Researchers analyzed diagnostic approaches to evaluating severe reactive hemophagocytic lymphohistiocytosis (HLH), and they reported their findings in the journal Hematological Oncology.

“To our knowledge, this is the first work studying the diagnostic strategy for trigger identification in severe [reactive] HLH,” wrote the researchers in their report.

The researchers explained that severe reactive HLH is a life-threatening but rare condition associated with immune deficiency and marked by a cytokine storm. Identification of a trigger for severe reactive HLH has been linked to lower mortality in hospitalized patients, according to the researchers.

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The research team, based in Paris, France, retrospectively examined tissue biopsies from 134 patients treated at the intensive care unit (ICU) of a tertiary hospital to study diagnostic approaches for evaluating for severe reactive HLH.

Patients had a median age of 47 years (interquartile range, 47-56), and an underlying immunodeficiency was known for 61.2%. Nearly half of the patients (44%) were treated with vasopressors while in the ICU. Mechanical ventilation was used with 53% of patients, and 38% had renal replacement therapy. Symptomatic treatment was given to 84.3% of patients, which mostly consisted of etoposide, while steroids and intravenous immunoglobulin were also given to some patients.

For 127 patients (94.8%), the researchers identified a trigger for reactive HLH. In most cases (74.6%), the trigger was a hematologic disorder, while infection was a trigger in 15.7%, and systemic rheumatic disease was a trigger in 4.5% of cases.

Treatment directed at the identified trigger was given to 67.9% of patients in the ICU. This included anticancer chemotherapy for 65 of 100 of patients with hematologic disease, antimicrobial therapy for 24 of the 26 patients with documented infection, and steroidal therapies for those with systemic disease.

Lymph node biopsies had a diagnostic yield of 74.5%; while for skin biopsies, the diagnostic yield was 50%; for bone marrow, it was 44.2%; for liver, it was 30%; and for the spleen, it was 76.9%.

The researchers presented a diagnostic strategy for evaluating patients with severe reactive HLH. This included blood tests and often bone marrow aspiration. Biopsies were chosen based on the presumed trigger, with evidence of organ involvement being required in order for a biopsy to be performed using the involved organ. Splenectomy was identified as useful as a diagnostic tool of last resort, given its hazardous nature.

“Further studies addressing [reactive] HLH trigger identification and treatment in severe [reactive] HLH management are warranted,” concluded the researchers in their report.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Tudesq JJ, Valade S, Galicier L, et al. Diagnostic strategy for trigger identification in severe reactive hemophagocytic lymphohistiocytosis: a diagnostic accuracy study. Hematol Oncol. Published October 25, 2020. doi:10.1002/hon.2819