Best Practice & Research Clinical Rheumatology RSS feed: Current Issue. Evidence-based updates of best clinical practice across the spectrum of musculoskeletal conditions Best Practice and Research Clinical Rheumatology keeps the clinician or trainee informed of the latest developments and current recommended practice in the rapidly advancing fields of musculoskeletal conditions and science. The series provides a continuous update of current clinical practice. It is a topical serial publication that covers the spectrum of musculoskeletal conditions in a 4-year cycle. Each topic-based issue contains around 200 pages of practical, evidence-based review articles, which integrate the results from the latest original research with current clinical practice and thinking to provide a continuous update. Each issue follows a problem-orientated approach that focuses on the key questions to be addressed, clearly defining what is known and not known. The review articles seek to address the clinical issues of diagnosis, treatment and patient management. Management is described in practical terms so that it can be applied to the individual patient. The serial is aimed at the physician in both practice and training. The Best Practice and Research Clinical Rheumatology series provides up-to-date and expert information and opinion by drawing on Guest Editors and authors renowned for their expertise. This ongoing review of topics makes the serial ideally suited to supporting everyday clinical practice, for training needs as well as for maintaining knowledge and competency. Volume 22 (Volume 2008) 1. Connective tissue diseases M. Matucci-Cerinic & D. Furst 2. Musculoskeletal science T. Pap & U. Muller-Ladner 3. How to manage chronic musculoskeletal conditions - the principles P. Brooks & P. Conaghan 4. Miscellanous inflammatory musculoskeletal conditions J. Sibilia & H. Zeidler 5. Musculoskeletal conditions in the developing world G. Mody & R. Handa 6. Imaging in musculoskeletal conditions M. Cimmino and W. Grassi Volume 23 (2009) 1. Early rheumatoid arthritis 2. Vasculitis 3. How to do - practical procedures 4. Back pain 5. Systemic lupus erythematosus 6. Osteoporosis Volume 24 (2010) 1. Osteoarthritis 2. Paediatric rheumatology 3. How to manage chronic musculoskeletal conditions - a systematic approach to specific problems 4. Pharmacotherapy 5. Spondylo-arthropathies 6. Prevention / epidemiology This free sample chapter is being provided to demonstrate the Journal's approach to topics across the spectrum of musculoskeletal conditions. http://www.bprclinrheum.com/?rss=yesElsevier Inc.en © 2012 Published by Elsevier Inc. All rights reserved. Best Practice & Research Clinical Rheumatology1521-6942261February 2012 © 2012 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.bprclinrheum.com/article/PIIS1521694212000228/abstract?rss=yesEditorial Board/Aims and Scope10.1016/S1521-6942(12)00022-8Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-0iiiiiihttp://www.bprclinrheum.com/article/PIIS1521694212000162/abstract?rss=yesThe development of autoimmunity and autoimmune diseases is believed to involve interactions between genes, hormones and the environment and was labelled in 1989 as ‘the mosaic of autoimmunity’. This complex interplay between the immune system and various stimuli that comprise the pebble of the mosaic is controlled by a wide array of mechanisms . In the last decade, there have been enormous strides in our understanding of autoimmune mechanisms which enabled us, to some extent, to predict and prevent diseases . The relationships between environmental factors such as infectious agents, vaccines, adjuvant and drugs as well as hormones such as vitamin D, ferritin and prolactin that can shift the immune perpendulum towards autoimmune inflammation have been extensively studied . Therefore, nowadays we aspire into an era where we can recommend preventive measurements that will ameliorate or postpone autoimmunity. Of which a proper diet, avoidance of exposure to certain hormones (i.e., oral contraceptive) or UV radiation, climatotherapy and the consumption of vitamin D have been reported . For instance, we have recently reported of an inverse association between vitamin D levels and thormoboses in patients with the anti-phospholipids syndrome . Moreover, in the same study the ability of vitamin D to prevent the production of tissue factor, an instrumental factor in the coagulation cascade, was documented, thus alluding to the notion that vitamin D may alter the main mechanism of thrombosis in this systemic autoimmune disease . Another aspect of this puzzle is the geo-epidemiology variability of autoimmune diseases. In other words, geo-epidemiology defines the crucial effects of different geographical areas, which represent diverse genetics susceptibilities and environmental factors, on determining which autoimmune disease will eventually develop. .The mirabilis period of autoimmunityNancy Agmon-Levin, Yehuda Shoenfeld10.1016/j.berh.2012.01.015Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-013http://www.bprclinrheum.com/article/PIIS1521694212000113/abstract?rss=yesThe immune system must be able to discriminate between self and non-self. However, mechanisms of doing so sometimes fail, causing the activation and clonal expansion of autoreactive lymphocytes and the development of autoimmune conditions. Although some autoimmune diseases have heritable components, these components are not sufficient to develop an autoimmune condition. A variety of environmental factors have been described as possible triggers of autoimmune diseases, including drugs, infectious agents, smoking, vaccination and adjuvants. The aim of this chapter is to review the most common environmental factors associated with autoimmune diseases.The role of environmental factors in the pathogenesis of non-organ-specific autoimmune diseasesCezar Augusto Muniz Caldas, Jozélio Freire de Carvalho10.1016/j.berh.2012.01.010Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-0511http://www.bprclinrheum.com/article/PIIS1521694212000125/abstract?rss=yesSystemic sclerosis (SSc) is a multisystem disease with a variable clinical course and a poor prognosis corresponding to extent of microangiopathy and skin and internal organ fibrosis. Microvascular damage provokes immune cells to produce autoantibodies, pro-inflammatory and pro-fibrotic cytokines and chemokines. The hallmark of SSc is excessive collagen production by activated fibroblasts and myofibroblasts, and its accumulation in skin and internal organs. Better understanding of SSc pathogenesis resulted in the development of drugs, such as prostanoids, endothelin-1 and phosphodiesterase inhibitors, for treatment of pulmonary arterial hypertension and digital ulcers. The use of biological therapies and anti-fibrotic agents is under investigation. Stem cell transplantation seems to be promising in restarting the immune system to diminish fibrosis and restore microvasculature. Future research will be directed at genetic factors, diagnostic and prognostic markers for fibrosis and microangiopathy, and development of drugs directed to pathogenic key cells and mediators.Scleroderma – New aspects in pathogenesis and treatmentAlexandra Balbir-Gurman, Yolanda Braun-Moscovici10.1016/j.berh.2012.01.011Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-01324http://www.bprclinrheum.com/article/PIIS1521694212000149/abstract?rss=yesInflammatory myopathies are chronic, immune-mediated diseases characterised by progressive proximal muscle weakness. They encompass a variety of syndromes with protean manifestations. The diagnosis is based on Bohan and Peter’s classification criteria, which nowadays seem to be obsolete. Our increasing knowledge about the risk factors, genetic susceptibility and immunological pathways in the disease mechanism leads to the establishment of a new, immunogenetically and serologically validated diagnostic criteria system.The treatment of idiopathic inflammatory myopathy is also a complex task requiring much experience. The aims of therapy are to increase muscle strength, prevent the development of contractures and manage the systemic manifestations of the disease. The most important one is the early detection of diseases and patients’ immunological control in special centres. Using the basis therapeutic drugs temporary or permanent remission can be achieved, which improves patientsG' quality of life and functional ability. Rehabilitation and physiotherapy in the remission period may significantly improve the outcome of patients with functional disorders. The introduction of new biological therapies further allows us to control the myositis patients’ state more effectively.The aim of this review is to summarise our knowledge about clinical symptoms, pathomechanism, as well as genetic, serologic and environmental risk factors. We would also like to present the way to diagnosis and the latest research about diagnostic criteria system, proposed outcome measures and therapeutic possibilities.Idiopathic inflammatory myopathiesMelinda Vincze, Katalin Danko10.1016/j.berh.2012.01.013Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-02545http://www.bprclinrheum.com/article/PIIS1521694212000150/abstract?rss=yesSuccessful pregnancy is considered a Th1–Th2 cooperation phenomenon (Th, T-helper), with a predominantly Th2-type lymphocytes response, together with the emerging role of interleukin (IL)-12, IL-15 and IL-18 and of other unidentified soluble factors dependent on natural killer (NK) cells. In the pathogenesis of recurrent spontaneous abortion (RSA), immunological factors have been involved such as decidual cells, complement system, cytokines and genes of the hystocompatibility complex that can determine the success or the failure of a pregnancy. A deeper insight into apparently unexplained RSA shows increasing evidences supporting both alloimmune and autoimmune mechanisms, with autoantibodies playing a major role. The best-characterised pathogenic autoantibodies are anti-phospholipid antibodies, and also other autoantibodies, such as anti-Ro/SSA and anti-La/SSB, have been found to be associated with an increased rate of abortion, poor pregnancy outcome and several other obstetric manifestations. This intriguing mixture has been unveiled only in the last few years with the discovery of novel pathogenic mechanisms that can be targeted in the prevention and treatment of obstetrical complications occurring in the course of an autoimmune disease.Pregnancy and autoimmunity: A common problemCarlo Perricone, Caterina de Carolis, Roberto Perricone10.1016/j.berh.2012.01.014Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-04760http://www.bprclinrheum.com/article/PIIS1521694212000101/abstract?rss=yesThe most common clinical manifestations of mixed connective disease are Raynaud’s phenomenon, arthralgias, swollen joints, esophageal dysfunction, muscle weakness and fingers sausage-like appearance together with the presence of anti-ribonucleoprotein (RNP) antibodies. However, organ involvement is more extensive than first descriptions reported. The disease can be serious with development of pulmonary, kidney, cardiovascular, gastrointestinal and central nervous system manifestations. The worst prognosis and high mortality are associated with the presence of pulmonary disease. Although a different set of clinical criteria have been proposed, there is no consensus about the most accurate. There is no full agreement about treatment and the initial impression of a satisfactory response to low doses of steroids is not always the rule. Herein, we review available evidence to a better approach to all previous topics.Mixed connective tissue disease: An overview of clinical manifestations, diagnosis and treatmentOscar-Danilo Ortega-Hernandez, Yehuda Shoenfeld10.1016/j.berh.2012.01.009Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-06172http://www.bprclinrheum.com/article/PIIS152169421200006X/abstract?rss=yesThe existence of systemic autoimmune diseases not fulfilling classification criteria for defined connective tissue diseases (CTDs) is a common clinical experience. These conditions have been variably defined as incomplete lupus erythematosus, early undifferentiated connective tissue diseases and undifferentiated connective tissue diseases (UCTDs). However, the definition of UCTD includes a wide spectrum of diseases ranging from ‘organ-dominant’ conditions (e.g., idhiopatic non-specific interstitial pneumonia) to simplified conditions (stable UCTD), to early CTDs or mild forms of CTDs.In the present article, the literature data on undifferentiated diseases and their clinical spectrum as well as the importance of the definition of new classificative criteria are discussed.Undifferentiated CTD: A wide spectrum of autoimmune diseasesMarta Mosca, Chiara Tani, Linda Carli, Stefano Bombardieri10.1016/j.berh.2012.01.005Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-07377http://www.bprclinrheum.com/article/PIIS1521694212000071/abstract?rss=yesAntiphospholipid syndrome is an auto-immune disorder characterised by recurrent thrombosis, pregnancy losses and the presence of antiphospholipid antibodies. Although it was initially considered an auto-immune coagulopathy, it is now clear that it is a complex and systemic disease. A large number of manifestations in different organs and tissues (cardiac, pulmonary, neurological, renal, cutaneous, haematologic, gastrointestinal, ocular, skeletal and endocrinologic) have been described in these patients. A small group of patients can have a microvascular involvement, which is the most common pathological finding in patients affected by the catastrophic variant of the syndrome.A strong relationship exists between the antiphospholipid syndrome and systemic lupus erythematosus, as demonstrated by common clinical, serological and genetic features and by the few but possible cases evolving from the first disease into the second one over years.Finally, the systemic nature of the antiphospholipid syndrome and the understanding of the mechanisms of antiphospholipid-mediated damage suggest a role of immunomodulation beyond anticoagulation in the therapeutic approach to the disease.Much more than thrombosis and pregnancy loss: The antiphospholipid syndrome as a ‘systemic disease’Mara Taraborelli, Laura Andreoli, Angela Tincani10.1016/j.berh.2012.01.006Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-07990http://www.bprclinrheum.com/article/PIIS1521694212000083/abstract?rss=yesPolymyalgia Rheumatica (PMR) is an inflammatory rheumatic disease that commonly affects individuals over 50 years of age, characterised by pain and morning stiffness of the shoulder and pelvic girdle. PMR can present as ‘isolated’ form or may be associated with giant cell arteritis. The progress of imaging techniques has helped in understanding different clinical patterns: subclinical vasculitis can occur in at least one-third of PMR patients, causing ischaemic complications. It is considered a polygenic disease and environmental factors may play a role in its pathogenesis, such as viral or bacterial triggers, both in the ‘wide’ form or assembled with adjuvants in vaccines. The response to steroid therapy is generally dramatic and side effects may occur, as well as the development of glucocorticoid resistance. The optimisation of therapy may require steroid-sparing agents as well as modified-release prednisone as ‘nighttime’ replacement therapy.Polymyalgia rheumatica in 2011Alessandra Soriano, Raffaele Landolfi, Raffaele Manna10.1016/j.berh.2012.01.007Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-091104http://www.bprclinrheum.com/article/PIIS1521694212000137/abstract?rss=yesAbstract: Sjögren’s syndrome is a chronic autoimmune disease characterised by progressive injury to exocrine glands accompanied by diverse extra-glandular manifestations. The spectrum of Sjögren’s manifestations expanded in recent years to include new symptoms and signs such as small fibre neuropathy, and also well-defined activity and prognostic indexes. Similar to other non-organ-specific autoimmune diseases, a mosaic of factors have been linked with the development and appearances of Sjögren’s syndrome. Progress has been made unravelling those factors, including susceptibility genes, immunological parameters and various environmental factors in the last decade, some of which may enable targeted therapies, biological and non-biological ones, for patients suffering from this disease.Thus, herein we review the postulated aetiologies, pathogenesis and new insights related to Sjögren’s syndrome.Sjögren’s syndrome, the old and the newYogev Peri, Nancy Agmon-Levin, Emanuel Theodor, Yehuda Shoenfeld10.1016/j.berh.2012.01.012Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-0105117http://www.bprclinrheum.com/article/PIIS1521694212000058/abstract?rss=yesObjective: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease, presenting with recurrent episodes of fever and polyserositis. Neurologic involvement in FMF is rare and usually considered fortuitous. The aim of this article is to review the spectrum of possible neurologic manifestations, which can be encountered in FMF patients, and to establish their relation to FMF.Methods: We reviewed the literature based on Pubmed search to find neurologic manifestations, which were reported in FMF patients. To that we added our own experience on the subject, abstracted from our computerised FMF registry of 12000 FMF patients of the National FMF Center and the computerised database of Sheba Medical Center.Results: A wide range of neurologic manifestations involving FMF patients was noted. A large part of these manifestations could be directly related to FMF, its complications, associated diseases and treatment adverse effects. The remaining were incidental, or of uncertain association to FMF.Conclusion: A physician, taking care of an FMF patient, can face various neurologic manifestations and should be aware of their origin. The current chapter provides an insight to this association of FMF.Neurologic and other systemic manifestations in FMF: Published and own experienceO. Feld, G. Yahalom, A. Livneh10.1016/j.berh.2012.01.004Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-0119133http://www.bprclinrheum.com/article/PIIS1521694212000034/abstract?rss=yesSpondyloarthropathies (SpA) are a group of common inflammatory rheumatic disorders characterised by axial and or peripheral arthritis, associated with enthesitis, dactylitis and potential extra-articular manifestations such as uveitis and skin rash. The diseases, which comprise the group, share a common genetic predisposition, the HLA-B27 gene; however, this association varies markedly among the various SpAs and among different ethnic groups. Environmental factors seem to be triggering the diseases in the genetically predisposed individuals. The radiographic hallmark of the group is sacroiliitis, which when present is of help in the diagnosis. Various sets of diagnostic and classification criteria were developed over the years including the European Spondyloarthropathy Study Group (ESSG) criteria which were until recently the most widely used. The new Assessment in SpondyloArthritis international Society (ASAS) international working group has recently proposed a new set of diagnostic criteria that would enable identification of SpA before structural changes develop in the spine. Magnetic resonance imaging (MRI) changes have now been included in the new classification criteria of early axial SpA and are now considered as a major tool in the diagnosis. Until recently, there were no real disease-modifying anti-rheumatic drugs which were able to halt the disease progression. Over the past decade, tumour necrosis factor (TNF)-alfa-blocking agents have been extensively investigated and became the mainstream of therapy providing the patients an effective treatment option.SpondyloarthropathiesMichael Ehrenfeld10.1016/j.berh.2012.01.002Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-0135145http://www.bprclinrheum.com/article/PIIS1521694212000046/abstract?rss=yesPsoriatic arthritis (PsA) is a chronic inflammatory spondyloarthritis that occurs in combination with psoriasis. The exact prevalence of PsA is unknown, and its pathogenesis has not yet been fully elucidated. Genetic, environmental, and immunologic factors have all been implicated. The appearance of arthritis might precede, succeed or occur concomitant with skin lesions. PsA is sometimes considered a benign form of arthritis, but it affects patient quality of life and also causes functional impairment. Up to 20% of affected patients exhibit extremely destructive and disfiguring forms of the disease, and PsA is associated with increased mortality. The treatment of PsA aims to provide relief from signs and symptoms of the disease, prevent structural damage to joints, improve patient quality of life and decrease mortality. The choice of treatment depends on the severity of clinical presentation. The use of immunobiological agents is restricted to cases that do not respond to conservative treatment.Psoriatic arthritisGleison Vieira Duarte, César Faillace, Jozélio Freire de Carvalho10.1016/j.berh.2012.01.003Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-0147156http://www.bprclinrheum.com/article/PIIS1521694212000022/abstract?rss=yesIn the past decade, tocilizumab, an anti interleukin-6 agent, has been successfully developed as a therapeutic agent for the treatment of rheumatoid arthritis and systemic onset juvenile idiopathic arthritis. In addition to countering inflammation, tocilizumab is also known affect B cell as well as T cell function, thus modulating immune function, and impact osteoclasts, as well as vascular endothelial growth factor. As such, its efficacy is currently being explored in a large number of autoiommune conditions including a number of vasculitides, systemic lupus erythematosus, systemic sclerosis, polymyositis, graft versus host disease, relapsing polychondritis, as well as Behcet's syndrome, spondyloarthropathies, and tumor necrosis factor receptor associated periodic syndrome.Tocilizumab – A novel therapy for non-organ-specific autoimmune diseasesLisa Kaly, Itzhak Rosner10.1016/j.berh.2012.01.001Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-0157165http://www.bprclinrheum.com/article/PIIS1521694212000265/abstract?rss=yesIndex10.1016/S1521-6942(12)00026-5Best Practice & Research Clinical Rheumatology 26, 1 (2012)2012-02-01Best Practice & Research Clinical Rheumatology2012-02-01261S1521-6942(12)X0002-0II