Hematologic findings in drug reaction with eosinophilia and systemic symptoms (<scp>DRESS</scp>)
Authors: Tatsiana Pukhalskaya, Siba El Hussein
Journal: American Journal of Hematology (2021)

A 51-years-old-man developed seizures after a traumatic fall. Following 4 weeks of carbamazepine administration, he developed drug reaction with eosinophilia and systemic symptoms (DRESS), associated with liver failure and elevated cardiac enzymes. Patient's cutaneous symptoms initially consisted of erythematous papules that coalesced into plaques on the arms, with focal follicular accentuation on the legs (Image 1A). He then developed acute generalized exanthematous pustulosis (AGEP)-like eruptions on the trunk (Image 1B), in addition to facial edema, and purpura on the arms (Image 1C). Representative plots from blood flow cytometry analysis reveal increased eosinophils (Image 2A,B), with abnormal monocytic (Image 2C,D) and granulocytic maturation patterns (Image 2E–G), increased CD8-positive T-lymphocytes, CD4-positive T-lymphocytes and a prominent NK-cell population (Image 2H). Peripheral blood smear examination shows prominent eosinophilia and atypical lymphocytosis characterized by large lymphocytes, deeply basophilic cytoplasm, irregular nuclear contours, clumped chromatin and conspicuous nucleoli (Image 3A–F). In addition, degranulated eosinophils (Image 3G) hypolobated and hypogranular neutrophils (Image 3H) and increased monocytes demonstrating immature features (hypolobated nuclei and prominent nucleoli) are noted (Image 3I–K). After administration of intravenous methylprednisolone, patient's rash and eosinophilia improved, however his liver failure worsened with time, and the patient expired shortly afterwards. Organ infiltration by eosinophils and lymphocytes in DRESS results in a severe clinical course, with potentially fatal fulminant hepatitis and myocarditis.1 Anticonvulsant medications tend the be the most common trigger: Drug metabolites are thought to stimulate T-lymphocytes leading to florid immune response; or alternatively cause viral activation (mainly HHV6, which was found to be negative in this case) leading to cytokine storm and downstream immune activation.1 AGEP is an adverse drug reaction which typically begins within 48 hours after drug exposure and has a more indolent clinical course than DRESS.2 Nevertheless, DRESS can rarely show AGEP-like features,3, 4 and it's clinically important to separate these two entities as management and prognoses are different. From a hematology point of view, unlike the characteristic hypereosinophilia in DRESS, AGEP presents predominantly with neutrophilia, with some cases demonstrating eosinophilia, following interleukin-2 and interleukin-5 secretion by upstream activation of drug-specific reactive T-lymphocytes.2 Although DRESS and AGEP are first and foremost hematologic reactions to drug metabolites with dermatologic manifestations, to date, the hematologic presentations of DRESS and AGEP are not well- illustrated in literature. Furthermore, available research is restricted to the pathobiologic description of these two entities,1, 2 and does not provide clinical clues regarding potential disease-unique features in other lineages, such as specific T-cell population expansion or characteristic monocytic/granulocytic maturation patterns by flow cytometry analysis in DRESS versus AGEP. The DRESS case we describe is characterized by prominent eosinophilia and atypical lymphocytosis, associated with abnormal granulocytic and monocytic features by morphologic examination and flow cytometry analysis. Awareness of these findings along with clinical presentation is key not confuse it for an underlying hematologic neoplastic process. The authors declare no conflict of interest.