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Reactivation of latent cytomegalovirus infection in patients with rheumatologic disease: a case–control study

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Abstract

The disease burden, risk factors and clinical sequelae of CMV reactivation in patients with rheumatologic conditions is poorly understood. We have described a cohort with underlying rheumatic disease and CMV, and compared a subgroup with systemic lupus erythematosus (SLE) to controls to identify potential risk factors for CMV reactivation. Adults with rheumatic disease and CMV infection from 2000–2015 were identified. SLE cases were matched 3:1 with controls based on age, sex and year of admission, and compared. Fourteen patients were included (6 SLE, 4 rheumatoid arthritis, 2 sarcoidosis, 1 psoriatic arthritis, 1 microscopic polyangiitis). Seven had viremia alone, the remainder tissue-invasive disease. Thirteen received glucocorticoids prior to CMV reactivation. Fever was the most common symptom, and coinfections were seen in eight including four with bacteremia. Thirteen received antiviral therapy (median 33 days), four died during hospitalization. Six patients with underlying SLE and CMV reactivation were compared to 18 SLE controls. Cases received more glucocorticoids prior to admission (median 36.5 vs. 2.5 mg/day, p = 0.006), had longer hospitalizations (median 47 vs. 7 days, p = 0.006) and more coinfections (67% vs. 17%, p = 0.04). There were no significant differences in symptoms at presentation. CMV reactivation occurs in patients with rheumatologic disease, can result in severe clinical sequelae, and is difficult to distinguish from a flare of the underlying disease. Patients with CMV received higher doses of glucocorticoids and developed more co-infections. CMV should be considered during the evaluation of a febrile illness in this complex patient population.

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Acknowledgements

The authors would like to acknowledge the assistance of Jacob Garrell and Shelley Bame-Aldred for help with data collection, and Robin Ruthazer for statistical support.

Funding

This work was supported by the Tufts Medical Center Division of Geographic Medicine and Infectious Disease Francis P. Tally MD Fellowship, and the National Institutes of Health Clinical and Translational Science Award (grant number UL1TR001064).

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Authors

Contributions

BG was involved in all aspects of this project including study design, data collection, analysis, interpretation and manuscript preparation. EH and RB contributed to data collection and manuscript preparation. JC and DS provided oversight and assisted with study design, analysis and manuscript editing. All authors read, contributed to and approved the final version of the manuscript and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Bradley J. Gardiner.

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Conflict of interest

DRS reports being on advisory boards for Merck, Shire, Chimerix, Takeda and Moderna and being a grant recipient from Merck, Summit, Actelion, Tetraphase and Seres Therapeutics. All other authors report no potential conflicts of interest.

Ethical standards

This study was approved by the Tufts Medical Center institutional review board (July 12, 2017, Approval Number 12618) and performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

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Informed consent was not required given its retrospective nature and minimal risk.

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Gardiner, B.J., Haas, E.M., Bailey, R.C. et al. Reactivation of latent cytomegalovirus infection in patients with rheumatologic disease: a case–control study. Rheumatol Int 39, 1229–1240 (2019). https://doi.org/10.1007/s00296-019-04324-6

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