Excerpt from Reticulate Pigmented Anomaly

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Background

Dowling¹ first delineated this genodermatosis as a distinct entity in 1938. In 1954, Degos and Ossipowski² described a patient with a similar case. Few patients with reticulate pigmented anomaly, also known as Dowling-Degos disease (DDD), have been reported.

DDD is characterized by flexural pigmented reticulate macules and sometimes comedolike papules on the back and/or the neck (dark dot follicles). Some patients have pitted perioral scars. Pruritus of affected flexural areas may be the only symptom. In both male and female patients, pigmented reticulate macules may also be evident on the genitalia, where they may be seen alone. The pigmented eruption on the male external genitalia may be a cutaneous marker of underlying testicular carcinoma,³ although the association is probably fortuitous. Bilateral nephroblastoma in familial Hay-Wells syndrome has been associated with familial reticulate pigmentation of the skin,⁴ another possibly fortuitous association.

The disease is slowly progressive. It is characterized by pigmented filiform epidermal papules closely resembling an adenoid seborrheic keratosis, but similar proliferations also develop around the variably dilated pilosebaceous follicles.

Galli-Galli disease is a rare genodermatosis in the spectrum of reticulate hyperpigmentation probably best regarded as an acantholytic variant of DDD.⁵

Pathophysiology

DDD is often familial and appears to be inherited in an autosomal dominant manner.⁶ A gene locus believed responsible in one Chinese patient was mapped to 17p13.3.⁷ A genome-wide linkage analysis of 2 German families mapped this disease to 12q.⁸ This region includes the keratin gene cluster, which was screened for mutations. Loss-of-function mutations were identified in the keratin 5 gene (KRT5) in all affected family members and in 6 unrelated patients with DDD.

A heterozygous frameshift mutation in the V1 domain of keratin 5 was identified in a family with DDD.⁹ This study confirmed that haploinsufficiency for K5 causes DDD and points to a prominent role for the keratin intermediate filament cytoskeleton within basal keratinocytes in epidermal pigment biology.

Frequency

International

DDD is a rare condition.

Sex

The disease affects both sexes. Although this disorder appears to be inherited in an autosomal dominant manner,¹⁰ a female predominance has been noted in some surveys.¹¹

Age

DDD tends to develop early in adult life, with the onset of pigmentation occurring in individuals before they are aged 24 years. A Chinese newborn with reticulate pigmented anomaly of the flexures was recently described.¹²

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