Significant improvement of dermatitis herpetiformis with tofacitinib.

Dermatitis herpetiformis (DH) is a rare autoimmune blistering disorder in which patients with celiac disease, a gluten-sensitive enteropathy, present with a severely pruritic papulovesicular eruption over extensor surfaces such as the knees, elbows, lower back, buttocks, and neck. Patients are instructed to adhere to a gluten-free diet for purposes of improving their skin disease and gluten-sensitive enteropathy; this is the only treatment that lowers risk of enteropathy-associated T cell lymphoma. Patients who adhere to a strict gluten-free diet often have remission of their skin disease over months to years. Dapsone is a rapid and extremely effective first-line treatment option and often used while transitioning to a gluten-free diet. Aside from gluten-free diet and dapsone, second-line treatment options include sulfapyridine, sulfasalazine, and colchicine. Some patients have difficulty adhering to a gluten-free diet or develop intolerable side effects to systemic therapies. Furthermore, there is limited data on the use of the second-line treatments. Recent studies have shed light on the role of JAK-STAT-dependent pathways in the pathogenesis of dermatitis herpetiformis. We present a patient treated with tofacitinib, 5mg twice daily, an oral JAK1/3 inhibitor, who demonstrated clinical improvement of DH and control of new lesion development.

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.

Dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease (CD), which causes an itching and blistering rash, typically on the elbows, knees and buttocks. DH and CD share a similar genetic background, small bowel mucosal alterations, and an autoimmune response against tissue transglutaminase in the serum and small bowel. DH is typically diagnosed during adulthood, and it is slightly more common among males than females. The incidence of DH seems to be decreasing, in contrast to the detected four-fold increase in the incidence of CD. In addition to typical clinical picture, diagnosis of DH relies on the demonstration by direct immunofluorescence of pathognomonic granular IgA deposits in the papillary dermis. Circulating tissue transglutaminase antibodies support the diagnosis, but their absence does not exclude DH. Obtainment of small bowel mucosal biopsies is not necessary when DH is diagnosed, but if performed, the majority of patients are found to have villous atrophy, and even those with normal villous architecture evince CD-type inflammation. The treatment of choice in DH is a strict, life-long adherence to a gluten-free diet (GFD). In addition to alleviating the symptoms of DH and healing the small bowel mucosal damage, a GFD increases the quality of life for patients, and decreases the risk for lymphoma in DH. Further, the mortality rate of patients with DH treated with a GFD seems to be lower than that of the general population. However, as changing to a GFD has a rather slow effect on the DH rash, patients with severe skin symptoms should additionally be treated with dapsone medication. This review article is based on a presentation given at the British Society for Medical Dermatology blistering skin diseases meeting 2019.

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.

[Dermatitis herpetiformis]. / Dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is a genetically determined, gluten sensitive autoimmune bullous dermatosis related to celiac disease in which granular, insoluble aggregates in the papillary dermis of epidermal transglutaminase (TG3), immunoglobulin A (IgA), and fibrinogen are present. Detection of the dermal IgA-TG3 immune complex is the gold standard of diagnosis. DH develops in a subpopulation of patients with gluten sensitive enteropathy, characterized by itching, erythematous, excoriated papules showing characteristic distribution over the knees, elbows and buttocks; vesicles are rarely seen. The primary therapy of DH is a strict, lifelong gluten-free diet, and it may be necessary to temporarily give dapsone in case of severe symptoms.

Dermatitis Herpetiformis: A Common Extraintestinal Manifestation of Coeliac Disease.

Dermatitis herpetiformis (DH) is a common extraintestinal manifestation of coeliac disease presenting with itchy papules and vesicles on the elbows, knees, and buttocks. Overt gastrointestinal symptoms are rare. Diagnosis of DH is easily confirmed by immunofluorescence biopsy showing pathognomonic granular immunoglobulin A (IgA) deposits in the papillary dermis. A valid hypothesis for the immunopathogenesis of DH is that it starts from latent or manifest coeliac disease in the gut and evolves into an immune complex deposition of high avidity IgA epidermal transglutaminase (TG3) antibodies, together with the TG3 enzyme, in the papillary dermis. The mean age at DH diagnosis has increased significantly in recent decades and presently is 40⁻50 years. The DH to coeliac disease prevalence ratio is 1:8 in Finland and the United Kingdom (U.K.). The annual DH incidence rate, currently 2.7 per 100,000 in Finland and 0.8 per 100,000 in the U.K., is decreasing, whereas the reverse is true for coeliac disease. The long-term prognosis of DH patients on a gluten-free diet is excellent, with the mortality rate being even lower than for the general population.

A retrospective study of dermatitis herpetiformis from an immunobullous disease clinic in north India.

BACKGROUND: Indian data on dermatitis herpetiformis (DH) is not available. The aim of this study was to investigate the demographic and clinicopathological characteristics of patients with DH and to study its association with other autoimmune diseases. METHODS: All data were collected from case record forms of patients registered in immunobullous disease clinic of our institute. The diagnosis was based on characteristic clinical and immuno/histopathological features. RESULTS: A total of 65 patients were included, which constituted 9.47% of the registered patients in the immunobullous disease clinic over 3.5 years. The male to female ratio was 1.4 : 1; the average age was 44.35 ± 15.52 years. Direct immunofluorescence showed granular IgA deposits at the papillary tips in 83.07% and basement membrane zone in 12.3% patients. Sixteen (24.1%) patients had associated celiac disease, and 15 (23.07%) patients had other autoimmune comorbidities such as hypothyroidism. Forty percent of patients on strict gluten-free diet achieved remission in 2 years, while 35.4% had frequent relapses as they continued gluten intake. CONCLUSIONS: Dermatitis herpetiformis is not a rare disease in northern India as previously believed. The clinical, histological, and immunopathological characteristics of Indian DH patients are similar to those reported in Caucasian populations. The limitations of our study include an absence of genetic testing for HLA-DQ2 or DQ8, nonavailability of kits for detecting IgA specific for epidermal transglutaminase (IgA eTG), and short follow-up period.

Gastrointestinal Symptoms Increase the Burden of Illness in Dermatitis Herpetiformis: A Prospective Study.

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of coeliac disease. The burden of illness in untreated coeliac disease is known to be considerable, but corresponding evidence for DH is lacking. In this study the burden of DH was evaluated prospectively in 52 patients newly diagnosed with DH using a study questionnaire and a validated Psychological General Well-Being (PGWB) questionnaire. The PGWB scores were compared with those of 110 healthy controls. Quality of life was significantly (p < 0.001) lower among patients with DH at the time of diagnosis, but after 1 year on a gluten-free diet their quality of life was at same level as that of the controls. The presence of gastrointestinal symptoms was shown to significantly increase the burden of untreated DH. We conclude that there is a significant burden related to untreated, but not to treated, DH, and the burden is even greater among DH patients with gastrointestinal symptoms.

Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease.

Dermatitis herpetiformis (DH) is an itchy blistering skin disease with predilection sites on elbows, knees, and buttocks. Diagnosis is confirmed by showing granular immunoglobulin A deposits in perilesional skin. DH is one manifestation of coeliac disease; the skin symptoms heal with gluten free diet (GFD) and relapse on gluten challenge. Of the first-degree relatives, 5% may be affected by either condition. Tissue transglutaminase (TG2) is the autoantigen in coeliac disease and epidermal transglutaminase (TG3) in DH. Both diseases conditions exhibit TG2-specific autoantibodies in serum and small bowel mucosa; patients with DH have IgA-TG3 in the skin. There are some divergencies between these two phenotypes. One-fourth of DH patients do not have small bowel mucosal villous atrophy, but virtually all have coeliac-type inflammatory changes. The skin symptoms respond slowly to GFD. The incidence of coeliac disease is increasing, whereas the opposite is true for DH. A female predominance is evident in coeliac disease, while DH may be more common in males. Coeliac disease carries the risk of small intestinal T-cell lymphoma; in DH B-cell lymphomas at any site may prevail. Adult coeliac disease carries a slightly increased elevated mortality risk, whereas in DH, the relative mortality rate is significantly decreased. Key messages Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease; both conditions are genetically determined and gluten-dependent. Gastrointestinal symptoms and the degree of villous atrophy are less obvious in dermatitis herpetiformis than in coeliac disease. Both show tissue transglutaminase (TG2) specific autoantibodies in serum and small bowel mucosa. In addition, TG3-targeted IgA antibodies are found in the skin of DH patients Both conditions carry an increased elevated risk of lymphoma, in coeliac disease small intestinal T-cell lymphoma, in dermatitis herpetiformis mainly B-cell lymphoma at various sites. Coeliac disease is currently eight times more common that DH; the incidence of DH is decreasing in contrast to that of coeliac disease, where it is increasing.

Nutritional therapy - Facing the gap between coeliac disease and gluten-free food.

The market of gluten-free bakery products is considerably growing since better diagnostic methods allow identifying an increasing number of people suffering coeliac disease and other gluten-related disorders such as dermatitis herpetiformis, gluten ataxia, wheat allergy and non-coeliac gluten sensitivity. The only and safe treatment available nowadays for these types of disorders is to follow a strict and permanent lifelong gluten-free diet. Beside the people needing to follow a gluten-free diet for health reasons, a new segment of consumers has arisen who consume gluten-free products as a lifestyle choice. Among the bakery products, bread is a major staple food consumed daily all over the world. The dough and bread quality characteristics (such as gas retaining ability, mixing tolerance, resistance to stretch and extensibility and crumb structure) are mostly attributed to the presence of gluten. Despite the improved quality of gluten-free breads in the last number of years, most products on the market are still described as low quality product. In addition to the low overall quality of gluten-free products, the nutritional value of a large number of them is quite poor. In this context, this review gives an overview on the consumers, which need to follow a gluten-free diet for health reasons. The trends in this gluten-free bakery segment will also be reviewed based on the current analysis of marketing studies. An overview of the major ingredients used in gluten-free bread products will be given. The choice of the ingredients discussed in this paper is based on a comprehensive study of the leading gluten-free breads available on the market, as well as a detailed study of the scientific literature. The impact of the various ingredients on bread-making process and bread quality is also part of this review. Major emphasis will be placed on the application of sourdough as a means to improve gluten-free bread quality.

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.