Carpal intra-articular blastomycosis in a Labrador retriever.

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Woods, Katharine S; Barry, Maureen; Richardson, Danielle

2013-02-01

A 6-month-old male castrated Labrador retriever was presented for coughing and forelimb lameness. Blastomyces dermatitidis was identified in cytology of sputum and synovial fluid. Repeat arthrocentesis 7 months later revealed resolution of septic arthritis. Fungal septic arthritis should be considered for cases of monoarthritis and may respond to oral itraconazole treatment.

Carpal intra-articular blastomycosis in a Labrador retriever

OpenAIRE

Woods, Katharine S.; Barry, Maureen; Richardson, Danielle

2013-01-01

A 6-month-old male castrated Labrador retriever was presented for coughing and forelimb lameness. Blastomyces dermatitidis was identified in cytology of sputum and synovial fluid. Repeat arthrocentesis 7 months later revealed resolution of septic arthritis. Fungal septic arthritis should be considered for cases of monoarthritis and may respond to oral itraconazole treatment.

[Ecology of various tropical dermatoses in Peru].

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Flores Cevallos, L

1985-01-01

Special circumstances: Mountains called "Los Andes", the Humbolt maritime current, subtropical region; which makes the peruvian territory present the ecosystem which influence the fauna, flora, and pothology. Contain diseases like parasite dermatosis (mal de Pinto, verruga peruana, leishmaniasis, blastomycosis and pain) have close relation with the different ecosystem of the peruvian territory. This study only includes these dermatosis and are resumed as follows: The disease called, mal del Pinto is only diffused in the arid coast, andean valleys and the virgin forest (it is found in altitudes of 800 to 1,000 m.). The verruga peruvian: Is found in the occidental part of the andean valleys (at 800 and 1,000 m. of altitude). Leishmaniasis exist in two forms: One like bottom of orient with only skin alteration called leishmaniasis andina (uta for the indians), its propagated in the coast and the andean valleys at 200 m. (amount 1,200 to 3,000); the otter form affects the mycosis, called leishmaniasis americana (espundia for the indians), its it propagates general in the virgin forest. The brazilian blastomycosis only exists in the virgin forest. The pain, disease does not exist in the arid coast, nor in the andean valleys. Geographically, for its propagation it is necessary heat, humidity and heavy rainy water, that is why it is only found in the virgin forest.

[Deep mycoses rarely described].

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Charles, D

1986-01-01

Beside deep mycoses very well known: histoplasmosis, candidosis, cryptococcosis, there are other mycoses less frequently described. Some of them are endemic in some countries: South American blastomycosis in Brazil, coccidioidomycosis in California; some others are cosmopolitan and may affect everyone: sporotrichosis, or may affect only immunodeficient persons: mucormycosis. They do not spare Africa, we may encounter basidiobolomycosis, rhinophycomycosis, dermatophytosis, sporotrichosis and, more recently reported, rhinosporidiosis. Important therapeutic progresses have been accomplished with amphotericin B and with antifungus imidazole compounds (miconazole and ketoconazole). Surgical intervention is sometime recommended in chromomycosis and rhinosporidiosis.

The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

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José F Muñoz

2015-10-01

Full Text Available Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics

The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

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Muñoz, José F; Gauthier, Gregory M; Desjardins, Christopher A; Gallo, Juan E; Holder, Jason; Sullivan, Thomas D; Marty, Amber J; Carmen, John C; Chen, Zehua; Ding, Li; Gujja, Sharvari; Magrini, Vincent; Misas, Elizabeth; Mitreva, Makedonka; Priest, Margaret; Saif, Sakina; Whiston, Emily A; Young, Sarah; Zeng, Qiandong; Goldman, William E; Mardis, Elaine R; Taylor, John W; McEwen, Juan G; Clay, Oliver K; Klein, Bruce S; Cuomo, Christina A

2015-10-01

Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics of genome evolution

Case Report: Molecular Confirmation of Lobomycosis in an Italian Traveler Acquired in the Amazon Region of Venezuela.

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Beltrame, Anna; Danesi, Patrizia; Farina, Claudio; Orza, Pierantonio; Perandin, Francesca; Zanardello, Claudia; Rodari, Paola; Staffolani, Silvia; Bisoffi, Zeno

2017-12-01

Lobomycosis is a chronic skin mycosis endemic in Amazon regions characterized by chronic nodular or keloidal lesions caused by Lacazia loboi , an uncultivable fungus. Imported cases in nonendemic countries are rare and diagnosed after years. We describe a case of lobomycosis in a healthy 55-year-old Italian traveler who had acquired the infection during 5-day-honeymoon in the Amazon region of Venezuela in 1999. Several weeks after return, he recalled pruritus and papular skin lesions on the left lower limb, subsequently evolving to a plaque-like lesion. Blastomycosis and cryptococcosis were hypothesized based on microscopic morphology of yeast-like bodies found in three consecutive biopsies, although fungal cultures were always negative. In 2016, exfoliative cytology and a biopsy specimen examination showed round yeast-like organisms (6-12 μm), isolated or in a chain, connected by short tubular projections fulfilling the morphologic diagnostic criteria of Lacazia spp. The microscopic diagnosis was confirmed by molecular identification.

Variation in clinical phenotype of human infection among genetic groups of Blastomyces dermatitidis

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Meece, Jennifer K.; Anderson, Jennifer L.; Gruszka, Sarah; Sloss, Brian L.; Sullivan, Bradley; Reed, Kurt D.

2013-01-01

Background. Blastomyces dermatitidis, the etiologic agent of blastomycosis, has 2 genetic groups and shows varied clinical presentation, ranging from silent infections to fulminant respiratory disease and dissemination. The objective of this study was to determine whether clinical phenotype and outcomes vary based on the infecting organism's genetic group.Methods. We used microsatellites to genotype 227 clinical isolates of B. dermatitidis from Wisconsin patients. For each isolate, corresponding clinical disease characteristics and patient demographic information were abstracted from electronic health records and Wisconsin Division of Health reportable disease forms and questionnaires.Results. In univariate analysis, group 1 isolates were more likely to be associated with pulmonary-only infections (P 1 month (P smoking status (P = .0001) remained predictors for group 2 infections.Conclusions. This study identified previously unknown associations between clinical phenotype of human infection and genetic groups of B. dermatitidis and provides a framework for further investigations of the genetic basis for virulence in B. dermatitidis.

Nocardial mycetoma: Diverse clinical presentations

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Sharma Nand

2008-01-01

Full Text Available Nocardia spp are gram-positive, aerobic, acid-fast bacteria which exist as saprophytes in nature. Invasive disseminated infections are particularly common in immunocompromised or debilitated hosts. Superficial infections with Nocardia spp occur as a result of local trauma and contamination of the wound. Clinically, it presents as acute infection (abscesses or cellulitis, mycetoma, or sporotrichoid infection. Differential diagnosis includes eumycetoma, chromomycosis, blastomycosis, coccidioidomycosis, sporotrichosis, tuberculosis, botryomycosis, syphilis, yaws, and neoplasia. Its diagnosis is confirmed by demonstrating the causative organism in exudates (as granules, tissue specimens, or cultures. Early diagnosis will obviate need for drastic surgical measures as early institution of chemotherapy is effective in most patients. However, its diagnosis is often delayed due to diverse clinical presentations and for want of clinical suspicion, particularly in non-endemic areas. This paper presents 4 clinical forms of this not so uncommon disease, emphasizing the importance of high index of clinical suspicion, especially in non-endemic regions; and the significance of repeated examination of exudates for Nocardia granules for an early diagnosis.

Laboratory and clinical assessment of ketoconazole in deep-seated mycoses.

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Drouhet, E; Dupont, B

1983-01-24

Forty-eight cases of deep mycoses were studied and treated with ketoconazole, each with in vitro evaluation of the minimum inhibitory concentrations (MIC) of the causative fungi, in vivo pharmacokinetic, clinical, and mycologic evaluations, several months to two years after the treatment was stopped. Excellent results were obtained in six cases of chronic mucocutaneous candidiasis, with restoration of immunologic disturbances; 23 cases of systemic candidiasis, including new aspects of heroin addicts with cutaneous, ocular, or osteoarticular manifestations; eight cases of histoplasmosis, five due to Histoplasma capsulatum and three to Histoplasma duboisii, with cure in seven and remission in one; one case of African blastomycosis (Blastomyces dermatitidis); three cases of mycetoma, two due to Monosporium apiospermum, one due to a dematiacious fungus; three cases of entomophthoromycosis with cure; one case of fungal arthritis, due to new hyphomycete similar to M. apiospermum, pathogenic for laboratory animals; one case of Drechslera longirostrata causing vertebral arthritis, following a fungal endocarditis and cured by combination of ketoconazole with amphotericin B, each agent alone being ineffective; and other deep mycoses.

Fungal osteomyelitis with vertebral re-ossification.

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O Guinn, Devon J; Serletis, Demitre; Kazemi, Noojan

2016-01-01

We present a rare case of thoracic vertebral osteomyelitis secondary to pulmonary Blastomyces dermatitides. A 27-year-old male presented with three months of chest pains and non-productive cough. Examination revealed diminished breath sounds on the right. CT/MR imaging confirmed a right-sided pre-/paravertebral soft tissue mass and destructive lytic lesions from T2 to T6. CT-guided needle biopsy confirmed granulomatous pulmonary Blastomycosis. Conservative management with antifungal therapy was initiated. Neurosurgical review confirmed no clinical or profound radiographic instability, and the patient was stabilized with TLSO bracing. Serial imaging 3 months later revealed near-resolution of the thoracic soft tissue mass, with vertebral re-ossification from T2 to T6. Fungal osteomyelitis presents a rare entity in the spectrum of spinal infections. In such cases, lytic spinal lesions are classically seen in association with a large paraspinous mass. Fungal infections of the spinal column may be treated conservatively, with surgical intervention reserved for progressive cases manifesting with neurological compromise and/or spinal column instability. Here, we found unexpected evidence for vertebral re-ossification across the affected thoracic levels (T2-6) in response to IV antibiotic therapy and conservative bracing, nearly 3 months later. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

PARACOCCCIDIOIDOMICOSE COM MANIFESTAÇÃO BUCAL -CASUÍSTICA EM VOLTA REDONDA-RJ NOS ANOS DE 2005 A 2008

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Oriental Luiz de Noronha Filho

2011-01-01

Full Text Available Paracoccidioidomycosis, formerly known as South American Blastomycosis, can be installed by inhalation or by skin lesions or mucous membranes. Poor hygiene and oral diseases are theports of entry most common for this fungus, once in the bloodstream becomes systemic to infect the lungs, spleen, liver, kidneys, pancreas, bones and lymph nodes. The fungus grows on plants and soils in geographical and climatic conditions common areas of the valley of the Paraíba do Sul. The disease has preferences for males, for white and aged between 41 and 50. The primary lesion compromises the oral tongue, gums, lips and other mucous, isolated or associated. The oral lesions appear as lesions located andbulky appearance of micro granules, resembling a blackberry. This study examined medical records of the Municipal Health Department of Volta Redonda, whose primary lesion was in the mouth. We selected 11patient records that corroborated with the literary data, emphasizing the language as the most affected andthe association with bad oral hygiene and oral habits such as smoking and alcohol consumption. All evaluated had pulmonary infection and were treated clinically by the administration of sulfa drugs, outpatient and six to twelve months. It was concluded this could be an endemic area and the importance of the role of the Dental Surgeon in the diagnosis of the disease.

Keratoacanthoma centrifugum marginatum: unresponsive to oral retinoid and successfully treated with wide local excision.

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Kapildev Das

2010-01-01

Full Text Available We describe a case of a 65-year-old male presenting with a large plaque with a rolled-out interrupted margin, atrophic center, and island of normal skin over the left arm. It grew peripherally with central healing, and there was a history of recurrence after inadequate excision. Investigations ruled out other clin­ical mimickers; namely, squamous cell carcinoma, lupus vulgaris, botryomycosis, and blastomycosis-like pyoderma. Histopathological sections showed irregularly shaped craters filled with keratin and epithelial pearl but no evidence of granuloma or cellular atypia. Clinico­pathological correlation proved the lesion to be keratoacanthoma centrifugum marginatum (KCM, a rare variant of keratoacanthoma, which spreads centrifugally, attains a huge size, and never involutes spontaneously. Treatment of KCM has been a problem always and, in our case, systemic retinoid (acitretin for three months proved ineffective. The patient also had a history of recurrence following surgical intervention previously, necessitating wide excision to achieve complete clearance of tumor cells. Hence, after failure of retinoid therapy, the decision of excision with a 1-centimeter margin was taken and the large defect was closed by a split thickness skin graft. The graft uptake was satisfactory, and the patient is being followed-up presently and shows no signs of recurrence after six months, highlighting wide local excision as a useful treatment option.

Blastomyces dermatitidis septins CDC3, CDC10, and CDC12 impact the morphology of yeast and hyphae, but are not required for the phase transition.

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Marty, Amber J; Gauthier, Gregory M

2013-01-01

Blastomyces dermatitidis, the etiologic agent of blastomycosis, belongs to a group of thermally dimorphic fungi that change between mold (22°C) and yeast (37°C) in response to temperature. The contribution of structural proteins such as septins to this phase transition in these fungi remains poorly understood. Septins are GTPases that serve as a scaffold for proteins involved with cytokinesis, cell polarity, and cell morphology. In this study, we use a GFP sentinel RNA interference system to investigate the impact of CDC3, CDC10, CDC12, and ASPE on the morphology and phase transition of B. dermatitidis. Targeting CDC3, CDC10, and CDC12 by RNA interference resulted in yeast with aberrant morphology at 37°C with defects in cytokinesis. Downshifting the temperature to 22°C promoted the conversion to the mold phase, but did not abrogate the morphologic defects. CDC3, CDC10, and CDC12 knockdown strains grew as mold with curved, thickened hyphae. Knocking down ASPE transcript did not alter morphology of yeast at 37°C or mold at 22°C. Following an increase in temperature from 22°C to 37°C, all septin knockdown strains were able to revert to yeast. In conclusion, CDC3, CDC10, and CDC12 septin- encoding genes are required for proper morphology of yeast and hyphae, but are dispensable for the phase transition.

Phylogenetic analysis reveals a cryptic species Blastomyces gilchristii, sp. nov. within the human pathogenic fungus Blastomyces dermatitidis.

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Elizabeth M Brown

Full Text Available Analysis of the population genetic structure of microbial species is of fundamental importance to many scientific disciplines because it can identify cryptic species, reveal reproductive mode, and elucidate processes that contribute to pathogen evolution. Here, we examined the population genetic structure and geographic differentiation of the sexual, dimorphic fungus Blastomyces dermatitidis, the causative agent of blastomycosis.Criteria for Genealogical Concordance Phylogenetic Species Recognition (GCPSR applied to seven nuclear loci (arf6, chs2, drk1, fads, pyrF, tub1, and its-2 from 78 clinical and environmental isolates identified two previously unrecognized phylogenetic species. Four of seven single gene phylogenies examined (chs2, drk1, pyrF, and its-2 supported the separation of Phylogenetic Species 1 (PS1 and Phylogenetic Species 2 (PS2 which were also well differentiated in the concatenated chs2-drk1-fads-pyrF-tub1-arf6-its2 genealogy with all isolates falling into one of two evolutionarily independent lineages. Phylogenetic species were genetically distinct with interspecific divergence 4-fold greater than intraspecific divergence and a high Fst value (0.772, P<0.001 indicative of restricted gene flow between PS1 and PS2. Whereas panmixia expected of a single freely recombining population was not observed, recombination was detected when PS1 and PS2 were assessed separately, suggesting reproductive isolation. Random mating among PS1 isolates, which were distributed across North America, was only detected after partitioning isolates into six geographic regions. The PS2 population, found predominantly in the hyper-endemic regions of northwestern Ontario, Wisconsin, and Minnesota, contained a substantial clonal component with random mating detected only among unique genotypes in the population.These analyses provide evidence for a genetically divergent clade within Blastomyces dermatitidis, which we use to describe a novel species

Lacaziose (doença de Jorge Lobo: revisão e atualização Lacaziosis (Jorge Lobo’s disease: review and update

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Arival Cardoso de Brito

2007-10-01

Full Text Available Lacaziose ou doença de Jorge Lobo é micose crônica, granulomatosa, causada por implantação traumática do fungo Lacazia loboi - patógeno não cultivável até o presente - nos tecidos cutâneo e subcutâneo, manifestando-se clinicamente por lesões nodulares queloidianas predominantes, envolvendo sobretudo pavilhões auriculares, face, membros superiores e inferiores, e não comprometendo as mucosas. A maioria dos casos humanos está registrada em países da América do Sul. Entretanto, a enfermidade apresenta aspectos epidemiológicos destacados, como o aparecimento em tribo Caiabi, no Brasil Central e em mamíferos não humanos, golfinhos de duas espécies (Tursiops truncatus e Sotalia guianensis capturados na costa da Flórida (EUA, na foz do rio Suriname, na costa de Santa Catarina (Brasil, no golfo de Gasconha (baía de Biscaia-Europa, com manifestações cutâneas e achados histopatológicos muito similares às encontradas no homem. O artigo objetiva abordar características do fungo e sua taxonomia, e aspectos históricos, ecoepidemiológicos, clínicos, imuno-histoquímicos, histopatológicos, ultra-estruturais e terapêuticos.Lacaziosis, also known as Jorge Lobo’s disease, lobomycosis and keloidal blastomycosis, is a chronic cutaneous and subcutaneous fungal granulomatous disease, caused by Lacazia loboi - an uncultivated fungal pathogen - characterized by the development of nodular keloidal lesions, particularly on the pinnae, face, upper and lower limbs, and with no involvement of mucous membranes. Most cases in humans were reported in South America, including the Caiabi Indians, in Central Brazil. The disease was described in non-human mammals, such as two species of dolphins (Tursiops truncatus and Sotalia guianensis inhabiting the coasts of Florida (USA, South America (Suriname River estuary, Santa Catarina-Brazil coast and Gulf of Gascony (Biscaya Bay, in Europe. The histopathological findings in dolphins were very similar

More experiences with the Tzanck smear test: cytologic findings in cutaneous granulomatous disorders.

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Durdu, Murat; Baba, Mete; Seçkin, Deniz

2009-09-01

Granulomatous dermatitis is a distinctive histopathologic cutaneous reaction pattern against various infectious and noninfectious agents. Cytologically, granulomatous dermatitis shows granulomas and multinucleated giant cells. Various etiologic agents of granulomatous diseases can also be identified. We aimed to investigate Tzanck smear findings in granulomatous skin diseases. Patients who had granulomas and/or multinucleated giant cells of Langhans, foreign body- and/or Touton type in Tzanck smear tests were included in the study. In these patients, Tzanck preparations were then further evaluated for additional cytologic findings. Samples stained with May-Grünwald-Giemsa stain were evaluated by the same dermatologist throughout the study. In some patients, methylene blue, Gram and/or Erlich-Ziehl-Nielsen stains were also performed. In all of the study cases, the final diagnosis was established after the evaluation of clinical and laboratory findings (including, when appropriate, potassium hydroxide examination; bacterial, leishmanial, and fungal cultures; histopathology; tuberculosis and leishmania polymerase chain reaction). We also calculated the sensitivity and specificity of the Leishman-Donovan body for cutaneous leishmaniasis. Over a 2-year period, 94 of 950 patients (9.9%) in whom Tzanck smear tests were performed had cytologic findings consistent with a granulomatous reaction. In 74 (78.7%) and 20 (21.3%) patients, the granulomatous reaction was due to infectious and noninfectious causes, respectively. Infectious causes included cutaneous leishmaniasis in 65 patients (87.8%), candidal granuloma in two patients, botyromycosis in two patients, and aspergillosis, blastomycosis, mucormycosis, leprosy, and cutaneous tuberculosis in one patient each. In 58 of 74 patients (78.4%) with infectious granulomatous dermatitis, the causes of the granulomas were identified. Noninfectious granulomatous reactions were due to granuloma annulare in 7 patients, sarcoidosis

The Infectious and Noninfectious Dermatological Consequences of Flooding: A Field Manual for the Responding Provider.

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Bandino, Justin P; Hang, Anna; Norton, Scott A

2015-10-01

can remain latent for many years before presenting as the host's immunocompetence wanes. It can present with a variety of skin findings or as a nonspecific febrile illness, and preferred treatment consists of ceftazidime or a carbapenem with trimethoprim/sulfamethoxazole (TMP/SMX) for 2 weeks, then continuing TMP/SMX for at least 3 months. Leptospirosis is a waterborne zoonosis that is often prevalent after heavy rains or flooding. Different forms exist, including Fort Bragg fever, which produces a distinctive erythematous papular rash on the shins. Doxycycline is often sufficient; however, volume and potassium repletion may be necessary if renal involvement exists. Chromobacterium violaceum infection may occur after open skin is exposed to stagnant or muddy water. Cultured colonies produce a unique violacein pigment, and treatment typically consists of a carbapenem. Both typical and atypical fungal infections are increased in the flooding disaster scenario, such as dermatophytosis, chromoblastomycosis, blastomycosis, and mucormycosis. Appropriate antifungals should be used. In addition, land inundated with water expands the habitat for parasites and/or vectors, thus increased vigilance for regional parasitic infections is necessary after a flood. Lastly, noninfectious consequences of a flooding disaster are also common and include miliaria, immersion foot syndromes, irritant and allergic contact dermatitis, traumatic wounds and animal bites, and arthropod assault, as well as exacerbation of existing skin conditions such as atopic dermatitis, psoriasis, and alopecia areata due to increased stress or nonavailability of daily medications.