Background/Purpose: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a disease entity characterized by inflammatory cell infiltration and necrosis of blood vessel walls. AAV usually needs intensive immunosuppressive treatment for remission induction, that sometimes brings about serious infection. Cytomegalovirus (CMV) reactivation is one of the opportunistic infections for immunosuppressed patients, therefore, identifying patients at risk for CMV reactivation is of importance. This study was to investigate risk factors relevant with CMV in patients with AAV during remission induction therapy.

Methods: All patients with AAV including microscopic polyangiitis (MPA), granuromatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA) in Keio University from April 2008 until May 2015 were retrospectively reviewed. Clinical information during remission induction therapy were collected from their medical charts. CMV reactivation was defined by the detection of detecting pp65 antigen in polymorphonuclear leukocytes from peripheral blood. Mean values and proportions were compared by Student’s t-test and chi-square test, respectively, and multivariate logistic analysis was performed.

Results: Seventy AAV patients (MPA 33, GPA 19, and EGPA 18) were enrolled in this study. In total of 102 cases were treated with glucocorticoid and/or immunosuppressive agents as a remission induction therapy irrelevant of new onset or recurrence. We analyzed 67 cases (MPA 34, GPA 21, and EGPA 12) in whom CMV pp65 antigen was regularly measured during the treatment course. Patient characteristics were as following; mean age 65.5 ± 13.7 years old, female 35 (52%), disease duration 70.1 ± 142.9 weeks, and recurrence case 20 (31%). The mean initial dose of prednisolone (PSL) was 44.7±14.7 mg. Steroid pulse therapy was conducted in 11 patients (30%) and intravenous cyclophosphamide (IVCY) therapy in 30 patients (42%).

 CMV was reactivated in 28 cases (42%). Six cases were treated with antiviral agents including 2 cases with organ involvement (CMV retinitis, and CMV colitis). While mean age and baseline performance status were not significantly different between the CMV-positive group (n = 28) and the CMV-negative group (n = 38), the initial prednisolone dose was higher (50.4 ± 11.4 mg vs. 40.6 ± 15.5 mg, p = 0.007), methylprednisolone pulse therapy (43% vs. 21%, p = 0.049) and IVCY (68% vs. 23%, p < 0.001) were more frequently conducted, and baseline serum creatinine level was higher (1.3 ± 0.8 mg/dl vs. 0.9 ± 0.3 mg/dl, p = 0.004) in CMV-positive group. Multivariate logistic analysis identified initial PSL dose ≥ 40 mg/day (p = 0.031), IVCY therapy (p = 0.005), recurrence case (p = 0.018), and higher Brinkmann index (p = 0.033) as independent risk factors for CMV reactivation. Correspondingly, all six cases treated with anti-CMV agents were treated with IVCY.

Conclusion: Initial PSL dose, IVCY, recurrence case, and high Brinkmann index are risk factors for CMV reactivation during induction therapy for AAV. Patients with those risks require a particular attention.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-factors-for-cytomegalovirus-reactivation-in-patients-with-antineutrophil-cytoplasmic-antibody-associated-vasculitis/