Abstract
INTRODUCTION: Haemophagocytic lymphohistiocytosis (HLH) is an extremely rare condition characterised by excessive immune activation leading to haemophagocytic activity and has seldom been reported in pregnancy. HLH manifests as relapsing fevers with features of multi- organ failure and has a high mortality. METHODS: A retrospective case series analysis using national data from MBRRACE-UK maternal death reports (n=5) and case notes from patients diagnosed with HLH during pregnancy at New Cross Hospital, Wolverhampton (n=2) between 2012 and 2021. RESULTS: A total of seven cases were included. Cases uniformly presented with fever and experienced prodromal illnesses consisting of lymphadenopathy, fevers, and malaise. Gestation at presentation ranged from 9/40 to 11 months postpartum. All patients had multiple cytopaenias. Other common features included elevated liver enzymes (n=5), hyperferritinaemia (n=5), splenomegaly (n=4), hypofibrinogenemia (n=4) and elevated soluble interleukin-2 receptor α (CD25) levels (n=3). Underlying causes were identified in four cases. Median time from presentation to diagnosis was 35 days. Bone marrow biopsy was diagnostic in a majority of cases. Corticosteroids and ciclosporin were the most frequently used treatments. In some cases early delivery by caesarean section or termination of pregnancy was necessary to permit maternal treatment. Progression to multi-organ failure resulting in maternal death occurred in five cases: two cases survived. Pregnancy outcomes were: livebirth at term (n=2), preterm livebirth (n=3), termination of pregnancy (n=1), and miscarriage (n=1). Of the surviving infants, one had bone marrow suppression with anaemia at birth and sensorineural deafness. CONCLUSIONS: Due to the rarity of the condition, diagnosis is often delayed. In view of the high mortality, clinicians should consider HLH early when reviewing pregnant patients with unexplained pyrexia and multi-organ dysfunction. Early involvement of haematology should be sought, as prompt diagnosis is crucial for meaningful attempts at curative therapy. Important treatment considerations include fetal viability, maternal condition and treatment toxicity.