The present and future research agenda of sporotrichosis on the silver anniversary of zoonotic sporotrichosis in Rio de Janeiro, Brazil

Twenty-five years have passed since the initial observation of endemic zoonotic sporotrichosis in Rio de Janeiro, Brazil. Since then, this disease has spread throughout South America. Accompanying the emergence of this mycosis, some progress has been made, including the expansion of a research network in this field and higher visibility of sporotrichosis within government authorities and funding agencies. However, there are still some challenges to curbing the expansion of this disease in the coming years. These include the development of rapid and accurate diagnostic tests, new antifungal drugs, particularly for the treatment of extracutaneous manifestations of sporotrichosis, and more comprehensive care for cats with sporotrichosis. Including these actions in the sporotrichosis research agenda is required so as to change the development of this disease in the years to come.

Primer aislamiento de Sporothrix brasiliensis en un caso humano de esporotricosis en Chile. Un hongo emergente y preocupante

Se describe el aislamiento de Sporothrix brasiliensis desde una biopsia de piel de un caso humano de esporotricosis linfocutánea, en la región de Valparaíso, Chile. Esta especie es la más virulenta del género y es de transmisión zoonótica, desde los gatos a los humanos. Hasta ahora, solo se había publicado un brote por esta especie en gatos domésticos y asilvestrados en el extremo sur de Chile, por lo que este aislamiento, en una mujer residente de un sector densamente poblado de la Región de Valparaíso, constituye una preocupación por su eventual diseminación hacia otros gatos y la población general.

The isolation of Sporothrix brasiliensis from a skin biopsy of a human case of lymphocutaneous sporotrichosis in the region of Valparaíso, Chile is described. This species is the most virulent of the genus and is zoonotic in transmission from cats to humans. Until now, only one outbreak of this species has been published in domestic and feral cats in the extreme south of Chile, so this isolation in a woman residing in a densely populated sector of the fifth region is a concern for its eventual spread to other cats and the general population.

In vitro evaluation of Sporothrix brasiliensis biotherapic

Sporothrix brasiliensisis one of themost virulent zoonosis which affects animals and humans. This fungus is responsible for subcutaneous infection and its contamination is possible through trauma to the skin. Sporotrichosis is highly prevalent in feline. And Rio de Janeiro appears to have the highest occurrence of cases. Objectives: This study aims to evaluate the in vitroefficacy of Sporothrix brasiliensisbiotherapic, with and without an association to allopathic medicine commonly used in the treatment.Methodology: Conidiumcells of Sporothrix brasiliensiswill be cultured in Potato dextrose agar (PDA) for 5 to 7 days and yeast cells in Brain heart infusion (BHI) for 3 to 5 days. After incubation, the cells will be scraped with a drigalski handle and filtered using cells strainer into a tube and centrifuge for 5 minutes at 3000 RPM. The cells will be resuspended with Phosphate buffered saline (PBS), centrifuge again,and finally resuspended in PBS. After preparing the inocule, the microplates will be prepared. There will be 5groups in vitro. The first one will be the control group, only fungi. The second will be the treatment of fungi with homeopathic medicine (Sporothrix brasiliensis30DH). The third group will be the homeopathic medicine in association with itraconazole. The fourth will be the treatment with itraconazole only. And the last group will be the fungi with dynamized distilled water 30DH. Sporothrix brasiliensis30DHwill be prepared according to Brazilian Homeopathic Pharmacopeia. Results and discussions: The experiments are still in progress and the results will be analyzed through Analysis of variance (ANOVA) to determine statistically significant differences. Previous articles based on biotherapic treatments demonstrated successful results, so our research group is conducting these experiments to evaluate the effect in this model. Conclusion: Experiments will be made to verify the efficacy of biotherapic on sporotrichosis treatments.

In vitro susceptibility of Sporothrix spp. to complexes coordinated with Co(II) and cobalt chloride hexahydrate

Abstract Sporothrix spp. are the major dimorphic fungus associated with a type of subcutaneous mycosis, sporotrichosis. The limitation of antifungal availability and the past reports of in vitro resistance of Sporothrix spp. clinical isolates makes it important to search for new compounds with antifungal activities. In this study, we therefore evaluate the in vitro activities of complexes coordinated with Co(II) and cobalt chloride hexahydrate against clinical isolates of Sporothrix spp. Broth microdilution test was performed as per M38-A2 from CLSI (2008) in duplicate for 31 clinical isolates of Sporothrix spp. (27 S. brasiliensis e 04 S. schenckii stricto sensu). The antifungal activities of the complexes coordinated with Co(II) and cobalt chloride hexahydrate were detected at a concentration range of 32-128 µg/mL for all isolates. None of the compounds demonstrated any cytotoxicity (to macrophage cells) at the concentration of 200 µg/mL. The activity against Sporothrix spp. recorded in this study instigate the continuity of experimental studies with Co(II) to search for the mechanisms of antifungal action as well as to evaluate its interaction with the commercial antifungal drugs.

In vitro activity of Schinus terebinthifolius extract and fractions against Sporothrix brasiliensis

BACKGROUND Sporothrix brasiliensis is the causative agent of zoonotic cases of sporotrichosis in Brazil and is associated with atypical and severe presentations in cats, dogs, and humans. Sporotrichosis treatment is usually time- and cost-consuming, sometimes with poor response and host toxicity. Schinus terebinthifolius has proven efficacy against bacteria and fungi of clinical interest. OBJECTIVE To determine the in vitro activity of S. terebinthifolius against S. brasiliensis. METHODS Five S. brasiliensis isolates and three reference strains were subjected to a hydroethanol extract derived from the leaves of S. terebinthifolius and its fractions. The minimal inhibitory concentration (MIC) was determined using the broth microdilution method according to the M38-A2 CLSI guidelines. Also, the fungicidal/fungistatic activity of the extract and fractions was studied. FINDINGS The crude extract of S. terebinthifolius inhibited the growth of S. brasiliensis (MIC: 0.5-1.0 µg/mL), while the partitioned extracts dichloromethane, ethyl acetate, and butanol demonstrated growth inhibition at 8 µg/mL due to a fungistatic activity. MAIN CONCLUSIONS Due to its in vitro efficacy against S. brasiliensis and its known pharmacological safety, S. terebinthifolius is a candidate to be tested using in vivo models of sporotrichosis.

Valor de las técnicas moleculares y de los factores de riesgo en el diagnóstico y evolución de la esporotricosis. A propósito de 2 casos por Sporothrix brasiliensis y S. globosa / Value of molecular techniques and risk factors in the diagnosis and evolution of sporotrichosis. About 2 cases of Sporothrix brasiliensis and S. globosa

La Esporotricosis es una micosis profunda causada por el hongo dimorfo Sporothrix schenckii, El advenimiento de técnicas moleculares como la reacción en cadena de la polimerasa ha hecho posible identificar varias especies dentro del complejo Sporothrix spp como S. brasiliensis, S. schenckii sensu stricto, S. globosa, S mexicana y S. albicans. Las diferencias son moleculares, pero también geográficas, macroscópicas, en asimilación de azúcares y crecimiento de colonias a 37º; determinando formas clínicas, evolución y respuestas terapéuticas diferentes. Comunicamos 2 casos de Esporotricosis diagnosticados en el Hospital Nacional de Paraguay, cuyos estudios de PCR del gen de la calmodulina hechos en el extranjero, determinaron ser producidos por S. brasiliensis y S. globosa respectivamente. El objetivo de la comunicación es resaltar la importancia de las técnicas moleculares para el diagnóstico preciso de la especie de Sporothrix spp, considerando los factores de riesgo asociados a la caracterización epidemiológica y a las diferencias clínico-evolutivas de los casos de esporotricosis.

Sporotrichosis is a deep mycosis caused by the dimorphic fungus Sporothrix schenckii. The advent of molecular techniques as the polymerase chain reaction has made it possible to identify several species within the Sporothrix spp complex such as S. brasiliensis, S. schenckii sensu stricto, S. globosa, S mexicana and S. albicans. The differences are molecular but also geographic, macroscopic, in sugar assimilation and colony growth at 37º, determining different clinical forms, evolution and therapeutic responses. We report 2 cases of sporotrichosis diagnosed in the National Hospital of Paraguay, whose studies of PCR of the calmodulin gene carried out abroad, determined to be produced by S. brasiliensis and S. globosa respectively. The objective of the communication is to highlight the importance of molecular techniques for the precise diagnosis of the species of Sporothrix spp, considering the risk factors associated with the epidemiological characterization and the clinical-evolutionary differences of the cases of sporotrichosis.

Direct PCR of lesions suggestive of sporotrichosis in felines / [PCR direta de lesões sugestivas de esporotricose em gatos]

A esporotricose é uma doença emergente e a incidência de esporotricose zoonótica tem aumentado, principalmente no Brasil; a maioria dos casos está relacionada à transmissão de gatos infectados. O diagnóstico definitivo da esporotricose felina é feito por cultura fúngica; no entanto, aguardar o longo período de cultura pode atrasar o início do tratamento. O objetivo deste estudo foi detectar e determinar as espécies de Sporothrix por PCR realizado diretamente das lesões de gatos, provenientes de área endêmica, nos quais a esporotricose fazia parte do diagnóstico diferencial. Um total de 87,1% dos casos foi positivo por PCR ou cultura fúngica para Sporothrix; 81,4% foram confirmados como S. brasiliensis por PCR, 71,4% por isolamento e 65,7% pelos dois métodos. Em conclusão, a análise direta por PCR de lesões sugestivas de esporotricose em gatos é um bom método para confirmar a infecção e determinar as espécies de Sporothrix, garantindo um diagnóstico rápido; esse método tem uma boa concordância com o isolamento fúngico.(AU)

Caracterização e avaliação da capacidade protetora dos peptí­deos imunogênicos de Sporothrix brasiliensis / Characterization and evaluation of the protective capacity of the immunogenic peptides of Sporothrix brasiliensis

A esporotricose é uma doença crônica que envolve o tecido subcutâneo afetando seres humanos e animais, causada pelo fungo termodimórfico Sporothrix spp.. A esporotricose é endêmica na América latina, principalmente no Brasil que teve o maior surto zoonótico já registrado, ocorrendo na cidade do Rio de Janeiro. A espécie Sporothrix brasiliensis é a mais diagnosticada no surto e a mais virulenta entre as especies de Sporothrix spp., causando formas mais graves da doença. A esporotricose em gatos é endêmica, fatal e um dos principais fatores pelo alto número de casos no Rio de Janeiro. O tratamento é longo e não vem sendo o suficiente para conter o número de casos da doença. Uma vacina contra a esporotricose poderia mudar esse paradigma no Brasil. O presente trabalho obteve o proteoma da cepa S. brasiliensis 5110 por meio de uma eletroforese 2D, e caracterizou e identificou as possíveis proteínas imunogênicas do fungo por espectrometria de massa. Por meio de programas de predição, foi avaliado e sintetizado 7 sequências de aminoácidos,das proteínas identificadas com maiores chances de se acoplar a molécula MHC de classe II. Apenas 3 foram capazes de induzir proliferação in vitro, os peptídeos ZR3, ZR4 e ZR8, que foram utilizados como vacina na esporotricose subcutânea e avaliados sua eficácia por meio da carga fúngica, diâmetro das lesões, perfil celular e níveis de citocinas. Neste trabalho concluímos que o peptídeo ZR8 foi o melhor candidato à vacina na esporotricose, pois foi capaz de diminuir o diâmetro das lesões, aumentar os níveis de citocinas protetoras (IFN-γ, IL-17A e IL-1ß) e aumentar o número de células TCD4+ e CD3-/CD19+, sendo assim induzindo uma resposta imunológica protetora na esporotricose subcutânea

Sporotrichosis is a chronic disease, which involves the subcutaneous tissue affecting humans and animals caused by the thermodymorphic fungus Sporothrix spp. Sporotrichosis is endemic in Latin America, mainly in Brazil that had the largest zoonotic outbreak ever recorded, occurring in the city of Rio de Janeiro. The Sporothrix brasiliensis is the species more diagnosed in the outbreak and most virulent, causing severe forms of the disease. Sporotrichosis in cats is endemic, fatal and the main factors due to the high number of cases of the disease in Rio de Janeiro. The treatment is long, and has not been enough to contain the number of cases of sporotrichosis. A vaccine against sporotrichosis could change this paradigm in Brazil. The present work obtained the proteome of S. brasiliensis 5110 strain by 2D electrophoresis, and characterized and identified possible immunogenic proteins by mass spectrometry. By prediction programs were evaluated and synthesized 7 peptide sequence from antigenic proteins that have the highest chances of coupling to the MHC class II molecule. From these 7 peptides only 3 were able to induce proliferation in vitro, called ZR3, ZR4 and ZR8 peptides, that were used as a vaccine in subcutaneous sporotrichosis and evaluated their efficacy through fungal load, lesion diameter, cell profile and cytokine levels. We conclude that ZR8 peptide was the best candidate for sporotrichosis vaccine, since it was able to decrease the lesion diameter, increase the levels of protective cytokines (IFN-γ, IL-17A and IL-1ß) and increase the number of CD4+ T cells and CD3-/CD19+ inducing a protective immune response in subcutaneous sporotrichosis

Caracterização e avaliação da capacidade protetora dos peptí­deos imunogênicos de Sporothrix brasiliensis / Characterization and evaluation of the protective capacity of the immunogenic peptides of Sporothrix brasiliensis

A esporotricose é uma doença crônica que envolve o tecido subcutâneo afetando seres humanos e animais, causada pelo fungo termodimórfico Sporothrix spp.. A esporotricose é endêmica na América latina, principalmente no Brasil que teve o maior surto zoonótico já registrado, ocorrendo na cidade do Rio de Janeiro. A espécie Sporothrix brasiliensis é a mais diagnosticada no surto e a mais virulenta entre as especies de Sporothrix spp., causando formas mais graves da doença. A esporotricose em gatos é endêmica, fatal e um dos principais fatores pelo alto número de casos no Rio de Janeiro. O tratamento é longo e não vem sendo o suficiente para conter o número de casos da doença. Uma vacina contra a esporotricose poderia mudar esse paradigma no Brasil. O presente trabalho obteve o proteoma da cepa S. brasiliensis 5110 por meio de uma eletroforese 2D, e caracterizou e identificou as possíveis proteínas imunogênicas do fungo por espectrometria de massa. Por meio de programas de predição, foi avaliado e sintetizado 7 sequências de aminoácidos,das proteínas identificadas com maiores chances de se acoplar a molécula MHC de classe II. Apenas 3 foram capazes de induzir proliferação in vitro, os peptídeos ZR3, ZR4 e ZR8, que foram utilizados como vacina na esporotricose subcutânea e avaliados sua eficácia por meio da carga fúngica, diâmetro das lesões, perfil celular e níveis de citocinas. Neste trabalho concluímos que o peptídeo ZR8 foi o melhor candidato à vacina na esporotricose, pois foi capaz de diminuir o diâmetro das lesões, aumentar os níveis de citocinas protetoras (IFN-γ, IL-17A e IL-1ß) e aumentar o número de células TCD4+ e CD3-/CD19+, sendo assim induzindo uma resposta imunológica protetora na esporotricose subcutânea

Sporotrichosis is a chronic disease, which involves the subcutaneous tissue affecting humans and animals caused by the thermodymorphic fungus Sporothrix spp. Sporotrichosis is endemic in Latin America, mainly in Brazil that had the largest zoonotic outbreak ever recorded, occurring in the city of Rio de Janeiro. The Sporothrix brasiliensis is the species more diagnosed in the outbreak and most virulent, causing severe forms of the disease. Sporotrichosis in cats is endemic, fatal and the main factors due to the high number of cases of the disease in Rio de Janeiro. The treatment is long, and has not been enough to contain the number of cases of sporotrichosis. A vaccine against sporotrichosis could change this paradigm in Brazil. The present work obtained the proteome of S. brasiliensis 5110 strain by 2D electrophoresis, and characterized and identified possible immunogenic proteins by mass spectrometry. By prediction programs were evaluated and synthesized 7 peptide sequence from antigenic proteins that have the highest chances of coupling to the MHC class II molecule. From these 7 peptides only 3 were able to induce proliferation in vitro, called ZR3, ZR4 and ZR8 peptides, that were used as a vaccine in subcutaneous sporotrichosis and evaluated their efficacy through fungal load, lesion diameter, cell profile and cytokine levels. We conclude that ZR8 peptide was the best candidate for sporotrichosis vaccine, since it was able to decrease the lesion diameter, increase the levels of protective cytokines (IFN-γ, IL-17A and IL-1ß) and increase the number of CD4+ T cells and CD3-/CD19+ inducing a protective immune response in subcutaneous sporotrichosis

Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis

BACKGROUND Sporothrix brasiliensis is the most virulent sporotrichosis agent. This species usually responds to antifungal drugs, but therapeutic failure can occur in some patients. Antifungal susceptibility tests have been performed on this species, but no clinical breakpoints (CBPs) are available. In this situation, minimal inhibitory concentration (MIC) distributions and epidemiological cutoff values (ECVs) support the detection of identification of resistant strains. OBJECTIVES To study the MIC distributions of five antifungal drugs against S. brasiliensis and to propose tentative ECVs. METHODS MICs of amphotericin B (AMB), itraconazole (ITR), ketoconazole (KET), posaconazole (POS), and terbinafine (TRB) against 335 S. brasiliensis strains were determined by the Clinical and Laboratory Standards Institute broth microdilution method. FINDINGS The proposed ECV, in µg/mL, for AMB, ITR, KET, POS, and TRB were 4.0, 2.0, 1.0, 2.0, and 0.25, respectively. Percentages of wild-type strains in our population for the above antifungal drugs were 98.48, 95.22, 95.33, 100, and 97.67%, respectively. MAIN CONCLUSIONS These ECVs will be useful to detect strains with resistance, to define CBPs, and to elaborate specific therapeutic guidelines for S. brasiliensis. Rational use of antifungals is strongly recommended to avoid the emergence of resistant strains and ensure the therapeutic effectiveness of sporotrichosis.

Sporothrix brasiliensis: aspectos imunológicos e virulência / Sporothrix brasiliensis: immunological aspects and virulence

A esporotricose caracteriza-se como uma micose subcutânea causada por fungos dimórficos do gênero Sporothrix, capazes de acometer o homem e uma grande variedade de animais, dentre eles os felinos. A princípio, Sporothrix schenckii era a única espécie conhecida como responsável pela esporotricose. Após estudos genotípicos e fenotípicos de isolados ambientais, clínicos humanos e animais, verificou-se alta variabilidade entre os isolados e estabeleceu-se a existência de um Complexo Sporothrix. Dentro deste, a maior causadora de surtos epidêmicos, justificada por uma maior virulência e capacidade de evasão da resposta imune, é a espécie Sporothrix brasiliensis. Nesse sentido, dada a ausência de estudos direcionados a está espécie, objetivou-se avaliar a importância de receptores Toll like-2 (TLR-2) e Toll like-4 (TLR-4) na infecção por S. brasiliensis. Além disso, utilizando técnicas de proteômica, procurou-se elucidar proteínas diferencialmente expressas em S. brasiliensis quando comparado à espécie S. schenckii. Para avaliação da resposta imune utilizaram-se modelos in vitro e in vivo de infecção, e para a investigação das proteínas diferencialmente expressas, utilizou-se a técnica de proteômica Bottom-up. A investigação da resposta imune in vitro mostrou a dependência dos receptores TLR-2 e TLR-4 no desencadeamento da resposta imune. Os ensaios in vivo mostraram a importância desses receptores no controle da infecção e dependência dos mesmos na produção de citocinas, principalmente nos primeiros 14 dias de infecção. Na ausência do receptor TLR-2, houve a polarização de resposta Th17 na tentativa de controle da infecção. Quando avaliadas as diferenças entre as espécies S. brasiliensis e S. schenckii, em termos de proteínas expressas, verificou-se que S. brasiliensis expressa diferencialmente 60 proteínas. Dentre essas, 9 são relatadas na literatura, como importantes na virulência e escape imunológico dos principais fungos de importância médica. Os resultados encontrados no presente trabalho permitem concluir que reconhecimento de S. brasiliensis é dependente dos receptores TLR-2 e TLR-4. Estudos que investiguem a utilização de outras vias de sinalização como mecanismos compensatórios, bem como, o sinergismo desses receptores no contexto da infecção por S. brasiliensis são fundamentais na compreensão da fisiopatologia dessa doença. No que tange a caracterização proteica, estudos com mutantes para cada uma das proteínas descritas nesse trabalho devem ser avaliados

Sporotrichosis is a subcutaneous mycosis caused by dimorphic fungi of the genus Sporothrix that affects humans and animals, predominantelly felines. Inicially, Sporothrix schenckii was the only specie associated to sporotrichosis. However, after genotypic and phenotypic studies of human and animal clinical isolates, a high variability among the isolates was found and was concluded the existence of a complex: the Sporothrix Complex. Inside the Sporothrix complex, the major cause of epidemic outbreaks, justified by a greater virulence and ability to evade the immune system, is Sporothrix brasiliensis. Concerning this, the absence of studies directed to this specific specie, the aim was to evaluate the importance of Toll like receptor-2 (TLR-2) and Toll like receptor-4 (TLR-4) during S. brasiliensis infection. In addition, was look using proteomics techniques, the proteins differentially expressed in S. brasiliensis when compared to S. schenckii. To evaluate the immune response, in vitro and in vivo tecniques were used, and for the investigation of differentially expressed proteins, the Bottom-up proteomics technique was used. The investigation of the in vitro immune response showed the dependence of TLR-2 and TLR-4 receptors on phagocytosis and the production of inflammatory mediators, such as cytokines and NO. In vivo assays showed the importance of these receptors to control the infection and their dependence on cytokine production during the first 14 days of infection. In the absence of the TLR-2 receptor, the Th17 response was polarized in an attempt to control the infection. Evaluating the differences between S. brasiliensis and S. schenckii, in terms of expressed proteins, it was verified that S. brasiliensis differentially expressed 60 proteins. Among these, 9 are reported in the literature, as important in the virulence and immune evasion among the most important medical fungi. The results found in the present study allow to conclude that S. brasiliensis recognition is dependent on TLR-2 and TLR-4 receptors. Studies investigating the use of other signaling pathways as compensatory mechanisms, as well as the synergism of these receptors in the context of S. brasiliensis infection, are fundamental to understand the pathophysiology of this disease. Regarding the protein characterization, studies with mutants for each of the proteins described in this work should be evaluated

Avaliação de fatores epidemiológicos, micológicos, clínicos e terapêuticos associados à esporotricose / Evaluation of epidemiological, mycological, clinical and therapeutic factors associated with sporotrichosis

Esporotricose é uma micose subcutânea causada pelo fungo dimórfico previamente descrito como uma única espécie, Sporothrix schenckii, agora entendido como um complexo de diferentes espécies de interesse clínico. A região metropolitana do Rio de Janeiro constitui área hiperendêmica de esporotricose zoonótica transmitida por gatos desde 1998. Clinicamente tem se caracterizado por formas clínicas pouco usuais, manifestações de hipersensibilidade e um número crescente de pacientes coinfectados com HIV. Este estudo teve como objetivo avaliar fatores epidemiológicos, micológicos, clínicos e terapêuticos associados às diversas formas clínicas de pacientes com esporotricose. Foram utilizados o banco hospitalar de registros de pacientes e o banco de cepas do laboratório de micologia do Instituto de Pesquisa Clínica Evandro Chagas (IPEC), bem como técnicas de identificação genotípica e laboratoriais clássicas para determinação de virulência e fenótipo dos isolados fúngicos. Foi verificado que a dacriocistite aguda (quatro casos entre 2008 e 2010) é uma manifestação da esporotricose que evolui com complicações (fístula e dacriocistite crônica) necessitando reparação cirúrgica. A Síndrome de Sweet foi observada em três pacientes até 2010 e deve ser incorporada como manifestação de hipersensibilidade da esporotricose...

Sporotrichosis is a subcutaneous mycosis caused by the dimorphic fungus previously described as a single species, Sporothrix schenckii, now understood as a complex of different species of clinical interest. The metropolitan region of Rio de Janeiro is an endemic area of zoonotic sporotrichosis transmitted by cats since 1998. Clinically, it has been characterized by unusual clinical presentations, manifestations of hypersensitivity and an increasing number of patients coinfected with HIV. This study aimed to evaluate epidemiological, mycological, clinical and therapeutic factors associated with different clinical aspects of patients with sporotrichosis. The hospital database of patient records and the stock strains of the laboratory of mycology of Instituto de Pesquisa Clínica Evandro Chagas (IPEC) were used, as well as techniques for genotypic identification and classical laboratory tools for determination of virulence and phenotype of the fungal isolates. It was found that acute dacryocystitis (4 cases between 2008 and 2010) is a manifestation of sporotrichosis which evolves with complications (fistula and chronic dacryocystitis) requiring surgical repair. Sweet syndrome was observed in three patients until 2010 and should be incorporated as a manifestation of hypersensitivity of sporotrichosis...