Hemophagocytic lymphohistiocytosis in the setting of HELLP Syndrome

A 30‐year‐old woman (G1P0) presented at 35 weeks' gestation with fever and jaundice. Fever persisted after delivery, and she was diagnosed ultimately with hemophagocytic lymphohistiocytosis (HLH). Her outcome was poor despite aggressive therapy. Reports of HLH in the setting of HELLP syndrome and acute fatty liver of pregnancy are rare. Hemophagocytic lymphohistiocytosis occurs when over‐reactive macrophages and histiocytes engulf erythrocytes in the bone marrow and spleen. Natural killer (NK) cell dysfunction leads to excess cytokine production from macrophages and cytotoxic lymphocytes. This uncontrolled release of cytokines leads to a spectrum of clinical symptoms ranging from flu‐like symptoms to end organ damage.1, 2, 3 Hemophagocytic lymphohistiocytosis is generally categorized as a primary or secondary phenomenon. Primary HLH occurs due to genetic mutations in the NK cell granzyme‐generating pathway and is generally diagnosed in childhood or early adulthood. Secondary HLH occurs in the setting of infection, autoimmune disease, or malignancy.4 Cases of HLH in pregnancy have only rarely been reported in the medical literature (Table ​(Table1).1). In some cases of secondary HLH, treating the underlying etiology (ie, initiating appropriate chemotherapy for the underlying malignancy or starting immunosuppression for rheumatologic disease) will lead to resolution of the HLH. In other cases, specific therapy targeting the HLH is necessary. There is no consensus standard of care therapy for HLH. The pediatric community's HLH‐94 protocol established the role of etoposide and dexamethasone as the backbone of therapy for primary HLH.5 The HLH‐2004 protocol has cyclosporine added to the protocol; long‐term results are pending.6 There is also published experience with CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) chemotherapy and anti‐thymocyte globulin with encouraging results from small, nonrandomized studies.7, 8 Left untreated, HLH is uniformly fatal. Table 1 Summation of available case reports of HLH diagnosed during pregnancy