关节镜在不同膝关节滑膜病变中的诊疗分析

目的观察关节镜在不同膝关节滑膜病变中的诊断、治疗作用,分析不同病变的临床疗效。方法选取50例关节镜下诊断、治疗的膝关节滑膜病变患者为研究对象,术前拟诊为类风湿性关节炎10例,色素沉着绒毛结节性滑膜炎11例,膝关节慢性感染5例,慢性非特异性滑膜炎12例,膝关节滑膜结核5例,半月板损伤4例,不明原因3例,记录关节镜对膝关节滑膜病变的诊治效果。结果关节镜结合病理检查结果,术后10例患者更正临床诊断,所有伤口均一期愈合,无严重并发症发生。出院后所有患者均获得随访,6例色素沉着绒毛结节性滑膜炎,2例类风湿性关节炎,1例滑膜结核,1例慢性非特异性滑膜炎术后复发,其余患者术后膝关节功能均获得显著改善,总有效率80.0%。结论关节镜检查有利于明确诊断,而且微创可彻底切除病变的滑膜组织,耐受性好。     

Stereological analysis of the synovial membrane in rheumatic disorders: diagnostic value of volume-weighted mean nuclear volume estimation

Quantitative evaluation of nuclear size of synoviocytes was performed on 48 synovial biopsies in various rheumatic disorders: osteoarthritis (n = 10), rheumatoid arthritis (11), and chronic non-specific synovitis (14). Thirteen tissue specimens from non-inflammatory synovial membrane were included as a control group. Using the point-sampled intercepts method, unbiased stereological estimates of volume-weighted mean nuclear volume (nuclear ν_v) were obtained. A slight increase in nuclear volume was observed in osteoarthritis in comparision with the control group with an overlap in 90% of cases. However, in rheumatoid arthritis there was a significant increase of nuclear ν_v. Significant differences were found between rheumatoid arthritis and the control and osteoarthritis groups (P0.001). In biopsies from patients diagnosed as chronic non-specific synovitis the averaged nuclear ν_v values were between those in osteoarthritis and rheumatoid arthritis with a wide range of data. Similar, but less significant differences were demonstrated between rheumatic disorders when using mean nuclear area. Further analysis of chronic non-specific synovitis patients in combination with nuclear ν_v estimates as a simple, unbiased, complementary tool are required to better establish the diagnostic value of nuclear stereology in the diagnosis of rheumatic disorders.     

Synovitis score: discrimination between chronic low-grade and high-grade synovitis

AIMS: To standardize the histopathological assessment of synovial membrane specimens in order to contribute to the diagnostics of rheumatic and non-rheumatic joint diseases. METHODS AND RESULTS: Three features of chronic synovitis (enlargement of lining cell layer, cellular density of synovial stroma, leukocytic infiltrate) were semiquantitatively evaluated (from 0, absent to 3, strong) and each feature was graded separately. The sum provided the synovitis score, which was interpreted as follows: 0-1, no synovitis; 2-4, low-grade synovitis; 5-9, high-grade synovitis. Five hundred and fifty-nine synovectomy specimens were graded by two independent observers. Clinical diagnoses were osteoarthrosis (n=212), post-traumatic arthritis (n=21), rheumatoid arthritis (n=246), psoriatic arthritis (n=22), reactive arthritis (n=9), as well as controls (n=49) from autopsies of patients without joint damage. Median synovitis scores when correlated with clinical diagnoses were: controls 1.0, osteoarthritis 2.0, post-traumatic arthritis 2.0, psoriatic arthritis 3.5, reactive arthritis 5.0 and rheumatoid arthritis 5.0. The scores differed significantly between most disease groups, especially between degenerative and rheumatic diseases. A high-grade synovitis was strongly associated with rheumatic joint diseases (P<0.001, sensitivity 61.7%, specificity 96.1%). The correlation between the two observers was high (r=0.941). CONCLUSION: The proposed synovitis score is based on well-defined, reproducible histopathological criteria and may contribute to diagnosis in rheumatic and non-rheumatic joint diseases.     

Utility of musculoskeletal ultrasonography in rheumatic diseases

Musculoskeletal ultrasonography (MSUS) possessing grey-scale and Doppler mode has become an established imaging modality for the diagnosis and follow up of patients with rheumatic diseases. Among rheumatic diseases, rheumatoid arthritis (RA) has been recognized as a good disorder to examine the joint inflammation as known synovitis. Early diagnosis and therapeutic intervention have given good outcomes to patients with RA. The 2010 RA classification criteria was reported and early arthritis patients has been diagnosed as RA, although the diagnostic and discriminative abilities of the 2010 criteria are not well known in Japanese. In the new criteria, synovitis is detected as joint swelling or tenderness on physical examination. Now we have expected if MSUS were used for detection of true synovitis, because we have confirmed that sensitivity of synovitis detection by MSUS was superior to that by physical examination.     

Computer-assisted validation of the synovitis score

Histopathological examination of synovial specimens can contribute to the diagnosis of chronic joint diseases. A so-called synovitis score has been introduced as a standardised grading system, based on the semi-quantitative evaluation of the three determining features of chronic synovitis: enlargement of synovial lining, density of synovial stroma and inflammatory infiltrate, giving a score between 0 and 9. The present study examines the reliability of this procedure by comparison with exact measurements using computer-assisted image analysis (CAIA). Seventy-one synovial specimens from patients with osteoarthritis (OA, n = 22), psoriatic arthritis (PsA, n = 7), rheumatoid arthritis (RA, n = 35) and from a control group (Co, n = 7) were evaluated using both the synovitis score and CAIA. The measurements were transformed to semi-quantitative values analogous to the synovitis score. The differences between the transformed CAIA scores and the pathologist's scores were 0 or +/-1 in 40 cases, whereas in 31 cases the difference was greater than 1 (correlation coefficient r = 0.725). The CAIA scores differed significantly between Co and RA cases (p = 0.000) as well as between OA and RA (p = 0.000). We conclude that the synovitis score was validated by CAIA and can be regarded a reliable grading system that contributes to the diagnostic procedure of chronic joint inflammation.     

The relationship between cell-mediated immunity and cartilage degradation in antigen-induced arthritis in the rabbit

The relative contributions of cellular and humoral immunity to cartilage destruction in chronic arthritis has been investigated in a model of chronic synovitis in the rabbit. In this model, antigen-induced arthritis, immunization with ovalbumin in Freund's complete adjuvant (FCA) followed by intra-articular injection of this protein produces a chronic synovitis associated with loss of proteoglycan from articular cartilage. In addition, the synovial lining cell population is metabolically activated. Similar treatment of animals immunized with ovalbumin in Freund's incomplete adjuvant (FIA) produced a resolving arthritis which initially (over the first 7 days) appears to be identical to that in FCA-immunized animals, apart from the lack of activation of synovial lining cells. Following this initial synovitis the joints return to apparent normality apart from a persistent 'low grade' synovitis consisting mainly of a plasma cell infiltrate. The most striking finding in the FIA-immunized animals is the rapid loss (greater than 30% by day 7) and recovery of proteoglycan from the matrix of articular cartilage. These findings show that the perpetuation of chronic destructive synovitis in the rabbit requires the presence of active cellular immunity.     

The relationship between cell-mediated immunity and cartilage degradation in antigen-induced arthritis in the rabbit.

The relative contributions of cellular and humoral immunity to cartilage destruction in chronic arthritis has been investigated in a model of chronic synovitis in the rabbit. In this model, antigen-induced arthritis, immunization with ovalbumin in Freund''s complete adjuvant (FCA) followed by intra-articular injection of this protein produces a chronic synovitis associated with loss of proteoglycan from articular cartilage. In addition, the synovial lining cell population is metabolically activated. Similar treatment of animals immunized with ovalbumin in Freund''s incomplete adjuvant (FIA) produced a resolving arthritis which initially (over the first 7 days) appears to be identical to that in FCA-immunized animals, apart from the lack of activation of synovial lining cells. Following this initial synovitis the joints return to apparent normality apart from a persistent ''low grade'' synovitis consisting mainly of a plasma cell infiltrate. The most striking finding in the FIA-immunized animals is the rapid loss (greater than 30% by day 7) and recovery of proteoglycan from the matrix of articular cartilage. These findings show that the perpetuation of chronic destructive synovitis in the rabbit requires the presence of active cellular immunity.     

Treatment of rheumatoid and degenerative diseases with copper complexes

This review presents a historical account of the treatment of rheumatoid and other degenerative diseases with copper complexes. Clinical data obtained from 1940 to 1971 are provided for about 1500 patients with rheumatoid arthritis (acute or chronic), rheumatic fever, ankylosing spondylitis, staphlococcal spondylitis, gonococcal arthritis, chronic gouty arthritis, polyarticular synovitis, coxitis, disseminated spondylitis, arthritis with psoriasis, Reiter's syndrome, lupus erythematosus, sarcoidosis, arthrosis deformans, erythema nodosum, sciatica (with and without lumbar involvement), cervical spine-shoulder syndrome or lumbar spine syndrome. The drugs used in these studies were Dicuprene, Alcuprin, Cuprimyl, and Permalon, a coppersalicylate preparation. A detailed presentation of toxicities associated with the use of these copper complexes is included.     

Induction of autologous lymphocyte transformation by synovial fluids from patients with rheumatoid arthritis

Appropriately diluted synovial fluids from thirteen of eighteen patients with rheumatoid arthritis induced in vitro transformation of autologous peripheral blood lymphocytes. By contrast, no significant transformation of autologous lymphocytes was induced by ten of eleven synovial fluids from patients without rheumatoid arthritis. These studies suggest that a similar blastogenic response in vivo may perpetuate subsynovial lymphoid hyperplasia and chronic synovitis in patients with rheumatoid arthritis.     

Persistent rubella virus infection associated with chronic arthritis in children

We isolated rubella virus from lymphoreticular cells in 7 of 19 children with chronic rheumatic disease, including patients with systemic-onset juvenile rheumatoid arthritis (Still's disease) (1 of 5), polyarticular juvenile rheumatoid arthritis (2 of 2), pauciarticular juvenile rheumatoid arthritis (2 of 6), and seronegative spondyloarthritis (2 of 6). In contrast, rubella virus was not isolated from the control group, which included eight normal subjects and eight patients with other connective tissue diseases or traumatic joint effusion. In most members of the study group, mononuclear cells from both synovial fluid and peripheral blood were examined. Rubella virus was isolated from both cell populations in three patients, from only peripheral blood in one, and from only synovial fluid in two. In the children with systemic-onset juvenile rheumatoid arthritis, only peripheral blood was examined, and of the five samples analyzed, one was shown to have rubella virus. Virus was isolated on more than one occasion from four of seven persons. Persistence of rubella virus in lymphoreticular cells in 35 per cent of these cases of juvenile arthritis supports the view that the virus may be an etiologic agent in chronic human joint disease, but further work will be required to support this suggestion.     

Is painless synovitis different from painful synovitis? A controlled,ultrasound, radiographic,clinical trial

OBJECTIVE:

This study compares the clinical, ultrasonography, radiography, and laboratory outcomes of painless and painful chronic synovitis in patients with established rheumatoid arthritis.

METHODS:

This cross-sectional study involved 60 patients with rheumatoid arthritis and synovitis in the metacarpophalangeal joints; 30 of the patients did not experience pain, and 30 had experienced pain for at least 6 months prior to the study. The radiocarpal, distal radioulnar, and metacarpophalangeal joints were evaluated using the ultrasound gray scale, power Doppler, and radiography. Past and present clinical and laboratory findings were also evaluated.

RESULTS:

There were no statistically significant differences between the groups for most of the outcomes. The group with pain scored worse on the disease activity indices (e.g., DAS 28 and SDAI), function questionnaires (HAQ and Cochin), and pinch strength test. A logistic regression analysis revealed that the use of an immunobiological agent was associated with a 3-fold greater chance of belonging to the group that experienced pain. The painless group had worse erosion scores in the second and fifth metacarpophalangeal with odd ratios (ORs) of 6.5 and 3.5, respectively. The painless group had more cartilage with grade 4 damage in the third metacarpophalangeal.

CONCLUSIONS:

The rheumatoid arthritis patients with both painless and painful synovitis exhibited similar disease histories and radiographic and ultrasound findings. However, the ultrasonography evaluation revealed worse scores in the second and fifth metacarpophalangeal of the synovitis patients who did not experience pain.     

Synovitis in rheumatoid arthritis: Scoring of characteristic histopathological features

Synovial tissue specimens obtained from the knee joints of 40 patients with rheumatoid arthritis (RA) and from 22 patients with osteoarthritis (OA) were examined histologically. The histopathological features of RA synovitis and OA synovitis were then compared. Seven criteria items of histopathological features characteristic to RA synovitis were given a score of 1-3 points each in order to evaluate the histological severity of the seven items. Their total scores were then calculated. A comparison of the total RA synovitis score and the total OA synovitis score revealed that RA synovitis showed more than 11 points (maximum 20 points), while OA synovitis showed less than 10 points in all but two cases. Furthermore, the total scores of RA synovitis were then determined in the same manner for other joints, where it was confirmed that five other joints had scores of more than 11 points as well; that is, the intercarpal, wrist, elbow, ankle and hip joints in 52 patients with RA. From these results, it was concluded that in the histological examination of biopsied synovial tissue of RA, if the total score for synovitis is more than 11 points (maximum 20 points), an histological diagnosis of RA synovitis can be confirmed.     

Clonal heterogeneity of synovial fluid T lymphocytes in inflammatory synovitis.

Several studies have examined patients with rheumatoid arthritis for the presence of oligoclonal populations of synovial T lymphocytes. The results of these studies have been conflicting. In this study one patient with rheumatoid arthritis and two with other forms of inflammatory synovitis were examined by Southern blot analysis of T cell clones generated from synovial fluid by primary limiting dilution. Evidence of oligoclonality was documented only in a patient with psoriatic arthritis. The distinguishing characteristics of this patient, in addition to the diagnosis, included the fact that only one joint was involved, the synovitis in the affected joint was of recent onset, and the synovial fluid lymphocytes from which the T cells were cloned responded strongly to soluble antigens. Because of the association with the strong response to soluble antigens, synovial fluid T lymphocytes from another patient with rheumatoid arthritis were cloned in response to a crude mycobacterial antigenic mixture. Three of the seven clones examined were identical by Southern blot analysis. These observations suggest that the presence of oligoclonality is limited in patients with inflammatory arthritis. The relationship of a specific antigen-driven response within the joint to the detection of oligoclonal T cells within that joint remains to be determined.     

Tyrosine Phosphorylated Proteins in Synovial Cells of Rheumatoid Arthritis

Two of the key events in the pathogenesis of rheumatoid arthritis are the synovial cell proliferation and lymphocyte infiltration into the synovium. The resulting synovitis is longlasting and leads to destructive arthritis, which is a hallmark of rheumatoid arthritis. Accumulating evidence suggests that one of the key biochemical events in the altered cell function of RA is phosphorylation of the tyrosine residues of proteins.

In this paper we review the cellular components participating in the chronic inflammation of RA joints. We present the results of analyzing tyrosine phosphorylated proteins of synovial cells from RA patients and discuss a possible pathogenic role of non-receptor tyrosine kinase in RA.     

Tyrosine phosphorylated proteins in synovial cells of rheumatoid arthritis

Two of the key events in the pathogenesis of rheumatoid arthritis are the synovial cell proliferation and lymphocyte infiltration into the synovium. The resulting synovitis is longlasting and leads to destructive arthritis, which is a hallmark of rheumatoid arthritis. Accumulating evidence suggests that one of the key biochemical events in the altered cell function of RA is phosphorylation of the tyrosine residues of proteins. In this paper we review the cellular components participating in the chronic inflammation of RA joints. We present the results of analyzing tyrosine phosphorylated proteins of synovial cells from RA patients and discuss a possible pathogenic role of non-receptor tyrosine kinase in RA.     

Focally regulated endothelial proliferation and cell death in human synovium.

Angiogenesis and vascular insufficiency each may support the chronic synovial inflammation of rheumatoid arthritis. We have shown by quantitative immunohistochemistry and terminal uridyl deoxynucleotide nick end labeling that endothelial proliferation and cell death indices were each increased in synovia from patients with rheumatoid arthritis compared with osteoarthritic and noninflamed controls, whereas endothelial fractional areas did not differ significantly among disease groups. Markers of proliferation were associated with foci immunoreactive for vascular endothelial growth factor and integrin alpha(v)beta3, whereas cell death was observed in foci in which immunoreactivities for these factors were weak or absent. No association was found with thrombospondin immunoreactivity. The balance between angiogenesis and vascular regression in rheumatoid synovitis may be determined by the focal expression of angiogenic and endothelial survival factors. Increased endothelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis.     

Metabolic reprogramming as a key regulator in the pathogenesis of rheumatoid arthritis

Inflammation Research - Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease with synovitis as pathological changes. The immune microenvironment of RA promotes metabolic...     

The Vδ Gene Usage by Freshly Isolated T Lymphocytes from Synovial Fluids in Rheumatoid Synovitis: a Preliminary Report

Taking advantage of the polymerase chain reaction we have studied the usage of variable delta-(V delta) region genes in freshly isolated synovial fluid T cells from patients with rheumatoid synovitis. Amplified mRNA from one patient with rheumatoid arthritis (RA) was cloned into an SmaI-cleaved pUC19 vector and colonies were screened with probes for three of the known human variable delta-gene families (V delta 1, V delta 2, V delta 3). Of 10 clones, seven used V delta 1, two V delta 2 and one V delta 3. This pattern of distribution is different from that of normal peripheral blood, where approximately 60% of T gamma delta cells are reported to use the V delta 2 gene. Furthermore, Northern blot hybridization analyses of mononuclear cells from two additional synovial fluids derived from another patient with RA and one with juvenile rheumatoid arthritis (JRA) also showed significant hybridization only with V delta 1. In summary, these preliminary results suggest a usage of V delta gene families in T gamma delta lymphocytes in synovial fluid of rheumatoid patients different to that found in normal peripheral blood.     

Involvement of IL-6, apart from its role in immunity, in mediating a chronic response during experimental arthritis

Interleukin-6 (IL-6) is highly produced during arthritis but its exact function is still unknown. In this study we examined if IL-6, apart from its role in immunity, was involved in the local inflammatory response in experimental arthritis. IL-6 deficient (IL-6(-/-)) and wild-type mice were first compared in the antigen-induced arthritis model. IL-6 deficiency resulted in a mild, transient inflammation whereas wild-type mice developed a chronic, destructive synovitis. Wild-type mice immunized with one-tenth of the normal antigen dose still developed chronic arthritis despite low antibody levels, excluding reduced humoral immunity in IL-6(-/-) mice as a crucial phenomenon. In addition, passive immune-complex-induced arthritis did not differ between wild-type and IL-6(-/-) mice. Another option is reduced levels of Th1 cells in IL-6(-/-) mice. However, transfer of antigen-specific wild-type lymph node cells to IL-6(-/-) mice enhanced acute joint inflammation and increased cartilage damage but still could not sustain chronic inflammation, suggesting involvement of nonimmune elements of IL-6 activity in chronicity. In line with this, nonimmunologically mediated zymosan-induced arthritis developed similarly in the first week, but only wild-type mice developed chronic synovitis. These results indicate an important role for IL-6 in propagation of joint inflammation, potentially independent of its role in immunity.     

IgG rheumatoid factor, complement and immune complexes in rheumatoid synovitis and vasculitis: comparative and serial studies during cytotoxic therapy.

IgG and IgM rheumatoid factors (IgG-RF and IgM-RF), complement and three assays for immune complexes were measured in 22 patients with rheumatoid arthritis (RA) complicated by either chronic active synovitis or vasculitis. Patients with vasculitis had relatively inactive arthritis but had higher titres of rheumatoid factors, especially IgG-RF, anticomplementary activity (ACA) and lower levels of C4 than those with synovitis. Clq-binding and platelet aggregation (PA) levels were similar in both groups. Serial measurements during cytotoxic therapy showed a close temporal relationship between the clinical features of vasculitis and levels of IgG-RF, ACA and C4 both with remission and with relapse. We suggest that immune complexes containing IgG-RF which activate complement and are detected by ACA are useful markers of rheumatoid vasculitis and may be important in its pathogenesis.