Background 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. However, little is known about risk factors for CMV reactivation, therefore, identifying patients at risk for CMV reactivation is of importance.
Objectives To investigate risk factors relevant with CMV reactivation in patients with CTD during remission induction therapy.
Methods All hospitalized patients with CTD who started immunosuppressive agents as induction therapy from 2012 until 2015 were retrospectively reviewed. Clinical information were collected from their medical charts. CMV reactivation was defined by the detection of CMV PP65 antigen in polymorphonuclear leukocytes from peripheral blood. Risk factors for CMV reactivation were statistically analyzed.
Results A total of 170 CTD cases with CMV pp65 measured during the induction therapy were enrolled in the analysis. Mean age was 56.9±16.9 years old and the female ratio was 68.8%. The CTDs were 43 systemic lupus erythematosus (25.3%), 35 antineutrophil cytoplasmic antibody -associated vasculitis (20.6%), 21 polymyositis/dermatomyositis (12.4%), 20 rheumatoid arthritis (11.8%), 10 adult-onset Still's disease 10 (5.9%), and 41 others 41 (24.1%). 112 cases (65.9%) were new-onset. All cases were treated with moderate to high dose of glucocorticoid (mean prednisolone (PSL) dose, 50.1±10.8 mg/day). Methylprednisolone (mPSL) pulse therapy was conducted in 56 (33.9%), and concomitant immunosuppressants were used in 113 (68.5%).
CMV was reactivated in 64 (37.6%) including 16 CMV infection (bone marrow suppression 12, pericarditis 2, liver injury 1, retinitis 1). Multivariate logistic analysis identified initial PSL dose (p=0.003, OR 1.066) and lower baseline serum albumin level (p=0.023, OR 1.946) as an independent risk factor for CMV reactivation. Among 34 patients who were observed without antiviral treatment, 11 required ganciclovir during the course owing to the exacerbation of CMV disease. The lymphocyte count at 2 week after the initiation of immunosuppressive therapy in those 11 cases was significantly less than the 23 cases in whom CMV disappeared spontaneously (710±709/μl vs 1116±766/μl, p=0.016).
Conclusions The study demonstrates the risk factors for CMV reactivation in CTD patients treated with intensive immunosuppressive therapy. The results lead us to improve the management of opportunistic infection in immunosuppressed patients with CTD.
Griffiths PD. Cytomegalovirus. In: Zuckerman AZ, editor.
Principles and practice Griffiths PD. Cytomegalovirus. In: Zuckerman AZ, editor.Principles and practice of clinical virology. 6th ed. Hoboken:Wiley; 2009. p. 161–98.
Disclosure of Interest None declared
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