Rheumatoid Arthritis

Seredjuk N. M. Miziuk V. M.

Ivano-Frankivsk, 2011

Rheumatoid Arthritis Diagnostic Criteria Pathophysiology Therapeutic Approach Disease Severity and Course

Joint Pain

most common symptom Pain (arthralgia) vs. Inflammation Inflammation:

(fibromyalgia)

(arthritis)

heat, redness, pain, swelling, loss of function inflammatory arthritis (RA, SLE) vs. pain syndrome

Number of Joints Affected

Monoarticular

Oligo/Polyarticular

Crystal-induced Infection Reactive Arthritis Hemarthrosis OA: joint effusions Autoimmune disease

Psoriasis, Behcet's

Monoarticular causes RA SLE Viral infection Acute Serum Sickness Untreated Crystal-induced Vasculidities

RA

Systemic inflammatory autoimmune disorder ~1% of population Onset: 52 years

40-70 years of age <60 - 3-5:1 female predominance

Immunology

Macrophages:

TNF- & IL-1:

Produce cytokines Cytokines (TNF-) cause systemic features Proliferation of T cells Activation of B cells Initiates proinflammatory/jointdamaging processes

TH-1 cells:

Mediate disease processes Activate B cells

B cells:

Release cytokines Plasma cells that produce Ab

Osteoclasts:

Bone erosion Juxta-articular & Systemic osteoporosis

Pathophysiology

Swelling of Synovial lining

Angiogenesis

Rapid division/growth of cells = Pannus

Synovial thickening/hyperplasia Inflammatory vascularized tissue

Cytokine release

Infiltration of leukocytes Change in cell-surface adhesion molecules & cytokines Destruction of bone & cartilage

Bottom Line

Proliferation Destruction of joints Disability

Disease Trigger

Subclinical vs. Viral trigger

Lab manifestations up to 10 yrs before clinical RF & anti-CCP (anticyclic citrullinated peptide) Ab Increased CRP subclinical inflammatory disease

Clinical Presentation

Gradual onset Stiffness & Swelling Intermittent or Migratory involvement Extraarticular manifestations Myalgia, fatigue, low-grade fever, depression

Stiffness & Swelling

Pain with pressure to joint Pain with movement of joint Swelling due to hypertrophy Effusion Heat Redness

Physical Exam

Decreased grip strength Boxing glove edema Carpal tunnel Ulnar deviation Boutonniere/Swan neck deformities Extensor tendon rupture

Extraarticular Involvement

Anemia Rheumatoid nodules Pleuropericarditis Neuropathy

Episcleritis, Scleritis Splenomegaly Vasculitis

Differential

Seronegative polyarthritis Erosive inflammatory OA Psoriatic arthritis Enteropathic arthritis Crystal-induced SLE

Tophaceous gout Pseudogout

Diagnostic Criteria

Symmetric peripheral polyarthritis Stiffness >1 hour Rheumatoid nodules Laboratory features Radiographic bone erosions

Rheumatoid Nodules

Extensor surfaces

elbows

Very Specific Only occur in ~30% Late in Disease

Other Lab Abnormalities

Thrombocytosis Leukocytosis Inflammatory synovial fluid Hypoalbuminemia

Radiology

Evaluate disease activity & joint damage Bony decalcification

Radiological Studies

Plain Films

Bilateral hands & feet Only 25% of lesions Less expensive Through bone cortex around joint margins

Color Doppler & MRI (magnetic resonance imaging)

Early signs of damage i.e. Erosions Bone Edema - even with normal findings on radiography

Mild Disease

Arthralgias >3 inflamed joints Mild functional limitation Minimally elevated CRP No erosions/cartilage loss No extraarticular disease i.e. anemia

Moderate Disease

6-20 Inflamed joints Moderate functional limitation Elevated CRP Radiographic evidence of inflammation No extraarticular disease

Severe Disease

>20 persistently inflamed joints Rapid decline in functional capacity Radiographic evidence of rapid progession of bony erosions & loss of cartilage Extraarticular disease:

Hypoalbuminemia

Prognostic Features

RF & Anti-CCP antibodies Early development of multiple inflamed joints and joint erosions Severe functional limitation Female Persistent joint inflammation for >12 weeks

Staging

Early

<3 months

Established/Persistent

6-12 months

End-stage

Significant joint destruction Functional disability

Management

Early and aggressive disease control

Rheumatologist Referral

Early/Undiagnosed: NSAIDs, short course Corticosteroids Late/Uncontrolled: depends on the presence or absence of joint damage, functional limitation, presence of predictive factors for poorer prognosis

Therapy

Non-Pharmacologic: Assistive devices Weight loss Smoking cessation

Pharmacologic: Anti-inflammatory Interrupt progression Development of erosions Joint space narrowing

Pharmacologic Therapy

Analgesics NSAIDs Glucocorticoids Anticytokine therapy

Analgesics

Topical Capsaicin Diclofenac

Oral Tylenol Opiods

Disease modification

SAARD slow acting antirheumatic drugs DMARD disease modifying antirheumatic drugs

Methotrexate

Dihydrofolate reductase inhibitor

Well tolerated, Mono/Combo Onset: 6-12 weeks

Leflunomide

Cyclophosphamide Anticytokine therapy

Inhibits dihydrooratate dehydrogenase Dec. activated T-cells Onset: rapid Efficacy: 6 weeks

Anti-TNF alpha agents

Azathioprine

Etanercept Infliximab Adalimumab

Disease Course

Long Remission

10%

Intermittent Disease

15-30%

Ankylosing Spondylitis
Clinical History
The patient is a 50-year-old female who is complaining of pelvic pain

AS: flat lumber spine, loss of lordosis, use hips for binding

Radiographic Findings

Ankylosis of sacroiliac joints Syndesmophytes in the lumbar spine Fusion of the interspinous ligament Arthropathy of both hips Enthesopathy of ischial tuberosity

Imaging Modalities

Radiographs are the most important for detection, diagnosis, and follow-up

limited in early sacroiliac changes

MRI able to assess early cartilage abnormalities and bone marrow edema magnetic resonance imaging

Recurrent Iritis caused Synechiae (adhesions between the lens and iris)

Early Sacroiliitis

Advanced Sacroiliitis, Fused SI joints

Syndesmophytes, apophyseal joint fusion, disc peripheral ossification

Left: squaring of vertebra, Rt.: ant. longitudinal calcification

Ankylosing Spondylitis: Bamboo spine, ossification follow the contour of intervertebral discs

Ankylosing Spondylitis: calcaneal spur and erosion

Apical fibrosis in Ankylosing Spondylitis

Differential Diagnosis

Gout Psoriatic arthritis Rieters syndrome Rheumatoid arthritis Spondylodiskitis

Ankylosing Spondylitis Features

Chronic & progressive form of seronegative arthritis with axial skeleton predominance Affects 0.1-0.2% of the population 90-95% of patients are HLA-B27 positive

7% of general population is positive, only 1% of positives will develop ankylosing spondylitis

Male:female 4-10:1

Features cont.

Age of onset 15-35 years old

juvenile onset associated with more frequent & severe hip & peripheral joint involvement

Life expectancy unaffected, although 20% morbidity

most patients able to maintain a normal lifestyle

Features cont.

Starts with sacroiliac joints

begins with sclerosis, eventually get ankylosis

Progresses to include facet joints, spine, iliac crest, ischial tuberosity, greater trochanter, hips, patella, calcaneus, glenohumeral joints

peripheral joint involvement in 30%

Features cont.

Enthesopathy - calcification & ossification of ligaments, tendons, joint capsules at insertion into bone Erosion of subligamentous bone due to inflammatory response Fusion of interspinous ligament

Dagger sign

Features cont.

Syndesmophytes - bony bridges between vertebrae & ossification of joint capsule

Bamboo spine

Resorption of vertebral endplates Soft tissue findings are new bone formation in outer layers of annulus fibrosis as well as chronic synovitis and capsular fibrosis

Physical Findings

Patients usually present with low back pain and stiffness, which improves with activity Decreased range of motion in lumbar spine Thoraco-cervical kyphosis (late) One-third of patients will have acute, unilateral uveitis

Other Complications

Pseudoarthrosis (Anderson lesion), cervical spine fracture, C1-C2 subluxation Peripheral joint ankylosis Restrictive lung disease, upper lobe fibrosis Aortic root dilation (20%) & murmur (2%)

Treatment

Posture training & range of motion exercises to prevent kyphosis Sleep prone or supine in firm bed, no pillow Breathing exercises NSAIDs for symptomatic relief

Gout

Gout

Gout is defined as a peripheral arthritis resulting from the deposition of sodium urate crystals in one or more joints.

Gout
Gout encompasses a group of disorders that occur alone or in combination and include hyperuricemia, attacks of acute, typically monarticular, inflammatory arthritis, tophaceous deposition of urate crystals in and around joints, interstitial deposition of urate crystals in renal parenchyma, and urolithiasis.

Gout

Affects less than 0.5% of the population Due to familial disposition, incidence may be as high as 80% in families affected by disorder.

Gout

Typical sequence involves progression through:

asymptomatic hyperuricemia acute gouty arthritis interval or intercritical gout chronic or tophaceous gout

Pathophysiology

Urate saturates in plasma at 7 mg/dL Urate crystals deposits in less vascular tissue

Cartilage Tendons/ligaments

There is a predilection for peripheral joint/tissue

Pathophysiology

Primary gout:

Overproducers: 10% Under-excretors: 90%

Secondary gout:

Excess nucleoprotein turnover (lymphoma, leukemia) Increased cell proliferation/death (psoriasis) Rare genetic disorder

Acute attack:

Over hours frequently nocturnal Excruciating pain Swelling, redness and tenderness Podagra: classic presentation May effect knees, wrist, elbow, and rarely hips.
Destructive tophacous Much greater chance if untreated Rarely presents as a chronic

Chronic:

Signs and Symptoms

Renal lithiasis Uric acid nephropathy Urate nephropathy

Diagnosis

Based on history and physical Confirmed by arthrocentesis Uric acid level non specific.

30% may show normal level

Urine collection:

<800 mg underexcertor

Microscopic Diagnosis

X-ray Acute
Soft

tissue swelling

Chronic

chronic tophaceous gouty arthritis, extensive bony erosions are noted throughout the carpal bones Sclerosis and joint-space narrowing are seen in the first metatarsophalangeal joint, as well as in the fourth interphalangeal joint .

Differential Diagnosis

Septic arthritis: must be excluded Acute Rheumatic fever Palindromic Rheumatism Psoriatic arthritis

Treatment

Acute:

NSAIDs anti-inflammatory doses Colchicine 0.5 mg po q2 hours, may require 6 mg.

Stop with response or side effect Can be used for chronic disease, increased risk for suppression

Aspirate followed by administration of corticosteroids Prednisone Solumedrol Opiates and Tylenol

Treatment

Chronic:

Diet will decrease uric acid 1 mg/dL at best Weight loss Modification of medications

Avoid low dose ASA, diuretics, etc.

Treatment

Chronic

Probenicid: Sulfinpyrazone: toxic side effects Avoid with renal disease Consider NSAIDs to avoid exacerbation of gout

Treatment

Chronic

Indications for Allopurinol

Tophaceous deposites Uric acid consistently >9 Impaired renal function

Consider NSAIDs to avoid exacerbation

Prognosis

Generally good Up to 50 % progress to chronic disease if untreated. Surgical intervention may be required for tophi.

Thank you!