Skip to content
2000
image of A Comprehensive Review of Acanthosis Nigricans: Pathogenesis, Clinical manifestation and Management

Abstract

Background

Acanthosis Nigricans is a dermatological condition characterized by hyperpigmented velvet plaques that can be observed in flexural areas such as the neck, axilla, and groin. AN is frequently associated with insulin resistance and obesity, however, it can also appear in non-obese people and as a paraneoplastic disease. Its prevalence varies across different populations, with higher rates observed in individuals with obesity, diabetes, and certain genetic syndromes. Classification of AN can be based on underlying etiology, distinguishing primary and secondary forms. Pathogenesis is the complex interplay of genetic, hormonal, and environmental factors, with insulin resistance playing a central role. Diagnosis relies on clinical evaluation of characteristics of skin changes, often requiring further investigation for underlying systemic disease. Topical therapies involve keratolytic agents, retinoids, and alpha hydroxyl acids to improve the cosmesis and reduce the plaque's thickness. Treatment strategies address underlying conditions by emphasizing lifestyle modifications and in some cases, pharmacological interventions.

Objective

This review aims to comprehensively examine the pathogenesis, clinical manifestation, and management of acanthosis nigricans.

Discussion

AN is closely linked to insulin resistance, characterized by impaired cellular response to insulin, leading to compensatory hyperinsulinemia. Recognizing AN’s clinical presentation is paramount for early diagnosis and appropriate management.

Conclusion

Acanthosis Nigricans is a skin condition characterized by dark, thickened patches of skin, typically occurring in skin folds and creases. It can be a sign of an underlying health issue such as insulin resistance, obesity, hormonal disorders, or certain medications. Proper diagnosis and management of the underlying conditions are crucial. Treatment may involve addressing the underlying causes, lifestyle changes, and topical medications to improve the appearance of the skin. Regular monitoring and follow-up with a health care professional are essential for optimal management and to prevent complications.

Loading

Article metrics loading...

/content/journals/raiad/10.2174/0127722708314530240919054410
2024-10-03
2024-10-22
Loading full text...

Full text loading...

References

  1. Burke J.P. Hale D.E. Hazuda H.P. Stern M.P. A quantitative scale of acanthosis nigricans. Diabetes Care 1999 22 10 1655 1659 10.2337/diacare.22.10.1655 10526730
    [Google Scholar]
  2. Ozlu E. Uzuncakmak T.K. Takır M. Akdeniz N. Karadag A.S. Comparison of cutaneous manifestations in diabetic and nondiabetic obese patients: A prospective, controlled study. North. Clin. Istanb. 2018 5 2 114 119 30374476
    [Google Scholar]
  3. Smid C.J. Modaff P. Alade A. Legare J.M. Pauli R.M. Acanthosis nigricans in achondroplasia. Am. J. Med. Genet. A. 2018 176 12 2630 2636 10.1002/ajmg.a.40506 30380187
    [Google Scholar]
  4. Higgins S.P. Freemark M. Prose N.S. Acanthosis Nigricans: A practical approach to evaluation and management. Dermatol. Online J. 2008 14 9 2 10.5070/D37MF6G290 19061584
    [Google Scholar]
  5. Popa M.L. Popa A.C. Tanase C. Gheorghisan-Galateanu A.A. Acanthosis nigricans: To be or not to be afraid. Oncol. Lett. 2019 17 5 4133 4138 30944606
    [Google Scholar]
  6. Varthakavi P.K. Waingankar A. Patel K.L. Wadhwa S.L. Khopkar U. Sengupta R.A. Merchant P.C. Mehtalia S.D. Nihalani K.D. Acanthosis nigricans: a dermatologic marker of metabolic disease. Venereology and Leprology. 2002 68 2 67 72 17656880
    [Google Scholar]
  7. González-Saldivar G. Rodríguez-Gutiérrez R. Ocampo-Candiani J. González-González J.G. Gómez-Flores M. Skin manifestations of insulin resistance: from a biochemical stance to a clinical diagnosis and management. Dermatol. Ther. (Heidelb.) 2017 7 1 37 51 10.1007/s13555‑016‑0160‑3 27921251
    [Google Scholar]
  8. Ng H.Y. Acanthosis nigricans in obese adolescents: prevalence, impact, and management challenges. Adolesc. Health Med. Ther. 2016 8 1 10 10.2147/AHMT.S103396 28031729
    [Google Scholar]
  9. Kanwar A.J. Sawatkar G.U. Dogra S. Bhadada S.K. Acanthosis nigricans--An uncommon cutaneous adverse effect of a common medication: Report of two cases. Indian J. Dermatol. Venereol. Leprol. 2013 79 4 553 10.4103/0378‑6323.113112 23760338
    [Google Scholar]
  10. Yu Q. Li X.L. Ji G. Wang Y. Gong Y. Xu H. Shi Y.L. Malignant acanthosis nigricans: an early diagnostic clue for gastric adenocarcinoma. World J. Surg. Oncol. 2017 15 1 208 10.1186/s12957‑017‑1274‑5 29178944
    [Google Scholar]
  11. Phiske M. An approach to acanthosis nigricans. Indian Dermatol. Online J. 2014 5 3 239 249 10.4103/2229‑5178.137765 25165638
    [Google Scholar]
  12. Bishnoi A. Parsad D. Velvety hyperpigmentation on hands and feet of a young girl: Acral acanthosis nigricans. J. Cutan. Med. Surg. 2018 22 3 323 10.1177/1203475417736282 29865956
    [Google Scholar]
  13. Kura M. Sanghavi S. Acral acanthosis nigricans in a case of scleroderma. Indian J. Dermatol. 2015 60 4 423 10.4103/0019‑5154.160540 26288450
    [Google Scholar]
  14. Cama A. de la Luz Sierra M. Kadowaki T. Kadowaki H. Quon M.J. Rüdiger H.W. Dreyer M. Taylor S.I. Two mutant alleles of the insulin receptor gene in a family with a genetic form of insulin resistance: a 10 base pair deletion in exon 1 and a mutation substituting serine for asparagine-462. Hum. Genet. 1995 95 2 174 182 10.1007/BF00209397 7860063
    [Google Scholar]
  15. Kim H.N. Fesseha B. Anzaldi L. Tsao A. Galiatsatos P. Sidhaye A. Antibody-mediated extreme insulin resistance: a report of three cases. Am. J. Med. 2018 131 1 102 106 10.1016/j.amjmed.2017.08.004 28822702
    [Google Scholar]
  16. Miquel J. Hadj-Rabia S. Boddaert N. Lascelles K. Bahi-Buisson N. Atypical presentation of neuropsychiatric lupus with acanthosis nigricans. Pediatr. Neurol. 2012 47 4 291 294 10.1016/j.pediatrneurol.2012.06.005 22964444
    [Google Scholar]
  17. Kondo Y. Umegaki N. Terao M. Murota H. Kimura T. Katayama I. A case of generalized acanthosis nigricans with positive lupus erythematosus-related autoantibodies and antimicrosomal antibody: autoimmune acanthosis nigricans? Case Rep. Dermatol. 2012 4 1 85 91 10.1159/000337751 22649336
    [Google Scholar]
  18. Imperato-McGinley J. Peterson R.E. Sturla E. Dawood Y. Bar R.S. Primary amenorrhea associated with hirsutism, acanthosis nigricans, dermoid cysts of the ovaries and a new type of insulin resistance. Am. J. Med. 1978 65 2 389 395 10.1016/0002‑9343(78)90838‑0 686026
    [Google Scholar]
  19. Hermanns-Lê T. Scheen A. Piérard G.E. Acanthosis nigricans associated with insulin resistance : pathophysiology and management. Am. J. Clin. Dermatol. 2004 5 3 199 203 10.2165/00128071‑200405030‑00008 15186199
    [Google Scholar]
  20. Brady MF Rawla P Acanthosis nigricans. StatPearls Treasure Island (FL): StatPearls Publishing 2024
    [Google Scholar]
  21. Torley D. Bellus G.A. Munro C.S. Genes, growth factors and acanthosis nigricans. Br. J. Dermatol. 2002 147 6 1096 1101 10.1046/j.1365‑2133.2002.05150.x 12452857
    [Google Scholar]
  22. Neagu M. Caruntu C. Constantin C. Boda D. Zurac S. Spandidos D.A. Tsatsakis A.M. Chemically induced skin carcinogenesis: Updates in experimental models (Review). Oncol. Rep. 2016 35 5 2516 2528 10.3892/or.2016.4683 26986013
    [Google Scholar]
  23. Rudman S.M. Philpott M.P. Thomas G.A. Kealey T. The role of IGF-I in human skin and its appendages: morphogen as well as mitogen? J. Invest. Dermatol. 1997 109 6 770 777 10.1111/1523‑1747.ep12340934 9406819
    [Google Scholar]
  24. Jeong K.H. Oh S.J. Chon S. Lee M.H. Resistance Syndrome: A Case Report Generalized Acanthosis Nigricans Related to Type B Insulin From the Department of Dermatology and the Department of Internal Medicine, College of Medicine, Kyunghee University, Seoul, Korea. Cutis 2010 86 6 299 21284281
    [Google Scholar]
  25. Napolitano M. Megna M. Monfrecola G. Insulin resistance and skin diseases. ScientificWorldJournal 2015 2015 1 479354 10.1155/2015/479354 25977937
    [Google Scholar]
  26. Blomberg M. Jeppesen E.M. Skovby F. Benfeldt E. FGFR3 mutations and the skin: report of a patient with a FGFR3 gene mutation, acanthosis nigricans, hypochondroplasia and hyperinsulinemia and review of the literature. Dermatology 2010 220 4 297 305 10.1159/000297575 20453470
    [Google Scholar]
  27. Mir A. Wu T. Orlow S.J. Cutaneous features of Crouzon syndrome with acanthosis nigricans. JAMA Dermatol. 2013 149 6 737 741 10.1001/jamadermatol.2013.3019 23571469
    [Google Scholar]
  28. Lane S.W. Manoharan S. Mollee P.N. Palifermin‐induced acanthosis nigricans. Intern. Med. J. 2007 37 6 417 418 10.1111/j.1445‑5994.2007.01340.x 17535389
    [Google Scholar]
  29. Krawczyk M. Mykała-Cieśla J. Kołodziej-Jaskuła A. Acanthosis nigricans as a paraneoplastic syndrome. Case reports and review of literature. Polish Archives of Internal Medicine 2009 119 3 180 183 10.20452/pamw.642 19514649
    [Google Scholar]
  30. James WD Elston D Berger T Andrew's diseases of the Skin E-book: Clinical dermatology Elsevier 2011
    [Google Scholar]
  31. Burns T. Breathnach S.M. Cox N. Griffiths C. Rook’s textbook of dermatology. John Wiley & Sons 2008
    [Google Scholar]
  32. Pavithran K. Karunakaran M. Palit A. Disorders of keratinization. IADVL Textbook of Dermatology. 3rd ed Valia R.G. Ameet R.V. Mumbai Bhalani Publishing House 2008 1009 1011
    [Google Scholar]
  33. Devpura S. Pattamadilok B. Syed Z.U. Vemulapalli P. Henderson M. Rehse S.J. Hamzavi I. Lim H.W. Naik R. Critical comparison of diffuse reflectance spectroscopy and colorimetry as dermatological diagnostic tools for acanthosis nigricans: a chemometric approach. Biomed. Opt. Express 2011 2 6 1664 1673 10.1364/BOE.2.001664 21698027
    [Google Scholar]
  34. Gupta A.K. Bluhm R. Cooper E.A. Summerbell R.C. Batra R. Seborrheic dermatitis. Dermatol. Clin. 2003 21 3 401 412 10.1016/S0733‑8635(03)00028‑7 12956195
    [Google Scholar]
  35. Hay R.J. Tinea capitis: current status. Mycopathologia 2017 182 1-2 87 93 10.1007/s11046‑016‑0058‑8 27599708
    [Google Scholar]
  36. Dunn C. Applebaum D.S. Dao H. Jr Widespread hyperpigmented rash present for 1 year. JAAD Case Rep. 2018 4 8 743 745 10.1016/j.jdcr.2018.04.012 30225330
    [Google Scholar]
  37. Erythrasma T-N.I. AgoEmergencias. 2018 30 4 283
    [Google Scholar]
  38. Raesi Vanani A. Mahdavinia M. Kalantari H. Khoshnood S. Shirani M. Antifungal effect of the effect of Securigera securidaca L. vaginal gel on Candida species. Curr. Med. Mycol. 2019 5 3 31 35 10.18502/cmm.5.3.1744 31850394
    [Google Scholar]
  39. Savvidou S. Pellagra: a non-eradicated old disease. Clin. Pract. 2014 4 1 637 10.4081/cp.2014.637 24847436
    [Google Scholar]
  40. Jaffar H. Shakir Z. Kumar G. Ali I.F. Ichthyosis vulgaris: An updated review. Skin Health Dis. 2023 3 1 e187 10.1002/ski2.187 36751330
    [Google Scholar]
  41. Nicholson CL Daveluy S Epidermal nevus syndromes. StatPearls Treasure Island (FL): StatPearls Publishing 2024
    [Google Scholar]
  42. Lucero R Horowitz D. Granular parakeratosis. StatPearls Treasure Island (FL): StatPearls Publishing 2024
    [Google Scholar]
  43. Ng H.Y. Young J.H. Huen K.F. Chan L.T. Acanthosis nigricans in obese Chinese children. Hong Kong Med. J. 2014 20 4 290 296 24762331
    [Google Scholar]
  44. Brickman W.J. Binns H.J. Jovanovic B.D. Kolesky S. Mancini A.J. Metzger B.E. Acanthosis nigricans: a common finding in overweight youth. Pediatr. Dermatol. 2007 24 6 601 606 10.1111/j.1525‑1470.2007.00547.x 18035980
    [Google Scholar]
  45. Otto D.E. Wang X. Garza V. Fuentes L.A. Rodriguez M.C. Sullivan P. Increasing body mass index, blood pressure, and Acanthosis Nigricans abnormalities in school-age children. J. Sch. Nurs. 2013 29 6 442 451 10.1177/1059840513483180 23553623
    [Google Scholar]
  46. Nsiah-Kumi P.A. Beals J. Lasley S. Whiting M. Brushbreaker C. Erickson J. Qiu F. Yu F. Canaris G. Larsen J.L. Body mass index percentile more sensitive than acanthosis nigricans for screening Native American children for diabetes risk. J. Natl. Med. Assoc. 2010 102 10 944 949 10.1016/S0027‑9684(15)30714‑8 21053710
    [Google Scholar]
  47. Berger B.J. Gross P.R. Another use for tretinoin--pseudoacanthosis nigricans. Arch. Dermatol. 1973 108 1 133 134 10.1001/archderm.1973.01620220087029 4716734
    [Google Scholar]
  48. Darmstadt G.L. Yokel B.K. Horn T.D. Treatment of acanthosis nigricans with tretinoin. Arch. Dermatol. 1991 127 8 1139 1140 10.1001/archderm.1991.01680070039003 1863071
    [Google Scholar]
  49. Adigun C.G. Pandya A.G. Improvement of idiopathic acanthosis nigricans with a triple combination depigmenting cream. J. Eur. Acad. Dermatol. Venereol. 2009 23 4 486 487 10.1111/j.1468‑3083.2008.02931.x 18721216
    [Google Scholar]
  50. Schwartz R.A. Efficacy of topical 0.1% adapalene gel for use in the treatment of childhood acanthosis nigricans: a pilot study. Dermatol. Ther. 2015 28 4 266 10.1111/dth.12224 25817595
    [Google Scholar]
  51. Gregoriou S. Anyfandakis V. Kontoleon P. Christofidou E. Rigopoulos D. Kontochristopoulos G. Acanthosis nigricans associated with primary hypogonadism: Successful treatment with topical calcipotriol. J. Dermatolog. Treat. 2008 19 6 373 375 10.1080/09546630802050506 18608738
    [Google Scholar]
  52. Zayed A. Sobhi R.M. Abdel Halim D.M. Using trichloroacetic acid in the treatment of acanthosis nigricans: a pilot study. J. Dermatolog. Treat. 2014 25 3 223 225 10.3109/09546634.2012.674194 22494198
    [Google Scholar]
  53. Katz R.A. Treatment of acanthosis nigricans with oral isotretinoin. Arch. Dermatol. 1980 116 1 110 111 10.1001/archderm.1980.01640250112027 7352756
    [Google Scholar]
  54. Özdemi˙r M. Toy H. Mevli˙toğlu İ. Demi˙rkesen C. Generalized idiopathic acanthosis nigricans treated with acitretin. J. Dermatolog. Treat. 2006 17 1 54 56 10.1080/09546630500497280 16511962
    [Google Scholar]
  55. Bellot-Rojas P. Posadas-Sanchez R. Caracas-Portilla N. Zamora-Gonzalez J. Cardoso-Saldaña G. Jurado-Santacruz F. Posadas-Romero C. Comparison of metformin versus rosiglitazone in patients with Acanthosis nigricans: a pilot study. J. Drugs Dermatol. 2006 5 9 884 889 17039655
    [Google Scholar]
  56. Romo A. Benavides S. Treatment options in insulin resistance obesity-related acanthosis nigricans. Ann. Pharmacother. 2008 42 7-8 1090 1094 10.1345/aph.1K446 18492785
    [Google Scholar]
  57. Sherertz E.F. Improved acanthosis nigricans with lipodystrophic diabetes during dietary fish oil supplementation. Arch. Dermatol. 1988 124 7 1094 1096 10.1001/archderm.1988.01670070082026 3389852
    [Google Scholar]
  58. Coates P. Shuttleworth D. Rees A. Resolution of nicotinic acid-induced acanthosis nigricans by substitution of an analogue (acipimox) in a patient with type V hyperlipidaemia. Br. J. Dermatol. 1992 126 4 412 414 10.1111/j.1365‑2133.1992.tb00692.x 1571266
    [Google Scholar]
  59. Patel N.U. Roach C. Alinia H. Huang W. Feldman S. Current treatment options for acanthosis nigricans. Clin. Cosmet. Investig. Dermatol. 2018 11 407 413 10.2147/CCID.S137527 30122971
    [Google Scholar]
  60. Greco MJ Bhutta BS Seborrheic keratosis. StatPearls Treasure Island (FL): StatPearls Publishing 2024
    [Google Scholar]
  61. Roh N.K. Hahn H.J. Lee Y.W. Choe Y.B. Ahn K.J. Clinical and histopathological investigation of seborrheic keratosis. Ann. Dermatol. 2016 28 2 152 158 10.5021/ad.2016.28.2.152 27081260
    [Google Scholar]
  62. Prabhu D. Dawe R.S. Mponda K. Pellagra a review exploring causes and mechanisms, including isoniazid‐induced pellagra. Photodermatol. Photoimmunol. Photomed. 2021 37 2 99 104 10.1111/phpp.12659 33471377
    [Google Scholar]
  63. Ben Ghorbel I. Litaiem N. Chelly I. Houman H. Pellagra in a patient with primary Sjögren's syndrome. BMJ Case Rep. 2014 2014 bcr2014204339
    [Google Scholar]
  64. Patel P. Malik K. Khachemoune A. Sebaceus and Becker’s nevus: overview of their presentation, pathogenesis, associations, and treatment. Am. J. Clin. Dermatol. 2015 16 3 197 204 10.1007/s40257‑015‑0123‑y 25782676
    [Google Scholar]
/content/journals/raiad/10.2174/0127722708314530240919054410
Loading
/content/journals/raiad/10.2174/0127722708314530240919054410
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test