Reticulate Pigmented Anomaly

Updated: Jul 18, 2017
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD  more...
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Overview

Background

Dowling [1] first delineated this genodermatosis as a distinct entity in 1938. In 1954, Degos and Ossipowski [2] described a patient with a similar case. Few patients with reticulate pigmented anomaly, also known as Dowling-Degos disease (DDD), have been reported.

Dowling-Degos disease (reticulate pigmented anomaly) 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.

Dowling-Degos disease (reticulate pigmented anomaly) 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.

Typical clinical Dowling-Degos disease (reticulate pigmented anomaly) may histopathologically be Galli-Galli disease. [5] Galli-Galli disease is a rare genodermatosis in the spectrum of reticulate hyperpigmentation, probably best regarded as an acantholytic variant of Dowling-Degos disease (reticulate pigmented anomaly). [6]

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Pathophysiology

Dowling-Degos disease (reticulate pigmented anomaly) is often familial and appears to be inherited in an autosomal dominant manner. [7, 8] A gene locus believed responsible in one Chinese patient was mapped to 17p13.3. [9] A genome-wide linkage analysis of 2 German families mapped this disease to 12q. [10] 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 Dowling-Degos disease (reticulate pigmented anomaly). Another study found the same KRT5 mutation in patients with reticulate pigmented anomaly and its acantholytic variant, Galli-Galli disease. [11] This variant has a genotype/phenotype correlation with mutations in the keratin 5 (KRT5) gene. [12] In analyzing 5 patients lacking a KRT5 mutation, mutations in POGLUT1, encoding protein O-glucosyltransferase 1, were identified. [13] Additional POFUT1 mutations in Dowling-Degos disease have been documented. [14, 15]

A heterozygous frameshift mutation in the V1 domain of keratin 5 was identified in a family with Dowling-Degos disease (reticulate pigmented anomaly). [16] This study confirmed that haploinsufficiency for K5 causes Dowling-Degos disease (reticulate pigmented anomaly) and points to a prominent role for the keratin intermediate filament cytoskeleton within basal keratinocytes in epidermal pigment biology.

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Epidemiology

Frequency

Dowling-Degos disease (reticulate pigmented anomaly) is a rare condition worldwide.

Sex

Dowling-Degos disease (reticulate pigmented anomaly) affects both sexes. Although Dowling-Degos disease (reticulate pigmented anomaly) appears to be inherited in an autosomal dominant manner, [17] a female predominance has been noted in some surveys. [18]

Age

Dowling-Degos disease (reticulate pigmented anomaly) 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. [19]

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Prognosis

Dowling-Degos disease (reticulate pigmented anomaly) is slowly progressive but not life threatening.

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Patient Education

The patient and his or her family should be educated about the common autosomal dominant nature of Dowling-Degos disease (reticulate pigmented anomaly).

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