A body of evidence points towards a close connection between susceptibility to fractures and osteoporosis. The incidence of osteoporotic fractures, both in absolute figures and in age-specific figures, has increased worldwide throughout this century. Although some reports show that the age-specific incidence is levelling-off, there will be a continuously increasing number of individuals with such fractures that will have implications from an economical point of view not only for the affected individual but for society as a whole. The outcome after such fractures, especially those of the hip, is by no means always favourable, partly due to insufficient results after orthopaedic treatment and partly due to an already high comorbidity. Therefore, trying to prevent osteoporotic fractures by non-pharmacological or pharmacological regimens is of utmost importance.

The improvement in survival with chemotherapy has resulted in a change of the natural history of the systemic vasculitic syndromes. The vasculitides are now viewed as chronic disease rather than fatal conditions. Their course is frequently characterized by relapse as well as the scars of irreversible organ damage from disease and drug toxicity. Assessment tools are available which can serve as outcome measures in clinical trials as well as a guide to better management of individual patients. Improvements in therapy in future are dependent on a better understanding of the pathogenesis of these conditions and the ability to assess disease accurately.

The primary vasculitides are diseases of unknown aetiology. They are characterized by inflammation of blood vessel walls. Measuring non-specific laboratory markers of inflammation is useful in the monitoring of patients with vasculitis. The diagnostic specificity of these markers is, however, restricted. In the last decade, autoantibodies reacting with myeloid granule proteins have been detected in the sera from patients with Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and the renal limited form of these vasculitides (i.e. idiopathic rapidly progressive glomerulonephritis). Anti-neutrophil cytoplasmic antibodies (ANCA) in the aforementioned disorders react with proteinase 3 (Pr3) or myeloperoxidase (MPO), and only incidentally to other antigens such as elastase and bactericidal-permeability increasing protein. The presence of ANCA alone, in particular perinuclear ANCA, as detected by indirect immunofluorescence, has a low specificity for those vasculitides. However, in combination with the presence of anti-Pr3 or anti-MPO antibodies as detected by enzyme-linked immunosorbent assay, sensitivity and specificity for the vasculitides is high. Several in vitro and in vivo data have suggested a pathophysiological role for anti-Pr3 and anti-MPO in the associated disorders. Measuring levels of the autoantibodies seems useful for the follow-up of patients with these vasculitides. The sensitivity and specificity of rises in ANCA levels for ensuing relapses appears somewhat lower than previously suggested. Refinement of the assays, for example, by measuring subclasses and functional characteristics of the autoantibodies, may improve their value in monitoring patients with vasculitides.

Systemic vasculitides, hitherto thought to be a rare clinical entity, are now rarely considered to be an uncommon disorder and patients are often seen between several departments, suffering from a non-infectious systemic disease with multi-organ involvement. Systemic vasculitis not only poses a major management problem but also has a significant impact on healthcare resources. The clinical outcome of a vasculitic illness depends on a number of factors, such as aetiology of the vasculitic process, site, size and number of blood vessels affected, duration and severity of the disease and also the complications associated with the disease or its therapy.

Behçet's syndrome can involve all sizes and kinds of blood vessels. There is an association between arterial involvement and venous thrombosis. Pulmonary arterial aneurysms and neurological involvement have a definite influence on mortality. Male sex and young age are indicators of a more severe disease course. Immunosuppressive treatment early in the disease may affect the long term prognosis favourably. Patients with familial Mediterranean fever may develop manifestations of vasculitis. The most common associations are with Schönlein-Henoch purpura and polyarteritis nodosa. In some patients the diagnosis of vasculitis precedes that of familial Mediterranean fever. Kawasaki disease, although rare, can be seen in adults. The coronary sequela of childhood disease can affect the prognosis later in life. Many conditions, like myxoma, cholesterol embolism, calciphylaxis may mimic vasculitic syndromes. These conditions should always be kept in mind because their pathophysiology and treatment are different from true vasculitides.

Vasculitis, one of the clinical features shared by connective tissue diseases, should be considered when signs and symptoms are observed that may result from tissue ischaemia due to damaged vessels. The lesions seem to result from specific and non-specific immunopathogenic mechanisms targeted at the vascular endothelium. Because of the therapeutic implications it is the physician's responsibility to document its presence and the extent of organ involvement. Prompt institution of immunosuppressive drugs may be lifesaving. On the other hand there are some forms of vasculitis accompanying connective tissue disease which are entirely benign. Patients with infarctions of extremities and progressive functional disturbances of the central nervous system or internal organs because of vasculitis should be treated with high dosages of corticosteroids in combination with cytostatic drugs. Remissions are frequently obtained within three to six months of initiation of treatment and can be maintained with a less aggressive treatment regimen.

Giant cell arteritis and Takayasu arteritis are separate but similar idiopathic diseases clinically characterized by constitutional symptoms, shared surrogate markers of systemic inflammation and indistinguishable granulomatous pan-arteritis of large vessels. This review emphasizes and analyses changing perceptions about the diseases. Recent series suggest that aortic involvement in giant cell arteritis may be more common than was previously appreciated. The case for and against inflammatory arthritis in giant cell arteritis is discussed. Ethnic new geographical variation in Takayasu arteritis-disease expression is reviewed. New philosophies of treatment are presented for both diseases. Prognosis in giant cell arteritis and its relationship to treatment is analysed. The utility of the laboratory for diagnosis and monitoring disease activity is appraised for each.

The revival of interest in systemic necrotizing vasculitis was initiated by the discovery of its association with anti-neutrophil cytoplasmic antibodies (ANCA). The close association of certain ANCA subspecificities, for example, proteinase 3 (Pr3) and myeloperxoidase ANCA, with Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome has led to their designation as 'ANCA-associated vasculitides'. This article describes the common and divergent clinical and immunological features of the members of this 'new' family of systemic necrotizing vasculitis, which continues to grow with the widespread use of ANCA testing. In addition, the 'standard' treatment for systemic necrotizing vasculitis (daily 'low dose' cyclophosphamide plus glucocorticosteroids or 'Fauci's scheme') is compared with new stage and activity adapted therapeutic regimens.

Cutaneous vasculitis is a heterogeneous group of disorders, which can be confined to the skin or may be part of an associated systemic disease. Various aetiological agents as well as conditions that mimic skin vasculitis, usually present with similar clinical features; mainly palpable purpura. The skin biopsies usually show leukocytoclastic vasculitis. This poses a great diagnositc and therapeutic challenge for the physician. The aetiologies, clinical features, diagnosis and treatment modalities for each form (drugs, infections, malignancies, systemic vasculitides, connective tissue disorders. Schönlein-Henoch purpura, cryoglobulinaemia, cutaneous periarteritis nodosa, livedoid vasculitis, erythema elevatum diutinum and urticarial vasculitis) are reviewed.

A definitive diagnosis of virtually all vasculitides requires histological documentation. Although each major type of systemic vasculitis may have its own unique features, variability and overlaps still exist, and histopathological specificity is rarely an absolute discriminator. The interpretation of biopsies for the diagnosis of vasculitis remains more an art than a science, and it requires full and complete correlation with historical, clinical, laboratory, and angiographic findings.

The systemic vasculitides are rare inflammatory conditions of blood vessel walls. A number of different classification schemes have been published since the first in 1952. The important developments have been the recognition of dominant blood vessel size, the distinction between primary and secondary vasculitis and the incorporation of pathogenic markers such as anti-neutrophil cytoplasmic antibodies. In 1990 the American College of Rheumatology (ACR) published criteria for the diagnosis of polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, hypersensitivity vasculitis, Schönlein-Henoch purpura, giant cell arteritis and Takayasu arteritis. Sensitivity and specificity rates varied considerably: 71.0-95.3% for sensitivity and 78.7-99.7% for specificity. The criteria were not tested against the general population or against patients with other connective tissue diseases or rheumatic conditions. Four years later the Chapel Hill Consensus Conference (CHCC) produced definitions for the major types of vasculitis, however, these have proved controversial. Comparison in unselected patients with systemic vasculitis (in particular polyarteritis nodosa and microscopic polyangiitis) has shown that the ACR criteria and CHCC definitions identify different patients. The systemic vasculitides are somewhat more common than previously believed. The overall annual incidence approaches 40/million adults. The most common form of primary systemic vasculitis is giant cell arteritis; Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome have similar incidences. Classical polyarteritis nodosa and Takayasu arteritis are very rare in the UK.

Guidelines provide explicit recommendations and seek to influence practice using a formal process to disseminate advice on most effective management in the light of scientific evidence. They provide a framework for the evaluation and treatment of common clinical problems, but are not intended to replace clinical judgement. There is considerable variation in rheumatology practice, fueled by uncertainty about the optimal measurement of disease outcome. Guidelines can help identify and eliminate ineffective or unnecessary care as they are systematically developed statements to assist practitioners and patients' decisions about appropriate health care. There are North American guidelines for the initial evaluation of adult patients with acute musculoskeletal symptoms, the management of rheumatoid arthritis and the management of osteoarthritis. These are discussed together with proposed guidelines for the management of early rheumatoid arthritis and areas of research into the value of guidelines. It is recommended that future work in this area should: (i) identify aspects of current guidelines which are directly related to outcome; (ii) educate clinicians in these aspects of care; (iii) ensure they are introduced into practice and the outcome of care subsequently improves; (iv) regularly update the guidelines to reflect current opinion. Present guidelines that give broadly similar recommendations from North American and UK perspectives. However, the available evidence all points to large variations between how clinicians practise and how they make their decisions and it may be unlikely that laying down exact recipes for practice will necessarily influence the clinician. Guidelines may appear relevant but they could prove to have very limited utility.

Economic evaluations of health-care technologies are playing an increasingly central role in determining which therapies are available to clinicians in the treatment of a whole range of conditions. In rheumatology, a large body of work has already been done on the cost effectiveness of alternative non-steroidal anti-inflammatory drugs (NSAIDs), and much of the current work on disease modifying therapies incorporates economic evaluations. This chapter describes the main techniques of economic evaluation and reviews the strengths and weaknesses of each. Two published economic evaluations are discussed in order to highlight what economic evaluations can offer to the care of people with rheumatoid arthritis, as well as the current limitations of economic evaluation. The objective of this chapter is to equip readers with a critical understanding of economic evaluation that can be used in considering the increasing volume of health economic data that they encounter in their clinical work.

Patient education is accepted as an essential component in the management of rheumatoid arthritis (RA) and this chapter provides an overview of patient education for practising clinicians. It includes an explanation of the need for patient education including the results of studies into what patients already know. The effectiveness of patient education and its benefits to patients are discussed in the light of recent research, reviews and meta-analyses. Alternative methods of delivering patient education are compared including, one-to-one teaching, opportunity education, group teaching and self-management programmes. Topics for inclusion in education programmes are suggested and the merits of written literature, audio-visual and computer assisted learning are explained. Practical guidance is given on methods of ensuring that written information is readily understandable by patients, including the use of readability formulae.

In increasingly cost-conscious, accountable and integrated health-care systems, the appropriate role of speciality care is under scrutiny. The data on the impact of rheumatologist care on outcomes in patients with rheumatoid arthritis (RA) is limited and inconclusive. However, based on a review of processes of care known to be related to superior patient outcomes it is suggested that rheumatologists should be the lead physicians in patients with RA. Rheumatologists but usually not generalists have the experience necessary to make an early diagnosis and to initiate appropriate disease modifying anti-rheumatic drug (DMARD) treatment. Rheumatologists have an in-depth understanding of new assessment methods to optimize medical treatment and to make best use of and co-ordinate multi-disciplinary care. To avoid delay of diagnosis and initiation of treatment, patients with polyarthritis should be referred to rheumatologists as soon as possible. This requires that access to rheumatologist care is guaranteed.

As the pathophysiology of rheumatoid arthritis (RA) becomes more clearly defined there is the expectation that biotechnological advances may allow additional forms of therapeutic intervention that are specific for the disease process. The purpose of this review is to describe the use of biological agents in the treatment of RA. Encouraging results in animal models using vaccines based on the pathogenic T-cell or the autoantigen have prompted the design of selective immune-based therapies. Preliminary studies following this strategy have not yet shown clinical efficacy. The results of early studies with monoclonal antibodies against leukocyte surface antigen were promising but were not sustained in controlled studies. Exciting data have been collected from placebo-controlled studies of monoclonal antibodies against TNF alpha. The development of biological agents in RA may not be as quick as expected but the steady progress makes it likely that our weapons to combat unwanted autoimmune responses will become more accurate and effective.

Treatment with slow-acting anti-rheumatic drugs (SAARDs) is nowadays initiated earlier in the disease course, preferably before any radiographic damage has occurred. SAARDs have the ability to decrease inflammatory synovitis as measured by clinical and laboratory variables, and there is some evidence that they improve physical function and decrease the progression rate of joint damage in patients with early rheumatoid arthritis. There is a clear difference in survival time between the various SAARDs. The efficacy/toxicity profiles of the SAARDs show equal variation. Rank order of prescription or disease duration may have an effect on drug survival, but different treatment strategies are also important sources of variation. Efficacy might be improved by combining different SAARDs (starting with a multiple drug regimen, or adding a drug to the first one), but further research is necessary to prove this hypothesis.

In rheumatoid arthritis nowadays a more aggressive treatment strategy is followed based on early consistent use of second-line agents frequently given in combination. This approach requires an accurate monitoring of the disease activity to follow the course of the disease and to evaluate therapeutic interventions. International consensus is reached over a core set of disease activity variables, including: a 28-joint count for tenderness and swelling, an acute phase reactant, patient's pain and global disease activity, physician's global disease activity, functional disability and radiographs. Guidelines for measurement techniques need to be further specified. Indices of disease activity are developed to improve the unambiguous interpretation of disease activity and comparability of trial results. These measures can be divided in measures for current disease activity and improvement criteria. Further validation will be necessary to adapt finally a uniform measurement technique. The usefulness of self-administered joint counts needs to be studied further.

This chapter will describe the reasons why prognostic factors that predict aggressive disease are helpful and what the problems are in interpreting studies in this field. A summary of cohort studies on prognosis of patients with early rheumatoid arthritis are presented. This is done separately for studies predicting radiographic damage, functional outcome and mortality. The overall conclusions of these studies and the value they have for the clinician are demonstrated.