Case Presentation: A 35 year old female with no significant past medical history developed fever late in the third trimester of her second pregnancy. The prior and current pregnancy had been uneventful.  The fever was believed to be viral and she rested at home.  After being seen by her OB with persistent fever, she was sent to the Hospital.  Patient’s initial labs were significant for elevated liver enzymes, anemia, and elevated lactate dehydrogenase, concerning for HELLP syndrome. Labor was induced and she delivered without complication. After delivery she was again febrile.  She was placed on broad spectrum antibiotic as the patient’s fever failed to subside.  Extensive infectious and rheumatologic workup was negative.  Computed tomography (CT) of chest/abdomen/pelvis did not show any abnormality. Further work up revealed elevated ferritin (4300) and Triglyceride level (507) suspicious for hemophagocytic lymphohistiocytosis (HLH).  A bone marrow biopsy was performed and the patient was started on high-dose steroids while awaiting results.  The patient defervesced and clinically improved. The bone marrow biopsy showed increased histiocytes with hemophagocytosis.  Soluble CD25 (IL-2 receptor alpha) was elevated (1721 pg/ml). Patient met the ⅝ of 2004 HLH diagnostic criteria with fever, hypertriglyceridemia, elevated ferritin, hemophagocytosis in bone marrow, elevated soluble CD25 and was diagnosed with HLH. She remained afebrile for the rest of the hospital stay and discharged to home with oral prednisone.  Outpatient follow up with hematology revealed that she remained afebrile and ferritin, triglycerides, and soluble CD25 levels normalized. She was tapered off steroid therapy.

Discussion:

HLH is an aggressive and life-threatening syndrome of excessive immune activation. It can occur as a familial or sporadic disorder and can be triggered by a variety of events that disrupt immune homeostasis. Early diagnosis is challenging as HLH is rare and has a varied presentation. The diagnosis of pregnancy related HLH is even more challenging as presentation can overlap with other obstectrical conditions, i.e. HELLP syndrome, sepsis, and acute fatty liver in pregnancy.  Currently there is no established treatment guideline for pregnancy related HLH.  Literature search showed 13 case reports of HLH during pregnancy and successful treatment with combinations of high dose steroids, IVIG, chemotherapy, and hematopoietic stem cell transplantation. For our patient, monotherapy with high dose dexamethasone was used effectively.

Conclusions:

This case illustrates the diagnostic and therapeutic challenges of pregnancy associated HLH.  After ruling out infections and pregnancy related emergencies, high suspicion for HLH should be raised in the presence of persistent fever with elevated ferritin and triglyceride level. Treatment should be initiated promptly for survival of patients with HLH. Choice of therapy should be tailored based on pregnancy stage, severity of disease, and the health of the fetus.