Dermatitis herpetiformis

Dermatitis herpetiformis (DH) is a rare, and intensely itchy, chronic skin condition associated with gluten enteropathy, although few patients have significant gastrointestinal symptoms.

This chapter is set out as follows:

• It is an immunobullous condition ie a blistering eruption caused by an abnormal immunological reaction
• Up to 10% of patients have a positive family history of DH or coeliac disease (syn. gluten enteropathy)
• There is an association with thyroid and other autoimmune conditions

• Age - most commonly presents between the age of 20-55, but may arise at any age
   
• Gender - two-thirds of cases are male
   
• Skin symptoms
  • The onset can be sudden or gradual
  • Lesions are intensely itchy
  • Some patients notice a fluctuation of symptoms related to the amount of gluten (found in grains such as wheat, barley and rye) in their diet
     
• GI symptoms
  • Although 90% of patients will have associated coeliac disease only a few are symptomatic, conversely 15-25% of patients with coeliac disease develop DH
  • Symptoms include fatigue, abdominal discomfort and bloating, diarrhoea or constipation, weight loss and pale stools that float on the surface of the toilet pan 

Distribution

• Symmetrical
• Extensor surfaces of limbs (classically the knees and just below the elbows), scalp, scapula and natal cleft are characteristic. Other sites can also be affected

Morphology

• Small papules or vesicles, which are often grouped together on erythematous patches of skin 
• Blisters 1-2 cm in diameter are less common
• The intense itch of DH normally provokes vigorous scratching, which frequently destroys areas of vesicles / blisters and leaves behind erosions

• Bloods tests for coeliac disease
• IgA and tissue transglutaminase levels 
• FBC (looking for a macrocytosis secondary to folate deficiency) and ferritin levels (looking for iron deficiency. Ferritin levels can be low, even in the presence of a normal FBC) 

• Skin biopsies
• An active lesion should be removed for histology, which should reveal a sub-epidermal blister - the typical histological features are most commonly seen in the area of erythema that surrounds the central blister/excoriation
• A second biopsy, of peri-lesional skin (within 2 cm of the blister), is also required for direct immunofluorescence (DIF). The sample must be put on top of a piece of plain gauze, which has been soaked in a small amount of normal saline, and placed into a dry pot, the specimen must be examined the same day. If the sample cannot be examined the same day it must be placed in a suitable transport media eg Michel's solution, in order to preserve the sample. The result of DIF can sometimes be false negative, and if needed a further biopsy sample can be taken from unaffected skin of the buttocks or thighs 

• Investigations and gluten-free diets
  • Patients on gluten free diets (or a very much reduced gluten diet) may have normal investigations (bloods, negative DIF and normal GI investigations), as such before starting investigating patients should be on a normal diet that contains gluten (one recommendation states a diet that includes six slices of bread a day) for approximately six weeks 

Step 1: general management principles

• Provide a patient information leaflet
• Moderately potent topical steroids can provide some symptom relief  

Step 2: dapsone and other second line treatments 

• A dermatology referral is required 

• Most patients will require dapsone, which will reduce itch substantially within a few days of starting treatment

• Dapsone can occasionally cause a widespread rash, haemolytic anaemia and, rarely agranulocytosis. Such complications normally occur early. Patients need regular monitoring tests, including an FBC, reticulocyte count, U&E and LFT. Patients must report immediately if they develop a skin rash, a high temperature, a sore throat or mouth ulcers, and any unexplained bruising or bleeding. Occasionally a distal motor neuropathy occurs, this is more commonly seen in patients on higher doses of long-term dapsone therapy 

• Glucose-6-phosphate deficiency (G6PD)
• Patients with G6PD have a two-fold increase in sensitivity towards dapsone-induced haemolytic anaemia 
• Patients should be tested for G6PD deficiency prior to treatment - people of Mediterranean, African and Asian ancestry are especially at risk and can be tested for this deficiency before dapsone is prescribed

• For patients unable to tolerate dapsone, particularly those who develop haemolysis, sulfasalazine (1–2 g/d), sulfapyridine (2–4 g/d), and sulfamethoxypyridazine (0.25–1.5 g/d) are valid alternatives 

• Other less effective treatments for dermatitis herpetiformis include colchicine, prednisolone, ciclosporin and azathioprine - the latter two should be used with caution in patients with dermatitis herpetiformis because of a potential increase in the risk of developing intestinal lymphomas. Phototherapy may provide some symptomatic relief  

Step 3: refer to a gastroenterologist 

• Patients need to be investigated for the possibility of coeliac disease  

Step 4: refer to a dietician 

• For a gluten-free diet
• Adherence to a gluten-free diet has two benefits in that it:
  • lowers the risk of intestinal lymphoma, a known complication of coeliac disease
  • improves control of DH meaning that some patients only need take dapsone periodically