Drug Safety

, Volume 5, Issue 1, pp 39–64 | Cite as

Clinical Features and Management of Severe Dermatological Reactions to Drugs

  • Mario C. Raviglione
  • Ariel Pablos-Mendez
  • Ruggero Battan
Review Article Drug Experience


Cutaneous adverse drug reactions are a frequent occurrence and have been reported in more than 2% of hospitalised patients. Among the most commonly involved drugs are sulphonamides, penicillins, anticonvulsants and non-steroidal anti-inflammatory drugs.

Two groups of mechanisms are involved in the pathogenesis of drug reactions: immunological, with all 4 types of hypersensitivity reactions described; and non-immunological, accounting for at least 75% of all drug reactions.

Besides minor skin reactions like urticaria, maculopapular rash, fixed eruptions or erythema nodosum, which are generally self-limited, severe life-threatening manifestations also occur. Erythema multiforme is secondary to drugs in half the cases; the minor form is characterised by typical target and iris lesions and is usually benign. However, a much more severe condition, erythema multiforme major or Stevens-Johnson syndrome, is associated with mucosal, ocular and visceral involvement, and carries a mortality of 5 to 15% if untreated. Toxic epidermal necrolysis, which could represent an even more dramatic form of the same disease, is characterised by severe widespread erythema, blisters and loss of skin in sheets, with denudation of more than 10% of the body surface area. This entity is frequently due to drugs. Mortality is 25 to 70%, and 90% of the survivors will have sequelae.

Exfoliative dermatitis is an erythematous scaling disease often produced by drugs and carrying significant mortality. Photodermatitis may at times present with severe eczematous features.

For clinical and epidemiological reasons it is important to try to identify the culprit drug following an approach based on previous experience with the drug, timing of events, patient reaction to dechallenge, patient reaction to rechallenge (if feasible), alternative aetiological candidates, and drug concentration or evidence of overdose.

Management of severe skin reactions to drugs should require admission to a burn unit, where patients should be placed in warmed air-fluidised beds, receive excellent nursing care, analgesics and tranquillisers. Peeling necrotic epidermis should be removed and denuded dermis covered with biological grafts or synthetic dressings. Fluid balance must be adequately maintained; nutritional support and careful monitoring of early signs of skin infections is mandatory to ensure immediate antimicrobial treatment. Ocular care must be excellent to avoid serious sight-threatening sequelae. Steroids are presently not recommended. With these therapeutic modalities, morbidity and mortality can be markedly decreased.


Contact Dermatitis Toxic Epidermal Necrolysis Sulphonamide Erythema Multiforme Exfoliative Dermatitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abraham GN, Petz LD, Fudenberg HH. Immunohematological cross-allergenicity between penicillin and cephalothin in humans. Clinical and Experimental Immunology 3: 343–357, 1968.PubMedGoogle Scholar
  2. Abrahams I, McCarthy JT, Sanders SL. One hundred and one cases of exfoliative dermatitis. Archives of Dermatology 87: 96–101, 1963.PubMedGoogle Scholar
  3. Ackerman AB, Penneys NS, Clark WH. Erythema multiforme exudativum: a distinctive pathological process. British Journal of Dermatology 84: 554–565, 1971.PubMedGoogle Scholar
  4. Aderka D, Livni E, Sharon C, Pinkhas J. The migration inhibition factor test for identification of hypersensitivity reaction to drugs. Annals of Allergy 56: 341–344, 1986.PubMedGoogle Scholar
  5. Adkinson Jr NF, Thompson W, Maddrey WC, Lichtenstein LM. Routine use of penicillin skin testing on an in patient service. New England Journal of Medicine 285: 22, 1971.PubMedGoogle Scholar
  6. Adzick NS, Kim SH, Bondoc CC, Quinby WC, Remensnyder JP. Management of toxic epidermal necrolysis in a pediatric burn center. American Journal of Diseases of Children 139: 499–502, 1985.PubMedGoogle Scholar
  7. Aihara M, Ikezawa Z. Evaluation of skin test reactions in patients with delayed type rash induced by penicillins and cephalosporins. Journal of Dermatology 14: 440–448, 1987.PubMedGoogle Scholar
  8. Amon RB, Dimond RL. Toxic epidermal necrolysis: rapid differentiation between staphylococcal- and drug-induced disease. Archives of Dermatology 111: 1433–1437, 1975.PubMedGoogle Scholar
  9. Anhalt G, Snelling CFT. Toxic epidermal necrolysis. Plastic and Reconstructive Surgery 61: 905–910, 1978.PubMedGoogle Scholar
  10. Araujo OE, Flowers FP. Stevens-Johnson syndrome. Journal of Emergency Medicine 2: 129–135, 1984.PubMedGoogle Scholar
  11. Arndt KA, Jick H. Rates of cutaneous reactions to drugs. Journal of the American Medical Association 235: 918–923, 1976.PubMedGoogle Scholar
  12. Arstikaitis MJ. Ocular aftermaths of Stevens-Johnson syndrome. Archives of Ophthalmology 90: 376, 1973.PubMedGoogle Scholar
  13. Ashby DW, Lazar T. Erythema multiforme exudativum major (Stevens-Johnson syndrome). Lancet 1: 1091–1095, 1951.PubMedGoogle Scholar
  14. Askenase PW. Role of basophils, mast cells, and vasoamines in hypersensitivity reactions with a delayed time course. Progress in Allergy 23: 199–320, 1977.PubMedGoogle Scholar
  15. Begaud B, Evreux JC, Jouglard J, Lagier G. Imputabilité des effets inattendus ou toxiques des médicaments: actualisation de la méthode utilisée en France. Thérapie 40: 111–118, 1985.PubMedGoogle Scholar
  16. Benichou C, Brini A, Abensour M, Grosshans E. Lesions oculopalpebrales dans les erythèmes polymorphes graves: prevention du symblepharon. Bulletin des Sociétés d’Ophthalmologie de France 88: 391–396, 1988.Google Scholar
  17. Bianchine JR, Macaraeg Jr PV, Lasagna L, Azarnoff DL, Brunk SF, et al. Drugs as etiologic factors in the Stevens-Johnson syndrome. American Journal of Medicine 44: 390–405, 1968.PubMedGoogle Scholar
  18. Björnberg A. Fifteen cases of toxic epidermal necrolysis (Lyell). Acta Dermato-Venereologica 53: 149–152, 1973.PubMedGoogle Scholar
  19. Burleson R, Eiseman B. Effect of skin dressings and topical antibiotics on healing of partial thickness skin wounds in rats. Surgical Gynecology and Obstetrics 136: 958, 1973.Google Scholar
  20. Cazzola G, Nicolussi M, Carraro F, Cavalieri S, Graziani MS. High-dose i.v. 7S immunoglobulin treatment in Stevens-Johnson syndrome. Helvetica Paediatrica Acta 41: 87–88, 1986.PubMedGoogle Scholar
  21. Centers for Disease Control. Health information for international travel 1988. US Department of Health and Human Services Publication No. (CDC) 88–8280, p. 102, Public Health Service, Atlanta, 1988Google Scholar
  22. Chan HL. Observations on drug-induced toxic epidermal necrolysis in Singapore. Journal of the American Academy of Dermatology 10: 973–978, 1984.PubMedGoogle Scholar
  23. Charlesworth EN. Phenytoin induced pseudolymphoma syndrome. Archives of Dermatology 113: 477, 1977.PubMedGoogle Scholar
  24. Chong BH, Pitney WR, Castaldi PA. Heparin induced thrombocytopenia: association of thrombotic complications with heparin dependent IgG antibody that induced thromboxane synthesis and platelet aggregation. Lancet 2: 1246–1249, 1982.PubMedGoogle Scholar
  25. Clouse LH, Comp PC. The regulation of hemostasis: the protein C system. New England Journal of Medicine 314: 1298–1305, 1986.PubMedGoogle Scholar
  26. Comaish JK, Kerr DN. Erythema multiforme and nephritis. British Medical Journal 2: 84, 1961.PubMedGoogle Scholar
  27. Coombes RRA, Gell PGH. Classification of allergic reactions responsible for clinical hypersensitivity and disease. In Gell (Ed.) Clinical aspects of Immunology, pp. 575–596, Oxford Ed., Oxford, 1968Google Scholar
  28. Crosby SS, Murray KM, Marvin JA, Heimbach DM, Tartaglione TA. Management of Stevens-Johnson syndrome. Clinical Pharmacology 5: 682–689, 1986.Google Scholar
  29. Davidson BL, Gilliam JN, Lipsky PE. Cimetidine-associated exacerbations of cutaneous lupus erythematosus. Archives of Internal Medicine 142: 166–167, 1982.PubMedGoogle Scholar
  30. Davidson BL, Hunt JL. Human cadaver homograft in toxic epidermal necrolysis. Journal of Burn Care and Rehabilitation 2: 94–96, 1981.Google Scholar
  31. Davies P, Ryan DW. Stevens-Johnson syndrome managed in the clinitron bed. Intensive Care Medicine 9: 87–89, 1983.PubMedGoogle Scholar
  32. DeFoe Jr CP. Erythema multiforme bullosum caused by 9-bromofluorene. Archives of Dermatology 94: 545–551, 1966.Google Scholar
  33. Demling RH. Burns. New England Journal of Medicine 313: 1389–1398, 1985.PubMedGoogle Scholar
  34. Demling RH, Ellerbe S, Lowe NJ. Burn unit management of toxic epidermal necrolysis. Archives of Surgery 113: 758–759, 1978.PubMedGoogle Scholar
  35. DeSwarte RD. Drug allergy. In Patterson (Ed.) Allergic diseases: diagnosis and management, pp. 505–661, JB Lippincott, Philadelphia, 1985Google Scholar
  36. Driks MR, Craven DE, Celli BR, et al. Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers: the role of gastric colonization. New England Journal of Medicine 317: 1376–1382, 1987.PubMedGoogle Scholar
  37. Dunagin WG, Millikan LE. Drug eruptions. Medical Clinics of North America 64: 983–1003, 1980.PubMedGoogle Scholar
  38. Eisen HN. Hypersensitivity to simple chemicals. In Sherwood (Ed.) Cellular and humoral aspects of the hypersensitive states, pp. 89–122, Hoeber-Harper, New York, 1959Google Scholar
  39. Elias PM, Fritsch PO. Erythema multiforme. In Fitzpatrick et al. (Eds) Dermatology in general medicine, pp. 555–563, McGraw-Hill Book Company, New York-St Louis, 1987Google Scholar
  40. Elsas T, Halan H. Fansidar indusert makulopati og dermatitis exfoliativa. Tidsskrift for den Norske Laegeforening 107: 1231–1232, 1987.PubMedGoogle Scholar
  41. Farah FS, Kern M, Eisen HN. Specific inhibition of wheal-and-erythema responses with univalent haptens and univalent antibody fragments. Journal of Experimental Medicine 112: 1211–1226, 1960.PubMedGoogle Scholar
  42. Ferguson J, Johnson BE. Retinoid associated phototoxicity and photosensitivity. Pharmacology and Therapeutics 40: 123–135, 1989.PubMedGoogle Scholar
  43. Finland M, Jolliffe LS, Parker Jr F. Pneumonia and erythema multiforme exudativum: report of 4 cases and 3 autopsies. American Journal of Medicine 4: 473–492, 1948.PubMedGoogle Scholar
  44. Finlay AY, Richards J, Holt PJA. Intensive therapy unit management of toxic epidermal necrolysis: practical aspects. Clinical and Experimental Dermatology 7: 55–60, 1982.PubMedGoogle Scholar
  45. Fischl MA, Dickinson GM. Fansidar prophylaxis of Pneumocystis pneumonia in the acquired immunodeficiency syndrome. Annals of Internal Medicine 105: 629, 1986.PubMedGoogle Scholar
  46. Freedberg IM, Baden HP. Exfoliative dermatitis. In Fitzpatrick et al. (Eds) Dermatology in general medicine, pp. 502–505, McGraw-Hill Book Company, New York-St. Louis, 1987Google Scholar
  47. Friedman SJ, Perry HO. Erythema multiforme associated with contact dermatitis. Contact Dermatitis 12: 21–23, 1985.PubMedGoogle Scholar
  48. Fritsch PO, Elias PM. Toxic epidermal necrolysis. In Fitzpatrick et al. (Eds) Dermatology in general medicine, McGaw-Hill Book Company, New York-St. Louis, 1987Google Scholar
  49. Garabiol B, Touraine R. Syndrome de Lyell de l’adulte: éléments de prognostic et déductions thérapeutiques: étude de 27 cas. Annales de Médecine Interne 127: 670–672, 1976.PubMedGoogle Scholar
  50. Gerard A. Lyell’s syndrome: treatment by plasma exchange. Plasma Therapy and Transfusion Technology 5: 259–260, 1984.Google Scholar
  51. Ginsburg CM. Stevens-Johnson syndrome in children. Pediatric Infectious Diseases 1: 155–158, 1982.Google Scholar
  52. Girard JP, Cattin S, Cuevas M. Immunologic mechanisms and diagnostic test in allergie drug reactions. Annals of Clinical Research 8: 74–84, 1976.PubMedGoogle Scholar
  53. Goldstein SM, Wintroub BW, Elias PM, Wuepper KD. Toxic epidermal necrolysis: unmudding the waters. Archives of Dermatology 123: 1153–1156, 1987.PubMedGoogle Scholar
  54. Griffith RD, Miller OF. Erythema multiforme following diphtheria and tetanus toxoid vaccination. Journal of the American Academy of Dermatology 19: 758–759, 1988.PubMedGoogle Scholar
  55. Guillaume JC, Roujeau JC, Revuz J, Penso D, Touraine R. The culprit drugs in 87 cases of toxic epidermal necrolysis (Lyell’s syndrome). Archives of Dermatology 123: 1166–1170, 1987.PubMedGoogle Scholar
  56. Halebian PH, Corder V, Herndon D, et al. A burn center experience with toxic epidermal necrolysis. Journal of Burn Care and Rehabilitation 4: 176–183, 1983.Google Scholar
  57. Halebian PH, Madden MR, Finklestein JL, Corder VJ, Shires GT. Improved burn center survival of patients with toxic epidermal necrolysis without corticosteroids. Annals of Surgery 204: 503–512, 1986.PubMedGoogle Scholar
  58. Heimbach DM, Engrav LH, Marvin JA, Harnar TJ, Grube BJ. Toxic epidermal necrolysis: a step forward in treatment. Journal of the American Medical Association 257: 2172–2175, 1987.Google Scholar
  59. Holst R, Kirby J. Magnusson B. Sensitization to tropical woods firing erythema multiforme-like eruptions. Contact Dermatitis 2: 295–296, 1976.PubMedGoogle Scholar
  60. Huff JC, Weston WL, Tonnesen MG. Erythema multiforme: a critical review of characteristics, diagnostic criteria and causes. Journal of the American Academy of Dermatology 8: 763–775, 1983.PubMedGoogle Scholar
  61. Hutchinson TA, Leventhal JM, Kramer MS, Karch FE, Lipman AG, et al. An algorithm for the operational assessment of adverse drug reactions. II. Demonstration of reproducibility and validity. Journal of the American Medical Association 242: 633–638, 1979.PubMedGoogle Scholar
  62. Ikeda N, Umetsu K, Suzuki T. A fatal case of sulindac-induced Lyell syndrome (toxic epidermal necrolysis). Zeitschrift für Rechtsmedizin 98: 141–146, 1987.Google Scholar
  63. Jackson AM, Polock AV. Skin necrosis after heparin injection. British Medical Journal 282: 1088–1089, 1981.Google Scholar
  64. Jones JK. Adverse reactions in community health setting. Family and Community Health 5: 58–67, 1982.PubMedGoogle Scholar
  65. Jorup-Rönström C, Keisu M, Wiholm B-E. Could Swedish ‘yellow cards’ be substituted by E-coded summaries? Drug Safety 5: 72–77, 1990.PubMedGoogle Scholar
  66. Juhlin L, Wide L. IgE antibodies and penicillin allergy. In Dash & Jones (Eds) Mechanisms in drug allergy, Glaxo symposium series, pp. 139–147, Williams & Wilkins Company, Baltimore, 1972Google Scholar
  67. Kalhan SB, Ditto SR. Anesthetic management of a child with Stevens-Johnson syndrome. Cleveland Clinical Journal of Medicine 55: 467–469, 1988.Google Scholar
  68. Kamanabroo D, Schmitz-Landgraf W, Czarnetzki BM. Plasmapheresis in severe drug-induced toxic epidermal necrolysis. Archives of Dermatology 121: 1548–1549, 1985.PubMedGoogle Scholar
  69. Kaplan AP. Drug-induced skin diseasea. Journal of Allergy and Clinical Immunology 74 (4 pt 2): 573–579, 1984PubMedGoogle Scholar
  70. Karch FE, Lasagna L. Toward the operational identification of adverse drug reactions. Clinical and Pharmacological Therapeutics 21: 247–254, 1977.Google Scholar
  71. Kazmierowski JA, Wuepper KA. Erythema multiforme: immune complex vasculitis of the superficial cutaneous vasculature. Journal of Investigative Dermatology 71: 366–369, 1978.PubMedGoogle Scholar
  72. Kim PS, Goldfarb IW, Gaisford JC, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: a pathophysiologic review with recommendations for a treatment protocoal. Journal of Burn Care & Rehabilitation 4: 91–100, 1983.Google Scholar
  73. Kint A, Geerts ML, de Weert J. Le syndrome de Lyell. Dermatologica 163: 433–454, 1981.PubMedGoogle Scholar
  74. Kirby JD, Darley CR. Erythema multiforme associated with a contact dermatitis to terpenes. Contact Dermatitis 4: 278, 1978.Google Scholar
  75. Kniker WT, Cochrane CG. The localization of circulating immune complexes in experimental serum sickness. The role of vasoactive amines and hydrodynamic forces. Journal of Experimental Medicine 127: 119–136, 1968.PubMedGoogle Scholar
  76. Kovacs JA, Masur H. Pneumocystis carinii pneumonia: therapy and prophylaxis. Journal of Infectious Diseases 158: 254–259, 1988.PubMedGoogle Scholar
  77. Kramer MS, Leventhal JM, Hutchinson TA, Feinstein A. An algorithm for the operational assessment of adverse drug reaction. I. Background, description, and instructions for use. Journal of the American Medical Association 242: 623, 1979.PubMedGoogle Scholar
  78. Lee SL, Chase PH. Drug-induced systemic lupus erythematosus: a critical review. Seminars in Arthritis and Rheumatism 5: 83–103, 1975.PubMedGoogle Scholar
  79. Lepage V, Douay C, Mallet C, BInet O, Lemarchand F, et al. Erythema multiforme is associated to HLA-Aw33 and DRw53. Tissue Antigens 32: 170–175, 1988.PubMedGoogle Scholar
  80. Levine BB. Immunochemical mechanisms of drug allergy. Annual Review of Medicine 17: 23–38, 1966.PubMedGoogle Scholar
  81. Levine BB. Immunological tests for hypersensitivity reactions of drugs. In Rose & Friedman (Eds) Manual of Clinical Immunology, p. 637, American Society for Microbiology, Washington, 1976Google Scholar
  82. Ljunggren B, Bjellerup M. Systemic drug photosensitivity. Photodermatology 3: 26–35, 1986.PubMedGoogle Scholar
  83. Lozada F. Levamisole in the treatment of erythema multiforme: a double blind trial in fourteen patients. Oral Surgery, Oral Medicine and Oral Pathology 53: 28–31, 1982.Google Scholar
  84. Lozada-Nur F, Gorsky M, Silverman S. Oral erythema multiforme: clinical observations and treatment of 95 patients. Oral Surgery, Oral Medicine and Oral Pathology 67: 36–40, 1989.Google Scholar
  85. Luger TA, Oppenheim JJ. Characteristics of interleukin-1 and epidermal cell-derived thymocyte activating factor. In Weissman (Ed.) Advances in inflammation research, pp. 1–25, Raven Press, New York, 1983Google Scholar
  86. Lyell A. Toxic epidermal necrolysis: an eruption resembling scalding of the skin. British Journal of Dermatology 68: 355, 1956.PubMedGoogle Scholar
  87. Lyell A. A review of toxic epidermal necrolysis. British Journal of Dermatology 79: 662–671, 1967.PubMedGoogle Scholar
  88. Lyell A. Toxic epidermal necrolysis (the scalded skin syndrome): a reappraisal. British Journal of Dermatology 100: 69–86, 1979.PubMedGoogle Scholar
  89. Marsden RA, Ryan TJ, Vanhegan RI, Walshe M, Hil H, et al. Pemphigus foliaceus induced by penicillamine. British Medical Journal 2: 1423–1424, 1976.PubMedGoogle Scholar
  90. Marvin JA, Heimbach DM, Engrav H, Harnar TJ. Improved treatment of the Stevens-Johnson syndrome. Archives of Surgery 119: 601–605, 1984.PubMedGoogle Scholar
  91. McDonald K, Johnson B, Prasad JK, Thompson PD. Rehabilitative considerations for patients with severe Stevens-Johnson syndrome or toxic epidermal necrolysis. Journal of Burn Care and Rehabilitation 10: 167–171, 1989.PubMedGoogle Scholar
  92. Melmon KL. Preventable drug-reactions — causes and cures. New England Journal of Medicine 284: 1361–1368, 1971.PubMedGoogle Scholar
  93. Michel DJ, Knodel LC. Comparison of three algorithms used to evaluate adverse drug reactions. American Journal of Hospital Pharmacy 43: 1709–1714, 1986a.PubMedGoogle Scholar
  94. Michel DJ, Knodel LC. Program coordinated by a drug information service to improve adverse drug reaction reporting in a hospital. American Journal of Hospital Pharmacy 43: 2202–2205, 1986b.PubMedGoogle Scholar
  95. Miller KD, Lobei HO, Satriale RF, Kuritsky JN, Stern R, et al. Severe cutaneous reactions among American travelers using pyrimethamine-sulfadoxine (Fansidar) for malaria prophylaxis. American Journal of Tropical Medicine and Hygiene 35: 451–458, 1986.PubMedGoogle Scholar
  96. Moore N, Paux G, Begaud B, et al. Adverse drug reaction monitoring: doing it the French way. Lancet 2: 1056–1058, 1985.PubMedGoogle Scholar
  97. Morison WL, McAuliffe DJ, Parrish JA, Bloch KJ. In vitro assay for phototoxic chemicals. Journal of Investigative Dermatology 78: 460–463, 1982.PubMedGoogle Scholar
  98. Nalbandian RM, Mader IJ, Barret JL, Pearce JF, Rupp EC. Petechiae, ecchymoses, and necrosis of skin induced by coumarin congeners. Journal of the American Medical Association 192: 603–608, 1965.PubMedGoogle Scholar
  99. Naranjo CA, Busto A, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clinical Pharmacology and Therapeutics 30: 239–245, 1981.PubMedGoogle Scholar
  100. Navin TR, Miller KD, Satriale RF, Obel HO. Adverse reactions associated with pyrimethamine-sulfadoxine prophylaxis for pneumocystis carinii infections in AIDS. Lancet 1: 1332, 1985.PubMedGoogle Scholar
  101. Nethercott JR, Choi BCK. Erythema multiforme (Stevens-Johnson syndrome) — chart review of 123 hospitalized patients. Dermatologica 171: 383–396, 1985.PubMedGoogle Scholar
  102. Nicolis GD, Helwig EB. Exfoliative dermatitis: a clinicopathol-ogic study of 135 cases. Archives of Dermatology 108: 788–797, 1973.PubMedGoogle Scholar
  103. Orfanos CE, Schaumburg-Lever G, Lever WF. Dermal and epidermal types of erythema multiforme: a histopathologic study of 24 cases. Archives of Dermatology 109: 682–688, 1974.PubMedGoogle Scholar
  104. Parker CW. Allergic drug response mechanisms and unsolved problems. Critical Reviews in Toxicology 1: 261–277, 1972.Google Scholar
  105. Parker CW. Drug allergy. New England Journal of Medicine 292: 511, 732, 957, 1975.PubMedGoogle Scholar
  106. Patterson JW, Parsons JM, Blaylock WK, Mills AS. Eosinophils in skin lesions of erythema multiforme. Archives of Pathology and Laboratory Medicine 113: 36–39, 1989.PubMedGoogle Scholar
  107. Payne FE, Giesecke TF. Multiple system reaction to trimethoprim-sulfamethoxazole. Southern Medical Journal 80: 275–276, 1987.PubMedGoogle Scholar
  108. Peltier GL, Poppe SR, Twomey JA. Controlled air suspension: an advantage in burn care. Journal of Burn Care and Rehabilitation 8: 558–560, 1987.PubMedGoogle Scholar
  109. Penneys NS. Gold dermatitis, a clinical and histopathological study. Archives of Dermatology 109: 372, 1974.PubMedGoogle Scholar
  110. Perry Jr HM, Sakamoto A, Tan EM. Relationship of actylating enzyme to hydralazine toxicity. Journal of Laboratory and Clinical Medicine 70: 1020–1021, 1967.Google Scholar
  111. Petz LD, Füdenberg H. Coombs-positive hemolytic anemia caused by penicillin administration. New England Journal of Medicine 274: 171–178, 1966.PubMedGoogle Scholar
  112. Prasad JK, Feller I, Thompson PD. Use of amnion for the treatment of Stevens-Johnson syndrome. Journal of Trauma 26: 945–946, 1986.PubMedGoogle Scholar
  113. Rassmussen JE. Erythema multiforme in children: response to treatment with systemic corticosteroids. British Journal of Dermatology 95: 181–186, 1976.Google Scholar
  114. Rassmussen JE. Update on the Stevens-Johnson syndrome. Cleveland Clinic Journal of Medicine 55: 412–414, 1988.Google Scholar
  115. Raviglione MC, Dinan WA, Pablos-Mendez A, Palagiano A, Sabatini MT. Fatal toxic epidermal necrolysis during prophylaxis with pyrimethamine and sulfadoxine in a human immunodeficiency virus-infected person. Archives of Internal Medicine 148: 2683–2685, 1988.PubMedGoogle Scholar
  116. Ressler C, Mendelson LM. Skin test for diagnosis of penicillin allergy — current status. Annals of Allergy 59: 167–170, 1987.PubMedGoogle Scholar
  117. Revuz J, Penso D, Roujeau JC, et al. Toxic epidermal necrolysis: clinical findings and prognosis factors in 87 patients. Archives of Dermatology 123: 1160–1165, 1987a.PubMedGoogle Scholar
  118. Revuz J, Roujeau JC, Guillaume JC, Penso D, Touraine R. Treatment of toxic epidermal necrolysis: Crétei’s experience. Archives of Dermatology 123: 1156–1158, 1987b.PubMedGoogle Scholar
  119. Rocklin RE, David JR. Detection in vitro of cellular hypersensitivity to drugs. Journal of Allergy and Clinical Immunology 48: 276, 1971.PubMedGoogle Scholar
  120. Roed-Petersen J. Erythema multiforme as an expression of contact dermatitis. Contact Dermatitis 1: 270–271, 1975.PubMedGoogle Scholar
  121. Romeu J, Clotet B, Tural C, Carles J, Foz M. Therapeutic challenge for Isospora belli enteritis in an AIDS patient who developed Lyell syndrome after co-trimoxazole therapy. American Journal of Gastroenterology 84: 207–208, 1989.PubMedGoogle Scholar
  122. Roujeau JC, Huynh TN, Bracq C, Guillaume JC, Revuz J, et al. Genetic susceptibility to toxic epidermal necrolysis. Archives of Dermatology 123: 1171–1173, 1987.PubMedGoogle Scholar
  123. Roujeau JC, Moritz S, Guillaume JC, Bombai C, Revuz J, et al. Lymphopenia and abnormal balance of T-lymphocyte subpopulations in toxic epidermal necrolysis. Archives of Dermatology Research 277: 24–27, 1985.Google Scholar
  124. Ruiz-Maldonado R. Acute disseminated epidermal necrosis types 1, 2, and 3: study of sixty cases. Journal of the American Academy of Dermatology 13: 623–635, 1985.PubMedGoogle Scholar
  125. Savel H, Madison JF, Meeker CI. Cutaneous eruptions and in vitro lymphocyte hypersensitivity associated with oral contraceptives and mestranol. Archives of Dermatology 101: 187–190, 1970.PubMedGoogle Scholar
  126. Schmidt LG, Dirschdl P, Grohmann R, Scherer J, Wunderlich O, et al. Consistency of assessment of adverse drug reactions in psychiatric hospitals: a comparison of an algorithm and an empirical approach. European Journal of Clinical Pharmacology 30: 199–204, 1986.PubMedGoogle Scholar
  127. Shapiro S, Slone D, Siskind V, Lewis GP, Herschel JICK. Drug rash with ampicillin and other penicillins. Lancet 2: 969–972, 1969.PubMedGoogle Scholar
  128. Shum S. Stevens-Johnson syndrome: a pediatric experience. Louisiana State Journal of Medicine 128: 331–333, 1976.Google Scholar
  129. Simons HW. Acute life threatening dermatologic disorders. Medical Clinics of North America 65: 227–243, 1981.PubMedGoogle Scholar
  130. Soter NA, Fitzpatrick TB. Cutaneous changes in disorders of altered reactivity: eczematous dermatitis. In Fitzpatrick et al. (Eds). Dermatology in general medicine, pp. 1367–1373, McGraw-Hill Book Company, New York-St. Louis, 1987Google Scholar
  131. Stein MR, Thompson CK, Sawicki JE, et al. Esophageal stricture complicating Stevens-Johnson syndrome. American Journal of Gastroenterology 62: 435–439, 1974.PubMedGoogle Scholar
  132. Stephens MDB. The diagnosis of adverse medical events associated with drug treatment. Adverse Drug Reactions and Acute Poisoning Reviews 6: 1–35, 1987.PubMedGoogle Scholar
  133. Stevens AM, Johnson FC. A New eruptive fever associated with stomatitis and ophthalmia. American Journal of Diseases of Children 24: 526–533, 1922.Google Scholar
  134. Straus DA. Generalized bullous eruption following testing for sulfonamide-hypersensitivity. New England Journal of Medicine 239: 956–958, 1948.PubMedGoogle Scholar
  135. Szczeklick A, Gryglewski RJ, Czerniawska-Mysik G, Zmuda A. Aspirin-induced asthma. Hypersensitivity to fenoprofen and ibuprofen in relation to their inhibitory action on prostaglandin generation by different microsomal enzymic preparations. Journal of Allergy and Clinical Immunology 58: 10–18, 1976.Google Scholar
  136. Ting HC, Adam BA. Erythema multiforme — response to corticosteroid. Dermatologica 169: 175–178, 1984.PubMedGoogle Scholar
  137. Ting HC, Adam BA. Stevens-Johnson syndrome: a review of 34 cases. International Journal of Dermatology 24: 587–591, 1985.PubMedGoogle Scholar
  138. Tonnesen MG, Soter NA. Erythema multiforme. Journal of the American Academy of Dermatology 1: 357–364, 1979.PubMedGoogle Scholar
  139. Tosti A, Bardazzi F, Valeri F, Toni F. Erythema multiforme with contact dermatitis to hair dyes. Contact Dermatitis 17: 321–322, 1987.PubMedGoogle Scholar
  140. Tseng SCG. Topical tretinoin treatment for severe dry-eye disorders. Journal of the American Academy of Dermatology 15: 860–866, 1986.PubMedGoogle Scholar
  141. Von Hebra F. On diseases of the skin including the exanthemata, Vol. 1, pp. 285–289, New Sydenham Society, London, 1866–1880Google Scholar
  142. Westly ED, Wechsler HL. Toxic epidermal necrolysis: granulocytic leukopenia as a prognostic indicator. Archives of Dermatology 120: 721–726, 1984.PubMedGoogle Scholar
  143. Wide L, Bennich H, Johansson SGO. Diagnosis of allergy by an in vitro test for allergen antibodies. Lancet 2: 1105–1107, 1967.PubMedGoogle Scholar
  144. Wintroub BU, Stern RS, Arndt KA. Cutaneous reactions to drugs. In Fitzpatrick et al. (Eds) Dermatology in general medicine, pp. 1353–1366, McGraw-Hill Book Company, New York-St. Louis, 1987Google Scholar
  145. Wong KS, Wong SN, Tham SN, Giam YC. Generalized exfoliative dermatitis — a clinical study of 108 patients. Annals of the Academy of Medicine 17: 522–525, 1988.Google Scholar
  146. Yaffee HS, Dressler DP. Topical application of mefenide acetate: its association with erythema multiforme. Archives of Dermatology 100: 277–281, 1969.Google Scholar

Copyright information

© ADIS Press Limited 1990

Authors and Affiliations

  • Mario C. Raviglione
    • 1
  • Ariel Pablos-Mendez
    • 1
  • Ruggero Battan
    • 1
  1. 1.Department of MedicineCabrini Medical CenterNew YorkUSA

Personalised recommendations