American Journal of Clinical Dermatology

, Volume 20, Issue 1, pp 97–114 | Cite as

Cutaneous Adverse Effects of Diabetes Mellitus Medications and Medical Devices: A Review

  • Patrick M. JedlowskiEmail author
  • Charisse H. Te
  • Robert J. Segal
  • Maryam T. Fazel
Review Article


Diabetes mellitus is one of the most prevalent chronic diseases in the USA. If uncontrolled, diabetes can lead to devastating complications. Diabetes medications and medical devices largely contribute to the significant financial expense that the disease inflicts on affected individuals and society. Alongside significant economic burden, there are numerous cutaneous adverse effects associated with diabetes medications and medical devices. Despite the large and increasing number of individuals living with diabetes and the wide use of the related medications and medical devices, there is limited literature that comprehensively documents their cutaneous adverse effects. These cutaneous adverse effects are significant as they can worsen glycemic control, increase disease distress, and may increase risk of associated complications. Thus, it is important that providers can recognize these cutaneous adverse effects, identify the culprit agents, and can properly manage them. In this article, we provide a critical review of the cutaneous adverse effects of medications and devices used in the management of diabetes and provide insight into risk factors and prevention and an overview of therapeutic management. An emphasis is placed on clinical recognition and treatment for use of the medical providers who, regardless of practice setting, will treat patients with diabetes.


Compliance with Ethical Standards

Conflict of interest

Dr. Fazel, Dr. Te, Dr. Segal, and Patrick Jedlowski have no conflicts of interest or financial disclosures to report.


No sources of funding were used to conduct this study or prepare this manuscript.

Supplementary material

40257_2018_400_MOESM1_ESM.pdf (134 kb)
Supplementary material 1 (PDF 133 kb)


  1. 1.
    Thorpe KE, Howard DH, Galactionova K. Differences in disease prevalence as a source of the U.S.-European health care spending gap. Health Aff (Millwood). 2007;26(6):w678–86.Google Scholar
  2. 2.
    Papatheodorou K, Papanas N, Banach M, Papazoglou D, Edmonds M. Complications of diabetes 2016. J Diabetes Res. 2016;2016:6989453.Google Scholar
  3. 3.
    Centers for Disease Control and Prevention. National diabetes statistics report, 2017. Atlanta: Centers for Disease Control and Prevention, US Department of Health and Human Services; 2017. p. 20.Google Scholar
  4. 4.
    American Diabetes Association. Economic costs of diabetes in the U.S. in 2017. Diabetes Care. 2018;41(5):917–28.Google Scholar
  5. 5.
    Bustan RS, Wasim D, Yderstraede KB, Bygum A. Specific skin signs as a cutaneous marker of diabetes mellitus and the prediabetic state—a systematic review. Dan Med J. 2017;64(1):A5316.Google Scholar
  6. 6.
    Rosen J, Yosipovitch G. Skin manifestations of diabetes mellitus. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, et al., editors. Endotext. South Dartmouth:; 2000.Google Scholar
  7. 7.
    Horton WB, Boler PL, Subauste AR. Diabetes mellitus and the skin: recognition and management of cutaneous manifestations. South Med J. 2016;109(10):636–46.Google Scholar
  8. 8.
    Karadag AS, Ozlu E, Lavery MJ. Cutaneous manifestations of diabetes mellitus and the metabolic syndrome. Clin Dermatol. 2018;36(1):89–93.Google Scholar
  9. 9.
    Sinikumpu SP, Auvinen J, Jokelainen J, Huilaja L, Puukka K, Ruokonen A, et al. Abnormal skin in toe webs is a marker for abnormal glucose metabolism. A cross-sectional survey among 1,849 adults in Finland. Sci Rep. 2017;7(1):9125.Google Scholar
  10. 10.
    Chen YM, Huang H. Allergy to soft cannula of insulin pump in diabetic patient. Pak J Med Sci. 2017;33(1):245–7.Google Scholar
  11. 11.
    Lima AL, Illing T, Schliemann S, Elsner P. Cutaneous manifestations of diabetes mellitus: a review. Am J Clin Dermatol. 2017;18(4):541–53.Google Scholar
  12. 12.
    Varghese GI, Mathew M, Marmur E, Varghese MC. Dermatological complications of diabetes mellitus; allergy to insulin and oral agents. In: Poreysky L, editor. Principles of diabetes mellitus. 3rd ed. New York: Springer Science+Business Media; 2017. p. 551–66.Google Scholar
  13. 13.
    Umpierrez GE, Klonoff DC. Diabetes technology update: use of insulin pumps and continuous glucose monitoring in the hospital. Diabetes Care. 2018;41(8):1579–89.Google Scholar
  14. 14.
    Yaffee HS. Stevens–Johnson syndrome caused by chlorpropamide. Report of a case. Arch Dermatol. 1960;82:636–7.Google Scholar
  15. 15.
    Byrd JB, Touzin K, Sile S, Gainer JV, Yu C, Nadeau J, et al. Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema. Hypertension. 2008;51(1):141–7.Google Scholar
  16. 16.
    Bene J, Moulis G, Bennani I, Auffret M, Coupe P, Babai S, et al. Bullous pemphigoid and dipeptidyl peptidase IV inhibitors: a case–noncase study in the French Pharmacovigilance Database. Br J Dermatol. 2016;175(2):296–301.Google Scholar
  17. 17.
    Deng N, Zhang X, Zhao F, Wang Y, He H. Prevalence of lipohypertrophy in insulin-treated diabetes patients: a systematic review and meta-analysis. J Diabetes Investig. 2018;1:1. Scholar
  18. 18.
    Al Ajlouni M, Abujbara M, Batieha A, Ajlouni K. Prevalence of lipohypertrophy and associated risk factors in insulin-treated patients with type 2 diabetes mellitus. Int J Endocrinol Metab. 2015;13(2):e20776.Google Scholar
  19. 19.
    Richardson T, Kerr D. Skin-related complications of insulin therapy: epidemiology and emerging management strategies. Am J Clin Dermatol. 2003;4(10):661–7.Google Scholar
  20. 20.
    Radermecker RP, Pierard GE, Scheen AJ. Lipodystrophy reactions to insulin: effects of continuous insulin infusion and new insulin analogs. Am J Clin Dermatol. 2007;8(1):21–8.Google Scholar
  21. 21.
    Gungor K, Telci Caklili O, Oguz A. Abdominal lipohypertrophy without insulin injection. Lancet Diabetes Endocrinol. 2015;3(1):90.Google Scholar
  22. 22.
    Famulla S, Hovelmann U, Fischer A, Coester HV, Hermanski L, Kaltheuner M, et al. Insulin injection into lipohypertrophic tissue: blunted and more variable insulin absorption and action and impaired postprandial glucose control. Diabetes Care. 2016;39(9):1486–92.Google Scholar
  23. 23.
    Heinemann L. Insulin absorption from lipodystrophic areas: a (neglected) source of trouble for insulin therapy? J Diabetes Sci Technol. 2010;4(3):750–3.Google Scholar
  24. 24.
    Gentile S, Strollo F, Della Corte T, Marino G, Guarino G. Insulin related lipodystrophic lesions and hypoglycemia: double standards? Diabetes Metab Syndr. 2018;12(5):813–8.Google Scholar
  25. 25.
    Blanco M, Hernandez MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab. 2013;39(5):445–53.Google Scholar
  26. 26.
    Spollett G, Edelman SV, Mehner P, Walter C, Penfornis A. Improvement of insulin injection technique: examination of current issues and recommendations. Diabetes Educ. 2016;42(4):379–94.Google Scholar
  27. 27.
    Kordonouri O, Biester T, Schnell K, Hartmann R, Tsioli C, Fath M, et al. Lipoatrophy in children with type 1 diabetes: an increasing incidence? J Diabetes Sci Technol. 2015;9(2):206–8.Google Scholar
  28. 28.
    Renold AE, Winegrad AI, Martin DB. Diabetes mellitus and the adipose tissue [in French]. Helv Med Acta. 1957;24(4):322–7.Google Scholar
  29. 29.
    Rosenbloom AL. Insulin injection lipoatrophy recidivus. Pediatr Diabetes. 2014;15(1):73–4.Google Scholar
  30. 30.
    Breznik V, Kokol R, Luzar B, Miljkovic J. Insulin-induced localized lipoatrophy. Acta Dermatovenerol Alp Pannonica Adriat. 2013;22(4):83–5.Google Scholar
  31. 31.
    Lopez X, Castells M, Ricker A, Velazquez EF, Mun E, Goldfine AB. Human insulin analog–induced lipoatrophy. Diabetes Care. 2008;31(3):442–4.Google Scholar
  32. 32.
    Holstein A, Stege H, Kovacs P. Lipoatrophy associated with the use of insulin analogues: a new case associated with the use of insulin glargine and review of the literature. Expert Opin Drug Saf. 2010;9(2):225–31.Google Scholar
  33. 33.
    Reeves WG, Allen BR, Tattersall RB. Insulin-induced lipoatrophy: evidence for an immune pathogenesis. Br Med J. 1980;280(6230):1500–3.Google Scholar
  34. 34.
    Ramos AJ, Farias MA. Human insulin-induced lipoatrophy: a successful treatment with glucocorticoid. Diabetes Care. 2006;29(4):926–7.Google Scholar
  35. 35.
    Chantelau EA, Prator R, Prator J. Insulin-induced localized lipoatrophy preceded by shingles (herpes zoster): a case report. J Med Case Rep. 2014;24(8):223.Google Scholar
  36. 36.
    Chantelau EA, Praetor R, Praetor J, Poll LW. Relapsing insulin-induced lipoatrophy, cured by prolonged low-dose oral prednisone: a case report. Diabetol Metab Syndr. 2011;3(1):33.Google Scholar
  37. 37.
    Chantelau E, Reuter M, Schotes S, Starke AA. Severe lipoatrophy with human insulin: successfully treated by CSII. Diabet Med. 1993;10(6):580–1.Google Scholar
  38. 38.
    Jacquier J, Chik CL, Senior PA. A practical, clinical approach to the assessment and management of suspected insulin allergy. Diabet Med. 2013;30(8):977–85.Google Scholar
  39. 39.
    Kim D, Baraniuk J. Delayed-type hypersensitivity reaction to the meta-cresol component of insulin. Ann Allergy Asthma Immunol. 2007;99(2):194–5.Google Scholar
  40. 40.
    Gin H, Aubertin J. Generalized allergy due to zinc and protamine in insulin preparation treated with insulin pump. Diabetes Care. 1987;10(6):789–90.Google Scholar
  41. 41.
    Sandler M, Jordaan HF. Cutaneous reaction to zinc—a rare complication of insulin treatment. A case report. S Afr Med J. 1989;75(7):342–3.Google Scholar
  42. 42.
    Ghazavi MK, Johnston GA. Insulin allergy. Clin Dermatol. 2011;29(3):300–5.Google Scholar
  43. 43.
    Bzowyckyj AS, Stahnke AM. Hypersensitivity reactions to human insulin analogs in insulin-naive patients: a systematic review. Ther Adv Endocrinol Metab. 2018;9(2):53–65.Google Scholar
  44. 44.
    Mishra S, Connors L, Tugwell B. Role of omalizumab in insulin hypersensitivity: a case report and review of the literature. Diabet Med. 2018;35(5):663–6.Google Scholar
  45. 45.
    Tella SH, Rendell MS. DPP-4 inhibitors: focus on safety. Expert Opin Drug Saf. 2015;14(1):127–40.Google Scholar
  46. 46.
    Bristol-Myers Squibb Company. Saxagliptin (BMS-477118). FDA’s Endocrinologic and Metabolic Drugs Advisory Committee briefing document for April 2009 meeting. Silver Spring: FDA; 2009. p. 133.Google Scholar
  47. 47.
    European Medicines Agency. Galvus, INN-vildagliptin. London: European Medicines Agency; 2007.Google Scholar
  48. 48.
    Hoffmann P, Bentley P, Sahota P, Schoenfeld H, Martin L, Longo L, et al. Vascular origin of vildagliptin-induced skin effects in Cynomolgus monkeys: pathomechanistic role of peripheral sympathetic system and neuropeptide Y. Toxicol Pathol. 2014;42(4):684–95.Google Scholar
  49. 49.
    Stricklin SM, Stoecker WV, Rader RK, Hood AF, Litt JZ, Schuman TP. Persistent edematous-plaque photosensitivity observed with sitagliptin phosphate (Januvia®). Dermatol Online J. 2012;18(2):9.Google Scholar
  50. 50.
    Fania L, Salemme A, Provini A, Pagnanelli G, Collina MC, Abeni D, et al. Detection and characterization of IgG, IgE, and IgA autoantibodies in patients with bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors. J Am Acad Dermatol. 2018;78(3):592–5.Google Scholar
  51. 51.
    Chuang TY, Korkij W, Soltani K, Clayman J, Cook J. Increased frequency of diabetes mellitus in patients with bullous pemphigoid: a case–control study. J Am Acad Dermatol. 1984;11(6):1099–102.Google Scholar
  52. 52.
    Gravani A, Gaitanis G, Tsironi T, Tigas S, Bassukas ID. Changing prevalence of diabetes mellitus in bullous pemphigoid: it is the dipeptidyl peptidase-4 inhibitors. J Eur Acad Dermatol Venereol. 2018. Scholar
  53. 53.
    Fania L, Di Zenzo G, Didona B, Pilla MA, Sobrino L, Panebianco A, et al. Increased prevalence of diabetes mellitus in bullous pemphigoid patients during the last decade. J Eur Acad Dermatol Venereol. 2018;32(4):e153–4.Google Scholar
  54. 54.
    Varpuluoma O, Forsti AK, Jokelainen J, Turpeinen M, Timonen M, Tasanen K, et al. Oral diabetes medications other than dipeptidyl peptidase-4 inhibitors are not associated with bullous pemphigoid: a Finnish nationwide case control study. J Am Acad Dermatol. 2018;1:1. Scholar
  55. 55.
    Kridin K, Zelber-Sagi S, Comaneshter D, Cohen AD. Association between pemphigus and neurologic diseases. JAMA Dermatol. 2018;154(3):281–5.Google Scholar
  56. 56.
    Jang H, Jin YJ, Yoon CH, Kim CW, Kim L. Bullous pemphigoid associated with chronic hepatitis C virus infection in a hepatitis B virus endemic area: a case report. Medicine (Baltimore). 2018;97(15):e0377.Google Scholar
  57. 57.
    Zaouri H, Hassam B. Bullous pemphigoid and Parkinson’s disease: about a case [in French]. Pan Afr Med J. 2017;28:111.Google Scholar
  58. 58.
    Pankakoski A, Sintonen H, Ranki A, Kluger N. Comorbidities of bullous pemphigoid in a Finnish cohort. Eur J Dermatol. 2018;28(2):157–61.Google Scholar
  59. 59.
    Stavropoulos PG, Soura E, Antoniou C. Drug-induced pemphigoid: a review of the literature. J Eur Acad Dermatol Venereol. 2014;28(9):1133–40.Google Scholar
  60. 60.
    Lloyd-Lavery A, Chi CC, Wojnarowska F, Taghipour K. The associations between bullous pemphigoid and drug use: a UK case–control study. JAMA Dermatol. 2013;149(1):58–62.Google Scholar
  61. 61.
    Benzaquen M, Borradori L, Berbis P, Cazzaniga S, Valero R, Richard MA, et al. Dipeptidyl peptidase IV inhibitors, a risk factor for bullous pemphigoid: Retrospective multicenter case–control study from France and Switzerland. J Am Acad Dermatol. 2018;78(6):1090–6.Google Scholar
  62. 62.
    Arai M, Shirakawa J, Konishi H, Sagawa N, Terauchi Y. Bullous pemphigoid and dipeptidyl peptidase 4 inhibitors: a disproportionality analysis based on the Japanese Adverse Drug Event Report Database. Diabetes Care. 2018;41(9):e130–2.Google Scholar
  63. 63.
    Pasmatzi E, Monastirli A, Habeos J, Georgiou S, Tsambaos D. Dipeptidyl peptidase-4 inhibitors cause bullous pemphigoid in diabetic patients: report of two cases. Diabetes Care. 2011;34(8):e133.Google Scholar
  64. 64.
    Skandalis K, Spirova M, Gaitanis G, Tsartsarakis A, Bassukas ID. Drug-induced bullous pemphigoid in diabetes mellitus patients receiving dipeptidyl peptidase-IV inhibitors plus metformin. J Eur Acad Dermatol Venereol. 2012;26(2):249–53.Google Scholar
  65. 65.
    Aouidad I, Fite C, Marinho E, Deschamps L, Crickx B, Descamps V. A case report of bullous pemphigoid induced by dipeptidyl peptidase-4 inhibitors. JAMA Dermatol. 2013;149(2):243–5.Google Scholar
  66. 66.
    Attaway A, Mersfelder TL, Vaishnav S, Baker JK. Bullous pemphigoid associated with dipeptidyl peptidase IV inhibitors. A case report and review of literature. J Dermatol Case Rep. 2014;8(1):24–8.Google Scholar
  67. 67.
    Mendonca FM, Martin-Gutierrez FJ, Rios-Martin JJ, Camacho-Martinez F. Three cases of bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors—one due to linagliptin. Dermatology. 2016;232(2):249–53.Google Scholar
  68. 68.
    Bene J, Jacobsoone A, Coupe P, Auffret M, Babai S, Hillaire-Buys D, et al. Bullous pemphigoid induced by vildagliptin: a report of three cases. Fundam Clin Pharmacol. 2015;29(1):112–4.Google Scholar
  69. 69.
    Garcia M, Aranburu MA, Palacios-Zabalza I, Lertxundi U, Aguirre C. Dipeptidyl peptidase-IV inhibitors induced bullous pemphigoid: a case report and analysis of cases reported in the European pharmacovigilance database. J Clin Pharm Ther. 2016;41(3):368–70.Google Scholar
  70. 70.
    Haber R, Fayad AM, Stephan F, Obeid G, Tomb R. bullous pemphigoid associated with linagliptin treatment. JAMA Dermatol. 2016;152(2):224–6.Google Scholar
  71. 71.
    Harada M, Yoneda A, Haruyama S, Yabuki K, Honma Y, Hiura M, et al. Bullous pemphigoid associated with the dipeptidyl peptidase-4 inhibitor sitagliptin in a patient with liver cirrhosis complicated with rapidly progressive hepatocellular carcinoma. Intern Med. 2017;56(18):2471–4.Google Scholar
  72. 72.
    Keseroglu HO, Tas-Aygar G, Gonul M, Gokoz O, Ersoy-Evans S. A case of bullous pemphigoid induced by vildagliptin. Cutan Ocul Toxicol. 2017;36(2):201–2.Google Scholar
  73. 73.
    Sakai A, Shimomura Y, Ansai O, Saito Y, Tomii K, Tsuchida Y, et al. Linagliptin-associated bullous pemphigoid that was most likely caused by IgG autoantibodies against the midportion of BP180. Br J Dermatol. 2017;176(2):541–3.Google Scholar
  74. 74.
    Schaffer C, Buclin T, Jornayvaz FR, Cazzaniga S, Borradori L, Gilliet M, et al. Use of dipeptidyl-peptidase IV inhibitors and bullous pemphigoid. Dermatology. 2017;233(5):401–3.Google Scholar
  75. 75.
    Garcia-Diez I, Ivars-Lleo M, Lopez-Aventin D, Ishii N, Hashimoto T, Iranzo P, et al. Bullous pemphigoid induced by dipeptidyl peptidase-4 inhibitors. Eight cases with clinical and immunological characterization. Int J Dermatol. 2018;57(7):810–6.Google Scholar
  76. 76.
    Mai Y, Nishie W, Izumi K, Yoshimoto N, Morita Y, Watanabe M, et al. Detection of anti-BP180 NC16A autoantibodies after the onset of dipeptidyl peptidase-IV inhibitor-associated bullous pemphigoid: a report of three patients. Br J Dermatol. 2018;179:790–1.Google Scholar
  77. 77.
    Mai Y, Nishie W, Sato K, Hotta M, Izumi K, Ito K, et al. Bullous pemphigoid triggered by thermal burn under medication with a dipeptidyl peptidase-iv inhibitor: a case report and review of the literature. Front Immunol. 2018;9:542.Google Scholar
  78. 78.
    Maki N, Nishie W, Takazawa M, Kakurai M, Yamada T, Umemoto N, et al. Dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid in a patient with acquired reactive perforating collagenosis. J Dermatol. 2018;45(5):600–2.Google Scholar
  79. 79.
    Oya K, Fujii M, Taguchi S, Nishie W, Izumi K, Shimizu H. Localized bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitor treatment. Eur J Dermatol. 2018;28(2):250–1.Google Scholar
  80. 80.
    Yoshiji S, Murakami T, Harashima SI, Ko R, Kashima R, Yabe D, et al. Bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors: a report of five cases. J Diabetes Investig. 2018;9(2):445–7.Google Scholar
  81. 81.
    Izumi K, Nishie W, Mai Y, Wada M, Natsuga K, Ujiie H, et al. Autoantibody profile differentiates between inflammatory and noninflammatory bullous pemphigoid. J Investig Dermatol. 2016;136(11):2201–10.Google Scholar
  82. 82.
    Nakama K, Koga H, Ishii N, Ohata C, Hashimoto T, Nakama T. Clinical and immunological profiles of 14 patients with bullous pemphigoid without IgG autoantibodies to the BP180 NC16A domain. JAMA Dermatol. 2018;154(3):347–50.Google Scholar
  83. 83.
    Chijiwa C, Takeoka S, Kamata M, Tateishi M, Fukaya S, Hayashi K, et al. Decrease in eosinophils infiltrating into the skin of patients with dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid. J Dermatol. 2018;45(5):596–9.Google Scholar
  84. 84.
    Bernard P, Antonicelli F. Bullous pemphigoid: a review of its diagnosis, associations and treatment. Am J Clin Dermatol. 2017;18(4):513–28.Google Scholar
  85. 85.
    Fuertes de Vega I, Iranzo-Fernandez P, Mascaro-Galy JM. Bullous pemphigoid: clinical practice guidelines. Actas Dermosifiliogr. 2014;105(4):328–46.Google Scholar
  86. 86.
    Feliciani C, Joly P, Jonkman MF, Zambruno G, Zillikens D, Ioannides D, et al. Management of bullous pemphigoid: the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology. Br J Dermatol. 2015;172(4):867–77.Google Scholar
  87. 87.
    Gaudin O, Seta V, Alexandre M, Bohelay G, Aucouturier F, Mignot-Grootenboer S, et al. Gliptin accountability in mucous membrane pemphigoid induction in 24 out of 313 patients. Front Immunol. 2018;9:1030.Google Scholar
  88. 88.
    Xu HH, Werth VP, Parisi E, Sollecito TP. Mucous membrane pemphigoid. Dent Clin N Am. 2013;57(4):611–30.Google Scholar
  89. 89.
    Sobolewska B, Deuter C, Zierhut M. Current medical treatment of ocular mucous membrane pemphigoid. Ocul Surf. 2013;11(4):259–66.Google Scholar
  90. 90.
    Wu MA, Perego F, Zanichelli A, Cicardi M. Angioedema phenotypes: disease expression and classification. Clin Rev Allergy Immunol. 2016;51(2):162–9.Google Scholar
  91. 91.
    Emanueli C, Grady EF, Madeddu P, Figini M, Bunnett NW, Parisi D, et al. Acute ACE inhibition causes plasma extravasation in mice that is mediated by bradykinin and substance P. Hypertension. 1998;31(6):1299–304.Google Scholar
  92. 92.
    Byrd JS, Minor DS, Elsayed R, Marshall GD. DPP-4 inhibitors and angioedema: a cause for concern? Ann Allergy Asthma Immunol. 2011;106(5):436–8.Google Scholar
  93. 93.
    Scott SI, Andersen MF, Aagaard L, Buchwald CV, Rasmussen ER. Dipeptidyl peptidase-4 inhibitor induced angioedema—an overlooked adverse drug reaction? Curr Diabetes Rev. 2018;14(4):327–33.Google Scholar
  94. 94.
    Brown NJ, Byiers S, Carr D, Maldonado M, Warner BA. Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitor-associated angioedema. Hypertension. 2009;54(3):516–23.Google Scholar
  95. 95.
    Gibbs JP, Fredrickson J, Barbee T, Correa I, Smith B, Lin SL, et al. Quantitative model of the relationship between dipeptidyl peptidase-4 (DPP-4) inhibition and response: meta-analysis of alogliptin, saxagliptin, sitagliptin, and vildagliptin efficacy results. J Clin Pharmacol. 2012;52(10):1494–505.Google Scholar
  96. 96.
    Saisho Y, Itoh H. Dipeptidyl peptidase-4 inhibitors and angioedema: a class effect? Diabet Med. 2013;30(4):e149–50.Google Scholar
  97. 97.
    Hamasaki H, Yanai H. The development of angioedema in a patient with type 2 diabetes due to a novel dipeptidyl peptidase-IV inhibitor, anagliptin. Int J Cardiol. 2013;168(3):e106.Google Scholar
  98. 98.
    Hudey SN, Westermann-Clark E, Lockey RF. Cardiovascular and diabetic medications that cause bradykinin-mediated angioedema. J Allergy Clin Immunol Pract. 2017;5(3):610–5.Google Scholar
  99. 99.
    Hahn J, Trainotti S, Hoffmann TK, Greve J. Drug-induced inhibition of angiotensin converting enzyme and dipeptidyl peptidase 4 results in nearly therapy resistant bradykinin induced angioedema: a case report. Am J Case Rep. 2017;25(18):576–9.Google Scholar
  100. 100.
    Hermanrud T, Bygum A, Rasmussen ER. Recurrent angioedema associated with pharmacological inhibition of dipeptidyl peptidase IV. BMJ Case Rep. 2017;10:2017.Google Scholar
  101. 101.
    Beaudouin E, Defendi F, Picaud J, Drouet C, Ponard D, Moneret-Vautrin DA. Iatrogenic angioedema associated with ACEi, sitagliptin, and deficiency of 3 enzymes catabolizing bradykinin. Eur Ann Allergy Clin Immunol. 2014;46(3):119–22.Google Scholar
  102. 102.
    Ashcroft FM. Mechanisms of the glycaemic effects of sulfonylureas. Horm Metab Res. 1996;28(9):456–63.Google Scholar
  103. 103.
    Bruze M. The chemical basis of para-amino compounds. Derm Beruf Umwelt. 1984;32(5):174–5.Google Scholar
  104. 104.
    Angelini G, Meneghini CL. Oral tests in contact allergy to para-amino compounds. Contact Dermatitis. 1981;7(6):311–4.Google Scholar
  105. 105.
    Fisher AA. Systemic contact dermatitis from Orinase and Diabinese in diabetics with para-amino hypersensitivity. Cutis. 1982;29(6):551, 556, 565 passim.Google Scholar
  106. 106.
    Wulf NR, Matuszewski KA. Sulfonamide cross-reactivity: is there evidence to support broad cross-allergenicity? Am J Health Syst Pharm. 2013;70(17):1483–94.Google Scholar
  107. 107.
    Reilly TP, Ju C. Mechanistic perspectives on sulfonamide-induced cutaneous drug reactions. Curr Opin Allergy Clin Immunol. 2002;2(4):307–15.Google Scholar
  108. 108.
    Rigberg LA, Robinson MJ, Espiritu CR. Chlorpropamide-induced granulomas. A probable hypersensitivity reaction in liver and bone marrow. JAMA. 1976;235(4):409–10.Google Scholar
  109. 109.
    Franz CB, Massullo RE, Welton WA. Lichenoid drug eruption from chlorpropamide and tolazamide. J Am Acad Dermatol. 1990;22(1):128–9.Google Scholar
  110. 110.
    Bukhalo M, Zeitouni NC, Cheney RT. Leukocytoclastic vasculitis induced by use of glyburide: a case of possible cross-reaction of a sulfonamide and a sulfonylurea. Cutis. 2003;71(3):235–8.Google Scholar
  111. 111.
    Ozuguz P, Kacar SD, Ozuguz U, Karaca S, Tokyol C. Erythroderma secondary to gliclazide: a case report. Cutan Ocul Toxicol. 2014;33(4):342–4.Google Scholar
  112. 112.
    Cheng JB, Anderson RC, Cruz PD Jr. Stevens–Johnson syndrome associated with glipizide therapy. Dermatitis. 2006;17(1):36–8.Google Scholar
  113. 113.
    Adams BB, Gadenne AS. Glipizide-induced pigmented purpuric dermatosis. J Am Acad Dermatol. 1999;41(5 Pt 2):827–9.Google Scholar
  114. 114.
    Ernst EJ, Egge JA. Celecoxib-induced erythema multiforme with glyburide cross-reactivity. Pharmacotherapy. 2002;22(5):637–40.Google Scholar
  115. 115.
    Contreras-Steyls M, Vilchez-Marquez F, Mota A, Moyano B, Herrera-Ceballos E. Acute generalized exanthematous pustulosis induced by gliclazide: a case report. Int J Dermatol. 2013;52(12):1591–3.Google Scholar
  116. 116.
    Noakes R. Lichenoid drug eruption as a result of the recently released sulfonylurea glimepiride. Australas J Dermatol. 2003;44(4):302–3.Google Scholar
  117. 117.
    Hammami S, Ksouda K, Affes H, Sahnoun Z, Zeghal K. Mucosal lichenoid drug reaction associated with glimepiride: a case report. Eur Rev Med Pharmacol Sci. 2015;19(12):2301–2.Google Scholar
  118. 118.
    Ponka D. Approach to managing patients with sulfa allergy: use of antibiotic and nonantibiotic sulfonamides. Can Fam Physician. 2006;52(11):1434–8.Google Scholar
  119. 119.
    Dodiuk-Gad RP, Chung WH, Valeyrie-Allanore L, Shear NH. Stevens–Johnson syndrome and toxic epidermal necrolysis: an update. Am J Clin Dermatol. 2015;16(6):475–93.Google Scholar
  120. 120.
    Wang CW, Yang LY, Chen CB, Ho HC, Hung SI, Yang CH, et al. Randomized, controlled trial of TNF-alpha antagonist in CTL-mediated severe cutaneous adverse reactions. J Clin Investig. 2018;128(3):985–96.Google Scholar
  121. 121.
    Wong A, Malvestiti AA, Hafner Mde F. Stevens–Johnson syndrome and toxic epidermal necrolysis: a review. Rev Assoc Med Bras. 2016;62(5):468–73.Google Scholar
  122. 122.
    Lee YH. Wound management strategies in Stevens–Johnson syndrome/toxic epidermal necrolysis: an unmet need. J Am Acad Dermatol. 2018;79(4):e87–8.Google Scholar
  123. 123.
    Cho YT, Chu CY. Treatments for severe cutaneous adverse reactions. J Immunol Res. 2017;2017:1503709.Google Scholar
  124. 124.
    Lerch M, Mainetti C, Terziroli Beretta-Piccoli B, Harr T. Current perspectives on Stevens–Johnson syndrome and toxic epidermal necrolysis. Clin Rev Allergy Immunol. 2018;54(1):147–76.Google Scholar
  125. 125.
    Malaisse WJ. Mechanism of action of a new class of insulin secretagogues. Exp Clin Endocrinol Diabetes. 1999;107(Suppl 4):S140–3.Google Scholar
  126. 126.
    Rojas P, Sanchez L, Santos A, Goomez MP, Blanco H, Laguna JJ. Hypersensitivity to repaglinide. J Investig Allergol Clin Immunol. 2011;21(3):245–7.Google Scholar
  127. 127.
    Yang JK, Wang L, PMSSC Group. Nateglinide in combination with metformin in Chinese patients with type 2 diabetes mellitus: a post-marketing surveillance study. Clin Drug Investig. 2013;33(3):185–91.Google Scholar
  128. 128.
    Doyle ME, Egan JM. Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther. 2007;113(3):546–93.Google Scholar
  129. 129.
    Shaefer CF Jr, Kushner P, Aguilar R. User’s guide to mechanism of action and clinical use of GLP-1 receptor agonists. Postgrad Med. 2015;127(8):818–26.Google Scholar
  130. 130.
    Norwood P, Liutkus JF, Haber H, Pintilei E, Boardman MK, Trautmann ME. Safety of exenatide once weekly in patients with type 2 diabetes mellitus treated with a thiazolidinedione alone or in combination with metformin for 2 years. Clin Ther. 2012;34(10):2082–90.Google Scholar
  131. 131.
    Frias JP, Nakhle S, Ruggles JA, Zhuplatov S, Klein E, Zhou R, et al. Exenatide once weekly improved 24-hour glucose control and reduced glycaemic variability in metformin-treated participants with type 2 diabetes: a randomized, placebo-controlled trial. Diabetes Obes Metab. 2017;19:40–8.Google Scholar
  132. 132.
    Grimm M, Han J, Weaver C, Griffin P, Schulteis CT, Dong H, et al. Efficacy, safety, and tolerability of exenatide once weekly in patients with type 2 diabetes mellitus: an integrated analysis of the DURATION trials. Postgrad Med. 2013;125(3):47–57.Google Scholar
  133. 133.
    Buse JB, Drucker DJ, Taylor KL, Kim T, Walsh B, Hu H, et al. DURATION-1: exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks. Diabetes Care. 2010;33(6):1255–61.Google Scholar
  134. 134.
    Shive MS, Anderson JM. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev. 1997;28(1):5–24.Google Scholar
  135. 135.
    DeYoung MB, MacConell L, Sarin V, Trautmann M, Herbert P. Encapsulation of exenatide in poly-(d, l-lactide-co-glycolide) microspheres produced an investigational long-acting once-weekly formulation for type 2 diabetes. Diabetes Technol Ther. 2011;13(11):1145–54.Google Scholar
  136. 136.
    Sandman C, Krainin B, Roper J. Don’t play with your nodule: case report of tachycardia and other adverse reactions from manipulation of an exenatide injection site nodule. J Emerg Med. 2018;54(6):e125–8.Google Scholar
  137. 137.
    Poszepczynska-Guigne E, Viguier M, Assier H, Pinquier L, Hochedez P, Dubertret L. Acute generalized exanthematous pustulosis induced by drugs with low-digestive absorption: acarbose and nystatin [in French]. Ann Dermatol Venereol. 2003;130(4):439–42.Google Scholar
  138. 138.
    Bruttomesso D, Costa S, Baritussio A. Continuous subcutaneous insulin infusion (CSII) 30 years later: still the best option for insulin therapy. Diabetes Metab Res Rev. 2009;25(2):99–111.Google Scholar
  139. 139.
    Kesavadev J, Shankar A, Sadasrian Pillai PB, Saboo B, Joshi S, Krishnan G, et al. CSII as an alternative therapeutic strategy for managing type 2 diabetes: adding the Indian experience to a global perspective. Curr Diabetes Rev. 2016;12(4):312–4.Google Scholar
  140. 140.
    Ross P, Gray AR, Milburn J, Kumarasamy IM, Wu F, Farrand S, et al. Insulin pump-associated adverse events are common, but not associated with glycemic control, socio-economic status, or pump/infusion set type. Acta Diabetol. 2016;53(6):991–8.Google Scholar
  141. 141.
    McAdams BH, Rizvi AA. An overview of insulin pumps and glucose sensors for the generalist. J Clin Med. 2016;5(1):E5.Google Scholar
  142. 142.
    Pickup JC, Yemane N, Brackenridge A, Pender S. Nonmetabolic complications of continuous subcutaneous insulin infusion: a patient survey. Diabetes Technol Ther. 2014;16(3):145–9.Google Scholar
  143. 143.
    Schober E, Rami B. Dermatological side effects and complications of continuous subcutaneous insulin infusion in preschool-age and school-age children. Pediatr Diabetes. 2009;10(3):198–201.Google Scholar
  144. 144.
    Deiss D, Adolfsson P, Alkemade-van Zomeren M, Bolli GB, Charpentier G, Cobelli C, et al. Insulin infusion set use: European perspectives and recommendations. Diabetes Technol Ther. 2016;18(9):517–24.Google Scholar
  145. 145.
    Evert AB, Bode BW, Buckingham BA, Nardacci E, Verderese CA, Wolff-McDonagh P, et al. Improving patient experience with insulin infusion sets: practical guidelines and future directions. Diabetes Educ. 2016;42(4):470–84.Google Scholar
  146. 146.
    Griffin ME, Feder A, Tamborlane WV. Lipoatrophy associated with lispro insulin in insulin pump therapy: an old complication, a new cause? Diabetes Care. 2001;24(1):174.Google Scholar
  147. 147.
    Heymann WR. Glucose monitoring dermopathy. Skinmed. 2018;16(1):74–5.Google Scholar
  148. 148.
    Berg AK, Olsen BS, Thyssen JP, Zachariae C, Simonsen AB, Pilgaard K, et al. High frequencies of dermatological complications in children using insulin pumps or sensors. Pediatr Diabetes. 2018;19(4):733–40.Google Scholar
  149. 149.
    Pfutzner A, Sachsenheimer D, Grenningloh M, Heschel M, Walther-Johannesen L, Gharabli R, et al. Using insulin infusion sets in CSII for longer than the recommended usage time leads to a high risk for adverse events: results from a prospective randomized crossover study. J Diabetes Sci Technol. 2015;9(6):1292–8.Google Scholar
  150. 150.
    Mecklenburg RS, Benson EA, Benson JW Jr, Fredlund PN, Guinn T, Metz RJ, et al. Acute complications associated with insulin infusion pump therapy. Report of experience with 161 patients. JAMA. 1984;252(23):3265–9.Google Scholar
  151. 151.
    Lenhard MJ, Reeves GD. Continuous subcutaneous insulin infusion: a comprehensive review of insulin pump therapy. Arch Intern Med. 2001;161(19):2293–300.Google Scholar
  152. 152.
    Chantelau E, Lange G, Sonnenberg GE, Berger M. Acute cutaneous complications and catheter needle colonization during insulin-pump treatment. Diabetes Care. 1987;10(4):478–82.Google Scholar
  153. 153.
    Renard E, Rostane T, Carriere C, Marchandin H, Jacques-Apostol D, Lauton D, et al. Implantable insulin pumps: infections most likely due to seeding from skin flora determine severe outcomes of pump-pocket seromas. Diabetes Metab. 2001;27(1):62–5.Google Scholar
  154. 154.
    Nowakowska M, Jarosz-Chobot P, Polanska J, Machnica L. Bacterial strains colonizing subcutaneous catheters of personal insulin pumps. Pol J Microbiol. 2007;56(4):239–43.Google Scholar
  155. 155.
    Jarosz-Chobot P, Nowakowska M, Polanska J. Seeking the factors predisposing to local skin inflammatory state development in children with type 1 diabetes (T1DM) treated with continuous subcutaneous insulin infusion (CSII). Exp Clin Endocrinol Diabetes. 2007;115(3):179–81.Google Scholar
  156. 156.
    Geldof BA, Oranje AP, van Joost T. Hand eczema associated with continuous subcutaneous insulin infusion. Contact Dermatitis. 1989;20(5):384–5.Google Scholar
  157. 157.
    Sasseville D. Acrylates in contact dermatitis. Dermatitis. 2012;23(1):6–16.Google Scholar
  158. 158.
    Heinemann L, Kamann S. Adhesives used for diabetes medical devices: a neglected risk with serious consequences? J Diabetes Sci Technol. 2016;10(6):1211–5.Google Scholar
  159. 159.
    Aalto-Korte K, Alanko K, Kuuliala O, Jolanki R. Occupational methacrylate and acrylate allergy from glues. Contact Dermatitis. 2008;58(6):340–6.Google Scholar
  160. 160.
    Horner KL, Anderson B. Acrylates. Dermatitis. 2009;20(4):218–9.Google Scholar
  161. 161.
    Dearman RJ, Betts CJ, Farr C, McLaughlin J, Berdasco N, Wiench K, et al. Comparative analysis of skin sensitization potency of acrylates (methyl acrylate, ethyl acrylate, butyl acrylate, and ethylhexyl acrylate) using the local lymph node assay. Contact Dermatitis. 2007;57(4):242–7.Google Scholar
  162. 162.
    van den Hove J, Jacobs MC, Tennstedt D, Lachapelle JM. Allergic contact dermatitis from acrylates in insulin pump infusion sets. Contact Dermatitis. 1996;35(2):108.Google Scholar
  163. 163.
    Busschots AM, Meuleman V, Poesen N, Dooms-Goossens A. Contact allergy to components of glue in insulin pump infusion sets. Contact Dermatitis. 1995;33(3):205–6.Google Scholar
  164. 164.
    Saccabusi S, Boatto G, Asproni B, Pau A. Sensitization to methyl methacrylate in the plastic catheter of an insulin pump infusion set. Contact Dermatitis. 2001;45(1):47–8.Google Scholar
  165. 165.
    Jolanki R, Kanerva L, Estlander T, Henriks-Eckerman ML, Suhonen R. Allergic contact dermatitis from phenoxyethoxy ethylacrylates in optical fiber coating, and glue in an insulin pump set. Contact Dermatitis. 2001;45(1):36–7.Google Scholar
  166. 166.
    Raison-Peyron N, Mowitz M, Bonardel N, Aerts O, Bruze M. Allergic contact dermatitis caused by isobornyl acrylate in OmniPod, an innovative tubeless insulin pump. Contact Dermatitis. 2018. Scholar
  167. 167.
    Oppel E, Hogg C, Summer B, Rueff F, Reichl FX, Kamann S. Isobornyl acrylate contained in the insulin patch pump OmniPod as the cause of severe allergic contact dermatitis. Contact Dermatitis. 2018. Scholar
  168. 168.
    Herman A, Aerts O, Baeck M, Bruze M, De Block C, Goossens A, et al. Allergic contact dermatitis caused by isobornyl acrylate in Freestyle® Libre, a newly introduced glucose sensor. Contact Dermatitis. 2017;77(6):367–73.Google Scholar
  169. 169.
    Kamann S, Aerts O, Heinemann L. Further evidence of severe allergic contact dermatitis from isobornyl acrylate while using a continuous glucose monitoring system. J Diabetes Sci Technol. 2018;12(3):630–3.Google Scholar
  170. 170.
    Schwensen JF, Friis UF, Zachariae C, Johansen JD. Sensitization to cyanoacrylates caused by prolonged exposure to a glucose sensor set in a diabetic child. Contact Dermatitis. 2016;74(2):124–5.Google Scholar
  171. 171.
    Kanerva L, Jolanki R, Estlander T. 10 years of patch testing with the (meth)acrylate series. Contact Dermatitis. 1997;37(6):255–8.Google Scholar
  172. 172.
    Ramos L, Cabral R, Goncalo M. Allergic contact dermatitis caused by acrylates and methacrylates—a 7-year study. Contact Dermatitis. 2014;71(2):102–7.Google Scholar
  173. 173.
    Schalock PC, Dunnick CA, Nedorost S, Brod B, Warshaw E, Mowad C. American Contact Dermatitis Society Core Allergen Series: 2017 update. Dermatitis. 2017;28(2):141–3.Google Scholar
  174. 174.
    Downs AM, Sansom JE. Colophony allergy: a review. Contact Dermatitis. 1999;41(6):305–10.Google Scholar
  175. 175.
    Uter W, Aberer W, Armario-Hita JC, Fernandez-Vozmediano JM, Ayala F, Balato A, et al. Current patch test results with the European baseline series and extensions to it from the ‘European Surveillance System on Contact Allergy’ network, 2007–2008. Contact Dermatitis. 2012;67(1):9–19.Google Scholar
  176. 176.
    Passanisi S, Lombardo F, Barbalace A, Caminiti L, Panasiti I, Crisafulli G, et al. Allergic contact dermatitis and diabetes medical devices: 2 clinical cases. Contact Dermatitis. 2018. Scholar
  177. 177.
    Boom BW, van Driel LM. Allergic contact dermatitis to epoxy resin in infusion sets of an insulin pump. Contact Dermatitis. 1985;12(5):280.Google Scholar
  178. 178.
    FDA Executive Summary. Senseonics Eversence continuous glucose monitoring system. Senseonics Inc. Silver Spring: FDA; 2018. p. 54.Google Scholar
  179. 179.
    Nguyen TV, Burnett JW. Local skin reaction caused by the plastic catheter tubing of the continuous subcutaneous insulin infusion system. Cutis. 1988;41(5):355–6.Google Scholar
  180. 180.
    Corazza M, Maranini C, Aleotti A, Virgili A. Nickel contact dermatitis due to the needle of an infusion pump, confirmed by microanalysis. Contact Dermatitis. 1998;39(3):144.Google Scholar
  181. 181.
    Szatkowski J, Schwartz RA. Acute generalized exanthematous pustulosis (AGEP): a review and update. J Am Acad Dermatol. 2015;73(5):843–8.Google Scholar
  182. 182.
    Samim F, Auluck A, Zed C, Williams PM. Erythema multiforme: a review of epidemiology, pathogenesis, clinical features, and treatment. Dent Clin N Am. 2013;57(4):583–96.Google Scholar
  183. 183.
    Mistry N, Gupta A, Alavi A, Sibbald RG. A review of the diagnosis and management of erythroderma (generalized red skin). Adv Skin Wound Care. 2015;28(5):228–36 (quiz 37–8).Google Scholar
  184. 184.
    White CR Jr. Histopathology of exogenous and systemic contact eczema. Semin Dermatol. 1990;9(3):226–9.Google Scholar
  185. 185.
    Aquino M, Rosner G. Systemic contact dermatitis. Clin Rev Allergy Immunol. 2018;1:1. Scholar
  186. 186.
    Mustafa SS, Ostrov D, Yerly D. Severe cutaneous adverse drug reactions: presentation, risk factors, and management. Curr Allergy Asthma Rep. 2018;18(4):26.Google Scholar
  187. 187.
    Russell JP, Gibson LE. Primary cutaneous small vessel vasculitis: approach to diagnosis and treatment. Int J Dermatol. 2006;45(1):3–13.Google Scholar
  188. 188.
    Le Cleach L, Chosidow O. Clinical practice. Lichen planus. N Engl J Med. 2012;366(8):723–32.Google Scholar
  189. 189.
    Kim DH, Seo SH, Ahn HH, Kye YC, Choi JE. Characteristics and clinical manifestations of pigmented purpuric dermatosis. Ann Dermatol. 2015;27(4):404–10.Google Scholar
  190. 190.
    Demols A, Le Moine O, Desalle F, Quertinmont E, Van Laethem JL, Deviere J. CD4(+)T cells play an important role in acute experimental pancreatitis in mice. Gastroenterology. 2000;118(3):582–90.Google Scholar
  191. 191.
    Willis RA. The place of histopathology in cancer research. Med Press. 1961;19(245):339–43.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.University of Arizona College of Medicine, TucsonTucsonUSA
  2. 2.Division of Endocrinology, Department of MedicineUniversity of Arizona College of Medicine, TucsonTucsonUSA
  3. 3.Division of Dermatology, Department of MedicineUniversity of Arizona College of Medicine, TucsonTucsonUSA
  4. 4.Department of Pharmacy Practice and Science and MedicineUniversity of Arizona Colleges of Pharmacy and Medicine, TucsonTucsonUSA

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