Extreme hyperferritinaemia, soluble interleukin‐2 receptor, and haemophagocytic lymphohistiocytosis

Haemophagocytic lymphohistiocytosis (HLH) following allogeneic haematopoietic stem cell transplantation (HSCT)—time to reappraise with modern diagnostic and treatment strategies?

“…Furthermore, the widespread availability, low cost and contribution to assessment of treatment response, mean the usefulness in the assessment of patients with suspected HLH cannot be overstated [52]. However ferritin remains a non-specific biomarker and several studies in the literature have reported high ferritin levels in association with transfusion, liver disease/hepatocellular injury, infection, haematological malignancy and renal failure more often than HLH [53].…”

“…It is an early marker of T-cell activation and high levels are associated with worse prognosis. Furthermore, it can be used as a dynamic disease activity marker with levels expected to fall in remission, and has been demonstrated to help differentiate HLH from mimics of HLH [53][54][55]. That sIL-2r reflects T-cell activation whereas ferritin reflects macrophage activation presents an opportunity for tailored therapeutics if measured concurrently [55,56].…”

Hemophagocytic lymphohistiocytosis in systemic mastocytosis treated with allogeneic bone marrow transplant: A case report

“…She met six of the eight diagnostic criteria according to HLH‐2004 (lacking splenomegaly and markedly elevated soluble IL‐2 receptor), so a diagnosis of hemophagocytic lymphohistiocytosis (HLH) was made . Although she clearly met the diagnostic criteria for HLH, the very high sensitivity and specificity of sIL‐2 in diagnosing HLH might suggest this is a similar inflammatory response rather than true HLH. Further testing did not reveal an underlying genetic mutation as the cause of her HLH.…”

Reevaluating the role of ferritin in the diagnosis of adult secondary hemophagocytic lymphohistiocytosis

“…Much of these data have focused on the criterion of serum ferritin, a non‐specific marker of inflammation which, when markedly abnormal, is often a primary driver of HLH workups among hospitalized patients . Studies examining serum ferritin thresholds >3000 ng/mL, 4000 ng/mL, 10 000 ng/mL, and 50 000 ng/mL have demonstrated that hyperferritinemia lacks specificity for HLH . However, extreme elevations in serum ferritin in the setting of critical illness continue to prompt strong consideration of HLH among clinicians, often precipitating intense concern and invasive testing .…”

“…7,8 Studies examining serum ferritin thresholds >3000 ng/mL, 4000 ng/mL, 10 000 ng/mL, and 50 000 ng/mL have demonstrated that hyperferritinemia lacks specificity for HLH. 9 However, extreme elevations in serum ferritin in the setting of critical illness continue to prompt strong consideration of HLH among clinicians, often precipitating intense concern and invasive testing. 10 Furthermore, recent guidelines issued by an expert panel reinforce the HLH-2004 criteria in their current form (including the ferritin criterion) as the gold standard for the diagnosis of adult secondary HLH.…”