Drug reaction with eosinophilia and systemic symptoms (DRESS): a complex interaction of drugs, viruses and the immune system.

The DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), also known as DIHS (drug-induced hypersensitivity syndrome), presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, producing damage in several systems, especially kidney, heart, lungs, and pancreas. The pathogenesis is related to specific drugs (especially the aromatic anticonvulsants), altered immune response, sequential reactivation of herpes virus, and association with some HLA alleles. Glucocorticoids are the basis for the treatment of the syndrome, which may be given with intravenous immunoglobulin and, in selected cases, ganciclovir. This article reviews current concepts regarding the interaction of drugs, viruses and immune responses during this complex adverse-drug reaction.

Toxic epidermal necrolysis-like cutaneous lupus erythematosus: A series of three patients.

Toxic epidermal necrolysis-like lesions have been described in the setting of lupus erythematosus, and have been considered as a specific hyperacute variant of cutaneous lupus erythematosus, with features different from classical drug-related toxic epidermal necrolysis. We report here a series of three patients with lupus erythematosus who presented with severe worsening of their cutaneous disease in a toxic epidermal necrolysis-like fashion. We compared these cases with cases reported previously. Based on this discussion, we speculate that some of these patients may have classical drug-related toxic epidermal necrolysis rather than lupus erythematosus-related toxic epidermal necrolysis.

Stevens-Johnson syndrome and toxic epidermal necrolysis - retrospective review of cases in a high complexity hospital in Brazil.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions characterized by epidermal necrosis, mostly caused by drugs. Despite the rarity of these conditions, morbidity and mortality are high (even in previously healthy patients), and they may be associated with permanent sequelae. METHODS: A retrospective study conducted at a quaternary hospital in Brazil in a period of 10 years. RESULTS: The sample was composed by 41 patients with SJS, SJS/TEN, and TEN confirmed by skin biopsy. Antibiotics and anticonvulsants were the most frequently implied drug classes, and phenytoin was the most important individual culprit drug. In this study, 12.2% of the patients had sequelae, being ophthalmological lesions the most common and one case of a newly described hearing loss. The mortality rate was 16.7% in patients with TEN. CONCLUSIONS: This study describes the largest Latin American case series of SJS and TEN with the diagnosis proven by skin biopsy and adds important data regarding the profile of the disease in Brazil. It also describes a novel sequelae of hearing loss.

Clinical and epidemiological profile of patients attended in a vulvar clinic of the dermatology outpatient unit of a tertiary hospital during a 4-year period.

BACKGROUND: Vulvar complaints are among the most frequent causes for a woman to visit a healthcare provider. The diseases of this area of the body may be a challenge to diagnose. In this study, we assess epidemiologic and clinical data of patients in an outpatient vulvar clinic in the dermatology department of a tertiary hospital. METHODS: We performed an observational retrospective study of patients who attended our consultation service for vulvar diseases at the Dermatology Division at Hospital das Clínicas da Faculdade de Medicina da USP during a 4-year period. Data were obtained by patient medical records and by phone. RESULTS: During the 4-year period under study, a total of 136 patients were treated in the outpatient service specialized in vulvar care. All patients were included in the study. The most frequent diagnoses were lichen sclerosus et atrophicus (64.7%), lichen planus (8.8%), and vitiligo (8%). We registered that 26.7% of the patients showed extravulvar involvement. CONCLUSIONS: Women with vulvar diseases need specific care, considering not only genital aspects but also all skin changes. In this context, the dermatologist is a very well trained professional to take good and complete care of these patients. However, ideally vulvar clinics should have a multidisciplinary team.

A Severe, Refractory Case of Mucous Membrane Pemphigoid After Treatment With Pembrolizumab: Brief Communication.

Pembrolizumab is a humanized antibody that targets the programmed death-1 receptor expressed in T cells with high selectivity. This therapeutic is of great importance in cancer immunotherapy yet managing the potential immune-related adverse events remains a concern. Here, we report a rare case of mucous membrane pemphigoid in the oral mucosa, upper respiratory tract, and conjunctiva of a patient with ovarian adenocarcinoma without cutaneous manifestation, which persisted even after pembrolizumab discontinuation. A brief review of pembrolizumab-related bullous pemphigoid cases is presented and possible mechanisms underlying these lesions are discussed.

Paraneoplastic pemphigus associated with pelvic inflammatory fibrosarcoma: a case report.

A 36-year-old African-American woman presented with an extensive stomatitis and pigmented cutaneous macules on the neck, axillae and hands. Subsequently she developed violaceus papules on the dorsa of the hands, histologically consistent with an interface dermatitis. After 18 months of progressive disease, paraneoplastic pemphigus was suspected and a search for an underlying neoplasm was initiated. An exploratory laparotomy revealed a pelvic mass and the histologic examination showed an inflammatory fibrosarcoma. The evidence of acantholysis on new cutaneous lesions and the positivity of indirect immunofluorescence with rodent urinary bladder epithelium reinforced the diagnostic criteria for paraneoplastic pemphigus, which is confirmed by the identification of strong protein bands at 210, 190 and 170 kd by immunoprecipitation. Paraneoplastic pemphigus should be considered when investigating atypical mucocutaneous manifestations of pemphigus vulgaris and lichen planus. Diagnostic screening for paraneoplastic pemphigus and a search for an underlying tumor should be performed.

Pemphigus foliaceus with neutrophilic spongiosis evolving to an atypical pemphigus phenotype.

A 46-year-old Brazilian man, with initial pustular lesions, neutrophilic spongiosis and subcorneal cleavage evolved to an atypical pemphigus phenotype, with suprabasal acantholysis. Interestingly, his autoantibody profile, tested by immunofluorescence, immunoblotting, enzyme-linked immunosorbent assay, and immunoprecipitation revealed exclusive IgG anti-desmoglein 1 antibodies in all phases of the disease.

Two Brazilian cases of IgA pemphigus.

IgA pemphigus is a rare, neutrophilic, acantholytic skin disorder with approximately 70 cases described in the literature. We report two patients with the subcorneal pustular dermatosis (SPD) type of IgA pemphigus. Initially, both patients were misdiagnosed as subcorneal pustular dermatosis of Sneddon and Wilkinson. The correct diagnosis was only made after detecting intercellular IgA depositions in the epidermis by direct immunofluorescence. Immunoblotting (IB) of normal human epidermal extracts, performed on both sera, was negative for Dsg 1, Dsg 3, BP 230, BP 180, 210 kDa envoplakin, and 190 kDa periplakin. ELISA for desmogleins (Dsg 1 and Dsg 3) showed that neither of the cases had IgA antibodies to Dsg. The c-DNA transfection test for desmocollins (Dsc) revealed that the IgA antibodies of both patients reacted with desmocollin 1. This result supports the hypothesis that the autoantigen in SPD type IgA pemphigus is desmocollin 1.

Epidermolysis bullosa acquisita in childhood.

Epidermolysis bullosa acquisita (EBA) is a subepidermal autoimmune blistering disease that is rarely reported in childhood. We describe a nine-month-old mulatto boy presenting with multiple, annular, widespread, tense blisters and oral lesions. The diagnosis of EBA was confirmed by histopathology, immunofluorescence, and immunoblotting analysis. The patient was successfully treated with systemic steroids (prednisone) and dapsone. After 20 months of initial treatment, clinical remission was observed, and dapsone remains as the current treatment. This case report emphasizes the rarity of EBA in childhood and the difficulties in reaching the final diagnosis.

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%) and 4 of 9 patients with pemphigus foliaceus (44%) 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.

Childhood oral mucous membrane pemphigoid presenting as desquamative gingivitis in a 4-year-old girl.

Mucous membrane pemphigoid is a chronic inflammatory, bullous subepithelial auto-immune disease, with predominant involvement of the mucosal surfaces. Oral mucous membrane pemphigoid occurring in childhood is extremely rare. We describe a new case of this entity occurring in a 4-year-old girl who presented with desquamative gingivitis. Diagnosis was based on clinical presentation, histopathology, immunofluorescence and immunoblotting examinations. Treatment and 2-year follow-up are described.

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.

Endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris: immunoglobulin G heterogeneity detected by indirect immunofluorescence.

UNLABELLED: Pemphigus are autoimmune intraepidermal blistering diseases in which immunoglobulin G (IgG) autoantibodies are directed against desmosomal glycoproteins. The aim of this study was to determine the IgG subclass profile of endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris utilizing indirect immunofluorescence. PATIENTS AND METHODS: Twenty-five patients with pemphigus vulgaris, 25 with endemic pemphigus foliaceus (fogo selvagem), and 25 healthy controls were analyzed by indirect immunofluorescence for circulating autoantibodies (total IgG and its subclasses). RESULTS: Our data revealed a significant correlation (P <.05) of disease activity and autoantibody levels in both forms of pemphigus, i.e., negative titers related to clinical remission, whereas positive results related to active disease. Immunoglobulin G subclass analysis in fogo selvagem demonstrated that in patients in remission, 56% showed positive immunoglobulin G4; in active disease, immunoglobulin G4 was the predominant subclass (100% positive in all cases). The IgG subclass profile in pemphigus vulgaris showed that in patients in remission, only 10% were positive for immunoglobulin G4; in active disease, positivity for immunoglobulin G4 was present in 78% to 88% of the cases. CONCLUSION: Subclass characterization of immunoglobulin G autoantibodies is a useful tool for pemphigus follow-up, since immunoglobulin G4 (IgG4) is the subclass that is closely related to recognition of pathogenic epitopes, and consequently with disease activity. Careful monitoring should be performed for fogo selvagem in clinical remission with a homogeneous IgG4 response, since this may indicate more frequent relapses.

Endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris: immunoglobulin G heterogeneity detected by indirect immunofluorescence

Pênfigos são enfermidades auto-imunes bolhosas intraepidérmicas, onde auto-anticorpos IgG se dirigem contra glicoproteínas desmossomais. O objetivo deste estudo foi determinar o perfil de subclasses de imunoglubulina G no pênfigo foliáceo endêmico (fogo selvagem) e no pênfigo vulgar através da imunofluorescência indireta. MÉTODOS: Vinte e cinco doentes de pênfigo foliáceo endêmico (fogo selvagem), 25 de pênfigo vulgar e 25 controles sadios foram analisados através da imunofluorescência indireta, com respeito aos auto-anticorpos circulantes (imunoglobulina G total e subclasses). RESULTADOS: Nossos dados mostram uma correlação estatisticamente significativa (p<0.05) entre atividade da doença e títulos de auto-anticorpos circulantes em ambas as formas de pênfigo, ou seja, títulos negativos relacionaram-se com remissão clínica, enquanto resultados positivos correlacionaram-se com doença em atividade. A análise de subclasses de IgG mostrou que 56% dos doentes de fogo selvagem em remissão apresentaram apenas IgG4 positiva; na doença ativa, IgG4 foi a subclasse predominante, sendo positiva em 100% dos casos. Nos doentes de pênfigo vulgar, apenas 10% dos doentes em remissão apresentaram positividade exclusiva para IgG4; na doença em atividade, IgG4 esteve presente em 78-83,3% dos casos. CONCLUSÕES: A caracterização de subclasses de imunoglobulina G consiste em um instrumento de grande valia no seguimento de doentes de pênfigo, uma vez que a IgG4 é a subclasse intimamente relacionada com o reconhecimento de epítopos patogênicos, e consequentemente com atividade da enfermidade. No fogo selvagem em remissão com uma resposta homogênea 'as custas de IgG4, uma monitoração cuidadosa deve ser realizada, uma vez que isto pode significar uma maior chance de reativação.