Hospital Consult

DRESS Syndrome: Clinical Myths and Pearls

In partnership with the Society for Dermatology Hospitalists

Cutis. 2018 November;102(5):322-326

Drug rash with eosinophilia and systemic symptoms (DRESS syndrome), also known as drug-induced hypersensitivity syndrome, is an uncommon severe systemic hypersensitivity drug reaction. It typically develops 2 to 6 weeks after exposure to a culprit medication and presents with widespread rash, facial edema, systemic symptoms (eg, fever, rigors, hypotension), lymphadenopathy, evidence of visceral organ involvement, and often eosinophilia. The clinical myths and pearls presented here highlight some of the commonly held assumptions regarding DRESS syndrome in an effort to illuminate subtleties of managing patients with this condition.

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Practice Points

Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a clinical diagnosis, and incomplete forms may not meet formal criteria-based diagnosis.
Although DRESS syndrome typically has a morbilliform eruption, different rash morphologies may be observed.
The myocarditis of DRESS syndrome may not present with chest pain; a high index of suspicion is warranted.
Autoimmune sequelae are more frequent in patients who have had an episode of DRESS syndrome.

References

Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med, 2011;124:588-597.
Kardaun SH, Sekula P, Valeyrie-Allanore L, 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;169:1071-1080.
Intarasupht J, Kanchanomai A, Leelasattakul W, et al. Prevalence, risk factors, and mortality outcome in the drug reaction with eosinophilia and systemic symptoms patients with cardiac involvement. Int J Dermatol. 2018;57:1187-1191.
Bourgeois GP, Cafardi JA, Groysman V, et al. A review of DRESS-associated myocarditis. J Am Acad Dermatol. 2012;66:E229-E236.
Husain Z, Reddy BY, Schwartz RA. DRESS syndrome: part I. clinical perspectives. J Am Acad Dermatol. 2013;68:693.e1-693.e14; quiz 706-708.
Lee T, Lee YS, Yoon SY, et al. Characteristics of liver injury in drug-induced systemic hypersensitivity reactions. J Am Acad Dermatol. 2013;69:407-415.
Lin IC, Yang HC, Strong C, et al. Liver injury in patients with DRESS: a clinical study of 72 cases. J Am Acad Dermatol. 2015;72:984-991.
Peyrière H, Dereure O, Breton H, 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. 2006;155:422-428.
Walsh S, Diaz-Cano S, Higgins E, et al. 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. 2013;168:391-401.
Raghavan R, Eknoyan G. Acute interstitial nephritis—a reappraisal and update. Clin Nephrol. 2014;82:149-162.
Matsuda H, Saito K, Takayanagi Y, et al. Pustular-type drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to carbamazepine with systemic muscle involvement. J Dermatol. 2013;40:118-122.
Wolf R, Davidovici B, Matz H, et al. Drug rash with eosinophilia and systemic symptoms versus Stevens-Johnson Syndrome—a case that indicates a stumbling block in the current classification. Int Arch Allergy Immunol. 2006;141:308-310.
Kumar A, Goldfarb JW, Bittner EA. A case of drug rash with eosinophilia and systemic symptoms (DRESS) syndrome complicating airway management. Can J Anaesth. 2012;59:295-298.
Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med. 2003;349:1628-1635.
Berbari EF, Kanj SS, Kowalski TJ, et al; Infectious Diseases Society of America. 2015 Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015;61:E26-E46.
Lam BD, Miller MM, Sutton AV, et al. Vancomycin and DRESS: a retrospective chart review of 32 cases in Los Angeles, California. J Am Acad Dermatol. 2017;77:973-975.
Eppenberger M, Hack D, Ammann P, et al. Acute eosinophilic myocarditis with dramatic response to steroid therapy: the central role of echocardiography in diagnosis and follow-up. Tex Heart Inst J. 2013;40:326-330.
Kirchhof MG, Wong A, Dutz JP. Cyclosporine treatment of drug-induced hypersensitivity syndrome. JAMA Dermatol. 2016;152:1254-1257.
Singer EM, Wanat KA, Rosenbach MA. A case of recalcitrant DRESS syndrome with multiple autoimmune sequelae treated with intravenous immunoglobulins. JAMA Dermatol. 2013;149:494-495.
Bommersbach TJ, Lapid MI, Leung JG, et al. Management of psychotropic drug-induced DRESS syndrome: a systematic review. Mayo Clin Proc. 2016;91:787-801.
Alexander T, Iglesia E, Park Y, et al. Severe DRESS syndrome managed with therapeutic plasma exchange. Pediatrics. 2013;131:E945-E949.
Daoulah A, Alqahtani AA, Ocheltree SR, et al. Acute myocardial infarction in a 56-year-old female patient treated with sulfasalazine. Am J Emerg Med. 2012;30:638.e1-638.e3.
Joly P, Janela B, Tetart F, et al. Poor benefit/risk balance of intravenous immunoglobulins in DRESS. Arch Dermatol. 2012;148:543-544.
Kano Y, Tohyama M, Aihara M, 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;42:276-282.
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Matta JM, Flores SM, Cherit JD. Drug reaction with eosinophilia and systemic symptoms (DRESS) and its relation with autoimmunity in a reference center in Mexico. An Bras Dermatol. 2017;92:30-33.
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Drug rash with eosinophilia and systemic symptoms (DRESS syndrome), also known as drug-induced hypersensitivity syndrome, is an uncommon severe systemic hypersensitivity drug reaction. It is estimated to occur in 1 in every 1000 to 10,000 drug exposures.¹ It can affect patients of all ages and typically presents 2 to 6 weeks after exposure to a culprit medication. Classically, DRESS syndrome presents with often widespread rash, facial edema, systemic symptoms such as fever, lymphadenopathy, and evidence of visceral organ involvement. Peripheral blood eosinophilia is frequently but not universally observed.^1,2

Even with proper management, reported DRESS syndrome mortality rates worldwide are approximately 10%² or higher depending on the degree and type of other organ involvement (eg, cardiac).³ Beyond the acute manifestations of DRESS syndrome, this condition is unique in that some patients develop late-onset sequelae such as myocarditis or autoimmune conditions even years after the initial cutaneous eruption.⁴ Therefore, longitudinal evaluation is a key component of management.

The clinical myths and pearls presented here highlight some of the commonly held assumptions regarding DRESS syndrome in an effort to illuminate subtleties of managing patients with this condition (Table).

Myth: DRESS syndrome may only be diagnosed when the clinical criteria satisfy one of the established scoring systems.

Patients with DRESS syndrome can have heterogeneous manifestations. As a result, patients may develop a drug hypersensitivity with biological behavior and a natural history compatible with DRESS syndrome that does not fulfill published diagnostic criteria.⁵ The syndrome also may reveal its component manifestations gradually, thus delaying the diagnosis. The terms mini-DRESS and skirt syndrome have been employed to describe drug eruptions that clearly have systemic symptoms and more complex and pernicious biologic behavior than a simple drug exanthema but do not meet DRESS syndrome criteria. Ultimately, it is important to note that in clinical practice, DRESS syndrome exists on a spectrum of severity and the diagnosis remains a clinical one.

Pearl: The most commonly involved organ in DRESS syndrome is the liver.

Liver involvement is the most common visceral organ involved in DRESS syndrome and is estimated to occur in approximately 45.0% to 86.1% of cases.^6,7 If a patient develops the characteristic rash, peripheral blood eosinophilia, and evidence of liver injury, DRESS syndrome must be included in the differential diagnosis.

Hepatitis presenting in DRESS syndrome can be hepatocellular, cholestatic, or mixed.^6,7 Case series are varied in whether the transaminitis of DRESS syndrome tends to be more hepatocellular⁸ or cholestatic.⁷ Liver dysfunction in DRESS syndrome often lasts longer than in other severe cutaneous adverse drug reactions, and patients may improve anywhere from a few days in milder cases to months to achieve resolution of abnormalities.^6,7 Severe hepatic involvement is thought to be the most notable cause of mortality.⁹

Allergen of the year may be nearer than you think

DRESS Syndrome: Clinical Myths and Pearls

In partnership with the Society for Dermatology Hospitalists

References

Myth: DRESS syndrome may only be diagnosed when the clinical criteria satisfy one of the established scoring systems.

Pearl: The most commonly involved organ in DRESS syndrome is the liver.

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