Darier Disease
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Direct answer
Darier disease is an autosomal dominant disorder of keratinisation caused by ATP2A2 mutations, which disturb calcium pumping and keratinocyte adhesion. It produces greasy, crusted papules in seborrhoeic areas, together with V-shaped nail notches and red and white longitudinal nail streaks. Histology shows suprabasal acantholysis with corps ronds and grains, and retinoids form the mainstay of treatment.
What you must remember
- Gene: ATP2A2 on chromosome 12q23-24.1, encoding the SERCA2 calcium pump; inheritance is autosomal dominant with variable expressivity.
- Skin: greasy, skin-coloured to brownish keratotic papules that coalesce into crusted plaques on seborrhoeic sites such as the face, scalp, chest, back and flexures.
- Nails: longitudinal red and white streaks, and V-shaped notches at the distal free edge.
- Mucosa: white papules and cobblestoning of the palate and tongue.
- Histology: suprabasal clefting with acantholysis; corps ronds are single round dyskeratotic cells in the spinous layer, and grains are dyskeratotic cells in the stratum corneum.
- Complications: eczema herpeticum (Kaposi varicelliform eruption) and bacterial superinfection, often after heat or sun exposure.
- Treatment: avoid heat and sun, use emollients and keratolytics, add topical retinoids, and use oral acitretin for widespread disease.
A step-by-step bedside approach
Darier disease is recognised by distribution and nail changes before biopsy. Work through the findings in order and confirm with histology when the picture is unclear.
- Note the distribution: seborrhoeic sites such as the chest, back, scalp and face, with greasy crusts and a characteristic odour.
- Examine the nails: look for red and white longitudinal streaks and the V-shaped notch at the distal free edge.
- Check the mouth: cobblestoned palate and white papules support the diagnosis.
- Take a biopsy: acantholysis with corps ronds and grains is diagnostic.
- Screen for infection: look for herpes simplex or bacterial superinfection, which can cause eczema herpeticum.
- Start therapy: emollients, sun and heat avoidance and topical retinoids first; acitretin for extensive disease, with strict contraception advice.
Where the look-alike questions trip candidates
Darier disease is often tested against related conditions with similar histology or nail changes.
- Trap: choosing Hailey-Hailey disease for any flexural acantholytic disease. Correct: Darier disease has seborrhoeic greasy papules and nail notches, whereas Hailey-Hailey disease has macerated flexural erosions without keratosis.
- Trap: treating acrokeratosis verruciformis of Hopf as unrelated. Correct: it is also linked to ATP2A2 and gives palmoplantar and dorsal warty lesions rather than a seborrhoeic distribution.
- Trap: treating an eczema herpeticum flare as simple eczema. Correct: monomorphic punched-out vesicles on Darier skin mean herpes simplex and need urgent antiviral therapy.
- Trap: assuming topical steroids are the main treatment. Correct: retinoids and sun avoidance form the core, since steroids do not correct keratinisation.
Frequently asked questions
What are corps ronds and grains in Darier disease?
Corps ronds are single round dyskeratotic keratinocytes in the spinous layer, while grains are dyskeratotic cells in the stratum corneum. Together with suprabasal acantholysis, they form the histological hallmark of Darier disease.
Which nail changes suggest Darier disease?
Red and white longitudinal bands on the nail plate and a V-shaped notch at the distal free edge suggest Darier disease. These nail findings are frequent and help confirm the diagnosis when the skin changes are doubtful.
Which gene is mutated in Darier disease?
Darier disease is caused by mutations in ATP2A2 on chromosome 12q23-24.1, which encodes the SERCA2 calcium pump. Loss of pump function disrupts keratinocyte adhesion and differentiation, causing both acantholysis and dyskeratosis.
Why is eczema herpeticum a concern in Darier disease?
Patients with Darier disease are prone to widespread herpes simplex infection, called eczema herpeticum or Kaposi varicelliform eruption, because the epidermal barrier is compromised. Monomorphic punched-out vesicles on affected skin need urgent antiviral treatment.
Which systemic drug treats extensive Darier disease?
Oral acitretin is used for extensive or refractory Darier disease, while topical retinoids help localised disease. Acitretin is teratogenic, so women of childbearing age need strict contraception advice before starting it.