What question did this study set out to answer?

This research aims to highlight the occurrence of immune reconstitution inflammatory syndrome (IRIS) in non-HIV patients with Pneumocystis jirovecii pneumonia (PJP).

June 1, 2026Open Access

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

Key Points

This research aims to highlight the occurrence of immune reconstitution inflammatory syndrome (IRIS) in non-HIV patients with Pneumocystis jirovecii pneumonia (PJP).
Case report of a 60-year-old woman with non-HIV PJP and immunosuppressive therapy history.
Review of previously reported cases of non-HIV-associated PJP-IRIS, totaling eight patients.
Assessment of inflammatory markers, including IL-6 levels, during treatment adjustments.
Patient developed IRIS after glucocorticoid tapering, presenting with worsening respiratory symptoms and elevated IL-6 levels.
Reinitiation of glucocorticoid therapy led to significant inflammatory marker decrease and respiratory improvement.
Case review indicated that most patients responded well to intensive glucocorticoid therapy after initial deterioration.

Abstract

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.

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