Background/Purpose:  Intensive immunosuppressive treatment for remission induction in connective tissue diseases (CTDs) sometimes causes serious infection. Cytomegalovirus (CMV) is a herpesvirus remaining latent after primary mild or asymptomatic infection, and the reactivation of CMV is one of the problematic opportunistic infections in immunocompromised patients. This study was to investigate the relationship between CMV reactivation and other infections.

Methods: All hospitalized patients with CTD who started immunosuppressive agents as induction　therapy from January 2012 until March 2016 were retrospectively reviewed. Clinical information including history of all infection until June 2016 were collected from their medical charts. CMV reactivation was defined by the detection of CMV PP65 antigen in polymorphonuclear leukocytes from peripheral blood. We defined severe infection as infections which required hospitalization. The relationship between CMV reactivation and other infections were statistically analyzed.

Results: A total of 179 CTD cases with CMV PP65 measured during the remission induction therapy were enrolled in the analysis. Mean age was 57.1±17.0 years old and the female ratio was 68.7%. The CTDs were 48 systemic lupus erythematosus (26.8%), 35 antineutrophil cytoplasmic antibody-associated vasculitis (19.6%), 23 polymyositis/dermatomyositis (12.8%), 21 rheumatoid arthritis (11.7%), 10 adult-onset Still’s disease (5.6%), and others 42 (23.4%). 118 cases (65.9%) were new-onset. All cases were treated with moderate to high dose of glucocorticoid (mean prednisolone (PSL) dose, 50.0±11.0 mg/day). Methylprednisolone (mPSL) pulse therapy was conducted in 55 (30.7%), and concomitant immunosuppressants were used in 129 (72.1%). CMV was reactivated in 71 (39.7%) including 18 CMV infection (bone marrow suppression 14, pericarditis 2, liver injury 1, retinitis 1) following the initiation of remission induction therapy. During the immunosuppressive treatment, severe infection occurred in 28 cases (15.6%), and it was more frequent in the CMV-positive cases than the CMV-negative cases with statistical significance (31.0% vs. 5.6%. p<0.001). The incidence of severe lung infection (18.3% vs. 3.7%. p=0.002) and sepsis (8.5% vs. 0.0%. p=0.003) were significantly higher in the CMV-positive cases than the CMV-negative cases. The mortality rate were 14.1% in the CMV-positive cases compared with 1.9% in the CMV-negative cases (p=0.002). The relapse-free survival rate for CTD was significantly lower in the CMV-positive cases by log-rank test (p=0.001).

Conclusion: CMV reactivation in connective tissue disease by immunosuppressive therapy predicts severe infection and high mortality. The cases with CMV reactivation require particular attention to other severe infection.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cytomegalovirus-reactivation-in-connective-tissue-disease-by-immunosuppressive-therapy-predicts-severe-infection-and-high-mortality/