Hemophagocytic Lymphohistiocytosis: Advances in Pathophysiology, Diagnosis, and Treatment

Chandrakasan, Shanmuganathan; Filipovich, Alexandra H.

doi:10.1016/j.jpeds.2013.06.053

Cited by 208 publications

(193 citation statements)

References 58 publications

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“…It is a recessive condition caused by mutations in genes important for NK and T-cell granule-mediated cytotoxic function. 7,8 When a cytotoxic T lymphocyte or NK cell encounters an infected cell or tumor cell, a series of coordinated steps are required for an effective cytotoxic response. This includes the trafficking, docking, priming, membrane fusion, and entry of cytotoxic granules into the target cell leading to apoptosis.…”

Section: Pathophysiology and Classification Of Hlhmentioning

confidence: 99%

How I treat hemophagocytic lymphohistiocytosis in the adult patient

Schram¹,

Berliner

2015

Blood

317

318

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Hemophagocytic lymphohistiocytosis (HLH) is a devastating disorder of uncontrolled immune activation characterized by clinical and laboratory evidence of extreme inflammation. This syndrome can be caused by genetic mutations affecting cytotoxic function (familial HLH) or be secondary to infectious, rheumatologic, malignant, or metabolic conditions (acquired HLH). Prompt recognition is paramount and, without early treatment, this disorder is frequently fatal. Although HLH is well described in the pediatric population, less is known about the appropriate work-up and treatment in adults. Here, we review the clinical characteristics, diagnosis, and treatment of HLH in adults.

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Section: Pathophysiology and Classification Of Hlhmentioning

confidence: 99%

How I treat hemophagocytic lymphohistiocytosis in the adult patient

Schram¹,

Berliner

2015

Blood

317

318

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“…Primary HLH is caused by genetic defects in proteins involved in cytotoxic function in T-lymphocytes and natural killer (NK) cells, and occurs most commonly in children [7]. Mutations occur most often in the perforin gene or in genes important for the function of cytotoxic T-lymphocytes [8,9].…”

Section: Introductionmentioning

confidence: 99%

Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis

2015

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Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by the activation of the mononuclear phagocytic system. The diagnosis of HLH in adults is challenging not only because the majority of the reported data are from pediatric patients, but also because HLH occurs in many disease entities. This study reports the clinical and laboratory findings and prognostic factors of adult HLH in a large cohort managed at a single medical center from 2003 to 2014. Seventy-three patients met the HLH-2004 diagnostic criteria. The median age was 51 years (range, 18-82 years); 41 (56.2%) were male. Patients manifested fever, cytopenias, and elevated ferritin in >85% of cases. Likely causes of HLH were as follows: 30 (41.1%) infections, 21 (28.8%) malignancies, 5 (6.8%) attributed to autoimmune disorders, 1 (1.4%) primary immunodeficiency, 2 (2.7%) post solid organ transplantation, and 13 (17.8%) idiopathic. The median overall survival was 7.67 months. Patients with malignancy-associated HLH had a markedly worse survival compared with patients with non-malignancy-associated HLH (median overall survival 1.13 vs. 46.53 months, respectively; P < 0.0001). In a multivariable analysis, malignancy (hazard ratio 5 12.22; 95% CI: 2.53-59.02; P 5 0.002) correlated with poor survival. Ferritin >50,000 mg/L correlated with 30-day mortality. Survival after a diagnosis of HLH is dismal, especially among those with malignancy-associated HLH. The development of a registry for adults with HLH would improve our understanding of this syndrome, validate diagnostic criteria, and help develop effective treatment strategies.

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“…The disorder is caused by genetic mutations affecting cytotoxic function (familial HLH) or secondary to infectious, rheumatologic, or malignant conditions (acquired HLH). [1][2][3][4][5][6][7] Although hyperferritinemia can be seen in a variety of conditions, markedly elevated serum ferritin concentrations are often thought to be exclusive to rheumatologic and inflammatory disorders, including adult-onset Still disease (AOSD), HLH, and the related macrophage activation syndrome (MAS). In the pediatric population, extremely elevated ferritin is highly sensitive and specific for HLH.…”

Section: Introductionmentioning

confidence: 99%

Marked hyperferritinemia does not predict for HLH in the adult population

Schram

Campigotto

Mullally

et al. 2015

Blood

175

132

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• Highly elevated ferritin is not specific for hemophagocytic lymphohistiocytosis in adults.• Marked hyperferritinemia in adults most often occurs in the setting of renal failure, hepatocellular injury, infection, or malignancy.Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of uncontrolled immune activation that has gained increasing attention during the last decade. The diagnosis of HLH is based on a constellation of clinical and laboratory abnormalities, including elevated serum ferritin levels. In the pediatric population, marked hyperferritinemia is specific for HLH. To determine what conditions are associated with profoundly elevated ferritin in the adult population, we performed a retrospective analysis in a large academic health care system. We identified 113 patients with serum ferritin levels higher than 50 000 mg/L. The most frequently observed conditions included renal failure, hepatocellular injury, infections, and hematologic malignancies. Our results suggest that marked hyperferritinemia can be seen in a variety of conditions and is not specific for HLH in adults. (Blood. 2015;125(10):1548-1552

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Hemophagocytic Lymphohistiocytosis: Advances in Pathophysiology, Diagnosis, and Treatment

Cited by 208 publications

References 58 publications

How I treat hemophagocytic lymphohistiocytosis in the adult patient

How I treat hemophagocytic lymphohistiocytosis in the adult patient

Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis

Marked hyperferritinemia does not predict for HLH in the adult population

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