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Patient: Male, 28-year-old Final Diagnosis: Kaposi sarcoma inflammatory cytokine syndrome (KICS) Symptoms: Abdominal pain • anemia • dyspnea • fever • shock • thrombocytopenia Medication: — Clinical Procedure: Skin biopsy Specialty: Infectious Diseases Objective: Background: Case Report: Conclusions: Unusual clinical course Kaposi Sarcoma Inflammatory Cytokine Syndrome (KICS) is a relatively new syndrome described in patients co-infected with Human Immunodeficiency Virus (HIV) and Kaposi Sarcoma (KS) Herpes Virus (KSHV). KICS clin-ically resembles Multicentric Castleman disease (MCD) and both present with various degrees of lymphade-nopathy, pancytopenia, HIV and KSHV viremia, and signs of systemic inflammatory syndrome (SIRS). KICS has higher mortality than MCD and is rarely recognized. Lymph node, bone marrow, or splenic biopsy can help dif-ferentiate between the 2 entities. We present a case of a 28-year-old African American man with advanced acquired immunodeficiency syndrome (AIDS) who was diagnosed with disseminated pulmonary and cutaneous KS. Following initiation of combined antiretroviral therapy (cART), rapid immunologic recovery occurred followed by rapid clinical deterioration (IRIS) with multiorgan failure, overwhelming SIRS, and ultimately death. The patient’s symptoms, signs, and laboratory findings during this episode could not be solely explained by KS-IRIS, and MCD versus KICS was diagnosed. SIRS in patients with uncontrolled HIV viremia and CD4 lymphopenia has a broad differential diagnosis, includ-ing infectious and noninfectious causes. It encompasses sepsis due to common bacterial pathogens, various HIV-specific opportunistic infections, immunological conditions such as hemophagocytic lymphohistiocytosis (HLH), and IRIS, malignancies such as primary effusion lymphoma (PEL) and MCD, and finally KCIS. Clinicians involved in treatment of these patients should have a high index of suspicion for less-known and recently described syndromes such as KICS to recognize it early and initiate timely treatment, which might improve the high mortality associated with KICS. © Am J Case Rep, 2020;.