Amiloidose nodular - relato de rara apresentação da amiloidose localizada cutânea / Nodular amyloidosis - report of a rare presentation of cutaneous localized amyloidosis

Contexto: Amiloidose é um grupo de doenças caracterizadas pelo depósito de proteínas fibrilares, denominadas substância amiloide. Podem ser divididas em formas localizadas ou sistêmicas, sendo que dentre as localizadas, a forma nodular é a mais rara. Descrição do caso: Relatamos o caso de amiloidose primária localizada cutânea nodular que se apresentou com nódulos violáceos no dorso, e placas acastanhadas na região cervical há 8 anos sem evidências de envolvimento sistêmico. Discussão: Como cerca de 1% a 7% dos casos de amiloidose nodular localizada cutânea podem evoluir com envolvimento sistêmico, o seguimento dos pacientes faz-se necessário. O tratamento não é obrigatório, a retirada das lesões pode ser feita se o paciente o desejar, contudo as recidivas são frequentes. Conclusões: Mesmo possuindo baixa prevalência, a amiloidose nodular deve ser reconhecida pelo risco de progredir para acometimento sistêmico e associação com discrasias plasmocitárias, como mieloma múltiplo.

Autoimmune bullous diseases in pregnancy: clinical and epidemiological characteristics and therapeutic approach

Abstract Autoimmune bullous dermatoses are a heterogeneous group of diseases with autoantibodies against structural skin proteins. Although the occurrence of autoimmune bullous dermatoses during pregnancy is low, this topic deserves attention, since the immunological and hormonal alterations that occur during this period can produce alterations during the expected course of these dermatoses. The authors review the several aspects of autoimmune bullous dermatoses that affect pregnant women, including the therapeutic approach during pregnancy and breastfeeding. Gestational pemphigoid, a pregnancy-specific bullous disease, was not studied in this review.

Diagnostic approach of eosinophilic spongiosis

Abstract Eosinophilic spongiosis is a histological feature shared by some distinct inflammatory disorders, and is characterized by the presence of intraepidermal eosinophils associated with spongiosis. Most often, isolated eosinophilic spongiosis indicates the early stages of a subjacent autoimmune bullous dermatosis, such as the pemphigus group and bullous pemphigoid. Herein, the main causes of eosinophilic spongiosis are discussed, as well as the supplementary investigation needed to elucidate its etiology.

Paraneoplastic pemphigus: a clinical, laboratorial, and therapeutic overview

Abstract: Paraneoplastic pemphigus is a rare and severe autoimmune blistering disease characterized by mucocutaneous lesions associated with benign and malignant neoplasms. Diagnostic criteria include the presence of chronic mucositis and polymorphic cutaneous lesions with occult or confirmed neoplasia; histopathological analysis exhibiting intraepidermal acantholysis, necrotic keratinocytes, and vacuolar interface dermatitis; direct immunofluorescence with intercellular deposits (IgG and C3) and at the basement membrane zone (IgG); indirect immunofluorescence with intercellular deposition of IgG (substrates: monkey esophagus and simple, columnar, and transitional epithelium); and, autoreactivity to desmogleins 1 and 3, desmocollins 1, 2, and 3, desmoplakins I and II, envoplakin, periplakin, epiplakin, plectin, BP230, and α-2-macroglobulin-like protein 1. Neoplasias frequently related to paraneoplastic pemphigus include chronic lymphocytic leukemia, non-Hodgkin lymphoma, carcinomas, Castleman disease, thymoma, and others. Currently, there is no standardized treatment for paraneoplastic pemphigus. Systemic corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, rituximab, cyclophosphamide, plasmapheresis, and intravenous immunoglobulin have been used, with variable outcomes. Reported survival rates in 1, 2, and 5 years are 49%, 41%, and 38%, respectively.

Consensus on the diagnostic and therapeutic management of chronic spontaneous urticaria in adults - Brazilian Society of Dermatology

Abstract: Background: Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous. Objectives: To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US). Methods: A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults. Results: Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence). Conclusions: Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.

Bullous pemphigoid

Abstract: Bullous pemphigoid is the most frequent autoimmune bullous disease and mainly affects elderly individuals. Increase in incidence rates in the past decades has been attributed to population aging, drug-induced cases and improvement in the diagnosis of the nonbullous presentations of the disease. A dysregulated T cell immune response and synthesis of IgG and IgE autoantibodies against hemidesmosomal proteins (BP180 and BP230) lead to neutrophil chemotaxis and degradation of the basement membrane zone. Bullous pemphigoid classically manifests with tense blisters over urticarial plaques on the trunk and extremities accompanied by intense pruritus. Mucosal involvement is rarely reported. Diagnosis relies on (1) the histopathological evaluation demonstrating eosinophilic spongiosis or a subepidermal detachment with eosinophils; (2) the detection of IgG and/or C3 deposition at the basement membrane zone using direct or indirect immunofluorescence assays; and (3) quantification of circulating autoantibodies against BP180 and/or BP230 using ELISA. Bullous pemphigoid is often associated with multiple comorbidities in elderly individuals, especially neurological disorders and increased thrombotic risk, reaching a 1-year mortality rate of 23%. Treatment has to be tailored according to the patient's clinical conditions and disease severity. High potency topical steroids and systemic steroids are the current mainstay of therapy. Recent randomized controlled studies have demonstrated the benefit and safety of adjuvant treatment with doxycycline, dapsone and immunosuppressants aiming a reduction in the cumulative steroid dose and mortality.

Bullous systemic lupus erythematosus ­ a case report

Skin involvement in systemic lupus erythematosus (SLE) occurs in more than 75% of patients with this condition. Vesicles and blisters in lupus erythematosus (LE) may be present in SLE secondary to interface vacuolar changes in the epidermis, in discoid LE also secondary to vacuolar epidermal changes, and in bullous LE secondary to antibodies anti-collagen VII deposits with neutrophilic aggregates. In addition, blisters can occur due to the association of SLE with other autoimmune blistering diseases (e.g. bullous pemphigoid). BSLE is a rare blistering disease that mainly occurs in females (30­40 years old), and less frequently in children and adolescents. The most common presentation is rapid and widespread development of tense vesicles and bullae over erythematous macules or plaques. Preferential sites are: superior trunk, proximal superior limbs, and face (lips) with symmetrical distribution. Mucosal involvement is common on perioral, pharyngeal, laryngeal, and genital areas. The involvement of sun-exposed areas is not mandatory. The lesions usually progress with no scarring, but hypo or hyperchromia may be present. We report an 18-year-old female patient with blistering lesions at admission, who was diagnosed with BSLE. She was initially treated with systemic prednisone and hydroxychloroquine. Her condition evolved with relapsing lesions, which required the introduction of Dapsone. The authors emphasize the relevance of recognizing BSLE­a rare presentation of SLE­which may evolve with marked clinical presentation

Gastrointestinal cytomegalovirus disease in a patient with pemphigus vulgaris treated with corticosteroid and mycophenolate mofetil

Pemphigus vulgaris is an autoimmune disease characterized by the formation of suprabasal intra-epidermal blisters on the skin and mucosal surfaces. Infectious diseases are the main cause of death in patients with pemphigus due to the disrupture of the physiological skin barrier, immune dysregulation, and the use of immunosuppressive medications leaving the patient prone to acquire opportunistic infections. We report the case of a 67-year-old woman diagnosed with pemphigus vulgaris, who was irregularly taking prednisone and mycophenolate mofetil. She was hospitalized because of a 1-month history of watery diarrhea and oral ulcers. Unfortunately, the patient died suddenly on the ward. The autopsy revealed a bilateral saddle pulmonary embolism, Gram-positive cocci bronchopneumonia, and gastrointestinal cytomegalovirus infection, causing extensive gastrointestinal mucosal ulcers.

Chronic urticaria in adults: state-of-the-art in the new millennium

Chronic urticaria has been explored in several investigative aspects in the new millennium, either as to its pathogenesis, its stand as an autoimmune or auto-reactive disease, the correlation with HLA-linked genetic factors, especially with class II or its interrelation with the coagulation and fibrinolysis systems. New second-generation antihistamines, which act as good symptomatic drugs, emerged and were commercialized over the last decade. Old and new drugs that may interfere with the pathophysiology of the disease, such as cyclosporine and omalizumab have been developed and used as treatments. The purpose of this article is to describe the current state of knowledge on aspects of chronic urticaria such as, pathophysiology, diagnosis and the current therapeutic approach proposed in the literature.

Evaluation of D-dimer serum levels among patients with chronic urticaria, psoriasis and urticarial vasculitis / Avaliação dos níveis séricos de D-dímeros entre doentes com urticária crônica, psoríase e urticária vasculite

BACKGROUND: It has been demonstrated that neutrophils, eosinophils and monocytes, under appropriated stimulus, may express tissue factor and therefore, activate the extrinsic pathway of coagulation. We performed a transversal and case-control study of patients with chronic urticaria and patients with psoriasis, in our outpatient clinic to evaluate the production of D-dimer. OBJECTIVE: To evaluate D-dimer serum levels in patients with chronic urticaria and its possible correlation with disease activity. PATIENTS AND METHODS: The study was conducted from October 2010 until March 2011. We selected 37 consecutive patients from our Allergy Unit and Psoriasis Unit, and divided them into three groups for statistical analysis: (i) 12 patients with active chronic urticaria (CU); (ii) 10 patients with chronic urticaria under remission and (iii) 15 patients with psoriasis (a disease with skin inflammatory infiltrate constituted by neutrophils, lymphocytes and monocytes). Another five patients with urticarial vasculitis were allocated in our study, but not included in statistical analysis. The serum levels of D-dimer were measured by Enzyme Linked Fluorescent Assay (ELFA), and the result units were given in ng/ml FEU. RESULTS: Patients with active chronic urticaria had the highest serum levels of D-dimer (p<0.01), when compared to patients with CU under remission and the control group (patients with psoriasis). CONCLUSIONS: Patients with active chronic urticaria have higher serum levels of D-dimer, when compared to patients with chronic urticaria under remission and patients with psoriasis. We found elevated serum levels of D-dimer among patients with urticarial vasculitis. .

FUNDAMENTOS: Tem sido demonstrado que os neutrófilos, eosinófilos e monócitos, sob estímulo apropriado, podem expressar fator tecidual e, portanto, ativar a via extrínseca da coagulação. Realizamos um estudo transversal e caso-controle de pacientes com urticária crônica e pacientes com psoríase em nosso ambulatório para avaliar a produção de dímero-D. OBJETIVO: Avaliar níveis de dímero-D em pacientes com urticária crônica e sua possível correlação com a atividade da doença. PACIENTES E MÉTODOS: O estudo foi conduzido de outubro de 2010 até março de 2011. Nós selecionamos 37 pacientes consecutivos da Unidade de Alergia e Unidade de Psoríase, divididos em três grupos para análise estatística: (i) 12 pacientes com urticária crônica ativa; (ii) 10 pacientes com urticária crônica em remissão e (iii) 15 pacientes com psoríase (uma doença com a pele infiltrado inflamatório constituído por neutrófilos, linfócitos e monócitos). Outros cinco pacientes com vasculite urticariforme foram alocados em nosso estudo, mas não incluídos na análise estatística. Os níveis séricos de D-dímero foram medidos por Enzyme Linked Fluorescent Assay (ELFA), e os resultados foram medidos em ng / ml FEU. RESULTADOS: Os pacientes com urticária crônica ativa tinham níveis séricos mais altos de dímero-D (p <0,01), quando comparados aos pacientes com urticária crônica em remissão e ao grupo controle (pacientes com psoríase). CONCLUSÕES: Os pacientes com urticária crônica ativa têm níveis séricos mais elevados de dímero-D, quando comparados aos pacientes ...

Pemphigoid gestationis: clinical and laboratory evaluation

INTRODUCTION: Pemphigoid gestationis, also known as herpes gestationis, is a rare autoimmune blistering disease associated with pregnancy. It usually occurs during the second or third trimester, but it may be present at any stage of pregnancy or the puerperium. The clinical, histologic, and immunopathological features of pemphigoid gestationis are similar to those of the pemphigoid group of disorders. METHODS: We hereby report seven patients who were diagnosed with pemphigoid gestationis and followed at the Autoimmune Blistering Disease Clinic in the Department of Dermatology of the University of Sao Paulo Medical School between 1996 and 2008. DISCUSSION: Demographic and clinical findings, such as median age, sites of involvement, and gestational age of onset of our patients, coincide with those described in previous reports. The majority of patients (85 percent) exhibited complement C3 or C3 and immunoglobulin G (IgG) deposition along the basement membrane zone (BMZ) on immunofluorescence. Herpes gestationis factor (HG) factor was postitive in four out of six patients (67 percent), and three out of five patients recognized the bullous pemphigoid recombinant antigen (BP180) by ELISA. CONCLUSION: This study revealed a good outcome of the newborns from pemphigoid gestationis affected mothers, based on the absence of pemphigoid gestationis cutaneous lesions, mean birth weight, and normal Apgar scores and gestational age at birth.

Significado do epitope spreading na patogênese dos pênfigos vulgar e foliáceo / Significance of epitope spreading in the pathogenesis of pemphigus vulgaris and foliaceus

Os pênfigos são dermatoses bolhosas auto-imunes, em que há a produção de auto-anticorpos direcionados contra moléculas de adesão dos epitélios, levando à perda da coesão celular. A produção de auto-anticorpos ocorre quando os pacientes desenvolvem um desequilíbrio da resposta imune (quebra da tolerância imunológica), passando a reconhecer antígenos próprios. A resposta é geralmente direcionada contra um único epítopo alvo; entretanto, como conseqüência da resposta inflamatória do processo primário e do extenso dano tecidual ocasionado, pode haver exposição de componentes protéicos ocultos, levando à produção de diferentes auto-anticorpos. Assim, é possível que surja uma nova doença cutânea auto-imune, em decorrência do fenômeno intra ou intermolecular de epitope spreading. São revistos os principais conceitos desse fenômeno e sua ocorrência nas dermatoses bolhosas auto-imunes, com ênfase nos pênfigos, grupo de dermatoses bolhosas autoimunes mais prevalente no Brasil.

Pemphigus comprises autoimmune blistering skin diseases in which autoantibodies directed against antigens (epithelial adhesion molecules) are found, leading to loss of cell cohesion. The production of autoantibodies occurs due to an immune imbalance (break of immune tolerance) driving to recognition of self- antigens. The response is usually directed against an exclusive target epitope; however, due to the inflammatory response and to the extensive tissue damage, it is possible that the exposure of hidden protein components leads to distinct autoantibody production. Hence, a new autoimmune disease may occur in consequence of an intra- or intermolecular epitope spreading phenomenon. The authors review the main concepts of this phenomenon, and its occurrence in autoimmune blistering diseases, with emphasis on pemphigus, the most prevalent disease of this group in our country.

Study on lymphocyte proliferation in nickel sensitive patients / Estudo da proliferação linfocitária em pacientes sensibilizados ao niquel

Fundamento: O diagnóstico da alergia ao níquel é estabelecido com a realização do teste de contato. Objetivo: Desenvolver um método diagnóstico mais sensível e específico.Casuísticas e Métodos: Dezenove pacientes com teste de contato positivo para o níquel e 25 controles foram submetidos ao teste da proliferação linfocitária. As células mononucleadas foram isoladas do sangue venoso periférico e cultivadas em triplicatas, em placas de cultura (2×105 células/orifício) com: meio de cultura apenas; sulfato de níquel (156,25; 78,13; 19,53; 9,77 e 2,44µM) e concentrações ideais do antígeno Candida albicans e dos mitógenos pokeweed, fito-hemaglutinina A e anticorpo anti-CD3 (OKT3). Timidina tritiada foi adicionada às placas, a radioatividade incorporada pelas células medida e os resultados expressos pelo índice de estimulação (IE).Resultados: A resposta proliferativa dos linfócitos dos casos foi superior à dos controles em todas as concentrações de níquel testadas. Considerando teste positivo para níquel quando IE ≥ 3, nenhum dos controles e 16 (84,21por cento) dos casos apresentaram teste positivo em pelo menos uma das cinco concentrações usadas. As respostas à Candida albicans e aos mitógenos foram semelhantes nos casos e controles, demonstrando a integridade da imunidade celular em ambos os grupos.Conclusão: O teste da proliferação linfocitária mostra-se útil no diagnóstico da alergia ao níquel

Nail manifestations in pemphigus vulgaris

Nail involvement in pemphigus vulgaris is rare. We describe 5 patients with pemphigus vulgaris presenting nail involvement. In this disease, nail manifestations present, by order of frequency, as chronic paronychia, onychomadesis, onycholysis, Beau's lines and trachyonychia. All our 5 cases presented with paronychia, and 1 of them also had Beau's lines. Treatment with prednisone and/or cyclophosphamide controlled mucocutaneous and nail manifestations in all cases

Retençäo de conhecimentos I: programas de dermatologia e de psiquiatria / Retention of knowledge I: dermatology and psychiatry programs

Os autores apresentam os resultados de uma investigacao educacional sobre retencao de conhecimentos. Foram estudados programas dos Departamentos de Dermatologia e de Psiquiatria que dispoem de uma disciplina no quarto ano e um estagio no internato de quinto ano. Foram comparadas as notas obtidas pelos alunos no quarto e no quinto ano, sendo a prova do quinto ano aplicada no primeiro dia do estagio, de mesmo conteudo da prova do quarto ano porem nao identica. Tais perdas nao foram influenciadas pelo tempo decorrido entre as duas provas, pelo sexo dos alunos, pela raca dos alunos (oriental e nao oriental) e pelo curriculo oculto pertinente aos programas estudados e eventualmente cumpridos pelos alunos