Dermatitis herpetiformis Duhring with linear deposits of IgA (linear IgA dermatosis)

Three patients with linear deposits of IgA along the epidermal basement membrane were studied. The clinical and histopathological picture as well as the response to dapsone were typical of dermatitis herpetiformis. Two of the three patients were HLA-B8/DR3-positive. By immunoelectron microscopy, the previously reported two types of linear IgA deposits were confirmed: in one patient, the IgA precipitates were localized below the basal lamina as in dermatitis herpetiformis, in the other two above the basal lamina in the lamina lucida as in bullous pemphigoid. The immunoelectron microscopic findings imply that in some patients with linear IgA dermatosis a pathomechanism different from that in classical dermatitis herpetiformis may be operative.     

Dermatitis herpetiformis. Cutaneous deposition of polyclonal IgA1

Dermatitis herpetiformis (DH) is a pruritic papulovesicular skin disorder of unknown cause, characterized by granular IgA deposits in the dermis along the dermoepidermal junction. It is associated with gluten-sensitive enteropathy and increased IgA production by gut lymphoid tissue. We report four cases of immunologically documented DH studied by immunofluorescence technique. Monoclonal antibodies against the IgA subclasses IgA1 and IgA2 were used. IgA1 without IgA2 was found in the cutaneous deposits in each case. The IgA1 had both kappa and lambda light chains in approximately equal quantities. Because normal gut-associated lymphoid tissue produces 70% IgA1 and 30% IgA2, while circulating IgA is primarily IgA1, it could be concluded that the IgA in the skin of DH patients is not produced in the gut. However, the subclass restriction of the IgA produced by pathologic gut-associated lymphoid tissue is unknown. Alternatively, both IgA1 and IgA2 may be produced by the gut, but only IgA1 is involved in the production of cutaneous lesions.     

Cutaneous IgA subclasses in dermatitis herpetiformis and linear IgA disease

The subclasses of the cutaneous IgA were studied in 8 patients with dermatitis herpetiformis and 4 with linear IgA disease. The cutaneous IgA in dermatitis herpetiformis consisted of both IgA1 and IgA2, although IgA1 predominated. This demonstrated that the IgA is polyclonal and may be both mucosal and blood derived. The IgA in linear IgA disease was exclusively IgA1, confirming previous work, and suggesting that mucosal IgA may not make a major contribution to the skin deposits.     

Dermatitis herpetiformis: extraction of intact IgA from granular deposits in dermal papillae

Dermatitis herpetiformis (DH) is characterized by the granular deposition of IgA in the dermal papillary tips. The source and antigenic specificity of this IgA are unknown, largely because of the previous inability to isolate it for study. These granular IgA deposits, pathognomonic of DH, have been specifically isolated from 4-mm punch biopsies. Specific isolation was achieved by removing contaminating serum IgA by a combination of washes in saline and sodium dodecyl sulfate without a reducing agent present and mechanical isolation of papillary dermis. The tissue IgA was then solubilized by a buffer containing 1% sodium dodecyl sulfate and 0.2 mM dithiothreitol, a reducing agent. Immunoreactive alpha chains were recovered in eluates of DH skin in 6-fold greater amounts than in eluates of normal skin, coincident with disappearance of immunofluorescent-staining granular deposits of IgA. Extracted specific IgA was recovered in sufficient quantity for detection by immunoenzymatic stain, was partially composed of a native (165 Kd) molecular mass, and had alpha and kappa staining material, all indicating that the extracted immunoglobulin was in part intact.     

The ultrastructural localization of IgA in skin of a patient with mixed form of dermatitis herpetiformis and bullous pemphigoid.

A case with mixed features of dermatitis herpetiformis and bullous pemphigoid was investigated by immuno-electron microscopy. There were clinical, histological, and ultrastructural characteristics of both diseases, the response to sulfapyridine was dramatic at the beginning, but intestinal lesions were absent. Direct immunofluorescence tests were made 6 times in the 4 year period and demonstrated in all biopsies exclusively linear IgA deposits. The IgA deposits were shown to occupy the entire lamina lucida and to adhere to the basal cell membranes and lamina densa, very much like IgG deposits in bullous pemphigoid. Antibodies against the basement membrane zone could not be demonstrated in the serum.     

Treatment of dermatitis herpetiformis and linear IgA bullous dermatosis

Dermatitis herpetiformis (DH) and linear IgA bullous dermatosis (LABD) are IgA-mediated autoimmune bullous diseases. They share an identical histopathology, but are differentiated on the basis of the pattern of IgA deposition on direct immunofluorescence. While DH responds to a gluten-free diet, LABD rarely responds to gluten restriction. In the management of DH, adhering to a gluten-free diet promotes healing of small intestine villus atrophy, resolution of cutaneous disease, and lowers the risk of lymphoma. Dapsone is palliative but not curative in the treatment of DH and LABD. Patients taking systemic dapsone or sulfa-based medication for the treatment of DH or LABD should have a reasonable knowledge of the inherent side effects.     

Dermatitis herpetiformis-like changes in cutaneous leucocytoclastic vasculitis with IgA deposition*

Histopathological studies in a patient with cutaneous vasculitis revealed sub-epidermal micro-abscess formation as seen in dermatitis herpetiformis (DH). Direct immunonfluorescence of perilesional skin revealed granular IgA fluorescence at the dermo-epidermal junction and deposition of IgA and C₃ within vessel walls, whereas immunofluorescence studies of uninvolved skin revealed IgA and C₄ deposition within upper dermal vessels only. IgA containing complexes were detected in the serum, and evidence of classical pathway activation was provided by demonstrating CIq and C₄ within vessel walls with absence of properdin. Prior to referral there had been a favourable therapeutic response to dapsone. This case illustrates that some forms of leucocytoclastic vasculitis may closely resemble DH and that direct immunofiuorescence of uninvolved skin is required to differentiate the two conditions.     

Dermatitis herpetiformis in Japan: an update

BACKGROUND: Although dermatitis herpetiformis (DH) is a relatively common disease in Caucasian populations, it is rare in Asian populations including the Japanese. We encountered a Japanese case of DH which showed granular IgA and C3 deposits in the papillary dermis and which was associated with gluten-sensitive enteropathy but no HLA-B8/DR3/DQ2. OBJECTIVE: The purpose of this study is to describe the characteristics of Japanese DH cases, since most of them have been reported in Japanese language and dermatologists outside Japan are not familiar with the characteristics of Japanese DH. METHODS: We have reviewed all 34 Japanese DH cases reported previously. RESULTS: We found several features of Japanese DH compared with Caucasian DH, such as a high frequency of the fibrillar pattern, rarity of gluten-sensitive enteropathy and an absence of the HLA-B8/DR3/DQ2 haplotype. CONCLUSION: There might be significant differences in pathophysiology between Caucasian and Japanese DH cases.     

Coexistence of linear IgA dermatitis herpetiformis and systemic lupus erythematosus

A vesiculobullous eruption of dermatitis herpetiformis and systemic lupus erythematosus developing simultaneously in a 26 year old woman is described. The lesions were characterized by pruritic urticarial vesicles, eosinophilic and neutrophilic abscesses, and the presence of the linear type of IgA deposition at the basement membrane zone. These lesions respond to dapsone, although high dosages of prednisone and cyclophosphamide were not effective.     

Dermatitis herpetiformis associated with relapsing polychondritis

A 35-year-old woman developed typical relapsing polychondritis within a year following the onset of dermatitis herpetiformis. This occurred during a reduction in the dapsone dose regimen. To our knowledge, the coexistence of these two conditions in a single patient has not yet been reported in the literature. Both the parallel course and the good response to dapsone suggest a pathogenic link between these two diseases.     

Dermatitis herpetiformis associated with ulcerative colitis

Over the past 20-years, it has been shown that the majority of patients with dermatitis herpetiformis (D.H.) suffer from coeliac disease of varying intensity. Dermatitis herpetiformis may also be associated with other autoimmune diseases but only exceptionally with chronic ulcerative colitis (U.C.).