The acute phase response in a given individual represents the integrated sum of multiple, separately regulated changes. Although many of these changes commonly occur together in affected individuals, clinical experience indicates that not all of them occur in all individuals, indicating that they must be individually regulated. For example, febrile patients may have normal blood levels of CRP and vice versa, leukocytosis does not always accompany other acute phase phenomena, and many instances of discordance between levels of the various acute phase proteins are seen. Cytokines function as part of a complex regulatory network, a signalling language in which information is conveyed to cells by combinations, and perhaps sequence, of intercellular messenger molecules. The effects of combinations of cytokines are complex. To use a somewhat crude simile, individual cytokines can be thought of as words which bear informational content and which may, on occasion, communicate a complete message. More commonly, however, the actual messages received by cells probably resemble sentences, in which combinations and sequences of words convey information. Currently available data suggest that hepatocytes receive a complex mixture of humoral or paracrine signals during the acute phase response. These are integrated by multiple interacting signal transducing mechanisms to cause finely regulated changes in plasma protein synthesis. Regulation largely occurs by transcriptional control, but post-transcriptional mechanisms, including translational regulation, may also participate. Both the extracellular and intracellular mechanisms that mediate the response of the hepatocyte to inflammatory stimuli appear to be highly complex and involve multiple overlapping, concurrent and parallel pathways. Enough is known at present to conclude that IL-6 is a major participant in these plasma protein changes. Regulation of non-hepatocyte acute phase phenomena has not been delineated as thoroughly, but clearly involves a number of inflammation-associated cytokines.

The treatment of psoriatic arthritis has acquired relevance in the past few years because of advances and better understanding of the pathogenetic mechanisms implicated in the disease, and also because of recognition that this disorder is not a benign disease as was previously thought. The general principles of management for any inflammatory arthritis, including pharmacological, surgical and rehabilitative treatment, are to be used, with concomitant therapeutic management of skin involvement. Non-steroidal anti-inflammatory drugs constitute the mainstay of pharmacological therapy for most patients, with a good clinical response observed in 75-85%. Early use of remittive agents, especially methotrexate, is indicated in patients with a poor response to NSAIDs or those with polyarticular and progressive joint involvement. Patients who are refractory to conventional therapy should be considered for newer and potentially more toxic therapeutic modalities such as cyclosporin A and retinoids.

The incidence of radiological change in psoriatic arthritis (PsA) is uncertain. The general pattern of the disease has been classified into five groups. This classification is still widely used, but recently a change of emphasis has been stressed in the classification and prevalence, particularly relating to the polyarthritic forms and the variability of symmetry and asymmetry. The plain film findings in the axial and appendicular skeleton are described. In the former, bulky paramarginal ossification in the thoracolumbar spine is a prominent feature; destructive as well as ankylosing disease is seen in the cervical spine. In the latter, the key features are marginal erosions associated with proliferative new bone, acro-osteolysis, preservation of bone density, periostitis and bony ankylosis. Progress of the disease is variable and, while the course is usually less severe than that in rheumatoid arthritis, progressive joint deformity occurs. Isotope scintigraphy is a useful technique for showing a general overview of joint involvement, but has limitations which impair its use in individual joints. CT is useful for looking at detailed bone anatomy and early demonstration of sacroiliitis. MRI may also be used to look at early sacroiliitis and has the potential for directly imaging the inflammatory process and the articular cartilage. Radiological differentiation of PsA from other arthritides may be difficult, particularly in the early stages, and in oligoarticular disease. The differential diagnosis is discussed.

Over recent years there has been a great deal of interest in the immunology, molecular biology and pathology of psoriasis and PsA. The pathogenetic mechanisms in PsA are less well understood than those described for psoriasis. There are almost certainly genetic and immune components. What is not clear is whether there is a primary immune defect or whether unknown stimuli lead to the recruitment of the immune system and establishment of the disease; nor is it absolutely clear whether PsA is an extension of psoriasis in certain prone individuals. Vascular abnormalities are the earliest histopathological changes to occur in the psoriatic plaque and are also prominent in the psoriatic synovium. Espinoza et al (1982) have suggested there may be a primary vascular defect in PsA. The fact that vascular changes occur before infiltration of immunocompetent cells and are the first changes to resolve with treatment of psoriasis is likely to be significant. Abnormalities in the cellular kinetics and growth factor sensitivity of keratinocytes, fibroblasts and synoviocytes have been highlighted previously. The ability of these cells to produce growth factors and express HLA class II antigens demonstrates the potential for them to initiate and maintain inflammation. The development and possible increased incidence of PsA in patients with such profound immunodeficiency as acquired immune deficiency syndrome suggests that T helper cells do not play a significant role in the establishment of the disease (Arnett et al, 1991). Previously, many immune changes were described. Unfortunately they are non-specific and do not indicate a fundamental defect or marker of PsA. Vasey (1985) has suggested that insidious exposure to Gram-positive bacteria from the gut, tonsils and psoriatic plaques results in chronically stimulated monocytes, macrophages and dendritic cells. These cells are able to migrate throughout the body. Repeated microtrauma may result in the homing of these cells to sites of injury in the skin, synovium and tendons. Interaction with genetically hyperactive synoviocytes and keratinocytes with concomitant release of growth factors may precipitate early lesions of psoriasis and PsA. This hypothesis needs to be substantiated, but it ties together some of the varying observations seen. Many abnormal laboratory findings have been described. Unfortunately, none of the serological changes is sufficiently specific to be of great help in diagnosis. CRP levels and the ESR remain the best promise as markers of the inflammatory component of the arthritis, while other indicators correlate with certain facets of the disease pathology, but as yet have not found a true niche in the management of PsA.(ABSTRACT TRUNCATED AT 400 WORDS)

Psoriasis is a common chronic skin disorder affecting 2% of the general population. Present evidence strongly suggests that it is an immunologically mediated disease; the evidence includes the results of disease association studies linking psoriasis to certain MHC antigens and immunohistochemical studies revealing early influx into lesions of activated T lymphocytes. Accumulation of these cells in skin is mediated by upregulated expression of leukocyte adhesion molecules on vascular endothelium and epidermal keratinocytes and by production of proinflammatory and chemotactic cytokines. Activation of cell-mediated immune mechanisms in lesional skin is highlighted by the increased antigen-presenting capacity of Langerhans cells isolated from psoriatic skin compared to normal skin. The nature of the antigens precipitating psoriasis, however, remains unknown although a role for streptococcal superantigens has been postulated. These studies have led to the belief that immunotherapy may hold great promise for the treatment of psoriasis. Indeed both cyclosporin A and FK506 are effective therapies and evidence suggests that anti-CD4 antibodies may be of great value.

Psoriasis and psoriatic arthritis are diseases of unknown aetiology characterized by chronic immune-mediated lesions in the skin and synovial joints respectively. The lesions are remarkably similar in appearance and in functional terms. The main differences reside in the fact, first, that the main antigen-presenting cell in the skin is the Langerhans' cell while in the joint it is probably the dendritic antigen-presenting cell and, second, that the main mesenchymal cell in the skin is the keratinocyte while in the joint it is the synoviocyte. Whether these differences merely reflect tissue-specific characteristics or are important in aetiopathogenesis is not known at present. However, the similarity in pathogenesis does mean that similar immunotherapeutic approaches can be used for their treatment.

The place of psoriatic arthritis in the spondarthritides has been examined in terms of past, present and future aspects. It is concluded that: 1. PsA is a definite entity and separate from rheumatoid arthritis. 2. The spondarthritis concept is universally accepted, although still in an evolving stage. 3. A more definitive picture of the spondarthritides and of PsA itself could arise from a number of new approaches, some entirely novel, some extensions of work already in progress. Avenues of future research that are likely to be fruitful include those involving: more refined clinical studies; further applications of molecular mapping; and, common to both, conceptual advances using mathematical models to provide a more 'three-dimensional' picture.

Psoriatic arthritis is a distinct form of inflammatory arthritis associated with psoriasis, which exists in a number of clinical presentations. Although a large number of patients have a mild form of arthritis, there is a population who present with a very aggressive, deforming and disabling arthritis. The prognostic factors for the development of this type of arthritis are unclear as yet. Therefore, PsA may not be as benign a condition as previously thought, and the approach to its management should be similar to that for rheumatoid arthritis. Current investigations are in progress to identify the prognostic factors associated with severe disease in PsA. Until the results of these studies are available, all patients should probably be treated more aggressively, and earlier.

The occurrence of musculoskeletal manifestations (including synovitis, chest wall arthro-osteitis and multifocal aseptic osteomyelitis) in association with severe acne, palmoplantar pustulosis and perhaps with some presentations of psoriasis, have been described by many authors in the past 30 years. These different multifaceted descriptions have been designated by a variety of terms. More recently, a possible link between these conditions and spondarthritides has also been underlined by a slightly increased prevalence of HLA-B27 and occasional occurrences of sacroiliitis, chronic inflammatory bowel disease and possibly psoriasis. An acronym, the SAPHO syndrome (which stands for Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) is proposed for this group of diseases because of the similarity of musculoskeletal manifestations in patients with severe acne and pustulosis. The clinical, epidemiological, pathophysiological, immunogenetic and diagnostic aspects, as well as the management of this syndrome, are reviewed.

From two studies (Lambert et al, 1976; Shore and Ansell, 1982), it was concluded that juvenile psoriatic arthritis is a distinct entity with one group of patients virtually indistinguishable from those with juvenile chronic arthritis initially, while all the patterns of psoriatic arthritis recorded in adults were seen in the remainder. A family history of psoriasis occurs in about half the patients, and one of arthritis in 20%. A swollen tendon sheath of a single finger or toe associated with synovitis in two or three joints of the digits is highly characteristic. Accurate diagnosis is important because these patients tend to go on to develop an asymmetrical destructive polyarthritis. This needs to be recognized early to utilize effective slow-acting drugs. Southwood and colleagues (1989) have defined two quite distinct groups of juvenile psoriatic arthritis: those young at onset, who are usually girls, and those in adolescence, who are more frequently boys. It is possible that there are other variants, including girls aged 8-10 years with a polyarthritic onset who may go on to develop arthritis mutilans. The concept of 'probable juvenile psoriatic arthritis' is supported by follow-up, in that a significant proportion of such patients do pass into the definite group. It is highly desirable that the suggested Vancouver criteria are validated by a long-term prospective study, which will probably need to be multicentred to ensure that the subgroups are large enough for satisfactory conclusions to be drawn. In the management of this serious arthritis in childhood, it is important to consider long-acting drugs early, before undue damage to joints has occurred. Again, multicentre studies are needed to determine which is the most useful. Presently, methotrexate appears to be the drug of choice.

Psoriatic skin disease is common; it occurs at all ages and co-exists with joint disease in approximately 10% of cases. All areas of skin, scalp and nails may be involved. In the typical case, the skin lesions are easy to recognize. Atypical forms of skin involvement and lesions at unusual sites are less easily diagnosed by non-specialists. The cause is unknown, but there is a clear genetic element, with external factors being important in precipitation and exacerbations of the condition. Topical treatment is successful in most patients, but in resistant cases combinations of systemic therapy and ultraviolet radiation usually give good control. Although there is no cure, the majority of sufferers live normal lives and, with the exception of severe erythrodermic or generalized pustular psoriasis, there is no mortality. Morbidity, particularly social and occupational, is more of a problem than is often acknowledged.

There is convincing evidence of a genetic basis for both psoriasis and psoriatic arthritis (PsA). Part of this genetic predisposition is due to genes within the major histocompatibility complex (MHC). In psoriasis, the primary association is with HLA-Cw6. Further work on specific nucleotide frequencies, especially those in the alpha 1 domain helix of the HLA-C molecule, will be of interest in determining whether a specific nucleotide frequency is present in all patients. The situation in PsA is considerably more complex. It is now established that there is an association between HLA-B27 and PsA, both in its peripheral arthropathy and in spinal disease in which radiological sacroiliitis is present. Spinal disease without radiological sacroiliitis is probably not associated with HLA-B27. There is some suggestion that HLA-B16 or its splits, HLA-B38 and HLA-B39, may also be associated with PsA, but there is considerable heterogeneity between the series, which prevents a firm conclusion being made. It is possible, but again not conclusive, that there is an association between HLA-DR4 and the symmetrical seronegative pattern of peripheral PsA. It is also likely that genes outwith the MHC predispose to psoriasis and PsA. It is further likely that a role will be found for environmental factors in both psoriasis and PsA. There is a tantalizing possibility of a complex interplay between a variety of environmental factors and genetic factors, both within and outwith the MHC, determining not only susceptibility but also the individual clinical pattern of disease. Further clarification of these possibilities is likely to depend primarily on understanding the role of genes within the MHC in predisposing to comparatively more homogeneous diseases, such as psoriasis and ankylosing spondylitis, before the mechanisms operating in PsA can be analysed and better understood.

Psoriatic arthritis was first described in the early part of the nineteenth century. Over the past 50 years, concepts of the disease have evolved as a result of clinical, epidemiological, radiological and immunogenetic study. Epidemiological and clinical investigations suggest that the disease is a unique arthropathy rather than the coincident occurrence of two common diseases. There are no validated criteria for classification; this is partly because of the heterogeneous clinical features associated with the disease, and the relapsing and remitting nature of both psoriasis and arthritis. Clinical subgroups have been proposed and have proved useful in study of the disease; however, there are inconsistencies and overlaps in the published data. The population prevalence of psoriatic arthritis is in the range of 2-10 per 10,000 although this is probably an underestimate as those with sacroiliac involvement only are not included. There are currently no incidence figures from population samples. The disease is slightly more common in females than males, although there is variation in the sex ratio by disease subgroup. There is evidence that hormonal and environmental factors play a role in the occurrence of disease.

1. Normal joints in individuals of all ages may tolerate prolonged and vigorous exercise without adverse consequences or accelerated development of OA. 2. Individuals who have underlying muscle weakness or imbalance, neurological abnormalities, anatomical variances, and who engage in significant amounts of exercise that stress the lower extremities, may accelerate the development of OA. 3. Individuals who have suffered injuries to supporting structures may also be susceptible to accelerated development of OA in weight-bearing joints, even without increased stress to the joint from exercise. 4. Certain individuals with established degenerative or inflammatory arthritis may benefit from supervised exercise programmes. 5. Still more information is needed so that physicians can identify subjects at risk for the development of OA, advise the millions of participants about the beneficial and deleterious effects of regular exercise and sports participation, and develop successful rehabilitation programmes for injured joints.

Physical activity epidemiological studies provide one of many types of research evidence that are necessary to assess the importance of physical activity to health. Available epidemiological evidence, when coupled with relevant experimental and clinical research, suggests that physical activity has the potential to favourably influence the development and progression of a variety of chronic diseases and conditions that are a burden to public health. The evidence is only beginning to emerge for elderly populations, however, thereby highlighting an important void in our scientific knowledge. Attempting to increase the level of physical activity of elderly people raises three important issues. First, improving adherence to a physically active life-style requires assistance of behavioural scientists, either through direct intervention, or through research that can help the elderly identify and overcome impediments to physical activity. Second, many elderly people have diseases that can limit their physical ability, but exercise scientists can assist by prescribing exercise that is both efficacious and safe given the level of limitation. Third, the number of injuries may increase with increased physical activity in elderly persons. Epidemiologists and exercise scientists working in the area of injury control can determine which activities are safe at specific levels of physical ability and function. To quote one of the originators of exercise physiology, Per Olaf Astrand (1992), 'As a consequence of diminished exercise tolerance, a large and increasing number of elderly people will be living below, at, or just above "thresholds" of physical ability, needing only a minor intercurrent illness to render them completely dependent'. Physical activity can help to push back that 'threshold of physical ability' and thereby improve physical functioning. As physical function improves, there is a propensity to perform even greater amounts of physical activity that may be essential to the quality and perhaps quantity of life for an elderly person.

Occupational physical activities over many years can induce osteoarthritis in selected joints. Well-studied examples include evidence of osteoarthritis of the knees and spine in miners, osteoarthritis of the hip in farmers and increased rates of osteoarthritis of otherwise not usually affected upper extremity joints in pneumatic drill operators. Occupation-induced osteoarthritis may not be limited to these uncommon occupations but may, in fact, account for a large proportion of osteoarthritis in the population. Additional studies of this issue, which incorporate high-quality ergonomic assessments of occupational physical activities, are needed. People with pre-existing arthritis often experience work disability, especially when faced with physically demanding jobs in which they have little control over the pace or the specific physical demands of their labour.

The data presented here document that exercise is associated with changes in immunological activity as assessed by a variety of in vitro assays. In general, these changes appear to be temporally associated with activity and are not persistent. In fact, most alterations are probably secondary to exercise-induced hormonal changes, with resultant effects on the intravascular composition of immunocompetent cells. Thus, changes in lymphocyte trafficking induced by hormonal effects lead to relative and absolute differences in cell numbers, which may be reflected in in vitro functional assays. These data argue against any profound impact of exercise on the immune system, which might impact on overall health. Furthermore, there is little information about exercise decreasing the number of infectious illnesses or diminishing the likelihood of immunologically mediated conditions or malignancies. Nevertheless, these results should not be construed as an argument against the tangible health benefits of exercise. The changes in life-style which often accompany exercise programmes, as well as the documented benefits for cardiovascular health, are reasons enough to support these activities.

Exercise testing is now widely used as both a diagnostic tool in the elderly and as a means of generating the information necessary to provide them with a valid exercise training prescription. An appropriate medical history and physical examination prior to exercise testing will allow for the adequate assessment of an individual's risk of undergoing an exercise test. Appropriate screening of the individual, assessment of risk prior to exercise, and appropriate monitoring during and following the exercise test have contributed to the relative safety of maximal exercise testing, with statistics indicating roughly one death occurs in every 10,000 clinical maximal exercise tests. When designing an exercise test protocol for use in the elderly, their reduced exercise capacities, increased prevalence of CV disease, and the reason for doing the test must be taken into consideration. The Bruce treadmill protocol is the most widely used exercise test in populations of all ages; however, because of its relatively high VO2 demands in the initial minutes of exercise, it may not be the optimal protocol for the elderly. Other alternative protocols including the Naughton and Balke tests may be more appropriate, especially when attempting to generate a valid exercise prescription. However, the modified Balke protocol, with a constant speed of 2 miles/h and starting on the level, is probably the best protocol for exercise testing in the elderly for the purposes of generating an exercise prescription. If individuals are unable to undergo exercise tests on a treadmill, cycle and arm ergometer tests provide alternative test modalities, but these have a number of inherent problems that must be considered prior to exercise testing. The interpretation of an elderly individual's ECG responses during a maximal exercise test is intimately related to their risk of having CV disease prior to the exercise test, though fewer false-positive tests will be evident because of the increased prevalence of CV disease in the elderly.