Abstract
Cutaneous adverse drug reactions comprise a significant proportion of all adverse drug reactions. They may mimic other dermatologic or systemic illnesses and may cause significant morbidity or mortality. Seven morphologic groups encompass the most commonly encountered cutaneous drug reaction syndromes: exanthematous (maculopapular), dermatitic/eczematous, urticarial, pustular, blistering, purpuric, and erythrodermic. Drug reactions may have significant downstream consequences for the older individual.
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References
Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365:2002–12. doi:10.1056/NEJMsa1103053.
Passarelli MCG, Jacob-Filho W, Figueras A. Adverse drug reactions in an elderly hospitalised population: inappropriate prescription is a leading cause. Drugs Aging. 2005;22:767–77.
Gurwitz JH, Field TS, Harrold LR, et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA. 2003;289:1107–16.
Koelblinger P, Dabade TS, Gustafson CJ, et al. Skin manifestations of outpatient adverse drug events in the United States: a national analysis. J Cutan Med Surg. 2013;17:269–75. doi:10.2310/7750.2013.12096.
Yalcin B, Tamer E, Toy GG, et al. The prevalence of skin diseases in the elderly: analysis of 4099 geriatric patients. Int J Dermatol. 2006;45:672–6. doi:10.1111/j.1365-4632.2005.02607.x.
Lange-Asschenfeldt C, Grohmann R, Lange-Asschenfeldt B, et al. Cutaneous adverse reactions to psychotropic drugs: data from a multicenter surveillance program. J Clin Psychiatry. 2009;70:1258–65. doi:10.4088/JCP.08m04563.
del Campos-Fernandez MM, de Leon-Rosales SP, Archer-Dubon C, Orozco-Topete R. Incidence and risk factors for cutaneous adverse drug reactions in an intensive care unit. Rev Invest Clin. 2005;57:770–4.
Bastuji-Garin S, Zahedi M, Guillaume JC, Roujeau JC. Toxic epidermal necrolysis (Lyell syndrome) in 77 elderly patients. Age Ageing. 1993;22:450–6.
Bigby M, Jick S, Jick H, Arndt K. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 198. JAMA. 1975;1986(256):3358–63.
van der Linden PD, van der Lei J, Vlug AE, Stricker BH. Skin reactions to antibacterial agents in general practice. J Clin Epidemiol. 1998;51:703–8.
Stern RS. Utilization of hospital and outpatient care for adverse cutaneous reactions to medications. Pharmacoepidemiol Drug Saf. 2005;14:677–84. doi:10.1002/pds.1065.
Hernandez-Salazar A, de Leon-Rosales SP, Rangel-Frausto S, et al. Epidemiology of adverse cutaneous drug reactions: a prospective study in hospitalized patients. Arch Med Res. 2006;37:899–902. doi:10.1016/j.arcmed.2006.03.010.
Park CS, Kim T-B, Kim SL, et al. The use of an electronic medical record system for mandatory reporting of drug hypersensitivity reactions has been shown to improve the management of patients in the university hospital in Korea. Pharmacoepidemiol Drug Saf. 2008;17:919–25. doi:10.1002/pds.1612.
Fiszenson-Albala F, Auzerie V, Mahe E, et al. A 6-month prospective survey of cutaneous drug reactions in a hospital setting. Br J Dermatol. 2003;149:1018–22.
Calderón-Larrañaga A, Poblador-Plou B, González-Rubio F, et al. Multimorbidity, polypharmacy, referrals, and adverse drug events: are we doing things well? Br J Gen Pract. 2012;62:e821–6. doi:10.3399/bjgp12X659295.
Guthrie B, Makubate B, Hernandez-Santiago V, Dreischulte T. The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995–2010. BMC Med. 2015;13:74. doi:10.1186/s12916-015-0322-7.
Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007;62:722–7.
Woo J, Leung J. Multi-morbidity, dependency, and frailty singly or in combination have different impact on health outcomes. Age Dordr Neth. 2014;36:923–31. doi:10.1007/s11357-013-9590-3.
Aarts S, Patel KV, Garcia ME, et al. Co-Presence of multimorbidity and disability with frailty: an examination of heterogeneity in the frail older population. J Frailty Aging. 2015;4:131–8. doi:10.14283/jfa.2015.45.
Rolland Y, Morley JE. Frailty and polypharmacy. J Nutr Health Aging. 2016;20:645–6. doi:10.1007/s12603-015-0510-3.
Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–56.
Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173:489–95. doi:10.1503/cmaj.050051.
Crome P, Lally F. Frailty: joining the giants. CMAJ. 2011;183:889–90. doi:10.1503/cmaj.110626.
Clegg A, Young J, Iliffe S, et al. Frailty in elderly people. Lancet. 2012;381:752–62. doi:10.1016/S0140-6736(12)62167-9.
Oresanya LB, Lyons WL, Finlayson E. Preoperative assessment of the older patient: a narrative review. JAMA. 2014;311:2110–20. doi:10.1001/jama.2014.4573.
Sullivan JR, Shear NH. Drug eruptions and other adverse drug effects in aged skin. Clin Geriatr Med. 2002;18:21–42. doi:10.1016/S0749-0690(03)00032-6.
Sassolas B, Haddad C, Mockenhaupt M, et al. ALDEN, an algorithm for assessment of drug causality in Stevens–Johnson syndrome and toxic epidermal necrolysis: comparison with case-control analysis. Clin Pharmacol Ther. 2010;88:60–8. doi:10.1038/clpt.2009.252.
Kardaun SH, Sekula P, Valeyrie-Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169:1071–80. doi:10.1111/bjd.12501.
Lin Y-F, Yang C-H, Sindy H, et al. Severe cutaneous adverse reactions related to systemic antibiotics. Clin Infect Dis. 2014;58:1377–85. doi:10.1093/cid/ciu126.
Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333:1600–7. doi:10.1056/NEJM199512143332404.
Mockenhaupt M, Viboud C, Dunant A, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol. 2008;128:35–44. doi:10.1038/sj.jid.5701033.
Sidoroff A, Dunant A, Viboud C, et al. Risk factors for acute generalized exanthematous pustulosis (AGEP): results of a multinational case-control study (EuroSCAR). Br J Dermatol. 2007;157:989–96. doi:10.1111/j.1365-2133.2007.08156.x.
Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med. 2003;139:683–93.
Tuchinda P, Chularojanamontri L, Sukakul T, et al. Cutaneous adverse drug reactions in the elderly: a retrospective analysis in Thailand. Drugs Aging. 2014;31:815–24. doi:10.1007/s40266-014-0209-x.
Coopman SA, Johnson RA, Platt R, Stern RS. Cutaneous disease and drug reactions in HIV infection. N Engl J Med. 1993;328:1670–4. doi:10.1056/NEJM199306103282304.
Stern RS. Exanthematous drug eruptions. N Engl J Med. 2012;366:2492–501. doi:10.1056/NEJMcp1104080.
Jick H, Porter JB. Potentiation of ampicillin skin reactions by allopurinol or hyperuricemia. J Clin Pharmacol. 1981;21:456–8.
Salahudeen MS, Duffull SB, Nishtala PS. Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review. BMC Geriatr. 2015;25(15):31. doi:10.1186/s12877-015-0029-9.
McDonald K, Trick L, Boyle J. Sedation and antihistamines: an update. Review of inter-drug differences using proportional impairment ratios. Hum Psychopharmacol Clin Exp. 2008;23:555–70. doi:10.1002/hup.962.
Beauregard S, Gilchrest BA. A survey of skin problems and skin care regimens in the elderly. Arch Dermatol. 1987;123:1638–43.
Fenske NA, Lober CW. Structural and functional changes of normal aging skin. J Am Acad Dermatol. 1986;15:571–85. doi:10.1016/S0190-9622(86)70208-9.
Farage MA, Miller KW, Berardesca E, Maibach HI. Clinical implications of aging skin: cutaneous disorders in the elderly. Am J Clin Dermatol. 2009;10:73–86.
Proksch E. Antilipemic drug-induced skin manifestations. Hautarzt Z Für Dermatol Venerol Verwandte Geb. 1995;46:76–80.
Hatwal A, Bhatt RP, Agrawal JK, et al. Spironolactone and cimetidine in treatment of acne. Acta Derm Venereol. 1988;68:84–7.
Clegg A, Young JB. Which medications to avoid in people at risk of delirium: a systematic review. Age Ageing. 2011;40:23–9. doi:10.1093/ageing/afq140.
Mangelsdorf HC, Fleischer AB, Sherertz EF. Patch testing in an aged population without dermatitis: high prevalence of patch test positivity. Am J Contact Dermat. 1996;7:155–7.
Goh CL, Ling R. A retrospective epidemiology study of contact eczema among the elderly attending a tertiary dermatology referral centre in Singapore. Singap Med J. 1998;39:442–6.
Walton S, Nayagam AT, Keczkes K. Age and sex incidence of allergic contact dermatitis. Contact Dermat. 1986;15:136–9.
Tavadia S, Bianchi J, Dawe RS, et al. Allergic contact dermatitis in venous leg ulcer patients. Contact Dermat. 2003;48:261–5.
Gooptu C, Powell SM. The problems of rubber hypersensitivity (types I and IV) in chronic leg ulcer and stasis eczema patients. Contact Dermatitis. 1999;41:89–93.
Isaksson M, Bruze M, Björkner B, et al. The benefit of patch testing with a corticosteroid at a low concentration. Am J Contact Dermat. 1999;10:31–3.
Winblad B, Grossberg G, Frölich L, et al. IDEAL: a 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease. Neurology. 2007;69:S14–22. doi:10.1212/01.wnl.0000281847.17519.e0.
Greenspoon J, Herrmann N, Adam DN. Transdermal rivastigmine: management of cutaneous adverse events and review of the literature. CNS Drugs. 2011;25:575–83. doi:10.2165/11592230-000000000-00000.
González E, González S. Drug photosensitivity, idiopathic photodermatoses, and sunscreens. J Am Acad Dermatol. 1996;35:871–85 (quiz 886–7).
Moore DE. Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management. Drug Saf. 2002;25:345–72.
Epstein JH. Phototoxicity and photoallergy. Semin Cutan Med Surg. 1999;18:274–84.
Kaidbey KH, Messenger JL. The clinical spectrum of the persistent light reactor. Arch Dermatol. 1984;120:1441–8.
Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics. Toronto, ON: Canadian Cancer Society; 2016.
Alley E, Green R, Schuchter L. Cutaneous toxicities of cancer therapy. Curr Opin Oncol. 2002;14:212–6.
Robert C, Soria J-C, Spatz A, et al. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol. 2005;6:491–500. doi:10.1016/S1470-2045(05)70243-6.
Lee WJ, Lee JL, Chang SE, et al. Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. Br J Dermatol. 2009;161:1045–51. doi:10.1111/j.1365-2133.2009.09290.x.
Melosky B, Burkes R, Rayson D, et al. Management of skin rash during EGFR-targeted monoclonal antibody treatment for gastrointestinal malignancies: Canadian recommendations. Curr Oncol Tor Ont. 2009;16:16–26.
Naidoo J, Page DB, Li BT, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26:2375–91. doi:10.1093/annonc/mdv383.
Luu M, Lai SE, Patel J, et al. Photosensitive rash due to the epidermal growth factor receptor inhibitor erlotinib. Photodermatol Photoimmunol Photomed. 2007;23:42–5. doi:10.1111/j.1600-0781.2007.00273.x.
Boussemart L, Routier E, Mateus C, et al. Prospective study of cutaneous side-effects associated with the BRAF inhibitor vemurafenib: a study of 42 patients. Ann Oncol. 2013;24:1691–7. doi:10.1093/annonc/mdt015.
Gelot P, Dutartre H, Khammari A, et al. Vemurafenib: an unusual UVA-induced photosensitivity. Exp Dermatol. 2013;22:297–8. doi:10.1111/exd.12119.
Cummings SR, Martin JS, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–65. doi:10.1056/NEJMoa0809493.
Jerschow E, Lin RY, Scaperotti MM, McGinn AP. Fatal anaphylaxis in the United States, 1999–2010: temporal patterns and demographic associations. J Allergy Clin Immunol. 2014;134(1318–28):e7. doi:10.1016/j.jaci.2014.08.018.
Harduar-Morano L, Simon MR, Watkins S, Blackmore C. Algorithm for the diagnosis of anaphylaxis and its validation using population-based data on emergency department visits for anaphylaxis in Florida. J Allergy Clin Immunol. 2010;126(98–104):e4. doi:10.1016/j.jaci.2010.04.017.
Ma L, Danoff TM, Borish L. Case fatality and population mortality associated with anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133:1075–83. doi:10.1016/j.jaci.2013.10.029.
Lieberman P, Simons FER. Anaphylaxis and cardiovascular disease: therapeutic dilemmas. Clin Exp Allergy. 2015;45:1288–95. doi:10.1111/cea.12520.
Kawano T, Scheuermeyer FX, Stenstrom R, et al. Epinephrine use in older patients with anaphylaxis: clinical outcomes and cardiovascular complications. Resuscitation. 2017;112:53–8. doi:10.1016/j.resuscitation.2016.12.020.
Campbell RL, Bellolio MF, Knutson BD, et al. Epinephrine in anaphylaxis: higher risk of cardiovascular complications and overdose after administration of intravenous bolus epinephrine compared with intramuscular epinephrine. J Allergy Clin Immunol Pract. 2015;3:76–80. doi:10.1016/j.jaip.2014.06.007.
Simon RA, Namazy J. Adverse reactions to aspirin and nonsteroidal antiinflammatory drugs (NSAIDs). Clin Rev Allergy Immunol. 2003;24:239–52. doi:10.1385/CRIAI:24:3:239.
Piller LB, Ford CE, Davis BR, et al. Incidence and predictors of angioedema in elderly hypertensive patients at high risk for cardiovascular disease: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens (Greenwich). 2006;8:649–56 (quiz 657–8).
Venzor J, Lee WL, Huston DP. Urticarial vasculitis. Clin Rev Allergy Immunol. 2002;23:201–16. doi:10.1385/CRIAI:23:2:201.
Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124:588–97. doi:10.1016/j.amjmed.2011.01.017.
Chen Y-C, Chang C-Y, Cho Y-T, et al. Long-term sequelae of drug reaction with eosinophilia and systemic symptoms: a retrospective cohort study from Taiwan. J Am Acad Dermatol. 2013;68:459–65. doi:10.1016/j.jaad.2012.08.009.
Botella-Estrada R, Sanmartín O, Oliver V, et al. Erythroderma: a clinicopathological study of 56 cases. Arch Dermatol. 1994;130:1503–7.
Akhyani M, Ghodsi ZS, Toosi S, Dabbaghian H. Erythroderma: a clinical study of 97 cases. BMC Dermatol. 2005;5:5. doi:10.1186/1471-5945-5-5.
Yuan X-Y, Guo J-Y, Dang Y-P, et al. Erythroderma: a clinical-etiological study of 82 cases. Eur J Dermatol. 2010;20:373–7. doi:10.1684/ejd.2010.0943.
Sigurdsson V, Toonstra J, Hezemans-Boer M, van Vloten WA. Erythroderma: a clinical and follow-up study of 102 patients, with special emphasis on survival. J Am Acad Dermatol. 1996;35:53–7.
Pal S, Haroon TS. Erythroderma: a clinico-etiologic study of 90 cases. Int J Dermatol. 1998;37:104–7.
Hasan T, Jansén CT. Erythroderma: a follow-up of fifty cases. J Am Acad Dermatol. 1983;8:836–40.
Loukas E. High-output heart failure in a patient with exfoliative erythrodermic psoriasis. J Hosp Med. 2010;5:162–3.
Rothe MJ, Bernstein ML, Grant-Kels JM. Life-threatening erythroderma: diagnosing and treating the “red man”. Clin Dermatol. 2005;23:206–17. doi:10.1016/j.clindermatol.2004.06.018.
Lin T-K, Hsu MM-L, Lee JY-Y. Clinical resemblance of widespread bullous fixed drug eruption to Stevens–Johnson syndrome or toxic epidermal necrolysis: report of two cases. J Formos Med Assoc Taiwan Yi Zhi. 2002;101:572–6.
Shiohara T. Fixed drug eruption: pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol. 2009;9:316–21. doi:10.1097/ACI.0b013e32832cda4c.
Lipowicz S, Sekula P, Ingen-Housz-Oro S, et al. Prognosis of generalized bullous fixed drug eruption: comparison with Stevens–Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol. 2013;168:726–32. doi:10.1111/bjd.12133.
Brenner S, Wolf R, Ruocco V. Contact pemphigus: a subgroup of induced pemphigus. Int J Dermatol. 1994;33:843–5. doi:10.1111/j.1365-4362.1994.tb01016.x.
Brenner S, Goldberg I. Drug-induced pemphigus. Clin Dermatol. 2011;29:455–7. doi:10.1016/j.clindermatol.2011.01.016.
Korman NJ, Eyre RW, Zone J, Stanley JR. Drug-induced pemphigus: autoantibodies directed against the pemphigus antigen complexes are present in penicillamine and captopril-induced pemphigus. J Invest Dermatol. 1991;96:273–6.
Langan SM, Smeeth L, Hubbard R, et al. Bullous pemphigoid and pemphigus vulgaris–incidence and mortality in the UK: population based cohort study. BMJ. 2008;337:a180. doi:10.1136/bmj.a180.
Huang Y-H, Kuo C-F, Chen Y-H, Yang Y-W. Incidence, mortality, and causes of death of patients with pemphigus in Taiwan: a nationwide population-based study. J Invest Dermatol. 2012;132:92–7. doi:10.1038/jid.2011.249.
Ahmed AR, Moy R. Death in pemphigus. J Am Acad Dermatol. 1982;7:221–8.
Hsu DY, Brieva J, Sinha AA, et al. Comorbidities and inpatient mortality for pemphigus in the U.S.A. Br J Dermatol. 2016;174:1290–8. doi:10.1111/bjd.14463.
Baican A, Chiorean R, Leucuta DC, et al. Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study. Orphanet J Rare Dis. 2015;10:48. doi:10.1186/s13023-015-0263-4.
Lee JJ, Downham TF. Furosemide-induced bullous pemphigoid: case report and review of literature. J Drugs Dermatol. 2006;5:562–4.
Patsatsi A, Vyzantiadis T-A, Chrysomallis F, et al. Medication history of a series of patients with bullous pemphigoid from northern Greece: observations and discussion. Int J Dermatol. 2009;48:132–5. doi:10.1111/j.1365-4632.2009.03839.x.
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.
Bastuji-Garin S, Joly P, Picard-Dahan C, et al. Drugs associated with bullous pemphigoid: a case-control study. Arch Dermatol. 1996;132:272–6.
Bastuji-Garin S, Joly P, Lemordant P, et al. Risk factors for bullous pemphigoid in the elderly: a prospective case-control study. J Invest Dermatol. 2011;131:637–43. doi:10.1038/jid.2010.301.
Lloyd-Lavery A, Chi C-C, Wojnarowska F, Taghipour K. The associations between bullous pemphigoid and drug use: a UK case-control study. JAMA Dermatol. 2013;149:58–62. doi:10.1001/2013.jamadermatol.376.
Pasmatzi E, Monastirli A, Habeos J, et al. Dipeptidyl peptidase-4 inhibitors cause bullous pemphigoid in diabetic patients: report of two cases. Diabetes Care. 2011;34:e133. doi:10.2337/dc11-0804.
Skandalis K, Spirova M, Gaitanis G, et al. Drug-induced bullous pemphigoid in diabetes mellitus patients receiving dipeptidyl peptidase-IV inhibitors plus metformin. J Eur Acad Dermatol Venereol. 2012;26:249–53. doi:10.1111/j.1468-3083.2011.04062.x.
Aouidad I, Fite C, Marinho E, et al. A case report of bullous pemphigoid induced by dipeptidyl peptidase-4 inhibitors. JAMA Dermatol. 2013;149:243–5. doi:10.1001/jamadermatol.2013.1073.
Roujeau J-C, Lok C, Bastuji-Garin S, et al. High risk of death in elderly patients with extensive bullous pemphigoid. Arch Dermatol. 1998;134:465. doi:10.1001/archderm.134.4.465.
Rzany B, Partscht K, Jung M, et al. Risk factors for lethal outcome in patients with bullous pemphigoid: low serum albumin level, high dosage of glucocorticosteroids, and old age. Arch Dermatol. 2002;138:903–8.
Joly P, Fontaine J, Roujeau J-C. The role of topical corticosteroids in bullous pemphigoid in the elderly. Drugs Aging. 2005;22:571–6.
Joly P, Roujeau J-C, Benichou J, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. N Engl J Med. 2002;346:321–7. doi:10.1056/NEJMoa011592.
Beissert S, Werfel T, Frieling U, et al. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of bullous pemphigoid. Arch Dermatol. 2007;143:1536–42. doi:10.1001/archderm.143.12.1536.
Fortuna G, Salas-Alanis JC, Guidetti E, Marinkovich MP. A critical reappraisal of the current data on drug-induced linear immunoglobulin A bullous dermatosis: a real and separate nosological entity? J Am Acad Dermatol. 2012;66:988–94. doi:10.1016/j.jaad.2011.09.018.
Fortuna G, Marinkovich MP. Linear immunoglobulin A bullous dermatosis. Clin Dermatol. 2012;30:38–50. doi:10.1016/j.clindermatol.2011.03.008.
Chanal J, Ingen-Housz-Oro S, Ortonne N, 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.
Mittmann N, Chan BC, Knowles S, Shear NH. IVIG for the treatment of toxic epidermal necrolysis. Skin Ther Lett. 2007;12:7–9.
Bastuji-Garin S, Fouchard N, Bertocchi M, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. 2000;115:149–53. doi:10.1046/j.1523-1747.2000.00061.x.
Sekula P, Dunant A, Mockenhaupt M, et al. Comprehensive survival analysis of a cohort of patients with Stevens–Johnson syndrome and toxic epidermal necrolysis. J Invest Dermatol. 2013;133:1197–204. doi:10.1038/jid.2012.510.
Chantaphakul H, Sanon T, Klaewsongkram J. Clinical characteristics and treatment outcome of Stevens–Johnson syndrome and toxic epidermal necrolysis. Exp Ther Med. 2015;10(2):519–24. doi:10.3892/etm.2015.2549.
McGill V, Kowal-Vern A, Gamelli RL. Outcome for older burn patients. Arch Surg. 2000;135:320–5. doi:10.1001/archsurg.135.3.320.
Mahar P, Wasiak J, Bailey M, Cleland H. Clinical factors affecting mortality in elderly burn patients admitted to a burns service. Burns. 2008;34:629–36. doi:10.1016/j.burns.2007.09.006.
Lundgren RS, Kramer CB, Rivara FP, et al. Influence of comorbidities and age on outcome following burn injury in older adults. J Burn Care Res. 2009;30:307–14. doi:10.1097/BCR.0b013e318198a416.
Von Wild T, Stollwerck PL, Namdar T, et al. Are multimorbidities underestimated in scoring systems of Stevens–Johnson syndrome and toxic epidermal necrolysis like in SCORTEN? EPlasty. 2012;12:e35.
Mittmann N, Chan B, Knowles S, et al. Intravenous immunoglobulin use in patients with toxic epidermal necrolysis and Stevens-Johnson syndrome. Am J Clin Dermatol. 2006;7:359–68.
Chen J, Wang B, Zeng Y, Xu H. High-dose intravenous immunoglobulins in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese patients: a retrospective study of 82 cases. Eur J Dermatol. 2010;20:743–7. doi:10.1684/ejd.2010.1077.
Barron SJ, Del Vecchio MT, Aronoff SC. Intravenous immunoglobulin in the treatment of Stevens–Johnson syndrome and toxic epidermal necrolysis: a meta-analysis with meta-regression of observational studies. Int J Dermatol. 2015;54:108–15. doi:10.1111/ijd.12423.
Gubinelli E, Canzona F, Tonanzi T, et al. Toxic epidermal necrolysis successfully treated with etanercept. J Dermatol. 2009;36:150–3. doi:10.1111/j.1346-8138.2009.00616.x.
Paradisi A, Abeni D, Bergamo F, et al. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014;71:278–83. doi:10.1016/j.jaad.2014.04.044.
Sidoroff A, Halevy S, Bavinck JN, et al. Acute generalized exanthematous pustulosis (AGEP): a clinical reaction pattern. J Cutan Pathol. 2001;28:113–9.
Chang S-L, Huang Y-H, Yang C-H, et al. Clinical manifestations and characteristics of patients with acute generalized exanthematous pustulosis in Asia. Acta Derm Venereol. 2008;88:363–5. doi:10.2340/00015555-0438.
Thienvibul C, Vachiramon V, Chanprapaph K. Five-year retrospective review of acute generalized exanthematous pustulosis. Dermatol Res Pract. 2015;2015:1–8. doi:10.1155/2015/260928.
Peermohamed S, Haber RM. Acute generalized exanthematous pustulosis simulating toxic epidermal necrolysis: a case report and review of the literature. Arch Dermatol. 2011;147:697–701. doi:10.1001/archdermatol.2011.147.
Hotz C, Valeyrie-Allanore L, Haddad C, et al. Systemic involvement of acute generalized exanthematous pustulosis: a retrospective study on 58 patients. Br J Dermatol. 2013;169:1223–32. doi:10.1111/bjd.12502.
Fernando SL. Acute generalised exanthematous pustulosis. Australas J Dermatol. 2012;53:87–92. doi:10.1111/j.1440-0960.2011.00845.x.
Krishna S, Ortega-Loayza A, Malakouti N, Brinster N. A rapidly progressive and fatal case of atypical acute generalized exanthematous pustulosis. J Am Acad Dermatol. 2014;71:e89–90. doi:10.1016/j.jaad.2014.03.007.
Vigano D’Angelo S, Comp PC, Esmon CT, D’Angelo A. Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states. J Clin Invest. 1986;77:416–25. doi:10.1172/JCI112319.
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.
McGehee WG, Klotz TA, Epstein DJ, Rapaport SI. Coumarin necrosis associated with hereditary protein C deficiency. Ann Intern Med. 1984;101:59–60.
Zauber NP, Stark MW. Successful warfarin anticoagulation despite protein C deficiency and a history of warfarin necrosis. Ann Intern Med. 1986;104:659–60.
Bauer KA. Coumarin-induced skin necrosis. Arch Dermatol. 1993;129:766–8.
Eby CS. Warfarin-induced skin necrosis. Hematol Oncol Clin North Am. 1993;7:1291–300.
Chan YC, Valenti D, Mansfield AO, Stansby G. Warfarin induced skin necrosis. Br J Surg. 2000;87:266–72. doi:10.1046/j.1365-2168.2000.01352.x.
Comp PC. Coumarin-induced skin necrosis: incidence, mechanisms, management and avoidance. Drug Saf. 1993;8:128–35. doi:10.2165/00002018-199308020-00003.
Sagi A, Ferder M, Strauch B. Skin necrosis and oral anticoagulant therapy: a review of the literature. Eur J Plast Surg. 1990;. doi:10.1007/BF00177808.
Miura Y, Ardenghy M, Ramasastry S, et al. Coumadin necrosis of the skin: report of four patients. Ann Plast Surg. 1996;37:332–7.
Ellis G, Whitehead MA, Robinson D, et al. Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials. BMJ. 2011;343:d6553–d6553. doi:10.1136/bmj.d6553.
Gelwix TJ, Beeson MS. Warfarin-induced skin necrosis. Am J Emerg Med. 1998;16:541–3. doi:10.1016/S0735-6757(98)90015-8.
Alves DW, Chen IA. Warfarin-induced skin necrosis. Hosp Physician. 2002;38:39–42.
Teepe RGC. Recurrent coumarin-induced skin necrosis in a patient with an acquired functional protein C deficiency. Arch Dermatol. 1986;122:1408. doi:10.1001/archderm.1986.01660240072019.
Kaiber FL, Malucelli TO, Baroni E, do RV, et al. Trombocitopenia induzida por heparina e necrose cutânea por varfarina: relato de caso. An Bras Dermatol. 2010;85:915–8. doi:10.1590/S0365-05962010000600024.
Taheri A, Abdali H. Warfarin induced massive and bilateral skin necrosis of the breasts: a case report and review of the literatures. Acta Med Iran. 2005;43:303–5.
Canturk E. Warfarin-induced skin necrosis: a “novel” solution to an old problem. Turk Kardiyol Dern Ars. 2014;42:787. doi:10.5543/tkda.2014.82342.
Bakoyiannis C, Karaolanis G, Patelis N, et al. Dabigatran in the treatment of warfarin-induced skin necrosis: a new hope. Case Rep Dermatol Med. 2016;2016:1–3. doi:10.1155/2016/3121469.
Carlos-Alves J, Soares I, Cruz J, Ferreira A. Severe skin necrosis induced by warfarin. Eur J Intern Med. 2013;24:e235. doi:10.1016/j.ejim.2013.08.601.
Srinivasan AF, Rice L, Bartholomew JR, et al. Warfarin-induced skin necrosis and venous limb gangrene in the setting of heparin-induced thrombocytopenia. Arch Intern Med. 2004;164:66. doi:10.1001/archinte.164.1.66.
Warkentin TE, Sikov WM, Lillicrap DP. Multicentric warfarin-induced skin necrosis complicating heparin-induced thrombocytopenia. Am J Hematol. 1999;62:44–8.
White PW, Sadd JR, Nensel RE. Thrombotic complications of heparin therapy: including six cases of heparin-induced skin necrosis. Ann Surg. 1979;190:595–608.
Tietge Schmidt, Jackel E, Trautwein C. Low molecular weight heparin-induced skin necrosis occurring distant from injection sites and without thrombocytopenia. J Intern Med. 1998;243:313–5. doi:10.1046/j.1365-2796.1998.00304.x.
Sherif K, Tello W, Nugent K. Enoxaparin-associated skin necrosis in an older patient: a rare side effect. Clin Geriatr. 2012;20:44–8.
Sallah S, Thomas DP, Roberts HR. Warfarin and heparin-induced skin necrosis and the purple toe syndrome: infrequent complications of anticoagulant treatment. Thromb Haemost. 1997;78:785–90.
Warkentin TE, Elavathil LJ, Hayward CP, et al. The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia. Ann Intern Med. 1997;127:804–12.
Coelho J, Izadi D, Gujral S. Enoxaparin-induced skin necrosis. Eplasty. 2016;16:ic4.
Tonn ME, Schaiff RA, Kollef MH. Enoxaparin-associated dermal necrosis: a consequence of cross-reactivity with heparin-mediated antibodies. Ann Pharmacother. 1997;31:323–6.
Fabris F, Luzzatto G, Soini B, et al. Risk factors for thrombosis in patients with immune mediated heparin-induced thrombocytopenia. J Intern Med. 2002;252:149–54.
Warkentin TE. Clinical presentation of heparin-induced thrombocytopenia. Semin Hematol. 1998;35:9–16 (discussion 35–6).
Menajovsky LB. Heparin-induced thrombocytopenia: clinical manifestations and management strategies. Am J Med. 2005;118(Suppl. 8A):21S–30S. doi:10.1016/j.amjmed.2005.06.005.
Skelley JW, Kyle JA, Roberts RA. Novel oral anticoagulants for heparin-induced thrombocytopenia. J Thromb Thrombolysis. 2016;42:172–8. doi:10.1007/s11239-016-1365-0.
Lewis BE, Wallis DE, Berkowitz SD, et al. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation. 2001;103:1838–43.
Calabrese LH, Duna GF. Drug-induced vasculitis. Curr Opin Rheumatol. 1996;8:34–40.
af Ekenstam E. Cutaneous leukocytoclastic vasculitis: clinical and laboratory features of 82 patients seen in private practice. Arch Dermatol. 1984;120:484. doi:10.1001/archderm.1984.01650400066014.
Martinez-Taboada VM, Blanco R, Garcia-Fuentes M, Rodriguez-Valverde V. Clinical features and outcome of 95 patients with hypersensitivity vasculitis. Am J Med. 1997;102:186–91.
Mullick FG, McAllister HA, Wagner BM, Fenoglio JJ. Drug related vasculitis: clinicopathologic correlations in 30 patients. Hum Pathol. 1979;10:313–25.
Michel BA, Hunder GG, Bloch DA, Calabrese LH. Hypersensitivity vasculitis and Henoch-Schönlein purpura: a comparison between the 2 disorders. J Rheumatol. 1992;19:721–8.
Jennette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med. 1997;337:1512–23. doi:10.1056/NEJM199711203372106.
Sais G, Vidaller A, Jucglà A, et al. Prognostic factors in leukocytoclastic vasculitis: a clinicopathologic study of 160 patients. Arch Dermatol. 1998;134:309. doi:10.1001/archderm.134.3.309.
Gao Y, Zhao M-H. Review article: drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrology. 2009;14:33–41. doi:10.1111/j.1440-1797.2009.01100.x.
Radić M, Martinović Kaliterna D, Radić J. Drug-induced vasculitis: a clinical and pathological review. Neth J Med. 2012;70:12–7.
Kallenberg CGM. Key advances in the clinical approach to ANCA-associated vasculitis. Nat Rev Rheumatol. 2014;10:484–93. doi:10.1038/nrrheum.2014.104.
Lai Q-Y, Ma T-T, Li Z-Y, et al. Predictors for mortality in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis: a study of 398 Chinese patients. J Rheumatol. 2014;41:1849–55. doi:10.3899/jrheum.131426.
Gallardo M de los A, Scolnik M, Pompermayer L, et al. Elderly versus younger patients with ANCA-associated vasculitis. Arthritis Rheumatol. 2015;67.
Sontheimer RD, Maddison PJ, Reichlin M, et al. Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus. Ann Intern Med. 1982;97:664–71.
Lowe GC, Lowe G, Henderson CL, et al. A systematic review of drug-induced subacute cutaneous lupus erythematosus. Br J Dermatol. 2011;164:465–72. doi:10.1111/j.1365-2133.2010.10110.x.
Reed BR, Huff JC, Jones SK, et al. Subacute cutaneous lupus erythematosus associated with hydrochlorothiazide therapy. Ann Intern Med. 1985;103:49–51.
Funke AA, Kulp-Shorten CL, Callen JP. Subacute cutaneous lupus erythematosus exacerbated or induced by chemotherapy. Arch Dermatol. 2010;146:1113–6. doi:10.1001/archdermatol.2010.258.
Zarkavelis G, Kollas A, Kampletsas E, et al. Aromatase inhibitors induced autoimmune disorders in patients with breast cancer: a review. J Adv Res. 2016;7:719–26. doi:10.1016/j.jare.2016.04.001.
Wong NY, Parsons LM, Trotter MJ, Tsang RY. Drug-induced subacute cutaneous lupus erythematosus associated with docetaxel chemotherapy: a case report. BMC Res Notes. 2014;7:785. doi:10.1186/1756-0500-7-785.
Marchetti MA, Noland MM, Dillon PM, Greer KE. Taxane associated subacute cutaneous lupus erythematosus. Dermatol Online J. 2013;19:19259.
Lamond NWD, Younis T, Purdy K, Dorreen MS. Drug-induced subacute cutaneous lupus erythematosus associated with nab-paclitaxel therapy. Curr Oncol. 2013;20:484. doi:10.3747/co.20.1546.
Grönhagen CM, Fored CM, Linder M, et al. Subacute cutaneous lupus erythematosus and its association with drugs: a population-based matched case-control study of 234 patients in Sweden. Br J Dermatol. 2012;167:296–305. doi:10.1111/j.1365-2133.2012.10969.x.
Darken M, McBurney EI. Subacute cutaneous lupus erythematosus-like drug eruption due to combination diuretic hydrochlorothiazide and triamterene. J Am Acad Dermatol. 1988;18:38–42.
Brown CW, Deng JS. Thiazide diuretics induce cutaneous lupus-like adverse reaction. J Toxicol Clin Toxicol. 1995;33:729–33.
Lorentz K, Booken N, Goerdt S, Goebeler M. Subacute cutaneous lupus erythematosus induced by terbinafine: case report and review of literature. J Dtsch Dermatol. 2008;6(823–7):823–8. doi:10.1111/j.1610-0387.2008.06806.x.
Kasperkiewicz M, Anemüller W, Angelova-Fischer I, et al. Subacute cutaneous lupus erythematosus associated with terbinafine. Clin Exp Dermatol. 2009;34:e403–4. doi:10.1111/j.1365-2230.2009.03380.x.
Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008;168:508–13. doi:10.1001/archinternmed.2007.106.
Tune LE. Serum anticholinergic activity levels and delirium in the elderly. Semin Clin Neuropsychiatry. 2000;5:149–53. doi:10.153/SCNP00500149.
Flacker JM, Cummings V, Mach JR, et al. The association of serum anticholinergic activity with delirium in elderly medical patients. Am J Geriatr Psychiatry. 1998;6:31–41.
Davies P. Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet. 1976;308:1403. doi:10.1016/S0140-6736(76)91936-X.
Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175:401. doi:10.1001/jamainternmed.2014.7663.
Agarwal V, O’Neill PJ, Cotton BA, et al. Prevalence and risk factors for development of delirium in burn intensive care unit patients. J Burn Care Res. 2010;31:706–15. doi:10.1097/BCR.0b013e3181eebee9.
Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2006;33:66–73. doi:10.1007/s00134-006-0399-8.
Gaudreau J-D, Gagnon P, Harel F, et al. Psychoactive medications and risk of delirium in hospitalized cancer patients. J Clin Oncol. 2005;23:6712–8. doi:10.1200/JCO.2005.05.140.
Gaudreau J-D, Gagnon P, Roy M-A, et al. Opioid medications and longitudinal risk of delirium in hospitalized cancer patients. Cancer. 2007;09:2365–73. doi:10.1002/cncr.22665.
Schreiber MP, Colantuoni E, Bienvenu OJ, et al. Corticosteroids and transition to delirium in patients with acute lung injury. Crit Care Med. 2014;42:1480–6. doi:10.1097/CCM.0000000000000247.
Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369:1306–16. doi:10.1056/NEJMoa1301372.
Sgonc R, Gruber J. Age-related aspects of cutaneous wound healing: a mini-review. Gerontology. 2013;59:159–64. doi:10.1159/000342344.
Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ. Will my patient fall? JAMA. 2007;297:77. doi:10.1001/jama.297.1.77.
Dodiuk-Gad RP, Olteanu C, Feinstein A, et al. Major psychological complications and decreased health-related quality of life among survivors of Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol. 2016;175:422–4. doi:10.1111/bjd.14799.
Jones C, Griffiths RD, Humphris G, Skirrow PM. Memory, delusions, and the development of acute posttraumatic stress disorder-related symptoms after intensive care. Crit Care Med. 2001;29:573–80.
Jackson JC, Pandharipande PP, Girard TD, et al. Depression, posttraumatic stress disorder, and functional disability in survivors of critical illness: results from the BRAIN ICU (bringing to light the risk factors and incidence of neuropsychological dysfunction in ICU survivors) Investigation: a longitudinal cohort study. Lancet Respir Med. 2014;2:369–79. doi:10.1016/S2213-2600(14)70051-7.
Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc. 2001;49:516–22.
Harari D, Hopper A, Dhesi J, et al. Proactive care of older people undergoing surgery (‘POPS’): designing, embedding, evaluating and funding a comprehensive geriatric assessment service for older elective surgical patients. Age Ageing. 2007;36:190–6. doi:10.1093/ageing/afl163.
Partridge JSL, Harari D, Martin FC, Dhesi JK. The impact of pre-operative comprehensive geriatric assessment on postoperative outcomes in older patients undergoing scheduled surgery: a systematic review. Anaesthesia. 2014;69(Suppl. 1):8–16. doi:10.1111/anae.12494.
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Young, J.W.S., Shear, N.H. Cutaneous Drug Reactions in the Elderly. Drugs Aging 34, 655–672 (2017). https://doi.org/10.1007/s40266-017-0483-5
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DOI: https://doi.org/10.1007/s40266-017-0483-5