Advertisement

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

  • Sylvia H. Kardaun
Chapter

Abstract

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a delayed, potentially life-threatening, hypersensitivity reaction characterized by a widespread, long-lasting skin eruption, fever, lymphadenopathy, hematological abnormalities, and organ involvement. Time to onset and course are relatively long; relapses may occur. Clinical and biological variability make DRESS a challenging diagnosis. Pathogenesis is not exactly known, but probably reflects a complex interplay of drug and viral-related factors in which genetics and abnormal metabolic pathways of drugs play an important role. Although associated with many drugs, DRESS is mainly observed after a limited number of “high risk” drugs. Early recognition, prompt withdrawal of the culprit, and treatment with corticosteroids are the mainstay of management.

Keywords

DRESS Drug hypersensitivity Eosinophilia Systemic symptoms Multi-organ involvement Viral reactivation HHV-6 

Abbreviations

AED

Antiepileptic drugs

cADR

Cutaneous adverse drug reactions

CBZ

Carbamazepine

D(I)HS

Drug (induced) hypersensitivity syndrome

DRESS

Drug reaction with eosinophilia and systemic symptoms

HHV-6

Herpes virus type 6

LTA

Lymphocyte toxicity assay

LTT

Lymphocyte transformation test

MPE

Maculopapular exanthema

Notes

Disclosure

Funding sources: None

Conflict of interest: None

References

  1. Barbaud A, Collet E, Milpied B et al (2013) A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions. Br J Dermatol 168:555–562CrossRefGoogle Scholar
  2. Barbaud A, Waton J, Herbeth B et al (2014) Comparison of cytokine gene polymorphism in drug-induced maculopapular eruption, urticaria and drug reaction with eosinophilia and systemic symptoms (DRESS). J Eur Acad Dermatol Venereol 28:491–499CrossRefGoogle Scholar
  3. Bastuji-Garin S, Rzany B, Stern RS et al (1993) Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 129:92–96CrossRefGoogle Scholar
  4. Bernstein DI, Carney J, Cherry JD (1983) Pseudo-toxic-shock syndrome due to a drug reaction. Clin Pediatr 22:524–525CrossRefGoogle Scholar
  5. Bocquet H, Bagot M, Roujeau JC (1996) Drug-induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms: DRESS). Semin Cutan Med Surg 15:250–257CrossRefGoogle Scholar
  6. Brown M, Schubert T (1986) Phenytoin hypersensitivity hepatitis and mononucleosis syndrome. J Clin Gastroenterol 8:469–477CrossRefGoogle Scholar
  7. Cacoub P, Musette P, Descamps V et al (2011) The DRESS syndrome: a literature review. Am J Med 124:588–597CrossRefGoogle Scholar
  8. Chaiken BH, Goldberg BI, Segal JP (1950) Dilantin sensitivity; report of a case of hepatitis with jaundice, pyrexia and exfoliative dermatitis. N Engl J Med 242:897–898CrossRefGoogle Scholar
  9. Chen YC, Chang CY, Cho YT et al (2013) Long-term sequelae of drug reaction with eosinophilia and systemic symptoms: a retrospective cohort study from Taiwan. J Am Acad Dermatol 68:459–465CrossRefGoogle Scholar
  10. Chi MH, Hui RC, Yang CH et al (2014) Histopathological analysis and clinical correlation of drug reaction with eosinophilia and systemic symptoms (DRESS). Br J Dermatol 170:866–873CrossRefGoogle Scholar
  11. Chiou CC, Chung WH, Hung SI et al (2006) Fulminant type 1 diabetes mellitus caused by drug hypersensitivity syndrome with human herpesvirus 6 infection. J Am Acad Dermatol 54(2 Suppl):S14–S17CrossRefGoogle Scholar
  12. Chiou CC, Yang LC, Hung SI et al (2008) Clinicopathological features and prognosis of drug rash with eosinophilia and systemic symptoms: a study of 30 cases in Taiwan. J Eur Acad Dermatol Venereol 22:1044–1049CrossRefGoogle Scholar
  13. Chung WH, Chang WC, Lee YS et al (2014) Genetic variants associated with phenytoin-related severe cutaneous adverse reactions. JAMA 312:525–534CrossRefGoogle Scholar
  14. Chung WH, Chang WC, Stocker SL et al (2015) Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin. Ann Rheum Dis 74:2157–2164CrossRefGoogle Scholar
  15. Descamps V, Ben Saïd B, Sassolas B et al (2010) Management of drug reaction with eosinophilia and systemic symptoms (DRESS). Ann Dermatol Venereol 137:703–708CrossRefGoogle Scholar
  16. Elzagallaai AA, Jahedmotlagh Z, Del Pozzo-Magaña BR et al (2010) Predictive value of the lymphocyte toxicity assay in the diagnosis of drug hypersensitivity syndrome. Mol Diagn Ther 14:317–322CrossRefGoogle Scholar
  17. Eshki M, Allanore L, Musette P et al (2009) Twelve-year analysis of severe cases of drug reaction with eosinophilia and systemic symptoms: a cause of unpredictable multiorgan failure. Arch Dermatol 145:67–72CrossRefGoogle Scholar
  18. Fruchter L, Laptook A (1981) Diphenylhydantoin hypersensitivity reaction associated with pulmonary infiltrates and hypereosinophilia. Ann Allergy 47:453–454PubMedGoogle Scholar
  19. Funck-Brentano E, Duong TA, Bouvresse S (2015) Therapeutic management of DRESS: a retrospective study of 38 cases. J Am Acad Dermatol 72:246–252CrossRefGoogle Scholar
  20. Ghislain PD, Roujeau JC (2002) Treatment of severe drug reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity syndrome. Dermatol Online J 8:5PubMedGoogle Scholar
  21. Gupta A, Eggo MC, Uetrecht JP et al (1992) Drug-induced hypothyroidism: the thyroid as a target organ in hypersensitivity reactions to anticonvulsants and sulfonamides. Clin Pharmacol Ther 51:56–67CrossRefGoogle Scholar
  22. Hicks RA, Murphy JV, Jackson MA (1988) Kawasaki-like syndrome caused by carbamazepine. Pediatr Infect Dis J 7:525–526CrossRefGoogle Scholar
  23. Hirsch LJ, Weintraub DB, Buchsbaum R, Spencer HT, Straka T, Hager M, Resor SR Jr (2006) Predictors of Lamotrigine-associated rash. Epilepsia 47:318–322CrossRefGoogle Scholar
  24. Houwerzijl J, De Gast GC, Nater JP et al (1977) Lymphocyte-stimulation tests and patch tests to carbamazepine hypersensitivity. Clin Exp Immunol 29:272–277PubMedPubMedCentralGoogle Scholar
  25. Hung SI, Chung WH, Liou LB et al (2005) HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 15:4134–4139CrossRefGoogle Scholar
  26. Ishida T, Kano Y, Mizukawa Y, Shiohara T (2014) The dynamics of herpesvirus reactivations during and after severe drug eruptions: their relation to the clinical phenotype and therapeutic outcome. Allergy 69:798–805CrossRefGoogle Scholar
  27. Iwatsuki K, Tsugiki M, Tagami H, Yamada M (1984) Infectious mononucleosis-like manifestations. An adverse reaction to sulfasalazine. Arch Dermatol 120:964–965CrossRefGoogle Scholar
  28. Kano Y, Shiohara T (2004) Sequential reactivation of herpesvirus in drug-induced hypersensitivity syndrome. Acta Derm Venereol 84:484–485PubMedGoogle Scholar
  29. Kano Y, Inaoka M, Shiohara T (2004) Association between anticonvulsant hypersensitivity syndrome and human herpesvirus 6 reactivation and hypogammaglobulinemia. Arch Dermatol 140:183–188CrossRefGoogle Scholar
  30. Kano Y, Hiraharas K, Sakuma K, Shiohara T (2006) Several herpesviruses can reactivate in a severe drug-induced multiorgan reaction in the same sequential order as in graft-versus-host disease. Br J Dermatol 155:301–306CrossRefGoogle Scholar
  31. Kano Y, Hirahara K, Mitsuyama Y et al (2007) Utility of the lymphocyte transformation test in the diagnosis of drug sensitivity: dependence on its timing and the type of drug eruption. Allergy 62:1439–1444CrossRefGoogle Scholar
  32. Kano Y, Hirahara K, Asano Y, Shiohara T (2008) HLA-B allele associations with certain drugs are not confirmed in japanese patients with severe cutaneous drug reactions. Acta Derm Venereol 88:616–618PubMedGoogle Scholar
  33. Kano Y, Ishida T, Hirahara K, Shiohara T (2010) Visceral involvements and long-term sequelae in drug-induced hypersensitivity syndrome. Med Clin North Am 94:743–759CrossRefGoogle Scholar
  34. Kardaun SH, Scheffer E, Vermeer BJ (1988) Drug induced pseudolymphomatous skin reactions. Br J Dermatol 118:545–552CrossRefGoogle Scholar
  35. Kardaun SH, Sidoroff A, Valeyrie-Allanore L et al (2007) Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol 156:609–611CrossRefGoogle Scholar
  36. Kardaun SH, Sekula P, Valeyrie-Allanore L et al (2013) Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol 169:1071–1080CrossRefGoogle Scholar
  37. Kardaun SH, Mockenhaupt M, Roujeau JC (2014) Comments on: DRESS syndrome. J Am Acad Dermatol 71:1000–1000.e2CrossRefGoogle Scholar
  38. Kleier RS, Breneman DL, Boiko S (1991) Generalized pustulation as a manifestation of the anticonvulsant hypersensitivity syndrome. Arch Dermatol 127:1361–1364CrossRefGoogle Scholar
  39. Knowles S, Shapiro L, Shear N (1996) Serious adverse reactions induced by minocycline: a report of 13 patients and review of the literature. Arch Dermatol 132:934–939CrossRefGoogle Scholar
  40. Knowles SR, Uetrecht J, Shear NH (2000) Idiosyncratic drug reactions: the reactive metabolite syndromes. Lancet 356:1587–1591CrossRefGoogle Scholar
  41. Lau G, Kwan C, Chong SM (2001) The 3-week sulphasalazine syndrome strikes again. Forensic Sci Int 122:79–84CrossRefGoogle Scholar
  42. Leeder JS, Cannon M, Nakhooda A, Spielberg SP (1988) Drug metabolite toxicity assessed in human lymphocytes with a purified, reconstituted cytochrome P-450 system. J Pharmacol Exp Ther 245:956–962PubMedGoogle Scholar
  43. Mahatma M, Haponik EK, Nelson S, Lopez A, Summer WR (1989) Phenytoin-induced acute respiratory failure with pulmonary eosinophilia. Am J Med 87:93–94CrossRefGoogle Scholar
  44. Manns MP, Obermayer-Straub P (1997) Cytochromes P450 and uridine triphosphate-glucuronosyltransferases: model autoantigens to study drug-induced, virus-induced, and autoimmune liver disease. Hepatology 26:1054–1066CrossRefGoogle Scholar
  45. Martel P, Laroche L, Courville P et al (2000) Cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with dysproteinemia. Arch Dermatol 136:881–886CrossRefGoogle Scholar
  46. Martin M, Wurpts G, Ott H et al (2010) In vitro detection and characterization of drug hypersensitivity using flow cytometry. Allergy 65:32–39CrossRefGoogle Scholar
  47. McCormack M, Alfirevic A, Bourgeois S et al (2011) HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 364:1134–1143CrossRefGoogle Scholar
  48. McMenamin RA, Davies LM, Craswell PW (1976) Drug induced interstitial nephritis, hepatitis and exfoliative dermatitis. Aust NZ J Med 6:583–587CrossRefGoogle Scholar
  49. Mennicke M, Zawodniak A, Keller M et al (2009) Fulminant liver failure after vancomycin in a sulfasalazine-induced DRESS syndrome: fatal recurrence after liver transplantation. Am J Transplant 9:2197–2202CrossRefGoogle Scholar
  50. Michael JR, Mitch WE (1976) Reversible renal failure and myositis caused by phenytoin hypersensitivity. J Am Med Assoc 236:2773–2775CrossRefGoogle Scholar
  51. Nyfeler B, Pichler WJ (1997) The lymphocyte transformation test for the diagnosis of drug allergy: sensitivity and specificity. Clin Exp Allergy 27:175–181CrossRefGoogle Scholar
  52. Ohtani T, Hiroi A, Sakurane M, Furukawa F (2003) Slow acetylator genotypes as a possible risk factor for infectious mononucleosis-like syndrome induced by salazosulfapyridine. Br J Dermatol 148:1035–1039CrossRefGoogle Scholar
  53. Ortonne N, Valeyrie-Allanore L, Bastuji-Garin S et al (2015) Histopathology of drug rash with eosinophilia and systemic symptoms syndrome: a morphological and phenotypical study. Br J Dermatol 173:50–58CrossRefGoogle Scholar
  54. Peyrière H, Dereure O, Breton H et al (2006) Network of the French pharmacovigilance centers. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol 155:422–428CrossRefGoogle Scholar
  55. Phillips EJ, Chung WH, Mockenhaupt M et al (2011) Drug hypersensitivity: pharmacogenetics and clinical syndromes. J Allergy Clin Immunol 127:S60–S66CrossRefGoogle Scholar
  56. Picard D, Janela B, Descamps V et al (2010) Drug reaction with eosinophilia and systemic symptoms (DRESS): a multiorgan antiviral T cell response. Sci Transl Med 2:46ra62CrossRefGoogle Scholar
  57. Pichler WJ, Tilch J (2004) The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy 59:809–820CrossRefGoogle Scholar
  58. Potter T, DiGregorio F, Stiff M, Hashimoto K (1994) Dilantin hypersensitivity syndrome imitating staphylococcal toxic shock. Arch Dermatol 130:856–858CrossRefGoogle Scholar
  59. Prussick R, Shear NH (1996) Dapsone hypersensitivity syndrome. J Am Acad Dermatol 35:346–349CrossRefGoogle Scholar
  60. Rieder MJ, Uetrecht J, Shear N et al (1989) Diagnosis of sulfonamide hypersensitivity reactions by in-vitro “rechallenge” with hydroxylamine metabolites. Ann Intern Med 110:286–289CrossRefGoogle Scholar
  61. Roujeau JC, Dupin N (2017) Virus reactivation in drug reaction with eosinophilia and systemic symptoms (DRESS) results from a strong drug-specific immune response. J Allergy Clin Immunol Pract 5:811–812CrossRefGoogle Scholar
  62. Roujeau JC, Stern RS (1994) Severe adverse cutaneous reactions to drugs. N Engl J Med 331:1272–1285CrossRefGoogle Scholar
  63. Sachs B, Erdmann S, Malte Baron J et al (2002) Determination of interleukin-5 secretion from drug-specific activated ex vivo peripheral blood mononuclear cells as a test system for the in vitro detection of drug sensitisation. Clin Exp Allergy 32:736–744CrossRefGoogle Scholar
  64. Sakuma K, Kano Y, Fukuhara M, Shiohara T (2008) Syndrome of inappropriate secretion of antidiuretic hormone associated with limbic encephalitis in a patient with drug-induced hypersensitivity syndrome. Clin Exp Dermatol 33:287–290CrossRefGoogle Scholar
  65. Santiago F, Gonçalo M, Vieira R et al (2010) Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS). Contact Dermatitis 62:47–53CrossRefGoogle Scholar
  66. Seishima M, Yamanaka S, Fujisawa T et al (2006) Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome. Br J Dermatol 155:344–349CrossRefGoogle Scholar
  67. Shaughnessy KK, Bouchard SM, Mohr MR et al (2010) Minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with persistent myocarditis. J Am Acad Dermatol 62:315–318CrossRefGoogle Scholar
  68. Shear NH, Spielberg SP (1988) Anticonvulsant hypersensitivity syndrome. In vitro assessment of risk. J Clin Invest 82:1826–1832CrossRefGoogle Scholar
  69. Shear N, Spielberg S, Grant D et al (1986) Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity. Ann Intern Med 105:179–184CrossRefGoogle Scholar
  70. Shiohara T, Kano Y (2017) Drug reaction with eosinophilia and systemic symptoms (DRESS): incidence, pathogenesis and management. Expert Opin Drug Saf 16:139–147PubMedGoogle Scholar
  71. Shiohara T, Inaoka M, Kano Y (2006) Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses. Allergol Int 55:1–8CrossRefGoogle Scholar
  72. Shiohara T, Iijima M, Ikezawa Z, Hashimoto K (2007) The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations. Br J Dermatol 156:1083–1084CrossRefGoogle Scholar
  73. Shiohara T, Kano Y, Takahashi R et al (2012) Drug-induced hypersensitivity syndrome: recent advances in the diagnosis, pathogenesis and management. Chem Immunol Allergy 97:122–138CrossRefGoogle Scholar
  74. Skowron F, Bensaid B, Balme B et al (2015) Drug reaction with eosinophilia and systemic symptoms (DRESS): clinicopathological study of 45 cases. J Eur Acad Dermatol Venereol 29:2199–2205CrossRefGoogle Scholar
  75. Skowron F, Bensaid B, Balme B et al (2016) Comparative histological analysis of drug-induced maculopapular exanthema and DRESS. J Eur Acad Dermatol Venereol 30:2085–2090CrossRefGoogle Scholar
  76. Spielberg S, Gordon G, Blake D et al (1981) Anticonvulsant toxicity in vitro: possible role of arene oxides. J Pharmacol Exp Ther 217:386–389PubMedGoogle Scholar
  77. Sullivan JR, Shear NH (2000) What are some of the lessons learnt from in vitro studies of severe unpredictable drug reactions? Br J Dermatol 142:205–207CrossRefGoogle Scholar
  78. Takahashi R, Kano Y, Yamazaki Y et al (2009) Defective regulatory T cells in patients with severe drug eruptions: timing of the dysfunction is associated with the pathological phenotype and outcome. J Immunol 182:8071–8079CrossRefGoogle Scholar
  79. Tas S, Simonart T (2003) Management of drug rash with eosinophilia and systemic symptoms (DRESS syndrome): an update. Dermatology 206:353–356CrossRefGoogle Scholar
  80. Tassaneeyakul W, Jantararoungtong T, Chen P et al (2009) Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population. Pharmacogenet Genomics 19:704–709CrossRefGoogle Scholar
  81. Tennis P, Stern R (1997) Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: a record linkage study. Neurology 49:542–546CrossRefGoogle Scholar
  82. Teraki Y, Shibuya M, Izaki S (2010) Stevens-Johnson syndrome and toxic epidermal necrolysis due to anticonvulsants share certain clinical and laboratory features with drug-induced hypersensitivity syndrome, despite differences in cutaneous presentations. Clin Exp Dermatol 35:723–728CrossRefGoogle Scholar
  83. Tohyama M, Hashimoto K (2011) New aspects of drug-induced hypersensitivity syndrome. J Dermatol 38:222–228CrossRefGoogle Scholar
  84. Tohyama M, Hashimoto K, Yasukawa M et al (2007) Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome. Br J Dermatol 157:934–940CrossRefGoogle Scholar
  85. Ushigome Y, Kano Y, Ishida T et al (2013) Short- and long-term outcomes of 34 patients with drug-induced hypersensitivity syndrome in a single institution. J Am Acad Dermatol 68:721–728CrossRefGoogle Scholar
  86. Vittorio CC, Muglia JJ (1995) Anticonvulsant hypersensitivity syndrome. Arch Intern Med 155:2285–2290CrossRefGoogle Scholar
  87. Wade AW, McDonald AT, Acott PD et al (1998) Human herpes virus-6 or Epstein-Barr virus infection and acute allograft rejection in pediatric kidney transplant recipients: greater risk for immunologically naive recipients. Transplant Proc 30:2091–2093CrossRefGoogle Scholar
  88. Walsh S, Diaz-Cano S, Higgins E et al (2013) Drug reaction with eosinophilia and systemic symptoms: is cutaneous phenotype a prognostic marker for outcome? A review of clinicopathological features of 27 cases. Br J Dermatol 168:391–401CrossRefGoogle Scholar
  89. Wei CH, Chung-Yee Hui R, Chang CJ et al (2011) Identifying prognostic factors for drug rash with eosinophilia and systemic symptoms (DRESS). Eur J Dermatol 21:930–937PubMedGoogle Scholar
  90. Zuliani E, Zwahlen H, Gilliet F, Marone C (2005) Vancomycin-induced hypersensitivity reaction with acute renal failure: resolution following cyclosporine treatment. Clin Nephrol 64:155–158CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Sylvia H. Kardaun
    • 1
  1. 1.Department of DermatologyUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands

Personalised recommendations