A case of fever in emergency medicine: the importance of clinical evaluation

A 38-years-old woman was referred to our subintensive medicine department for persistent fever associated to epigastric pain, nausea and vomiting. At the arrival, blood exams showed severe pancytopenia and increase of AST. Her clinical history did not reveal any significant associated pathology, but she complained of a recent history of three months of persistent fever, relapsing despite different antibiotic treatments and oral steroid treatment given by her general practitioner. Physical examination showed a marked increase of haepatic and splenic volume, signs of bilateral pleural effusion and the presence of continuous fever. Our first diagnostic hypotheses ranged between a subacute viral infection to a severe haematologic disorder. In the second day, blood examinations showed EBV-DNA positivity. Serum antibodies were not suggestive for autoimmunity. Despite this finding, we also observed markedly increased ferritin (> 500 ng/ml) and trygliceride levels (> 1000 mg/dl), a positive beta2-microglobilin and a markedly reduced serum haptoglobin and fibrinogen levels. A total body CT-scan showed diffuse lymphadenopathy and confirmed the bilateral pleural effusion and the marked hepato-splenomegaly observed clinically at the admission. For this reason, we proceeded with a peripheral blood cell immunophenotypization, which resulted suggestive for a chronic lymphoproliferative T-cell disorder. At this point, we felt confident in restricting our diagnostic hypotheses: particularly, the presence of a markedly increased serum ferritin and trygliceride levels and hypofibrinogenemia were strongly suggestive for lymphoma-associated haemophagocytic syndrome. For this reason, we evaluated serum IL-6 levels, which resulted markedly raised, and performed a bone marrow biopsy, showing "aspects of haemophagocytosis in perypheral T-cell lymphoma", confirming the diagnosis of haemophagocytic syndrome complicating a T-cell lymphoma. We started immediately both specific and supportive therapy for haemophagocytic syndrome, starting with high-dose metilprednisolone (1000 mg/die) and continuous haemodiafiltration to reduce rapidly serum cytokine levels. However, after an initial improvement in her clinical conditions, in the fifth day she developed acute respiratory failure and was urgently transferred to the intensive care unit, where she died the day after for multi-organ failure. Haemophagocytic lymphoistiocytosis, or haemofagocytic syndrome, is a rare group of pathologies commonly associated to several conditions, ranging from infections to autoimmunity and malignancies, characterized by a poor prognosis. Early recognition and aggressive treatment of this syndrome are essential to increase the survival probabilities, which still remain very low despite optimal medical treatment.