Non-HIV Pneumocystis jirovecii pneumonia–associated immune reconstitution inflammatory syndrome: a case report and systematic review

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a common opportunistic infection with high mortality among immunocompromised patients. Although adjunctive glucocorticoid therapy improves outcomes in HIV-associated PJP, its role in non-HIV patients remains controversial. Immune reconstitution inflammatory syndrome (IRIS), a potentially overlooked inflammatory response, may lead to rapid clinical deterioration. CASE PRESENTATION: A 60-year-old woman developed non-HIV-associated PJP following high-dose glucocorticoid therapy for anti-IgLON5 antibody-associated encephalopathy, which progressed to severe hypoxic respiratory failure. During anti-PJP treatment, glucocorticoids were rapidly tapered and discontinued because of concerns regarding immunosuppression. Subsequently, the patient developed recurrent fever, worsening oxygenation, and radiographic progression, while IL-6 levels increased from 5.3 pg/mL to 574 pg/mL. Microbiological testing revealed no evidence of new infection. Considering the recent immune reconstitution, PJP-associated IRIS was diagnosed. After glucocorticoid therapy was reinitiated while the original anti-PJP regimen was maintained, inflammatory markers decreased significantly, respiratory function improved, and mechanical ventilation was successfully discontinued. Additionally, we reviewed previously reported cases of non-HIV-associated PJP-IRIS. Combined with the present case, eight patients were included. Most cases had a clear immune reconstitution trigger and presented with progressive hypoxemia, radiographic deterioration, and inflammatory activation. Most patients improved after intensive glucocorticoid therapy. CONCLUSION: In non-HIV-associated PJP, clinical deterioration does not necessarily indicate antimicrobial treatment failure, and PJP-associated IRIS should be considered. Early recognition of inflammatory activation and timely immunomodulatory therapy may improve prognosis. Dynamic monitoring of inflammatory markers such as IL-6 may help guide glucocorticoid therapy.