Pigmented Villonodular Synovitis: A Retrospective Multicenter Study of 237 Cases

Purpose

To review clinical characteristics of pigmented villonodular synovitis (PVNS) in China.

Methods

Electronic medical records (EMR) of four Chinese institutes were queried for patients with histologically proven PVNS between January 2005 and February 2014. Their data were collected including gender, age at diagnosis, clinical presentation, affected site, symptom duration, comorbidities, treatment strategy, recurrence and routine laboratories.

Results

A total of 237 patients with biopsy-proven PVNS were investigated. The gender ratio was 1.35 for a female predominance (101 males and 136 females). The average age was 36 years (range, 2 to 83 years). The median delay from initial clinical symptom to diagnosis was 18 months. Main affected areas were the knee (73.84%) and the hip (18.14%). Forty patients had a clear history of joint trauma. Six patients were concurrently diagnosed with PVNS and avascular necrosis (AVN). Five patients suffered from PVNS following implantation of orthopaedic devices including artificial prosthesis, plate and wire. One hundred and twenty-nine patients underwent arthroscopic synovectomy and 108 open synovectomy. Altogether 48 patients (26 males and 22 females) had recurrence of disease. The relapse rate was 24% (knee) and 6.98% (hip), 20.93% (open surgery) and 19.44% (arthroscopy), respectively. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) rate were elevated in 45.83% and 38.41% of the patients respectively.

Conclusions

To our knowledge, this study is the largest sample size of PVNS patients reported as well as the largest sample of PVNS with concurrent AVN reported to date. Our outcomes suggest that PVNS shows a female predominance, occurs mostly between 20–40 years and favors the knee and hip. Recurrence is frequent, particularly in the knee. Serum ESR and CRP may be elevated in some patients. Additionally, the present study supports the theory of an association between PVNS and orthopedic surgery, which is not limited to joint replacement.     

Comparative analysis of cell populations involved in the proliferative and inflammatory processes in diffuse and localised pigmented villonodular synovitis

The aim of the present study was a comparative quantitative evaluation of cell populations involved in the proliferative and inflammatory compartment in both localised and diffuse pigmented synovitis villonodularis (PVNS). 15 cases of each localised and diffuse PVNS were examined by flow cytometry, immunohistochemistry, double immuno-fluorescence and confocal microscopy with quantitative evaluation of CD3-, CD4-, CD8-, CD20-, CD57-, CD55-, CD68-, CD163- and h4Ph positive (+) cells. The proliferative compartment of localised and diffuse PVNS was mainly composed of double-positive CD68+/h4Ph+ (CD163+/CD55+) synoviocytes. The number of double-positive synoviocytes for macrophage and fibroblast markers was significantly higher in diffuse compared to localised PVNS. The accompanying inflammatory infiltrate showed a predominance of cytotoxic cells (CD8+, CD57+), whereby the number of CD3+ and CD20+ cells was significantly higher in localised PVNS. The number of CD57+ NK cells was significantly higher in diffuse PVNS. The proliferating macrophage- like synovial cells and the cytotoxic lymphocytes could contribute to the aggressive behaviour of localised and diffuse PVNS. Moreover, with regard to the quantitative differences in cell composition between diffuse and localised PVNS and their different clinical behaviour, further studies should continue to analyse localised and diffuse PVNS separately.     

Apoptosis resistance in pigmented villonodular synovitis

OBJECTIVE: Pigmented villonodular synovitis (PVNS) is a proliferative lesion originating from synovial tissue with a locally aggressive behaviour. We analysed the pathogenetic role of apoptosis resistance for sustained cell proliferation in PVNS. METHODS: The expression of bcl-2, p53 and Ki-67 was examined in 80 cases of PVNS using immunohistochemistry. In 43 of these cases, DNA content and distribution of cell-cycle phases were investigated by flow cytometry. Additionally, 10 cases of PVNS were analysed by multi-parametric flow cytometry for expression of p53, caspase3, and bcl-2 and by TUNEL to detect DNA fragmentation. RESULTS: No apoptotic cell fractions were detected in any investigated cases. Expression of bcl-2 was found in 84% of cases (up to 6.5% of cells) and was significantly associated with DNA-fragmentation observed by TUNEL (p=0.037). Orthologous p53 expression was observed in 37% of cases. The level of p53 expression correlated with the proliferative activity and the expression of both caspase3 (p=0.017) and bcl-2 (p=0.0013). (No statistically significant correlations between expression of bcl-2, p53, caspase3, DNA fragmentation or proliferative index and age, sex of patients, disease recurrence, growth pattern or size of lesion were found). CONCLUSION: Apoptosis resistance is a critical event in the progression of PVNS and may contribute to the survival of the proliferating synovial cells in PVNS and to the permanent slow progression of these lesions.     

重组合异种骨治疗股骨非感染性骨不连的长期疗效观察

目的:探讨重组合异种骨治疗股骨非感染性骨不连的长期临床疗效。方法:对2000年1月至2006年9月间我院应用重组合异种骨(RBX)治疗的37例股骨非感染性骨不连患者进行回顾性分析,其中男26例,女11例;年龄4～70岁,平均31.6岁。骨折部位:股骨近端4例,中段30例,远端3例。骨不连类型:肥大型9例,营养不良型6例,萎缩型22例。固定方式:加压钢板24例,髓内钉11例,外固定架2例。结果:37例患者获得51-131个月的随访,平均90.2个月,骨不连一次手术愈合率:94.6%,4例股骨近端骨不连患者采用Harris评分系统评定疗效,优3例,良1例,差0例,优良率100%。3例股骨远端骨不连患者采用美国膝关节协会评分系统(KSS)评定疗效,优1例,例良1例,差1例,优良率66.7%。30例股骨干骨不连患者采用Harris评分系统和KSS评定疗效,优21例,良8例,差1例,优良率96.7。总优良率94.6%。长期观察均无免疫排斥反应表现。结论:RBX用于治疗股骨非感染性骨不连具有材料充足、骨折愈合率高、组织兼容性好长期应用无免疫排斥反应等优点,是一种良好的自体骨替代材料。     

Variability in synovial inflammation in rheumatoid arthritis investigated by microarray technology

In recent years microarray technology has been used increasingly to acquire knowledge about the pathogenic processes involved in rheumatoid arthritis. The present study investigated variations in gene expression in synovial tissues within and between patients with rheumatoid arthritis. This was done by applying microarray technology on multiple synovial biopsies obtained from the same knee joints. In this way the relative levels of intra-patient and inter-patient variation could be assessed. The biopsies were obtained from 13 different patients: 7 by orthopedic surgery and 6 by rheumatic arthroscopy. The data show that levels of heterogeneity varied substantially between the biopsies, because the number of genes found to be differentially expressed between pairs of biopsies from the same knee ranged from 6 to 2,133. Both arthroscopic and orthopedic biopsies were examined, allowing us to compare the two sampling methods. We found that the average number of differentially expressed genes between biopsies from the same patient was about three times larger in orthopedic than in arthroscopic biopsies. Using a parallel analysis of the tissues by immunohistochemistry, we also identified orthopedic biopsies that were unsuitable for gene expression analysis of synovial inflammation due to sampling of non-inflamed parts of the tissue. Removing these biopsies reduced the average number of differentially expressed genes between the orthopedic biopsies from 455 to 171, in comparison with 143 for the arthroscopic biopsies. Hierarchical clustering analysis showed that the remaining orthopedic and arthroscopic biopsies had gene expression signatures that were unique for each patient, apparently reflecting patient variation rather than tissue heterogeneity. Subsets of genes found to vary between biopsies were investigated for overrepresentation of biological processes by using gene ontology. This revealed representative 'themes' likely to vary between synovial biopsies affected by inflammatory disease.     

Further experience in rehabilitation of zone II flexor tendon repair with dynamic traction splinting

A review of all flexor tendon repairs in the "no man's land" performed from January of 1985 to June of 1987 was done to evaluate the efficacy of our method of rehabilitation. There were 60 fingers (57 patients) with complete laceration of the flexor digitorum profundus and flexor digitorum superficialis tendons in zone II. Fingers with phalangeal fractures, joint injuries, or significant skin loss were excluded. Follow-up ranged from 12 to 48 months. Rehabilitation consisted of a 12-week protocol using the U.S. military combined regimen of controlled motion. Features from the technique of controlled active extension against rubber band passive flexion as well as those of controlled passive extension and passive flexion were incorporated. The palmar pulley modification of Kleinert's dynamic traction splint was utilized. Strickland's total active motion formula was employed to determine results. The results were classified into the four categories of excellent, good, fair, and poor. Fifty-two fingers (86 percent) were rated excellent, 4 fingers (7 percent) were rated good, 1 finger (2 percent) was rated fair, and 3 fingers (5 percent) were rated poor.     

Détection fortuite d’une synovite villonodulaire extra-articulaire du muscle psoas en tomographie par émission de positons au 18F-fluorodésoxyglucose

Pigmented villonodular synovitis (PVNS) is a benign but locally aggressive disorder, which commonly involves large joints. This article reports a rare case of an extra-articular PVNS located within the left psoas muscle. This lesion has been accidentally discovered during a follow-up FDG PET/CT. The patient was asymptomatic and did not undergo any surgery. This article reports that FDG PET/CT could be helpful for monitoring PVNS.     

Elimination of rheumatoid synovium in situ using a Fas ligand 'gene scalpel'

Surgical synovectomy to remove the inflammatory synovium can temporarily ameliorate rheumatoid inflammation and delay the progress of joint destruction. An efficient medically induced programmed cell death (apoptosis) in the rheumatoid synovium might play a role similar to synovectomy but without surgical tissue damage. Gene transfer of Fas ligand (FasL) has increased the frequency of apoptotic cells in mouse and rabbit arthritic synovium. In this study, we investigated whether repeated FasL gene transfer could remove human inflammatory synovial tissue in situ and function as a molecular synovectomy. Briefly, specimens of human synovium from joint replacement surgeries and synovectomies of rheumatoid arthritis (RA) patients were grafted subcutaneously into male C.B-17 severe combined immunodeficiency (SCID) mice. Injections of a recombinant FasL adenovirus (Ad-FasL) into the grafted synovial tissue at the dosage of 10(11) particles per mouse were performed every two weeks. Three days after the fifth virus injection, the mice were euthanized by CO2 inhalation and the human synovial tissues were collected, weighed and further examined. Compared to the control adenovirus-LacZ (Ad-LacZ) and phosphate buffered saline (PBS) injected RA synovium, the Ad-FasL injected RA synovium was dramatically reduced in size and weight (P < 0.005). The number of both synoviocytes & mononuclear cells was significantly reduced. Interestingly, an approximate 15-fold increased frequency of apoptotic cells was observed in RA synovium three days after Ad-FasL injection, compared with control tissues. In summary, our in vivo investigation of gene transfer to human synovium in SCID mice suggests that repeated intra-articular gene transfer of an apoptosis inducer, such as FasL, may function as a 'gene scalpel' for molecular synovectomy to arrest inflammatory synovium at an early stage of RA.     

Angular dermoid cysts in the endoscopic era: retrospective analysis of aesthetic results using the direct, classic method

The concept of the endoscopic approach was recently introduced for the removal of angular dermoid cysts. Therefore, it was considered necessary to evaluate the conventional direct incisional approach for angular dermoid cyst excision, with respect to long-term aesthetic results and complications. The need to change from the direct excisional technique to the endoscopic approach in hair-bearing areas was investigated. During a 25-year period, 95 children were surgically treated by a single surgeon (H.G.T.) for removal of angular dermoid cysts. Only 22 patients (23 percent) were available for reassessment. The follow-up periods after the excisional procedure were 1 to 12 years. Assessments were performed by a 15-member team of assessors, who scored the aesthetic results of the scars with comparative slides. In addition, a questionnaire was mailed to each family, to document the family members' perceptions of the aesthetic appearance of the scar. Twenty-eight families (29 percent) responded. The complications were determined through the medical records department. For 19 of 22 patients (86 percent), the scar was scored by 85 percent of the assessors as excellent or good. No assessor stated that a scar was unacceptable. In the family questionnaires, 26 of 28 families (93 percent) reported an excellent scar and two (7 percent) reported a fair scar. No family stated that the scar was unacceptable. The operative notes for the 95 patients revealed that only two cysts had ruptured during the surgical procedure (2 percent) and only one infection had occurred (1 percent). No other major complications were reported. It is concluded that the direct method for dermoid cyst excision is an excellent approach, with a low complication rate and a very high aesthetic success rate, when performed through a supra-eyebrow or infra-eyebrow incision.     

Active synovial matrix metalloproteinase-2 is associated with radiographic erosions in patients with early synovitis

Serum and synovial tissue expression of the matrix metalloproteinase (MMP)-2 and -9 and their molecular regulators, MMP-14 and TIMP-2 was examined in 28 patients with inflammatory early synovitis and 4 healthy volunteers and correlated with the presence of erosions in the patients. Immunohistological staining of MMP-2, MMP-14 and TIMP-2 localized to corresponding areas in the synovial lining layer and was almost absent in normal synovium. Patients with radiographic erosions had significantly higher levels of active MMP-2 than patients with no erosions, suggesting that activated MMP-2 levels in synovial tissue may be a marker for a more aggressive synovial lesion.     

Human monoclonal rheumatoid synovial B lymphocyte hybridoma with a new disease-related specificity for cartilage oligomeric matrix protein

Joint-specific self-Ags are considered to play an important role in the induction of synovial T and B cell expansion in human rheumatoid arthritis (RA). However, the nature of these autoantigens is still enigmatic. In this study a somatically mutated IgG2 lambda B cell hybridoma was established from the synovial membrane of an RA patient and analyzed for its Ag specificity. A heptameric peptide of cartilage oligomeric matrix protein (COMP) could be characterized as the target structure recognized by the human synovial B cell hybridoma. The clonotypic V(H) sequences of the COMP-specific hybridoma could also be detected in synovectomy material derived from five different RA patients but in none of the investigated osteoarthritis cases (n = 5), indicating a preferential usage of V(H) genes closely related to those coding for a COMP-specific Ag receptor in RA synovial B cells. Moreover, the COMP heptamer was preferentially recognized by circulating IgG in RA (n = 22) compared with osteoarthritis patients (n = 24) or age-matched healthy controls (n = 20; both p < 0.0001). Hence, the COMP-specific serum IgG is likely to reflect local immune responses toward a cartilage- and tendon-restricted Ag that might be crucial to the induction of tissue damage in RA.     

Arthroscopic surgery of the knee.

In the first 1000 arthroscopic operations performed by one surgeon 136 patients had two or more procedures, making a total of 1168 during the 1000 operations. The indications for operation were internal mechanical derangements in 565 patients, anterior knee pain in 246, disorders of the synovium in 77, ligament injuries in 63, and degenerative joint disease in 49. Complications included fracture of instruments in the knee in five patients, haemarthrosis in 10, deep vein thrombosis in three, and synovial fistula in one. In no patient was the wound infected. A total of 26 different operations was performed.     

Osteopontin Level in Synovial Fluid Is Associated with the Severity of Joint Pain and Cartilage Degradation after Anterior Cruciate Ligament Rupture

Objective

To explore the molecular function of Osteopontin (OPN) in the pathogenesis of human OA, we compared the expression levels of OPN in synovial fluid with clinical parameters such as arthroscopic observation of cartilage damage and joint pain after joint injury.

Methods

Synovial fluid was obtained from patients who underwent anterior cruciate ligament (ACL) reconstruction surgery from 2009 through 2011 in our university hospital. The amounts of intact OPN (OPN Full) and it’s N-terminal fragment (OPN N-half) in synovial fluid from each patient were quantified by ELISA and compared with clinical parameters such as severity of articular cartilage damage (TMDU cartilage score) and severity of joint pain (Visual Analogue Scale and Lysholm score).

Results

Within a month after ACL rupture, both OPN Full and N-half levels in patient synovial fluid were positively correlated with the severity of joint pain. In contrast, patients with ACL injuries greater than one month ago felt less pain if they had higher amounts of OPN N-half in synovial fluid. OPN Full levels were positively correlated with articular cartilage damage in lateral tibial plateau.

Conclusion

Our data suggest that OPN Full and N-half have distinct functions in articular cartilage homeostasis and in human joint pain.     

关节镜清理术治疗前踝撞击征的疗效

目的:探讨踝关节镜对前踝撞击征的诊疗价值。方法:采用关节镜清理术治疗前踝撞击综合征33例,其中男23例,女10例。年龄平均39岁(18～72岁)。左踝16例,右踝17例。病史6个月至20年,有运动损伤史13例,踝关节扭伤病史17例,踝关节骨折史3例。临床表现为踝关节肿胀、疼痛和下蹲活动受限。X线片显示胫骨前唇和距骨骨质增生,MRI显示距骨软骨损伤,踝关节腔内积液。采用局麻关节镜下骨赘磨削,滑膜切除,踝关节清理术。结果:随访33例,平均时间35个月(4个月-6年)。术后踝关节背伸活动功能正常,按照McGuire踝关节评分系统对术前、术后踝关节功能进行评估,术前平均55分,术后平均80分,术后提高了25分。优13例,良15例,可3例,差2例,优良率84.8%。结论:局麻下踝关节镜骨赘切除、滑膜刨削和软骨修整可有效解除踝关节撞击症状,手术创伤小、功能恢复快,效果满意。     

A combined regimen of controlled motion following flexor tendon repair in "no man's land"

A program of controlled motion following repair of flexor tendons in the hand is presented. This regimen incorporates the features of active extension against rubber band passive flexion, as well as those of controlled passive extension and passive flexion. In this prospective study, 44 digits with complete lacerations of the flexor digitorum profundus and flexor digitorum superficialis in zone 2 were treated. Using the Strickland formula of total active motion of the interphalangeal joints, 36 fingers (82 percent) were rated "excellent"; 7 fingers (16 percent) were rated "good"; 1 finger (2 percent) was rated "fair"; none was rated "poor". There was no statistical difference between the results of delayed primary repair and immediate primary repair.     

Open Versus Arthroscopic Surgical Management for Recalcitrant Trochanteric Bursitis: A Systematic Review

BackgroundWhile excision of the trochanteric bursae to treat lateral hip pain has increased in popularity, no comparison exists between the surgical outcomes and complications of the open and arthroscopic techniques involving trochanteric bursectomy. The purpose of this study was to determine the efficacies and complication rates of arthroscopic and open techniques for procedures involving trochanteric bursectomy.MethodsThe terms “trochanteric,” “bursectomy,” “arthroscopic,” “open,” “outcomes,” and “hip” were searched in five electronic databases. Fifteen studies from 120 initial results were included. Patient-reported outcomes (PRO), pain, satisfaction, and complications were included for analysis.ResultsFive hundred-two hips in 474 total patients (77.7% female) were included in this study. The average age was 54. The fourteen distinct PRO scores that were reported by the included studies improved significantly from baseline to final mean follow-up (12-70.8 months for open; 12-42 months for arthroscopic) for both approaches, demonstrating statistically significant patient benefit in a variety of hip arthroscopy settings (P > 0.05). The complication rates of all procedures ranged from 0%-33% and failure to improve pain ranged from 0%-8%. Patient satisfaction with surgery was high at 95% and 82% reported a willingness to undergo the same surgery again. No significant mean differences were found between the open and arthroscopic techniques.ConclusionThe open and arthroscopic approaches for trochanteric bursectomy are both safe and effective procedures in treating refractory lateral hip pain. No significant differences in PROs, pain, total complications, severity of complications, and total failures were seen between technique outcomes.Level of Evidence: IV     

Expression of the interleukin-2 receptor in T lymphocytes of the rheumatoid synovial membrane

Indirect immunofluorescence was used to stain DR antigen and interleukin-2 receptor (Tac) of T-lymphocytes (Leu 4+). Tissue samples of synovial membrane were cut from arthroscopic biopsies of inflamed knees in four patients with active rheumatoid arthritis (RA). Consecutive cryostatic sections of rheumatoid sinovium were analysed using monoclonal antibodies. It was found that a high percentage of T-lymphocytes express DR antigen. In contrast the proportion of T cells expressing Tac was small. We conclude that T cell activation in synovial membrane is incomplete, and this disfunction may contribute to the chronic inflammation of RA.     

Outcome following implantation of a peripheral nerve stimulator in patients with chronic nerve pain

This study evaluated the usefulness of the implanted peripheral nerve stimulator in patients with pain following injury to a peripheral nerve. The patient sample (n = 17) consisted of 7 men and 10 women with a mean age of 48 years (SD = 18 years). The mean follow-up time since implantation of the stimulator was 21 months (SD = 15 months). Workers' compensation and/or litigation were involved in 11 cases. Peripheral nerve stimulators were placed in the upper extremity in 12 patients and in the lower extremity in 5 patients. Pain relief following implantation was rated as excellent by five patients, good by six patients, fair by four patients, and poor by two patients. A statistically significant decrease in reported pain level was found postoperatively (p < 0.0003). There was no statistically significant difference in postoperative pain level between men and women (p = 0.30), between cases involving workers' compensation or litigation and those not involving these issues (p = 1.0), or between patients who received an upper-extremity implant and those who received a lower-extremity implant (p = 0.56). Of the 12 patients who were unable to work before the operation, 6 returned to work after the operation. In conclusion, peripheral nerve stimulators can be useful in decreasing pain in carefully selected patients with severe neurogenic pain.     

Venous malformations of skeletal muscle

Intramuscular venous malformations are often mistaken for tumors because of a similar presentation and improper nomenclature. This is a review of 176 patients with venous malformations localized to skeletal muscle compiled from the Vascular Anomalies Center at Children's Hospital from 1980 through 1999. The female-to-male ratio was 2:1. Two-thirds of skeletal muscle venous malformations were noted at birth; the remainder manifested in childhood and adolescence. Venous malformations occurred in every muscle group, most often in the head and neck and extremities. Pain and swelling were the usual presenting complaints. Skeletal problems, such as fracture, deformation, or growth abnormalities, were rare. Hormonal exacerbation and intralesional bleeding were infrequent. Magnetic resonance imaging showed the lesions to be isointense to surrounding muscle on T1-weighted sequences and hyperintense on T2-weighted images. Characteristic tubular or serpentine components were oriented along the muscular long axis. Thrombi were hyperintense on T1-weighted and hypointense on T2-weighted sequences; phleboliths were seen as signal voids on all sequences. Gross examination of resected specimens revealed multicolored tissue with dilated vascular channels, frequently containing phleboliths. Light microscopy showed aggregates of primarily medium-sized, thin-walled vascular channels with flat endothelium and variable smooth muscle, most closely resembling dysplastic veins. Three lesions had a different histologic appearance consisting predominantly of small vessels with capillary structure and proliferative activity admixed with large feeding and draining vessels, similar to a lesion called intramuscular capillary hemangioma in the literature. The endothelium in these three lesions was negative for glucose transporter-1 by immunostaining. Eight percent of the patients, who had minor or no symptoms, were not treated. Twenty-four percent of the patients were managed conservatively (with aspirin and compressive garments); for 17 of these patients (10 percent of 176), noninvasive therapy was not successful, and they proceeded to sclerotherapy, excision, or both. A total of 31 percent of the patients had sclerotherapy, 20 percent had excision, and 27 percent had combined sclerotherapy and excision. Sclerotherapy was used for diffuse lesions, except for those with multiple intralesional thromboses, neurologic impairment, or compressive signs and symptoms. Resection was preferred for venous malformations well localized to a single muscle or muscle group, particularly if the muscles are expendable. Therapeutic outcomes were recorded in the charts or obtained by telephone interview in 122 of the patients (69 percent). Of these, compression garment and aspirin, resection, sclerotherapy, or combined excision and sclerotherapy improved symptoms in 121 patients (92 percent); no change was noted in 10 patients (8 percent). Only one patient was worse (self-reported) after intervention.     

Interleukin-18 induces serum amyloid A (SAA) protein production from rheumatoid synovial fibroblasts

Interleukin-18 (IL-18) is a novel proinflammatory cytokine that was recently found in synovial fluids and synovial tissues from patients with rheumatoid arthritis (RA). To investigate the role of IL-18 in rheumatoid synovitis, the levels of IL-18 and serum amyloid A (SAA) were measured in synovial fluids from 24 patients with rheumatoid arthritis (RA) and 13 patients with osteoarthritis (OA). The levels of IL-18 and SAA in the synovial fluids were elevated in RA patients. In contrast, the levels of IL-18 in synovial fluids from OA patients were significantly lower compared to those of RA patients. SAA was not detected in synovial fluids from OA patients. The expression of SAA mRNA in rheumatoid synovial cells was also examined. SAA4 mRNA, which was constitutively expressed by rheumatoid synovial cells, was not affected by IL-18 stimulation. Although acute phase SAA (A-SAA, SAA1 + 2) mRNA was not detected in unstimulated synovial cells, its expression was induced by IL-18 stimulation. By immunoblot, we demonstrated that IL-18 induced the SAA protein synthesis from rheumatoid synovial cells in a dose-dependent manner. These results indicate a novel role for IL-18 in rheumatoid inflammation through the synovial SAA production.