Dermatitis herpetiformis: diagnosis, diet and demography.

Author Gawkrodger DJ; Blackwell JN; Gilmour HM; Rifkind EA; Heading RC; Barnetson RS

Source Gut, 1984 Feb, 25:2, 151-7

Abstract We describe a long term study of 76 patients with dermatitis herpetiformis. Unlike patients with coeliac disease, where the peak incidence was during the first and fourth decades, no dermatitis herpetiformis patients presented in the first decade; also, there was a male preponderance in dermatitis herpetiformis which contrasts with the excess of females in coeliac disease. The apparent prevalence of dermatitis herpetiformis was 11 per 100 000 in our population; approximately one fifth of that of coeliac disease. Jejunal villous atrophy was present in 78% of our dermatitis herpetiformis patients, and a single jejunal biopsy was as effective at detecting this as the multiple biopsy technique. A majority of patients were able to stop, or radically reduce their dapsone or sulphapyridine treatment after the institution of a gluten free diet. Spontaneous remission of the skin lesion occurred in only two patients not receiving a gluten free diet. Gastric parietal or thyroid antibodies were detected in 38% of patients, and three cases of thyroid disease and two cases of pernicious anaemia were detected. Lymphoma developed in two patients, one being intestinal in origin. We conclude that a gluten free diet is of therapeutic benefit in dermatitis herpetiformis and that spontaneous remission is uncommon in those not on a diet. Despite patchiness of the enteropathy, a single jejunal biopsy is quite adequate to diagnose the presence of upper intestinal villous atrophy. 

Familial incidence of dermatitis herpetiformis.

Author Meyer LJ; Zone JJ

Address Department of Internal Medicine, Veterans Administration Hospital, Salt Lake City, UT.

Source J Am Acad Dermatol, 1987 Oct, 17:4, 643-7

Abstract Dermatitis herpetiformis and gluten-sensitive enteropathy are diseases in which exposure to gluten results in an inflammatory response. Both diseases are associated with certain human lymphocyte antigen alleles, and gluten-sensitive enteropathy is well known to cluster in families. Gluten-sensitive enteropathy has also been reported in families of patients with dermatitis herpetiformis. Despite this evidence that dermatitis herpetiformis is a genetic disease, reports of the familial occurrence of dermatitis herpetiformis are rare. We have obtained family histories from 92 patients with dermatitis herpetiformis with 740 first-degree relatives. Six of these relatives have dermatitis herpetiformis. Comparison of these data with the expected prevalence of dermatitis herpetiformis shows this incidence to be highly significant (p less than 0.0001), strongly suggesting that dermatitis herpetiformis is a familial disease, presumably because of shared genetic factors but possibly because of a shared environment. 

The pathogenesis of dermatitis herpetiformis: recent advances.

Author Hall RP

Source J Am Acad Dermatol, 1987 Jun, 16:6, 1129-44

Abstract Over the last two decades a rapid expansion of our knowledge regarding dermatitis herpetiformis has occurred, including the discovery of IgA in the skin, the discovery of an associated gluten-sensitive enteropathy, the noting of an increased prevalence of the human lymphocyte antigens (HLA)-B8 and -DRw3, and the documentation that the skin disease of many dermatitis herpetiformis patients can be controlled by a gluten-free diet. It has also been noted that two distinct forms of dermatitis herpetiformis occur, those with granular deposits of IgA at the dermoepidermal junction (85%-95% of dermatitis herpetiformis patients) and those with linear IgA deposits (10%-15% of dermatitis herpetiformis patients). These findings are reviewed with particular emphasis on the form of dermatitis herpetiformis associated with granular IgA deposits. The current findings regarding the nature and origin of the cutaneous IgA deposits, the role of the gluten-sensitive enteropathy, and the spectrum of both the immunologic and the nonimmunologic abnormalities associated with dermatitis herpetiformis are presented, and from these data pathophysiologic mechanisms are proposed that may be involved in dermatitis herpetiformis. 

Helicobacter pylori serology in patients with coeliac disease and dermatitis herpetiformis.

Author Crabtree JE; O'Mahony S; Wyatt JI; Heatley RV; Vestey JP; Howdle PD; Rathbone BJ; Losowsky MS

Address Department of Medicine, St James's University Hospital, Leeds.

Source J Clin Pathol, 1992 Jul, 45:7, 597-600

Abstract AIMS: To investigate whether Helicobacter pylori infection or autoimmune gastritis is responsible for the reported increase in gastric pathology and abnormalities of gastric function in patients with coeliac disease and dermatitis herpetiformis (DH). METHODS: Serum H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay and intrinsic factor antibodies by radioimmunoassay in 99 patients with coeliac disease and 58 patients with dermatitis herpetiformis from two geographic areas. RESULTS: H pylori positivity in patients with coeliac disease and dermatitis herpetiformis increased with age, reaching 50% and 70%, respectively, in patients over 50 years. The percentage H pylori seropositivity in coeliac disease did not differ from the percentage positivity observed in 250 similarly aged blood donors from the same geographic area (Leeds). Seropositivity in patients with dermatitis herpetiformis was not significantly different from the level of positivity observed in 98 age matched patients without dermatitis herpetiformis attending the same Edinburgh dermatology clinic. Only one patient with coeliac disease had positive intrinsic factor antibodies. H pylori seropositivity in Edinburgh control subjects under 30 years of age (41.9%) was significantly higher (p less than 0.03) than in Leeds controls (18%) of corresponding age. An increasing prevalence of H pylori seropositivity with age in coeliac disease and dermatitis herpetiformis paralleled that of the control groups. CONCLUSIONS: Gastritis in coeliac disease and dermatitis herpetiformis is largely caused by H pylori infection at a level that is no different from that of the general population. Any increase in the prevalence of gastritis in these two diseases might be caused by lymphocytic gastritis rather than pernicious anaemia.

 

The incidence and prevalence of dermatitis herpetiformis in Utah.

Author Smith JB; Tulloch JE; Meyer LJ; Zone JJ

Address Emergency Department, US Air Force Hospital Hill, Hill Air Force Base, Utah.

Source Arch Dermatol, 1992 Dec, 128:12, 1608-10

Abstract BACKGROUND AND DESIGN--The incidence and prevalence of dermatitis herpetiformis has never been formally evaluated in any area of the United States. Several northern European studies have shown prevalence rates ranging from 1.2 per 100,000 to 39.2 per 100,000. The present study was performed to evaluate the incidence and prevalence of dermatitis herpetiformis in Utah. Information from 240 patients diagnosed with dermatitis herpetiformis was compiled from hospital records throughout Utah, as well as the sole private dermatopathologist in the state, and from the university referral center of the state. Criteria for inclusion in the study were a clinical diagnosis of dermatitis herpetiformis plus granular deposition of IgA in dermal papillae by direct immunofluorescence of uninvolved skin, or histopathologic findings consistent with the disease. Clinical diagnosis and response to dapsone alone was considered insufficient for inclusion in the study. On the basis of these criteria, as well as exclusion of non-Utah residents, 188 of the original 240 patients qualified for the study. RESULTS--The prevalence of dermatitis herpetiformis in Utah in 1987 was 11.2 per 100,000. The mean incidence for the years 1978 through 1987 was 0.98 per 100,000 per year. The mean age at onset of symptoms for male patients was 40.1 years, and that for female patients was 36.2 years. The male-female ratio was 1.44:1. CONCLUSIONS--This represents the first evaluation of the incidence and prevalence of dermatitis herpetiformis in the United States. These results are similar to those of the previous studies, probably because of Utah's largely northern European ancestry. This population base, plus a much smaller than average black and Oriental population, is likely to have produced a higher incidence and prevalence in Utah than would be seen in other areas of the United States. 

25 years' experience of a gluten-free diet in the treatment of dermatitis herpetiformis.

Author Garioch JJ; Lewis HM; Sargent SA; Leonard JN; Fry L

Address Department of Dermatology, St Mary's Hospital, London, U.K.

Source Br J Dermatol, 1994 Oct, 131:4, 541-5

Abstract Gluten-free diets have been used in the treatment of patients with dermatitis herpetiformis in our department since 1967. Of the 212 patients with dermatitis herpetiformis attending between 1967 and 1992, 133 managed to take the diet, and 78 of these achieved complete control of their rash by diet alone. Of the remaining 55 patients taking a gluten-free diet, all but three were taking partial diets; over half of these patients managed to substantially reduce the dose of medication required. Of the 77 patients taking a normal diet, eight entered spontaneous remission, giving a remission rate of 10%; a further two patients who had been taking gluten-free diets were found to have remitted when they resumed normal diets. Loss of IgA from the skin was observed in 10 of 41 (24%) patients taking strict gluten-free diets. These patients had been taking their diets for an average of 13 years (range 5-24 years), and their rash had been controlled by diet alone for an average of 10 years (range 3-16 years). The advantages of a gluten-free diet in the management of patients with dermatitis herpetiformis are: (i) the need for medication is reduced or abolished; (ii) there is resolution of the enteropathy, and (iii) patients experience a feeling of well-being after commencing the diet. Thus, we propose that a gluten-free diet is the most appropriate treatment for patients with dermatitis herpetiformis.

 

The effect of an elemental diet with and without gluten on disease activity in dermatitis herpetiformis.

Author Kadunce DP; McMurry MP; Avots-Avotins A; Chandler JP; Meyer LJ; Zone JJ

Address Department of Medicine (Dermatology), University of Utah School of Medicine, Salt Lake City.

Source J Invest Dermatol, 1991 Aug, 97:2, 175-82

Abstract Elemental diets are reported to decrease activity of patients with dermatitis herpetiformis. We tested the hypothesis that gluten, given in addition to an elemental diet, is responsible for the intestinal abnormalities, cutaneous immunoreactant deposition, and skin disease activity in dermatitis herpetiformis. At entry eight patients with dermatitis herpetiformis, who were consuming unrestricted diets, were stabilized on their suppressive medications at dosage levels that allowed individual lesions to erupt. Six patients were then given an elemental diet plus 30 of gluten for 2 weeks, followed by the elemental diet alone for 2 weeks. Conversely, two patients received an elemental diet alone for 2 weeks followed by an elemental diet plus gluten during the final 2 weeks. Small bowel biopsies, skin biopsies, and clinical assessments were done at 0, 2, and 4 weeks. Suppressive medication dose requirement decreased over the 4 weeks by a mean of 66%. Six of eight subjects significantly improved clinically during the gluten-challenge phase of the elemental diet and all were improved at the end of the study. The amount of IgA in perilesional skin did not change significantly, but the amount of C3 increased in five of seven evaluable subjects after gluten challenge. Circulating anti-gluten and anti-endomysial antibodies were not significantly affected by the diets. All subjects completing evaluable small bowel biopsies (seven of seven) demonstrated worsening of their villus architecture (by scanning electron microscopy and intraepithelial lymphocyte counts) during gluten challenge and improvement (six of six subjects) after 2 weeks of elemental dietary intake. We conclude that 1) there is a significant improvement in clinical disease activity on an elemental diet, independent of gluten administration, 2) small bowel morphology improves rapidly on an elemental diet, and 3) complement deposition but neither IgA deposition nor circulating antibody levels correlate with gluten intake. It seems likely that dietary factors other than gluten are important in the pathogenesis of the skin lesions in dermatitis herpetiformis. 

Dermatitis herpetiformis: consequences of elemental diet.

Author Zeedijk N; van der Meer JB; Poen H; van der Putte SC

Source Acta Derm Venereol, 1986, 66:4, 316-20

Abstract The administration of an Elemental Diet to 5 patients with dermatitis herpetiformis, requiring high doses of Dapsone (diaminodiphenylsulfone, DDS), showed a rapid and beneficial effect on the skin lesions within two weeks. This effect was not influenced by simultaneous gluten challenge in one patient. A possible explanation is a reduction in the amount of harmful immune complexes due to the elimination of proteins from the diet. Subsequent introduction of a more comprehensive diet led to an increase of the minimal effective dose of Dapsone. These results underline the importance of dietary influences on the skin activity in dermatitis herpetiformis, other than gluten alone.

Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease.

Author Collin P; Pukkala E; Reunala T

Address Medical School, University of Tampere, Finland.

Source Gut, 1996 Apr, 38:4, 528-30

Abstract BACKGROUND--Dermatitis herpetiformis is a lifelong, gluten sensitive skin disease. Patients with dermatitis herpetiformis, similar to patients with coeliac disease not adhering to a gluten free diet, seem to have increased risk for lymphoma. AIMS--This study looked at the occurrence of malignancy and survival of patients with dermatitis herpetiformis and compared the results with those seen in patients with coeliac disease or in the general population. PATIENTS--A total of 305 adult patients with dermatitis herpetiformis diagnosed at the University Hospital of Tampere in 1970-1992 were studied. Most patients started a gluten free diet and at the end of the study 93% of the patients were adhering to the diet. A control group comprised 383 adult patients with coeliac disease, 81% of them adhered to a gluten free diet, 6% had a normal diet, and in 13% the diet history remained unknown. METHODS--The occurrence of malignant diseases and survival of the patients were assessed up to the end of 1993. Standardised incidence ratios (SIR) with 95% confidence intervals were used for the malignant diseases. The survival of the patients was compared with that of the general population. RESULTS--Thirteen (4.3%) patients with dermatitis herpetiformis developed 14 malignant disorders during the follow up (SIR 1.25; 95% confidence intervals 0.68 to 2.09). A non-Hodgkin's lymphoma occurred in four patients with dermatitis herpetiformis, significantly more than expected (SIR 10.3; 2.8-26.3). Thirteen (4.3%) patients with dermatitis herpetiformis died during the follow up but there was no increased general mortality. In coeliac disease, 13 (3.4%) patients developed malignancy (SIR 1.16; 0.62 to 1.97), 31 (8.1%) patients died but the survival rate did not differ from that in the general population. CONCLUSIONS--The incidence of non-Hodgkin's lymphoma was significantly increased in patients with dermatitis herpetiformis. The results also confirm that the patients with dermatitis herpetiformis treated mainly with a gluten free diet have no increased general mortality. 

Mortality and cancer incidence in patients with dermatitis herpetiformis: a cohort study.

Author Swerdlow AJ; Whittaker S; Carpenter LM; English JS

Address Office of Population Censuses and Surveys, London, U.K.

Source Br J Dermatol, 1993 Aug, 129:2, 140-4

Abstract One hundred and fifty-two patients in whom a diagnosis of dermatitis herpetiformis was made at St John's Hospital for Diseases of the Skin, London, during 1950-85, were followed from the date of diagnosis to the end of 1989 for mortality, and from 1971, or the date of diagnosis if later, to 1986 for cancer incidence. Thirty-eight deaths occurred under the age of 85, slightly fewer than expected on the basis of national general population rates [standardized mortality ratio (SMR) = 87; 95% confidence interval (CI) 61-119]. All-cause mortality was somewhat lower in patients who had followed a gluten-free diet (SMR = 51; 17-120) than in those who had not (SMR = 97; 66-136), but the difference in SMRs was not significant (P = 0.3). Cancer mortality was non-significantly below expectations from national rates (SMR = 72; 31-142), but cancer incidence was significantly increased [standardized registration ratio (SRR) = 394; 180-749]. No particular cancer site accounted for the cancer incidence excess. One death occurred from cancer of the small intestine (SMR = 4953, P = 0.04), and one lymphoma was incident (SRR = 1555, P = 0.12). Increased risks of these malignancies have previously been found to be associated with coeliac disease (which is present in many patients with dermatitis herpetiformis), and with dermatitis herpetiformis, respectively. Mortality from ischaemic heart disease (IHD) was significantly below national rates (SMR = 37; 95% CI 12-86), and was similar in patients who had followed a gluten-free diet and those who had not.  

Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease.

Author Collin P; Pukkala E; Reunala T

Address Medical School, University of Tampere, Finland.

Source Gut, 1996 Apr, 38:4, 528-30

Abstract BACKGROUND--Dermatitis herpetiformis is a lifelong, gluten sensitive skin disease. Patients with dermatitis herpetiformis, similar to patients with coeliac disease not adhering to a gluten free diet, seem to have increased risk for lymphoma. AIMS--This study looked at the occurrence of malignancy and survival of patients with dermatitis herpetiformis and compared the results with those seen in patients with coeliac disease or in the general population. PATIENTS--A total of 305 adult patients with dermatitis herpetiformis diagnosed at the University Hospital of Tampere in 1970-1992 were studied. Most patients started a gluten free diet and at the end of the study 93% of the patients were adhering to the diet. A control group comprised 383 adult patients with coeliac disease, 81% of them adhered to a gluten free diet, 6% had a normal diet, and in 13% the diet history remained unknown. METHODS--The occurrence of malignant diseases and survival of the patients were assessed up to the end of 1993. Standardised incidence ratios (SIR) with 95% confidence intervals were used for the malignant diseases. The survival of the patients was compared with that of the general population. RESULTS--Thirteen (4.3%) patients with dermatitis herpetiformis developed 14 malignant disorders during the follow up (SIR 1.25; 95% confidence intervals 0.68 to 2.09). A non-Hodgkin's lymphoma occurred in four patients with dermatitis herpetiformis, significantly more than expected (SIR 10.3; 2.8-26.3). Thirteen (4.3%) patients with dermatitis herpetiformis died during the follow up but there was no increased general mortality. In coeliac disease, 13 (3.4%) patients developed malignancy (SIR 1.16; 0.62 to 1.97), 31 (8.1%) patients died but the survival rate did not differ from that in the general population. CONCLUSIONS--The incidence of non-Hodgkin's lymphoma was significantly increased in patients with dermatitis herpetiformis. The results also confirm that the patients with dermatitis herpetiformis treated mainly with a gluten free diet have no increased general mortality.

 Intraepithelial lymphocyte mitosis in a jejunal biopsy correlates with intraepithelial lymphocyte count, irrespective of diagnosis.

Author Ferguson A; Ziegler K

Source Gut, 1986 Jun, 27:6, 675-9

Abstract When there is villus atrophy in a jejunal biopsy, intraepithelial lymphocyte (IEL) mitosis correlates with a diagnosis of coeliac disease. We have examined the significance of IEL mitosis in jejunal biopsies with normal villi. Counts of IEL per 100 villus enterocytes, and IEL mitosis per 1000 IEL, were carried out in 81 jejunal biopsies. Thirty one were from patients with coeliac disease or dermatitis herpetiformis, and many of these, from treated patients, were histologically normal; 40 were from patients with other diagnoses, selected to include biopsies with a high IEL count (greater than 40 IEL per 100 enterocytes) but normal villi. Three coeliacs and 10 dermatitis herpetiformis patients had an IEL count of less than 40, and no IEL mitoses were found in these biopsies. Two dermatitis herpetiformis patients had IEL counts of 43.7% and 43.9%, with no IEL mitoses, but in all other coeliac and dermatitis herpetiformis biopsies high IEL counts were associated with IEL mitotic indices between 0.05% and 1.77%. In the non-coeliac, non-dermatitis herpetiformis group, no IEL mitoses were found in the 22 biopsies with IEL count less than 43%. In the others, IEL counts ranged from 44.8% to 127.0%, and IEL mitoses were present, with mitotic indices ranging from 0.06% to 0.49%. This work shows that IEL mitosis in a jejunal biopsy is not specific for coeliac disease, but occurs whenever there is an increased density of IEL within the villus epithelium.

 

Intestinal permeability in patients with coeliac disease and dermatitis herpetiformis.

Author Bjarnason I; Marsh MN; Price A; Levi AJ; Peters TJ

Source Gut, 1985 Nov, 26:11, 1214-9

Abstract Intestinal permeability was investigated in patients with coeliac disease and dermatitis herpetiformis by a 51Chromium-labelled ethylenediaminetetraacetate (51Cr-EDTA) absorption test and the results correlated with histomorphometric analysis and intraepithelial lymphocyte counts of jejunal biopsies. The mean (+/- SD) 24 hour urine excretion of 51Cr-EDTA in 34 healthy volunteers was 1.9 +/- 0.5% of the orally administered test dose. Patients with untreated coeliac disease (19) or untreated dermatitis herpetiformis (five) excreted significantly more 51Cr-EDTA than controls (5.9 +/- 2.7% and 4.6 +/- 2.1%, respectively, p less than 0.001) and all were outside the normal range of 1.0-2.6%. Patients with coeliac disease (42) treated for 6 months-23 years (mean 5 years) and patients with dermatitis herpetiformis (11) treated for 6 months-8 years (mean 3 years) excreted significantly more 51Cr-EDTA than controls, 4.2 +/- 2.4% p less than 0.0001 and 3.0 +/- 0.9% p less than 0.003 respectively. Eleven of 14 (79%) treated patients with coeliac disease with an entirely normal jejunal mucosae demonstrated abnormal intestinal permeability. Intestinal permeability did not correlate significantly with either the mucosal height/crypt depth ratio or intraepithelial lymphocyte counts in jejunal biopsies from patients with untreated or treated coeliac disease. The demonstration of a persistent increase in intestinal permeability in patients with both coeliac disease and dermatitis herpetiformis may suggest a common pathogenetic mechanism in both disorders. It is postulated that altered permeability may facilitate the entry of gluten or a fraction thereof into the lamina propria where it causes a cascade of immunological events. 

Intestinal permeability in dermatitis herpetiformis.

Author Griffiths CE; Menzies IS; Barrison IG; Leonard JN; Fry L

Address Department of Dermatology, St. Mary's Hospital, London.

Source J Invest Dermatol, 1988 Aug, 91:2, 147-9

Abstract Differential absorption of D-xylose and 3-0-methyl-D-glucose, and unmediated intestinal permeation (simple diffusion) of lactulose and L-rhamnose, have been investigated in 20 patients with dermatitis herpetiformis. Both iso-osmolar and hyperosmolar test solutions were employed and the results were compared with those obtained from a group of healthy adult volunteers. The findings in each patient have been correlated with small intestinal histology. The majority of patients with villous atrophy had abnormally raised intestinal lactulose permeation and lactulose/rhamnose permeability ratios, whereas patients with normal small intestinal morphological grading did not differ significantly from the healthy control group in this respect. There was a high incidence of delayed plasma D-xylose absorption peaks in dermatitis herpetiformis irrespective of small intestinal histological findings. These results imply that abnormal intestinal permeability in dermatitis herpetiformis is the result of gluten-induced damage to the mucosa rather than an inherent primary defect. It is therefore improbable that the rash in this condition is purely a manifestation of increased intestinal permeation of antigen.  

Small intestinal function and dietary status in dermatitis herpetiformis.

Author Gawkrodger DJ; McDonald C; O'Mahony S; Ferguson A

Address Department of Dermatology, Royal Infirmary, Edinburgh.

Source Gut, 1991 Apr, 32:4, 377-82

Abstract Small intestinal morphology and function were assessed in 82 patients with dermatitis herpetiformis, 51 of whom were taking a normal diet and 31 a gluten free diet. Methods used were histopathological evaluation of jejunal mucosal biopsy specimens, quantitation of intraepithelial lymphocytes, cellobiose/mannitol permeability test, tissue disaccharidase values, serum antigliadin antibodies, and formal assessment of dietary gluten content by a dietician. There was no correlation between dietary gluten intake and the degree of enteropathy in the 51 patients taking a normal diet, whereas biopsy specimens were normal in 24 of the 31 patients on a gluten free diet, all previously having been abnormal. Eighteen patients on gluten containing diets had normal jejunal histology and in seven of these all tests of small intestinal morphology and function were entirely normal. Intestinal permeability was abnormal and serum antigliadin antibodies were present in most patients with enteropathy. Studies of acid secretion in seven patients showed that hypochlorhydria or achlorhydria did not lead to abnormal permeability in the absence of enteropathy. This study shows that a combination of objective tests of small intestinal architecture and function will detect abnormalities in most dermatitis herpetiformis patients, including some with histologically normal jejunal biopsy specimens. Nevertheless there is a small group in whom all conventional intestinal investigations are entirely normal. 

Increase of lymphocytes bearing the gamma/delta T cell receptor in the jejunum of patients with dermatitis herpetiformis.

Author Savilahti E; Reunala T; M?i M

Address Children's Hospital, University of Helsinki, Finland.

Source Gut, 1992 Feb, 33:2, 206-11

Abstract The densities of T cells and of cells bearing the T cell receptors gamma/delta and alpha/delta and the surface antigens CD4 and CD8 in jejunal specimens from 21 patients with dermatitis herpetiformis were compared with those in specimens from 13 untreated adults with coeliac disease and 13 control subjects. In the lamina propria of the jejunum the median density of gamma/delta+ cells was significantly (p less than 0.001) greater in untreated patients with dermatitis herpetiformis than in control subjects (114 v 36 cells/mm2) and similar to that found in the patients with coeliac disease (115 cells/mm2). The difference in gamma/delta+ cell density between patients with dermatitis herpetiformis and control subjects was much greater in the surface epithelium of the jejunum: the median density for 14 untreated patients with dermatitis herpetiformis was 39 cells/mm, for seven patients with dermatitis herpetiformis on a gluten free diet 34 cells/mm, and for control subjects 2 cells/mm; the coeliac patients had the same density as the patients with dermatitis herpetiformis (45 cells/mm). The higher density of cells bearing the alpha/delta T cell receptor in the epithelium (median 77 cells/mm) of untreated patients with dermatitis herpetiformis was associated with a gluten containing diet; in specimens taken from patients with dermatitis herpetiformis on a gluten free diet the median density was similar to that in the control subjects (44 v 39 cells/mm). The increase in the number of lymphocytes bearing the T cell receptor gamma/delta, particularly in the epithelium of the jejunum, seems to be a constant marker for these closely related diseases, whereas the density of alpha/delta+ T cells is dependent on the diet. 

Density of gamma/delta+ T cells in the jejunal epithelium of patients with coeliac disease and dermatitis herpetiformis is increased with age.

Author Savilahti E; Orm??; Arato A; Hacsek G; Holm K; Klemola T; Nemeth A; M?i M; Reunala T

Address The Children's Hospital, University of Helsinki, Finland.

Source Clin Exp Immunol, 1997 Sep, 109:3, 464-7

Abstract Increased density of gamma/delta T cell receptor (TCR)+ intraepithelial lymphocytes is the only characteristic in the jejunum of patients with coeliac disease and dermatitis herpetiformis which is not normalized on a gluten-free diet. We explored the age-dependent changes in intraepithelial gamma/delta and alpha/beta TCR+ cells from 137 biopsies from patients with coeliac disease and dermatitis herpetiformis and from controls. Biopsy specimens from 100 patients with coeliac disease and dermatitis herpetiformis and from 37 controls were studied with an immunohistochemical method using MoAbs to T cell receptors and peroxidase staining. An increase in the density of intraepithelial gamma/delta T cells above the mean +2 s.d. of the density in controls was present in 97 of 100 specimens from patients with coeliac disease and dermatitis herpetiformis. The density of gamma/delta+ cells of patients with coeliac disease and dermatitis herpetiformis on a normal gluten-containing diet showed a positive correlation with age (r = 0.45, P  

IgA antiendomysial antibodies in dermatitis herpetiformis

Author Peters MS; McEvoy MT

Address Immunodermatology Laboratory, Mayo Clinic, Rochester, MN 55905.

Source J Am Acad Dermatol, 1989 Dec, 21:6, 1225-31

Abstract Sera from 24 patients with dermatitis herpetiformis and 80 control subjects (patients with other bullous diseases, nonbullous dermatoses, and noncutaneous diseases) were studied to determine the usefulness of assay for IgA antiendomysial antibodies (IgA-EMA) in the diagnosis of dermatitis herpetiformis. The overall sensitivity of IgA-EMA for the diagnosis of dermatitis herpetiformis was 79% and the specificity was 96%. When the three patients with dermatitis herpetiformis who were faithfully following gluten-free diets were excluded, the sensitivity was 90% and the specificity was 96%. No patient in the bullous disease control group (including patients with linear IgA bullous dermatosis) had circulating IgA-EMA. One patient, who did not have direct immunofluorescence evidence for dermatitis herpetiformis but had IgA nephropathy, had a positive IgA-EMA result, an interesting association in light of the rare reports of dermatitis herpetiformis in patients with IgA nephropathy and IgA antigliadin antibodies associated with IgA nephropathy. Although direct immunofluorescence testing of skin biopsy specimens remains the most definitive diagnostic test for dermatitis herpetiformis, indirect immunofluorescence assay of serum for IgA-EMA is a minimally invasive study with a high sensitivity and specificity for dermatitis herpetiformis.  

Class-specific antibodies to gluten in dermatitis herpetiformis.

Author Lane AT; Huff JC; Zone JJ; Weston WL

Source J Invest Dermatol, 1983 May, 80:5, 402-5

Abstract An immune reaction to wheat protein has been previously proposed to explain the pathogenesis of dermatitis herpetiformis. In order to detect and characterize antibodies to gluten in human sera, we developed an enzyme immunoassay for class-specific antibodies. Results of this assay in 49 patients with dermatitis herpetiformis were compared with those of 38 normal control subjects, 11 patients with celiac disease, and 6 small-bowel bypass patients. IgA antibodies to gluten were significantly more frequent in dermatitis herpetiformis sera (28/49) than in normal control sera (4/38). IgG antibodies to gluten were significantly more frequent in both celiac disease (10/11) and dermatitis herpetiformis (16/49) sera than in control (5/38) sera. Dermatitis herpetiformis sera also had an increased prevalence of IgM antibodies to gluten (19/49). Small-bowel bypass patients demonstrated no antibody to gluten. Antibodies to gluten in dermatitis herpetiformis objectively mark a state of immune reactivity to wheat protein and may be involved in the genesis of the cutaneous IgA immune deposits and the skin disease. 

The prevalence of thyroid autoantibodies in dermatitis herpetiformis.

Author Weetman AP; Burrin JM; Mackay D; Leonard JN; Griffiths CE; Fry L

Address Department of Medicine, Royal Postgraduate Medical School, London, U.K.

Source Br J Dermatol, 1988 Mar, 118:3, 377-83

Abstract The prevalence of IgG class thyroglobulin and microsomal antibodies, estimated using a sensitive ELISA, was 48% in 115 patients with dermatitis herpetiformis, which was significantly greater than the prevalence of 16% in 107 unselected controls without dermatitis herpetiformis. IgA class thyroid antibodies were found in 29% of dermatitis herpetiformis patients. Overt thyroid disease had been diagnosed in six (5%) of the dermatitis herpetiformis group and a further six patients had elevated TSH levels. The presence of thyroid antibodies was not associated with particular HLA-DR antigens. These results demonstrate the frequent occurrence of thyroid antibodies in dermatitis herpetiformis, although thyroid failure is less commonly associated with this condition. Immune response genes outside the HLA-DR region may be involved in the immune hyper-responsiveness seen in dermatitis herpetiformis which is reflected in the high prevalence of thyroid autoimmunity.  

Antibodies to gliadin in adult coeliac disease and dermatitis herpetiformis.

Author Volta U; Cassani F; De Franchis R; Lenzi M; Primignani M; Agape D; Vecchi M; Bianchi FB; Pisi E

Source Digestion, 1984, 30:4, 263-70

Abstract Antibodies to gliadin, searched for by indirect immunofluorescence and a micro-ELISA, were detected in 16 (64%) of 25 sera from patients with adult coeliac disease and in 13 (45%) of 29 with dermatitis herpetiformis. Although the sensitivity of the two tests was relatively low in the whole groups, it increased when only cases with severe jejunum abnormalities were considered (93% for coeliac disease and 81% for dermatitis herpetiformis). A significant correlation was found between antigliadin antibodies and the severity of jejunum damage in both diseases. Moreover, most coeliac and dermatitis herpetiformis patients with antigliadin antibodies were on normal diet. The specificity of the tests was 100% for the immunofluorescence and fairly good for the micro-ELISA, as only 5 (11%) of the 46 disease control patients (Crohn's disease, ulcerative colitis) were positive for antigliadin antibodies. R1-reticulin antibody test was equally specific but less sensitive in both groups. We conclude that antigliadin antibodies are useful in the diagnosis of patients with active adult coeliac disease and dermatitis herpetiformis with gluten-sensitive enteropathy. Moreover, the two tests make it possible to monitor the compliance to gluten-free diet in both diseases. 

Demonstration of tissue 90 kD glycoprotein as antigen in circulating IgG immune complexes in dermatitis herpetiformis and coeliac disease.

Author Maury CP; Teppo AM

Source Lancet, 1984 Oct 20, 2:8408, 892-4

Abstract Mannose-rich 90 kD glycoprotein, a constituent of skin and small-bowel mucosa, was identified as antigen in circulating IgG-type immune complexes in dermatitis herpetiformis and coeliac disease by means of an enzyme-linked immunosorbent assay. High levels of 90 kD glycoprotein-IgG complexes were found in 7 out of 12 patients with dermatitis herpetiformis and in 10 out of 20 patients with coeliac disease but in only 2 out of 20 patients with systemic lupus erythematosus. The highest levels of 90 kD antigen-IgG complexes were found in patients with dermatitis herpetiformis. The amount of these complexes did not correlate with the degree of jejunal villous atrophy. The 90 kD glycoprotein-containing immune complexes with targets in skin and gut may be involved in the pathogenesis of dermatitis herpetiformis and coeliac disease. 

IgA-containing circulating immune complexes in dermatitis herpetiformis, Henoch-Sch?lein purpura, systemic lupus erythematosus and other diseases.

Author Hall RP; Lawley TJ; Heck JA; Katz SI

Source Clin Exp Immunol, 1980 Jun, 40:3, 431-7

Abstract The sera of patients with dermatitis herpetiformis, Henoch-Sch?lein purpura and systemic lupus erythematosus were examined for IgA-containing immune complexes using a newly described radioimmunoassay. The IgG Raji cell radioimmunoassay and the 125I-C1q binding assay were also used to detect IgG- and IgM- containing soluble immune complexes. IgA-containing immune complexes were found in the sera of twelve of forty-nine (24%) patients with dermatitis herpetiformis, four of six (67%) patients with Henoch-Sch?lein purpura, and seven of ten (70%) patients with systemic lupus erythematosus. IgG- or IgM- containing immune complexes were also found in six of forty-seven patients with dermatitis herpetiformis, in one of six patients with Henoch-Sch?lein purpura, and in nine of ten patients with systemic lupus erythematosus, by either the 125I-Clq binding assay or the IgG Raji cell assay. The finding of soluble IgA immune complexes in a high percentage of patients with systemic lupus erythematosus and Henoch-Sch?lein purpura suggests that they may play an important role in the pathogenesis of these diseases. In contrast, their low prevalence in patients with dermatitis herpetiformis suggests that IgA-containing immune complexes may not play a major role in the pathogenesis of dermatitis herpetiformis.  

Circulating immune complexes of IgA type in dermatitis herpetiformis.

Author Zone JJ; LaSalle BA; Provost TT

Source J Invest Dermatol, 1980 Aug, 75:2, 152-5

Abstract There is some evidence that dermatitis herpetiformis may be mediated by circulating immune complexes. This study attempts to define the antibody class of these complexes. All patients studied demonstrated granular deposition of IgA in the papillary dermis on direct immunofluorescence. Serum immune complexes were detected using the qualitative Raji cell immunofluorescent assay, as well as the quantitative immunoradiometric assay. A group of 25 dermatitis herpetiformis patients was found to have higher levels of IgA containing complexes compared to a group of normals.  

T lymphocytes bearing the gamma/delta T-cell receptor in cutaneous lesions of dermatitis herpetiformis.

Author Kell DL; Glusac EJ; Smoller BR

Address Department of Pathology, Stanford University Medical Center, CA 94305.

Source J Cutan Pathol, 1994 Oct, 21:5, 413-8

Abstract T lymphocytes bearing the gamma/delta T-cell receptor are a rare component of normal human GI epithelium and skin. Recently, however, an unusually high percentage of T lymphocytes with gamma/delta receptors has been described in gastrointestinal biopsies from patients with dermatitis herpetiformis, implicating the gamma/delta T cell subset in the pathogenesis of this disease. We investigated a possible role for this subset of lymphocytes in the pathogenesis of the cutaneous lesions of dermatitis herpetiformis. Using a standard immunoperoxidase technique, we labelled perilesional skin biopsies from patients with dermatitis herpetiformis and other inflammatory dermatoses with monoclonal antibodies to CD3, CD4, CD8, alpha/beta T cell receptor, gamma/delta T cell receptor, and IL-2 receptor. We found no differences in the percentage of gamma/delta positive T lymphocytes in skin lesions of dermatitis herpetiformis as compared to other selected inflammatory conditions. These findings suggest that the pathogenesis of the cutaneous lesions of dermatitis herpetiformis is not mediated through gamma/delta T cells, and that the cutaneous lesions may develop through mechanisms different from those operative in the gastrointestinal tract. 

Electron microscopic studies in dermatitis herpetiformis in relation to the pattern of immune deposits in the skin.

Author Dbrowski J; Jablosska S; Chorzelski TP; Jarz bek-Chorzelska M; Maciejewski W

Source Arch Dermatol Res, 1977 Sep 27, 259:3, 213-24

Abstract Electron microscopic studies were made in 12 cases of dermatitis herpetiformis: 6 of them with a continuous immunofluorescence line of IgA deposits at the dermo-epidermal junction, and the other 6 with granular IgA deposits in the dermal papillae. Six cases of bullous pemphigoid with a continuous immunofluorescence line of IgG deposits at the dermo-epidermal junction were examined similarly for comparison. In dermatitis herpetiformis with the continuous IgA line the ultrastructural characteristics both of dermatitis herpetiformis and bullous pemphigoid were present, even when the histological and clinical features as well as response to sulphapyridine and sulphones were typical of dermatitis herpetiformis. The ultrastructural pattern was essentially the same as in the cases with clinical and histological characteristics of the mixed dermatitis herpetiformis-bullous pemphigoid form, although in the latter there was some predominance of the characteristics of bullous pemphigoid.  

Dermatitis herpetiformis--a skin manifestation of a generalized disturbance in immunity.

Author Davies MG; Marks R; Nuki G

Source Q J Med, 1978 Apr, 47:186, 221-48

Abstract Detailed investigations on 42 patients with dermatitis herpetiformis (DH) are presented, emphasis being placed on the presence of other disorders having a prominent immunopathogenic basis. These patients and 42 age and sex matched controls were submitted to an extensive clinical and investigative search for the presence of disorders with an immunological basis including the atopic disorders. The findings provided further evidence supporting the association of dermatitis herpetiformis with thyroid disease and pernicious anaemia. A statistically increased incidence of Raynaud's phenomenon and atopy was found in the patients with dermatitis herpetiformis compared to the control group. In addition, of the patients with dermatitis herpetiformis, two had rheumatoid arthritis, two had ulcerative colitis, one had systemic lupus erythematosus and four had splenomegaly. The possible basis for these associations is discussed and it is suggested that dermatitis herpetiformis may be part of a wider spectrum of disease. Genetic linkage and the formation of immune complexes following exposure to a dietary antigen may both be responsible for the disorders associated with DH.  

Juvenile dermatitis herpetiformis: an immunologically proven case.

Author Hertz KC; Katz SI

Source Pediatrics, 1977 Jun, 59:6, 945-8

Abstract Subepidermal blistering diseases of childhood have, in the past, been thought to represent cases of juvenile dermatitis herpetiformis, bullous pemphigoid, or benign chronic bullous dermatosis of childhood. While the small-blister variety closely resembles adult-type dermatitis herpetiformis, the large-blister, or bullous, variety has clinical and histologic resemblances to bullous pemphigoid. The patient presented in this report clearly fits previous descriptions of the large-blister type of juvenile dermatitis herpetiformis, bullous pemphigoid, or benign chronic bullous dermatosis of childhood both clinically and histologically, while his therapeutic response to dapsone and the presence of in vivo bound IgA at the basement membrane of normal and perilesional skin are highly characteristic of the adult type of dermatitis herpetiformis. Immunofluorescent studies of similar cases reported in the literature, however, have shown variable results, thus obscuring their classification. Though the proper place of all such cases in the nosology of blistering diseases is not yet clear, at least some of them closely resemble adult-type dermatitis herpetiformis by two important criteria--immunologic and therapeutic.  

The cellular infiltrate of the jejunum in adult coeliac disease and dermatitis herpetiformis following the reintroduction of dietary gluten.

Author Lancaster-Smith M; Kumar PJ; Dawson AM

Source Gut, 1975 Sep, 16:9, 683-8

Abstract The cellular infiltrate of the jejunal mucosa has been studied in patients with both treated and untreated adult coeliac disease and dermatitis herpetiformis and serially in treated patients before and after the reintroduction of gluten to the diet. In adult coeliac disease and dermatitis herpetiformis the jejunal mucosa showed similar abnormalities of the cellular infiltrate which was characterized by an increase in intraepithelial lymphocytes and lamina propria plasma cells and eosinophils, with the greatest numbers of cells occurring in untreated patients. At 24-48 hours following a single 25-g gluten challenge there was an increase in lamina propria plasma cells, lymphocytes and eosinophils and intraepithelial lymphocytes. This rise was sustained after seven days on a gluten-containing diet for all of these cell groups except lamina propria lymphocytes. These responses were essentially similar in both adult coeliac disease and in those dermatitis herpetiformis patients who had jejunal lesions before treatment. In dermatitis herpetiformis patients with normal jejunal morphology on a normal diet there was an upward trend in lamina propria plasma cells and intraepithelial lymphocytes within one to three weeks of taking extra dietary gluten. These results are compatible with the view that more than one immunological mechanism may be responsible for the pathogenesis of the jejunal lesion of coeliac disease and dermatitis herpetiformis.  

Sensitivity and specificity of IgA-class antiendomysial antibodies for dermatitis herpetiformis and findings relevant to their pathogenic significance.

Author Beutner EH; Chorzelski TP; Kumar V; Leonard J; Krasny S

Source J Am Acad Dermatol, 1986 Sep, 15:3, 464-73

Abstract The specificity and sensitivity of the recently reported IgA-class antiendomysial antibody test for gluten-sensitive enteropathy were evaluated in four double-blind studies involving the sera of fifty-seven patients with dermatitis herpetiformis who were not on a gluten-free diet and ninety-seven assorted control sera. The control sera provided by the four centers included the sera of nineteen patients with dermatitis herpetiformis and two with celiac disease who were on a gluten-free diet, the sera of five normal subjects with human lymphocyte antigens (B8 locus), the sera of thirteen patients with linear IgA bullous dermatosis, and fifty-eight other control sera, mostly from patients with other bullous diseases and other dermatoses. The frequency of IgA antiendomysial antibody in these coded studies was zero of ninety-seven control sera and thirty-four of fifty-seven sera (60%) from patients with dermatitis herpetiformis who were not on a gluten-free diet. The pathogenic role of IgA antiendomysial antibodies in dermatitis herpetiformis and celiac disease is suggested not only by their high degree of disease sensitivity and specificity but also by their formation in response to gluten challenge, their appearance before gut changes, and the in vitro binding of gliadin to the antiendomysial antibody antigen sites. These and other findings in this study and in the literature suggest that gluten-sensitive enteropathy is immunologically mediated and that IgA antiendomysial antibodies play a significant pathogenetic role.  

The site of blister formation in dermatitis herpetiformis is within the lamina lucida.

Author Smith JB; Taylor TB; Zone JJ

Address Emergency Department, Hill Hospital, Hill Air Force Base, Salt Lake City, UT.

Source J Am Acad Dermatol, 1992 Aug, 27:2 Pt 1, 209-13

Abstract BACKGROUND: Because the initial neutrophilic infiltrate in dermatitis herpetiformis is within the dermal papillae, most investigators have assumed the vesicles occur in this same area. This was supported by electron microscopy studies. In 1983 Klein et al. refuted this concept, suggesting that vesicle formation was within the lamina lucida above the lamina densa. Despite this study, current literature continues to state that blister formation is below the lamina densa. OBJECTIVE: Our purpose was to determine the ultrastructural site of blister formation in early and late vesicles of dermatitis herpetiformis. METHODS: We evaluated eight biopsy specimens from four patients by immunomapping with antibodies to bullous pemphigoid antigen, laminin, type IV collagen, and epidermolysis bullosa acquisita antigen. RESULTS: In both early and late vesicles blister formation was found to be above the lamina densa in the lamina lucida. CONCLUSION: These findings are contrary to the commonly held concept that the blister in dermatitis herpetiformis is below the lamina densa and confirm the findings of Klein et al. that the site of blister formation in dermatitis herpetiformis is above the lamina densa within the lamina lucida.

 Dermatitis herpetiformis and Sj?ren's syndrome.

Author Fraser NG; Rennie AG; Donald D

Source Br J Dermatol, 1979 Feb, 100:2, 213-5

Abstract Two patients are described with dermatitis herpetiformis and Sj?ren's syndrome. The increased incidence of autoantibodies in dermatitis herpetiformis would suggest that this association is significant. Antinuclear antibodies commonly occur in dermatitis herpetiformis (Seah et al,, 1971) yet are rarely associated with autoimmune disease in these patients (Moncada, 1974). This report records two patients with dermatitis herpetiformis and Sj?ren's syndrome. 

IgA immunoreactive deposits collocal with fibrillin immunoreactive fibers in dermatitis herpetiformis skin.

Author Dahlb?k K; Sakai L

Address Department of Dermatology, University of Lund, University Hospital, Sweden.

Source Acta Derm Venereol, 1990, 70:3, 194-8

Abstract The IgA immunoreactive granules or fibrils, characteristically found in dermal papillae of patients with dermatitis herpetiformis, were previously reported to be associated with microfibrillar bundles. Recently, fibrillin, a component of such 8-12 nm microfibrils, was identified. In normal skin, the fibrillin immunoreactive microfibrils are present at the periphery of elastic fibers and are also present without concomitant amorphous elastin in the dermal papillae close to the lamina densa. The localization of the IgA immunoreactive material in the dermal papillae of 17 patients with dermatitis herpetiformis was compared with the distribution of the fibrillin immunoreactive fiber network. Immunofluorescence methods using FITC- and TRITC-labelled antibodies, an avidin-biotin-peroxidase complex technique, and standard elastin staining procedures, were used in several sequential and double staining procedures. In 13 specimens, in which the IgA reactivity was granular, most of the granules were located at the sites of fibrillin-reactive structures. As it could not be excluded that the collocality was coincidental, it could not be ascertained whether the IgA granules were in fact related to the fibrillin immunoreactive fibers in these specimens. However, in 4 specimens with both granular and fibrillar IgA immunoreactive deposits, these were clearly related to and located at the sites of fibrillin-reactive fibrils in the dermal papillae. The results confirm earlier reports of an association of IgA reactive deposits with microfibrillar bundles in dermatitis herpetiformis skin, though the possibility of their binding to other extracellular matrix component(s) has not been ruled out. The findings suggest that fibrillin may be the structural component (or one of them) to which IgA reactive deposits bind in the skin of patients with dermatitis herpetiformis.  

Avidity of antigliadin IgA and IgG antibodies in gluten-sensitive enteropathy and dermatitis herpetiformis.

Author Vainio E; Collin P; Lehtonen OP

Source Clin Immunol Immunopathol, 1986 Nov, 41:2, 295-300

Abstract Antigliadin antibodies (AGA) of IgG and IgA class were assayed with a modified enzymeimmunoassay in serum samples of 18 patients with gluten-sensitive enteropathy and 30 patients with dermatitis herpetiformis. No difference between antibody amount or avidity of the two groups of patients was observed. Avidity and total amount of AGA were also compared in 15 patients with a recent diagnosis of dermatitis herpetiformis and in 15 patients with a disease history of several years without a proper gluten-free diet. No difference in IgG antibodies was found but the amount of high avidity IgA antibodies was significantly higher in patients with several years' experience of dermatitis herpetiformis than in those with a recent diagnosis. The results indicate that in dermatitis herpetiformis, maturation of IgA response occurs. Further, clinically, maturation of anti-gliadin IgA response during the disease can increase the sensitivity of the patient against diet-derived gliadin.

Deposition of granular IgA relative to clinical lesions in dermatitis herpetiformis.

Author Zone JJ; Meyer LJ; Petersen MJ

Address Medicine Service, Veterans Affairs Medical Center, Salt Lake City, Utah, USA.

Source Arch Dermatol, 1996 Aug, 132:8, 912-8

Abstract OBJECTIVE: To compare the deposition of IgA and C3 in the skin of patients with active dermatitis herpetiformis relative to the sites of disease. DESIGN: In the phase 1 study, skin biopsy specimens were obtained from erythematous perilesional skin, nonerythematous perilesional skin, and never-involved skin. In the phase 2 study, specimens from the nonerythematous perilesional and uninvolved skin from the same anatomic region were sampled. SETTING: The Dermatology Clinic at the University of Utah Health Sciences Center, Salt Lake City. PATIENTS: Patients with known dermatitis herpetiformis: 19 patients in the phase 1 study and 15 patients in the phase 2 study. Suppressive medications were stopped for 48 to 72 hours after biopsy specimens were obtained. All patients had active disease at the time that biopsy specimens were taken. MAIN OUTCOME MEASURE: The intensity of IgA and C3 immunofluorescent staining in 6 sections from each skin biopsy specimen was graded by using a semiquantitative scale (0 to 3+) in a blinded fashion by a single observer. RESULTS: Deposition of IgA was more intense in noninflamed perilesional skin in 11 of 19 patients compared with that in erythematous skin  

Intracorneal nuclear dust aggregates in dermatitis herpetiformis. A clue to diagnosis.

Author Williams BT; Hampton MT; Mitchell DF; Metcalf JS

Address Department of Dermatology, Medical University of South Carolina, Charleston 29425.

Source Am J Dermatopathol, 1995 Feb, 17:1, 48-52

Abstract Dermatitis herpetiformis has a characteristic histologic pattern consisting of subepidermal blisters often containing fibrin, infiltrates of neutrophils and nuclear dust at tips of dermal papillae, and papillary dermal edema. These are features of early and evolving lesions. We present two cases of clinically typical dermatitis herpetiformis with previously unreported histologic features that may provide a significant diagnostic clue. In each of these cases there were focal collections of nuclear dust in the cornified layer of the epidermis, a finding that may represent a resolving phase of dermatitis herpetiformis, beyond the usual papillary dermal neutrophilic microabscesses seen in early lesions. Biopsy material was available for immunofluorescent studies in one of the cases presented. In addition to the granular pattern of IgA positivity at the dermal-epidermal junction, which is diagnostic of dermatitis herpetiformis, this biopsy also showed similar IgA positivity in the intracorneal nuclear dust aggregates. In the second case, initial sections showed only intracorneal nuclear dust, but at deeper levels there were more typical diagnostic microabscesses at the tips of dermal papillae.

 

Dermatitis herpetiformis and thyrotoxicosis.

Author Callen JP; Weston WF; Chanda JJ

Source Int J Dermatol, 1979 Apr, 18:3, 219-21

Abstract Dermatitis herpetiformis has been associated with a variety of thyroid abnormalties. A case of thyrotoxicosis in a patient with pre-existing dermatitis herpetiformis is reported. Thyroid antibodies were present in the serum. This may suggest an immunologic relationship between dermatitis herpetiformis and thyroid disorders, that may be more than fortuitous. 

Dermatitis herpetiformis and nephrotic syndrome.

Author Gaboardi F; Perletti L; Cambi?; Mihatsch MJ

Source Clin Nephrol, 1983 Jul, 20:1, 49-51

Abstract A 6 year old girl is reported who suffered from dermatitis herpetiformis, nephrotic syndrome and celiac disease. HLA typing in our patient disclosed the HLA antigens B8 and DW3, which are known to be frequently associated with nephrotic syndrome, celiac disease and dermatitis herpetiformis. In the literature six cases have been reported of the association of glomerulonephritis and dermatitis herpetiformis. An explanation for the development of different immunological diseases in one patient is offered by the HLA type. 

Detection of gluten in human sera by an enzyme immunoassay: comparison of dermatitis herpetiformis and celiac disease patients with normal controls.

Author Lane AT; Huff JC; Weston WL

Source J Invest Dermatol, 1982 Sep, 79:3, 186-9

Abstract We have developed a triple sandwich enzyme immunoassay to detect circulating gluten in human sera. With human sera containing known amounts of added gluten as controls, the assay was sensitive in the range of 0.75 to 75 micrograms of gluten per ml of serum. Forty-one control subjects were compared to 21 patients with dermatitis herpetiformis and 11 patients with celiac disease. The dermatitis herpetiformis and celiac disease patients had significant elevation of serum gluten values over the control subjects. Circulating gluten antigenemia is a previously unrecognized feature which may be important in understanding the pathogenesis of dermatitis herpetiformis and celiac disease.  

Prevalence of duodenal and jejunal lesions in dermatitis herpetiformis.

Author Primignani M; Agape D; Ronchi G; Falsitta M; Cipolla M; Vecchi M; Torgano G; Monti M; Berti E; de Franchis R

Address Istituto di Medicina Interna, Universit?egli Studi di Milano.

Source Ric Clin Lab, 1987 Jul-Sep, 17:3, 243-9

Abstract Sixty-eight patients with dermatitis herpetiformis underwent jejunal suction biopsies and/or multiple endoscopic duodenal biopsies to evaluate the incidence of small bowel mucosal atrophy and to compare the diagnostic yield of the two methods. Small bowel function tests were also performed to evaluate the extent of functional impairment. Small bowel lesions were observed in 89.4% of jejunal suction biopsies and in 100% of endoscopic duodenal biopsies. Of the 10 patients who underwent both procedures, one had lesions only in the duodenum, one had more severe lesions in the duodenum than in the jejunum, while the remaining 8 patients showed identical lesions at both sites. The 1-h blood d-xylose test after a dose of 5 g proved more sensitive than xylosuria or serum folic acid assay in detecting subclinical malabsorption. Finally, histological features of gluten-sensitive enteropathy can be found in nearly 100% of patients with dermatitis herpetiformis. Upper gastrointestinal endoscopy with duodenal biopsies is at least as sensitive as jejunal suction biopsy in assessing small bowel involvement in dermatitis herpetiformis.

 Similarities in intestinal humoral immunity in dermatitis herpetiformis without enteropathy and in coeliac disease

Author O'Mahony S; Vestey JP; Ferguson A

Address Gastrointestinal Unit, University of Edinburgh, Western General Hospital, UK.

Source Lancet, 1990 Jun 23, 335:8704, 1487-90

Abstract Intestinal humoral immunity was examined in eight patients with dermatitis herpetiformis and normal jejunal histology (as determined by quantitative morphometry) on a gluten-containing diet. Jejunal aspirate was taken at the time of jejunal biopsy, and levels of total immunoglobulins (IgA, IgM, IgG) and specific antibody to gliadin and two other dietary proteins, betalactoglobulin and ovalbumin, were measured. The pattern of secretory immune responses in the dermatitis herpetiformis patients was similar to that in twenty-six patients with untreated coeliac disease--ie, higher than normal concentrations of IgA, IgM, and IgG and high levels of specific antibodies (IgA and IgM) to the three dietary proteins. Serum levels of IgA antigliadin were similar in the dermatitis herpetiformis and control (twenty-eight patients who underwent jejunal biopsy to exclude coeliac disease) groups, and serum levels of IgG antigliadin were intermediate between those of the control and coeliac disease groups. These findings suggest that investigation of gut humoral immunity may provide a diagnostic index of latent coeliac disease. The definition of coeliac disease as a permanent gluten-sensitive enteropathy may have to be revised if the proposed two-stage model is confirmed. 

A freeze-fracture study of the enteropathy associated with dermatitis herpetiformis: a comparative investigation with coeliac disease.

Author Contini D; Torti A; Monti M; Caputo R; Gasparini G; Vecchi M; de Franchis R

Source J Cutan Pathol, 1986 Aug, 13:4, 293-300

Abstract Jejunal biopsies from patients with either dermatitis herpetiformis or coeliac disease were freeze-fractured and compared with normal jejunal biopsies. The intestinal mucosa of the normal biopsies showed a normal structure, with well-developed and tightly packed microvilli; in dermatitis herpetiformis and coeliac disease degenerative changes of the intestinal mucosa occurred. These changes appeared to be segmental in dermatitis herpetiformis and diffuse in coeliac disease. Emphasis is placed on changes in the tight junctional net at the base of the microvilli, which could represent cellular damage related to increased intestinal permeability to macromolecules in these diseases. An interpretative hypothesis for these observations is presented.

Ultrastructural localization of immunoglobulins in skin of patients with dermatitis herpetiformis.

Author Stingl G; H?igsmann H; Holubar K; Wolff K

Source J Invest Dermatol, 1976 Oct, 67:4, 507-12

Abstract A multistep immunocytochemical method utilizing horseradish peroxidase as an immunologically bound marker was used to detect and localize IgA deposits in skin of patients with dermatitis herpetiformis at the ultrastructural level. IgA was found in the upper papillary dermis forming irregular aggregates in seemingly haphazard distribution. These aggregates were associated with microfibrillar bundles and with the microfibrillar component of the elastic tissue. IgA was also detected on anchoring fibrils, but showed no topical relationship to the basal lamina which was always spared. This finding indicates that basal lamina components do not serve as target sites for the immunologic reaction occurring in dermatitis herpetiformis. The selective affinity of IgA deposits to microbfibrillar bundles may be relevant to the hypothesis that the skin pathology in dermatitis herpetiformis is caused by circulating gluten-antigluten complexes, trapped in the skin by reticulin-bound antireticulin antibodies which cross-react with gluten. 

Immunoelectron microscopic findings in oral mucosa of patients with dermatitis herpetiformis and linear IgA disease.

Author Rantala I; Hietanen J; Soidinm?i H; Reunala T

Source Scand J Dent Res, 1985 Jun, 93:3, 243-8

Abstract Two patients with dermatitis herpetiformis and one with linear IgA disease were examined. Two of the patients had oral lesions and all three showed IgA deposits detected by direct immunofluorescence in apparently normal buccal mucosa. To localize the target structures for IgA deposition, biopsy specimens were taken from normal appearing buccal mucosa for immunoelectron microscopy. The patients with dermatitis herpetiformis had distinct IgA deposits in the upper connective tissue. These were often associated with elastic fibers and occasionally also with capillary walls. In contrast, the patient with linear IgA disease had IgA deposition at the subbasal lamina. Though the clinical expressions may be similar the present immunoelectron microscopic findings in oral mucosa clearly differentiate dermatitis herpetiformis from liner IgA disease. 

Dermatitis herpetiformis bodies.

Author K?p?i S; Meurer M; Stolz W; Schrallhammer K; Krieg T; Braun-Falco O

Address Heim P? Hospital for Children, Budapest, Hungary.

Source Arch Dermatol, 1990 Nov, 126:11, 1469-74

Abstract Skin samples from three adult patients with dermatitis herpetiformis (DH) and granular IgA deposits in the papillary tips were studied using ultrastructural immunogold technique. IgA positive, so-called DH bodies were identified as amorphous clumps--most probably immunocomplex aggregates--scattered throughout the upper papillary dermis. Dermatitis herpetiformis bodies were seen underneath the basement membrane, sometimes along microfibrillar bundles, as well as adjacent to the papillary collagen fibers and within the surface (microfibrillar) region of elastic tissue. Some DH bodies, however, were not related to any fibrillar components. The collagen and elastic fibers, microfibrillar bundles, anchoring fibrils, and elastic microfibrils themselves were unlabeled. Dermatitis herpetiformis bodies were not found in normal human skin. The results of our ultrastructural study indicate that DH bodies either are bound to a nonfibrillar component of dermal connective tissue or represent deposits of immune complexes trapped in DH skin. 

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

Author K?nai I; K?p?i S; T?? E; Bucsky P; Gy?i E

Source Eur J Pediatr, 1985 Nov, 144:4, 404-5

Abstract 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. 

Risk of lymphoma in patients with dermatitis herpetiformis.

Author Sigurgeirsson B; Agnarsson BA; Lindel? B

Address Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.

Source BMJ, 1994 Jan 1, 308:6920, 13-5

Abstract OBJECTIVE--To provide accurate estimates of the risk of lymphoma in patients with dermatitis herpetiformis. DESIGN--Comparison of observed and expected incidence of cancer in patients with dermatitis herpetiformis. SUBJECTS--976 patients aged 4 to 97 years with no clinical signs of coeliac disease who were admitted to hospital between 1963 and 1983. SETTING--Data from Swedish Cancer Registry. MAIN OUTCOME MEASURES--Incidence and type of cancer. RESULTS--106 cancers were diagnosed in 94 patients. The relative risk was 1.4 (95% confidence interval 1.1 to 1.7) in male patients and 1.2 (0.8 to 1.7) in female patients. When the individual cancer sites were analysed a significant risk was found only for malignant, non-Hodgkin's lymphoma in male patients, with a relative risk of 5.4 (2.2 to 11.1). CONCLUSIONS--The risk of lymphoma is greater in male patients with dermatitis herpetiformis, and this calls for increased surveillance in these patients. 

IgA endomysium antibody in children with dermatitis herpetiformis treated with gluten-free diet.

Author Chorzelski TP; Jablonska S; Chadzynska M; Maciejowska E; Sulej J

Source Pediatr Dermatol, 1986 Sep, 3:4, 291-4

Abstract The IgA antibody to endomysium of smooth muscle (IgA-EmA) was measured in 32 children with confirmed dermatitis herpetiformis who were eating gluten-free diets. One patient had IgA-EmA before treatment but had a negative test one month later while on the diet. Two so treated for less than one year still had antibody, but of seven children treated for more than one year with gluten-free diet, none had detectable antibody. It was present in 13 of 20 children not adhering to the prescribed diet. The antibody was absent in 4 children with linear IgA bullous dermatosis and 43 children with various skin and intestinal diseases. These findings correspond to those in adults with dermatitis herpetiformis and indicate that IgA-EmA is also a marker for gluten-sensitive enteropathy in children.  

Papular dermatitis herpetiformis. Report of a case with localized, facial lesions.

Author Komura J; Imamura S

Source Dermatologica, 1977, 155:6, 350-4

Abstract A male patient with unusual clinical features of dermatitis herpetiformis is reported. The eruption consisting mainly of erythematous papules developed symmetrically around the mouth and later around the eyes, and has been circumscribed within these areas for 4 years. The dermatitis herpetiformis nature of the lesion was confirmed by direct immunofluorescent testing. 

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

Author Reunala T; Kosnai I; Karpati S; Kuitunen P; T?? E; Savilahti E

Source Arch Dis Child, 1984 Jun, 59:6, 517-22

Abstract 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

Atopic disease and dermatitis herpetiformis.

Author Davies MG; Fifield R; Marks R

Source Br J Dermatol, 1979 Oct, 101:4, 429-34

Abstract Patients with dermatitis herpetiformis were found to have an increased incidence of atopic disorders compared to an age and sex matched control group. The increase in incidence was statistically significant for atopic eczema and any atopic disorder. Serum immunoglobulins (including IgE) were estimated in forty-five dermatitis herpetiformis patients and no significant abnormalities were found. 

Ultrastructural binding sites of endomysium antibodies from sera of patients with dermatitis herpetiformis and coeliac disease.

Author K?p?i S; Meurer M; Stolz W; B?gin-Wolff A; Braun-Falco O; Krieg T

Address Dermatology Department, Ludwig-Maximilian University, Munich, Germany.

Source Gut, 1992 Feb, 33:2, 191-3

Abstract The ultrastructural binding sites of endomysium antibodies, specific serological markers of gluten sensitive enteropathy, were investigated in the rabbit oesophagus using the immunogold technique. Endomysium antibodies from sera of patients with dermatitis herpetiformis and with coeliac disease bound in an identical manner in a non-fibrillar material closely associated with fine collagenous-reticulin fibrils and also with similar fibrils connecting smooth muscle cells and elastic tissue in the endomysial connective tissue. These observations suggest that IgA antibodies in sera from patients with dermatitis herpetiformis and coeliac disease recognise a common antigen in an amorphous component associated with the reticular connective tissue of oesophageal lamina muscularis mucosae and thus confirm the probable identity of IgA class endomysium and jejunal antibodies. 

Serum antibodies to gliadin and small-intestinal morphology in dermatitis herpetiformis. A controlled clinical study of the effect of treatment with a gluten-free diet.

Author Kilander AF; Gillberg RE; Kastrup W; Mobacken H; Nilsson LA

Source Scand J Gastroenterol, 1985 Oct, 20:8, 951-8

Abstract Serum gliadin antibodies of the IgA and IgG classes were determined by the diffusion-in-gel enzyme-linked immunosorbent assay in 41 patients with dermatitis herpetiformis before treatment with a gluten-free diet. Increased gliadin antibody levels were found more frequently in patients with subtotal villous atrophy (9 out of 17 patients, or 53%; p less than 0.05) than in patients with partial villous atrophy (2 out of 13 patients, or 15%) or normal villous appearance (2 out of 10 patients, or 20%). The gliadin antibody levels were negatively correlated with the urinary xylose excretion (r = -0.40, p less than 0.02 for the IgA class and r = -0.64, p less than 0.001 for the IgG class). Intestinal morphology improved and mean gliadin antibody levels of the IgA and IgG classes decreased during treatment with a gluten-free diet for 16-36 months (mean, 20 months) (p less than 0.005, n = 26), whereas no significant changes of the gliadin antibody levels or the small-intestinal morphology were observed in the other 15 patients, who continued on a non-restricted diet for 17-35 months (mean, 20 months). Thus, gliadin antibody levels in sera from patients with dermatitis herpetiformis seem to be correlated with the severity of the intestinal disease. However, all patients with villous atrophy are not detected by determination of serum gliadin antibodies.

 IgA anti-endomysial antibody detection in the serum of patients with dermatitis herpetiformis following gluten challenge.

Author Leonard JN; Chorzelski TP; Beutner EH; Sulej J; Griffiths CE; Kumar VJ; Fry L

Source Arch Dermatol Res, 1985, 277:5, 349-51

Abstract This study reports the appearance of IgA-class anti-endomysial antibodies in the serum of 8 out of 12 patients with dermatitis herpetiformis who were challenged with gluten after a number of years of control of the rash with a strict gluten-free diet. Although there was no evidence for the antibodies having any pathogenic role in the rash of dermatitis herpetiformis, their presence may be related to the deterioration in the gluten-sensitive enteropathy. 

Dermatitis herpetiformis: immune complex detection with C1q and monoclonal rheumatoid factor.

Author Jordon RE; Tappeiner G; Kahl JC; Wolff K

Source Br J Dermatol, 1981 Aug, 105:2, 159-65

Abstract To determine the significance of circulating immune complexes in dermatitis herpetiformis, serum samples from thirty patients with active disease were tested by a C1q binding radioassay, while serum samples from twenty-one of these patients were tested by a monoclonal rheumatoid factor (mRF) inhibition radioassay. By direct immunofluorescence, all patients demonstrated typical IgA deposition in dermal papillae. Using the C1q binding assay, only seven of forty-two serum samples had elevated C1q binding activity, while by the mRF inhibition assay, thirteen of twenty-five samples had elevated immune complex levels. Nine of these latter thirteen positive serum samples, however, were minimally elevated. Thus, IgG and/or IgM containing immune complexes are infrequently present, or at very low levels, in sera of patients with active dermatitis herpetiformis. 

Dermatitis herpetiformis: a comparative assessment of skin and bowel abnormality.

Author Cooney T; Doyle CT; Buckley D; Whelton MJ

Source J Clin Pathol, 1977 Oct, 30:10, 976-80

Abstract We reviewed 18 patients with a clinical diagnosis of dermatitis herpetiformis who were being treated with dapsone and were on an unrestricted diet. Diagnosis was confirmed by finding IgA deposits in the dermal papillae of unaffected skin. Dapsone was discontinued and biopsy of affected skin was carried out when the typical rash reappeared. The biopsy findings were graded according to the severity of the histological changes. Small bowel tissue from each patient was examined and graded by stereo- and routine microscopy. Thirteen specimens (72%) were stereomicroscopically abnormal; all 18 showed villous atrophy, either partial or subtotal; and in 13 (72%) the interepithelial lymphocyte count was increased. No correlation was found between the histological severity of the skin and the small bowel lesions. Seemingly the severity of the skin rash in dermatitis herpetiformis is no guide to the degree of small bowel abnormality. 

Thyroid abnormalities in dermatitis herpetiformis. Prevalence of clinical thyroid disease and thyroid autoantibodies.

Author Cunningham MJ; Zone JJ

Source Ann Intern Med, 1985 Feb, 102:2, 194-6

Abstract We studied thyroid abnormalities in 50 patients with dermatitis herpetiformis. Two patients had a history of hyperthyroidism, and 5 had hypothyroidism and were on thyroid replacement therapy. Three patients had had thyroidectomies for nodules, and 5 had asymptomatic goiter. Two patients were clinically euthyroid with elevated thyrotrophin and low normal thyroxine levels, indicating early thyroid insufficiency. Thyroid microsomal antibodies were seen in 38% of patients with dermatitis herpetiformis compared to 12% of controls. The presence of clinical or serologic thyroid abnormalities in 26 of 50 patients shows a significant but unexplained association between dermatitis herpetiformis and thyroid disease. 

Wheat grain immunofluorescent antibodies as an indication of gluten sensitivity?

Author Kalimo K; Vainio E

Source Br J Dermatol, 1980 Dec, 103:6, 657-61

Abstract An immunofluorescence method using whole sections of wheat grains as the substrate was applied to detect circulating antibodies to wheat gluten in dermatitis herpetiformis patients and in controls. Only IgG class antibodies were detected. From dermatitis herpetiformis patients 22% had these antibodies as had 22% of the atopic dermatitis group. Among the controls who had no skin problems 12% were faintly positive. It is evident that the test as such is non-specific and does not have diagnostic significance in dermatitis herpetiformis.

 

The role of cytokines in the generation of skin lesions in dermatitis herpetiformis.

Author Graeber M; Baker BS; Garioch JJ; Valdimarsson H; Leonard JN; Fry L

Address Department of Dermatology, St Mary's Hospital, London, U.K.

Source Br J Dermatol, 1993 Nov, 129:5, 530-2

Abstract The infiltration of polymorphonuclear neutrophils (PMN) into the upper dermis which characterizes the skin lesions of dermatitis herpetiformis (DH) has never been satisfactorily explained. This study has shown that lesional skin of patients with DH has increased expression of endothelial leukocyte adhesion molecules (ELAM) in the deep dermis, combined with a markedly increased staining for interleukin 8 (IL-8) in the basal epidermal layer. Dendritic cells which stained for granulocyte macrophage colony stimulating factor (GM-CSF) were also observed at the dermo-epidermal junction, and this phenomenon was more pronounced in lesional than in uninvolved DH skin. ELAM, IL-8 and GM-CSF are known to promote infiltration and activation of PMN, and it is suggested that these cytokines may play a key role in the generation of DH lesions.

A simple method for elution of IgA deposits from the skin of patients with dermatitis herpetiformis.

Author Jones P; Kumar V; Beutner EH; Chorzelski TP

Address Department of Oral Biology, School of Dentistry, University at Buffalo, Suny, Buffalo, NY.

Source Arch Dermatol Res, 1989, 281:6, 406-10

Abstract To better understand the role of autoimmunity in the pathogenesis of dermatitis herpetiformis, linear IgA bullous dermatosis or other skin disorders, the antigenic specificity of the immune reactants bound in vivo in the skin must be identified. In order to do so, one must first be able to elute these immune reactants from the skin. We describe here a simple method of eluting not only specifically bound IgG, but also IgA and other immunoglobulins and complement components from skin biopsy material. The method involves cutaneous washing of the entrapped serum proteins in PBS pH 7 and pH 5 buffers followed by specific immunoglobulin elutions at pH 3 and 2. The IgA deposits which could not be removed by this treatment were eluted by a combination of low pH (0.5 M citrate pH 2) and a chaotropic agent (2 M NaCl). The relative concentration of IgA in eluates when quantitated by fluoroimmunoassay were three- to five-fold higher in dermatitis herpetiformis skin biopsy specimens, than in eluates of bullous pemphigoid or normal skin biopsy specimens. 

Comparison of IgA-class reticulin and endomysium antibodies in coeliac disease and dermatitis herpetiformis

Author H?lstr? O

Address Department of Clinical Microbiology and Immunology, University Central Hospital, Tampere, Finland.

Source Gut, 1989 Sep, 30:9, 1225-32

Abstract The occurrence of IgA class reticulin and endomysium antibodies was examined with the standard immunofluorescence method in coeliac disease and dermatitis herpetiformis. Similar high antibody frequencies were detected in 32 untreated adults (91%) and 18 children (100%) with coeliac disease and in 14 dermatitis herpetiformis patients with subtotal villous atrophy (reticulin antibodies 93% and endomysium antibodies 100%). The specificity of IgA class reticulin antibodies and endomysium antibodies was high because all 45 adult patients with ulcerative colitis or Crohn's disease, 24 non-coeliac children with abdominal symptoms and 99/100 healthy blood donors were negative for these antibodies. The only positive blood donor had both IgA class reticulin antibodies and endomysium antibodies but also she was found to have coeliac disease. IgA class reticulin antibodies and endomysium antibodies declined in parallel during treatment with a gluten free diet and increased on gluten challenge. This suggests that these antibodies can be used to screen for gluten sensitive enteropathy and to monitor dietary treatment. To characterise the tissue specificity of reticulin antibodies and endomysium antibodies four positive sera were absorbed with human and several rodent liver homogenates. Absorption with rat or other rodent livers removed the rodent-specific reticulin antibodies but not the reticulin antibodies detectable with human tissues or the endomysium antibodies detectable with monkey esophagus. These results show that reticulin antibodies can be divided into the rat and human subtypes. The human subtype could not be separated from endomysium antibodies in the present absorption experiments. 

Preferential activation of CD4 T lymphocytes in the lamina propria of gluten-sensitive enteropathy.

Author Griffiths CE; Barrison IG; Leonard JN; Caun K; Valdimarsson H; Fry L

Address Department of Dermatology, St Mary's Hospital, London.

Source Clin Exp Immunol, 1988 May, 72:2, 280-3

Abstract The distribution and activation of T-lymphocyte subsets in the small intestinal mucosa of coeliac disease and dermatitis herpetiformis subjects on a normal diet has been studied and compared to normal controls. Double-labelling immunofluorescence techniques with monoclonal antibodies were used on cryostat tissue sections. Intestinal epithelial cells demonstrated staining for HLA-DR, the intensity being proportional to the degree of enteropathy. In both patients and controls nearly all (97%) intra-epithelial lymphocytes were of the CD8 subset and not activated as judged by HLA-DR expression. In the lamina propria there was an approximate 50-fold increase in T cells in the patients as compared with the controls. Whilst the ratio of total CD4 to total CD8 cells was unchanged, the CD4 subset was preferentially activated in the patients. Thus in the normal controls the median ratio of activated CD4 cells to activated CD8 cells was 1.67 whilst for dermatitis herpetiformis and coeliac disease it was 3.42 and 6.07 respectively. These findings suggest that the lamina propria is a site of vigorous T-cell activity in gluten-sensitive individuals and is consistent with the view that the enteropathy of dermatitis herpetiformis and coeliac disease is the result of a delayed-type hypersensitivity against gliadin. 

Cutaneous IgA subclasses in dermatitis herpetiformis and linear IgA disease.

Author Wojnarowska F; Delacroix D; Gengoux P

Address Slade Hospital, Oxford, England.

Source J Cutan Pathol, 1988 Oct, 15:5, 272-5

Abstract The subclasses of the cutaneous IgA were studied in 8 patients with dermatitis herpetiformis and 4 with linear IgA disease. The cutaneous IgA in dermatitis herpetiformis consisted of both IgA1 and IgA2, although IgA1 predominated. This demonstrated that the IgA is polyclonal and may be both mucosal and blood derived. The IgA in linear IgA disease was exclusively IgA1, confirming previous work, and suggesting that mucosal IgA may not make a major contribution to the skin deposits. 

Dermatitis herpetiformis associated with ulcerative colitis.

Author Lambert D; Collet E; Foucher JL; Escallier F; Dalac S

Address Department of Dermatology, Chu le Bocage, Dijon, France.

Source Clin Exp Dermatol, 1991 Nov, 16:6, 458-9

Abstract Over the past 20-years, it has been shown that the majority of patients with dermatitis herpetiformis (D.H.) suffer from coeliac disease of varying intensity. Dermatitis herpetiformis may also be associated with other autoimmune diseases but only exceptionally with chronic ulcerative colitis (U.C.).  

Lack of proliferative response by gluten-specific T cells in the blood and gut of patients with dermatitis herpetiformis.

Author Baker BS; Garioch JJ; Bokth S; Thomas H; Walker MM; Leonard JN; Fry L

Address Department of Dermatology, St Mary's Hospital, London, UK.

Source J Autoimmun, 1995 Aug, 8:4, 561-74

Abstract The majority of patients with Dermatitis Herpetiformis (DH) have a gluten-sensitive enteropathy which may be triggered by a T cell-mediated immune response to gluten. Using a proliferative assay, the responses to gluten fraction III, recall antigens and mitogens of peripheral blood mononuclear cells (PBMC) and gut T cell lines (TCL) isolated from patients with Dermatitis Herpetiformis (DH) and normal controls were studied. In most cases, neither PBMC nor gut T cell lines (which were predominantly CD3+, CD4+, TCR alpha beta +) from either controls or patients proliferated in response to gluten fraction III alone. However, the addition of 10 U/ml IL-2 to PBMC cultures containing gluten fraction III resulted in a marked increase in proliferation in 9/19 DH patients and 7/11 controls compared to IL-2 alone. Furthermore, gluten-induced upregulation of IL-2 receptor (CD25) expression was demonstrated on PBMC from 4/4 patients with DH and 2/3 controls after 7 days' culture with antigen. A similar effect by exogenous IL-2, or the same concentration of IL-4, was observed in 8/11 (P = 0.02) and 5/6 respectively DH, and 3/4 normal gut T cell lines. No difference was observed in the response of DH and control PBMC to Tetanus toxin, Candida albicans and PPD; both normal and DH gut T cell lines were unresponsive to these antigens. However, the addition of IL-2 increased the response to Candida albicans by DH gut T cell lines. Moreover, the response of DH gut T cell lines to PHA (P

Dermatitis herpetiformis and celiac disease associated with Addison's disease.

Author Reunala T; Salmi J; Karvonen J

Source Arch Dermatol, 1987 Jul, 123:7, 930-2

Abstract We treated two patients with dermatitis herpetiformis and Addison's disease, and one patient with celiac disease without the rash, but with Addison's disease and juvenile diabetes. In two of the patients, the concomitant diseases also included a thyroid disease. The predisposing factors to the multiple endocrine disorders in these patients with gluten-sensitive skin and/or small intestinal disease remained unknown. Two of the three patients had HLA-B8, none was known to have affected relatives, and the Addison's disease appeared before, at the same time, or after the patients contracted dermatitis herpetiformis or celiac disease. 

Patients with dermatitis herpetiformis, acne, psoriasis and Darier's disease have low epidermal zinc concentrations.

Author Micha?sson G; Ljunghall K

Address Department of Dermatology, University Hospital, Uppsala, Sweden.

Source Acta Derm Venereol, 1990, 70:4, 304-8

Abstract Zinc concentration was determined in epidermis, papillary dermis and serum in patients with dermatitis herpetiformis, acne or psoriasis and in two small groups of patients with ichthyosis vulgaris and Darier's disease. Except in ichthyosis vulgaris the zinc level in epidermis was decreased in all these disorders. The mean serum zinc concentration was, however, significantly decreased only in men with dermatitis herpetiformis. There was no correlation between the concentration of zinc in epidermis or dermis and that in serum. The decreased epidermal zinc concentration indicates that many of the patients have a zinc deficiency in spite of a "normal" serum zinc value. Supplementation of zinc might therefore be of value in patients with these disorders.  

T lymphocytes in lesional skin of patients with dermatitis herpetiformis.

Author Garioch JJ; Baker BS; Leonard JN; Fry L

Address Department of Dermatology, St Mary's Hospital, London, U.K.

Source Br J Dermatol, 1994 Dec, 131:6, 822-6

Abstract Ten patients with dermatitis herpetiformis had biopsies taken from involved and uninvolved skin. Monoclonal antibodies and the avidin-biotin peroxidase staining technique were used to stain for T cells and Langerhans cells in skin sections. A significant increase in the number of CD3-positive T cells was observed in the upper dermis of involved compared with uninvolved skin. 

Dermatitis herpetiformis and glomerulonephritis. Case report and review of the literature.

Author Heironimus JD; Perry EL

Source Am J Med, 1986 Mar, 80:3, 508-10

Abstract A patient who had a history of successfully treated dermatitis herpetiformis and in whom membranous glomerulopathy later developed is described. The predominant immunoglobulin present in the renal biopsy specimen was IgA. It is suggested that the dermatologic and renal diseases had a common immunologic origin. A review of the literature dealing with dermatitis herpetiformis and glomerulonephritis is included. 

Dermatitis herpetiformis cured by hormone replacement for panhypopituitarism.

Author Spitzweg C; Hofbauer LC; Heufelder AE

Address Division of Endocrinology, Medizinische Klinik, Klinikum Innenstadt Ludwig-Maximilians-University, Munich, Germany.

Source Endocr J, 1997 Jun, 44:3, 437-40

Abstract Dermatitis herpetiformis is an autoimmune skin disorder frequently associated with gastrointestinal diseases. We report a 53-year-old male with a four-year history of refractory dermatitis herpetiformis associated with hypopituitarism. Endocrine testing, ophthalmological examination and magnetic resonance imaging revealed hypopituitarism due to a non-functioning pituitary macroadenoma. Following transsphenoidal removal of the pituitary tumor and appropriate hormone replacement, complete remission of the skin disorder was obtained. We discuss the permissive role of panhypopituitarism in the course of dermatitis herpetiformis. 

Binding of wheat gliadin in vitro to reticulum in normal and dermatitis herpetiformis skin.

Author Unsworth DJ; Johnson GD; Haffenden G; Fry L; Holborow EJ

Source J Invest Dermatol, 1981 Feb, 76:2, 88-93

Abstract We have demonstrated by indirect immunofluorescence that wheat gliadin binds in vitro to reticulin-like fibrils present in cryostat sections of human skin, and rat liver, kidney and stomach. Gliadin was seen to bind to fibrils throughout the dermis of both normal and dermatitis herpetiformis skin, and this was particularly striking in the dermal papillae. Serum from 2 dermatitis herpetiformis patients who did not have antireticulin antibody gave reticulin staining when retested by immunofluorescence on cryostat sections of rat tissue pretreated with gliadin. Gliadin treated sections may prove useful in screening patients with gluten sensitive enteropathy for anti-gliadin antibody. Binding of gliadin to skin sites in dermatitis herpetiformis patients and subsequent deposition of antigliadin antibody at these sites may be involved in the development of skin lesions. 

Coeliac-type dental enamel defects in patients with dermatitis herpetiformis.

Author Aine L; M?i M; Reunala T

Address Department of Oral and Maxillofacial Surgery, University Hospital of Tampere, Finland.

Source Acta Derm Venereol, 1992, 72:1, 25-7

Abstract The teeth of 30 adult patients with dermatitis herpetiformis and 66 sex- and age-matched healthy controls were examined for dental enamel defects. Sixteen of the patients (53%) with dermatitis herpetiformis, opposed to only one (2%) of the healthy controls (p less than 0.001), were found to have coeliactype permanent-tooth enamel defects. The grades of these defects were milder than those described for severe coeliac disease. There was no correlation between the degree of enamel defects and jejunal villous atrophy. The present finding of frequent coeliactype dental enamel defects in adults with dermatitis herpetiformis suggests that these patients were already suffering from subclinical gluteninduced enteropathy in early childhood, at the time when the crowns of permanent teeth develop. 

T-cell and plasma cell populations in coeliac small intestinal mucosa in relation to dermatitis herpetiformis.

Author Jenkins D; Goodall A; Scott B

Address Department of Medicine, Lincoln County Hospital.

Source Gut, 1989 Jul, 30:7, 955-8

Abstract Differential lymphocyte and plasma cell counts and measurements of mucosal architecture were studied in small intestinal biopsies from 17 controls and 17 patients with untreated uncomplicated coeliac disease of whom five also had dermatitis herpetiformis. Intraepithelial T-cell and plasma cell counts and measurements of mucosal architecture were not significantly different in the two coeliac groups but both groups differed from the controls. Lamina propria T-cell counts were significantly higher in the patients who also had dermatitis herpetiformis than in uncomplicated coeliac disease, with a significant increase in the Leu 2 (CD8) positive (cytotoxic/suppressor) T-cell subset. This suggests a specific abnormality of T-cell control of immune responsiveness in the pathogenesis of the skin manifestations of dermatitis herpetiformis which is not found in uncomplicated coeliac disease. 

Protective effect of gluten-free diet against development of lymphoma in dermatitis herpetiformis.

Author Lewis HM; Renaula TL; Garioch JJ; Leonard JN; Fry JS; Collin P; Evans D; Fry L

Address Department of Dermatology, St. Mary's Hospital, London, UK.

Source Br J Dermatol, 1996 Sep, 135:3, 363-7

Abstract A retrospective study of 487 patients with dermatitis herpetiformis showed that lymphoma developed in eight patients, the expected incidence being 0.21 (standardized registration ratio 3810). All lymphomas occurred in patients whose dermatitis herpetiformis had been controlled without a gluten-free diet (GFD) or in those who had been treated with a GFD for less than 5 years. The results are suggestive of a protective role for a GFD against lymphoma in dermatitis herpetiformis and give further support for advising patients to adhere to a strict GFD for life. 

Increased jejunal intraepithelial lymphocytes bearing gamma/delta T-cell receptor in dermatitis herpetiformis.

Author Vecchi M; Crosti L; Berti E; Agape D; Cerri A; De Franchis R

Address Department of Internal Medicine, University of Milan, Italy.

Source Gastroenterology, 1992 May, 102:5, 1499-505

Abstract T-cell receptor 1 (gamma/delta) expression was studied in 19 jejunal or duodenal specimens from patients with dermatitis herpetiformis and in 16 jejunal or duodenal specimens showing normal histology. In normal specimens, gamma/delta+ cells represented 10.8% of intraepithelial CD3+ lymphocytes. Around 50% of these cells were recognized by the A13 monoclonal antibody, which detects products of the V gamma 1/V delta 1 gene rearrangement and the non-disulfide-linked form of T-cell receptor 1. The remaining 50% reacted with the BB3 monoclonal antibody, which recognizes products of the V gamma 9/V delta 2 rearrangement and the disulfide-linked form of receptor. Very few gamma/delta+ cells were observed in the lamina propria. In jejunal specimens from patients with dermatitis herpetiformis, a significant increase in the prevalence of gamma/delta+ intraepithelial lymphocytes was observed (P less than 0.001). This finding was largely accounted for by an increase in those cells recognized by the A13 monoclonal antibody, thus possibly expressing the V gamma 1/V delta 1 rearrangement and the nondisulfide-linked form of receptor. These data suggest that similar pathogenetic mechanisms may be active in determining the jejunal damage in celiac disease and dermatitis herpetiformis. 

Recurrent pericarditis and dermatitis herpetiformis. Evidence for immune complex deposition in the pericardium.

Author Afrasiabi R; Sirop PA; Albini SM; Rosenbaum HM; Piscatelli RL

Address Department of Medicine, St. Mary's Hospital, Waterbury, CT 06706.

Source Chest, 1990 Apr, 97:4, 1006-7

Abstract Recurrent pericarditis can be associated with many chronic illnesses. Dermatitis herpetiformis is a chronic papulovesicular eruption which is characterized by granular IgA deposits in the dermal papillary tips and associated with a gluten-sensitive enteropathy. We describe the first case of recurrent pericarditis in association with dermatitis herpetiformis. This supposition is supported by exclusion of other possible etiologies and pericardial biopsy which revealed the deposition of IgG, IgA and complement. 

Celiac disease or dermatitis herpetiformis in three patients with porphyria.

Author Mustajoki P; Vuoristo M; Reunala T

Source Dig Dis Sci, 1981 Jul, 26:7, 618-21

Abstract Celiac disease was diagnosed in one patient with variegate porphyria, and dermatitis herpetiformis in two patients, one with acute intermittent porphyria and the other with erythropoietic protoporphyria. The probability that celiac disease or dermatitis herpetiformis should occur in three patients with porphyria in Finland is less than 0.2%. Neither a consistent HLA pattern nor any other explanation can be offered for the association between these diseases.