Pediatric Drug Eruptions of the Skin


Cutaneous adverse cutaneous drug reactions (CADRs) are common among the pediatric population. Although they are rarely considered serious, CADRs account for approximately 35 % of all adverse drug reactions. Because viral exanthems are extremely common in children, clinicians are often faced with a diagnostic dilemma when children are taking many medications and present with a rash. If a child is taking numerous medications, establishing causality to a specific drug can be multifaceted and difficult. We discuss the most common pediatric drug eruptions according to the pattern of the cutaneous eruption: urticarial, exanthematous, pustular, and vesicobullous. We also include a miscellaneous group for completeness. Proper management of a CADR requires an efficient method of accurately estimating the probability of a drug association, determining the likelihood of a relapse with drug re-challenge, and relaying this information to patients and their families. A hasty diagnosis of a drug “allergy” will follow a child through his or her life, and possibly increase their exposure to more toxic medications unnecessarily. Unless a re-challenge is performed, the vast majority of CADRs in children can only be considered as possibly associated with a drug.


Pediatric cutaneous drug eruption Drug reaction Cutaneous adverse drug reactions (CADRs) Urticarial Exanthematous Pustular Vesicobullous 

Suggested Reading

  1. Bigby M. Rates of cutaneous reactions to drugs. Arch Dermatol. 2001;137(6):765–70.PubMedGoogle Scholar
  2. Bilgili SG, Calka O, Karadag AS, Akdeniz N, Kosem M. Nonsteroidal anti-inflammatory drugs induced generalized fixed drug eruption: two cases. Hum Exp Toxicol. 2012;31(2):197–200.CrossRefPubMedGoogle Scholar
  3. Bircher AJ. Uncomplicated drug-induced disseminated exanthemas. Chem Immunol Allergy. 2012;97:79–97.CrossRefPubMedGoogle Scholar
  4. Boorboor P, Vogt PM, Bechara FG, Alkandari Q, Aust M, Gohritz A, et al. Toxic epidermal necrolysis: use of Biobrane or skin coverage reduces pain, improves mobilisation and decreases infection in elderly patients. Burns. 2008;34(4):487–92.CrossRefPubMedGoogle Scholar
  5. Brahimi N, Routier E, Raison-Peyron N, Tronquoy AF, Pouget-Jasson C, Amarger S, et al. A three-year-analysis of fixed drug eruptions in hospital settings in France. Eur J Dermatol. 2010;20(4):461–4.PubMedGoogle Scholar
  6. Cacoub P, Musette P, Descamps V, Meyer O, Speirs C, Finzi L, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588–97.CrossRefPubMedGoogle Scholar
  7. Cardoza-Torres MA, Liy-Wong C, Welsh O, Gómez-Flores M, Ocampo-Candiani J, González-Llano O, et al. Skin manifestations associated with chemotherapy in children with hematologic malignancies. Pediatr Dermatol. 2012;29(3):264–9.CrossRefPubMedGoogle Scholar
  8. Carroll MC, Yueng-Yue KA, Esterly NB, Drolet BA. Drug induced hypersensitivity syndrome in pediatric patients. Pediatrics. 2001;108(2):485–92.CrossRefPubMedGoogle Scholar
  9. Cetkovska P, Pizinger K. Childhood pemphigus associated with montelukast administration. Clin Exp Dermatol. 2003;28(3):328–9.CrossRefPubMedGoogle Scholar
  10. Chovel-Sella A, Ben Tov A, Lahav E, Mor O, Rudich H, Paret G, et al. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Pediatrics. 2013;131(5):1424–7.CrossRefGoogle Scholar
  11. Chung WH, Hung SI. Recent advances in the genetics and immunology of Stevens-Johnson syndrome and toxic epidermal necrosis. J Dermatol Sci. 2012;66(3):190–6.CrossRefPubMedGoogle Scholar
  12. 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(6982):486.CrossRefPubMedGoogle Scholar
  13. Crowson AN, Magro CM. Recent advances in the pathology of cutaneous drug eruptions. Dermatol Clin. 1999;17(3):537–60, viii.CrossRefPubMedGoogle Scholar
  14. Dorafshar AH, Dickie SR, Cohn AB, Aycock JK, O’Connor A, Tung A, et al. Antishear therapy for toxic epidermal necrolysis: an alternative treatment approach. Plast Reconstr Surg. 2008;122(1):154–60.CrossRefPubMedGoogle Scholar
  15. Erbagci Z. Childhood bullous pemphigoid following hepatitis B immunization. J Dermatol. 2002;29(12):781–5.CrossRefPubMedGoogle Scholar
  16. Fathallah N, Ben Salem C, Slim R, Boussofara L, Ghariani N, Bouraoui K. Acetaminophen-induced cellulitis-like fixed drug eruption. Indian J Dermatol. 2011;56(2):206–8.PubMedCentralCrossRefPubMedGoogle Scholar
  17. Fernando SL. Acute generalised exanthematous pustulosis. Australas J Dermatol. 2012;53(2):87–92.CrossRefPubMedGoogle Scholar
  18. 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(4):723–8.CrossRefPubMedGoogle Scholar
  19. Fisler RE, Saeb M, Liang MG, Howard RM, McKee PH. Childhood bullous pemphigoid: a clinicopathologic study and review of the literature. Am J Dermatopathol. 2003;25(3):183–9.CrossRefPubMedGoogle Scholar
  20. Gallagher RM, Mason JR, Bird KA, Kirkham JJ, Peak M, Williamson PR, et al. Adverse drug reactions causing admission to a paediatric hospital. PLoS One. 2012;7(12), e50127.PubMedCentralCrossRefPubMedGoogle Scholar
  21. Guegan S, Bastuji-Garin S, Poszepczynska-Guigné E, Roujeau JC, Revuz J. Performance of the SCORTEN during the first five days of hospitalization to predict the prognosis of epidermal necrolysis. J Invest Dermatol. 2006;126(2):272–6.CrossRefPubMedGoogle Scholar
  22. Guillon JM, Joly P, Autran B, Denis M, Akoun G, Debré P, et al. Minocycline-induced cell-mediated hypersensitivity pneumonitis. Ann Intern Med. 1992;117(6):476–81.CrossRefPubMedGoogle Scholar
  23. Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis. 2010;5:39.PubMedCentralCrossRefPubMedGoogle Scholar
  24. Heelan K, Shear NH. Cutaneous drug reactions in children: an update. Paediatr Drugs. 2013;15(6):493–503.CrossRefPubMedGoogle Scholar
  25. Ho JC, Ng PL, Tan SH, Giam YC. Childhood linear IgA bullous disease triggered by amoxicillin-clavulanic acid. Pediatr Dermatol. 2007;24(5):E40–3.CrossRefPubMedGoogle Scholar
  26. Huang SH, Yang PS, Wu SH, Chang KP, Lin TM, Lin SD, et al. Aquacel Ag with Vaseline gauze in the management of toxic epidermal necrolysis (TEN). Burns. 2010;36(1):121–6.CrossRefPubMedGoogle Scholar
  27. Hurwitz RM. Steroid acne. J Am Acad Dermatol. 1989;21(6):1179–81.CrossRefPubMedGoogle Scholar
  28. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: part I. Clinical perspectives. J Am Acad Dermatol. 2013;68(5):693.e1–14.CrossRefGoogle Scholar
  29. Kardaun SH, Sekula P, Valeyrie-Allanore L, Liss Y, Chu CY, Creamer D, 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(5):1071–80.CrossRefPubMedGoogle Scholar
  30. Kearns GL, Wheeler JG, Childress SH, Letzig LG. Serum sickness-like reactions to cefaclor: role of hepatic metabolism and individual susceptibility. J Pediatr. 1994;125(5 Pt 1):805–11.CrossRefPubMedGoogle Scholar
  31. Khaled A, Kharfi M, Ben Hamida M, El Fekih N, El Aidli S, Zeglaoui F, et al. Cutaneous adverse drug reactions in children. A series of 90 cases. Tunis Med. 2012;90(1):45–50.PubMedGoogle Scholar
  32. Kress DW. Pediatric dermatology emergencies. Curr Opin Pediatr. 2011;23(4):403–6.CrossRefPubMedGoogle Scholar
  33. Lang BA, Finlayson LA. Naproxen-induced pseudoporphyria in patients with juvenile rheumatoid arthritis. J Pediatr. 1994;124(4):639–42.CrossRefPubMedGoogle Scholar
  34. Lansang P, Weinstein M, Shear N. Drug reactions. In: Schachner LA, Hansen RC, editors. Pediatric dermatology. 4th ed. London: Mosby Elsevier; 2011. p. 1698–711.Google Scholar
  35. Lee HY, Chung WH. Toxic epidermal necrolysis: the year in review. Curr Opin Allergy Clin Immunol. 2013;13(4):330–6.PubMedGoogle Scholar
  36. Levi N, Bastuji-Garin S, Mockenhaupt M, Roujeau JC, Flahault A, Kelly JP, et al. Medications as risk factors of Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a pooled analysis. Pediatrics. 2009;123(2):e297–304.CrossRefPubMedGoogle Scholar
  37. Mahboob A, Haroon TS. Drugs causing fixed eruptions: a study of 450 cases. Int J Dermatol. 1998;37(11):833–8.CrossRefPubMedGoogle Scholar
  38. Menniti-Ippolito G, Raschetti R, Da Cas R, Giaquinto C, Cantarutti L. Active monitoring of adverse drug reactions in children. Italian Paediatric Pharmacosurveillance Multicenter Group. Lancet. 2000;355(9215):1613–4.CrossRefPubMedGoogle Scholar
  39. Mintz EM, Morel KD. Clinical features, diagnosis, and pathogenesis of chronic bullous disease of childhood. Dermatol Clin. 2011;29(3):459–62.CrossRefPubMedGoogle Scholar
  40. Mockenhaupt M. Severe drug-induced skin reactions: clinical pattern, diagnostics and therapy. J Dtsch Dermatol Ges. 2009;7(2):142–60.PubMedGoogle Scholar
  41. Mockenhaupt M. Epidemiology of cutaneous adverse drug reactions. Chem Immunol Allergy. 2012;97:1–17.CrossRefPubMedGoogle Scholar
  42. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45.CrossRefPubMedGoogle Scholar
  43. Nigen S, Knowles SR, Shear NH. Drug eruptions: approaching the diagnosis of drug-induced skin diseases. J Drugs Dermatol. 2003;2(3):278–99.PubMedGoogle Scholar
  44. Nussinovitch M, Prais D, Ben-Amitai D, Amir J, Volovitz B. Fixed drug eruption in the genital area in 15 boys. Pediatr Dermatol. 2002;19(3):216–9.CrossRefPubMedGoogle Scholar
  45. Ott H. Hypersensitivity reactions to drugs. In: Irvine AD, Hoeger PH, Yan AC, editors. Harper’s textbook of pediatric dermatology. 3rd ed. Oxford: Blackwell Publishing Ltd; 2011. p. 2816.Google Scholar
  46. Ozkaya E. Fixed drug eruption: state of the art. J Dtsch Dermatol Ges. 2008;6(3):181–8.CrossRefPubMedGoogle Scholar
  47. Paller AS, Mancini AJ. Allergic reactions. In: Paller AS, Mancini AJ, editors. Hurwitz clinical pediatric dermatology. 4th ed. Philadelphia: Elsevier Saunders; 2011. p. 454–82.CrossRefGoogle Scholar
  48. Patel S, Mancini AJ. Serum sickness-like reaction in children: a retrospective review. J Am Acad Dermatol. 2009;60 Suppl 1:AB1–276.Google Scholar
  49. Peroni A, Colato C, Schena D, et al. Urticarial lesions: if not urticaria, what else? The differential diagnosis of urticaria: part I. Cutaneous diseases. J Am Acad Dermatol. 2010;62(4):541–55.CrossRefPubMedGoogle Scholar
  50. Revuz J, Valeyrie-Allanore L, et al. Drug reactions in dermatology. In: Jean L, Bolognia M, Julie V, editors. Dermatology. 3rd ed. Philadelphia: Elsevier Inc; 2012. p. Cp21.Google Scholar
  51. Ribeiro-Vaz I, Marques J, Demoly P, Polónia J, Gomes ER. Drug-induced anaphylaxis: a decade review of reporting to the Portuguese Pharmacovigilance Authority. Eur J Clin Pharmacol. 2013;69(3):673–81.CrossRefPubMedGoogle Scholar
  52. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med. 1994;331(19):1272–85.CrossRefPubMedGoogle Scholar
  53. 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(9):1333–8.CrossRefPubMedGoogle Scholar
  54. Segal AR, Doherty KM, Leggott J, Zlotoff B. Cutaneous reactions to drugs in children. Pediatrics. 2007;120(4):e1082–96.CrossRefPubMedGoogle Scholar
  55. Sharma VK, Dhar S. Clinical pattern of cutaneous drug eruption among children and adolescents in North India. Pediatr Dermatol. 1995;12(2):178–83.CrossRefPubMedGoogle Scholar
  56. Shear NH, Spielberg SP. Anticonvulsant hypersensitivity syndrome: in vitro assessment of risk. J Clin Invest. 1988;82(6):1826–32.PubMedCentralCrossRefPubMedGoogle Scholar
  57. Sidoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized exanthematous pustulosis (AGEP)—a clinical reaction pattern. J Cutan Pathol. 2001;28(3):113–9.CrossRefPubMedGoogle Scholar
  58. Stern RS. Clinical practice: exanthematous drug eruptions. N Engl J Med. 2012;366(26):2492–501.CrossRefPubMedGoogle Scholar
  59. Tolpinrud WL, Bunick CG, King BA. Serum sickness-like reaction: histopathology and case report. J Am Acad Dermatol. 2011;65(3):e83–5.CrossRefPubMedGoogle Scholar
  60. White-Koning M, Civade E, Geoerger B, Thomas F, Le Deley MC, Hennebelle I, et al. Population analysis of erlotinib in adults and children reveals pharmacokinetic characteristics as the main factor explaining tolerance particularities in children. Clin Cancer Res. 2011;17(14):4862–71.CrossRefPubMedGoogle Scholar

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© Springer-Verlag London 2015

Authors and Affiliations

  1. 1.PathologyUniversity of VermontBurlingtonUSA

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