Hemophagocytic Lymphohistiocytosis

Abstract

To investigate the clinical features of adult patients with hemophagocytic lymphohistiocytosis (HLH) and to explore possible risk factors for death, we retrospectively reviewed the medical records of 103 adult HLH patients hospitalized from 1997 to 2012. We analyzed the underlying diseases, clinical characteristics, 1aboratory findings, outcomes, and prognostic factors. The most common cause of HLH was hematologic malignancies (n = 49), followed by infectious diseases (n = 24) and autoimmune disorders (n = 14); 24 cases were of unknown etiology. Eight patients had a combination of underlying diseases. HLH was clinically characterized by high fever (96.1%), splenomegaly (79.6%), hepatomegaly (65.0%), lymphadenopathy (53.4%), proteinuria (31.1%), skin rash (25.2%), gastrointestinal hemorrhage (14.6%), disseminated intravascular coagulation (13.6%), increased creatinine (7.8%), and central nervous system involvement (12.6%) including altered mental status (9.7%) and cranial hemorrhage (2.9%). Laboratory abnormalities included cytopenia (99.0%), serum ferritin >500 ug/L (98.4%), liver dysfunction (98.1%), hypertriglyceridemia (88.5%), hemophagocytosis in bone marrow smear (87.4%), and hypofibrinogenemia (60.9%).In addition to the treatment they received for the underlying causes, patients received therapy for HLH consisting of corticosteroids, immunosuppressive drugs, and intravenous immunoglobulin. Twenty-six patients (25.2%) recovered after treatment, and 19 of them achieved long-term remission during follow-up. Seventy-seven patients (74.8%) died because of tumor, sepsis, multiple organ failure, or HLH-related organ hemorrhage and coagulopathy. The deceased patients were more likely to be older at disease onset, male, and to present with splenomegaly and thrombocytopenia, compared to the survivors. Treatment for the underlying diseases combined with corticosteroids, immunosuppressive agents, and immunoglobulin therapy may improve the prognosis of HLH. More attention should be paid to high-risk patients to prevent the development of serious complications associated with HLH.

Synchronous brain and intravascular B‐cell lymphoma after remission of an adult hemophagocytic syndrome

“…These abnormalities are not usually considered a feature of adult HLH, although this case, like others 8, suggests that this may be a wrong assumption. Compared to other published cases of adult HLH 2, 8, our case has a detailed documentation of HLH neurological involvement and resembles a children primary HLH. Moreover, it has the particularity of remission of HLH markers after treatment with an almost complete resolution of CNS lesions, and the resurgence of CNS lesions without reappearance of HLH blood markers leading to death and the post‐mortem diagnosis of IVL.…”

“…T‐cell lymphoma and Epstein‐Barr virus infection are the most common causes of adult HLH 1, 2, 3. B‐cell lymphoma presenting with HLH is less common and it is mostly seen in the Asian‐variant of IVL 9, but not in western countries 9, 10.…”

“…Hemophagocytic lymphohistiocytosis (HLH) 1 is a rare and life‐threatening hyperinflammatory syndrome caused by genetic mutations (primary HLH) or systemic acquired conditions (secondary HLH) which in adults is most commonly associated with hematological malignancies 2, 3. Although primary and secondary HLH have usually been considered distinct entities, recent evidence has pointed to an increase in the frequency of heterozygous mutations in PRF1 , UNC13D , and STXBP2 genes, suggesting an increased overlap between the two forms of the disease 4.…”

“…In adults, neurological manifestations have been reported in up to 25% of cases 1, 2, although HLH is not usually considered in the differential diagnosis of white matter abnormalities in this age group.…”

Tratamiento exitoso de linfohistiocitosis hemofagocítica y coagulación intravascular diseminada secundarios a histoplasmosis en un paciente con VIH/sida

“…Se caracteriza clínicamente por fiebre, hepatoesplenomegalia, citopenias, hiperferritinemia, hipertrigliceridemia e hipofibrinogenemia. El tratamiento se basa principalmente en el control de la enfermedad de base, sin embargo, en muchos casos se requieren esteroides y quimioterapia (2,3), y de todas maneras, la mortalidad es alta (4).…”