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Drug Eruptions and Hypersensitivity Syndromes

  • Nicole N. Harter
  • Minnelly LuuEmail author
Chapter
  • 901 Downloads

Abstract

Drug eruptions and hypersensitivity reactions are commonly encountered diagnoses in inpatient pediatric dermatology and can range from simple cutaneous eruptions to severe, life-threatening systemic reactions. Although etiology varies by diagnosis, these reactions are most often triggered by medication exposure and/or infectious agents. In this chapter, we review the presentation, pathogenesis, diagnosis, and management of the most common and/or severe drug and hypersensitivity reactions with emphasis on features distinct in the pediatric population. Case discussions include acute urticaria, urticaria multiforme, erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, morbilliform drug eruption, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, and erythema nodosum. Dermatologists, pediatricians, and inpatient pediatric providers should be familiar with the presentation and differential diagnoses of these conditions and their unique characteristics in children.

Keywords

Pediatric Children Hypersensitivity Drug eruption Drug reaction Acute urticaria Urticaria multiforme Stevens–Johnson Syndrome (SJS) Toxic epidermal necrolysis (TEN) Morbilliform Drug reaction with eosinophilia and systemic symptoms (DRESS) Acute generalized exanthematous pustulosis (AGEP) Erythema nodosum (EN) 

Abbreviations

AGEP

Acute generalized exanthematous pustulosis

ALT

Amino alanine transferase

ANA

Anti-nuclear antibody

ASO

Anti-streptolysin O

AST

Aspartate amino transferase

BSA

Body surface area

CBC

Complete blood count

CMP

Complete metabolic panel

Cr

Creatinine

CRP

C-reactive protein

CMV

Cytomegalovirus

DIF

Direct immunofluorescence

DIHS

Drug-induced hypersensitivity syndrome

DNAse B

Deoxyribonuclease B

DRESS

Drug reaction with eosinophilia and systemic symptoms

EBV

Epstein–Barr virus

EKG

Electrocardiogram

EM

Erythema multiforme

EN

Erythema nodosum

ENT

Ear-nose-and-throat

ESR

Erythrocyte sedimentation rate

EN

Erythema nodosum

Gamma GT

Gamma glutamyl transpeptidase

G-CSF

Granulocyte colony-stimulating factor

H

High

Hct

Hematocrit

HIV

Human immunodeficiency virus

Hgb

Hemoglobin

HHV-6

Human herpes virus-6

HLA

Human leukocyte antigen

HSV

Herpes simplex virus

IIF

Indirect immunofluorescence

IL-5

Interleukin-5

IV

Intravenous

IVIG

Intravenous immunoglobulin

LFT

Liver function test

L

Low

N

Normal

NSAID

Non-steroidal anti-inflammatory drug

NUD

Neutrophilic urticarial dermatosis

OTC

Over-the-counter

PO

Per Os

Plt

Platelet

SJS

Stevens–Johnson syndrome

SSSS

Staphylococcal scalded skin syndrome

TEN

Toxic epidermal necrolysis

TNF-α

Tumor necrosis factor-alpha

WBC

White blood cells

WNL

Within normal limits

References

  1. 1.
    Langley EW, Gigante J. Anaphylaxis, urticaria, and angioedema. Pediatr Rev. 2013;34(6):247–57.CrossRefPubMedGoogle Scholar
  2. 2.
    Paller A, Mancini AJ, Hurwitz S. Hurwitz clinical pediatric dermatology. Edinburgh: Elsevier; 2011. https://libproxy.usc.edu/login?url=http://ZB5LH7ED7A.search.serialssolutions.com/?V=1.0&L=ZB5LH7ED7A&S=JCs&C=TC0000551457&T=marc.
  3. 3.
    Pite H, Wedi B, Borrego LM, Kapp A, Raap U. Management of childhood urticaria: current knowledge and practical recommendations. Acta Derm Venereol. 2013;93(5):500–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Godse KV, Zawar V, Krupashankar D, Girdhar M, Kandhari S, Dhar S, et al. Consensus statement on the management of urticaria. Indian J Dermatol. 2011;56(5):485–9.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Greaves MW. Pathology and classification of urticaria. Immunol Allergy Clin North Am. 2014;34(1):1–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Mortureux P, Léauté-Labrèze C, Legrain-Lifermann V, Lamireau T, Sarlangue J, Taïeb A. Acute urticaria in infancy and early childhood: a prospective study. Arch Dermatol. 1998;134(3):319–23.CrossRefPubMedGoogle Scholar
  7. 7.
    Eichenfield LF, Frieden IJ, Mathes EF, Zaenglein AL. Neonatal and infant dermatology. London: Elsevier; 2015. https://libproxy.usc.edu/login?url=http://ZB5LH7ED7A.search.serialssolutions.com/?V=1.0&L=ZB5LH7ED7A&S=JCs&C=TC0001398876&T=marc.Google Scholar
  8. 8.
    Heelan K, Shear NH. Cutaneous drug reactions in children: an update. Paediatr Drugs. 2013;15(6):493–503.CrossRefPubMedGoogle Scholar
  9. 9.
    Marrouche N, Grattan C. Childhood urticaria. Curr Opin Allergy Clin Immunol. 2012;12(5):485–90.CrossRefPubMedGoogle Scholar
  10. 10.
    Dilek N, Özkol HU, Akbaş A, Kılınç F, Dilek AR, Saral Y, et al. Cutaneous drug reactions in children: a multicentric study. Postepy Dermatol Alergol. 2014;31(6):368–71.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Rosenblatt AE, Stein SL. Cutaneous reactions to vaccinations. Clin Dermatol. 2015;33(3):327–32.CrossRefPubMedGoogle Scholar
  12. 12.
    Mathur AN, Mathes EF. Urticaria mimickers in children. Dermatol Ther. 2013;26(6):467–75.CrossRefPubMedGoogle Scholar
  13. 13.
    Sackesen C, Sekerel BE, Orhan F, Kocabas CN, Tuncer A, Adalioglu G. The etiology of different forms of urticaria in childhood. Pediatr Dermatol. 2004;21(2):102–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Kolivras A, Theunis A, Ferster A, Lipsker D, Sass U, Dussart A, et al. Cryopyrin-associated periodic syndrome: an autoinflammatory disease manifested as neutrophilic urticarial dermatosis with additional perieccrine involvement. J Cutan Pathol. 2011;38(2):202–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Sarkar S, De A. Urticaria multiforme. Indian Pediatr. 2015;52(7):633.CrossRefPubMedGoogle Scholar
  16. 16.
    Shah KN, Honig PJ, Yan AC. “Urticaria multiforme”: a case series and review of acute annular urticarial hypersensitivity syndromes in children. Pediatrics. 2007;119(5):e1177–83.CrossRefPubMedGoogle Scholar
  17. 17.
    Emer JJ, Bernardo SG, Kovalerchik O, Ahmad M. Urticaria multiforme. J Clin Aesthet Dermatol. 2013;6(3):34–9.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Huff JC, Weston WL, Tonnesen MG. Erythema multiforme: a critical review of characteristics, diagnostic criteria, and causes. J Am Acad Dermatol. 1983;8(6):763–75.CrossRefPubMedGoogle Scholar
  19. 19.
  20. 20.
    Zaoutis LB, Chiang VW. Comprehensive pediatric hospital medicine. Philadelphia: Mosby/Elsevier; 2007. https://libproxy.usc.edu/login?url=http://ZB5LH7ED7A.search.serialssolutions.com/?V=1.0&L=ZB5LH7ED7A&S=JCs&C=TC0000387293&T=marc.Google Scholar
  21. 21.
    Sokumbi O, Wetter DA. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Int J Dermatol. 2012;51(8):889–902.CrossRefPubMedGoogle Scholar
  22. 22.
    Schalock PC, Dinulos JG, Pace N, Schwarzenberger K, Wenger JK. Erythema multiforme due to Mycoplasma pneumoniae infection in two children. Pediatr Dermatol. 2006;23(6):546–55.CrossRefPubMedGoogle Scholar
  23. 23.
    Keller N, Gilad O, Marom D, Marcus N, Garty BZ. Nonbullous erythema multiforme in hospitalized children: a 10-year survey. Pediatr Dermatol. 2015;32(5):701–3.CrossRefPubMedGoogle Scholar
  24. 24.
    Forman R, Koren G, Shear NH. Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a review of 10 years’ experience. Drug Saf. 2002;25(13):965–72.CrossRefPubMedGoogle Scholar
  25. 25.
    Katoulis AC, Liakou A, Bozi E, Theodorakis M, Alevizou A, Zafeiraki A, et al. Erythema multiforme following vaccination for human papillomavirus. Dermatology. 2010;220(1):60–2.CrossRefPubMedGoogle Scholar
  26. 26.
    Auquier-Dunant A, Mockenhaupt M, Naldi L, Correia O, Schröder W, Roujeau JC, et al. Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study. Arch Dermatol. 2002;138(8):1019–24.CrossRefPubMedGoogle Scholar
  27. 27.
    Moreau JF, Watson RS, Hartman ME, Linde-Zwirble WT, Ferris LK. Epidemiology of ophthalmologic disease associated with erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis in hospitalized children in the United States. Pediatr Dermatol. 2014;31(2):163–8.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Weston WL, Morelli JG. Herpes simplex virus-associated erythema multiforme in prepubertal children. Arch Pediatr Adolesc Med. 1997;151(10):1014–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Canavan TN, Mathes EF, Frieden I, Shinkai K. Mycoplasma pneumoniae-induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: a systematic review. J Am Acad Dermatol. 2014;72(2):239–45.CrossRefGoogle Scholar
  30. 30.
    Léauté-Labrèze C, Lamireau T, Chawki D, Maleville J, Taïeb A. Diagnosis, classification, and management of erythema multiforme and Stevens-Johnson syndrome. Arch Dis Child. 2000;83(4):347–52.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Rizzo JA, Johnson R, Cartie RJ. Pediatric toxic epidermal necrolysis: experience of a tertiary burn center. Pediatr Dermatol. 2015;32(5):704–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Noguera-Morel L, Hernández-Martín Á, Torrelo A. Cutaneous drug reactions in the pediatric population. Pediatr Clin North Am. 2014;61(2):403–26.CrossRefPubMedGoogle Scholar
  33. 33.
    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
  34. 34.
    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
  35. 35.
    Quirke KP, Beck A, Gamelli RL, Mosier MJ. A 15-year review of pediatric toxic epidermal necrolysis. J Burn Care Res. 2015;36(1):130–6.CrossRefPubMedGoogle Scholar
  36. 36.
    Del Pozzo-Magana BR, Lazo-Langner A, Carleton B, Castro-Pastrana LI, Rieder MJ. A systematic review of treatment of drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in children. J Popul Ther Clin Pharmacol. 2011;18:e121–33.PubMedGoogle Scholar
  37. 37.
    Koh MJ, Tay YK. An update on Stevens-Johnson syndrome and toxic epidermal necrolysis in children. Curr Opin Pediatr. 2009;21(4):505–10.CrossRefPubMedGoogle Scholar
  38. 38.
    Worswick S, Cotliar J. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of treatment options. Dermatol Ther. 2011;24(2):207–18.CrossRefPubMedGoogle Scholar
  39. 39.
    Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: part II. Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol. 2013;69(2):187.e1–16. quiz 203-4.CrossRefGoogle Scholar
  40. 40.
    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
  41. 41.
    Yildirim Cetin G, Sayar H, Ozkan F, Kurtulus S, Kesici F, Sayarlioglu M. A case of toxic epidermal necrolysis-like skin lesions with systemic lupus erythematosus and review of the literature. Lupus. 2013;22(8):839–46.CrossRefPubMedGoogle Scholar
  42. 42.
    Villada G, Roujeau JC, Cordonnier C, Bagot M, Kuentz M, Wechsler J, et al. Toxic epidermal necrolysis after bone marrow transplantation: study of nine cases. J Am Acad Dermatol. 1990;23(5 Pt 1):870–5.CrossRefPubMedGoogle Scholar
  43. 43.
    Macedo FI, Faris J, Lum LG, Gabali A, Uberti JP, Ratanatharathorn V, et al. Extensive toxic epidermal necrolysis versus acute graft versus host disease after allogenic hematopoietic stem-cell transplantation: challenges in diagnosis and management. J Burn Care Res. 2014;35(6):e431–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Jeanmonod P, Hubbuch M, Grünhage F, Meiser A, Rass K, Schilling MK, et al. Graft-versus-host disease or toxic epidermal necrolysis: diagnostic dilemma after liver transplantation. Transpl Infect Dis. 2012;14(4):422–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Beck A, Quirke KP, Gamelli RL, Mosier MJ. Pediatric toxic epidermal necrolysis: using SCORTEN and predictive models to predict morbidity when a focus on mortality is not enough. J Burn Care Res. 2015;36(1):167–77.CrossRefPubMedGoogle Scholar
  46. 46.
    Spies M, Sanford AP, Aili Low JF, Wolf SE, Herndon DN. Treatment of extensive toxic epidermal necrolysis in children. Pediatrics. 2001;108(5):1162–8.CrossRefPubMedGoogle Scholar
  47. 47.
    Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg. 1996;15(4):250–7.CrossRefPubMedGoogle Scholar
  48. 48.
    Kardaun SH, Sidoroff A, Valeyrie-Allanore L, Halevy S, Davidovici BB, Mockenhaupt M, et al. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol. 2007;156(3):609–11.CrossRefPubMedGoogle Scholar
  49. 49.
    Shiohara T, Iijima M, Ikezawa Z, Hashimoto K. The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations. Br J Dermatol. 2007;156(5):1083–4.CrossRefPubMedGoogle Scholar
  50. 50.
    Belver MT, Michavila A, Bobolea I, Feito M, Bellón T, Quirce S. Severe delayed skin reactions related to drugs in the paediatric age group: a review of the subject by way of three cases (Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS). Allergol Immunopathol (Madr). 2016;44(1):83–95.CrossRefGoogle Scholar
  51. 51.
    Camous X, Calbo S, Picard D, Musette P. Drug reaction with eosinophilia and systemic symptoms: an update on pathogenesis. Curr Opin Immunol. 2012;24(6):730–5.CrossRefPubMedGoogle Scholar
  52. 52.
    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
  53. 53.
    Walsh SA, Creamer D. Drug reaction with eosinophilia and systemic symptoms (DRESS): a clinical update and review of current thinking. Clin Exp Dermatol. 2011;36(1):6–11.CrossRefPubMedGoogle Scholar
  54. 54.
    Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: part I. Clinical perspectives. J Am Acad Dermatol. 2013;68(5):693.e1–14. quiz 706-8.CrossRefGoogle Scholar
  55. 55.
    Thankachen J, Agarwal V. Challenges in diagnosis, management, and treatment of allopurinol-induced DRESS syndrome: case report and literature review. Am J Ther. 2015;22(3):e77–83.CrossRefPubMedGoogle Scholar
  56. 56.
    Kano Y, Tohyama M, Aihara M, Matsukura S, Watanabe H, Sueki H, et al. Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR). J Dermatol. 2015;42(3):276–82.CrossRefPubMedGoogle Scholar
  57. 57.
    Alexander T, Iglesia E, Park Y, Duncan D, Peden D, Sheikh S, et al. Severe DRESS syndrome managed with therapeutic plasma exchange. Pediatrics. 2013;131(3):e945–9.CrossRefPubMedGoogle Scholar
  58. 58.
    Meadows KP, Egan CA, Vanderhooft S. Acute generalized exanthematous pustulosis (AGEP), an uncommon condition in children: case report and review of the literature. Pediatr Dermatol. 2000;17(5):399–402.CrossRefPubMedGoogle Scholar
  59. 59.
    Ersoy S, Paller AS, Mancini AJ. Acute generalized exanthematous pustulosis in children. Arch Dermatol. 2004;140(9):1172–3.CrossRefPubMedGoogle Scholar
  60. 60.
    Shin HT, Chang MW. Drug eruptions in children. Curr Probl Pediatr. 2001;31(7):207–34.PubMedGoogle Scholar
  61. 61.
    Hammerbeck AA, Daniels NH, Callen JP. Ioversol-induced acute generalized exanthematous pustulosis: a case report. Arch Dermatol. 2009;145(6):683–7.CrossRefPubMedGoogle Scholar
  62. 62.
    Torrelo A, Hernández A. Panniculitis in children. Dermatol Clin. 2008;26(4):491–500. vii.CrossRefPubMedGoogle Scholar
  63. 63.
    Requena L, Yus ES. Erythema nodosum. Dermatol Clin. 2008;26(4):425–38. v.CrossRefPubMedGoogle Scholar
  64. 64.
    Aydın-Teke T, Tanır G, Bayhan GI, Metin O, Oz N. Erythema nodosum in children: evaluation of 39 patients. Turk J Pediatr. 2014;56(2):144–9.PubMedGoogle Scholar
  65. 65.
    Kakourou T, Drosatou P, Psychou F, Aroni K, Nicolaidou P. Erythema nodosum in children: a prospective study. J Am Acad Dermatol. 2001;44(1):17–21.CrossRefPubMedGoogle Scholar
  66. 66.
    Cengiz AB, Kara A, Kanra G, Seçmeer G, Ceyhan M. Erythema nodosum in childhood: evaluation of ten patients. Turk J Pediatr. 2006;48(1):38–42.PubMedGoogle Scholar
  67. 67.
    Polcari IC, Stein SL. Panniculitis in childhood. Dermatol Ther. 2010;23(4):356–67.CrossRefPubMedGoogle Scholar
  68. 68.
    Blake T, Manahan M, Rodins K. Erythema nodosum—a review of an uncommon panniculitis. Dermatol Online J. 2014;20(4):22376.PubMedGoogle Scholar
  69. 69.
    Fathalla BM, Miller L, Brady S, Schaller JG. Cutaneous polyarteritis nodosa in children. J Am Acad Dermatol. 2005;53(4):724–8.CrossRefPubMedGoogle Scholar
  70. 70.
    Labbé L, Perel Y, Maleville J, Taïeb A. Erythema nodosum in children: a study of 27 patients. Pediatr Dermatol. 1996;13(6):447–50.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of DermatologyChildren’s Hospital Los Angeles, Keck School of Medicine of USCLos AngelesUSA

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