In this chapter an attempt has been made to draw together the known biology of cartilage and some of the mechanisms thought to be responsible for its failure in arthritis. The picture is far from complete but we are now in a good position to use this information to help appraise the pros and cons of the wide range of drugs now available to treat articular disorders. For convenience, these drugs were classified as NSAIDs, corticosteroids and chondroprotective agents. The influence of each of these classes on the metabolism of cartilage was examined in the light of published laboratory and clinical studies. It has been clearly shown that not all NSAIDs are the same. While many of the older drugs provided no benefit to cartilage metabolism, and in some instances suppressed it, the more recently discovered molecules appear to be free of these undesirable effects. Tiaprofenic acid, diclofenac and piroxicam emerged as drugs with little or no harmful effects on cartilage metabolism when used at concentrations within the human therapeutic range. For all NSAIDs, their potential effects on cartilage must be weighed against their respective anti-inflammatory potency, half-life, and effects on the gastric mucosa and other tissues. Other chapters in this book have addressed these important problems. The long-acting corticosteroids, betamethasone and triamcinolone hexacetonide, also appear to offer some benefit in the management of OA; however, as in RA, their use should be restricted to short-term applications. In terms of cartilage metabolism the chondroprotective agents pentosan polysulphate, Arteparon and Rumalon have been the most extensively studied class of drugs. While the laboratory studies have provided convincing evidence of their chondroprotective efficacy, it has been difficult to prove this clinically. This dichotomy of opinion (laboratory versus clinical) stems largely from the inadequacy of the methodologies currently available for the objective clinical assessment of patient response to anti-rheumatic drug therapy. With the advent of nuclear magnetic resonance imaging techniques and monoclonal antibodies to detect specific proteoglycan breakdown fragments in synovial fluid and plasma, the prospects for a unified research approach for the evaluation of these agents may now be possible.

Joint cartilage consists of cells embedded in a matrix of fibrous collagen within a concentrated water-proteoglycan gel. The integrity of this matrix is crucial for the biomechanical properties of the joint cartilage. The different components of the matrix are synthesized and degraded by the cartilage cells, a process regulated by the amount of mechanical stress applied to the chondrocytes as well as by peptide factors and hormones present in synovial fluid. The proteoglycans are large macromolecules consisting of a protein core to which are attached multiple chains of glycosaminoglycans and oligosaccharides. During normal and pathological turnover, degradation products are released to the synovial fluid and to the circulation. Newly developed assays allow the sensitive and specific detection of these fragments in joint fluid and serum. Results of experimental and clinical investigations suggest that these assays will be of value in efforts to diagnose, grade and predict the outcome of inflammatory and degenerative joint disease.

In patients with osteo-arthritis, renal disease will almost invariably be the consequence of unrelated coincidental renal pathology. In polyarthritic rheumatoid arthritis and ankylosing spondylitis, renal disease can arise as part of the pathology of a systemic disease, or more likely its treatment. As a rule amyloidosis is the most important complication in terms of progressive irreversible loss of renal function. By contrast, SLE, polyarteritis and Sjögren's disease carry a much higher risk of renal involvement. The regular evaluation of renal function in such patients can enable the kidney damage to be assessed at an early stage and allow treatment to be instituted early.

There is evidence for both oxygen-centred free radicals and products of complement activation acting as mediators of inflammation. Evidence for the generation and reaction of free radicals at sites of inflammation can only be indirect and circumstantial due to their very transient nature. Evidence for complement activation in several inflammatory conditions, including rheumatoid arthritis is strong. These mediator classes individually possess a range of potential proinflammatory activities. Their effects may be linked through the formation of immune complexes and the activation of polymorphonuclear leukocytes. Their actions will also be linked with and modulated by the activities of other mediators mentioned only briefly in this chapter. The relative importance of the different mediators in any particular inflammatory condition is difficult to ascertain. The importance of free radicals and complement will be better understood when drugs specifically and unequivocally aimed at their control are identified. This potential for therapeutic advances in the treatment of inflammatory disorders has yet to be realized.

Despite 50 years of intensive research in the field of RFs, autoimmunity and chronic inflammation, some of the serological tests used for measuring autoantibodies remain an anachronism. Clinical chemistry has the potential technology to provide the rheumatologist with automated quantitative antibody/antigen measurements. It can also widen the range of tests available for disease monitoring, which would be helpful in the management of the chronic rheumatic diseases. Traditional laboratory tests must be superseded by new developments, derived from fundamental research, if we are to improve the diagnosis and management of the rheumatic diseases.

Patients with rheumatic complaints are the subject of some 10% of the general practitioner's work. Approximately half of this work is related to the hitherto relatively neglected group of varied soft-tissue conditions, most of which are self-limiting and of a minor nature. Against a background of such diagnostic 'noise', the general practitioner has to remain alert for the fainter 'signal' of serious disease--rheumatic and non-rheumatic--at an early stage. Continuity of care calls on special qualities, behaviours and abilities in the doctor to boost and maintain morale, to coordinate management and to participate in team care. In addition to more traditional therapeutic measures, including analgesics, NSAIDs, disease-modifying drugs and physiotherapy, joint replacement is seen as a significant contribution. There is room for improvement in the structure process and outcomes of delivery of care as it may relate to rheumatic diseases. A simple illustration, based on a general practice audit of gout, is suggested as a possible model by which quality of care could be enhanced at the level of individual patients. While there is not a great deal of scope afforded to the general practitioner in the exercise of primary prevention of the rheumatic diseases, early diagnosis and timely support for carers of patients suffering from chronic rheumatic diseases are areas worth attention. Promotion of self-help is seen as a worthwhile activity in humanitarian and economic terms, though it calls for an appropriate balance to be struck.

We have attempted to review the epidemiology of a group of diseases collectively termed the seronegative spondarthritides. In discussing environmental influences on these diseases we have reviewed shared aetiological hypotheses and how these have been, and may be, manipulated to influence disease development. The socioeconomic impact of disease has been discussed, together with some of the strategies we might adopt to prevent further disability and handicap. Recent developments, particularly in the laboratory, promise imminent advances in the aetiopathogenesis of this group of chronic inflammatory disorders.