Disseminated mpox with suspected immune reconstitution inflammatory syndrome in a person living with HIV: A case report from South Kivu, Democratic Republic of the Congo.

Background: Severe mpox is increasingly reported in people living with HIV (PLHIV). While immune reconstitution inflammatory syndrome (IRIS) is well-characterised in other opportunistic infections, its role in the acute clinical course of mpox remains poorly understood. Case presentation: A 42-year-old man from eastern South Kivu, Democratic Republic of the Congo (DRC), with newly diagnosed HIV initiated tenofovir/lamivudine/dolutegravir. Two weeks later, he developed severe disseminated clade I mpox, confirmed by PCR, with more than 250 polymorphic lesions. Around day 7 of admission, while afebrile, he experienced paradoxical clinical worsening with confluent hemorrhagic and necrotic plaques, which were highly suggestive of mpox-associated IRIS. A pragmatic management protocol consisting of a 6-week tapered course of oral prednisone, broad-spectrum oral antibiotics (levofloxacin and clindamycin), high-dose acyclovir, and supportive care led to progressive skin healing and clinical recovery while ART was continued. He was discharged after 62 days at the family's request. Unfortunately, 3.5 weeks post-discharge, he died at home following the application of traditional topical preparations to residual lesions. Conclusions: This case highlights the need to consider mpox-associated IRIS in the differential diagnosis of unexplained clinical worsening of mpox in PLHIV who recently initiated ART. Although definitive confirmation of IRIS was not possible because of limited immunological investigations, the temporal association with ART initiation and the clinical course were consistent with this diagnosis. This case underscores the need for standardized diagnostic criteria, prospective evaluation of adjunctive anti-inflammatory therapies, and strengthened post-discharge community follow-up in resource-limited settings.