Kaisa Hervonen

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.

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.

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 3/1000 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.

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.

Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease

Abstract 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.

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).

Dermatitis herpetiformis: pathognomonic transglutaminase IgA deposits in the skin and excellent prognosis on a gluten-free diet.

Dermatitis herpetiformis (DH) is an itchy, blistering skin disease with sites of predilection at the elbows, knees and buttocks. Although DH is mostly asymptomatic, all patients exhibit small bowel villous atrophy or at least coeliac-type inflammatory changes. Deposition of immunoglobulin A (IgA) in the papillary dermis is a key diagnostic feature of DH. Epidermal transglutaminase (TG3) is the antigen for IgA deposited in the skin, and tissue transglutaminase (TG2) is the antigen for IgA deposited in the small bowel mucosa. Clinically silent, but immunologically active coeliac disease in the gut appears to result in IgA TG3 antibody complexes aggregated into DH skin. The prevalence of DH in northern Europe is high (30-75/100,000), but its incidence is decreasing, possibly due to increased recognition of subclinical coeliac disease. The rash and small bowel heal on a gluten-free diet, which is a life-long treatment. The risk of non-Hodgkins lymphoma is increased, but in patients with DH who adhere strictly to a gluten-free diet long-term prognosis is excellent.

IgA antiepidermal transglutaminase antibodies in dermatitis herpetiformis: a significant but not complete response to a gluten-free diet treatment

us to reach different depths with the lowest possible energy (i.e. selectivity). Intralesional PDT is well tolerated, effective, cheaper than systemic therapy and less invasive than surgery. In conclusion, intralesional PDT may be an effective treatment for HS that can provide lasting results. The best results are achieved in isolated fistulas, axillary, sacral and breast locations, where the majority of cases are found (Fig. 1). Multiple and interconnected fistulas require more sessions. A randomized controlled trial, including dose-finding exercises and patient-related outcome measures would be an important next step in the evaluation of this therapeutic technique. This could determine what future role intralesional PDT, either alone or in combination with other treatments, will have in the treatment of this very debilitating condition.

Dermatitis herpetiformis in children: a long-term follow-up study.

DEAR EDITOR, Dermatitis herpetiformis (DH) is an itching, blistering skin disease that typically presents with a rash on the elbows, knees and buttocks. Diagnosis is confirmed by direct immunofluorescence demonstrating granular IgA deposits in the papillary dermis. The majority of patients with DH have coeliac-type enteropathy in the small intestine, and the rash responds to a gluten-free diet (GFD). Currently, it is recognized that DH is an extraintestinal manifestation of coeliac disease, and that these two conditions occur frequently in the same families or in identical twins. Coeliac disease often appears in childhood, whereas DH seems to be rare in children. All children with DH in our prospectively collected series were followed up, and special attention was paid to the success of the GFD treatment. Eighteen children with DH were diagnosed in the period 1970–2009 (Table 1). All children presented with a classical clinical picture of DH. Two sisters with DH (patients 15 and 16; see Table 1) also had moderate atopic dermatitis, which camouflaged DH symptoms. Small bowel biopsy performed at diagnosis showed subtotal villous atrophy in nine children (50%), partial villous atrophy in seven (39%) and normal mucosa in two (11%; see Table 1). After diagnosis, all children with DH adhered to a GFD. Eleven children also received diamino-diphenyl sulfone (dapsone) to control the skin symptoms (Table 1). Dapsone was stopped in all but one child after a mean of 12 months (range 3–24) on a GFD. Long-term follow-up was performed 4–38 years after the diagnosis (Table 1). All but one of the patients with DH continued on a strict GFD. This male patient (patient 8; see Table 1), now aged 41 years, had developed psoriasis and had stopped adhering strictly to a GFD 5 years earlier. He was free of DH rash but skin immunofluorescence biopsy still revealed IgA deposits. The patient (patient 14; see Table 1) who needed dapsone treatment continuously was re-examined at the age of 22 years. He still had the DH rash and IgA deposits in the dermis; as at the time of diagnosis, small bowel biopsy showed normal mucosa. A dietician did not find any fault in this patient’s adherence to a strict GFD. Over 40 years we diagnosed 18 (3 8%) children among 476 patients with DH. The annual incidence of childhood DH is 0 56 per 100 000 population. This figure is more than six times lower than the annual incidence of adult patients with DH and about 20 times lower than the incidence of childhood coeliac disease in Finland. These figures indicate that in Finland, where the prevalence of DH is the highest reported (75 3 per 100 000 population), this disorder rarely appears in children. Two previous series – one of 76 children with DH from Italy and one of 45 children with DH from Hungary – suggest that childhood DH would be more com-

Small bowel transglutaminase 2-specific IgA deposits in dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of coeliac disease. Untreated coeliac disease patients are known to have transglutaminase 2 (TG2)-targeted IgA deposits in the small bowel mucosa. To evaluate whether similar intestinal IgA deposits are also present in DH and whether the deposits disappear with gluten-free diet, 47 untreated and 27 treated DH patients were studied. Seventy-nine percent of untreated and 41% of the treated DH patients had TG2-specific IgA deposits in the small bowel, and the presence of the deposits showed a significant association with the degree of small bowel villous atrophy (p < 0.001). Other coeliac-disease related inflammatory markers were also investigated, and the density of small bowel mucosal intraepithelial γδ(+) T cells was increased in 91% of untreated and 73% of treated DH patients. The results show that the majority of untreated DH patients have similar gluten-dependent TG2-specific IgA deposits the small bowel mucosa as coeliac disease patients.