Immunoglobulin A deposition in jejunal mucosa of children with dermatitis herpetiformis.

Previously we have shown by indirect immunofluorescence (IF) technique that a special IgA antibody in the sera of patients with dermatitis herpetiformis (DH) binds to the structures of the normal jejunum. Now we show by direct IF that specific IgA deposits are present in the proximal jejunum of 11/12 DH and 2/2 celiac patients before a gluten-free diet (GFD). The IgA deposition was in a tubular pattern underlying the villous and crypt epithelial basement membranes and in the lamina propria. This IgA deposition diminished or was not detectable in DH patients under a GFD for a year, and became detectable under gluten challenge in three DH patients. One patient with celiac disease and IgA deficiency, four with other intestinal diseases, and four without jejunal damage had neither jejunal IgA deposition nor circulating IgA anti-jejunal antibody. The deposition of IgA in the jejunum seemed to be correlated with the presence of IgA anti-jejunal antibody in the serum and with the presence of jejunal damage, but the degree of jejunal atrophy, the titer of the anti-jejunal antibody, and the intensity of jejunal IgA deposition in DH patient were not clearly related. Deposition of IgA in the jejunum in DH did not clearly correlate with the activity of the skin symptoms and thus may not be directly related to the pathogenesis of the skin disease of DH.

IgA class antibody against human jejunum in sera of children with dermatitis herpetiformis.

Sera of 44 children with dermatitis herpetiformis with granular IgA deposits in the papillary dermis were investigated on cryostat sections of normal jejunum of three children aged 2 months, 1 year, and 10 years by indirect immunofluorescence. Eighteen of 25 patients on a normal diet had an IgA class antibody showing the following staining patterns on substrate jejunums: tubular positivity in the lamina propria--around the crypts, beneath the villous epithelial basement membrane, and in some instances in the middle of the villous also, following the capillary system of villi; coalescence of tubular positivity at the muscularis mucosae; and positive blood vessels and smooth muscle endomysium. Eleven of 18 children with positive sera were put on a gluten-free diet (GFD) and their sera became negative. One of these 11 patients was challenged with gluten and the antibody reappeared. Nineteen patients examined only on a GFD and 30 healthy blood donors did not have this antibody. There was no strict correlation between the titer of antibody and the severity of jejunal mucosal damage.

Gluten challenge in children with dermatitis herpetiformis: a clinical, morphological and immunohistological study.

Twenty one children with dermatitis herpetiformis were studied in an attempt to evaluate the response in the skin, in jejunal morphology, and in jejunal immunoglobulin containing cell counts to gluten elimination and subsequent gluten challenge. In all of the 15 patients whose jejunal biopsy was studied after the eventual gluten challenge the jejunal lesion had returned in 2.4 to 28 months. The numbers of IgA- and IgM-containing cells were similarly raised in primary and postchallenge biopsies. In the 13 patients whose skin improved during a gluten free diet and who were challenged with gluten the rash worsened and the dapsone/sulphapyridine requirement increased. The jejunal deterioration was equally marked in the six patients whose gluten challenge was stopped because of an intractable rash as it was in those who completed the preplanned challenge. The specimens of the former, however, had significantly more IgA-containing cells than specimens of the latter. The number of intraepithelial lymphocytes clearly reflected the degree of intestinal damage. IgA-containing cells proved to be the most sensitive indicator of an immune reaction taking place in the gut of these patients. Even in the two children with initially normal or nearly normal jejunal mucosa, the IgA cell counts in the jejunal lamina propria were markedly raised.

Antigliadin and antireticulin antibodies in children with dermatitis herpetiformis.

The serum samples of 27 children with dermatitis herpetiformis (DH) were examined for the presence of antigliadin (AGA) and antireticulin (ARA) antibodies. AGA were determined with an enzyme-linked immunosorbent assay (ELISA) and ARA with an immunofluorescence method. Increased IgA or IgG class AGA levels were found in four of ten children on a normal diet, in two of 25 on a gluten-free diet (GFD), and in two of four children on gluten challenge. The corresponding figures for ARA were nine of ten, two of 25, and four of four, respectively. All nine patients with ARA on a normal diet had either subtotal or partial villous atrophy, whereas the patient negative for ARA had a normal jejunal mucosa. ARA were mostly of IgA class, and after gluten withdrawal, increased levels fell to normal range. Four children were challenged with gluten, and they all developed subtotal villous atrophy and demonstrated IgA class ARA. These results suggest that in childhood DH, ARA is a more sensitive indicator of gluten-sensitive enteropathy than AGA, but both antibody determinations can be used in monitoring adherence to GFD treatment.

Discrete palmar and plantar symptoms in children with dermatitis herpetiformis Duhring.

Unusual, discrete palmar and plantar symptoms observed in thirty of forty-seven children with dermatitis herpetiformis are described. The diagnosis was verified in every case by the demonstration of granular IgA deposits in the skin. Forty-five of the children showed villous atrophy in jejunal biopsy specimens. In four cases extensive, exudative, bullous palmar symptoms, similar mild plantar changes, and healing with desquamation were observed. At least once during treatment we found very discrete, reddish-brown spots or small blisters on the flexor surface of the fingers and on the palms in thirty patients. Similar lesions occurred on the soles and plantar surface of the toes in only three patients. In asymptomatic patients and those treated with either a gluten-free diet or sulfone/sulfapyridine, the phenomenon was not manifest.

HLA antigens, jejunal morphology and associated diseases in children with dermatitis herpetiformis.

Forty-five Hungarian and Finnish children from 1.5 to 15 years with dermatitis herpetiformis were studied for HLA antigens, jejunal morphology on gluten-containing diet and associated diseases in the patients and their relatives. A strong association with HLA-B8 was found in patients of both nationalities, the relative risks were 12.8 and 9.6, respectively. The Hungarian patients were also typed for HLA-DR locus, and an association with DR3 but not with DR7 was observed. Patients with subtotal villous atrophy had slightly more often HLA-B8 and DR3 than those with milder intestinal lesions. Atopic eczema occurred in 20% of the patients and family history of atopy seemed to have an inverse correlation with HLA-B8 and DR3.

Dermatitis herpetiformis in monozygous twins: discordance for dermatitis herpetiformis and concordance for gluten-sensitive enteropathy.

A monozygous female twin pair discordant for dermatitis herpetiformis and concordant for gluten-sensitive enteropathy is reported. The diagnosis of dermatitis herpetiformis was verified by demonstrating granular IgA deposits in the uninvolved skin. Gluten-sensitive enteropathy was confirmed according to the ESPGAN criteria. Monozygosity was proved by the standard genetic characteristics.

Simultaneous occurrence of diabetes mellitus and coeliac disease.

Subtotal villous atrophy in the proximal jejunum was observed in six patients affected by juvenile diabetes. Introduction of gluten free diet invariably led to clinical improvement, in the four patients in whom also rebiopsy was performed the jejunal mucosa exhibited improvement. In all cases gluten sensitive enteropathy was diagnosed after the onset of diabetes. Marked stunting in growth, strikingly labile carbohydrate tolerance, pronounced proneness to hypoglycaemia or development of Mauriac's syndrome were the symptoms pointing to coeliac disease. Protracted diarrhoea was seen only in two patients, pronounced deceleration in weight development occurred in none of the six children. In four patients out of six the presence of both HLA B8 and DR3 antigens was demonstrated, in a fifth patient only DR3 was present; this suggests a common genetic background of the simultaneous occurrence of the two disorders. Untreated coeliac disease aggravates preexisting diabetes. The importance of early recognition of latent coeliac disease is stressed.

Dermatitis herpetiformis: jejunal findings and skin response to gluten free diet.

Fifty seven children with dermatitis herpetiformis, 18 from Finland and 39 from Hungary, were studied. Diagnostic criteria included the finding of granular IgA deposits in the skin of all patients. The mean age at onset of the rash was 7 X 2 years and favoured sites were the elbows, knees, and buttocks. Symptoms suggesting small intestinal disease were rare but in 35 (61%) of the children subtotal villous atrophy and in 16 (28%) partial villous atrophy were found on jejunal biopsy. Eighteen children underwent a second biopsy after a mean of 21 months on a gluten free diet; villous height was found to be increased and the intraepithelial lymphocyte count decreased in all these patients. Gluten challenge caused a reversal in the two children who underwent a third biopsy. The effect of the gluten free diet on the rash was examined in Finnish children by observing the daily requirements of dapsone, a drug used to control the rash at the beginning of the diet. Eight (67%) of the 12 children were able to stop taking dapsone after a mean of 11 months on the diet and all three patients treated with diet alone became asymptomatic after three to 6 months on the diet. These results confirm that most children with dermatitis herpetiformis have jejunal villous atrophy, though they rarely have gastrointestinal symptoms. The central role of gluten in childhood dermatitis herpetiformis is evidenced by the fact that a gluten free diet helps the damaged jejunal mucosa to recover and controls the rash even in those children who do not have an abnormal jejunal biopsy.

Mast cells and eosinophils in the jejunal mucosa of patients with intestinal cow's milk allergy and celiac disease of childhood.

We counted the number of granulated mast cells with high iron diamine staining, and the number of eosinophils with hematoxyline-eosin staining, in the lamina propria of the jejunum in 12 untreated patients with intestinal cow's milk allergy (CMA), 47 with celiac disease (CD), and 14 controls. A decreased number of mast cells and an increased number of eosinophils were found in 58% of patients with CMA, and in 60% of those with CD. The number of mast cells showed a significant positive correlation with the villous height, and the number of eosinophils a negative correlation with both the villous height, and the number of mast cells. Appropriate dietary treatment resulted in a rise in the number of granulated mast cells and a decrease in the number of eosinophils in both patient groups.

Morphometric study of the jejunal mucosa in various childhood enteropathies with special reference to intraepithelial lymphocytes.

A morphometric study of intraepithelial (IE) lymphocytes per 100 epithelial cells, villous heights (VH), crypt depths (CrD), and epithelial cell heights (ECH) was made on jejunal specimens of 17 patients with cow's-milk allergy (CMA), 52 with celiac disease (CD), seven with congenital lactase deficiency (CLD), four with acrodermatitis enteropathica (AE), four with giardiasis, and four with dermatitis herpetiformis (DH). The aim of this study was to investigate how the morphometric parameters correlate with each other. All cases with CMA, CD, and DH had villous atrophy with hyperplasia of the crypts, both signs being more severe in cases with CD and DH than with CMA. IE lymphocyte infiltration was more intense in specimens of patients with CD and DH (mean 76.0), than those with CMA (mean 62.5). The ECH were equally reduced in patients with CD and CMA. In a follow-up specimen at 1 year and 10 months for CD patients and 11 months for CMA patients the inflammation was reduced, and the VH were increased but still differed from the controls. In CLD cases the morphology of the villi and crypts of the jejunum was quite normal, with no IE lymphocyte infiltration; ECH were reduced. Minor morphological changes were seen in the specimens of patients with AE and giardiasis. In the whole study group there was a significant linear correlation, either positive or negative, between all variables measured (IE lymphocytes, VH, CrD, and ECH).