Haemophagocytic lymphohisticytosis—an underrecognized hyperinflammatory syndrome

Abstract

Haemophagocytic lymphohisticytosis (HLH) is a syndrome of uncontrolled, severe systemic inflammation (hyperinflammation) arising either from a genetic immune system defect [primary (pHLH)] or triggered as a complication of malignancy, infection, or rheumatologic disease [secondary (sHLH)]. Patients with HLH often have non-specific symptoms and become progressively and critically unwell, with fever, cytopenia and multi-organ failure. Untreated, HLH is almost universally fatal, but even when treated, mortality is high, particularly when HLH complicates malignancy. HLH is managed with immunosuppression, and this can seem difficult to justify in such unwell patients. This review aims to examine the diagnostic and treatment challenges posed by sHLH and to improve recognition among rheumatologists who, being expert in the management of multisystem diseases and in the use of immunosuppression, are ideally placed to deliver care and build an evidence base for better disease characterization and treatment.

Defining the scourge of COVID-19 hyperinflammatory syndrome

“…5 To estab lish criteria specific to COVID-19, Webb and colleagues did a systematic review of clinical and laboratory parameters linked to cHIS and compared those with other disease-associated cytokine storm syndrome criteria, particularly the 2016 systemic juvenile idiopathic arthritis macrophage activation syndrome criteria (appendix). 6 This approach lends credence to the concept that various hyperinflammatory syndromes triggered by different aetiologies, although not identical, share similar features and can be usefully categorised under the umbrella term of cytokine storm syndrome. 5 Webb and colleagues report that meeting two or more cHIS criteria place patients with COVID-19 at increased risk of mortality and requiring invasive mechanical ventila tion (odds ratio 1 3 The cHIS score also correlates with severity of oxygen requirement and risk for clinical deterioration of people with severe COVID-19.…”

“… 5 To establish criteria specific to COVID-19, Webb and colleagues did a systematic review of clinical and laboratory parameters linked to cHIS and compared those with other disease-associated cytokine storm syndrome criteria, particularly the 2016 systemic juvenile idiopathic arthritis macrophage activation syndrome criteria ( appendix ). 6 This approach lends credence to the concept that various hyperinflammatory syndromes triggered by different aetiologies, although not identical, share similar features and can be usefully categorised under the umbrella term of cytokine storm syndrome. 5 …”

Be-careful! Behind the storm of severe COVID-19, could be hidden macrophage activation syndrome. A case report with excellent outcome.

“…[5,8,10] In the case report of this patient, as he is elderly, with multiple comorbidities that could predispose the possibility of secondary bacterial infection, we opted in addition to coverage with antibiotics, started IVIg and corticosteroids. This strategy has already by Hutchinson et al [13] that suggested immediate use of IVIg 2g/kg associated with intravenous methylprednisolone (1g from 3 to 5 days). As our patient is diabetic, we chose to make 1g of methylprednisolone only on the rst day, and 250 mg on the next two days, always reevaluating the need or not to increase the dose through the results of laboratory tests and clinical signs, and it was not necessary increase as we could demonstrate.…”

Potential application of mesenchymal stem cells and their exosomes in lung injury: an emerging therapeutic option for COVID-19 patients

“…Secondary HLH could be precipitated by a genetic defect in cytolytic pathways or observed in during infection, malignancy, and rheumatic disease. HLH is characterized by a predominance of inflammatory cytokines and expansion of tissue macrophages displaying hemophagocytic activity [ 15 ]. Cytopenias, a state of elevated inflammatory cytokines or hypercytokinaemia, unremitting fever, elevated ferritin level, and multi-organ damage, are among the key characteristics of HLH seen in seriously ill COVID-19 patients [ 8 ].…”