Introducere Reumatologie English

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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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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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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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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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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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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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
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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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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 +++ + ? +



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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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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



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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



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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



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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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Documents

Introducere Reumatologie English