Comorbid fibromyalgia: A qualitative review of prevalence and importance.

Fibromyalgia (FM) may be an unrecognized cause of suffering for persons with an array of medical conditions. This is especially true for illness that is characterized by pain of any nature. Once believed to be a unique diagnosis, FM is recently reported to occur concomitantly with various rheumatic diseases, and importantly adversely impacts global health status. However, there is increasing report of FM associated with other diseases that are not defined by chronic pain. This qualitative review examines the evidence for comorbid FM in illness, and where available the effect of FM on the primary disease. Other than for musculoskeletal disorders, the published literature reporting an association of FM with illness is limited with scanty reports for some neurological, gastrointestinal, mental health and other overlapping pain conditions. Comorbid FM adversely affects both health status and outcome for rheumatic diseases, but with limited study in other diseases. When unrecognized, comorbid FM may be mistaken as poor control of the primary disease, leading to incorrect treatment decisions. FM may be a neglected condition that pervades many conditions and may contribute to the burden of illness. Physicians should be alert to the possibility of comorbid FM, and symptoms of FM should be specifically addressed. SIGNIFICANCE: Comorbid fibromyalgia (FM) in other medical conditions is largely unrecognized. When reported as accompanying rheumatic diseases, FM adversely affects global health status. With limited reports of comorbid FM with other conditions, neglect to diagnose comorbid FM may misdirect treatments.

Medical cannabis: A forward vision for the clinician.

Medical cannabis has entered mainstream medicine and is here to stay. Propelled by public advocacy, the media and mostly anecdote rather than sound scientific study, patients worldwide are exploring marijuana use for a vast array of medical conditions including management of chronic pain. Contrary to the usual path of drug approval, medical cannabis has bypassed traditional evidence-based study and has been legalized as a therapeutic product by legislative bodies in various countries. While there is a wealth of basic science and preclinical studies demonstrating effects of cannabinoids in neurobiological systems, especially those pertaining to pain and inflammation, clinical study remains limited. Cannabinoids may hold promise for relief of symptoms in a vast array of conditions, but with many questions as yet unanswered. Rigorous study is needed to examine the true evidence for benefits and risks for various conditions and in various patient populations, the specific molecular effects, ideal methods of administration, and interaction with other medications and substances. In the context of prevalent use, there is an urgency to gather pertinent clinical information about the therapeutic effects as well as risks. Even with considerable uncertainties, the health care community must adhere to the guiding principle of clinical care 'primum non nocere' and continue to provide empathetic patient care while exercising prudence and caution. The health care community must strongly advocate for sound scientific evidence regarding cannabis as a therapy. SIGNIFICANCE: Legalization of medical cannabis has bypassed usual drug regulatory procedures in jurisdictions worldwide. Pending sound evidence for effect in many conditions, physicians must continue to provide competent empathetic care with attention to harm reduction. A vision to navigate the current challenges of medical cannabis is outlined.

Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management - An overview of systematic reviews.

Medicinal cannabis has already entered mainstream medicine in some countries. This systematic review (SR) aimed at evaluating the efficacy, acceptability and safety of cannabis-based medicines for chronic pain management. Qualitative systematic review of SRs of randomized controlled trials with cannabis-based medicines for chronic pain management. The Cochrane databases of SRs, Database of Abstracts of Reviews of Effects and PubMed were searched for SR published in the period January 2009 to January 2017. Assessment of the methodological quality of SR was performed by the AMSTAR checklist. Out of 748 papers identified, 10 SRs met the inclusion criteria. The methodological quality was high in four and moderate in six SRs. There were inconsistent findings of four SRs on the efficacy of cannabis-based medicines in neuropathic pain and of one SR for painful spasms in multiple sclerosis. There were consistent results that there was insufficient evidence of any cannabis-based medicine for pain management in patients with rheumatic diseases (three SRs) and in cancer pain (two SRs). Cannabis-based medicines undoubtedly enrich the possibilities of drug treatment of chronic pain conditions. It remains the responsibility of the health care community to continue to pursue rigorous study of cannabis-based medicines to provide evidence that meets the standard of 21st century clinical care. SIGNIFICANCE: We provide an overview of systematic reviews on the efficacy, tolerability and safety of cannabis-based medicines for chronic pain management. There are inconsistent findings of the efficacy of cannabinoids in neuropathic pain and painful spasms in multiple sclerosis. There are inconsistent results on tolerability and safety of cannabis-based medicines for any chronic pain.

Medical use of cannabis products: Lessons to be learned from Israel and Canada.

INTRODUCTION: The German government intends to reduce the barriers for the medical use of cannabis products. A discussion on the indications and contraindications of the medical use of cannabis and on the changes of the regulatory framework has already begun in Germany. It is useful to draw from the experiences of other countries with a more liberal medical use of cannabis. METHODS: The Israeli and Canadian experience is outlined by physicians who have been charged with expertise on the medical use of cannabis by their jurisdiction. RESULTS: In Israel, only the plant-based cannabinoid nabiximol (mixture of tetrahydrocannabinol/cannabidiol) can be prescribed for spasticity/chronic pain in multiple sclerosis and for cancer pain. The costs of nabiximole are reimbursed by some, but not by all health maintenance organizations. The medical use of marijuana is permitted; however, it is strictly regulated by the government. Selected companies are allowed to produce marijuana for medical use, and only certain physicians are licensed to prescribe marijuana as a therapeutic drug for specific indications such as chronic neuropathic, and cancer pain, inflammatory bowel diseases, or posttraumatic stress disorder if conventional treatments have failed. The costs of marijuana are not reimbursed by health insurance companies. In Canada, synthetic cannabinoids and the plant-based (nabiximol) are licensed for neuropathic and cancer pain, HIV-related anorexia and chemotherapy-associate nausea. The costs of these synthetic cannabinoids are covered by health insurance companies. The medical use of marijuana as a treatment option is allowed for individual patients suffering from any medical condition when authorized by a medical practitioner or nurse. Licensed producers are the only source for patients to newly access medical cannabis, although those with previous permission to grow may continue cultivation at the present time. The costs of marijuana are not reimbursed by health insurance companies. There are multiple contraindications for the medical use of cannabis products in both countries. CONCLUSIONS: The use of standardized, synthetic, and plant-based cannabis products should be allowed in Germany for defined medical conditions when high-level evidence of efficacy and safety exists. The costs should be reimbursed by the health insurance companies. Contraindications for the medical use of cannabis should be defined. Growing marijuana by patients for their medical use should not be allowed.

Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): A systematic review of randomized controlled trials.

BACKGROUND: In the absence of an ideal treatment for chronic pain associated with rheumatic diseases, there is interest in the potential effects of cannabinoid molecules, particularly in the context of global interest in the legalization of herbal cannabis for medicinal use. METHODS: A systematic search until April 2015 was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org and clinicaltrials.gov for randomized controlled trials with a study duration of at least 2 weeks and at least ten patients per treatment arm with herbal cannabis or pharmaceutical cannabinoid products in fibromyalgia syndrome (FMS), osteoarthritis (OA), chronic spinal pain, and rheumatoid arthritis (RA) pain. Outcomes were reduction of pain, sleep problems, fatigue and limitations of quality of life for efficacy, dropout rates due to adverse events for tolerability, and serious adverse events for safety. The methodology quality of the randomized controlled trials (RCTs) was evaluated by the Cochrane Risk of Bias Tool. RESULTS: Two RCTs of 2 and 4 weeks duration respectively with nabilone, including 71 FMS patients, one 4-week trial with nabilone, including 30 spinal pain patients, and one 5-week study with tetrahydrocannbinol/cannabidiol, including 58 RA patients were included. One inclusion criterion was pain refractory to conventional treatment in three studies. No RCT with OA patients was found. The risk of bias was high for three studies. The findings of a superiority of cannabinoids over controls (placebo, amitriptyline) were not consistent. Cannabinoids were generally well tolerated despite some troublesome side effects and safe during the study duration. CONCLUSIONS: Currently, there is insufficient evidence for recommendation for any cannabinoid preparations for symptom management in patients with chronic pain associated with rheumatic diseases.

The clinimetric properties of the World Health Organization Disability Assessment Schedule II in early inflammatory arthritis.

OBJECTIVE: To assess the clinimetric properties of a new health-related quality of life (HRQOL) instrument, the World Health Organization Disability Assessment Schedule II (WHODAS II), in patients with early inflammatory arthritis. METHODS: Internal consistency as well as criterion, construct, and discriminative validity of the WHODAS II were assessed in 172 patients with early inflammatory arthritis who completed the WHODAS II, the Medical Outcomes Study Short Form 36 (SF-36), and other measures of disease severity, functioning, pain, depression, and resource use. Test-retest reliability of the WHODAS II was assessed by having a subset of 20 patients complete the WHODAS II a second time, 1 week after the first assessment. RESULTS: The WHODAS II had high internal consistency (Cronbach's alpha = 0.96 for patients working or in school and 0.93 for patients not working or in school). Test-retest intraclass correlation coefficients of the WHODAS II total score and subscales ranged from 0.82-0.96. The WHODAS II total score was strongly correlated with the SF-36 physical component score (Kendall's tau-b 0.51, P < 0.001) and moderately correlated with the SF-36 mental component score (tau-b 0.43, P < 0.001). WHODAS II correlations with disease outcomes ranged from Kendall's tau-b 0.15-0.55. The WHODAS II significantly differentiated between every aspect of disease severity assessed with the exception of measures of health resource use. CONCLUSION: The WHODAS II is a valid and reliable measure of HRQOL in cross-sectional studies of patients with early inflammatory arthritis. Research is still required to investigate potential item redundancy and determine its usefulness in longitudinal studies.

A randomized clinical trial of an individualized home-based exercise programme for women with fibromyalgia.

OBJECTIVE: To determine the efficacy of a 12-week individualized home-based exercise programme on physical functioning, pain severity and psychological distress for women with fibromyalgia (FM). METHODS: Seventy-nine women with a primary diagnosis of FM were randomized to a 12-week individualized home-based moderate-intensity exercise programme or to a usual care control group. Outcomes were functional capacity (Fibromyalgia Impact Questionnaire), pain severity and psychological distress. Outcomes were measured at study entry, at the end of the 12-week intervention, and at 3 and 9 months following completion of the intervention. RESULTS: On the basis of intention-to-treat analyses, a significant improvement in functional capacity at 3 and 9 months following treatment for participants in the exercise group who were more functionally disabled at study entry was observed. At both 3 and 9 months post-treatment, the mean estimated benefit of the intervention was more than 10 points [-12.3 (95% CI, -21.9 to -2.8); -10.8 (95% CI, -21.5 to -0.2)]. Compared with the control group, statistically significant improvements in upper body pain were evident in the exercise group at post-treatment. These between-group differences in upper body pain were maintained at 3 and 9 months post-treatment. No statistically significant group differences on lower body pain and psychological distress were found. CONCLUSIONS: Home-based exercise, a relatively low-cost treatment modality, has the potential to improve important health outcomes in FM.

Medication non-adherence in women with fibromyalgia.

OBJECTIVE: To identify the determinants of medication non-adherence in women with fibromyalgia (FM). METHODS: Participants included 10 rheumatologists and 127 women recruited from tertiary care hospitals and the community. Demographic, clinical and psychosocial characteristics and patient-physician discordance were assessed at the baseline visit. Non-adherence was assessed 2 weeks later. Multivariable generalized estimating equations were used to identify determinants of non-adherence to medication. RESULTS: The average age of the women was 50.4 (s.d. 10.5) yr and the mean disability score was 60.3 (16.0) yr. Sixty (47.2%) women were non-adherent to medication; 20 (33.3%) of these were intentionally non-adherent, 24 (40.0%) were unintentionally non-adherent, and the remaining subjects were both. Overall non-adherence was predicted by higher patient-physician discordance. Unintentional non-adherence was predicted by community subjects, not being under a rheumatologist's care, less disease activity, less use of instrumental coping, and higher patient-physician discordance. Intentional non-adherence was predicted by shorter duration under a rheumatologist's care and higher patient-physician discordance. CONCLUSION: The therapeutic relationship, in addition to clinical and psychosocial characteristics, influenced non-adherence to medication.

The assessment of cartilage degradation in vivo: development of an immunoassay for the measurement in body fluids of type II collagen cleaved by collagenases.

A monoclonal antibody has been developed which recognizes a neoepitope in type II collagen which is generated by the intrahelical cleavage of collagenases. Antibody reactivity is directed at the carboxyl-terminus of the TCA or 3/4 piece of the degraded alpha1(II) chain. Reactivity is dependent upon hydroxylation of proline. Evidence is provided suggesting that epitope binding involves the recognition of a conformational neoepitope. Using an ELISA, we show that this neoepitope can be detected in the urines and sera of nonarthritic persons and patients with rheumatoid arthritis (RA). An increased content is observed in the sera and urines of patients. The assay may be of value in studying cartilage type II degradation both in vitro and in vivo such as in those with arthritis.

Inaccuracy in the diagnosis of fibromyalgia syndrome: analysis of referrals.

OBJECTIVE: To examine prospectively the accuracy of an initial diagnosis for fibromyalgia (FM). METHODS: All patients newly referred for rheumatology consultation in a 6-month period were evaluated prospectively for either a preceding, current or subsequent diagnosis of FM. Clinical characteristics, previous and subsequent management and health care utilization were assessed. The final diagnosis at 6 months was verified and accuracy regarding the diagnosis of FM was assessed. RESULTS: Seventy six (12%) of all new patients were either referred with a question of FM or finally diagnosed with FM. At the final evaluation the accuracy of the diagnosis regarding FM by either the referring physician or by the rheumatologist at the time of the initial visit was correct in 34% of patients. The FM group in comparison with those with some other rheumatological diagnosis had more tender points (12.5 vs 4) and were more fatigued. In contrast, prolonged early morning stiffness and limitation of lumbar spinal mobility in more than one plane was more common in the non-FM group. CONCLUSION: There is a disturbing inaccuracy, mostly observed to be overdiagnosis, in the diagnosis of FM by referring physicians. This finding may help explain the current high reported rates of FM and caution physicians to consider other diagnostic possibilities when addressing diffuse musculoskeletal pain.

Previous pain experience in women with fibromyalgia and inflammatory arthritis and nonpainful controls.

OBJECTIVE: To examine the frequency of commonly occurring pain and adverse experiences throughout life by self-report in women with fibromyalgia (FM) and chronic inflammatory arthritis (IA) and nonpainful healthy women. METHODS: Fifty-one patients with FM and 44 with IA and 52 nonpainful healthy controls were consecutively interviewed in a tertiary clinic setting regarding the occurrence of lifetime common pain experience and adverse events, as well as a family history of FM and/or a childhood pain environment. RESULTS: Patients with FM reported significantly more irritable bowel syndrome, migraine headaches, severe menstrual pain, physical and psychological trauma affecting well being, family history of FM, and family pain environment than subjects with IA or controls. Both patient groups had more adult hospitalizations and surgeries than the controls. CONCLUSION: Patients with FM report a high rate of varied pain and adverse experiences throughout life. This real or perceived experience of pain supports the concept that FM is a lifetime disorder of pain processing.

Pain and pain relief in fibromyalgia patients followed for three years.

OBJECTIVE: To examine the natural clinical course of pain in fibromyalgia (FM) and patients' reports of the use of interventions for pain relief. METHODS: This prospective 3-year study examined pain, and the treatment thereof, in a cohort of 82 women with FM, of whom 59 (72%) were reassessed on 3 subsequent occasions. Pain was measured by the following parameters: visual analog scale (VASpain), tender point count (TP), and the occurrence of widespread pain (WP). Function was assessed by the Health Assessment Questionnaire and the Fibromyalgia Impact Questionnaire, and depression and anxiety by the Arthritis Impact Measurement Scales. All treatments for FM were recorded, and patients identified the treatment that they believed had helped their symptoms of FM. RESULTS: Pain reporting as measured by all parameters decreased significantly for the whole group over the duration of the study. The mean VASpain decreased from 66 to 55, the mean TP count decreased from 13.5 to 10.5, and the number of patients with WP decreased from 100% to 63%. VASpain correlated positively with TP and WP. One third of patients experienced a reduction in pain by at least 30% from baseline as well as a better outcome in overall status of FM. There was a decline in the use of prescribed medications, whereas the use of alternative products increased. Physical treatment modalities were more often perceived to be of benefit than prescribed medications. CONCLUSION: We have observed a spontaneous improvement in pain reporting and less medication use in FM patients, suggesting that the course of this condition may be more favorable than has previously been reported.

A community rheumatology practice offers an educational experience comparable to that of a university tertiary care center.

OBJECTIVE: To compare the teaching value of rheumatology patients seen in either a community rheumatology practice or in a tertiary care university center. METHODS: Consecutive patients seen at the 2 sites over a one month period were assessed for rheumatology diagnosis, complexity of rheumatologic disease, and treatments received, including number of interventions performed. The overall pedagogic value of the encounter was rated by the rheumatologist for both medical students and postgraduate trainees. RESULTS: Rheumatology patients were comparable at the 2 sites for overall pedagogic value, rheumatology diagnostic category, and complexity of disease. At the community site, however, there were more patients evaluated, more procedures performed, and more new treatments introduced. CONCLUSION: Contrary to current perceptions, comparable pedagogic value of rheumatology patients was observed outside a tertiary care setting. In the changing climate of education, and considering resource limitations that influence current rheumatology practice, community based rheumatology has the potential to offer a valuable educational experience.

Consequences of delayed therapy with second-line agents in rheumatoid arthritis: a 3 year followup on the hydroxychloroquine in early rheumatoid arthritis (HERA) study.

OBJECTIVE: To assess the longterm effect of delaying therapy with second-line agents in patients with early rheumatoid arthritis (RA). METHODS: One hundred nineteen patients who participated in a 9 month placebo controlled randomized trial of hydroxychloroquine sulfate (HCQ) were followed prospectively for an additional 3 years. Those randomized to HCQ are referred to as the early treatment group and those randomized to placebo as the delayed treatment group. Participants were assessed annually for pain [Arthritis Impact Measurement Scales (AIMS) and Stanford Health Assessment Questionnaire (HAQ)], physical disability (AIMS and HAQ), and the RA global well being scale (AIMS). Conversion of results into standard deviation (SD) units permitted defining a substantial difference as per Felson as > 0.30 SD units and a clinically indistinguishable difference as < or = 0.06 SD units. RESULTS: One hundred fifteen patients (97%) participated and complete data were available on 104 (87%). Compared to the early treatment group, the delayed group remained worse for both the pain and the physical disability outcomes over the additional 3 year followup. The difference in the RA global well being score became clinically indistinguishable for the early and delayed groups only after the 2 year post-trial assessment. The between-group differences were not explained by post-trial therapy with corticosteroids, other second-line agents, or nonsteroidal antiinflammatory drugs and analgesic preparations. CONCLUSION: These findings show that a delay in instituting therapy with second-line agents, even a 9 month delay in instituting a moderately powerful second-line agent such as HCQ, has significant effects on longterm patient outcome, and provides strong evidence in support of early therapy in RA.

Determinants of health status in fibromyalgia: a comparative study with systemic lupus erythematosus.

OBJECTIVE: To compare perceived health status in women with fibromyalgia (FM) and systemic lupus erythematosus (SLE) using the Medical Outcomes Study (MOS) Short Form Health Survey (SF-36); and to identify determinants of physical and mental health in each patient group. METHODS: A cross sectional study of 46 women with FM (mean age 48.13 yrs, SD 9.40) and 59 women with SLE (mean age 42.36 yrs, SD 11.31). Patients with FM were recruited from a rheumatology clinic and a rheumatology practice, while patients with SLE were recruited from 4 rheumatology clinics. Clinical examination determined disease activity (by Systemic Lupus Activity Measure) in SLE and a tender point count was used for FM. Patients completed questionnaires assessing health status (SF-36), stress (Hassles), social support (Social Support Questionnaire 6), and coping (Coping Inventory for Stressful Situations). RESULTS: Patients with FM reported more impairment on the following SF-36 subscales: physical function (p < 0.001), role physical (p < 0.001), bodily pain (p < 0.001), and vitality (p < 0.001). Physical component summary scores were also significantly lower (p < 0.001) for the FM group. Four hierarchical regression analyses were computed to determine factors related to physical and mental health in each patient group, with the following variables in the equation: age, income, disease activity (Step 1), hassles (Step 2), emotional and task coping, and social support (Step 3). Better physical health in FM was related to higher income (R2 = 0.17, p < 0.05). In the SLE group, better physical health was associated with younger age, less disease activity, and lower hassles (R2 = 0.37, p < 0.0001). Worse mental health among women with FM was associated with more hassles, more emotional coping, and less satisfaction with social support (R2 = 0.64, p < 0.0001), while lower income, higher hassles, and more emotional coping were linked to worse mental health in SLE (R2 = 0.46, p < 0.0001). CONCLUSION: Health related quality of life (HRQL) is impaired among women with FM and SLE, with FM patients reporting greater impairment along several dimensions. Enhancing the HRQL of patients with FM and SLE requires targeting specific modifiable psychosocial factors.

Is fibromyalgia a distinct clinical entity? The approving rheumatologist's evidence.

Fibromyalgia is a challenge to the modern day physician. Today's practice of medicine is evidence-based, but fibromyalgia shifts this paradigm. There is even still debate as to whether this diffuse musculoskeletal pain syndrome, with a reduced pain threshold, and tender points on examination constitutes a definitive entity or disease process. We do not have the luxury of measurable abnormal findings on clinical examination or laboratory testing. The diagnosis of this condition is not aided by the use of any modern-day technology, and is simply a clinical syndrome. No treatment which we prescribe for fibromyalgia is universally successful in managing symptoms. Our skills as physicians are constantly challenged by treatment options offered to patients by non-conventional medicine. Even so, as physicians, our role should be to support our patients and continue to pursue scientific study in order to better understand this enigma.

The needs of patients with arthritis: the patient's perspective.

OBJECTIVE: To identify concerns and learning interests of patients with arthritis. METHODS: A questionnaire was developed, pilot tested, and then used to evaluate 197 patients with arthritis, including osteoarthritis (OA) (n = 41), rheumatoid arthritis (RA) (n = 57), back disease (n = 55), systemic lupus erythematosus (n = 27), and systemic sclerosis (SSc) (n = 17). Twenty concerns and 12 learning interests were rated. Questionnaires were also administered to assess physical disability (Health Assessment Questionnaire), psychological disability (Arthritis Impact Measurement Scales 2), and pain (visual analog scale). Participants addressed accessibility of health services, satisfaction with their physician, psychosocial needs, use of self-help groups, and behavioral strategies used to assist coping. Patients with RA, OA, and back disease, at both a community and a hospital center, were tested to assess whether concerns and learning interests differed based on site of treatment. Analytic methods included analysis of variance, factor analysis, and multiple linear regression. RESULTS: There were no differences in concerns or learning interests based on treatment site. Between diagnostic groups, patients with SSc were more interested in learning about self-help groups. The most frequently reported concern was worsening of the illness. The majority of respondents were interested in learning more about topics that were illness specific. The physician was chosen as the preferred source of information, and the preferred format was in writing. On factor analysis, the 20 concerns were reduced to 5 factors: psychological, coping, medication, social, and financial. Three factors were identified for learning interests: the illness, traditional health management topics, and nontraditional health management topics. Stepwise multiple linear regression revealed predictors for the 5 concern and 3 learning interest factors. The concerns were best predicted by self-reported disease severity, physical disability, and psychological distress, while learning interests were best predicted by self-reported disease severity, pain, and self-help group membership. CONCLUSION: Concerns and learning interests of persons with arthritis did not differ based on the center of treatment or the diagnosis, but can be predicted by the level of pain and simple measures of disability. Better understanding of the relationship between health status and patient-perceived needs will result in improved patient-centered care.

Immune responses to cartilage link protein and the G1 domain of proteoglycan aggrecan in patients with osteoarthritis.

OBJECTIVE: To determine whether patients with osteoarthritis (OA) express cellular immunity to cartilage link protein (LP) and the G1 globular domain of proteoglycan (PG) aggrecan, and whether immunity to the G1 domain is influenced by the removal of keratan sulfate (KS). METHODS: LP and the G1 globular domain of PG were isolated from human and/or bovine cartilage and used in proliferation assays with peripheral blood lymphocytes (PBL) from 42 patients with OA and 40 healthy control subjects. RESULTS: Patients with OA expressed a higher prevalence of cellular immunity to human cartilage LP (42.4%) compared with the control group (13.3%). The prevalence of immune reactivity to bovine LP in patients with OA was lower (35.7%) compared with the immunity to human LP, but remained similar in the control group (13.8%). PBL from patients with OA exhibited low reactivity to the native G1 domain of bovine PG. However, removal of KS chains from the G1 globular domain resulted in increased cellular immune responses to the G1 domain in OA patients (45.8%) compared with the control group (7.7%). CONCLUSION: These results indicate the presence of immunity to cartilage-derived LP and the G1 globular domain of PG aggrecan in patients with OA and the inhibitory effect of KS chains on the G1 domain on the expression of this immunity in OA patients. This immune reactivity is commonly observed in patients with inflammatory joint disease and can experimentally induce arthritis. Thus, it may be involved in the pathogenesis of OA.