S2k guidelines (consensus statement) for diagnosis and therapy of dermatitis herpetiformis initiated by the European Academy of Dermatology and Venereology (EADV).

INTRODUCTION: Dermatitis herpetiformis (DH) is a chronic, pruritic, gluten-induced skin disorder characterized by subepidermal granular IgA deposition and a variable degree of enteropathy identical to that seen in coeliac disease. So far, there has been no European consensus about the management of DH. METHODS: The guidelines were created by small subgroups of a guideline committee consisting of 26 specialists from various medical fields and one patients' representative. The members of the committee then discussed the guidelines and voted for the final version at two consensus meetings. The guidelines were developed under the support of the European Academy of Dermatology and Venereology (EADV) and in collaboration with the European Dermatology Forum (EDF). RESULTS: The guidelines summarize evidence-based and expert-based recommendations (S2 level) for the management of DH (see Appendix). CONCLUSION: These guidelines will improve the quality of management of DH and support dermatologists in their diagnostic and therapeutic decisions.

Reduced mortality in dermatitis herpetiformis: a population-based study of 476 patients.

BACKGROUND: Dermatitis herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease and most patients adhere to a life-long gluten free diet (GFD). Increased mortality rates have been reported in coeliac disease but knowledge in DH is scanty. OBJECTIVES: To survey the mortality rate and causes of death in a large cohort of patients with DH. MATERIAL AND METHODS: Patients with DH (n = 476 consecutive patients) diagnosed from 1970 onwards at the Tampere University Hospital were analysed for causes of death during 1971-2010. A questionnaire survey on key aspects of health behaviour was performed in patients with DH and comparisons were made with the Finnish population. RESULTS: The total number of deaths during 9079 person years followed up was 77 whereas 110 were expected. The standardized mortality rate (SMR) for all causes of death was significantly reduced, being 0·70 (95% CI 0·55-0·87), and similar in both sexes. The SMR was equal in the patients with DH with (0·73) and without (0·77) small bowel villous atrophy. The SMR was significantly reduced (0·38) for deaths due to cerebrovascular diseases. The SMR due to lymphoproliferative malignancies was significantly increased (6·86) in the first 5 years of follow-up but not thereafter. The questionnaire survey documented that 97·7% of the patients with DH adhered to a GFD. The patients reported significantly less hypercholesterolaemia and there were fewer current and past smokers compared with the age- and sex-matched control population. CONCLUSIONS: The present long-term follow-up study of DH documented significantly reduced all-cause and cerebrovascular disease mortality. Strict adherence to a GFD, less smoking and hypercholesterolaemia may play a role in the observed health benefit.

Prevalence and incidence of dermatitis herpetiformis: a 40-year prospective study from Finland.

BACKGROUND: Dermatitis herpetiformis (DH) is an external manifestation of coeliac disease presenting with blistering rash and pathognomonic cutaneous IgA deposits. Better knowledge of subclinical forms and serological testing has resulted in a sharp increase in the incidence and prevalence of coeliac disease. OBJECTIVES: To investigate the prevalence of DH and analyse whether the incidence of DH changed when the occurrence of coeliac disease increased. METHODS: All 477 patients with DH diagnosed from 1970 onwards at the Tampere University Hospital were analysed for prevalence in 2009. The incidence of DH was calculated in three 10-year periods from the year 1980. RESULTS: The prevalence of DH was 75·3 per 100,000 which is eight times lower than the prevalence of coeliac disease in our area. The annual incidence of DH in the whole period was 3·5 per 100,000, and in the three 10-year periods 5·2, 2·9 and 2·7 per 100,000, respectively. The decrease in incidence between the first and second 10-year period was significant (P<0·001). The male to female ratio of DH was 1·1:1. The mean age at diagnosis increased significantly during the study, in men from 35·3 to 51·1 years and in women from 36·3 to 45·8 years. CONCLUSIONS: The present study shows the highest prevalence of DH reported to date. Although the overall incidence of DH was also high, a significant decrease occurred in the 1990s, which is in contrast to the incidence of coeliac disease.

Malignancies and mortality in patients with coeliac disease and dermatitis herpetiformis: 30-year population-based study.

BACKGROUND AND AIM: To assess the long-term risks of malignant diseases and mortality in patients with coeliac disease and dermatitis herpetiformis in a centre, where the prevalence of these diseases is high. The risks have probably been overestimated, as patients with subtle forms have earlier remained undetected. PATIENTS: The study comprised 17,245 person-years of follow-up in 1147 patients. METHODS: The observed numbers of malignancies and causes of deaths were assessed, and compared to those expected, and standardised incidence ratio and standardised mortality ratio given. RESULTS: The occurrence of all malignant conditions was equal to that in the population both in coeliac disease and dermatitis herpetiformis: standardised incidence ratios of 1.2 (95% confidence intervals 0.9-1.5) and 1.0 (0.6-1.5), respectively. Five patients with coeliac disease and seven with dermatitis herpetiformis had developed non-Hodgkin lymphoma; standardised incidence ratios of 3.2 (1.0-7.5) and 6.0 (2.4-12.4), respectively. Four patients with coeliac disease and one with dermatitis herpetiformis had enteropathy-associated T-cell lymphoma, associated with inadequate dietary compliance. Mortality was increased (standardised mortality ratio 1.26; 1.00-1.55) in coeliac disease, but decreased in dermatitis herpetiformis (standardised mortality ratio 0.52; 0.36-0.72). CONCLUSION: The overall prognosis in our patients was good. Non-Hodgkin lymphoma emerged in patients with undiagnosed or poorly treated coeliac disease. The mortality rate in dermatitis herpetiformis was even lower than in the population. Our data support the early diagnosis and dietary treatment of these conditions.

Concordance of dermatitis herpetiformis and celiac disease in monozygous twins.

Celiac disease can be defined as the classical manifestation of gluten sensitivity, which primarily affects the small intestine. Gluten sensitivity has also a skin manifestation, i.e., dermatitis herpetiformis. Both diseases have a strong genetic association with HLA DQ on chromosome 6. In this study we tried to estimate how much different clinical expressions of gluten sensitivity are determined by genetic factors, and hence how feasible they are for genetic mapping; therefore, we studied all six monozygous twin pairs found among 1292 prospectively collected patients of dermatitis herpetiformis in Finland. Three of the six twin pairs were concordant for dermatitis herpetiformis and for simultaneous enteropathy, celiac disease. Two other twin pairs were partially discordant, one of each pair had dermatitis herpetiformis and celiac disease, whereas the other had solely the gut manifestation of gluten sensitivity, i.e., celiac disease. Only one pair was found to be discordant for gluten sensitivity. All the pairs had typical risk alleles for gluten sensitivity, i.e., either HLA DQ2 or DQ8. These results demonstrate that the genetic component in gluten sensitivity as broadly defined is very strong (5/6 concordant). Genetically identical individuals can have clearly distinguished phenotypes, either dermatitis herpetiformis or celiac disease, suggesting that environmental factors determine the exact phenotype of this multifactorial disease. These findings are of importance in genetic linkage analyses, which focus to only certain phenotypic properties of a complex trait.

Lymphoma in patients with dermatitis herpetiformis and their first-degree relatives.

BACKGROUND: The risk for lymphoma is increased in both dermatitis herpetiformis (DH) and in coeliac disease. The lymphoma most associated with coeliac disease is enteropathy-associated T-cell lymphoma. OBJECTIVES: To study the occurrence and type of lymphoma in a large series of patients with DH and their first-degree relatives. METHODS: The occurrence of lymphoma was studied in 1104 patients consecutively diagnosed with DH in two university hospitals during 1969-2001. A questionnaire was sent to 341 patients to examine the occurrence of lymphoma in their 1825 first-degree relatives. To analyse whether the DH patients with lymphoma had adhered to a gluten-free diet similarly to the patients without lymphoma, two age- and sex-matched patients with DH served as controls for each index case. Data on the gluten-free diet were collected from prospectively completed dietary forms and also from medical records. RESULTS: Eleven (1%) patients contracted lymphoma 2-31 years after the diagnosis of DH. Eight had B-cell-type lymphoma, two enteropathy-associated T-cell lymphoma and one remained unclassified due to missing material. Three (0.2%) of the first-degree relatives contracted lymphoma, all B-cell type. The 11 DH patients with lymphoma had adhered to a gluten-free diet significantly less strictly than the DH controls without lymphoma. CONCLUSIONS: The present study documents that patients with DH can have both B- and T-cell lymphoma. The DH patients with lymphoma had not adhered as strictly to the gluten-free diet as the control patients without lymphoma. The occurrence of lymphoma in the first-degree relatives was lower than in the patients with DH.

The occurrence of type 1 diabetes in patients with dermatitis herpetiformis and their first-degree relatives.

BACKGROUND: The increased prevalence of type 1 diabetes (T1D) is well documented in patients with coeliac disease, whereas evidence is scanty in patients with dermatitis herpetiformis (DH). OBJECTIVES: To assess the prevalence of T1D in patients with DH and their first-degree relatives, and to study how DH patients with associated T1D respond to a gluten-free diet (GFD) treatment. METHODS: A series of 1104 consecutive patients with DH was recorded and a specific questionnaire sent to 341 of these for familial disease surveillance. Sex- and age-matched patients with isolated DH served as controls in the diet treatment analysis. RESULTS: Twenty-five (2.3%) patients with DH were affected by T1D and three (3.0%) of their first-degree relatives also were affected by T1D, the frequencies being significantly higher than in the general population. Most DH patients with T1D and with isolated DH could adhere strictly to the GFD. The response was good or moderate in 84% of the DH patients with T1D and in 94% of the patients with isolated DH. CONCLUSIONS: The prevalence of T1D is increased in patients with DH and their first-degree relatives. The rash in DH patients with T1D responds to a GFD in a way similar to that seen in patients with isolated DH.

First-degree relatives are frequently affected in coeliac disease and dermatitis herpetiformis.

BACKGROUND: Coeliac disease and dermatitis herpetiformis are phenotypically distinct gluten-sensitive diseases. Coeliac disease is known to cluster in families, whereas there is little evidence for dermatitis herpetiformis and for the occurrence of both diseases in the same families. METHODS: The study group comprised 380 patients with coeliac disease and 281 patients with dermatitis herpetiformis, with a total of 3158 first-degree relatives, followed up for a mean of 14 years. The patients were questioned about affected first-degree relatives. The prevalence and incidence of biopsy-proven coeliac disease and dermatitis herpetiformis in relatives were determined. RESULTS: Seventy-three (19.2%) patients with coeliac disease and 51 (18.1%) with dermatitis herpetiformis had affected first-degree relatives. The prevalence among relatives was similar for both diseases; 4.7% and 3.9% of the relatives had coeliac disease and 0.8% and 1.5% had dermatitis herpetiformis, respectively. The disease prevalence was 7% among siblings, 4.5% among parents and 3.5% among children. The annual incidence was 3/1,000 relatives, which is 15 times higher than among the general population. Coeliac disease and dermatitis herpetiformis were mixed in several multiple-case families. CONCLUSIONS: The present long-term follow-up study of coeliac disease and dermatitis herpetiformis shows that every fifth patient can have affected first-degree relatives, and that the prevalence among relatives is 5.5%. Dermatitis herpetiformis segregates also in the families of patients with coeliac disease, and vice versa, indicating the same genetic background.