Abstract
Adverse cutaneous reactions to drugs are frequent, mostly secondary to antibacterials, however, serious adverse cutaneous reactions are infrequent. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are a spectrum of the same disease. They are the more severe drug eruptions, with a mortality around 30% for TEN. The confusion between erythema multiforme major and SJS means that erythema multiforme major is the main differential diagnosis. Skin disorders involving desquamation, in particular after pustulosis, are also common differential diagnoses. Mechanical or autoimmune blistering are also potential misdiagnoses of TEN/SJS.
Hypersensitivity Syndrome (HSS) or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) is a severe cutaneous drug reaction with often a long duration of eruption and serious other organ involvement. Exfoliative dermatitis, whether caused by psoriasis, dermatitis or lymphoma, can be thought of as a differential diagnosis of DRESS/HSS. Angio-immunoblastic lymphadenopathy, viral eruption and vasculitis are other differential diagnoses of DRESS/HSS.
Prompt recognition of a severe drug reaction and withdrawal of the culprit drug is often the most important therapeutic action. Alternatively, a delay in starting a specific treatment for a disease misdiagnosed as a drug eruption could be deleterious.
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References
Bigby M, Jick S, Jick H, et al. Drug-induced cutaneous reactions: a report from the Boston Collaborative Drug Surveillance Program on 15 438 consecutive inpatients, 1975 to 1982. JAMA 1986; 256: 3358–63
Bigby M. Rates of cutaneous reactions to drugs. Arch Dermatol 2001; 137: 765–70
Hunziker T, Kunzi UP, Braunschweig S, et al. Comprehensive hospital drug monitoring: adverse skin reactions, a 20-year survey. Allergy 1997; 52: 388–93
Swanbeck G, Dahlberg E. Cutaneous drug reactions: an attempt to quantitative estimation. Arch Dermatol Res 1992; 284: 215–8
Ewards IR, Aronson JK. Adverse drug reaction: definition, diagnosis, and management. Lancet 2000; 356: 1255–9
Naldi L, Conforti A, Venegoni M, et al. Cutaneous reactions to drugs: an analysis of spontaneous reports in four Italians regions. Br J Clin Pharmacol 1999; 48: 839–46
Roujeau JC, Stern RS. Severe cutaneous reactions to drugs. N Engl J Med 1994; 331: 1272–85
Garcia-Doval I, LeCleach L, Bocquet H, et al. Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol 2000; 136: 323–7
Bastuji-Garin S, Rzany B, Stern RS, et al. A clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme. Arch Dermatol 1993; 129: 92–6
Stevens AM, Johnson FC. A new eruptive fever associated with stomatitis and ophtalmia: report of two cases in children. Am J Dis Child 1922; 24: 526–33
Lyell A. Toxic epidermal necrolysis: an eruption resembling scalding of the skin. Br J Dermatol 1956; 68: 355–61
Bastuji-Garin S, Zahedi M, Guillaume JC, et al. Toxic epidermal necrolysis (Lyell syndrome) in 77 elderly patients. Age Ageing 1993; 22: 450–6
Auquier-Dunant A, Mockenhaupt M, Naldi L, et al. Erythema Multiforme Majus, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: correlations between clinical patterns and causes. Results of an international prospective study. Arch Dermatol 2002; 138: 1019–24
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
Fagot JP, Mockenhaupt M, Bouwes-Bavinck JN, et al. Nevirapine and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. AIDS 2001; 28: 1843–8
Rasmussen JE. Update to the Stevens-Johnson syndrome. Cleve Clin J Med 1988; 55: 412–4
Roujeau JC, Guillaume JC, Febre JP, et al. Toxic epidermal necrolysis (Lyell syndrome): incidence and drug etiology in France, 1981–1985. Arch Dermatol 1990; 126: 37–42
Schöpf E, Stühmer A, Rzany B, et al. Toxic epidermal necrolysis and Stevens-Johnson syndrome: an epidemiologic study from West Germany. Arch Dermatol 1991; 127 (6): 839–42
Fournier S, Bastuji-Garin S, Mentec H, et al. Toxic epidermal necrolysis associated with mycoplasma pneumoniae infection [letter]. Eur J Clin Microbiol Infect Dis 1995; 14: 558–9
Tay YK, Huff JC, Weston WL. Mycoplasma pneumoniae infection is associated with Stevens-John syndrome, not erythema multiforme (von Hebra). J Am Acad Dermatol 1996; 35: 757–60
de Groot R, Oranje AP, Vuzevski VD, et al. Toxic epidermal necrolysis probably due to Klebsiella pneumoniae sepsis. Dermatologica 1984; 169: 88–9
Picard E, Gillis D, Klapholz L, et al. Toxic epidermal necrolysis associated with Klebsiella pneumoniae sepsis. Pediatr Dermatol 1994; 11: 331–4
Bachot N, Roujeau JC. Physiopathology and treatment of severe drug eruptions. Curr Opin Allergy Clin Immunol 2001; 1: 293–8
Becker DS. Toxic epidermal necrolysis. Lancet 1998; 351: 1417–20
Avakian R, Flowers FP, Araujo OE, et al. Toxic epidermal necrolysis: a review. J Am Acad Dermatol 1991; 25: 69–79
Revuz J. New advances in severe adverse drug reactions. Dermatol Clin 2001; 19: 697–709
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
Prins C, Kerdel FA, Padilla RS, et al. Treatment of toxic epidermal necrolysis with high-dose intravenous immunoglobulins: multicenter retrospective analysis of 48 consecutive cases. Arch Dermatol 2003; 139: 26–32
Trent JT, Kirsner RS, Romanelli P, et al. Analysis of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis using SCORTEN: The University of Miami Experience. Arch Dermatol 2003; 139: 39–43
Bachot N, Revuz J, Roujeau JC. Intravenous immunoglobulin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis: a prospective noncomparative study showing no benefit on mortality or progression. Arch Dermatol 2003; 139: 33–6
Assier H, Bastuji-Garin, S, et al. Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes. Arch Dermatol 1995; 131: 539–43
Leauté-Labreze C, Lamireay T, Chawki D, et al. Diagnosis, classification and management of erythema multiforme and Stevens-Johnson syndrome. Arch Dis Child 2000; 83: 347–52
Machet L, Martin L, Vaillant L. Pustulose exanthématique aiguë généralisée. Ann Dermatol Venereol 2001; 128: 73–9
Beylot C, Bioulac P, Doutre MS. Pustuloses exanthématiques aiguës généralisées. A propos de 4 cas. Ann Dermatol Venereol 1980; 107: 37–48
Roujeau JC, Bioulac-Sage P, Bourseau C, et al. Acute generalized exanthematous pustulosis. Arch Dermatol 1991; 127: 1333–8
Sidoroff A, Halevy S, Bavinck JN, et al. Acute generalized exanthematous pustulosis (AGEP): a clinical reaction pattern. J Cutan Pathol 2001; 28: 113–9
Cohen AD, Cagnano E, Halevy S. Acute generalized exanthematous pustulosis mimicking toxic epidermal necrolysis. Int J Dermatol 2001; 40: 458–61
De Coninck AL, Van Strubarq AS, Pipeleers-Marichal MA, et al. Acute generalized exanthematous pustulosis induced by paracetamol: a case with severe hemodynamic disturbances. Dermatology 1996; 193: 338–41
Plano LR, Adkins B, Woischnik M, et al. Toxin levels in serum correlate with the development of staphylococcal scalded skin syndrome in a murine model. Infect Immun 2001; 69: 5193–7
Kuechle MK, Stegemeir E, Maynard B, et al. Drug-induced linear IgA bullous dermatosis: report of six cases and review of the literature. J Am Acad Dermatol 1994; 30: 187–92
Nousari HC, Kimyai-Asadi A, Caeiro JP, et al. Clinical, demographic, and immunohistologic features of Vancomycin-Induced Linear Bullous Disease of the skin. Medicine 1999; 78: 1–8
Schneck B, Termeer C, Mockenhaupt M, et al. Linear IgA dermatosis in an adult with clinical signs of Stevens-Johnson syndrome. Hautarzt 1999; 50: 288–91
Kaur S, Thami GP, Mohan H, et al. Kikuchi disease with facial rash and erythema multiforme. Pediatr Dermatol 2001; 18: 403–5
Roustan G, Salas C, Barbadillo C, et al. Lupus erythematosus with an erythema multiforme-like eruption. Eur J Dermatol 2000; 10: 459–62
Marzano AV, Berti E, Gasparini G, et al. Lupus erythematosus with antiphospholipid syndrome and erythema multiforme-like lesions. Br J Dermatol 1999; 141: 720–4
Robinson ND, Hashimoto T, Amagai M, et al. The new pemphigus variants. J Am Acad Dermatol 1999; 40: 649–71
Nguyen VT, Ndoye A, Bassler KD, et al. Classification, clinical manifestations, and immunopathological mechanisms of the epithelial variant of paraneoplastic autoimmune multiorgane syndrome. Arch Dermatol 2001; 137: 193–206
Speron S, Gamelli R. Toxic epidermal necrolysis syndrome versus mycosis fungoides. J Burn Care Rehabil 1997; 18: 421–3
Saltzstein S, Ackerman L. Lymphadenopathy induced by anticonvulsivant drugs and mimicking clinically and pathologically malignant lymphomas. Cancer 1959; 12: 164–82
Shear N, Spielberg S. Anticonvulsivant hypersensitivity syndrome: in vitro assessment of risk. J Clin Invest 1988; 82: 1826–32
Bocquet H, Bagot M, Roujeau JC. Drug induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinopholia and systemic symptoms-DRESS). Semin Cutan Med Surg 1996; 15: 250–7
Sullivan JR, Shear NH. The drug hypersensitivity syndrome: what is the pathogenesis? Arch Dermatol 2001; 137: 357–64
Descamp V, Valence A, Edlinger C, et al. Association of human herpes virus 6 infection with drug reaction with eosiniphilia and systemic symptoms. Arch Dermatol 2001; 137: 301–4
Martel P, Laroche L, Courville P, et al. Cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with dysproteinemia. Arch Dermatol 2000; 136: 881–6
Sigurdsson V, Toonstra J, Hezemans-Boer M, et al. A clinical and follow-up study of 102 patients, with special emphasis on survival. J Am Acad Dermatol 1996; 35: 53–7
Asai T, Horiuchi Y. Senile erythroderma with serum hyper-IgE. Int J Dermatol 1989; 28: 225–8
Abel EA. Diagnosis of drug-induced psoriasis. Semin Dermatol 1992; 11: 269–74
Wilson NJ, Evans S. Severe pustular psoriasis provoked by oral terbinafine. Br J Dermatol 1998; 139: 168
Papa CA, Miller OF. Pustular psoriasiform eruption with leukocytosis associated with terbinafine. J Am Acad Dermatol 1998; 39: 115–7
Gupta AK, Lynde CW, Lauzon GJ, et al. Cutaneous adverse effects associated with terbinafine therapy: 10 case reports and a review of the literature. Br J Dermatol 1998; 138: 529–32
De Silva BD, Benton EC, Tidman MJ. Generalized pustular psoriasis following withdrawal of oral cyclosporin treatment for palmo-plantar pustulosis. Clin Exp Dermatol 1999; 24: 10–3
Davis MDP, Daoud MS, McEvoy MT, et al. Cutaneous mainfestations of Churg-Strauss syndrome: a clinicopathologic correlation. J Am Acad Dermatol 1997; 37: 199–203
Guillevin L, Le THD, Godeau P, et al. Clinical findings and prognosis of polyarteritis nodosa and Churg and Strauss angiitis: a study in 165 patients. Br J Rheumatol 1988; 27: 258–64
Pinching AJ, Lockwood CM, Pussel BA, et al. Wegener’s granulomatosis: observations on 18 patients with severe renal disease. Q J Med 1983; 208: 435–60
Cardinali C, Giomi B, Caproni M, et al. Maculopapular lupus rash in a young woman with systemic involvement. Lupus 2000; 9: 713–6
Schacker T, Collier AC, Hughes J, et al. Clinical and epidemiologic features of primary HIV infection. Ann Intern Med 1996; 125: 257–64
Stoeckle MY. The spectrum of human herpesvirus 6 infection: from roseola infantum to adult disease. Annu Rev Med 2000; 51: 423–30
Renn CN, Straff W, Dorfmüller A, et al. Amoxicillin-induced exanthema in young adults with infectious mononucleosis: demonstration of drug-specific lymphocyte reactivity. Br J Dermatol 2002; 147: 1166–70
Barbaud A, Goncalo M, Bruynzeel D, et al. Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions. Contact Dermatitis 2001; 45: 321–8
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Bachot, N., Roujeau, JC. Differential Diagnosis of Severe Cutaneous Drug Eruptions. Am J Clin Dermatol 4, 561–572 (2003). https://doi.org/10.2165/00128071-200304080-00006
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DOI: https://doi.org/10.2165/00128071-200304080-00006