Assessment of inflammation in the rheumatoid knee joint: correlation between clinical, radioisotopic, and thermographic methods.

Standard clinical methods of assessing joint inflammation are being supplemented increasingly by radioisotopic and thermographic studies. However, the correlation between these different methods has not been firmly established. In the quantification of synovitis by infrared thermography we have shown that the heat distribution index (HDI) based on thermal pattern is more reliable and is less affected by diurnal variations in joint temperature than the commonly used thermographic index, which is based on average skin temperature values. In 20 patients with rheumatoid arthritis whose knees were being treated with intra-articular steroid we obtained 184 serial paired observations over a period of 24 weeks for clinical assessment, HDI, and 99mTc pertechnetate uptake. We found significant correlations (p less than 0.001) between the three methods of assessment (except for pain and HDI (p = 0.116)).     

Bidirectional erosion of cartilage in the rheumatoid knee joint.

Specimens of cartilage with contiguous bone and overlying synovial pannus were obtained from 22 rheumatoid knee joints and examined histologically using specific histochemical staining techniques. All showed significant erosions of cartilage by synovial cells, but seven specimens also showed substantial cartilage erosion by cells from the subchondral bone region. This bidirectional attack on rheumatoid knee cartilage did not represent an 'underpinning' of cartilage by synovial pannus, as judged by serial sectioning and the identification of specific cells. Whereas cartilage-pannus junctions had mainly macrophagic or fibroblastic cells, cartilage-bone lesions were usually characterised by chondroclasts and blood vessels. Lymphocytes were generally absent from all sites of cartilage erosion. The bidirectional attack on articular knee cartilage suggests that changes have occurred within the cartilage that make it vulnerable to cellular invasion and erosion. Such changes might reflect a deficiency in 'anti-invasion factors', or the exposure of hidden epitopes and subsequent immunogenicity, or a combination of both.     

Scintigraphic findings in the rheumatoid knee joint

An increased uptake of 99m-technetium methylenediphosphonate was found in 42 knees of 24 patients afflicted with rheumatoid arthritis. All the 23 knees which were painful and the 21 knees which had synovitis showed an increased concentration of isotope. Articular space narrowing was observed in 26 joints, all but one of which were subjected to increased isotopic accumulation and synovitis. The degree of radiologic cartilage destruction correlated significantly with the isotopic uptake. In the early stages of rheumatoid arthritis, the isotopic uptake was found to be heterogeneous within the joint in one half of the cases. In the later stages, with a narrowed articular space and valgus angulation, the isotope was concentrated to the lateral side of the joint, while joints with varus angulation had a more symmetric distribution. The degree and distribution of uptake seemed to be governed by several factors, among others, inflammatory activity and mechanical load.     

Intra-articular rheumatoid nodules of the knee joint

Intra-articular rheumatoid nodules found in 6 knee joints of 4 patients with rheumatoid arthritis were reported with histological findings. All patients were women, ranging in age from 32 to 61 years, with 6 to 41-year history of rheumatoid arthritis. The masses were exclusively in the anterolateral aspect of the joint. Snapping occurred when the joint was flexed by 20 degrees in four joints and by 60 degrees in two. The masses had the sizes of a thumb tip to index-finger tip, and were elastic and soft. Histologic examination of the masses revealed the typical formation of rheumatoid nodule in two joints. Myxomatous degeneration and granulation tissue consistent with rheumatoid arthritis were found in two joints. Perivascular fibrosis and myxomatous degeneration were mainly demonstrated in two joints which had developed masses two months before excision.     

Intra-articular rheumatoid nodules and triggering of the knee joint.

Rheumatoid nodules are a common extra-articular manifestation in rheumatoid arthritis. Intra-articular localisation of these nodules is rare and may produce clinical symptoms. Seven patients with walking problems due to an intra-articular rheumatoid nodule, which became entrapped on the ridge of the tibial plateau of the knee joint resulting in a phenomenon referred to as trigger knee, are described. After excision of the nodules all symptoms completely disappeared.     

Development of large pseudocysts adjacent to the knee joint in rheumatoid arthritis. Assessment of radiological and histopathological approaches

Abstract

?This study examined the pathogenesis of large pseudocysts adjacent to knee joints in rheumatoid arthritis (RA). The radiological and histopathological features of 17 large subarticular pseudocysts in 12 knee joints of 10 patients were analyzed. Nine of the 10 patients were classified as class 2 according to Steinbrocker's functional class. Eight large pseudocysts were located at the lateral femoral condyle, seven were at the proximal part of the tibia, one was at the medial femoral condyle, and one was at the patella. The large pseudocysts were divided into two groups according to whether they did or did not connect with the joint cavity. Serial radiographs revealed that all large pseudocysts in communication with the joint cavity had enlarged gradually over the past several months. They extended from the subarticular area toward the bone marrow. Histopathological findings confirmed that holes allowing communication were located at a transitional zone between the ligament and the hyaline cartilage, and that rheumatoid granulation tissue invaded the large pseudocyst through these holes. The results of this study indicate that large pseudocysts are formed by the extension of articular inflammation. Moreover, repeated extrinsic mechanical stress due to walking and the aggressive inflammatory nature of rheumatoid arthritis play important roles in the formation of large pseudocysts.     

Development of large pseudocysts adjacent to the knee joint in rheumatoid arthritis. Assessment of radiological and histopathological approaches

 This study examined the pathogenesis of large pseudocysts adjacent to knee joints in rheumatoid arthritis (RA). The radiological and histopathological features of 17 large subarticular pseudocysts in 12 knee joints of 10 patients were analyzed. Nine of the 10 patients were classified as class 2 according to Steinbrocker's functional class. Eight large pseudocysts were located at the lateral femoral condyle, seven were at the proximal part of the tibia, one was at the medial femoral condyle, and one was at the patella. The large pseudocysts were divided into two groups according to whether they did or did not connect with the joint cavity. Serial radiographs revealed that all large pseudocysts in communication with the joint cavity had enlarged gradually over the past several months. They extended from the subarticular area toward the bone marrow. Histopathological findings confirmed that holes allowing communication were located at a transitional zone between the ligament and the hyaline cartilage, and that rheumatoid granulation tissue invaded the large pseudocyst through these holes. The results of this study indicate that large pseudocysts are formed by the extension of articular inflammation. Moreover, repeated extrinsic mechanical stress due to walking and the aggressive inflammatory nature of rheumatoid arthritis play important roles in the formation of large pseudocysts. Received: April 16, 2001 / Accepted: September 21, 2001     

Responses of blood vessels in the rabbit knee to acute joint inflammation.

These experiments examined the responses of articular blood vessels in the rabbit knee to induction of acute joint inflammation by intraarticular injection of 4% kaolin suspension. This produced an inflammatory response, which became evident about four hours after injection. Electrical stimulation of the nerve supply to the knee joint before induction of inflammation produced a biphasic response--an initial vasoconstriction during the stimulation phase followed by dilatation after stimulation stopped. These responses were followed up for eight hours and it was noted that the constrictor response became progressively greater, producing a further 19% decrease in blood flow during nerve stimulation about three hours after the injection of kaolin. The sensitivity of postjunctional alpha adrenoceptors, however, showed still greater increase in the inflamed joint as close intraarterial injection of 10(-6) M adrenaline produced an additional 30% reduction in blood flow four hours after kaolin injection compared with the control response. Possibly, the smaller enhancement of the constrictor response to nerve stimulation in the inflamed joint may reflect sensitisation of prejunctional alpha adrenoceptors in addition to the effects exerted on postjunctional alpha adrenoceptors by the inflammatory process. The dilator response also increased over eight hours, though this rise was less marked. These findings indicate that even over the limited time span of the experiments, significant alterations occurred in factors which influence the calibre of articular blood vessels.     

Measurement of joint inflammation in rheumatoid arthritis with indium-111 chloride.

Studies in the collagen and rabbit models of arthritis have indicated that indium-111 chloride (111InCl3) scintigraphy objectively measures synovial inflammation. Indium-111 chloride scans, with imaging three days after 19 MBq intravenous injection, were performed on 21 patients with definite or classical rheumatoid arthritis (RA), all of whom were functional class II. Standard clinical indices of disease activity were recorded at the time of imaging by the same investigator, who was unaware of the results of joint scans. In addition, eight patients with severe osteoarthritis, four of whom were considered to need hip or knee joint replacement, were similarly scanned. In each patient 16 joints were graded as 0 to 5, based on increasing degrees of 111InCl3 uptake, by a single investigator blinded to the patient's diagnosis and clinical status. In the group with RA significant correlations were observed between individual joint uptake on scan and peripheral joints with swelling, joints reported to be painful, and joints with any abnormality on physical examination. In the group with osteoarthritis joints positive on scan correlated with the presence of pain. A total scan score (sum of individual joint scores) was calculated for each patient. In the patients with RA values ranged from 0 to 42 with a mean (SEM) of 20.7 (2.7) and correlated with the number of swollen joints and decreasing grip strength. In the group with osteoarthritis the mean total scan score (9.2 (1.5), range 3-14) was significantly lower than in the patients with RA. These data show that 111InCl3 scanning can measure joint involvement by RA.     

Neurogenic component of different models of acute inflammation in the rat knee joint.

This study was performed to investigate whether different models of acute joint inflammation showed a neurogenic component and to establish whether this is mediated through sensory afferent or sympathetic efferent nerve fibres. Intra-articular injection of 2% carrageenan, 20 micrograms substance P, 1% formalin, and 2% urate all produced an inflammatory response. Prior surgical denervation of the joint significantly inhibited this response in the carrageenan and formalin models, but not the others. Pretreatment of the joint with 1% capsaicin (about one week previously) significantly reduced the inflammatory response in all models except formalin. In animals pretreated long term with reserpine (to deplete sympathetic nerve endings of their neurotransmitters) significant reductions occurred in the inflammatory responses to substance P and urate. Intraarticular injection of compound 48/80 produced a marked inflammatory response, which was only significantly reduced by capsaicin pretreatment. These results suggest that both the formalin and carrageenan models of inflammation depend to some extent on the integrity of the sensory innervation of the joint, and thus have a neurogenically mediated component to the inflammatory process they generate. In these models there seems to be little contribution from sympathetic efferent fibres. Each model of inflammation showed a different pattern of response to the pretreatments, suggesting that the mediators of the inflammatory process may differ in each case.     

Listeria monocytogenes infection in a prosthetic knee joint in rheumatoid arthritis.

The prosthetic knee joint of a 64 year old woman with severe rheumatoid arthritis was found to be infected with Listeria monocytogenes. After treatment with intravenous antibiotics, symptoms gradually resolved. She subsequently received prolonged treatment with oral co-trimoxazole and 18 months later remained well.     

Articular indices of joint inflammation in rheumatoid arthritis. Correlation with the acute-phase response

The joints of 30 rheumatoid arthritis patients were assessed by one observer for signs of inflammation. Computer analysis was then used to calculate 70 different articular indices for each patient. Pearson correlation coefficients were calculated between serum C-reactive protein levels and the articular indices. The results show that: findings in a restricted set of examined joints were equivalent to those in a more complete set; the simultaneous presence of joint tenderness and swelling yielded higher correlation than did either variable alone; and joint "weighting" for size yielded higher correlation than did simple counts.     

Treatment of rheumatoid joint inflammation with triamcinolone hexacetonide

Prolonged (more than 1 year) reversal of inflammation, as judged by decreased swelling, tenderness and synovial thickening, occurred in 12 patients in whom the joints of one hand and the wrist were treated locally with triamcinolone hexacetonide. Better preservation of grip strength, structural joint integrity and range of motion on the treated side were evidence of a beneficial effect on function. Fewer new lesions developed on the treated side as observed radiographically over the period of follow-up, which averaged 21 months. Recurrence and progression of arthritis, both clinical and radiologic, definitely occurred in some injected joints. Unwanted effects such as soft tissue atrophy and periarticular calcification were common; their true incidence and the significance of the latter remain to be determined. The doses used here are regarded as experimental and, while promising, warrant further study before adoption as a possible method of “medical synovectomy”.     

Role of early synovectomy of the knee joint in rheumatoid arthritis

The prospective study of 32 knees in 26 patients with rheumatoid arthritis was carried out with an average followup of 3 years. Relief of pain and control of inflammation locally were obtained in 22 of 32 knees (69%). Articular cartilage was preserved in 20 of 28 knees (71%) and the synovitis recurred in 9 knees (28%), 7 of which showed progressive loss of cartilage. Therefore, it appears that synovectomy, if performed at a stage in which articular cartilage is still normal and after medical therapy has failed, is a very effective method for preserving articular cartilage and controlling inflammation locally. However, with a longer followup the disease with loss of articular cartilage will recur in a large number of cases. In patients whose disease progresses rapidly, no form of therapy effectively controls joint destruction.     

Assessment of pain in patients with juvenile rheumatoid arthritis: relation between pain intensity and degree of joint inflammation.

The relation between pain and joint inflammation in patients with juvenile rheumatoid arthritis has not previously been systematically evaluated. Eighteen patients with juvenile rheumatoid arthritis completed paediatric pain questionnaires and the joints affected were examined by thermography. Although significant correlations were shown between parent and doctor pain intensity ratings and joint temperature, correlations of patient pain intensity ratings and joint temperature were only significant in younger children. The degree of joint inflammation is only one factor of several contributing to the amount of subjective pain experienced by children with juvenile rheumatoid arthritis, indicating the need for a comprehensive assessment of the relatively independent variables of inflammation and pain in children with juvenile rheumatoid arthritis.