Overlap between hemophagocytic lymphohistiocytosis and drug reaction and eosinophilia with systemic symptoms: a review

Abstract

Drug reaction and eosinophilia with systemic symptoms (DRESS), also known as drug‐induced hypersensitivity syndrome (DIHS), shares features with hemophagocytic lymphohistiocytosis (HLH), most notably fever, rash, and internal organ involvement. However, there is increasing recognition of drug‐induced (secondary) HLH and biopsy‐proven hemophagocytosis in DRESS, suggesting that HLH and DRESS not only overlap but also may be diseases on the same spectrum of immune dysfunction. To characterize existing literature on HLH/DRESS overlap, we queried the PubMed/MEDLINE database for 23 cases of HLH‐DRESS codiagnosis. Average time‐to‐onset of rash after exposure to inciting drug was 2.7 weeks. Fourteen cases (61%) clinically worsened despite initial therapy, prompting a workup with diagnosis of HLH on average 2.3 weeks after diagnosing DRESS. Nine cases met HLH diagnostic criteria and had a RegiSCAR score ≥4. Nine cases met one set of criteria with a presentation suggestive of the other. Five cases met neither criteria. A patient presenting with fever, generalized rash, bicytopenia, and internal organ involvement after drug exposure was most predictive of meeting diagnostic criteria for both HLH and DRESS. Treatment was highly variable, although most initiated systemic corticosteroids with/without IVIG, plasmapheresis, or etoposide. Patients with poor outcomes in this review were treated using steroid monotherapy and had viral reactivation. Dermatologists should consider the possibility of HLH in any patient presenting with fever, rash, internal organ involvement, and cytopenia. Additional studies will be necessary to further characterize HLH and DRESS overlap and determine optimal management.

Hypersensitivity reactions to IL-1 and IL-6 inhibitors are linked to common HLA-DRB1*15 alleles

“…7 In 39/56 (70%) sJIA/AOSD DHR cases, AST-ALT elevation was noted in the absence of macrophage activation syndrome (MAS) or other explanation. Also, cytokine storm during inhibitor treatment, which can be a manifestation of DRESS 1,2,18,19 , was significantly more common in DHR patients than in drug-tolerant sJIA/AOSD (p=8.5×10 −10 ). When MAS occurred during drug treatment, eosinophilia typically preceded this by months, consistent with evolution of DRESS-associated features.…”

“…These patients meet classification criteria for DRESS, a potentially fatal, eosinophilic systemic syndrome that can lead to organ failure and can stimulate a cytokine storm. 1,2,18,19 In relatively short-term exposure of KD patients to anakinra, a subset of patients also developed clinical manifestations consistent with drug reaction. In sJIA/AOSD and KD, the drug reactions are delayed type and differ from the immediate, anaphylactic reactions to tocilizumab we observed in association with DLD in sJIA.…”

Drug rash with eosinophilia and systemic symptoms complicated by haemophagocytic lymphohistiocytosis: is screening required?

“…HLH has rarely been reported to be triggered by DRESS, and we present this case to add to the recently growing awareness among the dermatology community of this significant and potentially life-threatening complication. 3 The reported mortality for DRESS is 10%, 4 but the figure for secondary HLH is significantly higher at 40%. 5 DRESS and HLH may be difficult to differentiate from each other (and could lie on a spectrum of immunological hypersensitivity) as they have several features in common, including fever, rash, lymphadenopathy, hepatic and renal dysfunction, and neurological abnormalities.…”

“…5 DRESS and HLH may be difficult to differentiate from each other (and could lie on a spectrum of immunological hypersensitivity) as they have several features in common, including fever, rash, lymphadenopathy, hepatic and renal dysfunction, and neurological abnormalities. 3 Laboratory findings more suggestive of DRESS include eosinophilia and atypical lymphocytosis. Features more specific to HLH include multiple cytopenias, hyperferritinaemia (this appears to be the most sensitive marker and is the most weighted parameter on the HScore), hypertriglyceridaemia and hypofibrinogenaemia.…”

“…2 Electronic devices are omnipresent in modern society, resulting in a continual rise in the amount of 'screen time' (time spent in front computers, smartphones, tablets or television). 3 Owing to this recent extensive use of digital devices, there is increasing scientific and public interest in the effects of their screens, which have a peak emission in the 400-490 nm range, on skin.…”