bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal pain
Authors: Gaffney Karl , Hamilton Louise
Published: February 2014

Spinal pain is a very common complaint, and one which rheumatologists must be confident in managing. While most cases are non-specific and self-limiting it is important not to miss the small proportion of patients with pain caused by inflammation, infection, or infiltration. A thorough history is of key importance in this respect, and the approach to the patient with back pain is discussed including physical examination and the value of targeting investigations. The management of common and important causes of back pain is outlined.
Obstetrics and pregnancy
Authors: Østensen Monika , Dolhain Radboud , Ruiz-Irastorza Guillermo
Published: February 2014

Rheumatic diseases occur preferentially in women, often during their childbearing years. Most women with rheumatic disease wish to have children, even when functional disability is present. Better therapy and better prognosis for many of the rheumatic diseases has resulted in more patients considering pregnancy. The interaction of pregnancy and the rheumatic diseases is varied, ranging from spontaneous improvement to aggravation, sometimes severe, of disease symptoms. Likewise, rheumatic diseases differ with regard to the occurrence of complications during pregnancy, and pregnancy outcome. This chapter describes fertility, the course of maternal disease during pregnancy, and fetal outcome.
Nervous system
Authors: Graham Andrew , Galton Clare
Published: February 2014

Rheumatological conditions may be complicated by a
variety of both central and peripheral nervous system disorder. Common complications such as
entrapment neuropathies are familiar to rheumatologists but accurate diagnosis of less
common neurological disorders may be challenging; careful clinical reasoning is essential,
supplemented where necessary by imaging, neurophysiology, and other special investigations
including cerebrospinal fluid examination. Complications vary according to the nature of
background condition. In rheumatoid arthritis, neurological involvement is typically related
to the mechanical consequences of advancing disease; the commonest complications are carpal
tunnel syndrome and cervical myelopathy due to atlantoaxial subluxation. By contrast,
neurological involvement in systemic lupus erythematosus (SLE) tends to occur earlier in the
disease course, with a much wider range of manifestations. The management of stroke or
seizures in SLE is not necessarily any different from that in the general population, unless
complicated by the antiphospholipid syndrome. However, less common neurological syndromes
may demand more specific investigation and treatment. For example, longitudinally extensive
transverse myelitis and recurrent optic neuritis (neuromyelitis optica, or Devic's disease)
is frequently associated with antibodies to aquaporin-4, and is highly likely to relapse
unless treated vigorously with humoral immunosuppression. Nervous system involvement in
vasculitis is common. Finally, not all neurological disorder in rheumatological disease is
necessarily due to the underlying condition; neurological complications of disease-modifying
therapy are increasingly recognized, in particular central and peripheral nervous system
demyelination associated with TNF-α‎ inhibitors.
Cardiovascular system
Authors: Coghlan J. Gerry , Schreiber Benjamin E.
Published: February 2014

Rheumatology, as a specialty that encounters many multisystem diseases, requires knowledge of many of the more exotic cardiovascular conditions including large- and small-vessel vasculitis, pulmonary hypertension, and myopericarditis. In addition, many rheumatology patients will suffer from cardiovascular pathology due to its common nature and association with an older population, since many previously lethal conditions are now associated with better survival. This requires a detailed knowledge of the drug—drug interactions that arise and the off-target consequences of rheumatological therapies that may aggravate atheroma and hypertension. The rheumatologist therefore needs a broad knowledge of cardiovascular diseases.
Respiratory system
Authors: Hoyles Rachel K. , Wells Athol U.
Published: February 2014

Pulmonary involvement is common in the connective tissue diseases (CTDs) and is associated with significant morbidity and mortality. Improved management of systemic disease has led to increasing numbers of surviving patients with clinically significant pulmonary disease. Screening for pulmonary complications highlights the frequency of subclinical involvement. In this chapter, the pulmonary manifestations of the more common CTDs are detailed, including rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), Sjögren's syndrome (SS), and, more briefly, ankylosing spondylitis (AS). A broad spectrum of pulmonary disorders are seen in association with the CTDs or the drugs used to treat the underlying disorder, including interstitial lung disease, pulmonary infections, airways disease, pulmonary nodules, pleural disease, chest wall pathology and pulmonary vascular disease; the discussion is stratified by pulmonary complication. In many cases, two or more pulmonary manifestations of CTD coexist or there are other concurrent diseases such as asthma and lung cancer, resulting in potentially confusing mixed imaging and pulmonary function abnormalities. This chapter presents a comprehensive approach to the investigation, screening, prognostic evaluation, and treatment decisions in pulmonary disease associated with the CTDs.
Social aspects (work)
Authors: Wilkie Ross
Published: February 2014

The impact of musculoskeletal disorders on work is demanding more attention from all stakeholders, including clinicians and policy-makers. Musculoskeletal disorders are the most frequently cited reason for absence from work and there is a need for new approaches and attitudes to assess and reduce the burden. For many rheumatologists, inflammatory arthritis is the most frequently encountered condition that interferes with work. However, the cumulative burden of non-inflammatory arthropathies and disorders such as back pain, osteoarthritis, and limb pain as a whole, results in a much greater economic and human cost to society than inflammatory disease. As the incidence of these conditions increases with age and as working lives extend, there will be many more employees with musculoskeletal problems in years to come.
Significantly, new information supports the view that work loss need not be a consequence of a musculoskeletal disorder or disability. This presents an achievable challenge to everyone and underlines the importance of a biopsychosocial and interdisciplinary approach involving interaction between those with a musculoskeletal condition, clinicians, employers, and policy-makers. This chapter outlines the challenges (i.e. the size of the problem and reasons for work restriction) and opportunities to reduce the burden of musculoskeletal conditions on work. It draws on the results of empirical studies to highlight potential targets to reduce work restriction.
Outcomes of paediatric rheumatic disease
Authors: Minden Kirsten
Published: February 2014

Paediatric rheumatic illnesses are among the most common chronic diseases in children and adolescents. These illnesses have important impacts on patient's body functions and structures, activities, and social participation. Knowledge about the effect and consequences of these diseases is necessary to formulate appropriate aims of treatments. The multidimensional outcomes of paediatric rheumatic diseases and their measurement are reviewed in this chapter.
Outcome measurement is complex in patients who have growing needs and changing expectations as they develop, especially in chronic conditions that have a variable and often unpredictable course, such as juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, and juvenile dermatomyositis. Considerable work has been conducted recently in an effort to better define and value global outcomes for these patients. New and reliable outcome measures have been developed to capture all aspects of the patient's life and integrate the patients' perspective.
Existing outcome studies of paediatric rheumatic diseases have consistently shown, even though differing in their methodology, that patient outcomes have improved over the last decade. More patients with chronic inflammatory rheumatic conditions survive into adulthood, and patients' long-term health, functional, and quality of life outcomes have improved. However, outcomes are still less than ideal. More than one-half of the patients with paediatric rheumatic diseases have ongoing active disease in early adulthood. Over one-third have evidence of disability and organ damage, with each underlying disease being associated with specific complications. Clearly, given the inherent potential for disability, morbidity, even mortality, young people with paediatric-onset rheumatic diseases require ongoing medical care into adulthood.
Assessment of paediatric rheumatic disease
Authors: Matheson Loren A. , Duffy Ciarán M.
Published: February 2014

Assessment of children with rheumatic diseases has evolved significantly over the past 20 years. Previously, assessment focused primarily on the measurement of disease activity status, an evaluation that provided information that was mainly physician-derived. More recently, emphasis has been placed on the need to incorporate estimates of physical, social, and mental functioning into health assessment. Consequently, there has been tremendous growth in the development of measurement instruments that evaluate health status, functional status, disability, and health-related quality of life (HRQoL). An array of these broader instruments has been developed for children with rheumatic diseases. These latter measures are mainly patient-derived. Clearly, in an era of patient-centred care, the latter approach is critical to appropriate patient assessment. Despite this, such measurement is restricted to research studies rather than clinical practice. Most of these measures are used in the assessment of juvenile idiopathic arthritis; however, increasingly, measures are being developed for other diseases including juvenile dermatomyositis and juvenile systemic lupus erythematosus. Herein, we review the measures that are currently available to highlight their utility, with particular emphasis on their potential roles as supported by recent literature.
Genetics of juvenile rheumatic diseases
Authors: Hinks Anne , Thomson Wendy
Published: February 2014

Juvenile rheumatic diseases are heterogeneous, complex genetic diseases; to date only juvenile idiopathic arthritis (JIA) has been extensively studied in terms of identifying genetic risk factors. The MHC region is a well-established risk factor but in the last few years candidate gene and genome-wide association studies have been utilized in the search for non-HLA risk factors. There are now an additional 12 JIA susceptibility loci with evidence for association in more than one study. In addition, some subtype-specific associations are emerging. These risk loci now need to be investigated further using fine-mapping strategies and then appropriate functional studies to show how the variant alters the gene function. This knowledge will not only lead to a better understanding of disease pathogenesis for juvenile rheumatic diseases but may also aid in the classification of these heterogeneous diseases. It may identify new pathways for potential therapeutic targets and help in the prediction of disease outcome and response to treatment.
Cellular side of acquired immunity (B cells)
Authors: Dörner Thomas , Lipsky Peter E.
Published: February 2014

B cells have gained interest in rheumatoid arthritis (RA) beyond being the precursors of antibody-producing plasma cells since they are also a broader component of the adaptive immune system. They are capable of functioning as antigen-presenting cells for T-cell activation and can produce an array of cytokines. Disturbances of peripheral B-cell homeostasis together with the formation of ectopic lymphoid neogenesis within the inflamed synovium appears to be a characteristic of patients with RA. Enhanced generation of memory B cells and autoreactive plasma cells producing IgM-RF and ACPA-IgG antibodies together with formation of immune complexes contribute to the maintenance of RA, whereas treatment with B-cell-directed anti-CD20 therapy provides clinical benefit.
Bone turnover
Authors: Schett Georg
Published: February 2014

Bone is a dynamic tissue, which undergoes continuous remodelling throughout life. This process requires deposition of new bone, a process which is controlled by the bone-forming osteoblasts, as well as the degradation of bone, exerted by the bone-resorbing osteoclasts. Osteoblast differentiate from mesenchymal precursors and are metabolically active cells, which produce bone matrix proteins such as collagen and osteocalcin, as well as alkaline phosphatase. These proteins can be used to measure osteoblast function in humans. Osteoclasts are haematopoietic cells of the monocyte linage degrading the bone by enzymes cleaving collagen such as metalloproteinases and cathepsins. Collagen cleavage products are indicators for bone resorption in the body. Osteoblast-osteoclast actions are controlled by a fine network of bone cells, osteocytes, which are responsible for sensing bone damage and directing bone remodelling to the right anatomical locations. Finally, mineralization of the newly formed bone is governed by vitamin D and parathyroid hormones, the key regulators of calcium homeostasis in our body.
Skeletal muscle physiology and damage
Authors: Dinser Robert , Müller-Ladner Ulf
Published: February 2014

This chapter summarizes muscle structure and physiology, the genesis and adaptions of muscle throughout life, and clinical assessment of muscle disease. The anatomical and molecular structure of muscle tissue is described, as well as the basic function of the neuromuscular junction, the energy metabolism of muscle tissue, and the mechanisms of fatigue. Key elements of embryological myogenesis, the adaptions of muscle to exercise and damage, and physiological ageing are depicted. A summary of the clinical analysis of muscle function including laboratory, electrophysiological, and imaging testing is provided.
Vascular biology
Authors: Thornton Clare , Mason Justin
Published: February 2014

Vascular biology is the study of the physiology of the vasculature and how it may be the target for disease processes. An understanding of vascular biology is central to the study of rheumatic disease for three reasons: it is an integral part of a functioning immune system; it is the primary site of pathology in many conditions; and it is the site of the important secondary complications of chronic inflammation, endothelial dysfunction and atherosclerosis. Vascular biology requires a detailed knowledge of the anatomy and physiology of the vasculature and its constituent vessels. The multistep process by which leucocytes interact with endothelium lining postcapillary venules in order to leave the circulation and migrate towards a site of inflammation is central to the pathology of inflammatory disease. The vasculature is the primary site of injury in several rheumatic diseases, including the vasculitides. It may also be damaged by chronic inflammation, leading to endothelial dysfunction and accelerated atherosclerosis. Thrombosis is also a critical pathological process in several chronic inflammatory diseases, particularly the anti-phospholipid antibody syndrome and Behçet's syndrome. The vascular endothelium is central to angiogenesis, the process of new capillary outgrowth, upon which synovial proliferation in inflammatory arthritis is dependent. Angiogenesis is inhibited by current anti-rheumatic therapies and may become a target for novel anti-rheumatic drugs. An increasing area of research concerns the direct effects of drugs used in the treatment of atherosclerosis and inflammatory disease on the endothelium, and whether these agents are beneficial or harmful. Of particular interest to rheumatologists are the vascular effects of statins, disease-modifying anti-rheumatic drugs (DMARDs), immunosuppressants, and cyclooxygenase inhibitors.
Complement
Authors: Pickering Matthew C. , Bakshi Jyoti
Published: February 2014

In this chapter we summarize clinically important aspects of complement biology. This information is used to present a comprehensive overview of complement deficiency states and provide a logical basis for understanding complement assays in clinical practice. Hypocomplementaemic urticarial vasculitis syndrome, a condition associated with anti-C1q antibodies and complement consumption, is discussed. We summarize the use of eculizumab, a monoclonal antibody that targets and inhibits complement C5, in the treatment of haemolysis in paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome.
Radiographic imaging
Authors: Rowbotham Emma L. , Grainger Andrew J.
Published: February 2014

Plain film radiography is often the first imaging modality employed in the assessment of patients with a rheumatological condition. More recently this has been superseded by cross-sectional imaging, in particular ultrasound and MRI, which have improved sensitivity in detection of early disease when compared with plain film imaging. However, there remains a role for conventional radiography in both the initial diagnosis and monitoring of disease progression.
A standard approach to assessing radiographs in the context of arthropathy is usually employed by radiologists; by following this structured review a diagnosis or narrow differential may be reached on plain film imaging alone. Plain film radiograph findings of the most common rheumatological disorders are covered in detail in this chapter including osteoarthritis, the inflammatory arthritides, and crystal arthropathy. Findings in the connective tissue disorders are then covered, followed by less commonly encountered conditions such as SAPHO, neuropathic arthropathy, and haemochromotosis.
Nuclear medicine
Authors: Al-Nahhas Adil , Zerizer Imene
Published: February 2014

The application of nuclear medicine techniques in the diagnosis and management of rheumatological conditions relies on its ability to detect physiological and pathological changes in vivo, usually at an earlier stage compared to structural changes visualized on conventional imaging. These techniques are based on the in-vivo administration of a gamma-emitting radionuclide whose distribution can be monitored externally using a gamma camera. To guide a radionuclide to the area of interest, it is usually bound to a chemical label to form a 'radiopharmaceutical'. There are hundreds of radiopharmaceuticals in clinical use with different 'homing' mechanisms, such as 99 mTc HDP for bone scan and 99 mTc MAA for lung scan. Comparing pre- and posttherapy scans can aid in monitoring response to treatment.
More recently, positron emission tomography combined with simultaneous computed tomography (PET/CT) has been introduced into clinical practice. This technique provides superb spatial resolution and anatomical localization compared to gamma-camera imaging. The most widely used PET radiopharmaceutical, flurodeoxyglucose (18F-FDG), is a fluorinated glucose analogue, which can detect hypermetabolism and has therefore been used in imaging and monitoring response to treatment of a variety of cancers as well as inflammatory conditions such as vasculitis, myopathy, and arthritides. Other PET radiopharmaceuticals targeting inflammation and activated macrophages are becoming available and could open new frontiers in PET imaging in rheumatology.
Nuclear medicine procedures can also be used therapeutically. Beta-emitting radiopharmaceuticals, such as yttrium-90, invoke localized tissue damage at the site of injection and can be used in the treatment of synovitis.
Imaging in children
Authors: Johnson Karl
Published: February 2014

The radiological findings of the rheumatological conditions that occur in childhood, are in the majority of cases similar to those in the adult. However, there are some specific and unique features seen only in the paediatric population. Often these features reflect the immature nature of the child's skeleton and the fact that growth is not yet complete. Radiology is important in helping to establish the diagnosis and in the long-term management of the child.
The most appropriate test, promptly performed and avoiding the child unnecessary discomfort, is the ideal. An understanding of the disease process, as well as the advantages and the limitations of each imaging modality, by both clinician and radiologist, is important. Collaboration between the requesting physician and radiologist will improve the quality of the service provided to the child.
Assessment of synovial joint fluid
Authors: Abdelattif Engy , Freemont Anthony J.
Published: February 2014

Assessment of synovial joint fluid is a simple, cheap, and relatively non-invasive test that can be applied to the whole spectrum of joint diseases, provided there is sufficient fluid within the joint to aspirate. The chapter outlines the key steps in undertaking microscopic analysis of synovial fluid in order to maximize the diagnostic and prognostic return, while placing the features seen within the context of some of the most important joint diseases. The chapter also examines the changing face of microbiological examination of synovial fluid to diagnose joint infection as a primary event and also the increasingly important problem of infection secondary to joint replacement surgery.
Multidisciplinary treatment
Authors: Ryan Sarah , Adams Jo , O’Brien Anne , Williams Anita
Published: February 2014

Multidisciplinary treatment is required to optimize the physical, psychological, and social function of people living with a long-term musculoskeletal condition. Multidisciplinary treatment is usually provided by a team which includes doctors, nurses, and allied health professionals. Each member of the team provides their own unique contribution with the shared goal of suppressing the activity and impact of the condition while educating and supporting people to manage their own symptoms effectively. This chapter focuses on treatment from the perspective of four disciplines: nursing, physiotherapy, occupational therapy, and podiatry.
Glucocorticoids
Authors: Jacobs Johannes W. G. , Spies Cornelia M. , Bijlsma Johannes W. J. , Buttgereit Frank
Published: February 2014

Glucocorticoids are anchor drugs of therapeutic regimens in most inflammatory and autoimmune rheumatic conditions and vasculitides, for reasons of effectiveness, versatility, and low cost. In this chapter on glucocorticoid therapy in rheumatology, basic mechanisms and pharmacological effects, indications, adverse advents, monitoring, and new developments are discussed. Throughout, emphasis is placed on clinically relevant implications for daily clinical practice.
Biologics in paediatric rheumatic diseases
Authors: Lovell Daniel J. , Ruperto Nicolino , Brunner Hermine I. , Martini Alberto
Published: February 2014

The introduction of biological therapies into the treatment of children with rheumatic diseases has dramatically changed our expectation about treatment goals in children with a wide variety of forms of chronic arthritis. The outcomes of these children have been dramatically improved. The application of biological therapies to other paediatric rheumatic diseases has been much more limited and a change in treatment of these other rheumatic diseases has been less impacted by the introduction of biological therapies. The overall safety profile of biological therapies in children reveal issues that are similar to those in adults both in the frequency and types of toxicities. The paediatric-specific safety issues are childhood vaccinations and varicella. Biologic therapies have been included in recently developed validated treatment guidelines for juvenile idiopathic arthritis (JIA). Biologic therapies for children with rheumatic diseases have advanced greatly in the last decade and many exciting studies are ongoing and in development.
Stem cell therapies
Authors: Tyndall Alan , van Laar Jacob M.
Published: February 2014

Since the start of the international project in 1997, over 1500 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, with overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity.
Multipotent mesenchymal stromal cells (MSC) have been recently tested in various autoimmune diseases, exploiting their immune modulating properties and apparent low acute toxicity. MSC display immune privilege in that the patient requires no immunosuppression prior to allogeneic MSC infusion. Despite encouraging small phase I/II studies, no positive data from randomized prospective studies are as yet available in the peer-reviewed literature.
Vaccination in immunocompromised adults
Authors: van Assen Sander , Bijl Marc
Published: February 2014

This chapter addresses all important questions regarding vaccination of patients with autoimmune inflammatory rheumatic diseases (AIIRD). First, the incidence of vaccine-preventable infections in these patients is discussed. Pulmonary infections, including influenza and pneumococcal infection, occur more often in AIIRD patients; herpes zoster and human papillomavirus are also more frequent.
The efficacy of vaccination for all European registered vaccines is discussed. Treatment with disease-modifying anti-rheumatic drugs (DMARDs) and biologicals (in particular TNFα‎-blocking agents) do not hamper, or only slightly hamper, the immune responses to most vaccines. Rituximab is an exception, severely reducing humoral responses following influenza and pneumococcal vaccination, at least during the first 6 months after administration.
Safety of vaccination is an important issue in patients with autoimmune diseases, since increased disease activity of the underlying disease as a result of vaccination is theoretically possible. The available evidence is summarized, suggesting that vaccination is safe in AIIRD patients. Live vaccines, however, are contraindicated in immunosuppressed patients with AIIRD. Finally, the European League Against Rheumatism (EULAR) recommendations are highlighted, summarizing the 'do's' and 'don'ts' of vaccination in adults with AIIRD.
Principles of management of juvenile idiopathic arthritis
Authors: Ruperto Nicolino , Ravelli Angelo
Published: February 2014

The management of juvenile idiopathic arthritis (JIA) is based on a combination of pharmacological interventions, physical and occupational therapy, and psychosocial support. Ideally, the management is conducted by a multidisciplinary team composed by a paediatric rheumatologist, specialist nurse, physical therapist, occupational therapist, and psychologist. The treatment is aimed to achieve disease control, to relieve pain, to foster normal nutrition and growth, to maintain physical and psychological well-being, and to prevent long-term damage related to the disease or its therapy. First-line pharmacological interventions are based on non-steroidal anti-inflammatory drugs and intra-articular corticosteroids. Patients who are refractory to these therapies are candidates to receive disease-modifying anti-rheumatic medications, namely methotrexate or, in case of enthesitis-related arthritis, sulfasalazine. If therapeutic response is inadequate or suboptimal, the introduction of a biologic response modifier is considered. Systemic corticosteroids are used in selected instances, which include the management of extra-articular manifestations of systemic arthritis or the achievement of quick disease control while are awaiting the full therapeutic effect of a disease-modifying agent in patients with severe polyarthritis. To help physician select the safest and most effective treatment for JIA, the American College of Rheumatology (ACR) has issued a set of recommendations that were meant to be as evidence based as possible. The British Society for Paediatric and Adolescent Rheumatology (BSPAR) has developed the standards of care for patients with JIA, which are aimed to help the paediatric rheumatology teams to improve the service they provide.
Lyme borreliosis
Authors: Krause Andreas , Fingerle Volker
Published: February 2014

Lyme borreliosis (LB) is a multisystem infectious disease caused by the tick-borne spirochete Borrelia burgdorferi. The most frequent clinical manifestations include erythema migrans, meningoplyneuritis, and arthritis. Diagnosis of LB is made on clinical grounds and usually supported by a positive serology. Early diagnosis and treatment almost always leads to a rapid healing of the disease. However, in late manifestations gradual remission of symptoms may take several weeks to months. In rare cases, the pathogen can persist for many years or induce a persisting immunopathological response that may cause acrodermatitis chronica atrophicans, chronic neuroborreliosis of the central nervous system, or antibiotic resistant Lyme arthritis. However, even these chronic manifestations usually slowly regress after thorough antibiotic and symptomatic therapy, although in part with irreversible organ defects.
Brucellar arthritis
Authors: Merino Esperanza , Pascual Eliseo
Published: February 2014

Joint infection is the most common local complication of brucellosis and is a frequent cause of infectious arthritis in endemic areas. Brucellosis is prevalent in countries of the Mediterranean basin, the Near East, South America, and possibly sub-Saharan Africa. Brucella melitensis and B. abortus are the most common species. Arthralgia occurs in 70% of patients with brucellosis, Large peripheral joints are a common site of localized infection. The sacroiliac joint is frequently involved (30–75%) in recent series. First-line treatment is with doxycycline combined with either streptomycin or gentamycin.
Parasitic infection
Authors: Ogunbambi Olabambo , Patel Yusuf I.
Published: February 2014

Parasitic infections remain prevalent, particularly in the developing world. However, increasing global travel poses a risk of contracting parasitic infections while travelling through endemic areas and therefore all medical practitioners should remain aware of parasitic infections and investigate for them when appropriate. Increased understanding of the relationship of parasites with the immune system has led to some progress with therapeutics but this still lags behind other infectious diseases. In this chapter we outline the musculoskeletal manifestations of parasitic infection and updated therapeutic approaches to these infections. The burden of disease may change with increasing use of potent biologic immunosuppressants and global travel, as seen in HIV-related immunosuppression, but as yet no significant increased incidence of parasitic infection has been reported within 'rheumatic diseases' cohorts around the world.
Rheumatoid arthritis—clinical features
Authors: Feist Eugen , Burmester Gerd-R.
Published: February 2014

Rheumatoid arthritis (RA) presents with variable clinical features, making this most frequent chronic systemic autoimmune disease with characteristic joint involvement a diagnostic and therapeutic challenge. This chapter describes in detail the different clinical, laboratory and imaging findings in patients with RA. In addition to the characteristic arthritic involvement, which can lead to severe joint changes with progressive destruction and loss of function, other systemic disease manifestations as well as an increased risk for cardiovascular events and non-Hodgkin's lymphoma with relevance for patients' prognosis are described. Recent approaches to early diagnosis and stratification of patients by predictive factors for a severe course of disease are discussed. These patient profiles include increased inflammatory markers, the presence of autoantibodies, and erosive changes at the time of diagnosis. The novel classification criteria for RA and the significance of autoantibody status, namely seropositivity for antibodies against citrullinated antigens as highly specific diagnostic markers, are highlighted to further promote early differentiation of RA from other arthritic disease entities.
Reactive arthritis and enteropathic arthropathy
Authors: Gaston J. S. Hill
Published: February 2014

Reactive arthritis (ReA), and enteropathic arthritis secondary to inflammatory bowel disease, are forms of spondyloarthritis, all of which share an association with HLA B27 and can involve both axial and peripheral joints. Genetic studies strongly implicate the cytokines IL-17 and IL-23 in their pathogenesis, and evidence for autoimmunity is lacking. ReA is triggered by particular bacteria, mainly affecting the gut and genitourinary tract, though infections are sometimes asymptomatic. Classically an acute oligo- or monoarthritis with enthesitis occurs, often with inflammatory back pain, though mild polyarthritis can also occur. Septic and crystal-induced arthritis are the principal differential diagnoses. Extra-articular features may aid diagnosis, which otherwise requires laboratory evidence of preceding infection. Bacterial components traffic to the joint (which is nevertheless sterile), and elicit local proinflammatory immune responses. Most ReA is self-limiting, but persistent cases may require disease-modifying anti-rheumatic drugs or even biologics.
Paediatric-onset systemic lupus erythematosus
Authors: Watson Louise , Beresford Michael W.
Published: February 2014

Paediatric or juvenile-onset systemic lupus erythematosus (JSLE) is a rare autoimmune condition, differing from the adult form in terms of severity, organ manifestations, and a less striking female predominance. The diagnosis relies on the adult-derived American College of Rheumatology SLE classification criteria. Genetic, autoantibody, and host immune responses, characteristic of this disease, result in a clinically heterogeneous phenotype. A proportion of paediatric SLE patients will have evidence of a genetic deficiency known to be associated with SLE, such as C1q deficiency, and screening for these is required. A challenging diagnosis to make in the younger age group, the management of JSLE compared to adult-onset SLE requires special consideration towards the significant long-term consequences of the disease and treatment toxicity, combined with an onset during a fundamental time with regards to growth and development. A comprehensive, multidisciplinary team approach to the management of JSLE is essential. With a more severe phenotype and limited comorbidities, patients with JSLE represent an invaluable opportunity for investigating the pathogenesis. To date, clinical trials informing interventions in JSLE are very limited and treatment choices rely on the outcome of adult trials. Patient and family involvement in research to improve outcomes and understanding is essential. New treatments, including biological therapies, are becoming available for clinical use and new treatment combinations have been used to induce and maintain clinical remission.
Treatment of ANCA-associated vasculitis
Authors: Jayne David
Published: February 2014

The goals of treatment in anti-neutrophil cytoplasm antibody (ANCA) vasculitis are to stop vasculitic activity, to prevent vasculitis returning, and to address longer-term comorbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk. Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as methotrexate or azathioprine, to prevent relapse. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Additional therapy with intravenous methylprednisolone and plasma exchange is employed in severe presentations with failing vital organ function.
Drug toxicity contributes to comorbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem, with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn. Disease relapse occurs in 50% and requires early detection at a stage when it will not adversely affect outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator.
Outcomes of vasculitis depend heavily on the level of tissue damage at diagnosis, especially renal dysfunction, but are also influenced by patient age, ANCA subtype, disease extent, and response to therapy. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)is treated along similar principles to granulomatosis with polyangiitis (GPA) and microscopic polyangiitis but the persistence of steroid-dependent asthma in over one-third and differences in pathogenesis has suggested alternative treatment approaches. Chronic morbidity results from tissue damage and is especially common in the upper and lower respiratory tract and kidneys. Tracheobronchial disease is a severe late complication of GPA, while deafness, nasal obstruction, and chronic sinusitis are sequelae of nasal and ear vasculitis. Chronic infection of damaged epithelial surfaces acts as a drive for vasculitic activity and adequate infection control is necessary for stable remission. Chronic kidney disease can stabilize for many years but the risks of endstage renal disease (ESRD) are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful, with similar outcomes to other causes of ESRD.
Polymyalgia rheumatica
Authors: Dasgupta Bhaskar
Published: February 2014

This chapter reviews advances in pathogenesis; European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria with clinical, laboratory, and ultrasound criteria for classification as polymyalgia rheumatica (PMR); the heterogeneity and overlap between PMR, inflammatory arthritis, and large-vessel vasculitis as illustrated by representative cases; recent guidelines on early and correct recognition, investigations, and management of PMR; the scope of disease-modifying agents; socio-economic impact, outcomes, and patient experience in PMR. It also discusses areas for future research including clinical trials with biological agents and newer steroid formulations, standardized outcome assessments, and the search for better biomarkers in PMR.
PMR is one of the common inflammatory rheumatic diseases of older people and represents a frequent indication for long-term glucocorticoid (GC) therapy. It is characterized by abrupt-onset pain and stiffness of the shoulder and pelvic girdle muscles. Its management is subject to wide variations of clinical practice and it is managed in primary or secondary care by general practitioners (GPs), rheumatologists, and non-rheumatologists.
The evaluation of PMR can be challenging, as many clinical and laboratory features may also be present in other conditions, including other rheumatological diseases, infection, and neoplasia. PMR is usually diagnosed in the primary care setting, but standard clinical investigations and referral pathways for suspected PMR are unclear.
The response to standardized therapy is heterogeneous, and a significant proportion of patients do not respond completely. There is also an overlap with inflammatory arthritis and large-vessel vasculitis for which adjuvant disease-modifying medications are often used. Prolonged corticosteroid therapy is associated with a variety of side effects, especially when high-dose glucocorticoid therapy is employed.
Giant cell arteritis (GCA) is also often linked to PMR. It is a vasculitis of large- and medium-sized vessels causing critical ischaemia. GCA is a medical emergency because of the high incidence of neuro-ophthalmic complications. Both conditions are associated with a systemic inflammatory response and constitutional symptoms. The pathogenesis is unclear. The initiating step may be the recognition of an infectious agent by aberrantly activated dendritic cells. The key cell types involved are CD4+ T cells and macrophages giving rise to key cytokines such as interferon-γ‎ (implicated in granuloma formation), PDGF (intimal hyperplasia), and interleukin (IL)-6 (key to the systemic response).
The pathogenesis of PMR may be similar to that of GCA, although PMR exhibits less clinical vascular involvement. The mainstay of therapy is corticosteroids, and disease-modifying therapy is currently indicated in relapsing disease.
Paget’s disease of bone
Authors: Ralston Stuart H.
Published: February 2014

Paget's disease of bone (PDB) affects up to 1% of people of European origin aged 55 years and above. It is characterized by focal abnormalities of bone remodelling which disrupt normal bone architecture, leading to expansion and reduced mechanical strength of affected bones. This can lead to various complications including deformity, fracture, nerve compression syndromes, and osteoarthritis, although many patients are asymptomatic. Genetic factors play a key role in the pathogenesis of PDB. This seems to be mediated by a combination of rare genetic variants which cause familial forms of the disease and common variants which increase susceptibility to environmental triggers. Environmental factors which have been suggested to predispose to PDB include viral infections, calcium and vitamin D deficiency, and excessive mechanical loading of affected bones. The diagnosis can be made by the characteristic changes seen on radiographs, but isotope bone scans are helpful in defining disease extent. Serum alkaline phosphatase levels can be used as a measure of disease activity. Inhibitors of bone resorption are the mainstay of medical management for PDB and bisphosphonates are regarded as the treatment of choice. Bisphosphonates are highly effective at reducing bone turnover in PDB and have been found to heal osteolytic lesions, and normalize bone histology. Although bisphosphonates can improving bone pain caused by elevated bone turnover, most patients require additional therapy to deal with symptoms associated with disease complications. It is currently unclear whether bisphosphonate therapy is effective at preventing complications of PDB.
Skeletal dysplasias
Authors: Wordsworth B. P.
Published: February 2014

Bone is metabolically active throughout life and metabolic disturbances may have wide-ranging consequences that are not restricted to altering its mechanics. The study of some genetic bone diseases has already provided remarkable insights into the normal regulation of bone metabolism. Skeletal dysplasias are developmental disorders of the chondro-osseous tissues commonly resulting in short stature, which is often disproportionate. The underlying mutations are often in the structural genes encoding components of the matrix but may also involve growth factors or cell signalling. In contrast, the dysostoses tend to affect single bones or groups of bones, reflecting the transient nature of the many different signalling factors to which they are responsive during development.
Abnormalities of bone density (high or low) may be due to primary deficiency of bone matrix synthesis (e.g. osteogenesis imperfecta and hypophosphatasia) but may also reflect an imbalance between bone formation and resorption. This may be caused by abnormalities of bone formation (e.g. hyperostosis/sclerosteosis and osteoporosis pseudoglioma syndrome) or bone resorption (e.g. classic osteopetrosis and fibrous dysplasia).
Cervical and lumbar spine
Authors: Walsh David A.
Published: February 2014

Cervical and lumbar spine pain are major causes of disability and distress. Careful assessment is needed of the nature and extent of the problem, for diagnosis and exclusion of important (treatable) differential diagnoses, and for the formulation and engagement of the patient in an appropriate treatment plan. Acute spinal pain frequently does not indicate underlying joint pathology. Chronic spinal pain is often associated with intervertebral disc disease or which is often classified together with facet joint osteoarthritis as spondylosis. Sciatica, brachalgia, or spinal claudication may each be a consequence of either spondylosis or intervertebral disc prolapse. Simple mechanical low back and neck pain may respond well to conservative management with analgesics and physiotherapy. Specific spinal problems, such as neuronal compromise, may require additional treatments. The roles of injections and surgery in the management of spinal pain continue to evolve. Although ongoing management is largely determined by the individual's clinical response, comprehensive health economic analyses inform healthcare policies which may limit treatment availability. Many people with spinal problems suffer long-term or recurrent pain and disability, with significant psychological and social impact. Multidisciplinary approaches are needed to facilitate pain management and enable people with spinal pain to lead fulfilling lives when the underlying condition cannot be cured.
Childhood regional conditions
Authors: Houghton Kristin
Published: February 2014

Musculoskeletal (MSK) complaints are common in childhood. The majority of causes are benign and self-limiting, but MSK symptoms may be the presenting feature of serious life-threatening illness or chronic disease. Pain is often attributed to minor trauma, and atraumatic causes including infectious, inflammatory, and oncologic conditions, amplified musculoskeletal pain syndromes, and normal skeletal growth variants need to be considered. The age of the child helps identify the possible developmental conditions unique to the growing paediatric skeleton. Evaluation and management requires a thorough history and physical examination, and understanding of normal development.
This chapter reviews common MSK regional conditions in childhood.