Darier's Disease

Nishkarsh Chugh

1. DARIER’S DISEASE Dr. Nishkarsh Chugh PGJR1 Dermatology AKA DARIER-WHITE DISEASE, KERATOSIS FOLLICULARIS, DYSKERATOSIS FOLLICULARIS

2. INTRODUCTION It is a rare congenital acantholytic disorder transmitted as an autosomal dominant trait, characterized clinically by Persistent eruption of greasy hyperkeratotic papules in seborrheic regions Nail abnormalities Mucous membrane changes and histologically by Acantholysis Dyskeratosis

3. ETIO PATHOGENESIS ATP2A2 gene located at chromosome 12q24.1 is responsible for encoding SERCA2 . Mutation in this gene causes severe disruption of Ca2+ homeostasis by the defects in protein expression and/or transport of desmosomal proteins to cell membrane resulting in acantholysis. Electron microscopy reveals loss of desmosomes, breakdown of desmosome-keratin intermediate filament attachment, and perinuclear aggregates of keratin intermediate filaments.

4. CLINICAL FEATURES The disease usually begins during childhood. The onset is insidious and slowly progressive. Both sexes are affected with equal frequency. Most patients of Darier’s disease have a family history of a similar condition.

5. CLINICAL FEATURES Heat, sweat, humidity, sunlight, UVB exposure, lithium, oral corticosteroids, and mechanical trauma have been reported to exacerbate the condition. Females may experience premenstrual flares. Most cases improve in winter.

6. CLINICAL FEATURES The earliest lesions may be seen behind the ears followed by eruptions in other seborrheic areas Lesions are associated with pruritus. It is characterized by development of multiple, dirty, warty, papular excrescences, symmetrically involving the face, limbs, and trunk

7. CLINICAL FEATURES Each lesion starts as a small, firm, skin colored papule that soon becomes covered with a dark, dirty-looking, greasy crust. When the crust is removed, a small pit-like depression is seen at the summit of the papule. Later, the papules coalesce to form large plaques and malodorous papillomatous growths over the body flexures like the axillae, groins, and gluteal crease.

8. CLINICAL FEATURES The scalp may show greasy crusts but the loss of hair is exceptional since most papules in this condition are nonfollicular in location. In many patients, numerous, depigmented, spotty macules (guttate leukoderma) may be seen intermingled with papules.

9. CLINICAL FEATURES The involvement of hands is very common. Numerous pinpoint-to-pinhead-sized spots are located mainly over the hypothenar area of palms. A generalized horny thickening of the palms and soles occurs due to innumerable closely set papules.

10. CLINICAL FEATURES Crusting, fissuring, and ulceration of the lips may occur. White cobblestone-like papules may be seen on the palate and tongue Nail changes include longitudinal, red and white streaks with subungual keratosis, thinning of the nail plate, fragility and splintering, and triangular nicking of the free edges.

11. CLINICAL SUBTYPES Type 1 segmental variant (acantholytic dyskeratotic epidermal nevi) - Keratotic papules are localized and unilateral in distribution following lines of Blaschko . Type 2 segmental variant Acral hemorrhagic type - Red to bluish–black, irregularly shaped, sharply demarcated macules on the palms and soles as well as on the dorsal aspects of the hands. Acrokeratosis verruciformis of Hopf - Flat wart-like papules on the dorsal aspects of the extremities Other variants include erosive or bullous form , vegetative form in the intertriginous area, pruritic and papulovesicular lesions .

12. SEVERITY GRADING GRADE SEVERITY CLINICAL FEATURES SUBCLINICAL Asymptomatic but associated with acrokeratosis or nail dystrophy with positive family history 1 MILD Localized keratotic papules up to 10% with pruritus or mild irritation 2 MODERATE Extensive papular and sub confluent crusted lesions with secondary infections affect 10–30% 3 SEVERE Widespread confluent eroded/crusted/ hyperkeratotic/bullous rash affects >30% of the trunk or limbs or flexures

13. The histopathological features include dyskeratosis, acantholysis , and papillomatosis . Dyskeratosis results in corps ronds and grains . There is suprabasal acantholysis leading to the formation of suprabasal lacunae . Papillae lined by a single layer of basal cells project into the lacunae and are called villi . In the dermis, we can see a chronic inflammatory infiltrate . HISTOPATHOLOGY

14. COMPLICATIONS The keratotic and papillomatous lesions in Darier disease are prone to secondary infection with bacteria, yeast, or dermatophytes, often leading to vegetating, malodorous lesions. Anergy and inability to produce leucocyte inhibitory factor render patients susceptible to infections particularly by viruses like the herpes simplex virus and vaccinia. Kaposi varicelliform eruption and eczema vaccinatum Salivary duct narrowing Most patients are of normal intellect, but clinical experience suggests that mild degrees of learning difficulty are common. A few case reports of cutaneous squamous cell carcinomas (SCCs)

15. DIFFERENTIAL DIAGNOSIS Classical form - Seborrheic dermatitis, Seborrheic keratoses , Candida infection ( submammary ). Papular vesicular form - Grover disease Erosive or bullous forms - Hailey-Hailey disease, Pemphigus vulgaris, Langerhans cell histiocytosis , candida infection, or impetigo. Acral forms - plane warts and acrokeratosis verruciformis of Hopf Vegetative forms - Pemphigus vegetans .

16. TREATMENT GENERAL MEASURES Lightweight clothes and sunscreen help prevent aggravation due to heat, sweating, and sun exposure. Daily skin care includes the use of antimicrobial cleansers to prevent malodorous bacterial colonization and keratolytic emollients to reduce scaling and irritation

17. TREATMENT TOPICAL THERAPY Topical retinoids – Tretinoin, Adapalene, Tazarotene Topical Corticosteroids Topical Tacrolimus Keratolytics - Salicylic acid, Sulfur

18. TREATMENT SYSTEMIC THERAPY Oral vitamin A (50,000 IU thrice daily) Isotretinoin (initially at a dose of 0.5 mg/kg/day, increasing to a maximum of 4 mg/kg/day for 16 weeks) Acitretin (initial dose 25–30 mg/day for 2–4 weeks, and if the drug is well tolerated, the dose can be increased up to 60 mg for 2 months) Etretinate (50 mg daily)

19. TREATMENT SURGERY Dermabrasion Er:YAG or CO2 laser excision Surgical excision and grafting

20. THANK YOU Dr. Nishkarsh Chugh PGJR1 Dermatology