Pemphigus foliaceus converting into bullous pemphigoid: the first case reported in China / 中华皮肤科杂志

A 58-year-old female patient presented with painful and itchy skin lesions on the head, neck, chest and back for 20 days, and was admitted to the hospital in February 2010. The skin lesions manifested as superficial erosions on an erythematous base with positive Nikolsky′s sign. Histopathological examination showed fissures above the granular and spinous cell layers, and scattered dyskeratotic cells. Direct immunofluorescence (DIF) assay revealed IgG and C3 deposits between spinous cells. The patient was initially diagnosed with pemphigus foliaceus. After the treatment with triamcinolone (24 mg/d) , tripterygium glycosides (60 mg/d) , nicotinamide (300 mg/d) and tetracycline (2 g/d) , skin lesions gradually subsided. In June 2017, the patient was readmitted due to itchy skin lesions on the head, neck, chest, back and hands for 15 days, which manifested as tense bullae on an erythematous base with negative Nikolsky′s sign. Histopathological examination showed subepidermal blisters and infiltration of eosinophils and lymphocytes in the blisters and superficial dermis, DIF assay revealed the deposition of IgG and C3 along the basement membrane zone, and enzyme-linked immunosorbent assay showed positive results for anti-BP180 antibody but negative results for anti-Dsg1 and Dsg3 antibodies. Then, a diagnosis of bullous pemphigoid was confirmed. The patient was treated with oral triamcinolone (12 mg/d) , nicotinamide (300 mg/d) and tetracycline (2 g/d) , and the lesions rapidly subsided.

Evaluation of non-endemic pemphigus foliaceus in a large series of patients: a single-center retrospective study from Turkey focuses on the relapses

Abstract Background: Pemphigus foliaceus is exceedingly rare around the world, except within the few regions where it occurs as an endemic variant. Various factors can trigger immune mechanisms that induce pemphigus foliaceus or worsen its course. Objective: To determine the demographic and clinical characteristics of the patients with pemphigus foliaceus in a large series from a non-endemic country, investigate the triggering factors, and seasonal patterns. Methods: The data of the patients diagnosed with pemphigus foliaceus in the study's center between 1989-2018 were retrospectively analyzed. Results: Sixty-eight patients (mean age, 45.7 ± 14.5 years) were included in the study. The number of onsets reached its peak in spring-summer (p = 0.008). A total of 117 relapses occurred in 42 patients and were most common in spring-summer (not significant). Specific trigger factors were detected in 45 relapses. In the other 72 relapses, the peak was observed in spring-summer (p = 0.005). There were no significant differences in the demographic and clinical variables investigated between relapsed and non-relapsed patients. Study limitations: Retrospective design. Conclusions: Triggering factors could not be identified in more than half of the relapses in the study's series. The subgroup of relapses (without identified causes), as well as the onsets of the disease, showed a significant seasonal variation with a peak in spring-summer; however, the seasonal variable did not justify the total group of relapses. Although the seasonal variation may be caused by a combination of factors, UV radiation should be considered a trigger factor for the peaks in spring-summer, particularly in Turkey.

The mechanism of chloroquine/hydroxychloroquine and its application in stomatological diseases / 口腔疾病防治

@#Chloroquine and hydroxychloroquine are both classic 4-aminoquinoline antimalarial drugs with similar chemical structures and mechanisms of action. As the toxicity and side effects of hydroxychloroquine are lower than those of chloroquine, hydroxychloroquine is the main clinical application at present, with good efficacy and safety. Chloroquine and hydroxychloroquine are widely used in the clinic because of their immunosuppressive, anti-inflammatory, antiviral, antitumor and photoprotective effects. The main mechanisms by which chloroquine/hydroxychloroquine inhibits immunity include inhibiting lysosome activity, autophagy, immune response signaling pathways production of proinflammatory cytokines. Chloroquine stabilizes the lysosomal membrane and reduces the release of lysosomal enzymes. As a prostaglandin antagonist, chloroquine can reduce the production of prostaglandins and leukotrienes, thus playing an anti-inflammatory role. Chloroquine/hydroxychloroquine can inhibit virus proliferation in the early stage of virus replication by inhibiting the glycosylation of the angiotensin converting enzyme 2 receptor. At present, hydroxychloroquine has been found to have significant efficacy in discoid lupus erythematosus, oral lichen planus, chronic cheilitis, pemphigus foliaceus, Sjögren’s syndrome and other stomatological diseases. However, eye damage is the most important adverse reaction of hydroxychloroquine, and its occurrence is related to the cumulative dose of drugs.

Comparative study of direct and indirect immunofluorescence for diagnosis of canine pemphigus foliaceus / Estudo comparativo da imunofluorescência direta e indireta para o diagnóstico do pênfigo foliáceo canino

Pemphigus foliaceus (PF) is the most common autoimmune skin disease in dogs. It is characterized by pustules, erosions, and crusts which occur due to the presence of autoantibodies that target intercellular adhesion. Histopathological examination is considered the gold standard pattern in the diagnosis, but may sometimes be inconclusive, especially when the characteristic findings are not identified. New diagnostic tests are continuously being developed and immunofluorescence assays, could be a valuable alternative diagnostic tool. This study aimed to evaluate the applicability of direct and indirect immunofluorescence (DIF and IIF) tests for the diagnosis of canine PF. Twenty eight dogs were divided into two groups: Group I with 14 dogs with PF and Group II (control) with 14 dogs with Superficial pyoderma (differential diagnoses of PF). All animals were submitted to skin biopsy to histopathological and DIF. Blood samples were collected to assess IIF. Comparing the DIF results against the histopathology test, there was an agreement of 75% (9/12) with a Kappa index of 0.77 (P<0.001). Considering IIF, the agreement was 100% (14/14), with a Kappa index of 1.0 (P<0.001). We conclude that DIF and IIF are highly effective and were useful and effective complementary examination tests for an improvement in the diagnosis of canine PF.(AU)

O pênfigo foliáceo (PF) é considerado uma das doenças tegumentares autoimunes mais frequentes em cães. Clinicamente, caracteriza-se pela presença de pústulas, erosões e crostas. O exame histopatológico é considerado o teste diagnóstico de eleição, porém pode se mostrar inconclusivo, sobretudo quando os achados característicos da doença não são observados. Novas ferramentas diagnósticas têm sido desenvolvidas e os testes de imunofluorecência são uma valiosa alternativa. Este estudo teve como objetivo avaliar a aplicabilidade das reações de imunofluorescência direta (IFD) e indireta (IFI) para o diagnóstico do PF canino. Vinte e oito cães foram divididos em dois grupos: grupo I com 14 cães com PF e grupo II (controle) com 14 cães com piodermite superficial (um dos principais diagnósticos diferenciais do PF). Todos os animais foram submetidos à biópsia cutânea, seguida de exame histopatológico e IFD. Amostras de sangue foram coletadas para realização da IFI. Comparando-se os valores de IFD com o histopatológico, obtiveram-se valores de concordância de 75% (9/12), com índice Kappa de 0,77 (P<0,001). Já na IFI, a concordância foi de 100% (14/14), com índice Kappa de 1,0 (P<0,001). Concluiu-se, então, que a IFD e a IFI apresentaram excelentes resultados e podem ser consideradas novas alternativas diagnósticas do PF canino.(AU)

Pênfigo Foliáceo Endêmico (Fogo Selvagem) e sua associação com fatores ambientais e ocupacionais em Ouro Preto, Minas Gerais, Brasil / Endemic Pemphigus Foliaceus (Fogo Selvagem) and its association with environmental and occupational factors in Ouro Preto, Minas Gerais, Brazil

Resumo Pênfigo compreende grupo de doenças bolhosas autoimunes que possuem tendência à progressão, com evolução ilimitada e crônica e com prognóstico potencialmente fatal. O tipo mais comum é o Pênfigo Foliáceo Endêmico (PFE), caracterizado pela presença de lesões cutâneas com formação de bolhas na face, no couro cabeludo e na região interescapular. Fatores de ordem ambiental, genéticos e imunológicos podem desencadear a enfermidade. Entre os fatores ambientais, exposição a mercúrio, poeiras minerais e a picada do mosquito Simulium nigrimanum devem ser considerados. Buscou-se, neste artigo, relatar a ocorrência do PFE entre a população de Antônio Pereira, distrito rural de Ouro Preto, Minas Gerais, bem como identificar possíveis associações da doença com fatores ocupacionais e ambientais locais. Foi constatada uma prevalência de 4,57 casos de PFE/1.000 habitantes, considerada bastante elevada. Observou-se associação estatística entre a doença e contato com barragem de rejeitos de mineração (p = 0,048) e exposição ao mercúrio (p = 0,008). Os resultados indicam a necessidade de vigilância epidemiológica eficaz das comunidades afetadas, assim como adequada assistência à saúde dos pacientes acometidos pela doença.

Abstract Pemphigus comprises a group of autoimmune bullous diseases, which have a tendency of progression, with unlimited and chronic development and with a potentially to fatal disease prognosis. The most common type is the Endemic Pemphigus Foliaceus (EPF), characterized by the presence of skin lesions with blistering located on the face, scalp and interscapular region. Environmental, genetic and immunological factors may trigger the disease. Among the environmental factors, exposure to mercury, mineral dust and Simulium nigrimanum mosquitoes bite should be considered. Sought to, in this article, it is reported the occurrence of PFE among the population of Antonio Pereira, rural district of Ouro Preto, Minas Gerais, and identify their possible association with occupational and environmental local factors. A prevalence of 4.57 cases of EPF/1.000 inhabitants, considered high was found. There was association between the disease and contact with dam tailings mining (p=0.048); and exposure to mercury (p=0.008). The results indicate the need for effective surveillance of the affected communities, as well as adequate health care of patients affected by the disease.

Análise espacial da distribuição de pênfigo vulgar e foliáceo no âmbito de três bacias hidrográficas presentes no nordeste do Estado de São Paulo e a relação com fatores ambientais / Analysis of the spatial distribution of pemphigus vulgaris and pemphigus foliaceus under three watersheds present in the northeastern state of São Paulo and the relationship with environmental factors

Focos geográficos bem definidos de pênfigo prevalecem no mundo todo, inclusive no Brasil. Nas últimas décadas vem sendo estudada a possibilidade de fatores ambientais participarem do desencadeamento da doença. A região nordeste do Estado de São Paulo, onde localizam-se três Bacias Hidrográficas, apresenta prevalência de duas formas clínicas do pênfigo, pênfigo vulgar (PV) e pênfigo foliáceo endêmico (PFE) sendo uma importante área para o estudo da doença. Nesse estudo, foi utilizado um Sistema de Informação Geográfica (SIG) para descrever a distribuição espacial e o comportamento temporal de PV e PFE nessa região do Estado de São Paulo nas últimas cinco décadas e caracterizar o uso e ocupação do solo no município com maior número de ocorrências de pênfigo. Os pacientes foram identificados baseados nos prontuários médicos entre 1965 e 2014. Os mapas temáticos foram desenvolvidos com o software ArcGIS 10.2. Para representar a distribuição espacial do pênfigo, os mapas foram organizados em décadas de 1965 a 2014. Para o município com maior número de ocorrências de PV e PFE, o uso e ocupação do solo, de acordo com a hidrografia, a vegetação nativa, à área agrícola, o solo exposto e a área urbana, foi analisado em um raio de 2 km no entorno da residência dos pacientes no momento do surgimento dos sintomas. Como análise adicional, mapas ilustrando a distribuição dos casos de pênfigo de acordo com as classes hipsométricas, declividade do solo e densidade populacional por distrito do município (Norte, Sul, Leste, Oeste e Central) foram também desenvolvidos. Quatrocentos e vinte e seis casos foram analisados. Os casos de PFE predominaram, com 285 (67%) dos casos. De acordo com a distribuição espacial e evolução temporal, PV não foi reportado de 1965 a 1974, entretanto, os casos de PV tiveram um aumento contínuo nas próximas décadas e ultrapassou o número de casos de PFE na última década. Analisando de forma acumulada os casos, tanto o PV quanto o PFE tiveram aumento ao longo do período estudado, revelando uma expansão espacial. A Bacia Hidrográfica do Rio Pardo teve o maior número de casos com um total de 153 (41% PV e 59% PFE). No período de 1965 a 2014 o número de cidades com registros de casos de PV e PFE aumentou de 0 para 49 e de 13 para 60, respectivamente, com Ribeirão Preto e Batatais sendo os principais focos geográficos de PV e PFE, respectivamente. Ribeirão Preto foi o município com maior ocorrência de pênfigo (35 casos de PV e 37 casos de PFE). A área agrícola (42%) e o solo exposto (33,2%) foram os usos do solo que predominam no município. Além disso, todos os pacientes com PV ou PFE moram perto de rios e área agrícola. Em Ribeirão Preto, os casos de pênfigo estão concentrados nos distritos norte e oeste, os casos de PFE estão distribuídos em baixas altitudes quando comparadas com o PV e tanto o PV quanto o PFE predominam em áreas com baixa porcentagem de declividade do solo. No contexto da saúde pública, o SIG se tornou uma importante ferramenta que ajuda os pesquisadores entenderem a ocorrência e tendência de certos eventos, conduzindo nas melhores estratégias de controle de doenças. As análises de distribuição espacial e evolução temporal mostraram que os casos de PV e PFE aumentaram na região nordeste do Estado de São Paulo nas últimas cinco décadas. Esse monitoramento também ajudou a identificar os principais focos geográficos de pênfigo nessa região. A predominância de agricultura e solo exposto em Ribeirão Preto e a proximidade dos casos com rios e agricultura reforça a hipótese de que os fatores ambientais desempenham um importante papel na etiopatogênese do pênfigo

Defined foci of pemphigus prevalence worldwide, including Brazil, raise the possibility that environmental factors trigger the onset of this disease. The northeastern region of the state of São Paulo is located within three Watersheds and is an appropriate site to investigate pemphigus because this disease is prevalent in both clinical forms--endemic pemphigus foliaceus (PFE) and pemphigus vulgaris (PV)--therein. In this study, we have used Geographic Information Systems (GIS) to describe the spatial distribution and temporal behavior of PV and PFE in this region of the state of São Paulo over the last five decades; we have also characterized land use in the city with the highest number of cases. Patients were identified based on patients' medical records between 1965 and 2014. Thematic maps were developed with the ArcGIS 10.2 software. To represent the spatial distribution of pemphigus, maps were organized in decades from 1965 to 2014. For the city with the highest occurrence of PFE and PV cases, land use regarding hydrography, native vegetation, agriculture, exposed soil, and urbanization was analyzed within a 2-km buffer surrounding from the patients' residencies considering the address where the pemphigus clinical signs and symptoms started. For additional analysis, thematic maps illustrating the distribution of pemphigus cases according to hypsometric classes, soil declivity, and population density by sector (North, South, East, West, and Central) were designed. Four hundred and twenty-six cases were analyzed. PFE cases predominated: they corresponded to 285 or 67% of the cases. Regarding spatial distribution and temporal evolution, PV was not reported from 1965 to 1974; notwithstanding, PV rose in the following four decades and overcame the number of PFE cases in the last decade. Regarding cumulative cases, both PV and PFE increased throughout the studied period, which revealed spatial expansion. The Pardo River Basin had the highest number of cases with a total of 153 (41% PV and 59% PFE). In the studied period, the number of cities with recorded cases of PV and PFE increased from 0 to 49 and from 13 to 60, respectively, with Ribeirão Preto and Batatais being the main geographical foci of PV and PFE, respectively. Ribeirão Preto was the city with the highest occurrence of pemphigus--35 PV cases and 37 PFE cases. Agricultural area (42%) and exposed soil (33.2%) were the land uses that predominated in the city. In addition, all patients with PV and PFE lived close to rivers and agricultural areas. In Ribeirão Preto, pemphigus cases were concentrated in the northern and western sectors; PFE cases were distributed at lower altitudes as compared to PV; and both PV and PFE predominated in areas with lower percentage of declivity. In the context of public health, GIS has become a powerful tool that helps researchers to understand the occurrence and trend of some events, leading to improved interventional strategies and disease control. The spatial distribution and temporal evolution analyses showed PV and PFE increased in the northeastern region of the state of São Paulo over the last five decades. This monitoring also helped to identify the main geographical foci of pemphigus. The predominance of agriculture and exposed soil in Ribeirão Preto and the proximity of the cases to rivers and agriculture reinforced the hypothesis that environmental factors play a role in pemphigus etiopathogenesis

Aspectos etiológicos e epidemiológicos do pênfigo foliáceo endêmico (fogo selvagem) / Etiological and epidemiological aspects of pemphigus foliaceus (wild fire)

Introdução: Durante a primeira metade do século XX, o pênfigo foliáceo endêmico (fogo selvagem) teve importante impacto social, econômico e político no Brasil. Após mais de um século desde seus primeiros relatos essa doença ainda guarda interrogações sobre o envolvimento de fatores ambientais desencadeantes e sua característica autoimune e endêmica. O objetivo do trabalho é revisar trabalhos publicados por mais de um século, destacando os aspectos epidemiológicos da doença (das diferentes formas endêmicas pelo mundo) e avanços no estudo da sua etiologia. Material e Métodos: Utilizaram-se de trabalhos no PubMed, LILACS, CAPES, Google Acadêmico, Anais Brasileiros de Dermatologia. Resultados: O fogo selvagem sofreu grande redução do número de casos, principalmente a partir da década de 80 do século XX. O número de estudos sobre a doença vem diminuindo a cada década, várias informações sobre seus aspectos etiológicos e epidemiológicos permanecem há mais de um século sem comprovação precisa. Conclusões: Concluímos que o reduzido número de trabalhos atuais sobre o fogo selvagem se deve a redução considerável da sua incidência após mudanças ecológicas, avanços tecnológicos e melhoria das condições de vida da população das áreas endêmicas. As autoridades deveriam torná-la de notificação compulsória, facilitando a identificação de novos casos e de possíveis áreas endêmicas nos dias atuais. Mais estudos na área contribuiriam também ao estudo das doenças autoimunes em geral e dos fatores relacionados com o aumento da incidência de pênfigo vulgar em áreas endêmicas para fogo selvagem.

Presentación simultánea de pénfigos vulgar y foliáceo / Simultaneous presentation of pemphigus vulgaris and foliaceus / Apresentação simultânea de pênfigo vulgar e foliáceo

El pénfigo foliáceo y el pénfigo vulgar son enfermedades autoinmunes caracterizadas por vesículas y ampollas que se rompen fácilmente dejando erosiones superficiales. Las ampollas están localizadas en diferentes sitios de la epidermis dependiendo del perfil inmunológico con el que cursen. Se reporta el caso de una paciente con presentación simultánea de pénfigo vulgar y pénfigo foliáceo, una asociación de baja incidencia con pocos casos informados en la literatura.

Pemphigus foliaceus and vulgaris are autoimmune diseases characterized by blisters that break easily leaving behind superficial erosions, with different locations in the epidermis depending on the immunologic profile with which they present. We report the case of a patient with simultaneous presentation of pemphigus vulgaris and pemphigus foliaceus, an association of low incidence with few cases reported in the literature.

O pênfigo foliáceo e o pênfigo vulgar são doenças autoimunes caracterizadas por vesicular e bolhas que se quebram facilmente deixando erosões superficiais. As bolhas ficam localizadas em diferentes regiões da epidermes dependendo do perfil imunológico. Reportamos o caso de um paciente com apresentação simultânea de pênfigo vulgar e pênfigo foliáceo, uma associação de baixa incidência com poucos casos informados na literatura.

Pénfigo foliáceo variedad seborreica: reporte de un caso / Pemphigus foliaceus seborrheic variety: a case report / Pénfigo foliáceo variedade seborreica: relato de caso

El pénfigo eritematoso o seborréico, también denominado síndrome de Senear-Usher es la variedad leve y localizada del pénfigo foliáceo, de baja incidencia. La mayor parte de los casos se han reportado en adultos entre la segunda y tercera década de la vida, promedio de 54 años, sin predominio entre razas o sexo. Su etiología se debe a la presencia de anticuerpos anti IgG contra la desmogleina 1 de los queratinocitos de la capa granulosa. Clínicamente se presenta en forma de placas eritematoescamosas o eritematocostrosas bien definidas, de aspecto y distribución seborreica (cara, cuello y tronco), que se exacerban a la exposición solar. Su diagnóstico clínico puede ser difícil, ya que se superpone clínicamente con el lupus eritematoso discoide y la dermatitis seborreica, por lo cual es importante tenerlo en cuenta como diagnóstico diferencial en lesiones infiltradas en dorso nasal y región malar en patrón de alas de mariposa. Se presenta el caso clínico de un paciente con pénfigo foliáceo variedad seborreica una entidad de baja incidencia.

Pemphigus erythematosus or seborrheic, also called Senear - Usher syndrome,is a mild, localized variety of pemphigus foliaceus, an entity of low incidence. Most cases have been reported in adults between second and third decades of life, average 54 years, no difference between race or sex. Etiology is due to the presence of IgG antibodies against desmoglein 1 in keratinocytes of the granular layer. Clinically, defined erythematous plaques, seborrheic distribution aspect (face, neck and trunk), which are exacerbated by sun exposure. Clinical diagnosis can be difficult as clinically overlaps with discoid lupus erythematosus and seborrheic dermatitis. So, it is important to be considered as differential diagnosis in infiltrated nasal lesions, dorsum and malar region butterfly pattern. We report a case of pemphigus foliaceus- seborrheic variety, a low incidence entity.

O pênfigo eritematoso do tipo seborréico, também chamada de síndrome Senear -Usher é variedade leve e localizada do pênfigo foliáceo , de baixa incidência , a maioria dos casos foram relatados em adultos entre a segunda e terceira década de vida , com idade media de 54 anos, sem predominância entre raças ou sexo. A sua etiologia é devido à presença de anticorpos anti - IgG de desmogleína 1 dos queratinócitos da camada granular . Clinicamente, apresenta-se como placas eritematosas ou eritematocostrosas bem definidos, de aspecto e distribuição seborreica (face, pescoço e tronco), que são agravadas pela exposição ao sol. Seu diagnóstico clínico pode ser difícil, pois se sobrepõe clinicamente com lúpus eritematoso discóide e dermatite seborreica, por isso é importante te-lo em mente como diagnóstico diferencial nas lesões infiltradas no dorso da nariz e região malar com asas de borboleta. Apresenta-se o caso de um paciente com pênfigo foliáceo do tipo seborreico uma entidade de baixa incidência com poucos casos relatados na literatura.

Pemphigus Erythematosus / 대한피부과학회지

Pemphigus is a group of blistering autoimmune diseases that affect the skin and mucous membranes with autoantibodies against desmoglein. Among the pemphigus subtypes, pemphigus erythematosus is one of the rare lupus-like variant subtypes of pemphigus that shares common clinical and histopathological manifestations with systemic lupus erythematosus. The lesions appear clinically as erythematous erosive patches on the face in a butterfly distribution, and they manifest subcorneal acantholysis histopathologically. There is concomitant basement membrane zone deposition of immunoglobulin and complement in lesional skin in addition to intercellular space staining in the epidermis. Two cases of pemphigus erythematosus have been reported domestically. Here, we report a case of pemphigus erythematosus in an 18-year old woman.

Pemphigus Foliaceus Associated with Psoriasis during the Course of Narrow-Band UVB Therapy: A Simple Coincidence?

Although psoriasis and bullous diseases are considered to be completely different disease entities, the literature has reported a few cases of psoriasis associated with bullous diseases, most of which are bullous pemphigoid. In limited cases, pemphigus foliaceus has also been reported in association with psoriasis. In most of them, pemphigus lesions usually developed on an untreated patient with a chronic history of psoriasis. Herein, we report a case of 53-year-old male with a chronic history of psoriasis who first developed generalized erosive lesions after 26 cycles of narrow-band ultraviolet B (NBUVB) therapy. A diagnosis of pemphigus foliaceus was made based on skin biopsy and direct immunofluorescence assay. Pemphigus lesions were well controlled with combination therapy of oral steroid and azathioprine. This is the first case where pemphigus foliaceus co-occurred with psoriasis during NBUVB therapy.

Analysis of the reactivity of indirect immunofluorescence in patients with pemphigus foliaceus and pemphigus vulgaris using rat bladder epithelium as a substrate

OBJECTIVES: To evaluate the reactivity of indirect immunofluorescence using rat bladder epithelium as a substrate in patients with pemphigus foliaceus and pemphigus vulgaris from the Department of Dermatology, University of São Paulo Medical School, Brazil. METHODS: Thirty-two patients (8 male and 24 female) from the Department of Dermatology, University of São Paulo Medical School, were selected. Three had mucosal pemphigus vulgaris, 20 had mucocutaneous pemphigus vulgaris, and 9 had pemphigus foliaceus. Patients’ sera were tested by indirect immunofluorescence performed on human foreskin and rat bladder epithelium and by ELISA assays utilizing baculovirus-expressed recombinant desmoglein 3 and desmoglein 1. RESULTS: No patients with mucosal pemphigus vulgaris, 5 of 20 patients with mucocutaneous pemphigus vulgaris (25 percent) and 4 of 9 patients with pemphigus foliaceus (44 percent) had positive indirect immunofluorescence using rat bladder epithelium as a substrate. CONCLUSION: Indirect immunofluorescence using rat bladder epithelium as a substrate is recommended whenever a diagnosis of paraneoplastic pemphigus is considered. The identification of a subset of pemphigus foliaceus and pemphigus vulgaris patients that recognizes desmoplakins by this laboratory tool is critical to avoid the misdiagnosis of paraneoplastic pemphigus.

Pénfigo foliáceo endémico en tres regiones de la amazonía peruana: enero-diciembre 2004 / Endemic Pemphigus foliaceus in three regions of Peruvian Amazonia: January-December 2004

OBJETIVO: Determinar las características epidemiológicas y clínicas del pénfigo foliáceo endémico(PFE) en tres regiones de la Amazonía Peruana durante el año 2004. MATERIAL Y MÉTODOS: Estudio descriptivo, prospectivo y observacional realizado en tres regiones de la amazonía peruana. Los pacientes con PFE fueron captados en el Hospital de Apoyo de Chachapoyas (Amazonas), Hospital Hermilio Valdizán Medrano (Huánuco), Posta Médica EsSalud Santa Lucía-Uchiza (San Martín), en los centros de salud de cada departamento y mediante búsqueda activa durante Enero y Diciembre del año 2004. El diagnóstico se realizó en base a los criterios epidemiológico, clínico, histopatológico e inmunológico. RESULTADOS: Se captó un total de 10 casos de PFE en los departamentos de Amazonas, Huánuco y San Martín. Se determinó áreas endémicas de PFE en Tingo María, Tournavista y La Unión (Huánuco), Moyobamba (San Martín), Tuemal y Bagua (Amazonas). La mayor frecuencia de pacientes fueron de sexo masculino, menores de 40 años, de forma clínica generalizada con régimen de tratamiento irregular. Se detectó casos en Moyobamba y Tuemal a una altitud de 886 y 1172 msnm respectivamente, con características clínicas similares a la de los casos detectados a altitudes inferiores a 800 msnm. CONCLUSIÓN: De las regiones estudiadas, Huánuco es la que presenta mayor frecuencia de pacientes con PFE mientras que en San Martín y Amazonas la frecuencia es marcadamente inferior. Existen casos de PFE en San Martín y Amazonas a altitudes superiores a los 800 msnm.

OBJECTIVE: To determine clinical and epidemiological characteristics of Endemic Pemphigus Foliaceus (EPF) in three regions of Peruvian Amazon during 2004. MATERIAL AND METHODS: Descriptive, prospective and observational study realized in three regions of Peruvian Amazonia. Patients with EPF were enrolled in Chachapoyas Hospital (Amazonas), Hermilio Valdizan Medrano Hospital (Huanuco), Santa Lucia-Uchiza Essalud Health Station (San Martin), in Health Centers of each department and through active search during January and December of 2004. The diagnosis was realized based to clinical epidemiologic, histopathologic and immunologic features. RESULTS: It was enrolled a total of 10 cases with EPF in departments of Amazonas, Huanuco and San Martin. It was determined endemic areas of EPF in Tingo Maria, Tournavista and La Union (Huanuco), Moyobamba (San Martin), Tuemal and Bagua (Amazonas). The major frequency of patients was male, under of 40 years, generalized clinical form with regimen of irregular treatment. It was detected cases in Moyobamba and Tuemal at a height of 886 and 1172 masl respectively, with clinical characteristics similar to the cases detected at heights under 800 masl. CONCLUSION: Huanuco is area which present major frequency of patients with EPF, while in San Martin and Amazonas, the frequency is extremely lower. There are cases of EPF in San Martin and Amazonas at heights above 800 masl.

Matrix Metalloproteinases and Autoimmune Bulbous Diseases: Expression of MMP-2, -3, and -9 in Bullous Pemphigoid, Pemphigus Vulgaris, and Pemphigus Foliaceus / 대한피부과학회지

BACKGROUND: Matrix metalloproteinases (MMPs) participate in extracellular matrix degradation and may play an important role in basal membrane damage in many dermatologic diseases. Recent studies implicated the importance of MMP-9 in the pathogenesis of bulla formation of bullous pemphigoid (BP). Various autoimmune bullous diseases are strongly associated with desmosome or hemidesmosome pathologies, and show an increased level of lesional MMP and exposed autoantigens from these structures. OBJECTIVE: This study evaluated the level of MMP-2, -3, and -9 in three types of autoimmune bullous disease [BP, pemphigus vulgaris (PV), pemphigus foliaceus (PF)] with the aim of investigating the role of MMPs in the pathogenesis of autoimmune bullous diseases. METHODS: Sample specimens were obtained from skin lesions of patients with BP (n=12), PV (n=10), and PF (n=12), and from normal controls (n=8). The immunohistochemical expression of MMP-2, -3, and -9 was analyzed and serum levels of MMP-2, -3, and -9 were measured by enzyme-linked immunosorbant assay (ELISA). The results were analyzed with reference to graded levels of clinical severity. RESULTS: Expression of dermal MMP-2, -3, and -9 were increased in BP, PV, and PF (p=0.036, 0.022, and 0.015, respectively). However, decreased expression of the three MMPs in the epidermis of skin lesions may have resulted from epidermal destruction. ELISA-determined serum levels of MMP-2, -3, and -9 increased in BP, PV and PF. Interestingly, MMP-2 was significantly increased in the sera of BP patients (p=0.015), consistent with the previous studies concerning the role of gelatinase (MMP-2 and -9) in the pathogenesis of BP. In BP patients, clinical severity was proportional to increased levels of MMP-2 in both skin lesions and and sera. CONCLUSION: The increased expression of MMP-2, -3, and -9 in skin lesions and sera may reflect the involvement of these enzymes in the mechanism of bulla formation in autoimmune bullous diseases including BP. In addition, expression of MMP and clinical severity may be closely connected.

Lesional Expression of Heat Shock Protein 70 in Pemphigus / 대한피부과학회지

BACKGROUND: Heat shock proteins (HSP), especially the HSP 70 family, may play certain roles in the immunophysiology of some skin diseases such as psoriasis, pemphigus, and lichen planus. HSPs generally induce down-regulation of the process of apoptosis that is considered to be one of the acantholysis-producing pathways in pemphigus. OBJECTIVE: We planned to examine possible roles of HSPs 70/105 in the blistering process in pemphigus vulgaris (PV) and pemphigus foliaceus (PF), in connection with the detection results of apoptosis in local tissue specimens. METHODS: Immunohistochemical stainings and Western blot analysis were performed for the detection and semiquantitation of HSPs 70/105 in skin specimens from lesional, nonlesional, and normal control sites. Hoechst 33342 staining was simultaneously carried out to examine features of apoptosis in lesional skin specimens. RESULTS: The findings on expression of HSP were as follows. In PV, the expression of HSP 70 was minimum or negative; however, in PF, the expression was obvious and recognizable in lesional and perilesional normal skin. In contrast, HSP 105 was not detected in all cases of PV and PF. The features of apoptosis were evident at the lesional skin of all cases of pemphigus with acantholytic changes. CONCLUSION: PV and PF had different relative intensities of HSPs in lesional tissue stainings, especially in cases with HSP 70. This suggests that there may be subtle differences in the mechanisms causing acantholysis between PV and PF.

Pênfigo foliáceo em eqüino: relato de caso / Equine pemphigus foliaceous: case report

Diagnosticou-se pênfigo foliáceo em um eqüino macho, castrado, quatro anos de idade da raça Árabe apresentando dermatite generalizada caracterizada por placas escamo-crostosas e presença de dermatite pustular acantolítica subcorneal

Pemphigus foliaceus was diagnosed in a four-year-old Arabian equine gelding, with generalized dermatitis characterized by scaling and crusting plaques and acantholytic subcorneal pustular dermatitis

Inmunopatología de sujetos sanos de un área endémica para pénfigo foliáceo en Perú: Estudio comparativo con familiares / Immunopathologic characterization of healthy subjects in an endemic area for pemphigus foliaceus: Comparative study with relatives.

Introducción: el pénfigo foliáceo endémico (PFE) ha sido descrito a principios de los años 50 en la selva peruana. En el 2006, Ortega y col. reportaron la presencia de anticuerpos anti-desmogleina 1 en Pueblo Libre, Ucayali. Sin embargo, no existen reportes inmunológicos sobre los familiares de pacientes con PFE en la zona. Objetivos: comparar las características inmunopatológicas de los sujetos sanos de Pueblo Libre (Campo Verde-Ucayali) endémico para pénfigo foliáceo, con familiares sanos de pacientes con PFE y controles sanos de áreas no endémicas. Material y métodos: estudio prospectivo y multicéntrico realizado de junio a agosto del 2006 que incluyó a 41 sujetos sanos de la comunidad de Pueblo Libre, 11 familiares de pacientes con PFE y 20 sujetos sanos de áreas no endémicas de la enfermedad de los que se obtuvo muestras de sangre para la realización del estudio inmunopatológico (ELISA para anticuerpos anti desmogleína 1 y anti desmogleína 3) comparándose las características de cada grupo de investigación. Para fijar los valores de corte se realizó la estandarización del ELISA usando el análisis de características operativas del receptor (ROC). Resultados: en Pueblo Libre se encontró una prevalencia de anticuerpos anti desmogleína 1 de 46,3%. El patrón predominante fue el IgG2 (62,5%) y el IgG1 (56,3%). En el 31,7% se detectó anticuerpos anti-desmogleína 3. Existió alta correlación entre los valores índice de anticuerpos anti desmogleína 1 y anti desmogleína 3 (r=0,76), significativa a un nivel α=0,01. Para los familiares de los pacientes con PFE, el 45,5% fueron positivos para anticuerpos anti-desmogleνna 1 con un patrσn predominante IgG1 (63,6%) e IgG2 (54,5%). Se detectó anticuerpos anti-desmogleína 1 en el 10 % de sujetos sanos de áreas no endémicas; no se detectó anticuerpos anti desmogleína 3 en este grupo. Conclusiones: las personas sanas expuestas a factores ambientales de los focos endémicos de PFE y los familiares de pacientes desarrollan anticuerpos no patogénicos anti desmogleína 1 y 3 con características inmunopatológicas similares.

Introduction: endemic pemphigus foliaceus (PFE) has been described at the beginning of the 50s in the peruvian forest. In 2006,Ortega & col. reported the presence of desmoglein 1 antibodies in Pueblo Libre, Ucayali. Nevertheless, immune reports does not exist on patients’ relatives with PFE in the zone. Objetives: to compare the immunopathologic profiles of healthy subjects from Pueblo Libre (an area in Ucayali, endemic for pemphigus foliaceus), with healthy relatives of patients with endemic pemphigus foliaceus (EPF) and healthy controls from non-endemic areas. Materials and methods: this is a prospective multicentric study performed from June to August 2006. The sample consisted of 41 healthy subjects from the Pueblo Libre community, 11 relatives of EPF patients and 20 healthy subjects from non-endemic areas. Blood samples were obtained for immunopathologic studies (ELISA technique for antibodies against desmoglein-1 and desmoglein- 3). The immunopathologic profiles of each group were compared. Standardization of ELISA was performed using the analysis of receptor operative characteristics (ROC) to find appropriate cut-off values. Results: in Pueblo Libre, the prevalence of antibodies against desmoglein-1 was 46,3%. The predominant pattern was 56,3% for IgG1 and 62,5% for IgG2. Antibodies against desmoglein-3 were found in 31,7% of the sample. A high correlation was found between the index values of antibodies against desmoglein-1 and desmoglein-3. (r=0.76); this is statistically significant, with an alpha = 0,001. The frequency of antibodies against desmoglein-1 was 45,5% in the relatives of EPF patients; the predominant pattern was 63,6% for IgG1 and 54,5% for IgG2. Antibodies against desmoglein-1 were detected in two healthy subjects from non-endemic areas; antibodies against desmoglein-3 were not detected. Conclusion: healthy subjects who are exposed to environmental factors in a focus of endemic pemphigus foliaceus and the relatives of patients with EPF develop non-pathogenic antibodies against desmoglein-1 and -3 with similar immunologic profiles.

Bilateral Herpetic Keratitis in a Patient with Pemphigus Foliaceus

PURPOSE: To report a case of bilateral herpetic keratitis in a patient during glucocorticoid treatment of pemphigus foliaceus. METHODS: A 71-year-old man presented with pain and epiphora in both eyes for a week. He had a history of pemphigus foliaceus for a 6-month period and was on glucocorticoid treatment. Anterior segment examination showed conjunctival injection and corneal geographic epithelial defects in both eyes. He was diagnosed with herpetic keratitis and was given a topical antiviral ointment. RESULTS: One week after the initial antiviral treatment, the corneal epithelial defect of the right eye had fully improved, whereas the left eye showed increased stromal edema with enlarged epithelial defects. Oral antiviral agents were given with topical broad spectrum antibiotics, and artificial tears added for the left eye. A week later, the stromal edema of the left eye had decreased but the epithelial defect was stationary. Amniotic membrane transplantation was performed on the left eye. The corneal epithelial defects of the left eye healed remarkably. CONCLUSIONS: Herpetic keratitis is, in general, a unilateral disease. Bilateral herpetic keratitis is much rarer, and has been described mostly in patients with an altered immune system. The disease progress is known to be similar in both eyes in most cases of bilateral herpetic keratitis, whereas in this case, the fellow eye showed delayed healing. Amniotic membrane transplantation seems to be an effective treatment modality on persistent epithelial defect due to herpetic keratitis.

A Case of Norwegian Scabies in a Patient with Pemphigus Foliaceus / 대한피부과학회지

Norwegian scabies can be defined as a generalized, severe scabies infestation which usually affects immunocompromised patients. The diagnosis is commonly missed, and can lead to mismanagement. We describe a patient with Norwegian scabies affecting the whole body. The patient had suffered with pemphigus foliaceus for several years and had an immunosuppressed status due to long-term use of oral corticosteroids. He was admitted to our hospital. At first, we made a diagnosis of exfoliative dermatitis secondary to pemphigus foliaceus. However, no improvement of the condition was seen after an increased dosage of oral corticosteroids, azathioprine, and mycophenolate mofetil. We then identified adult scabietic mites, eggs and scybala upon microscopic examination of skin scales. He was treated with an application of gamma benzene hexachloride cream. We recommend that the diagnosis of scabies be considered in immunocompromised patients with thick skin scales and associated night pruritus.

Factors Relevant to Aggravation of Skin Lesions in Pemphigus Foliaceus / 대한피부과학회지

There may be some exacerbating factors which aggravate skin lesions of pemphigus foliaceus, including exposure to sun and/or heat. However, the degree of aggravation induced by these factors varies in individuals. We examined possible aggravating factors of skin lesions in a 47-years-old woman with pemphigus foliaceus who had managed her disease with topical and/or sublesional use of corticosteroids for 20 years. The lesion- provoking or exacerbating factors recognized in the patient were sleeplessness/fatigue, emotional stress, menstruation, mechanical trauma, external heat and alcohol.