Review Article
Diabetes Mellitus and the Skin: Recognition and Management of Cutaneous Manifestations
Abstract
Diabetes mellitus (DM) is a heterogeneous condition characterized by hyperglycemia as a consequence of defects in insulin secretion and variable degrees of insulin resistance. DM is the most common endocrine disorder in the United States, affecting 9.3% of the population (29.1 million people) in 2014. Skin disorders are present in 79.2% of patients with DM, and cutaneous disease may appear as the first sign of DM or develop at any time in the course of the disease. Given the increasing incidence and prevalence of DM in the United States, primary care physicians should be aware of the associated cutaneous manifestations. This clinical review provides a brief guide to primary care physicians for recognizing and managing skin conditions that they may encounter when caring for patients with DM.This content is limited to qualifying members.
Existing members, please login first
If you have an existing account please login now to access this article or view purchase options.
Purchase only this article ($25)
Create a free account, then purchase this article to download or access it online for 24 hours.
Purchase an SMJ online subscription ($75)
Create a free account, then purchase a subscription to get complete access to all articles for a full year.
Purchase a membership plan (fees vary)
Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.
References
1. Karalliedde J, Gnudi L. Diabetes mellitus, a complex and heterogenous disease, and the role of insulin resistance as a determinant of diabetic kidney disease. Nephrol Dial Transplant 2016;31:206-213.
2. Centers for Disease Control and Prevention. National diabetes fact sheet, 2014. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf. Accessed February 14, 2016.
3. Demirseren DD, Emre S, Akoglu G, et al. Relationship between skin diseases and extracutaneous complications of diabetes mellitus: clinical analysis of 750 patients. Am J Clin Dermatol 2014;15:65-70.
4. Duff M, Demidova O, Blackburn S, et al. Cutaneous manifestations of diabetes mellitus. Clin Diabetes 2015;33:40-48.
5. Geiss LS, Wang J, Cheng YJ, et al. Prevalence and incidence trends for diagnosed diabetes among adults aged 20 to 79 years, United States, 1980-2012. JAMA 2014;312:1218-1226.
6. Lipsky BA, Berendt AR, Cornia PB, et al. Executive summary: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012;54:1679-1684.
7. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014;59:e10-e52.
8. Higgins JC, Maher MH, Douglas MS. Diagnosing common benign skin tumors. Am Fam Physician 2015;92:601-607.
9. Banik R, Lubach D. Skin tags: localization and frequencies according to sex and age. Dermatologica 1987;174:180-183.
10. Kahana M, Grossman E, Feinstein A, et al. Skin tags: a cutaneous marker for diabetes mellitus. Acta Derm Venereol 1987;67:175-177.
11. Sari R, Akman A, Alpsoy E, et al. The metabolic profile in patients with skin tags. Clin Exp Med 2010;10:193-197.
12. Kalus AA, Chien AJ, Olerud JE. Diabetes mellitus and other endocrine diseases. In: Goldsmith LA, Katz SI, Gilchrest BA, et al., eds. Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: McGraw-Hill, 2012.
13. Hud JA, Jr Cohen JB, Wagner JM, et al. Prevalence and significance of acanthosis nigricans in an adult obese population. Arch Dermatol 1992;128:941-944.
14. Cruz PD, Hud JA. Excess insulin binding to insulin-like growth factor receptors: proposed mechanism for acanthosis nigricans. J Invest Dermatol 1992;98(6 Suppl):82S-85S.
15. Puri N. A study of pathogenesis of acanthosis nigricans and its clinical implications. Indian J Dermatol 2011;56:678-683.
16. Brickman WJ, Huang J, Silverman BL, et al. Acanthosis nigricans identifies youth at high risk for metabolic abnormalities. J Pediatr 2010;156:87-92.
17. Paron NG, Lambert PW. Cutaneous manifestations of diabetes mellitus. Prim Care 2000;27:371-383.
18. Abdelghany M, Massoud S. Eruptive xanthoma. Cleve Clin J Med 2015;82:209-210.
19. Durrington P. Dyslipidaemia. Lancet 2003;362:717-731.
20. Parker F. Xanthomas and hyperlipidemias. J Am Acad Dermatol 1985;13:1-30.
21. Robson KJ, Piette WW. Cutaneous manifestations of systemic diseases. Med Clin North Am 1998;82:1359-1379.
22. Ladizinski B, Lee KC. Eruptive xanthomas in a patient with severe hypertriglyceridemia and type 2 diabetes. CMAJ 2013;185:1600.
23. Martinez DP, Diaz JO, Bobes CM. Eruptive xanthomas and acute pancreatitis in a patient with hypertriglyceridemia. Int Arch Med 2008;1:6.
24. Levy L, Zeichner JA. Dermatologic manifestations of diabetes. J Diabetes 2012;4:68-76.
25. Ferringer T, Miller F. Cutaneous manifestations of diabetes mellitus. Dermatol Clin 2002;20:483-492.
26. Murphy-Chutorian B, Han G, Cohen SR. Dermatologic manifestations of diabetes mellitus: a review. Endocrinol Metab Clin North Am 2013;42:869-898.
27. Cole GW, Headley J, Skowsky R. Scleredema diabeticorum: a common and distinct cutaneous manifestation of diabetes mellitus. Diabetes Care 1983;6:189-192.
28. Brik R, Berant M, Vardi P. The scleroderma-like syndrome of insulin-dependent diabetes mellitus. Diabetes Metab Rev 1991;7:120-128.
29. Martin C, Requena L, Manrique K, et al. Scleredema diabeticorum in a patient with type 2 diabetes mellitus. Case Rep Endocrinol 2011;2011:560273.
30. Seyger MM, van den Hoogen FH, de Mare S, et al. A patient with a severe scleroedema diabeticorum, partially responding to low-dose methotrexate. Dermatology 1999;198:177-179.
31. Ikeda Y, Suehiro T, Abe T, et al. Severe diabetic scleredema with extension to the extremities and effective treatment using prostaglandin E1. Intern Med 1998;37:861-864.
32. Taieb A, Picardo M, , VETF Members. The definition and assessment of vitiligo: a consensus report of the Vitiligo European Task Force. Pigment Cell Res 2007;20:27-35.
33. Spritz RA. The genetics of generalized vitiligo. Cur Dir Autoimmun 2008;10:244-257.
34. Kahaly GJ, Hansen MP. Type 1 diabetes associated autoimmunity. Autoimmun Rev 2016;15:644-648.
35. Matz H, Tur E. Vitiligo. Curr Probl Dermatol 2007;35:78-102.
36. Parsad D, Dogra S, Kanwar AJ. Quality of life in patients with vitiligo. Health Qual Life Outcomes 2003;1:58.
37. Wake N, Fang JC, , Images in clinical medicine. Necrobiosis lipoidica diabeticorum. N Engl J Med 2006;355:e20.
38. Haralambous S, Blackwell C, Mappouras DG, et al. Increased natural autoantibody activity to cytoskeleton proteins in sera from patients with necrobiosis lipoidica, with or without insulin-dependent diabetes mellitus. Autoimmunity 1995;20:267-275.
39. O’Toole EA, Kennedy U, Nolan JJ, et al. Necrobiosis lipoidica: only a minority of patients have diabetes mellitus. Br J Dermatol 1999;140:283-286.
40. Lowitt MH, Dover JS. Necrobiosis lipoidica. J Am Acad Dermatol 1991;25(5 Pt 1):735-748.
41. Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum. A clinical and pathological investigation of 171 cases. Arch Dermatol 1966;93:272-281.
42. Roy S, Shayaan M. Unsightly rash on shin. Necrobiosis lipoidica diabeticorum. J Fam Pract 2012;61:215-217.
43. Wee E, Kelly R. Pentoxifylline: an effective therapy for necrobiosis lipoidica. Australas J Dermatol 2015 Nov 12. [Epub ahead of print].
44. Wilson TC, Snyder RJ, Southerland CC. Bullosis diabeticorum: is there a correlation between hyperglycemia and this symptomatology? Wounds 2012;24:350-355.
45. Ghosh SK, Bandyopadhyay D, Chatterjee G. Bullosis diabeticorum: a distinctive blistering eruption in diabetes mellitus. Int J Diabetes Dev Ctries 2009;29:41-42.
46. Larsen K, Jensen T, Karlsmark T, et al. Incidence of bullosis diabeticorum-a controversial cause of chronic foot ulceration. Int Wound J 2008;5:591-596.
47. Lipsky BA, Baker PD, Ahroni JH. Diabetic bullae: 12 cases of a purportedly rare cutaneous disorder. Int J Dermatol 2000;39:196-200.
48. Oursler JR, Goldblum OM, , Blistering eruption in a diabetic. Bullosis diabeticorum. Arch Dermatol 1991;127:247-250.
49. Bernstein JE, Medenica M, Soltani K, et al. Bullous eruption of diabetes mellitus. Arch Dermatol 1979;115:324-325.
50. Lopez PR, Leicht S, Sigmon JR, et al. Bullosis diabeticorum associated with a prediabetic state. South Med J 2009;102:643-644.
51. Tabor CA, Parlette EC. Cutaneous manifestations of diabetes. Signs of poor glycemic control or new-onset disease. Postgrad Med 2006;119:38-44.
52. Shemer A, Bergman R, Linn S, et al. Diabetic dermopathy and internal complications in diabetes mellitus. Int J Dermatol 1998;37:113-115.
53. Ko CJ. Dermal hypertrophies and benign fibroblastic/myofibrolastic tumors. In: Goldsmith LA, Katz SI, Gilchrest BA, et al., eds. Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: McGraw-Hill, 2012.
54. McCash S, Emanuel PO. Defining diabetic dermopathy. J Dermatol 2011;38:988-992.
55. Huntley AC. Cutaneous manifestations of diabetes mellitus. Dermatol Clin 1989;7:531-546.
56. Bauer M, Levan NE. Diabetic dermangiopathy. A spectrum including pigmented pretibial patches and necrobiosis lipoidica diabeticorum. Br J Dermatol 1970;83:528-535.
57. Binkley GW, Giraldo B, Stoughton RB. Diabetic dermopathy: a clinical study. Cutis 1967;3:955-958.
58. Jelinek JE. Cutaneous manifestations of diabetes mellitus. Int J Dermatol 1994;33:605-617.
59. Jennings MB, Alfieri DM, Parker ER, et al. A double-blind clinical trial comparing the efficacy and safety of pure lanolin versus ammonium lactate 12% cream for the treatment of moderate to severe foot xerosis. Cutis 2003;71:78-82.
60. Yoon HS, Baik SH, Oh CH. Quantitative measurement of desquamation and skin elasticity in diabetic patients. Skin Res Technol 2002;8:250-254.
61. Norman RA. Xerosis and pruritis in the elderly: recognition and management. Dermatol Ther 2003;16:254-259.
62. Egawa M, Oguri M, Kuwahara T, et al. Effect of exposure of human skin to a dry environment. Skin Res Technol 2002;8:212-218.
63. Merola JF, Li T, Li WQ, et al. Prevalence of psoriasis phenotyptes among men and women in the USA. Clin Exp Dermatol 2016;41:486-489.
64. Romano G, Moretti G, Di Benedetto A, et al. Skin lesions in diabetes mellitus: prevalence and clinical correlations. Diabetes Res Clin Pract 1998;39:101-106.
65. Richards HL, Fortune DG, O'Sullivan TM, et al. Patients with psoriasis and their compliance with medication. J Am Acad Dermatol 1999;41:581-583.
66. Bartos S, Hill D, Feldman SR. Psoriasis: a review of diagnosis and treatment in the primary care setting. Consultant 2016;56:119-122.
67. Honigsmann H. Phototherapy for psoriasis. Clin Exp Dermatol 2001;26:343-350.
68. Richard EG, Honigsmann H. Phototherapy, psoriasis, and the age of biologics. Photodermatol Photoimmunol Photomed 2014;30:3-7.
69. Keimig EL. Granuloma annulare. Dermatol Clin 2015;33:315-329.
70. Buechner SA, Winkelmann RK, Banks PM. Identification of T-cell subpopulations in granuloma annulare. Arch Dermatol 1983;119:125-128.
71. Fayazzi A, Schweyer S, Eichmeyer B, et al. Expression of IFNgamma, coexpression of TNFalpha and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare. Arch Dermatol Res 2000;292:384-390.
72. Mempel M, Musette P, Flageul B, et al. T-cell receptor repertoire and cytokine pattern in granuloma annulare: defining a particular type of cutaneous granulomatous inflammation. J Invest Dermatol 2002;118:957-966.
73. Gupta D, Hess B, Bachegowda L. Granuloma annulare. Scientific World Journal 2010;10:384-386.
74. Muhlemann MF, Williams DR. Localized granuloma annulare is associated with insulin-dependent diabetes mellitus. Br J Dermatol 1984;111:325-329.
75. Haim S, Friedman-Birnbaum R, Haim N, et al. Carbohydrate tolerance in patients with granuloma annulare. Study of fifty-two cases. Br J Dermatol 1973;88:447-451.
76. Grogg KL, Nascimento AG. Subcutaneous granuloma annulare in childhood: clinicopathologic features in 34 cases. Pediatrics 2001;107:E42.
77. Nebesio CL, Lewis C, Chuang TY. Lack of an association between granuloma annulare and type 2 diabetes mellitus. Br J Dermatol 2002;146:122-124.
78. Studer EM, Calza AM, Saurat JH. Precipitating factors and associated diseases in 84 patients with granuloma annulare: a retrospective study. Dermatology 1996;193:364-368.
79. Sahin MT, Turel-Ermertcan A, Ozturkcan S, et al. Generalized granuloma annulare in a patient with type II diabetes mellitus: successful treatment with isotretinoin. J Eur Acad Dermatol Venereol 2006;20:111-114.
80. Thornsberry LA, English JC, 3rd. Etiology, diagnosis, and therapeutic management of granuloma annulare: an update. Am J Clin Dermatol 2013;14:279-290.
81. Karpouzis A, Giatromanolaki A, Sivridis E, et al. Acquired reactive perforating collagenosis: current status. J Dermatol 2010;37:585-592.
82. Farrell AM. Acquired perforating dermatosis in renal and diabetic patients. Lancet 1997;349:895-896.
83. Saray Y, Seckin D, Bilezikci B. Acquired perforating dermatosis: clinicopathological features in twenty-two cases. J Eur Acad Dermatol Venereol 2006;20:679-688.
84. Maurice PD, Neild GH. Acquired perforating dermatosis and diabetic nephropathy-a case report and review of the literature. Clin Exp Dermatol 1997;22:291-294.
85. Kawakami T, Saito R. Acquired reactive perforating collagenosis associated with diabetes mellitus: eight cases that meet Faver’s criteria. Br J Dermatol 1999;140:521-524.
86. Namazi MR, Jorizzo JL, Fallahzadeh MK. Rubeosis faciei diabeticorum: a common, but often unnoticed, clinical manifestation of diabetes mellitus. ScientificWorldJournal 2010;10:70-71.
87. Gitelson S, Wertheimer-Kaplinski N. Color of the face in diabetes mellitus observations on a group of patients in Jerusalem. Diabetes 1965;14:201-208.
88. Landau J, Davis E. The small blood-vessels of the conjunctiva and nailbed in diabetes mellitus. Lancet 1960;2:731-734.
89. Ngo BT, Hayes KD, DiMiao DJ, et al. Manifestations of cutaneous diabetic microangiopathy. Am J Clin Dermatol 2005;6:225-237.
90. Millikan LE, Powell DW, Drake LA. Quality of life for patients with onychomycosis. Int J Dermatol 1999;38( Suppl 2 ):13-16.
91. Mutluoglu M, Uzun G, Karabacak E. Toenail onychodystrophy of the diabetic foot. BMJ Case Rep 2012;2012. pii: bcr2012007314.
92. Seyhan M, Ozcan H, Sahin I, et al. High prevalence of glucose metabolism disturbance in patients with lichen planus. Diabetes Res Clin Pract 2007;77:198-202.
93. Manolache L, Seceleanu-Petrescu D, Benea V. Lichen planus patients and stressful events. J Eur Acad Dermatol Venereol 2008;22:437-441.
94. Puri N. A study on cutaneous manifestations of diabetes mellitus. Our Dermatol Online 2012;3:83-86.
95. Mahajan S, Koranne RV, Sharma SK. Cutaneous manifestations of diabetes mellitus. Indian J Dermatol Venereol Leprol 2003;69:105-108.
96. Wagner G, Rose C, Sachse MM. Clinical variants of lichen planus. J Dtsch Dermatol Ges 2013;11:309-319.
97. Lodi G, Carrozzo M, Furness S, et al. Interventions for treating oral lichen planus: a systematic review. Br J Dermatol 2012;166:938-947.
98. Remoroza R, Wu GY. Extra hepatic manifestations of chronic hepatitis C. Chin J Dig Dis 2003;4:93-99.
99. Gorouhi F, Davari P, Fazel N. Cutaneous and mucosal lichen planus: a comprehensive review of clinical subtypes, risk factors, diagnosis, and prognosis. ScientificWorldJournal 2014;2014:742826.
100. Iijima W, Ohtani H, Nakayama T, et al. Infiltrating CD8+ T cells in oral lichen planus predominantly express CCR5 and CXCR3 and carry respective chemokine ligands RANTES/CCL5 and IP-10/CXCL10 in their cytolytic granules: a potential self-recruiting mechanism. Am J Pathol 2003;163:261-268.
101. Usatine RP, Tinitigan M. Diagnosis and treatment of lichen planus. Am Fam Physician 2011;84:53-60.
102. Le Cleach L, Chosidow O, , Clinical practice. Lichen planus. N Engl J Med 2012;366:723-732.
103. Cribier B, Frances C, Chosidow O. Treatment of lichen planus. An evidence-based medicine analysis of efficacy. Arch Dermatol 1998;134:1521-1530.
104. Lehman JS, Tollefson MM, Gibson LE. Lichen planus. Int J Dermatol 2009;48:682-694.
