Dr. Müge Bıçakçıgil Kalaycı

Second most common form of chronic arthritis

Chronic, insidious, autoimmune inflammatory disorder

Symmetric polyarthritis affecting mainly small joints in the hand and feet, as well as larger joints such as the wrist and shoulders

Characteristic deformities include subluxations, dislocations, rheumatoid nodules, and joint contractures.

Crippling disease Shortens survival quality of life

Twin and family studies demonstrate a heritability of 60%; approximately 30% of genetic risk is attributed to the shared epitope encoded on the human leukocyte antigen molecules.

Patients with HLA-DRB1 alleles may have a poorer prognosis

Hormonal and reproductive factors contribute to the female excess and parity, breast feeding, and exogenous hormones are modifiers of risk.

Smoking is the strongest known environmental risk factor for RA

The cause of rheumatoid arthritis is unknown

Genetic predisposition Enviromental event (such as infection) inappropriate self-directed immune response

Infectious agents,Immunoregulatory and hormonal irregularities

Immune mediated chronic inflammation

Trigger:Environmental

Antigen

Genetic (30%)Self Antigen

T cell activation

Chronic InflammationLymphoid cells infiltrate synovium

New blood vessels form in synoviumSynovial proliferation

Joint destruction

Synovial mass stretches joint capsule and ligaments: joint swelling, instability & deformity

Cytokine and proteolytic enzyme rich synovial fluid destroys cartilage joint space narrowing on X-rays

Infiltration of cartilage and later bone by invading synovium (pannus) marginal erosions

Prevalence 0.05-0.15/1000 in developed nations.

Disease onset most common at 25-55 years of age

Incidence rises with age

Women:men 2.5:1

The distribution of involved joint is a critical clue to the underlying diagnosis.

RA can effect any of the synovial joints.

The disease starts in the MCF, PIP,MTF joints Followed by the wrist, knees, elbows, ankles,

hips, and shoulders

Symptoms include pain , swelling, and stiffness

Stiffness often predominating in the mornings

Early treatment helps limit the number of joints involved

RA almost always spares DIP joints

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MCP joints Synovitis Ulnar deviation

PIP joints Synovitis Swan neck deformity Boutonniere deformity

Z-deformity of thumb Tendons

Flexor tenosynovitis Extensor tenosynovitis

Poor grip: power and pinch

Wrist

Synovitis Subluxation Radial deviation Ankylosis Carpal tunnel syndrome

Synovitis Flexion contracture Decreased, painful pronation and

supination Olecranon bursitis RA nodules

MTP Synovitis Subluxation with hammer toe and

metatarsalgia Toe deviation/overriding

Collapse of medial arch of foot

Ankle Synovitis Retrocalcaneal bursitis

Tenosynovitis/rupture Peroneal tendons Tibialis posterior

Subtalar arthritis Reduced and painful movement

Synovitis Effusions Baker’s cyst +/- rupture Instability/ deformity eg valgus

deformity Flexion contracture

Arthritis (usually late) Pain especially on weight bearing Reduced movement

Trochanteric bursitis

SHOULDER Subacromial bursitis Rotator cuff tendinitis Glenohumeral joint arthritis Acromio-clavicular arthritis

Involved in 70% patients with longstanding RA

Occipital pain made worse by movement

Subluxation of C1-2 with compression of spinal cord during neck flexion Significant if >10 mm instability on flexion Usually slowly developing myelopathy

TMJ: reduced mouth opening

Sternoclavicular

Crico-arytenoid

Ossicles of ears

Systemic features;

-fatigue, -weight loss, and -low grade fevers (≤ 38 ⁰C)

-more common in those patients with rheumatoid factor (seropositive)

Approximately one –quarter of patients In patients who are seropositive for rheumatoid

factor.

Nodules may ocur almost anywhere lungs, heart, and eye,

Most commonly occur subcutaneously on extensor surfaces particullary forearms , over joints or pressure

points

Firm on examination

Usually nontender( unless traumatized)

Tought to be triggered by small vessel vasculitis.

Lungs Pleurisy Pleural effusions ( exudate!) RA nodules single/multiple (Caplan

syndrome if huge nodules in coal miners) Lung fibrosis

RA associated small vessel vasculitis Digital infarcts Leukocytoclastic vasculitis should prompt more aggressive treatment

with disease – modifying antirheumatic drugs (DMARDs).

Pyoderma gangrenosum

Patients with RA have significantly increased morbidity and mortality from coronary artery disease.

chronic inflammation, some of medications used, and sedantary lifestyle may be significant risk

factors.

Pericardial effusions common (detected in up to 50 % of patients by

echocardiography) usually asymptomatic. Rarely, may result in a fibrinous pericarditis,

and constrictive pericarditis

Uncommonly, rheumatoid nodules may occur in the conduction system and cause heart block.

 

Secondary Sjögren syndrome Episcleritis Scleritis Scleromalacia perforans

Peripheral nerve entrapment syndromes Carpal tunel syndrome Tarsal tunel syndrome

Vasculitis - monoeuritis multiplex

Subluxations at C1-C2 -myelopati.

Rheumatoid nodules in the central nervous system usually asymptomatic

The triad of RA, Splenomegaly, and Neutropenia.

In patients with severe , seropositive disease

May be accompanied by hepatomegaly, thrombocytopenia, lympadenopathy and fevers

Most patients -do not require specific therapy

Treatment should be focused on severe RA.

Splenectomy -if severe neutropenia exists (<500 cells/µL) a

- recurrent bacterial infections

Infections More susceptible to any infection (RA,

steroids, MTX) ESPECIALLY susceptible to joint infections

Always suspect septic arthritis if sudden increase in symptoms in one joint

Osteoporosis and fractures RA Immobility Steroids

Amyloidosis Rare Longstanding disease Proteinuria/decreased renal function

Lymphoma

DIAGNOSIS & EVALUATION

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Laboratory ESR/ CRP Rheumatoid factor: performed only at

baseline to establish the dx; may be repeated 6-12 ms after disease onset if negative initially

ANA Anti-CCP (anti-cyclic citrullinated

peptide)

CBC, electrolyte, Cr, hepatic panel, U/A, : performed at baseline to assess organ dysfunction due to comorbid diseases, before starting medications

SF analysis: performed at baseline if necessary, to rule out other disease; may be repeated during disease flares to rule out septic arthritis

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Radiography Radiography of selected involved joints May have limited diagnostic value early in

the disease, but helps to establish a baseline for periodically monitoring disease progression and response to treatment

bone scan, MRI

Post viral (parvo, rubella) Reactive arthritis SLE Polyarticular Gout Polyarticular OA

1. Morning stiffness in and around the joints lasting at least 1 hour

2. At least 3 joint areas simultaneously have had soft tissue swelling or fluid (PIP, MCP, wrist, elbow, knee, ankle, and MTP)

3. At least 1 area swollen (as defined above) in a wrist, MCP, or PIP joint

4. Symmetical involvement of the same joint areas (as defined in 2)

5. Subcutaneous nodules over bony prominences, extensor surfaces, or in juxta-articular regions

6. Postive serum Rheumatoid Factor7. Radiographic changes typical of rheumatoid arthritis

on hand and wrist radiographs (must include erosions )

Need 4 of 7 for Diagnosis

Joints (0-5)1 large joint 02-10 large joints 11-3 small joints (large joints not counted) 24-10 small joints (large joints not counted) 3>10 joints (at least one small joint) 5Serology (0-3)Negative RF and negative ACPAs 0Low-positive RF or low-positive ACPAs 2High-positive RF or high-positive ACPAs 3Symptom duration (0-1)<6 weeks 0≥6 weeks 1Acute-phase reactants (0-1)Normal CRP and normal ESR 0Abnormal CRP or abnormal ESR 1

ACR/EULAR 2010 CLASSIFICATION CRITERIA FOR RHEUMATOID ARTHRITIS

Cutpoint for RA: ≥ 6/10).

RFs are human auto-Abs that react with the Fc portion of normal polyclonal IgG.

Named thus because their first description was in patients with rheumatoid arthritis

RF test is approximately 65%-75% sensitive for the diagnosis

The presence of RF, even in high titers or large amounts, is not specific for RA

Rheumatologic Diseases Rheumatoid arthritis (~70%) Sjögren’s syndrome (~90%) Lupus (~20%) Cryoglobulinemia syndrome (90%)

Lung Diseases Interstitial fibrosis Silicosis

Infections Hepatitis C virus Acute viral infections Endocarditis Tuberculosis

Miscellaneous Sarcoidosis Malignancies Aging

There are other RA-associated auto-Abs known to be specific for rheumatoid arthritis Perinuclear factor Antikeratin antibodies

Early stage Soft tissue swelling

Intermediate stage Mild juxtaarticular

osteoporosis Narrowing of joint

spaceand bone erosions

Late stage Large erosions,

anatomic deformities, ankylosisBower AC. In: Klippel JH, Dieppe PA, eds. Bower AC. In: Klippel JH, Dieppe PA, eds. RheumatologyRheumatology. .

Vol 1. 2nd ed. Philadelphia, PA: WB Saunders; 1998;5:5.1–5.8.Vol 1. 2nd ed. Philadelphia, PA: WB Saunders; 1998;5:5.1–5.8.Resnick D et al. In: Kelley WN et al, eds. Resnick D et al. In: Kelley WN et al, eds. Textbook of RheumatologyTextbook of Rheumatology. 5th ed. . 5th ed. Philadelphia, PA: WB Saunders; 1997:626–685.Philadelphia, PA: WB Saunders; 1997:626–685.

MANAGEMENT & THERAPY

Nonpharmacologic rest

fatigue, splinting pain relief

cold, ultrasound,massage physical therapy occupational therapy Patient education

Pharmacologic analgesics NSAIDs - full dose corticosteroids

prednisone at low dose - “bridge”, “burst” intra-articular steroids

every patient should be considered for at least one modifying agent

limitations may not prevent damage

may not be tolerated due to toxicity

Methotrexate Sulfasalazine Antimalarials Gold Salts Penicillamine Cyclophosphami

de Azathioprin

hydroxychloroquine mild non-erosive disease combinations 200 mg bid eye exams

Sulfasalazine 1 gm bid - tid CBC, LFTs onset 1 - 2 months

Methotrexate most commonly used drug fast acting (4-6 weeks) po, SQ - weekly CBC, LFTs

Leflunomide (Arava)

Tumor Necrosing Factor InhibitorsEtanercept (Enbrel)Infliximab (Remicade)Adalimumab (Humira)

Interleukin – 1 Receptor Antagonists

Soft tissue: Carpal tunnel release Synovectomy Tendon transfers

Joint replacement Arthodesis

Life expectancy reduced by 7 years in men 3 years in women

Severe morbidity sudden onset do better than gradual early knee involvement bad Bad RA has a worse prognosis than

Hodgkins disease