Groups and methods
Seventy-one patients were included in this research; we divided all of them into two groups. Forty-three patients with RA (43 knee joints) aged 22–68 (on average 50, 1 year) and 19 SPA patients (19 knee joints) aged 20–70 (on average 42, 6 years) were treated with RS and then observed during 6 months. Among 19 SPA patients, 8 were treated due to ankylosing spondylitis (AS), 4 due to psoriatic arthritis (PsA), and 7 due to undifferentiated inflammatory spondyloarthropaty.
On the basis of knee X-rays taken not longer than 1 month before RS, considering those pictures, 23 knee joints patients with RA were classified as I grade according to Steinbröcker staging, 18 knee joints patients with RA as II grade, and 2 knee joints patients with RA as III anatomical grade.
Indication for RS was moderate or severe, persistent knee joint effusion that was recurrent in spite of local corticosteroid injections (minimum of 3 given in 4–6 weekly intervals) and optimal systemic treatment of disease with modifying drugs in a stable dose for a period not shorter than 4 weeks before RS. Intraarticular injection with corticosteroid was prohibited within 4 weeks before RS. Patients were assigned randomly to the therapeutic appropriate procedure, and DMARDs were sustained in stable doses for 6-month observation period after RS. Any DMARDs dose change or intraarticular corticosteroid injection within 6 months after RS excluded patient from further observation. Those patients were treated as RS failure.
Each patient signed an informed consent form before any study related procedure and further observation after therapy. The written approval for conducting the study and obtaining an informed consent form was given by the Independent Ethics Committee of the Medical University in Lublin, Poland.
Discussion
The primary inflammatory process primarily involving synovial membrane is an essential phenomenon in systemic arthritis; it leads to secondary changes in composition and physico-chemical specificity of synovial fluid. Breakout of synovio-vessel barrier by activated macrophages and lymphocytes, infiltration, and interaction of these cells with synoviocytes, dendritic, and endothelial cells results in fibroblastes expansion, neovascularization, increasing expression of proinflammatory cytokines, chemokines, and metaloproteinases [
5,
6]. The newly synthesised pathological tissue named pannus is responsible for destruction of all joint structures. The purpose of RS is obliteration of hypertrophic and infiltrated synovial membrane and joint protection before damage [
7].
In our research, we took into consideration, beyond clinical examination, results of laboratory tests, scintigraphic investigations, and generally used in daily practice scales and questionnaires for general disease activity evaluation. According to collected data, we observed that mentioned parameters undergo dynamic changes influenced by local therapy used. Results interchangeably indicate not only local efficiency of RS but also favorable influence of procedure on systemic inflammatory process as well.
The presence of knee effusion during physical examination in the sixth month of observation was the most important feature of treatment efficiency.
Treatment of knee effusion with the use of RS was safe and efficient—we did not observe any procedure-related adverse events.
We found only a few articles in professional literature available evaluating influence of RS on unspecific, systemic inflammatory process, and the reports are contradictory [
8,
9]. Spooren and co-workers did not find any influence of
90Y RS on red blood cells count, ESR, and rheumatoid factor level in osteoarthritis and in patients with RA [
9]. Schutte and Rau came to the different conclusions. In patient’s group with improvement after RS, they observed simultaneously increased level of hemoglobin and decreased level of ESR [
8].
We found in our research statistically essential decrease in CRP concentration and ESR in the first and sixth month after RS in patients with RA. We observed decrease in DAS (disease activity score), RADAI (rheumatoid arthritis disease activity index), HAQ (health assessment questionnaire), VAS (visual analog scale)—physician evaluation of disease activity, VAS—patient’s pain and disease activity assessment scales, and swollen and tender joint counts in the first and sixth month after RS.
The obtained results indicate the favorable influence of local RS therapy on unspecific, systemic inflammatory process and general disease activity.
In RA and SPA patients with good and very good treatment results, local and general improvement was obtained within the first month and had a permanent character, lasted for the whole 6-month observation period.
It is known that RS has influence on different synovial cells metabolism, refractory to this phenomenon, secretion of some markers activity have been changing, among others HA, which is synthesized by fibroblastes (synoviocytes B in synovium) penetrates blood via lymph vessels and it is eliminated by liver. Research conducted on animals and humans in vivo confirmed its protective role for articular cartilage provides chondrocytes viability and decreases proliferation of synovial cells. HA has anti-inflammatory properties and binds free ties. It plays important role in correct joints’ motion, reduces friction, and creates kind of “lubrication” covering articular surfaces [
10‐
13].
The highest concentration of HA is observed in patients with RA, a little bit lower in AS and PsA patients; in osteoarthritis patients, HA level is comparable to population of healthy persons [
14,
15]. It is known that HA concentration correlates with objective markers of inflammatory process in RA and AS such as CRP level and ESR value and additionally in AS with a scope of spine motion. The higher level of HA is presented in AS patients with peripheral joints involvement [
15]. High level of HA in patients with systemic inflammatory arthritis results from overproduction of polysaccharide within synovial membrane, while it is not related to poor liver elimination, it reflects the degree of cartilage degradation [
16,
17]. Some authors include HA to one of the most important markers of RA and juvenile arthritis activity [
18].
We found in our research highly significant statistically decrease in serum HA level in patients with RA in the first and sixth month after RS which suggests important influence on this treatment on reducing of local inflammatory process through interaction on synovial membrane of the treated knee joint. However, increase in the HA level was observed in SPA patients in the sixth month after RS.
Another group of proteins used in monitoring of inflammatory activity and taking part in maintaining bone tissue homeostasis is a system of receptors and ligands of cancer necrosis factors. OPG is a protein belonging to a family of receptors of cancer necrosis factors, universally it is found in a body, produced within the heart, lungs, kidneys, intestines, bones, and by hematopoetic cells. OPG is produced in large quantities by synovial membrane fibroblasts. RANKL (receptor activator NF-κB ligand) belongs to a family of proteins of cancer necrosis factors, produced by mature osteoblats and their precursors, macrophages, and activated lymphocytes T [
19,
20]. RANKL regulates differentiation of osteoclasts and dendritic cells, acts through a receptor RANK (receptor activator NF-κB) situated on a surface of target cells [
19]. OPG has ability of binding RANKL, it constitutes its soluble receptor, binding block of RANK from RANKL stops osteoclasts maturation just at its initial stages. Differentiation, maturation, and activity of osteoclasts, and so intensity of the bone resorption depend on relative balance between the concentration of RANKL and OPG. The RANKL advantage over OPG is increasing pathologically the process of the bone resorption, a phenomenon responsible for the generalized and periarticular osteoporosis development, and for bone erosions in systemic arthritides [
19‐
21].
In conducted examinations, we stated an essential statistical increase in the OPG concentration after the first month from RS in SPA patients and after the sixth month from RS in patients with RA, which suggests the protective influence of this procedure on joint cartilage and on sub-cartilage bone layer.
In the group of SPA patients after RS, we observed essential statistically decrease in the SAA concentration after the first and sixth month from performing the procedure.
SAA is produced in the liver, after being released to blood, it is bound with HDL (high density lipoproteins) fulfills anti-inflammatory functions; its concentration in serum repeatedly grows during the inflammatory reaction. It is a fundamental marker of acute phase, SAA synthesis is mainly stimulated by Il 1 and Il 6. RA and SPA are included in typical inflammatory chronic arthritides, where SAA high concentrations in the patients’ serum are stated. HDL molecules are protecting SAA from the proteolysis. Complexes HDL-SAA are responsible for chemotaxis of monocytes, lymphocytes, mast cells and are activating tissue proteinases: collagenase and stromyelysin. Complexes HDL-SAA are the source of cholesterol for the regeneration of cells damaged by the inflammatory process and simultaneously can act as the carrier of lipids by binding the excess of cholesterol in serum, which is being freed from destroyed tissues. The SAA excess in the chronic inflammable process in relation to the organic protein deposition leads to the reactive amyloidosis. The frequency of amyloidosis appearance in RA fluctuates from 11 to 30%, most often accompanies AS on the SPA course (6%).
In own examinations statistically essential negative correlation was stated between the anatomical stage and the effectiveness of therapy. This observation is matching data in literature [
22,
23].
No essential statistical relations were found between the age of patients, sex, duration of illness, number of RS performed earlier, number of modifying drugs used earlier, and the subjective and objective evaluation of the joint treated before the procedure with the therapy effectiveness.
Initial, general activity of arthritis evaluated on the basis of the concentration of acute phase proteins (CRP, fibrinogen, albumin), OPG, HA, SAA in serum, number of painful and swollen joints, questionnaires (HAQ), indices (RADAI), scores (DAS), and local evaluation based on articular liquid examination (pleocytosis with smear) did not correlate with the therapy effectiveness.
The response to treatment in groups of RA and SPA patients after RS was also determined on the basis of changes in the third metabolic phase of the three-phase scintigraphy of knee joints. Statistically significant positive correlation between the effectiveness of therapy evaluated on the basis of the physical examination was stated toward the effusion and the initial value of the J/B rate established before the treatment. Achieved results are matching data from the literature [
23‐
27]. The effectiveness of therapy negatively correlated with the J/B value after 6 months observation. So the initial value of the J/B rate is prognosing the effectiveness of therapy. The J/B rate is not correlating with the subjective evaluation made before and after 6 monthly period of observation.