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7/29/2019 Introducere Reumatologie English
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INTRODUCTION TORHEUMATOLOGY
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The origins of Rheumatology
Rheumatology - a branch of medicine devoted tothe study of rheumatic diseases and disorders ofthe function and / or structure of themusculoskeletal system.
In the I century AD was the first appeared in theliterature, the concept of rheuma (revma). Theword "rheuma" of Greek origin. Rheuma refers to"a substance that flows", probably formed fromphlegm. This is the "primary juice," by definition ofthe ancients, which was formed in the brain andflowed in different parts of the body, causingillness.
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The origins of Rheumatology
In 1642, the term
"rheumatism" was
introduced in the
literature by frenchphysician Dr. G.
Baillou, who
supposed that
arthritis can be a
manifestation of
systemic disease.
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The origins of Rheumatology
In 1928, in the USA Dr. R.Pemberton organized theAmerican Committee forthe treatment ofrheumatism, which was
renamed the AmericanAssociation for the Studyand Treatment ofrheumatic diseases (1934),followed by the AmericanAssociation of
rheumaticism (1937) and,finally, the AmericanRheumatology Association(1988).
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The origins of Rheumatology
In 1940, Bernard Comroe suggestedthe term "rheumatologist.
In 1949, Hollander uses the term"rheumatology" in his textbook onarthritis and painful condition(Arthritis and Allied Conditions).
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History of the discovery of some
rheumatic diseases
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Acute rheumatic fever
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Acute rheumatic fever
The doctrine of rheumatism has a long history. For thefirst time information about rheumatic arthritis appearedin 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 ofthe joints and rheumatism.
Classic works consecrated to the ARF, have beenwritten by Jean-Bapite Bomllard and Walter B Cheadleand 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 manyorgans: kidneys, skin, nervous system, liver and lungs.
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Acute rheumatic fever
In 1904 morphologist Ludwig Aschoff firstdiscovered and described the morphologicalsubstrate of rheumatic fever - a kind of cellgranuloma. In 1929 Talalayev showed thatrheumatic granuloma Aschoff - only one
stage, but it has 3 phases: exudative,proliferative phase, cell proliferation andsclerosis. So now the rheumatic granuloma-called Aschoff Talalayev.
In 1933, Rebecca Lancefield was divided intogroups hemolytic streptococci, helpingresearchers clarify the epidemiology of thedisease. For the first time the criteria forleadership in the diagnosis of ARF weredeveloped by Dr. T Duckett Jones andpublished in 1944. Later they were adoptedand revised by the American Heart
Association.
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Rheumatoid arthritis
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Rheumatoid arthritis
The earliest signs of rheumatoidarthritis were found in 4500 BC. Theywere 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 arthritisdates back to 123 a year.
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The first clinical description of
this pathology in 1800, is credited
with Augustin-Jacob Landre-
Beauvais. The author called thedisease variant of gout - a "simple
asthenic gout" (goutte asthenique
primitif).
Benjamin Brodie described theslow progression of synovitis by
involving joint capsule and tendonsheath.
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Joint swelling in earlyrheumatoid arthritis
Deformities of long-standing
rheumatoid arthritis
http://knol.google.com/k/-/-/jF3hM3MH/lYohRg/Ulnar%20Deviation.bmphttp://knol.google.com/k/-/-/jF3hM3MH/lYohRg/Ulnar%20Deviation.bmphttp://knol.google.com/k/-/-/jF3hM3MH/lYohRg/Ulnar%20Deviation.bmphttp://knol.google.com/k/-/-/jF3hM3MH/lYohRg/Early%20RA.bmp7/29/2019 Introducere Reumatologie English
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Rheumatoid arthritis
A. Garrod
suggested the term
"rheumatoid
arthritis" in 1858 anddifferentiate it from
gout in 1892, the
disease got its
present name.
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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 hungrywolf.
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This disease is known to doctors since
1828, after describing the Frenchdermatologist Biett skin symptoms
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45 years later
Kaposhi
(dermatologist)observed that
some patients
with skin
symptoms are
also symptoms
of internal
organs.
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In 1845, Ferdinand
von Hebra
described a rash
on the type of"butterflies" on her
nose and cheeks.
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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 foridentification of antinuclear antibodies.
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Spondyloarthropathies
(ankylosing spondylitis)
The archaeological study of Egyptian mummiesfound the disease, which is now called ankylosingspondylitis is known to mankind since ancienttimes.
The first historical description of the disease in theliterature refers to 1559, when Realdo Colombodescribed the two skeletons with typical changes ofankylosing spondylitis in his book "Anatomy.
100 years later, in 1693, an Irish physician BernardConnor described the skeleton of a man with signsof scoliosis, in which the sacrum, hip bone, lumbarvertebrae and 10 thoracic vertebrae with ribs arefused into one bone.
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Spondyloarthropathies
(ankylosing spondylitis)
In the late 1890s, Russiandoctor, Vladimir Bekhterevand French doctors AdolfStrumpell and Pierre Mariedescribed ankylosingspondylitis.
Linking disease to a geneclass I HLA-B27 belongs tothe Americans LeeSchlosstein, RodneyBluestone and Paul
Terasaki, as well as theBritish Derrick Brewerton,Caffrey and Nichols.
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Classification of rheumatic / musculoskeletal
syndromes in different years
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Rheumatology as a specialty
Rheumatology as an independent scientific
and practical discipline was formed 45 years
ago.
Rheumatic diseases are one of the mostcommon pathologies of the human body.
The term "rheumatic disease" include a variety
of origins of the disease predominantlysystemic, less local character, proceeding with
persistent or transient articular syndrome.
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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.).
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Working classification and nomenclature ofrheumatic 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 hoegren 6.0. Mixed connective tissue disease
7.0. Rheumatic polimialgia 8.0. Recurrent polihondritis, including Tietze
disease
9.0. Recurrent pannikulitis (Weber-Christiandisease)
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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)
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Working classification and nomenclature ofrheumatic diseases (1999)
IV. Rheumatoid arthritisV. Juvenile arthritisVI. Ankylosing spondylitis (Bechterew)VII. Arthritis, combined with spondylarthritis
1.0. psoriatic arthritis2.0. Reiter's disease3.0. Arthritis in chronic nonspecific bowel
disease (ulcerative colitis, ileitis regionar-ny
Crohn's disease)4.0. Arthritis, and (or) sacroiliitis unspecified
etiology
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VIII. Arthritis associated with infection
1.0. infectious arthritis
1.1. Bacterial (staphylococcal, brucellosis,
syphilis, spirochetal, mycobacterial,tuberculosis, etc.)
1.1.1. Lyme disease
1.1.2. Whipple's disease
1.2. viral1.3. fungal
1.4. parasitic
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2.0. Reactive arthritis
2.1. Postenterocolitic (shigellosis, yersiniosis,
salmonellosis, klebsiellosis, etc.)
2.2. Urogenital (excluding Reiter's disease andgonorrhea)
2.3. After nasopharyngeal infection2.4. After vaccination
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2.0.
2.1. (, , ,
.)
2.2. ( )
2.3.
2.4.
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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
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(1999)
IX.
1.0.
2.0. (,
, .)
3.0. ()
4.0.
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X. osteoarthritis
XI. Other joint diseases
1.0. palindromic rheumatism
2.0. intermittent hydrarthrosis3.0. multiple retikulohystiocytosis
4.0. Sinovioma
5.0. chondromatosis of the joint
6.0. Villonodulary synovitis
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X.
XI.
1.0.
2.0.
3.0.
4.0.
5.0. 6.0.
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XII. Non-rheumatic diseases witharthropathy
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
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(1999)
XII.
1.0.
2.0. 2.1. 2.2. 2.3. 2.4.
3.0.
3.1. 3.2.
( ) 3.3. 3.4.
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4.0. endocrine diseases
5.0. nervous
6.0. Diseases of the blood
7.0. Paraneoplastic syndrome (malignanttumors of various sites)
8.0. occupational diseases
9.0. Other diseases 9.1. Sarcoidosis is 9.2.
Periodic disease 9.3. Chronic active hepatitis9.4. hypovitaminosis C
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4.0.
5.0.
6.0.
7.0. ( )
8.0.
9.0. 9.1. 9.2.
9.3.
9.4.
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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)
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(1999)
XIII. 1.0.
1.1. 1.2.
2.0.
3.0. 4.0, .
5.0.
( )
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XIV. Bone disease and osteochondropathy
1.0. bone disease
1.1. Osteoporosis (osteopenia), generalized
1.2. osteomalacia1.3. Osteopathy hypertrophic pulmonary
(Marie-Bamberger syndrome)
1.4. Osteitis deformans (Paget's disease)
1.5. Osteolysis (unspecified etiology)
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XIV.
1.0.
1.1. ()
1.2.
1.3. (-
)
1.4. ( )
1.5. ( )
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2.0. osteochondropathy
2.1. Aseptic necrosis of the femoral head
(Perthes disease) and other sites (Khler'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
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2.0.
2.1.
( )
( I II, .) 2.2.
2.3. (
May, )
2.4. (
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Laboratory studies
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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.
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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
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Laboratory studies in rheumatic diseases
Transaminases, bilirubin - Increase - Pathology of the liverwith "rheumatologic" manifestations of the toxicity of drugs(methotrexate, NSAIDs)
Uric acid - Hyperuricemia Gout
Markers of inflammation
Increased ESR - Active inflammation , a diagnostic criterion forpolymyalgia rheumatica and giant cell arteritis, intercurrentinfection
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
The value of immunological tests in rheumatic
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The value of immunological tests in rheumatic
diseases
Test DiseaseDiagnosis
in tipical
clinic
manifestDif-
Diagnosis Scrining Monitoring
Anti-nuclear SLE +++ ++ - ?Anti-DNA SLE +++ + - +++Anti-body -Sm,
RNP SLE,Mixtpath
+++ +++ - -
3, 4 Nephropaties in
SLE++ ++ - +++
50 SLE + + - +Rheumatoid
factor RA +++ + ? +
The value of immunological tests in rheumatic
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The value of immunological tests in rheumatic
diseases
Test Disease Diagnosis intipical clinicmanifest
Dif-Diagnosis Scrining Monitoring
CRP AR + + - +++Cryoglobulins AR, SLE + - ? +SL-0 ARF ++ ++ - +ANCA Vasculiti
dis +++ ++ - +nti-
phosfolipides APhS +++ ++ - +HLA B-27 AS ++ - - -Anti-body at
Lyme
Lyme d. +++ ++ - +
The disease in which can increase
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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
Autoantibodies in rheumatic
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Autoantibodies in rheumatic
diseases
Type Description Clinical interfacentids DNA Antibodies to double strand of
DNA, have greater specificity
than antibodies to ssDNA
Highly specific for SLE, rarely
detected in other diseases and in
healthy peopleAntiHiston Most diagnostic tools are not
shared by antibodies to the five
main types of histonesSLE, lupus medication, other
autoimmune diseases
Anti ENA Typical diagnosticum to 2
extractable nuclear antibodies
(Sm and RNP -
ribonucleoprotein)
Highly specific for SLE
Anti SSA/Ro ribonucleoprotein SLE (especially subacutecutaneous lupus), lupus neonatal
syndrome ShogrenAnti SSB/La ribonucleoprotein Shogren's syndrome, lupus
erythematosus, SLE newborn
Autoantibodies in rheumatic
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Autoantibodies in rheumaticdiseases
Type Description Clinical interfaceAnti
centromer Antibodies to the centromere /kinetochore region ofchromosome
Limited scleroderma (CREST)
Anti Scl 70 Antibodies to topoisomerase 1DNA
sclerodermaAnti Jo-1 Antibodies to the transfer-RNA
synthetase Poly / dermatomyositis, particularlyin patients with insterstitsialnymlung disease, Raynaud's
phenomenon, cracked skin of
hands (mechanical arm), arthritis,
and resistance to therapyAnti PM-Scl Antibodies to nuclear
components of granular Polymyositis / scleroderma OverlapsyndromeAnti Mi-2 Antibodies to nuclear antigens
of unknown function dermatomyositis
The main indications for diagnostic
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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
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The value of radiology in rheumatic diseases
Disease Thorax Handand foot Sacroiliac Knee joints other
Rheumatoid
arthritis + +++ + + The thoracic spineOsteoarthritis - ++ +++ +++ -AS - - +++ - Lumbar spineReactive arthritis - ++ +++ - Heel boneSLE +++ ++ ++ - -Scleroderma +++ ++ - - The EsophagusGout - ++ - - -Osteoporosis - - - - Densitometry, spine
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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 forprotein
Microscopic analysis ofsynovial fluid, includingcrystals
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
Mi i t f di hi t di t
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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
Application of the morphological study (biopsy) in
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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
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Drugs used to treat rheumatic diseases
Non-steroidal anti-inflammatory drugs for
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Non-steroidal anti-inflammatory drugs fortreatment of rheumatic diseases
Medication Dose Possible side effectsDiclofenac
potassium 100-200 mg/24 h, divided into 2-4 reception
For all NSAIDS:
abdominal pain, orstomach, cramps,
discomfort, edema
(oedema), diarrhea,
nausea, vomiting,
heartburn, dizziness,
headache, allergic
reactions
Diclofenac sodium 100-200 mg/24 h, divided into 2-4, or 100 mgin the form of retard
Etodolak 800-1200 mg/24 h, divided into 2-4 reception.In the form of retard 1 dose 400-1000mg/24 h
Ibuprofen 1200-3200 mg/24 h, divided into 3-4 receptionIndomethacin 50-200 mg/24 h, divided into 2-4, either in the
form of retard 75 mg 1 times a day, 75 mg 2
times dailyKetoprofen 200-225 mg/24 h divided into 3-4 reception or
retard-150-200 mg/24 h 1 times
Meloxicam 7.5 -15 mg/24 h 1 times per dayNaproxen 500-1500 mg/24 h divided 2 receptionNimesulide 100-200 mg/24 to 1-2 receptionPiroxicam 20 mg/24 h in 1-2 reception
Prevention and treatment of GASTROINTESTINAL
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Prevention and treatment of GASTROINTESTINALpathologies resulting from receiving NSAIDS
Antacidshave no data about their effectiveness
H2-blockers
Cure duodenal injury duodenal injury in Warn high
doses were effective at the level of the stomach andeliminate symptoms caused by NSAIDS
Improve semiology
Inhibitors proton pump
is effective for the prevention and treatment of
gastroduodenal of defeatsImproves semiology
Risk factors for the development of renal
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Risk factors for the development of renal
failure in the application of NSAIDs
High riskReducing the volume of circulating blood, as significant bleeding or
hemodynamic disturbances on the type of shock
Severe heart failure
Cirrhosis of the liver with / without ascites
Clinically significant dehydration
Low - medium risk
True kidney disease
diabetic nephropathy
nephrotic syndromehypertensive nephropathy
beginning of anesthesia
The controversial risk
advanced age
C ti t id
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Corticosteroids
Corticosteroids are widely used in the treatment ofinflammatory forms of arthritis and relatedsystemic autoimmune diseases.
In addition to their strong anti-inflammatory effect,
they regulate a wide range of metabolic,immunological and central nervous systemfunction.
For systemic therapy have been issued numerous
synthetic derivatives, but the prednisone,prednisolone, and methylprednisolone are usedmost widely.
C ti t id
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Corticosteroids
Form Relative anti-inflammatorypotential
Equivalent
dose (mg) Elimination half-life (h)Hydrocortisone 1 20 8-12Cortisone 0,8 25 8-12Prednisone 4 5 12-36Methylprednisolone 5 4 12-36Prednisolone 5 4 12-36Dexamethasone 20-30 0,75 36-54
Side effects of long-term
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Side effects of long term
Cortico-Therapy
Frequent Hypertension
Negative calcium balance and secondaryhyperparathyroidism
Negative nitrogen balance Obesity, moon face, supraclavicular fat
accumulation in the area, fat accumulation in theform of a mountain on his back,
Slowing of wound healing, erythema face, thin,fragile skin, blue striae, petechiae and ecchymosis
Acne
Side effects of long term Cortico Therapy
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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
Side effects of long-term
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Side effects of long term
Cortico-Therapy
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
Side effects of long-term
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S de e ects o o g te
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, secondaryamenorrhea
Hepatomegaly as a result of fatty liver
exophthalmosAllergies to synthetic corticosteroids (urticaria,
angioedema)
Pathogenic (Basic) therapy of inflammatory
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Pathogenic (Basic) therapy of inflammatory
rheumatic diseases
Disease modifying antirheumatic drugs(DMARDs) - the basic drugs from diverse group offunds that reduce the symptoms of rheumatoidarthritis (RA) and other inflammatory autoimmunediseases.
In addition, there is increasing evidence thattreatment with DMARD, especially if appointedearly in the course of the disease, can delay theprogression of cartilage and bone.
When the RA is not responding to treatmentDMARD, can be applied biological therapy.Biologicals alter the action of cytokines
Basic therap
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Basic therapy
When to start - an understanding that changes in the jointscan occur within the first 12 months of the debut of RA, led tothe earlier introduction of DMARD and more aggressivecombination DMARD.
Monotherapy - Methotrexate is considered standard therapyfor DMARD.
Combination therapy - Join one or two DMARD therapy withmethotrexate for the background is often used in an attempt
to improve clinical response in those patients who did notgive an answer to monotherapy with methotrexate. The mostcommonly used combinations of DMARD - "triple therapy"(methotrexate + hydroxychloroquine sulfosalazin +) ormethotrexate plus a biological agent.
P th ti (B i ) d
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Pathogenetic (Basic) drugs
Medication Dosage Possible side effectsAzathioprine 50-150 mg/day in 1-3
reception Leukopenia, increasedtransaminaseWobenzym 15-9 drops in 3 reception
Flatulence, change the
color and smell of urine,
rarely allergic reactions in
the form of urticariaCyclophosphamide 50-150 mg per day in
single doseHematuria, hair loss,
leukopenia, amenorrhea,
nausea, vomiting
Cyclosporine 100-400 mg daily in 2receptionHypertension, increased
hair growth, reduced
kidney function,hypertrophy of gum,
tremorHydroxychloroquine 200-600 mg daily in 2-1
reception Violation of, diarrhea, rash
P th ti (B i ) d
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Pathogenetic (Basic) drugs
Medication Dosage Possible side effectsLeflunomid
10-20 mg/day in 1. Treatment
begins with a dose of 100 mg
support screens from 3
consecutive days
Diarrhea, dizziness, hair loss,
hypertension, increased
transaminase, leukopenia, rash on
the skin
Methotrexate 7.5-20 mg/weekDiscomfort in the stomach, skin
rash, headache, photosensitivity,increased transaminase,
leukopenia, ulcers in the mouth,
weakness, fatigueMycophenolate
Mikofenolat 1.5-day Diarrhea, moderate leukopenia
Sulfasalazine 500-3000 mg daily in 2-4reception
Abdominal pain, diarrhea,increased sensitivity, reduced
appetite, nausea, vomiting, rash
on the skinWobenzym 9-15 drops in 3 reception The feeling of crowding in thestomach, nausea, allergies (skin
rashes).
Treatment strategies with drugs
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Treatment strategies with drugs
1. Sequential monotherapy
2. Step-up (ascending) combinationtherapy
3. Step-down (descending) combinationtherapy
4. Combination with a biological agent
Biological therapy
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Biological therapy
One of the most important achievements of thepharmacotherapy of inflammatory rheumaticdiseases associated with the development ofentirely 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 theimmunopathogenesis of these diseases,especially RA.
Immunomodulating and proinflammatory effects of
t ki i th th i f i fl t h ti
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cytokines in the pathogenesis of inflammatory rheumatic
diseases (1)
Vascular endothelial cells - enhance the expression ofadhesion molecules (ISAM-1, VSAM-1, E-selectin)through the activation of NF-kV stimulate angiogenesis,leading to disruption of anticoagulant activity (stimulationof the synthesis of tissue factor, suppression of
synthesis of thrombomodulin).
Lymphocytes - contribute to the development oflymphoid tissue, modification of SV44 and the ability tobind to the ligand.
Dendritic cells - cells induce the maturation andmigration from nonlymphoid organs to secondarylymphocyte organs.
Neutrophils and platelets - contribute to activation.
Immunomodulating and proinflammatory effects of
c tokines in the pathogenesis of inflammator rhe matic
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cytokines in the pathogenesis of inflammatory rheumaticdiseases (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 thesynthesis of PGE2 through activation of COX-2,leukotrienes, platelet activating factor, nitric oxide andreactive oxygen species.
Metalloproteinases - induce the synthesis of
collagenase, gelatinase, stromelysin. Other effects - increase pain, induce cachexia, induce
fever, mobilize calcium from the bones; modulateapoptosis.
Biological therapy
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Biological therapy
The particular interest is the use of monoclonalantibodies.
These drugs have very high specificity, whichprovides a selective effect on certain links in the
immunopathogenesis of disease, minimallyaffecting normal functioning mechanisms of theimmune system.
This can significantly reduce the risk of
"generalized" imunosupresed, which is typical ofmany drugs, especially glucocorticoids andcytotoxic drugs.
Monoclonal antibody to TNF
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Monoclonal antibody to TNF-
Adalimumab
(Adalimumab)
Humman
Mouse
Kimerik
Hummanised
5% -10% protein of the
mouse
100% human protein
25% protein of themouse
100% mouse protein
Infliximab
Adalimumab
Golimumab
Biological therapy
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Biological therapy
The main target for anticytokine monoclonalantibody therapy is:
TNF-alpha (infliximab, adalimumab, etc.)
IL-6 (tocilizumab)CD20 B cells (rituximab)
IL-1, IL-2, etc.
Contraindications of biological
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g
therapy
Congestive heart failure,
Severe infection
Latent tuberculosis
Malignant neoplasms
Pregnancy and lactation.
The need for biological specimens
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The need for biological specimens
Biologicals
Corticosteroids
Basic drugs(methotrexate, sulfasalazine, leflunomid)Thegravityofthecon
ditionofthe
patient
Thenumberofpatients
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THANK YOU!
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What is 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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