Clinical presentations of hemophagocytic lymphohistiocytosis (HLH) and septic shock share many similarities, including multiple organ dysfunction and overall clinical and biological symptoms. However, these life-threatening conditions require specific and opposing treatments. Currently, no single biomarker is available to differentiate septic shock from HLH at patient admission [1, 2]. HLH is classified as a primary (genetically inherited) or a secondary, i.e., induced by various inflammatory conditions (viral infections, autoimmune processes, lymphoid malignancies, or drug allergies), immune disorder. We report here the case of a young woman with febrile shock which proved to be a HLH caused by drug-induced hypersensitivity syndrome (DIHS). As septic shock was initially suspected, the patient benefited from broad immunological screening during the first week of evolution [3]. Strikingly, this revealed massively increased expression of monocyte human leukocyte antigen-DR (mHLA-DR) at 137,021 ABC (antibody bound per cell), even though expected values in septic shock are usually drastically decreased [3]. In addition, a positive response to increasing doses of corticosteroids was observed over time (Fig. 1). More precisely, while the patient’s mHLA-DR expression was measured at 137,021 ABC at admission, it decreased to 38,961 ABC after the introduction of corticosteroids (day 3). Following the reactivation of inflammatory processes (day 5), mHLA-DR rose again (66,829 ABC). Finally, mHLA-DR returned to a normal range after increasing corticosteroid doses (20,499 ABC, day 8). All clinical features are provided in Additional file 1.

Fig. 1
figure 1

Time course of mHLA-DR in a HLH patient. Blue squares depict mHLA-DR values in the HLH patient. Red circles represent pediatric septic shock values [3]. Gray range represents interquartile range values obtained previously in healthy children [3]. *Corticosteroids introduced, receiving 2 mg/kg/day; **corticosteroid adjustment to 4 mg/kg/day

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In the present patient, the extremely increased inaugural mHLA-DR value (i.e., 137,021 ABC) helped to unequivocally exclude a diagnosis of septic shock. Indeed, in our experience (more than 600 septic shock patients monitored over several years), the vast majority of mHLA-DR values measured within the first 3 days after septic shock are reported to be < 30,000 ABC and mostly found below 10,000 ABC (normal values ranged from 15,000 to 40,000 ABC). This agrees with pathophysiology since HLH is secondary to overproduction of interferon-γ (IFN-γ), a cytokine known to be a strong inducer of mHLA-DR expression, whereas sepsis induces downregulation of mHLA-DR expression.

In conclusion, mHLA-DR may discriminate septic shock from HLH at admission despite both situations with multiple organ dysfunction sharing very common clinical and biological features (e.g., sCD25, elevated ferritin levels) [4, 5]. This result obviously needs further assessment in various types of HLH. Upon confirmation, as these two deadly conditions (i.e., septic shock and HLH) would require opposing treatments, mHLA-DR may be of crucial help for clinicians regarding patients’ care and management.