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PubMed1984

IgA deposits in the oral mucosa of patients with dermatitis herpetiformis and linear IgA disease.

The oral mucosa of seven patients with dermatitis herpetiformis (DH) and one with linear IgA disease was studied. None of the patients with DH showed any macroscopic oral lesions, but direct immunofluorescence (IFL) examination of the buccal mucosa revealed granular IgA deposits in all patients. IgA deposits were found just below the basement membrane zone or slightly deeper in the connective tissue, i.e. a deposition pattern which is pathognomonic to DH. In three patients C3 deposits occurred in the same area as IgA. The patient with linear IgA disease had small white erythematous patches, nonspecific both clinically and histologically, on the palatal mucosa. However, oral IFL specimens showed heavy linear IgA deposits in the basement membrane zone, indicating that the oral mucosa is also involved in this rare disease. Buccal mucosal biopsy specimens were stained with four FITC-conjugated lectins (Ulex europaeus I, soybean, peanut and lentil). The lectin staining was similar in patients with DH and linear IgA disease and did not markedly differ from normal oral mucosa. Our results show that buccal IFL examination is a useful diagnostic aid in both DH and linear IgA disease.

Adult↗
PubMed2002

Cancer incidence in a population-based cohort of individuals hospitalized with celiac disease or dermatitis herpetiformis.

BACKGROUND & AIMS: Studies of cancer risk in celiac disease (CD) or dermatitis herpetiformis (DH) indicate increased risks for malignant lymphoma and occasionally other neoplasms, but are characterized by small numbers, lack of systematic cancer assessment, and subjects identified from referral institutions. METHODS: By using Swedish population-based inpatient and cancer registry data, we followed-up 12,000 subjects with CD or DH, and evaluated cancer incidence by using standardized incidence ratios (SIR). RESULTS: Adults (but not children and adolescents) with CD had an elevated overall risk for cancer (SIR = 1.3) that declined with time and eventually reached unity. Elevated risks were found for malignant lymphomas, small-intestinal, oropharyngeal, esophageal, large intestinal, hepatobiliary, and pancreatic carcinomas. The excess occurrence of malignant lymphomas was confined to adults, decreased with time of follow-up evaluation, and decreased over successive calendar periods. Decreased risks were found for breast cancer. Subjects with DH had a slightly increased overall cancer risk (SIR = 1.2) owing to excesses of malignant lymphoma and leukemia, but no increases of gastrointestinal carcinomas. CONCLUSIONS: Albeit increased, the relative risks for lymphomas and gastrointestinal cancers in this study are lower (and declining) than in most previous reports. The overall cancer risk is only moderately increased, and nonelevated during childhood and adolescence.

Adolescent↗
PubMed1993

Confocal laser scanning microscopic and immunoelectron microscopic studies of the anatomical distribution of fibrillar IgA deposits in dermatitis herpetiformis.

BACKGROUND AND DESIGN: The fibrillar immunofluorescent pattern of IgA deposition in dermatitis herpetiformis is considered by most authorities to be a variant of the granular IgA pattern. It has been hypothesized that the fibrillar vs the granular pattern is related to longitudinal vs transverse sectioning of affected dermal microfibril bundles. However, direct evidence for this possibility has yet to be presented. Confocal laser scanning microscopy and immunoelectron microscopy were performed to determine the anatomical distribution of fibrillar IgA deposits, using skin specimens from a patient with typical fibrillar IgA deposition. OBSERVATIONS: Confocal laser scanning microscopy showed numerous fibrils stained with anti-IgA extending from the dermoepidermal junction to a depth of 50 to 110 microns in the dermis. They crossed each other at various angles to form a three-dimensional network. Immunoelectron microscopy demonstrated a diffuse dispersion of immune deposits on the surface of microfibrils of dermal microfibril bundles, with sporadic distribution of small aggregates, 0.1 to 0.3 micron in diameter. CONCLUSIONS: To our knowledge, this is the first article to present evidence for the actual distribution of fibrillar IgA. Insofar as the present case is concerned, the distribution of fibrillar IgA is greatly at variance with that indicated in previous reports on granular IgA. However, studies on more cases should be conducted to determine whether this is a distinctive feature of the fibrillar type of IgA deposition.

Dermatitis Herpetiformis↗
PubMed1989

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.

Adolescent↗
PubMed1984

Dermatitis herpetiformis: preparation of papillary dermis and the effect of proteolytic enzymes on the IgA deposits.

A technique has been devised to isolate the thin papillary part of the dermis from punch biopsies. Papillary dermis has been treated with various proteolytic enzymes in order to release or solubilize the granular IgA deposits from the papillary dermis of patients with dermatitis herpetiformis. Incubation of the thin skin preparations with pepsin caused a disappearance of the specific fluorescence with antibodies to human IgA. After peptic digestion small amounts of IgA could be detected in the supernatants. There was some evidence that this amount was larger for preparations from patients with dermatitis herpetiformis than from controls. Corresponding procedures with trypsin, collagenase, or elastase had no detectable effect on the IgA deposits. The experiments with elastase seemed to give support for previous reports on association between the granular IgA deposits and the microfibrils of elastic fibers.

Biopsy, Needle↗
PubMedDate not supplied

Coeliac disease presenting as dermatitis herpetiformis in infancy.

The incidence of reporting and diagnosis of coeliac disease (CD) in children is increasing with the improvement in sensitivity and specificity of screening markers. This in turn has led to an increasing awareness of gluten-sensitive enteropathy and associated disorders. We report the unusual case of an 8-month-old child presenting to his general practitioner with pruritic skin lesions, subsequently proven to be dermatitis herpetiformis (DH) as the first sign of gluten-sensitive disease. This infant is the youngest child presenting with DH who could be identified from published report dating from 1966 onwards. Dermatitis herpetiformis is the commonest associated pathology of CD, although rare in infancy, it should be considered in any child presenting with failure to thrive and atypical, chronic rash not responding to simple measures.

Celiac Disease↗
PubMedDate not supplied

Diagnostic significance of the immunofluorescent pattern in dermatitis herpetiformis.

Despite significant clinical, histologic, immunopathologic and other differences between typical cases of dermatitis herpetiformis (DH) and bullous pemphigoid (BP), the differential diagnosis may be difficult. Our direct immunofluorescent studies in 59 cases of DH and 134 cases of BP indicate the diagnostic value of immunopathologic studies.

Adult↗
PubMed1983

Renal involvement and circulating immune complexes in dermatitis herpetiformis.

A fine-needle kidney biopsy was performed on eleven patients with dermatitis herpetiformis (DH) who had no previous signs or symptoms of renal disease. Of the eight patients whose biopsy specimens were representative, electron microscopic examination showed mesangial deposits in five. A subsequent conventional renal biopsy was obtained from one of these five, and immunofluorescence microscopy revealed IgA and complement deposits in the glomeruli. Renal involvement was not related either to the degree of jejunal villous atrophy or to the deposition of IgA and complement in the skin. Glomerular deposits, however, were associated with a high frequency of circulating IgA and IgG class immune complexes and IgA class antigliadin and antireticulin antibodies. These results suggest that, in DH, immune complexes or antibodies derived from the gut can be deposited in the kidney.

Adult↗
PubMed1982

Dermatitis herpetiformis: IgA deposits in gingiva, buccal mucosa, and skin.

Fourteen patients who had dermatitis herpetiformis of the skin with no gingival lesions were studied. In each patient biopsy specimens of normal gingiva, buccal mucosa, and perilesional skin were examined for IgA and IgG deposits. Depending on the method of handling biopsy specimens for immunofluorescence, IgA deposits were detected in 21 to 25 percent of gingival specimens, 27 to 46 percent of buccal mucosal specimens, and 64 to 76 percent of skin specimens. The occurrence of IgA deposits in the gingival papillae, a site where lesions of DH have not been reported in the past or observed in this study, suggests that these IgA deposits alone may not play a primary role in the pathogenesis of this disease. Similar immunofluorescent findings of IgA deposits were observed in both quick-frozen biopsy specimens and those placed in holding solution, indicating the suitability of the holding solution for transporting suggested DH biopsy material.

Adolescent↗
PubMed1983

Immunoelectron microscopic examination of IgA deposition in dermatitis herpetiformis.

Ultrastructural localization of IgA in the skin of three Japanese patients with dermatitis herpetiformis (DH) was studied with the immunoelectron microscopic technique using periodate-lysine-paraformaldehyde fixation. In direct immunofluorescence studies, two of the three cases showed fine fibrillar deposition of IgA and the other case fine granules in the dermal papillae. In the former, the reaction products of IgA were present in the upper dermis forming various-sized aggregates which were occasionally arranged perpendicularly to the epidermis and appeared to be associated with microfibrillar bundles of the elastic tissue. Reaction products were also deposited to a lesser extent on the microfibrillar component of the elastic fibers at the lower part of the dermal papillae. However, in the latter, the reaction products were found to form smaller aggregates on and around the collagen fibrils rather than on the elastic tissue. Such a localization of IgA reaction products has not yet been reported in DH. The difference of the distribution patterns of IgA and the possible singularity of Japanese DH cases are discussed.

Adult↗
PubMed1990

Gastric histology and function tests in Italian patients with dermatitis herpetiformis.

Gastric mucosal histology and function were evaluated in 57 Italian subjects with dermatitis herpetiformis (DH), by means of multiple endoscopic biopsies, gastrin and pepsinogen I (Pg I) serum levels, and parietal cell antibodies (PCA). One hundred and forty-nine patients with nonulcer dyspepsia served as reference population for the prevalence of atrophic gastritis of the body. Seventeen DH patients (30%) and 23 controls (15.4%) showed atrophic gastritis of the body mucosa (p less than 0.05). Nine of the DH patients with atrophic gastritis of the body also had atrophic changes in the antrum. Six patients, all with severe atrophic gastritis, had high gastrin levels and PCA; five of these six also had low Pg I levels. We found an increased prevalence of abnormal indirect function tests among patients with atrophic gastritis is due to the younger age of the patients in our series. Thus, atrophic gastritis can be detected early on a histologic basis, but functional impairment occurs later, as the mucosal damage increases in severity.

Adolescent↗
PubMed1984

Influence of the amount of dietary gluten on gastrointestinal morphology and function in dermatitis herpetiformis.

The individual daily intake of gluten was calculated in 45 patients with dermatitis herpetiformis (DH) on the basis of a depth interview about food habits. Gastric and small intestinal morphology and function were studied concurrently. Mean daily gluten intake was estimated to be 15 g, a figure which corresponds well to the average gluten intake in Sweden. There was a significant correlation between the degree of morphological mucosal changes of the small intestine and the quantity of gluten ingested. All patients with jejunal villous atrophy consumed more than 10 g gluten daily and all but one patient with normal jejunal villous structure had a gluten intake of less than 10 g/d. The findings suggest a dose-dependent effect of gluten on the intestinal mucosa. Conversely, the daily gluten intake was not correlated to gastric morphology, gastric acid secretion, serum gastrin levels or serum parietal cell antibodies. Patients with reduced ability to secrete gastric acid did not differ from the remaining patients in this respect. Whereas the coeliac-like enteropathy in DH seems to be caused by ingested gluten, the frequently occurring achlorhydric atrophic gastritis must be assumed to be of different immunopathogenesis.

Achlorhydria↗
PubMed1978

IgA and C3 complement in the uninvolved skin in dermatitis herpetiformis after gluten withdrawal.

IgA deposits in the skin in 53 patients with dermatitis herpetiformis (DH) have been studied in relation to treatment. In 19 patients the disorder was controlled by a gluten-freen diet (GFD) alone, in 13 patients by dapsone and GFD and in 18 by dapsone alone. In 3 patients the skin disorder became insignificant and required no treatment. Of the patients taking a GFD alone, six had been clear of skin lesions for 7 years, 5 for 3--5 years, and 8 for periods of 6 months--3 years. IgA deposits were found in all patients in an initial biopsy in a second biopsy after treatment for periods varying from 1 to 7 years. There was no difference in the quantity of IgA, as assessed by the amount of fluorescence, whether patients were controlled with a GFD alone, GFD and dapsone, dapsone alone, or in those in clinical remission. The C3 component of complement was present in the skin in 3 of the 19 patients (16%) controlled by a GFD alone, 6 of the 13 patients (46%) of those controlled by a GFD and dapsone, and in 12 of 18 (66%) of the patients taking dapsone alone, and in one of the patients in clinical remission.

Adult↗
PubMed1975

Immunoglobulins in the skin in dermatitis herpetiformis and their relevance in diagnosis.

Eighty skin biopsies from fifty patients with dermatitis herpetiformis (DH) have been examined for immunoglobulin deposits by direct immunofluorescence. IgA was found in all fifty patients. However, in two patients no IgA was detected in their first biopsy, and it is stressed that if the clinical suspicion of DH is high and no IgA is found in a single biopsy, then the biopsy should be repeated. There are two distinct patterns of immunoglobulin deposition in DH. The most common form of deposition is seen in the dermal papillae, termed the 'papillary' pattern. This pattern was the only one present in sixty-seven of the seventy-eight biopsies. A less common pattern is that of a 'continuous' line along the dermo-epidermal junction. This was the only pattern of immunoglobulin deposition in nine of the seventy-eight biopsies. In two biopsies both the papillary and continuous patterns were present. IgA was found in all seventy-eight of the positive biopsies and was the only immunoglobulin detected in sixty-seven biopsies. In addition to IgA, IgM was present in seven biopsies, and IgG in two biopsies. In one biopsy IgM and IgG were present with the IgA. The detection of IgA in the uninvolved skin in patients with DH is a simple test to perform, and at the present time is the most reliable way of establishing the diagnosis

Adult↗