Examining Reactivation of Latent Cytomegalovirus Infection in Rheumatic Disease

When evaluating febrile illnesses in patients with rheumatic diseases, physicians should consider the presence of cytomegalovirus (CMV), a condition associated with significant morbidity and mortality in this patient population, according to research published in Rheumatology International.

Researchers conducted a retrospective case-control study at Tufts Medical Center in Boston, Massachusetts, examining adults with positive test results for CMV and an underlying diagnosis of inflammatory or autoimmune rheumatic disease.

They also reviewed clinical and laboratory data from medical records, including symptoms at the time of hospital admission and CMV diagnosis. They collected laboratory results from the day of admission, CMV reactivation, and discharge. In addition, they reviewed microbiology records  to identify the presence of coinfections one month before or after index admission. Finally, researchers assessed each patient’s immunosuppressive treatment history.

In total, 14 patients were included in the final cohort (mean age 54 ± 19.5 years; 86% women). The most common underlying diagnosis was systemic lupus erythematosus (SLE). All patients had received treatment for their rheumatic disease within 3 months of the CMV reactivation date, and 93% of patients received glucocorticoids, 64% received a nonbiologic steroid-sparing agent, and 14% received a biologic agent. At the time of CMV reactivation, the most common symptoms were fever (86% of patients), fatigue (71%), and gastrointestinal symptoms (64%); 57% of patients had thrombocytopenia and/or leukopenia.

Within the cohort, 12 patients had CMV DNAemia and 2 had end-organ disease without viral load testing. A total of 5 patients had both DNAemia and a positive CMV test at a nonblood site: 2 pulmonary and 3 gastrointestinal tract. In terms of treatment, 13 (93%) patients received antiviral therapy, and one patient died before treatment could begin. The treatment methods included intravenous ganciclovir and oral valganciclovir. The median duration of antiviral treatment was 33 (range, 13-171) days. Coinfections (n = 14) were diagnosed in 8 patients.

In total, 6 patients with both SLE and CMV were matched to 18 control patients. In both groups of patients, the most common presenting symptom was fever, present in half of all patients, followed by gastrointestinal and respiratory symptoms. Laboratory values at admission were also similar between the groups, with “no significant differences” in anti-dsDNA, C3, C4, and lymphocyte counts. When compared with control participants, the researchers noted that patients with SLE received significantly higher doses of glucocorticoids before hospital admission, developed more coinfections (67% vs 17%; P =.04), and were more likely to be admitted to the intensive care unit during their hospital stay.

Limitations of this study included the small, retrospective nature of the research, limited by the sample size. Researchers were unclear if these low numbers resulted from the rarity of the condition or a lack of testing in the patient population.

The role of CMV reactivation as a pathogen in patients with the underlying rheumatic disease is not well understood, according to researchers.

They concluded, “Clinicians should consider appropriate diagnostic testing for CMV during the evaluation of fevers in this patient population, especially in those with an apparent flare of their underlying disease.”

One researcher reported serving on advisory boards for Chimerix, Inc.; Merck & Co., Inc; Moderna, Inc.; Shire; and Takeda Pharmaceuticals North America, Inc. and received grant funding from Actelion Pharmaceuticals, Ltd; Merck & Co., Inc.; Seres Therapeutics; Summit Pharmaceuticals International Corporation; and Tetraphase Pharmaceuticals.

Reference

Gardiner BJ, Haas EM, Bailey RC, Chow JK, Snydman DR. Reactivation of latent cytomegalovirus infection in patients with rheumatologic disease: a case-control study [published online May 10, 2019]. Rheumatol Int. doi:10.1007/s00296-019-04324-6