Sex-differences in Gluten-free Dietary Adherence and Clinical Symptoms in Patients with Long-term Treated Dermatitis Herpetiformis.

Dermatitis herpetiformis is a blistering autoimmune skin disease, and a cutaneous manifestation of coeliac disease. The burden of coeliac disease is increased especially in females, but studies concerning sex differences in patients with long-term treated dermatitis herpetiformis are scarce. This questionnaire study compared adherence to a gluten-free diet, clinical symptoms and well-being between females and males in a cohort of 237 long-term treated (median 24 years) patients with dermatitis herpetiformis. Females had better adherence to a gluten-free diet (p = 0.022) and they used dapsone significantly less often at the time of the study than did males (4% vs 13%, p = 0.017). The occurrence of skin symptoms was equal in both sexes, but dermatological quality of life was lower in females (p = 0.024), and gastrointestinal symptoms were more severe among females with dermatitis herpetiformis than among males (p = 0.027). In conclusion, long-term treated female patients with dermatitis herpetiformis have better adherence to a gluten-free diet, but they also experience more severe clinical symptoms compared with males.

Persistent Skin Symptoms after Diagnosis and on a Long-term Gluten-free Diet in Dermatitis Herpetiformis.

Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease treated with a gluten-free diet. However, the itching and blistering rash alleviates slowly after gluten withdrawal and occasionally persists despite a long-term gluten-free diet. This study investigated the prevalence and factors associated with prolonged (i.e. >2 years) and ongoing skin symptoms in 237 patients with dermatitis herpetiformis. Data were gathered from medical records and via questionnaires. Among patients with dermatitis herpetiformis, 38% had prolonged symptoms after diagnosis, and 14% had ongoing skin symptoms at follow-up (median duration of gluten-free diet 24 years). A severe rash at diagnosis was associated with both prolonged and ongoing cutaneous symptoms. In addition, patients with dermatitis herpetiformis with ongoing skin symptoms at follow-up had been on the dietary treatment for a shorter time (median duration 16 vs 25 years) and were less often on a strict diet (53% vs 78%) compared with patients with dermatitis herpetiformis without ongoing skin symptoms.

Anaemia in Dermatitis Herpetiformis: Prevalence and Associated Factors at Diagnosis and One-year Follow-up.

Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease. Anaemia is a common finding in patients with untreated coeliac disease, but little is known about the occurrence of anaemia in those with dermatitis herpetiformis. This study investigated the prevalence of anaemia and factors associated with anaemia in 250 patients with dermatitis herpetiformis, at diagnosis and one year after diagnosis. As controls, 139 patients with coeliac disease were included. Patient records were reviewed to gather baseline clinical, histological, and laboratory data. Follow-up data for patients with dermatitis herpetiformis were collected from patient records and via questionnaires or at follow-up visits. The prevalence of anaemia was 12% in patients with dermatitis herpetiformis and 17% in patients with coeliac disease at diagnosis (p = 0.257). Anaemia in patients with dermatitis herpetiformis was not associated with the severity of skin symptoms or small bowel damage. The prevalence of anaemia at a 1-year follow-up had increased to 19%, but it was associated mainly with dapsone treatment.

The Long-Term Safety and Quality of Life Effects of Oats in Dermatitis Herpetiformis.

The treatment of choice for dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is a life-long gluten-free diet (GFD). In a GFD, wheat, rye and barley should be strictly avoided, but the role of oats is more controversial. This study aimed to investigate the safety and long-term quality of life and health effects of oat consumption in 312 long-term treated DH patients. Baseline data were gathered from patient records and follow-up data from questionnaires or interviews, and validated questionnaires were used to assess quality of life. We found that altogether 256 patients (82%) were consuming oats as part of their GFD at the follow-up. Long-term follow-up data showed that there were no differences in the presence of long-term illnesses, coeliac disease complications or the usage of medication between those consuming and not consuming oats. However, oat consumers had a better quality of life and reported ongoing gastrointestinal symptoms less frequently (4% vs 19%, p = 0.004) at the follow-up than those not consuming oats. The study established that oats are safe for DH patients and in the long-term seem to improve the quality of life of DH patients.

Intestinal TG3- and TG2-Specific Plasma Cell Responses in Dermatitis Herpetiformis Patients Undergoing a Gluten Challenge.

Dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is characterized by transglutaminase (TG) 3-targeted dermal immunoglobulin A (IgA) deposits. The treatment for DH is the same as for coeliac disease, namely a life-long gluten-free diet. DH patients typically have gluten-dependent circulating autoantibodies targeting TG3 and TG2, and plasma cells secreting such autoantibodies have been detected in the small intestinal mucosa. This study investigates the gluten-responsiveness of intestinal TG3 and TG2 antibody-secreting plasma cells in 16 treated DH patients undergoing a gluten challenge. The frequency of both plasma cell populations increased significantly during the challenge, and their frequency correlated with the corresponding serum autoantibody levels at post-challenge. TG3-specific plasma cells were absent in all 18 untreated coeliac disease patients and seven non-coeliac control subjects on gluten-containing diets. These findings indicate that, in DH, both intestinal TG3- and TG2-antibody secreting plasma cells are gluten-dependent, and that TG3-antibody secreting plasma cells are DH-specific.

Gluten Challenge Induces Skin and Small Bowel Relapse in Long-Term Gluten-Free Diet-Treated Dermatitis Herpetiformis.

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of celiac disease causing an itchy, blistering rash. Granular IgA deposits in the skin are pathognomonic for DH, and the treatment of choice is a lifelong gluten-free diet (GFD). Preliminary evidence suggests that there are patients with DH who redevelop gluten tolerance after adherence to a GFD treatment. To evaluate this, we performed a 12-month gluten challenge with skin and small-bowel mucosal biopsy samples in 19 patients with DH who had adhered to a GFD for a mean of 23 years. Prechallenge biopsy was negative for skin IgA and transglutaminase 3 deposits in 16 patients (84%) and indicated normal villous height-to-crypt depth ratios in the small bowel mucosa in all 19 patients. The gluten challenge caused a relapse of the rash in 15 patients (79%) in a mean of 5.6 months; of these 15 patients, 13 had skin IgA and transglutaminase 3 deposits, and 12 had small-bowel villous atrophy. In addition, three patients without rash or immune deposits in the skin developed villous atrophy, whereas one patient persisted without any signs of relapse. In conclusion, 95% of the patients with DH were unable to tolerate gluten even after long-term adherence to a GFD. Therefore, lifelong GFD treatment remains justified in all patients with DH.

Prognosis of Dermatitis Herpetiformis Patients with and without Villous Atrophy at Diagnosis.

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. At diagnosis, the majority of patients have villous atrophy in the small bowel mucosa. The objective of this study was to investigate whether the presence or absence of villous atrophy at diagnosis affects the long-term prognosis of DH. Data were gathered from the patient records of 352 DH and 248 coeliac disease patients, and follow-up data via questionnaires from 181 DH and 128 coeliac disease patients on a gluten-free diet (GFD). Of the DH patients, 72% had villous atrophy when DH was diagnosed, and these patients were significantly younger at diagnosis compared to those with normal small bowel mucosa (37 vs. 54 years, p < 0.001). Clinical recovery on a GFD did not differ significantly between the DH groups, nor did current adherence to a GFD, the presence of long-term illnesses, coeliac disease-related complications or gastrointestinal symptoms, or quality of life. By contrast, the coeliac disease controls had more often osteopenia/osteoporosis, thyroid diseases, malignancies and current gastrointestinal symptoms compared to the DH patients. In conclusion, villous atrophy at the time of DH diagnosis does not have an impact on the clinical recovery or long-term general health of DH patients.

Self-Reported Fractures in Dermatitis Herpetiformis Compared to Coeliac Disease.

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased bone fracture risk is known to associate with coeliac disease, but this has been only scantly studied in DH. In this study, self-reported fractures and fracture-associated factors in DH were investigated and compared to coeliac disease. Altogether, 222 DH patients and 129 coeliac disease-suffering controls were enrolled in this study. The Disease Related Questionnaire and the Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires were mailed to participants; 45 out of 222 (20%) DH patients and 35 out of 129 (27%) of the coeliac disease controls had experienced at least one fracture (p = 0.140). The cumulative lifetime fracture incidence did not differ between DH and coeliac disease patients, but the cumulative incidence of fractures after diagnosis was statistically significantly higher in females with coeliac disease compared to females with DH. The DH patients and the coeliac disease controls with fractures reported more severe reflux symptoms compared to those without, and they also more frequently used proton-pump inhibitor medication. To conclude, the self-reported lifetime bone fracture risk is equal for DH and coeliac disease. After diagnosis, females with coeliac disease have a higher fracture risk than females with DH.

Diagnostic Delay in Dermatitis Herpetiformis in a High-prevalence Area.

Dermatitis herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease. The highest currently reported prevalence of DH is in Finland, but knowledge of diagnostic delay is limited. This study investigated the duration of rash prior to diagnosis in 446 patients with DH, analysing the results in 3 periods of 15 years. The diagnosis was considered delayed when the duration of rash before diagnosis was 2 years or longer. Factors associated with delayed diagnosis were analysed. Within the 45 years, the median duration of rash before diagnosis decreased significantly, from 12.0 to 8.0 months (p?=?0.002) and the occurrence of a delayed diagnosis decreased from 47% to 25% (p?=?0.002). Female sex, the presence of villous atrophy, and a diagnosis of DH before the year 2000 were significantly associated with delayed diagnosis. In conclusion, the present study showed that one-quarter of patients currently have a diagnostic delay of 2 years or more, which is far from ideal.

The Decreasing Prevalence of Severe Villous Atrophy in Dermatitis Herpetiformis: A 45-Year Experience in 393 Patients.

GOALS: We analyzed from our prospectively collected series of patients with dermatitis herpetiformis (DH) whether small-bowel histologic findings are changing and how serum tissue transglutaminase (TG2) IgA antibodies correlate to mucosal damage. BACKGROUND: DH is an extraintestinal manifestation of celiac disease presenting with itchy blistering rash and pathognomonic IgA deposits in the skin. Prominent gastrointestinal symptoms are rare, and small-bowel findings range from severe villous atrophy (SVA) and partial villous atrophy (PVA) to normal mucosa with inflammatory changes. METHODS: The cohort included 393 patients (214 male and 179 female) with DH having small-bowel biopsies performed at Tampere University Hospital since 1970. The small-bowel findings were calculated in the three 15-year periods, and in the last period they were correlated with serum IgA class TG2 antibody levels measured by enzyme-linked immunosorbent assay. RESULTS: The prevalence of SVA decreased significantly (P=0.032), from 42% in the first study period to 29% in the last study period. A concomitant increase was seen in PVA, from 33% to 41%, and normal villous architecture, from 25% to 30%. The patients with SVA (P<0.001) and PVA (P=0.046) had significantly higher TG2 antibody levels than those with normal villous architecture. CONCLUSIONS: This long-term study in patients with DH disclosed a significant decrease in the occurrence of SVA. Serum IgA TG2 antibody levels correlated to damage in the small bowel. The trend toward milder small-bowel histology in DH suggests that a similar pattern could occur in the pool of undiagnosed celiac disease from which DH develops.