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Case Reports
. 2025 Apr 12:55:102213.
doi: 10.1016/j.rmcr.2025.102213. eCollection 2025.

Immune reconstitution inflammatory syndrome (IRIS): Case series and review of the literature

Sebastian Schregenberger  1 , Vera Graup  2 , Adrian Schibli  3 , Benjamin Preiswerk  3 , Irène Laube  4 , Lars C Huber  5 , Melina Stüssi-Helbling  5
Affiliations
Case Reports

Immune reconstitution inflammatory syndrome (IRIS): Case series and review of the literature

Sebastian Schregenberger et al. Respir Med Case Rep. .

Abstract

Background: Immune-reconstitution inflammatory syndrome (IRIS) is a dysregulated host inflammatory response following the initiation of appropriate therapy targeting an infectious disease. It is most commonly reported in human immunodeficiency virus patients following the initiation of antiretroviral therapy; however, IRIS can also be seen in immunocompromised patients without HIV, when the immune system is recovering. The diagnosis is confirmed using clinical and laboratory data after excluding differential diagnoses and concomitant infections.

Case series: Here, we describe three cases of patients with IRIS that were treated at our tertiary care center. The first case involves a paradoxical IRIS in an HIV-positive patient with TB, where the re-initiation of ART led to an inflammatory response despite effective anti-tuberculous treatment (ATT). The second case highlights unmasking IRIS in an HIV-positive patient, where the initiation of ART revealed an underlying Epstein-Barr virus (EBV)-associated B-cell lymphoma. The third case describes paradoxical worsening of pulmonary TB in an HIV-negative patient, expanding the scope of IRIS beyond its conventional association with HIV infection.

Conclusion: These cases illustrate the various manifestations of IRIS and emphasize the need for timely diagnosis and appropriate management strategies to mitigate the potentially severe outcomes associated with this syndrome. Our report highlights the challenges faced in the diagnosis of IRIS which impede prompt onset of therapy.

Keywords: HIV; IRIS; Immune reconstitution inflammatory syndrome; Lymphoma; TB; Tuberculosis.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
case 1: CT of the chest before therapy (left) revealing bilateral consolidations, bilateral mediastinal and hilar lymphadenopathy, and middle lobe atelectasis. CT of the chest after therapy (right) with resolution of pulmonary infiltrates.
Fig. 2
Fig. 2
case 1: Bronchoscopy (left) revealing an endobronchial mass in the middle lobe bronchus. Endobronchial biopsies (H&E) revealing granulomatous inflammation (right).
Fig. 3
Fig. 3
case 2: T2-weighted MRI scan from August 2020 (left) and upon presentation in November 2020 (right), the latter showing a ring-enhancing lesion in the left frontal cortex.
Fig. 4
Fig. 4
case 2: Brain biopsy with immune histochemistry staining in H&E on the left, and prominent B-cell proliferation and expression of the oncogene latent membrane protein 1 (LMP-1) on the right.
Fig. 5
Fig. 5
case 3: CT scan of the chest with pathognomonic findings before (left and middle) and after (right) therapy.
See this image and copyright information in PMC

References

    1. Hirsch H.H., Kaufmann G., Sendi P., Battegay M. Immune reconstitution in HIV-infected patients. Clin. Infect. Dis. 2004;38:1159–1166. doi: 10.1086/383034. - DOI - PubMed
    1. Shelburne S.A., Hamill R.J., Rodriguez-Barradas M.C., Greenberg S.B., Atmar R.L., Musher D.W., et al. Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy. Medicine. 2002;81:213–227. doi: 10.1097/00005792-200205000-00005. - DOI - PubMed
    1. Namale P.E., Abdullahi L.H., Fine S., Kamkuemah M., Wilkinson R.J., Meintjes G. Paradoxical TB-IRIS in HIV-infected adults: a systematic review and meta-analysis. Future Microbiol. 2015;10:1077–1099. doi: 10.2217/fmb.15.9. - DOI - PubMed
    1. Cadena J., Thompson G.R., Ho T.T., Medina E., Hughes D.W., Patterson T.F. Immune reconstitution inflammatory syndrome after cessation of the tumor necrosis factor alpha blocker adalimumab in cryptococcal pneumonia. Diagn. Microbiol. Infect. Dis. 2009;64(3):327–330. doi: 10.1016/j.diagmicrobio.2009.03.019. - DOI - PubMed
    1. Sun H.Y., Alexander B.D., Huprikar S., Forrest G.N., Bruno D., Lyon G.M., et al. Predictors of immune reconstitution syndrome in organ transplant recipients with cryptococcosis: implications for the management of immunosuppression. Clin. Infect. Dis. 2015;60(1):36–44. doi: 10.1093/cid/ciu711. - DOI - PMC - PubMed

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