Abstract
We report on the successful management of severe immune reconstitution inflammatory syndrome (IRIS) in a 28-year-old Indonesian male with advanced HIV/AIDS, complicated by disseminated histoplasmosis. This case highlights the clinical challenges and innovative approaches in treating severe IRIS, where conventional management strategies proved inadequate. The patient presented with progressive clinical deterioration briefly after initiation of antiretroviral therapy (ART). Disseminated histoplasmosis was suspected based on clinical and radiographic findings and later confirmed as the underlying infectious trigger of IRIS, guiding targeted therapeutic strategies. Clinical management involved the novel use of a Janus kinase (JAK) inhibitor and a cytokine adsorption filter (CytoSorb(®)), alongside escalated antifungal and immunosuppressive therapies. This multifaceted approach not only stabilized the patient's condition but also highlighted the importance of considering advanced therapeutic options in severe IRIS cases. The use of JAK inhibition in this context provides new insights into the modulation of immune responses in IRIS, while cytokine adsorption therapy offered a method to control the systemic inflammatory response that characterizes this condition. This case underscores the critical need for awareness of uncommon pathogens like Histoplasma in IRIS and illustrates the potential for integrating novel therapeutic modalities to improve outcomes in these complex scenarios. Our experience suggests that early consideration of advanced immunomodulatory therapies should be considered in severe IRIS cases refractory to standard treatments.