Claudia Giuli Santi

Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) / Drug-induced Hypersensitivity Syndrome (DIHS): a review of current concepts

The Drug Reaction with Eosinophilia and Systemic Symptoms syndrome, also known as 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, causing damage to several systems, especially to the kidneys, heart, lungs, and pancreas. Recognition of this syndrome is of paramount importance, since the mortality rate is about 10% to 20%, and a specific therapy may be necessary. The pathogenesis is related to specific drugs, especially the aromatic anticonvulsants, altered immune response, sequential reactivation of herpes virus and association with HLA alleles. Early recognition of the syndrome and withdrawal of the offending drug are the most important and essential steps in the treatment of affected patients. Corticosteroids are the basis of the treatment of the syndrome, which may be associated with intravenous immunoglobulin and, in selected cases, Ganciclovir. The article reviews the current concepts involving this important manifestation of adverse drug reaction.

Pemphigus herpetiformis is a rare clinical expression of nonendemic pemphigus foliaceus, fogo selvagem, and pemphigus vulgaris

BACKGROUND Pemphigus herpetiformis is a rare and atypical variant of pemphigus that resembles dermatitis herpetiformis. Most patients show antiepidermal autoantibodies that stain the epidermal intercellular spaces by immunofluorescence, similar to pemphigus autoantibodies, and lack the immunopathologic features of dermatitis herpetiformis. OBJECTIVE The study was aimed at characterizing the specificity of the antiepidermal autoantibodies in seven patients with pemphigus herpetiformis. METHODS The antiepidermal autoantibodies were characterized by immunofluorescence, immunoblotting, and immunoprecipitation studies in seven patients who fulfilled the clinical, histologic, and immunofluorescence diagnostic criteria for pemphigus herpetiformis. RESULTS Five patients with features of pemphigus herpetiformis either had classic pemphigus foliaceus, or their disease evolved into classic pemphigus foliaceus. One of these patients had fogo selvagem. Two of the seven patients showed features of or had disease that evolved into pemphigus vulgaris. The antiepidermal autoantibodies present in all seven patients recognized desmoglein 1. CONCLUSION Pemphigus herpetiformis is a rare clinical and histologic expression of nonendemic pemphigus foliaceus, fogo selvagem, and pemphigus vulgaris.

Clinical and immunopathological evaluation of epidermolysis bullosa acquisita

Background.  Epidermolysis bullosa acquisita (EBA) is a subepidermal blistering disease with IgG antibodies against collagen VII. The disease is heterogeneous and can lead to significant morbidity.

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 or C3 of our patients, coincide with those described in previous reports. The majority of patients (85%) exhibited complement 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%), 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.

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.

Drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome: clinical features of 27 patients

Drug reaction with eosinophilia and systemic symptoms (DRESS) [also called drug‐induced hypersensitivity syndrome (DIHS)] includes severe reactions to drugs that need to be promptly recognized by physicians.

Changes in the autoimmune blistering response: a clinical and immunopathological shift from pemphigus foliaceus to bullous pemphigoid

We describe a 64‐year‐old Brazilian man who developed bullous pemphigoid (BP) 12 years after pemphigus foliaceus (PF) was diagnosed. On his first presentation in 1992, histological examination revealed intraepidermal blistering and acantholysis at the granular layer, direct immunofluorescence (DIF) demonstrated intercellular deposits of C3 in the epidermis, and indirect immunofluorescence showed the presence of IgG antibodies against the intercellular spaces. In 2004, laboratory findings revealed a subepidermal blister with neutrophils and eosinophils (by histology), DIF demonstrated deposition of IgG and C3 along the basement membrane zone, salt‐split skin showed IgG deposition in the epidermal side of the blister, and immunoblotting showed reactivity against BP180. The occurrence of two autoimmune blistering conditions in the same patient is a rare event, and may suggest an intermolecular epitope‐spreading phenomenon.

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.

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.

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, Beaus lines and trachyonychia. All our 5 cases presented with paronychia, and 1 of them also had Beaus lines. Treatment with prednisone and/or cyclophosphamide controlled mucocutaneous and nail manifestations in all cases.