Dermatosis ampollosa inducida por inmunoglobulina A lineal con clínica de síndrome DRESS por sulfasalazina

Linear immunoglobulin (Ig) A dermatosis is an immune-mediated bullous disease characterized by linear deposits of IgA along the basal membrane. While usually idiopathic, it can occasionally be induced by drug exposure. We report the case of a 60-year-old woman with rheumatoid arthritis being treated with sulfasalazine who developed linear IgA dermatosis and drug rash with eosinophilia and systemic symptoms (DRESS). The dermatosis and associated symptoms resolved following withdrawal of the drug and treatment with systemic corticosteroids for 2 months. This is the first report of sulfasalazine-induced linear IgA dermatosis in association with DRESS and we believe that sulfasalazine should be added to the list of drugs that can cause linear IgA dermatosis.     

Vancomycin-associated linear IgA dermatosis. A report of three cases.

BACKGROUND: Linear IgA dermatosis is an autoantibody-mediated, subepidermal blistering disease that is rarely associated with drug exposure. OBJECTIVE: We report the development of linear IgA dermatosis in three patients associated with the administration of vancomycin and further characterize the immunopathology. METHODS: Direct and indirect immunofluorescence assays were performed to characterize the immunoreactants, determine the subclass of the IgA deposits, and map the site of antibody deposition. RESULTS: A subepidermal blistering disease developed in all patients shortly after vancomycin was initiated, which resolved on discontinuation of the drug. Immunofluorescence studies revealed linear deposits of IgA1 only at the basement membrane zone, below the lamina lucida. Circulating IgA anti-basement membrane zone antibodies were not detected. CONCLUSION: Three patients had linear IgA dermatosis in association with the administration of vancomycin. All patients had linear deposits of IgA1 localized to the sublamina densa zone. Immunophenotypically, the disease in these patients mimics the pattern of IgA deposits seen in the majority of patients with idiopathic linear IgA dermatosis.     

Linear IgA dermatosis presenting with erythema annulare centrifugum lesions: report of three cases in adults

Linear IgA dermatosis presented with erythema annulare centrifugum lesions in three elderly women. Search for underlying malignancy revealed low-grade B-cell lymphoma in one case. In addition to subepidermal blistering, histology showed a typical mixed infiltrate of granulocytes and eosinophils and, occasionally, papillar microabsesses in one case. In the two other subjects, characteristic subepidermal lining with granulocytes was observed. Immunofluorescence studies confirmed the diagnosis, while autoantibodies characteristic for dermatitis herpetiformis were absent. To our knowledge this is the second report of adult linear IgA dermatosis in association with erythema annulare centrifugum lesions. Our observations concord with several other reports of figurate erythema associated with autoimmune blistering disease and other immune disorders. Common antibody-related immunological mechanisms indicate that the two distinct clinical pictures are probably stages of the same pathogenic entity.     

Linear IgA deposition associated with cutaneous varicella-zoster infection: a case report

The homogeneous linear deposition of IgA along the basement membrane zone of uninvolved skin is a distinguishing feature of linear IgA dermatosis in adults and chronic bullous dermatosis of childhood. Although linear IgA deposition may be seen in other cutaneous diseases, to our knowledge, there are no previous reports of a direct association with cutaneous infection. We describe the finding of intense fluorescence, in a linear pattern, of IgA at the basement membrane zone in an elderly man with disseminated cutaneous varicella-zoster infection.     

Linear IgA bullous dermatosis associated with ulcerative colitis: A case report and literature review

We report the case of a 59-year-old Japanese woman who developed linear IgA bullous dermatosis during treatment for ulcerative colitis that manifested as pruritic vesicles with erythema on the trunk and scalp. Histopathological examination revealed subepidermal bulla with neutrophil and eosinophil infiltration in the upper dermis. Direct immunofluorescence revealed linear IgA deposits at the basement membrane zone, and indirect immunofluorescence using split skin revealed IgA reaction to the epidermal side (lamina lucida type). We reviewed 33 reported cases of linear IgA bullous dermatosis associated with ulcerative colitis and found that ulcerative colitis preceded the onset of linear IgA bullous dermatosis in 94% of the patients and that IgA-positive patients in split skin indirect immunofluorescence all showed the lamina lucida type, indicating that target antigens for serum IgA antibodies may reside in the lamina lucida. Regarding the pathogenetic association of ulcerative colitis and linear IgA bullous dermatosis, intestinal inflammation may induce the exposure and presentation of intestinal antigens that are cross-reactive to cutaneous antigens, stimulating autoimmune response to antigens of cutaneous basement membrane zones.     

Linear IgA Dermatosis associated with ulcerative colitis: complete and sustained remission after total colectomy

Linear IgA dermatosis has been increasingly associated with inflammatory bowel diseases, particularly ulcerative colitis. A 13-year-old male patient with an 11-month history of ulcerative colitis developed vesicles, pustules and erosions on the skin of the face, trunk and buttocks and in the oral mucosa. The work-up revealed a neutrophil-rich sub-epidermal bullous disease and linear deposition of IgA along the dermoepidermal junction, establishing the diagnosis of linear IgA dermatosis. The patient experienced unsatisfactory partial control of skin and intestinal symptoms despite the use of adalimumab, mesalazine, prednisone and dapsone for some months. After total colectomy, he presented complete remission of skin lesions, with no need of medications during two years of follow-up. A review of previously reported cases of the association is provided here and the role of ulcerative colitis in triggering linear IgA dermatosis is discussed.     

Circulating antibodies to gliadin subfractions in dermatitis herpetiformis and linear IgA dermatosis of adults and children

Dermatitis herpetiformis (DH) and coeliac disease (CD) are linked but their association with linear IgA dermatosis (LAD) is unclear. Thirty-seven patients with DH and 27 with linear IgA dermatosis were investigated, of which 23/37 DH patients and 1/10 LAD patients had small intestinal enteropathy. Elevated IgG and IgA gliadin antibodies were found in the DH patients with enteropathy (CD). IgG gliadin antibodies in DH patients were directed against alpha, beta, gamma and omega gliadin subfractions. Elevated IgA gliadin antibodies in the adult LAD patients (n= 14) suggests that this condition may be associated with enteropathy or an IgA diathesis.     

Linear IgA dermatosis and Hodgkin's lymphoma--report of a case in an African and review of the literature

Linear IgA dermatosis and Hodgkin's lymphoma were diagnosed at the same time in a 47-year-old Black South African man. Skin changes of linear IgA dermatosis responded to a combined treatment with dapsone and MOPP regimen. Prior administration of dapsone alone did not result in improvement of the skin condition. Four documented cases of linear IgA dermatosis and lymphoma outside the gastrointestinal tract, three of them of Hodgkin's type, have been reported in the literature. Review of the literature suggests that different forms of lymphoma seem to be associated with linear IgA dermatosis and dermatitis herpetiformis. The present patient represents the first immunologically verified case of linear IgA dermatosis in an adult Black African.     

成人线状IgA大疱性皮病5例临床分析

目的：了解5例成人线状IgA大疱性皮病的临床特点,以提高对该病的认识。方法：对5例成人线状IgA大疱性皮病的临床资料、组织病理、免疫荧光进行分析,并对相关文献进行复习。结果：5例患者中男3例,女2例,年龄在66—87岁之间,均表现为在红斑基础上的水疱,或外观正常的皮肤上出现的水疱,病理组织活检和免疫荧光确诊为成人线状IgA大疱性皮病。结论：成人线状IgA大疱性皮病好发年龄为〉60岁的老年人,皮疹表现类似大疱性类天疱疮、疱疹样皮炎,多数兼有两病的特点,容易误诊,直接免疫荧光检查发现沿基底膜带有均质型线状IgA沉积具有诊断价值。     

Childhood cicatricial pemphigoid with linear IgA deposits

Four cases showing a unique combination of scarring conjunctivitis and widespread blistering, commencing in childhood are described. In all cases linear deposits of IgA were present at the dermo-epidermal junction in association with low titres of circulating IgA antibasement membrane zone antibody in three cases. The relationship of this entity to chronic bullous disease of childhood, cicatricial pemphigoid and linear IgA disease of adults is as yet unclear and it may be a distinct bullous dermatosis.     

Burn-induced linear IgA dermatosis

There have been several reports of linear IgA dermatosis (LAD) associated with drug exposure and lymphoproliferative malignancy, but trauma and burns have been suggested only in patients with bullous pemphigoid. We present a case of burn-induced LAD in a 48-year-old caucasian male presenting with a recent history of blistering eruption on the periphery of a cicatricial area caused by boiling methyl alcohol. Clinically, he presented a widespread bullous eruption. The direct immunofluorescence examination of a perilesional biopsy revealed an intense homogeneous linear pattern of IgA deposition consistent with the diagnosis of LAD. The patient responded to therapy with systemic steroids.     

Pyoderma gangrenosum associated with subcorneal pustular dermatosis and IgA myeloma

We report a 57-year-old woman with a 12-year history of ulcerative pyoderma gangrenosum (PG). Five years after the onset of PG, she developed subcorneal pustular dermatosis (SPD) and biclonal IgA and IgG gammopathy. She developed PG at two bone-marrow biopsy sites, showing pathergy. Finally, she developed multiple myeloma. Although PG and SPD may occur without associated underlying malignancy, these patients should be followed up for any prospective malignancy because of the association between these disorders.     

Linear IgA Dermatosis of Childhood: Case Report with an Immunoelectron Microscopic Study

A 7-year-old girl developed a cutaneous bullous eruption with genital and nasal mucous membrane involvement. Direct immunofluorescence revealed linear deposits of IgA and IgM at the basement membrane zone. No circulating antibasement membrane zone antibodies were detected. Small bowel biopsies showed a partial villous atrophy. The clinical, histologic, and immunopathologic findings were consistent with a diagnosis of linear IgA dermatosis of childhood. Immunoelectron microscopy revealed IgA deposits in the lamina lucida in association with hemidesmosomes, confirming results of two recent studies.     

成人与儿童线状IgA大疱病的比较观察

本文对免疫病理表现有线状IgA沉积在BMZ的24例患者(成人18例、儿童6例)进行了临床、病理与免疫病理的分析观察,发现成人与儿童在临床症状、皮损形态与分布以及免疫病理等方面均有不同之处,说明成人与儿童线状IgA大疱病是线状IgA大疱病病谱中的两个分立疾患.本文也对免疫球蛋白在BMZ的沉积型进行了分析,发现除了线状沉积外,其中有2例成人的沉积型为颗粒状线状,而且既沉积在BMZ,也沉积在真皮乳头.认为这两例应考虑为(DH)与(BP)的混合型.另1例呈颗粒状线状沉积在BMZ,考虑为IgA BP.     

Treatment of linear IgA bullous dermatosis of childhood with colchicine

Linear IgA bullous dermatosis of childhood is the most common immunobullous disorder of childhood. First-line treatment includes dapsone or sulfapyridine. We report a child with linear IgA dermatosis who was treated successfully with colchicine after developing hemolytic anemia from dapsone. We recommend colchicine as an alternative therapy for linear IgA dermatosis of childhood in patients in whom first-line treatment is contraindicated or who fail first-line treatment or develop side effects from it.     

IgA autoimmune disorders: development of a passive transfer mouse model

IgA is present in the skin in several dermatoses, including dermatitis herpetiformis, linear IgA bullous dermatosis, and Henoch-Schoenlein purpura. The neutrophilic infiltration in the area of the IgA deposition suggests that IgA is responsible for the associated inflammatory events. The mechanism for this process is unproven, but is likely to involve IgA-mediated neutrophil chemotaxis with inhibition of chemotaxis by dapsone. Elucidation of the mechanism of IgA-mediated inflammation will require an animal model. We have established a model for linear IgA bullous dermatosis as a prototype disease to be studied. IgA mouse monoclonal antibodies against a linear IgA bullous dermatosis antigen have been passively transferred to SCID mice with human skin grafts. This has produced neutrophil infiltration and basement membrane vesiculation in 4 of 12 mice tested. We conclude that an animal model for the pathogenesis of IgA dermatoses with IgA deposition and inflammation can be produced by passive transfer of mouse IgA antibodies against a linear IgA antigen.     

Dermo-epidermal blister formation by linear IgA dermatosis sera in normal human skin in organ culture

Fresh normal human skin samples were cultured at 37^°C for 48 hours with sera from 3 patients with linear IgA dermatosis and 2 patients with dermatitis herpetiformis (DH). Dermo-epidermal separation (DES) occurred in the skin samples cultured with the sera from linear IgA dermatosis patients, and linear IgA deposition was observed in the dermo-epidermal junction zone. However, no IgA deposition or DES was observed in the skin cultured with the sera of DH patients or normal individuals. The results were the same when sera of patients with linear IgA dermatosis were heated at 56^°C for 30 minutes before culturing with skin samples, but DES was prevented when a proteinase inhibitor, aprotinin (50%), or α₂-macroglobulin (10 mg/dl) was added to the cultures. Our results suggest that IgA deposition in the basement membrane and proteinases are involved in the formation of vesicles in patients with linear IgA dermatosis, but complements are not directly involved.     

线状IgA大疱皮病8例分析

线状IgA大疱皮病是一种少见的自身免疫性大疱性皮肤病 ,近 10年在我科的临床患者中 ,通过临床表现、皮肤病理检查及免疫荧光检查明确诊断为线状IgA皮病并长期随访的患者仅 8例 ,男 5例 ,女 3例 ;儿童型 5例 ,成人型 3例。 7例患者使用DDS治疗 ,皮疹得到完全控制 ,无不良作用发生。DDS可作为治疗线状IgA大疱皮病的首选药物。     

IgA linear dermatosis of childhood (chronic Bullous disease of childhood)

Of twenty-seven cases of subepidermal blistering disease of children twelve corresponded clinically, histologically and immunologically to dermatitis herpetiforms of adults, six to bullous pemphigoid, and eight to chronic bullous disease of childhood (CBDC), i.e. IgA linear dermatosis. This latter disease seems to be a distinct entity, different from both dermatitis herpetiformis and bullous pemphigoid, and is characterized immunopathologically by linear IgA deposits at the basement membrane zone. These cases usually do not show intestinal involvement and respond well to combined treatment with sulphones and corticosteroids, whereas sulphones or sulphapyridine alone are, even in very high doses, not sufficient for full control of the disease. CBDC or IgA linear dermatosis of childhood may be regarded as a counterpart of IgA linear dermatosis of adults.