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INTRODUCTION TO RHEUMATOLOGY. The origins of Rheumatology  Rheumatology - a branch of medicine devoted to the study of rheumatic diseases and disorders.

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Presentation on theme: "INTRODUCTION TO RHEUMATOLOGY. The origins of Rheumatology  Rheumatology - a branch of medicine devoted to the study of rheumatic diseases and disorders."— Presentation transcript:

1 INTRODUCTION TO RHEUMATOLOGY

2 The origins of Rheumatology  Rheumatology - a branch of medicine devoted to the study of rheumatic diseases and disorders of the function and / or structure of the musculoskeletal system.  In the I century AD was the first appeared in the literature, the concept of rheuma (revma). The word "rheuma" of Greek origin. Rheuma refers to "a substance that flows", probably formed from phlegm. This is the "primary juice," by definition of the ancients, which was formed in the brain and flowed in different parts of the body, causing illness.

3 The origins of Rheumatology  In 1642, the term "rheumatism" was introduced in the literature by french physician Dr. G. Baillou, who supposed that arthritis can be a manifestation of systemic disease.

4 The origins of Rheumatology  In 1928, in the USA Dr. R. Pemberton organized the American Committee for the treatment of rheumatism, which was renamed the American Association for the Study and Treatment of rheumatic diseases (1934), followed by the American Association of rheumaticism (1937) and, finally, the American Rheumatology Association (1988).

5 The origins of Rheumatology  In 1940, Bernard Comroe suggested the term "rheumatologist.“  In 1949, Hollander uses the term "rheumatology" in his textbook on arthritis and painful condition (Arthritis and Allied Conditions).

6 History of the discovery of some rheumatic diseases

7 Acute rheumatic fever

8  The doctrine of rheumatism has a long history. For the first time information about rheumatic arthritis appeared in the writings of Hippocrates. There was humoralism (Latin humor - fluid) - current through the joint process.  In the early XX century, all were regarded as diseases of the joints and rheumatism.  Classic works consecrated to the ARF, have been written by Jean-Bapite Bomllard and Walter B Cheadle and published in 1836, which detailed the "rheumatic arthritis" and carditis.  At one time Lasegue said: "Rheumatism licks the joints but bites the heart.“  S. Botkin has been shown that ARF affects many organs: kidneys, skin, nervous system, liver and lungs.

9 Acute rheumatic fever  In 1904 morphologist Ludwig Aschoff first discovered and described the morphological substrate of rheumatic fever - a kind of cell granuloma. In 1929 Talalayev showed that rheumatic granuloma Aschoff - only one stage, but it has 3 phases: exudative, proliferative phase, cell proliferation and sclerosis. So now the rheumatic granuloma-called Aschoff Talalayev.  In 1933, Rebecca Lancefield was divided into groups hemolytic streptococci, helping researchers clarify the epidemiology of the disease. For the first time the criteria for leadership in the diagnosis of ARF were developed by Dr. T Duckett Jones and published in Later they were adopted and revised by the American Heart Association.

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12 Rheumatoid arthritis

13  The earliest signs of rheumatoid arthritis were found in 4500 BC. They were found on the remains of skeletons of Indians in Tennessee, USA.  The first paper describing the symptoms are very reminiscent of the symptoms of rheumatoid arthritis dates back to 123 a year.

14  The first clinical description of this pathology in 1800, is credited with Augustin-Jacob Landre-Beauvais. The author called the disease variant of gout - a "simple asthenic gout" (goutte asthenique primitif).  Benjamin Brodie described the slow progression of synovitis by involving joint capsule and tendon sheath.

15  Joint swelling in early rheumatoid arthritis Deformities of long-standing rheumatoid arthritis

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17 Rheumatoid arthritis  A. Garrod suggested the term "rheumatoid arthritis" in 1858 and differentiate it from gout in 1892, the disease got its present name.

18 Systemic lupus erythematosus  The name lupus, the Latin version as Lupus erythematosus, comes from the Latin "lupus", which means wolf and "eritematozus" - red, because of its similarity to the bite injuries hungry wolf. 

19  This disease is known to doctors since 1828, after describing the French dermatologist Biett skin symptoms

20  45 years later Kaposhi (dermatologist) observed that some patients with skin symptoms are also symptoms of internal organs. 

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22  In 1845, Ferdinand von Hebra described a rash on the type of "butterflies" on her nose and cheeks.

23 Systemic lupus erythematosus  In 1948,William Hargraves described the LE-cells. This discovery allowed doctors to identify many patients with systemic lupus erythematosus.  In 1956, Miescher, described the absorption of LE- cell factor kernels.  In 1958, George Friou described a method for identification of antinuclear antibodies.

24 Spondyloarthropathies (ankylosing spondylitis)  The archaeological study of Egyptian mummies found the disease, which is now called ankylosing spondylitis is known to mankind since ancient times.  The first historical description of the disease in the literature refers to 1559, when Realdo Colombo described the two skeletons with typical changes of ankylosing spondylitis in his book "Anatomy.“  100 years later, in 1693, an Irish physician Bernard Connor described the skeleton of a man with signs of scoliosis, in which the sacrum, hip bone, lumbar vertebrae and 10 thoracic vertebrae with ribs are fused into one bone.

25 Spondyloarthropathies (ankylosing spondylitis)  In the late 1890s, Russian doctor, Vladimir Bekhterev and French doctors Adolf Strumpell and Pierre Marie described ankylosing spondylitis.  Linking disease to a gene class I HLA-B27 belongs to the Americans Lee Schlosstein, Rodney Bluestone and Paul Terasaki, as well as the British Derrick Brewerton, Caffrey and Nichols.

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27 Classification of rheumatic / musculoskeletal syndromes in different years

28 Rheumatology as a specialty  Rheumatology as an independent scientific and practical discipline was formed 45 years ago.  Rheumatic diseases are one of the most common pathologies of the human body.  The term "rheumatic disease" include a variety of origins of the disease predominantly systemic, less local character, proceeding with persistent or transient articular syndrome.

29 The origins of the classification  Theoretical basis for combining these various diseases in the same group was the fact that their basis is a preferential loss of connective tissue, as dense, which include the dermis, tendons, ligaments, cartilage, bone and others, and its special types (synovial and serous membranes, basal membranes of blood vessels and epithelium, etc.).

30 Working classification and nomenclature of rheumatic diseases (1999)  I. Rheumatism (rheumatic fever)  II. Diffuse diseases of connective tissue  1.0. Lupus Erythematosus  2.0. Systemic Scleroderma  3.0. Diffuse Fasciitis  4.0. Dermatomyositis (polimiozit)  5.0. Disease Šhoegren  6.0. Mixed connective tissue disease  7.0. Rheumatic polimialgia  8.0. Recurrent polihondritis, including Tietze disease  9.0. Recurrent pannikulitis (Weber-Christian disease)

31  Working classification and nomenclature of rheumatic diseases (1999)  III. Systemic Vasculitis  1.0. periarteritis nodosa  2.0. Granulomatous arteritis: 2.1. Wegener's granulomatosis 2.2. Eosinophilic granulomatous vasculitis 2.3. Giant cell arteritis temporal (Horton's disease) 2.4. Nonspecific aortoarteriit (Takayasu's disease) 3.0. Hyperergic angiitis 3.1. Hemorrhagic vasculitis (Henoch disease - purpura) 3.2. Goodpasture's syndrome 3.3. Mixed cryoglobulinemia (cryoglobulinemc purpura) 4.0. Thromboangiitis obliterans (Buerger's disease) 5.0. Behcet's syndrome 6.0. Kawasaki syndrome (muco-cutaneous-glandular syndrome)

32 Working classification and nomenclature of rheumatic diseases (1999)  IV. Rheumatoid arthritis V. Juvenile arthritis VI. Ankylosing spondylitis (Bechterew) VII. Arthritis, combined with spondylarthritis 1.0. psoriatic arthritis 2.0. Reiter's disease 3.0. Arthritis in chronic nonspecific bowel disease (ulcerative colitis, ileitis regionar-ny Crohn's disease) 4.0. Arthritis, and (or) sacroiliitis unspecified etiology

33  VIII. Arthritis associated with infection 1.0. infectious arthritis 1.1. Bacterial (staphylococcal, brucellosis, syphilis, spirochetal, mycobacterial, tuberculosis, etc.) Lyme disease Whipple's disease 1.2. viral 1.3. fungal 1.4. parasitic

34  2.0. Reactive arthritis 2.1. Postenterocolitic (shigellosis, yersiniosis, salmonellosis, klebsiellosis, etc.) 2.2. Urogenital (excluding Reiter's disease and gonorrhea) 2.3. After nasopharyngeal infection 2.4. After vaccination

35  2.0. Реактивные артриты  2.1. Постэнтероколитические ( шигеллез, иерсиниоз, сальмонеллез, клебсиеллез и др.)  2.2. Урогенитальные ( исключая болезнь Рейтера и гонорею )  2.3. После носоглоточной инфекции  2.4. Поствакцинальные

36  IX. microcrystalline arthritis 1.0. primary gout 2.0. Gout secondary (drug, renal insufficiency, lead intoxication, etc.) 3.0. Chondrocalcinosis (pseudogout) 4.0. hydroxyapatite arthropathy

37 Рабочая классификация и номенклатура ревматических болезней (1999)  IX. Микрокристаллические артриты  1.0. Подагра первичная  2.0. Подагра вторичная ( лекарственная, при почечной недостаточности, свинцовой интоксикации и др.)  3.0. Хондрокальциноз ( псевдоподагра )  4.0. Гидроксиапатитовая артропатия 

38  X. osteoarthritis XI. Other joint diseases 1.0. palindromic rheumatism 2.0. intermittent hydrarthrosis 3.0. multiple retikulohystiocytosis 4.0. Sinovioma 5.0. chondromatosis of the joint 6.0. Villonodulary synovitis

39  X. Остеоартроз  XI. Другие болезни суставов  1.0. Палиндромный ревматизм  2.0. Интермиттирующий гидрартроз  3.0. Множественный ретикулогистиоцитоз  4.0. Синовиома  5.0. Хондроматоз сустава  6.0. Виллонодулярный синовит

40 XII. Non-rheumatic diseases with arthropathy  1.0. allergic diseases 2.0. Metabolic disorders 2.1. Amyloidosis 2.2. Ochronosis 2.3. Hyperlipidemia 2.4. hemochromatosis 3.0. Congenital defects of the connective tissue metabolism 3.1. Marfan's syndrome 3.2. Desmogenez imperfecta (Ehlers - Danlos syndrome) 3.3. Hypermobility syndrome 3.4. MPS

41 Рабочая классификация и номенклатура ревматических болезней (1999)  XII. Артропатии при неревматических заболеваниях  1.0. Аллергические заболевания  2.0. Метаболические нарушения 2.1. Амилоидоз 2.2. Охроноз 2.3. Гиперлипидемия 2.4. Гемохроматоз  3.0. Врожденные дефекты метаболизма соединительной ткани 3.1. Синдром Марфана 3.2. Десмогенез несовершенный ( синдром Элерса — Данло ) 3.3. Синдром гипермобильности 3.4. Мукополисахаридоз

42  4.0. endocrine diseases 5.0. nervous 6.0. Diseases of the blood 7.0. Paraneoplastic syndrome (malignant tumors of various sites) 8.0. occupational diseases 9.0. Other diseases 9.1. Sarcoidosis is 9.2. Periodic disease 9.3. Chronic active hepatitis 9.4. hypovitaminosis C

43  4.0. Эндокринные заболевания  5.0. Поражения нервной  6.0. Болезни системы крови  7.0. Паранеопластический синдром ( при злокачественных опухолях различной локализации )  8.0. Профессиональные болезни  9.0. Другие заболевания 9.1. Саркоидоз 9.2. Периодическая болезнь 9.3. Хронический активный гепатит 9.4. Гиповитаминоз С

44  XIII. Diseases of the extra-articular soft tissues 1.0. Diseases of the muscles of  1.1. Myositis  1.2. Ossifitsiruyuschy myositis  2.0. Diseases of the tissues around  3.0. Diseases of the fascia and aponeuroses 4.0, subcutaneous disease. Fat  5.0. Poliosteoartromialgiya (psychogenic rheumatism)

45 Рабочая классификация и номенклатура ревматических болезней (1999)  XIII. Болезни внесуставных мягких тканей 1.0. Болезни мышц 1.1. Миозиты 1.2. Оссифицирующий миозит 2.0. Болезни околосуставных тканей 3.0. Болезни фасций и апоневрозов 4.0, Болезнь подкожной. жировой клетчатки 5.0. Полиостеоартромиалгия ( психогенный ревматизм ) 

46  XIV. Bone disease and osteochondropathy 1.0. bone disease 1.1. Osteoporosis (osteopenia), generalized 1.2. osteomalacia 1.3. Osteopathy hypertrophic pulmonary (Marie- Bamberger syndrome) 1.4. Osteitis deformans (Paget's disease) 1.5. Osteolysis (unspecified etiology)

47  XIV. Болезни костей и Остеохондропатии  1.0. Болезни костей  1.1. Остеопороз ( остеопения ) генерализованный  1.2. Остеомаляция  1.3. Остеопатия гипертрофическая легочная ( Мари - Бамбергера синдром )  1.4. Деформирующий остеит ( болезнь Педжета )  1.5. Остеолиз ( неуточненной этиологии )

48  2.0. osteochondropathy 2.1. Aseptic necrosis of the femoral head (Perthes disease) and other sites (Köhler's disease I and II, disease Kenbeka, etc.) 2.2. osteochondritis dissecans 2.3. Osteochondropathy vertebral disease (Sheyermana - May, Calve's disease) 2.4. Osteochondropathy tuberosity of the tibia (Osgood disease - Schlatter

49  2.0. Остеохондропатии  2.1. Асептические некрозы головки бедренной кости ( болезнь Пертеса ) и других локализаций ( болезнь Келера I и II, болезнь Кенбека и др.)  2.2. Рассекающий остеохондрит  2.3. Остеохондропатии тел позвонков ( болезнь Шейермана — May, болезнь Кальве )  2.4. Остеохондропатии бугристости большеберцовой кости ( болезнь Осгуда — Шлаттера

50 Laboratory studies

51 The values ​​ of laboratory data  Laboratory tests may help in diagnosis and to confirm data obtained by history taking and examination, but are not independently diagnostic criteria.  In addition, laboratory tests can help monitoring disease activity, but they are meaningful only when correlated with clinical outcome.

52 Laboratory studies in rheumatic diseases  Anemia  Normochromic - Correlation with disease activity  Iron - NSAID-associated gastrointestinal pathology  Hemolytic - SLE, APS  Aplastic - Citostatic, phenylbutazone, D-penicillamine, etc.  Leukocytes  Leukocytosis - A high activity of inflammation, with Still, the infection  Leukopenia - SCR (lymphopenia), with m-Felty (neutropenia)  Platelets  Thrombocytosis - The high activity of inflammation  Thrombocytopenia - SLE, APS  KLF - Increase - Inflammatory myopathies

53 Laboratory studies in rheumatic diseases  Transaminases, bilirubin - Increase - Pathology of the liver with "rheumatologic" manifestations of the toxicity of drugs (methotrexate, NSAIDs)  Uric acid - Hyperuricemia – Gout  Markers of inflammation  Increased ESR - Active inflammation, a diagnostic criterion for polymyalgia rheumatica and giant cell arteritis, intercurrent infection  Increased CRP - PA - activity of inflammation, joint destruction, SLE - intercurrent infection  Uroscopy  Microhematuria – nephritidis (SLE, systemic vasculitis), toxic drugs  Proteinuria – nephritidis (SLE, systemic vasculitis, amyloidosis), the toxicity of drugs

54 The value of immunological tests in rheumatic diseases

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56 The disease, in which can increase the RF in the serum  Subacute bacterial endocarditis  Leprosy  Chronic inflammatory disease of unknown etiology  Tuberculosis  Syphilis  Sarcoidosis  Lyme Disease  Periodontal disease  Interstitial lung disease  Viral diseases  Liver disease  Rubella  Cytomegalovirus  Mixed cryoglobulinemia

57 Autoantibodies in rheumatic diseases

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59 The main indications for diagnostic arthrocentesis  Monoartritis  Trauma with effusion into the joint cavity  Suspected purulent arthritis  Suspicion of microcrystalline (urate, hydroxyapatite), arthritis  unclear diagnosis

60 The value of radiology in rheumatic diseases

61 Minimum set of laboratory tests to diagnose the causes of joint pain  The total blood count,  platelets  ESR  Bilirubin  Transaminase  CK  Creatinine  uric acid  Urinalysis, daily urine for protein  Microscopic analysis of synovial fluid, including crystals  CRP  rheumatoid factor  antinuclear factor  Anti-DNA  A/b to extractable nuclear antigen (RNP)  ANCA  ASL-O  Determination of chlamydial antigen A/b to B.burgdorferi  HLA B-27

62 Minimum set of radiographic studies to diagnose the causes of joint pain  Chest  Hands and distal foot in front projection  Pelvis in frontal projection  Knee in frontal and lateral projections  Cervical spine in a straight line and lateral projections  The lumbar spine and lateral projections  Heel bone  Esophagus  Densitometry

63 Application of the morphological study (biopsy) in diagnosis of rheumatic diseases and their complications  Polymyositis  Sjogren's disease  Diffuse eosinophilic fasciitis  Systemic vasculitis  Secondary amyloidosis  Differential Diagnosis in subcutaneous sites (rheumatoid nodule / tophi)  Differential diagnosis of suspected tumor of the synovial

64 Drugs used to treat rheumatic diseases

65 Non-steroidal anti-inflammatory drugs for treatment of rheumatic diseases

66 Prevention and treatment of GASTROINTESTINAL pathologies resulting from receiving NSAIDS

67 Risk factors for the development of renal failure in the application of NSAIDs

68 Corticosteroids  Corticosteroids are widely used in the treatment of inflammatory forms of arthritis and related systemic autoimmune diseases.  In addition to their strong anti-inflammatory effect, they regulate a wide range of metabolic, immunological and central nervous system function.  For systemic therapy have been issued numerous synthetic derivatives, but the prednisone, prednisolone, and methylprednisolone are used most widely.

69 Corticosteroids

70 Side effects of long-term Cortico- Therapy  Frequent  Hypertension  Negative calcium balance and secondary hyperparathyroidism  Negative nitrogen balance  Obesity, moon face, supraclavicular fat accumulation in the area, fat accumulation in the form of a mountain on his back,  Slowing of wound healing, erythema face, thin, fragile skin, blue striae, petechiae and ecchymosis  Acne

71  Growth retardation in children  Adrenal insufficiency, resulting in suppression of the hypothalamic-pituitary-adrenal system  Hyperglycemia, diabetes mellitus, dyslipidemia, atherosclerosis  Sodium retention, hypokalemia  Increased risk of infection, neutrophilia, lymphopenia  Osteoporosis, compression fractures of vertebrae, Osteonecrosis  Mood changes such as euphoria, emotional lability, insomnia, depression, increased appetite  subcapsular cataract Side effects of long-term Cortico-Therapy

72  medium frequency  metabolic alkalosis  Diabetic ketoacidosis, hyperosmolar diabetic coma  Peptic ulcer (usually the stomach), gastric bleeding  "Silent" intestinal perforation  Increased intraocular pressure and glaucoma  Mild intracranial hypertension or pseudotumor of the brain  spontaneous fractures  psychosis

73 Side effects of long-term Cortico- Therapy  Rare  Sudden death in the rapid introduction of high-dose, pulse therapy  Valvular damage in SLE  In susceptible patients may develop heart failure  Cellulitis (after cancellation)  Hirsutism or virilism, impotence, secondary amenorrhea  Hepatomegaly as a result of fatty liver exophthalmos  Allergies to synthetic corticosteroids (urticaria, angioedema)

74 Pathogenic (Basic) therapy of inflammatory rheumatic diseases  Disease modifying antirheumatic drugs (DMARDs) - the basic drugs from diverse group of funds that reduce the symptoms of rheumatoid arthritis (RA) and other inflammatory autoimmune diseases.  In addition, there is increasing evidence that treatment with DMARD, especially if appointed early in the course of the disease, can delay the progression of cartilage and bone.  When the RA is not responding to treatment DMARD, can be applied biological therapy. Biologicals alter the action of cytokines

75 Basic therapy  When to start - an understanding that changes in the joints can occur within the first 12 months of the debut of RA, led to the earlier introduction of DMARD and more aggressive combination DMARD.  Monotherapy - Methotrexate is considered standard therapy for DMARD.  Combination therapy - Join one or two DMARD therapy with methotrexate for the background is often used in an attempt to improve clinical response in those patients who did not give an answer to monotherapy with methotrexate. The most commonly used combinations of DMARD - "triple therapy" (methotrexate + hydroxychloroquine sulfosalazin +) or methotrexate plus a biological agent.

76 Pathogenetic (Basic) drugs

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78 Treatment strategies with drugs 1.Sequential monotherapy 2.Step-up (ascending) combination therapy 3. Step-down (descending) combination therapy 4. Combination with a biological agent

79 Biological therapy  One of the most important achievements of the pharmacotherapy of inflammatory rheumatic diseases associated with the development of entirely new group of drugs, which are called "biological" agents.  Their mechanism of action is associated with suppression of synthesis of "inflammatory" cytokines, play a fundamental role in the immunopathogenesis of these diseases, especially RA.

80 Immunomodulating and proinflammatory effects of cytokines in the pathogenesis of inflammatory rheumatic diseases (1)  Vascular endothelial cells - enhance the expression of adhesion molecules (ISAM-1, VSAM-1, E-selectin) through the activation of NF-kV stimulate angiogenesis, leading to disruption of anticoagulant activity (stimulation of the synthesis of tissue factor, suppression of synthesis of thrombomodulin).  Lymphocytes - contribute to the development of lymphoid tissue, modification of SV44 and the ability to bind to the ligand.  Dendritic cells - cells induce the maturation and migration from nonlymphoid organs to secondary lymphocyte organs.  Neutrophils and platelets - contribute to activation.

81 Immunomodulating and proinflammatory effects of cytokines in the pathogenesis of inflammatory rheumatic diseases (2)  Fibroblasts and synoviocytes - lead to proliferation.  Pro-inflammatory cytokines - in addition induce the synthesis of IL-1, IL-6, granulocyte-macrophage colony-stimulating factor.  Other pro-inflammatory mediators - induce the synthesis of PGE2 through activation of COX-2, leukotrienes, platelet activating factor, nitric oxide and reactive oxygen species.  Metalloproteinases - induce the synthesis of collagenase, gelatinase, stromelysin.  Other effects - increase pain, induce cachexia, induce fever, mobilize calcium from the bones; modulate apoptosis.

82 Biological therapy  The particular interest is the use of monoclonal antibodies.  These drugs have very high specificity, which provides a selective effect on certain links in the immunopathogenesis of disease, minimally affecting normal functioning mechanisms of the immune system.  This can significantly reduce the risk of "generalized" imunosupresed, which is typical of many drugs, especially glucocorticoids and cytotoxic drugs.

83 Monoclonal antibody to TNF- α Adalimumab (Adalimumab) Humman Mouse Kimerik Hummanised 5% -10% protein of the mouse 100% human protein 25% protein of the mouse 100% mouse protein Infliximab Adalimumab Golimumab

84 Biological therapy  The main target for anticytokine monoclonal antibody therapy is:  TNF-alpha (infliximab, adalimumab, etc.)  IL-6 (tocilizumab)  CD20 B cells (rituximab)  IL-1, IL-2, etc.

85 Contraindications of biological therapy  Congestive heart failure,  Severe infection  Latent tuberculosis  Malignant neoplasms  Pregnancy and lactation.

86 The need for biological specimens Biologicals Corticosteroids Basic drugs (methotrexate, sulfasalazine, leflunomid) The gravity of the condition of the patient The number of patients

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88 THANK YOU!

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90  What i s Rheumatology?  Rheumatology is the non-surgical subspecialty of internal medicine that focuses on common and complex problems that may affect the entire body, and frequently involves the musculoskeletal system. Such diseases include: rheumatoid arthritis; gout; lupus; scleroderma; osteoporosis; fibromyalgia and spondylitis. Common problems such as tendonitis, back pain, bursitis and carpel tunnel syndrome can be a result of rheumatologic disorders as well.  There are more than 100 types of rheumatological disorders, some of which are very serious and difficult to diagnose and treat. 

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