The arthropathies are a group of musculoskeletal diseases affecting the joints, including osteoarthritis and inflammatory disorders as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and reactive arthritis, among others [19,20,21,22]. While neurological impairment associated with HTLV-1 infection, characterized as HAM/TSP, is well-known [4, 5], joint pain despite very frequent is not well studied in HTLV-1-infected patients. While polyarthralgia was observed in 56% of HTLV-1 infected subjects only 27% of age- and gender-matched seronegative individuals complained of these manifestations [16]. Despite cases of HTLV-1-infected patients with severe joint involvement characterized by synovitis have been reported [23], the predominant joint complaint in infected individuals is polyarthralgia, with scant evidence of arthritis [16]. Here HTLV-1 associated arthropathy was clinically characterized by symmetrical polyarthralgia and the main radiographic finding was the occurrence of enthesophytes in the absence of osteophytes and joint space narrowing.
As HTLV-1-associated diseases are more frequently observed after the fifth decade of life, osteoarthritis is expected to occur in infected individuals, which can represent a confounding factor in the establishment of criteria for HTLV-1 associated arthropathy. Here we compared clinical manifestations and radiographic findings between HTLV-1-infected individuals with a history of joint pain for at least one year and patients with osteoarthritis. As inflamed joint is not a common manifestation in HTLV-1 infected subjects, we did not considerer to include as control patients with systemic rheumatic disease. Our findings indicate that while a polyarticular and symmetrical pattern of joint involvement was observed in HTLV-1-infected patients, individuals with osteoarthritis presented predominantly an oligoarticular and asymmetrical involvement. While osteophytes and joint space narrowing was more frequent in patients with osteoarthritis, enthesophytes were the main radiographic finding in individuals with HTLV-1.
The incidence of osteoarthritis and most systemic rheumatic diseases is greater in females [24] and in our series joint pain was more frequent in females of both groups. Accordingly, we cannot exclude that the greater number of women studied herein may be related to women's greater interest in seeking medical care [25]. HTLV-1-associated diseases, including arthropathy, are more frequently observed in patients with HAM/TSP than in carriers [26]. However, in our study, the observed rates of chronic joint pain were similar in HTLV-1 carriers and in patients with HAM.
Radiographic findings in osteoarthritis are mainly characterized by the presence of osteophytes, joint space narrowing, bone cysts and subchondral bone sclerosis [19]. Accordingly, we found a higher frequency of osteophytes and joint space narrowing in controls with osteoarthritis compared to HTLV-1 infected patients. Alternatively, enthesophytes were more common in the HTLV-1 group. Enthesophytes are calcification that result from an inflammatory process where a tendon, ligament, aponeurosis or joint capsule is inserted into bone structure. This is a very common finding in inflammatory seronegative arthropathies, which include ankylosing spondylitis and psoriatic arthritis [27]. Here in addition to the enthesophytes bursitis and osteitis were found in the MRI of ankles in HTLV-1 infected subjects. The most relevant finding in the HTLV-1 infected group was the high frequency of enthesophytes. They were documented in the hips, knees and ankles, but were more frequent in the ankles of HTLV-1 infected individuals than in the control group. Enthesophytes are also common in patients with osteoarthritis and they were observed in the control group. However, the occurrence of enthesopathy in the absence of osteophytes and joint space narrowing was only observed in HTLV-1-infected subjects.
The majority of the diseases associated to HTLV-1 are mainly observed in patients with definite HAM/TSP [5,6,7]. However, we have previously shown that HTLV-1 carriers present higher frequency of HTLV-1 associated diseases than seronegative controls. Here the pattern of joint pain, the main joint involved and the radiographic features were similar in HTLV-1 carriers and in patients with probable and definite HAM/TSP indicating that the pathogenesis of the HTLV-1 associated arthropathy may be different from the one related to neurologic diseases, but future studies are necessary to determine how the virus and or the abnormalities in the immune response observed in HTLV-1 infection may cause arthropathy.
One of the limitations of our study was the fact that more specific and more sensitive imaging techniques for the detection of joint involvement were not used. However, conventional radiography, besides being a cheap, rapid and easily accessible method, does contribute to characterization of joint pathologies in the patients studied. Importantly, alterations detected on conventional radiography continue to be part of the diagnostic criteria for osteoarthritis [17]. In rheumatoid arthritis, joint features detected in conventional radiography were part of the diagnostic criteria of the disease up to 2010 when due to the limitation to detect of early changes in the count it was list out [28]. In patients with rheumatoid arthritis a characteristic finding of the disease is joint destruction [29] and it is important to highlight that in the present study, joint destruction was not observed in any HTLV-1 infected patient with joint pain.
Understanding the existence and importance of structures adjacent and related to the enthesis that contribute to dissipate the forces of stress helps to better understand the processes that affect the entheses. The study of enthesis of the calcaneus tendon should be extended to adjacent fibrocartilage, bursa, fat and fascia [30]. While the calcaneus enthesis is avascular in its fibrocartilaginous region, vessel growth may occur in association with the tissue repair response. The synovium, present in the retrocalcaneal bursa, is vascularized and vulnerable to inflammation and the high levels of pro-inflammatory cytokines observed in HTLV-1 infection may explain a higher frequency of retrocalcaneal bursitis and osteitis in the HTLV- 1 infected subjects compared to patients with osteoarthritis.