The incidence of HL-A antigens in dermatitis herpetiformis

In dermatitis herpetiformis (DH) there are small intestinal abnormalities similar to those in adult coeliac disease (ACD) and there is evidence of other similarities between the two conditions, including immunological disturbances. Two reports of patients with ACD have shown a distinctive distribution of HL-A phenotypes, with a high incidence of HL-Ai and 8. A recent paper has described an increased incidence of HL-A8 in DH. We report a similar study of patients with DH. Twenty-one of thirty-five patients had HL-A8, an incidence of 60%, as compared to 33% of 175 controls. This difference is significant. The relationship of those patients with HL-A8 to those with abnormal jejunal biopsies, and also to those with circulating auto-antibodies, is discussed.     

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.     

Neutrophil CD11b,L-selectin and Fc IgA receptors in patients with dermatitis herpetiformis

BACKGROUND: The skin lesions found in patients with dermatitis herpetiformis (DH) are characterized by the presence of neutrophils at the dermal papillary tips in areas where the diagnostic cutaneous IgA deposits are found. Although the presence of the skin lesions of DH is known to be associated with gluten-sensitive enteropathy, the mechanisms that control the development of skin lesions are not known. OBJECTIVES: To determine if circulating neutrophils from patients with DH have evidence of priming as shown by increased expression of CD11b, decreased expression of L-selectin and increased function of neutrophil Fc IgA receptor. METHODS: Neutrophils from 12 normal subjects and 10 DH patients with active, ongoing disease and 14 DH patients with quiescent disease activity were examined by fluorescence-activated cell sorter for expression of cell surface CD11b, L-selectin expression, Fc IgA expression (CD89) and for the function of the Fc IgA receptor by determining the binding capacity of neutrophils for monoclonal human IgA. RESULTS: Neutrophils from patients with active, ongoing DH had increased expression of CD11b when compared with patients with inactive DH or normal subjects [mean net geometric mean channel fluorescence (GMCF): active DH, 403.3; inactive DH, 237.8; normal subjects, 290.5; P < 0.05]. L-selectin expression in both groups of DH patients was significantly lower than that seen in normal subjects (mean net GMCF: active DH, 363.2; inactive DH, 375.2; normal subjects, 432.7; P < 0.05). No difference in CD89 expression was seen in any of the groups; however, the function of Fc IgA receptor was increased in patients with active DH when compared with patients with inactive DH and normal subjects. CONCLUSIONS: Neutrophils from patients with active, ongoing DH show an increased expression of CD11b, decreased expression of L-selectin and increased ability to bind IgA, consistent with a pattern of priming of the neutrophils. This priming may occur in the gut as a result of the ongoing mucosal immune response that is present in patients with DH on a gluten-containing diet and may predispose neutrophils to localize in the skin of patients with DH.     

Two Japanese cases of dermatitis herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom or circulating immunoglobulin A antibodies to any known antigens

Dermatitis herpetiformis (DH) is common in some Caucasian populations but extremely rare in Japanese, probably because of different immunogenetic backgrounds. We report two Japanese DH cases with typical clinical, histological and direct immunofluorescence features. However, no symptom of gluten‐sensitive enteropathy was shown. The diagnosis was confirmed by eliminating other autoimmune blistering diseases by indirect immunofluorescence, enzyme‐linked immunosorbent assays and immunoblotting. However, circulating immunoglobulin (Ig)A anti‐endomysium, reticulin and gliadin antibodies were not detected. IgA antibodies to tissue and epidermal transglutaminases were also negative. One case was associated with lung cancer and the other one with autoimmune pancreatitis. On review of 17 cases of DH reported in Japan over the previous 10 years, including our cases, one case was associated with gluten‐sensitive enteropathy, four with malignant neoplasms, two with autoimmune systemic disorders and one with psoriasis. Although our cases were typical of DH in clinical, histopathological and IgA deposit features, they showed different human leukocyte antigen haplotypes, no gluten‐sensitive enteropathy and no DH‐specific IgA antibodies, including those to epidermal and tissue transglutaminases. These results suggest that studies of unique characteristics in Japanese DH patients should facilitate further understanding of pathogenesis in DH.     

DNA sequence analysis and restriction fragment length polymorphism (RFLP) typing of the HLA-DQw2 alleles associated with dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is a blistering autoimmune skin disease associated with a 95-100% incidence of the HLA class II antigen HLA-DQw2. Although the precise role of this antigen in the pathogenesis of DH is unclear, one theory proposes that patients with DH possess a molecularly unique subtype of the HLA-DQw2 antigen that causes immune abnormalities eventuating in the clinical manifestations of DH. To test this hypothesis, we performed DNA sequence analysis on the highly polymorphic HLA-DQB1 and HLA-DQA1 loci of eight patients with dermatitis herpetiformis. All DQB1 alleles sequenced were identical to the previously described HLA-DQB*0201 allele from HLA-DQw2 normal subjects. In addition, DQA1 alleles sequenced were identical to those alleles previously associated with HLA-DQw2 (DQA*0201, DQA*0501). These data document that although HLA-DQw2 appears to be a necessary element in the pathogenesis of DH, the development of DH is not dependent on the presence of a unique HLA-DQw2 antigen. HLA-DQ allelic typing by restriction fragment length polymorphism analysis of PCR-amplified HLA-DQA1 and HLA-DQB1 fragments was also performed in ten patients with DH to determine the allelic distribution among both HLA-DR3 (eight patients) and non-DR3 (two patients) DH patients. At the HLA-DQ beta chain locus, all patients possessed the DQB1*0201 allele. At the HLA-DQ alpha chain locus, all HLA-DR3 patients and one non-DR3 patient displayed a pattern consistent with the DQA1*0501 allele, whereas one non-DR3 patient displayed a pattern consistent with the DQA1*0201 allele. These data document that patients with DH do not express a unique HLA-DQw2 heterodimer, that the HLA-DQw2 molecules present in patients with DH have no DNA sequence differences from those found in normal HLA-DQw2 subjects and therefore that susceptibility to DH is not due to a unique HLA-DQw2 molecule.     

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.     

Serum IL-8 in patients with dermatitis herpetiformis is produced in response to dietary gluten

Patients with dermatitis herpetiformis (DH) have a gluten-sensitive enteropathy and while on gluten-containing diets have elevated levels of serum IL-8. We hypothesized that the mucosal immune response to gluten is responsible for the elevated serum IL-8. Six DH patients were studied while on a gluten-free diet (GFD), whereas four continued on a normal diet. Patients were followed for a mean 2.2 years and serum IL-8 was analyzed. Small bowel biopsies from five DH patients on normal diets, two DH patients on GFD, and six subjects with no small bowel abnormalities were analyzed for IL-8 mRNA. Serum IL-8 levels normalized in five of six patients on GFD and decreased in one, whereas serum IL-8 levels showed no statistically significant change in DH patients on normal diets. Small bowel biopsies from DH patients on normal diets had increased expression of IL-8 mRNA compared to normal subjects, whereas patients on a GFD showed no significant increase in small bowel mRNA. No significant IL-8 mRNA was detected in normal skin biopsies from patients with DH. These observations suggest that the IL-8 in the serum of patients with DH originates from the small bowel as a mucosal immune response to gluten ingestion.     

TCR Vbeta expression in the small bowel of patients with dermatitis herpetiformis and gluten sensitive enteropathy. Limited expression in dermatitis herpetiformis and treated asymptomatic gluten sensitive enteropathy

Dermatitis herpetiformis (DH) is a blistering skin disease characterized by cutaneous deposits of IgA and an associated, most often asymptomatic, gluten sensitive enteropathy (GSE). Gluten sensitive enteropathy is also seen in patients that do not have skin disease or cutaneous IgA deposits, but do have significant gastrointestinal (GI) complaints. Patients with DH and with GSE without skin disease have similar small bowel morphologic changes and HLA associations and both the skin disease and the GI symptoms can be controlled by a gluten free diet. It is not known what factors allow almost all patients with DH to continue to eat gluten and not develop symptomatic gastrointestinal disease. We have examined the expression of the Vbeta T-cell receptor (TCR) in the small bowel of patients with DH (n=11) and of patients with both symptomatic (n=10) and asymptomatic (n=7) GSE without skin disease to determine if differences in the pattern of TCR Vbeta expression are associated with differences in the clinical manifestations of these diseases. TCR Vbeta expression was analyzed using RT-PCR from small bowel biopsies. Patients with DH and those with GSE without skin disease that were on a gluten free diet and asymptomatic were found to express 6.6 and 5.6 out of 20 Vbeta families respectively, with no single family preference. Examination of peripheral blood lymphocytes from these patients did not reveal any restriction of TCR Vbeta family expression. In contrast, patients with symptomatic GSE expressed 12.6 Vbeta families (P< 0.05), with no consistent preferential expression of any single Vbeta family between patients. Patients with DH, who are continuing to ingest wheat, show a more restricted pattern of TCR Vbeta utilization, similar to that of treated patients with GSE without skin disease, and significantly different from GSE without skin disease patients eating gluten. These findings suggest that the restricted nature of the TCR Vbeta expression may play a role in the different clinical manifestations of dermatitis herpetiformis and isolated gluten sensitive enteropathy.     

Circulating antibodies to gliadin subfractions in dermatitis herpetiformis and linear IgA dermatoses

Dermatitis herpetiformis (DH) and coeliac disease are associated and the rash of DH is gluten-dependent. The gliadin fraction responsible for the rash is unknown. In linear IgA dermatoses the role of gluten in the skin eruption remains controversial.
Anti-gliadin antibodies (AGA) were measured by an enzyme-linked immunosorbent assay in 10 normal controls; 35 patients with dermatitis herpetiformis (DH); 14 adults with linear IgA disease; and 13 patients with chronic bullous dermatosis of childhood. The presence of enteropathy was assessed by jejunal biopsy and intra-epithelial lymphocyte (IEL) counts.
DH with normal IEL counts on normal diet: IgG and IgA-AGA identical to controls. DH with raised IEL counts on gluten-free diet: slightly elevated IgG and IgA-AGA. DH with raised IEL counts on a normal diet: IgG and IgA were higher, with median IgG 1:2048 (control 1:512) median IgA 1:512 (control 1:128). DH patients with high IgG AGA had elevated titres to α, β, γ, and ω subfractions. The highest levels were for α and the lowest for ω.
For linear IgA disease IgG is normal but adults had raised IgA-AGA compared to controls ( P = 0.005).
In dermatitis herpetiformis the presence of anti-gliadin antibody was dependent on the degree of enteropathy, and, if present, was directed against all gliadin subfractions. The significance of the elevated IgA—AGA in the linear IgA disease is unknown.     

Antiendomysial antibody — useful serological indicator of dermatitis herpetiformis

Summary Antiendomysial antibodies (EmA) of the IgA class are directed against reticulin components of the primate smooth muscle and are markers of gluten-sensitive enteropathy. These antibodies occur in essentially all active cases of celiac disease and in about 70% of dermatitis herpetiformis (DH) patients. IgA deposits in the dermal papillae of the skin are the hallmark of DH and are employed routinely in establishing its diagnosis. The incidence of IgA deposits in skin varies depending upon the site and type of biopsy specimen taken.We studied sera and skin biopsy specimens for EmA and for IgA deposits in the skin from 11 DH patients. EmA were detected in the sera of 10 of the 11 cases. Of these 11 patients, 9 were positive for IgA deposits in their skin, as revealed by direct immunofluorescence (IF). The immune deposits were detected in the normal, and not in the lesional skin. DH cases that were initially negative on biopsy and serum positive for EmA were found to be positive when a repeat biopsy of the normal skin was performed. Thus, serological studies in conjunction with direct IF studies of the normal skin are useful in making a diagnosis of DH.Presented at the Society for Investigative Dermatology Meeting, Washington, DC, May 2, 1986     

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.     

Linear IgA disease in adults

A multi-centre study is described in which thirty-five adult patients with papillary IgA dermatitis herpetiformis (DH) were compared with forty-two patients with linear IgA deposits, of whom thirty-four had homogeneous-linear (HL) and eight had granular-linear (GL) IgA deposits. The three groups were similar with regard to age of onset, presence of circulating immune complexes and auto-antibodies, incidence of spontaneous remission, histology of lesional skin and response to dapsone. There was a female predominance in the HL group in contrast to the male predominance in the other two. It was not possible to diagnose the HL group clinically. Some patients had a rash typical of DH whilst others resembled pemphigoid. In the majority, however, no specific diagnosis could be made with confidence. The GL group clinically resembled the DH group. The incidence of positive potassium iodide patch tests was greater in the DH group than in the other two. An associated enteropathy was found in 24% of patients in the HL group, 30% of patients in the GL group and 85 % of patients in the DH group. Fifty-six percent of HL patients had HLA-B8 compared with 50% in the GL group and 88% in the DH group.     

Dermatitis herpetiformis

Dermatitis herpetiformis (DH) is a chronic, polymorphic, pruritic skin disease that develops mostly in patients with latent gluten-sensitive enteropathy. DH patients usually present with skin manifestations only and are not aware of the underlying small-bowel problems. Owing to the granular immunoglobulin (Ig) A deposition at the tips of the papillary dermis and to the subepidermal blister formation associated with neutrophilic accumulations underlying the basement membrane, DH is considered to be an autoimmune blistering disease. Contrary to the other bullous disorders, DH patients have no circulating autoantibodies binding to the cutaneous basement membrane components or to other adherent structures of the skin, but they have gluten-induced IgA autoantibodies against transglutaminase (TG) 2 and TG3. The serum IgA against tissue TG2 is a most specific and sensitive serologic marker of gluten-sensitive enteropathy and is equivalent to the perviously described IgA endomysium antibodies. DH could be a cutaneous IgA-epidermal TG3 immunocomplex disease, developing only in a few patients with gluten-sensitive enteropathy as a second gluten-dependent disease. The main treatment of DH today is a strict, life-long gluten-free diet. Untreated DH patients should be regularly monitored for malabsorption and lymphomas. Associated autoimmune diseases are more common among DH patients. Family screening for gluten sensitivity is also strongly suggested.     

Clinical, pathologic, and immunopathologic features of dermatitis herpetiformis: review of the Mayo Clinic experience

BACKGROUND: Dermatitis herpetiformis (DH) is a cutaneous manifestation of gluten sensitivity, occasionally associated with other autoimmune disorders, and reportedly associated with an increased risk of lymphoproliferative disorders. We describe a series of patients with DH, focusing on associated disorders (particularly celiac disease), incidence of lymphoma, histopathology, and sensitivity of direct immunofluorescence (DIF) testing and serologic testing with antiendomysium antibodies for the diagnosis of DH. METHODS: The medical records of 264 patients with DH diagnosed between 1970 and 1996 were reviewed retrospectively. In addition, the records of six patients evaluated before the advent of DIF testing between 1932 and 1969 were reviewed. RESULTS: Established celiac disease was present in 12.6% of patients with DH, autoimmune systemic disorders in 22.2%, malignant neoplasms in 10.4%, sarcoidosis in four patients, and ulcerative colitis in six patients. Lymphoproliferative disorders were found in seven patients. The histopathologic examinations showed a marked predominance of neutrophils in the inflammatory infiltrate. DIF testing was positive in 92.4% of the patients tested. Indirect immunofluorescence assay indicated circulating antiendomysial antibodies in the sera of 40 of the 63 patients tested (63.5%). CONCLUSIONS: In this large series of patients with DH from a single institution, patients had a low incidence of symptomatic gluten-sensitive enteropathy, low risk of lymphoproliferative disorders, and associations with other systemic autoimmune disorders. The value of DIF testing in the diagnosis of DH was confirmed. The detection of antiendomysial antibodies by indirect immunofluorescence was less sensitive than indicated by other reports.     

An HLA class II region restriction fragment length polymorphism (RFLP) in patients with dermatitis herpetiformis: association with HLA-DP phenotype

Dermatitis herpetiformis (DH) is characterized in part by an associated gluten-sensitive enteropathy (GSE), and a strong association with the HLA antigens HLA-A1, -B8, -DR3, and -DQw2, essentially identical to that seen in patients with isolated GSE (celiac disease). A 4.0-kb RsaI RFLP has been identified using a DQ beta-chain cDNA and localized to the HLA-DP beta-chain region. This RFLP has been found more frequently in patients with isolated GSE than in normal HLA matched controls. We have analyzed genomic DNA from 24 patients with DH and 15 HLA-matched controls to determine if this 4.0-kb RsaI RFLP was present in patients with DH. Twenty-one of 24 (87%) of patients with DH were found to have this RFLP as compared to 7 of 10 (70%) HLA-DR3, -DQw2 matched control subjects (p = 0.23). Thus, the 4.0-kb RsaI RFLP detected in patients with isolated GSE is also present in patients with DH; however, its frequency in DH patients does not differ significantly from that of HLA matched controls. Family studies of patients with DH revealed that although the 4.0-kb RsaI RFLP segregated with the HLA-A1, -B8, -DR3, -DQw2 haplotype in one family, it did not segregate with this disease-associated haplotype in two other families. In both patient and control populations, this RFLP was associated with HLA-DPw1 or -DPw3 phenotypes; 25 of 26 (96%) HLA-DPw1 or -DPw3 subjects were found to have this RFLP compared to only 1 of 6 (17%) who did not express HLA-DPw1 or -DPw3 (pc = 0.0009). These population and family data suggest that this 4.0-kb RsaI RFLP is primarily associated with the HLA-DPw1, -DPw3 phenotype, rather than the clinical manifestations of DH. These data further document that the strongest association of DH with HLA antigens remains with HLA-DQw2 and HLA-DR3 antigens.     

Dermatitis herpetiformis: an evaluation of diagnostic criteria

Forty-two patients in whom a clinical diagnosis of dermatitis herpetiformis (DH) had been, made, were studied. All patients had a small intestinal biopsy, a biopsy of uninvolved skin for detection of the presence of IgA deposits by immunofluorescence, serum and red cell folate estimations and examination of the serum for anti-reticulin antibody. The response of the skin eruption to dapsone was noted. Thirty patients had biopsies of skin lesions for routine histological examination. IgA deposits were found in the uninvolved skin of thirty-five of the forty-two patients. Evidence of an enteropathy was found in thirty-four of those thirty-five patients. Of the seven patients who did not have IgA in the uninvolved skin, only one showed evidence of enteropathy, which was slight, and this patient was shown subsequently to have pemphigus and not DH. Of the thirty biopsies of skin lesions, only five showed all the features usually considered to be characteristic of DH. And-reticulin antibody was found in eight patients, and in all of these IgA was present in the uninvolved skin. Low red cell folate levels were found in eleven patients (all of whom had an enteropathy and IgA in the uninvolved skin). Low serum folate levels were found in thirty-four patients, thirty-one of whom had IgA deposits in the uninvolved skin and an enteropathy; in the other three patients who did not have IgA deposits or an enteropathy, all were on dapsone and this may have accounted for the abnormal result. In forty-one of the forty-two patients the rash was dapsone responsive. The patient who showed no response to dapsone had no IgA in the uninvolved skin and no evidence of enteropathy. Follow-up showed that of the seven patients with no IgA in the skin, one had pemphigus, and in three the rash eventually cleared spontaneously and the patients no longer required treatment. There was no evidence of spontaneous remissions in the patients with IgA in the uninvolvcd skin. It would appear that the presence of IgA deposits in the uninvolved skin is part of the syndrome of DH and that the diagnosis should not be made unless these deposits are found.     

IgA class antibodies in dermatitis herpetiformis: reaction with tissue antigens

The mechanism for deposition of IgA in dermatitis herpetiformis (DH) remains unclear. To test the hypothesis that a circulating IgA class antibody in DH patients binds to constituents of normal human skin, we employed the highly sensitive methods of immunoblotting and indirect immunofluorescence. Sera from 64 DH patients, 67 randomly selected normal control subjects, 29 histocompatibility locus antigen (HLA) B8/DR3/DQw2 controls, and 12 psoriatic patients were tested for IgA binding to various substrates, including dermal and epidermal extracts, fibroblast and keratinocyte supernatants, monkey esophagus sections, and whole and saline-split normal human skin sections. Significant differences observed among the groups in the frequency of detectable IgA antibodies reacting with various substrates were as follows: 1) IgA antibodies in 30% of both DH and HLA B8/DR3/DQw2 sera bound to a 60-Kd protein in dermal extracts (p less than 0.25 versus non-HLA matched controls); 2) IgA antiendomysial antibodies were present in 38% of DH patients (predominantly those not on gluten-free diets), whereas both normal control groups had frequencies of 5-10% (p less than 0.025); 3) there was more nonspecific IgA antibody-binding to dermal, epidermal, and bovine proteins in DH and HLA control sera than in normal sera; and 4) IgA antibodies directed against the basement membrane were present with an increased frequency of 25% in both DH and HLA B8/DR3/DQw2 sera (p less than 0.1 versus non-HLA matched controls). Therefore, these results do not support the hypothesis that there is an unique antigen within normal human skin to which IgA antibodies from DH sera bind.     

Histocompatibility (HL-A) antigens in psoriasis.

In 101 white psoriatic patients, two histocompatibility (HL-A) specificities were significantly altered from expected values. The levels of W16 and W17 were found to be substantially increased, suggesting that persons with these antigens are at increased risk of having psoriasis. Clinically distinct patient groups were also observed. Antigens W16 or W17 or both were more prevalent in psoriatic patients who had extensive disease involvement, and patients with W17 antigen had an earlier age of onset as compared to patients with W16 antigen. In one family in this study, a linkage between psoriasis and a specific HL-A haplotype was also observed, further supporting the concept that the HL-A system may serve as a marker for genes affecting specific disease susceptibility.     

Dermatitis herpetiformis (author's transl)]

Detailed investigations of 9 patients with dermatitis herpetiformis are presented. In all cases cutaneous lesions were controlled by dapsone alone or by dapsone and gluten free diet. Granular IgA deposits were found in 7 patients, linear IgA deposits in one, and C3 component of complement in one. 3 patients out of 8 tested, carried the specific HLA-B8 antigen. Despite an extensive investigation, no malabsorption was detected. Jejunal biopsies were performed in 8 cases. Jejunal villous flattening was observed in one patient. It improved after a 2 months gluten free diet on subsequent jejunal biopsies. D. H. seems peculiar in France as compared with case reports from other countries: low prevalence of gluten sensitive enteropathy; rare occurrence of the specific HLA-B8 antigen; incidence of D. H. seems to be low in France. It is noticeable that french incidence of coeliac disease is low as well. This suggests a genetic difference in the investigated population (low prevalence of HLA-B8 antigen) and/or different alimentary habits, particularly a low dietary gluten amount.     

Incidence of familial dermatitis herpetiformis

Dermatitis herpetiformis (DH) and coeliac disease (CD) are gluten-sensitive diseases which have a common immunogenetic background, with the histocompatibility locus antigen (HLA) alleles DQ Al*0501 and Bl*0201 in the short arm of chromosome 6. CD is well known to cluster in families whereas DH has not been generally regarded as a familial disease. To study the familial incidence of DH, a prospective study was started in 1969 at the Department of Dermatology of Helsinki University Hospital and in 1976 at the Department of Dermatology of Tampere University Hospital. A total of 1018 patients with DH were diagnosed and questioned for positive family histories. Of the 999 unrelated DH patients. 105 (10·5%) had one or several affected first-degree relatives. The disease in the relatives was either DH (4–4%) or CD (6·1%), Analysis of the 105 families showed that 13·6% of parents, 18·7% of siblings and 14·0% of children were affected, a segregation pattern which fits well to a dominant mode of Mendelian inheritance. Gender may also be important because the first-degree relatives affected with DH were more often females and those affected with CD twice as often females as males. In contrast, there were more males among the 105 propositi with DH and also among the 894 DH patients with no affected relatives The present study clearly shows that DH is a familial disease in which the first-degree relatives can be affected both with DH and CD, presumably because of a common genetic background. The environmental factors which could cause the rather high penetrance of DH and CD in the first-degree relatives of DH patients remain unknown.