DISEASE CARD

Disease group Keratinization disorders
DISEASE NAME DOWLING-DEGOS DISEASE
Synonymous Dowling-Degos Disease-1, Reticular pigment anomaly of flexures
Estimated prevalence Unknown
OMIM 179850
Inheritance Autosomal dominant
Gene (s) KRT5 (148040)

Definition

Dowling-Degos disease (DDD) belongs to the genetically heterogeneous group of reticulate pigment disorders of the skin. This group of disorders further includes Galli-Galli disease (GGD), Kitamura's disease (RPK), Haber's syndrome (HS), and reticulate acropigmentation of Dohi (RAD). The clinical appearance of these disorders is similar, but can differ in age of onset and in associated clinical features [1].

DDD is the main representative within the group of reticulate pigment disorders. It was first differentiated from acanthosis nigricans by Dowling and Freudenthal in 1938 [2], and described as a reticuate pigmentation dermatosis by Degos and Ossipowski in 1954 [3]. DDD shares many clinical features with GGD, and both diseases are caused by mutations in the KRT5 gene (12q13.13) [4, 5].

Clinical Description

Onset of the disease is during early or middle adolescence. Patients present with reticulated hyperpigmented macules, mainly located in the flexures and large body folds. Perioral acne-like scars are additional features, as well as comedo-like hyperkeratotic follicular papules on the neck and axillae [1]. Pruritus in flexural areas has been reported [6]. Genital and perianal reticulated pigmented lesions have also been described [7].

Pathogenesis

The pathomechanism is not entirely clear, but mutations in the KRT5 gene are also responsible for other skin disorders that include pigmentation abnormalities, e.g., epidermolysis bullosa simplex with mottled pigmentation. These similarities suggest a role of KRT5, and probably its partner KRT14, in melanin transfer from melanocytes to keratinocytes [4].

Diagnosis

The different reticulate pigment disorders share many clinical features, which makes them hard to distinguish, based solely on clinical and histopathological findings. This is especially the case for DDD and GGD, which share most of their clinical characteristics, and it was suggested that GGD is a variant of DDD [5]. Histologically, GGD shows a moderate to severe acantholysis of the suprabasal epidermis, which is a hallmark to distinguish it from DDD. Further histopathologic criteria of DDD include hyperkeratosis, thinning of the suprapapillary epithelium, elongated rete ridges with basal hyperpigmentation, dermal melanosis and fibrosis along rete ridges. There is no increase in melanocyte number [1].

Treatment

Treatment is symptomatic, e.g., with skin lightening cosmetics. Topical steroids can be applied against pruritus. Hyperpigmentation was successfully treated with Er:YAG laser [8]. Systemic retinoids have been unsuccessful, but topically applied adapalene has been reported effective in one patient [9].

References

1
Müller CSL, Tremezaygues L, Pföhler C, Vogt T. (2012) The spectrum of reticulate pigment disorders of the skin revisited. Eur J Dermatol 22:596-604.

2
Dowling GB, Freudenthal W. (1938) Acanthosis Nigricans. Proc R Soc Med 31:1147-1150.

3
Degos R, Ossipowski B. (1954) Reticulated pigmentary dermatosis of the folds: relation to acanthosis nigricans. Ann Dermatol Syphiligr 81:147-151.

4
Betz RC, Planko L, Eigelshoven S, Hanneken S, Pasternack SM, Bussow H, Van Den Bogaert K, Wenzel J, Braun-Falco M, Rutten A, Rogers MA, Ruzicka T, Nöthen MM, Magin TM, Kruse R. (2006) Loss-of-function mutations in the keratin 5 gene lead to Dowling-Degos disease. Am J Hum Genet 78:510-519.

5
Hanneken S, Rutten A, Pasternack SM, Eigelshoven S, El Shabrawi-Caelen L, Wenzel J, Braun-Falco M, Ruzicka T, Nothen MM, Kruse R, Betz RC. (2010) Systematic mutation screening of KRT5 supports the hypothesis that Galli-Galli disease is a variant of Dowling-Degos disease. Br J Dermatol 163: 197-200.

6
Kim YC, Davis MD, Schanbacher CF, Su WP. (1999) Dowling-Degos disease (reticulate pigmented anomaly of the flexures): a clinical and histopathologic study of 6 cases. J Am Acad Dermatol 40:462-467.

7
Jafari R, Tronnier M, Vakilzadeh F. (2003) Morbus Dowling-Degos in genitoperianal localisation in a mother and daughter. Akt Derm 29: 240-242.

8
Yun JH, Kim JH, Choi JS, Roh JY, Lee JR. (2013) Treatment of Dowling-Degos disease with fractional Er:YAG laser. J Cosmet Laser Ther 15:336-339.

9
Altomare G, Capella GL, Fracchiolla C, Frigerio E. (1999) Effectiveness of topical adapalene in Dowling-Degos disease. Dermatology 198:176-177.