The sources of pain in osteoarthritis: a pathophysiological review.

The pain of osteoarthritis (OA) has multifaceted etiologies within and outside the joint. It is believed to be driven by both nociceptive and neuropathic mechanisms, as well as abnormal excitability in the pain pathways of the peripheral and central nervous system. Inflammation in the joint triggers a cascade of events that leads to peripheral sensitization, increased sensitivity of nociceptive primary afferent neurons, and hyperexcitability of the nociceptive neurons in the central nervous system. Pain receptors have been found in the synovium, ligaments, capsule, subchondral bone and surrounding tissues, with the exception of articular cartilage. The bone-related causes of pain in OA include subchondral microfractures, bone stretching with elevation of the periosteum due to osteophyte growth, bone remodeling and repair, bone marrow lesions, and bone angina caused by decreased blood flow and increased intra-osseous pressure. Central factors alter pain processing by setting the gain in such a way that, when a peripheral input is present, it is processed against a background of central factors that can enhance or diminish the experience of pain. As a complex phenomenon with a strong subjective component, pain can also be influenced by the nature of the underlying disease, personal predisposition (biological and psychological), and environmental and psychosocial factors. This review examines the current literature regarding the sources and mechanisms of pain in OA.

Pain assessment strategies in patients with musculoskeletal conditions.

Valid and reliable assessment of pain is fundamental for both clinical trials and effective pain management. The nature of pain makes objective measurement impossible. Chronic musculoskeletal pain assessment and its impact on physical, emotional and social functions require multidimensional qualitative tools and healthrelated quality of life instruments. The recommendations concerning outcome measurements for pain trials are useful for making routine assessments that should include an evaluation of pain, fatigue, disturbed sleep, physical functioning, emotional functioning, patient global ratings of satisfaction, and quality of life. Despite the growing availability of instruments and theoretical publications related to measuring the various aspects of chronic pain, there is still little agreement and no unified approach has been devised. There is, therefore, still a considerable need for the development of a core set of measurement tools and response criteria, as well as for the development and refinement of the related instruments, standardized assessor training, the cross-cultural adaptation of health status questionnaires, electronic data capture, and the introduction of valid, reliable and responsive standardized quantitative measurement procedures into routine clinical care. This article reviews a selection of the instruments used to assess chronic musculoskeletal pain, including validated newly developed and well-established screening instruments, and discusses their advantages and limitations.

Preliminary identification of key clinical domains for outcome evaluation in fibromyalgia using the Delphi method: the Italian experience.

OBJECTIVE: Fibromyalgia (FM) is a complex syndrome that, in Italy, affects at least 2% of the adult population. It is characterized by chronic widespread musculoskeletal pain often accompanied by multiple other symptoms. The aim of this study was to identify a set of clinical domains for FM considered relevant by both clinicians and patients using a consensus process. METHODS: Consensus was achieved using the Delphi method based on questionnaires and systematic, controlled opinion feedback. The Delphi exercise involved a panel of 252 rheumatologists and 86 patients with FM as defined by the American College of Rheumatology criteria. All of the patients and clinicians were asked to rank the relative different domains of FM in order of priority. The content validity index (CVI) was used to establish the percentage agreement. The importance of each item was ranked on a 0-3 Likert scale. The frequency, mean relevance scores, and frequency importance product were also calculated. RESULTS: The Delphi exercise showed that the domains ranked highest by patients were similar to those of the clinicians, with the exception of tender point intensity (considered relevant by the clinicians but not by the patients) and environmental sensitivity (considered important by the patients but not by the clinicians). A final 8-item model was developed which was considered to demonstrate adequate validity. CONCLUSIONS: The Delphi exercises identified and ranked relevant key clinical domains that need to be assessed in FM research. On the basis of these results, a new patient-reported composite outcome index can be developed and used in clinical trials.

Colour Doppler ultrasonography evaluation of vascularization in the wrist and finger joints in rheumatoid arthritis patients and healthy subjects.

OBJECTIVES: To evaluate the presence of blood flow by colour Doppler ultrasonography (CDUS) in the wrist and finger joints of rheumatoid arthritis (RA) patients and healthy subjects and to define a cut-off value of CDUS resistive index (RI). METHODS: Forty-three patients with RA and 43 healthy controls were examined by CDUS. The wrists, second and third metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints were evaluated in each patient and healthy subject. Spectral Doppler analysis was performed in order to characterize the type of flow and a mean RI was measured to define a cut-off level. The area under receiver operating characteristic curve was used to evaluate the screening method's performance. RESULTS: Flow was detected in 219 of the 430 total joints (50.9%) of RA patients (111 in the wrists, 49 in the MCP and 30 in the PIP joints). Healthy subjects had a quantifiable flow in 45 of the 430 joints (10.5%) and, in particular, 39 (86.4%) in the wrist, 5 (11.14%) in the MCP and 1 (2.2%) in the PIP joints. The intra- and inter-reader agreements for the detection of Doppler signal were very good (kappa 0.82 and 0.89, respectively). Mean RI values were 0.72±0.06 in RA patients and 0.86±0.06 in healthy subjects (p<0.01). At cut-off point of RI<0.79 the sensitivity was 89.6% and the specificity was 78.8% (positive likelihood ratio 4.22). CONCLUSION: DUS is a useful tool for the detection of abnormal blood flow in inflammatory joints of RA patients.

A comparison of utility measurement using EQ-5D and SF-6D preference-based generic instruments in patients with rheumatoid arthritis.

OBJECTIVES: The purposes of this study were to analyse and compare aspects of validity (concurrent and discriminant) of the two widely used indirect utility instruments, the EuroQol-5D (EQ-5D) and the Short Form-6D (SF-6D) in a representative cohort of patients with rheumatoid arthritis (RA). METHODS: Five hundred and eighty-three consecutive adult patients (435 women, 148 men) with RA and referred to the outpatient Clinic were evaluated. Patients were asked to complete EQ-5D and SF-36. SF-6D utility scores were calculated using the eight mean SF-36 scores, according to published algorithms. Disease-related characteristics included disease duration, co-morbidities, a measure for disease activity [Disease Activity Score-28 joint (DAS28)] and for radiographical damage (Sharp van der Heijde scoring method, SHS). The agreement between the utility instruments was evaluated by Bland-Altman analysis. Construct validity was assessed using the Kruskal-Wallis test, Mann-Whitney U-test, Spearman's correlations, and receiver operating characteristic (ROC) curves. Multivariate analyses were used to assess the relationship among HRQoL and disease-related characteristics and socio-demographic data. RESULTS: A comparison of means showed that SF-6D values exceeded EQ-5D values (p<0.0001). Agreement between both measures was only moderate. Utility scores and domains and summary scores of the SF-36 were highly correlated. The EQ-5D and SF-6D both detected change in different health status (<0.0001). The discriminatory power of both indexes was good, without significant difference, with an AUC of 0.869 and 0.820, respectively for EQ-5D and SF-6D. The EQ-5D and SF-6D both detected change over different health status among RA patients (both al level of p<0.0001) although EQ-5D was more efficient in detecting differences between groups in almost all cases. Comparison of EQ-5D and SF-6D scores within VAS groups showed that, for less healthy individuals (VAS scores 0-50), the median EQ-5D score was significantly lower than the median SF-6D score. The multivariate regression models for EQ-5D and SF-6D included both SHS and DAS28 (p=0.0001). The relative contribution of these domains differed substantially between patients with short and long standing disease duration. The presence of multiple chronic conditions also appeared to contribute to reduce the levels of utility of both instruments. CONCLUSIONS: Although EQ-5D and SF-6D appeared to measure similar constructs, these instruments are quite different from each other in the assessment of RA. For worse health status the median EQ-5D scores were significantly lower than the median SF-6D scores. Moreover, EQ-5D and SF-6D appeared both significantly influenced by disease activity, radiological damage and co-morbidity. For that reason, we advise caution in the employment of these preference-based instruments, especially in RA patients with severe disease.

Comparison of the Recent-Onset Arthritis Disability questionnaire with the Health Assessment Questionnaire disability index in patients with rheumatoid arthritis.

BACKGROUND: Physical disability in patients with rheumatoid arthritis (RA) is often assessed by questionnaires. We compared the Recent-Onset Arthritis Disability (ROAD) questionnaire with the Health Assessment Questionnaire (HAQ) disability index (DI) in a cohort of RA patients. The aim of this study was to obtain information on several aspects of construct validity of these measures. METHODS: A cross-sectional multicentre study was carried out among patients with RA who were attending hospital outpatient clinics. The patient group included 196 patients partially or not responding to disease modifying anti-rheumatic drugs. For the evaluation of the psychometric properties of the ROAD in comparison with HAQ-DI this population has been compared to another cohort of 247 outpatients with RA who were participating in a long-term observational study. All patients completed the ROAD and HAQ-DI. Additional comparator composite indices of disease activity were analysed. The ROAD structural validity was first assessed using exploratory factor analysis. Concurrent validity was analysed by Spearman's correlations and cross-tabulations. Discriminant validity to distinguish patients with active and non-active disease was assessed with receiver operating characteristic (ROC) curve analysis. For agreement analysis Bland and Altman plots were calculated. RESULTS: Factor analysis yielded a two-factor ROAD score that accounted for 68.74% of the explained variance in the questionnaire. The first factor, namely upper extremity function/activity daily living and work (ROAD-upper) accounted for 55.6% of the explained variance. The second factor, namely lower extremity function (ROAD-lower) accounted for 13.1% of the explained variance. Significant correlations were found between the scores of the ROAD and the other clinical variables with a high ability to measure pain and disease activity, supporting the concept of convergent construct validity. The discriminatory power of both questionnaires to assess inactive and active RA patients was good, without significant difference. CONCLUSIONS: ROAD is a good alternative to the HAQ-DI for the assessment of physical disability in RA. Use of the ROAD makes it easier and less costly to collect data and reduces the burden on RA patients and should be applied in both clinical trials and routine clinical care settings.

A clinical prediction rule combining routine assessment and power Doppler ultrasonography for predicting progression to rheumatoid arthritis from early-onset undifferentiated arthritis.

OBJECTIVES: The ability to predict the development of rheumatoid arthritis (RA) in patients with an early-onset undifferentiated arthritis (UA) is highly required if the remission or an adequate response to the treatment are the main goal. The aim of the study was to develop a predictive rule combining clinical variables, serological biomarkers and power Doppler ultrasonography (PDUS) for the progression from an early-onset UA to RA in daily rheumatological practice. METHODS: A prediction rule was developed after a 12 months study of 149 adult patients with a recent-onset UA. The combination of routine assessment variables and PDUS findings was investigated. Logistic regression analysis was performed to identify the independent factors for the development of RA and global predictive score was calculated. The score of the predictive rule ranged from 0 to 10. The area under the receiver operating characteristic curve was used to evaluate the diagnostic performance of the rule. The post-test probability (post-TP) was evaluated using the Bayes theorem. RESULTS: Sixty-two patients (41.6%) developed a RA. The rule demonstrated excellent discriminative ability, with an AUC of 0.919 (p=0.0001). With the optimal cut-off point of 5, sensitivity was 89.9%, specificity was 88.6% and positive likelihood ratio was 7.89. If a threshold of 6.5 was applied a higher value of specificity (97.7%) was obtained, but sensitivity (47.6%) decreased. The post-TP value of the two different cut-off points mentioned above were 62% and 80%, respectively. CONCLUSIONS: Our predictive rule, which includes PDUS assessment, revealed an excellent discriminative ability for assessing the likelihood of development of RA in patients with an early-onset UA. Further studies are required to confirm the results and to tailor a therapeutic approach in patients with an early-onset UA.

Assessment instruments for patients with fibromyalgia: properties, applications and interpretation.

A comprehensive assessment of the multiple symptom domains associated with fibromyalgia (FM) and the impact of FM on multidimensional aspects of function should form a routine part of the care of FM patients. Clinical trials and long-term clinical registries have used various outcome measures, but the key domains include pain, fatigue, disturbed sleep, physical functioning, emotional functioning, patient global ratings of satisfaction, and their health-related quality of life (HRQL). A number of measures have been ''borrowed'' from the fields of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and adapted to FM, and others are being developed specifically for FM. However, despite the burgeoning theoretical literature and the proliferation of instruments for measuring various health status domains, no unified approach has been developed and there is little agreement concerning the meaning of the results. There is, therefore, still a need for further consensus and the development of a core set of measures and response criteria, more refined measuring instruments, standardised assessor training, cross-cultural adaptations of health status questionnaires, electronic data capture, and the introduction of standardised quantitative measurements into routine clinical care. This article discusses the advantages and limitations of a selection of both newly developed and well-established and validated distress screening instruments that underlines the continuing challenge of assessing FM.

Calcium pyrophosphate dihydrate crystal deposition disease: sonographic findings.

High-resolution sonography is a rapidly evolving technique that is gaining an increasing success in the assessment of crystalline arthropathies. In calcium pyrophosphate dihydrate crystal deposition disease, the sonographic features of crystal deposition include hyperchoic spots within hyaline cartilage and/or fibrocartilage and soft tissue calcifications. The aim of this pictorial essay was to present the main findings evocative of crystal deposition in patients with pyrophosphate arthropathy.

Inter-observer agreement of standard joint counts in early rheumatoid arthritis: a comparison with grey scale ultrasonography--a preliminary study.

OBJECTIVES: The aims of the present study were to assess the inter-observer agreement of standard joint count and to compare clinical examination with grey scale ultrasonography (US) findings in patients with early rheumatoid arthritis (RA). METHODS: The study was conducted on 44 RA patients with a disease duration of <2 yrs. Clinical evaluation was performed independently by two rheumatologists for detection of tenderness in 44 joints and swelling in 42 joints. All patients underwent US assessment by a rheumatologist experienced in this method and blinded to the clinical findings. Joint inflammation was detected by US when synovial fluid and/or synovial hypertrophy was identified using OMERACT preliminary definitions. The inter-observer reliability was calculated by overall agreement (percentage of observed exact agreement) and kappa (kappa)-statistics. The reliability of US was calculated in 12 RA patients. RESULTS: There was fair to moderate inter-observer agreement on individual joint counts for either tenderness or joint swelling apart from the glenohumeral joint. US detected a higher number of inflamed joints than did clinical examination. The mean (+/-S.D.) US joint count for joint inflammation was 19.1 (+/-4.1), while the mean (+/-S.D.) number of swollen joints was 12.6 (+/-3.6), with a significant difference of P = 0.01. CONCLUSIONS: Our results provide evidence in favour of the hypothesis that clinical examination is far from optimal for assessing joint inflammation in patients with early RA. Furthermore, this study suggests that US can considerably improve the detection of signs of joint inflammation both in terms of sensitivity and reliability.

[Sonographic monitoring of gout]. / Il monitoraggio ecografico della gotta.

OBJECTIVE: To assess the role of grayscale and power Doppler sonography in short-term monitoring of acute gouty synovitis. METHODS: Clinical and sonographic assessments were performed in a patient with gout. Clinical and sonographic evaluations were performed within the first day of the acute onset of synovitis of the first metatarsophalangeal joint of the left foot and 7 and 14 days after the baseline assessments. The patient was treated only with colchicine. RESULTS: At baseline, both grayscale and power Doppler sonography revealed clearly evident findings of acute synovitis (joint cavity widening, thickening of periarticular soft tissues and power Doppler signal). After seven days, a complete clinical remission occurred. Ultrasound examination revealed marked improvement with respect to the basic findings, even if all the sonographic features of joint inflammation were still detectable. Two weeks after the onset of the acute attack, clinical remission was maintained and all the sonographic features of synovitis disappeared. CONCLUSION: Sonography is a sensitive and reliable tool for assessing and short-term monitoring of acute gouty attack.