Over 100 papers describing and utilizing the Stanford Health Assessment Questionnaire (HAQ) have been published since 1980. A brief overview of the HAQ is presented along with a guide to the accumulated literature. The topics covered include: studies using the disability, pain, economic, and drug side effect dimensions of the HAQ; reliability and validity studies; applications to various rheumatic diseases; language adaptations; modifications and derivative scales; studies correlating the HAQ with sociodemographic, health status, laboratory, and physical measures; and randomized controlled trials and observational studies using the HAQ. A few comments regarding future directions for research are also presented.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1790050303

The health assessment questionnaire 1992. Status and review

Cytokines in osteoarthritis: mediators or markers of joint destruction?

OBJECTIVES—To determine concentrations of chondroitin sulphate (CS) and keratan sulphate (KS) epitopes, glycosaminoglycans (GAGs) and hyaluronan (HA) in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables may be used as markers of the OA process.
METHODS—OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA). Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Knee SF was examined by enzyme linked immunosorbent assay for: CS epitopes, using monoclonal antibodies 3-B-3 and 7-D-4; KS epitope using monoclonal antibody 5-D-4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAGs were measured by dye binding with 1:9 dimethylmethylene blue.
RESULTS—Increased SF 3-B-3 concentrations and 3-B-3/GAG ratio were found in OA, compared with RA or normal knees, with higher 3-B-3 and 3-B-3/GAG in LJOA and NGOA than in CPA. SF 7-D-4 and 7-D-4/GAG were reduced in RA, compared with normal and OA; SF 5-D-4 was reduced in OA compared with normal. GAG and HA concentrations were decreased in both OA and RA. No correlations with radiographic scores were observed, but SF 7-D-4 was lower in `inflamed' compared with `non-inflamed' RA and OA knees. In patients with bilateral samples there were strong correlations between right and left knees for all SF variables.
CONCLUSIONS—Changed concentrations of SF CS and KS can be detected in OA with a profile that differs from that seen in RA. Clinical subgrouping and local joint inflammation may influence these measures, supporting different pathogenesis within OA subgroups and requirement for careful patient characterisation in SF studies.

https://ard.bmj.com/content/annrheumdis/56/5/299.full.pdf

Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in arthritic and normal knees

OBJECTIVE To measure serum levels of tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) in patients with rheumatoid arthritis (RA) and age-matched control subjects and to study how these correlate with serum levels of hyaluronan (HA) and antigenic keratan sulfate (KS) and other biochemical as well as clinical indicators of disease activity METHODS Immunoassays were used to measure levels of TNF alpha, IL-6, HA, and antigenic KS in the serum of 35 patients with RA and a group of age- and sex-matched control subjects Clinical disease activity in the RA group was assessed using the Lansbury index Drug intake was recorded and the erythrocyte sedimentation rate, and levels of fibrinogen, creatinine, bilirubin, alkaline phosphatase, lactate dehydrogenase, and aminotransferase were measured RESULTS Serum levels of TNF alpha, IL-6, and HA were significantly higher in the RA population than in the control group In patients with RA, serum levels of HA correlated positively with serum levels of TNF alpha and with clinical joint scores, but only weakly with other laboratory parameters of inflammation Serum levels of antigenic KS correlated negatively with levels of circulating TNF alpha, but much more weakly with other clinical and biochemical parameters of disease activity CONCLUSION These in vivo data support in vitro studies which have shown that TNF alpha is a potent stimulator of HA synthesis by synovial lining cells The results strengthen the contention that serum HA may be a unique marker of synovial involvement and inflammation, rather than of only inflammation, in RA

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780360409

Levels of circulating tumor necrosis factor alpha and interleukin-6 in patients with rheumatoid arthritis. Relationship to serum levels of hyaluronan and antigenic keratan sulfate.

Markers of cartilage matrix metabolism in human joint fluid and serum: the effect of exercise*

Sensitive measurements of serum keratan sulfate (KS), a glycosaminoglycan found in large quantities in the proteoglycans of human cartilage, can be obtained using an enzyme-linked immunosorbent-inhibition assay. Patients who are undergoing chemonucleolysis (CN) provide a clinical opportunity to monitor the large-scale proteolytic degradation of cartilage. By measuring serum KS levels both pre- and post-CN, we have demonstrated that serum KS levels rise predictably after CN, in a manner that reflects major catabolic events of cartilage.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/anr.1780320118

Rosemarie Jeffery

Papers

The effect of chemonucleolysis on serum keratan sulfate levels in humans