The autosomal-dominant genodermatoses
Darier disease and
Hailey-Hailey disease present special challenges to dermatologists. Despite their similar pathogenesis featuring impaired adhesion of suprabasal keratinocytes as a result of defective
ATPases in epidermal
calcium channels, the two diseases differ considerably in clinical presentation and therapeutic options.
Darier disease is characterized by reddish brown, keratotic papules in seborrheic and intertriginous areas, which may coalesce into extensive lesions. Individuals affected with
Hailey-Hailey disease primarily develop intertriginous papulovesicles and small
blisters, which often evolve into erythematous plaques with erosions and painful fissures. Quality of life is significantly reduced because of complaints (itch, burning sensation,
pain), body malodor and chronicity. Therapeutic options remain limited.
Antiseptics and intermittent topical
corticosteroids are a cornerstone of
therapy, and systemic anti-infective treatment is often required in cases of
superinfection. Ablative surgical interventions such as
dermabrasion and
CO2 laser surgery can lead to long-term remissions in intertriginous
Hailey-Hailey disease, while temporary relief may also be achieved by
intralesional injections of
botulinum toxin. Of the systemic medications available for
Darier disease,
acitretin, which is approved for this purpose, has the best supporting evidence. The efficacy of
immunosuppressants and immune modulators is inconsistent. Low-dose
naltrexone produces more satisfactory results in Hailey-Hailey than
Darier disease. The present CME article summarizes current knowledge of the two
dermatoses, taking recent developments into account.