Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening hyperinflammatory syndrome that can complicate vaso-occlusive crises (VOC) in sickle cell disease (SCD). Steroids are commonly used for HLH, but they may exacerbate sickle cell crises. We present a case of secondary HLH triggered by fat embolism syndrome and multiorgan failure in a patient with SCD, successfully managed with Anakinra. Case Presentation A 51-year-old female with Hemoglobin SC disease presented with back and leg pain consistent with her VOC, a week after receiving triamcinolone facial injections. Initial labs revealed leukocytosis (19), thrombocytosis (691), elevated LDH (729), transaminitis (AST 87, ALT 60), elevated creatinine (1.3) and lactate (4), and a low reticulocyte count. On day 2, she developed new fevers, altered mental status, worsening lactic acidosis (12), multiorgan failure, and acute hypoxemic respiratory failure requiring ICU transfer and intubation. Imaging revealed small right segmental pulmonary emboli with right heart strain. This was likely due to fat embolism in the context of her VOC. Exchange transfusion was performed, and anticoagulation was initiated. Despite supportive care, the patient developed high-grade fevers, hepatomegaly, worsening liver enzymes (AST 1130 and ALT 887), elevated ferritin (16,000), CRP (244), triglycerides (958); low total complement (17) and C4 levels (13) with a normal C3, and persistently low reticulocyte count. Infectious workup was negative. A high H-score pointed toward HLH. Corticosteroids were withheld due to the risk of rebound VOC. A multidisciplinary team, including rheumatology, initiated Anakinra (300 mg IV daily). Her condition significantly improved with the resolution of fever, better laboratory markers, and recovery of organ function. Discussion This case highlights the rare and life-threatening occurrence of HLH secondary to fat embolism syndrome in patients with sickle cell disease (SCD). HLH in this context likely resulted from an uncontrolled inflammatory cascade initiated by vaso-occlusion, tissue necrosis, and fat embolism-induced cytokine release. Low complement levels in this case support a hyperinflammatory state. Although corticosteroids are traditionally the first-line treatment for HLH, their use in SCD is known to increase the risk of rebound VOC, acute chest syndrome, and thrombotic complications. Anakinra, a recombinant IL-1 receptor antagonist, was chosen as a steroid-sparing alternative. Emerging evidence supports the efficacy of Anakinra in secondary HLH and sepsis-related hyperinflammation. In our patient, clinical improvement was observed soon after initiation of Anakinra, without the risks associated with corticosteroids. Conclusion Anakinra may serve as a promising steroid-sparing option in the management of HLH in patients with sickle cell disease. This abstract is funded by: none
Butt et al. (Fri,) studied this question.