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[Dermatitis herpetiformis and latent celiac disease in two siblings].

The association between coeliac disease (CD) and dermatitis herpetiformis (DH) is well known. Moreover, this cutaneous disease may be the only sign of an otherwise asymptomatic CD. Subjects presenting with both CD and DH generally show an HLA pattern in which A1, B8, DR2, DR7, DQw2 are the most frequent antigens one can find. We report about 2 brothers presenting with DH, clinically asymptomatic, without antigliadin serum antibodies (AGA), but positive to the research of antiendomysial (EMA) ones. The biopsy performed by digestive endoscopy showed a complete atrophy of duodenal villi and the diagnosis of CD was confirmed according to the European Society for Pediatric Gastroenterology and Nutrition (ESPGAN) criteria. The diet without gluten caused the DH to recovery and the duodenal villi microscopic aspect to normalize as well. Both the brothers had the same HLA pattern: A1, B8, DR3-DR2, DQw2. Our clinical study suggests that it is very important, especially for the general practitioner, to recognize a DH and in every child presenting with a dermatitis like that it will be mandatory to perform a laboratory research of both AGA and EMA.

Adolescent↗
PubMed1987

Relationship of dietary gluten intake to dapsone dose in dermatitis herpetiformis.

The gluten intake was quantitated utilizing a dietary history method in 43 patients with dermatitis herpetiformis on non-restricted diet. The mean daily gluten intake was 15 g. The individual intake of gluten was related to the maintenance dose of dapsone. It was significantly higher in patients on 100-150 mg dapsone daily than in those taking 0-25 mg daily. There was a significant correlation between amount of gluten in the diet and the dapsone dose (p less than 0.01, rs = 0.43). Villous atrophy was not related to the dapsone dose. It is suggested that the gluten-sensitive enteropathy changes the intestinal permeability and thus contributes to the development of blisters.

Adolescent↗
PubMed1969

Results of treatment of dermatitis herpetiformis with a gluten-free diet after one year.

Twenty-one patients with dermatitis herpetiformis initially controlled by dapsone or sulphonamides have been treated with a gluten-free diet and reassessed at intervals for up to 15 months (mean 11.9 months). According to routine histological and dissecting microscope criteria the small-bowel lesion improved in 10, but when mean epithelial cell height was used as a measure 15 patients improved. Five of the patients with diarrhoea improved after withdrawing gluten from the diet but none reverted to completely normal bowel habit. The tests for malabsorption showed little improvement in the treatment period. Twelve patients needed less dapsone to control their skin complaint, the mean dose falling from 144 mg. to a mean of 70 mg. per day; of these three stopped using this drug altogether.

Adolescent↗
PubMed1976

Histocompatibility antigens and dermatitis herpetiformis with special reference to jejunal abnormalities and acetylator phenotype.

Sixty-one patients with dermatitis herpetiformis (DH) were studied. Of these fifty-three (87%) had the histocompatibility (HL-A) antigen HL-A8 as compared with 17% of a control population; the difference is significant. This incidence of HL-A8 among patients with DH is higher than that reported earlier for such patients and is similar to that reported for patients with adult coeliac disease. The incidence of HL-A1 was also significantly greater in the patient group, and was attributed to the increased frequency of haplotype HL-A1, 8. The frequency of HL-A8 was about equal in patients in whom DH was associated with jejunal abnormalities and in those in whom it was not. When correlated with rate of acetylation, there was no significant difference in the occurrence of various HL-A antigens.

Acetylation↗
PubMed1986

Serum antibodies to wheat germ agglutinin and gluten in patients with dermatitis herpetiformis.

It has been speculated that gluten may play a role in the pathogenesis of dermatitis herpetiformis (DH) because it can act as a lectin. The lectin activity of gluten preparations was recently identified as wheat germ agglutinin (WGA). IgG and IgA serum antibodies to WGA and gluten were therefore measured in patients with DH and coeliac disease (CD) by an enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, both patients categories had increased IgG and IgA activities to WGA and gluten, the CD group showing the highest antibody levels. DH patients with subtotal villous atrophy tended to have higher activities than those with no villous changes or only minor changes. No significant difference in the gluten-to-WGA ratio of IgA or IgG antibodies was found when DH patients were compared with CD patients. If WGA plays a pathogenetic role in DH, then DH patients must have dermal characteristics, as yet undefined, that explain the initiation of their skin disease.

Adult↗
PubMed1979

Dermatitis herpetiformis: lymphocytes, immunoglobulins and complement factors in peripheral blood.

Peripheral blood lymphocytes from patients with dermatitis herpetiformis and healthy controls were investigated in order to determine the percentages of B-lymphocytes, T-lymphocytes and cells with receptors for the Fc part of human IgG (EA-RFC). Furthermore, the serum concentrations of IgG, IgA, IgM, IgD and IgE and the complement factors C3 and C4 were also measured. An increase in the mean percentages of lymphocytes with membrane-bound IgA and IgD, as well as an increase in the mean percentage of cells with receptors for the Fc part of human IgG (EA-RFC) were found in the patient group as compared with the control group. No differences between patient group and control group were found concerning the mean percentage of B-lymphocytes or T-lymphocytes. The mean serum concentrations of the various immunoglobulins and the complement factors investigated did not differ significantly between the two groups.

Adolescent↗
PubMed1992

Correlation between IgA antiendomysial antibodies and subtotal villous atrophy in dermatitis herpetiformis.

Serum IgA antiendomysial antibodies (EmA) were present in 20 (64.5%) of 31 patients with dermatitis herpetiformis (DH) on a normal diet. A significant correlation was found between these antibodies and the severity of gluten-induced jejunum damage. IgA EmA were positive in 19 (86%) of the 22 DH patients with subtotal villous atrophy, in comparison with the positivity of only one (11%) of the nine DH patients with less severe intestinal involvement (partial villous atrophy or mild abnormalities). The specificity of this test for gluten-sensitive enteropathy was 100%, these antibodies being consistently negative in biopsied disease controls showing a normal jejunal mucosa. Moreover, IgA EmA proved to be useful in monitoring the response to gluten withdrawal in DH patients, as these antibodies always disappeared in all the DH cases studied after 1 year of gluten-free diet together with the regrowth of jejunal villi. The strict relationship between IgA EmA and subtotal villous atrophy is more helpful still since the enteropathy present in DH is usually symptomless and therefore difficult to suspect.

Adult↗
PubMed2006

Dermatitis herpetiformis and partial IgA deficiency.

Although the specific IgA autoantibody responsible for the pathogenesis of dermatitis herpetiformis (DH) is unknown, the presence of IgA is considered essential in the pathogenesis of DH. To date, no cases of IgA deficiency have been reported in DH. In contrast, IgA deficiency is found in 2% to 3% of patients with celiac disease, a rate 10 to 15 times higher than the normal population. We report 2 patients with DH who also have partial IgA deficiency. We evaluated the sera of these patients for the presence of IgA autoantibodies to endomysium, tissue transglutaminase, epidermal transglutaminase, and gliadin. Both patients were found to have IgA endomysial and tissue transglutaminase antibodies, and serologic markers for DH. Corresponding IgG autoantibodies were not useful serologic markers of DH in the setting of IgA deficiency, as they often are in celiac disease. We then screened 98 DH sera for total IgA levels and identified 1 additional case with IgA deficiency. In conclusion, DH may develop in patients with partial IgA deficiency, indicating that pathogenically directed IgA antibodies are likely sufficient for cutaneous IgA deposition in this disease.

Adult↗
PubMed1981

Inflammatory cells, IgA, C3, fibrin and fibronectin in skin lesions in dermatitis herpetiformis.

Skin lesions were produced by application of 50% potassium iodide to twelve patients with dermatitis herpetiformis (DH). Perivascular cellular infiltrates were found to be characteristic of developing lesions. The cells were mainly round cells; alpha-naphthyl acetate esterase staining revealed that in 24-h lesions the mean percentage of T-lymphocytes was 43%, that of mononuclear phagocytes 6% and that of non-T/non-M cells (mainly B-lymphocytes) 44%. The percentage of the latter was highest (mean 81%) in 6-h specimens, suggesting that these cells are participating in the early stages of lesion formation. The infiltrating cells in dermal papillae and within subepidermal vesicles were predominantly polymorphonuclear leukocytes (mean 86%) with some mononuclear phagocytes and non-T/non-M cells. Immunofluorescence examination confirmed that fibrin deposition is characteristic of the initial lesions of DH and showed that the same is true of fibronectin. Seven out of eight patients had fibronectin deposits in dermal papillae. IgA was found in all and C3 in most of the specimens and, with the exception of papillary vesicles and blister cavities, the intensity of IgA and C3 fluorescence showed no marked alterations during the development of lesions.

Complement C3↗
PubMed1977

Gluten-free diet in dermatitis herpetiformis. I. Clinical response of skin lesions in 81 patients.

Eighty-one patients with dermatitis herpetiformis were treated with a gluten-free diet (GFD) for periods varying from 6 to 36 months. At the end of the treatment the daily requirement of dapsone was significantly lower in patients treated with a GFD than in 49 patients on a normal diet. 93% of the patients on a GFD were able to reduce the dose of dapsone whereas only 16% of the patients on a normal diet were able to do this. Complete remissions occurred only in patients on a GFD. 28% of the patients on a GFD were able to stop dapsone completely and were continuously asymptomatic when they observed a strict diet. A response to a GFD was noted on the mean daily requirement of dapsone as soon as the treatment was initiated although the length of time for an individual response varied. After one year on a GFD the patients needed on average about 40% and after 3 years about 20% of the dose required to control skin symptoms at the beginning of the diet. The patients responded to a GFD irrespective of changes found in the jejunal mucosa and irrespective of the presence of absence of HLA-B8.

Adolescent↗
PubMed1980

Small intestinal biopsies and HLA types in dermatitis herpetiformis patients with granular and linear IgA skin deposits.

In this study we determined whether dermatitis herpetiformis patients whose skin contained linear IgA deposits differ from those whose skin contained granular IgA deposits with regard to the presence of gluten-sensitive enteropathy and with regard to the prevalence of certain histocompatibility antigens. We performed multiple Rubin tube intestinal biopsies on 11 patients, 6 with linear and 5 with granular IgA deposits. The gut biopsies were evaluated histopathologically in a blinded fashion. We found that none of the patients with linear deposits (5 with lamina lucida and 1 with sub-basal lamina deposits) h-d detectable jejunal abnormalities whereas all of those with granular deposits had jejunal abnormalitites (villous atrophy and increased numbers of intraepithelial lymphocytes). In parallel studies HLA typing was performed in 10 patients with linear IgA deposits and in 49 patients with granular deposits. Only 30% of those with linear deposits had HLA-B8, a prevalence not significantly different from that of the normal population (24%); in contrast, 88% of those with granular deposits had HLA-B8, a prevalence significantly greater than in the normal population ( less than 0.001). We therefore conclude that patients with linear IgA deposits have a disease which is pathophysiologically different from those with granular IgA deposits.

Adolescent↗
PubMed1993

Dermatitis herpetiformis--an autoimmune disease due to cross-reaction between dietary glutenin and dermal elastin?

Dermatitis herpetiformis (DH), is associated with skin eruptions and granular depositions of IgA in the papillary dermis, but this is not a feature of coeliac disease (CD). The specificity of the IgA in the skin is unknown. High molecular weight glutenin (HMW-g), a component of gluten, has been shown to have structural similarities to human elastin. This paper reports immunoadsorption studies which suggest that human serum may contain antibodies which cross-react with HMW-g and elastin. DH patients had significantly lower levels of IgA antibodies to HMW-g and to elastin than both CD patients and healthy controls. Furthermore, introduction of a gluten-free diet (GFD) was associated with a further reduction in the amount of IgA antibodies to elastin in the DH patients. This diet-associated decrease of elastin antibodies was restricted to the IgA isotype. A significant correlation was observed between IgA antibodies to HMW-g and elastin in healthy controls and CD patients, while no such correlation was found in patients with DH. These findings could indicate that HMW-g induces production of antibodies to elastin, which are deposited in the skin, and that when the antigenic stimulus is removed, these antibodies are further reduced due to continuous dermal deposition. It is postulated that DH may be an autoimmune disease due to cross-reactivity between dietary glutenin and dermal elastin.

Adult↗
PubMed2005

Immunoglobulin, complement and epidermal transglutaminase deposition in the cutaneous vessels in dermatitis herpetiformis.

BACKGROUND: Recently, epidermal transglutaminase (TG) has been identified within the papillary IgA granules in dermatitis herpetiformis (DH). Although IgA type autoantibodies to tissue and epidermal TGs are characteristic serological markers for DH, these antibodies do not bind to normal papillary skin structures. AIMS: To test the possibility of IgA immune complex precipitation within the vessel walls as a first step in the pathogenesis of skin symptoms, we analysed immunoglobulin, complement, and epidermal TG deposition along the vascular system of DH skin. METHODS: Punch biopsy specimen were taken from 116 DH patients' skin, and evaluated for the presence of vascular immune precipitates by direct immunofluorescence. Skin samples from 16 DH patients were also studied for tissue and epidermal TGs. RESULTS: In 74 (64%) of the 116 DH skin studied, significant vascular staining accompanied the DH-specific granular IgA fluorescence (IgA and C3 in 39 patients; IgA alone in 18; IgA, C3 and IgM together in five; IgM alone in 12). In most cases (92%), the precipitates were detected in the small vessels of the papillary dermis; however, a subpapillary vascular fluorescence was also observed in a few patients (8%). Skin IgA colocalized with epidermal TG in the vessel walls and within the scattered papillary peri- and intervascular DH bodies. Tissue TG did not colocalize either with the immunoglobulins or with the complement precipitates of the dermis. Furthermore, we could not detect keratinocyte TG in the DH bodies nor in the vessel walls. CONCLUSIONS: These findings support possible immune complex precipitation in the vessel walls of DH skin and further confirm the significance of epidermal but not tissue TG in the pathomechanism of skin symptoms.

Adolescent↗
PubMed2000

Dermatitis herpetiformis is associated with atrophic but not with goitrous variant of Hashimoto's thyroiditis.

BACKGROUND: Dermatitis herpetiformis (DH) is a gluten-sensitive skin disease that is associated with a variety of autoimmune disorders. Several investigations demonstrated an association between DH and autoimmune thyroid disease. However, it has not been shown if DH is associated with atrophic or goitrous variant of Hashimoto's thyroiditis. MATERIALS AND METHODS: We investigated a cohort of 41 DH patients (18 male, 23 female) and a control group (11 male, 19 female; sex and age matched healthy volunteers) to find out which variant of Hashimoto's thyroiditis is associated with DH. All patients had thyroid hormones and antibodies measured. In addition to that, thyroid sonography as well as detailed history-taking of previous thyroid disease were performed. RESULTS: In the control group no individual with elevated levels of thyroid antibodies nor abnormal thyroid hormones nor thyroid atrophy was found. Median thyroid volume in the control group was 11 mL (range 4.8-24.7 mL). However, in nine DH patients (22%) elevated levels of antithyroid microsomal (TM) antibodies were seen (P < 0.01). Three of them had abnormal thyroid hormones (7%). In the group of DH patients a significantly smaller thyroid volume was found (median 8 mL, range 1. 6-25.2 mL; P < 0001). Thyroid atrophy (volume < 4.4 mL) was found in 10 DH patients (24%) of whom 9 were females. All patients with elevated levels of TM antibodies or abnormal thyroid hormones and all patients with a history of previous hypothyroidism had a thyroid volume < 7 mL. Goitrous variant of Hashimoto's thyroiditis was not seen in any of the DH patients. CONCLUSIONS: Our findings demonstrate that DH is associated with atrophic but not with goitrous variant of Hashimoto's thyroiditis.

Adult↗
PubMed1983

IgA nephropathy associated with celiac disease and dermatitis herpetiformis.

IgA nephropathy was found in three patients with celiac disease; two of them also had dermatitis herpetiformis. These observed associations widen the spectrum of the diseases that have been reported to coexist with IgA nephropathy. This study focused on the possible intestinal origin of the glomerulonephritis.

Adult↗
PubMed1980

Treatment of dermatitis herpetiformis with colchicine.

Oral colchicine therapy was used successfully in the treatment of three patients with dermatitis herpetiformis, although the degree of disease control varied. The condition of a fourth patient did not improve. A trial of colchicine is suggested when conventional therapy with dapsone or sulfapyridine is contraindicated or when a gluten-free diet cannot be employed.

Administration, Oral↗
PubMed1976

Dermatitis herpetiformis and leiomyomas with HLA-B8, a marker of immune diseases.

Multiple cutaneous leiomyomas and dermatitis herpetiformis (DH) were found in the same patient. This association has not been previously described, although the association of malignant tumours and DH is well known. HLA-B8 was found in this patient as well as in an older brother with polymyositis; this antigen is known to be associated with other immune diseases.

Dermatitis Herpetiformis↗