Benefit of treatment with tocilizumab in hemophagocytic lymphystiocytosis secondary to visceral leishmaniasis infection
Authors: M. E. C. Calvo, J. A. P. Gonzalez, A. M. Hellin, F. A. Santos
Journal: HemaSphere (2021)

Background: Visceral Leishmaniasis (VL) is a zoonotic infection produced by the Leishmania spp parasite transmitted through the bite of the Phlebotomus or Lutzomya mosquito. It is more frequent in endemic areas and a common, although underdiagnosed, cause of secondary hemophagocytic lymphohistiocytosis (HHL), consisting of a dysregulation of T lymphocytes and NK cells and uncontrolled macrophage activation. The generated cytokines storm (IFN-gamma, IL-1, 6, 10, 12, and 18) and uncontrolled hemophagocytosis result in a life-threatening hyperinflammatory state. The clinical-analytical manifestations between HLH and VL may overlap, making diagnosis difficult. Amphotericin B is the treatment of choice, together with corticosteroids and immunoglobulins in case of LHHs and no response to initial treatment. Aims: To express the importance of controlling the cytokine storm in Hemophagocytic Lymphohistiocytosis to avoid the development of the hyperinflammation state. Methods: Description of clinical case and sample of response to treatment with Tocilizumab. The follow-up was carried out until January 31, 2021. Results: A 51-year-old man with a personal history of psoriasis arthritis treated with Adalimumab and Methotrexate and cutaneous leishmaniasis on the pinna in February 2019, untreated. Consultation in the Emergency Service for a 2-week fever and general malaise, presenting progressive pancytopenia without remarkable findings in the peripheral blood smear. Viral serologies and PCR for SARS-CoV2 were negative;antigenuria for Leishmania was positive. Abdominal CT showed mild hepatomegaly and splenomegaly of 19 cm. Treatment is started with Liposomal Amphotericin B. The subsequent analytical study showed CRP 77.4 mg/L, IL-6 19.2 pg/mL, Ferritin> 4,500 ng/mL, triglycerides 217 mg/dL, AST/ALT 221/135 U/L and CD25s> 7500 U/mL. A bone marrow aspirate was performed which, together with a positive Leishmania PCR in peripheral blood and bone marrow and HScore with a probability of 94% HLH-2004 score with 6/8 items completed, LHHs to LV were diagnosed, adding Dexamethasone according to the HLH- 2004 protocol and Gammaglobulin. Despite the instaured measures, pancytopenia, fever> 38oC, liver involvement and hyperinflammatory status with IL-6 87.5 pg/mL persisted, deciding to administer a single dose of Tocilizumab 8 mg/Kg. The fever disappeared and the laboratory abnormalities were normalized in 1.5 months. Dexamethasone decrease was performed according to protocol. Currently Adalimumab has been restarted and continues with monthly doses of Amphotericin B. Summary/Conclusion: There is little scientific evidence about the targeted management of the cytokine storm generated in LHHs. Blocking the action of IL-6 with Tocilizumab at standard doses allowed adequate management of the pro-inflammatory state and the infection, without side effects and with good tolerance. Experience with Tocilizumab in LV LHHs is extremely limited. Understanding the pathophysiology of this entity and its similarity to other states of hyperactivation and immune dysregulation will allow better therapeutic regimens to be established. There is little scientific evidence about the targeted management of the cytokine storm generated in LHHs. Blocking the action of IL-6 with Tocilizumab at standard doses allowed adequate management of the pro-inflammatory state and the infection, without side effects. Experience with Tocilizumab in LV LHHs is extremely limited. Understanding the pathophysiology of this entity and its similarity to other states of hyperactivation and immune dysregulation will allow to establish better therapeutic regimens.