Dowling-degos disease Q82.8

Very rare, sporadic but also familial, chronically progressive, genodermatosis with autosomal-dominant inheritance (different penetrance), characterized by reticular pigmentation of the intertrigines.

Worldwide occurrence; people of Asian descent are increasingly affected; no gender preference;

Several mutations have been identified in this phenotype. Of importance is the loss-of-function mutation in the keratin 5 gene(KRT5) located on chromosome 12q13. This gene mutation has also been described in Galli-Galli disease, the acantholytic variant of Dowling Degos disease.

Whether other disorders in the reticular hyperpigmentation group such as:

• Erythromelanosis follicularis faciei et colli
• Haber syndrome
• Dyschromatosis symmetrica hereditaria

are separate entities, or different phenotypes of this mutation will emerge in the future.

Of note is the association of Dowling-Dego disease with hidradenitis suppurativa. The familial form of hidradenitis suppurativa can occur with /without signs of Dowling-Degos disease and is associated with mutations in the PSEN2 gene.

Mostly in the 2nd half of life (2-5 years of age).

Spots or flat raised, reticularly configured, hyperpigmented stains or plaques. The changes begin in the axillae and groin, and over the years spread to the neck, nape of neck and trunk of the body. In addition, often follicular hyperkeratoses; punctiform dimples perioral and nasal.

Basally hyperpigmented epithelial strands directed into the corium, branching like deer antlers but not confluent. The epidermis is slightly atrophic. Hair follicles are dilated and hyperkeratotic. The basal keratinocytes are hyerpigmented. A rare acantholytic variant is defined as Galli-Galli disease (Müller CS et al. 2009).

• Clinical:
  • Acanthosis nigricans: rather extensive velvety, hyperpigmented skin thickening.
  • Papillomatosis confluens et reticularis: extensive velvety, hyperpigmented skin thickening; intermammary and interscapular. Probably variant of acanthosis nigricans.
  • Haber syndrome (possibly identical genotype)
  • M. Galli-Galli (acantholytic variant of M. Dowling-Degos)
• Histological:
  • Netted acanthoid type of Verruca seborrhoica: similar pattern. Clinical and histological review necessary.
  • Acanthosis nigricans: papillomatosis and hyperkeratosis, slight mostly irregular acanthosis, basal hyperpigmentation, partly pseudohorn cysts. The antler-like pattern of the reteleis is missing.

Remember! The identically proven gene mutations in M. Dowling-Degos and M. Galli-Galli support the thesis that they are different variants of the same disease.

DD: see also Reticular acropigmentation of Kitamura (reticulate acropigmentation of Kitamura) and Dyschromatosis symmetrica hereditaria (Dohi).

1. Braun-Falco M et al (2003) Enhanced cytoplasmic expression of desmocollin 3 in epidermal rete ridges of Dowling-Degos syndrome. Br J Dermatol 149: 1293-1296
2. Betz RC et al (2006) Loss-of-function mutations in the keratin 5 gene lead to M. Dowling-Degos disease. At J Hum Genet 78: 510-519
3. Degos R, Ossipowski B (1954) Dermatosis pigmentaire reticulee des plis (discussion de l'acanthosis nigricans). Ann Dermatol 81: 147-151
4. Dowling GD, Freudenthal W (1938) Acanthosis nigricans. Proc Roy Soc Med 31: 1147-1150
5. Mild P et al (1992) Dowling-Degos disease with exclusively genital manifestation. dermatologist 43: 369-372
6. Müller CS et al (2009) Changing a concept--controversy on the confusing spectrum of the reticulatepigmented
   disorders of the skin. J Cutan Pathol 36:44-48.
7. 1Oppolzer G et al. (1987) M. Dowling-Degos: Frustrating therapy attempt with retinoids. Dermatologist 38: 615-618
8. Ujihara M et al (2002) Dowling-Degos disease associated with squamous cell carcinomas on the dappled pigmentation. Br J Dermatol 147: 568-571
9. Wenzel G et al (2003) Treatment of Dowling-Degos disease with Er:YAG-laser: results after 2.5 years. Dermatol Surgery 29: 1161-1162
10. Wenzel J et al (2002) Successful treatment of Dowling-Degos disease with Er:YAG laser. Dermatol Surgery 28: 748-750