Dermatitis herpetiform

This extremely itchy condition is a chronic subepidermal vesicular condition in which the herpes simplex-like vesicles erupt at the dermo-epidermal junction. 

• Persistent immunobullous disease
• Linked to coeliac disease
• Blisters are in clusters – (hence herpetic)

Who Gets Dermatitis Herpetiformis?

• Prevalence: 10 per 100,000 population.
• Predominantly affects Caucasians aged 15–50 years.
• Rare in African and Asian ancestry; most common in Irish and Swedish people.
• Mean age at diagnosis: 40–50 years.
• Male predominance: 2:1.
• More females <20 years affected; males present at a later age.
• Genetic predisposition: association with HLA DQ2 and DQ8.
• ~90% of coeliac disease patients carry HLA-DQ2.
• 10–15% have an affected first-degree relative.
• Associated with other autoimmune diseases (e.g., thyroid disease, type 1 diabetes).

Pathology

• Intolerance to gliadin fraction of gluten (wheat, rye, barley).
• Gluten triggers IgA antibodies and autoimmune response targeting skin and gut.
• Associated with gluten-sensitive enteropathy in >90% of patients.
• 90% will have intestinal disease
• Of coeliacs 15-20% have concurrent dermatitis herpetiformis – marker of more severe disease

Differential Diagnosis of Dermatitis Herpetiformis

• Linear IgA bullous disease.
• Bullous pemphigoid.
• Atopic dermatitis/eczema.
• Scabies.
• Papular urticaria.
• Prurigo nodularis/nodular prurigo.

Disease	Differentiating features
Dermatitis herpetiformis	Pruritic, polymorphic, grouped and symmetrical lesions consisting of erythema, urticarial plaques, papules, vesicles and blisters, followed by erosions, abrasions and hyperpigmentation Extensor surfaces of knees/elbows, shoulders, buttocks, sacral region and scalp More frequent in males and adults aged 15–40 years It is most common in patients of northern European and northern Indian ancestry, and is associated with the human leukocyte antigen (HLA) haplotype HLA-DQ2 or HLA-DQ8 along with coeliac disease and gluten sensitivity
Pompholyx eczema	Abrupt onset of small, clear vesicles or bullae on the palms and/or solesProdromal itching and burning sensation on palms/solesVesicles and bullae dry out and resolve without rupturing desquamation two to three weeks after This condition can occur at any age but is usually seen in adults under 40, and is more common in women Factors such as stress, sensitivity to metal compounds (such as nickel, cobalt or chromate), heat and sweating can aggravate this condition
Infections	Scabies: Pruritus worse at night, Burrows are pathognomonic Viral: Herpes zoster: Unilateral vesicular eruption of one to three dermatomes, painful or pruritic lesions, rarely bilateral or disseminated Viral:  Herpes simplex virus (HSV) infection: Clusters of sometimes painful fluid-filled blisters or sores, classic sites are lower back, buttocks and thighs in HSV-2 infection, and face in HSV-1 Bullous impetigo: Caused by coagulase positive Staphylococcus aureus Blisters on face (around mouth, nose) or site of trauma that rupture easily leaving crusted edges and honey-coloured crusts
Erythema multiforme	immune-mediated typically self-limiting mucocutaneous condition characterised by ‘target’ lesions. Palms, neck and face mucosal involvement in up to 70% of cases precipitated by HSV infection alternative triggers : other infections CMV, EBV, Orf, medications (Erythromycin, Penecillin, Antiepileptics, NSAIDs), and vaccinations, IBD, Hep C, Leukemia/Lymphoma DDx: Steven Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Rare	Bullous pemphigoid More prevalent in elderly patients with neurological disease or psoriasisLarge, tense bullae that rupture, forming crusted erosionsAny part of the skin surface, predilection for flexural areas Bullous systemic lupus erythematosus Widespread vesiculobullous eruption that develops very fast, ranging from large, tense bullae to small, grouped vesiclesUsually in the superior part of the trunk, proximal upper extremities, neck and facePruritus of variable intensityCan present with systemic lupus symptoms Linear IgA dermatosis May have prodromal or transitory pruritusClear or haemorrhagic vesicles or bullae on normal, erythematous, or urticarial skin. Arranged in rings or a ‘cluster of jewels’Ocular symptoms (eg grittiness, burning, discharge) are common

CLINICAL FEATURES

Complications of Dermatitis Herpetiformis and Coeliac Disease

• Aphthous ulcers, angular cheilitis.
• Dry skin, nail, hair abnormalities.
• Dental problems: thin enamel.
• Neurological issues: ataxia, polyneuropathy, epilepsy.
• Heart problems: pericarditis, cardiomyopathy.
• Recurrent miscarriages.
• Fatty liver with abnormal liver function tests.
• Increased risk of Non-Hodgkin lymphoma (NHL), especially in the first 5 years post-diagnosis. Reduced risk with a gluten-free diet.

Clinical

• Vesicles rarely seen by doctors
• Blisters eroded by scratching
• Prurigo – itchy papules, and vesicles
• Underlying skin normal or red
• Presents as excoriation with eczematous changes
• Most common in young adults
• Symmetrical
• Vesicles over
  • elbows
  • knees (extensor surfaces)
  • trunk
  • buttocks
  • shoulders

• Associated – aphthous ulcers, angular chelitits, dry skin/nail/hair
• Masquerades as scabies, excoriated eczema or insect bites
• Typically lasts for decades

Diagnosis of Dermatitis Herpetiformis

• Skin biopsy for confirmation.
• Lesional skin: subepidermal blisters, neutrophil and eosinophil inflammatory cells.
• Perilesional skin biopsy with direct immunofluorescence: granular deposits of IgA (90–95% sensitivity, 95–100% specificity).
• Blood tests: full blood count, liver function, serum calcium, iron, ferritin, zinc, vitamin B12, folate, thyroid function.
• Specific autoantibody tests: IgA anti-endomysial antibodies, IgA tTG, IgA eTG, IgA and IgG dGP, total IgA level.
• Small intestinal biopsy if abnormal blood results: look for small bowel villous atrophy.
• HLA haplotype testing: HLA-DQ2 or HLA-DQ8.

TREATMENT

1. Gluten-free diet, which may suppress the condition but is slow to take effect.
   • Reduces medication requirement
   • Improves enteropathy, nutrition, bone density.
   • May reduce risk of other autoimmune conditions and lymphoma.
   • Full effect may take up to 2 years.
2. Dapsone 50 mg (o) daily, increasing up to 200 mg (o) daily with caution (usually dramatic response)
   • SSide effects: agranulocytosis, dapsone hypersensitivity, methaemoglobinaemia.
3. Alternatives:
   • ultra-potent topical steroids
   • systemic steroids
   • colchicine
   • ciclosporin
   • azathioprine
   • sulfapyridine
   • rituximab.
   • Combination therapy: dapsone and sulfasalazine.
   • Topical dapsone 5% gel as an adjuvant treatment.
4. Patients require follow-up with a multidisciplinary team that includes a dermatologist, gastroenterologist and dietitian

Outcome for Dermatitis Herpetiformis

• Good prognosis with a strict gluten-free diet and medication.
• Lifelong gluten-free diet required.
• Increased incidence of T cell lymphoma but lower overall disease mortality compared to the general population
  • it tends to occur predominantly in individuals who do not follow a gluten-free diet
  • Celiac disease (CD) is associated with intestinal lymphoma and other forms of cancer,
    • especially adenocarcinoma of the small intestine, of the pharynx, and of the esophagus