Hemophagocytic lymphohistiocytosis: what's new in old diagnostic and clinical criteria?

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a condition of overexpressed inflammatory response resulting in hypercytokinemia, macrophages infiltration and subsequent multiple organ failure. Without treatment, it leads to death. The main etiological factors include: viral, bacterial and parasitic infections, malignancies and autoinflammatory diseases. The main clinical manifestations are: high fever ≥38°C, lymphadenopathy, splenomegaly, hepatomegaly. Central nervous system involvement occurs in 30–70% of cases. Less common symptoms include: dyspnea, cough, arrhythmias, jaundice, peripheral edema, rashes, albinism and diarrhea. The picture of the disease seen in laboratory tests consists of: duopenia, hypofibrinogenemia ( < 150 mg/dL) high D-dimers level, hyperferritinemia. Other abnormalities include hypertiglyceridemia, elevated liver enzymes, hyperbilirubinemia, hypoalbuminemia and hyponatremia. Diagnostics include: laboratory tests, histopathological examination, lumbar puncture, radiological imaging, functional test and genetic checking. It is important to rule out factors mimicking HLH. Some of the old, well known criteria are no more relevant nowadays. The aim of the therapy is immunosuppressive, immunomodulatory and anti-cytokine treatment, using HLH-2004 protocol. In secondary HLH, elimination of the causative agent is critical. In case of primary HLH, or relapse of secondary forms allogenic transplantation is the only curative treatment. The prognosis is uncertain.