Haemophagocytic lymphohistiocytosis secondary to disseminated adenovirus infection twenty-five years post heart-lung transplant

Disseminated adenovirus infection is recognised in transplant patients, often occurring early and associated with a high mortality rate. Treatment options are poorly understood and potentially toxic. Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory response.

A 75-year-old ex-banker presented following a fall, with a 2-week history of fevers, cough and high stoma output after a recent cruise. Past medical history included heart-lung transplant (25 years previously), diverticular disease and diabetes mellitus. Initially, he was febrile and tachycardic and blood tests showed an acute kidney injury (AKI), transaminitis and pancytopenia. Chest radiograph and urinalysis were unremarkable. Initial treatment was with co-amoxiclav and intravenous fluids for neutropenic sepsis. Computerised tomography of thorax and abdomen showed moderate splenomegaly with no lymphadenopathy or pneumonitis.

After 48 hours, he remained febrile with worsening renal and hepatic function. Nasopharyngeal swabs returned positive for adenovirus. Blood cultures were negative with undetectable serum cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA.

On day 4 he developed fulminant multi-organ failure. Further investigations were suggestive of HLH. Cidofovir/Brincidofovir were discussed as potential treatments but were difficult to obtain with concern regarding toxicity. On day 6, intravenous immunoglobulins for HLH was commenced. On day 8 he died. Adenovirus was later isolated from urine, stool and serum samples.

Early diagnosis and treatment for infection in immunosuppressed patients is crucial. The 25-year interval between transplant and disseminated adenovirus infection in this case is unprecedented. Difficulty in obtaining adenovirus treatment combined with their toxicity and uncertainty of effectiveness prevented their immediate use in this patient.