Eosinophilic Drug Allergy

Abstract

While peripheral or tissue eosinophilia may certainly characterize drug eruptions, this feature is hardly pathognomonic for a medication-induced etiology. While delayed drug hypersensitivity reactions with prominent eosinophilic recruitment have been typically classified as type IVb reactions, their pathophysiology is now known to be more complex. Eosinophilic drug reactions have a diversity of presentations and may be benign and self-limited to severe and life-threatening. The extent of clinical involvement is also heterogeneous, ranging from isolated peripheral eosinophilia or single organ involvement (most often the skin and lung) to systemic disease affecting multiple organs, classically exemplified by drug-reaction with eosinophilia and systemic symptoms (DRESS). The spectrum of implicated medications in the causation of DRESS is ever expanding, and multiple factors including drug metabolites, specific HLA alleles, herpes viruses, and immune system activation have been implicated in pathogenesis. Due to this complex interplay of various factors, diagnostic workup in terms of skin and laboratory testing has not been validated. Similarly, the lack of controlled trials limits treatment options. This review also describes other localized as well as systemic manifestations of eosinophilic disease induced by various medication classes, including their individual pathophysiology, diagnosis, and management. Given the multitude of clinical patterns associated with eosinophilic drug allergy, the diagnosis can be challenging. Considerable deficits in our knowledge of these presentations remain, but the potential for severe reactions should be borne in mind in order to facilitate diagnosis and institute appropriate management.

Systemic Steroid Treatment for Imatinib-Associated Severe Skin Rash in Patients with Gastrointestinal Stromal Tumor: A Phase II Study

“…In the present study, median eosinophil count was high (1,059/μL), and 75.9% of patients had eosinophilia at enrollment. Because peripheral eosinophilia characterizes drug hypersensitivity, frequent presentation of eosinophilia may support the role of hypersensitivity in imatinib‐associated severe skin rash [32]. In addition, although no significant association was found between eosinophil count at enrollment and treatment success or recurrence of skin rash in this study, monitoring eosinophil levels is recommended in patients with imatinib‐associated skin rash to predict progression of rash and determine dose and duration of treatment.…”

Eosinophils from Physiology to Disease: A Comprehensive Review

“…The onset of DRESS usually occurs 2–8 weeks after starting the culprit drug, which implies an even higher temporal delay, when compared to other dDHR. In addition, persistence or evolution of the rash and of the organ failure despite drug discontinuation may occur, possibly as the consequence of concomitant viral reactivation [ 224 ]. The diagnostic work-up of DRESS includes patch tests and intradermal skin test with delayed reading, when clinical history is not able to identify the culprit drug.…”

Severe meningo-/encephalitis after daclizumab therapy for multiple sclerosis

“…The European Registry of Severe Cutaneous Adverse Reaction Criteria are applied for clinical diagnosis of DRESS. 12 Six patients fulfilled these criteria (Table 6). Three or more criteria are required for clinical diagnosis of DRESS.…”