Dermatitis Herpetiformis

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disease associated with a gluten sensitive enteropathy. It may be the initial presentation of coeliac disease but usually it presents at a rather later age.

It is sometimes called Durhing's disease.

It is unexplained why gluten sensitivity usually presents as coeliac disease in young people and DH later in life. There may be other skin disorders that are also associated with gluten sensitivity.¹

Prevalence in the UK is between 1 in 10,000 and 1 in 20,000. This is about 10 times lower than coeliac disease. It is rare in children. There is a slight male preponderance. In Glamorgan the incidence of coeliac disease, especially in adults and especially in women is rising but there is no change in the incidence of DH.²

• It occurs more frequently in those of Northern European ancestry and is rare in those of Asian or African origin. Certain HLA types are more common.
• Onset is usually 2nd to 4th decade.
• It is associated with IgA antibody formation and gluten sensitive enteropathy but 90% have no gastrointestinal symptoms.
• NSAIDs may exacerbate the disease but ibuprofen appears to be safe.
• Iodides may start or exacerbate the disease.

Symptoms

• Skin lesions are extremely itchy and groups of vesicles appear most frequently on extensor surfaces. There is burning, stinging, and intense pruritus, often before new lesions appear.
• Less than 10% of patients have bloating, diarrhoea, or symptoms of malabsorption although 20 to 30% have iron or folate deficiency.

Signs

• Erythematous vesicles appear in a typical pattern. They are symmetrical over the extensor surfaces including elbows, knees, buttocks, shoulders, and the nuchal area.
• Erythematous papules and plaques of urticaria occur less frequently whilst bullae are rare.
• There may be crusts or erosions if there are no vesicles.
• Patients often complain of stinging or burning of the skin before the appearance of new lesions.
• Oral mucosa is uncommonly involved.
• Palms and soles are usually unaffected.
• It is a chronic disease, although periods of exacerbation and remission occur.

• Erythema Multiforme
• Herpes Gestationalis
• Linear IgA Dermatosis
• Eczema
• Neurotic excoriations
• Papular urticaria
• Scabies.

• Biopsy is required for diagnosis. Simple light microscopy is inadequate and direct immunofluorescence is necessary to confirm the diagnosis.
• Biopsies for direct immunofluorescence should include normal skin³ around the lesion as neutrophils may degrade the IgA in active lesions. Granular IgA deposits in dermal papillae of perilesional skin, observed by direct immunofluorescence are the "gold standard" of diagnosis.
• Endomysial antibodies are commoner in DH than other bullous diseases⁴ but are not completely specific. Similar IgA antibodies⁵ are also found in coeliac disease.
• Iron or folate is deficient in 20 to 30% of patients.
• Endoscopy is not performed as a routine in the absence of gastrointestinal symptoms but two thirds are said to have villous atrophy.

• Coeliac disease.
• Patients with DH are also more likely to suffer from dermatomyositis, type 1 diabetes, myasthenia gravis, rheumatoid arthritis, Sjogren's disease, systemic lupus erythematosis, thyroid abnormalities, gastric atrophy, pernicious anaemia, lymphoma of the gut and non-Hodgkin's lymphoma.

• About 80% will show improvement with a gluten-free diet and some will be able to stop medication but it may take 6 to 12 months before this can be done. The degree of benefit is dependent upon the strictness of the diet. It will also aid any gastrointestinal problems. Those who do not respond fully may still need less medication.
• There may be other adverse influences in the diet and elemental diets⁶ have been better than gluten free.

Drugs

• Dapsone and sulfapyridine are the drugs most commonly used. Improvement with dapsone is rapid but the response is not diagnostic as other diseases respond too.
• Dapsone is usually first line with sulfapyridine for patients unable to tolerate dapsone. Improvement with dapsone may be dramatic with benefit apparent within a few hours. No new lesions form for up to 2 days after a dose of dapsone but it does not improve the pathology of the intestinal mucosal.
• Dapsone often has a dramatic effect on the skin but it does not improve pathology in the gut.
• Less effective treatments include colchicine, cyclosporine, and prednisolone. Cyclosporine should be used with caution in patients with DH because of a potential increase in intestinal lymphoma.
• For an adult the dose of dapsone is between 25 and 400mg a day but the usual dose is 50mg twice daily. If there is severe anaemia this should be treated before starting dapsone. With G6PD deficiency there is risk of haemolysis. Problems with dapsone are commoner in DH than other conditions such as leprosy because higher doses are used. Adverse events occur in up to 20% of patients. The commonest are nausea, vomiting, headache, weakness, dizziness, fatigue, and nervousness. There is often a 1 to 2g drop in haemoglobin because of reduced erythrocyte survival time. This is most likely with doses above 100mg daily. Methaemoglobin may occur, especially in older or younger patients.
• Sulfapyridine may be better tolerated in older patients, especially with cardiopulmonary problems, and patients who do not tolerate dapsone. Haemolysis and methaemoglobinemia are less of a problem than with dapsone.

As with other forms of gluten sensitive enteropathies there is an increased risk of lymphoma of the small intestine and non-Hodgkin's lymphoma. The latter seems more prevalent in male patients.⁷ The risk of lymphoma or other cancers is statistically significant but the numbers seem small and may be falling,⁸ possibly due to better compliance with diet. There is rather more data about lymphoma and coeliac disease than with DH but the former is 10 times more common. There does appear to be an increased risk of lymphoma in patients with DH, especially those who are more lax about their diet. There is also a lower risk, but higher than the general population, in first degree relatives.⁹

It is a chronic disease but adherence to a strict gluten-free diet should keep it suppressed.¹⁰

People with coeliac disease have modest increases in overall risks of malignancy and mortality. Most of this excess risk occurs in the year after diagnosis. Presumably, malignancy was initiated before the introduction of the diet. People with coeliac disease also have a significantly reduced risk of breast cancer. The mechanism of this merits further attention as it may provide insights into the cause of this common malignancy.¹¹