Medical algorithm: Diagnosis and treatment of Drug reaction with eosinophilia and systemic symptoms
Authors: Brüggen Marie-Charlotte , Traidl Stephan , mitamura yasutaka , Walsh Sarah , French Lars , Maverakis Emanual , Oro Saskia 
Published: July 2022

Drug reaction with eosinophilia and systemic symptoms (DRESS), also
known as Drug-induced hypersensitivity syndrome (DIHS), is a rare but
severe delayed-type drug hypersensitivity reaction
[[](#ref-0001)1]. Its reported incidence ranges between 2 and 5
cases per million per year and the mortality between 5 and 10%
[[](#ref-0002)2]. DRESS is characterized by the occurrence of
an extensive rash with face edema, lymphadenopathy and fever and organ
damage, all of which seems to result from massive drug-directed T cell
response and associated eosinophilia. DRESS is a complex condition, its
clinical presentation varies depending on the cutaneous
manifestation(s), affected target organ(s) and reaction severity. The
diagnosis of DRESS is further challenged by the clinical overlay with
autoimmune, infectious and lymphoproliferative conditions, which have to
be considered in the differential diagnosis (Table 1). Eosinophilia is
detected in only 80 % of DRESS patients and can be masked by e.g. the
administration of systemic glucocorticoids (GCS). Furthermore, there are
various differences in the DRESS diagnostic criteria (Table 1) developed
by the Japanese SCAR (JSPS) [[](#ref-0003)3] and RegiSCAR
[[](#ref-0004)4] groups, the most notable being the inclusion
of herpes viremia in the criteria developed by the JSPS. All these
clinical challenges underline the importance of a systematic and
comprehensive approach when encountering a patient with suspected DRESS.
Based on the most recent literature and our clinical expertise, we
therefore suggest the medical algorithm depicted in Figure 1. DRESS
should be evoked as a differential diagnosis in patients with a rash
suspected to be drug-related and associated with head-and-neck edema
[[](#ref-0005)5]. Clinical history-taking is a critical element
to consolidate or discard a drug-related etiology: most importantly,
this should explore the dynamics of both possible DRESS clinical
symptoms and drug exposure(s) (date of onset, way and length of
administration, previous exposures / reactions). A long drug exposure
prior to disease onset, i.e. 2-8 weeks, is indicative for DRESS rather
than other drug hypersensitivities – but the duration may vary
depending on the causative drug. A thorough clinical examination, basic
laboratory work-up, electrocardiogram, and - if a rash is present - a
skin biopsy should also be performed. If the clinical presentation and
drug exposure history substantiate the DRESS diagnosis, additional
investigations should be performed depending on the suspected target
organ damage (cf. case “complementary, patient-specific work-up”).
Once the diagnosis is established, a severity assessment is warranted,
since DRESS can range from mild forms with very limited organ damage to
fulminant ones, e.g. characterized by (multi-)organ failure. There are
no consensual severity scoring. In this algorithm, we suggest the
scoring system used in France (RCT DRESSCODE, https://clinicaltrial.gov
NCT01987076).