• hematology
• vaccines
• COVID-19

We report three cases of haemophagocytic lymphohistiocytosis (HLH) following the ChAdOx1 Astrazeneca vaccine. HLH is a rare but often fatal dysregulated hyperimmune response that clinically resembles sepsis.1 It is classified as either familial, with known genetic defects in lymphocyte cytotoxicity identified (such as PRF1 or UNC13D mutations) or acquired/secondary HLH (sHLH). sHLH in adults is usually secondary to infection, malignancy or autoimmune disease, although HLH triggered by conventional vaccination such as influenza has been reported.2

The pathogenesis of sHLH is poorly understood but results from disruption to immune homeostasis, with aberrant activation of T cells, natural killer cells and macrophages leading to overproduction of inflammatory cytokines such as tumour necrosis factor (TNF)-alpha,TNF-gamma, interleukin (IL)-1, IL-2, IL-6 and haemophagocytosis.

Patients present with recurrent fever, cytopaenia, liver dysfunction, organomegaly, elevated ferritin and inflammatory markers and can rapidly progress to multiorgan failure. Early symptoms are often non-specific including wasting, fatigue, purpura, dyspnoea, diarrhoea, bleeding, rash, arthralgia and lymphadenopathy.3 The Histiocyte Society diagnostic criteria (HLH-2004) that were developed for paediatric-HLH diagnosis are commonly used in adult sHLH.

Patient 1, a male in his 60s with tablet-controlled type 2 diabetes mellitus was admitted to hospital 10 days after receiving the first dose of the ChAdOx1 vaccine. He presented with breathlessness, fevers and myalgia with onset of symptoms 5 days postvaccination. He was commenced on broad spectrum antibiotics for presumed infection. CT pulmonary angiography excluded pulmonary emboli but highlighted bilateral pleural effusions. Echocardiogram showed normal biventricular systolic function. An elevated …