Abstract

BackgroundImmunosuppressive treatment is a common cause of cytomegalovirus (CMV) reactivation.ObjectivesTo elucidate the characteristics of CMV-positive and negative patients during the treatment for rheumatic diseases.MethodsWe retrospectively evaluated consecutive patients admitted to our department from January 2006 to October 2021 whose C7-HRP antigen were measured. We collected their age, sex, primary problem and its lesion, and test results within 3 months before C7-HRP measurement. We also investigated the use of immunosuppressants, and maximum and cumulative dose of administered prednisolone within 6 months before C7-HRP measurement. Maximum and cumulative dose of prednisolone contained methylprednisolone pulse, which was converted into prednisolone equivalent. We investigated the characteristics of CMV-positive and negative patients, and those of CMV-positive patients with or without anti-CMV drug use.ResultsOf a total of 472 patients, 85 were positive and 387 were negative for C7-HRP. The average age was 71.2 vs. 64.4 (p=0.0021). Their male-to-female ratio was 20/65 vs. 120/267 (p=0.0290). The following diseases were significantly common among CMV-positive patients: microscopic polyangiitis (21.2% vs. 3.9%, p<0.0001), adult-onset Still’s disease (7.1% vs. 1.3%, p=0.0002), and systemic sclerosis (4.7% vs. 2.1%, p=0.0273). Significantly common comorbidities of CMV-positive patients were interstitial lung disease (35.3% vs. 16.0%, p<0.0001), nephritis (23.5% vs. 11.6%, p=0.0005), peripheral nervous system disorders (11.8% vs. 5.7%, p=0.0070), alveolar hemorrhage (5.9% vs. 0.8%, p=0.0001), and peripheral circulatory disorders (4.7% vs. 1.6%, p=0.0111). Average neutrophil counts (7720 /μL vs. 6440 /μL, p=0.0001), serum creatinine (1.0 mg/dL vs. 0.9 mg/dL, p=0.0104), and hemoglobin A1c (6.3% vs. 5.7%, p=0.0030) were significantly higher among CMV-positive patients, whereas hemoglobin (10.1 g/dL vs. 11.1 g/dL, p<0.0001), lymphocyte counts (820 /μL vs. 1190 /μL, p<0.0001), platelet counts (233000 /μL vs. 259000 /μL, p<0.0001), and serum albumin (2.9 g/dL vs. 3.4 g/dL, p<0.0001) were lower. Higher maximum dose of prednisolone (534.9 mg/day vs. 135.5 mg/day, p<0.0001), intravenous cyclophosphamide (27.1% vs. 11.4%, p<0.0001), rituximab (9.4% vs. 2.1%, p<0.0001), azathioprine (23.5% vs. 14.2%, p=0.0053), cyclosporin (8.2% vs. 3.6%, p=0.0101) were significantly more often used among CMV-positive patients. Average cumulative dose of prednisolone was 3022.6 mg vs. 1408.7 mg (p<0.0001). We also performed multivariate analysis, including the patients’ age, sex, maximum and cumulative dose of prednisolone, and the use of intravenous cyclophosphamide, rituximab, azathioprine, and cyclosporin. Elderly (p=0.0006), female (p=0.0293), high cumulative dose of prednisolone (p=0.0155), and the use of cyclosporin (p=0.0479) were significantly associated with CMV-positivity. Anti-CMV drug was administered to 63.5% of CMV-positive patients. The average age was significantly higher in anti-CMV-drug-treated patients than untreated patients (73.7 vs. 67.1, p=0.0492). The CMV-treated patients had significantly higher neutrophil counts (8540 /μL vs. 6280 /μL, p<0.0001), erythrocyte sedimentation rate (57.6 mm/h vs. 40.5 mm/h, p<0.0001), and C-reactive protein (5.3 mg/dL vs. 2.6 mg/dL, p<0.0001) than the untreated patients while the other data such as complete blood counts and serum chemistry revealed no significant difference. Average maximum dose of prednisolone was significantly higher in CMV-treated patients (617.1 mg/day vs. 391.1 mg/day, p=0.0261) while average cumulative dose of prednisolone and the use of any other immunosuppressants revealed no significant difference.ConclusionIntense immunosuppression, especially with higher dose of glucocorticoids, seemed to be the major risk factor of CMV reactivation. These medications may often require anti-CMV therapy.Disclosure of InterestsNone declared

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