Systemic Sclerosis Treatment may Heighten Risk Factors

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ACE inhibitors appear to heighten the risk of scleroderma renal crisis (SRC), a potentialy deadly complication in patients with systemic sclerosis.

Reported in the July 25 issue of the journal BMC Nephrology, researchers with the Walter Reed National Military Medical Center in Bethesda found that even after they adjusted for age, race and prednisone use, the odds ratio was four to one.

"The results suggest that it may be a passive marker of known SRC risk factors, such as proteinuria, or evolving disease. Systemic sclerosis patients that require ACE inhibitors should be more closely monitored for scleroderma renal crisis," researchers wrote.

With 31 cases, this is the first-known large study to evaluate treatments for systemic sclerosis and the risk of scleroderma renal crisis. Researchers compared the use of ACE (angiotensin-converting enzyme) inhibitors, angiotensin receptor blocker (ARB), calcium channel blocker (CCB), endothelin receptor blocker (ERB), non-steroidal anti-inflammatory drug (NSAID), fluticasone, and mycophenolate mofetil (MMF).

While ACE inhibitors were found to increase the risk for scleroderma renal crisis, the risk only occured in the presence of proteinuria. Doubling the dose of ACE inhibitors was found to increase risk by 61 percent. Even at a maximum dose, the risk of developing scleroderma renal crisis was 45 percent.

CCB, ARB, NSAIDs, ERB, fluticasone, and MMF use were not significantly associated with the developmetn of the condition.

"The association of ACE inhibitors in systemic sclerosiswith the development scleroderma renal crisis (SRC) is counterintuitive because it is a proven efficacious treatment for SRC, but previous studies do not contradict this conclusion," the authors wrote.

The study has potential clinical implications, but the findings are complex. The study shows that ACE inhibitors are likely a "surrogate" for established risk factors---but not the cause of scleroderma renal crisis. Nonetheless, patients should be closely monitored for the development of complications, such as hypertension and proteinuria, the authors wrote.

REFERENCE

Gordon SM, Hughes JB, Nee R, et al. "Systemic sclerosis medications and risk of scleroderma renal crisis."BMC Nephrol. 2019 Jul 25;20(1):279. doi: 10.1186/s12882-019-1467-y.