Makindo Medical Notes

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🧠 About

• Darier’s disease (Keratosis Follicularis) is a rare inherited disorder of keratinisation, characterised by acantholysis (loss of adhesion between keratinocytes) and abnormal keratin buildup causing rough, warty papules.
• It most often affects seborrhoeic areas — face, chest, back, scalp — and may also involve nails and mucous membranes.
• First described by Ferdinand-Jean Darier in 1889, it remains a model condition linking dermatopathology to calcium homeostasis.

🧬 Genetics & Pathogenesis

• Inherited in an autosomal dominant pattern with variable expressivity.
• Mutations occur in the ATP2A2 gene on chromosome 12q23–24, which encodes the SERCA2 calcium pump in the endoplasmic reticulum.
• Defective calcium transport disrupts desmosomal adhesion and keratinocyte differentiation → acantholysis and dyskeratosis.
• Can arise de novo or appear mild in carriers (hence undetected family history).

🌞 Aetiology & Triggers

• Defective calcium signalling weakens cell–cell junctions (“bricks without mortar”).
• Flare triggers include:
  • ☀️ Sunlight (UV exposure)
  • 💦 Heat and sweating
  • 🧴 Skin friction and irritation
  • 🦠 Secondary bacterial or HSV infection
  • 📅 Hormonal changes — flares pre-menstrually in some women

🎨 Clinical Features

• Usually appears in childhood or adolescence; mild disease may go unrecognised for years.
• Rough, greasy, crusted or keratotic brown-red papules coalescing into warty plaques over seborrhoeic areas (face, scalp, chest, upper back).
• In flexures (groin, axilla, under breasts) lesions can become mac­erated, malodorous, or secondarily infected.
• Patients may complain of itching, soreness, or offensive odour.
• Nail changes: longitudinal red or white streaks, V-shaped nicks at free edge, and distal brittleness.
• Mucosal lesions: white papules on buccal mucosa with central depression (“cobblestone pattern”).
• Hands: flat-topped “wart-like” papules over dorsum of hands or feet.
• Recurrent secondary infections with Staphylococcus aureus or HSV are common.

🔬 Investigations

• Skin biopsy: diagnostic — shows suprabasal acantholysis with “corps ronds” and “grains” (dyskeratotic cells) in the upper epidermis.
• Consider genetic testing for ATP2A2 mutation if strong family history or atypical presentation.
• Swabs or cultures if superinfection suspected.

💊 Management

• 🎯 No cure — aim to minimise flares and secondary infection.
• 🧴 General care:
  • Wear loose cotton clothing, avoid sweating and friction.
  • Use gentle antiseptic or emollient washes; keep skin dry and clean.
  • Regular emollients reduce irritation and scaling.
  • Use high-factor sunscreen to prevent UV-triggered exacerbations.
• 🌿 Topical therapy:
  • Topical corticosteroids for inflammation and itch.
  • Topical antibiotics or antiseptics if secondarily infected.
  • Topical retinoids (tretinoin, adapalene) for keratin regulation — combine with emollients to limit irritation.
  • Topical 5-fluorouracil or photodynamic therapy have anecdotal success in resistant plaques.
• 💊 Systemic therapy:
  • Oral antibiotics for secondary infection; aciclovir for HSV reactivation.
  • Systemic retinoids (acitretin, isotretinoin) for widespread or severe disease — reduce hyperkeratosis and flare frequency.
  • Short courses of ciclosporin may help refractory inflammation.
• 🩻 Procedural options: CO₂ laser ablation, dermabrasion, or surgical excision of thick plaques — useful for localised, disfiguring lesions.

💡 Prognosis

• Chronic relapsing course; tends to improve with age.
• Heat and sun avoidance, and good skin hygiene, markedly reduce attacks.
• Scarring or pigmentary changes may persist after healing.

📘 Teaching Points

• Darier’s disease exemplifies a genodermatosis of desmosomal dysfunction — a key concept for dermatology exams.
• Compare with Hailey–Hailey disease (another calcium-pump defect, ATP2C1) — clinically similar but more flexural and erosive.
• Remember the triad: seborrhoeic papules + nail notching + mucosal cobblestoning.
• Topical retinoids can both help and irritate — always counsel patients on gradual introduction and moisturiser use.

📚 References

• BNF: Retinoids and Ciclosporin
• Oji V et al. J Am Acad Dermatol 2019;80:1380–1393 — Consensus on inherited disorders of keratinisation.
• DermNet NZ (2024): Darier disease overview.
• Burton JL et al., Rook’s Textbook of Dermatology, 10th ed., Wiley-Blackwell.