General Aspects of Adverse Cutaneous Drug Reactions

  • Esen Özkaya
  • Kurtuluş Didem Yazganoğlu


Adverse cutaneous drug reactions (ACDR) or drug eruptions represent one of the most common types of adverse reactions to drug therapy. The overall incidence rate is estimated around 2–3 % in hospitalized patients. Antibiotics, nonsteroidal antiinflammatory drugs (NSAIDs), and anticonvulsants are usually regarded as the most common inducers, but almost every drug may cause skin reactions. Advanced age, polypharmacy, and female gender are among the main factors predisposing to ACDR.


Drug eruption Cardiovascular drugs Maculopapular Erythema multiforme Acute generalized exanthematous pustulosis Photosensitivity Hyperpigmentation Vasculitis Angioedema Erythroderma Stevens–Johnson syndrome Toxic epidermal necrolysis Drug rash with eosinophilia and systemic symptoms 


  1. 1.
    Lee A, Thomson J. Drug-induced skin reactions. In: Adverse drug reactions. 2nd ed. London: Pharmaceutical Press; 2006. p. 125–56.Google Scholar
  2. 2.
    Turk BG, Gunaydin A, Ertam I, Ozturk G. Adverse cutaneous drug reactions among hospitalized patients: five year surveillance. Cutan Ocul Toxicol. 2013;32:41–5. doi: 10.3109/15569527.2012.702837.PubMedGoogle Scholar
  3. 3.
    Valeyrie-Allanore L, Sassolas B, Roujeau JC. Drug-induced skin, nail and hair disorders. Drug Saf. 2007;30:1011–30.PubMedGoogle Scholar
  4. 4.
    Al-Niaimi F. Drug eruptions in dermatology. Expert Rev Dermatol. 2011;6:273–86.Google Scholar
  5. 5.
    Andersen WK, Feingold DS. Adverse drug interactions clinically important for the dermatologist. Arch Dermatol. 1995;131:468–73.PubMedGoogle Scholar
  6. 6.
    Roujeau JC. Clinical heterogeneity of drug hypersensitivity. Toxicology. 2005;209:123–9.PubMedGoogle Scholar
  7. 7.
    Haymore BR, Yoon J, Mikita CP, Klote MM, DeZee KJ. Risk of angioedema with angiotensin receptor blockers in patients with prior angioedema associated with angiotensin-converting enzyme inhibitors: a meta-analysis. Ann Allergy Asthma Immunol. 2008;101:495–9. doi: 10.1016/S1081-1206(10)60288-8.PubMedGoogle Scholar
  8. 8.
    Pichler WJ, Beeler A, Keller M, Lerch M, Posadas S, Schmid D, et al. Pharmacological interaction of drugs with immune receptors: the p-I concept. Allergol Int. 2006;55:17–25.PubMedGoogle Scholar
  9. 9.
    Andersen KE, Hjorth N, Menné T. The baboon syndrome: systemically-induced allergic contact dermatitis. Contact Dermatitis. 1984;10:97–100.PubMedGoogle Scholar
  10. 10.
    Özkaya E. Current understanding of Baboon syndrome. Exp Rev Dermatol. 2009;4:163–75.Google Scholar
  11. 11.
    Lerch M, Bircher AJ. Systemically induced allergic exanthem from mercury. Contact Dermatitis. 2004;50:349–53.PubMedGoogle Scholar
  12. 12.
    Häusermann P, Harr T, Bircher AJ. Baboon syndrome resulting from systemic drugs: is there strife between SDRIFE and allergic contact dermatitis syndrome? Contact Dermatitis. 2004;51:297–310.PubMedGoogle Scholar
  13. 13.
    Summers EM, Bingham CS, Dahle KW, Sweeney C, Ying J, Sontheimer RD. Chronic eczematous eruptions in the aging: further support for an association with exposure to calcium channel blockers. JAMA Dermatol. 2013;149:814–8. doi: 10.1001/jamadermatol.2013.511.PubMedGoogle Scholar
  14. 14.
    Pfeiff B, Pullmann H. Baboon-artiges Arzneiexanthem auf heparin. Dermatologe. 1991;39:559–60.Google Scholar
  15. 15.
    Tan SC, Tan JW. Symmetrical drug-related intertriginous and flexural exanthema. Curr Opin Allergy Clin Immunol. 2011;11:313–8. doi: 10.1097/ACI.0b013e3283489d5f.PubMedGoogle Scholar
  16. 16.
    Almeida J, Levantine A. Lichenoid drugs eruptions. Br J Dermatol. 1971;85:604–7.Google Scholar
  17. 17.
    Woo V, Bonks J, Borukhova L, Zegarelli D. Oral lichenoid drug eruption: a report of a pediatric case and review of the literature. Pediatr Dermatol. 2009;26:458–64. doi: 10.1111/j.1525-1470.2009.00953.x.PubMedGoogle Scholar
  18. 18.
    Fessa C, Lim P, Kossard S, Richards S, Peñas PF. Lichen planus-like drug eruptions due to β-blockers: a case report and literature review. Am J Clin Dermatol. 2012;13:417–21. doi: 10.2165/11634590-000000000-00000.PubMedGoogle Scholar
  19. 19.
    Özkaya E. Fixed drug eruption: state of the art. J Dtsch Dermatol Ges. 2008;6:181–8.PubMedGoogle Scholar
  20. 20.
    Özkaya E. Oral mucosal fixed drug eruption: characteristics and differential diagnosis. J Am Acad Dermatol. 2013;69:e51–8. doi: 10.1016/j.jaad.2012.08.019.PubMedGoogle Scholar
  21. 21.
    Ahmed I, Reichenberg J, Lucas A, Shehan JM. Erythema multiforme associated with phenytoin and cranial radiation therapy: a report of three patients and review of the literature. Int J Dermatol. 2004;43:67–73.PubMedGoogle Scholar
  22. 22.
    Wöhrl S, Loewe R, Pickl WF, Stingl G, Wagner SN. EMPACT syndrome. J Dtsch Dermatol Ges. 2005;3:39–43.PubMedGoogle Scholar
  23. 23.
    Fabbrocini G, Panariello L, Pensabene M, Lauria R, Matano E, Martellotta D, et al. EMPACT syndrome associated with phenobarbital. Dermatitis. 2013;24:37–9. doi: 10.1097/DER.0b013e31827ede32.PubMedGoogle Scholar
  24. 24.
    Stavropoulos PG, Soura E, Antoniou C. Drug-induced pemphigoid: a review of the literature. J Eur Acad Dermatol Venereol. 2014;28:1133–40. doi: 10.1111/jdv.12366.
  25. 25.
    Brenner S, Goldberg I. Drug-induced pemphigus. Clin Dermatol. 2011;29:455–7. doi: 10.1016/j.clindermatol.2011.01.016.PubMedGoogle Scholar
  26. 26.
    Ramsay CA. Drug induced pseudoporphyria. J Rheumatol. 1991;18:799–800.PubMedGoogle Scholar
  27. 27.
    Maruani A, Machet MC, Carlotti A, Giraudeau B, Vaillant L, Machet L. Immunostaining with antibodies to desmoglein provides the diagnosis of drug-induced pemphigus and allows prediction of outcome. Am J Clin Pathol. 2008;130:369–74.PubMedGoogle Scholar
  28. 28.
    Chanal J, Ingen-Housz-Oro S, Ortonne N, Duong TA, Thomas M, Valeyrie-Allanore L, et al. Linear IgA bullous dermatosis: comparison between the drug-induced and spontaneous forms. Br J Dermatol. 2013;169:1041–8. doi: 10.1111/bjd.12488.PubMedGoogle Scholar
  29. 29.
    Newby CS, Barr RM, Greaves MW, Mallet AI. Cytokine release and cytotoxicity in human keratinocytes and fibroblasts induce d by phenols and sodium dodecyl sulfate. J Invest Dermatol. 2000;115:292–8.PubMedGoogle Scholar
  30. 30.
    Feliciani C, Toto P, Amerio P, Pour SM, Coscione G, Shivji G, et al. In vitro and in vivo expression of interleukin-1α and tumor necrosis factor-α mRNA in pemphigus vulgaris: interleukin-1α and tumor necrosis factor-α are involved in acantholysis. J Invest Dermatol. 2000;114:71–7.PubMedGoogle Scholar
  31. 31.
    Ruocco V, De Angelis E, Lombardi ML. Drug-induced pemphigus. II. Pathomechanisms and experimental investigations. Clin Dermatol. 1993;11:507–13.PubMedGoogle Scholar
  32. 32.
    Fernando SL. Acute generalised exanthematous pustulosis. Australas J Dermatol. 2012;53:87–92. doi: 10.1111/j.1440-0960.2011.00845.x.PubMedGoogle Scholar
  33. 33.
    Roujeau JC, Bioulac-Sage P, Bourseau C, Guillaume JC, Bernard P, Lok C, et al. Acute generalized exanthematous pustulosis. Analysis of 63 cases. Arch Dermatol. 1991;127:1333–8.PubMedGoogle Scholar
  34. 34.
    Sidoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized exanthematous pustulosis (AGEP)–a clinical reaction pattern. J Cutan Pathol. 2001;28:113–9.PubMedGoogle Scholar
  35. 35.
    Momin SB, Peterson A, Del Rosso JQ. A status report on drug-associated acne and acneiform eruptions. J Drugs Dermatol. 2010;9:627–36.PubMedGoogle Scholar
  36. 36.
    Scheinfeld NS, Chernoff K, Derek Ho MK, Liu YC. Drug-induced photoallergic and phototoxic reactions – an update. Expert Opin Drug Saf. 2014;13:321–40. doi: 10.1517/14740338.2014.885948.PubMedGoogle Scholar
  37. 37.
    Badri T, Ben Tekaya N, Cherif F, Ben Osman Dhahri A. Photo-onycholysis: two cases induced by doxycycline. Acta Dermatovenerol Alp Panonica Adriat. 2004;13:135–6.Google Scholar
  38. 38.
    Drucker AM, Rosen CF. Drug-induced photosensitivity: culprit drugs, management and prevention. Drug Saf. 2011;34:821–37. doi: 10.2165/11592780-000000000-00000.PubMedGoogle Scholar
  39. 39.
    Dereure O. Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment. Am J Clin Dermatol. 2001;2:253–62.PubMedGoogle Scholar
  40. 40.
    Conroy EA, Liranzo MO, McMahon J, Steck WD, Tuthill RJ. Quinidine-induced pigmentation. Cutis. 1996;57:425–7.PubMedGoogle Scholar
  41. 41.
    Gonzalez-Arriagada WA, Silva AR, Vargas PA, de Almeida OP, Lopes MA. Facial pigmentation associated with amiodarone. Gen Dent. 2013;61:e15–7.PubMedGoogle Scholar
  42. 42.
    Cox NH, Walsh ML, Robson RH. Purpura and bleeding due to calcium-channel blockers: an underestimated problem? Case reports and a pilot study. Clin Exp Dermatol. 2009;34:487–91. doi: 10.1111/j.1365-2230.2008.03048.x.PubMedGoogle Scholar
  43. 43.
    Dootson G, Byatt C. Amiodarone-induced vasculitis and a review of the cutaneous side-effects of amiodarone. Clin Exp Dermatol. 1994;19:422–4.PubMedGoogle Scholar
  44. 44.
    Veloso HH, De Paola AA. Thrombophlebitis: a common complication of amiodarone. Am Fam Physician. 2004;70:1448.PubMedGoogle Scholar
  45. 45.
    Al-Niaimi F, Lyon C. Felodipine-induced eruptive telangiectasia following mastectomy and radiotherapy. Br J Dermatol. 2010;162:210–1. doi: 10.1111/j.1365-2133.2009.09497.x.PubMedGoogle Scholar
  46. 46.
    Pendergraft WF, Niles JL. Trojan horses: drug culprits associated with antineutrophil cytoplasmic autoantibody (ANCA) vasculitis. Curr Opin Rheumatol. 2014;26:42–9. doi: 10.1097/BOR.0000000000000014.PubMedGoogle Scholar
  47. 47.
    Papagrigoraki A, Gisondi P, Rosina P, Cannone M, Girolomoni G. Erythema nodosum: etiological factors and relapses in a retrospective cohort study. Eur J Dermatol. 2010;20:773–7. doi: 10.1684/ejd.2010.1116.PubMedGoogle Scholar
  48. 48.
    Sharma G, Govil DC. Allopurinol induced erythroderma. Indian J Pharmacol. 2013;45:627–8. doi: 10.4103/0253-7613.121381.PubMedCentralPubMedGoogle Scholar
  49. 49.
    Finkelstein Y, Soon GS, Acuna P, George M, Pope E, Ito S, et al. Recurrence and outcomes of Stevens-Johnson syndrome and toxic epidermal necrolysis in children. Pediatrics. 2011;128:723–8. doi: 10.1542/peds.2010-3322.PubMedGoogle Scholar
  50. 50.
    Pereira FA, Mudgil AV, Rosmarin DM. Toxic epidermal necrolysis. J Am Acad Dermatol. 2007;56:181–200.PubMedGoogle Scholar
  51. 51.
    Castelain F, Humbert P. Toxic epidermal necrolysis. Curr Drug Saf. 2012;7:332–8.PubMedGoogle Scholar
  52. 52.
    Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. 2000;115:149–53.PubMedGoogle Scholar
  53. 53.
    Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: part II. Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol. 2013;69:187.e1–16. doi: 10.1016/j.jaad.2013.05.002; quiz 203–4.Google Scholar
  54. 54.
    Verma R, Vasudevan B, Pragasam V. Severe cutaneous adverse drug reactions. Med J Armed Forces India. 2013;69:375–83.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Garcia-Doval I, LeCleach L, Bocquet H, Otero XL, Roujeau JC. Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol. 2000;136:323–7.PubMedGoogle Scholar
  56. 56.
    Ständer S, Metze D, Luger T, Schwarz T. Drug reaction with eosinophilia and systemic symptoms (DRESS): a review. Hautarzt. 2013;64:611–22. doi: 10.1007/s00105-013-2615-0; quiz 623–4.PubMedGoogle Scholar
  57. 57.
    Kardaun SH, Sidoroff A, Valeyrie-Allanore L, Halevy S, Davidovici BB, Mockenhaupt M, et al. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol. 2007;156:609–11.PubMedGoogle Scholar
  58. 58.
    Yazganoglu KD, Özkaya E, Ergin-Özcan P, Çakar N. Vancomycin-induced drug hypersensitivity syndrome. J Eur Acad Dermatol Venereol. 2005;19:648–50.PubMedGoogle Scholar
  59. 59.
    Choi TS, Doh KS, Kim SH, Jang MS, Suh KS, Kim ST. Clinicopathological and genotypic aspects of anticonvulsant-induced pseudolymphoma syndrome. Br J Dermatol. 2003;148:730–6.PubMedGoogle Scholar
  60. 60.
    Mutasim DF. Lymphomatoid drug eruption mimicking digitate dermatosis: cross reactivity between two drugs that suppress angiotensin II function. Am J Dermatopathol. 2003;25:331–4.PubMedGoogle Scholar
  61. 61.
    Pulitzer MP, Nolan KA, Oshman RG, Phelps RG. CD30+ lymphomatoid drug reactions. Am J Dermatopathol. 2013;35:343–50. doi: 10.1097/DAD.0b013e31826bc1e5.PubMedGoogle Scholar
  62. 62.
    Nazarian RM, Van Cott EM, Zembowicz A, Duncan LM. Warfarin-induced skin necrosis. J Am Acad Dermatol. 2009;61:325–32. doi: 10.1016/j.jaad.2008.12.039.PubMedGoogle Scholar
  63. 63.
    Katz U, Zandman-Goddard G. Drug-induced lupus: an update. Autoimmun Rev. 2010;10:46–50. doi: 10.1016/j.autrev.2010.07.005.PubMedGoogle Scholar
  64. 64.
    Levine D, Switlyk SA, Gottlieb A. Cutaneous lupus erythematosus and anti-TNF-alpha therapy: a case report with review of the literature. J Drugs Dermatol. 2010;9:1283–7.PubMedGoogle Scholar
  65. 65.
    Marzano AV, Vezzoli P, Crosti C. Drug-induced lupus: an update on its dermatologic aspects. Lupus. 2009;18:935–40. doi: 10.1177/0961203309106176.PubMedGoogle Scholar
  66. 66.
    Callen JP. Drug-induced subacute cutaneous lupus erythematosus. Lupus. 2010;19:1107–11. doi: 10.1177/0961203310370349.PubMedGoogle Scholar
  67. 67.
    Sontheimer RD, Henderson CL, Grau RH. Drug-induced subacute cutaneous lupus erythematosus: a paradigm for bedside-to-bench patient-oriented translational clinical investigation. Arch Dermatol Res. 2009;301:65–70. doi: 10.1007/s00403-008-0890-x.PubMedGoogle Scholar
  68. 68.
    Srivastava M, Rencic A, Diglio G, Santana H, Bonitz P, Watson R, et al. Drug-induced, Ro/SSA-positive cutaneous lupus erythematosus. Arch Dermatol. 2003;139:45–9.PubMedGoogle Scholar
  69. 69.
    Bulut M, Yazganoglu KD, Buyukbabani N, Özkaya E. Subacute cutaneous lupus erythematosus-like eruption possibly induced by filgrastim, a granulocyte colony-stimulating factor. EADV 22nd Congress, İstanbul, 2–6 October 2013, Programme book. p. 152 (P 109).Google Scholar
  70. 70.
    Milavec-Puretić V, Mance M, Ceović R, Lipozenčić J. Drug induced psoriasis. Acta Dermatovenerol Croat. 2011;19:39–42.PubMedGoogle Scholar
  71. 71.
    Tsankov N, Angelova I, Kazandjieva J. Drug-induced psoriasis. Recognition and management. Am J Clin Dermatol. 2000;1:159–65.PubMedGoogle Scholar
  72. 72.
    Wolf R, Ruocco V. Triggered psoriasis. Adv Exp Med Biol. 1999;455:221–5.PubMedGoogle Scholar
  73. 73.
    Yerushalmi J, Zvulunov A, Halevy S. Serum sickness-like reactions. Cutis. 2002;69:395–7.PubMedGoogle Scholar
  74. 74.
    Ständer S, Darsow U, Mettang T, Gieler U, Maurer M, Ständer H, et al. S2k guideline–Chronic Pruritus. J Dtsch Dermatol Ges. 2012;10 Suppl 4:S1–27. doi: 10.1111/j.1610-0387.2012.08005.x.PubMedGoogle Scholar
  75. 75.
    Claeys A, Weber-Muller F, Trechot P, Cuny JF, Georges MY, Barbaud A, et al. Cutaneous, perivulvar and perianal ulcerations induced by nicorandil. Br J Dermatol. 2006;155:494–6.PubMedGoogle Scholar
  76. 76.
    Ghersetich I, Rindi L, Teofoli P, Tsampau D, Palleschi GM, Lotti T. Pityriasis rosea-like skin eruptions caused by captopril. G Ital Dermatol Venereol. 1990;125:457–9.PubMedGoogle Scholar
  77. 77.
    Sugita K, Kabashima K, Nakamura M, Tokura Y. Drug-induced papuloerythroderma: analysis of T-cell populations and a literature review. Acta Derm Venereol. 2009;89:618–22.PubMedGoogle Scholar
  78. 78.
    Sugita K, Kabashima K, Nakashima D, Tokura Y. Papuloerythroderma of Ofuji induced by furosemide. J Am Acad Dermatol. 2008;58(2 Suppl):S54–5. doi: 10.1016/j.jaad.2006.05.046.PubMedGoogle Scholar
  79. 79.
    Sugita K, Koga C, Yoshiki R, Izu K, Tokura Y. Papuloerythroderma caused by aspirin. Arch Dermatol. 2006;142:792–3.PubMedGoogle Scholar
  80. 80.
    Thompson DF, Montarella KE. Drug-induced Sweet’s syndrome. Ann Pharmacother. 2007;41:802–11.PubMedGoogle Scholar
  81. 81.
    Roujeau JC. Neutrophilic drug eruptions. Clin Dermatol. 2000;18:331–7.PubMedGoogle Scholar
  82. 82.
    Bremner R, Simpson E, White CR, Morrison L, Deodhar A. Palisaded neutrophilic and granulomatous dermatitis: an unusual cutaneous manifestation of immune-mediated disorders. Semin Arthritis Rheum. 2004;34:610–6.PubMedGoogle Scholar
  83. 83.
    Magro CM, Crowson AN, Schapiro BL. The interstitial granulomatous drug reaction: a distinctive clinical and pathological entity. J Cutan Pathol. 1998;25:72–8.PubMedGoogle Scholar
  84. 84.
    Magro CM, Cruz-Inigo AE, Votava H, Jacobs M, Wolfe D, Crowson AN. Drug-associated reversible granulomatous T cell dyscrasia: a distinct subset of the interstitial granulomatous drug reaction. J Cutan Pathol. 2010;37 Suppl 1:96–111.PubMedGoogle Scholar
  85. 85.
    Perrin C, Lacour JP, Castanet J, Michiels JF. Interstitial granulomatous drug reaction with a histological pattern of interstitial granulomatous dermatitis. Am J Dermatopathol. 2001;23:295–8.PubMedGoogle Scholar
  86. 86.
    Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK. Interstitial and granulomatous drug reaction presenting as erythema nodosum-like lesions. Acta Derm Venereol. 2002;82:473–4.PubMedGoogle Scholar
  87. 87.
    Yazganoğlu KD, Tambay E, Mete Ö, Özkaya E. Interstitial granulomatous drug reaction due to thalidomide. J Eur Acad Dermatol Venereol. 2009;23:490–3. doi: 10.1111/j.1468-3083.2008.02953.x.PubMedGoogle Scholar
  88. 88.
    Cheshire WP, Fealey RD. Drug-induced hyperhidrosis and hypohidrosis: incidence, prevention and management. Drug Saf. 2008;31:109–26.PubMedGoogle Scholar
  89. 89.
    Torpet LA, Kragelund C, Reibel J, Nauntofte B. Oral adverse drug reactions to cardiovascular drugs. Crit Rev Oral Biol Med. 2004;15:28–46.PubMedGoogle Scholar
  90. 90.
    Habbab KM, Moles DR, Porter SR. Potential oral manifestations of cardiovascular drugs. Oral Dis. 2010;16:769–73. doi: 10.1111/j.1601-0825.2010.01686.x.PubMedGoogle Scholar
  91. 91.
    Pillans PI, Woods DJ. Drug-associated alopecia. Int J Dermatol. 1995;34:149–58.PubMedGoogle Scholar
  92. 92.
    Piraccini BM, Iorizzo M, Rech G, Tosti A. Drug-induced hair disorders. Curr Drug Saf. 2006;1:301–5.PubMedGoogle Scholar
  93. 93.
    Piraccini BM, Alessandrini A. Drug-related nail disease. Clin Dermatol. 2013;31:618–26. doi: 10.1016/j.clindermatol.2013.06.013.PubMedGoogle Scholar
  94. 94.
    Kynaston HG, Roberts DH, Davies WT. Peripheral gangrene associated with beta-blockade. Br J Surg. 1987;74:760.PubMedGoogle Scholar
  95. 95.
    Coombs PR, Gell PG. Classification of allergic reactions responsible for clinical hypersensitivity and disease. In: Gell RR, editor. Clinical aspects of immunology. Oxford: Oxford University Press; 1968. p. 575–96.Google Scholar
  96. 96.
    Friedmann PS, Ardern-Jones M. Patch testing in drug allergy. Curr Opin Allergy Clin Immunol. 2010;10:291–6. doi: 10.1097/ACI.0b013e32833aa54d.PubMedGoogle Scholar
  97. 97.
    Posadas SJ, Pichler WJ. Delayed drug hypersensitivity reactions – new concepts. Clin Exp Allergy. 2007;37:989–99.PubMedGoogle Scholar
  98. 98.
    Yawalkar N, Pichler WJ. Mechanisms of cutaneous drug reactions. J Dtsch Dermatol Ges. 2004;2:1013–23.PubMedGoogle Scholar
  99. 99.
    Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med. 2003;139:683–93.PubMedGoogle Scholar
  100. 100.
    Lee HY, Chung WH. Toxic epidermal necrolysis: the year in review. Curr Opin Allergy Clin Immunol. 2013;13:330–6. doi: 10.1097/ACI.0b013e3283630cc2.PubMedGoogle Scholar
  101. 101.
    Chung WH, Hung SI, Yang JY, Su SC, Huang SP, Wei CY, et al. Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis. Nat Med. 2008;14:1343–50. doi: 10.1038/nm.1884.PubMedGoogle Scholar
  102. 102.
    Özkaya E, Babuna G. A challenging case: symmetrical drug related intertriginous and flexural exanthem, fixed drug eruption, or both? Pediatr Dermatol. 2011;28:711–4. doi: 10.1111/j.1525-1470.2011.01656.x.PubMedGoogle Scholar
  103. 103.
    Schnyder B, Burkhart C, Schnyder-Frutig K, von Greyerz S, Naisbitt DJ, Pirmohamed M, et al. Recognition of sulfamethoxazole and its reactive metabolites by drug-specific CD4+ T cells from allergic individuals. J Immunol. 2000;164:6647–54.PubMedGoogle Scholar
  104. 104.
    Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002;359:727–32.PubMedGoogle Scholar
  105. 105.
    Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 2004;428:486.PubMedGoogle Scholar
  106. 106.
    Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A. 2005;102:4134–9.PubMedCentralPubMedGoogle Scholar
  107. 107.
    Pellicano R, Ciavarella G, Lomuto M, Di Giorgio G. Genetic susceptibility to fixed drug eruptions: evidence for a link with HLA-B22. J Am Acad Dermatol. 1994;30:52–4.PubMedGoogle Scholar
  108. 108.
    Pellicano R, Lomuto M, Ciavarella G, Di Giorgio G, Gasparini P. Fixed drug eruptions with feprazone are linked to HLA-B22. J Am Acad Dermatol. 1997;36:782–4.PubMedGoogle Scholar
  109. 109.
    Ozkaya E, Akar U. Fixed drug eruption induced by trimethoprim-sulfamethoxazole: evidence for a link to HLA-A30 B13 Cw6 haplotype. J Am Acad Dermatol. 2001;45:712–7.Google Scholar
  110. 110.
    Shapiro LE, Shear NH. Drug interactions: proteins, pumps, and P-450 s. J Am Acad Dermatol. 2002;47:467–84.PubMedGoogle Scholar
  111. 111.
    Gex-Collet C, Helbling A, Pichler WJ. Multiple drug hypersensitivity-proof of multiple drug hypersensitivity by patch and lymphocyte transformation tests. J Investig Allergol Clin Immunol. 2005;15:293–6.PubMedGoogle Scholar
  112. 112.
    Asero R. Multiple drug allergy syndrome: a distinct clinical entity. Curr Allergy Rep. 2001;1:18–22.PubMedGoogle Scholar
  113. 113.
    Halevy S, Grossman N. Multiple drug allergy in patients with cutaneous adverse drug reactions diagnosed by in vitro drug-induced interferon-gamma release. Isr Med Assoc J. 2008;10:865–8.PubMedGoogle Scholar
  114. 114.
    Voltolini S, Bignardi D, Minale P, Pellegrini S, Troise C. Phenobarbital- induced DiHS and ceftriaxone hypersensitivity reaction: a case of multiple drug allergy. Eur Ann Allergy Clin Immunol. 2009;41:62–3.PubMedGoogle Scholar
  115. 115.
    Özkaya E. Eczematous type multiple drug allergy from isoniazid and ethambutol with positive patch test results. Cutis. 2013;92:121–4.PubMedGoogle Scholar
  116. 116.
    Özkaya E, Yazganoglu KD. Sequential development of eczematous type “multiple drug allergy” to unrelated drugs. J Am Acad Dermatol. 2011;65:e26–9. doi: 10.1016/j.jaad.2010.12.028.PubMedGoogle Scholar
  117. 117.
    Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45.PubMedGoogle Scholar
  118. 118.
    Moore N, Biour M, Paux G, Loupi E, Begaud B, Boismare F, et al. Adverse drug reaction monitoring: doing it the French way. Lancet. 1985;2(8463):1056–8.PubMedGoogle Scholar
  119. 119.
    The Uppsala Monitoring Centre. The use of the WHO-UMC system for standardised case causality assessment. Accessed 31 Mar 2014.
  120. 120.
    Seitz CS, Rose C, Kerstan A, Trautmann A. Drug-induced exanthems: correlation of allergy testing with histologic diagnosis. J Am Acad Dermatol. 2013;69:721–8. doi: 10.1016/j.jaad.2013.06.022.PubMedGoogle Scholar
  121. 121.
    Barbaud A, Reichert-Penetrat S, Tréchot P, Jacquin-Petit MA, Ehlinger A, Noirez V, et al. The use of skin testing in the investigation of cutaneous adverse drug reactions. Br J Dermatol. 1998;139:49–58.PubMedGoogle Scholar
  122. 122.
    Romano A, Demoly P. Recent advances in the diagnosis of drug allergy. Curr Opin Allergy Clin Immunol. 2007;7:299–303.PubMedGoogle Scholar
  123. 123.
    Sanz ML, García BE, Prieto I, Tabar A, Oehling A. Specific IgE determination in the diagnosis of beta-lactam allergy. J Investig Allergol Clin Immunol. 1996;6:89–93.PubMedGoogle Scholar
  124. 124.
    Pichler WJ, Tilch J. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy. 2004;59:809–20.PubMedGoogle Scholar
  125. 125.
    Goossens C, Sass U, Song M. Baboon syndrome. Dermatology. 1997;194:421–2.PubMedGoogle Scholar
  126. 126.
    Kanny G, Pichler W, Morisset M, Franck P, Marie B, Kohler C, et al. T cell-mediated reactions to iodinated contrast media: evaluation by skin and lymphocyte activation tests. J Allergy Clin Immunol. 2005;115:179–85.PubMedGoogle Scholar
  127. 127.
    Halevy S, Cohen AD, Grossman N. Clinical implications of in vitro drug-induced interferon gamma release from peripheral blood lymphocytes in cutaneous adverse drug reactions. J Am Acad Dermatol. 2005;52:254–61.PubMedGoogle Scholar
  128. 128.
    Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernandez J, et al. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy. 2003;58:854–63.PubMedGoogle Scholar
  129. 129.
    Mahajan VK, Handa S. Patch testing in cutaneous adverse drug reactions: methodology, interpretation, and clinical relevance. Indian J Dermatol Venereol Leprol. 2013;79:836–41. doi: 10.4103/0378-6323.120751.PubMedGoogle Scholar
  130. 130.
    Ozkaya E, Bayazit H, Ozarmagan G. Drug related clinical pattern in fixed drug eruption. Eur J Dermatol. 2000;10:288–91.Google Scholar
  131. 131.
    Méndez J, Sanchís ME, de la Fuente R, Stolle R, Vega JM, Martínez C, et al. Delayed-type hypersensitivity to subcutaneous enoxaparin. Allergy. 1998;53:999–1003.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Esen Özkaya
    • 1
  • Kurtuluş Didem Yazganoğlu
    • 1
  1. 1.Department of Dermatology and VenereologyIstanbul University Istanbul Medical FacultyIstanbulTurkey

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