; Luczay, A.; Varga, L.; Zanichelli, A.; Aberer, Werner; Andrejevic, Sladjana; Aygoeren?P?rs?n, Emel; Banerji, Alena
BACKGROUND: The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1-INH-HAE.METHODS: During an expert panel meeting that took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015 (www.haenet.hu), ped...
Doña, I; Blanca-López, N; Torres, M J; Gómez, F; Fernández, J; Zambonino, M A; Monteseirín, F J; Canto, G; Blanca, M; Cornejo-García, J A
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent medicaments involved in drug hypersensitivity reactions, with NSAID-induced urticaria/angioedema (NIUA) being the most frequent clinical entity. The natural evolution of NIUA has been suggested to lead to chronic urticaria (CU) in an important proportion of patients, such that NIUA may therefore precede CU. Our aim was to verify whether these entities are related by following up a large cohort of patients with NIUA as well as a control group over a long period of time. The study comprised three groups: (i) patients with a confirmed history of NIUA (more than two episodes with at least two different NSAIDs or positive drug provocation tests), (ii) patients with more than two episodes of urticaria/angioedema to a single NSAID with good tolerance to a strong COX-1 inhibitor and/or evidence by in vivo tests supporting specific IgE antibodies to the drug (single NSAID-induced urticaria/angioedema, SNIUA), and (iii) controls who tolerated NSAIDs. All cases in the three groups were followed up over a period of 12 years. There were 190 patients with NIUA (64.6% female; mean age 43.71 ± 15.82 years, 110 with SNIUA, and 152 controls. At the 12-year evaluation, 12 patients with NIUA (6.15%) had developed CU over a 1- to 8-year period. Similar proportions were seen in SNIUA and controls. Nonsteroidal anti-inflammatory drugs-induced urticaria/angioedema does not seem to precede the onset of CU over the medium term. Further research including a longer follow-up is necessary to verify this observation. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Faisant, Charles; Armengol, Guillaume; Bouillet, Laurence; Boccon-Gibod, Isabelle; Villier, Céline; Lévesque, Hervé; Cottin, Judith; Massy, Nathalie; Benhamou, Ygal
Bradykinin-mediated angioedema (AE) is a rare side effect of some medications, including angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). In France, side-effects to treatments are reported to the national pharmacovigilance database. The national MedDRA database was searched using the term "angioedema". Patients were included if they met the clinical criteria corresponding to bradykinin-mediated AE, if their C1-inhibitor levels were normal, and if they were treated with an ACEi or an ARB. 7998 cases of AE were reported between 1994 and 2013. Among these, 112 met the criteria for bradykinin-mediated AE with normal C1-inhibitor levels. On the 112 drug-AE, patients were treated with an ARB in 21% of cases (24 patients), or an ACEi in 77% of cases (88 patients), in combination with another treatment in 17 cases (mTORi for 3 patients, iDPP-4 for 1 patient, hormonal treatment for 7 patients). ENT involvement was reported in 90% of cases (tongue: 48.2%, larynx: 23.2%). The median duration of treatment before the first attack was 720 days, and the mean duration of attacks was 36.6 h. Forty-one percent (19/46) of patients relapsed after discontinuing treatment. Angioedema triggered by medication blocking the renin/angiotensin system is rare but potentially severe, with a high risk of recurrence despite cessation of the causative drug.
Full Text Available Acquired angioedema due to C1 inhibitor deficiency (C1INH-AAE is a rare and potentially fatal syndrome of bradykinin-mediated angioedema characterized by episodes of angioedema without urticaria. It typically manifests with nonpitting edema of the skin and edema in the gastrointestinal (GI tract mucosa or upper airway. Edema of the upper airway and tongue may lead to life-threatening asphyxiation. C1INH-AAE is typically under-diagnosed because of its rarity and its propensity to mimic more common abdominal conditions and allergic reactions. In this article, we present the case of a 62-year-old male with a history of recently diagnosed chronic lymphocytic leukemia (CLL who presented to our hospital with recurrent abdominal pain, initially suspected to have Clostridium difficile colitis and diverticulitis. He received a final diagnosis of acquired angioedema due to C1 esterase inhibitor deficiency due to concomitant symptoms of lip swelling, cutaneous nonpitting edema of his lower extremities, and complement level deficiencies. He received acute treatment with C1 esterase replacement and icatibant and was maintained on C1 esterase infusions. He also underwent chemotherapy for his underlying CLL and did not experience further recurrence of his angioedema.
Kowalski, Marek L; Woessner, Katharine; Sanak, Marek
Nonsteroidal anti-inflammatory drug (NSAID)-induced urticarial and angioedema reactions are among the most commonly encountered drug hypersensitivity reactions in clinical practice. Three major clinical phenotypes of NSAID-induced acute skin reactions manifesting with angioedema, urticaria, or both have been distinguished: NSAID-exacerbated cutaneous disease, nonsteroidal anti-inflammatory drug-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria and angioedema. In some patients clinical history alone might be sufficient to establish the diagnosis of a specific type of NSAID hypersensitivity, whereas in other cases oral provocation challenges are necessary to confirm the diagnosis. Moreover, classification of the type of cutaneous reaction is critical for proper management. For example, in patients with single NSAID-induced reactions, chemically nonrelated COX-1 inhibitors can be safely used. However, there is cross-reactivity between the NSAIDs in patients with NSAID-exacerbated cutaneous disease and NIUA, and thus only use of selective COX-2 inhibitors can replace the culprit drug if the chronic treatment is necessary, although aspirin desensitization will allow for chronic treatment with NSAIDs in some patients with NIUA. In this review we present a practical clinical approach to the patient with NSAID-induced urticaria and angioedema. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Gunatilake, Sonali Sihindi Chapa; Wimalaratna, Harith
Acquired angioedema is a rare but recognized manifestation of lymphoproliferative disorders due to deficiency in C1 esterase inhibitor. Normal level of C1 esterase inhibitor proteins in association with angioedema due to lymphoproliferative disease is a rare and an uncommon finding caused by antibodies produced from the underlying disease. Antibodies cause inactivation of C1 esterase inhibitor, thus resulting in C1 esterase inhibitor dysfunction despite of normal quantity of C1 esterase inhibitor. A 50-year-old Sri Lankan male presented with first episode of angioedema without any family history. Physical examination revealed mild pallor with swelling of tongue, lips and perioral region. On investigations, erythrocyte sedimentation rate was persistently high and bone marrow with immunohistochemistry revealed infiltration with B-cell type low grade non-Hodgkin lymphoma. Computed tomography scan of the chest and abdomen showed paratracheal and subcarinal lymphadenopathy and splenomegaly, with the findings being compatible with lymphoma. He had normal C1 esterase inhibitor protein level with reduced activity and low C1q, C4 levels indicating antibodies against C1 esterase inhibitor causing dysfunctional C1 esterase inhibitor. Adult onset angioedema should prompt physicians to suspect underlying lymphoproliferative disorder despite of C1 esterase inhibitor protein level being normal. Though uncommon, presence of antibodies against C1 esterase inhibitor secondary to lymphoproliferative disorder should be considered in the presence of normal C1 esterase inhibitor protein levels with low functional capacity in the background of acquired angioedema.
Wang, Y-X; Li, Y-Q; Chen, Y; Zhang, C-H; Dong, Z; Wang, Z; Zhao, S-N; Li, C-H; Zhang, P-L
Orolingual angioedema (OA) is a rare clinical complication with a potentially fatal risk that occurs after the intravenous application of alteplase (rt-PA) in patients with acute ischemic stroke. The purpose of this work is to investigate the related factors of OA in patients with acute ischemic stroke after the administration of intravenous thrombolytic therapy, to improve the predictive ability of OA during intravenous thrombolytic therapy, and to reduce the prevalence of complications. We recruited 1223 cases of patients with acute ischemic stroke that were treated in the Department of Neurology No. 4 of the Tianjin Huanhu Hospital from June 2014 to April 2015. The clinical manifestations of rt-PA related OA were recorded, the clinical prevalence was counted, related factors of OA after intravenous thrombolytic therapy were analyzed, and the risk assessment of rt-PA related OA was conducted. 14 cases of patients developed OA, with a prevalence rate of 1.14%. Among them, 5 had a history of urticaria, 4 of drug allergy, and 3 of food allergy. Among the 14 cases of patients, 10 developed OA in the process of intravenous thrombolysis and 4 after intravenous thrombolysis, 12 showed lip edema, 9 showed extensive swelling of tongue, 3 showed swelling of lateral tongue, 3 were complicated by respiratory distress, 10 showed infarction in the middle cerebral artery territory, and 6 had previously been given oral ACEI drugs. Orolingual angioedema is a rare complication that occurs after rt-PA intravenous thrombolytic therapy; when serious, it may endanger a patient's life. If patients take an oral hypotension such as ACEI drugs before the onset of OA, they have a history of allergies, or the lesion is an infraction in the dominated area of the middle cerebral artery, the risk of OA after rt-PA intravenous thrombolytic therapy will be increased. The prevalence of OA should be monitored during the rt-PA intravenous thrombolytic therapy process; timely detection and early
Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Boysen, Henrik B; Caballero, Teresa
To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a condition on a patient's life; a score of 0.0 reflects death and 1.0 reflects full health. The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D) domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks. Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation of EQ-5D-based utilities. The mean utilities for an HAE attack and between attacks were 0.44 and 0.72, respectively. Utilities for an acute attack were dependent on the severity of pain of the last attack (0.61 for no pain or mild pain, 0.47 for moderate pain, and 0.08 for severe pain). There were no significant differences across countries. Mean utilities derived from the study approach compare sensibly with other disease states for both acute attacks and between attacks. The impacts of HAE translate into substantial health status disutilities associated with acute attacks as well as between attacks, documenting that the detrimental effects of HAE are meaningful from the patient perspective. Results were consistent across countries with regard to pain severity and in comparison to similar disease states. The results can be used to raise awareness of HAE as a serious disease with wide-ranging personal and social impacts.
Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Boysen, Henrik B; Caballero, Teresa
Objective To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a condition on a patient’s life; a score of 0.0 reflects death and 1.0 reflects full health. Study design and methods The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D) domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks. Results Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation of EQ-5D-based utilities. The mean utilities for an HAE attack and between attacks were 0.44 and 0.72, respectively. Utilities for an acute attack were dependent on the severity of pain of the last attack (0.61 for no pain or mild pain, 0.47 for moderate pain, and 0.08 for severe pain). There were no significant differences across countries. Mean utilities derived from the study approach compare sensibly with other disease states for both acute attacks and between attacks. Conclusion The impacts of HAE translate into substantial health status disutilities associated with acute attacks as well as between attacks, documenting that the detrimental effects of HAE are meaningful from the patient perspective. Results were consistent across countries with regard to pain severity and in comparison to similar disease states. The results can be used to raise awareness of HAE as a serious disease with wide
Kupryś-Lipińska, Izabela; Korczyńska, Paulina; Tworek, Damian; Kuna, Piotr
Omalizumab is a monoclonal antibody against IgE, nowadays approved for the treatment of persistent severe (EU) or moderate-to severe (USA) IgE-mediated asthma but there is also some evidence (case reports and four published clinical trials) on the effectiveness of this medication in urticaria and angioedema. The case of a 42-year-old woman suffering from severe allergic asthma and severe chronic urticaria with concomitant angioedema is presented in the article. She had a life-threatening episode of bronchospasm and larynx edema after exposure to house dust recorded in her medical history. The patient did not respond to standard therapy. The improvement in asthma control and remission of chronic urticaria and angioedema was achieved after introducing the therapy with omalizumab.
Caballero, Teresa; Farkas, Henriette; Bouillet, Laurence
BACKGROUND: There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH). OBJECTIVE: We sought to elaborate guidelines for optimizing the management of gynecologic/obstetri......BACKGROUND: There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH). OBJECTIVE: We sought to elaborate guidelines for optimizing the management of gynecologic...... section. Regional anesthesia is preferred to endotracheal intubation. Breast cancer: Attenuated androgens should be avoided. Antiestrogens can worsen angioedema symptoms. In these cases anastrozole might be an alternative. Other issues addressed include special features of HAE-C1-INH treatment in female...
Full Text Available Contrast induced angioedema is a rapidly progressive state involving a number of organ systems including the upper airway tract; which is usually a type I anaphylactic reaction also known as immediate hypersensitivity reaction. Prompt preservation of the respiratory tract is the cornerstone of this situation. The use of fiberoptic bronchoscope for tracheal intubation though very helpful, has some special considerations due to the anatomic distortions created by edema.This manuscript describes a patient with contrast induced angioedema managed successfully. Serum levels of IgE were highly increased during the first hours after the event; while serum levels of complement were normal. However, rapid airway management and prophylactic intubation saved the patient and prevented the possible aftermath of airway obstruction.Keywords: airway management; type I anaphylactic reaction, angioedema; fiberoptic bronchoscope.Conflict of interest: none of the authors has any conflict of interest.
Gou, Kun; Pence, Thomas J
Angioedema is a tissue-swelling pathology due to rapid change in soft tissue fluid content. Its occurrence in the trachea is predominantly localized to the soft mucous tissue that forms the innermost tracheal layer. The biomechanical consequences, such as airway constriction, are dependent upon the ensuing mechanical interactions between all of the various tissues that comprise the tracheal tube. We model the stress interactions by treating the trachea organ as a three-tissue system consisting of swellable mucous in conjunction with nonswelling cartilage and nonswelling trachealis musculature. Hyperelastic constitutive modeling is used by generalizing the standard anisotropic, incompressible soft tissue framework to incorporate the swelling effect. Finite element stress analysis then proceeds with swelling of the mucous layer providing the driving factor for the mechanical analysis. The amount of airway constriction is governed by the mechanical interaction between the three predominant tissue types. The detailed stress analysis indicates the presence of stress concentrations near the various tissue junctions. Because of the tissue's nonlinear mechanical behavior, this can lead to material stiffness fluctuations as a function of location on the trachea. Patient specific modeling is presented. The role of the modeling in the interpretation of diagnostic procedures and the assessment of therapies is discussed. Copyright © 2017 John Wiley & Sons, Ltd.
Boccon-Gibod, I; Bouillet, L
We evaluated the efficacy and safety of icatibant self-administration in 15 patients with hereditary angioedema (HAE) types I or III, for 55 acute attacks (mostly severe or very severe). Icatibant self-administration was generally effective: first symptom improvement occurred in 5 min–2 h (HAE type I; n = 17) and 8 min–1 h (HAE type III; n = 9) for abdominal attacks and 5–30 min (HAE type I; n = 4) and 10 min–12 h (HAE type III; n = 6) for laryngeal attacks. Complete symptom resolution occurred in 15 min–19 h (HAE type I; n = 8) and 15 min–48 h (HAE type III; n = 9) for abdominal attacks and 5–48 h (HAE type I; n = 3) and 8–48 h (HAE type III; n = 5) for laryngeal attacks. No patient required emergency hospitalization. The only adverse events were mild, spontaneously resolving injection site reactions. Patients reported that carrying icatibant with them gave them greater confidence in managing their condition. PMID:22519593
Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M.; Drouet, Christian; Braley, Hal; Nolte, Marc W.; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas
Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. PMID:26193639
Full Text Available Hereditary angioedema (HAE is a rare autosomal dominant disorder caused by mutations of the SERPING1 or the Factor 12 genes. It is potentially fatal, particularly if not identified at an early stage. Apart from androgens, which are contraindicated in children and in pregnant women, a range of effective, albeit very expensive treatments have recently become available for HAE patients. The cost of these new treatments is beyond the reach of most developing countries. At this time, there is no cure for the disorder. In spite of mutations of the SERPING1 gene, autoimmunity and infections are not prominent features of the condition. Here we present the argument that HAE should be viewed primarily as a metabolic liver disorder. This conceptual paradigm shift will stimulate basic research and may facilitate new therapeutic approaches to HAE outlined in this paper. We suggest several novel potential treatment options for HAE from the perspectives of clinical immunology, molecular biology and liver transplantation. Many of these offer the prospect of curing the disorder. The effectiveness of these options are rapidly improving in many cases and their risks are decreasing. Given the very high costs of treating HAE, some of these curative options may become feasible in the next decade.
Teranishi, Rie; Makino, Yumi; Amano, Eizou; Shibuya, Hiromi; Okada, Toshiki
Hereditary angioedema (HAE) is a very rare disease that occurs in about 1 in 50,000 to 150,000 people. HAE is caused by low levels or inproper function of the plasma protein C1 inhibitor (C1-INH) which regulates activation of the complement system and the coagulation system. The typical symptom of HAE is regional swellings without pain nor itching, usually triggered by physical trauma or emotional stress. Unlike allergic edema, HAE attacks do not respond to antihistamines, corticosteroids noradrenaline. The swelling attacks against face and throat are potentially life-threatening, and should be treated as a medical emergency. We report a patient with HAE who underwent radical cystectomy of the upper gum under general anesthesia. Because the oral surgery with tracheal intubation is known to be a risk factor of laryngeal edema in a patient with HAE, she was given C1-INH before operation to prevent laryngeal edema according to HAE Guideline 2010 by the Japanese Association for Complement Research. Her pharynx and larynx were checked with Airwayscope before intubation and with bronchofiberscope before extubation, but no edema was recognized. Postoperatively, she was given C1-INH on the next morning again. She was discharged seven days after operation without any complications.
Nordenfelt, Patrik; Nilsson, Mats; Lindfors, Anders; Wahlgren, Carl-Fredrik; Björkander, Janne
Health-related quality of life (HR-QoL) is impaired in patients with hereditary angioedema (HAE) but has not yet been satisfactorily described. To study HR-QoL in patients with HAE by combining different HR-QoL instruments with disease activity assessment. All adults in the Swedish HAE registry were invited to take part in this questionnaire study, which used the generic HR-QoL instruments, EuroQol 5 Dimensions 5 Level (EQ-5D-5L) and the RAND Corporation Short Form 36 (RAND-36), the disease-specific Angioedema Quality of Life instrument (AE-QoL), the recently introduced Angioedema Activity Score (AAS) form, and questionnaires on sick leave and prophylactic medication. Sixty-four of 133 adults (26 men, 38 women) between 18 and 91 years old responded. The most affected HR-QoL dimensions in the EQ-5D-5L were pain/discomfort and anxiety/depression; in the RAND-36, energy/fatigue, general health, pain; and, in the AE-QoL, fears/shame and fatigue/mood. Women had lower HR-QoL in the RAND-36 for general health and energy/fatigue (p 0 had significantly impaired HR-QoL. There were significant associations (p depression, and fatigue/mood are important aspects of HAE but the AE-QoL disregards pain. HR-QoL was not significantly affected by prophylaxis. Increased disease activity was associated with impaired HR-QoL, which justifies more active disease management.
Bonner, Nicola; Panter, Charlotte; Kimura, Alan; Sinert, Rich; Moellman, Joseph; Bernstein, Jonathan A
The use of angiotensin-converting enzyme inhibitors (ACEI) has been associated with the development of bradykinin-mediated angioedema. With ever-widening indications for ACEI in diseases including hypertension, congestive heart failure and diabetic nephropathy, a concomitant increase in ACEI-Angioedema (ACEI-A) has been reported. At present there is no validated severity scoring or discharge criteria for ACEI-A. We sought to develop and validate an investigator rating scale with corresponding discharge criteria using clinicians experienced in treating ACEI-A. In-depth, 60-min qualitative telephone interviews were conducted with 12 US-based emergency physicians. Beforehand, clinicians were sent four case studies describing patients experiencing different severities of angioedema attacks. Clinicians were initially asked open-ended questions about their experience of patients' symptoms, treatment and discharge decisions. Clinicians then rated each patient case study and discussed patient diagnoses, ratings of symptom severity and discharge evaluation. The ratings were used to assess inter-rater reliability of the scale using the intra-class correlation coefficient (ICC) using IBM SPSS analysis Version 19 software. The findings provide support focusing on four key symptoms of airway compromise scored on a 0-4 scale: 1) Difficulty Breathing, 2) Difficulty Swallowing, 3) Voice Changes and 4) Tongue Swelling and the corresponding discharge criteria of a score of 0 or 'No symptoms' for Difficulty Breathing and Difficulty Swallowing and a score of 0 or 1 indicating mild or absence of symptoms for Voice Change and Tongue Swelling. Eleven clinicians agreed the absence of standardized discharge criteria supported the use of this scale. All physicians concurred with the recommended discharge criteria. The clinician ratings provided evidence of strong inter-rater reliability for the rating scale (ICC > 0.80). The investigator rating scale and discharge criteria are
Boccon‐Gibod, Isabelle; Launay, David; Gompel, Anne; Kanny, Gisele; Fabien, Vincent; Fain, Oliver
Abstract Introduction The clinical characteristics and icatibant‐treatment outcomes of patients with hereditary angioedema with normal C1 inhibitor (HAE‐nC1 INH) are limited. Methods We retrospectively analyzed data from French HAE patients enrolled in the Icatibant Outcome Survey registry (from July 2009 to September 2013) to compare disease characteristics and the effectiveness and safety of acute icatibant‐treated angioedema attacks in patients with HAE‐nC1 INH, HAE with C1 INH deficiency (type I), or dysfunction (type II). Results One center in Grenoble contributed 22 patients with HAE‐nC1 INH and a family history of HAE while 15 centers across France contributed 153 patients with HAE type I and seven patients with HAE type II. Patients with HAE‐nC1 INH compared to HAE type I, respectively, were more likely to be female (88.1% vs. 63.4%), older at median age of disease onset (21 years vs. 15 years), and have a greater rate of abdominal (80% vs. 61%) and laryngeal (23% vs. 14%) attacks. Icatibant was effective in both groups though the median time to resolution of attack was significantly longer in the HAE‐nC1 INH group (20.0 h, 37 attacks) versus the HAE type I group (14.0 h, 67 attacks). Icatibant was self‐administered for 96.1% of attacks in patients with HAE‐nC1 INH and 75.8% in patients with HAE type I. No serious adverse side effects related to icatibant were reported. Conclusions These data help further define the disease characteristics of HAE‐nC1 INH in the French population and extend the limited data reporting the safe and effective use of icatibant in acute treatment of angioedema in French patients diagnosed with HAE‐nC1 INH. PMID:28250922
Aygören-Pürsün, Emel; Soteres, Daniel; Moldovan, Dumitru; Christensen, Jim; Van Leerberghe, Arthur; Hao, James; Schranz, Jennifer; Jacobson, Kraig W.; Martinez-Saguer, Inmaculada
Background Hereditary angioedema (HAE) is a rare genetic disease causing unpredictable and potentially life-threatening subcutaneous and submucosal edematous attacks. Cinryze® (Shire ViroPharma Inc., Lexington, MA, USA), a nanofiltered C1 inhibitor (C1-INH), is approved in Europe for the treatment, preprocedure prevention, and routine prophylaxis of HAE attacks, and for the routine prophylaxis of attacks in the USA. This phase 3 study assessed the safety and efficacy of 2 C1-INH doses in preventing attacks in children aged 6–11 years. Methods A randomized single-blind crossover study was initiated in March 2014. Results for the first 6 patients completing the study are reported here. After a 12-week qualifying observation period, patients were randomly assigned to 1 of 2 C1-INH doses, 500 or 1,000 U, every 3–4 days for 12 weeks and crossed over to the alternative dose for a second 12-week period. The primary efficacy endpoint was the number of angioedema attacks per month. Results Six females with HAE type I and a median age of 10.5 years received 2 doses of C1-INH (500 and 1,000 U). The mean (SD) difference in the number of monthly angioedema attacks between the baseline observation period and the treatment period was −1.89 (1.31) with 500 U and −1.89 (1.11) with 1,000 U. During the treatment periods, cumulative attack severity, cumulative daily severity, and the number of attacks needing acute treatment were lower. No serious adverse events or study drug discontinuations occurred. Conclusions Interim findings from this study indicate that routine prevention with intravenous administration of C1-INH is efficacious, safe, and well tolerated in children ≥6 years of age. PMID:28662509
Bloom, Adam S; Schranz, Craig
Angioedema is an infrequent complication of the use of angiotensin-converting enzyme inhibitors (ACEi) that has an incidence of up to 0.5%. The oropharynx is most commonly affected. Angioedema of the small bowel is a much rarer occurrence; it uniformly presents with abdominal pain of variable duration. A 51-year-old man presented to the emergency department (ED) with generalized abdominal pain, emesis, diarrhea, and bloating. Medical history was significant for hypertension and medications included captopril, metoprolol and aspirin. Vital signs and laboratory tests were unremarkable. Due to the presence of significant abdominal tenderness with guarding on examination, a FAST (focused assessment with ultrasound in trauma) examination was performed and revealed free fluid in the abdomen. A computed tomography scan of the abdomen was quickly obtained, which revealed a large amount of simple-appearing free fluid within the abdomen and mucosal edema throughout the small bowel. The patient underwent an emergent diagnostic laparoscopy and was ultimately diagnosed with angioedema of the small bowel, deemed secondary to captopril usage. Captopril was discontinued and symptoms gradually resolved with supportive care. When imaging is obtained in cases such as this one, small bowel submucosal edema and ascites are often present. Supportive care and cessation of ACEi usage are the cornerstones of treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In patients on ACEi, it is important to keep this diagnosis in mind to potentially avoid an unneeded surgical intervention, as the condition is self-limiting and can be treated primarily with supportive measures. Published by Elsevier Inc.
Full Text Available We report a case of acute facial oedema in an elderly hospitalized patient which was initially misdiagnosed as angioedema secondary to antibiotics in a patient with an allergic diathesis. We describe the differential aetiologies and then the true cause of the oedema, which was an uncommon complication of a very common condition in the elderly: a pneumomediastinum with subcutaneous emphysema probably due to rupture of an emphysematous lung bulla during chronic obstructive pulmonary disease (COPD exacerbation. Lastly, we focus on the therapeutic procedures instituted for the treatment of the pneumomediastinum.
Levi, Marcel; Choi, Goda; Picavet, Charles; Hack, C. Erik
BACKGROUND: Administration of C1-inhibitor concentrate is effective for prophylaxis and treatment of severe angioedema attacks caused by C1-inhibitor deficiency. The concentrate should be administered intravenously and hence needs to be administered by health care professionals, which might cause
Alharbi, Fawaz F.; Kholod, Anzhelika A.V.; Souverein, Patrick C.; Meyboom, Ron H.; de Groot, Mark; De Boer, Anthonius; Klungel, Olaf H.
Background: Little is known about the effect of age and gender on reporting of cough/ angioedema with renin angiotensin system (RAS) inhibitors (angiotensin- converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and aliskiren, a direct renin inhibitor (DRI). Objectives: To assess
Hansen, Cecilie Bo; Csuka, Dorottya; Munthe-Fog, Lea
C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP...
Alharbi, Fawaz F; Kholod, Anzhelika A V; Souverein, Patrick C; Meyboom, Ronald H; de Groot, Mark C H; de Boer, Anthonius; Klungel, Olaf H
The purpose of this study was to assess the impact of age and sex on the reporting of cough and angioedema related to renin-angiotensin system (RAS) inhibitors. A case/noncase study was performed in VigiBase. Two case groups were identified, reports of cough and reports of angioedema, and noncases were all reports of all other adverse events. Logistic regression analysis was used to assess the association between reporting of cough and angioedema with each class of RAS inhibitors stratified by age/sex and to control for confounding. The reporting of cough with angiotensin-converting enzyme (ACE) inhibitors was significantly higher in women than in men [adjusted reporting odds ratio (ROR): 44.0, 95% CI (43.2-44.8) for women vs. 29.2, 95% CI (28.5-29.9) for men]. There was no difference in reporting of cough linked to angiotensin receptor blockers (ARBs) and aliskiren between men and women. In contrast, the reporting of angioedema with ACE inhibitors and ARBs was significantly higher in men than in women, but for aliskiren, women had a significantly higher ROR than men [adjusted ROR: 5.20, 95% CI (4.18-6.46) for women vs. 3.04, 95% CI (2.30-4.02) for men]. The reporting of cough with ACE inhibitors was increased with age until reaching a plateau at middle adulthood (40-59 years) and the reporting of angioedema with ACE inhibitors was increased with age until elderly (60-79 years). Age had only a slight effect on the reporting of cough and angioedema with ARBs and aliskiren. Both age and sex have substantial effects on the reporting of cough and angioedema with RAS inhibitors and in particular ACE inhibitors. Further study is needed to determine whether these differences mainly express different adverse drug reaction risks in subgroups or also can be explained by factors influencing reporting. © 2017 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.
Caballero, Teresa; Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Wait, Suzanne; Boysen, Henrik B
Hereditary angioedema (HAE) is a rare but potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The broad range of consequences of HAE on patients' lives is not well understood. The study objective was to comprehensively characterize the burden of illness and impact of HAE types I and II from the patient perspective. The HAE Burden of Illness Study in Europe was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective via a one-time survey, which included items on clinical characteristics and physical and emotional impacts. One hundred eighty-six patients participated; 59% reported having an attack at least once a month, 67% reported moderate-to-severe pain during their last attack, and 74% reported moderate-to-severe swelling. The most common sites of the last attack were the abdomen and extremities; 24% experienced an attack in more than one site. The impact of HAE on daily activities was high during attacks and did not vary significantly by body site affected; patients also reported that HAE impacted their daily activities between attacks. Patients reported substantial anxiety about future attacks, traveling, and passing HAE to their children. Based on Hospital Anxiety and Depression Scale scores, 38 and 14% had clinically meaningful anxiety and depression, respectively. Despite standard of care, HAE patients still have frequent and painful attacks. Patients experience substantial impairment physically and emotionally both during and between attacks. A better understanding of these effects may help in the clinical management of HAE patients.
Full Text Available Abstract Background Hereditary angioedema (HAE is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation. While there have been major advancements in our understanding of the immunogenetics of HAE, there are significant gaps in the literature regarding understanding of the humanistic and economic impact of the disease, particularly in Europe. The purpose of the HAE Burden of Illness Study-Europe (HAE-BOIS-Europe, the development and methodology of which is described here, is to better understand the management and impact of HAE from the patient perspective in Europe. Methods/Design This is a cross-sectional study in which retrospective data were also collected being conducted in Denmark, Germany and Spain. The study is open to patients ages 12 and older with a diagnosis of HAE-I or HAE-II. Data collection includes: (i a survey on individuals’ health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale; and (ii one-on-one interviews to collect detailed descriptive data and patient testimonials on the impact of HAE on patients’ health-related quality of life. Discussion The present manuscript describes the development and plans for implementing a multi-country European study with the aim of characterizing the humanistic and economic burden of HAE from the patient perspective. This study will help raise awareness of HAE as a rare but debilitating condition with wide-ranging impacts.
Bygum, Anette; Aygören-Pürsün, Emel; Caballero, Teresa; Beusterien, Kathleen; Gholizadeh, Shadi; Musingarimi, Patience; Wait, Suzanne; Boysen, Henrik
Hereditary angioedema (HAE) is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation. While there have been major advancements in our understanding of the immunogenetics of HAE, there are significant gaps in the literature regarding understanding of the humanistic and economic impact of the disease, particularly in Europe. The purpose of the HAE Burden of Illness Study-Europe (HAE-BOIS-Europe), the development and methodology of which is described here, is to better understand the management and impact of HAE from the patient perspective in Europe. This is a cross-sectional study in which retrospective data were also collected being conducted in Denmark, Germany and Spain. The study is open to patients ages 12 and older with a diagnosis of HAE-I or HAE-II. Data collection includes: (i) a survey on individuals' health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale); and (ii) one-on-one interviews to collect detailed descriptive data and patient testimonials on the impact of HAE on patients' health-related quality of life. The present manuscript describes the development and plans for implementing a multi-country European study with the aim of characterizing the humanistic and economic burden of HAE from the patient perspective. This study will help raise awareness of HAE as a rare but debilitating condition with wide-ranging impacts.
Wang, Adrian; Fouche, Andrew; Craig, Timothy J
Early therapy of hereditary angioedema (HAE) decreases morbidity, improves outcomes, decreases absenteeism, and possibly decreases mortality. This can be accomplished best with self-therapy. Previously, the authors examined barriers to self-therapy from the perspective of the nurse and the physician, but data are lacking on what patients perceive as major barriers to self-administered therapy for HAE. To identify those barriers in a prospective fashion by patient interview. After approval from the institutional review board, a telephone survey was performed of patients with HAE from a database of patients who were recently seen in the clinic. The survey focused on anxiety, depression, stress, concerns regarding method of administration, the ability to inject themselves, and what they perceived as barriers to providing self-care. Ninety-two patients were contacted and 59 agreed to participate. With 69% of those patients currently undergoing self-administered treatment, the results showed minimal depression and anxiety, a high satisfaction with treatment, and significant compliance with treatment. Most of those not yet on self-administered therapy wanted to start despite being satisfied with the care received in the emergency department. They also believed care at home would be optimal. The main concern of the 2 groups was not being able to treat themselves in the event of an HAE attack. From these data, it is obvious that most patients are willing to self-treat. This suggests that physicians should encourage self-treatment of HAE to improve outcomes and quality of life of patients with HAE. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Hack, C Erik; Relan, Anurag; Baboeram, Aartie; Oortwijn, Beatrijs; Versteeg, Serge; van Ree, Ronald; Pijpstra, Rienk
Recombinant human C1-inhibitor (rhC1INH) purified from milk of transgenic rabbits is used for the treatment of acute attacks in patients with hereditary angioedema (HAE) due to C1-inhibitor (C1INH) deficiency. The objective was to investigate the risk of rhC1INH inducing IgE antibodies or eliciting anaphylactic reactions. In subjects treated with rhC1INH, we retrospectively analysed the frequency and clinical relevance of pre-exposure and potentially newly induced IgE antibodies against rabbit and other animal allergens including cow's milk by the ImmunoCAP(®) Specific IgE blood test system. 130 HAE patients and 14 healthy subjects received 300 administrations of rhC1INH, 65 subjects (47.4 %) on one occasion; 72 (52.6 %) on at least two occasions (range 2-12; median 2). Five subjects had pre-existing anti-rabbit epithelium IgE; the subject with the highest levels and a previously undisclosed rabbit allergy developed an anaphylactic reaction upon first exposure to rhC1INH, whereas the other four subjects with lower pre-existing IgE levels (Class 1-3), did not. No other anaphylactic reactions were identified in any of the subjects exposed to rhC1INH. Analysis of post-exposure samples revealed that the risk of inducing new or boosting existing IgE responses to rabbit or cow's milk allergens was negligible. The propensity of rhC1INH to induce IgE antibodies following repeated administration of rhC1INH is low. Subjects with substantially elevated anti-rabbit epithelium IgE antibodies and/or clinical allergy to rabbits may have an increased risk for an allergic reaction. No other risk factors for allergic reactions to rhC1INH have been identified.
Farrell, Colm; Hayes, Siobhan; Relan, Anurag; van Amersfoort, Edwin S; Pijpstra, Rienk; Hack, C Erik
To characterize the pharmacokinetics (PK) of recombinant human C1 inhibitor (rhC1INH) in healthy volunteers and hereditary angioedema (HAE) patients. Plasma levels of C1INH following 294 administrations of rhC1INH in 133 subjects were fitted using nonlinear mixed-effects modelling. The model was used to simulate maximal C1INH levels for the proposed dosing scheme. A one-compartment model with Michaelis-Menten elimination kinetics described the data. Baseline C1INH levels were 0.901 [95% confidence interval (CI): 0.839-0.968] and 0.176 U ml(-1) (95% CI: 0.154-0.200) in healthy volunteers and HAE patients, respectively. The volume of distribution of rhC1INH was 2.86 l (95% CI: 2.68-3.03). The maximal rate of elimination and the concentration corresponding to half this maximal rate were 1.63 U ml(-1) h(-1) (95% CI: 1.41-1.88) and 1.60 U ml(-1) (95% CI: 1.14-2.24), respectively, for healthy volunteers and symptomatic HAE patients. The maximal elimination rate was 36% lower in asymptomatic HAE patients. Peak C1INH levels did not change upon repeated administration of rhC1INH. Bodyweight was found to be an important predictor of the volume of distribution. Simulations of the proposed dosing scheme predicted peak C1INH concentrations above the lower level of the normal range (0.7 U ml(-1)) for at least 94% of all patients. The population PK model for C1INH supports a dosing scheme on a 50 U kg(-1) basis up to 84 kg, with a fixed dose of 4200 U above 84 kg. The PK of rhC1INH following repeat administration are consistent with the PK following the first administration. © 2013 The British Pharmacological Society.
Daniel Elenius Madsen
Full Text Available Hereditary angioedema (HAE is a potentially life-threatening disease caused by mutations in the gene encoding the serine protease inhibitor (serpin C1 inhibitor (C1-inh. The mutations cause decreased functional plasma levels of C1-inh, which triggers unpredictable recurrent edema attacks. Subjects suffering from HAE have been classified in type I patients with decreased functional and antigenic levels of C1-inh, and type II patients with decreased functional but normal antigenic C1-inh levels. However, a few reports have demonstrated that some mutations cause C1-inh polymerization in vitro, and it is speculated that C1-inh polymers may exist in patient plasma, challenging the current classification of HAE patients. To investigate the presence of C1-inh polymers in patient plasma samples, we developed an immunological method, where monoclonal antibodies produced against polymerized C1-inh were applied in native PAGE western blotting. Using this approach we analyzed genuine plasma samples from 31 Danish HAE families, and found that plasma samples from three genotypically distinct HAE type I families (classified upon C1-inh plasma concentrations contained C1-inh polymers. Identical C1-inh polymerization phenotypes were observed in four affected family members from one of these families. Genotyping of the families revealed that the polymerogenic mutations of two families were located in proximity to the reactive center loop insertion site in C1-inh (p.Ile271Thr and p.Ser258_Pro260del,and one mutation affected helix C (p.Thr167Asn. In conclusion, we demonstrate that C1-inh polymers are present in the plasma of a subgroup of HAE type I patients.
Gianni, Panagiota; Loules, Gedeon; Zamanakou, Maria; Kompoti, Maria; Csuka, Dorottya; Psarros, Fotis; Magerl, Markus; Moldovan, Dimitru; Maurer, Marcus; Speletas, Matthaios G; Farkas, Henriette; Germenis, Anastasios E
In view of the large heterogeneity in the clinical presentation of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), great efforts are being made towards detecting measurable biological determinants of disease severity that can help to improve the management of the disease. Considering the central role that plasma kallikrein plays in bradykinin production, we investigated the contribution of the functional polymorphism KLKB1-428G/A to the disease phenotype. We studied 249 C1-INH-HAE patients from 114 European families, and we explored possible associations of C1-INH-HAE clinical features with carriage of KLKB1-428G/A, combined or not with that of the functional F12-46C/T polymorphism. Carriers of the G allele of the KLKB1-428G/A polymorphism exhibited a significantly delayed disease onset (i.e., by 4.1 years [p < 0.001], depending on the zygocity status), while carriers of both the KLKB1-428G/A and the F12-46C/T polymorphism displayed an 8.8-year delay in disease onset (p < 0.001) and a 64% lower probability of needing long-term prophylactic treatment (p = 0.019). These findings support our initial hypothesis that functional alterations in genes of proteins involved in bradykinin metabolism and function affect the clinical phenotype and possibly contribute to the pathogenesis of C1-INH-HAE. Given that an earlier onset of symptoms is inversely correlated with the subsequent course of the disease and, eventually, the need for long-term prophylaxis, these polymorphisms may be helpful prognostic biomarkers of disease severity. © 2017 S. Karger AG, Basel.
Defendi, Federica; Charignon, Delphine; Ghannam, Arije; Habib, Mohammed; Drouet, Christian
Background Angioedema without wheals (AE) is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh), but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases. Objectives We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker. Methods We retrospectively investigated high molecular weight kininogen (HK) cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis. Results Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98–175μg/mL, n = 51) and in healthy women (90–176μg/mL, n = 74), while HK cleavage was lower (p14.4% HK cleavage for men; 33.0% HK cleavage for women, with >98% specificity achieved for all parameters. In plasma from patients undergoing recovery two months after oestrogen/progestin combination withdrawal (n = 13) or two weeks after AE attack (n = 2), HK cleavage was not fully restored, suggesting its use as a post-attack assay. Conclusion As a diagnostic tool, HK cleavage can offer physicians supportive arguments for kinin production in suspected AE cases and improve patient follow-up in clinical trials or prophylactic management. PMID:27685806
Full Text Available Abstract Background Hereditary Angioedema (HAE is a rare, autosomal dominant (AD disorder caused by a C1 esterase inhibitor (C1-inh deficiency or qualitative defect. Treatment of HAE in many parts of the world fall short and certain items need to be addressed in future guidelines. Objective To identify those individuals who should be on long-term prophylaxis for HAE. Additionally, to determine if prodromal symptoms are sensitive and specific enough to start treatment with C-1 INH and possibly other newly approved therapies. Also, to discuss who is appropriate to self-administer medications at home and to discuss training of such patients. Methods A literature review (PubMed and Google was performed and articles published in peer-reviewed journals, which addressed HAE prophylaxis, current HAE treatments, prodromal symptoms of HAE and self-administration of injected home medications were selected, reviewed and summarized. Results Individuals whom have a significant decrease in QOL or have frequent or severe attacks and who fail or are intolerant to androgens should be considered for long-term prophylaxis with C1INH. Prodromal symptoms are sensitive, but non-specific, and precede acute HAE attacks in the majority of patients. Although the treatment of prodromal symptoms could lead to occasional overtreatment, it could be a viable option for those patients able to adequately predict their attacks. Finally, self-administration, has been shown to be feasible, safe and effective for patients who require IV therapy for multiple other diseases to include, but not limited to, hemophilia. Conclusions Prophylactic therapy, treatment at the time of prodromal symptoms and self-administration at home all should allow a reduction in morbidity and mortality associated with HAE.
Smith, Aaron; Ray, Meredith; Jain, Nikhita; Zhang, Hongmei; Sebelik, Merry
Angioedema (AE) is a condition that may prompt a visit to an emergency department (ED), and can quickly progress to airway obstruction. To optimize treatment of AE, it is necessary to understand epidemiology and practice patterns. This study measured the magnitude of AE ED visits and characterized demographics, management, frequency of airway interventions, and mortality. Analysis of two national data sets. From the Nationwide Emergency Department Sample and National Hospital Ambulatory Medical Care Survey, we identified all patients presenting from 2006 to 2010 with a primary diagnosis of AE, characterized by the International Classification of Diseases, Ninth Edition, Clinical Modification code 995.1. The discharges were weighted and stratified by comorbidities, age, treatments, and region. χ 2 , t test, and linear regression were employed for comparisons. Total discharges increased from 87,481 (29.3 of 100,000 people) to 111,116 (35.8 of 100,000 people). More females were afflicted (57%), and 41.1% were African American. The majority (83%) of patients were discharged from the ED. Twelve percent of cases were attributed to antihypertensive adverse reaction, and these patients were older (P < .0001, odds ratio [OR] = 1.02), and had more comorbidities (P < .0001, OR = 5.66), hospital admissions (P < .0001, OR = 4.83), and intubations (P < .03, OR = 2.07). Overall, patients required intubation infrequently (<1%) and mortality was low (0.08%). The AE burden on EDs has increased over time. Patients with adverse reactions to antihypertensives are older, have more comorbidities, and require admission and intubation more frequently. Further investigation is needed to better delineate causation and outcome predictors, and to understand regional practice variance. 2c. Laryngoscope, 127:828-834, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.
Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients’ quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophylactic agents are associated with breakthrough attacks, therefore an acute treatment plan is essential for every patient. Experience has shown that higher doses of C1 inhibitor than previously recommended may be desirable, although only recombinant C1 inhibitor has been subject to full dose–response evaluation. Treatment of early symptoms of an attack, with any licensed therapy, results in milder symptoms, more rapid resolution and shorter duration of attack, compared with later treatment. All therapies have been shown to be well-tolerated, with low risk of serious adverse events. Plasma-derived C1 inhibitors have a reassuring safety record regarding lack of transmission of virus or other infection. Thrombosis has been reported in association with plasma-derived C1 inhibitor in some case series. Ruconest was associated with anaphylaxis in a single rabbit-allergic volunteer, but no further anaphylaxis has been reported in those not allergic to rabbits despite, in a few cases, prior IgE sensitization to rabbit or milk protein. Icatibant is associated with high incidence of local reactions but not with systemic effects. Ecallantide may cause anaphylactoid reactions and is given under supervision. For children and pregnant women, plasma-derived C1 inhibitor has the best evidence of safety and currently remains first-line treatment. PMID:29594115
Full Text Available The benefits of the worldwide approval of new drugs for the treatment of acute C1-INH-HAE attacks may still not reach all patients. Identifying the current barriers in the access to medication, as well as conducting a detailed assessment of the progress in this area, is essential to achieve universal treatment. Two hundred and twenty five patients registered in the Argentina Hereditary Angioedema Patient Association (AHAEPA were randomly selected and invited to participate in a web based questionnaire on accessibility to icatibant and pdC1-INH, self-treatment, delay to treatment, and coverage. The data retrieved was compared to our previous reports in 2008 and 2013. We collected 156/225 answers. One hundred and eighteen (76% patients have either pdC1-INH (n = 86, icatibant (n = 10 or both (n = 22, while 38 (24% do not have access to treatment. In 2008, 26% had access while 82% had it in 2013. Thirty-two subjects (22% self-inject themselves, similar to 29% in 2013, even though between studies, widespread self-injection training activities have taken place. However, considering injections by proxy, home treatment reached 56%. Only half of the patients decide to receive treatment early during the attack. Ninety-nine patients (63% have full coverage, thirty (19% have no coverage at all and the rest only obtain partial reimbursement. Twenty-nine families (31% share a single treatment dose of the medication, better than 36% in 2013. Argentina's C1-INH-HAE patients had a sustained improvement in their access to medication. Efforts should continue to further improve accessibility and optimal management of HAE acute attacks to all patients in the country.
Full Text Available Angioedema without wheals (AE is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh, but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases.We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker.We retrospectively investigated high molecular weight kininogen (HK cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis.Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98-175μg/mL, n = 51 and in healthy women (90-176μg/mL, n = 74, while HK cleavage was lower (p14.4% HK cleavage for men; 33.0% HK cleavage for women, with >98% specificity achieved for all parameters. In plasma from patients undergoing recovery two months after oestrogen/progestin combination withdrawal (n = 13 or two weeks after AE attack (n = 2, HK cleavage was not fully restored, suggesting its use as a post-attack assay.As a diagnostic tool, HK cleavage can offer physicians supportive arguments for kinin production in suspected AE cases and improve patient follow-up in clinical trials or prophylactic management.
Full Text Available Huamin Henry Li Institute for Asthma and Allergy, Chevy Chase, MD, USA Abstract: Hereditary angioedema (HAE is a rare genetic disease characterized by episodic subcutaneous or submucosal swelling. The primary cause for the most common form of HAE is a deficiency in functional C1 esterase inhibitor (C1-INH. The swelling caused by HAE can be painful, disfiguring, and life-threatening. It reduces daily function and compromises the quality of life of affected individuals and their caregivers. Among different treatment strategies, replacement with C1-INH concentrates is employed for on-demand treatment of acute attacks and long-term prophylaxis. Three human plasma-derived C1-INH preparations are approved for HAE treatment in the US, the European Union, or both regions: Cinryze®, Berinert®, and Cetor®; however, only Cinryze is approved for long-term prophylaxis. Postmarketing studies have shown that home therapy (self-administered or administered by a caregiver is a convenient and safe option preferred by many HAE patients. In this review, we summarize the role of self-administered plasma-derived C1-INH concentrate therapy with Cinryze at home in the prophylaxis of HAE. Keywords: C1-INH concentrate, hereditary angioedema, disease management, first line, prophylaxis, self-administration
Kasperska-Zając, A; Grzanka, A; Czecior, E; Misiolek, M; Rogala, B; Machura, E
Active chronic urticaria, identified as a mast cell- and basophil-dependent inflammatory disorder of the skin is able to elicit acute phase response (APR). However, systemic inflammatory response in different types of urticaria is poorly characterized. To determine APR pattern in a clearly defined group of patients with acute urticaria and/or angioedema - induced by NSAIDs. Plasma IL-6 and serum C-reactive protein (CRP) concentrations were studied in 17 patients with NSAIDs-induced acute urticaria/angioedema (NSAIDsAU) and in 20 healthy controls. Eleven patients who used NSAIDs were presented at the emergency room with acute urticaria/angioedema while the remaining six manifested the symptoms during the aspirin challenge test. Patients were examined in a dynamic manner: during the acute phase, and next, after subsidence of the symptoms. CRP and IL-6 concentrations increased significantly in patients with NSAIDsAU as compared with their asymptomatic period and the healthy subjects. In addition, NSAIDsAU patients showed elevated concentration of the biomarkers following aspirin provocation with the baseline values recovered in the asymptomatic period. These results indicate that an acute systemic inflammatory response is activated in patients with NSAIDs-induced urticaria and/or angioedema. The study supports the evidence proving that up-regulation of CRP and IL-6 in urticaria/angioedema does not necessarily reflect any concomitant infection or other inflammatory processes, but may be due to the disease itself. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.
Prior, Nieves; Remor, Eduardo; Pérez-Fernández, Elia; Caminoa, Magdalena; Gómez-Traseira, Carmen; Gayá, Francisco; Aabom, Anne; Aberer, Werner; Betschel, Stephen; Boccon-Gibod, Isabelle; Bouillet, Laurence; Bygum, Anette; Csuka, Dorottya; Farkas, Henriette; Gomide, Maria; Grumach, Anete; Leibovich, Iris; Malbran, Alejandro; Moldovan, Dumitru; Mihaly, Eniko; Obtulowicz, Krystyna; Perpén, Cecilia; Peveling-Oberhag, Adriane; Porebski, Grzegorz; Chavannes, Celine Rayonne; Reshef, Avner; Staubach, Petra; Wiednig, Michaela; Caballero, Teresa
Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) may affect health-related quality of life (HRQoL). A specific HRQoL questionnaire for adult patients with C1-INH-HAE, the HAE-QoL, has recently been developed in Spain. The objective of this study was to perform a cross-cultural validation and psychometric study of the HAE-QoL in an international setting. Cross-cultural adaptation of the Spanish HAE-QoL draft version and an international rating phase with experts were performed. The resultant version of the HAE-QoL, a clinical questionnaire, and Short Form 36-item Health Survey Version 2.0 (SF-36v2) were pilot tested internationally. Item reduction was based on both descriptive and exploratory factor analysis. Psychometric properties were assessed. Cross-cultural adaptation of the HAE-QoL was performed in 18 countries. The draft version of the HAE-QoL was pilot tested in 332 patients, and accurate data were obtained from 290 patients from 11 countries. The reduction process resulted in a new version with 25 items and 7 dimensions (treatment difficulties, physical functioning and health, disease-related stigma, emotional role and social functioning, concern about offspring, perceived control over illness, and mental health). Strong psychometric properties were observed (Cronbach's α 0.92; test-retest reliability 0.87). Convergent validity showed mild to moderate correlations with SF-36v2 physical and mental component summaries (0.45 and 0.64, respectively) and with SF-36v2 dimensions (P < .004). HAE-QoL scores discriminated significantly among severity groups (median: asymptomatic 133.5 vs severe 84.0; P < .001); between patients with and without long-term prophylaxis (median: 101 vs 90; P = .001); and between patients with and without psychiatric and/or psychological care (median: 74 vs 103; P ≤ .001). The HAE-QoL, currently available in 18 languages, showed good reliability and validity evidence. Copyright © 2016 American Academy of Allergy
María Dulfary Sánchez
Conclusión. Este estudio provee información sobre la primera familia caracterizada con angioedema hereditario de tipo 1 en el Valle de Aburrá, Colombia. Aunque para ello se usó un instrumento genérico, se confirmó, además, el efecto negativo de la enfermedad en la calidad de vida de los individuos que la padecen.
Culley, Colleen M; DiBridge, Julie N; Wilson, Gregory L
To evaluate the place in therapy of fresh frozen plasma (FFP), C1 esterase concentrate (C1-INH), ecallantide, and icatibant in the management of angiotensin-converting enzyme inhibitor-induced angioedema (ACEI-IA). A literature search was performed using PubMed (1946 through August 2015) and Embase (angioedema, another bradykinin-mediated event, may be effective for use in ACEI-IA. Positive efficacy results were reported with FFP and C1-INH while mixed results have been seen with ecallantide. Off-label icatibant has the most evidence supporting its use in ACEI-IA with rapid symptom resolution (10 minutes to 6 hours) and avoidance of intubation and tracheotomy in several cases. These agents were well-tolerated in ACEI-IA. ACEI-IA is typically a self-limiting event. First-line therapies include ACEI discontinuation, observation, and supportive medications (eg, corticosteroids, antihistamines, and epinephrine). Symptom progression can be life-threatening and may require interventions such as tracheotomy and intubation. Off-label use of FFP and medications approved for hereditary angioedema have resulted in rapid resolution of symptoms and avoidance of intubation. Among these agents, icatibant has the most supporting evidence and has been incorporated into practice guidelines and algorithms as a second-line agent for serious life-threatening ACE-IA. © The Author(s) 2015.
Antoneicka L. Harris
Full Text Available Chronic urticaria is a common condition characterized by recurrent hives lasting several weeks or months and is usually idiopathic. Approximately half of the individuals with chronic urticaria will present with episodes of angioedema that can be severe and debilitating. In this report, we describe a 47-year-old Hispanic male who presented initially for an evaluation of chronic hives following hospitalization due to hive-induced anaphylaxis. The individual had a history significant for urticaria and angioedema beginning in his early 30s. Interestingly, both the individual’s 41-year-old sister and 12-year-old daughter were also affected with chronic urticaria and severe angioedema. Whole exome sequencing of the proband and several family members revealed a heterozygous variant of uncertain significance in exon 2 of TNFAIP3, denoted as c.65G>A (p.R22Q, in all affected members. Variants in TNFAIP3 have been associated with multiple autoimmune diseases, susceptibility to allergy and asthma, and periodic fever syndromes, suggesting that this variant could potentially play a role in disease.
Ayuso, Pedro; Plaza-Serón, María del Carmen; Doña, Inmaculada; Blanca-López, Natalia; Campo, Paloma; Cornejo-García, José A; Perkins, James R; Torres, Maria J; Blanca, Miguel; Canto, Gabriela
NSAIDs-induced urticaria and/or angioedema (NIUA) is the most frequent entity of hypersensitivity reactions to NSAIDs. The underlying cause is considered to be because of a nonspecific immunological mechanism in which mast cells are key players. We studied the association of nine single nucleotide polymorphisms in five genes involved in mast cell activation (SYK, LAT1, PLCG1, PLA2G4A, and TNFRSF11A) in 450 NIUA patients and 500 controls. We identified several statistically significant associations when stratifying patients by symptoms: PLA2G4A rs12746200 (urticaria vs. controls, Pc=0.005). PLCG1 rs2228246 (angioedema vs. controls; Pc=0.044), and TNFRS11A rs1805034 (urticaria+angioedema vs. controls; Pc=0.041). The frequency of haplotype PLCG1 rs753381-rs2228246 (C-G) in angioedema-NIUA patients was lower than that in controls (Pc=0.040). In addition, the haplotype frequency of TNFRS11A rs1805034-rs35211496 (C-T) was higher among urticaria-NIUA and urticaria+angioedema-NIUA patients than the controls (Pc=0.045 and 0.046). Our results shed light on the involvement of variants in genes related to non-immunological mast cell activation in NIUA.
Lumry, William R; Craig, Timothy; Zuraw, Bruce; Longhurst, Hilary; Baker, James; Li, H Henry; Bernstein, Jonathan A; Anderson, John; Riedl, Marc A; Manning, Michael E; Keith, Paul K; Levy, Donald S; Caballero, Teresa; Banerji, Aleena; Gower, Richard G; Farkas, Henriette; Lawo, John-Philip; Pragst, Ingo; Machnig, Thomas; Watson, Douglas J
Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) impairs health-related quality of life (HRQoL). The objective of this study was to assess HRQoL outcomes in patients self-administering subcutaneous C1-INH (C1-INH[SC]; HAEGARDA) for routine prevention of HAE attacks. Post hoc analysis of data from the placebo-controlled, crossover phase III COMPACT study (Clinical Studies for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy). Ninety patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH(SC) 40 or 60 IU/kg twice weekly for 16 weeks, preceded or followed by 16 weeks of twice weekly placebo injections. All HAE attacks were treated with open-label on-demand treatment as necessary. HRQoL assessments at week 14 (last visit) included the European Quality of Life-5 Dimensions Questionnaire (EQ-5D-3L), the Hospital Anxiety and Depression Scale (HADS), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Treatment Satisfaction Questionnaire for Medication (TSQM). Compared with placebo (on-demand treatment alone), treatment with twice weekly C1-INH(SC) (both doses combined) was associated with better EQ-5D visual analog scale general health, less HADS anxiety, less WPAI presenteeism, work productivity loss, and activity impairment, and greater TSQM effectiveness and overall treatment satisfaction. More patients self-reported a "good/excellent" response during routine prevention with C1-INH(SC) compared with on-demand only (placebo prophylaxis) management. For each HRQoL measure, a greater proportion of patients had a clinically meaningful improvement during C1-INH(SC) treatment compared with placebo. In patients with frequent HAE attacks, a treatment strategy of routine prevention with self-administered twice weekly C1-INH(SC) had a greater impact on improving multiple HAE-related HRQoL impairments, most notably anxiety and work productivity, compared with on
Lumry, William R; Castaldo, Anthony J; Vernon, Margaret K; Blaustein, Marc B; Wilson, David A; Horn, Patrick T
Hereditary angioedema (HAE) is a rare, autosomal dominant disorder characterized by recurrent acute attacks of swelling of the larynx, abdomen, and periphery. This study was designed to assess the humanistic burden of illness associated with HAE. HAE burden was assessed via a web-based survey of patients that solicited information on attack characterization, treatment, side effects, pain, and functional and emotional burden of disease management. In addition to HAE-specific sections, the survey used three standardized instruments to compare HAE patient data to normative (healthy) and chronic disease populations: the 12-Item Short Form (SF-12) Health Survey, the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire, and the Hamilton Depression Inventory-Short Form (HDI-SF). A total of 457 HAE patients responded to the survey (response rate, ∼19%). Patients reported significantly poorer health-related quality of life versus population norms, based on the SF-12 Physical Component Summary (mean, 43.7 versus 49.6; p 8.5, indicative of depressive symptomatology. Productivity was also markedly impaired in all WPAI-GH categories, including 34% overall work impairment. Because of their most recent HAE attack, workers lost a mean of 3.3 days; students lost a mean of 1.9 days. HAE results in considerable humanistic burden to patients across physical and mental health domains; negatively impacts education, career, and work productivity; and compounds the substantial economic burdens that are reported separately.
Wintenberger, C; Boccon-Gibod, I; Launay, D; Fain, O; Kanny, G; Jeandel, P Y; Martin, L; Gompel, A; Bouillet, L
Angioedema (AE) is a clinical syndrome characterized by localised swelling lasting several hours. The swelling is often recurring and can be lethal if it is located in the laryngeal region. Much progress has been made recently in the treatment of acute episodes, but no consensus has been reached on maintenance treatment. We have performed a national retrospective observational study to assess the use of tranexamic acid (TA) as maintenance treatment for non-histaminergic AE [hereditary AE (HAE) or idiopathic non-histaminergic AE]. Records for 64 cases were collected from 1 October 2012 to 31 August 2013; 37 of these were included (12 HAE with C1-inhibitor deficiency, six with HAE with normal C1-inhibitor and 19 idiopathic non-histaminergic AE). When treated with TA over six months, the number of attacks was reduced by 75% in 17 patients, 10 patients showed a lower level of reduction and 10 had the same number of attacks. In no instances were symptoms increased. No thromboembolic events were observed, and the main side effects were digestive in nature. Thus, TA, which is well tolerated and inexpensive, appears to be an effective maintenance treatment for some patients with HAE or idiopathic non-histaminergic AE. PMID:24827773
Bygum, Anette; Martinez-Saguer, Inmaculada; Bas, Murat
BACKGROUND: Treatment of hereditary angioedema (HAE) in 'older adults' (those aged ≥65 years) has not been well studied. The international Berinert Patient Registry collected data on the use of intravenous plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH; Berinert......(®)/CSL Behring) in patients of any age, including many older adults. METHODS: This observational registry, conducted from 2010 to 2014 at 30 US and seven European sites, gathered prospective (post-enrollment) and retrospective (pre-enrollment) usage and adverse event (AE) data on subjects treated with pnfC1-INH....... RESULTS: The registry documented 1701 pnfC1-INH infusions in 27 older adults. A total of 1511 HAE attacks treated with pnfC1-INH administration were reported among 25 of the 27 (92.6 %) older adults. Among the older adults, mean (standard deviation [SD]) (8.8 [4.1] IU/kg) and median (6.4 IU/kg) pnfC1-INH...
Ceyda Tunakan Dalgıç
Full Text Available Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE is a rare, autosomal dominant disorder. The management of pregnant patients with C1-INH-HAE is a challenge for the physician. Intravenous plasma-derived nanofiltered C1-INH (pdC1INH is the only recommended option throughout pregnancy, postpartum, and breastfeeding period. In order to increase pregnancy rates, physicians use fertilization therapies increasing endogen levels of estrogens. Therefore, these techniques can provoke an increase in the number and severity of edema attacks in C1-INH-HAE. Our patient is a 32-year-old female, diagnosed with C1-INH-HAE type 1 since 2004. She had been taking danazol 50–200 mg/day for 9 years. Due to her pregnancy plans in 2013, danazol was discontinued. PdC1INH was prescribed regularly for prophylactic purpose. Triplet pregnancy occurred by in vitro fertilization using luteinizing hormone-releasing hormone (LHRH injections. In our patient, LHRH injections were done four times without causing any severe attack during in vitro fertilization. Angioedema did not worsen during pregnancy and delivery due to the prophylactic use of intravenous pdC1INH in our patient. According to the attack frequency and severity, there was no difference between the three pregnancy trimesters. To our knowledge, this is the first published case of C1-INH-HAE receiving in vitro fertilization therapies without any angioedema attacks during pregnancy and delivery and eventually having healthy triplets with the prophylactic use of intravenous pdC1INH.
Vilaça, MJ; Coelho, M; Faísco, A; Carmona, C
O angioedema hereditário (AEH), com uma prevalência estimada de 1:50000 pessoas, é uma doença rara mas potencialmente fatal. Pode se apresentar com edema sistêmico recorrente do tecido subcutâneo e das mucosas. Os doentes com AEH têm um risco acrescido de agudização clínica com o estresse cirúrgico, podem desenvolver síndromes de dificuldade respiratória por compromisso da via aérea e de instabilidade hemodinâmica. A abordagem perioperatória desses doentes requer intervenções e...
Engel, Ruchira; Rensink, Irma; Roem, Dorina; Brouwer, Mieke; Kalei, Asma; Perry, Dawn; Zeerleder, Sacha; Wouters, Diana; Hamann, Dörte
Neutralizing autoantibodies (NAbs) against plasma serpin C1-inhibitor (C1-inh) are implicated in the rare disorder, acquired angioedema (AAE). There is insufficient understanding of the process of antibody formation and its correlation with disease progression and severity. We have developed an ELISA for detecting neutralizing capacity of anti-C1-inh positive plasma samples that can be used to study changes in NAb repertoire in patient plasma over the course of disease. The ELISA is based on the specific interaction of active C1-inh with its target protease C1s. Decrease in the amount of C1s bound to immobilized C1-inh in the presence of test samples is proportional to the neutralizing capacity of the sample. Assay specificity, intra- and inter-assay variation and assay cut-off are determined using anti-C1-inh antibodies. Assay capability is demonstrated using plasma samples from AAE patients. The assay is specific to a neutralizing anti-C1-inh antibody and shows no interference by a non-neutralizing anti-C1-inh antibody or by the plasma matrix. Intra-assay and inter-assay variations are determined as 17 and 18% respectively. Neutralizing capacity of antibody positive AAE patient plasma samples (n=16) with IgG or IgM type antibodies is readily determined. All samples show positive neutralizing capacity. We have developed a robust, specific and semi-quantitative assay to detect the neutralizing capacity of plasma samples containing anti-C1-inh antibodies. This assay can be an important tool for the study of clinical implications of anti-C1-inh NAbs. Copyright © 2015 Elsevier B.V. All rights reserved.
Regis Albuquerque Campos
Full Text Available CONTEXT AND OBJECTIVE: Hereditary angioedema (HAE with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil.DESIGN AND SETTING: Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients.METHODS: Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored.RESULTS: 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age. The symptoms were: subcutaneous edema (22/24; abdominal pain (15/24 and upper airway obstruction (10/24. The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%; 10-20 (5/24; 20.8%; 20-30 (8/24; 33.4%; 30-60 (5/24; 20.8%; and 2 hours (1/24; 4.3%. The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6.CONCLUSION: HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.
Gómez-Traseira, C; Pérez-Fernández, E; López-Serrano, M C; García-Ara, M C; Pedrosa, M; López-Trascasa, M; Caballero, T
Hereditary angioedema due to C1-esterase inhibitor deficiency (HAE-C1-INH) is a life-threatening disease. To describe the clinical characteristics and management of patients with HAE-C1-INH during routine clinical practice. An observational, retrospective study was performed in patients with HAE-C1-INH. Demographic, clinical, and analytical data were collected from 2 periods: period A (October 2009-September 2010) and period B (October 2007-September 2009). We studied 112 patients with HAE-C1-INH (57.1% females). Age at onset of symptoms was 14.4 years (lower in patients who had experienced attacks in the previous year). In period B (n=87), 62.1% of patients presented at least 1 edema attack (median, 3.5 attacks/patient/2 years), and 19.1% of attacks were treated. In period A (n=77), 58.4% of patients were on maintenance therapy. Stanozolol was the most widely used drug (48.9%), with a mean weekly dose of 6.7 mg. At least 1 attack was recorded in 72.7% of patients (median, 3.0 attacks/patient/year), and 31.5% of the attacks were treated. Treatment of acute attacks increased by 12.4%. Age at onset of symptoms is associated with clinical expression of disease. The higher age at onset of symptoms, the fewer number of attacks per patient and year, and the lower dose of attenuated androgens necessary to control the disease than in other series lead us to hypothesize that HAE-C1-INH could have a less severe expression in Spain. Acute attacks seem to be treated increasingly often.
Full Text Available Lise Aagaard,1 Anette Bygum,2 1Section for Clinical Pharmacology, Institute of Public Health, Faculty of Health Sciences, University of Southern Denmark, 2Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark Abstract: Information about long-term safety issues from use of orphan drugs in treatment of hereditary angioedema (HAE is limited and must be studied further. As clinical trials in patients with rare diseases are limited, prescribers and patients have to rely on spontaneous adverse drug reaction (ADR reports for obtaining major information about the serious, rarely occurring, and unknown ADRs. In this study, we aimed to characterize ADRs reported for HAE medications in Europe from 2007 to 2013. ADR reports submitted for C1-inibitors and bradykinin receptor antagonists to the European ADR database, EudraVigilance (EV, were included in this study. The ADR reports were categorized with respect to age and sex of the patients, category of the reporter, type and seriousness of the reported ADRs, and medications. The unit of analysis was one adverse event (AE. Totally, 187 AEs were located in EV, and of these, 138 AEs were reported for Cinryze® (C1-inhibitor (73% of the total and 49 AEs for Firazyr® (icatibant (26% of the total AEs. Approximately 60% of all AEs were serious, including three fatal cases. Less than 5% of AEs were reported in children. In total, 62% of AEs were reported for women and 38% for men. For both Cinryze® and Firazyr®, the majority of reported AEs were of the type “general disorders and administration site conditions”. For Cinryze®, a large number of AEs of the type “HAE” and “drug ineffective” was reported, but only few of these were serious. For Firazyr®, several nonserious reports on injection site reactions were reported. In conclusion, this study showed that in EV, several ADR reports from use of HAE medications were identified, and a large number of these were
Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C.; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J.; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M.; Ayuso, Pedro; Fernández, Javier; Laguna, José J.; Agúndez, José A. G.; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13×10−6), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs. PMID:24618698
Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen
.001). Among patients who sought medical care during the last attack (23%), more than half utilized the emergency department. The last attack prevented patients from their normal activities an average of 4-12 hours. Patient and caregiver absenteeism increased with attack severity and frequency. Among patients...... who were working or in school (n = 120), 72 provided work/school absenteeism data, resulting in an estimated 20 days missing from work/school on average per year; 51% (n = 84) indicated that HAE has hindered their career/educational advancement. CONCLUSION: HAE poses a considerable burden on patients...... and their families in terms of direct medical costs and indirect costs related to lost productivity. This burden is substantial at the time of attacks and in between attacks....
Grumach, Anete Sevciovic; Ferraroni, Natasha; Olivares, Maria Margarita
are common. HAE attacks may be fatal when upper-airway edema occurs, if proper treatment with a C1 inhibitor concentrate or BK receptor antagonist is not administered or an emergency tracheostomy is not performed. We propose a mnemonic method for the warning signs of HAE for the use as a diagnostic tool, i...
Feb 9, 2009 ... ACE inhibitors are often prescribed in the treatment of hypertension, heart failure and kidney disease. These drugs are on the Essential Drugs List, and are therefore used at ... autopsy findings, including total IgE and mast cell tryptase levels (these were within normal reference values). The cause of death ...
Riedl, Marc A; Bygum, Anette; Lumry, William
of this study was to describe safety and usage patterns of pnfC1-INH. METHODS: A multicenter, observational, registry was conducted between 2010 and 2014 at 30 United States and 7 European sites to obtain both prospective (occurring after enrollment) and retrospective (occurring before enrollment) safety...... and usage data on subjects receiving pnfC1-INH for any reason. RESULTS: Of 343 enrolled patients, 318 received 1 or more doses of pnfC1-INH for HAE attacks (11,848 infusions) or for prophylaxis (3142 infusions), comprising the safety population. Median dosages per infusion were 10.8 IU/kg (attack treatment......, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless...
Longhurst, Hilary; Bygum, Anette
on the psychological outcomes is scarce, but the limited information available suggests that access to specialist advice and treatment leads to psychological as well as physical improvement.HAE also has profound effects on individual and family economic output, directly via absenteeism from school or work...
Hermanrud, Thorbjørn; Bygum, Anette; Rasmussen, Eva Rye
-converting enzyme inhibitors (ACEI-AAE) is well known, but other pharmaceutical agents also affect the degradation of bradykinin and substance P. We present a middle-aged man with recurrent episodes of severe AE of the oral cavity, hypopharynx and larynx due to pharmacological inhibition of dipeptidyl peptidase IV....
Full Text Available Se actualiza el diagnóstico de la urticaria crónica (UC y los conceptos, definiciones y sugerencias basados en la evidencia para su tratamiento. La urticaria ocurre en al menos 20% de la población en algún momento de la vida. Su etiología difiere en la forma aguda (menos de 6 semanas, y en la crónica. No es posible pronosticar si las formas agudas evolucionarán a UC, ya que todas son agudas al comienzo. La UC ocurre como espontánea (UCE o inducible (UCI. El diagnóstico es sencillo, pero incluye un minucioso estudio para descartar diagnósticos diferenciales; para UCI son útiles las pruebas de provocación en la caracterización y manejo. Los estudios complementarios se deben limitar y orientar según sospecha clínica. El tratamiento se divide en tres enfoques: evitación, eliminación o tratamiento del estímulo desencadenante o de la causa, y tratamiento farmacológico. Recientemente éste se modificó, con empleo de antihistamínicos de segunda generación como primera línea y aumento de dosis de antihistamínicos H1 no sedantes, hasta 4 veces, como segunda línea. Los antihistamínicos son fundamentales para tratar la UC; sin embargo, un 40% de los pacientes no logra un buen control pese al aumento de dosis y requiere otro medicamento adicional. La evidencia más reciente considera que un grupo de fármacos puede utilizarse como tercera línea en estos casos, para mejorar la calidad de vida y limitar la toxicidad por el uso frecuente o crónico de esteroides sistémicos. Se recomiendan para esta tercera línea solo 3 fármacos: omalizumab, ciclosporina A o antileucotrienos.
Jorge Máspero; Hugo Cabrera; Ledit Ardusso; Mónica De Gennaro; Ramón Fernández Bussy; José Galimany; Daniel Galimberti; Marcelo Label; Marta La Forgia; Iris Medina; Hugo Neffen; Patricia Troielli
Se actualiza el diagnóstico de la urticaria crónica (UC) y los conceptos, definiciones y sugerencias basados en la evidencia para su tratamiento. La urticaria ocurre en al menos 20% de la población en algún momento de la vida. Su etiología difiere en la forma aguda (menos de 6 semanas), y en la crónica. No es posible pronosticar si las formas agudas evolucionarán a UC, ya que todas son agudas al comienzo. La UC ocurre como espontánea (UCE) o inducible (UCI). El diagnóstico es sencillo, pero i...
Stipić Marković, Asja; Rožmanić,, Vojko; Anić, Branimir; Aberle, Neda; Račić, Goran; Novak, Srđan; Sunara, Davor; Grdinić, Boris; Karadža-Lapić, Ljerka; Ražov Radas, Melanija; Karanović, Boris; Kvenić, Barbara
Hereditarni angioedem (HAE) rijetka je, ali potencijalno za život opasna bolest zbog nepredvidivih napadaja bezbolnih, ograničenih, recidivirajućih otoka supkutanog ili submukoznog, intersticijskog tkiva u trajanju od nekoliko sati do nekoliko dana. Oboljelih od HAE u RH ima oko 100 (ali vjerojatno ima više nedijagnosticiranih). Poseban kvalitativni napredak u usklađivanju dogovora o liječenju HAE jesu Smjernice Svjetske alergološke organizacije koje su donesene 2012. Oslanjajući se na taj do...
Rasmussen, Eva Rye; von Buchwald, Christian; Wadelius, Mia
intubation or tracheostomy. 74 admissions took place during the study period with a total of 143 days spent in the hospital. The diagnosis codes most often used for this condition were "DT783 Quincke's oedema" and "DT78.4 Allergy unspecified". Complement C1 inhibitor was normal in all tested patients...
Elenius Madsen, Daniel; Hansen, Søren Werner Karlskov; Gram, Jørgen Brodersen
phenotypes were observed in four affected family members from one of these families. Genotyping of the families revealed that the polymerogenic mutations of two families were located in proximity to the reactive center loop insertion site in C1-inh (p.Ile271Thr and p.Ser258_Pro260del),and one mutation...... affected helix C (p.Thr167Asn). In conclusion, we demonstrate that C1-inh polymers are present in the plasma of a subgroup of HAE type I patients....
Caballero, Teresa; Zanichelli, Andrea; Aberer, Werner
in the literature. We examined disease characteristics and icatibant treatment effectiveness in patients stratified by BMI in the Icatibant Outcome Survey, an ongoing, international, observational study monitoring the real-world safety and effectiveness of icatibant. Methods: Attack and treatment characteristics......) were analyzed. There was no significant difference in the frequency and severity of attacks across BMI groups, although obese patients tended to have more attacks of high severity. There was no impact of BMI on the frequency of laryngeal attacks, but patients with normal BMI had fewer cutaneous attacks......) and treated attacks earlier than patients with normal BMI (P = 0.007). Furthermore, time to resolution and duration of attack were shorter for patients with high BMI (P normal). Conclusion: Overall, icatibant was comparatively effective in treating attacks...
Prior, Nieves; Remor, Eduardo; Pérez-Fernández, Elia
was to perform a cross-cultural validation and psychometric study of the HAE-QoL in an international setting. METHODS: Cross-cultural adaptation of the Spanish HAE-QoL draft version and an international rating phase with experts were performed. The resultant version of the HAE-QoL, a clinical questionnaire......, and Short Form 36-item Health Survey Version 2.0 (SF-36v2) were pilot tested internationally. Item reduction was based on both descriptive and exploratory factor analysis. Psychometric properties were assessed. RESULTS: Cross-cultural adaptation of the HAE-QoL was performed in 18 countries. The draft...... and social functioning, concern about offspring, perceived control over illness, and mental health). Strong psychometric properties were observed (Cronbach's α 0.92; test-retest reliability 0.87). Convergent validity showed mild to moderate correlations with SF-36v2 physical and mental component summaries (0...
Salehi, Nooshin; Choi, Eric D.; Garrison, Roger C.
Patient: Male, 32 Final Diagnosis: Miller Fisher syndrome Symptoms: Ataxia ? headache ? ophthalmoplegia Medication: ? Clinical Procedure: Plasmapheresis Specialty: Neurology Objective: Rare co-existance of disease or pathology Background: Miller Fisher Syndrome is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia, and is considered to be a variant of Guillain-Barre Syndrome. Miller Fisher Syndrome is observed in approximately 1?5% of all Guillain-Barre cases in Wes...
Aabom, Anne; Nguyen, Dan; Fisker, Niels
-INH-HAE, including possible correlations to disease severity and attack frequency. Methods: All Danish children ages 2-18 years with C1-INH-HAE were invited to complete questionnaires regarding HRQoL; 14 (93%) agreed. Child self-report forms were used for children ages ≥5 years. The instruments used...... scores for healthy children and better than the scores in the only other study dedicated to HRQoL in children. Children with recent attacks had lower scores, whereas HRQoL scores were not correlated to overall disease severity or age. Surprisingly, home therapy was associated with lower HRQoL; however......, home therapy was also correlated to a higher overall severity score and more frequent attacks. There was a strong child-parent agreement in the PedsQL forms, but scores were independent of whether the child had a family history of C1-INH-HAE or sporadic C1-INH-HAE and whether the parent completing...
Kozel, Martina M. A.; Moein, M. Chloé Ansari; Mekkes, Jan R.; Meinardi, Marcus M. H. M.; Bossuyt, Patrick M. M.; Bos, Jan D.
In this retrospective study, the feasibility and implementation of a clinical guideline was evaluated in 130 consecutive patients with chronic urticaria. We analysed how often a questionnaire was used, how often routine laboratory tests were performed and on what information (history-taking,
Kozel, M. M.; Mekkes, J. R.; Bossuyt, P. M.; Bos, J. D.
BACKGROUND: Information about spontaneous remission of chronic urticaria is limited. OBJECTIVE: To investigate the natural course of urticaria, we followed up 220 adults in a prospective study. METHODS: Patients were followed up for 1 to 3 years to evaluate interventions, to detect latent causes,
Conclusions: AE developed in Japanese young females and likely showed a single course. In AE, the count of eosinophil of 104/μL was observed. Only eosinophil count increased among leukocyte series. Serum C- reactive protein and IgE levels remained almost normal. The eosinophil count in AE patients will return to the normal level within 8 weeks even without corticosteroid therapy.
Full Text Available H01006 Hereditary angioedema Hereditary angioedema (HAE) is a rare genetic disorde...r, manifested by recurrent episodes of angioedema localized to the skin or mucosa of the gastrointestinal tr...act or larynx. The laryngeal angioedema is potentially lethal. The classic forms, HAE types I and II, result...6100 PMID:14572810 (description, gene) ... AUTHORS ... Davis AE 3rd ... TITLE ... The pathogenesis of hereditary angioedema... (drug) ... AUTHORS ... Antoniu SA ... TITLE ... Therapeutic approaches in hereditary angioedema. ... JOURNAL ... Clin
Zanichelli, A; Maurer, M; Aberer, W
. A total of 143 SAEs occurred in 59 (10.6%) patients; only three events (drug inefficacy, gastritis, and reflux esophagitis) in two patients were considered related to icatibant. Notably, no SAEs related to icatibant occurred in patients with cardiovascular disease, nor in those using icatibant...
fact , that the plasma level of C1INH was significantly reduced in 75 PiZZ children compared to 35 control children (14%, p ɘ.01). A similar...constructed all plasmids and performed mutagenesis Funding Support: None Name: Astrid Doerner Project Role: Project Scientist Research
Kozel, Martina M. A.; Bossuyt, Patrick M. M.; Mekkes, Jan R.; Bos, Jan D.
Background : The value of laboratory tests in chronic urticaria is still controversial. Objective: Our aim was to assess this value in clinical studies, and to identify factors explaining the variation in the number of identified causes. Methods: A total of 4 electronic databases were searched, and
Full Text Available : C1 inhibitor deficiency (hereditary angioedema); C4 binding protein alpha deficiency; C4 binding protein b... subcutaneous and submucosal layers, identified as angioedema (hereditary or acquired). Genetic deficiency o
Fast, Søren; Henningsen, Emil; Bygum, Anette
A 78 year-old woman with life-threatening angiotensin-converting enzyme inhibitor (ACE-i) induced angioedema was unresponsive to conventional treatment with corticosteroids, antihistamines and epinephrine. She was successfully treated with icatibant licensed for treatment of hereditary angioedema...... knowing that both conditions involve bradykinin induced activation of bradykinin B2 receptors. Randomised, controlled trials are warranted to document the efficacy of icatibant in ACE-i angioedema....
Johansen, E C; Johansen, J B; Døssing, H
illustrate problems in the diagnosis and management of this life-threatening condition, and also demonstrate that angioedema re-occurs if the ACE inhibitor is not discontinued. If angioedema is suspected, therapy with any angiotensin converting-enzyme inhibitor should be discontinued promptly, respiratory...
Carlota Gutiérrez García-Rodrigo
Full Text Available We present a case of intense genital swelling because of a hereditary angioedema. This rare disease should be included in the differential diagnosis of acute and asymptomatic genital edema, because it may prevent future potentially life-threatening episodes of visceral angioedema.
Hereditary angioderma: an uncommon cause of acute abdomen. Abdominal computed tomography and ultrasound findings; Angioedema hereditario: una causa infrecuente de abdomen agudo. Hallazgos en la TC e ecografia abdominal
Cruz, R.A. de la; Oliver, J. M.; Bueno, A.; Albillos, J. C. [Fundacion Hospital Alcorcon. Madrid (Spain)
We present an uncommon case of acute abdomen in a patient with hereditary angioderma. The ultrasound and CT findings described may suggest this diagnosis, thus avoiding useless surgical interventions in patients in whom the disease has not been previously diagnosed. (Author) 19 refs.
... glomerular diseases. Narcolepsy. Huntington's Disease. Depression. Autism. Peripheral neuropathy.... Cancer and depression. Clotting disorders (e.g., hemophilia A (factor VIII deficiency) and von Willebrand... globulins (e.g., chronic inflammatory demyelinating polyneuropathy). Hereditary angioedema. Alpha-1...
Full Text Available |Oan#S38831641 PREDICTED: Ornithorhynchus anatinus similar to serpin peptidase inhibitor, clade G (C1 inhibitor), member 1, (angioede...ma, hereditary), (LOC100079402), partial mRNA /cds=p(1,9
Full Text Available |Oan#S38831641 PREDICTED: Ornithorhynchus anatinus similar to serpin peptidase inhibitor, clade G (C1 inhibitor), member 1, (angioede...ma, hereditary), (LOC100079402), partial mRNA /cds=p(1,9
... not well controlled with medicine Hives and angioedema Food allergies Skin rashes ( dermatitis ), in which the skin becomes ... prick test may also be used to diagnose food allergies. Intradermal tests are not used to test for ...
Jensen, O C; Bach, B
A case of arthritis and angioedema which developed on occupational exposure to formaldehyde in textiles is described. Possible pathological mechanisms are discussed. The suspicion that an unknown immunological reaction may be the cause is raised.......A case of arthritis and angioedema which developed on occupational exposure to formaldehyde in textiles is described. Possible pathological mechanisms are discussed. The suspicion that an unknown immunological reaction may be the cause is raised....
Joseph, Kusumam; Tholanikunnel, Baby G; Bygum, Anette
. Prolonged incubation of plasma deficient in both factor XII and C1-INH led to conversion of prekallikrein to kallikrein and cleavage of HK, as was seen in plasma from patients with hereditary angioedema but not plasma from healthy subjects. CONCLUSIONS: These results indicate that C1-INH stabilizes...... the prekallikrein-HK complex to prevent HK cleavage either by prekallikrein or by prekallikrein-HK autoactivation to generate kallikrein. In patients with hereditary angioedema, kallikrein and bradykinin formation can occur without invoking factor XII activation, although the kallikrein formed can rapidly activate...
Jignesh B Vaishnani
Full Text Available Malaria is an infectious disease caused by protozoa of the genus Plasmodium. Cutaneous lesions in malaria are rarely reported and include urticaria, angioedema, petechiae, purpura, and disseminated intravascular coagulation (DIC. Here, five malaria cases associated with cutaneous lesions have been described. Out of the five cases of malaria, two were associated with urticaria and angioedema, one case was associated with urticaria, and other two were associated with reticulated blotchy erythema with petechiae. Most of the cutaneous lesions in malaria were nonspecific and reflected the different immunopathological mechanism in malarial infection.
Rasmussen, Eva Rye; Mey, Kristianna; Bygum, Anette
A case of snoring-induced angioedema of uvula is described in a patient who was treated with ACE inhibitor. The patient partially responded to complement C1-inhibitor concentrate and did not suffer any recurrences after the medication was withdrawn. When encountering a patient suffering from...... swellings of the orofacial area it should be considered whether the mechanism is mast-cell associated or not, as classical antiallergic treatment is ineffective in non-mast-cell-associated disease (ie, bradykinin-mediated angioedema). Other causes of uvular oedema are also discussed....
Christiansen, Sandra C; Bygum, Anette; Banerji, Aleena
Availability of effective treatment for acute attacks is expected to transform the care of hereditary angioedema (HAE) patients. We felt that it would be of interest to test these assumptions by examining the perceptions of HAE patients regarding the impact that these therapies have had on their ......Availability of effective treatment for acute attacks is expected to transform the care of hereditary angioedema (HAE) patients. We felt that it would be of interest to test these assumptions by examining the perceptions of HAE patients regarding the impact that these therapies have had...
Litvyakova, L I; Bellanti, J A
BACKGROUND AND CONCLUSION: A case of a 41-year-old patient with a 5-year history of chronic recurrent angioedema, refractory to conservative treatment is presented. The results of the case report suggest that in differential diagnosis of angioedema, in addition to usual causes, the allergist-immunologist needs to consider Melkersson-Rosenthal syndrome, which can present with a variety of symptom-combinations of the classic triad. The distinguishing characteristics of the Melkersson-Rosenthal syndrome are its refractoriness to the usual anti-inflammatory therapy and the need to consider corrective cosmetic surgery, which may benefit some patients.
16. Soteres DF, El-Dahr JM. Reinstitution of methotrexate despite history of erythema multiforme and angioedema. Jr of Allergy and Clinical Immunology. 2004; 113: 312. 17. Schalock PC, Dinulos JGH, Pace N,. Schwarzenberger K, Wegner JK. Erythema multiforme due to. Mycoplasma pneumoniae infection in two children.
Acute poisoning by PPD causes characteristic severe angio-edema of the upper airway, often requiring tracheostomy, accompanied by a swollen, dry, hard and protruding tongue. PPD intoxication results in multisystem involvement and can cause rhabdomyolysis and acute kidney injury (AKI), flaccid paralysis, severe ...
Apr 4, 2018 ... of this case report is to describe the lifesaving use of a novel C1‑INH protein concentrate in a patient with mild‑to‑moderate dyspnea caused by swelling of the upper airway (larynx) and tongue. Keywords: C1 esterase inhibitor protein, hereditary angioedema, laryngeal edema, oropharyngeal swelling.
Lucinda J. Berglund
We describe the first reported case of repeated anaphylaxis after ingestion of Moringa oleifera, causing significant hypotension, angioedema and elevation of serum tryptase. Moringa oleifera seedpod was confirmed as the causative allergen by skin testing with the fresh pod. Moringa oleifera is widely consumed, both as a vegetable and in herbal medicines.
Fatal angioedema induced by angiotensin conversion enzyme (ACE) inhibitors · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. M Tiemensma, EH Burger, JJ Dempers, SA Wadee. http://dx.doi.org/10.1080/20786204.2010.10873974 ...
http://dx.doi.org/10.1080/20786204.2005.10873255 · Urticaria and angioedema: a practical approach. BA Muller, J Roy, A Lucille. Effectiveness and safety of newgeneration antihistamines in allergenic rhinitis and urticaria · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL ...
Overgaard Bach, Rasmus; Bygum, Anette
Hereditary angioedema (HAE) is a rare, but potentially life-threatening condition, clinically characterized by recurrent and self-limiting episodes of swelling which affect the skin, gastrointestinal tract and upper airways, and are caused by a lack of complement-C1-inhibitor (C1-INH). Within...
Ademola, A.D.. Vol 14, No 1 (2016) - Articles A case report of suspected angioedema in a child after administration of mebendazole, cotrimoxazole and leaf extracts. Abstract PDF. ISSN: 1597-1627. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL ...
Nasnas, R.; Awky, J.; Aoun, N.; Haddad, S.; Slaba, S.; Atallah, N. [Hotel Dieu de France, Beirut (Lebanon). Service de Maladies infectieuses, Service de Radiologie
We present a case of hereditary angioedema with cutaneous and intestinal manifestations mimicking as small bowel tumor on computed tomography, and in which unnecessary surgery was avoided by follow-up computed tomography. We discuss the pathophysiology, clinical and radiological manifestations of the disease, as well as its computed tomographic appearance. (authors)
Hereditary angioedema is an autosomal‑dominant disorder caused by mutation of the gene encoding the C1 esterase inhibitor (C1‑INH). It manifests as painless, nonpruritic, nonpitting episodic swelling of the subcutaneous tissues, gastrointestinal, and upper respiratory tracts in the absence of urticaria. An attack typically ...
Role of tropomyosin as a cross-reacting allergen in sensitization to cockroach in patients from Martinique (French Caribbean island) with a respiratory allergy to mite and a food allergy to crab and shrimp
Purohit, A.; Shao, J.; Degreef, J. M.; van Leeuwen, A.; van Ree, R.; Pauli, G.; de Blay, F.
BACKGROUND: Tropomyosin has been described as cross-reacting allergen between mite, cockroach and shrimp. METHODS: In 13 patients with asthma and/or rhinitis sensitized to mite and/or German cockroach and presenting urticaria, oral allergy syndrome or angio-edema upon eating shrimp and/or crab, we
The clinical manifestations of KD include per- sistent fever, non-purulent conjunctivitis, diffuse muco- sal inflammation, polymorphous skin rashes, indurative angioedema of the hands and feet, and non-suppurative cervical lymphadenopathy3. In about 20% of patients vasculitis will lead to coronary artery lesions as detect-.
Apr 4, 2018 ... concentrate in a patient with mild‑to‑moderate dyspnea caused by swelling of the upper airway (larynx) and tongue. Keywords: C1 esterase inhibitor protein, hereditary angioedema, laryngeal edema, oropharyngeal swelling. Usefulness of C1 Esterase Inhibitor Protein Concentrate in the. Management of ...
Urgert, M. C.; Van Den Elzen, M. T.; Tupker, R. A.; Franken, S. M.; Van Zuuren, E. J.; Knulst, A. C.
The Dutch Guideline on urticaria is currently being developed. Whilst awaiting the guideline, this article already discusses the classification and score system. Chronic urticaria is defined as the occurrence of spontaneous wheals, angioedema or both for a period of at least six weeks. In the
Full Text Available H01799 Vibratory urticaria; Vibratory angioedema Vibratory urticaria is a rare typ... headache. The histamine release that is associated with urticarias has implicated aberrant degranulation of... mast cells in their pathogenesis. A missense variant in ADGRE2 gene has been found in families with vibratory urticaria
oedema.. Case report. A 50-year-old woman presented to Tygerberg. Hospital, Cape Town, South Africa (SA), with dysuria, and suprapubic and lower abdominal pain. ... angio-oedema involving the face, lips and tongue, but .... Decloedt E, Freercks R, Maartens G. Cerebral angioedema associated with enalapril. Br J Clin.
Geenen, Joost W.; Baranova, Ekaterina V.; Asselbergs, Folkert W.; de Boer, Anthonius; Vreman, Rick A.; Palmer, Colin Na; Maitland-van der Zee, Anke H.; Hövels, Anke M.
Aim: To assess the required characteristics (cost, sensitivity and specificity) of a pharmacogenomic test for being a cost-effective prevention of angiotensin-converting enzyme inhibitors induced angioedema. Furthermore, we assessed the influence of only testing high-risk populations. Materials &
Full Text Available There have been multiple reports of allergic reactions associated with acute coronary syndromes. This has been classically described as Kounis syndrome. We present an unusual case of 70-year-old male with multiple prior hypersensitivity reactions and history of coronary artery bypass grafting who presented recurrent episode of severe angioedema and anaphylaxis. He responded to epinephrine but subsequently developed a non-ST elevation myocardial infarction with worsening heart failure. Our case is unique in that, unlike classic Kounis syndrome, the acute coronary event in this case did not present concurrently with the allergic reaction; rather it took nearly 48 hours to present. Subsequent angiogram revealed patent grafts and significant decline in the left ventricular systolic function as compared to his own ECHO a year ago. We postulate that slow mediators of inflammation may play a role in delayed development of acute coronary events with associated LV dysfunction following episodes of angioedema and anaphylaxis.
Nish, W A; Whisman, B A; Goetz, D W; Ramirez, D A
Annatto dye is an orange-yellow food coloring extracted from the seeds of the tree Bixa orellana. It is commonly used in cheeses, snack foods, beverages, and cereals. Previously reported adverse reactions associated with annatto dye have included urticaria and angioedema. We present a patient who developed urticaria, angioedema, and severe hypotension within 20 minutes following ingestion of milk and Fiber One cereal, which contained annatto dye. Subsequent skin tests to milk, wheat, and corn were negative. The patient had a strong positive skin test to annatto dye, while controls had no response. The nondialyzable fraction of annatto dye on SDS-PAGE demonstrated two protein staining bands in the range of 50 kD. Immunoblotting demonstrated patient IgE-specific for one of these bands, while controls showed no binding. Annatto dye may contain contaminating or residual seed proteins to which our patient developed IgE hypersensitivity. Annatto dye is a potential rare cause of anaphylaxis.
Tekin, Murat; Kati, Ismail
Melkersson Rosenthal Syndrome (MRS) is a rare disorder characterized by relapsing facial paralysis, persistent or recurrent orofacial edema, and lingua plicata. It may cause difficult airway, drug allergy, and angioedema. In our anesthetic management of two patients with MRS, preanesthetic immunological blood examination and skin tests for hypersensitivity to anesthetic drugs were applied. Because the principal goal is to avoid all factors that may stimulate, an allergic reaction, anesthetic drugs known to trigger urticaria were avoided. Body and operating room temperatures, changes of which may trigger allergic reactions, were kept constant during the perioperative period. Emergency precautions were taken for probable angioedema. MRS is a rare syndrome, and if its manifestations are misunderstood as simple facial paralysis, it may be overlooked by anesthesiologists. Anesthesiologists must be careful of several problems in patients with MRS.
Rasmussen, Finn (Odense University Hospital (Denmark). Department of Diagnostic Radiology); Antonsen, Steen (Odense University Hospital (Denmark). Department of Clinical Chemistry); Georgsen, Joergen (State University Hospital, Copenhagen (Denmark). Department of Clinical Immunology)
An anaphylactoid reaction following angiography with ioxaglate in a 59-year-old man implied generalized pruritis, angioedema, bronchospasm and hypotension. Leucocytosis and an increased number of neutrophils were observed from 90 min to 8 h after the reaction. Elevated values of the neutrophil specific enzymes elastase and lactoferrin were demonstrated . The concentrations of C3d and CH50 did not change which indicate that no complement activation took place. (author). 32 refs.; 1 fig.
Kulthanan, Kanokvalai; Tuchinda, Papapit; Chularojanamontri, Leena; Chanyachailert, Pattriya; Korkij, Wiwat; Chunharas, Amornsri; Wananukul, Siriwan; Limpongsanurak, Wanida; Benjaponpitak, Suwat; Wisuthsarewong, Wanee; Aunhachoke, Kobkul; Wessagowit, Vesarat; Chatchatee, Pantipa; Wattanakrai, Penpun; Jirapongsananuruk, Orathai; Klaewsongkram, Jettanong; Noppakun, Nopadon; Vichyanond, Pakit; Suthipinittharm, Puan; Ruxrungtham, Kiat; Singalavanija, Srisupalak; Ngamphaiboon, Jarungchit
Urticaria is a common skin condition that can compromise quality of life and may affect individual performance at work or school. Remission is common in majority of patients with acute spontaneous urticaria (ASU); however, in chronic cases, less than 50% had remission. Angioedema either alone or with urticaria is associated with a much lower remission rate. Proper investigation and treatment is thus required. This guideline, a joint development of the Dermatological Society of Thailand, the Allergy, Asthma, and Immunology Association of Thailand and the Pediatric Dermatological Society of Thailand, is graded and recommended based on published evidence and expert opinion. With simple algorithms, it is aimed to help guiding both adult and pediatric physicians to better managing patients who have urticaria with/without angioedema. Like other recent guideline, urticaria is classified into spontaneous versus inducible types. Patients present with angioedema or angioedema alone, drug association should be excluded, acetyl esterase inhibitors (ACEIs) and non-steroidal anti-inflammatory drugs (NSAIDs) in particular. Routine laboratory investigation is not cost-effective in chronic spontaneous urticaria (CSU), unless patients have clinical suggesting autoimmune diseases. Non-sedating H1-antihistamine is the first-line treatment for 2-4 weeks; if urticaria was not controlled, increasing the dose up to 4 times is recommended. Sedating first-generation antihistamines have not been proven more advantage than non-sedating antihistamines. The only strong evidence-based alternative regimen for CSU is an anti-IgE: omalizumab; due to very high cost it however might not be accessible in low-middle income countries. Non-pharmacotherapeutic means to minimize hyper-responsive skin are also important and recommended, such as prevention skin from drying, avoidance of hot shower, scrubbing, and excessive sun exposure.
Park, Kyung Hee; Yun, Il Seon; Choi, Soo-Young; Lee, Jae-Hyun; Hong, Chein-Soo; Park, Jung-Won
We experienced a case of immunoglobulin E (IgE) mediated anaphylaxis to levodropropizine. The patient was an 18-year old Korean woman. After taking the common cold medication including acetaminophen, domperidone, and levodropropizine, skin rash, angioedema and anaphylaxis were developed immediately. As she was tolerable to acetaminophen alone, we thought the culprit agent was maybe a levodropropizine tablet. To confirm the culprit, she underwent skin prick test and oral drug provocation test ...
M.P. Simón Díaz
Full Text Available Dermatologic emergencies represent about 8–20% of the diseases seen in the Emergency Department of hospitals. It is often a challenge for primary care physicians to differentiate mundane skin ailments from more serious, life threatening conditions that require immediate intervention. In this review we included the following conditions: Stevens-Johnson syndrome/toxic epidermal necrosis, pemphigus vulgaris, toxic shock syndrome, fasciitis necrotising, angioedema/urticaria, meningococcemia, Lyme disease and Rocky Mountain spotted fever.
Hide, Michihiro; Hiragun, Takaaki
Several guidelines for urticaria and angioedema have been published in Europe and United States since 1997. General principles for diagnosis and treatments of them are similar. However, each guideline has its own characteristics and shows differences in areas such as the coverage of urticaria subtypes, nomenclatures, and hierarchy of the medications. In Japan, the Japanese Dermatological Association (JDA) published its first guideline for urticaria and angioedema in 2005. It established a new classification of urticaria and angioedema together with the definition of each subtype. It emphasized the importance of discriminating idiopathic urticaria, consisting of acute urticaria and chronic urticaria from inducible urticaria, such as allergic urticaria, physical urticaria and cholinergic urticaria. It contains several unique algorithms for diagnosis and treatment of urticaria from a view point of clinical practices, and was further enforced by a style of EBM in 2011. Nevertheless, these guidelines have not been recognized outside of Japan, because of a language barrier. In this article, the outline of the newest guidelines by JDA are introduced and compared with the guidelines in other countries published in English.
Qualidade de vida em urticária crônica: inquérito em ambulatório público universitário, Botucatu (Brasil Quality of life in chronic urticaria: a survey at a public university outpatient clinic, Botucatu (Brazil
Maria Regina Cavariani Silvares
Full Text Available OBJETIVO: Avaliar o impacto da urticária crônica na qualidade de vida dos pacientes de ambulatório universitário a partir do questionário DLQI (Dermatology Life Quality Index. MÉTODOS: Inquérito sobre o impacto na qualidade de vida infligido pela urticária crônica a partir do questionário DLQI validado para a língua portuguesa. Pacientes foram entrevistados durante suas consultas em ambulatório especializado, entre maio de 2009 e maio de 2010, em serviço público brasileiro (Botucatu-SP. Os escores do DLQI foram analisados segundo subgrupos: idade, gênero, escolaridade, tempo de doença e presença de angioedema. RESULTADOS: Foram entrevistados 100 pacientes com urticária crônica. Predominou o gênero feminino (86%, a idade média foi de 41,8 anos, duração média da doença foi de seis anos e angioedema ocorreu em 82% dos pacientes. O escore médio do DLQI foi de 13,5, caracterizando grave impacto à qualidade de vida, superior a hanseníase, psoríase, eczema atópico e carcinoma basocelular. Presença de angioedema se associou a maiores escores: 14,5 x 9,9 (p OBJECTIVE: To evaluate the impact of chronic urticaria on quality of life of outpatients through the university questionnaire Dermatology Life Quality Index (DLQI. METHODS: Survey of the impact on quality of life caused by chronic urticaria, using the DLQI questionnaire validated for the Portuguese language. Patients were interviewed during visits to a specialized outpatient clinic between May 2009 and May 2010 at a Brazilian public service (Botucatu-SP. DLQI scores were analyzed according to the following subgroups: age, gender, education, disease duration, and presence of angioedema. RESULTS: We interviewed 100 patients with chronic urticaria. There was a female predominance (86%, mean age 41.8 years, mean disease duration of 6 years, and angioedema occurrence in 82% of patients. The mean DLQI score was 13.5, characterized by serious impact on quality of life, higher
Ana Paula Fusel de Ue
Full Text Available FUNDAMENTOS: A urticária crônica compromete o doente por interferir nas atividades diárias, prejudicar a autoestima e as relações interpessoais. Os profissionais de saúde subestimam seu impacto na qualidade de vida dos doentes. OBJETIVOS: Avaliar a qualidade de vida com questionário específico e genérico. Compará-la entre os tipos clínicos de urticária crônica e avaliar se o angioedema piora a qualidade de vida. MÉTODOS: Participaram 62 doentes com urticária crônica, com sinais e sintomas da doença até 7 dias da consulta, que foram divididos em urticária crônica comum, urticária crônica física e urticária crônica mista. RESULTADOS: Observou-se predominância de mulheres (72,6%, idade média de 39,8 anos, angioedema associado em 75,8% dos doentes. Apresentaram mais angioedema doentes com urticária crônica comum (p=0,011 e mulheres (p=0,024. Quanto aos tipos clínicos, 32,3% apresentaram urticária crônica comum, 27,4% urticária crônica física e 40,3% urticária crônica mista. O escore médio total do questionário específico foi 10,4. No questionário específico, os domínios mais comprometidos foram "Sintomas e sentimentos" e "Atividades diárias", e, no SF-36, "Aspectos físicos" e "Vitalidade". Houve comprometimento da qualidade de vida nas mulheres, nos doentes com até 30 anos, em primeira consulta, nos mais escolarizados, naqueles com até 1 ano de doença e naqueles com angioedema. CONCLUSÃO: A urticária crônica compromete a qualidade de vida medida pelos questionários específico e genérico. Não houve diferença estatisticamente significante na qualidade de vida entre os tipos clínicos. A presença do angioedema conferiu pior qualidade de vida aos doentes. Houve correlação estatisticamente significante entre os escores do questionário específico e do questionário genérico.BACKGROUND: Chronic urticaria affects patients by interfering with their daily activities, damaging their self-esteem and
Otto, Hans F; England, Ronald W; Quinn, James M
Few studies have examined inpatient referral patterns for fellowship training programs and none for allergy/immunology (AI) since 2003. The primary end point was the reason for consultation, and secondary end points included the AI diagnosis made and outcomes. We retrospectively reviewed all inpatient AI consultations from July 1, 2001 through June 30, 2007. These 6 years of data were combined with 14 years of data examining the reason for consult from a previous study. The data were analyzed for trends and changes over the entire 20-year period. A total of 254 AI inpatient consults were reviewed over the 6 years studied. Thirty-six percent (92/254) of inpatient consults were for evaluation of adverse drug reactions (ADRs), 22% (55/254) miscellaneous reasons, 17% (43/254) urticaria/angioedema, 13% (32/254) for possible immunodeficiency, 9% (23/254) for anaphylaxis, and 3% (8/254) for asthma. AI inpatient consults show a significant decline over the recent 6-year period (p = 0.0023) despite stable total hospital admissions since 1998. Over the last 20 years, an 85% decrease (p < 0.00001) in inpatient asthma consults and increases (p < 0.05) in immunodeficiency, rash, and urticaria/angioedema evaluations have been observed. Not following AI recommendations resulted in a 16.6 odds ratio (95% CI, 5.55-49.93) that a patient's clinical status would be worse or unchanged. Inpatient AI consults have declined with associated reduction in asthma inpatient consults. Although ADRs and anaphylaxis consults have been stable, evaluations for immunodeficiency, rash, and urticaria/angioedema have increased. Following inpatient AI recommendations is associated with improved patient outcomes.
Kasperska-Zajac, A; Jarząb, J; Żerdzińska, A; Bąk, K; Grzanka, A
Despite the excellent efficacy and safety profile of omalizumab in chronic spontaneous urticaria (CSU), there are scarce data concerning its role in the treatment of refractory cases with different phenotypes of urticaria. We describe our experience with the therapy of nine patients with CSU co-existing with delayed pressure urticaria (DPU) or angioedema or both and refractory to treatment with high-dose antihistamines. The first patient, with severe CSU and recurrent angioedema, did not respond well to cyclosporine A or corticosteroids and suffered from numerous side effects of long-term corticosteroid therapy. The second patient presented with severe symptoms of DPU, which first of all prevented any daily activities of the professional routines. Both patients showed a complete remission of urticaria after the first injection of omalizumab. The third patient with CSU and severe DPU had been ineffectively treated for more than 20 years with various medications. Following the administration of omalizumab, the symptoms of CSU subsided but those of DPU intensified, and the drug was withdrawn after two cycles. In another four patients with refractory CSU and angioedema, the symptoms subsided after the first administration of omalizumab, and the patients have been in remission for about 5 weeks. In the remaining two patients, the symptoms did not resolve despite four 300 mg doses of omalizumab. It is important to establish a therapeutic regimen with omalizumab (150-300 mg; every 4-8 weeks) tailored to individual patient's needs and dependent on the type of urticaria; this may minimize unnecessary the medication exposure, adverse drug effects, and healthcare costs. © The Author(s) 2015.
Full Text Available Ayad K AliDepartment of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USABackground: The purpose of this study was to examine the postmarketing safety profile of aliskiren hemifumarate, a first-in-class direct renin inhibitor.Methods: The US Adverse Event Reporting System (AERS was utilized to conduct a retrospective pharmacovigilance analysis by applying the Multi-item Gamma Poisson Shrinker data mining algorithm to calculate empiric Bayes geometric mean (EBGM values of aliskiren-related adverse event reports. Reports received from January 2007 through December 2008 are included in this analysis.Results: In total, 1592 reports for aliskiren are identified in the AERS. Aliskiren was associated with reports of angioedema (EBGM 3.9, 95% confidence interval [CI] 3.2–4.7 and renal dysfunction (EBGM 3.4, 95% CI 2.6–4.5. Reports of hyperkalemia, dry cough, and diarrhea were also linked to aliskiren (EBGM 7.4, 95% CI 3.4–13.0, EBGM 11.0, 95% CI 7.8–14.2, EBGM 4.3, 95% CI 3.2–5.8, respectively.Conclusion: Angioedema and renal dysfunction are potential adverse events associated with exposure to aliskiren. Patients with signs and symptoms of angioedema should stop aliskiren and seek urgent medical help. Aliskiren should not be used by patients with a risk of renal impairment. Additional studies are warranted to quantify further the risk of these events in patients with hypertension.Keywords: aliskiren, postmarketing safety surveillance, adverse event reporting system
Buquicchio, Rosalba; Ventura, Maria T; Traetta, Pier L; Nenna, Saverio; Iadarola, Giuseppe; Magrone, Thea
Allergy to Anisakis simplex (s.) is spreading due to the increased consumption of raw, smoked or marinated fish. In man, Anisakis s. can directly attack the gastrointestinal mucosa, provoking a parasitosis known as anisakiasis, or giving rise to the formation of IgE and, finally, inducing IgE-mediated reactions like urticaria, angioedema and anaphylactic shock. During recent years, a dietary approach to Anisakis s. infestation has also been addressed. A total of 620 patients with urticaria, angioedema, or both and a history of anaphylaxis following consumption of raw, smoked or marinated fish were recruited, evaluated for specific IgE levels to Anisakis s. and subjected to Skin Prick test. Following 18 month fish-free diet, patients were reevaluated at 6, 12 and 18 months, respectively. Patients undergoing diet were selected among those who had a clinical history with multiple accesses to first aid. After 6-month fish-free diet, we recorded an improvement of symptoms and a remarkable reduction of specific IgE levels. The extension of the diet over 6 months in some cases resulted in a further reduction of specific IgE levels. Data obtained confirm the importance of a fish-free diet in patients with severe symptoms since a new antigenic exposure coincides with a relapse of symptoms and increased IgE levels. This last point should be kept in mind and carefully evaluated in patients at risk for anaphylaxis or angioedema. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Zariquiey-Esteva, G; Santa-Candela, P
The care plan of a 42-year-old woman with anaphylactic shock, secondary to ingestion of amoxicillin/clavulanic acid, with upper airway involvement due to laryngeal angioedema, is presented. Previously she had had two episodes of angioedema of unknown origin. The incidence of this phenomenon is between 3.2 and 10 cases/100,000 people/year. An evaluation was made and three altered necessities stood out: breathing and circulation (she needed mechanical ventilation and noradrenalin perfusion), elimination (she required furosemide to keep an acceptable diuresis time), and hygiene and skin protection (she presented generalised hyperaemia, lip, lingual and oropharyngeal oedema). The hospital's Clinical Research Ethics Committee requested the patient's informed consent to access her clinical history. According to the altered necessities, seven diagnoses were prioritised according to NANDA taxonomy: risk of allergic response, risk of infection, risk of ineffective renal perfusion, decreased cardiac output, impaired spontaneous ventilation, risk of unstable blood glucose level, and risk of dysfunctional gastrointestinal motility. Scores of outcome criteria showed a favourable evolution after 24hours. The development of a standardised NANDA-NOC-NIC language in the clinical case presented allowed us to organise the nursing work, facilitating recording and normalising clinical practice. As a limitation of this case, we didn't have serial plasma levels of histamine and tryptase to assess the evolution of anaphylactic symptoms. Highlight the importance of health education in a patient with a history of angioedema. Copyright © 2016 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Publicado por Elsevier España, S.L.U. All rights reserved.
Nonallergic hypersensitivity to nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, radiocontrast media, local anesthetics, volume substitutes and medications used in general anesthesia.
Jurakić Toncić, Ruzica; Marinović, Branka; Lipozencić, Jasna
Urticaria and angioedema are common allergic manifestations and medications are one of common triggering factors. The most severe immediate drug reaction is anaphylaxis. Apart from the well established IgE-mediated immediate type hypersensitivity reactions, the pathogenesis of drug-induced urticaria, angioedema and anaphylaxis often remains obscure. In this article, emphasis is put on nonallergic reactions to the most commonly used drug groups of nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, radiocontrast media, volume expanders and drugs used in general anesthesia. Urticaria is the second most common drug eruption after maculopapular exanthema. The mechanisms of acute urticarial reactions are multiple, mostly IgE mediated, but some drugs can induce immune complex reactions and activate complement cascade, while others can induce direct activation of mast cells and degranulation or activation of complement by non-immune mechanisms. With different types of medications different pathomechanisms are involved. Non-steroid anti-inflammatory drugs are thought to cause reaction due to cyclooxygenase-1 inhibition and overproduction of leukotrienes, blamed for cutaneous and respiratory symptoms. Angiotensin-converting enzyme inhibitors can cause fatal angioedema, which is partially explained with bradykinin excess and impairment of aminopeptidase P and dipeptidyl peptidase IV that are involved in the metabolism of substance P and bradykinin. It remains unknown what additional mechanisms are involved. Radiocontrast media and local anesthetics mostly cause nonallergic hypersensitivity reaction, but in rare cases true allergic reaction can occur. Dextran is known to cause IgG mediated, immune complex anaphylaxis and it is recommended to use human serum albumin as the safest colloid.
Full Text Available Background and Design: To determine the clinical and etiological features of inpatients with acute urticaria and angioedema and to assess the need for laboratory tests. Material and Methods: We recruited 105 patients with acute urticaria and angioedema who were admitted to our inpatient unit. The lesions and the characteristics of the patients were analyzed. Routine diagnostic tests including complete blood count, thyroid function tests, hepatitis panel, stool parasite, total IgE levels, cultures, erythrocyte sedimentation rate, C-reactive protein, anti-nuclear antibody, and posterior anterior lung X-ray were ordered. A psychiatric consultation was obtained, when needed. The results were analyzed with SPSS 15.0 statistical software.Results: Among 105 patients, 28 (26.7% had urticaria, 7 (6.7% had angioedema, and 70 (66.7% suffered from both urticaria and angioedema. The most common accompanying symptoms were itching (91.4% and burning (34.3%. The most common systemic symptoms were fatigue (15.2% and headache (12.4%. The lesions usually appeared in the evening hours (24.8%. Twenty-five patients were waking up due to itching during the night. Some lesions were associated with physical activities. Systemic diseases accompanied the lesions in 12 patients (11%. In terms of etiological factors, 33 patients (22.5% had infections. Food- related lesions were encountered in 14 (13% patients. Thirty patients (28.5% had history of medication use. Stress was detected in 37.1% of the patients; anxiety was diagnosed in 3% of patients. The stool was positive for parasites in 10 (9% patients. Conclusion: Acute urticaria is a benign disorder. Although the underlying cause of urticaria can not always be identified, infections and medications are the most common causes. A comprehensive and detailed history is very important to discover the underlying cause. The diagnostic tests should be ordered according to the patient’s history. Conducting diagnostic tests
Full Text Available Cold urticaria consists of an allergic immune response to cold temperatures with symptoms ranging from pruritic wheals to life-threatening angioedema, bronchospasm, or anaphylactic shock. Adequate planning to maintain normothermia perioperatively is vital due to impaired hypothalamic thermoregulation and overall depression of sympathetic outflow during deep sedation and general anesthesia. This case report describes the successful perioperative management of a 45-year-old female with a history of cold urticaria undergoing a laparoscopic Nissen fundoplication for refractory gastroesophageal reflux disease and discusses how to appropriately optimize the care of these patients.
R. F. J. Criado
Full Text Available Chronic urticaria and concurrent angioedema are disappoiting problems for both physicians and patients. The disease can result from multiple causes and probably does not have a single etiology. Several factors have been identified that appear to be important in the pathogenesis of individual cases, some drugs, food additives, physical factors and internal diseases. In some cases no pathogenesis are identified and those cases are classified as idiopathic. In recent years several articles has emphasized autoimmunity and infections due to Helicobacter pylori. Our article reviewed the etiology of chronic urticaria at current concepts.
Rho, Young Hee; Woo, Jin-Hyun; Choi, Seong Jae; Lee, Young Ho; Ji, Jong Dae; Song, Gwan Gyu
Lupus is a systemic autoimmune disease of an unknown origin, and systemic lupus erythematosus (SLE) can be triggered by numerous stimuli. Bee venom therapy is an alternative therapy that is believed to be effective for various kinds of arthritis. We present here a case of a 49-year-old female who experienced a new onset lupus after undergoing bee venom therapy, and this looked like a case of angioedema. The patient was successfully treated with high dose steroids and antimalarial drugs. We discuss the possibility of bee venom contributing to the development of SLE, and we suggest that such treatment should be avoided in patients with lupus.
Misbah Nasheela Ghazanfar
Full Text Available Chronic spontaneous urticaria is an itching skin disease characterised by wheals, angioedema, or both present for more than six weeks. Omalizumab is a humanized anti-IgE monoclonal antibody recently approved for treatment of chronic urticaria. Several randomised controlled trials have investigated the safety, tolerability, and efficacy of omalizumab for chronic urticaria. The safety of omalizumab in pregnancy is not known. We describe a female patient with chronic spontaneous urticaria who was treated with omalizumab continuously through two consecutive pregnancies with convincing results and no apparent toxicity.
Ghazanfar, Misbah Nasheela; Thomsen, Simon Francis
Purpose of Review The purpose of this study was to review real-life studies on effectiveness and safety of omalizumab in chronic urticaria (CU). Recent Findings CU is an itching skin disease characterized by wheals, angioedema, or both (present >6 weeks). Omalizumab is a humanized anti...... of 7–82 years, on the effectiveness and safety of omalizumab used for CU since 2013. A complete response to omalizumab was seen among 64% of the patients, whereas 25% obtained partial response. On average, 15% had no or very limited response. Fifteen patients from five studies reported side effects....... Overall, omalizumab was effective and well-tolerated for patients with antihistamine-resistant CU....
Ghazanfar, Misbah Nasheela; Thomsen, Simon Francis
Chronic spontaneous urticaria is an itching skin disease characterised by wheals, angioedema, or both present for more than six weeks. Omalizumab is a humanized anti-IgE monoclonal antibody recently approved for treatment of chronic urticaria. Several randomised controlled trials have investigated...... the safety, tolerability, and efficacy of omalizumab for chronic urticaria. The safety of omalizumab in pregnancy is not known. We describe a female patient with chronic spontaneous urticaria who was treated with omalizumab continuously through two consecutive pregnancies with convincing results...
Full Text Available Chronic urticaria is a spontaneous or inducible group of diseases characterized by the occurrence of wheals (and, in about half of cases, angioedema for more than 6 weeks. These are rather frequent conditions that may severely affect patients' quality of life and sometimes represent a challenge for doctors as well. The causes of chronic urticaria are still poorly defined, although there is growing evidence that different biologic systems including immunity, inflammation, and coagulation may take part in the pathomechanism eventually leading to mast cell and basophil degranulation and hence to wheal formation. This review will discuss the main findings that are (slowly shedding light on the pathogenesis of this disorder.
Full Text Available Blepharochalasis is a disorder characterized by recurrent episodes of painless edema of the eyelid skin, which leads to atrophy and relaxation of the eyelid structures and ptosis. The condition typically manifests itself in childhood or adolescence. The author reported a 16-year-old girl who has been suffered from recurrent painless swelling episodes on the upper eyelids for three years and laxity and wrinkling predominantly on the right upper eyelid for one year. This case was presented for the disorder is a rarely encountered disease and may easily misdiagnosed as recurrent angioedema, especially in its early stage.
Kring Tannert, Line; Stahl Skov, Per; Bjerremann Jensen, Louise
Cold urticaria is a skin condition characterized by rapid appearance of itchy wheals and occasionally angioedema in response to cold stimulation. Antihistamines do not sufficiently protect all patients from symptoms, even when used in higher than standard doses. In these patients, desensitization...... to cold can be beneficial. The aim was to investigate whether desensitization can lower temperature thresholds and reduce release of histamine in the skin. Cold urticaria patients were subjected to desensitization and assessed for skin responses to cold stimulation and codeine before and after. Histamine...... prevented histamine release after skin exposure to cold. Surprisingly, skin histamine levels and release after codeine injection were found to be normal in desensitized patients....
Axelsson, Anna; Iversen, Kasper; Vejlstrup, Niels
18 years and older) with obstructive or non-obstructive hypertrophic cardiomyopathy were randomly assigned via computer-based system to losartan (100 mg per day) or placebo for 12 months. Patients and investigators were masked to assigned treatment. The primary endpoint was change in left ventricular......·0001) confirmed drug compliance; blood pressure did not decrease in the placebo group. Two (2%) patients, both in the placebo group, died from sudden cardiac death during follow-up. In the losartan group, one (1%) patient had angioedema, one (1%) had deterioration of renal function, and one (1%) had hyperkalaemia...
Maurer, M; Staubach, P; Raap, U; Richter-Huhn, G; Bauer, A; Ruëff, F; Jakob, T; Yazdi, A S; Mahler, V; Wagner, N; Lippert, U; Hillen, U; Schwinn, A; Pawlak, M; Behnke, N; Chaouche, K; Chapman-Rothe, N
Most data on chronic spontaneous urticaria (CSU) originate from highly selected patient populations treated at specialized centres. Little is known about CSU patient characteristics and the burden of CSU in routine clinical practice. AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is an ongoing global study designed to assess chronic urticaria in the real-life setting. To describe the baseline characteristics of the first 1539 German AWARE patients with H1-antihistamine-refractory CSU. This prospective non-interventional study included patients (18-75 years) with a diagnosis of H1-antihistamine-refractory CSU for > 2 months. Baseline demographic and disease characteristics, comorbidities, and pharmacological treatments were recorded. Quality of life (QoL) was assessed using the dermatology life quality index (DLQI), chronic urticaria QoL questionnaire (CU-Q 2 oL), and angioedema QoL questionnaire (AE-QoL, in cases of angioedema). Previous healthcare resource utilization and sick leave data were collected retrospectively. Between March and December 2014, 1539 patients were assessed in 256 sites across Germany. The percentage of females, mean age, and mean body mass index were 70%, 46.3 years, and 27 kg/m 2 , respectively. The mean urticaria control test score was 7.9, one in two patients had angioedema, and the most frequent comorbidities were chronic inducible urticaria (CIndU; 24%), allergic rhinitis (18.2%), hypertension (18.1%), asthma (12%), and depression (9.5%). Overall, 57.6% of patients were receiving at least one pharmacological treatment including second-generation H1-antihistamines (46.3%), first-generation H1-antihistamines (9.1%), and corticosteroids (15.8%). The mean DLQI, total CU-Q 2 oL, and total AE-QoL scores were 8.3, 36.2, and 46.8, respectively. CSU patients reported frequent use of healthcare resources, including emergency services (29.7%), general practitioners (71.9%), and additional allergists or
Diego S. Fernández Romero; Alejandro Malbrán
La urticaria crónica es una enfermedad frecuente, caracterizada por la presencia de ronchas y/o angioedema con una duración superior a las 6 semanas. En un número importante de pacientes se comporta como una enfermedad autoinmune asociada frecuentemente con alteraciones en la función tiroidea y con la presencia de anticuerpos antitiroideos. Presentamos una serie de 70 pacientes consecutivos con diagnóstico de urticaria crónica a los cuales les investigamos la función tiroidea y la presencia d...
Soriano Hern??ndez, Isabel; Orgaz Molina, Jacinto; Arias Santiago, Salvador; El-Ahmed, Husein; Ortego-Centeno, Norberto; Callejas, Jos?? L.; Fern??ndez Pugnaire, M. Antonia; Naranjo Sintes, Ram??n Jos??
La urticaria vasculitis es una enfermedad cr??nica que se caracteriza por episodios urticariales o de angioedema que puede asociarse a niveles bajos de complemento. Hemos realizado un estudio descriptivo retrospectivo que incluye a 20 pacientes con urticaria vasculitis diagnosticados en los ??ltimos 5 a??os donde analizamos los s??ntomas m??s frecuentes y los tratamientos que se han empleado. A continuaci??n se ha dise??ado un protocolo diagn??stico-terap??utico de Urticaria Vascu...
Park, Kyung Hee; Yun, Il Seon; Choi, Soo-Young; Lee, Jae-Hyun; Hong, Chein-Soo; Park, Jung-Won
We experienced a case of immunoglobulin E (IgE) mediated anaphylaxis to levodropropizine. The patient was an 18-year old Korean woman. After taking the common cold medication including acetaminophen, domperidone, and levodropropizine, skin rash, angioedema and anaphylaxis were developed immediately. As she was tolerable to acetaminophen alone, we thought the culprit agent was maybe a levodropropizine tablet. To confirm the culprit, she underwent skin prick test and oral drug provocation test with the suspected one. Finally we detected levodropropizine specific IgE and confirmed the specificity by inhibition enzyme-linked immunosorbent assay (ELISA).
Full Text Available Atrial fibrillation (AF is the most common observed arrhythmia in clinical practice. In the literature, AF events associated with drug induction are available. Cetirizine is a second-generation histamine antagonist used in the treatment of allergies, angioedema, and urticaria. We wish to present an atypical case who took cetirizine medication for relieving symptoms of upper tract respiratory system infection, experienced rapid ventricular response AF and treated successfully. To best of our knowledge, this is the first case of cetirizine-induced AF.
Christel Bolte, M.
Las drogas son sustancias químicas que pueden interferir con el sistema inmune y a veces conducen a reacciones inusuales y severas. Éstas pueden amenazar la vida, requerir hospitalizaciones prolongadas o dejar secuelas significativas. Cerca del 2% de las reacciones cutáneas inducidas por fármacos se consideran graves. Estas son el angioedema, el shock anafiláctico, el síndrome de Stevens-Johnson (SSJ), la necrolisis epidérmica tóxica (NET), y el síndrome de hipersensibilidad (DRESS), entre ot...
Deckert, James; Deckert, Linda
Vocal cord dysfunction involves inappropriate vocal cord motion that produces partial airway obstruction. Patients may present with respiratory distress that is often mistakenly diagnosed as asthma. Exercise, psychological conditions, airborne irritants, rhinosinusitis, gastroesophageal reflux disease, or use of certain medications may trigger vocal cord dysfunction. The differential diagnosis includes asthma, angioedema, vocal cord tumors, and vocal cord paralysis. Pulmonary function testing with a flow-volume loop and flexible laryngoscopy are valuable diagnostic tests for confirming vocal cord dysfunction. Treatment of acute episodes includes reassurance, breathing instruction, and use of a helium and oxygen mixture (heliox). Long-term management strategies include treatment for symptom triggers and speech therapy.
Ward, David Ian
On the last night of disaster relief operations in Sumatra, Indonesia, a mass casualty event occurred that involved deployed Australian Defence Force personnel. Symptoms of acute urticaria, angioedema, wheeze and gastrointestinal upset were experienced to varying degrees by 16% of the deployed element. The present report describes a presumed scombroid poisoning cluster and demonstrates the difficulties of operating in a deployed environment, the confusion that might be associated with evolving non-kinetic mass casualties, and provides a learning opportunity for an unusual mass casualty incident. © 2011 The Author. EMA © 2011 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.
Shen, Y; Hong, S L; Zhang, M; Ke, X
Objective: To investigate the systemic adverse effects of specific subcutaneous immunotherapy (SCIT) in patients with allergic rhinitis (AR) and explore the possible risk factors. Methods: A retrospective study was conducted on AR patients who underwent SCIT from January 2014 to January 2017 in Department of Otorhinolaryngology, the First Affiliated Hospital of Chongqing Medical University. For patients with adverse reactions, the detailed medical history during treatment was reviewed. Results: A total of 1608 injections were performed on 102 patients, there were 12 cases / 21 times systemic adverse events, including systemic urticaria, angioedema and Grade Ⅰ systemic adverse reactions. There were 3 cases of grade Ⅳ adverse reactions. Systemic adverse reaction was prone to an initial treatment phase where the dose and concentration of the injection were increasing. Meanwhile, it was more common in young patients aged 20-40 years old and easy to occur in May and June. About the possible risk factors, the most common one was obvious local adverse reactions (17/21), followed by prolonged injection interval (9/21), the recent exposure to a large number of allergens (7/21) and strong positive skin prick results (7/21). Conclusions: The systemic adverse effects, which were induced by SCIT, mainly included systemic urticaria, angioedema and Grade Ⅰ systemic adverse reactions. Systemic adverse reaction was prone to an initial treatment phase where the dose and concentration of the injection were increasing.
Giménez-Arnau, Ana M
Chronic spontaneous urticaria (CSU) is characterized by the recurrence of itchy hives and/or angioedema for greater than six weeks, with no known external trigger. Omalizumab, a humanized, recombinant, monoclonal anti-IgE antibody, is the only approved add-on therapy for H1-antihistamine refractory CSU patients. Areas covered: The objective of this article is to discuss the mechanism of action, pharmacokinetics and pharmacodynamics of omalizumab for the treatment of CSU. The review also summarizes efficacy and safety data from proof-of-concept, phase II (X-CUISITE, MYSTIQUE), and pivotal phase III omalizumab studies (ASTERIA I, ASTERIA II, and GLACIAL). Expert opinion: Omalizumab is a clinically effective and safe biological therapy for treating H1-antihistamine refractory CSU patients. It significantly reduces CSU symptoms (hives, itch and angioedema), and improves patient health-related quality of life. While omalizumab is already integral to the treatment of antihistamine refractory CSU, widespread use will depend on legal and economic factors, as well as improvements in the early and accurate diagnosis of CSU patients who would benefit from treatment.
Sussman, G L; Dorian, W
Allergic reactions from handling psyllium have been reported since 1970. Health professionals and workers in laxative-manufacturing plants are at greatest risk. Sensitized people are at risk of life-threatening anaphylactic reactions. Two illustrative cases are presented. The first is A 39-year-old female dialysis nurse with a 3-year history of nasal and eye symptoms from exposure to psyllium. She obtained an over-the-counter psyllium bulk laxative, took it for constipation and developed flushing, tachycardia, urticaria, angioedema, laryngeal edema, and lightheadedness. An epicutaneous skin test and radioallergosorbent test for psyllium were both strongly positive. The second is a 42-year-old female nurse with a history of asthma who had allergic nasal and eye symptoms while dispensing psyllium. She received a prescription for crystallized psyllium, took it by mouth, and developed immediate flushing, tachycardia, urticaria, and angioedema. With subsequent ingestion of psyllium she had, in addition, severe wheezing, lightheadedness, and loss of consciousness. A psyllium epicutaneous skin test was strongly positive. These patient reports illustrate the risk of severe allergic reactions in sensitized people. Ingestion by sensitized people, such as from a routine postoperative and postpartum order, is potentially dangerous.
Gonzalez, Meera N; Weston, Brian; Yuce, Tarik K; Carey, Ann M; Barnette, Rodger E; Goldberg, Amy; McNamara, Robert M
At our institution, there were a number of adverse patient events related to an unstable airway that led to the formation of a designated critical airway response team (CAT). It was hoped that this would improve patient outcomes in such matters. Our aim was to evaluate the impact of the creation of the CAT. A review of the activations of the CAT for 1 year was conducted. We reviewed 51 CAT activations, the majority (71%) occurred in the emergency department (ED) and the most common reasons for activation were angioedema (41%) and epiglottitis (12%). Fiber optic intubation was the most common method used to secure the airway, 22% of the cases were transported to the operating room for management. Only one surgical airway was required and no adverse outcome related to the airway occurred in the studied group. The creation of a critical airway has been considered a success in terms of patient management at our institution. It has been most commonly used in the management of life-threatening angioedema in the ED. Copyright © 2016 Elsevier Inc. All rights reserved.
Patra, Ambika Prasad; Shaha, Kusa Kumar; Rayamane, Anand P; Dash, Shreemanta Kumar; Mohanty, Manoj Kumar; Mohanty, Sachidananda
Paraphenylenediamine poisoning is among one of the emerging causes of poisoning in Asian countries, because it is a constituent of hair dye formulations and is easily available in market at low cost. Hair dyes are rampantly used in Asian households compared with the western world. Locally, hair dye constituents may have allergic adverse effects, and acute systemic poisoning presents with characteristic angioedema, upper airway obstruction, rhabdomyolysis, methemoglobinemia, myoglobinuria, and acute renal failure. This study reports about the death of a 24-year-old Indian housewife who committed suicide by taking hair dye emulsion. She had an argument with her husband, and because of fit of rage, took a bowlful (80 mL) of hair dye emulsion kept prepared for the use by husband. She developed angioedema, cervical swelling, and rhabdomyolysis and died of acute renal failure within 24 hours. Toxicological analysis of viscera and blood revealed varying levels of paraphenylenediamine. Histopathological samples of kidney showed features of acute tubular necrosis and myoglobin casts in renal tubules. The aim of the study is to create awareness about the adverse effects of the hair dye, its poisoning outcome, and possible preventive measures.
Sande, Margaret; Thompson, David; Monte, Andrew A
Ingestion of ethanol in the presence of disulfiram may cause a histamine-like reaction due to accumulation of acetaldehyde. These disulfiram-ethanol reactions (DERs) are manifested by hypotension, tachycardia, gastritis, and angioedema. Fomepizole, an inhibitor of alcohol dehydrogenase, may halt progression of this reaction by blocking ethanol metabolism to acetaldehyde. We present 2 cases of disulfiram and alcohol overdose leading to severe reactions unresponsive to fluid resuscitation and treated with a single dose of fomepizole. Case 1: A 20-year-old woman presented after ingestion of vodka and disulfiram. After 11 hours of resuscitation, she had skin flushing, lip swelling, tachycardia, and hypotension. Antihistamines, steroids, and an additional 2 L of normal saline were given without improvement. Fomepizole 15 mg/kg was given with improvement within 1.5 hours, and she was ultimately discharged with no clinical sequelae. Case 2: A 47-year-old woman presented after overdose of vodka and disulfiram. She was tachycardic and hypotensive upon presentation. After administration of 3 L of normal saline, she remained hypotensive and tachycardic. One dose of fomepizole 15 mg/kg was given. Within 1 hour following fomepizole infusion, her blood pressure and heart rate normalized, and she had no further sequelae from her ingestion. Fomepizole may be a safe and effective treatment of severe DERs. We suggest that 1 dose of fomepizole for severe DERs with hypotension unresponsive to fluid resuscitation or for angioedema unresponsive to antihistamines be administered.
Williams, Paul; Kavati, Abhishek; Pilon, Dominic; Xiao, Yongling; Zhdanava, Maryia; Balp, Maria-Magdalena; Lefebvre, Patrick; Ortiz, Benjamin; Hernandez-Trujillo, Vivian
Chronic idiopathic urticaria (CIU)/spontaneous urticaria (CSU) is defined by the presence of wheals, angioedema, or both for ≥6 weeks, with or without an identifiable trigger. Real-world health care data among children with CIU/CSU remain scarce. To describe treatment patterns, health care resource utilization (HRU), and costs in pediatric patients with CIU/CSU (<12 years old) and to compare these with pediatric patients without CIU/CSU. A commercial administrative claims data base (September 2013 to June 2016) was used. The CIU/CSU cohort included pediatric patients with either two or more claims for a diagnosis of urticaria ≥6 weeks apart or one or more claims for a diagnosis of urticaria and one or more claims for a diagnosis of angioedema ≥6 weeks apart (index was defined as the first claim). The control cohort comprised pediatric patients without urticaria or angioedema (index randomly assigned). Patients with <6 months of eligibility before and after the index date were excluded. HRU and costs were compared between the cohorts during the observation period after propensity score matching. A total of 6109 pediatric patients with CIU/CSU were selected, and 6107 were 1:1 matched with controls. The patients with CIU/CSU who had a mean ± standard deviation age of 4.58 ± 3.36 years, and 47.9% were girls. CIU/CSU-related medication use increased after diagnosis (e.g., baseline versus 6-month follow-up, 2.2 versus 8.0% for nonsedating prescription H1 antihistamines; 7.4 versus 17.4% for oral corticosteroids). Relative to the controls, the patients with CIU/CSU had higher rates of HRU (incidence rate ratios of 1.71, 2.39, and 2.07 for inpatient, emergency department, and outpatient visits, respectively; all p < 0.01), and higher all-cause per patient per year costs (mean cost differences of $2090, $1606, and $483 for total, medical, and pharmacy costs, respectively; all p < 0.01). This study highlighted unmet needs in pediatric patients with CIU/CSU who had
Full Text Available Endurance exercise after orange ingestion cause anaphylaxis which is food-dependent exercise-induced anaphylaxis (FDEIA which is a form of exercise-induced anaphylaxis. In this article, an individual develops symptoms such as flushing, itching, urticaria, angioedema, and wheezing after eating a food allergen and proceeds to exercise. Neither the food alone nor exercise alone is sufficient to induce a reaction. This case report describes a 36-year-old asthmatic male athlete who experienced nausea, vomiting, flushing, urticaria, and facial swelling while exercising in a gymnasium after eating oranges. Neither oranges alone nor exercise alone induced the reaction. Total avoidance of suspected food allergens would be ideal. Persons with FDEIA should keep at hand an emergency kit with antihistamines, injectable rapid action corticoids, and adrenaline.
Nath, Proggananda; Basher, Ariful; Harada, Michiyo; Sarkar, Santana; Selim, Shahjada; Maude, Richard J; Noiri, Eisei; Faiz, Abul
Liposomal amphotericin-B (AmBisome) is now becoming first choice for the treatment of visceral leishmaniasis (kala-azar) patients due to high efficacy and less toxicity. The reported incidence of hypersensitivity reactions to liposomal amphotericin-B (AmBisome), especially during therapy, is very rare. We report two patients with kala-azar: one developed breathing difficulties and hypotension followed by shock and the other had facial angioedema with chest tightness during treatment. Both patients were managed with immediate action of injection: adrenaline, diphenhydramine and hydrocortisone. In our experience, AmBisome can cause severe hypersensitivity reactions that warrant proper support and close supervision. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Pineda, F.; Ariza, A.; Mayorga, C.
Immediate hypersensitivity reactions to clavulanic acid (CLV) seem to be on the increase. Diagnosis is mainly based on skin testing and the drug provocation test (DPT), procedures that are not risk free. The aim of this study was to evaluate whether the histamine release test (HRT) could help eva...... allergy to CLV is less than 60%. However, the passive HRT has the advantage that it is based on the testing of serum samples that can be handled more easily than fresh blood samples. © 2016 S. Karger AG, Basel........ Results: The clinical symptoms were anaphylaxis (n = 6), urticaria (n = 9) and urticaria-angioedema (n = 3). The median time interval between the reaction and the study was 225 days (interquartile range, IQR: 120-387.5) and between drug intake and the development of symptoms 30 min (IQR: 6.25-30). We...
Full Text Available Acute Generalized Exanthematous Pustulosis (AGEP, is a rare cutaneous rash characterized by widespread sterile non-follicular pustules. AGEP is a rare disease in childhood and it is often due to drugs. Antibiotics, sulphanamides and antipyretic-analgesics are the main reasons of this drug reaction . Cetirizine is a second generation antihistamine is often used in the treatment of angioedema, atopic dermatitis and urticaria in children. Cetirizine induced AGEP was not reported in the literature. In this case a twelve year old child was admitted with urticarial plaques located on her trunk. She developed maculopapular lesions and pustular eruption with Cetirizine (once a day treatment. Cetirizine was stopped and the nonfollicular pustules cleared with a desquamation. The result of the oral challenge test was positive. We present this rare case to show that the antihistamines (cetirizine may cause AGEP in childhood.
Full Text Available Acute Generalized Exanthematous Pustulosis (AGEP, is a rare cutaneous rash characterized by widespread sterile non-follicular pustules. AGEP is a rare disease in childhood and it is often due to drugs. Antibiotics, sulphanamides and antipyretic-analgesics are the main reasons of this drug reaction . Cetirizine is a second generation antihistamine is often used in the treatment of angioedema, atopic dermatitis and urticaria in children. Cetirizine induced AGEP was not reported in the literature. In this case a twelve year old child was admitted with urticarial plaques located on her trunk. She developed maculopapular lesions and pustular eruption with Cetirizine (once a day treatment. Cetirizine was stopped and the nonfollicular pustules cleared with a desquamation. The result of the oral challenge test was positive. We present this rare case to show that the antihistamines (cetirizine may cause AGEP in childhood.
Zuberbier, T; Aberer, W; Asero, R
of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international...... societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect...... performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence...
Zuberbier, T.; Aberer, W.; Asero, R.
of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international...... societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect...... performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence...
Turner, Paul J; Kemp, Andrew S
'Food intolerance' is often confused with a range of adverse symptoms which may be coincidental to ingestion of food. 'Food intolerance' is defined as a reaction in which symptoms must be objectively reproducible and not known to involve an immunological mechanism. A more precise term is non-allergic food hypersensitivity, which contrasts with food allergies which are due to an immunological mechanism. Some children will experience food reactions to food additives. Reported symptoms range from urticaria/angioedema to hyperactive behaviours. While parents/carers report that over one fifth of children experience of food reaction, only 1 in 20 of these are confirmed to have a non-allergic food hypersensitivity on testing. © 2010 The Authors. Journal of Paediatrics and Child Health © 2010 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
Full Text Available Simon Francis Thomsen,1,2 Freja Lærke Sand1,2 1Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark; 2Department of Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkWe read with interest the recent paper by Cooke et al about the use of biologic agents for intractable urticaria.1 Particularly, the authors reckon that the evidence supporting the use of anti-TNFs is limited by the small numbers of patients in non-controlled studies, often with urticarial disorders not typical of chronic urticaria such as vasculitis and delayed pressure urticaria. However, we want to draw the authors’ and readers’ attention to our report from 2013 about the use of adalimumab and etanercept in 20 patients with chronic urticaria with or without angioedema2 (updated in 2015 with an additional five patients.3View original article by Cooke et al
Inoue, Tomoko; Yagami, Akiko; Shimojo, Naoshi; Hara, Kazuhiro; Nakamura, Masashi; Matsunaga, Kayoko
We report here a case of immediate hypersensitivity to beer, in which a female patient developed angioedema of the eyelids shortly after consuming beer. In skin prick tests, the patient showed positive reactions to the base ingredients of beer, particularly malt and barley. The specific serum immunoglobulin E antibodies against barley and malt displayed weakly positive reactivity. To identify the immunoreactive antigens, malt and barley proteins were separated by 2-D polyacrylamide gel electrophoresis and immunoreacted with the patient's serum. The results of mass spectrometric analysis revealed that the main antigen was a protein with similarity to protein z-type serpin. Notably, the identified antigen had a molecular weight of 20-25 kDa, which is markedly smaller than that previously reported for protein Z4 (44 kDa). Taken together, these analyses indicate that a possible new antigen which belongs to the protein Z family elicits immediate hypersensitivity to beer. © 2015 Japanese Dermatological Association.
Wüthrich, B; Stern, A; Johansson, S G
A 33-year-old woman without history of previous atopic diseases or drug allergies developed a severe anaphylactic reaction with asthma, vomiting, itching, generalized urticaria, and angioedema during artificial insemination with her husband's sperm. The sperm-processing medium contained bovine serum albumin (BSA). Skin prick test and RAST demonstrated an IgE-mediated hypersensitivity to BSA as well as a polyvalent atopic sensitization to pollens, animal danders, cow's milk, beef, pork, and mutton. SDS-PAGE studies indicated serum albumin to be the appropriate allergen with a high degree of cross-reactivity between serum albumin from different animal species. Artificial insemination with fluid containing potential allergens can, therefore, represent an unnecessary risk for atopic females, even in the absence of prior clinical symptoms of allergic diseases. Preoperative testing with the medium is recommended.
Mathews, K.P.; Curd, J.G.; Hugli, T.E.
Serum carboxypeptidase N (SCPN) is the primary inactivator of the C3a, C4a, and C5a anaphylatoxins as well as an inactivator of bradykinin. Thus, SCPN deficiency potentially could result in significant pathophysiologic consequences. Previous studies identified a deficient subject afflicted with frequent episodes of angioedema, and other family members also had SCPN deficiency. To delineate this abnormality further, the fractional catabolic rate (FRC) and enzyme synthesis were determined in three members of the afflicted kindred as well as in five normal persons following the infusion of homogeneous /sup 125/I-SCPN. The mean FCR and synthesis rates for SCPN in the normal subjects were 1.3%/hr and 20,793 U/kg/hr, respectively. Reduced synthesis was concluded to be primarily responsible for the low SCPN levels in the afflicted kindred. The high FRC of SCPN discourages attempted maintenance therapy with infusions of enriched SCPN preparations.
Full Text Available Belatacept has been found to be efficient at preserving good kidney function in maintenance kidney-transplant patients. Herein, we report on the use of belatacept as a rescue therapy for two kidney-transplant patients presenting with severe adverse events after treatment with calcineurin inhibitors (CNIs and mammalian target-of-rapamycin (mTOR inhibitors. Two kidney-transplant patients developed severely impaired kidney function after receiving CNIs. The use of everolimus was associated with severe angioedema. Belatacept was then successfully used to improve kidney function in both cases, even though estimated glomerular-filtration rate before conversion was <20 mL/min. These case reports show that belatacept can be used as a rescue therapy, even if kidney function is very low in kidney-transplant patients who cannot tolerate CNIs and/or mTOR inhibitors.
Full Text Available Angioimmunoblastic T cell lymphoma (AITL is a rare but distinct type of T cell lymphoma with an aggressive course and high mortality. Most patients are diagnosed late in the disease and usually present with generalized lymphadenopathy. A minority have skin lesions at the time of diagnosis, more commonly in the form of nonspecific maculopapular rash with or without pruritus. We report a rare case of AITL presenting with chronic, recurrent angioedema and urticaria-like lesions and no palpable peripheral adenopathy. Primary Care physicians, dermatologists, and allergists must maintain a high index of suspicion for cutaneous manifestations of lymphoma, especially if the skin lesions are refractory to standard treatment. Timely diagnosis is essential to improve survival.
Full Text Available Food additives used to preserve flavor or to enhance the taste and appearance of foods are also available in oral hygiene products. The aim of this review is to provide information concerning food additives in oral hygiene products and their adverse effects. A great many of food additives in oral hygiene products are potential allergens and they may lead to allergic reactions such as urticaria, contact dermatitis, rhinitis, and angioedema. Dental practitioners, as well as health care providers, must be aware of the possibility of allergic reactions due to food additives in oral hygiene products. Proper dosage levels, delivery vehicles, frequency, potential benefits, and adverse effects of oral health products should be explained completely to the patients. There is a necessity to raise the awareness among dental professionals on this subject and to develop a data gathering system for possible adverse reactions.
Full Text Available We report 2 patients with cold urticaria with different response to treatment with omalizumab (Xolair®. Cold contact urticaria (CCU is a common subtype of physical urticaria. It is characterized by the development of wheal and/or angioedema within minutes after cold contact. Clinical manifestation of CCU can range from mild, localized whealing to life-threatening anaphylactic shock reactions. Omalizumab has been described to be useful in cases of chronic urticaria and may be an interesting option for treatment of CCU. We describe one patient with significant and long-lasting improvement of symptoms and one without any improvement after anti-immunoglobulin E therapy. In our case reports, we want to highlight that there is still a small group of patients without benefit from omalizumab treatment. It is necessary to identify this minor subgroup of patients where omalizumab does not represent an effective treatment possibility.
M. Christel Bolte, Dra.
Full Text Available Las drogas son sustancias químicas que pueden interferir con el sistema inmune y a veces conducen a reacciones inusuales y severas. Éstas pueden amenazar la vida, requerir hospitalizaciones prolongadas o dejar secuelas significativas. Cerca del 2% de las reacciones cutáneas inducidas por fármacos se consideran graves. Estas son el angioedema, el shock anafiláctico, el síndrome de Stevens-Johnson (SSJ, la necrolisis epidérmica tóxica (NET, y el síndrome de hipersensibilidad (DRESS, entre otros. Requieren atención especial ya que los síntomas clínicos son heterogéneos y pueden imitar diferentes enfermedades, lo que lleva a retardar el diagnóstico correcto.
Chan, Robin Y C; Oppenheimer, John J
Allergic contact dermatitis to Alstroemeria has been well documented; however, occupational allergy to this decorative flower has never been reported in the literature. We describe a florist with complaints of a sense of throat tightness, allergic rhinoconjunctivitis, urticaria, and facial angioedema attributable to the handling of this popular flower. An allergy skin testing by the puncture technique and a challenge test are performed in a private office. A staff member is used as a control for the skin testing. Main outcome measures are the subject's clinical symptoms. The allergy skin testing reveals positive response to Alstroemeria (Peruvian lily), but negative to Stargazer lily, solidago, and few other flower extracts. In the challenge test, the subject develops conjunctival injection, postnasal drip with nasal congestion, and cough. This is the first report of a type I allergic reaction to Alstroemeria and illustrate the ease of in-office performance of skin testing and challenge to flowering plants.
Tuncer Budanur, Damla; Yas, Murat Cengizhan; Sepet, Elif
Food additives used to preserve flavor or to enhance the taste and appearance of foods are also available in oral hygiene products. The aim of this review is to provide information concerning food additives in oral hygiene products and their adverse effects. A great many of food additives in oral hygiene products are potential allergens and they may lead to allergic reactions such as urticaria, contact dermatitis, rhinitis, and angioedema. Dental practitioners, as well as health care providers, must be aware of the possibility of allergic reactions due to food additives in oral hygiene products. Proper dosage levels, delivery vehicles, frequency, potential benefits, and adverse effects of oral health products should be explained completely to the patients. There is a necessity to raise the awareness among dental professionals on this subject and to develop a data gathering system for possible adverse reactions.
Longhurst, Hilary J; Aberer, Werner; Bouillet, Laurence
PURPOSE: Phase 3 icatibant trials showed that most hereditary angioedema (HAE) (C1 inhibitor deficiency) acute attacks were treated successfully with one injection of icatibant, a selective bradykinin B2 receptor antagonist. We conducted a post hoc analysis of icatibant reinjection for HAE type I...... and II attacks in a real-world setting by using data from the Icatibant Outcome Survey, an ongoing observational study that monitors the safety and effectiveness of icatibant treatment. METHODS: Descriptive retrospective analyses of icatibant reinjection were performed on Icatibant Outcome Survey data...... (February 2008 to December 2012). New attacks were defined as the onset of new symptoms after full resolution of the previous attack. Potential associations between the patient and attack characteristics and reinjection were explored by using logistic regression analysis. RESULTS: Icatibant was administered...
Ana Luiza Castro Fernandes
Full Text Available The understanding of the interaction of carbon nanotubes and fullerenes with the constituents of the skin, especially the skin immune unit, is relevant to the determina-tion of toxicological endpoints. A systematic review was done focused on such aspects. Considerable part of the found references concentrated in cytotoxicity and skin per-meation. On a smaller scale, there are articles on immunomodulation and activation of immune cells and other elements. Few of the found studies deal specifically with cutaneous immune response, limiting the related knowledge. The findings suggest that nanomaterials studied may be involved in skin problems such irritant contact dermatitis, anaphylactoid reactions, urticaria, angioedema, and raised the need for performing additional studies to confirm the findings. The standardization of the description and testing of nanomaterials characteristics used in experiments can facilitate comparison of results.
Amaya, Daniel; Sánchez, Andrés; Sánchez, Jorge
Inducible urticaria is a heterogeneous group of skin disorders characterized by the appearance of wheals, pruritus and/or angioedema, sometimes accompanied by systemic symptoms caused by innocuous stimuli (cold, heat, pressure, etc.). This group of disorders compromises people's quality of life and most of the literature in this regard comes from case reports and case series since its epidemiology has been poorly studied and some cases are very rare. The aim of this review is to show an up-to-date overview of the available literature for various types of inducible urticarias, always beginning with an illustrative case and then describing their pathophysiological mechanisms, clinical manifestations, and treatment.
Singleton, Reid; Halverstam, Caroline P
Cold urticaria is a physical urticaria characterized by a localized or systemic eruption of papules upon exposure of the skin to cold air, liquids, and/or objects. In some cases, angioedema and anaphylaxis also may occur. The symptoms of cold urticaria can have a negative impact on patients' quality of life. Second-generation H1 antihistamines are the first line of treatment in cold urticaria; however, patients who are unresponsive to initial treatment with H1 antihistamines may require further management options. Avoidance of cold exposure is the most effective prophylactic measure. In mild to moderate cases, the primary goal of therapy is to improve the patient's quality of life. In more severe cases, treatment measures to protect the patient's airway, breathing, and circulation may be necessary. We report the case of a 23-year-old man with cold urticaria who was refractory to initial therapy with H1 antihistamines. A review of the literature also is provided.
Zuberbier, T; Aberer, W; Asero, R
societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect...... performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence......-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS)....
Coattrenec, Yann; Harr, Thomas; Chizzolini, Carlo; Jandus, Peter
Hereditary angioedema (HA) is a disabling and potentially fatal condition. The management of HA includes treatment of acute attacks, short-term prophylaxis to prevent an attack, and long-term prophylaxis to minimize the frequency and severity of recurrent attacks. In this article, we will present new therapeutic alternatives for long term prophylaxis. Glucocorticoids (GC) usage leads to a number of severe side-effects. In giant cell arteritis, the use of tocilizumab in conjunction with low doses of GC reduces the number of relapses. In ANCA-associated vasculitis the use of an anti-C5R (avacopan) alone or in conjunction with low doses of GC results in similar remission rates to those induced by high dose GC.
Kendigelen, Pinar; BaktirClinic Of Anesthesiology And Reanimation Afşin State Hospital Afşin Kahramanmaraş Tureky, Mehmet; Sucu, Asena; Kaya, Guner
Anaphylaxis is a serious systemic hypersensitivity reaction that is rapid in onset and can cause death. Premature newborns, whose immunological system is immature, are less likely to develop anaphylaxis. Administration of amikacin, containing sodium metabisulfite, to a 3-day-old premature newborn, induced a near fatal anaphylaxis. After suspicion of sepsis, the baby was started on amikacin. Clinical improvement was observed after initiation of treatment. On the third day of treatment with amikacin, the newborn suddenly developed tachypnea, tachycardia, angioedema and cyanosis. Anaphylaxis was diagnosed and treated. Latent reaction occurred after one hour of clinical improvement. The baby was intubated immediately. Anaphylaxis is a medical emergency; therefore the clinicians should have a rapid and careful assessment about this potentially fatal reaction. Even after successful treatment of anaphylaxis, the patient should be under observation for 72 hours because of the possibility of a biphasic reaction. Sociedad Argentina de Pediatría.
Davison, F W
When dealing with acute laryngeal obstruction, the first important consideration is the differential diagnosis of the cause. The author considers the following six types: acute laryngotracheobronchitis, acute epiglottitis, diphtheria, supraglottic allergic edema (angioedema), subglottic allergic edema (spasmodic croup) and foreign body in the larynx or trachea. He traces the development of the treatments that have in 50 years lowered the mortality rate from 70% to practically zero. High humidity, best supplied by an ultrasonic nebulizer, antibiotics, and corticosteroids in very high dose have been the prime effective measures. There still is controversy about the choice between tracheostomy and nasotracheal intubation if medical therapy is delayed or ineffective. The primary physician must know when and where to send these children in order to prevent the fatalities so frequent in previous years.
Schatz, Michael; Sicherer, Scott H; Zeiger, Robert S
As editors, we concluded that it would be helpful to our readers to write a Year in Review article that highlights the Review, Original, and Clinical Communication articles published in 2016 in The Journal of Allergy and Clinical Immunology: In Practice. We summarized articles on the topics of asthma, rhinitis/rhinosinusitis, food allergy, anaphylaxis, drug allergy, urticarial/angioedema, eosinophilic disorders, and immunodeficiency. Within each topic, epidemiologic findings are presented, relevant aspects of prevention are described, and diagnostic and therapeutic advances are enumerated. Diagnostic tools described include history, skin tests, and in vitro tests. Treatments discussed include behavioral therapy, allergen avoidance therapy, positive and negative effects of pharmacologic therapy, and various forms of immunologic and desensitization management. We hope this review will help you, our readers, consolidate and use this extensive and practical knowledge for the benefit of your patients. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Reis, Edimara S.; Mastellos, Dimitrios C.; Yancopoulou, Despina; Risitano, Antonio M.; Ricklin, Daniel; Lambris, John D.
Around 350 million people worldwide suffer from rare diseases. These may have a genetic, infectious, or autoimmune basis, and several include an inflammatory component. Launching of effective treatments can be very challenging when there is a low disease prevalence and limited scientific insights into the disease mechanisms. As a key trigger of inflammatory processes, complement has been associated with a variety of diseases and has become an attractive therapeutic target for conditions involving inflammation. In view of the clinical experience acquired with drugs licensed for the treatment of rare diseases such as hereditary angioedema and paroxysmal nocturnal hemoglobinuria, growing evidence supports the safety and efficacy of complement therapeutics in restoring immune balance and preventing aggravation of clinical outcomes. This review provides an overview of the candidates currently in the pharmaceutical pipeline with potential to treat orphan diseases and discusses the molecular mechanisms triggered by complement involved with the disease pathogenesis. PMID:26341313
Should the host reaction to anisakiasis influence the treatment?: Different clinical presentations in two cases ¿Debe la reacción frente la anisakiasis influir sobre el tratamiento?: Presentación clínica
Full Text Available Gastrointestinal anisakiasis is a parasitic infection occurring in people that consume raw or inadequately cooked fish or squid. It is frequently characterized by severe epigastric pain, nausea and vomiting caused by the penetration of the larvae into the gastric wall. Acute gastric anisakiasis with severe chest discomfort is rarely reported in Italy. On the other hand, gastro-allergic anisakiasis with rash, urticaria and isolated angioedema or anaphylaxis is a clinical entity that has been described only recently. Also, if patients usually develop symptoms within 12 hours after raw seafood ingestion, not always endoscopic exploration can promptly identify the Anisakis larvae. Moreover, some authors consider the prevailing allergic reaction as a natural and effective defense against the parasitic attack. We report two cases of peculiar manifestations of anisakiasis in both acute and chronic forms (severe chest discomfort and anaphylactoid reaction.
Full Text Available Gastrointestinal anisakiasis is a parasitic infection occurring in people that consume raw or inadequately cooked fish or squid. It is frequently characterized by severe epigastric pain, nausea and vomiting caused by the penetration of the larvae into the gastric wall. Acute gastric anisakiasis with severe chest discomfort is rarely reported in Italy. On the other hand, gastro-allergic anisakiasis with rash, urticaria and isolated angioedema or anaphylaxis is a clinical entity that has been described only recently. Also, if patients usually develop symptoms within 12 hours after raw seafood ingestion, not always endoscopic exploration can promptly identify the Anisakis larvae. Moreover, some authors consider the prevailing allergic reaction as a natural and effective defense against the parasitic attack. We report two cases of peculiar manifestations of anisakiasis in both acute and chronic forms (severe chest discomfort and anaphylactoid reaction.
Ewing, Whitney Merrill; Allen, Patricia Jackson
Cow milk protein intolerance (CMPI) affects 3% of infants under the age of 12 months and is often misdiagnosed as GERD or colic, risking dangerous exposure to antigens. Most infants out grow CMPI by 12 months; however, those with IgE-mediated reactions usually continue to be intolerant to cow's milk proteins and also develop other allergens including environmental allergens that cause asthmatic symptoms. Clinical manifestations of CMPI include diarrhea, bloody stools, vomiting, feeding refusal, eczema, atopic dermatitis, urticaria, angioedema, allergic rhinitis, coughing, wheezing, failure to thrive, and anaphylaxis. The research and literature showed that CMPI is easily missed in the primary care setting and needs to be considered as a cause of infant distress and clinical symptoms. This article focuses on correctly diagnosing CMPI and managing it in the primary care setting.
la Barra, Paula de; Vial, Verónica; Labraña, Yenis; Álvarez, Ana María; Seguel, Helena
In Chile, loxoscelism is caused by the bite of the Loxosceles laeta spider. The clinical presentation has two different forms: cutaneous loxoscelism (CL) and vicero-cutaneous loxoscelism, which is less frequent. Cutaneous loxoscelism includes an uncommon clinical variation (4%), called CL with edematous predominance (CLEP). We present a 5-year-old patient with sudden pain and edema on his right eyelid associated with fever, which progressed rapidly involving the right hemifacial area, frontal region, and left eyelid. Angioedema and pre-orbital cellulitis were discarded and CLEP was suspect. Cutaneous loxoscelism with an edematous predominance is self-limited, benign and with little or no necrotic injury due to the edema, which dilutes the toxin-induced enzymatic process causing necrosis. As in the reported cases it usually responds well to medical treatment and does not cause visceral involvement.
Graham, Michelle T; Andorf, Sandra; Spergel, Jonathan M; Chatila, Talal A; Nadeau, Kari C
Food allergies (FAs) are a growing epidemic in western countries with poorly defined etiology. Defined as an adverse immune response to common food allergens, FAs present heterogeneously as a single- or multi-organ response that ranges in severity from localized hives and angioedema to systemic anaphylaxis. Current research focusing on epithelial-derived cytokines contends that temporal regulation by these factors impact initial sensitization and persistence of FA responses upon repeated food allergen exposure. Mechanistic understanding of FA draws insight from a myriad of atopic conditions studied in humans and modeled in mice. In this review, we will highlight how epithelial-derived cytokines initiate and then potentiate FAs. We will also review existing evidence of the contribution of other atopic diseases to FA pathogenesis and whether FA symptoms overlap with other atopic diseases.
Gagne, Joshua J; Wang, Shirley V; Rassen, Jeremy A; Schneeweiss, Sebastian
The aim of this study was to develop and test a semi-automated process for conducting routine active safety monitoring for new drugs in a network of electronic healthcare databases. We built a modular program that semi-automatically performs cohort identification, confounding adjustment, diagnostic checks, aggregation and effect estimation across multiple databases, and application of a sequential alerting algorithm. During beta-testing, we applied the system to five databases to evaluate nine examples emulating prospective monitoring with retrospective data (five pairs for which we expected signals, two negative controls, and two examples for which it was uncertain whether a signal would be expected): cerivastatin versus atorvastatin and rhabdomyolysis; paroxetine versus tricyclic antidepressants and gastrointestinal bleed; lisinopril versus angiotensin receptor blockers and angioedema; ciprofloxacin versus macrolide antibiotics and Achilles tendon rupture; rofecoxib versus non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs) and myocardial infarction; telithromycin versus azithromycin and hepatotoxicity; rosuvastatin versus atorvastatin and diabetes and rhabdomyolysis; and celecoxib versus ns-NSAIDs and myocardial infarction. We describe the program, the necessary inputs, and the assumed data environment. In beta-testing, the system generated four alerts, all among positive control examples (i.e., lisinopril and angioedema; rofecoxib and myocardial infarction; ciprofloxacin and tendon rupture; and cerivastatin and rhabdomyolysis). Sequential effect estimates for each example were consistent in direction and magnitude with existing literature. Beta-testing across nine drug-outcome examples demonstrated the feasibility of the proposed semi-automated prospective monitoring approach. In retrospective assessments, the system identified an increased risk of myocardial infarction with rofecoxib and an increased risk of rhabdomyolysis with cerivastatin years
Full Text Available Bradykinin (BK, generated from high-molecular-weight kininogen (HK is the major mediator of swelling attacks in hereditary angioedema (HAE, a disease associated with C1-inhibitor deficiency. Plasma kallikrein, activated by factor XIIa, is responsible for most of HK cleavage. However other proteases, which activate during episodes of angioedema, might also contribute to BK production. The lectin pathway of the complement system activates after infection and oxidative stress on endothelial cells generating active serine proteases: MASP-1 and MASP-2. Our aim was to study whether activated MASPs are able to digest HK to release BK. Initially we were trying to find potential new substrates of MASP-1 in human plasma by differential gel electrophoresis, and we identified kininogen cleavage products by this proteomic approach. As a control, MASP-2 was included in the study in addition to MASP-1 and kallikrein. The proteolytic cleavage of HK by MASPs was followed by SDS-PAGE, and BK release was detected by HPLC. We showed that MASP-1 was able to cleave HK resulting in BK production. MASP-2 could also cleave HK but could not release BK. The cleavage pattern of MASPs is similar but not strictly identical to that of kallikrein. The catalytic efficiency of HK cleavage by a recombinant version of MASP-1 and MASP-2 was about 4.0×10(2 and 2.7×10(2 M(-1 s(-1, respectively. C1-inhibitor, the major inhibitor of factor XIIa and kallikrein, also prevented the cleavage of HK by MASPs. In all, a new factor XII- and kallikrein-independent mechanism of bradykinin production by MASP-1 was demonstrated, which may contribute to the pro-inflammatory effect of the lectin pathway of complement and to the elevated bradykinin levels in HAE patients.
Boisson, Bertrand; Quartier, Pierre; Casanova, Jean-Laurent
All the human primary immunodeficiencies (PIDs) recognized as such in the 1950s were Mendelian traits and, whether autosomal or X-linked, displayed recessive inheritance. The first autosomal dominant (AD) PID, hereditary angioedema, was recognized in 1963. However, since the first identification of autosomal recessive (AR), X-linked recessive (XR) and AD PID-causing genes in 1985 (ADA; severe combined immunodeficiency), 1986 (CYBB, chronic granulomatous disease) and 1989 (SERPING1; hereditary angioedema), respectively, the number of genetically defined AD PIDs has increased more rapidly than that of any other type of PID. AD PIDs now account for 61 of the 260 known conditions (23%). All known AR PIDs are caused by alleles with some loss-of-function (LOF). A single XR PID is caused by gain-of-function (GOF) mutations (WASP-related neutropenia, 2001). In contrast, only 44 of 61 AD defects are caused by LOF alleles, which exert dominance by haploinsufficiency or negative dominance. Since 2003, up to 17 AD disorders of the third kind, due to GOF alleles, have been described. Remarkably, six of the 17 genes concerned also harbor monoallelic (STAT3), biallelic (C3, CFB, CARD11, PIK3R1) or both monoallelic and biallelic (STAT1) LOF alleles in patients with other clinical phenotypes. Most heterozygous GOF alleles result in auto-inflammation, auto-immunity, or both, with a wide range of immunological and clinical forms. Some also underlie infections and, fewer, allergies, by impairing or enhancing immunity to non-self. Malignancies are also rare. The enormous diversity of immunological and clinical phenotypes is thought provoking and mirrors the diversity and pleiotropy of the underlying genotypes. These experiments of nature provide a unique insight into the quantitative regulation of human immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.
Filho, Silvio Lima
Background Describe the frequency of positive results in autologus serum skin test among patients with cronic urticaria. Methods Trans-sectional study of patients with CIU refered to traitment in policlínica geral do Rio de Janeiro, brazil. Autologus serum intradermal injections were used to estabilished the sensitivity. Negative and positive controls were made with 0.9% intradermal saline solution and skin prick test with histamina 1:100 solution. Autoreactivity was considered positive when wheal reached 3 mm at least, 1.5 mm larger than saline solution at 30 minute interval. Antihistamines drugs were interrupeted 72 hours before test. Dates on race, age, sex, and informations about length and how often the symptoms persist, personal history of atopy (PHA) and angioedema (AE), autoimmune disease (AID) and physical (PF) and not physical factors (NPF) related with the worsening of urticaria were registered during appointment. K square and τ student tests were used in this work. Results Eighteen patients, from 2008, march to 2011, march, were investigated (15 f; 12 w; age 50,67 ± 16,93 yr). Eleven patients presented positive AAST (61.1%) with a mean wheal diameter = 9,64 ± 2,66 mm (negative control = 6,33 ± 3,63 mm; P 0.05). Conclusions The positive asst frequency was 61%, comparable to values found in the liretature. Association among social-demographic and clinical aspects was not observed. We emphasize the prevalence of joint pain and angioedema as associated symptoms and the more frequence of AID laborotory finds. The procedure proved safe and precise and worth value in the screening diagnosis of autoimune etiology for patients with CIU.
Maria Lúcia Teixeira Polônio
Full Text Available Este estudo visa a contextualizar por meio de uma revisão sistemática da literatura, os riscos acarretados pelo consumo de aditivos alimentares. Em relação aos resultados dos estudos associando o consumo de aditivos ao aparecimento do câncer, os efeitos adversos à saúde foram observados principalmente nos estudos em que a Ingestão Diária Aceitável (IDA foi excedida. Também apontou uma carência de pesquisas sobre o transtorno do déficit de atenção e hiperatividade. Já em relação à hipersensibilidade não específica, o número de estudos foi significativo e os resultados mais consistentes quanto às manifestações clínicas de rinite, urticária e angioedema provocadas pelos aditivos, em particular pelos os corantes artificiais. As crianças aparecem como grupo vulnerável, em razão do consumo potencial de alimentos com aditivos alimentares, particularmente corantes artificiais. Os resultados indicam que estudos de consumo de aditivos alimentares deveriam servir de base para a elaboração de estratégias de vigilância alimentar e nutricional, com a finalidade de promover hábitos alimentares saudáveis.This study uses a systematic literature review to contextualize the risks associated with food additive intake. Studies comparing food additive intake and cancer showed that adverse health effects appeared when Acceptable Daily Intake (ADI was exceeded. The review also detected a lack of studies on attention deficit-hyperactivity disorder. There were more studies on non-specific hypersensitivity, highlighting such clinical manifestations as rhinitis, urticaria, and angioedema, all associated with food additives, particularly artificial colorants. Children are a vulnerable group as potential consumers of food additives, particularly artificial colorants. Studies on food additive intake should provide the basis for effective food and nutritional surveillance strategies, aiming to promote healthy eating habits.
Oehling, A; Fernández, M; Córdoba, H; Sanz, M L
According to Hansen's contact rule, the digestive system should be considered as the main shock organ, yet in food allergy, this is not the case. Very often specific food triggers clinical manifestations not involving the digestive system; that is, reactions are manifested either in the respiratory system, as asthma or rhinitis, or in the skin. In these cases the BALT (broncho-alveolar lymphoid tissue) and GALT (gastrointestinal lymphoid tissue) units play a basic role in the sensitizations. The purpose of this study was to determine the most frequent skin manifestations of food allergy among children, and the most frequently involved foods. We also thought it interesting to evaluate the diagnostic reliability of the different standard immunological parameters utilized by the study team in food allergy. All patients underwent intracutaneous tests with 12 groups of the most frequent food allergens, as well as serum IgE, antigen-specific IgE against foods, and antigen-specific histamine release tests. Antigen-specific IgG4 determination was performed in some cases. The results obtained confirmed previous studies, the most common manifestations being: angioedema (48%), followed by urticaria (31%) and atopic dermatitis (21%). Regarding the frequency of sensitization to different food allergens, in mono- or polisensitization, fish and egg stand out in our environment. Certain food allergens are more frequently responsible for specific skin manifestations. Thus, for fish sensitization, the most frequent skin manifestation is atopic dermatitis (50%); for egg sensitization, angioedema is the most frequent skin manifestation (50%); and for milk, urticaria (50%). Finally, and in agreement with previous works regarding the diagnostic reliability of in vitro techniques, we found that the histamine release test offered the highest percentage of diagnostic reliability. Only for sensitization to milk proteins did antigen-specific IgE demonstrate higher reliability. Once again, we
Hack, C Erik; Mannesse, Maurice; Baboeram, Aartie; Oortwijn, Beatrijs; Relan, Anurag
Recombinant human C1-inhibitor (rhC1INH) is used to treat acute angioedema attacks in hereditary angioedema (HAE) due to a genetic C1INH deficiency. Recombinant proteins in general may induce antibody responses and therefore evaluation of such responses in the target population is an essential step in the clinical development program of a recombinant protein. Here we report the assessment of the immunogenicity of rhC1INH in symptomatic HAE patients. Blood samples collected before and after administration of rhC1INH were tested for antibodies against plasma-derived (pd) or rhC1INH, or against host-related impurities (HRI). Above cut-off screening results were confirmed with displacement assays, and also tested for neutralizing anti-C1INH antibodies. Finally, the relation of antibodies to clinical efficacy and safety of rhC1INH was analyzed. Data from 155 HAE patients who received 424 treatments with rhC1INH were analyzed. 1.5% of all pre-exposure tests and 1.3% of all post-exposure tests were above the cut-off level in the screening assay for anti-C1INH antibodies. Six patients (3.9%) had anti-rhC1INH antibodies positive in the confirmatory assay. In two patients, confirmed antibodies were pre-existing with no increase post-exposure; in three patients, the antibodies occurred on a single occasion post-exposure; and in one patient, on subsequent occasions post-exposure. Neutralizing anti-pdC1INH antibodies were not found. Anti-HRI antibodies in the screening assay occurred in <0.7% of the tests before exposure to rhC1INH, in <1.9% after first exposure and in <3.1% after repeat treatment with rhC1INH. Five patients had anti-HRI antibodies positive in the confirmatory assay. In one patient, the antibodies were pre-existing, whereas in three of the 155 rhC1INH-treated patients (1.9%), confirmed anti-HRI antibodies occurred at more time points. Antibody findings were not associated with altered efficacy of rhC1INH or adverse events. These results indicate a reassuring
Full Text Available Abstract Background Isocyanates are extensively used in the manufacture of polyurethane foams, plastics, coatings or adhesives. They are a major cause of occupational asthma in a proportion of exposed workers. Recent findings in animal models have demonstrated that isocyanate-induced asthma does not always represent an IgE-mediated sensitization, but still a mixed profile of CD4+ Th1 and TH2, as well as a CD8+ immune response. Despite immunologic similarities between this pathology and IgE-mediated food allergies, this co-morbidity is rarely reported. Case presentation A 50-year old man employed as vehicle body painter, for 8 years complained about breathlessness, wheezing, sneezing, nasal obstruction and excessive production of mucus during the use of DuPont Refinish Centari Tintings – an acrylic enamel tint. Symptoms occurred 15–20 minutes after workplace exposure and usually persisted until evening, or at times, up to two consecutive days. The above mentioned symptoms were associated with a decrease of lung functions parameters. The use of inhaled adrenergic bronchio-dilatators and steroids relived the symptoms. In addition, three years ago he developed an anaphylactic reaction due to peanut consumption, experiencing urticaria, angioedema and airway obstruction. He was successfully treated in the hospital. Later, the subject exhibited labial itching, as well as orbital and perioral angioedema, 20 minutes after stationary performance of challenge test with peanuts. Evaluating the reported data, this process might be developed rather due to induction of a TH2 profile, because in both cases have occurred IgE-mediated symptoms. A less plausible mechanism could be the presence of isocyanates in peanuts due to a probable contamination by pesticides resulting in an allergic reaction after "consumption" of di-isocyanate as long as the isocyanate contamination of peanuts has not been proven. Conclusion Despite the lack of relevant laboratory
Fernandez-Gotico, Hannah; Lightfoot, Tiffany; Meighan, Melissa
The approved treatment by the Food and Drug Administration for acute ischemic stroke is intravenous tissue-type plasminogen activator (IV tPA). After IV tPA administration, patients are monitored for adverse events using an American Heart Association/American Stroke Association guideline instituted in 1996. There is limited evidence describing the safest and most efficient method to monitor patients during the first 24 hours after tPA administration. Although the overall rates of adverse events have been reported, the time when patients may be at most risk for an event has not been studied. The purpose of this study was to identify the time of adverse event occurrences in the first 24 hours after IV tPA administration. This was a descriptive, retrospective chart review study of patients admitted to an integrated health system and treated with IV tPA for acute stroke between July 2010 and July 2012. Charts were reviewed for adverse events using the Institute for Healthcare Improvement's Global Trigger Tool for Measuring Adverse Events. Possible chart indicators of adverse events or "triggers" included neurological decline, vital signs elevated above specified parameters, and emergent imaging. Adverse events included episodes of neurological decline, angioedema, allergic reactions, bleeding, and intracerebral hemorrhage (ICH). The timing of each detected event was determined, and descriptive statistics were used for data analysis. Fourteen adverse events (2.8%) were detected in a population of 498 patients. Reactions consisted of allergic reaction (n = 1), angioedema (n = 1), neurological decline without ICH (n = 1), gastrointestinal bleeding (n = 1), bleeding gums (n = 1), and high-risk ICH (n = 9). Thirteen of the 14 adverse events (92.9%) occurred within the first 12 hours after IV tPA administration. Close monitoring during the first 12 hours after IV tPA treatment may be essential. However, close monitoring after 12 hours may not contribute significantly to
Flávia Andréia MARIN
Full Text Available O látex está sendo considerado o alergênico do ano 2000, tendo em vista que inúmeros indivíduos, principalmente profissionais da área de saúde e pacientes submetidos a várias intervenções diagnósticas e terapêuticas, estão freqüentemente expostos aos alérgenos do látex, presentes em produtos de borracha natural. As manifestações clínicas conseqüentes às reações alérgicas de hipersensibilidade imediata vão desde rinite, urticária, conjuntivite, angioedema, asma, até anafilaxia. Estudos recentes estão demonstrando que pacientes alérgicos ao látex desenvolvem concomitantemente sensibilização a certos alimentos de origem vegetal, especialmente frutas como papaia, figo, banana, abacate, kiwi, pêssego, abacaxi, melão e castanha, acreditando-se numa provável ocorrência de reações cruzadas entre os alérgenos do látex e destas frutas. Faz-se, então, uma revisão sobre a alergia ao látex, em particular sobre os grupos de risco, incluindo a presença de reatividade cruzada entre o látex e as frutas.The latex is being considered the allergenic agent of the year 2000, taking into account that several individuals, mainly health care professionals, and patients who had undergone many diagnostic and therapeutic interventions, are frequently exposed to latex allergens, which are present in natural rubber latex products. The clinical manifestations, derived from allergic reactions of immediate hypersensitivity vary from since rhinitis, conjunctivitis, urticaria, angioedema, asthma, to anaphylaxis. Recent researches are demonstrating that patients allergic to latex develop concomitantly sensitization to certain vegetable foods, especially fruits like papaya, fig, banana, avocado, kiwi, peach, pineapple, melon and chestnut, and a probable occurrence of cross reaction between allergens of latex and of these fruits is believed. A review is made about latex allergy, in particular about risk groups, including the presence of
Kelava, Nikolina; Lugović-Mihić, Liborija; Duvancić, Tomislav; Romić, Renata; Situm, Mirna
Oral allergy syndrome (OAS) is one of the most common types of food allergy. The syndrome includes itching and swelling of the lips, palate and tongue, usually after consuming fresh fruits and vegetables. The underlying pathogenic mechanism is cross-reactivity between IgE antibodies specific to pollen, and antigens in food, such as fresh fruits, vegetables and nuts that are structurally similar to pollen. Both pollen and food antigens can bind to IgE and trigger type I immune reaction. Diagnosis is primarily based on the patient's history, and confirmed by skin tests, in vitro tests, and oral provocation tests. Differential diagnoses include many diseases (such as burning mouth syndrome, angioedema, hay fever, various other oral diseases, etc.), and for this reason a multidisciplinary approach is necessary, as different specialists need to be involved in the diagnostic procedure. Therapy includes avoiding, or thermal processing of, fruit and vegetables known to trigger a reaction, and antihistamine medications. If a more severe anaphylactic reaction develops, more aggressive therapy is required. The goal of this article is to present OAS, its etiopathogenesis, clinical picture, and symptoms, diagnostic approach and therapy for OAS.
Pipet, A; Veyrac, G; Wessel, F; Jolliet, P; Magnan, A; Demoly, P; Bousquet, P J
More perioperative cefazolin use has resulted in an increased risk of cefazolin-associated reactions. The aim of this article is to study immediate reactions to cefazolin and attempt to determine possible allergic cross-reactivity with other ß-lactams using data from the Drug Allergy and Hypersensitivity Database (DAHD). All 25 cefazolin-associated reactions in the DAHD were reviewed. The cases identified were then investigated according to the European Network for Drug Allergy (ENDA) recommendations by skin testing and challenges. A total of 10 individuals with proven IgE-mediated cefazolin hypersensitivity were identified between January 1999 and July 2009. All the index reactions were compatible with an acute IgE-mediated process, six with anaphylaxis, two with systemic allergic reactions without hypotension, and two with urticaria/angioedema. Cefazolin skin tests were positive in seven individuals and cefazolin challenges were positive in three more individuals. In the eight cefazolin allergic patients who had challenges with other ß-lactams, there was no positive reaction noted. In this cohort of patients with IgE-mediated reactions to cefazolin, a majority tolerated amoxicillin and several patients tolerated other cephalosporins. This implies that the R1 side-chain may play an essential role in IgE-mediated reactions to cefazolin. No clear rule to predict cross-reactivity with other ß-lactams could be determined. More research on IgE-mediated hypersensitivity to cefazolin and other cephalosporins is needed. © 2011 Blackwell Publishing Ltd.
Drug hypersensitivity reactions affect more than seven percent of the population and are a concern for patients and doctors alike. In a substantial part of such reactions, IgE-mediated mechanisms have been documented. Clinical manifestations of immediate reactions, which occur directly after drug intake (mostly ≤ 1 h), are acute urticaria, angioedema, dyspnea and other symptoms of anaphylaxis in the skin, gastrointestinal tract, respiratory tract or cardiovascular system. Although normally leading to milder reactions, drugs are also the most frequent elicitors of fatal anaphylaxis. The median time interval between systemic drug application and clinical death is 5 min. The most common elicitors of immediate reactions are analgesics, antibiotics, radiocontrast media and muscle relaxants. The aim of history and experience guided skin tests ± laboratory tests is to document a sensitization, which depends on the eliciting drug and is only successful in less than half of the patients. Else a drug provocation test under controlled conditions is necessary to clarify the diagnosis and to confirm or exclude a drug hypersensitivity reaction. Therapy consists in drug avoidance or in pressing indications in tolerance induction by a "drug desensitization".
Fischer, Jörg; Biedermann, Tilo
The development of component-resolved diagnostics instead of whole extracts has brought about major advances in recent years. Particularly remarkable has been the identification of new disease entities based on the detection of IgE antibodies against specific individual components. In this context, delayed immediate-type hypersensitivity to red meat and innards plays a key role. This disorder is more common in German-speaking countries and likely still underdiagnosed. Affected individuals exhibit delayed type I reactions following the consumption of red meat or innards (responses to the latter are more rapid). All patients have IgE antibodies against the oligosaccharide galactose-α-1,3-galactose - alpha-gal. Those affected also have to avoid alpha-gal-containing drugs such as cetuximab or gelatin-containing colloidal solutions. Also referred to as alpha-gal syndrome, this condition is unique in that it is characterized by type I hypersensitivity to a sugar instead of a protein. Given that many patients have a history of recurrent episodes of acute urticaria or angioedema, dermatologists should be familiar with the alpha-gal syndrome. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.
Gaeta, Francesco; Torres, Maria J; Valluzzi, Rocco Luigi; Caruso, Cristiano; Mayorga, Cristobalina; Romano, Antonino
Hypersensitivity reactions to β-lactam antibiotics are commonly reported. They can be classified as immediate or non-immediate according to the time interval between the last drug administration and their onset. Immediate reactions occur within one hour after the last drug administration and are manifested clinically by urticaria and/or angioedema, rhinitis, bronchospasm, and anaphylactic shock; they may be mediated by specific IgEantibodies. Non-immediate reactions occur more than one hour after the last drug administration. The most common manifestations are maculopapular exanthemas; specific T lymphocytes may be involved in this type of manifestation. In the diagnostic evaluation of hypersensitivity reactions to β -lactam antibiotics, the patient's history is fundamental. The allergy examination is based on in vitro and in vivo tests selected on the basis of the clinical features and the type of reaction, immediate or non-immediate. Immediate reactions can be assessed in vitro by serum specific IgE assays and basophil activation tests and in vivo by immediate-reading skin tests and, in selected cases, drug provocation tests (DPTs). Non-immediate reactions can be evaluated mainly by delayed-reading skin tests, patch tests, and DPTs. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Pérez-Alzate, D; Cornejo-García, J A; Pérez-Sánchez, N; Andreu, I; García-Moral, A; Agúndez, J A; Bartra, J; Doña, I; Torres, M J; Blanca, M; Blanca-López, N; Canto, G
Individuals who develop drug hypersensitivity reactions (DHRs) to chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs) are considered cross-hypersensitive. The hallmark for this classification is that the patient presents a reaction after intake of or challenge with acetylsalicylic acid (ASA). Whether patients react to 2 or more NSAIDs while tolerating ASA remains to be studied (selective reactions, SRs). Objective: To identify patients with SRs to 2 or more NSAIDs including strong COX-1 inhibitors. Patients who attended the Allergy Service of Hospital Infanta Leonor, Madrid, Spain with DHRs to NSAIDs between January 2011 and December 2014 were evaluated. Those with 2 or more immediate reactions occurring in less than 1 hour after intake were included. After confirming tolerance to ASA, the selectivity of the response to 2 or more NSAIDs was demonstrated by in vivo and/or in vitro testing or by controlled administration. From a total of 203 patients with immediate DHRs to NSAIDs, 16 (7.9%) met the inclusion criteria. The patients presented a total of 68 anaphylactic or cutaneous reactions (mean [SD], 4.2 [2.1]). Most reactions were to ibuprofen and other arylpropionic acid derivatives and to metamizole. Two different NSAIDs were involved in 11 patients and 3 in 5 patients. Patients with NSAID-induced anaphylaxis or urticaria/angioedema should not be considered cross-hypersensitive unless tolerance to ASA is verified.
Full Text Available Analgésicos (ANA e antiinflamatórios não-hormonais (AINH podem causar reações que simulam as alérgicas ou agravam asma e urticária. OBJETIVO: Verificar as manifestações clínicas de pacientes com história de reação a analgésicos (ANA e antiinflamatórios não-hormonais (AINH. MÉTODO: Análise e retrospectiva de prontuários de 183 pacientes com história de sensibilidade a ANA e AINH. RESULTADOS: Eram 93 (51% pacientes do sexo feminino e 90 (49% do sexo masculino; 63 (34% com idade igual ou inferior a 15 anos e 120 (66% com idade superior a 15 anos. Havia um predomínio de pacientes do sexo feminino com idade superior a 15 anos que foi estatisticamente significativo (p = 0,02. A idade por ocasião da primeira reação com medicamentos variou de 7 meses a 65 anos (média de 15 anos. Testes cutâneos para aeroalérgenos foram positivos para pelo menos um alérgeno testado em 100/138 (72%. As manifestações clínicas encontradas foram angioedema (86%, urticária (39%, reações sistêmicas (30%, reações nasais e oculares (15% e crise de asma (14%. Não havia diferença quanto à freqüência de sintomas com relação à idade. Havia história familiar de sensibilidade a ANA/AINH em sete pacientes (3,8%. As doenças associadas foram rinite (55%, urticária crônica (47%, asma (37% e conjuntivite (17,5%. As drogas causavam crise de asma com maior freqüência em asmáticos do que em não asmáticos (p = 0,001. Reações repetidas a mais de uma droga ocorreram em 107 (58% pacientes. CONCLUSÕES: Reações a ANA e AINH foram freqüentes em atópicos; crianças e adultos reagiam igualmente; foram mais comuns em adultos do sexo feminino; angioedema palpebral foi a manifestação clínica mais freqüente; broncoespasmo foi mais comum nos asmáticos e a maioria dos pacientes tinha reações repetidas a mais de uma droga.BACKGROUND: Analgesics (ANA and nonsteroidal antiinflammatory drugs (NSAID may simulate an allergic reaction or aggravate
Cardinale, F; Mangini, F; Berardi, M; Sterpeta Loffredo, M; Chinellato, I; Dellino, A; Cristofori, F; Di Domenico, F; Mastrototaro, M F; Cappiello, A; Centoducati, T; Carella, F; Armenio, L
Contrary to common believing, the prevalence of the intolerance to food additives in the general population is rather low. Nowadays many doubts persist with regard both to the pathogenetic mechanisms and to the clinical and diagnostic aspects in this field. Symptoms due to, or exacerbated from, food additives usually involve non-IgE-mediate mechanisms (pseudo-allergic reactions, PAR) and are usually less severe of those induced by food allergy. The most frequent clinical feature of the intolerance to food additives still remains the urticaria-angioedema syndrome, although these substances are really involved only in a minority of patients. Other possible clinical features include anaphylaxis, atopic eczema, behaviour disturbances, asthma and non-allergic rhinitis. The diagnostic approach consists in diary cards, reporting symptoms and food habits, elimination diet and double blinded placebo-controlled oral challenge with suspected additives. However, such procedure still remains poorly standardized and numerous uncertainties persist with regard to optimal conditions for performing and interpret the challenge results. The therapeutic approach consists in the exclusion of foods and products containing the additive involved, and, in patients not compliant to the diet, in treatment with symptomatic drugs.
Vega, Jesús; Vega, Jose María; Moneo, Ignacio; Armentia, Alicia; Caballero, Maria Luisa; Miranda, Alberto
Cutaneous lesions caused by the pine processionary caterpillar Thaumetopoea pityocampa (TP) are frequent in pinewood areas. In the present study, 30 patients diagnosed with occupational immunologic urticaria from this caterpillar were included. Immediate hypersensitivity was demonstrated by performing prick and IgE-immunoblotting tests. Workers were grouped according to their common tasks. Occupations at risk of exposure to TP were pine-cone collectors/woodcutters (14), farmers/stockbreeders (8), other forestry personnel (4), construction workers (2), residential gardeners (1) and entomologists (1). Besides contact urticaria, angioedema (60%), papular lesions of several days of evolution (30%) and anaphylactic reactions (40%) were also detected. The most frequently detected molecular weight bands by immunoblot were 15 (70%), 17 (57%) and 13 kDa (50%). The appearance of isolated bands corresponds with the least serious cases. Only 8 subjects had bands higher than 33 kDa, which was present in the 3 most severe cases of anaphylactic reactions. By presenting these cases, we wish to offer the largest series reported so far of occupational immunologic contact urticaria caused by TP. We include the first cases described in certain occupations, some of them not directly related to forestry work. Pine-cone or resin collectors, woodcutters, farmers and stockbreeders were the most frequently and severely affected workers.
Baxter, C-M; Clothier, H J; Perrett, K P
Immediate hypersensitivity reactions (IHR) are rare but potentially serious adverse events following immunization (AEFI). Surveillance of Adverse Events following Vaccination in the Community (SAEFVIC) is an enhanced passive surveillance system that collects, analyses and reports information about AEFI in Victoria, Australia. We describe the incidence, timing and type of potential IHR following vaccination in preschool children reported over an 8-year period. A total of 2110 AEFI were reported in 1620 children, of which 23.5% (496) were classified as potential IHR. Of these, 37.1% (184) were suspected to be IgE-mediated, (including anaphylaxis, angioedema and/or urticaria) and 83.5% (414) occurred within 15 minutes of vaccination. The incidence of potential IHR was 5.4 per 100,000 doses, with that of suspected IgE-mediated IHR being 2.0 per 100,000 doses. The incidence of anaphylaxis was extremely low (0.13 per 100,000 doses) and is consistent with other published studies. Potential IHR following immunization should be reported to appropriate local pharmacovigilance systems and patients reviewed by specialists able to evaluate, investigate and manage future vaccinations.
Full Text Available In recent years occupational skin and respiratory diseases have been more and more frequently diagnosed in small production and service enterprises. The awareness of occupational exposure and its possible health effects among their workers and employers is not sufficient. Beauty salons, in addition to hairdressers and beauticians, frequently employ manicurists and pedicurists. The workers often happen to perform various activities interchangeably. The health status of beauty salons workers has rarely been assessed. The most numerous reports concern hairdressers. In this occupational group, the occurrence of skin lesions induced by wet work and frequent allergy to metals, hair dyes and bleaches and perm solutions has been emphasized, while information about health hazards for being a manicurist or pedicurist in beauty salons is seldom reported. The aim of this paper is to present professional activities (manicure and pedicure, methods of nail stylization, occupational exposure and literature data on work-related adverse health effects in manicurists and pedicurists. Wet work and exposure to solvents, fragrances, resins, metals, gum, detergents may cause skin disorders (contact dermatitis, urticaria, angioedema, photodermatoses, conjunctivitis, anaphylaxis, respiratory tract diseases, including asthma. The discussed occupations are also associated with the increased incidence of bacterial (particularly purulent, viral and fungal infections and cancer. Med Pr 2013;64(4:579–591
Kim, K T; Hussain, H
There have been reports of increased prevalence of certain food allergies in patients with Type I latex allergy (LA). A detailed food allergy history was obtained from 137 patients with LA. Latex allergy was defined by positive history of IgE mediated reactions to contact with latex and positive skin prick test to latex and/or positive in vitro test (AlaSTAT and/or Pharmacia CAP). Food allergy was diagnosed by a convincing history of possible IgE mediated symptoms occurring within 60 minutes of ingestion. We identified 49 potential allergic reactions to foods in 29 (21.1%) patients. Foods responsible for these reactions include banana 9 (18.3%), avocado 8 (16.3%), shellfish 6 (12.2%), fish 4 (8.1%), kiwi 6 (12.2%), tomato 3 (6.1%), watermelon, peach, carrot 2 (4.1%) each, and apple, chestnut, cherry, coconut, apricot, strawberry, loquat, one (2.0%) each. Reactions to foods included local mouth irritation, angioedema, urticaria, asthma, nausea, vomiting, diarrhea, rhinitis, or anaphylaxis. Our study confirms the earlier reports of increased prevalence of food allergies in patients with LA. We also report increased prevalence of shellfish and fish allergy not previously reported. The nature of cross reacting epitopes or independent sensitization between latex and these foods is not clear.
Libert, N; Schérier, S; Dubost, C; Franck, L; Rouquette, I; Tortosa, J-C; Rousseau, J-M
Hereditary and acquired angioedema (HAE/AAE) are the clinical translation of a qualitative or a quantitative deficit of C1 esterase inhibitor (C1 INH). The frequency and severity of clinical manifestations vary greatly, ranging from a moderate swelling of the extremities to obstruction of upper airway. Anaesthesiologists and intensivists must be prepared to manage acute manifestations of this disease in case of life-threatening laryngeal edema. Surgery, physical trauma and labour are classical triggers of the disease. The anaesthesiologists should be aware of the drugs used as prophylaxis and treatment of acute attacks when considering labour and caesarean section. Androgens are contraindicated during pregnancy. If prophylaxis is required, tranexamic acid may be used with caution. The safest obstetric approach appears to be to administer a predelivery infusion of C1 INH concentrate. It is important to avoid manipulation of the airway as much as possible by relying on regional techniques. We report the case of a patient suffering from an HAE discovered during pregnancy. The management included administration of C1 INH during labor and early epidural analgesia for pain relief. A short review of the pathophysiology and therapeutic options follows.
Selmi, Carlo; Crotti, Chiara; Meroni, Pier Luigi
Allergy and clinical immunology are examples of areas of knowledge in which working hypotheses are dominant over mechanistic understanding. As such, sometimes scientific efforts follow major streams and overlook some epidemiologically prevalent conditions that thus become underestimated by the research community. For this reason, we welcome the present issue of Clinical Reviews in Allergy and Immunology that is dedicated to uncommon themes in clinical immunology and allergy. First, comprehensive discussions are provided for allergy phenomena of large potential impact in clinical practice such as reactions to cephalosporins or aspirin-induced asthma and in everyday life such as allergies to food additives or legumes. Further, the issue addresses other uncommon themes such as urticaria and angioedema, cercarial dermatitis, or late-onset inflammation to soft tissue fillers. Last, there will be discussion on transversal issues such as olfactory defects in autoimmunity, interleukin 1 beta pathway, and the search for new serological markers in chronic inflammation. As a result, we are convinced that this issue will be of help to clinicians involved in internal medicine as well as to allergists and clinical immunologists. More importantly, we are convinced that these discussions will be of interest also to basic scientists for the numerous translational implications.
Hamelin, A; Vial-Dupuy, A; Lebrun-Vignes, B; Francès, C; Soria, A; Barete, S
Patent blue (PB) is a lymphatic vessel dye commonly used in France for sentinel lymph node detection in breast cancer, and less frequently in melanoma, and which may induce hypersensitivity reactions. We report a case of acute blue urticaria occurring within minutes of PB injection. Ten minutes after PB injection for sentinel lymph node detection during breast cancer surgery, a 49-year-old woman developed generalised acute blue urticaria and eyelid angioedema without bronchospasm or haemodynamic disturbance, but requiring discontinuation of surgery. Skin testing using PB and the anaesthetics given were run 6 weeks after the episode and confirmed PB allergy. PB was formally contra-indicated. Immediate hypersensitivity reactions to PB have been reported for between 0.24 and 2.2% of procedures. Such reactions are on occasion severe, chiefly involving anaphylactic shock. Two mechanisms are probably associated: non-specific histamine release and/or an IgE-mediated mechanism. Skin tests are helpful in confirming the diagnosis of PB allergy. Blue acute urticaria is one of the clinical manifestations of immediate hypersensitivity reactions to patent blue dye. Skin tests must be performed 6 weeks after the reaction in order to confirm the diagnosis and formally contra-indicate this substance. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Melike Korkmaz Toker
Full Text Available In this case report, the anaphylactoid reaction against to atropine had been reported in a 51 years old woman patient who had undertaken to total abdominal hystrectomy and bilateral salphingooferectomy surgery. At the end of the surgery, the anesthesia maintenance finished during the extubation procedure consequtively atropine had given intravenously 0,01 mg.kg-1 for preventing the neostigmine’s cholinergic effects. After the enjection of atropine tachycardia occured, nonpitting edema, maculopapular skin rash beginning from the periferal veins especially head and neck region spread out althrough the body observed. Anaphylactoid reaction developing like angioedema at the head and neck region threated the airway safety, therefore methylprednisolone 4 mg.kg-1, ranitidine 50 mg and feniramine maleat 1 mg.kg-1 intravenously administered. For safety of the airway the patient transferred to intensive care unit as intubated. After 24 hours follow up patient had clinically recovered and extubated. With our case report we try to emphasise the anaphylactoid reaction against to atropine and raise awareness of the anesthesiologists.
Díez-Gómez, M L; Quirce, S; Aragoneses, E; Cuevas, M
Ficus benjamina or weeping fig is a plant used increasingly for indoor decoration that can cause allergic rhinitis and asthma. We report a clinical and immunologic study in a patient with perennial asthma caused by F. benjamina latex in whom several episodes of angioedema of the oropharyngeal tract and tongue followed ingestion of figs and kiwi. Hypersensitivity to latex from F. benjamina and from Hevea brasiliensis, fig fruit, kiwi, papain, and bromelain was investigated by means of skin prick test, specific IgE determination by CAP, histamine release test, and bronchial provocation test to F. benjamina latex. CAP-inhibition assays were carried out to study possible cross-reactivity among these antigens. Hypersensitivity to F. benjamina latex, fig, kiwi, and proteases was demonstrated by means of skin prick test, determination of specific IgE and histamine release test. Bronchial provocation test with F. benjamina latex resulted in a dual asthmatic reaction, confirming the etiologic role of this plant. A rise of eosinophil cationic protein in patient's serum was observed 21 hours after bronchial challenge, suggesting activation of eosinophils. Inhibition assays showed that F. benjamina latex as liquid-phase inhibited up to 95% the CAP to fig and up to 57% the CAP to papain. Neither sensitization nor cross-allergenicity with H. brasiliensis latex was found. Hypersensitivity to F. benjamina latex may cause IgE-mediated respiratory allergy. The association with allergy to fig and papain is likely due to the existence of cross-reactive allergen structures.
Muthu Sendhil Kumaran
Full Text Available Aim: The objective of this study was to assess autologous serum skin test (ASST vs autologous plasma skin test (APST response in chronic spontaneous urticaria (CSU patients and study the significance of intensity of positive responses in relation to clinicoepidemiological parameters. Materials and Methods: One hundred CSU patients and 100 age and sex-matched controls were recruited. The demographic and clinical features were recorded in all patients and routine investigations were performed. ASST and APST tests were performed as per the standard guidelines. Results: The mean duration of illness was 4.85 ± 5.07 years, 90% patients were APST (+, 68% ASST (+, and 22 patients were only APST (+. Positive predictive value (PPV of ASST and APST was 90.7% and 95.7%, respectively. A significant inverse association was seen between thyroid status and serum IgE levels with APST and ASST positivity. Conclusion: APST appears to have better PPV and high intensity of positive response on autologous tests, and correlates with ANA positivity and angioedema.
Full Text Available Shinsaku Imashuku1, Ikuyo Ueda2, Tohru Inaba3 1Divisions of Pediatrics and Hematology, Takasago-seibu Hospital, Takasago, Japan; 2Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan Abstract: We report the treatment course of a 29-year-old man who has had unique oscillating FIP1L1-PDGFRA fusion gene-negative hypereosinophilic syndrome (HES for nearly 6 years. His periodic oscillating pattern of eosinophilia associated with angioedematous soft tissue swelling has shown two to three seasonal peaks (>15,000/µL absolute eosinophil counts [AEC] a year. Initially, the patient, who was thought to have distinct HES not compatible with previously described cases, did not respond to treatment except for a temporary response to imatinib mesylate. For 6 years, from 2005 to 2010, he was treated with a combination of oral cyclosporine A, suplatast tosilate, and a small dose of prednisolone, which significantly reduced the peak heights of AEC as well as blunting the oscillating patterns. Keywords: hypereosinophilic syndrome, eosinophilia, angioedema, IgM, sIL-2R, treatment, cyclosporin A, suplatast tosilate
Full Text Available Targeting the renin-angiotensin-aldosterone system (RAAS, specifically the effector peptide angiotensin II (Ang II, represents a major opportunity for slowing the progression of cardiovascular disease (CVD and, in turn, reducing the risk of morbidity and mortality. Inhibition of angiotensin-converting enzyme (ACE and selective blockade of Ang II AT1 receptors are two approaches through which the pathophysiological effects of Ang II can be targeted. Numerous clinical studies have established the benefits of ACE inhibitors P, (ACE-Is in lessening the morbidity and mortality burden of CVD. There are, however, tolerability concerns associated with ACE-Is, such as angioedema and dry cough. By blocking Ang II at the AT1 receptor level, Ang II receptor blockers (ARBs provide a more specific and complete blockade of the deleterious effects of Ang II and tend to have more favourable tolerability. A number of clinical trials have shown that ARBs are not only associated with positive outcomes across the CVD continuum but may also have a role in the prevention or delay of diabetes (a major cardiovascular risk factor. Ongoing trials are aiming to define the place of such agents in lessening morbidity and mortality from CVD.
Full Text Available Background: The contact allergic reactions from p-phenylenediamine (PPD in hair dyes vary from mild contact dermatitis to severe life- threatening events (angioedema, bronchospasm, asthma, renal impairment. Objectives: To study the clinical patterns and PPD contact sensitivity in patients with hair-dye dermatitis. Materials and Methods: Eighty (M: F 47:33 consecutive patients aged between 18 and 74 years suspected to have contact allergy from hair dye were studied by patch testing with Indian Standard Series including p-phenylenediamine (PPD, 1.0% pet. Results: 54 Fifty-four (M: F 21:33 patients showed positive patch tests from PPD. Eight of these patients also showed positive patch test reaction from fragrance mix, thiuram mix, paraben mix, or colophony. Fifty-seven (71% patients affected were aged older than 40 years. The duration of dermatitis varied from 1 year with exacerbation following hair coloring. Forty-nine patients had dermatitis of scalp and/or scalp margins and 23 patients had face and neck dermatitis. Periorbital dermatitis, chronic actinic dermatitis, and erythema multiforme-like lesions were seen in 4, 2, and 1 patients, respectively. Conclusions: Hair dyes and PPD constitute a significant cause of contact dermatitis. There is an urgent need for creating consumer awareness regarding hair-dyes contact sensitivity and the significance of performing sensitivity testing prior to actual use.
The off-label use of medicines is a common and extensive clinical practice. Omalizumab has been licensed for use in severe allergic asthma and chronic urticaria. Omalizumab dosing was based on body weight and baseline serum IgE concentration. All patients are required to have a baseline IgE between 30 and 700 IU/ml and body weight not more than 150 kg. The use of off-label drugs may lead to several problems including adverse effects and an increased risk/benefit balance. In this article, there are summarized off-label uses of omalizumab in the last recent years in diseases in which IgE maybe or certainly has a corner role such as allergic rhinitis, allergic bronchopulmonary aspergillosis, anaphylaxis, keratoconjunctivitis, food allergy, drug allergy, urticaria, angioedema, non-atopic asthma, atopic dermatitis, nasal polyps, Churg-Strauss syndrome, eosinophilic otitis media, chronic rhinosinusitis, bullous pemphigoid, contact dermatitis, and others. Use in pregnancy asthmatic women and pre-co-administration with specific immunotherapy will also be revised.
Full Text Available Chronic urticaria is a condition characterized by the appearance of wheals and/or angioedema that last for at least 6 weeks. According to the recent recommendations, if H1-antihistamines used in four times licensed doses remain ineffective, add-on treatment with omalizumab, cyclosporine A or montelukast should be applied. This paper offers a literature review of the studies on using omalizumab in chronic spontaneous urticaria (CSU treatment. Moreover, it presents our own experience with the use of omalizumab in the treatment of two patients with CSU. Both patients were treated with H1-antihistamines in four times licensed doses recommended by European guidelines, oral corticosteroids, montelukast, and methotrexate – all without satisfactory results. During the time of the omalizumab therapy both patients achieved a significant improvement measured by the decrease in the Average Urticaria Activity Score for 7 days (UAS7 – the first patient from 34 to 11.8 points, the second one from 41 to 5.76.
Full Text Available Abstract Omalizumab, a humanized monoclonal anti-IgE antibody has the potential to alter allergen processing. Recently, it has been postulated the assessment of PHA-stimulated adenosine triphosphate (ATP activity as maker of CD4+ T cells activity in peripheral blood cells. We present the case report of a 35-year-old woman with a history of chronic idiopathic urticaria and angioedema of 8 years of development with poor response to treatment. The patient was partially controlled with cyclosporine at doses of 100 mg/12 h. However, she was still developing hives daily. Finally treatment with omalizumab was started at dose of 300 mg every 2 weeks. The patient experienced a decrease in urticarial lesions 2 days after starting therapy. We also evaluated the effects of omalizumab therapy on the activity of peripheral blood CD4+ T cells from the patient, in order to determine the potential modification of anti-IgE therapy on the process of antigen presentation-recognition. Activity of CD4+ cells by ATP release was clearly increased demonstrating an enlarged CD4 activity. Omalizumab may be useful in the treatment of severe chronic urticaria. ATP activity of peripheral blood CD4+ T cells might be a non-subjective method to assess Omalizumab activity.
Incorvaia, Cristoforo; Mauro, Marina; Russello, Marina; Formigoni, Chiara; Riario-Sforza, Gian Galeazzo; Ridolo, Erminia
A large number of trials show that the anti-immunoglobulin (Ig) E antibody omalizumab is very effective in patients with severe allergic asthma. This is acknowledged in consensus documents. The drug also has a good safety profile and a pharmacoeconomic advantage due to a reduction in the number of hospitalizations for asthma attacks. In recent years, some studies have shown that omalizumab is effective also in nonallergic asthma. Effects on the complex signaling mechanisms leading to activation of effector cells and to mediator release may account for this outcome. Indeed, omalizumab has been reported to be effective in a number of IgE-mediated and non-IgE-mediated disorders. Concerning the former, clinical efficacy has been observed in rhinitis, allergic bronchopulmonary aspergillosis, latex allergy, atopic dermatitis, allergic urticaria, and anaphylaxis. In addition, omalizumab has been demonstrated to be able to prevent systemic reactions to allergen immunotherapy, thus enabling completion of treatment in patients who otherwise would have to stop it. Concerning non-IgE-mediated disorders, omalizumab has been reported to be effective in nasal polyposis, autoimmune urticaria, chronic idiopathic urticaria, physical urticaria, idiopathic angioedema, and mastocytosis. Current indications for treatment with omalizumab are confined to severe allergic asthma. Consequently, any other prescription can only be off-label. However, it is reasonable to expect that the use of omalizumab will be approved for particularly important indications, such as anaphylaxis, in the near future. PMID:24532966
Labrador-Horrillo, Moises; Ferrer, Marta
Chronic spontaneous urticaria (CSU) is a disease with significant morbidity and relative prevalence that has important effects on the quality of life (QoL) of those who suffer from it. Omalizumab is a recombinant humanized anti-immunoglobulin E (IgE) antibody that binds to the Cε3 domain of the IgE heavy chain and prevents it from binding to its high-affinity receptor FcεRI. It has been largely studied in the field of asthma and is currently approved for the treatment of both adult and pediatric (children; >6-year-old) patients. In addition, in recent, well-controlled clinical trials in patients with CSU resistant to antihistamines, add-on therapy with subcutaneous omalizumab significantly reduced the severity of itching, and the number and size of hives, and increased patients' health-related QoL and the proportion of days free from angioedema compared with placebo, with an excellent tolerance. Thus, omalizumab is an effective and well-tolerated add-on therapy for patients with CSU who are symptomatic despite background therapy with H1 antihistamines. In this review, we cover the following points: epidemiology, pathogenesis, assessment of activity, impact on QoL, and treatment of CSU, and finally, we focus on omalizumab in the treatment of CSU including the pharmacokinetic properties and mechanism of action, and use in pregnant women, nursing infants, and children.
Danve, Abhijeet; Perry, Lisa; Deodhar, Atul
Pregnancy can lead to flares in systemic lupus erythematosus (SLE), and the presence of SLE in pregnancy could lead to a poor outcome for the mother and the fetus. To describe a patient whose active SLE (including lupus nephritis) was managed with the use of belimumab throughout pregnancy. A case report and review of relevant literature is presented. A 38-year-old Caucasian woman with SLE was seen for advice regarding planning a pregnancy and management of her active lupus (cutaneous lupus, angioedema, lupus nephritis, leukopenia, and anti-phospholipid antibody syndrome) that could only be controlled by mycophenolate, a drug contraindicated in pregnancy. Azathioprine, hydroxychloroquine, rituximab, and moderate doses of prednisone were either unable to control her disease or led to unacceptable toxicity. After detailed discussions, she was treated with belimumab, which controlled her SLE and allowed withdrawal of mycophenolate. Belimumab was continued throughout the pregnancy, leading to well-controlled SLE and uneventful course, albeit with the presence of mild Ebstein's anomaly in the baby. To our knowledge, this is the first case report of belimumab use throughout pregnancy for controlling active SLE. Data from the belimumab pregnancy registry would be useful to confirm our findings and to further assess safety of this agent for use in pregnancy. Copyright © 2014 Elsevier Inc. All rights reserved.
Maas, Coen; Renné, Thomas
Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. The factor XII-driven-contact system starts coagulation and inflammatory mechanisms via the intrinsic pathway of coagulation and the bradykinin-producing kallikrein-kinin system, respectively. The biochemistry of the contact system in vitro is well understood, however its in vivo functions are just beginning to emerge. Challenging the concept of the coagulation balance, targeting factor XII or its activator polyphosphate provides protection from thromboembolic diseases without interfering with hemostasis. This suggests that the polyphosphate/factor XII axis contributes to thrombus formation while being dispensable for hemostatic processes. In contrast to deficiency in factor XII providing safe thromboprotection, excessive FXII activity is associated with the life-threatening inflammatory disorder hereditary angioedema. The current review summarizes recent finding of the polyphosphate/factor XII-driven contact system at the intersection of procoagulant and proinflammatory disease states. Elucidating the contact system offers the exciting opportunity to develop strategies for safe interference with both thrombotic and inflammatory disorders. Copyright © 2018 American Society of Hematology.
Lozano, Natalia A; Lozano, Alejandro; Sasia, Laura V; Saranz, Ricardo J; Agresta, María Fernanda; del Pilar Bovina Martijena, María; Ianiero, Luciano; Grenat, Andrés R
Primary immunodeficiencies (PID) are low-prevalence diseases. There are warning signs that may raise clinical suspicion. The objectives of this study were to describe the clinical characteristics and warning signs of patients with PID and to compare the clinical differences between selective immunoglobulin A (IgA) deficiency and other PIDs. Eighty-nine patients were studied; their median age at the time of diagnosis was 6 years old (4.08-11.67). Fifty-three (59.5%) patients were male. Fifty-four (60.7%) patients had selective IgA deficiency, and 35 (39.3%) had other PIDs. The main clinical manifestations were rhinopharyngitis in 65 (73.03%) patients and atopy in 39 (43.82%). Twenty- four (26.97%) patients showed warning signs, and none had selective IgA deficiency. Patients with other PIDs had a higher incidence of lower respiratory tract infection, sepsis, skin infections, mucocutaneous candidiasis, dental alterations, cardiovascular malformations, angioedema, hospitalizations and death. Ten (28.57%) patients received intravenous gammaglobulin, 15 (42.85%) antibiotic prophylaxis, and 2 (2.24%) antifungal prophylaxis.
Sánchez-Borges, M; Capriles-Hulet, A; Caballero-Fonseca, F; González-Aveledo, L
Monoclonal anti-IgE antibodies (omalizumab) are able to induce clinically significant benefits in patients with severe chronic spontaneous urticaria (CS). Those results led clinicians and investigators to reconsider a possible pathogenic role not previously supported for IgE and its receptors in this disease, and to investigate additional approaches for understanding its pathogenesis. IgE antibodies to unknown environmental allergens able to trigger chronic urticaria are not generally regarded as the etiologic factor for the disease. Other proposed mechanisms for the production of wheals and angioedema in CSU include IgG autoantibodies and CD4-positive T cells directed to the high-affinity IgE receptor, autoantibodies to IgE itself, IgE autoantibodies directed to thyroid and nuclear autoantigens, highly cytokinergic IgE, and histamine-releasing factors able to bind to IgE and cause mast cell activation. It is expected that a better knowledge on the mechanisms leading to CSU and the clarification of the immunological effects of anti-IgE will provide novel therapies for this frequent condition.
Full Text Available A seventeen-year-old girl was admitted to our clinic with complaint of rubor, swelling, and pain on the left upper eyelid. Her medical history revealed that she had received high-dose oral steroid treatment for one week for the diagnosis of acute angioedema in another clinic. On ophthalmologic examination, her left upper eyelid had edema, swelling, and hyperemia. Additionally, she had restriction in up-gaze in the left eye. Her best-corrected visual acuity was 0.7. The patient’s computerized tomography revealed ethmoidal, maxillary and frontal sinusitis, as well as subperiostal orbital abscess, and frontal epidural abscess. Intravenous antibiotic treatment has been arranged. Due to persistence of the clinical signs, surgical drainage of the abscesses has been performed. Following, she has been discharged from the hospital on oral antibiotic treatment. Postoperatively, at the first-month visit, the left eye’s up-gaze restriction was recovered, and visual acuity was improved to 1.0. If a patient presents with eyelid swelling, differential diagnosis should be performed carefully before making the decision to start steroid treatment. Sinusitis, which is seen frequently in clinical practice, should be kept in mind due to its potential to cause orbital abscess, epidural abscess, and intracranial complications. (Turk J Ophthalmol 2013; 43: 464-7
Full Text Available Introduction. Ingestion is the principal route for food allergens to trigger allergic reaction in atopic persons. However, in some highly sensitive patients severe symptoms may develop upon skin contact and by inhalation. The clinical spectrum ranges from mild facial urticaria and angioedema to life-threatening anaphylactic reactions. Outline of Cases. We describe cases of severe anaphylactic reactions by skin contact, induced by kissing in five children with prior history of severe anaphylaxis caused by food ingestion. These cases were found to have the medical history of IgE mediated food allergy, a very high total and specific serum IgE level and very strong family history of allergy. Conclusion. The presence of tiny particles of food on the kisser's lips was sufficient to trigger an anaphylactic reaction in sensitized children with prior history of severe allergic reaction caused by ingestion of food. Allergic reaction provoked with food allergens by skin contact can be a risk factor for generalized reactions. Therefore, extreme care has to be taken in avoiding kissing allergic children after eating foods to which they are highly allergic. Considering that kissing can be a cause of severe danger for the food allergic patient, such persons should inform their partners about the risk factor for causing their food hypersensitivity.
Carnovale, Carla; Brusadelli, Tatiana; Zuccotti, GianVincenzo; Beretta, Silvia; Sullo, Maria Giuseppa; Capuano, Annalisa; Rossi, Francesco; Moschini, Martina; Mugelli, Alessandro; Vannacci, Alfredo; Laterza, Marcella; Clementi, Emilio; Radice, Sonia
To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed 'Monitoring of the Adverse Effects in Pediatric population' (MEAP). Adverse drug reactions (ADRs) were collected for individuals aged 0 - 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use. We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization. The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.
Dal, T; Ciçek, M; Uçmak, D; Akkurt, M; Tekin, A; Dal, M S; Tekin, R; Kalkanl, S T
Chronic urticaria (CU) is defined by recurrent episodes occurring at least twice a week for 6 weeks and generally characterized by the rapid appearance of wheals and/or angioedema and may be associated with parasitic infections. We aimed to investigate the seroprevalance of Toxocara canis and Fasciola species in patients with CU. We included 55 patients (in age 16-55) with urticaria admitted in study. As a control group we recruited 30 healthy volunteers they had no history of urticaria, rhinitis, asthma, atopic eczema/dermatitis syndrome (AEDS), or other relevant diseases. IgG antibodies to Toxocara canis and Fasciola species were investigated by ELISA method. In a total of 55 patients (mean age: 31.85 ± 8.92), 8 patients (14.5%) were positive for IgG antibodies to Toxocara canis. Among seropositive patients (mean age: 38.62 ± 12.46) 6 patients were female. No patient was positive for Fasciola by ELISA. Six of Toxocara canis seropositive cases were frequently visited or lived in rural areas and had contact with pets. Patients with urticaria, should be tested for Toxocara canis and treated with anthelminthic drugs in endemics areas for toxocariasis.
Bernstein, Jonathan A; Kavati, Abhishek; Tharp, Michael D; Ortiz, Benjamin; MacDonald, Karen; Denhaerynck, Kris; Abraham, Ivo
Chronic idiopathic/spontaneous urticaria (CIU/CSU) is a dermatological condition characterized by itchy wheals and/or angioedema of continuous or intermittent duration of ≥6 weeks with a high burden of disease and impact on quality of life. Omalizumab is a recombinant humanized monoclonal antibody that inhibits the binding of IgE to high affinity receptors, and is approved for the CIU/CSU indication. The objective of this systematic review was to evaluate and synthesize the evidence on the real-world effectiveness of omalizumab in CIU/CSU in daily clinical practice. Areas covered: This review of 84 observational effectiveness studies covers treatments (dosing, medication use), clinical outcomes (treatment response, disease activity, quality of life), and safety. Expert opinion: The clinical outcomes observed across studies underscore the real-world effectiveness of omalizumab in the management of CIU/CSU. Continued treatment may assist patients showing an initial response to achieve a complete treatment response. Response rates are aligned with observed changes in disease activity, symptom experience, and quality of life, and this across subtypes of CIU/CSU. The positive therapeutic profile is complemented by a positive safety profile. The real-world evidence summarized here points convincingly at the high degree of effectiveness of omalizumab in the treatment of CIU/CSU in daily clinical practice.
Gangemi, Sebastiano; Ricciardi, Luisa; Minciullo, Paola Lucia; Cristani, Mariateresa; Saitta, Salvatore; Chirafisi, Joselita; Spatari, Giovanna; Santoro, Giusy; Saija, Antonella
Nickel sensitization can not only induce allergic contact dermatitis (ACD), but also can induce an overlapping disease referred to as "systemic nickel allergy syndrome" (SNAS), characterized by urticaria/angioedema and gastrointestinal symptoms correlated to the ingestion of nickel-containing foods. This study was designed to determine if oxidative stress occurs in patients with nickel allergy. Thirty-one female patients (mean age 31.26 + 13.04 years, range 16-64 years) with confirmed nickel CD underwent oral nickel challenge because of clinically suspected SNAS; serum concentrations of protein carbonyl groups (PCGs) and nitrosylated proteins (NPs; biomarkers of oxidative stress) were measured before and after oral nickel challenge as well as in healthy female controls. Twenty-three of these 31 patients were diagnosed with SNAS because they had a positive reaction to the oral nickel challenge, and 8 patients had no reaction and therefore were classified as patients with contact nickel allergy only. Although both nickel-allergic patients and controls presented similar serum levels of PCGs, NP values in nickel-allergic patients appeared higher than in controls and tended to decrease after the challenge; furthermore, serum levels of NPs in patients affected by SNAS were higher (although not significantly) than in patients with nickel ACD only. The involvement of specific biomarkers of oxidative stress such as NPs and the lack of involvement of other biomarkers such as PCGs may help to better understand the alteration of the redox homeostasis occurring in nickel ACD and particularly in SNAS.
Full Text Available Infection from Toxocara species may give rise to a large array of clinical symptoms, including apparent manifestations of allergy such as asthma, urticaria/angioedema, and dermatitis. We report a case, thus far not described, of contact dermatitis attributed to nickel allergy but caused by Toxocara infection. The patient was a 53-year-old woman presenting from 10 years a dermatitis affecting head, neck, and thorax. Patch tests initially performed gave a positive result to nickel, but avoidance of contact with nickel did not result in recovery. The patient referred to our Allergy Service in 2010 because of dermatitis to feet. Patch testing confirmed the positive result for nickel, but expanding the investigation a positive result for IgG antibodies to Toxocara was detected by Western blotting and ELISA. Treatment with mebendazole achieved immediate efficacy on feet dermatitis. Then, two courses of treatment with albendazole resulted in complete regression of dermatitis accompanied by development of negative ELISA and Western blotting for Toxocara antibodies. This report adds another misleading presentation of Toxocara infection as apparent contact dermatitis caused by nickel and suggests bearing in mind, in cases of contact dermatitis not responding to avoidance of the responsible hapten and to medical treatment, the possible causative role of Toxocara.
Figueredo, E; Quirce, S; del Amo, A; Cuesta, J; Arrieta, I; Lahoz, C; Sastre, J
We report on a 21-year-old atopic woman who developed urticaria, angioedema of the face, and wheezy dyspnea shortly after drinking beer and after eating a corn-made snack. Skin prick tests and specific IgE determinations to beer ingredients and cereal extracts were performed. Immunoblotting inhibition assays were carried out to investigate possible common allergens shared by barley and malt with corn. Skin prick tests and specific IgE measurements with beer, barley, malt, wheat, corn, rye, rice, and oat flour were positive. Ten pollen-allergic patients showed negative skin tests to beer. Double-blind, placebo-controlled, oral challenge tests with sodium metabisulfite and wheat flour were negative. Immunoblotting demonstrated several IgE-binding bands at 31-56 kDa in malt and barley extracts, and a major band at 38 kDa in the beer extract. Immunoblot inhibition assays showed that malt extract was able to inhibit most of the IgE-binding bands in wheat and corn extracts, whereas corn did not produce significant inhibition to barley and malt extracts. This patient developed type I hypersensitivity to barley/malt and corn. Although she also showed IgE reactivity to wheat and other cereals, no symptoms were elicited upon ingestion of these cereals, probably indicating latent sensitization to them.
Hiragun, Makiko; Ishii, Kaori; Hiragun, Takaaki; Shindo, Hajime; Mihara, Shoji; Matsuo, Hiroaki; Hide, Michihiro
Recently, an increasing number of patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) have been reported in Japan. Most of them had developed this condition during or after using hydrolyzed wheat protein (HWP)-containing soap (HWP-WDEIA). To clarify the relation between WDEIA and HWP-containing soap and their prognosis, we retrospectively studied the patients who visited Hiroshima University Hospital and were diagnosed as WDEIA from January 2010 to June 2011. We took detailed clinical histories, performed skin prick tests, serum immunoassays for antigen-specific IgE and basophil histamine release test, and followed up their clinical courses after the diagnosis. Among 36 patients with WDEIA, 30 patients had used only one type of HWP-soap. The patients with HWP-WDEIA were mainly women and had developed facial symptoms and angioedema. They suffered from blood pressure reductions less frequently than patients with conventional WDEIA. The levels of gluten-specific IgE were higher than those of omega-5 gliadin in patients with HWP-WDEIA (P soap. The development of HWP-WDEIA is associated with the use of HWP-soap. The sensitivity to HWP that cross reacts with non-processed wheat may be reduced or possibly cured after the discontinuation of HWP-soap.
Hiragun, Makiko; Ishii, Kaori; Hiragun, Takaaki; Shindo, Hajime; Mihara, Shoji; Matsuo, Hiroaki; Hide, Michihiro
Recently an increasing number of patients with wheat-dependent exercise-induced anaphylaxis (WDEIA), developed during or after using hydrolyzed wheat protein (HWP)-containing soap (HWP-WDEIA), were reported in Japan. To clarify the relation between WDEIA and HWP-containing soap and their prognosis, we investigated the patients who visited Hiroshima University Hospital and were diagnosed as WDEIA from January 2010 to June 2011. We took detailed clinical histories, performed skin prick tests, serum immunoassays for antigen-specific IgE and basophil histamine release test, and followed up their clinical courses after the diagnosis. Among 36 patients with WDEIA, 30 patients had used only one type of HWP-soap. The patients with HWP-WDEIA were mainly women and had developed facial symptoms and angioedema. They suffered from blood pressure reductions less frequently than patients with conventional WDEIA. The levels of glutens-specific IgE were higher than those of ω-5 gliadin in patients with HWP-WDEIA (psoap. The development of HWP-WDEIA is associated with the use of HWP-soap. The sensitivities to HWP that cross reacts with non-processed wheat may be reduced or possibly cured after the discontinuation of HWP-soap.
Romano, Antonino; Caubet, Jean-Christoph
Hypersensitivity reactions to β-lactam and non-β-lactam antibiotics are commonly reported. They can be classified as immediate or nonimmediate according to the time interval between the last drug administration and their onset. Immediate reactions occur within 1 hour after the last drug administration and are manifested clinically by urticaria and/or angioedema, rhinitis, bronchospasm, and anaphylactic shock; they may be mediated by specific IgE-antibodies. Nonimmediate reactions occur more than 1 hour after the last drug administration. The most common manifestations are maculopapular exanthems; specific T lymphocytes may be involved in this type of manifestation. The diagnostic evaluation of hypersensitivity reactions to antibiotics is usually complex. The patient's history is fundamental; the allergic examination is based mainly on in vivo tests selected on the basis of the clinical features and the type of reaction, immediate or nonimmediate. Immediate reactions can be assessed by immediate-reading skin tests and, in selected cases, drug provocation tests. Nonimmediate reactions can be assessed by delayed-reading skin tests, patch tests, and drug provocation tests. However, skin tests have been well validated mainly for β-lactams but less for other classes of antibiotics. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Staubach, P; Zuberbier, T; Vestergaard, C; Siebenhaar, F; Toubi, E; Sussman, G
This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. Despite the clear international guideline, there remain a number of controversies and challenges in the management of patients with chronic urticaria (CU). As a result of major advancements in urticaria over the past 4 years, the current EAACI/GA(2) LEN/EDF/WAO urticaria guideline treatment algorithm requires updating. Case studies from patients with chronic spontaneous urticaria (CSU) [also called chronic idiopathic urticaria (CIU)], chronic inducible urticaria (CIndU) or diseases and syndromes related to CU are useful in describing and exploring challenges in disease management. Case studies of specific CSU patient populations such as children with CU or patients with angio-edema but no hives also require consideration as potentially challenging groups with unmet needs. The current EAACI/GA(2) LEN/EDF/WAO urticaria guideline provides a general framework for the management of patients with CU but, as these cases highlight, a personalized approach based on the expert knowledge of the physician may be required. © 2016 European Academy of Dermatology and Venereology.
Rajesh, Gurumoorthy; Keerthi, Subramaniam; Karthikeyan, Kaliaperumal; Venkatesan, Murugan
Objective: Treatment of chronic urticaria (CU) can be difficult in many patients. Achieving long-term remission and reducing the requirement of antihistamines are vital in CU. The objective of this study was to assess the effectiveness of injection histaglobulin, a complex of histamine and human immunoglobulin, in producing relief in patients with CU. Materials and Methods: Fifty-one patients with CU were enrolled into this prospective clinical study. Patients were administered 1 ml of injection histaglobulin subcutaneous for 8 consecutive weeks. They were also prescribed tablet levocetirizine 5 mg to be taken when required (but not more than the permitted dosage). Efficacy was assessed using urticaria activity score (UAS) which has a maximum score of 33/day, during each weekly visit. Final assessment was done after 24 weeks. Results: Twenty-nine patients had completed the entire 8-week drug regimen. Mean basal UAS was 18.9 ± 6.3 and it reduced to 80.4% by 8 weeks. The angioedema sub-score reduced by 89.8%. Anti-histamine pill burden also reduced significantly. By 24 weeks of starting the therapy, 23 patients (45%) had attained complete remission. No adverse effects to the drug were observed. Conclusions: Histaglobulin was found to be effective in producing long-term remission and it reduced the antihistamine requirement as well. Thus, it can serve as an effective alternative to existing treatment modalities. PMID:27298500
Zuberbier, Torsten; Maurer, Marcus
Urticaria is a common and often debilitating dermatological condition defined by the sudden appearance of wheals, angioedema or both. It is further classified into specific subtypes based on duration and specific triggers. Awareness and understanding of urticaria are important to ensure a correct initial diagnosis and initiate appropriate guideline-based treatment outlining a stepwise approach. However, in chronic urticaria, approximately 50% of patients are refractory to the first step, the use of licensed doses of second-generation H1-antihistamines. If the second step, an increase in the dose of the second-generation H1-antihistamines, is also not successful, in the third step omalizumab (Xolair™, Novartis Pharma AG(©)/Genentech, Inc.(©)), an anti-IgE therapy, is recommended as an add-on. Of all alternative treatments mentioned in the guidelines, omalizumab is currently the only licensed treatment for H1-antihistamine-refractory chronic spontaneous urticaria, has a favorable risk/benefit ratio and was well tolerated in clinical studies.
Cavkaytar, Ozlem; Arik Yilmaz, Ebru; Buyuktiryaki, Betul; Sekerel, Bulent E; Sackesen, Cansin; Soyer, Ozge U
Nonsteroidal anti-inflammatory drug (NSAID) exacerbated cutaneous disease is defined as the exacerbation of wheals and/or angioedema in patients with a history of chronic spontaneous urticaria (CSU). The objective of this study was to define 'aspirin-hypersensitive' children and adolescents in a clearly defined group of patients with CSU and to describe their clinical features. Eighty-one children with a history of CSU were enrolled over a 3-year period. The daily or almost daily (>4 days a week) presence of urticaria was defined as 'chronic persistent urticaria' (CPU), while the presence of urticaria for 2-4 days a week was defined as 'chronic recurrent urticaria' (CRU). Single-blind, placebo-controlled provocation tests (SBPCPTs) with aspirin were performed for children with CSU. Patients with CRU had a longer duration of cutaneous symptoms [1.6 (0.5-4) vs 0.6 (0.3-1.5) years], and stress was less frequently experienced as an eliciting factor in patients with CRU compared with the patients with CPU (P urticaria, determination of NSAID hypersensitivity in a well-controlled clinical setting will help to avoid severe drug hypersensitivity reactions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Vestergaard, Christian; Deleuran, Mette
Chronic urticaria is a debilitating disease characterized by itching and hives with or without angioedema lasting for more than 6 weeks. The disease carries a significant emotional and economic burden for the patient and often results in an odyssey between doctors of different specialities. Patients suffering from chronic urticaria are considered more difficult to satisfy, treat and to have a bigger emotional burden than the average patient in dermatology, paediatric and general practice settings. A joint initiative under the Dermatology section of the European Academy of Allergy and Clinical immunology (EAACI), the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) has resulted in recently published guidelines for the diagnosis, classification and treatment of chronic urticarial: these guidelines are clinically useful and have a high success rate when followed in daily clinical practice. The treatment of choice for chronic urticaria is still nonsedating antihistamines although other treatments are available, with omalizumab (humanized IgG anti IgE antibodies) as the newest therapy. The pathogenesis of urticaria is poorly understood but autoimmunity is considered as one of the major underlying causes for this disease, although other theories exist. PMID:26568807
Soria, A; Francès, C
Urticaria is a common inflammatory skin disease. It is clinically defined as the occurrence of transient papular skin and/or mucosal lesions or subcutaneous lesions called angioedema. Chronic urticaria is defined as a clinical course over more than 6weeks. Different clinical forms of urticaria can coexist in the same patient. Urticaria results of mast cell activation. The diagnosis of urticaria is based on clinical examination. An allergic etiology for acute urticaria, although rare, is always to find and remove. Chronic urticaria is not allergic. Diagnosis is based on questioning and a careful clinical examination to rule out differential diagnoses. Few diagnostic tests are necessary for diagnosis and management, and are especially useful in case of doubtful diagnosis. The treatment of urticaria is symptomatic and based on anti-H1 second generation antihistamines as first-line therapy. In some chronic urticarial, antihistamines up dosing may be necessary. In the majority of patients, this treatment is sufficient to control chronic urticaria. In case of antihistamines failure, other treatment particularly immunomodulatory treatments can be offered in specialized departments. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.