A 36-year-old Malawian woman with HIV diagnosed nine years prior, on ART (tenofovir, lamivudine, and efaverinz), presented with a one-year history of malaise, fatigue, subjective fever, and weight loss. She had no other relevant family, medical, or social history. Over the previous eight months, she had developed progressive cervical and axillary lymphadenopathy. The largest lymph node was two cm in diameter. There was no evidence of KS on examination. Laboratory examination was significant for hemoglobin 11.4 g/dL, platelets 157 x 103/uL, HIV RNA 4,244 copies/mL and CD4 count 62 cells/mm3 ( Table 1 ). A chest x-ray and abdominal ultrasound were normal. An excisional lymph node biopsy ( Figure 1 ) showed non-specific histologic features compatible with HIV-lymphadenopathy, with generally uniform geminal centers and prominent paracortical hyperplasia. Scattered, small lymphoid cells showed expression of latency-associated nuclear antigen-1 (LANA-1), but neither histology nor staining pattern were typical of KSHV-MCD and plasma KSHV DNA was detectable but 500 copies/mL. Similarly, there was no evidence of lymphoma or KS. Diagnostic challenges included lack of access to advanced imaging such as CT scan and PET scan as well as access to only a limited immunohistochemical antibody profile. Given documented ART virologic failure, the patient was switched to second-line ART (zidovudine, lamivudine, atazanavir/ritonavir).
Four months later, she returned with worsening diffuse lymphadenopathy, fatigue and myalgias. Her body weight had decreased from 60.4 kg to 56.5 kg. Her hemoglobin had decreased to 8.7 g/dL and her platelet count was 189 x 103/uL ( Table 1 ). Her HIV viral load was now undetectable. Repeat chest x-ray and abdominal ultrasound were normal. A differential diagnosis of IRIS secondary to tuberculosis, disseminated fungal infection, or lymphoma was considered. We also considered Kaposi sarcoma inflammatory cytokine syndrome (KICS), an inflammatory syndrome resembling MCD driven by KSHV, but KICS would require an absence of other pathology on lymph node biopsy. A repeat excisional biopsy ( Figure 1 ) showed features strongly consistent with KSHV-MCD including variably involuted germinal centers rimmed by LANA-1 positive plasmablasts and did not demonstrate tuberculosis, fungal infection, or other lymphoma.
The patient was diagnosed with MCD-IRIS and treated with eight cycles of cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, and prednisone 60 mg/m2, every three weeks. She had no serious adverse events during treatment and tolerated treatment well. After eight cycles, lymphadenopathy and systemic symptoms completely resolved, weight increased to 63.0 kg, hemoglobin increased to 12.0 g/dL, platelets increased to 233 x 103/uL, HIV viral load remained undetectable, and CD4 count increased to 191 cells/uL ( Table 1 ). KSHV viral load was undectable after chemotherapy. The patient has subsequently remained in remission for 24 months.