eMedicine Specialties > Dermatology > Pediatric Diseases

Reticulate Pigmented Anomaly

Author: Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): Borys Savchyk, MD, PhD, Director, Molecular Biology Institute, Medical University of Lviv, Ukraine; Alexander Zajchenko, MD, Head, Professor, Department of Skin and Venereal Diseases, Medical University of Lviv, Ukraine
Contributor Information and Disclosures

Updated: May 1, 2008

Introduction

Background

Dowling1 first delineated this genodermatosis as a distinct entity in 1938. In 1954, Degos and Ossipowski2 described a patient with a similar case. Few patients with reticulate pigmented anomaly, also known as Dowling-Degos disease (DDD), have been reported.

DDD 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.

The disease 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.

Galli-Galli disease is a rare genodermatosis in the spectrum of reticulate hyperpigmentation probably best regarded as an acantholytic variant of DDD.5

Pathophysiology

DDD is often familial and appears to be inherited in an autosomal dominant manner.6 A gene locus believed responsible in one Chinese patient was mapped to 17p13.3.7 A genome-wide linkage analysis of 2 German families mapped this disease to 12q.8 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 DDD.

A heterozygous frameshift mutation in the V1 domain of keratin 5 was identified in a family with DDD.9 This study confirmed that haploinsufficiency for K5 causes DDD and points to a prominent role for the keratin intermediate filament cytoskeleton within basal keratinocytes in epidermal pigment biology.

Frequency

International

DDD is a rare condition.

Sex

The disease affects both sexes. Although this disorder appears to be inherited in an autosomal dominant manner,10 a female predominance has been noted in some surveys.11

Age

DDD 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.12

Clinical

History

This rare pigmentary disorder is characterized by reticulate pigmentation of the flexures, prominent comedolike lesions and pitted scars.

  • Some patients report pruritus in the involved regions.
  • Most patients in the authors' experience report increased pigmentation in the neck, the axillae, or the groin, with an onset varying from childhood to adult life.
  • It has been described in one family as occurring together with dyschromatosis universalis hereditaria.13
  • A rare association has been described between hidradenitis suppurativa and DDD, in one case together with multiple epidermal cysts. This may reflect a single underlying defect of follicular proliferation.14

Physical

  • The flexural pigmentation has its onset from childhood to adult life. It may be intense, with a brownish black color and sometimes steel blue or navy overtones. However, if the condition is less severe, it is stippled in shades of brown.
  • No verrucous or velvety papillomatosis is present, as might be seen in acanthosis nigricans.
  • If the patches are palpable, it is because of lichenification that produces a glossy and at times somewhat wrinkled appearance.
  • The margins may show tiny pigmented comedones.
  • In some cases, comedolike papules may be present on the back and/or neck.
  • Some patients have pitted perioral scars.
  • In addition, speckled macules involving the dorsum of the hands, the proximal nail folds, or the scrotum3 may be seen. Fingernail dystrophy may be present.11 The finding of speckled macules on the scrotum is isolated and limited to the scrotal and penile skin.3 This pigmented eruption on the male external genitalia is possibly a cutaneous marker of underlying testicular carcinoma. In female patients, speckled macules may be found on the vulva.15,16

Causes

  • See Pathophysiology.
  • DDD may coexist with hidradenitis suppurativa. The follicular occlusion inherent in DDD may predispose to the development of hidradenitis suppurativa.17

More on Reticulate Pigmented Anomaly

Overview: Reticulate Pigmented Anomaly
Differential Diagnoses & Workup: Reticulate Pigmented Anomaly
Treatment & Medication: Reticulate Pigmented Anomaly
Follow-up: Reticulate Pigmented Anomaly
Multimedia: Reticulate Pigmented Anomaly
References
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References

  1. Dowling GD, Freudenthal W. Acanthosis nigricans. Proc Roy Soc Med. 1938;31:1147-50.

  2. Degos R, Ossipowski B. [Reticulated pigmentary dermatosis of the folds: relation to acanthosis nigricans.]. Ann Dermatol Syphiligr (Paris). Mar-Apr 1954;81(2):147-51. [Medline].

  3. Schwartz RA, Birnkrant AP, Burgess GH, Stoll HL Jr, Yaqub M, Fox MD. Reticulate pigmented anomaly. Cutis. Oct 1980;26(4):380-1. [Medline].

  4. Drut R, Pollono D, Drut RM. Bilateral nephroblastoma in familial Hay-Wells syndrome associated with familial reticulate pigmentation of the skin. Am J Med Genet. Jun 15 2002;110(2):164-9. [Medline].

  5. El Shabrawi-Caelen L, Rutten A, Kerl H. The expanding spectrum of Galli-Galli disease. J Am Acad Dermatol. May 2007;56(5 Suppl):S86-91. [Medline].

  6. Brown WG. Reticulate pigmented anomaly of the flexures. Case reports and genetic investigation. Arch Dermatol. Jul 1982;118(7):490-3. [Medline].

  7. Li CR, Xing QH, Li M, Qin W, Yue XZ, Zhang XJ, et al. A gene locus responsible for reticulate pigmented anomaly of the flexures maps to chromosome 17p13.3. J Invest Dermatol. Jun 2006;126(6):1297-301. [Medline].

  8. Betz RC, Planko L, Eigelshoven S, Hanneken S, Pasternack SM, Bussow H, et al. Loss-of-function mutations in the keratin 5 gene lead to Dowling-Degos disease. Am J Hum Genet. Mar 2006;78(3):510-9. [Medline].

  9. 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. Feb 2007;127(2):298-300. [Medline].

  10. Jones EW, Grice K. Reticulate pigmented anomaly of the flexures. Dowing Degos disease, a new genodermatosis. Arch Dermatol. Aug 1978;114(8):1150-7. [Medline].

  11. 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. Mar 1999;40(3):462-7. [Medline].

  12. Zuo YG, Ho MG, Jin HZ, Wang BX. Case report: a case of newborn onset reticulate pigmented anomaly of the flexures in a Chinese female. J Eur Acad Dermatol Venereol. Jan 22 2008;[Medline].

  13. Sandhu K, Saraswat A, Kanwar AJ. Dowling-Degos disease with dyschromatosis universalis hereditaria-like pigmentation in a family. J Eur Acad Dermatol Venereol. Nov 2004;18(6):702-4. [Medline].

  14. Loo WJ, Rytina E, Todd PM. Hidradenitis suppurativa, Dowling-Degos and multiple epidermal cysts: a new follicular occlusion triad. Clin Exp Dermatol. Nov 2004;29(6):622-4. [Medline].

  15. O'Goshi K, Terui T, Tagami H. Dowling-Degos disease affecting the vulva. Acta Derm Venereol. May 2001;81(2):148. [Medline].

  16. Massone C, Hofmann-Wellenhof R. Dermoscopy of Dowling-Degos disease of the vulva. Arch Dermatol. Mar 2008;144(3):417-8. [Medline].

  17. Bedlow AJ, Mortimer PS. Dowling-Degos disease associated with hidradenitis suppurativa. Clin Exp Dermatol. Jul 1996;21(4):305-6. [Medline].

  18. Braun-Falco M, Volgger W, Borelli S, Ring J, Disch R. Galli-Galli disease: an unrecognized entity or an acantholytic variant of Dowling-Degos disease?. J Am Acad Dermatol. Nov 2001;45(5):760-3. [Medline].

  19. Gilchrist H, Jackson S, Morse L, Nesbitt LT. Galli-Galli disease: A case report with review of the literature. J Am Acad Dermatol. Feb 2008;58(2):299-302. [Medline].

  20. Ee HL, Tan SH. Reticulate hyperpigmented scleroderma: a new pigmentary manifestation. Clin Exp Dermatol. Mar 2005;30(2):131-3. [Medline].

  21. Zhang RZ, Zhu WY. A study of immunohistochemical and electron microscopic changes in Dowling-Degos disease. J Dermatol. Jan 2005;32(1):12-8. [Medline].

  22. Altomare G, Capella GL, Fracchiolla C, Frigerio E. Effectiveness of topical adapalene in Dowling-Degos disease. Dermatology. 1999;198(2):176-7. [Medline].

  23. Boyle J, Burton JL. Reticulate pigmented anomaly of the flexures and seborrhoeic warts. Clin Exp Dermatol. Jul 1985;10(4):379-83. [Medline].

  24. Fenske NA, Groover CE, Lober CW, Espinoza CG. Dowling-Degos disease, hidradenitis suppurativa, and multiple keratoacanthomas. A disorder that may be caused by a single underlying defect in pilosebaceous epithelial proliferation. J Am Acad Dermatol. May 1991;24(5 Pt 2):888-92. [Medline].

  25. Kikuchi I. Evolution of Dowling Degos disease. J Dermatol. Dec 2000;27(12):806. [Medline].

  26. Lee SJ, Lee HJ, Kim DW, Jun JB, Chung SL, Bae HI. A case of Dowling-Degos disease suggesting an evolutional sequence. J Dermatol. Sep 2000;27(9):591-7. [Medline].

  27. Oiso N, Tsuruta D, Ota T, Kobayashi H, Kawada A. Spotted and rippled reticulate hypermelanosis: a possible variant of Dowling-Degos disease. Br J Dermatol. Jan 2007;156(1):196-8. [Medline].

  28. Starzycki Z. [Case of reticulate pigmented anomaly of the flexures Dowling-Degos]. Przegl Dermatol. May-Jun 1981;68(3):383-7. [Medline].

  29. Tappero JW, Kershenovich J, Berger TG. Combined acral and flexural reticulate pigmentary anomaly. Arch Dermatol. Oct 1992;128(10):1411-2. [Medline].

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Further Reading

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Keywords

Dowling-Degos disease, dark dot disease, Dowling Degos Ossipowski disease, DDD

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Contributor Information and Disclosures

Author

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Borys Savchyk, MD, PhD, Director, Molecular Biology Institute, Medical University of Lviv, Ukraine
Disclosure: Nothing to disclose.

Alexander Zajchenko, MD, Head, Professor, Department of Skin and Venereal Diseases, Medical University of Lviv, Ukraine
Disclosure: Nothing to disclose.

Medical Editor

Mark A Crowe, MD, Assistant Clinical Instructor, Department of Medicine, Division of Dermatology, University of Washington School of Medicine
Mark A Crowe, MD is a member of the following medical societies: American Academy of Dermatology and North American Clinical Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: 3M Pharmaceutical Grant/research funds Other; Graceway Pharmaceuticals Grant/research funds Other

Managing Editor

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey
Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

 
 
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