Safe usage of anakinra and dexamethasone to treat refractory hemophagocytic lymphohistiocytosis secondary to acute disseminated histoplasmosis in a patient with HIV/AIDS

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a serious life-threatening disease if not recognised early. In patients with HIV/AIDS, this association has been reported following acute opportunistic infections, including histoplasmosis. However, optimal treatment is not known. We describe a male aged 46 years with AIDS who developed HLH following acute disseminated histoplasmosis. Presenting symptoms included fever, hepatosplenomegaly and pancytopenia. Bone marrow biopsy confirmed HLH. Initially, he was refractory to the treatment with amphotericin B, antiretroviral therapy and intravenous immunoglobulin (IVIG). Anakinra, an interleukin-1 receptor antagonist, and dexamethasone were initiated. He improved clinically, did not exhibit any harmful effects and ultimately was discharged from the hospital. This, we believe, is the first reported treatment of HLH with anakinra in a patient with AIDS and acute disseminated histoplasmosis.

Continuous Intravenous Anakinra Infusion to Calm the Cytokine Storm in Macrophage Activation Syndrome

“…Despite its FDA designation, anakinra is used off label to treat a variety of autoinflammatory diseases. Although limited, there are now case reports and series showing both sIJA‐related MAS (19‐22) and other HLH secondary subtypes (22‐27) responding favorably to anakinra. As such, it appears that anakinra may be viewed as an emerging and effective therapy in the treatment of MAS.…”

Disseminated CMV infection and HLH in a patient with well-controlled HIV and ulcerative colitis

“…HIV-associated HLH can occur at seroconversion as well as in the context of advanced HIV infection 9 10. In such contexts, uncontrolled HIV infection can be the primary trigger of HLH or lead to an immunosuppressed state so that the patient is susceptible to other infectious causes 11. Although uncommon in patients with virally suppressed HIV infection, HLH has still been reported in the contexts of other immunological triggers including malignancy12 or systemic immunosuppressant use.…”

An observational study demonstrating the efficacy of interleukin-1 antagonist (anakinra) in critically-ill patients with hemophagocytic lymphohistiocytosis

“…Renal failure, cytopenia, coagulopathy and cholestasis have been associated with elevated levels of IL-6 and IFN-γ (2,18,28). IL-1β activates lymphocytes responsible for production of these same cytokines (2,7,18,28). IL-1Ra is a competitive inhibitor of IL-1β (7,29).…”

“…Two of our patients died from opportunistic fungal infections. Fatal fungal infections have previously been reported to occur in patients receiving treatment for HLH who did not receive anakinra (28) and are likely a result of multiple risk factors including the underlying immune dysregulation associated with HLH, other immunosuppressive therapies and invasive procedures related to ICU care (30,31), and therefore these infections cannot be specifically attributed to anakinra. We consider prophylactic posaconazole or amphotericin therapy in selected ICU patients at high risk for fungal infections given the evidence of invasive fungal infection prophylaxis including mucormycosis in similarly immunocompromised patients (30,31).…”