Case Presentation: A 57-year-old male with HIV/AIDS and Kaposi sarcoma (KS) was admitted to the hospital with intermittent fever, fatigue, night sweats, and dry cough of six-week duration. He had been on dolutegravir and emtricitabine-alafenamide for one month but was previously non-compliant. His admission CD4 cell count was 34 cells/μL and HIV RNA was 179 copies/mL. Pancytopenia and hypoalbuminemia were also present. An infectious evaluation revealed negative cultures (blood, urine) and no evidence of opportunistic infections including cytomegalovirus, Mycobacterium avium complex, Histoplasma, Cryptococcus, or Aspergillus. Flow cytometry and bone marrow biopsy were negative for lymphoma or leukemia. CT abdomen/pelvis showed diffuse lymphadenopathy and a left inguinal lymph node core biopsy was consistent with KS. Serum human herpesvirus-8 (HHV-8) DNA was over 10 million copies/mL and CRP was 21.49 mg/L. IL-6 level was over 17 times the upper limit of normal and IL-10 was >1600 pg/mL. The diagnosis was narrowed to Kaposi sarcoma herpesvirus-associated multicentric Castleman disease (KSHV-MCD) versus Kaposi sarcoma inflammatory cytokine syndrome (KICS). Clinical status deteriorated necessitating intensive care with ventilatory and vasopressor support. Chemotherapy with doxorubicin and rituximab was started with a dramatic decrease in HHV-8 DNA, IL-10, and IL-6 after one cycle. The patient’s clinical status mildly improved but he was unable to wean off the ventilator. The patient was subsequently transitioned to comfort measures and passed away.
Discussion: KSHV-MCD and KICS are rare disorders affecting HIV-positive individuals with concomitant HHV-8 infection and are characterized by severe systemic inflammation, HHV-8 viremia, and cytokine elevation. They are indistinguishable based on clinical features alone with differentiation based on histopathologic findings on excisional lymph node biopsy (presence of plasmacytoid cells in lymph nodes in KSHV-MCD). The manifestations of these conditions can be easily mistaken for sepsis or immune reconstitution inflammatory syndrome, leading to serious consequences, as treatment is chemotherapy rather than antibiotics. Both conditions carry a high mortality rate of 50-60% unless treated early. KSHV-MCD is treated with rituximab and liposomal doxorubicin or high-dose zidovudine and valganciclovir. There are no standard treatments for KICS, but given its similarities to KSHV-MCD, the same therapy is used.
Conclusions: Although rare, the recognition of various inflammatory conditions in the setting of HIV/ HHV-8, such as KSHV-MCD and KICS, is important, especially in the hospital setting. Early identification of these conditions with appropriate, timely workup and treatment could lead to improved outcomes in these otherwise high-mortality disease entities.