Dermatitis herpetiformis

What is dermatitis herpetiformis?

Dermatitis herpetiformis (DH) is a rare but persistent immunobullous disease that has been linked to coeliac disease (American spelling celiac), a gluten-sensitive enteropathy.

The name herpetiformis is derived from the tendency for blisters to appear in clusters, resembling herpes simplex. However, DH is not due to viral infection.

DH is also known as Duhring-Brocq disease.

Who gets dermatitis herpetiformis?

• DH predominantly affects Caucasians aged 15–40 years, but may occur in those younger or older and in other races.
• There is a 2:1 male-to-female ratio.
• More females under the age of 20 are affected than males.
• There is a genetic predisposition and association with human leukocyte antigens (HLAs) DQ2 and DQ8.
• Some patients have a personal or family history of other autoimmune disorders including thyroid disease, pernicious anaemia, type 1 diabetes, vitiligo, Addison disease and alopecia areata.

What causes dermatitis herpetiformis?

• DH and coeliac disease are due to intolerance to the gliadin fraction of gluten found in wheat, rye and barley.
• Gluten triggers production of IgA antibodies and an autoimmune process that targets the skin and gut.
• In coeliac disease, gluten causes intestinal inflammation resulting in diarrhoea, tiredness, weight loss and abdominal discomfort.
• The majority (> 90%) of patients with DH also have gluten-sensitive enteropathy. Gastrointestinal symptoms may be mild to severe; some patients remain symptom-free.
• Around 15–25% coeliac patients have concurrent DH. These patients tend to have a more severe intestinal pathology in comparison to those with mainly DH.

What are the clinical features of dermatitis herpetiformis?

• DH has a symmetrical distribution.
• Lesions most commonly appear on scalp, shoulders, buttocks, elbows and knees.
• It is characterised by prurigo (extremely itchy papules) and vesicles on normal or reddened skin.
• They often appear in groups or serpiginous clusters.
• Blisters are often eroded and crusted due to immediate scratching.
• DH may also present initially as digital petechiae.
• Flat red patches, thickened plaques and wheals may occur resembling other inflammatory skin conditions such as dermatitis, scabies and papular urticaria.
• Lesions resolve to leave postinflammatory hypopigmentation and hyperpigmentation.

What are the complications of DH and coeliac disease?

The following conditions may affect patients with DH, especially when it is associated with coeliac disease:

• Aphthous ulcers and angular cheilitis
• Dry skin, nail and hair abnormalities
• Dental problems: thin enamel
• Neurological problems: ataxia (loss of balance), polyneuropathy, epilepsy
• Heart problems: pericarditis and cardiomyopathy
• Recurrent miscarriages (spontaneous abortion)
• Fatty liver resulting in abnormal liver function
• *Non-Hodgkin lymphoma (NHL) affecting the intestines or any part of the body

*The risk of NHL is increased among DH patients. Strict adherence to gluten-free diet reduces this rare but serious long-term complication.

How is dermatitis herpetiformis diagnosed?

Skin biopsy

Skin biopsy is usually necessary to confirm DH. Characteristic histological appearances of DH are:

• Subepidermal blisters
• Neutrophil and eosinophil inflammatory cells in dermal papillae
• Granular IgA deposits in the dermal papillae on direct immunofluorescence

Screen for nutritional deficiencies

Patients with DH are commonly offered the same blood tests used for patients with coeliac disease to screen for nutritional deficiencies. These include:

• Full blood count, liver function tests and serum calcium
• Iron, vitamin B12 and folate
• Thyroid function tests

Mild anaemia may be caused by iron or folic acid deficiency (or both) due to malabsorption associated with gluten-sensitive enteropathy. Thyroid function tests are usually recommended due to the association between DH and thyroid disease.

Diagnostic blood tests

Specific autoantibody tests for DH are:

• IgA anti-endomysial antibodies
• IgA tissue transglutaminase antibody, tTG
• *IgA epidermal transglutaminase antibodies, eTG (when available)
• IgA and IgG deamidated gliadin peptide antibody, dGP
• IgA and IgG gliadin assay
• Total IgA level

*DH is associated with IgA antibodies directed against epidermal transglutaminase (eTG), which is not the case in coeliac disease.

Borderline results may be difficult to interpret.

Small intestinal biopsy

• DH patients with abnormal blood results usually proceed to have small intestinal biopsy to confirm gluten-sensitive enteropathy.
• This is histologically characterised by small bowel villous atrophy. This means that instead of being highly convoluted, the lining of the intestines is smooth and flattened.
• The bowel may appear normal because of treatment (gluten-free diet and/or medication), skip lesions (the sample was taken from an unaffected site) or the intestine may be unaffected by the disease.

Other tests

HLA haplotype, a set of DNA variations, testing may reveal HLA-DQ2 or HLA-DQ8. This is present in almost all patients with DH (and coeliac disease).

What is the treatment for dermatitis herpetiformis?

Gluten-free diet

Gluten-free diet for life is strongly recommended in patients with DH, as it:

• Reduces the requirement for medication to control DH
• Improves associated gluten-sensitive enteropathy
• Enhances nutrition and bone density
• May reduce the risk of developing other autoimmune conditions
• May reduce the risk of intestinal lymphoma

Medication

Dapsone is the treatment of choice for DH, as it usually reduces itch within 3 days.

• Dose varies from 25 mg to 300 mg daily
• Dapsone has potential side effects and monitoring requirements
• It may be gradually weaned off in those who have been on a stable gluten-free diet

If intolerant or allergic to dapsone, the following may be useful:

• Ultra-potent topical steroids
• Systemic steroids
• Sulfapyridine (not available in New Zealand)
• Rituximab

What is the outcome for dermatitis herpetiformis?

DH usually has good prognosis, with the majority of patients responding well to a strict gluten-free diet and medication. The response rate varies between individuals (days to years).