DRESS Syndrome: Clinical Myths and Pearls
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.
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.
Pearl: New-onset proteinuria, hematuria, and sterile pyuria indicate acute interstitial nephritis that may be associated with DRESS syndrome.
Acute interstitial nephritis (AIN) is a drug-induced form of acute kidney injury that can co-occur with DRESS syndrome. Acute interstitial nephritis can present with some combination of acute kidney injury, morbilliform eruption, eosinophilia, fever, and sometimes eosinophiluria. Although AIN can be distinct from DRESS syndrome, there are cases of DRESS syndrome associated with AIN.10 In the correct clinical context, urinalysis may help by showing new-onset proteinuria, new-onset hematuria, and sterile pyuria. More common causes of acute kidney injury such as prerenal etiologies and acute tubular necrosis have a bland urinary sediment.
Myth: If the eruption is not morbilliform, then it is not DRESS syndrome.
The most common morphology of DRESS syndrome is a morbilliform eruption (Figure 1), but urticarial and atypical targetoid (erythema multiforme–like) eruptions also have been described.9 Rarely, DRESS syndrome secondary to use of allopurinol or anticonvulsants may have a pustular morphology (Figure 2), which is distinguished from acute generalized exanthematous pustulosis by its delayed onset, more severe visceral involvement, and prolonged course.11
Another reported variant demonstrates overlapping features between Stevens-Johnson syndrome/toxic epidermal necrolysis and DRESS syndrome. It may present with mucositis, atypical targetoid lesions, and vesiculobullous lesions.12 It is unclear whether this reported variant is indeed a true subtype of DRESS syndrome, as Stevens-Johnson syndrome/toxic epidermal necrolysis may present with systemic symptoms, lymphadenopathy, hepatic, renal, and pulmonary complications, among other systemic disturbances.12
,Pearl: Facial edema noted during physical examination is an important clue of DRESS syndrome.
Perhaps the most helpful findings in the diagnosis of DRESS syndrome are facial edema and anasarca (Figure 3), as facial edema is not a usual finding in sepsis. Facial edema can be severe enough that the patient’s features are dramatically altered. It may be useful to ask family members if the patient’s face appears swollen or to compare the current appearance to the patient’s driver’s license photograph. An important complication to note is laryngeal edema, which may complicate airway management and may manifest as respiratory distress, stridor, and the need for emergent intubation.13
