Background/Purpose: Cytomegalovirus (CMV) infection is a well-recognized complication in immunocompromised individuals, yet there islimited evidence guiding surveillance strategies in patients with rheumatic diseases on immunosuppressants. This study aimed to identify risk factors for CMV infection and define a high-risk subgroup warranting active screening among patients receiving prolonged, high-dose glucocorticoids.

Methods: We retrospectively analyzed 2,343 patients with rheumatic diseases who received ≥30 mg/day of prednisolone-equivalent glucocorticoids for ≥28 consecutive days at nationwide tertiary referral centers in South Korea. Clinical, laboratory, and immunosuppressant data were collected during a 28-day lead-in period from the high-dose glucocorticoid initiation. The observation period was one year following the lead-in period. Quantitative CMV PCR or pp65 antigenemia tests were performed at the discretion of the treating physician. Cox proportional hazard model was used to identify independent predictors of 1-year CMV infection. Kaplan–Meier curves were used to present a CMV infection-free survival by risk group.

Results: During the follow-up of 2131 person-years, 223 (9.7%) patients underwent CMV testing. Of these, 104 (46.6%) were diagnosed with CMV infection, and 33 (31.7%) of them met criteria for CMV disease. Multivariable analysis identified female sex (HR 0.53 [95% CI 0.33–0.83]), Sjögren’s syndrome (HR 3.17[1.35–7.44]), hypertension (HR 1.66 [1.10–2.51]), diabetes (HR 1.96 [1.29–2.98]), interstitial lung disease (HR 3.21 [2.09–4.92]), renal impairment (azotemia: HR 2.02 [1.27–3.21]; hemodialysis: HR 53.79 [1.84–7.81]), previous solid organ transplantation (HR 14.43 [5.44–38.31]), use of lymphocyte-targeting immunosuppressants (HR 2.16 [1.39–3.35]), rituximab (HR 2.02 [1.11–3.68]), leukopenia (lymphocyte < 800/μL; HR 1.96 [1.25–3.07]), anemia (Hb < 8 g/dL; HR 3.10 [1.76–5.46]), and thrombocytopenia (platelet< 150k; HR 1.68 [1.04–2.73]) as independent risk factors (Table 1). The final model demonstrated strong discriminatory performance with AUCs ranging from 0.799 to 0.891 throughout the follow-up period. High-risk patients identified by the model showed a significantly higher incidence of CMV infection than those in the low-risk group (HR 14.82 [9.687 – 22.67]) (Figure 1). Of 34 CMV disease cases, 11 (32.4%) died within one year. Disease risk was significantly associated with lymphopenia and elevated CMV titers (antigenemia >10 or PCR >1000).

Conclusion: This risk stratification model identifies patients at increased risk for CMV infection who may benefit from active surveillance. Prospective validation is needed to optimize CMV monitoring strategies in this high-risk population.

Table 1. Univariable and Multivariable Cox Regression Analyses of Risk Factors for CMV Infection

Abbreviations: AAV, ANCA associated vasculitis; IIM, Idiopathic inflammatory myopathy; IPAF, interstitial pneumonia with autoimmune features; SLE, Systemic Lupus erythematosus; AST, aspartate aminotransferase;

* Included variables with significant association in the univariable analysis. Final variable selection was performed using backward selection based on AIC

† Anemia defined as Hb < 8 g/dL; leukopenia as WBC < 800/μL; thrombocytopenia as PLT < 150 × 10³/μL.

‡ Removed from the final model based on variable selection process

§ HR and 95% CI was not calculated due to complete separation of the outcome.

¶ Cumulative steroid dose (based on prednisone) administered over the 6 months prior to index date.

£ Lymphocyte-targeting immunosuppressants include tacrolimus, cyclosporine, and mycophenolate mofetil.

Figure 1. Kaplan–Meier estimates of CMV infection–free survival by predicted risk group.

Risk stratification was based on a multivariable Cox proportional hazards model incorporating female sex, Sjögren’s syndrome, hypertension, diabetes, interstitial lung disease, renal impairment (azotemia or hemodialysis), prior solid organ transplantation, lymphocyte-targeting immunosuppressants, rituximab, leukopenia (lymphocytes < 800/μL), anemia (hemoglobin < 8 g/dL), and thrombocytopenia (platelets < 150×10³/μL). Time zero represents 28 days after initiation of high-dose corticosteroids (lead-in period). Shaded bands indicate 95% confidence intervals. Log-rank test p < 0.001.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-factors-for-cytomegalovirus-infection-in-patients-receiving-prolonged-high-dose-corticosteroids-for-rheumatic-diseases-a-retrospective-cohort-study/