Background/Purpose: Intensive immunosuppressive treatment is often required for patients with autoimmune diseases, and those who are thus treated have a high risk of opportunistic infections. It is therefore important to investigate the risk of opportunistic infections to ensure appropriate management of patients with autoimmune disease. Cytomegalovirus (CMV) infection is one of the most common opportunistic infections. Since 2011 we have been performing routine weekly evaluation of CMV pp65 antigen for such patients. Here we investigated the predictive risk factors for CMV infection under remission-induction therapy in patients with autoimmune disease.

Methods: We enrolled 96 patients (male 34, female 62) with autoimmune disease who received remission-induction therapy with prednisolone at over 0.5 mg/kg/day in Niigata University Hospital between January 2017 and December 2018. We retrospectively analyzed their clinical features and laboratory data at the baseline, the treatment regimens used, and the results of CMVpp65 antigen analysis. The presence of more than 5 CMVpp65 antigen-positive cells/2 slides was defined as a positive result. We conducted univariate and multivariate analyses to identify risk factors for CMV positivity.

Results: The enrolled patients included 26 systemic lupus erythematosus (SLE), 18 anti-nucleolar cytoplasmic antibody-associated vasculitis (AAV), 8 interstitial pneumonia with anti-aminoacyl tRNA synthetase antibody, 6 mixed connective tissue disease (MCTD), 6 rheumatoid arthritis, 5 clinically amyopathic dermatomyositis (CADM), 5 adult-onset Still’s disease (AOSD), 5 Takayasu’s aortitis, and 17 other conditions. Methylprednisolone pulse therapy, intravenous cyclophosphamide, oral calcineurin inhibitor, methotrexate, azathioprine, and mycophenolate mofetil were applied in 36 (37.5%), 17 (17.7%), 7 (7.29%), 4 (4.17%), 4 (4.17%), and 3 (3.13%) patients, respectively. The median follow-up duration was 62.5 days, and 21 patients became CMV antigenemia-positive (SLE 9, AOSD 4, AAV 2, CADM 2, MCTD 2, and others 2). Univariate analysis showed that the positivity was associated with a low total lymphocyte count (TLC) (710/μl vs 1330/μl; p< 0.001), a low serum albumin level (2.70 g/dl vs 3.50 g/dl; p< 0.001), a high HbA1c level (6.4% vs 5.9%; p< 0.001), and a high initial prednisolone dosage (0.97 mg/kg/day vs 0.86 mg/kg/day; p< 0.001). Fifteen of the 21 patients in the positive group received steroid pulse therapy (p< 0.001). The Cox hazard regression model indicated that a higher age by decade (OR; 1.46 [95％CI 1.06- 2.00]), a lower TLC per 100/mL (OR; 0.827 [95%CI 0.731-0.935]), a higher HbA1c level per 1% (OR; 2.37 [1.25-4.53]), and mPSL pulse therapy (OR; 3.92 [1.33-11.5]) were independent risk factors for CMV positivity.

Conclusion: Lower TLC, lower serum albumin, higher HbA1c, and receiving steroid pulse therapy were risk factors for CMV pp65 antigen positivity. Careful monitoring is therefore necessary for such patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-factors-for-cytomegalovirus-infection-in-patients-with-autoimmune-diseases/