Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS/DIHS)

  • Koji Hashimoto
  • Mikiko Tohyama
  • Tetsuo Shiohara
  • Drug-induced hypersensitivity syndrome (DIHS/DRESS) is an adverse drug-induced reaction of severity similar to that of Stevens–Johnson syndrome.

  • DIHS is distinguished from other drug reactions by certain characteristics: late onset, clinical similarity to mononucleosis-like syndrome, and prolonged course.

  • Human herpesvirus 6 (HHV-6) can be reactivated 2–3 weeks after the onset of rash in the vast majority of DIHS patients.

  • Patients with HHV-6 reactivation show more severe symptoms, including long-lasting fever, lymphadenopathy, leukocytosis, appearance of atypical lymphocytes, and hepatitis.

  • DIHS may involve encephalitis, non-autoimmune (idiopathic) fulminant type 1 diabetes mellitus and myocarditis.

  • The mortality rate for DIHS is 8%, which is higher than the mortality rate for Stevens– Johnson syndrome.


Hypersensitivity Syndrome Johnson Syndrome Atypical Lymphocyte Causative Drug Giant Cell Myocarditis 
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  1. 1.
    Singer JZ, Wallace SL (1986) The allopurinol hypersensitivity syndrome. Arthritis Rheu 29:82–87CrossRefGoogle Scholar
  2. 2.
    Tomecki KJ, Catalano CJ (1981) Dapsone hypersensitivity: the sulfone syndrome revisited. Arch Dermatol 117:38–39PubMedCrossRefGoogle Scholar
  3. 3.
    Vittorio CC, Muglia JJ (1995) Anticonvulsant hypersensitivity syndrome. Arch Intern Med 155:2285–2290PubMedCrossRefGoogle Scholar
  4. 4.
    Roujeau JC, Stern RS (1994) Severe adverse cutaneous reactions to drugs. New Engl J Med 331:1272–1285PubMedCrossRefGoogle Scholar
  5. 5.
    Bocquet H, Bagot M, Roujeau JC (1996) Drug-induced pseudo-lymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg 15:250–257PubMedCrossRefGoogle Scholar
  6. 6.
    Peyrière H, Dereure O, Breton H et al (2006) Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol 155:422–428PubMedCrossRefGoogle Scholar
  7. 7.
    Descamps V, Bouscarat F, Laglenne S et al (1997) Human her-pesvirus 6 infection associated with anticonvulsant hypersensitivity syndrome and reactive haemophagocytic syndrome. Br J Dermatol 137: 605–608PubMedCrossRefGoogle Scholar
  8. 8.
    Tohyama M, Yahata Y, Yasukawa M et al (1998) Severe hypersensitivity syndrome due to sulfasalazine associated with human herpesvirus 6. Arch Dermatol 134:1113–1117PubMedCrossRefGoogle Scholar
  9. 9.
    Suzuki Y, Inagi R, Aono T et al (1998) Human herpesvirus 6 infection as a risk factor for the development of severe drug-induced hypersensitivity syndrome. Arch Dermatol 134:1108–1112PubMedCrossRefGoogle Scholar
  10. 10.
    Callot V, Roujeau JC, Bagot M et al (1996) Drug-induced pseudolymphoma and hypersensitivity syndrome. Arch Dermatol 132:1315–1321PubMedCrossRefGoogle Scholar
  11. 11.
    Sekiguchi A, Kashiwagi T, Ishida-Yamamoto A et al (2005) Drug-induced hypersensitivity syndrome due to mexiletine associated with human herpesvirus 6 and cytomegalovirus reactivation. J Dermatol 32:278–281PubMedGoogle Scholar
  12. 12.
    Shear NH, Spielberg S, Grant D et al (1986) Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity. Ann Intern Med 105:179–194PubMedGoogle Scholar
  13. 13.
    Shiohara T, Iijima M, Ikezawa Z et al (2007) The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations. Br J Dermatol 155:1083–1084CrossRefGoogle Scholar
  14. 14.
    Salahuddin SZ, Ablashi DV, Markham PD et al (1986) Isolation of a new virus, HBLV, in patients with lymphopro-liferative disorders. Science 234:596–601PubMedCrossRefGoogle Scholar
  15. 15.
    Yamanishi K, Okuno T, Shiraki K et al (1988) Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet 1:1065–1067PubMedCrossRefGoogle Scholar
  16. 16.
    Santoro F, Kennedy PE, Locatelli G et al (1999) CD46 is a cellular receptor for human herpesvirus 6. Cell 99:817–827PubMedCrossRefGoogle Scholar
  17. 17.
    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 157:934–940PubMedCrossRefGoogle Scholar
  18. 18.
    Kano Y, Hirahara K, Sakuma K et al (2006) Several herpes-viruses can reactivate in a severe drug-induced multiorgan reaction in the same sequential order as in graft-versus-host disease. Br J Dermatol 155:301–306PubMedCrossRefGoogle Scholar
  19. 19.
    Komura K, Hasegawa M, Hamaguchi Y et al (2005) Drug-induced hypersensitivity syndrome associated with human herpesvirus 6 and cytomegarovirus reactivation. J Dermatol 32:976–981PubMedGoogle Scholar
  20. 20.
    Shear NH, Spielberg SP (1988) Anticonvulsant hypersensitivity syndrome. In vitro assessment of risk. J Clin Invest 82:1826–1832Google Scholar
  21. 21.
    Masaki T, Fukunaga A, Tohyam M et al (2003) Human herpes virus 6 encephalitis in allopurinol-induced hypersensitivity syndrome. Acta Derm Venereol 83:128–131PubMedCrossRefGoogle Scholar
  22. 22.
    Fujino Y, Nakajima M, Inoue H et al (2002) Human herpes-virus 6 encephalitis associated with hypersensitivity syndrome. Ann Neurol 51:771–774PubMedCrossRefGoogle Scholar
  23. 23.
    Descamps V, Collot S, Houhou N et al (2003) Human herpes-virus-6 encephalitis associated with hypersensitivity syndrome [letter]. Ann Neurol 53:280PubMedCrossRefGoogle Scholar
  24. 24.
    Sommers LM, Schoene RB (2002) Allopurinol hypersensitivity syndrome with pancreatic exocrine abnormalities and new-onset diabetes mellitus. Arch Intern Med 162:1190–1192PubMedCrossRefGoogle Scholar
  25. 25.
    Sekine N, Motokura T, Oki T et al (2001) Rapid loss of insulin secretion in a patient with fulminant type 1 diabetes mellitus and carbamazepine hypersensitivity syndrome. JAMA 285:1153–1154PubMedCrossRefGoogle Scholar
  26. 26.
    Daniels PR, Berry GJ, Tazelaar HD et al (2000) Giant cell myocarditis as a manifestation of drug hypersensitivity. Cardiovasc Pathol 95:287–291CrossRefGoogle Scholar
  27. 27.
    Chan YC, Tay YK, Ng SK (2002) Allopurinol hypersensitivity syndrome and acute myocardial infarction-two case reports. Ann Acad Med Singapore 31:231–233PubMedGoogle Scholar
  28. 28.
    Rahman Z, Weinberg J, Scheinfeld N (2002) Minocycline hypersensitivity syndrome manifesting with rhabdomyolysis. Int J Dermatol 147:618–619Google Scholar
  29. 29.
    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 51:56–67PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Koji Hashimoto
    • 1
  • Mikiko Tohyama
    • 1
  • Tetsuo Shiohara
    • 2
  1. 1.Department of DermatologyEhime University Graduate School of MedicineShitsukawa, ToonJapan
  2. 2.Department of DermatologyKyorin University School of MedicineShitsukawa, ToonJapan

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