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How to Manage Drug-Induced Exanthema in Children

  • Drug Allergy (MJ Torres Jaén, Section Editor)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Opinion statement

Exanthemas are frequently encountered in the pediatric population and often occur while patients concomitantly receive a drug, leading to a high prevalence of suspicion of drug allergy in children. Although the vast majority of these exanthemas are due to the underlying infection, most of those patients are falsely labeled as “drug allergic” without appropriate testing, mostly due to fear of life-threatening reactions. Overdiagnosis of drug allergy constitutes a major public health problem by increasing health costs and by contributing to overall antibiotic resistance. Thus, an accurate diagnosis is considered as a major contribution to cost-effective health care and will be based on a complete allergic workup (i.e., clinical history, skin tests, in vitro tests, and/or drug provocation test). Specific aspects of the management of drug allergy have been highlighted recently, particularly regarding the importance and safety of the drug provocation test as well as the low diagnostic value of skin tests in the diagnosis of betalactam allergy.

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Abbreviations

NSAID:

Nonsteroidal anti-inflammatory drugs

BL:

Betalactams

EBV:

Epstein-Barr virus

DPT:

Drug provocation test

SCARs:

Severe cutaneous adverse drug reactions

AGEP:

Acute generalized exanthematic pustulosis

DIHS:

Drug-induced hypersensitivity syndrome

SJS:

Stevens-Johnson syndrome

TEN:

Toxic epidermal necrolysis

LTT:

Lymphocyte transformation test

LAT:

Lymphocyte activation test

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Rebelo Gomes E, et al. Drug allergy claims in children: from self-reporting to confirmed diagnosis. Clin Exp Allergy. 2008;38(1):191–8.

    CAS  PubMed  Google Scholar 

  2. Le J, et al. Adverse drug reactions among children over a 10-year period. Pediatrics. 2006;118(2):555–62.

    Article  PubMed  Google Scholar 

  3. Lange L, Koningsbruggen SV, Rietschel E. Questionnaire-based survey of lifetime-prevalence and character of allergic drug reactions in German children. Pediatr Allergy Immunol. 2008;19(7):634–8.

    CAS  PubMed  Google Scholar 

  4. Macy E, Poon KYT. Self-reported antibiotic allergy incidence and prevalence: age and sex effects. Am J Med. 2009;122(8):778 e1–7.

    Article  Google Scholar 

  5. • Caubet JC, et al. The role of penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge. J Allergy Clin Immunol. 2011;127(1):218–22. A prospective study demonstrating overdiagnosis of betalactam allergy in children and suggesting a viral cause in the majority of children developing a rash while treated by betalactam

  6. • Ponvert C, et al. Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests. Pediatr Allergy Immunol. 2011;22(4):411–8. One of the largest pediatric study on betalactam allergy in children, evaluating the diagnostic value of the available diagnostic tools (skin tests, specific IgE and/or drug provocation test)

    Article  CAS  PubMed  Google Scholar 

  7. Erkocoglu M, et al. Prevalence of confirmed immediate type drug hypersensitivity reactions among school children. Pediatr Allergy Immunol. 2013;24(2):160–7.

    Article  PubMed  Google Scholar 

  8. Rubio M, et al. Results of drug hypersensitivity evaluations in a large group of children and adults. Clin Exp Allergy. 2012;42(1):123–30.

    Article  CAS  PubMed  Google Scholar 

  9. Aberer W, et al. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy. 2003;58(9):854–63.

    Article  CAS  PubMed  Google Scholar 

  10. • Zambonino MA, et al. Diagnostic evaluation of hypersensitivity reactions to beta-lactam antibiotics in a large population of children. Pediatr Allergy Immunol. 2014;25(1):80–7. Prospective pediatric study highlighting the importance of the drug provocation test in the diagnosis of nonimmediate benign reactions to betalactams

    Article  PubMed  Google Scholar 

  11. Solensky R. Penicillin allergy as a public health measure. J Allergy Clin Immunol. 2014;133(3):797–8.

    Article  PubMed  Google Scholar 

  12. Solensky R. The time for penicillin skin testing is here. J Allergy Clin Immunol Pract. 2013;1(3):264–5.

    Article  PubMed  Google Scholar 

  13. van Dijk SM, et al. The high impact of penicillin allergy registration in hospitalized patients. J Allergy Clin Immunol Pract. 2016;4(5):926–31.

    Article  PubMed  Google Scholar 

  14. •• Gomes ER, et al. Drug hypersensitivity in children: report from the pediatric task force of the EAACI Drug Allergy Interest Group. Allergy. 2016;71(2):149–61. This paper summarizes our knowledge on drug allergy in children, highlighting the lack of pediatric data, and including a general algorithm for the management of children with a suspicion of drug allergy

    Article  CAS  PubMed  Google Scholar 

  15. Schachner L, Hansen R. Pediatric Dermatology, 4th Edition, 2011.

  16. Folster-Holst R, Kreth HW. Viral exanthems in childhood—infectious (direct) exanthems. Part 1: classic exanthems. J Dtsch Dermatol Ges. 2009;7(4):309–16.

    PubMed  Google Scholar 

  17. Vega Alonso T, et al. Incidence and clinical characteristics of maculopapular exanthemas of viral aetiology. Aten Primaria. 2003;32(9):517–23.

    Article  CAS  PubMed  Google Scholar 

  18. Goodyear HM, et al. Acute infectious erythemas in children: a clinico-microbiological study. Br J Dermatol. 1991;124(5):433–8.

    Article  CAS  PubMed  Google Scholar 

  19. Folster-Holst R, Kreth HW. Viral exanthems in childhood—infectious (direct) exanthems. Part 2: other viral exanthems. J Dtsch Dermatol Ges. 2009;7(5):414–9.

    PubMed  Google Scholar 

  20. • Onodi-Nagy K, et al. Amoxicillin rash in patients with infectious mononucleosis: evidence of true drug sensitization. Allergy Asthma Clin Immunol. 2015;11(1):1. This is a review discussing extensively the potential role of EBV in patients treated by amoxicillin and developing a skin rash

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. •• Demoly P, et al. International consensus on drug allergy. Allergy. 2014;69(4):420–37. International guidelines for the management of patients with a suspicion of drug allergy

    Article  CAS  PubMed  Google Scholar 

  22. Shiohara T, Kano Y. A complex interaction between drug allergy and viral infection. Clin Rev Allergy Immunol. 2007;33(1–2):124–33.

    Article  CAS  PubMed  Google Scholar 

  23. White KD, et al. Evolving models of the immunopathogenesis of T cell-mediated drug allergy: the role of host, pathogens, and drug response. J Allergy Clin Immunol. 2015;136(2):219–34. quiz 235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Atanaskovic-Markovic M, et al. Non-immediate hypersensitivity reactions to beta-lactam antibiotics in children—our 10-year experience in allergy work-up. Pediatr Allergy Immunol. 2016;27(5):533–8.

    Article  PubMed  Google Scholar 

  25. Mattheij M, de Vries E. A suspicion of antibiotic allergy in children is often incorrect. J Allergy Clin Immunol. 2012;129(2):583. author reply 583-4

    Article  PubMed  Google Scholar 

  26. Mill C, et al. Assessing the diagnostic properties of a graded oral provocation challenge for the diagnosis of immediate and non-immediate reactions to amoxicillin in children. JAMA Pediatr. 2016;170(6):e160033.

    Article  PubMed  Google Scholar 

  27. Alves C, et al. Non-steroidal anti-inflammatory drug hypersensitivity in children. Allergol Immunopathol (Madr). 2017;45(1):40–7.

    Article  CAS  Google Scholar 

  28. Guvenir H, et al. Nonsteroidal anti-inflammatory drug hypersensitivity among children. Allergy Asthma Proc. 2015;36(5):386–93.

    Article  PubMed  Google Scholar 

  29. Stur K, Karlhofer FM, Stingl G. Soluble FAS ligand: a discriminating feature between drug-induced skin eruptions and viral exanthemas. J Invest Dermatol. 2007;127(4):802–7.

    Article  CAS  PubMed  Google Scholar 

  30. Bircher AJ. Symptoms and danger signs in acute drug hypersensitivity. Toxicology. 2005;209(2):201–7.

    Article  CAS  PubMed  Google Scholar 

  31. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105(4):259–73.

  32. Romano A, Caubet JC. Antibiotic allergies in children and adults: from clinical symptoms to skin testing diagnosis. J Allergy Clin Immunol Pract. 2014;2(1):3–12.

    Article  PubMed  Google Scholar 

  33. Blanca M, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. 2009;64(2):183–93.

    Article  CAS  PubMed  Google Scholar 

  34. Mori F, et al. Amoxicillin allergy in children: five-day drug provocation test in the diagnosis of non-immediate reactions. J Allergy Clin Immunol Pract. 2015;3(3):375–80 e1.

    Article  PubMed  Google Scholar 

  35. Moral L, et al. Short protocol for the study of paediatric patients with suspected betalactam antibiotic hypersensitivity and low risk criteria. Allergol Immunopathol (Madr). 2011;39(6):337–41.

    Article  CAS  Google Scholar 

  36. Vezir E, et al. Direct oral provocation tests in non-immediate mild cutaneous reactions related to beta-lactam antibiotics. Pediatr Allergy Immunol. 2016;27(1):50–4.

    Article  PubMed  Google Scholar 

  37. Pichler WJ, Tilch J. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy. 2004;59(8):809–20.

    Article  CAS  PubMed  Google Scholar 

  38. Beeler A, et al. CD69 upregulation on T cells as an in vitro marker for delayed-type drug hypersensitivity. Allergy. 2008;63(2):181–8.

    CAS  PubMed  Google Scholar 

  39. Caubet JC, et al. Skin tests and in vitro allergy tests have a poor diagnostic value for benign skin rashes due to beta-lactams in children. Pediatr Allergy Immunol. 2015;26(1):80–2.

    Article  PubMed  Google Scholar 

  40. •• Kuyucu S, et al. Hypersensitivity reactions to non-betalactam antibiotics in children: an extensive review. Pediatr Allergy Immunol. 2014;25(6):534–43. Exentive review of the literature summarizing the available data regarding hypersensitivity reactions to non-betalactam antibiotics in children

    PubMed  Google Scholar 

  41. Ibia EO, Schwartz RH, Wiedermann BL. Antibiotic rashes in children: a survey in a private practice setting. Arch Dermatol. 2000;136(7):849–54.

    Article  CAS  PubMed  Google Scholar 

  42. Orhan F, et al. Parental-reported drug allergy in 6- to 9-yr-old urban schoolchildren. Pediatr Allergy Immunol. 2008;19(1):82–5.

    PubMed  Google Scholar 

  43. Tan VA, Gerez IF, Van Bever HP. Prevalence of drug allergy in Singaporean children. Singap Med J. 2009;50(12):1158–61.

    CAS  Google Scholar 

  44. Lusini G, et al. Antibiotic prescribing in paediatric populations: a comparison between Viareggio, Italy and Funen, Denmark. Eur J Pub Health. 2009;19(4):434–8.

    Article  Google Scholar 

  45. Blanca-Lopez N, Andreu I, Torres Jaen MJ. Hypersensitivity reactions to quinolones. Curr Opin Allergy Clin Immunol. 2011;11(4):285–91.

    Article  CAS  PubMed  Google Scholar 

  46. Burke P, Burne SR. Allergy associated with ciprofloxacin. BMJ. 2000;320(7236):679.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Iannini P, et al. Cutaneous adverse events and gemifloxacin: observations from the clinical trial program. J Chemother. 2006;18(1):3–11.

    Article  CAS  PubMed  Google Scholar 

  48. Forget EJ, Menzies D. Adverse reactions to first-line antituberculosis drugs. Expert Opin Drug Saf. 2006;5(2):231–49.

    Article  CAS  PubMed  Google Scholar 

  49. Tan WC, et al. Two years review of cutaneous adverse drug reaction from first line anti-tuberculous drugs. Med J Malaysia. 2007;62(2):143–6.

    CAS  PubMed  Google Scholar 

  50. Chintu C, et al. Cutaneous hypersensitivity reactions due to thiacetazone in the treatment of tuberculosis in Zambian children infected with HIV-I. Arch Dis Child. 1993;68(5):665–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Panova LV, Ovsiankina ES. Incidence of adverse reactions to chemotherapy and their types in adolescents with tuberculosis. Probl Tuberk. 2003;1:28–30.

    Google Scholar 

  52. Nemir RL, O'Hare D. Tuberculosis in children 10 years of age and younger: three decades of experience during the chemotherapeutic era. Pediatrics. 1991;88(2):236–41.

    CAS  PubMed  Google Scholar 

  53. Ormerod LP, Horsfield N. Frequency and type of reactions to antituberculosis drugs: observations in routine treatment. Tuber Lung Dis. 1996;77(1):37–42.

    Article  CAS  PubMed  Google Scholar 

  54. •• Brockow K, et al. Skin test concentrations for systemically administered drugs—an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy. 2013;68(6):702–12. Important position paper providing optimal concentration for skin tests for systemically administered drugs

    Article  CAS  PubMed  Google Scholar 

  55. Chia FL, Thong BY. Macrolide allergy: which tests are really useful? Allergol Immunopathol (Madr). 2011;39(4):191–2.

    Article  CAS  Google Scholar 

  56. Kelly TE, Hackett PH. Acetazolamide and sulfonamide allergy: a not so simple story. High Alt Med Biol. 2010;11(4):319–23.

    Article  CAS  PubMed  Google Scholar 

  57. Eustace N, O'Hare B. Use of nonsteroidal anti-inflammatory drugs in infants. A survey of members of the Association of Paediatric Anaesthetists of Great Britain and Ireland. Paediatr Anaesth. 2007;17(5):464–9.

    Article  PubMed  Google Scholar 

  58. Neubert A, et al. The prescribing of analgesics and non-steroidal anti-inflammatory drugs in paediatric primary care in the UK, Italy and the Netherlands. Pharmacol Res. 2010;62(3):243–8.

    Article  PubMed  Google Scholar 

  59. Valkhoff VE, et al. Population-based analysis of non-steroidal anti-inflammatory drug use among children in four European countries in the SOS project: what size of data platforms and which study designs do we need to assess safety issues? BMC Pediatr. 2013;13:192.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Mayorga C, et al. Cutaneous symptoms in drug allergy: what have we learnt? Curr Opin Allergy Clin Immunol. 2009;9(5):431–6.

    Article  CAS  PubMed  Google Scholar 

  61. Kowalski ML, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68(10):1219–32.

    Article  CAS  PubMed  Google Scholar 

  62. •• Blanca-Lopez N, et al. Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in children and adolescents: selective reactions. J Investig Allergol Clin Immunol. 2015;25(6):385–95. Review of the literature regarding selective reactions to nonsteroidal anti-inflammatory drugs in children

    CAS  PubMed  Google Scholar 

  63. Faulkner L, et al. The importance of hapten-protein complex formation in the development of drug allergy. Curr Opin Allergy Clin Immunol. 2014;14(4):293–300.

    Article  CAS  PubMed  Google Scholar 

  64. Kretz-Rommel A, Boelsterli UA. Diclofenac covalent protein binding is dependent on acyl glucuronide formation and is inversely related to P450-mediated acute cell injury in cultured rat hepatocytes. Toxicol Appl Pharmacol. 1993;120(1):155–61.

    Article  CAS  PubMed  Google Scholar 

  65. Ikegawa S, et al. The enantioselective immunoaffinity extraction of an optically active ibuprofen-modified peptide fragment. Anal Biochem. 2001;296(1):63–72.

    Article  CAS  PubMed  Google Scholar 

  66. Kowalski ML, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs)—classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*. Allergy. 2011;66(7):818–29.

    Article  CAS  PubMed  Google Scholar 

  67. Hassani A, et al. Hypersensitivity to cyclooxygenase inhibitory drugs in children: a study of 164 cases. Eur J Dermatol. 2008;18(5):561–5.

    CAS  PubMed  Google Scholar 

  68. Zambonino MA, et al. Drug provocation tests in the diagnosis of hypersensitivity reactions to non-steroidal anti-inflammatory drugs in children. Pediatr Allergy Immunol. 2013;24(2):151–9.

    Article  PubMed  Google Scholar 

  69. Kidon MI, et al. Hypersensitivity to paracetamol in Asian children with early onset of nonsteroidal anti-inflammatory drug allergy. Int Arch Allergy Immunol. 2007;144(1):51–6.

    Article  CAS  PubMed  Google Scholar 

  70. Yilmaz O, et al. Challenge-proven nonsteroidal anti-inflammatory drug hypersensitivity in children. Allergy. 2013;68(12):1555–61.

    Article  CAS  PubMed  Google Scholar 

  71. Ordoqui E, et al. Cross-sensitivity among oxicams in piroxicam-caused fixed drug eruption: two case reports. Allergy. 1995;50(9):741–4.

    Article  CAS  PubMed  Google Scholar 

  72. Gomez-Traseira C, et al. Paracetamol-induced fixed drug eruption at an unusual site. Recent Patents Inflamm Allergy Drug Discov. 2013;7(3):268–70.

    Article  CAS  Google Scholar 

  73. Atanaskovic-Markovic M, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis in children. Pediatr Allergy Immunol. 2013;24(7):645–9.

    Article  PubMed  Google Scholar 

  74. Kelso JM. Allergic reactions after immunization. Ann Allergy Asthma Immunol. 2013;110(6):397–401.

    Article  PubMed  Google Scholar 

  75. • Caubet JC, et al. Managing a child with possible allergy to vaccine. Pediatr Allergy Immunol. 2014;25(4):394–403. Review including discussion of practical aspects of the management of a child with possible allergy to vaccine

    Article  PubMed  Google Scholar 

  76. Sukumaran L, et al. Adverse events following measles, mumps, and rubella vaccine in adults reported to the Vaccine Adverse Event Reporting System (VAERS), 2003-2013. Clin Infect Dis. 2015;60(10):e58–65.

    PubMed  PubMed Central  Google Scholar 

  77. Gold M, et al. Re-vaccination of 421 children with a past history of an adverse vaccine reaction in a special immunisation service. Arch Dis Child. 2000;83(2):128–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Jacobs RL, Lowe RS, Lanier BQ. Adverse reactions to tetanus toxoid. JAMA. 1982;247(1):40–2.

    Article  CAS  PubMed  Google Scholar 

  79. Andre FE. Overview of a 5-year clinical experience with a yeast-derived hepatitis B vaccine. Vaccine. 1990;(8 Suppl):S74–8. discussion S79-80

  80. McMahon BJ, et al. Frequency of adverse reactions to hepatitis B vaccine in 43,618 persons. Am J Med. 1992;92(3):254–6.

    Article  CAS  PubMed  Google Scholar 

  81. Long SS, et al. Longitudinal study of adverse reactions following diphtheria-tetanus-pertussis vaccine in infancy. Pediatrics. 1990;85(3):294–302.

    CAS  PubMed  Google Scholar 

  82. Szmuness W, et al. Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med. 1980;303(15):833–41.

    Article  CAS  PubMed  Google Scholar 

  83. Siegrist CA. Mechanisms underlying adverse reactions to vaccines. J Comp Pathol. 2007;137(Suppl 1):S46–50.

    Article  CAS  PubMed  Google Scholar 

  84. •• Dreskin SC, et al. International Consensus (ICON): allergic reactions to vaccines. World Allergy Organ J. 2016;9(1):32. International guidelines on the management of patients with a suspicion of allergy to vaccines

    Article  PubMed  PubMed Central  Google Scholar 

  85. Vogt T, Landthaler M, Stolz W. Generalized eczema in an 18-month-old boy due to phenoxyethanol in DPT vaccine. Contact Dermatitis. 1998;38(1):50–1.

    Article  CAS  PubMed  Google Scholar 

  86. Ghadially R, Ramsay CA. Gentamicin: systemic exposure to a contact allergen. J Am Acad Dermatol. 1988;19(2 Pt 2):428–30.

    Article  CAS  PubMed  Google Scholar 

  87. Idsoe O, et al. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull World Health Organ. 1968;38(2):159–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Neeno DNT. Anaphylaxis to benzathine penicillin G. Pediatr Asthma Allergy Immunol. 2000;14:329.

    Article  Google Scholar 

  89. Romano A, et al. Diagnosis and management of drug hypersensitivity reactions. J Allergy Clin Immunol. 2011;127(3 Suppl):S67–73.

    Article  CAS  PubMed  Google Scholar 

  90. Macy E. The clinical evaluation of penicillin allergy: what is necessary, sufficient and safe given the materials currently available? Clin Exp Allergy. 2011;41(11):1498–501.

    Article  CAS  PubMed  Google Scholar 

  91. Fox S, Park MA. Penicillin skin testing in the evaluation and management of penicillin allergy. Ann Allergy Asthma Immunol. 2011;106(1):1–7.

    Article  PubMed  Google Scholar 

  92. Bousquet PJ, et al. Oral challenges are needed in the diagnosis of beta-lactam hypersensitivity. Clin Exp Allergy. 2008;38(1):185–90.

    CAS  PubMed  Google Scholar 

  93. • Torres MJ, et al. Clavulanic acid can be the component in amoxicillin-clavulanic acid responsible for immediate hypersensitivity reactions. J Allergy Clin Immunol. 2010;125(2):502–505 e2. Study highlighting the possibility of specific hypersensitivity to clavulanic acid itself in patients reacting to amoxicillin-clavulanic acid

    Article  CAS  PubMed  Google Scholar 

  94. Sanchez-Morillas L, et al. Selective allergic reactions to clavulanic acid: a report of 9 cases. J Allergy Clin Immunol. 2010;126(1):177–9.

    Article  CAS  PubMed  Google Scholar 

  95. Park MA, et al. Patients with positive skin test results to penicillin should not undergo penicillin or amoxicillin challenge. J Allergy Clin Immunol. 2015;135(3):816–7.

    Article  PubMed  Google Scholar 

  96. Green GR, Rosenblum AH, Sweet LC. Evaluation of penicillin hypersensitivity: value of clinical history and skin testing with penicilloyl-polylysine and penicillin G. A cooperative prospective study of the penicillin study group of the American Academy of Allergy. J Allergy Clin Immunol. 1977;60(6):339–45.

    Article  CAS  PubMed  Google Scholar 

  97. Sogn DD, et al. Results of the National Institute of Allergy and Infectious Diseases collaborative clinical trial to test the predictive value of skin testing with major and minor penicillin derivatives in hospitalized adults. Arch Intern Med. 1992;152(5):1025–32.

    Article  CAS  PubMed  Google Scholar 

  98. Macy E, Burchette RJ. Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up. Allergy. 2002;57(12):1151–8.

    Article  CAS  PubMed  Google Scholar 

  99. Adkinson Jr NF, et al. Routine use of penicillin skin testing on an inpatient service. N Engl J Med. 1971;285(1):22–4.

    Article  PubMed  Google Scholar 

  100. Levine BB, Zolov DM. Prediction of penicillin allergy by immunological tests. J Allergy. 1969;43(4):231–44.

    Article  CAS  PubMed  Google Scholar 

  101. Chambel M, et al. Drug provocation tests to betalactam antibiotics: experience in a paediatric setting. Allergol Immunopathol (Madr). 2010;38(6):300–6.

    Article  CAS  Google Scholar 

  102. Waton J, et al. Negative predictive value of drug skin tests in investigating cutaneous adverse drug reactions. Br J Dermatol. 2009;160(4):786–94.

    Article  CAS  PubMed  Google Scholar 

  103. Marrs T, et al. The diagnosis and management of antibiotic allergy in children: systematic review to inform a contemporary approach. Arch Dis Child. 2015;100(6):583–8.

    Article  PubMed  Google Scholar 

  104. Ponvert C, et al. Allergy to betalactam antibiotics in children: a prospective follow-up study in retreated children after negative responses in skin and challenge tests. Allergy. 2007;62(1):42–6.

    Article  CAS  PubMed  Google Scholar 

  105. Sanz ML, Gamboa PM, Mayorga C. Basophil activation tests in the evaluation of immediate drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2009;9(4):298–304.

    Article  CAS  PubMed  Google Scholar 

  106. Atanaskovic-Markovic M, et al. Immediate allergic reactions to cephalosporins and penicillins and their cross-reactivity in children. Pediatr Allergy Immunol. 2005;16(4):341–7.

    Article  PubMed  Google Scholar 

  107. Atanaskovic-Markovic M. Educational case series: beta-lactam allergy and cross-reactivity. Pediatr Allergy Immunol. 2011;22(8):770–5.

    Article  PubMed  Google Scholar 

  108. Romano A, et al. Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins. Ann Intern Med. 2004;141(1):16–22.

    Article  CAS  PubMed  Google Scholar 

  109. Novalbos A, et al. Lack of allergic cross-reactivity to cephalosporins among patients allergic to penicillins. Clin Exp Allergy. 2001;31(3):438–43.

    Article  CAS  PubMed  Google Scholar 

  110. Miranda A, et al. Cross-reactivity between a penicillin and a cephalosporin with the same side chain. J Allergy Clin Immunol. 1996;98(3):671–7.

    Article  CAS  PubMed  Google Scholar 

  111. Audicana M, et al. Allergic reactions to betalactams: studies in a group of patients allergic to penicillin and evaluation of cross-reactivity with cephalosporin. Allergy. 1994;49(2):108–13.

    Article  CAS  PubMed  Google Scholar 

  112. Sastre J, et al. Clinical cross-reactivity between amoxicillin and cephadroxil in patients allergic to amoxicillin and with good tolerance of penicillin. Allergy. 1996;51(6):383–6.

    Article  CAS  PubMed  Google Scholar 

  113. Perez Pimiento A, et al. Aztreonam and ceftazidime: evidence of in vivo cross allergenicity. Allergy. 1998;53(6):624–5.

    Article  CAS  PubMed  Google Scholar 

  114. Adkinson Jr NF. Immunogenicity and cross-allergenicity of aztreonam. Am J Med. 1990;88(3C):12S–5S. discussion 38S-42S

    Article  PubMed  Google Scholar 

  115. Saxon A, et al. Lack of cross-reactivity between aztreonam, a monobactam antibiotic, and penicillin in penicillin-allergic subjects. J Infect Dis. 1984;149(1):16–22.

    Article  CAS  PubMed  Google Scholar 

  116. Adkinson Jr NF, et al. Cross-allergenicity and immunogenicity of aztreonam. Rev Infect Dis. 1985;7(Suppl 4):S613–21.

    Article  CAS  PubMed  Google Scholar 

  117. Atanaskovic-Markovic M, et al. Tolerability of imipenem in children with IgE-mediated hypersensitivity to penicillins. J Allergy Clin Immunol. 2009;124(1):167–9.

    Article  CAS  PubMed  Google Scholar 

  118. Frumin J, Gallagher JC. Allergic cross-sensitivity between penicillin, carbapenem, and monobactam antibiotics: what are the chances? Ann Pharmacother. 2009;43(2):304–15.

    Article  CAS  PubMed  Google Scholar 

  119. Romano A, et al. IgE-mediated hypersensitivity to cephalosporins: cross-reactivity and tolerability of penicillins, monobactams, and carbapenems. J Allergy Clin Immunol. 2010;126(5):994–9.

    Article  CAS  PubMed  Google Scholar 

  120. Craft JC, Siepman N. Overview of the safety profile of clarithromycin suspension in pediatric patients. Pediatr Infect Dis J. 1993;12(12 Suppl 3):S142–7.

    Article  CAS  PubMed  Google Scholar 

  121. Odio C, et al. Adverse reactions to vancomycin used as prophylaxis for CSF shunt procedures. Am J Dis Child. 1984;138(1):17–9.

    CAS  PubMed  Google Scholar 

  122. Levy M, et al. Vancomycin-induced red man syndrome. Pediatrics. 1990;86(4):572–80.

    CAS  PubMed  Google Scholar 

  123. Sivagnanam S, Deleu D. Red man syndrome. Crit Care. 2003;7(2):119–20.

    Article  PubMed  Google Scholar 

  124. Myers AL, et al. Defining risk factors for red man syndrome in children and adults. Pediatr Infect Dis J. 2012;31(5):464–8.

    Article  PubMed  PubMed Central  Google Scholar 

  125. Wazny LD, Daghigh B. Desensitization protocols for vancomycin hypersensitivity. Ann Pharmacother. 2001;35(11):1458–64.

    Article  CAS  PubMed  Google Scholar 

  126. Earl HS, Sullivan TJ. Acute desensitization of a patient with cystic fibrosis allergic to both beta-lactam and aminoglycoside antibiotics. J Allergy Clin Immunol. 1987;79(3):477–83.

    Article  CAS  PubMed  Google Scholar 

  127. Spigarelli MG, Hurwitz ME, Nasr SZ. Hypersensitivity to inhaled TOBI following reaction to gentamicin. Pediatr Pulmonol. 2002;33(4):311–4.

    Article  PubMed  Google Scholar 

  128. Ben Said B, et al. Usefulness of basophil activation tests for the diagnosis of IgE-mediated allergy to quinolones. Allergy. 2010;65(4):535–6.

    Article  CAS  PubMed  Google Scholar 

  129. •• Blanca-Lopez N, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs in children and adolescents: cross-intolerance reactions. J Investig Allergol Clin Immunol. 2015;25(4):259–69. Review of the literature regarding cross intolerance reactions to nonsteroidal anti-inflammatory drugs in children

    CAS  PubMed  Google Scholar 

  130. Asero R. Intolerance to nonsteroidal anti-inflammatory drugs might precede by years the onset of chronic urticaria. J Allergy Clin Immunol. 2003;111(5):1095–8.

    Article  CAS  PubMed  Google Scholar 

  131. Church MK, et al. Chronic spontaneous urticaria in children: itching for insight. Pediatr Allergy Immunol. 2011;22(1 Pt 1):1–8.

    Article  PubMed  Google Scholar 

  132. Kidon MI, et al. Early presentation with angioedema and urticaria in cross-reactive hypersensitivity to nonsteroidal antiinflammatory drugs among young, Asian, atopic children. Pediatrics. 2005;116(5):e675–80.

    Article  PubMed  Google Scholar 

  133. Olze H, Lau S, Forster U. Samter’s triad and eicosanoid imbalance in children with recurrent nasal polyps. Pediatr Allergy Immunol. 2012;23(5):500.

    Article  PubMed  Google Scholar 

  134. Reisfeld S, Goldberg A, Confino-Cohen R. Management of patients with known drug hypersensitivity in an emergency department in Israel. Int Arch Allergy Immunol. 2011;155(4):361–6.

    Article  PubMed  Google Scholar 

  135. Viola M, et al. Assessing potential determinants of positive provocation tests in subjects with NSAID hypersensitivity. Clin Exp Allergy. 2011;41(1):96–103.

    Article  CAS  PubMed  Google Scholar 

  136. Blanca-Lopez N, et al. Value of the clinical history in the diagnosis of urticaria/angioedema induced by NSAIDs with cross-intolerance. Clin Exp Allergy. 2013;43(1):85–91.

    Article  CAS  PubMed  Google Scholar 

  137. Dona I, et al. Characteristics of subjects experiencing hypersensitivity to non-steroidal anti-inflammatory drugs: patterns of response. Clin Exp Allergy. 2011;41(1):86–95.

    Article  CAS  PubMed  Google Scholar 

  138. Zent O, et al. Immediate allergic reactions after vaccinations—a post-marketing surveillance review. Eur J Pediatr. 2002;161(1):21–5.

    Article  CAS  PubMed  Google Scholar 

  139. Bohlke K, et al. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics. 2003;112(4):815–20.

    Article  PubMed  Google Scholar 

  140. Wood RA, et al. An algorithm for treatment of patients with hypersensitivity reactions after vaccines. Pediatrics. 2008;122(3):e771–7.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Child and Adolescent, University Hospitals of Geneva and Medical School of The University of Geneva, Geneva, Switzerland

    Jean-Christoph Caubet MD

  2. Département de Pédiatrie, Hôpitaux Universitaires de Genève, 6 rue Willy-Donzé, CH-1211, Genève 14, Switzerland

    Jean-Christoph Caubet MD

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  1. Jean-Christoph Caubet MD
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Caubet, JC. How to Manage Drug-Induced Exanthema in Children. Curr Treat Options Allergy 4, 222–238 (2017). https://doi.org/10.1007/s40521-017-0131-7

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