Epidemiologia e imunopatologia da doença articular crônica pelo vírus Chikungunya em pacientes do Mato Grosso

Abstract

Chikungunya virus (CHIKV) is an arbovirus transmitted by Aedes mosquitoes and responsible for acute febrile illness characterized by fever and arthralgia, that may evolve to debilitating chronic articular disease. This longitudinal study aimed to investigate articular histological findings and the cytokine serum profile of 17 patients with chronic articular disease post-CHIKV followed up at a rheumatology outpatient clinic every 90 days until symptoms remission, between 2017 and 2022. Patients were all females with mean age of 50 years (±13.67) showing 12 months (29.41%), 24 months (52.94%) or 36 months (17.64%) of chronic articular disease induced by CHIKV when biopsy was collected, with mean of 12 painful rigid joints (01-28); 41.17% exhibited moderate disease activity through CDAI (mean 9; 3-25); 58.82% hypertensive, 58.82% in corticosteroids use, 41.17% using non-steroid anti-inflammatories (AINES). Joint biopsies showed the presence of collagen deposition suggestive of fibrosis (10/17), intense (3/17) or mild (14/17) inflammatory cell infiltrate, synovitis with histiocyte presence (4/17) and fat necrosis (1/17), in addition to moderate (57.14%) labeling of CHIKV E1 antigen, detected in 14/17 patients by immunohistochemistry, suggesting the persistence of inflammation even in the absence of viral RNA detection by RT-qPCR in these tissues. The cytokine profile revealed elevated serum levels of TNF-α, MCP-1, IP-10, IL-17, IL-4 and IL-2 in the 17 patients. Progressive improvement in pain and disease activity was associated with reduced levels of inflammatory cytokines and less gradual use of symptomatic medications such as corticosteroids and NSAIDs. In addition, 226 patients infected with CHIKV subjected to four clinical evaluations in semesters (V1 to V4) were allocated into two groups: patients recovered in the acute phase (Group 1; n=73) and patients who developed chronic joint disease (Group 2; n=153). Statistical analysis of clinical and epidemiological parameters showed that 195/226 were female with a mean age of 51.3±14.2 years of age, and a mean of 6 (4-9) painful joints when included in the study. Hypertension (34.6% versus 11.0%; p< 0.001), osteopenia (7.9% versus 0.0%; p=0.010), and morning stiffness (62.7% versus 43.8%; p=0.010) were significantly more frequent in Group 2. The longitudinal follow-up of Group 2 revealed a significant reduction in CDAI (15.0±7.6 in V1 to 8.3±10.3 in V4) and in the number of painful joints (7.2±4.7 in V1 to 4.0±6.5 in V4), with improvement in symptoms over time (34.6% in V1 to 72.5% of patients in V4). Post-CHIKV chronic joint disease is associated with the perpetuation of inflammation, even in the absence of viral RNA, demonstrating the importance of continuous clinical follow-up in the management of the disease, preventing disability and evolution of joint damage, especially in patients who have risk factors for progression to chronic forms of post-Chikungunya joint disease.