Polysynovitis and Uveitis in Horses With Rhodococcus equi Infection

Rhodococcus equi is a gram-positive facultative intracellular bacteria that commonly affects foals. R. equi—infected foals frequently suffer from pyogranulomatous pneumonia, but they can also develop extrapulmonary infections that can worsen prognosis.

Polysynovitis (synovial effusion without lameness) and uveitis (inflammation of the uvea) have been described in foals with natural R. equi infections. Because R. equi is rarely isolated from the synovial membrane or iris of infected foals, and because anti—R. equi antibodies are infrequently detected in these structures, polysynovitis and uveitis are widely believed to be immune-mediated processes. However, in a study in which foals were experimentally infected with a high inoculum of virulent R. equi, foals developed polysynovitis and R. equi was detected in the synovial effusion, suggesting a septic process.

Given that immunosuppressive drugs can be detrimental for treating infections, “understanding the pathogenesis of polysynovitis and uveitis is important,” wrote the investigators, whose findings were published in PLoS ONE.

Experimental Infection

Twenty-eight healthy foals, aged 3 to 4 weeks, received intratracheal injections of R. equi. Sixteen foals received 10 mL of inoculum (high; 1 x 10⁸ CFU) and 12 received 1 mL inoculum in 9 mL of sterile phosphate-buffered saline (low; 1 x 10⁷ CFU). They were examined twice daily and euthanized 14 days post-infection (dpi), after which the researchers conducted several postmortem analyses.

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Results

Beginning 9 dpi, rectal temperature in foals with the high inoculum was significantly higher than both baseline and in foals with the low inoculum; heart and respiratory rates did not increase significantly from baseline or vary between the treatment groups at any time point.

Polysynovitis developed in 71% (20/28) of foals; starting at 6 dpi, the risk of developing polysynovitis was higher with the high inoculum than the low inoculum. Uveitis developed in 56% (14/25) of foals. All foals with uveitis also had polysynovitis, indicating a strong association between the 2 diseases.

Over 90% (26/28) of foals developed pneumonia and bronchial lymphadenopathy. Severe cranioventral and accessory lobe consolidation, multiple coalescing lesions, and caseous necrosis were observed.

Histopathology

Affected lungs had severe, diffuse, chronic pyogranulomatous pneumonia. The mean percentage of affected lung was significantly higher with the high inoculum (32%) than the low inoculum (14%) and higher in foals with polysynovitis and uveitis. Synovial membranes in foals with polysynovitis demonstrated marked synoviocyte hyperplasia, lymphohistiocytic and suppurative infiltration, and moderate edema.

Culture

Aqueous humor was culture positive for R. equi in 11 of 25 foals (5 with uveitis) and synovial fluid was culture positive for R. equi in 14 of 28 foals (12 with polysynovitis), indicating hematogenous spread. Positive cultures in foals without polysynovitis and uveitis were likely due to subclinical infections, the researchers believed.

Protein Concentration

Aqueous humor protein concentration was significantly higher in foals with uveitis and receiving the high inoculum. Synovial fluid protein concentration was significantly higher in foals with polysynovitis. For both structures, protein concentration was positively correlated with percentage of affected lung.

Concluding Thoughts

The presence of R. equi in the aqueous humor and synovial membranes indicates that polysynovitis and uveitis are septic, rather than immune-mediated, processes. This septic origin, along with the relationship between these conditions and lung disease severity, has important therapeutic implications. “Additional studies are required before systemic corticosteroids are recommended for the treatment of [polysynovitis and uveitis],” the researchers concluded.

Dr. Pendergrass received her doctor of veterinary medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.