Approach Considerations

The dermoscopic findings of Dowling-Degos disease (reticulate pigmented anomaly) are not specific, but they may be useful in selected patients to rule out melanoma of the vulva.^[35]

In some patients, molecular genetic analysis can facilitate making the diagnosis.^[46]

Histologic Findings

Histopathologically in Dowling-Degos disease (reticulate pigmented anomaly), pigmented rete ridge elongation with thinning of the suprapapillary epithelium, dermal melanosis, and perivascular lymphohistiocytic infiltration is present. The downward elongations are composed of regular pigmented basaloid cells.

A small study showed all pigmented cells in the basal layer were recognized by anti-PEP-1, anti-PEP-2, HMB-45, and NKI/beteb antibodies.^[47]Supranuclear "caps" of brown granules were observed within most basal keratinocytes in the hyperpigmentation area. The melanocytes contained regular melanosomes in all stages of maturation in their cytoplasms. Melanosomes, mainly of stages III and IV, were evident within keratinocytes, distributed either as scattered patterns or forming caps over the nucleus. Note the image below.

Histologic view showing elongated thin rete ridges with melanin concentrated at the tips (hematoxylin and eosin).

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Treatment & Management

Dowling GD, Freudenthal W. Acanthosis nigricans. Proc Roy Soc Med. 1938. 31:1147-50.
Degos R, Ossipowski B. [Reticulated pigmentary dermatosis of the folds: relation to acanthosis nigricans.]. Ann Dermatol Syphiligr (Paris). 1954 Mar-Apr. 81(2):147-51. [QxMD MEDLINE Link].
Stephan C, Kurban M, Abbas O. Dowling-Degos disease: a review. Int J Dermatol. 2020 Dec 23. [QxMD MEDLINE Link].
Hanneken S, Rütten A, Pasternack SM, Eigelshoven S, El Shabrawi-Caelen L, Wenzel J, et al. Systematic mutation screening of KRT5 supports the hypothesis that Galli-Galli disease is a variant of Dowling-Degos disease. Br J Dermatol. 2010 Mar 5. [QxMD MEDLINE Link].
Hanneken S, Rütten A, Eigelshoven S, Braun-Falco M, Pasternack SM, Ruzicka T, et al. [Galli-Galli disease. Clinical and histopathological investigation using a case series of 18 patients]. Hautarzt. 2011 Nov. 62(11):842-51. [QxMD MEDLINE Link].
Basmanav FB, Oprisoreanu AM, Pasternack SM, Thiele H, Fritz G, Wenzel J, et al. Mutations in POGLUT1, encoding protein O-glucosyltransferase 1, cause autosomal-dominant Dowling-Degos disease. Am J Hum Genet. 2014 Jan 2. 94(1):135-43. [QxMD MEDLINE Link]. [Full Text].
Basmanav FB, Fritz G, Lestringant GG, Pachat D, Hoffjan S, Fischer J, et al. Pathogenicity of POFUT1 in Dowling-Degos disease: additional mutations and clinical overlap with reticulate acropigmentation of kitamura. J Invest Dermatol. 2015 Feb. 135(2):615-8. [QxMD MEDLINE Link].
Kono M, Suganuma M, Takama H, Zarzoso I, Saritha M, Bodet D, et al. Dowling-Degos disease with mutations in POFUT1 is clinico-pathologically distinct from reticulate acropigmentation of Kitamura. Br J Dermatol. 2015 Feb 1. [QxMD MEDLINE Link].
Duchatelet S, Clerc H, Machet L, Gaboriaud P, Miskinyte S, Kervarrec T, et al. A new nonsense mutation in the POGLUT1 gene in two sisters with Dowling-Degos disease. J Eur Acad Dermatol Venereol. 2018 Mar 23. [QxMD MEDLINE Link].
Kono M, Sawada M, Nakazawa Y, Ogi T, Muro Y, Akiyama M. A Japanese Case of Galli-Galli Disease due to a Previously Unreported POGLUT1 Mutation. Acta Derm Venereol. 2019 Apr 1. 99 (4):458-459. [QxMD MEDLINE Link].
García-Gil MF, Monte Serrano J, Ramirez-Lluch M, Valero Torres A, López-Giménez MT, Lezcano Biosca V. A novel mutation in POFUT1 gene associated with Dowling-Degos disease and hidradenitis suppurativa. Int J Dermatol. 2021 Jan. 60 (1):e25-e27. [QxMD MEDLINE Link].
Ren J, Zeng LY. Scrotal Dowling-Degos disease caused by a novel frameshift variant in gamma-secretase subunit presenile enhancer gene. Australas J Dermatol. 2020 Nov. 61 (4):e399-e402. [QxMD MEDLINE Link].
Müller CS, Pföhler C, Tilgen W. Changing a concept--controversy on the confusing spectrum of the reticulate pigmented disorders of the skin. J Cutan Pathol. 2009 Jan. 36(1):44-8. [QxMD MEDLINE Link].
El Shabrawi-Caelen L, Rütten A, Kerl H. The expanding spectrum of Galli-Galli disease. J Am Acad Dermatol. 2007 May. 56(5 Suppl):S86-91. [QxMD MEDLINE Link].
Brown WG. Reticulate pigmented anomaly of the flexures. Case reports and genetic investigation. Arch Dermatol. 1982 Jul. 118(7):490-3. [QxMD MEDLINE Link].
Yu W, Gan L, Wu J, Sun J, Jiang Y. Dowling-Degos disease with mutation in the exon 1 of the keratin 5 gene. J Eur Acad Dermatol Venereol. 2017 Jun 24. [QxMD MEDLINE Link].
Li CR, Xing QH, Li M, et al. A gene locus responsible for reticulate pigmented anomaly of the flexures maps to chromosome 17p13.3. J Invest Dermatol. 2006 Jun. 126(6):1297-301. [QxMD MEDLINE Link].
Betz RC, Planko L, Eigelshoven S, et al. Loss-of-function mutations in the keratin 5 gene lead to Dowling-Degos disease. Am J Hum Genet. 2006 Mar. 78(3):510-9. [QxMD MEDLINE Link].
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. 2007 Feb. 127(2):298-300. [QxMD MEDLINE Link].
Bedlow AJ, Mortimer PS. Dowling-Degos disease associated with hidradenitis suppurativa. Clin Exp Dermatol. 1996 Jul. 21(4):305-6. [QxMD MEDLINE Link].
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. 1991 May. 24(5 Pt 2):888-92. [QxMD MEDLINE Link].
Khaddar RK, Mahjoub WK, Zaraa I, Sassi MB, Osman AB, Debbiche AC, et al. [Extensive Dowling-Degos disease following long term PUVA therapy]. Ann Dermatol Venereol. 2012 Jan. 139(1):54-7. [QxMD MEDLINE Link].
Jones EW, Grice K. Reticulate pigmented anomaly of the flexures. Dowing Degos disease, a new genodermatosis. Arch Dermatol. 1978 Aug. 114(8):1150-7. [QxMD MEDLINE Link].
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. 1999 Mar. 40(3):462-7. [QxMD MEDLINE Link].
Zuo YG, Ho M, 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. 2008 Jul. 22(7):901-3. [QxMD MEDLINE Link].
Sandhu K, Saraswat A, Kanwar AJ. Dowling-Degos disease with dyschromatosis universalis hereditaria-like pigmentation in a family. J Eur Acad Dermatol Venereol. 2004 Nov. 18(6):702-4. [QxMD MEDLINE Link].
Loo WJ, Rytina E, Todd PM. Hidradenitis suppurativa, Dowling-Degos and multiple epidermal cysts: a new follicular occlusion triad. Clin Exp Dermatol. 2004 Nov. 29(6):622-4. [QxMD MEDLINE Link].
Naveen KN, Athaniker SB, Hegde SP, Shetty R, Radha H, Parinitha SS. Atypical cases of Dowling-Degos disease. Indian Dermatol Online J. 2016 Mar-Apr. 7 (2):99-102. [QxMD MEDLINE Link].
Ghosh A, Kumar P, Das A. Generalized Dowling-Degos disease with hypopigmented lesions: A diagnostic challenge. Indian J Dermatol Venereol Leprol. 2018 Jan-Feb. 84 (1):70-72. [QxMD MEDLINE Link].
Singh S, Khandpur S, Verma P, Singh M. Follicular Dowling Degos disease: a rare variant of an evolving dermatosis. Indian J Dermatol Venereol Leprol. 2013 Nov-Dec. 79(6):802-4. [QxMD MEDLINE Link].
Schwartz RA, Birnkrant AP, Burgess GH, Stoll HL Jr, Yaqub M, Fox MD. Reticulate pigmented anomaly. Cutis. 1980 Oct. 26(4):380-1. [QxMD MEDLINE Link].
Batycka-Baran A, Baran W, Hryncewicz-Gwozdz A, Burgdorf W. Dowling-Degos disease: case report and review of the literature. Dermatology. 2010. 220(3):254-8. [QxMD MEDLINE Link].
Taskapan O, Gokce E, Akin O, Erkilinc AC, Demirkesen C. Dowling-Degos disease with diffuse penile pigmentation. J Eur Acad Dermatol Venereol. 2014 Jan 15. [QxMD MEDLINE Link].
O'Goshi K, Terui T, Tagami H. Dowling-Degos disease affecting the vulva. Acta Derm Venereol. 2001 May. 81(2):148. [QxMD MEDLINE Link].
Massone C, Hofmann-Wellenhof R. Dermoscopy of Dowling-Degos disease of the vulva. Arch Dermatol. 2008 Mar. 144(3):417-8. [QxMD MEDLINE Link].
Coco V, Guerriero C, Esposito I, De Vincenzo RP, Peris K. A familial case of Dowling-Degos disease on the vulva. Clin Exp Dermatol. 2019 Jan 21. [QxMD MEDLINE Link].
Lee SJ, Lee HJ, Kim DW, Jun JB, Chung SL, Bae HI. A case of Dowling-Degos disease suggesting an evolutional sequence. J Dermatol. 2000 Sep. 27(9):591-7. [QxMD MEDLINE Link].
Nishizawa A, Nakano H, Satoh T, Takayama K, Sawamura D, Yokozeki H. Haber's syndrome may be a clinical entity different from Dowling-Degos disease. Br J Dermatol. 2009 Jan. 160(1):215-7. [QxMD MEDLINE Link].
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. 2001 Nov. 45(5):760-3. [QxMD MEDLINE Link].
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. 2008 Feb. 58(2):299-302. [QxMD MEDLINE Link].
Ee HL, Tan SH. Reticulate hyperpigmented scleroderma: a new pigmentary manifestation. Clin Exp Dermatol. 2005 Mar. 30(2):131-3. [QxMD MEDLINE Link].
Shen Z, Chen L, Ye Q, Hao F, Vitorino Mdos S, Yang X, et al. Coexistent Dowling-Degos disease and reticulate acropigmentation of kitamura with progressive seborrheic keratosis. Cutis. 2011 Feb. 87(2):73-5. [QxMD MEDLINE Link].
Rongioletti F, Fausti V, Christana K, Montinari M, Parodi A, Fiocca R. Atypical Variant of Galli-Galli Disease (Grover-Like Eruption With Lentiginous Freckling) in a Liver Transplant Patient. Am J Dermatopathol. 2011 Jan 19. [QxMD MEDLINE Link].
Müller CS, Tremezaygues L, Pföhler C, Vogt T. The spectrum of reticulate pigment disorders of the skin revisited. Eur J Dermatol. 2012 Sep-Oct. 22(5):596-604. [QxMD MEDLINE Link].
Strausburg M, Linos K, Staser K, Mousdicas N. Dowling-Degos disease co-presenting with Darier disease. Clin Exp Dermatol. 2016 Jun. 41 (4):410-2. [QxMD MEDLINE Link].
Knuever J, Persa OD, Illerhaus A, Ralser DJ, Hartmann K, Betz RC, et al. Mast cell activation in Dowling-Degos disease. Br J Dermatol. 2019 Dec. 181 (6):1312-1314. [QxMD MEDLINE Link].
Zhang RZ, Zhu WY. A study of immunohistochemical and electron microscopic changes in Dowling-Degos disease. J Dermatol. 2005 Jan. 32(1):12-8. [QxMD MEDLINE Link].
Yun JH, Kim JH, Choi JS, Roh JY, Lee JR. Treatment of Dowling-Degos disease with fractional Er:YAG laser. J Cosmet Laser Ther. 2013 Mar 6. [QxMD MEDLINE Link].
Tambe SA, Patil PD, Saple DG. Successful Management of Dowling-Degos Disease with Combination of Q-switched Nd: YAG and Fractional Carbon Dioxide Laser. J Cutan Aesthet Surg. 2017 Jan-Mar. 10 (1):60-62. [QxMD MEDLINE Link].
Gupta A, Huilgol SC. Successful treatment of Dowling-Degos disease using intense pulsed light. Australas J Dermatol. 2014 Dec 13. [QxMD MEDLINE Link].
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. 2002 Jun 15. 110(2):164-9. [QxMD MEDLINE Link].

Media Gallery

Speckled macules on the male external genitalia.
Histologic view showing elongated thin rete ridges with melanin concentrated at the tips (hematoxylin and eosin).

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Acknowledgements

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.

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.

Reticulate Pigmented Anomaly Workup

Approach Considerations

Histologic Findings

References

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