Rheumatoid Arthritis

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IN THE NAME OF GODRheumatoid Arthritis2 Rheumatoid ArthritisA chronic multisystem disease

Characteristic feature:Persistent inflammatory synovitis

Peripheral joints

Symmetric

Cartilage damage and bone erosions

Destruction3

Epidemiology and Genetics4 EpidemiologyMost common form of chronic inflammatory arthritis

Prevalence :~1% (range 0.32.1%)

women: 3 times more often than men

Throughout world; all races

5 EpidemiologyOnset: 4 and 5 decades of life

Incidence between 25 and 50 y6 GeneticsFirst-degree relative 2-10 times

Concordant in monozygotic twins 1520%

7 GeneticsMajor genetic risk factors class II HLA

HLA-DR4 (DR1*0401) and related alleles

8 Environmental factors Climate and urbanization Incidence and severity of RA

Smoking : Relative Risk: 1.5-3.5

Severe RA with antibodies to CCP

9 Etiology 1011ANTIGENGenetic BackgroundMACROPHAGE12DRMACROPHAGEIL -1 CD80/8613ANTIGENDRMACROPHAGET-CELLCD4+IL -1 CD80/86CD 2814Genetic BackgroundIL- 1ANTIGENMACROPHAGET CELLIL 2B CellANTIBODY15AUTOIMMUNE REACTIONGenetic BackgroundIL- 1ANTIGENMACROPHAGET CELLIL 2B CellIMMUNE COMPLEXANTIBODY16AUTOIMMUNE REACTIONGenetic BackgroundIL- 1ANTIGENMACROPHAGET CELLIL 2B CellANTIBODYIMMUNECOMPLEXCOMPLEMENTTARGETINFLAMMATION17HYPOTHALAMUS PITUITARY GLAND ADRENAL CORTISOL IL-1, IL-6, TNFDHEABRAIN STEMESTROGENAUTONOM SYNOVITISRA: Plasma cortisolNature 2007Cortisol Cortisone11 -HSD111 -HSD2Arth Rheum 2005Abnormal receptor

Abnormal postreceptor ADENOSIN ONSET18 OnsetIn 2/3 of patients begins with: - Fatigue, anorexia, generalized weakness

This prodrome may persist for weeks or months

19 OnsetSpecific symptoms appear gradually - Especially: hands, wrists, knees, feet - Symmetric

1/3 of patients Initially one or a few joints

20 ARTICULAR SIGNS & SYMPTOMS21 Articular Most common manifestation: - Pain

An almost invariable feature: - Morning stiffness of >1-h

Constitutional symptoms: - Weakness, easy fatigability, anorexia, and weight loss22 Articular Synovial inflammation causes: Swelling

Tenderness

Limitation of motion

Warmth

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Articular Initially, impairment in physical function is caused by: - Pain and inflammation

Later: - Fibrous or bony ankylosis 24 Articular Symmetric Certain specific joints: - Wrist joints - MCP, PIP - Synovitis of the elbow Flexion contractures - Knee - Forefoot, ankles, and subtalar - Hip & shoulder DIP: rareNot affect lumbar and thoracic spine

25 Articular Synovial joints of C1-C2: - On occasion - Atlantoaxial subluxation - Pain in the occiput - Rarely: compression of the cord

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Articular Characteristic joint changes: Hand: - "Z" deformity Radial deviation at wrist Ulnar deviation digits27

Articular Characteristic joint changes: Hand: - Swan-neck deformity PIP hyperextension DIP Flexion 28

Articular Characteristic joint changes: Hand: - Boutonnire deformity PIP flexion DIP extension 29

Articular Characteristic joint changes: Hand: - Thumb Hyperextension of the first IP Flexion of the first MCP 30

Articular Characteristic joint changes: Foot: - Hallux valgus - Eversion at hindfoot - Plantar subluxation of the metatarsal heads - Widening of the forefoot - Lateral deviation and dorsal subluxation of the toes 31

EXTRAARTICULAR MANIFESTATION 32 Extraarticular ManifestationRA is a systemic disease

40% of patients

As a rule: occur in high titers of RF or antiCCP33 Rheumatoid noduleIn 2030%

On areas subjected to mechanical pressure

Elsewhere34

Rheumatoid noduleCommon locations: Olecranon bursa, proximal ulna, Achilles tendon, occiput

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Vasculitis Severe RA and high titers of RF

Can affect nearly any organ

Polyneuropathy and mononeuritis multiplexCutaneous ulceration and dermal necrosisDigital gangreneVisceral infarction

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Vasculitis Uncommon

Renal vasculitis is rare

37 Pleuropulmonary Pleuritis: - Most common pulmonary manifestation

- Autopsy Common

- Symptomatic Infrequent

38 Pleuropulmonary ILD

Pulmonary nodules

39 Cardiovascular Pericarditis: - Asymptomatic - 50% in autopsy

Congestive heart failure

IHD

40 Cardiovascular Most common cause of death

Inflammatory markers

41 Nervous systemCentral nervous system Spare

Vasculitis Peripheral neuropathy

Atlantoaxial subluxation

Nerve entrapment 42

Eye