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Antibodies to gliadin in adult coeliac disease and dermatitis herpetiformis.

Antibodies to gliadin, searched for by indirect immunofluorescence and a micro-ELISA, were detected in 16 (64%) of 25 sera from patients with adult coeliac disease and in 13 (45%) of 29 with dermatitis herpetiformis. Although the sensitivity of the two tests was relatively low in the whole groups, it increased when only cases with severe jejunum abnormalities were considered (93% for coeliac disease and 81% for dermatitis herpetiformis). A significant correlation was found between antigliadin antibodies and the severity of jejunum damage in both diseases. Moreover, most coeliac and dermatitis herpetiformis patients with antigliadin antibodies were on normal diet. The specificity of the tests was 100% for the immunofluorescence and fairly good for the micro-ELISA, as only 5 (11%) of the 46 disease control patients (Crohn's disease, ulcerative colitis) were positive for antigliadin antibodies. R1-reticulin antibody test was equally specific but less sensitive in both groups. We conclude that antigliadin antibodies are useful in the diagnosis of patients with active adult coeliac disease and dermatitis herpetiformis with gluten-sensitive enteropathy. Moreover, the two tests make it possible to monitor the compliance to gluten-free diet in both diseases.

Adolescent↗

Tolerance to oats in dermatitis herpetiformis.

OBJECTIVES: Recent studies on coeliac disease have shown that oats can be included in a gluten-free diet without adverse effects on the small bowel. The presence of a rash is also a sensitive indicator of gluten ingestion in dermatitis herpetiformis, and this was used to study whether patients with this disease could also tolerate oats. PATIENTS/METHODS: Eleven patients with dermatitis herpetiformis in remission on a gluten-free diet were challenged daily with 50 g oats for six months. Clinical symptoms were recorded, serum samples taken, and skin and small bowel biopsies performed before and after the oat challenge. A control group comprised of 11 patients with dermatitis herpetiformis on a conventional gluten-free diet was also studied. RESULTS: Eight patients challenged with oats remained asymptomatic, two developed a transient rash, and one withdrew because of the appearance of a more persistent but mild rash. Three of the 11 controls also developed a transient rash. IgA endomysial antibodies remained negative in all patients. The small bowel villous architecture, the densities of intraepithelial CD3 and alpha/beta and gamma/delta T cell receptor positive lymphocytes and crypt epithelial cell DR expression remained unaltered during the oat challenge. CONCLUSIONS: The results confirm the absence of oat toxicity on the gluten sensitive small bowel mucosa and suggest that the rash in patients with dermatitis herpetiformis is not activated by eating oats.

Adult↗

Dapsone and human polymorphonuclear leucocyte chemotaxis in dermatitis herpetiformis.

Polymorphonuclear leucocyte chemotaxis was investigated in 6 patients with active dermatitis herpetiformis in the untreated state and when under control with Dapsone. Control studies were undertaken in 7 healthy volunteers. No significant difference in chemotaxis was demonstrated between the active, treated and control groups. Furthermore, when Dapsone in physiological concentrations was added separately in all three groups there was no additional effect on chemotaxis. These results clearly show that polymorphonuclear leucocytes from active untreated dermatitis herpetiformis have normal chemotactic activity compared with those from the same patients in the treated state and controls. Additional Dapsone did not alter these findings.

Adult↗

Clinical response of dermatitis herpetiformis skin lesions to a gluten-free diet.

Patients with dermatitis herpetiformis have been studied prospectively for 2 years to assess the effect of a gluten-free diet (GFD) on control of the skin lesions. Daily requirements for oral medication with sulphapyridine or dapsone were reduced by GFD treatment and if complete clinical remission of the skin disease occurred, it was maintained while the diet was strictly observed. However, complete remission did not occur significantly more often in GFD-treated patients than in patients taking a normal diet. Many of the latter group exhibited variation in their drug dose requirements during the period of study. GFD treatment seems desirable for the majority of patients with dermatitis herpetiformis, not only to correct the intestinal abnormality but also to minimize the dose of drugs necessary to control the skin lesions.

Adolescent↗

Increased jejunal intraepithelial lymphocytes bearing gamma/delta T-cell receptor in dermatitis herpetiformis.

T-cell receptor 1 (gamma/delta) expression was studied in 19 jejunal or duodenal specimens from patients with dermatitis herpetiformis and in 16 jejunal or duodenal specimens showing normal histology. In normal specimens, gamma/delta+ cells represented 10.8% of intraepithelial CD3+ lymphocytes. Around 50% of these cells were recognized by the A13 monoclonal antibody, which detects products of the V gamma 1/V delta 1 gene rearrangement and the non-disulfide-linked form of T-cell receptor 1. The remaining 50% reacted with the BB3 monoclonal antibody, which recognizes products of the V gamma 9/V delta 2 rearrangement and the disulfide-linked form of receptor. Very few gamma/delta+ cells were observed in the lamina propria. In jejunal specimens from patients with dermatitis herpetiformis, a significant increase in the prevalence of gamma/delta+ intraepithelial lymphocytes was observed (P less than 0.001). This finding was largely accounted for by an increase in those cells recognized by the A13 monoclonal antibody, thus possibly expressing the V gamma 1/V delta 1 rearrangement and the nondisulfide-linked form of receptor. These data suggest that similar pathogenetic mechanisms may be active in determining the jejunal damage in celiac disease and dermatitis herpetiformis.

Animals↗

Dermatitis herpetiformis in a Japanese patient with anaplastic large cell lymphoma.

We report a 73-year-old Japanese man with dermatitis herpetiformis which developed after diagnosis of anaplastic large cell lymphoma. The patient suffered fever, sweating, shivering, and multiple enlarged cervical lymph nodes. The diagnosis of anaplastic large cell lymphoma was confirmed by the histologic features of a biopsied cervical lymph node. The patient underwent combination chemotherapy. However, one month after the initial therapy, pruritic erythematous skin lesions with peripheral vesicles appeared on his buttocks. A skin biopsy showed subepidermal blister formation associated with polymorphonuclear and mononuclear cell infiltrates. Direct immunofluorescence examination of the area adjacent to the lesion showed granular deposits of IgA at the dermoepidermal junction. While it is well-known that dermatitis herpetiformis can develop into lymphoma, there have been only a few reports of its appearance after a diagnosis of lymphoma. This case suggests that dermatitis herpetiformis may be induced by anaplastic large cell lymphoma.

Aged↗

Sensitivity and specificity of IgA-class antiendomysial antibodies for dermatitis herpetiformis and findings relevant to their pathogenic significance.

The specificity and sensitivity of the recently reported IgA-class antiendomysial antibody test for gluten-sensitive enteropathy were evaluated in four double-blind studies involving the sera of fifty-seven patients with dermatitis herpetiformis who were not on a gluten-free diet and ninety-seven assorted control sera. The control sera provided by the four centers included the sera of nineteen patients with dermatitis herpetiformis and two with celiac disease who were on a gluten-free diet, the sera of five normal subjects with human lymphocyte antigens (B8 locus), the sera of thirteen patients with linear IgA bullous dermatosis, and fifty-eight other control sera, mostly from patients with other bullous diseases and other dermatoses. The frequency of IgA antiendomysial antibody in these coded studies was zero of ninety-seven control sera and thirty-four of fifty-seven sera (60%) from patients with dermatitis herpetiformis who were not on a gluten-free diet. The pathogenic role of IgA antiendomysial antibodies in dermatitis herpetiformis and celiac disease is suggested not only by their high degree of disease sensitivity and specificity but also by their formation in response to gluten challenge, their appearance before gut changes, and the in vitro binding of gliadin to the antiendomysial antibody antigen sites. These and other findings in this study and in the literature suggest that gluten-sensitive enteropathy is immunologically mediated and that IgA antiendomysial antibodies play a significant pathogenetic role.

Animals↗

Dermatitis herpetiformis bodies. Ultrastructural study on the skin of patients using direct preembedding immunogold labeling.

Skin samples from three adult patients with dermatitis herpetiformis (DH) and granular IgA deposits in the papillary tips were studied using ultrastructural immunogold technique. IgA positive, so-called DH bodies were identified as amorphous clumps--most probably immunocomplex aggregates--scattered throughout the upper papillary dermis. Dermatitis herpetiformis bodies were seen underneath the basement membrane, sometimes along microfibrillar bundles, as well as adjacent to the papillary collagen fibers and within the surface (microfibrillar) region of elastic tissue. Some DH bodies, however, were not related to any fibrillar components. The collagen and elastic fibers, microfibrillar bundles, anchoring fibrils, and elastic microfibrils themselves were unlabeled. Dermatitis herpetiformis bodies were not found in normal human skin. The results of our ultrastructural study indicate that DH bodies either are bound to a nonfibrillar component of dermal connective tissue or represent deposits of immune complexes trapped in DH skin.

Actin Cytoskeleton↗

Concomitant immunohistochemical characteristics of pemphigoid and dermatitis herpetiformis in a patient with atypical bullous dermatosis.

We report a patient who developed a vesiculobullous eruption which clinically and histologically showed features of pemphigoid and dermatitis herpetiformis, responded to prednisone but doubtfully to dapsone, and demonstrated 'classical' immunopathologic characteristics of phemphigoid and dermatitis herpetiformis. Peribullous and unaffected skin featured deposition of IgG and C3c in a homogeneous-linear pattern at the epidermal basement membrane, while the unaffected skin demonstrated concomitantly granular IgA deposits in the dermal papillae. Circulating IgG class anti-basement membrane antibody was found in a titre of 1:80 when using guinea-pig oesophagus, and of 1:320 when using human oral mucosa as antigenic substrate. Our findings add another piece to the puzzle that continues to stimulate discussion among dermatologists as how to classify patients with overlapping features of pemphigoid and dermatitis herpetiformis. (Received February 18, 1983.)

Aged↗

Malabsorption of dietary folate (Pteroylpolyglutamates) in adult coeliac disease and dermatitis herpetiformis.

Tests of absorption of folic acid (pteroylglutamic acid) and of dietary folates (pteroylpolyglutamates) were performed in 10 patients with untreated adult coeliac disease, five with dermatitis herpetiformis, and three with nutritional folate deficiency. Absorption of pteroylglutamic acid was impaired in eight patients with coeliac disease and in two with dermatitis herpetiformis. Absorption of pteroylpolyglutamates was impaired in all 10 coeliac patients and in four of the five patients with dermatitis herpetiformis. Absorption of both forms of folate was normal in all three patients with nutritional folate deficiency.

Adult↗

A simple method for elution of IgA deposits from the skin of patients with dermatitis herpetiformis.

To better understand the role of autoimmunity in the pathogenesis of dermatitis herpetiformis, linear IgA bullous dermatosis or other skin disorders, the antigenic specificity of the immune reactants bound in vivo in the skin must be identified. In order to do so, one must first be able to elute these immune reactants from the skin. We describe here a simple method of eluting not only specifically bound IgG, but also IgA and other immunoglobulins and complement components from skin biopsy material. The method involves cutaneous washing of the entrapped serum proteins in PBS pH 7 and pH 5 buffers followed by specific immunoglobulin elutions at pH 3 and 2. The IgA deposits which could not be removed by this treatment were eluted by a combination of low pH (0.5 M citrate pH 2) and a chaotropic agent (2 M NaCl). The relative concentration of IgA in eluates when quantitated by fluoroimmunoassay were three- to five-fold higher in dermatitis herpetiformis skin biopsy specimens, than in eluates of bullous pemphigoid or normal skin biopsy specimens.

Buffers↗

Linear IgA bullous dermatosis v dermatitis herpetiformis. Quantitative measurements of dermoepidermal alterations.

Linear IgA bullous dermatosis (LAD), also known as "atypical dermatitis herpetiformis," is a disorder that is distinct from classic dermatitis herpetiformis (DH). In eight patients with DH and six with LAD, quantitative assessment of a variety of histopathologic variables was made. The number of rete tips with neutrophils in basal vacuoles and the length of the epidermal basement membrane zone (BMZ) associated with these findings were greater in LAD than DH. The number of microabscesses of neutrophils in the dermal papillae and the length of epidermal BMZ associated with them were greater in DH than in LAD. By using the number of microabscesses and the number of rete tips with neutrophils in basal vacuoles in a probability model, we found by retrospective analysis that a correct diagnosis could be made for LAD in 75% of biopsy specimens with a probability of 97% and in all cases of DH with a probability of 92%. Using this model, we made no misdiagnoses. This is the first diagnostic probability model in dermatopathology that expresses a confidence level in diagnosis.

Adult↗

Small intestinal function and dietary status in dermatitis herpetiformis.

Small intestinal morphology and function were assessed in 82 patients with dermatitis herpetiformis, 51 of whom were taking a normal diet and 31 a gluten free diet. Methods used were histopathological evaluation of jejunal mucosal biopsy specimens, quantitation of intraepithelial lymphocytes, cellobiose/mannitol permeability test, tissue disaccharidase values, serum antigliadin antibodies, and formal assessment of dietary gluten content by a dietician. There was no correlation between dietary gluten intake and the degree of enteropathy in the 51 patients taking a normal diet, whereas biopsy specimens were normal in 24 of the 31 patients on a gluten free diet, all previously having been abnormal. Eighteen patients on gluten containing diets had normal jejunal histology and in seven of these all tests of small intestinal morphology and function were entirely normal. Intestinal permeability was abnormal and serum antigliadin antibodies were present in most patients with enteropathy. Studies of acid secretion in seven patients showed that hypochlorhydria or achlorhydria did not lead to abnormal permeability in the absence of enteropathy. This study shows that a combination of objective tests of small intestinal architecture and function will detect abnormalities in most dermatitis herpetiformis patients, including some with histologically normal jejunal biopsy specimens. Nevertheless there is a small group in whom all conventional intestinal investigations are entirely normal.

Adolescent↗

Glomerulonephritis in dermatitis herpetiformis. A case study.

A patient with dermatitis herpetiformis, proteinuria and reduced renal function is described. A renal biopsy studied by light and immunofluorescence microscopy revealed a glomerulonephritis with deposits of predominantly IgA and complement C3. Deposits of IgA and C3 were also demonstrated in a biopsy from normal skin, and a common pathway for the skin and renal lesions is suggested.

Complement C3↗

Dermatitis herpetiformis exacerbated by indomethacin.

Thirteen adults with dermatitis herpetiformis (DH) controlled by dapsone or sulphamethoxypyridazine were given indomethacin or placebo in a double-blind cross-over study. In nine of the thirteen patients the rash and pruritus of DH were exacerbated more by indomethacin than by placebo. Dapsone and sulphamethoxypyridazine requirements were increased during the indomethacin period. The involvement of lipoxygenase products in the pathogenesis of the DH skin lesions is postulated.

Adult↗

Specific B-cell antigens associated with gluten-sensitive enteropathy and dermatitis herpetiformis.

Gluten-sensitive enteropathy (G.S.E.) and dermatitis herpetiformis (D.H.) are associated with an increased frequency of the histocompatability antigen HLA-B8. These diseases were found to be even more strongly associated with a specific B-lymphocyte surface antigen recognised by maternal antisera. Two antisera (B-1 and W-1) reacted with B lymphocytes form G.S.E. and D.H. patients. Antiserum B-1 reacted with cells from thirteen of sixteen G.S.E. patients and from fifteen of nineteen D.H. patients, while antiserum W-1 reacted with cells from fifteen of sixteen G.S.E. patients and from fifteen of fifteen D.H. patients. None of the sera tested reacted with B lymphocytes from thirty-seven normal individuals, whether or not they were HL8-B8 positive. The identification of this specific antigen provides further insight into the pathogenesis of G.S.E. and D.H. and might form the basic of a diagnostic test for these diseases.

Adolescent↗