Dowling-Degos Disease with Asymmetrical Axillary Distribution and No KRT 5 Exon 1 Mutation

Abstract

Dowling-Degos disease (DDD) is a rare disorder characterized by acquired pigniented maeules and papules in a reticulate pattern, particularly affecting the flexural areas and other major skin folds (I, 2). A female patient presented with dotted and reticulate pigmentation ofthe axilla, and was diagnosed as DDD both clinically and histopathologically. However, the asymmetrical distribution ofthe eruption was distinct from classical DDD. In contrast to recent reports in Caucasian patients with DDD (3,4), we found no evidence of mutation of exon 1 ofthe keratin 5 (KRT5) gene, suggesting an aetiological heterogeneity of this disorder. CASE REPORTA 47-year-old Japanese woman presented at our department with development of reticulate pigmentation on her axilla. She had first noticed dotted pigmentation on her left axilla 8 years previously, which had gradually increased and coalesced. Similar pigmentation subsequently emerged on her right axilla 2 years previously. There were no clinical symptoms, such as pruritus, and she had no axillary hyperhidrosis. On examination, miliary brown macules and papules were seen distributed over the vault of her axilla, coalescing to give rise to reticulated patches. The lesion on the left side was more pronounced than that on the right (Fig. 1). The eruptions were slightly hyperkeratotic, with no apparent scaling on the surface. Some macules were in linear alignment, suggesting the presence of Koebner's phenomenon. The patient was otherwise healthy. There was no pigmentation in other areas, such as the groin, neck or other flexures. No other family members had pigmentary abnormalities. A biopsy specimen from the early lesion on the right axilla showed slight orthokeratosis and acanthosis. characterized by irregular elongation of rete ridges and basal hyperpigmentation (Fig. 2). There was no papilloniatosis. A subsequent biopsy from the older lesion on the left side showed an identical histological picture (not shown). Slight oedema and infiltration of lymphocytes around capillaries were seen in the upper dermis. Considering the characteristic clinical picture and the histopathological findings, a diagnosis of DDD was made. Repeated cryosurgery using liquid nitrogen was partially effective in resolving the lesion (not shown).DISCUSSION DDD (1.2) usually presents in adults, commonly women, and most frequently during the fourth decade of life. Although DDD is usually inherited in an autosomal dominant fashion, some sporadic cases have been reported, as in our patient. The axilla and groin arc the most common sites, but other areas may be involved, including the intergluteal and infra-mammary folds, neck, scalp, trunk and arms. Other possible cutaneous manifestations include perioral pitted scars and comedo-like lesions on the neck and back. Occasional Fig. ]. (a) Muitiple, small brown macules and papules in relicular distribution localized on tbe axilla. The lesion on tbe left side was more pronouneed tban tliat on ibe rigbt. (b) Ciose-up ol' Ibc lell axilla.

Systematic mutation screening of KRT5 supports the hypothesis that Galli-Galli disease is a variant of Dowling-Degos disease

“…The finding that some patients with DDD (or GGD) did not carry mutations in the coding regions of KRT5 in this report and others 12,16 suggests that mutations in KRT5 exist outside the coding regions, or that mutations in at least one other gene besides KRT5 can cause the disease. Interestingly, differing clinical presentations were observed in patients with KRT5 mutations and those without KRT5 mutations: patients with KRT5 mutations presented with reticular pigmentation and erythematous erosive papules that were found mainly in the flexures, whereas patients without the KRT5 mutation presented with disseminated lentigo‐like macules lacking the typical flexural pattern of distribution.…”

Analysis of POFUT1 Gene Mutation in a Chinese Family with Dowling-Degos Disease

“…In 2006,Betz et al performed a genomewide linkage analysis of two German families and identified loss-of-function mutations in the keratin 5 gene ( KRT5 ) [2]. However, no KRT5 mutations were identified in more than 50% of DDD familial cases and sporadic cases [3], [15], suggesting the genetic heterogeneity of DDD.…”

Type 1 Segmental Galli-Galli Disease Resulting from a Previously Unreported Keratin 5 Mutation

“…Further mutations in the KRT5 gene in DDD have been reported afterwards (Liao et al, 2007;Guo et al, 2011). It has to be emphasized that by far not in all patients with DDD a KRT5 mutation could be revealed (Asahina et al, 2007). The mutation c.418dupA was found in eight further patients, two of them having been diagnosed as GGD (Hanneken et al, 2010).…”