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ID PMID Title PublicationDate abstract
9249143 Do synovial fluid acute phase proteins from patients with rheumatoid arthritis originate f 1997 Jun This study was performed in order to gain insight into the occurrence, glycosylation and the possible origin of the acute-phase proteins alpha1-acid glycoprotein (AGP) and alpha1-protease inhibitor (PI) in sera and synovial fluid from patients with rheumatoid arthritis (RA). Therefore paired sera and synovial fluid samples from patients with RA, and paired synovial fluid samples from right and left knees of patients with varying degrees of arthritis were studied. Crossed affinity immunoelectrophoresis (CAIE) was used with concanavalin A and Aleuria aurantia lectin for the detection of the degree of branching and fucosylation, respectively, and the monoclonal CSLEX-1 for the detection of Sialyl Lewis(X) (SLe(X)) groups on AGP. For PI, not only CAIE, but also high-pressure-anion-exchange chromatography with pulsed amperometric detection was used to study the glycosylation. It was established that the concentrations of AGP and PI were increased in the serum of RA patients compared to normal healthy controls, but that the concentration of both proteins, as well as albumin, was significantly lower in synovial fluid than in serum. Furthermore, the type of glycosylation of both AGP and PI found in RA was significantly different from that found in normals, with increased fucosylation, but there were no major differences in the degree of branching of AGP- or PI-glycans in RA, compared to normals. No differences in glycosylation could be established between serum and synovial fluid in RA. For PI an increased fucosylation was found, both in serum and synovial fluid, using both methods of detection, and it could be established that only the alpha1-->3- and not the alpha1-->6-fucosylation of PI was affected by RA. The increased fucosylation of AGP resulted in an increased expression of SLe(X) on AGP-glycans. Since the alpha1-->3-fucosylation of AGP was significantly increased in both serum and synovial fluid from RA patients, and this correlated with systemic but not with local disease parameters, it can be suggested that acute phase proteins in synovial fluid are most probably of hepatic origin.
10210770 Possible genetic association between interleukin-1alpha gene polymorphism and the severity 1999 Mar Interleukin-1 (IL-1) has been implicated in the pathogenesis of rheumatoid arthritis (RA). IL-1alpha gene polymorphism was analysed for the exon V and promoter region in 51 patients with destructive and 47 with non-destructive RA, as well as in 94 controls. The two biallelic polymorphisms in the promoter region and the exon V were 100% linked. The rare IL-1A2 allele carriage rate was 45% in the control population. It was increased in destructive (54.4%) and decreased in non-destructive RA (26.8%, destructive versus non-destructive, p < 0.007). All indices of disease activity and joint destruction were significantly lower in the patients positive for IL-1A1, and higher in those positive for IL-1A2. The present findings suggest that this IL-1alpha gene polymorphism may contribute to the pathogenesis of chronic polyarthritis. The presence of the IL-1A2 allele could constitute a risk factor for the development of destructive arthritis and could be used early in the course of the disease as a prognostic marker.
10989678 [The importance of Helicobacter--beyond the stomach too]. 2000 The discovery of H. pylori as causative agent for peptic ulcers was a milestone in gastroenterology. Apart from peptic ulcer, H. pylori may play a role in the pathogenesis of coronary heart disease, rheumatoid arthritis, Sjoegren's syndrome and hepatic encephalopathy. These associations are still controversial and need further studies. Other strains (H. bilis, H. hepaticus, H. rappani, H. pullorum) may cause chronic hepatobiliary diseases or diarrhea. The possible role of such strains in carcinogenesis is very interesting and should be further explored.
10381040 Identification and prevalence of rheumatoid nodules in the finger tendons using high frequ 1999 Jun OBJECTIVE: Rheumatoid nodules are classical diagnostic feature of rheumatoid arthritis (RA). The prevalence of rheumatoid nodules in the finger tendons is not known. We determined the prevalence of rheumatoid nodules of finger tendons in patients with RA, using high frequency linear transducers with high resolution ultrasonography. METHODS: The study comprised 54 consecutive patients with RA and 20 controls. Dynamic ultrasound examination of various tendons was performed using real-time equipment, the Apogee 800 ATL, with an 11 MHz linear array transducer. RESULTS: RA nodules were identified in 9 patients (16.66%); their sizes ranged from 0.21 to 0.95 cm (mean 0.35+/-0.12 cm), in 4 cases (7.4%) the nodules were intratendinous. The flexor tendons were affected in the 9 patients. The finger tendon ultrasonography identified RA nodules that had escaped routine clinical detection. CONCLUSION: The ultrasonography technique was valuable in the confirmation of rheumatoid nodule involvement of the finger tendons. The prevalence of rheumatoid nodule in finger tendons was 16.66%. We believe that ultrasonography should be the screening procedure of choice for diagnosis of RA nodules of the fingers.
11529644 Rheumatoid arthritis induced by alpha-interferon therapy. 2001 Interferon (IFN) therapy has been used for the treatment of common diseases such as hepatitis C, myeloproliferative disorders, autoimmune diseases and various types of cancer. Given the biological properties of interferon, it is not surprising that there are a larger number of side effects due to its use. Although rheumatoid arthritis (RA) is one of the most common autoimmune diseases found in clinical practice, it does not seem to be frequently related to IFN therapy. We report a 40-year-old female patient who, after high doses of IFN-alpha therapy for malignant melanoma, developed symmetrical polyarthritis, with pain and oedema in small and large joints, associated with prolonged morning stiffness. She had positive rheumatoid factor and DR4 HLA phenotype. She was treated with deflazacort (6 mg/day), chloroquine and NSAIDs, with a partial response. In conclusion, although the development of RA after IFN therapy is a rare event, IFN may work as a 'trigger' for such complication, leading to deregulation in the immune cascade in a person genetically predisposed.
9037344 Psychosocial factors and health status in women with rheumatoid arthritis: predictive mode 1997 Jan INTRODUCTION: Health status, and consequently productivity and quality of life, depends on a multitude of factors. Numerous psychosocial factors have been associated with the concurrent health status of individuals with chronic disease. Previous studies have examined the relationship between singular psychosocial factors and health status in rheumatoid arthritis. This study evaluated the simultaneous interrelationships among selected psychosocial variable and health outcomes using data from a study of younger women diagnosed with rheumatoid arthritis (RA). METHODS: The hypothesized models were examined using data from a survey of 185 women with a mean age of 43 years, diagnosed with RA for an average of 6.6 years. Participants in the study completed the following measures: (1) Arthritis Impact Measurement Scales, (2) Multidimensional Pain Inventory, (3) Daily Hassles Scale, (4) Interpersonal Support Evaluation List, and (5) Perceived Self-Efficacy Scale. RESULTS: Using path analysis, the information provided by the LISREL program, and extant theory, two models were tested. The data provided support for all but two of the hypothesized relationships in the model predicting physical functioning. Pain severity and self-efficacy emerged as important variables in understanding individual variations in perceived physical functioning. In the second model, using perceived well-being as the outcome, two bidirectional relationships were noted: one between affective distress and social support, and the second between perceived well-being and daily stress. CONCLUSIONS: The models evaluated in this study support the provision of multifaceted interventions aimed at enhancing a woman's ability to manage her pain and stress while also enhancing her beliefs in her own abilities.
10728741 Treatment with leflunomide slows radiographic progression of rheumatoid arthritis: results 2000 Mar OBJECTIVE: To determine whether treatment with leflunomide (LEF), methotrexate (MTX), or sulfasalazine (SSZ) for 6-12 months retards progression of radiographic damage and to identify clinical variables that correlate with radiographic progression. METHODS: Radiographs of the hands and feet were performed at baseline and at the end of study or early exit in 3 randomized controlled trials. Protocol US301 was a 12-month controlled trial of LEF or MTX treatment compared with placebo in 482 patients randomized in a 3:3:2 ratio. Protocol MN301 compared 6 months of LEF or SSZ treatment with placebo in 358 patients, randomized in a 3:3:2 ratio, with continued blinded treatment in the active control arms for 12 months. Protocol MN302 compared 12 months of LEF treatment with MTX in 999 patients. Radiographs were blinded for sequence and treatment and were scored for erosions and joint space narrowing. All analyses were by intent-to-treat. Sensitivity analyses were performed to account for missing data. RESULTS: LEF, MTX, and SSZ treatment resulted in statistically significantly less radiographic progression compared with placebo at 6 and 12 months: for protocol US301, LEF versus placebo P = 0.0007 and MTX versus placebo P = 0.0196; for protocol MN301, LEF versus placebo P = 0.0004 and SSZ versus placebo P = 0.0484. The effect of LEF treatment was similar to that of MTX and SSZ. CONCLUSION: These are the first 6- and 12-month randomized placebo- and active drug-controlled trials to demonstrate retardation of radiographic progression by a new disease-modifying antirheumatic drug (DMARD), LEF, as well as 2 commonly used DMARDs, MTX and SSZ.
9458198 Prevalence of rheumatoid arthritis in circumpolar native populations. 1998 Jan OBJECTIVE: To compare the prevalence of rheumatoid arthritis (RA) in related, but geographically separate, indigenous circumpolar populations. METHODS: Cases were identified by community survey in Russia and by examination of cases located through arthritis registries, a computerized patient information database, and query of local health care providers in Alaska. All possible cases were verified by examination and application of the American College of Rheumatology 1987 criteria. RESULTS: The prevalence rates of RA (age standardized to US population of 1980) varied from 0.62% in the Alaskan Yupik to 1.78% in the Alaskan Inupiat. The Russian Chukchi rate was 0.73% and that of the Siberian Eskimo was 1.42%. CONCLUSION: The Alaskan Yupik Eskimo and Chukchi natives had prevalence rates of RA within the usual range of North American Caucasian groups, in contrast to the Russian Siberian Eskimo and the Alaskan Inupiat Eskimo of the Barrow region, whose high rates approached those of unrelated North American native groups living in very different environments. The Alaskan Inupiat rate was significantly higher than that of the Alaskan Yupik (OR = 2.51, 95% CI 1.25-5.07; p = 0.013), but statistical inferences are limited in the Russian study populations by the small case numbers. The high prevalence rates probably have a genetic basis, although an environmental influence cannot be excluded.
9313387 Commercial wrist extensor orthoses: a descriptive study of use and preference in patients 1997 Feb OBJECTIVE: To describe patients' functional uses of 3 commercial wrist orthoses, to describe patients' preference patterns for the orthoses, and to clarify orthotic attributes that are viewed positively and negatively. METHODS: Using a cross-over design, 42 patients with definite rheumatoid arthritis used each of 3 commercial orthoses for one week. There was a one-week wash-out between each week of use. At the end of the study, private semi-structured interviews were conducted with each participant. Data from close-ended questions were tabulated. Open-ended data were analyzed using qualitative methods. RESULTS: Patients reported that the 3 commercial wrist orthoses reduced wrist pain similarly, but that comfort and a sense of security during functional tasks were only found if the orthoses were comfortable and well-fitting. Most subjects preferred the padded, short forearm orthosis, though a small number found it uncomfortably warm, and many complained that it was difficult to use when wearing long-sleeved garments. Common complaints about the two elastic orthoses included chafing at the thumb webspace and chafing at the proximal closures. Longer forearm length was often perceived as providing unnecessarily high levels of wrist support. CONCLUSIONS: No single orthosis suited all subjects. Satisfaction with an orthosis appears to be based not only on its therapeutic effect, but also the comfort and ease of its use. To maximize patient satisfaction and improve the likelihood of appropriate fit and comfort, several styles of commercial orthoses should be available. The current trend toward restricted clinic stocks appears contrary to both therapeutic goals and patient satisfaction.
9733450 Why not use OSRA? A comparison of Overall Status in Rheumatoid Arthritis (RA) with ACR cor 1998 Sep OBJECTIVE: The Overall Status in Rheumatoid Arthritis (OSRA) is a recently validated measure designed for routine immediate clinical use in patients with rheumatoid arthritis (RA). It is composed of demographic data, activity score (activity total), damage score (damage total), and drug treatment. We tested the hypothesis that this tool relates to existing measures and pooled indices of disease activity, including the SF-36. METHODS: Demographic information, OSRA, SF-36, and the ACR core set [inflammatory indicators (ESR, CRP), tender and swollen joints, visual analog scale for pain, Patient and Physician Global Assessment, and Health Assessment Questionnaire (HAQ)] were collected for 86 consecutive outpatients with RA who were starting or changing second-line therapy and again at 6 months. OSRA measures were examined for their relationship to all core set variables (SF-36, HAQ, Stoke Index, Disease Activity Score, and Mallya-Mace) using Spearman's rank correlation. OSRA was used to audit 246 consecutive outpatients with RA to determine its clinical utility. RESULTS: The median age was 58 years (range 29-82); median disease duration 63 mo (range 3-384); OSRA disease activity (mean 3.8, range 0-8) and damage (mean 2.7, range 0-7) scores were strongly associated with specific ACR core set and SF-36 measures, and all pooled indices examined. OSRA disease activity was significantly higher in outpatients in whom second-line therapy was changed. CONCLUSION: (1) The OSRA was highly correlated with HAQ and core set measures of disease activity: (2) the OSRA damage total was strongly associated with HAQ and correlated strongly with both duration and Larsen score; (3) OSRA scores also correlated well with specific SF-36 measures (activity total with Physical Functioning and Bodily Pain; damage total with Physical and Social Functioning); (4) OSRA shows good correlation with pooled indices that cannot be performed immediately in clinic; and (5) the OSRA activity score shows a strong association with clinical decisions made in the outpatient department.
11035127 Association of rheumatoid factors and anti-filaggrin antibodies with severity of erosions 2000 Oct OBJECTIVES: To evaluate and to compare the association of two types of autoantibodies-rheumatoid factors (RF) and anti-filaggrin antibodies (AFA)-with clinical severity and joint damage progression in rheumatoid arthritis (RA) patients. METHODS: In a cross-sectional study, we determined RF and AFA titres in 199 RA patients and 65 controls. Erosions apparent on X-rays were quantified using the Larsen score in 143 patients, and the distribution of these scores was studied according to disease duration in patients who were positive and negative for RF and AFA. RESULTS: RF were detected in 72% and AFA in 47% of RA patients. AFA were highly specific for RA (100%). RF positivity was correlated with the presence of subcutaneous nodules, sicca syndrome and the severity of erosions for a given disease duration. AFA positivity was correlated only with the presence of the HLA-DRB1 shared epitope. CONCLUSIONS: Since no significant correlation was observed between joint damage progression and AFA positivity, the determination of AFA does not appear to be useful in assessing the prognosis of RA. However, AFA, which appear early in RA, could be helpful for the diagnosis of RA in patients who do not fulfil four American College of Rheumatology criteria.
11578014 Randomized, double-blind trial of anti-interferon-gamma antibodies in rheumatoid arthritis 2001 INTRODUCTION: An increasing body of evidence indicates that interferon (IFN )-gamma is an immunoregulator and may play a key role in the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). OBJECTIVE: To assess the efficacy and tolerability of anti-IFN-gamma in patients with active RA. METHODS: In a randomized, double-blind trial, 30 patients with active RA were randomly assigned to receive intramuscular injections of anti-IFN-gamma, anti-TNF-alpha, or placebo for 5 consecutive days. RESULTS: Both anti-cytokines were significantly superior to placebo. Patients stopping treatment due to lack of efficacy included I receiving anti-TNF-alpha, 2 receiving anti-IFN-gamma, and 9 receiving placebo. According to the physician's assessment, improvement was achieved by the 7th day in 9 patients receiving anti-TNF-alpha, 7 receiving anti-IFN-gamma, and 2 receiving placebo. By day 28 the corresponding figures were 8, 8, and 0, respectively. CONCLUSION: Antibodies to IFN-gamma could be a promising approach to treating RA, especially its treatment-resistant forms.
10402163 Nuclear factor kappaB (NF-kappaB) pathway as a therapeutic target in rheumatoid arthritis. 1999 Jun Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint swelling and progressive destruction of cartilage and bone. Current RA treatments are largely empirical in origin and their precise mechanism of action is uncertain. Increasing evidence shows that chronic inflammatory diseases such as RA are caused by prolonged production of proinflammatory cytokines including tumor necrosis factor (TNF) and interleukin 1 (IL-1). The nuclear factor kappaB (NF-kappaB) plays an essential role in transcriptional activation of TNF and IL-1. NF-kappaB is induced by many stimuli including TNF and IL-1, forming a positive regulatory cycle that may amplify and maintain RA disease process. NF-kappaB and enzymes involved in its activation can be a target for anti-inflammatory treatment. Aspirin and sodium salicylate inhibit activation of NF-KB by blocking IkappaB kinase, a key enzyme in NF-kappaB activation. Glucocorticoids suppress expression of inflammatory genes by binding glucocorticoid receptor with NF-kappaB, and increasing expression of inhibitory protein of NF-kappaB, IkappaBalpha. Sulfasalazine and gold compounds also inhibit NF-kappaB activation. Continuing advances in our understanding of action mechanism of antirheumatic agents will benefit the future development of RA regimens with greater efficacy and less toxicity.
10024928 Wasting of the small hand muscles in upper and mid-cervical cord lesions. 1998 Oct Four patients are described with destructive rheumatoid arthritis of the cervical spine and neurogenic wasting of forearm and hand muscles. The pathological connection is not immediately obvious, but a relationship between these two observations is described here with clinical, radiological, electrophysiological and necropsy findings. Compression of the anterior spinal artery at upper and mid-cervical levels is demonstrated to be the likely cause of changes lower in the spinal cord. These are shown to be due to the resulting ischaemia of the anterior part of the lower cervical spinal cord, with degeneration of the neurones innervating the forearm and hand muscles. These findings favour external compression of the anterior spinal artery leading to ischaemia in a watershed area as the likeliest explanation for this otherwise inappropriate and bizarre phenomenon.
9569071 HLA-DRB1 alleles associated with rheumatoid arthritis in Northern Italy: correlation with 1998 Feb The aim of the study was to evaluate the relationship between the presence of the 'rheumatoid epitope', defined by a sequence motif in the HLA-DRB1 alleles, rheumatoid factor and disease severity in Northern Italian patients with rheumatoid arthritis (RA). Twenty-nine DR4-positive and 57 DR4-negative RA patients were studied. Each DR4-positive patient was matched with two DR4-negative controls of similar disease duration and sex. HLA-DRB1 alleles were determined in the 86 patients and 351 controls from the same geographical area. The patients were retrospectively evaluated for extra-articular features (EAF) and radiographic damage. The rheumatoid epitope was expressed in 45% of patients. No significant differences in the presence of rheumatoid factor, EAF and articular damage were observed between patients with no, one or two doses of epitope. However, the patients encoding the epitope by an HLA-DR4 allele had a higher number of eroded joints and a higher Larsen score compared to those without the epitope. No differences were present between patients expressing HLA-DRB1*01 alleles and those lacking the rheumatoid epitope. Even in the absence of expression of the rheumatoid epitope, seropositive patients had more EAF and more erosive disease compared to those who were seronegative. Even if most Northern Italian RA patients do not express the rheumatoid epitope, the radiological severity of disease is associated with HLA-DRB1*04 alleles.
11665963 Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison 2001 Oct OBJECTIVE: To compare the efficacy of minocycline with that of a conventional disease-modifying antirheumatic drug (DMARD), hydroxychloroquine, in patients with early seropositive rheumatoid arthritis (RA). METHODS: Sixty patients with seropositive RA of <1 year's duration who had not been previously treated with DMARDs were randomized to receive minocycline, 100 mg twice per day, or hydroxychloroquine, 200 mg twice per day, in a 2-year, double-blind protocol. All patients also received low-dose prednisone. The primary end points of the study were 1) the percentage of patients with an American College of Rheumatology (ACR) 50% improvement (ACR50) response at 2 years, and 2) the dosage of prednisone at 2 years. RESULTS: Minocycline-treated patients were more likely to achieve an ACR50 response at 2 years compared with hydroxychloroquine-treated patients (60% compared with 33%, respectively; P = 0.04). Minocycline-treated patients were also receiving less prednisone at 2 years compared with the hydroxychloroquine group (mean 0.81 mg/day compared with 3.21 mg/day, respectively; P < 0.01). In addition, patients treated with minocycline were more likely to have been completely tapered off prednisone (P = 0.03). Trends favoring the minocycline treatment group were seen when outcomes were assessed according to components of the ACR core criteria set, with the differences reaching statistical significance for patient's global assessment of disease activity (P = 0.004). CONCLUSION: Minocycline is an effective DMARD in patients with early seropositive RA. Patients treated with minocycline were more likely to achieve an ACR50 response and did so while receiving less prednisone. In addition, minocycline-treated patients were more likely to have discontinued treatment with prednisone at 2 years.
9619895 Measuring health status in British patients with rheumatoid arthritis: reliability, validi 1998 Apr The objective was to assess the performance of the SF-36 health survey (SF-36) in a sample of patients with rheumatoid arthritis (RA) stratified by functional class. The eight SF-36 subscales and the two summary scales (the physical and mental component scales) were assessed for test retest reliability, construct validity and responsiveness to self-reported change in health. In 233 patients with RA, the SF-36 scales were: reliable (intra-class correlation coefficients 0.76-0.93); correlated with American College of Rheumatology (ACR) core disease activity measures [Spearman r = -0.12 (erythrocyte sedimentation rate) to -0.89 (Modified Health Assessment Questionnaire)]; and responsive to improvements in health (standardized response means 0.27-0.9). The distribution of scores on four of the eight subscales (physical function, role limitations physical, role limitations emotional and social function) was clearly non-Gaussian. Very marked floor effects were noted with the physical function scale, and both ceiling and floor effects with the other three subscales. The two SF-36 physical and mental component summary scales are reliable, valid and responsive measures of health status in patients with RA. Six of the eight subscales meet standards required for comparing groups of patients, and the physical function and general health scales may be suitable for monitoring individuals. The two scales measuring role limitations have poor measurement characteristics. The SF-36 pain and physical function scales may be suitable for use as patient self-assessed measures of pain and physical function within the ACR core disease activity set.
9632062 P-selectin as a circulating molecular marker in rheumatoid arthritis with thrombocytosis. 1998 Jun OBJECTIVE: To compare plasma concentrations of soluble P-selectin (sP-selectin) in patients with rheumatoid arthritis (RA) and thrombocytosis with those with RA with normal platelet counts and healthy controls, and to explore the relationship between clinical and serological measures of disease activity. METHODS: Nineteen patients with RA with marked thrombocytosis, 20 with normal platelet counts, and 24 controls were enrolled. Ritchie articular index and morning stiffness were recorded as clinical markers of disease activity. Blood samples were collected for platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma sP-selectin determinations. Correlations between sP-selectin and clinical and serological markers of disease activity were noted. RESULTS: Patients with RA and thrombocytosis compared to patients with normal platelet counts showed evidence of more active disease when ESR, CRP, morning stiffness, and Ritchie articular index were considered. The thrombocyte count in patients with RA with marked thrombocytosis revealed a positive correlation with CRP and Ritchie articular score. Plasma sP-selectin levels were found to be significantly higher in patients with RA compared to controls. sP-selectin levels were significantly higher in patients with RA with thrombocytosis compared to those with normal platelet counts, and positive correlations were observed between plasma sP-selectin levels and Ritchie index, morning stiffness, and thrombocyte counts in those patients. CONCLUSION: Elevated plasma sP-selectin levels in RA could indicate the presence of a continuous underlying inflammatory stimulus. In addition, the augmented increase in patients with RA and thrombocytosis and its correlation with clinical activity may imply the cytokine-adhesion molecule interaction mediates the chronic inflammation of RA.
10829806 [YKL 40: marker of disease activity in rheumatoid arthritis?]. 1999 Nov In patients with rheumatoid arthritis the serum and synovial fluid levels of a glycoprotein called YKL 40 are correlated to the severity of disease. YKL 40 may be related to disease activity in RA; it is induced by vitamine D and is reduced by TGF b. YKL 40 has been isolated from bovine mammary secretions during non lactating period and from Human osteosarcoma cell line MG-63. Some observations on experimental and clinical studies are presented.
11421639 Iron(III)-mediated intra-articular crystal deposition in arthritis: a therapeutic role for 2001 Jul Crystal deposition in arthritic diseases has attracted much interest. Many reports have established the presence of calcium pyrophosphate (CPPD), hydroxyapatite (HAP) and urate crystals throughout the range of arthritic diseases. In particular, HAP crystals have been detected in 30-60% of synovial fluid (SF) samples from patients suffering from osteoarthritis (OA) and 33% of those suffering from rheumatoid arthritis (RA). In OA, crystal deposition has been linked to greater joint deterioration. The mechanism of intra-articular calcification is unknown. Nucleation is required to transform a 'metastable' phosphate- and calcium-rich biofluid into one that generates crystals. Ferric ions have been demonstrated to induce crystallization of these stable supersaturated solutions via the process of nucleation. The inflamed arthritic joint is prone to iron loading. Microbleeding from compromised vasculature contributes to intra-articular iron loading in arthritic conditions. Low-molecular-mass redox-active iron complexes have been detected in SF in inflammatory joint diseases. These species are credited with mediating oxidative stress via interaction with peroxides and superoxide. In addition, adventitious low-molecular-mass iron complexes can cause nucleation leading to crystal growth within the joint. Decorporating agents capable of removing this misplaced iron from the arthritic joint would have the joint benefit of relieving oxidative stress and preventing crystal nucleation. Systemic side effects could be overcome by the targeting suitable chelators using bioreductive delivery systems that are activated in hypoxic inflamed synovial tissue.