Background New onset of joint inflammation in patients under anti-TNF-alpha for inflammatory bowel disease (IBD) has been previously described. However, histological characterization of synovial and bowel compartments has not been reported so far.

Objectives Aim of the study was to evaluate the histological characteristics of paired synovial (ST) and colonic tissues in IBD patients under TNF-alpha blockers.

Methods Consecutive IBD patients without history of co-existing joint involvement who developed peripheral arthritis under TNF-alpha blockers, were prospectively enrolled. Each patient underwent rheumatological evaluation and ultrasound (US) assessment (using Gray scale for synovial hyperthrophy and Power Doppler Signal) of the affected joints. Each patient underwent US guided ST biopsy of the knee, following a standardized procedure¹ and colonoscopy with mucosal biopsies. Each ST and colonic paired sample was stained through immunohistochemistry (IHC) for CD68, CD21, CD20, CD3 and CD117². H&E staining was performed for Paneth cells identification. Clinical and immunological parameters [Anti-citrullinated peptides antibodies (ACPA), IgM-Rheumatoid Factor (RF) and IgA-RF respectively] were collected for each patient.

Results 10 patients with IBD [46.0±9.7 years old, 13.2±9.9 years of disease duration, 2.5±1.6 years of TNF-alpha blockers exposure, 6 with Crohn's Disease and 4 with Ulcerative Colitis respectively] were studied. All patients were negative for ACPA, IgM-RF or IgA-RF and 4 patients were under Methorexate therapy. 5 (50.0%) patients showed endoscopic and histologically proven inflammation of colonic mucosa. Moreover, IHC revealed that 6 (60.0%) patients had diffuse and 4 (40.0%) had follicular synovitis, respectively. In particular, there was a direct correlation between CD68⁺, CD21⁺, CD3⁺, CD20⁺ and CD117⁺ cells distribution in paired ST and gut tissues in the whole cohort (p<0.05). No significant differences in terms of disease duration (p=0.48), TNF-alpha blockers exposure time (p=0.29), ESR (p=0.26) and CRP (p=0.91) values were found comparing patients with follicular and diffuse synovitis respectively.

Conclusions Our findings suggest that patients with IBD may develop histologically proven synovitis during TNF-alpha treatment, showing similar histological features in terms of CD68⁺, CD21⁺, CD20⁺, CD3⁺ and CD117⁺ cells between synovial and colonic compartments. Molecular mechanisms triggered by TNF-alpha blockers leading to joint inflammation have to be clarified.

References

1. van de Sande MJT et al. Ann Rheum Dis 2011.

2. Alivernini S. et al. Nat Communications 2016.

References

Disclosure of Interest None declared