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Dermatitis Herpetiformis

Dermatitis herpetiformis (DH), also known as Duhring's disease, is a chronic autoimmune blistering skin condition characterised by intensely itchy blisters filled with watery fluid. It is a cutaneous manifestation of coeliac disease, although the exact causal mechanism is not fully understood. Despite its name, DH is neither related to nor caused by the herpes virus.

Characteristic rash of dermatitis herpetiformis
Characteristic rash of dermatitis herpetiformis

Epidemiology

DH typically affects individuals aged 15 to 40, but it can also appear in children and the elderly. Men are slightly more affected than women. Prevalence estimates range from 1 in 400 to 1 in 10,000, with higher rates observed in Northern European and Northern Indian populations. DH is associated with the human leukocyte antigen (HLA) haplotypes HLA-DQ2 or HLA-DQ8 and is linked to coeliac disease and gluten sensitivity.

Signs and Symptoms

Characteristic rash of dermatitis herpetiformis
Characteristic rash of dermatitis herpetiformis

Dermatitis herpetiformis rash resembles herpes and is seen on extensor surfaces such as the buttocks, back of the neck, scalp, elbows, knees, back, hairline, groyne, and face. The blisters, which vary in size from very small to 1 cm across, are extremely itchy, often causing patients to scratch them off before a physician can examine them. Intense itching or burning sensations may precede the appearance of blisters.

The symptoms tend to appear around the ages of 30 to 40, although all ages may be affected. The rash rarely occurs on mucous membranes except the mouth or lips, and symptoms range from mild to severe. These symptoms often disappear if gluten ingestion is avoided and appropriate treatment is administered. Dermatitis herpetiformis symptoms are chronic, recurring in response to gluten intake. Accompanying gastrointestinal symptoms of coeliac disease, such as abdominal pain, bloating, loose stools, weight loss, and fatigue, may also be present.

Pathophysiology

Cross-reactivity hypothesis for the onset of dermatitis herpetiformis in people with celiac disease
Cross-reactivity hypothesis for the onset of dermatitis herpetiformis in people with celiac disease

The primary autoantigen in DH is epidermal transglutaminase (eTG). Various factors, including genetics and gluten sensitivity, play roles in its development. Gliadin proteins in gluten are absorbed by the gut and modified by tissue transglutaminase (tTG), becoming more immunogenic. This leads to the activation of immune cells and the production of autoantibodies, which may cross-react with eTG in the skin, causing the lesions of dermatitis herpetiformis. IgA deposits in the dermal papillae are a hallmark of this condition.

Diagnosis

Micrograph of dermatitis herpetiformis
Micrograph of dermatitis herpetiformis

DH may be misdiagnosed as other skin conditions. A definitive diagnosis can be made via a blood test for IgA antibodies against tissue transglutaminase and a skin biopsy revealing IgA deposits in the dermal papillae. These tests should be performed before starting a gluten-free diet, as dietary changes might produce false negatives.

Treatment

First-line Therapy

A strict gluten-free diet is essential and typically lifelong. This reduces intestinal damage and the risk of complications. Dapsone is the initial drug of choice, effectively alleviating rash and itching within days. However, it does not affect intestinal damage. Long-term dapsone use requires regular blood monitoring due to potential adverse effects like hemolytic anaemia.

Alternative Treatment Options

For those intolerant to dapsone, alternatives include colchicine, lymecycline, nicotinamide, tetracycline, sulfamethoxypyridazine, and sulfapyridine. Combination therapy with nicotinamide and tetracyclines has been effective for some individuals. Topical steroids may also be used to alleviate itchiness.

Prognosis

DH generally responds well to medication and a strict gluten-free diet. However, individuals with DH are more prone to other autoimmune conditions such as thyroid disease, insulin-dependent diabetes, lupus erythematosus, and Sjögren's syndrome. The risk of non-Hodgkin lymphoma is also increased but decreases with a strict gluten-free diet.

Notable Cases

It has been suggested that French revolutionary Jean-Paul Marat had DH. Marat's painful skin disease required him to immerse himself in an herbal bath for relief, and he was assassinated in this tub, as depicted in The Death of Marat.


Self-assessment MCQs (single best answer)

Certainly! Here are the formatted multiple-choice questions based on the provided information about Dermatitis Herpetiformis (DH):

What is the primary autoantigen in Dermatitis Herpetiformis (DH)?



Which population has a higher prevalence of DH?



What is the initial drug of choice for treating DH?



Which of the following is NOT a common area for DH rash outbreaks?



Which human leukocyte antigen (HLA) haplotypes are associated with DH?



The hallmark of DH in a skin biopsy is the presence of:



What dietary change is essential for managing DH?



Which autoimmune condition is NOT commonly associated with DH?



Which symptom is NOT typically associated with DH?



In historical context, which French revolutionary is suggested to have suffered from DH?



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