Darier Disease

Darier disease (keratosis follicularis) is an autosomal dominant genodermatosis caused by mutations in ATP2A2, encoding the SERCA2 calcium pump, leading to defective keratinocyte adhesion and abnormal keratinisation.

• Prevalence is about 1 in 30,000 to 100,000. Onset between 6 and 20 years; penetrance is complete but expression variable.
• Exacerbated by heat, humidity, sweating, sun exposure, friction, stress, infection, and drugs (lithium, oral corticosteroids).
• Neuropsychiatric associations: bipolar disorder, depression, epilepsy, intellectual disability, and schizophrenia in some families.
• Complications: bacterial infection (Staphylococcus), eczema herpeticum (Kaposi varicelliform eruption), and malodour.

• Greasy, brown red, keratotic papules coalescing into crusted plaques in seborrhoeic areas (scalp, forehead, chest, back, flexures).
• Palmoplantar pits and punctate keratoses, dorsal hand acrokeratosis verruciformis like papules, and mucosal cobblestoning.
• Nail changes: red and white longitudinal bands, V-shaped distal notching, and subungual hyperkeratosis (pathognomonic).
• Segmental (mosaic) variants follow Blaschko lines.

• Clinical diagnosis with characteristic nail and palmar changes.
• Biopsy: suprabasal acantholysis with dyskeratosis ("corps ronds" and "grains") and villi in suprabasal clefts.
• Genetic testing: ATP2A2 sequencing.
• Cultures for secondary infection, HSV PCR if painful vesicles, and mental health screening.
• Exclude Hailey-Hailey disease, seborrhoeic dermatitis, transient acantholytic dermatosis (Grover), pemphigus, and acanthosis nigricans.

• Sun protection (SPF 50+), loose cotton clothing, cooling, and avoidance of triggers and irritants.
• Topical: emollients, topical retinoids (tretinoin 0.05%, adapalene, tazarotene), 5-fluorouracil 5% cream, tacrolimus 0.1%, and calcipotriol; mild to moderate steroids for inflammation.
• Antimicrobial care: antiseptic washes, topical mupirocin, oral flucloxacillin 500 mg four times daily or doxycycline 100 mg twice daily for bacterial infection; antifungals if needed; valaciclovir 1 g three times daily or aciclovir 400 mg five times daily for eczema herpeticum (urgent).
• Systemic retinoids for moderate to severe disease: acitretin 0.5 mg/kg/day (25 to 50 mg) or isotretinoin 0.5 to 1 mg/kg/day; start low, titrate to response; strict contraception with acitretin.
• Alternatives: ciclosporin 3 to 5 mg/kg, naltrexone, oral steroids short term for flares, and botulinum toxin for hyperhidrosis.
• Procedures: dermabrasion, CO2 laser ablation, and surgical excision of localised plaques.
• Genetic counselling, mood screening, and multidisciplinary support.