Cases Of Dermatitis Herpetiformis Research Articles

Diagnostic Utility of Direct Immunofluorescence on Paraffin-Embedded Skin Biopsy Samples for the Diagnosis of Autoimmune Vesiculobullous Lesions.

Background Autoimmune vesiculobullous diseases (AIBDs) are a group of diseases characterized by blisters of the skin/mucosa due to the presence of circulating autoantibodies against antigens in the epidermis or the dermo-epidermal junction. Direct immunofluorescence (DIF) for immunoglobulin (Ig)G, IgC3, and IgA on fresh-frozen tissue is the gold standard diagnostic test for AIBDs. However, DIF in the absence of frozen tissue is challenging for the diagnosis of AIBDs. This study aimed to analyze the practical utility of DIF using paraffin-embedded skin biopsy rather than fresh frozen tissue for the diagnosis of AIBDs. Methodology This cross-sectional comparative study included 30 cases of AIBDs. DIF for IgG and IgA was performed on paraffin-embedded tissue (PE-DIF) after proteinase digestion on histopathologically confirmed 15 pemphigus vulgaris (PV), three pemphigus foliaceous (PF), four bullous pemphigoid (BP), three dermatitis herpetiformis (DH), three subcorneal pustular dermatosis (SCPD), and one case each of linear IgA disease and pemphigoid gestationis (PG). PE-DIF staining pattern was compared with the DIF on fresh frozen tissue (FF-DIF). Results All cases of PV and PF showed an intercellular IgG chicken wire staining pattern similar to FF-DIF. However, background staining was more intense in PV cases while less intense in PF cases. Three BP cases showed linear IgG staining in PE-DIF. DH, SCPD, linear IgA disease, and PG cases did not show IgG positivity. Out of three DH cases, two cases showed granular IgA positivity while linear IgA positivity along the basement membrane was seen in a single case of linear IgA disease. Negative IgG staining was observed in SCPD. Immunofluorescence in PE-DIF was rapidly deteriorating than in FF-DIF. Conclusions DIF done on paraffin-embedded tissue can be used as a supplement and salvage technique with histopathology for the diagnosis of AIBDs,particularly when a cryostat facility for frozen tissue is not available and the patient is unable to undergo a second biopsy procedure.

Mast cells and thymic stromal lymphopoietin (TSLP) expression positively correlates with pruritus intensity in dermatitis herpetiformis.

Pruritus is one of the leading symptoms of dermatitis herpetiformis (DH), however, studies on the pathogenesis of pruritus are scarce. Currently, skin mast cells (MCs) have been indicated to play a role in pruritus in autoimmune bullous disease. To study the role of mast cells and related mediators involved in the pathogenesis of pruritus in DH. The number of MCs and expression of histamine and thymic stromal lymphopoietin (TSLP) was investigated in lesions of 29 DH cases and 15 healthy skin donors by immunohistochemistry. Fourteen patients were assessed for severity of pruritus based on the Numeric Rating Scale and Pruritus Grading System. The levels of histamine and TSLP in the serum of 18 DH patients and 15 healthy controls were also investigated. A significant increase in the number of MCs and degranulation was observed in DH lesions, which positively correlated with intensity of pruritus. In addition, skin TSLP but not histamine was shown to correlate with intensity of pruritus. No significant difference in expression of serum TSLP or histamine was observed between DH patients and healthy controls. These results suggest that skin MCs and TSLP might be involved in the pathogenesis of pruritus in DH which should be further clarified in future studies.

The utility of tissue and epidermal transglutaminase immunohistochemistry in dermatitis herpetiformis

Dermatitis herpetiformis (DH), also known as Duhring-Brocq dermatitis, is an autoimmune, chronic subepidermal blistering disorder characterized by an intensely pruritic, papulovesicular eruption. It is linked to gluten sensitivity and considered to be a cutaneous manifestation of celiac disease. It has been demonstrated that sera from most patients with DH demonstrate autoantibodies against epidermal transglutaminase (eTG) and tissue transglutaminase (tTG). Therefore, the aim of the study was to evaluate the diagnostic utility of eTG and tTG immunohistochemistry in identifying patients with DH. A total of 15 skin biopsies from patients with an established diagnosis of DH confirmed by histopathology and direct immunofluorescence (DIF) studies were evaluated. Six cases were used as controls in which the clinical differential included DH and were found to be nondiagnostic by both histopathology and DIF evaluations. Eight (55%) of the DH cases were positive for eTG expression, while none of the controls showed any immunoreactivity (P = 0.0456). All 15 (100%) DH cases showed faint granular staining for tTG in the epidermal basal layers with similar results in all 6 (100%) control cases. Our study indicates eTG immunohistochemistry may aid in identifying patients with DH, with a diagnostic sensitivity and specificity of 55% and 100%, respectively. tTG does not appear to be a useful immunomarker in this setting.

Declining trend in the incidence of biopsy-verified coeliac disease in the adult population of Finland, 2005-2014.

The frequency of coeliac disease (CD) has been on the rise over the past decades, especially in Western Europe, but current trends are unclear. To research the recent temporal changes in the incidence of adult, biopsy-verified coeliac disease and dermatitis herpetiformis (DH) in Finland, a country with a high frequency of coeliac disease. All coeliac disease and DH cases diagnosed at age 20-79 years during 2005-2014 were retrieved from a nationwide database documenting all applicants for monthly compensation to cover the extra cost of maintaining a gluten-free diet. This benefit is granted on the basis of histology, not socioeconomic status. Temporal trends in the annual incidences were estimated using Poisson regression analyses. The total incidence of coeliac disease decreased from 33/100 000 during the years 2005-2006 to 29/100 000 during 2013-2014. The mean annual incidence of coeliac disease was nearly twice as high among women as among men, 42 vs 22 per 100 000, respectively. For middle- and old-aged women, the average rate of decrease in incidence was 4.8% (95% CI 3.9-5.7) per year and for men 3.0% (1.8-4.1) (P for linear trend <.001, for both). Similarly, the annual incidence of DH declined. For young adults, the rate of change remained low and nonsignificant throughout the period 2005-2014. Although the awareness of coeliac disease has increased during the past decades, the incidence of biopsy-verified diagnoses is not increasing, which suggests that exposure to yet unidentified triggering factors for coeliac disease has plateaued among the Finnish adult population.

Utility of Direct Immunofluorescence Studies in Subclassification of Autoimmune Sub-Epidermal Bullous Diseases: A 2-Year Study in a Tertiary Care Hospital.

Sub-epidermal bullous disorders belong to immunobullous diseases which develop as a result of autoantibody action against epidermal basement membrane proteins. Clinically, they are tense bullae and do not rupture easily. They are classified into various forms based on histopathology and direct immunofluorescence patterns. This study was undertaken to assess the incidence of various sub-epidermal bullous disorders and the utility of direct immunofluorescence in accurately classifying them, and to study the intensity and pattern of immunofluorescence in various sub-epidermal bullous disorders Material and Method: A 2-year study of 38 cases of sub-epidermal bullous disorders sent for direct immunofluorescence studies formed the study group. The specimens were processed as per standard protocols. The clinical details were obtained from case files and requisition sent for histopathological and direct immunofluorescence studies. Thirty-eight patients were diagnosed to have sub-epidermal bullous disorders over the period of 2 years. Twenty five cases of Bullous Pemphigoid, 5 cases of Dermatitis Herpetiformis, 3 cases of Linear IgA Bullous disorder, 2 cases of Bullous Systemic Lupus Erythematoses and 1 case each of Epidermolysis Bullosa Acquisita, Cicatricial Pemphigoid and Pemphigus Gestationis was diagnosed. Positive direct immunofluorescence was seen in 91.3% of the cases. Histopathology alone cannot classify sub-epidermal bullous disorders and direct immunofluorescence studies are mandatory in all of them. Bullous Pemphigoid needs to be distinguished from Epidermolysis Bullosa Acquisita which requires Salt split direct immunofluorescence studies. Dermatitis Herpetiformis, Bullous Systemic Lupus Erythematosus and Linear IgA Bullous disorder show more or less similar histological picture with neutrophilic microabscess. Direct immunofluorescence studies help in the majority of cases but further testing such as immunoblotting, immunoelectron microscopy or indirect immunofluorescence becomes essential in cases with overlapping features.

Dermatitis Herpetiformis Refractory to Gluten-free Dietary Treatment

Dermatitis herpetiformis (DH) is a blistering skin disease, which is regarded as an extra-intestinal manifestation of coeliac disease. Refractory cases of coeliac disease, that do not respond to a gluten-free diet and which carry an increased risk of lymphoma, are well-known in coeliac disease. To determine whether refractory cases of DH with active rash and persistent small bowel atrophy occur we analysed our series of 403 patients with DH. Seven (1.7%) patients, who had been on a gluten-free diet for a mean of 16 years, but who still required dapsone to treat the symptoms of DH, were identified. Of these, one patient died from mucinous adenocarcinoma before re-examination. At re-examination skin immunoglobulin A (IgA) deposits were found in 5/6 refractory and 3/16 control DH patients with good dietary response. Small bowel mucosa was studied at re-examination from 5 refractory and 8 control DH patients and was normal in all 5 refractory and 7/8 control DH patients. One refractory DH patient died from adenocarcinoma, but no lymphoma developed in any of the patients. This study documents for the first time refractory DH, in which the rash is non-responsive to a gluten-free diet, but the small bowel mucosa heals. This differs from refractory coeliac disease, in which the small bowel mucosa does not heal on a gluten-free diet.

Utility of direct immunofluorescence testing for IgA in patients with high and low clinical suspicion for dermatitis herpetiformis.

The purpose of this study was to examine the utility of direct immunofluorescence (DIF) testing for the characteristic immunoglobulin A deposits of dermatitis herpetiformis (DH) in patients stratified into high and low clinical suspicion subgroups. We retrospectively analyzed the results of H&E and DIF testing in 77 cases of suspected DH and separated them into high and low clinical suspicion subgroups based on clinical impression at the time of biopsy. The overall sensitivity and specificity of routine (H&E) histologic evaluation were 0.75 and 0.951, respectively. Although there were 13 cases of DH (of 36 total cases) in the high clinical suspicion subgroup, there were only three (of 41 total cases) in the low clinical suspicion subgroup. In the high clinical suspicion subgroup, the positive predictive value (PPV) was 0.9, and the negative predictive value (NPV) was 0.846. Alternatively, the PPV was 0.6 and the NPV was 1.0 for the low clinical suspicion subgroup. Histologic false negatives did occur, but all were in patients within the high clinical suspicion subgroup. It is anticipated that the NPV and PPV will vary due to differing clinical practice characteristics; however, in patients with a low clinical suspicion for DH, these data argue that it may be reasonable to first perform a biopsy for routine histologic evaluation before requesting DIF analysis.

Incidence and Prevalence of Celiac Disease and Dermatitis Herpetiformis in the UK Over Two Decades: Population-Based Study

OBJECTIVES:Few studies have quantified the incidence and prevalence of celiac disease (CD) and dermatitis herpetiformis (DH) nationally and regionally by time and age groups. Understanding this epidemiology is crucial for hypothesizing about causes and quantifying the burden of disease.METHODS:Patients with CD or DH were identified in the Clinical Practice Research Datalink between 1990 and 2011. Incidence rates and prevalence were calculated by age, sex, year, and region of residence. Incidence rate ratios (IRR) adjusted for age, sex, and region were calculated with Poisson regression.RESULTS:A total of 9,087 incident cases of CD and 809 incident cases of DH were identified. Between 1990 and 2011, the incidence rate of CD increased from 5.2 per 100,000 (95% confidence interval (CI), 3.8–6.8) to 19.1 per 100,000 person-years (95% CI, 17.8–20.5; IRR, 3.6; 95% CI, 2.7–4.8). The incidence of DH decreased over the same time period from 1.8 per 100,000 to 0.8 per 100,000 person-years (average annual IRR, 0.96; 95% CI, 0.94–0.97). The absolute incidence of CD per 100,000 person-years ranged from 22.3 in Northern Ireland to 10 in London. There were large regional variations in prevalence for CD but not DH.CONCLUSIONS:We found a fourfold increase in the incidence of CD in the United Kingdom over 22 years, with large regional variations in prevalence. This contrasted with a 4% annual decrease in the incidence of DH, with minimal regional variations in prevalence. These contrasts could reflect differences in diagnosis between CD (serological diagnosis and case finding) and DH (symptomatic presentation) or the possibility that diagnosing and treating CD prevents the development of DH.

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

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

Novel Advances in Dermatitis Herpetiformis

Dermatitis herpetiformis (DH) is an inflammatory cutaneous disease with a chronic-relapsing course that presents with pruritic polymorphic lesions mainly distributed in typical areas such as the extensor aspects of the limbs, the sacral region, and the buttocks. There is growing evidence that DH should be considered the specific phenotypic cutaneous expression of a gluten-sensitive enteropathy indistinguishable from celiac disease (CD). Histologically, DH is characterized by subepidermal blister and accumulation of neutrophils and very few eosinophils at the dermal papillae, while the typical immunopathological finding consists in granular IgA deposits along the basement membrane zone, mainly localized at the papillary tips. Recent studies demonstrated that such IgA are directed against epidermal transglutaminase. However, in the last years, several papers from the literature reported the presence of atypical findings in patients with DH, suggesting that the features described previously probably need a significant revision and leaving many critical points that should be investigated further in the near future. In the present issue, the recent advances of clinical, pathogenetic, and therapeutic aspects of DH will be addressed. About the clinical presentation, an increasing number of papers have recently described uncommon features in patients with DH, as reviewed in the present issue by V. C. Bonciolini et al. Accordingly, Ohata et al. in their paper reported 91 Japanese DH cases showing atypical distribution of the lesions and, interestingly, showed that only two of the eight patients (25%) with DH were biopsied in their case series exhibited histopathological signs of CD. However, patients with DH may present the widest spectrum of histological findings of enteropathy, ranging from normal-appearing epithelium to a flat mucosa; moreover, patients with DH significantly increased the frequency of chronic atrophic gastritis than healthy controls, as demonstrated by A. Alakoski et al. in this issue. From a pathogenetic point of view, the presence of a subepidermal cleft with neutrophilic infiltration at the tips of dermal papillae has been considered the histopathologic hallmark of DH, suggesting a major role for neutrophil granulocytes in the pathogenesis of the skin lesions, as described by D. Bonciani et al. and K. Nakajima in this issue. Besides neutrophils, another cell type has been suggested as a major actor in the pathogenesis of DH, namely, CD4+ T cells. The presence of such cells, with a cytokine expression pattern belonging to the Th2 phenotype, has been documented in recent DH skin lesions as well as in the perilesional skin, suggesting their role in the early phases of DH skin inflammation. Moreover, in this issue, Z. Agnieszka et al. focused the attention on apoptosis, a physiological process that has been shown to play a role in several autoimmune diseases. Finally, in the present issue, A. Fasano reviewed novel therapeutic approaches for DH. Since DH is considered the specific cutaneous manifestation of CD, besides the symptomatic therapies often used in DH patients to control the skin flares at least in the first phases (i.e., dapsone), gluten-free diet (GFD) is still regarded as the only curative approach to the disease. However, a GFD is very hard to comply with, and different approaches are still under investigations. In conclusion, some of the more recent advances in DH are presented in this issue. DH is a complex disease, where the skin represents a clue for the identification of a gluten-sensitive enteropathy. The knowledge of the different clinical and immunopathological features of the disease as well as the understanding of its pathogenesis may lead to a better care of our patients.

Spectrum of subepidermal immunobullous disorders seen at the National Skin Centre, Singapore: a 2-year review

The subepidermal immunobullous disorders (SEIBDs) comprise bullous pemphigoid (BP), cicatricial pemphigoid (CP), epidermolysis bullosa acquisita (EBA), linear IgA disease (LAD), dermatitis herpetiformis (DH), pemphigoid gestationis (PG) and bullous systemic lupus erythematosus (BSLE). They are thought to be rarer in the Far East than in western Europe. This 2-year retrospective study investigates the spectrum seen at our centre and the minimum estimated incidence of each. A total of 67 patients seen at the National Skin Centre (NSC), Singapore between January 1998 and December 1999 were diagnosed as having an SEIBD. Fifty-nine (88%) had BP, four (6%) had EBA, two (3%) LAD and two (3%) BSLE. There were no cases of CP, DH or PG diagnosed during this period. The minimum estimated incidence in our local population was 7.6, 0.5, 0.26 and 0.26 per million population per year, respectively. The mean age of onset was 77, 68, 65 and 31 years, respectively. BP is the commonest SEIBD seen locally, with an incidence at least equal to that in western Europe. It is diagnosed at our centre three times more frequently than pemphigus. There is a predilection for ethnic Chinese but not Indian. EBA is twice as common as in western Europe and shows a predilection for ethnic Indians. LAD is rare here compared to China, despite the predominant Chinese population. BSLE is also rare. In contrast to western Europe, CP, DH and PG are very rare in Singapore. This is the first study from this region to show that certain SEIBDs are not rarer in the Far East, as previously thought.

Characterization of a Subgroup of Patients With Dermatitis Herpetiformis With Nonclassical Histologic Features.

Dermatitis herpetiformis (DH) is an autoimmune disease mediated by IgA antibodies. The diagnosis of DH is based on clinical presentation, biopsy for hematoxylin and eosin, and direct immunofluorescence. The chief hematoxylin and eosin finding is a subepithelial blister with neutrophils in dermal papillae. The direct immunofluorescence findings are deposition of IgA and sometimes C3 at the basement membrane with accentuation in dermal papillae. Immunofluorescence is thought to be a sensitive and specific assay in DH, and there are no other known diseases with this pattern of immunofluorescence. The aim of this project was to determine the prevalence of nonclassical histologic findings in DH. We studied 24 cases of DH received at our institution. All cases had clinical findings of DH as well as positive direct immunofluorescence with IgA. We found that 9 of 24 cases (37.5%) had nonspecific H&E findings of a lymphocytic infiltrate only with fibrosis in the dermal papillae and ectatic capillaries. The remaining 15 cases had classic findings of multilocular neutrophilic microabscesses in the dermal papillae. These findings were reproduced on step sectioning. These findings suggest that routine histology may be quite nonspecific in DH and direct immunofluorescence or other more specific immunologic assay is an essential adjunct to diagnosis.

Tissue transglutaminase and endomysial antibodies-diagnostic markers of gluten-sensitive enteropathy in dermatitis herpetiformis.

The association of Durhing's disease, commonly referred to as dermatitis herpetiformis (DH), with gluten-sensitive enteropathy (GSE) is supported by the presence of villous atrophy and endomysial antibodies (EMA). EMA are found to be a marker of GSE both in celiac disease (CD) and in DH. Since tissue transglutaminase (tTG) is believed to be the major autoantigen in GSE, the aim of our study was to determine the specificity and sensitivity of anti-tTG antibody ELISA compared to the EMA indirect immunofluorescence test. We studied 44 cases of DH, confirmed by the presence of IgA immune deposits in the dermal papillae, and 58 cases of CD conforming to the International Criteria of Diagnosing CD. The control group comprised 161 sera from patients with vesiculobullous disorders other than DH and 106 sera from normal healthy blood donors. Anti-tTG antibodies were detected in 36 of 44 DH (79%) and in 32 of 58 CD (55%) patients. EMA were positive in 33 of 44 DH (74%) and in 36 of 58 CD (62%) patients. Both the EMA and the antibodies to tTG were present in the majority of patients with DH and CD when they were on a normal gluten-containing diet and were absent when on a gluten-free diet for an extended period of time. There were, however, small discrepancies in positivity and negativity in tTG antibody-positive and EMA-negative patients and vice versa. There seems to be a correlation between the EMA titers and the anti-tTG antibody levels. This study confirms the high specificity and sensitivity of anti-tTG antibody ELISA for GSE and its strong correlation with EMA both in CD and in DH. The results of anti-tTG antibody and EMA assays were comparable; however, in DH, tTG was somewhat more sensitive than the EMA test. For screening of DH, it is advisable to perform both EMA and anti-tTG antibody tests.

A case of dermatitis herpetiformis with IgA endomysial antibodies but negative direct immunofluorescent findings

A patient with clinical findings of dermatitis herpetiformis (DH), negative direct immunofluorescent (DIF) findings for junctional IgA deposits in 2 biopsy specimens, and positive for IgA endomysial (AEmA) and tissue transglutaminase (tTG) antibodies responded initially to dapsone. After dapsone had to be discontinued because of side effects, a gluten-free diet and supportive therapy controlled the disease; the AEmA and tTG antibodies became negative. Our data on 10 consecutive DH cases examined by DIF and by serum studies for AEmA and antibodies to tTG, point to frequencies of 90% DIF positive and 70% AEmA and tTG positive cases. The use of both DIF and serum tests for AEmA and tTG reveals DH cases not detected by DIF alone that respond to gluten-free diet. Findings on autoantibodies to tTG, an enzyme that metabolizes gliadin, points to a role of tTG in the immunopathology of gluten-sensitive enteropathy and helps to explain the need for a gluten-free diet in the management of DH cases. (J Am Acad Dermatol 2000;43:329-32.)

A case of dermatitis herpetiformis with IgA endomysial antibodies but negative direct immunofluorescent findings

A patient with clinical findings of dermatitis herpetiformis (DH), negative direct immunofluorescent (DIF) findings for junctional IgA deposits in 2 biopsy specimens, and positive for IgA endomysial (AEmA) and tissue transglutaminase (tTG) antibodies responded initially to dapsone. After dapsone had to be discontinued because of side effects, a gluten-free diet and supportive therapy controlled the disease; the AEmA and tTG antibodies became negative. Our data on 10 consecutive DH cases examined by DIF and by serum studies for AEmA and antibodies to tTG, point to frequencies of 90% DIF positive and 70% AEmA and tTG positive cases. The use of both DIF and serum tests for AEmA and tTG reveals DH cases not detected by DIF alone that respond to gluten-free diet. Findings on autoantibodies to tTG, an enzyme that metabolizes gliadin, points to a role of tTG in the immunopathology of gluten-sensitive enteropathy and helps to explain the need for a gluten-free diet in the management of DH cases. (J Am Acad Dermatol 2000;43:329-32.)

Fibrillar IgA deposition may be associated with atypical dermatitis herpetiformis – a report of two cases

AbstractWe report two cases of known dermatitis herpetiformis (DM) who presented with atypical clinical dermatological features. The first case, a 31‐year‐old woman, presented with an itchy urticated eruption on the abdomen and trunk, while the second case, a 50‐year‐old woman developed a scaly psoriasiform eruption on the extensor aspects of her knees and elbows. In each case, direct immunofluorescence of a perilesional skin biopsy showed a fibrillar pattern of IgA deposition at the basement membrane zone. Pre‐embedding immunoelectron microscopy of these 2 specimens, using a 1 nm gold probe and silver enhancement, showed colloid gold panicle deposition around microfibril bundles in the dermal papillae. Recent studies have shown that fibrillin, a 350 kDa glycoprotein, is also associated with these microfibril bundles.Serological tissue typing in our first case confirmed the presence of HLA‐B8. B18. DR3 and DQw2 antigens consistent with dermatitis herpetiformis. In the second case, there was a notable absence of the antigens B17 and B27 typically found in psoriasis but HLA‐AI, BX and DQ1 antigens were present, as commonly seen in dermatitis herpetiformis. Our findings would suggest that cases of dermatitis herpetiformis with fibrillar IgA deposition at the BMZ on direct IMF may show an atypical clinical presentation. In addition, our imunoelectron microscopy findings may provide a further clue to an ultrastructural abnormality in this disease.

Fibrillar IgA deposition may be associated with atypical dermatitis herpetiformis — a report of two cases

We report two cases of known dermatitis herpetiformis (DH) who presented with atypical clinical dermatological features. The first case, a 31-year-old woman, presented with an itchy urticated eruption on the abdomen and trunk, while the second case, a 50-year-old woman developed a scaly psoriasiform eruption on the extensor aspects of her knees and elbows. In each case, direct immunofluorescence of a perilesional skin biopsy showed a fibrillar pattern of IgA deposition at the basement membrane zone. Pre-embedding immunoelectron microscopy of these 2 specimens, using a 1 nm gold probe and silver enhancement, showed colloid gold particle deposition around microfibril bundles in the dermal papillae. Recent studies have shown that fibrillin, a 350 kDa glycoprotein, is also associated with these microfibril bundles.Serological tissue typing in our first case confirmed the presence of HLA-B8, B18, DR3 and DQw2 antigens consistent with dermatitis herpetiformis. In the second case, there was a notable absence of the antigens B17 and B27 typically found in psoriasis but HLA-A1, B8 and DQ1 antigens were present, as commonly seen in dermatitis herpetiformis. Our findings would suggest that cases of dermatitis herpetiformis with fibrillar IgA deposition at the BMZ on direct IMF may show an atypical clinical presentation. In addition, our imunoelectron microscopy findings may provide a further clue to an ultrastructural abnormality in this disease.

Diagnosis of Dermatitis Herpetiformis by an Avidin-Biotin-Peroxidase Method

Immunofluorescence detection of stippled IgA in dermal papillae has been considered the gold standard in the diagnosis of dermatitis herpetiformis (DH). We have developed an immunohistochemical technique using the avidin-biotin-peroxidase complex that is equally effective as direct immunofluorescence in detecting IgA. We retrospectively studied 43 paraffin-embedded biopsy specimens obtained from patients with DH and a variety of other diseases for the presence of IgA along the basement membrane zone. Eleven immunofluorescence-proved cases of DH were found positive for IgA with the avidin-biotin-peroxidase method. One biopsy specimen originally classified as DH was identified and reclassified as linear IgA bullous disease based on the immunoperoxidase findings. All the samples that were positive on direct immunofluorescence were positive with the avidin-biotin-peroxidase method. Control samples of bullous pemphigoid, discoid lupus erythematosus, pemphigus vulgaris, and dermatitis were all negative for IgA deposition. The diagnosis of DH on formalin-fixed tissue is possible with the use of an avidin-biotin-peroxidase method, which is convenient and cost-effective.

Correlation between IgA antiendomysial antibodies and subtotal villous atrophy in dermatitis herpetiformis.

Serum IgA antiendomysial antibodies (EmA) were present in 20 (64.5%) of 31 patients with dermatitis herpetiformis (DH) on a normal diet. A significant correlation was found between these antibodies and the severity of gluten-induced jejunum damage. IgA EmA were positive in 19 (86%) of the 22 DH patients with subtotal villous atrophy, in comparison with the positivity of only one (11%) of the nine DH patients with less severe intestinal involvement (partial villous atrophy or mild abnormalities). The specificity of this test for gluten-sensitive enteropathy was 100%, these antibodies being consistently negative in biopsied disease controls showing a normal jejunal mucosa. Moreover, IgA EmA proved to be useful in monitoring the response to gluten withdrawal in DH patients, as these antibodies always disappeared in all the DH cases studied after 1 year of gluten-free diet together with the regrowth of jejunal villi. The strict relationship between IgA EmA and subtotal villous atrophy is more helpful still since the enteropathy present in DH is usually symptomless and therefore difficult to suspect.

Location of basement membrane Type IV collagen beneath subepidermal bullous diseases

Using standard immunohistochemical methods, routinely processed sections, and a polyclonal antibody to Type IV collagen, we have determined the location of Type IV collagen, a substance located in the lamina densa of basement membrane, in a spectrum of acquired subepidermal bullous diseases. Type IV collagen was attached to the blister roof in five cases of well-established epidermolysis bullosa acquisita and to the blister base in 25 cases of bullous pemphigoid, four cases of dermatitis herpetiformis and 12 cases of porphyria cutanea tarda. Immunohistochemical localization of Type IV collagen in epidermal-dermal basement membrane is a simple, rapid and reliable technique which can be utilized to exclude and possibly to confirm the diagnosis of epidermolysis bullosa acquisita in routinely fixed paraffin-embedded tissues.