Dowling-Degos Disease

Dowling-Degos disease is a rare, autosomal dominant genodermatosis with slowly progressive reticulate hyperpigmentation of the flexures, with small pigmented macules and comedone like lesions.

Onset is usually in the third or fourth decade. Men and women are equally affected. It is described in many populations, with higher recognition in Asian families.

The main cause is haploinsufficiency of KRT5. Variants in POFUT1, POGLUT1 and PSENEN cause related forms, and the Galli-Galli disease variant has acantholysis.

Pathophysiology.

Loss of keratin 5 or of Notch signalling proteins disrupts melanosome transfer from melanocytes to keratinocytes and abnormal keratinocyte function, leading to hyperpigmentation at the tips of elongated rete ridges.

• Brown, reticulate macules in the axillae, groin and neck folds, which spread to the submammary area, inner thighs, trunk and face.
• Comedone like dark follicular papules on the back and neck, pitted perioral scars and hyperkeratotic papules on the dorsum of the hands.
• Mild itch in flexures, especially in Galli-Galli disease.

• Clinical diagnosis. Dermoscopy shows brown stellate and reticular pigmentation with follicular plugging.
• Skin biopsy: elongated, thin, filiform rete ridges with hyperpigmentation of the basal layer and the tips ("antler" pattern), and acantholysis in Galli-Galli disease.
• Genetic testing (KRT5, POFUT1, POGLUT1, PSENEN) when the diagnosis is unclear or for family counselling.

Differential diagnosis.

• Acanthosis nigricans, Kitamura reticulate acropigmentation (hands and feet) and Haber syndrome.
• Confluent and reticulated papillomatosis, pityriasis versicolor and erythrasma.
• Hailey-Hailey disease, Darier disease and Galli-Galli disease.

• Explain that the condition is benign but chronic, and not curable.
• Topical treatments have limited benefit: tretinoin 0.05% or adapalene 0.1% nightly, azelaic acid 15 to 20% twice daily, hydroquinone 4% (for no more than 3 months, to avoid ochronosis), and topical corticosteroids for itch. Calcineurin inhibitors have been used.
• Oral isotretinoin 0.5 mg/kg daily for 4 to 6 months has helped some patients, with relapse on stopping. Avoid in pregnancy.
• Laser: ablative erbium:yttrium aluminium garnet or fractional lasers for pits and pigment, with variable results. Q-switched lasers can lighten pigment.
• Sun protection and camouflage.

Special groups. Women who may become pregnant: effective contraception is needed before and after isotretinoin.

Monitoring. Review every 6 to 12 months.

Referral and escalation. Dermatology; genetics for family counselling.