The small intestine in dermatitis herpetiformis.

Small intestinal biopsies from 43 patients with dermatitis herpetiformis have been studied. The diagnosis of dermatitis herpetiformis was made on clinical and histological criteria and the presence of IgA deposits in the uninvolved skin. The macroscopic appearance of the intestinal biopsy was flat in 13, convoluted in 10, leaves only in eight, and fingers and leaves in 12. Twenty small intestinal biopsies from patients who did not have dermatitis herpetiformis or gastrointestinal disorder showed leaves only in three and fingers and leaves in 17. The mean total lymphocyte count per 1000 epithelial cells for this control group was 159 +/- SE 13; for the dermatitis herpetiformis patients with flat biopsies it was 464 +/- SE 27; for the convoluted biopsies 365 +/- SE 59; for leaves only 535 +/- SE 39; and for the fingers and leaves biopsies 301 +/- SE 31. The counts for all four groups are significantly greater than the control group (P < 0.001). Three of the 43 patients with dermatitis herpetiformis had lymphocyte counts below 200 per 1000 epithelial cells, and four of our controls had counts greater than 200 but none above 300. In the control group the mean counts for lymphocytes per 1000 epithelial cells in the basal position of the intestinal epithelium was 79 +/- SE 8; in the dermatitis herpetiformis flat biopsies it was 89 +/- SE 11; for the convoluted biopsies 93 +/- SE 12; for the leaves only biopsies 121 +/- SE 18 and for the fingers and leaves 98 +/- SE 13. However, the mean lymphocyte count in the perinuclear position was 81 +/- SE 7 for the controls, 362 +/- SE 23 for the flat dermatitis herpetiformis biopsies; 251 +/- SE 46 for the convoluted specimens; 402 +/- SE 43 for the leaves only specimens, and 195 +/- SE 25 for the fingers and leaves biopsies. The mean lymphocyte count for the supranuclear position was 0.55 +/- SE 0.22 for the control group; 13.7 +/- SE 2.3 for the flat dermatitis herpetiformis biopsies; 20.0 +/- SE 6.9 for the convoluted biopsies; 14.5 +/- SE 3.3 for the leaves only biopsies; and 8.3 +/- SE 2.6 for the fingers and leaves biopsies. Thus in gluten-sensitive enteropathy the increase in lymphocytes in the intestinal epithelium is in the perinuclear and supranuclear position. The ratio of basal lymphocytes to peri- and supranuclear lymphocytes appears to be 1:1 in normal intestinal epithelium, but approximately 1:4 in the gluten-sensitive enteropathy of dermatitis herpetiformis.

Zosteriform herpes simplex.

Herpes simplex virus (HSV) infection, though most commonly seen in the oral, perioral and genital areas, can occur anywhere on the body. After primary infection, HSV then establishes latency in sensory nerve ganglia and reactivates intermittently, precipitated by various factors. These reactivations may be recurrent and appear in a dermatomal distribution, mimicking herpes zoster, often leading to misdiagnosis if no confirmatory laboratory tests are carried out. We report a 65-year-old man who presented with recurrent episodes of a "zosteriform eruption", who was initially clinically diagnosed and treated as for recurrent herpes zoster, but was subsequently found to have recurrent herpes simplex virus type 2 after laboratory investigations.

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

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.

Splenic atrophy in dermatitis herpetiformis.

Twenty-four patients with dermatitis herpetiformis were investigated for splenic atrophy by splenic scan and clearance of (51)Cr-labelled heat-damaged red blood cells. Eight of them had definite splenic atrophy. The average splenic cross-sectional area of the remaining 16 with normal clearance times was substantially smaller than normal, suggesting some degree of splenic atrophy. No relationship of splenic hypofunction to intestinal biopsy findings, folate status, reticulin antibody, or treatment with a gluten-free diet or dapsone was evident.

Lymphocytic infiltration of epithelium in diagnosis of gluten-sensitive enteropathy.

The macroscopic appearance of the mucosa of the small intestine and the lymphocytic infiltration of the epithelium were studied in 27 patients with dermatitis herpetiformis and in 11 control subjects. The mucosa was abnormal in appearance in 13 of the patients and normal in 14 patients and in all the controls. In 25 (93%) of the patients the intraepithelial lymphocyte count was significantly raised compared with the controls. The increased lymphocytic infiltration of the epithelium in the patients probably represented an underlying immunological reaction of the small intestine to gluten, since the infiltration lessened in five out of six patients after a year on a gluten-free diet and in all of four patients after three years on a gluten-free diet.Increased lymphocytic infiltration of the epithelium of the small intestine seems a surer sign of gluten sensitivity than the macroscopic appearance of the mucosa, and a diagnosis of gluten-sensitive enteropathy may no longer be excluded when the mucosa appears normal. Further evidence of the significance of increased lymphocytic infiltration is that patients with normal-looking mucosa but with raised intraepithelial lymphocyte counts often had low serum folate levels.

The ultrastructural changes in the skin in dermatitis herpetiformis after withdrawal of dapsone.

The development of skin lesions in patients with dermatitis herpetiformis after the withdrawal of their dapsone therapy was studied with the electron microscope. In control biopsies from patients prior to cessation of treatment, membrane-bound vacuoles were found beneath the basal lamina of the epidermis as previously described. After dapsone withdrawal, there was an apparent increase in the number of vacuoles and occasionally several vacuoles appeared to have coalesced forming an early blister. At this stage, the basal lamina and associated hemidesmosomes were normal although in places there were small discontinuities in the basal lamina. Where the reaction was more intense, vacuoles and cells, mainly eosinophils, were embedded in fibrin de posits. Above this, the basal lamina was usually disrupted with involvement of the basal epidermal cells. These results suggest that the vacuoles do play a part in the formation of the pathological lesion in dermatitis herpetiformis. In addition, the basal lamina is shown to be only secondarily involved. The nature of the vacuoles has still to be elucidated.

Antireticulin antibody: incidence and diagnostic significance.

Sera from 101 patients with adult coeliac disease, 46 patients with childhood coeliac disease, 50 patients with dermatitis herpetiformis, and 479 patients with various other diseases, including skin, gastrointestinal, haematological, and immunological disorders, have been tested for the presence of the antireticulin antibody. Positive sera were retested at higher dilutions. Antireticulin antibody was only found in a significant proportion of patients with three diseases, ie, coeliac disease, dermatitis herpetiformis, and Crohn's disease. Antireticulin antibody was present in 38 out of 101 patients (38%) with adult coeliac disease, 27 out of 46 patients (59%) with childhood coeliac disease, 11 out of 50 patients (22%) with dermatitis herpetiformis, and nine out of 38 patients (24%) with Crohn's disease. In the 434 other patients with various disorders the antireticulin antibody was present in only six 1.4%) (two patients were pregnant, one had vitiligo, one had tropical sprue, one had reticulum cell sarcoma, and one had pernicious anaemia). In patients with gluten-sensitive enteropathy, ie, coeliac disease and dermatitis herpetiformis, there was a significantly higher incidence in patients taking a normal diet compared with those on a gluten-free diet. The presence of antireticulin antibody would appear to be particularly helpful in diagnosing childhood coeliac disease as it was found in 22 out of 26 patients (85%) taking a normal diet.

A comparison of histocompatibility antigens in dermatitis herpetiformis and adult coeliac disease.

The incidence of histocompatibility antigens HL-A, 4a and 4b was studied in thirty-eight patients with dermatitis herpetiformis (DH) and thirty-six patients with adult coeliac disease (ACD). The 4b antigen was found in all the DH and ACD patients. HL-A 8 was found in 89% of patients with ACD--similar to the incidence reported in previous studies--and in 79% of patients with DH, a higher incidence than in previous studies which may be due to stricter criteria being used here to diagnose DH. There was no significant difference in the incidence of HL-A 8 between those patients with DH whose small intestinal biopsies appeared macroscopically abnormal and those with a normal macroscopic appearance. These findings suggest that patients with DH form a single disease group and do not support the concept previously postulated that there are two groups of patients with DH, one with an increased incidence of HL-A 8 antigen similar to that in ACD who have a gluten sensitive enteropathy (GSE), and another with a normal incidence of HL-A 8 antigen and without enteropathy.