Manuscript
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
[1]. Its reported incidence ranges
between 2 and 5 cases per million per year and the mortality between 5
and 10% [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)
[3] and RegiSCAR
[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
[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).
In terms of treatment, steroids, either topically applied (TCS) or
systemically administered (GCS) are, besides the retrieval of the
culprit drug(s), the current mainstay of DRESS treatment
[6]. There is no consensus on the
dosage of either GCS or TCS, but there is evidence supporting that very
high-potency TCS are sufficient to treat mild, maybe even moderate DRESS
[7, 8].
GCS are the cornerstone of the management of severe DRESS cases. In
therapy-refractory patients, systemic immunosuppressants and more
recently JAK inhibitors and anti-IL5R or anti-IL5 antibodies can been
used as a second-line treatment [1,
9]. The benefit of antivirals (e.g.
valacyclovir) to treat herpes virus reactivations (especially
cytomegalovirus) is debated, since the use of a new medication in a
DRESS patient may bear the risk of multiple drug hypersensitivity
[10]. TCS/GCS should be tapered very
carefully over months. Given the risk of DRESS relapses and/or
autoimmune sequelae, patients should be regularly monitored for these.
Our medical algorithm highlights the importance of a systematic
diagnostic approach to patients with suspected DRESS. With regard to the
presented treatment algorithm, we should keep in mind that so far, the
use of all drugs to treat DRESS relies on case reports / case series and
retrospective analyses, prospective clinical trials are missing.