A neglected disease. Human sporotrichosis in a densely populated urban area in São Paulo, Brazil: clinical-epidemiological and therapeutic aspects.

Human sporotrichosis is caused by different Sporothrix species; however, Sporothrix brasiliensis is the main species, usually related to cat transmission in urban areas. A retrospective descriptive study was conducted at the Institute of Infectology Emílio Ribas from 2010 to 2018. Demography, clinical, diagnostic, and therapeutic data were obtained from medical records. Polymerase chain reaction of the calmodulin gene was performed to identify Sporothrix species. In addition, to evaluate the spread of the disease across São Paulo metropolitan region, TerraView version 4.2.2 software was used for geocoding cases according to residence addresses. Kernell's maps using QGIS software version 2.16.3 were constructed to determine the concentration of cases. Results: 260 cases of sporotrichosis were diagnosed between 2010 and 2018. We observed a 700% increment in the number of human cases in the 2016-2018 triennium compared with the 2013-2015 triennium. Female adults with a median age of 46 years old were the predominant infected group associated with cats' exposition at home care, although the age range of all patients was 01 to 86 years old. The main epidemiological risk of acquiring sporotrichosis was contact with cats, reported by 96.5% of the patients. Molecular identification showed that most of the tested isolates were Sporothrix brasiliensis. Lymphocutaneous form was observed in 59.2% and fixed cutaneous form in 37.5% of the patients. Regarding treatment, itraconazole was the main drug used (94.2%) with a cure rate of 98.8%. We observed an important spread of human sporotrichosis involving cat transmission caused by Sporothrix brasiliensis in a densely populated area of São Paulo state. These results are important to alert clinicians and dermatologists about the occurrence and progression of a neglected tropical disease in an urban area and the urgent necessity to include sporotrichosis as a differential diagnosis in the clinical investigation routine.

Extracellular matrix alterations in the skin of patients affected by psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease dependent upon a complex interaction between genetic predisposition and immunological factors. It is characterized by skin lesions throughout the body, causing great morbidity and affecting life quality. The present study aimed to evaluate the protein and mRNA expression of heparanase-1 (HPSE), heparanase-2 (HPSE2), syndecan-1 (SYND1), metalloproteinases (MMP2, MMP9), and tissue inhibitor metalloproteinases 2 (TIMP2) in skin samples. METHODS: From each psoriasis patient, two samples were collected, one sample from a psoriasis plaque (n = 23) and the other sample from non-affected skin (n = 23), as well as tissue collected by blepharoplasty from control individuals (n = 18). Protein expression was investigated by immunohistochemistry, followed by digital quantification. Quantitative RT-PCR obtained mRNA expression. Statistical analyses were done, and p values < 0.05 were considered significant. RESULTS: A significant increase in protein and mRNA expression was observed in both heparanases (HPSE and HPSE2), and higher protein levels of MMP9 and TIMP2 were observed in the psoriasis plaque compared to the non-affected skin. The data point to a probable activation of MMP2 by TIMP2. Moreover, there was a significant increase in HPSE2, SYND1, MMP9, and TIMP2 in non-affected skin samples from patients with psoriasis than in the control sample (tissue obtained by individuals who do not have psoriasis). CONCLUSIONS: These results show a possible correlation between the characteristic inflammatory process and alterations in the expression of the extracellular matrix in psoriasis. The increased expression of HPSE2, SYND1, MMP9, and TIMP2, even in the absence of psoriatic plaque, indicates that these molecules may be involved with extracellular matrix changes in the initial alterations the psoriatic process and may be candidates for the development of target treatments.

Unusual manifestation of genital cutaneous leishmaniasis in an immunocompetent patient from São Paulo, Brazil: A case report.

A 31-year-old male patient developed an ulcer on the glans penis that evolved for three months without healing. We diagnosed it as leishmaniasis using polymerase chain reaction. No immunosuppression or associated diseases were observed. The patient was treated with meglumine antimoniate that cured the lesion in a month post-treatment. Here, we report this case of cutaneous leishmaniasis lesion at the unusual location of glans penis in an immunocompetent individual. The lesion likely developed due to the bite of a vector, highlighting the need for considering cutaneous leishmaniasis among differential diagnosis of sexually transmitted diseases in areas endemic for leishmaniasis.

Socioeconomic impact of high-cost drugs in Brazilian dermatology. Legal and financial aspects, and impact on clinical practice

Abstract The technological advancement of the pharmaceutical industry, resulting from the techniques of molecular biology and expansion of the knowledge of immunopathogenesis, has modified the therapeutic arsenal used in dermatology. Scientific research and regulatory standards cause drug costs to rise, thus making their use impossible in most public policies. In order to make high-cost drugs viable in the public health network, the Specialized Pharmaceutical Assistance Component was created. However, despite the frequent incorporation of medications, the constant requirement of drugs through lawsuits leads to exorbitant costs to the state budget. The present work analyzed through a descriptive observational study, the current situation of the Specialized Component and the involvement of medicines used in dermatology, through legal reviews, financial analyses, and medical articles, aiming at future incorporations for the specialty. When assessing the legal demands for dermatological drugs in the state of São Paulo, the specialty still has a low participation and psoriasis is the main disease involved in requiring drugs through the judicial system in the state. New methods of access to raw materials must be created to reduce legal issues. Cost-effectiveness and public planning studies are mandatory for incorporating new dermatological therapies.

Socioeconomic impact of high-cost drugs in Brazilian dermatology. Legal and financial aspects, and impact on clinical practice.

The technological advancement of the pharmaceutical industry, resulting from the techniques of molecular biology and expansion of the knowledge of immunopathogenesis, has modified the therapeutic arsenal used in dermatology. Scientific research and regulatory standards cause drug costs to rise, thus making their use impossible in most public policies. In order to make high-cost drugs viable in the public health network, the Specialized Pharmaceutical Assistance Component was created. However, despite the frequent incorporation of medications, the constant requirement of drugs through lawsuits leads to exorbitant costs to the state budget. The present work analyzed through a descriptive observational study, the current situation of the Specialized Component and the involvement of medicines used in dermatology, through legal reviews, financial analyses, and medical articles, aiming at future incorporations for the specialty. When assessing the legal demands for dermatological drugs in the state of São Paulo, the specialty still has a low participation and psoriasis is the main disease involved in requiring drugs through the judicial system in the state. New methods of access to raw materials must be created to reduce legal issues. Cost-effectiveness and public planning studies are mandatory for incorporating new dermatological therapies.

Unusual manifestation of genital cutaneous leishmaniasis in an immunocompetent patient from São Paulo, Brazil: A case report

Abstract A 31-year-old male patient developed an ulcer on the glans penis that evolved for three months without healing. We diagnosed it as leishmaniasis using polymerase chain reaction. No immunosuppression or associated diseases were observed. The patient was treated with meglumine antimoniate that cured the lesion in a month post-treatment. Here, we report this case of cutaneous leishmaniasis lesion at the unusual location of glans penis in an immunocompetent individual. The lesion likely developed due to the bite of a vector, highlighting the need for considering cutaneous leishmaniasis among differential diagnosis of sexually transmitted diseases in areas endemic for leishmaniasis.

Assessment of psoriasis severity in Brazilian patients with chronic plaque psoriasis attending outpatient clinics: a multicenter, population-based cross-sectional study (APPISOT).

PURPOSE: Data on chronic plaque psoriasis severity and its potential clinical and lifestyle implications in the Brazilian population are limited. The primary aim of this study was to assess the clinical severity of plaque psoriasis in Brazil. Further objectives included evaluating potential associations between disease severity and demographic, lifestyle, and clinical characteristics, health-related quality of life (HRQOL), and work productivity. MATERIALS AND METHODS: This observational (non-interventional) cross-sectional study was conducted in 26 dermatologic clinics across 11 Brazilian states. Psoriasis severity was assessed using investigator judgment and Finlay's Rule of Tens: a Psoriasis Area and Severity Index (PASI) score >10, a Body Surface Area (BSA) > 10%, or a Dermatology Life Quality Index (DLQI) score >10. RESULTS: Among 1125 patients, 205 (18.2%) had moderate-to-severe disease. On multiple regression analyses, psoriasis severity was significantly (directly) associated with the presence of physical inactivity and comorbid pain, anxiety, and depression; and significantly (inversely) associated with HRQOL and work productivity. LIMITATIONS: Cross-sectional studies cannot assess temporal trends, and observational studies cannot conclusively determine causality or exclude biases and confounding due to unmeasured variables. CONCLUSIONS: Among Brazilian patients with moderate-to-severe psoriasis, disease severity had far-reaching adverse impacts on lifestyle, comorbidities, HRQOL, and work productivity.

Para-kala-azar dermal leishmaniasis in a patient in Brazil: a case report.

Visceral leishmaniasis is common in Brazil and is caused by Leishmania (Leishmania) infantum/chagasi. Post-kala-azar dermal leishmaniasis frequently follows visceral leishmaniasis caused by L. donovani, and para-kala-azar dermal leishmaniasis refers to an uncommon presentation wherein it occurs simultaneously along with visceral leishmaniasis. While post-kala-azar dermal leishmaniasis only occurs occasionally in L. infantum/chagasi infections, it frequently occurs in patients with concomitant immunosuppression (HIV co-infection). Here, we describe the first case of para-kala-azar dermal leishmaniasis in Brazil. It is important to raise awareness of post- and para-kala-azar dermal leishmaniasis in L. infantum endemic areas as these patients may contribute to visceral leishmaniasis transmission.

Para-kala-azar dermal leishmaniasis in a patient in Brazil: a case report

Abstract Visceral leishmaniasis is common in Brazil and is caused by Leishmania (Leishmania) infantum/chagasi. Post-kala-azar dermal leishmaniasis frequently follows visceral leishmaniasis caused by L. donovani, and para-kala-azar dermal leishmaniasis refers to an uncommon presentation wherein it occurs simultaneously along with visceral leishmaniasis. While post-kala-azar dermal leishmaniasis only occurs occasionally in L. infantum/chagasi infections, it frequently occurs in patients with concomitant immunosuppression (HIV co-infection). Here, we describe the first case of para-kala-azar dermal leishmaniasis in Brazil. It is important to raise awareness of post- and para-kala-azar dermal leishmaniasis in L. infantum endemic areas as these patients may contribute to visceral leishmaniasis transmission.

Efficiency of noninvasive sampling methods (swab) together with Polymerase Chain Reaction (PCR) for diagnosing American Tegumentary Leishmaniasis.

Traditional diagnostic methods used to detect American Tegumentary Leishmaniasis, such as histopathology using biopsy samples, culture techniques, and direct search for parasites, have low sensitivity and require invasive collection procedures. This study evaluates the efficiency of noninvasive sampling methods (swab) along with Polymerase Chain Reaction (PCR) for diagnosing American Tegumentary Leishmaniasis using skin and mucous samples from 25 patients who had tested positive for leishmaniasis. The outcome of the tests performance on swab samples was compatible with PCR results on biopsy samples. The findings have also shown that PCR-kDNA test is more efficient than PCR-HSP70 and qPCR tests (sensitivity of 92.3%, 40.7%, and 41%, respectively). Given the high sensitivity of the tests and the fact that the sampling method using swabs affords greater patient comfort and safety, it could be said that this method is a promising alternative to conventional biopsy-based methods for the molecular diagnosis of leishmaniasis.

Efficiency of noninvasive sampling methods (swab) together with Polymerase Chain Reaction (PCR) for diagnosing American Tegumentary Leishmaniasis

ABSTRACT Traditional diagnostic methods used to detect American Tegumentary Leishmaniasis, such as histopathology using biopsy samples, culture techniques, and direct search for parasites, have low sensitivity and require invasive collection procedures. This study evaluates the efficiency of noninvasive sampling methods (swab) along with Polymerase Chain Reaction (PCR) for diagnosing American Tegumentary Leishmaniasis using skin and mucous samples from 25 patients who had tested positive for leishmaniasis. The outcome of the tests performance on swab samples was compatible with PCR results on biopsy samples. The findings have also shown that PCR-kDNA test is more efficient than PCR-HSP70 and qPCR tests (sensitivity of 92.3%, 40.7%, and 41%, respectively). Given the high sensitivity of the tests and the fact that the sampling method using swabs affords greater patient comfort and safety, it could be said that this method is a promising alternative to conventional biopsy-based methods for the molecular diagnosis of leishmaniasis.

The management of pemphigus ulcers: a challenge and learning opportunity for brazilian nurses / Tratamento de úlceras secundárias ao pênfigo: um desafio e oportunidade de aprendizado para as enfermeiras brasileiras

Pemphigus is a group of autoimmune disorders characterised by the production of antibodies against glycoprotein that connects skin cells, leading to mucocutaneous blistering. While pemphigus foliaceus is regularly found in some areas of Brazil, other variants that affect the deeper layer of skin such as pemphigus vulgaris (PV) is also common. In general, pemphigus often result in extensive skin loss, leading to scar formation and adherence of articular skin folds, limiting joint and limb movements. In this case series, we report the experience of using essential fatty acid (EFA) oil for patients with PV skin lesions in a Brazilian state hospital in the city of São Paulo. An interprofessional team was involved in the provision of comprehensive treatment for pemphigus-related skin lesions and complications. Patients treated with EFA achieved a significant reduction in pain, faster healing and fewer complications compared to previous convention treatment approach

Pênfigo é um grupo de doenças autoimmune caracterizadas pela produção de anticorpos contra glicoproteínas que conectam as células cutâneas ocasionando bolhas mucocutâneas. Enquanto o pênfigo foliáceo é endêmico em algumas áreas do Brasil, outras variantes que afetam camadas mais profundas da pele, como o pênfigo vulgar, também são comuns. Muitas vezes o pênfigo resulta em extensa perda da epiderme, levando a formação de cicatrizes e aderência das pregas articulares, acarretando limitação de movimentos. Nesta série de casos, reportamos a experiência do uso do óleo de ácidos graxos essenciais (AGE) em pacientes com úlceras cutâneas secundárias ao pênfigo vulgar em um hospital estadual brasileiro na cidade de São Paulo. Uma equipe interdisciplinar esteve envolvida na provisão de um tratamento holístico para as úlceras secundárias ao pênfigo e suas complicações. Os pacientes tratados com AGE apresentaram redução significativa da dor, cicatrização mais rápida e menos complicações quando comparado ao tratamento convencional

Photodynamic therapy using methylene blue to treat cutaneous leishmaniasis.

OBJECTIVE: The purpose of this study was to show the efficiency and underlying mechanism of action of photodynamic therapy (PDT) using methylene blue (MB) and non-coherent light sources to treat cutaneous leishmaniasis (CL). BACKGROUND DATA: Systemic treatment can cause severe side effects, and PDT using porphyrin precursors as sensitizers has been used as an alternative to treat CL. MB has been used under illumination or in the dark to treat a wide range of medical conditions, and it exhibits antimicrobial activity against protozoa and viruses. METHODS: In in vitro tests, the cell viability (via a MTT colorimetric assay) of Leishmania amazonensis parasites was evaluated as a function of MB concentration. In in vivo experiments, we analyzed the treatment of two lesions from a patient with leishmaniasis. The patient received a low dose of pentavalent antimony (SbV), and one lesion was treated with PDT. RESULTS: We observed IC(50) decreases from 100 to 20 µM in response to PDT when MB was used in different concentrations in in vitro tests. Use of SbV in combination with the PDT protocol produced faster wound recovery when compared with the use of SbV alone. CONCLUSIONS: The in vitro experiments and the results from the clinical case suggest that the inexpensive PDT protocol that is based on MB and RL50® may be used to treat CL caused by L. amazonensis.

Profile of patients with Baggio-Yoshinari Syndrome admitted at "Instituto de Infectologia Emilio Ribas" / Perfil dos pacientes com Síndrome Baggio-Yoshinari admitidos no "Instituto de Infectologia Emilio Ribas"

The aim of this study was to evaluate the epidemiological, clinical and laboratorial profile of patients with Baggio-Yoshinari Syndrome (BYS), who underwent internment at the Instituto de Infectologia Emilio Ribas in São Paulo, Brazil, during the period from July 1990 to July 2006. BYS is a new Brazilian tick-borne disease caused by Borrelia burgdorferi sensu lato microorganisms that resembles features of Lyme disease (LD), except for its epidemiological, clinical and laboratorial particularities. From 60 patients' records with positive serology to B. burgdorferi done by ELISA and Western-blotting methods, 19 cases were diagnosed as having BYS, according to criteria adopted at LIM-17 HCFMUSP, the Brazilian Reference Laboratory for the research of BYS. The other 41 remaining patients displayed miscellaneous infections or auto-immune processes. The beginning of symptoms in BYS group varied from one day to six years, from the onset of the disease. Four of 19 patients were included in acute disease stage, and 15 in latent. General unspecific symptoms were identified in almost all cases, with high frequencies of fever (78.9 percent) and lymphadenomegaly (36.8 percent). Six patients had skin lesions (31.5 percent); six arthralgia or arthritis (31.5 percent) and eight neurological symptoms (42 percent). Interestingly, two patients showed antibodies directed to B. burgdorferi exclusively in cerebrospinal fluid. Since BYS is a new emergent Brazilian zoonosis and its diagnosis is sometimes complex, all the new knowledge about BYS must be scattered to Brazilian Medical specialists, aiming to teach them how to diagnose this amazing tick-borne disease and to avoid its progression to chronic irreversible sequels.

O objetivo do estudo foi avaliar o perfil epidemiológico, clínico e laboratorial dos pacientes com Síndrome Baggio-Yoshinari (SBY), internados no Instituto de Infectologia Emilio Ribas, São Paulo, Brasil, no período de julho de 1990 a julho de 2006. SBY é uma nova doença transmitida por carrapatos, causada pela Borrelia burgdorferi sensu lato, que se assemelha a Doença de Lyme (DL), exceto pelas particularidades epidemiológicas, clínicas e laboratoriais. A partir dos registros de 60 pacientes com sorologia positiva para B. burgdorferi pelos métodos de ELISA e Western-blotting, 19 casos foram diagnosticados como SBY, de acordo com critérios adotados pelo LIM-17 HCFMUSP, laboratório de referência para a pesquisa de SBY no Brasil. Os outros 41 pacientes restantes foram classificados como tendo infecções diversas ou processos auto-imunes. O início dos sintomas no grupo SBY variou de um dia a seis anos. Quatro dos 19 pacientes foram incluídos na fase aguda da doença e 15 na fase latente. Os sintomas gerais inespecíficos foram identificados em quase todos os casos, com altas freqüências de febre (78,9 por cento) e linfoadenomegalia (36,8 por cento). Seis pacientes tiveram lesões de pele (31,5 por cento); seis artralgia ou artrite (31,5 por cento) e oito sintomas neurológicos (42 por cento). Curiosamente, dois pacientes apresentaram anticorpos para B. burgdorferi exclusivamente no líquido cefalorraquidiano. Uma vez que a SBY é uma zoonose emergente brasileira e seu diagnóstico é complexo, todo o conhecimento novo sobre SBY deve ser difundido para os médicos brasileiros, com o objetivo de ensiná-los a diagnosticar esta surpreendente doença transmitida por carrapatos, evitando-se a sua progressão para sequelas crônicas irreversíveis.

Profile of patients with Baggio-Yoshinari Syndrome admitted at "Instituto de Infectologia Emilio Ribas".

The aim of this study was to evaluate the epidemiological, clinical and laboratorial profile of patients with Baggio-Yoshinari Syndrome (BYS), who underwent internment at the Instituto de Infectologia Emilio Ribas in São Paulo, Brazil, during the period from July 1990 to July 2006. BYS is a new Brazilian tick-borne disease caused by Borrelia burgdorferi sensu lato microorganisms that resembles features of Lyme disease (LD), except for its epidemiological, clinical and laboratorial particularities. From 60 patients' records with positive serology to B. burgdorferi done by ELISA and Western-blotting methods, 19 cases were diagnosed as having BYS, according to criteria adopted at LIM-17 HCFMUSP, the Brazilian Reference Laboratory for the research of BYS. The other 41 remaining patients displayed miscellaneous infections or auto-immune processes. The beginning of symptoms in BYS group varied from one day to six years, from the onset of the disease. Four of 19 patients were included in acute disease stage, and 15 in latent. General unspecific symptoms were identified in almost all cases, with high frequencies of fever (78.9%) and lymphadenomegaly (36.8%). Six patients had skin lesions (31.5%); six arthralgia or arthritis (31.5%) and eight neurological symptoms (42%). Interestingly, two patients showed antibodies directed to B. burgdorferi exclusively in cerebrospinal fluid. Since BYS is a new emergent Brazilian zoonosis and its diagnosis is sometimes complex, all the new knowledge about BYS must be scattered to Brazilian Medical specialists, aiming to teach them how to diagnose this amazing tick-borne disease and to avoid its progression to chronic irreversible sequels.

Phase II randomized, placebo-controlled trial of M. vaccae-derived protein (PVAC) for the treatment of psoriasis.

The treatment effect against psoriasis of an antigen (delipidated, deglycolipidated form of M. vaccae-PVAC) was investigated. One hundred and sixty-five patients were enrolled in three arms (50 or 15 microg or placebo), each receiving a total of two intradermal injections (days 0 and 21). At week 12, a 75% decrease in psoriasis area and severity index was similar among the studied groups (13, 9 and 18%, p=0.429). The overall incidence of adverse events was significantly higher in the PVAC treated groups when compared to placebo (98.2, 87.3 and 70.9%; p<0.001) largely due to local reactions that were limited for the most part to grades 1 and 2 in severity and were self-limiting. Despite its overall safety, PVAC was not clearly indicated to be superior to placebo in the treatment of psoriasis in this study.