bluuebunny/crossref_metadata_2025 huggingface dataset:
Injection therapy
Authors: Platt Philip , Atchia Ismael
Published: February 2014

Joint and soft tissue injections with glucocorticoids and other agents remain a critical aspect of the management of musculoskeletal conditions. Injection therapy has previously consisted mainly of glucocorticoid and local anaesthetic, but other agents such as hyaluronic acid, radioactive agents, plasma-rich products, and biologics have also been introduced in the practice of musculoskeletal clinicians.
Overall glucocorticoid injection remains the most widely performed procedure, and is an effective treatment for an inflamed joint or soft tissue. This procedure has been widely used for at least five decades. Hydrocortisone was the initial steroid used but longer-acting steroid agents are now favoured for large joints. There is evidence of efficacy not only for inflammatory arthritis conditions, but also for osteoarthritis. There are certain contraindications for injection therapy. Hyaluronic acid (viscosupplementation) injection has become part of the management of osteoarthritis. More recently other agents such as disease-modifying anti-rheumatic drugs (DMARDs) and biologics have been injected with varying degree of success.
The ability to deliver an injection accurately depends on appropriate knowledge of the anatomy and, as for any procedures, the experience and skill of the clinician. The approach to different joints and soft tissue structures is described in this chapter.
Alternative therapies
Authors: Ernst Edzard
Published: February 2014

Alternative therapies are used by many patients suffering from rheumatic conditions. In this chapter, the efficacy and safety of various forms of alternative medicine will be discussed based on the evidence from clinical trials and systematic reviews. The following treatments will be considered: acupuncture, Ayurvedic medicine, chiropractic, dietary supplements, herbal remedies, homeopathy, massage, osteopathy, t'ai chi, and yoga.
Principles of spine surgery
Authors: Fairbank Jeremy , Batista Nuno
Published: February 2014

Spine surgery addresses pain, loss of function and deformity of the spine. Earlier conceptions of chronic pain have changed, but there is still a limited role for surgery to manage painful spinal pathology. Loss of function is caused by tumours, fractures and infections, all of which can be helped by surgery. Deformity is called scoliosis and/or kyphosis, and be corrected by surgery. Spinal deformity is increasingly recognized in adults as an important cause of disability, especially when there is loss of sagittal balance. Advances in anaesthesia and implant technology have allowed the spine surgeon greater opportunities to help seriously disabled patients in ways not possible 20 years ago. Fractures occur following trauma, but are also associated with impaired bone strength, particularly through osteoporosis.
Anti-rheumatic drugs in pregnancy and lactation
Authors: Marshall Tarnya , Abdulkader Rita
Published: February 2014

Anti-rheumatic drugs in pregnancy and lactation are increasingly a common clinical dilemma. With the shift towards early, aggressive control of autoimmune diseases and with the advent of newer therapeutic agents, there is a need to understand the effects of these medicines in pregnancy and lactation, on fertility in both men and women, and on the process of spermatogenesis, in order to understand the risk of teratogenesis.
Although there are some limited data available for the use of anti-rheumatic drugs in pregnancy and lactation, much of our knowledge is derived from animal models and from limited clinical experience in human pregnancy.
The balance of therapeutic benefits and risks of harm to mother and fetus should always be carefully considered: it may vary between individuals and should be assessed on a case by case basis. Because of these issues, pregnancy should always be discussed and planned in advance, in part to reduce disease activity prior to conception but also to minimize risk to the fetus.
In this chapter we use the available evidence to discuss medicines which are commonly used in the treatment of rheumatological autoimmune diseases, and cover disease-modifying anti-rheumatic drugs (DMARDS) and biological agents.
Septic arthritis in adults
Authors: McGregor Laura , Gupta Monica N. , Field Max
Published: February 2014

Septic arthritis (SA) is a medical emergency with mortality of around 15%. Presentation is usually monoarticular but in more than 10% SA affects two or more joints. Symptoms include rapid-onset joint inflammation with systemic inflammatory responses but fever and leucocytosis may be absent at presentation. Treatment according to British Society of Rheumatology/British Orthopaedic Association (BSR/BOA) guidelines should be commenced if there is a suspicion of SA.
At-risk patients include those with primary joint disease, previous SA, recent intra-articular surgery, exogenous sources of infection (leg ulceration, respiratory and urinary tract), and immunosupression because of medical disorders, intravenous drug use or therapy including tumour necrosis factor (TNF) inhibitors.
Synovial fluid should be examined for organisms and crystals with repeat aspiration as required. Most SA results from haematogenous spread-sources of infection should be sought and blood and appropriate cultures taken prior to antibiotic treatment. Causative organisms include staphylococcus (including meticillin-resistant Staphylococcus aureus, MRSA), streptococcus, and Gram-negative organisms (in elderly patients), but no organism is identified in 43%, often after antibiotic use before diagnosis.
Antibiotics should be prescribed according to local protocols, but BSR/BOA guidelines suggest initial intravenous and subsequent oral therapy. Medical treatment may be as effective as surgical in uncomplicated native SA, and can be cost-effective, but orthopaedic advice should be sought if necessary and always in cases of infected joint prostheses.
In addition to high mortality, around 40% of survivors following SA develop limitation of joint function. Guidelines provide physicians with treatment advice aiming to limit mortality and morbidity and assist future research.
Bone and joint infections in children
Authors: Sukhtankar Priya , Clark Julia , Faust Saul N.
Published: February 2014

Bone and joint infections in children are uncommon, but they affect all ages and there is a wide range of disease. The mode of infection may be haematogenous or by direct inoculation from a wound. The child may present acutely unwell or with a chronic infection. Clinical features include fever, reluctance to move the affected limb, pain, and swelling. Laboratory tests and medical imaging are used to confirm diagnosis.
Medical treatment is with initial intravenous antibiotic therapy, usually followed by oral treatment. Surgical treatment may be necessary if abscess or joint collection is present. In general prognosis is good with timely initiation of treatment, although complications such as pathological fracture are occasionally seen.
Osteomyelitis
Authors: Field Jeremy , Upadhyay Neil
Published: February 2014

The word osteomyelitis is derived from Greek words osteon denoting bone, myelo meaning marrow, and itis, inflammation. Infection may involve one part of bone or extend through marrow, cortex, and periosteum, and even into surrounding tissues. Osteomyelitis results from a microorganism that leads to necrosis and bone destruction.
The aetiopathogenesis of osteomyelitis in the United Kingdom is changing. Ageing populations, orthopaedic surgery, peripheral vascular disease, decubitus ulcers, and immunocompromised patients (from either disease or immune-modulating agents) all affect the epidemiology and provide new challenges.
Despite new imaging techniques, diagnosis is often delayed, thus heightened index of suspicion for the condition particularly in high-risk patient groups is required. Identification of the causative organisms is essential for diagnosis, treatment, and prognosis of osteomyelitis.
Management of osteomyelitis can prove difficult and result in significant morbidity and disability. Early recognition and commencement of appropriate treatment is vital. A combined antimicrobial and surgical approach should be considered in all cases; however, antimicrobial therapy alone may be appropriate in treatment of acute osteomyelitis in certain situations. Chronic osteomyelitis necessitates a multidisciplinary approach with specialized teams. Surgical strategies such as meticulous debridement and dead-space management coupled with cancellous bone grafts and circular frame cancellous-distraction osteogenesis have enabled eradication of infection and limb preservation in previously unsalvageable situations. That said, there remains a subgroup of patients who should be recognized, with chronic infection and concomitant systemic disease, in whom surgical intervention will not alter the prognosis.
Viral arthritis
Authors: Naides Stanley J.
Published: February 2014

Viral infection may cause sudden onset polyarthralgia or polyarthritis. Recognizing viral syndromes during the acute phase of illness is critical as markers of acute infection may fade during convalescence. While joint symptoms and signs in many cases are self limited, in others joint involvement may persist for months to years. Acute and chronic findings may resemble classic idiopathic diseases such as rheumatoid arthritis or systemic lupus erythematosus. Some viral infections may manifest with rash, vasculitis, or organ involvement. Understanding of epidemiology, geography, clinical presentation, virus behaviour and host response assists diagnosis and selection of appropriate management. Understanding virus-host interactions may offer insights into mechanisms of pathogenesis in idiopathic rheumatic diseases.
Rheumatic fever
Authors: Steer Andrew
Published: February 2014

Rheumatic fever is an autoimmune inflammatory condition that follows infection with the group A streptococcus. It is a common condition in tropical developing countries, but has become a rare disease in developed temperate countries. The most frequent clinical presentation of rheumatic fever is fever and arthritis, often with carditis. The carditis, which manifests as a valvulitis, can progress to rheumatic valvular disease. Rheumatic heart disease is a chronic and disabling condition associated with considerable morbidity and premature mortality. Management of rheumatic fever includes treatment of the inflammation of the disease using aspirin or other non-steroidal anti-inflammatory drugs and assessment and management of any cardiac involvement. Secondary prophylaxis is the mainstay of long-term management and patients usually require antibiotic prophylaxis for many years after the initial episode.
Rheumatoid arthritis—diagnosis
Authors: Aletaha Daniel , Radner Helga
Published: February 2014

Rheumatoid arthritis (RA) is among the most disabling form of chronic inflammatory joint disease. Not all forms of arthritis develop into RA; on the contrary, it may be very challenging to differentiate RA from cases of arthritis that are self-limiting or caused by another disease. Evaluation of early arthritis includes some basic steps, such as excluding trauma, crystal, or infectious-related disease, as well as considering additional features that may guide towards a specific diagnosis. If no specific diagnosis can then be made, the presentation can be labelled as undifferentiated arthritis. Typical differential diagnoses of RA include viral polyarthritis, seronegative spondylarthropathies, polymyalgia rheumatic, and other systemic rheumatic diseases.
In 2010, new classification criteria were published that led to a change in the approach to RA. Compared to the previous criteria, the American College of Rheumatology (ACR) 1987 criteria, a scoring system was devised, appreciating the type and number of affected joints (up to 5 points), as well as serology (up to 3 points), elevated acute-phase reactants (1 point), and a symptom persistence of 6 weeks or longer (1 point). If 6 or more points are reached, then classifiable RA is present. Importantly, classification status, which is used for study purposes, is not always identical to the diagnostic status, which often leads to clinical treatment.
Rheumatoid arthritis—management
Authors: Deighton Chris
Published: February 2014

Influential guidelines on rheumatoid arthritis (RA) management agree on most key recommendations. Early diagnosis of persistent synovitis, and identification of poor prognostic markers, is essential. Rapid intervention is vital with drugs to suppress inflammation, slow down damaging disease components, and prevent disability.
The label of RA covers a broad spectrum of disease severity, and there is controversy on:
• whether the same interventions are needed for all patients
• whether monotherapy or combination treatment is appropriate
• the role of steroids in RA
• the appropriate introduction of biological therapies.
Treating to specified targets is optimal evidence-based practice, where patients are reviewed regularly for disease activity assessments, and inadequate control rectified. Aiming for remission is the ultimate goal, though for some patients minimal disease activity may be appropriate. Patient education addressing self-management is important, and the multidisciplinary team (MDT: specialist nurses, physiotherapists, occupational therapists, podiatrists, psychologists) needs to be involved from the start to minimize the impact on quality of life of the patient.
For established disease, rapid access is important for flares, and to consider whether disease management could be improved. An intermittent overview of established disease is important with access to the MDT, and assessments for comorbidities such as ischaemic heart disease, osteoporosis, and depression, as well as complications of the disease itself such as cervical spine disease, vasculitis, and lung and eye complications. An informed patient needs to be central to all decision making.
Ankylosing spondylitis
Authors: Sieper Joachim
Published: February 2014

Ankylosing spondylitis (AS) is a chronic inflammatory disease predominantly of the sacroiliac joint (SIJ) and the spine. It starts normally in the second decade of life and has a slight male predominance. The prevalence is between 0.2 and 0.8% and is strongly dependent on the prevalence of HLA B27 in a given population. For the diagnosis of AS, the presence of radiographic sacroiliitis is mandatory. However, radiographs do not detect active inflammation but only structural bony damage. Most recently new classification criteria for axial spondyloarthritis (SpA) have been developed by the Assessement of Spondylo-Arthritis international Society (ASAS) which cover AS but also the earlier form of non-radiographic axial SpA. MRI has become an important new tool for the detection of subchondral bone marrow inflammation in SIJ and spine and has become increasingly important for an early diagnosis. HLA B27 plays a central role in the pathogenesis but its exact interaction with the immune system has not yet been clarified. Besides pain and stiffness in the axial skeleton patients suffer also from periods of peripheral arthritis, enthesitis, and uveitis. New bone formation as a reaction to inflammation and subsequent ankylosis of the spine determine long-term outcome in a subgroup of patients. Currently only non-steroidal anti-inflammatory drugs (NSAIDs) and tumour necrosis factor (TNF) blockers have been proven to be effective in the medical treatment of axial SpA, and international ASAS recommendations for the structured management of axial SpA have been published based on these two types of drugs. Conventional disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate are not effective.
Psoriatic arthritis
Authors: Coates Laura C. , Helliwell Philip S.
Published: February 2014

Psoriasis is a chronic skin condition affecting about 3% of Europeans and North Americans. About 15% of people afflicted with psoriasis will develop psoriatic arthritis—cutaneous risk factors for this are psoriasis of the nails, scalp, and flexures. Since most cases of arthritis develop in people with psoriasis, new screening tools, both clinical and imaging, are available. Some genetic factors may also explain susceptibility and severity. Historically, five clinical subgroups have been described but these may be simplified to axial and peripheral involvement, the latter dividing into oligo- and polyarticular patterns. The importance of these clinical subdivisions is still under debate and research but it is clear that there is marked heterogeneity in all manifestations of this disease. In recent times the importance of extra-articular features has gained prominence such that the metabolic syndrome and cardiovascular morbidity are now seen as important features of 'psoriatic disease'. The diverse changes seen in bone on imaging reflect both the underlying pathogenic mechanisms and the ways in which the disease progresses. Recent work with animal models and immunohistochemistry has further advanced our understanding of these features. In the biologic era renewed interest in psoriatic arthritis has stimulated research into outcome assessment and permitted clearer understanding of how these new drugs work on the different aspects of the disease. In addition, improved recognition of the impact of the disease on the person has stimulated the development of new patient-reported outcome tools.
Juvenile idiopathic arthritis
Authors: Baildam Eileen
Published: February 2014

Juvenile idiopathic arthritis (JIA) is defined as arthritis lasting for 6 weeks or more presenting in childhood at any age up to 17 years. Arthritis is diagnosed clinically by the presence of joint pain, stiffness, and swelling with inflammation limiting the range of individual joint movement. There are subtypes that tend to follow distinct courses and with phenotypes that vary widely from a serious systemic inflammatory disorder of systemic JIA to single-joint monoarthritis. The differential diagnosis of JIA is wide and the best chance of long-term remission is where treatment is started as early as possible. However, there is often delay in diagnosis in childhood and there is no single reliable diagnostic test so pattern recognition is fundamental. There are associated disorders such as silent uveitis that must be screened for and managed as part of essential multidisciplinary care. Systemic JIA is complicated by potentially life-threatening macrophage activation syndrome that is often underdiagnosed but where the diagnosis is based on easy clinical tests and where awareness is vital. This chapter covers descriptions of the classification criteria for chronic arthritis in children, clinical presentations and likely course for the various subtypes.
Systemic lupus erythematosus—management
Authors: Dey Ida Dzifa , Isenberg David
Published: February 2014

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with varied presentation and a disease course characterized by remission and flares. Over the last 50 years, the prognosis of SLE has improved considerably. The introductions of corticosteroids and later of cytotoxic drugs, dialysis, and renal transplantation were the major contributors to this improvement.
Nevertheless, the treatment and general management of lupus continues to present a challenge. While lupus may, for some patients, represent a relatively mild set of problems, many others require large doses of immunosuppressive drugs, which carry long-term concerns about side effects.
New immunotherapeutic drugs, with actions more closely targeted to the immune cells and molecules involved in the pathogenesis of SLE, are being introduced and the future looks promising. The role of early atherosclerosis and cardiovascular disease as a cause of death in patients with SLE is increasingly recognized and will present further challenges in the future.
Anti-phospholipid antibody syndrome
Authors: Khamashta Munther A. , Hughes Graham R. V. , Ruiz-Irastorza Guillermo
Published: February 2014

The anti-phospholipid syndrome (APS) described almost 30 years ago, is now recognized as a major cause of deep vein thrombosis, stroke, and heart attacks in young people (<45 years of age). It is also the commonest treatable cause of recurrent miscarriages and a major cause of late fetal death. Other clinical manifestations are cardiac valvular disease, livedo reticularis, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, epilepsy, and cognitive impairment.
The presence of anti-phospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop the clinical features. Lupus anticoagulant is generally thought to be more strongly associated with the risk of clinical manifestations of APS than anticardiolipin and anti ?2-glycoprotein I antibodies.
The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Therapy of thrombosis is based on long-term oral anti-coagulation and patients with arterial events should be treated aggressively. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin.
Systemic sclerosis
Authors: Denton Christopher P. , Moinzadeh Pia
Published: February 2014

The term 'scleroderma' describes a group of conditions in which the development of thickened, fibrotic skin is a cardinal feature. This includes localized forms of scleroderma (e.g. morphoea) and also systemic forms of the disease that are more correctly termed systemic sclerosis.
Systemic sclerosis (SSc) is a multiorgan, autoimmune disease that has a high clinical burden and mortality, due to affecting the skin as well as internal organs. As with other related diseases there is a female predominance and marked clinical diversity. The pathogenesis of SSc is not fully elucidated; it includes endothelial cell injury fibroblast activation and autoimmunity that lead to skin and internal organ manifestations. The majority of cases exhibit characteristic serum autoantibodies. Some of these antibodies are scleroderma-specific reactivities including anti-centromere (ACA), anti-topoisomerase-1 (ATA or Scl 70) or anti-RNA polymerase III antibodies. These anti-nuclear antibody (ANA) patterns are generally mutually exclusive and serve as useful clinical markers of disease subgroups. Additional subsetting of scleroderma cases, based on the extent of skin sclerosis, permits classification into limited and diffuse subsets. Because of the heterogeneity of the disease patients may suffer from different organ manifestations, such as lung fibrosis, hypertensive renal crisis, severe cardiac disease, gastrointestinal involvement, and pulmonary arterial hypertension. Although outcomes have improved recently, systemic sclerosis still has the highest case-specific mortality of any of the autoimmune rheumatic diseases and requires careful and systematic investigation, management and follow-up. Treatment includes symptomatic strategies with attention to each involved organ system; it is still an area where therapeutic progress and better understanding of pathogenesis is increasingly anticipated.
Nephrogenic systemic fibrosis
Authors: Orteu Cate H.
Published: February 2014

Nephrogenic systemic fibrosis (NSF) is a severe and disabling fibrosing condition of the skin and systemic organs. It occurs in patients with renal failure who have been exposed to gadolinum-based contrast agents (GBCAs). The development of NSF should be preventable if adequate precautions are taken in relation to GBCA exposure in susceptible patients. New cases should be reported to the European Medicines Agency and/or the United States Food and Drug Administration.
Polymyositis and dermatomyositis
Authors: Chinoy Hector , Cooper Robert G.
Published: February 2014

Polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM) form part of the idiopathic inflammatory myopathies (IIM), a heterogeneous group of rare autoimmune diseases characterized by an acquired proximal muscle weakness, raised muscle enzymes (including creatine kinase), inflammatory cell infiltrates in muscle biopsy tissue, electrophysiological abnormalities, and presence of circulating myositis-specific/myositis-associated autoantibodies. The underlying aetiology of IIM is poorly understood, but likely involves interactions between environmental and genetic risk factors. Myositis may also manifest in association with other connective tissue disorders. The predominant clinical presentation of IIM is skeletal muscle weakness, but many extramuscular features can also occur.
Access to good neuropathological support is essential in securing an accurate IIM diagnosis and excluding non-inflammatory myopathies, although IBM is often difficult to distinguish from PM. Antibody testing can help define IIM clinical subtypes, including cancer-associated myositis, predict prognosis, and help in optimizing treatment decisions. MRI can be invaluable for differentiating disease activity from damage, and detecting treatment-induced interval changes. Therapeutic effectiveness of new and existing treatments (where the evidence base remains poor) depends on making a prompt diagnosis and initiating early and appropriately aggressive treatment to prevent establishment of muscle damage.
This chapter attempts to summarize the salient features of IIM and update the reader about currently used diagnostics and treatment paradigms in this rare and understudied disease.
Paediatric polymyositis and dermatomyositis
Authors: Pilkington Clarissa , McCann Liza
Published: February 2014

Juvenile polymyositis and dermatomyositis are inflammatory myopathies that affect muscle. Dermatomyositis also affects skin, and can have many extramuscular manifestations. Inflammatory myopathies are uncommon in childhood, with dermatomyositis occurring more than polymyositis. For this reason, published research has concentrated on juvenile dermatomyositis. The spectrum of disease severity ranges from mild cases that can recover completely without treatment, to multisystem inflammation that can be fatal. Treatments have improved over the decades, reducing mortality from 30% before the era of steroids, to less than 1% in the present day. Juvenile cases of dermatomyositis differ from those seen in adulthood, without tendency for associated malignancy, and a far greater incidence of calcinosis. Calcinosis can be deposited as small calcinotic lumps or as sheets of calcinosis. It is very difficult to treat and causes extensive morbidity, and depending on where the calcinosis is deposited, it can cause severe disability or even death.
Over the last decade, international collaborative work has concentrated on developing disease activity and assessment tools for both adult and juvenile forms of myositis. This will enable more subjective study of these rare diseases in multinational cohort studies, and enable clinical trials to investigate drug treatments. This work led to the first international double-blind placebo controlled trial of treatment in both adults and children with dermatomyositis (using rituximab as the drug). Further international collaboration has led to the development of core outcome variables, a definition of disease flare, and ongoing work on classification criteria.
Sjögren’s syndrome—clinical features
Authors: Bowman Simon , Hamburger John , Price Elizabeth , Rauz Saaeha
Published: February 2014

Sjögren's syndrome is a chronic, immune-mediated, condition of unknown aetiology characterized by focal lymphocytic infiltration of exocrine glands associated with dry mouth and eyes. It occurs in its own right (primary Sjögren's syndrome, pSS), or as a late feature of other rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus or scleroderma (secondary Sjögren's syndrome).
There is a strong female bias. pSS typically affects women in their middle years with an estimated prevalence of 0.1–0.6%. 75% of patients have anti-Ro and/or anti-La antibodies, often with raised immunoglobulin levels (hypergammaglobulinaemia). In patients without these antibodies the diagnosis can be confirmed by salivary gland biopsy.
Treatment is generally symptomatic using artificial tears, saliva replacements/stimulants and good dental hygiene. Three-quarters of patients with pSS report significant fatigue with a negative impact on quality of life. This can be the most disabling symptom. Approximately 20% of patients develop systemic features including persistent salivary gland swelling, cutaneous vasculitis, peripheral neuropathy, interstitial lung disease, autoimmune cytopenias or renal tubular acidosis. Hydroxychloroquine and corticosteroids are the most widely used therapies for systemic features.
There is a 44fold increased risk of mucosa-associated lymphoid tissue (MALT) B-cell lymphoma in pSS, typically affecting the salivary glands. On account of abnormalities in the B-cell system in pSS there is current interest in the use of anti-B-cell directed monoclonal antibodies to treat pSS and a number of clinical trials are in progress. This approach is already successfully in use for treating MALT lymphoma in pSS.
Sjögren’s syndrome—management
Authors: Ng Wan-Fai , Vissink Arjan , Theander Elke , Figueiredo Francisco
Published: February 2014

Management of Sjögren's syndrome (SS) encompasses confirmation of diagnosis, disease assessment, and treatment of glandular and systemic manifestations including special situations such as pregnancy and SS-related lymphoma. The American European Consensus Group classification criteria 2002 are the current gold standard for the diagnosis of SS. Salivary gland sialometry, sialochemistry, and ultrasound and tear osmolarity may be useful adjuncts. Symptoms of SS are non-specific and must be actively explored. When assessing patients with SS, it is important to consider not only objective parameters such as abnormalities in blood tests and changes in tear and salivary flow, but also patient-reported outcome measures and impact on quality of life. Current management of patients with SS is hampered by the lack of evidence-based strategies. The symptoms experienced by patients with SS are often not fully appreciated by clinicians, which may contribute to the suboptimal management of the condition. Management of fatigue remains a major challenge and a holistic, multidisciplinary approach is recommended. Factors that may contribute to fatigue should be fully addressed. Recent advances in the understanding of the pathogenic mechanisms of SS have informed more targeted therapeutic strategies with some promising data. Optimal management of SS requires expertise from different disciplines. Combined clinics with rheumatology, oral medicine, and ophthalmology input will improve care and communications as well as reduce the number of clinic visits for patients and healthcare-related cost. Effective link between pSS specialists, dentists, opticians, and general practitioners will facilitate early diagnosis and reduce risk of long-term disability of SS.
Overlap/undifferentiated syndromes
Authors: Herrick Ariane
Published: February 2014

Undifferentiated connective tissue disease (UCTD) and overlap syndromes both form part of the broad spectrum of connective tissue disease. They are difficult to define, as the boundaries between them and specific diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and myositis are often not clear-cut. This chapter gives a broad overview of diagnosis, clinical features, outcomes, and management.
Patients with UCTD have clinical and/or serological features of connective tissue disease but do not fulfil the criteria for any one defined disease. Raynaud’s phenomenon and puffy fingers are often the presenting features but there are many possible others, including arthralgia, sicca symptoms, and breathlessness due to pulmonary fibrosis, usually in the context of a positive anti-nuclear antibody (ANA). A proportion of patients evolve into a defined connective tissue disease: in those who do, this is generally within 5 years of onset. Treatment is dependent upon the clinical features: for examplem vasodilators for Raynaud’s phenomenon, or hydroxychloroquine for arthralgia/arthritis.
Patients with overlap syndromes have features of more than one defined connective tissue disease. Overlap syndromes are therefore highly heterogeneous as many combinations of clinical and serological features can occur. Mixed connective tissue disease (MCTD) is the overlap syndrome that has been most described and includes overlapping features of SLE, SSc, and myositis in patients who are anti-U1 ribonucleoprotein (RNP) antibody positive. Treatment is of the specific clinical manifestations. Patients with overlap syndromes should be kept under regular review to allow early identification of internal organ involvement.
Vasculitis—classification and diagnosis
Authors: Watts Richard A. , Scott David G. I.
Published: February 2014

The vasculitides are a group of conditions characterized by inflammation and necrosis of blood vessels; they are generally of unknown aetiology. The classification of vasculitides is based on the size of vessel involved and whether there is a known cause (secondary) or not (primary). This approach has stood the test of time. The American College of Rheumatology (ACR) in 1990 produced classification criteria for the major types of vasculitis and in 1994 definitions were promulgated by the Chapel Hill Consensus Conference. These did not include anti-neutrophil cytoplasm antibodies (ANCA) and the ACR scheme did not include microscopic polyangiitis. The definitions have recently been updated to include modern concepts of pathogenesis including ANCA. No validated diagnostic criteria are available for routine clinical practice.
The diagnosis of vasculitis requires a high index of suspicion, especially in the systemically unwell patient with multiorgan involvement. The key to diagnosis is a detailed and systematic approach to patient assessment involving all potentially involved organs. In a patient with suspected vasculitis immediate urinalysis is mandatory as the severity of renal involvement at presentation is a major determinant of outcome. Each potentially involved organ should be comprehensively evaluated. Tissue biopsy should be obtained whenever possible, as treatment is potentially toxic using glucocorticoids combined with cytotoxic agents. Biopsy should not, however, delay initiation of treatment. Potential alternative diagnosis should be considered, especially infection and malignancy, and excluded whenever possible.
Behçet’s syndrome
Authors: Yurdakul Sebahattin , Seyahi Emire , Yazici Hasan
Published: February 2014

Behçet's syndrome is a systemic inflammatory panvasculitis (affecting all sizes of vessels) of unknown aetiology. It is in vogue to include it among the systemic autoinflammatory conditions. Behçet's syndrome is more frequent along the ancient 'Silk Route' across Asia than it is in Western countries. The usual onset is the second or third decade, equally affecting either gender. However, young patients and male patients have more severe disease. Almost all patients have recurrent oral ulceration. Scar-forming genital ulcers, a variety of skin lesions including acneiform, erythema nodosum-like lesions, arthritis, potentially blinding panuveitis, thrombophlebitis, gastrointestinal disease, central nervous system (CNS) involvement, and life-threatening bleeding pulmonary artery aneurysms are seen. The pathergy phenomenon is a heightened tissue inflammatory response. The strongest genetic association is with HLA B51. There are immunological aberrations but not prominent enough to call it an autoimmune disease. Similarly, Behçet's syndrome does not fit easily into the broad concept of autoinflammatory diseases. The histopathology is also non-specific and the diagnosis is mainly clinical. Differentiation from Crohn's disease is very difficult. In more than one-half of the patients the disease burns out in time, thus only symptomatic therapy is indicated in some patients. However, eye involvement, pulmonary vascular disease, thrombophilic complications, CNS involvement, and gastrointestinal disease need prompt recognition and treatment. Brief courses of glucocorticosteroids along with immunosuppressives including the newer biologicals, interferon, and colchicine are commonly used. However, controlled clinical trials are not available for some of these medications especially when thrombophilia, CNS, and gastrointestinal disease are present.
Paediatric vasculitis
Authors: Eleftheriou Despina , Brogan Paul A.
Published: February 2014

Systemic vasculitis is characterized by blood vessel inflammation which may lead to tissue injury from vascular stenosis, occlusion, aneurysm, and/or rupture. Apart from relatively common vasculitides such as Henoch-Schönlein purpura (HSP) and Kawasaki's disease (KD), most of the primary vasculitic syndromes are rare in childhood, but are associated with significant morbidity and mortality. New classification criteria for childhood vasculitis have recently been proposed and validated. The cause of most vasculitides is unknown, although it is likely that a complex interaction between environmental factors such as infections and inherited host responses trigger the disease and determine the vasculitis phenotype. Several genetic polymorphisms in vasculitis have now been described that may be relevant in terms of disease predisposition or development of disease complications. Treatment regimens continue to improve, with the use of different immunosuppressive medications and newer therapeutic approaches such as biologic agents. We provide an overview of paediatric vasculitides focusing on HSP, KD, and polyarteritis nodosa (PAN). Key differences (where relevant) between paediatric and adult vasculitis are highlighted. In addition we discuss new emerging challenges particularly in respect to the long-term cardiovascular morbidity for children with systemic vasculitis, and emphasize the importance of future international multicentre collaborative studies to further increase and standardize the scientific base of investigating and treating childhood vasculitis.
Miscellaneous vasculitides
Authors: Watts Richard A. , Ntatsaki Eleana
Published: February 2014

The vasculitides are a group of relatively rare conditions with a broad spectrum of clinical presentations that can cause significant morbidity and mortality. Classification of the vasculitic syndromes is done according to the size of the vessels affected and also the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Vasculitides can be either primary or secondary to an underlying systemic disease, malignancy, or infection. This chapter covers the spectrum of the secondary vasculitides; some of the non-ANCA-associated primary vasculitides and miscellaneous types of vasculitic syndromes.
Secondary vasculitis can occur in the background of systemic rheumatic diseases such as rheumatoid arthritis, spondyloarthropathies, or other connective tissue diseases. Vasculitis can also present in relation to precipitants such as drugs (propylthiouracil, hydralazine, leucotriene antagonists) or vaccines. Infection (bacterial, mycobacterial, viral, and fungal) has been associated with vasculitis either as a trigger or as a consequence of iatrogenic immunosuppression. Infection-related vasculitis can affect all types and sizes of vessels. Certain forms of vasculitis such as cryoglobulinaemia are closely associated with viral infections and more specifically with HCV infection. There are forms of vasculitis, which appear to be isolated or localized to a single organ, or site (skin, gastrointestinal, genital, and primary central nervous system vasculitis) that may be histologically similar to systemic syndromes, but have a different prognosis. Other conditions that may mimic vasculitis and miscellaneous conditions such as Cogan's syndrome and relapsing polychondritis are also discussed.
Pathogenesis of osteoarthritis
Authors: Vincent Tonia L. , Troeberg Linda
Published: February 2014

Understanding pathogenic mechanism in disease is critical for development of targeted therapeutic strategies. Although there are, at this time, only a handful of experimental approaches for treating osteoarthritis (OA), until 10 years ago this disease was almost universally considered an unmodifiable condition. Emerging data during this time, largely fuelled by studies in rodent models, has completely changed the paradigm of disease pathogenesis and has for the first time, generated novel, realistic targets for this highly prevalent and disabling condition. These targets include the aggrecanases, members of the ADAMTS family, and collagenases, which together are critical for the early breakdown of the extracellular matrix of cartilage. Some recent success has also been demonstrated by targeting bone in disease. Development of pain in OA is complex and likely arises from different tissues at different stages of disease. In the following section we describe the pathological features of OA, and discuss the evolution of theories of OA pathogenesis and factors that have limited mechanistic clarity in this disease. We summarize the molecular pathways that are now known to be active in disease, and consider how these identified molecular pathways could be linked to known epidemiological risk factors. We finish by discussing possible future therapeutic strategies that will emerge from these discoveries and the current limitations in implementing new therapies in OA.
Clinical features of osteoarthritis
Authors: Abhishek Abhishek , Doherty Michael
Published: February 2014

Osteoarthritis (OA), the commonest arthropathy, targets specific joints e.g. the knees, hips, interphalangeal joints, and first carpometacarpal joints. Most patients develop symptoms in their middle or older age. Usage-related (’mechanical’) joint pain, short-lived morning stiffness, and locomotor restriction are the common presenting symptoms. Pain at extremes of movement and joint line tenderness may be present in early disease. Crepitus, bony enlargement, and reduced range of movement suggest more severe OA. Advanced OA is characterized by rest pain, night pain, muscle wasting, and deformity. Notably, symptoms and signs of inflammation are absent or only modest, although mild-moderate effusions are not uncommon at the knee. OA may be diagnosed on clinical grounds alone in the at-risk age group, in the presence of typical symptoms and signs. Radiographic changes of OA are commonly asymptomatic. In general there is poor correlation between symptoms, signs, radiographic changes, and disability in OA, and due care should be used to differentiate the ’disease OA’ from the ’illness OA’. More inflammatory symptoms and signs suggest coexistence of calcium crystal deposition. Evaluation of people with OA should include targeted assessment for treatable comorbidities such as depression and obesity that compound disability from OA.
Osteoarthritis—management
Authors: Wenham Claire Y. J. , Conaghan Philip G.
Published: February 2014

Osteoarthritis (OA) is a common condition which often causes pain and functional limitation, significantly impacting on a person's quality of life. A comprehensive assessment of the impact of OA should be performed before selecting therapies and treatment goals. Current recommended therapies include a combination of pharmacological and non-pharmacological therapies, which should be considered for all people with OA, regardless of anatomical site of involvement. Non-pharmacological treatments include education, muscle strengthening and aerobic exercises, weight loss if appropriate, splints and devices, and aids. Pharmacological therapies include paracetamol, oral and topical non-steroidal anti-inflammatory drugs, topical capsaicin, intra-articular corticosteroid injections, and opioids. Many existing therapies have only a small analgesic effect size and, in the case of drug therapies, may be associated with important side effects, so an individual's symptoms and comorbidities must be taken into account when selecting therapies. For those who do not respond to these treatments, surgery such as a total joint arthroplasty may be required. There is a strong need for new analgesic treatments for OA. As it is becoming increasingly clear that the sources of pain in OA are complex and multifactorial, future treatments for OA will need to target both peripheral and central pain mechanisms.
Calcium pyrophosphate crystal deposition (CPPD)
Authors: Roddy Edward , Doherty Michael
Published: February 2014

Calcium pyrophosphate crystal deposition (CPPD) in articular cartilage is a common age-related phenomenon. Recent important advances in our understanding of the pathophysiology of pyrophosphate metabolism include the identification of a mutation within the ANK gene which associates with familial CPPD, and elucidation of the interleukin-1β‎ (IL-1β‎)-dependent mechanisms by which crystals invoke an inflammatory response. Risk factors for CPPD include age, prior joint damage and osteoarthritis, genetic factors, and occasionally metabolic diseases (hyperparathyroidism, haemochromatosis, hypomagnesaemia, and hypophosphatasia). CPPD is commonly asymptomatic or may present as osteoarthritis with CPPD, acute calcium pyrophosphate (CPP) crystal arthritis, or chronic CPP crystal inflammatory arthritis. Although radiographic chondrocalcinosis is often taken to be synonymous with CPPD, other calcium crystals can also have this appearance and definitive diagnosis requires identification of CPP crystals by compensated polarized light microscopy of aspirated synovial fluid. Recently, the ultrasonographic appearances of CPPD have been described. Treatment of CPPD is targeted to the clinical presentation. Acute CPP crystal arthritis is treated by aspiration and injection of glucocorticosteroid, local ice packs, non-steroidal anti-inflammatory drugs (NSAIDS), low-dose colchicine, oral or parenteral glucocorticosteroids, or adrenocorticotrophic hormone (ACTH). Treatment of osteoarthritis with CPPD is very similar to the treatment of osteoarthritis alone. There is no specific therapy for chronic CPP crystal inflammatory arthritis: options include NSAID, low-dose colchicine, low-dose glucocorticosteroid, methotrexate, and hydroxychloroquine. Recommendations for the management of CPPD are derived from a small evidence base and largely based on clinical experience and extrapolation from gout. Further research into diagnosis and management including novel treatment strategies such as IL-1β‎ blockade is much needed.
Paediatric metabolic bone disease
Authors: Bishop Nick
Published: February 2014

Childhood metabolic bone disease is developing as a specialty in its own right, but many skeletal diseases will present to the general paediatrician as well as those with an interest or specialism in endocrinology, genetics, neonatology, nephrology, or rheumatology. As well as de-novo presentations of skeletal disease, the adverse effects of inflammation, immobilization, altered nutrition, and drugs on the skeleton can become apparent during the management of childhood rheumatological conditions.
Childhood metabolic bone diseases typically present with fracture, bony deformity, bone pain, or short stature, either alone or in combination. It is important to distinguish disorders that result in the loss of bone tissue—osteoporoses—from those where mineral is lost but matrix preserved—rickets and osteomalacia. Both have reduced bone density, but treatment is directed in the former group to arresting bone loss and increasing, where possible, bone formation and in the latter group to the appropriate provision of vitamin D or its active metabolites, often with calcium and phosphate supplementation. High bone mass disorders are much less common; in such situations it is again important to distinguish those in which there is reduced bone resorption as opposed to increased bone formation, as treatment options are very different.
Treatment options often reflect those in adult practice, but there are important differences in the management of bone disease in the growing skeleton that are detailed here.