Dermatology

Dowling-Degos Disease (Reticular Pigmented Anomaly of the Flexures)

Are You Confident of the Diagnosis?

Characteristic findings on physical examination

Dowling-Degos disease is characterized by asymptomatic, symmetrical hyperpigmentation that arises most commonly in the axillae and groin, but occasionally in the intergluteal or inframammary creases, genitalia, scalp, neck, and arms. The pigmentary changes are initially noted to be small round hyperpigmented macules and, less commonly, flat papules. Over time, the macules become more numerous and a reticulate configuration develops. Comedones and pitted scars may be noted, particularly around the mouth (Figure 1).

Figure 1.

Reticular hyperpigmentation of the axilla.

Expected results of diagnostic studies

Diagnosis is confirmed by routine skin biopsy, which reveals diagnostic skin findings. These features include

  • --Irregular acanthosis of the rete ridges

  • --Increased melanin (with normal melanocyte counts) at the tips of the rete ridges

  • --Follicular plugging

Diagnosis confirmation

Other diagnoses to consider include

  • Haber syndrome - rare syndrome characterized by a rosacea-like dermatitis along with hyperpigmented, hyperkeratotic papules in the axilla and neck, and pitted scars

  • Galli-Galli disease - closely related disease that combines features of Dowling-Degos disease and transient acantholytic dermatosis (Grover's disease)

  • Reticulate acropigmentation of Kitamura - rare pigmentary disorder characterized by reticulate, slightly atrophic hyperpigmented macules on the dorsal hands and feet, along with palmar pitting

  • Acanthosis nigricans - differs in that the pigmentation is more confluent and there are pronounced velvety textural changes

  • Confluent and reticulated papillomatosis - differs in that the distribution is more truncal and less flexural

  • Neurofibromatosis, type I - neurocutaneous syndrome of which axillary freckling (Crowe's sign) is a major feature. The pigmentation is very similar to early changes of Dowling-Degos disease but it never gets as confluent or reticulated.

Who is at Risk for Developing this Disease?

Dowling-Degos disease is a rare autosomal-dominant disorder that affects men and women equally. The pigmentation arises in the second or third decade of life.

What is the Cause of the Disease?

Dowling-Degos disease is a familial disorder that is believed to be caused by loss of function mutations in the keratin 5 gene (KRT5). These mutations lead to abnormal epidermal growth and impaired melanin transfer.

Systemic Implications and Complications

Dowling-Degos disease has been associated with hidradenitis suppurativa, severe acne, and other components of the follicular occlusion tetrad. There are no systemic implications of this disorder. The disease may be complicated by furuncular lesions in the creases. There are rare reports of squamous cell carcinoma arising in the perianal area in patients with this disease. Rosacea-like changes may indicate the patient has Haber's syndrome, a disorder that overlaps with Dowling-Degos disease.

Treatment Options

  1. 1. Observation and reassurance

  2. 2. Medical treatment options

Topical

  • --Tretinoin 0.02% to 0.1% cream apply daily

  • --Adapalene 0.1% cream or lotion apply daily

  • --Hydroquinone 4% cream apply twice daily

Systemic

  • --Isotretinoin 1mg/kg QD, BID

3. Surgical treatment options

  • --Laser: The only reported laser to date to work has been the Er:YAG, though other lasers such as the carbon dioxide laser would theoretically be considered as well.

Erbium: YAG laser: Spot size: 3 to 5mm; Frequency: 8Hz; Pulse energy: 1000 to 1200mJ

Optimal Therapeutic Approach for this Disease

Observation and reassurance is the best approach to this disease. None of the medical treatment options above have been shown to help, although results may vary from patient to patient. The relative safety of the topical agents may lead to a therapeutic trial of one or more of them for 2 to 3 months to the affected area. The Erbium:YAG laser has been utilized to reduce the hyperpigmentation in a limited number of patients. Evaluation for concomitant hidradenitis suppurativa is recommended.

Patient Management

Patients with Dowling-Degos disease should have a discussion regarding the benign nature of the disease, the genetic implications, and the lack of available treatments. Routine follow-up or monitoring is not necessary, unless the patient develops hidradenitis suppurativa. Erbium:YAG laser therapy is worth considering.

Unusual Clinical Scenarios to Consider in Patient Management

Galli-Galli disease, as mentioned above, is a variant of Dowling-Degos disease that has features of transient acantholytic dermatosis. Histopathologic examination of the eruption reveals the characteristic downward protrusion of digitate rete ridges seen in Dowling-Degos disease along with focal acantholysis such as that typically seen in transient acantholytic dermatosis (Grover’s disease) or benign familial pemphigus (Hailey-Hailey disease).

Although dyskeratosis was identified in the original two cases, it is not an essential finding. These patients also demonstrate the KRT5 gene mutation. On examination, red pruritic papules are found in the areas affected by the hyperpigmentation. The onset of pruritus or red papules in a patient with Dowling-Degos disease may suggest this specific diagnosis.

What is the Evidence?

Altomare, G, Capella, GL, Fracchiolla, C, Frigerio, E. "Effectiveness of topical adapalene in Dowling-Degos disease". Dermatology. vol. 198. 1999. pp. 176-7.

(Concludes that topical adapalene is not effective in the treatment of Dowling-Degos disease.)

Batycka-Baran, A, Baran, W, Hryncewicz-Gwozdz, A, Burgdorf, W. "Dowling-Degos disease: case report and review of the literature". Dermatology. vol. 220. 2010. pp. 254-8.

(Case report of one patient with Dowling-Degos. The authors conclude that Dowling-Degos is on a spectrum of morphologically related disorders.)

Gilchrist, H, Jackson, S, Morse, L, Nicotri, T, Nesbitt, LT. "Galli-Galli disease: A case report with review of the literature". J Am Acad Dermatol. vol. 58. 2008. pp. 299-302.

(A case report of Galli-Galli disease with review of previously reported cases. The authors postulate that keratin 5 mutations may be responsible for this disease as well as Dowling-Degos.)

Kim, YC, Davis, MD, Schanbacher, CF, Su, WP. "Dowling-Degos disease (reticulate pigmented anomaly of the flexures): a clinical and histopathologic study of 6 cases". J Am Acad Dermatol. vol. 40. 1999. pp. 462-7.

(A case series of 6 cases of Dowling-Degos disease.)

Liao, H, Zhao, Y, Baty, DU, McGrath, JA, Mellerio, JE, McLean, WH. "A heterozygous frameshift mutation in the V1 domain of keratin 5 in a family with Dowling-Degos disease". J Invest Dermatol. vol. 127. 2007. pp. 298-300.

(A report on the identification of a frameshift mutation in keratin 5 that confirms that haploinsufficiency is responsible for Dowling-Degos disease.)

Loo, WJ, Rytina, E, Todd, PM. "Hidradenitis suppurativa, Dowling-Degos and multiple epidermal cysts: a new follicular occlusion triad". Clin Exp Dermatol. vol. 29. 2004. pp. 622-4.

(Describes a case of a patient with Dowling-Degos disease and hidradenitis suppurativa. In addition the patient has multiple epidermal cysts.)

Wenzel, J, Tappe, K, Gerdsen, R, Uerlich, M, Philipp-Dormston, W, Bieber, T. "Successful treatment of Dowling-Degos disease with Er:YAG laser". Dermatol Surg. vol. 28. 2002. pp. 748-50.

(The patient treated in the article had a good clinical result with the ER:YAG laser.)

Wu, YH, Lin, YC. "Generalized Dowling-Degos disease". J Am Acad Dermatol. vol. 57. 2007. pp. 327-34.

(A report of a family with generalized hyperpigmentation and hypopigmentation as the presentation of Dowling-Degos disease.)

Zhang, RZ, Zhu, WY. "A study of immunohistochemical and electron microscopic changes in Dowling-Degos disease". J Dermatol. vol. 32. 2005. pp. 12-8.

(An article describing the immunohistochemical and electron microscopy features of Dowling-Degos disease.)
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