RHEUMATOID ARTHRITIS

Dr Dhananjaya Sabat MS DNB MNAMSAssistant Professor Orthopedics

Maulana Azad Medical College, New Delhi

• Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints.

• Affects 1-3% of adult population• F>M: 3 to 1• Peak age of onset -35 and 45

Diagnostic criteria

• ACR criteria (1987); 4 of the following– Morning stiffness > 1hr around joints > 6weeks– Arthritis (pain + effusion) > 3 joints of the 7 joint groups

(PIP, MCP, wrist, elbow, knee, ankle, MTP) > 6weeks – Arthritis of hand joints; PIP, MCP, wrist > 6 weeks– Symmetric arthritis – at least 1 area > 6 weeks– Rheumatoid nodule– +ve Rheumatoid factor– Positive radiological changes (symmetric joint

destruction, erosions, periarticular osteopenia)

2010 ACR-EULAR classification criteria for rheumatoid arthritis

Target population Patients who have at least 1 joint with definite clinical synovitis (swelling) with the synovitis not better explained by another disease

Classification criteria for RA (score-based algorithm: add score of categories A - D;a score of ≥6/10 is needed for classification of a patient as having definite RA).

The metacarpophalangeal joints, proximal interphalangeal joints, the interphalangeal joint of the thumb, second through fifth metatarsophalangeal joint and wrist as small joints, and shoulders, elbows, hip joints, knees, and ankles as large joints

A. Joint involvement 1 large joint 0 2-10 large joints 1 1-3 small joints (with or without involvement of large joints) 2 4-10 small joints (with or without involvement of large joints) 3 >10 joints (at least 1 small joint) 5B. Serology (at least 1 test result is needed for classification) Negative RF and negative ACPA 0 Low-positive RF or low-positive ACPA 2 High-positive RF or high-positive ACPA 3C. Acute-phase reactants (at least 1 test result is needed for classification) Normal CRP and normal ESR 0 Abnormal CRP or abnormal ESR 1D. Duration of symptoms <6 weeks 0 ≥6 weeks 1

PATHOLOGY

• Combination of genetic and environmental factors • An important early event may result from the interaction

of antigen presenting macrophages with T cells (helper/inducer)

• HLA- DR4 is associated • It is defined as an antibody against the Fc portion of IgG• Although clinical laboratories measure IgM rheumatoid

factor, other classes of RF have been described• Generally believed that complexes of IgG rheumatoid

factor with IgG can deposit in blood vessels and lead to vasculitis

Cellular inflammation:• Inflammation in the joint cavity can be intense• Monocyte is most responsible for mediating tissue

destruction; neutrophils also invade• Leading to degradation of articular cartilage, menisci, and

ligaments without restriction

Inciting causes:• Hepatitis B vaccine: rare • potential association between RA and two herpesvirus

infections: Epstein-Barr virus (EBV) and Human Herpes Virus 6 (HHV-6)

Synovitis:• Normally delicate synovial membrane becomes infiltrated with

macrophages, lymphocytes, plasma cells, and granulocytes• Synovitis in RA invades cartilage, ligaments, and subchondral

bone

Rheumatoid nodule: • Central fibrinoid necrosis surrounded by palisades of histiocytes• Seen in 30% cases

Stages:• Proliferative: Swelling, pain with motion, limited

movement, nerve compression• Destructive: Synovial erosion causes irreversible changes

(tendon rupture, capsular weakness and disruption, bone erosion, joint subluxation and deformity)

• Reparative: Fibrosis replaces inflammation (adhesions, ankylosis, fixed deformity)

PRESENTATION

• Monocyclic (10%) – One attack• Polycyclic (45%) – Variable duration, severity

and intervals• Progressive (45%) – Unremitting

CLINICAL MANIFESTATIONS

• Symmetrical polyarthralgia, morning stiffness, and fatigue are common

• Morning stiffness results from increases in extracellular fluid in & around joint

• Later on, there may be limitation of motion due to pain or joint destruction

• Predilection for wrists and hands; MP joints, PIP joints, and wrists are first to become symptomatic

• Ulnar deviation, and swan-neck or boutonniere deformities are common

EXTRA ARTICULAR MANIFESTATIONS:

Patients with extraarticular manifestations have –• High-titer RF• More severe disability • Increased mortality rate

• Heart- pericarditis, cardiomyopathy, and valvular incompetence, interstitial fibrosis

• Lungs: Rheumatoid lung (Honeycombed appearance on CXR due to multiple nodules), Caplan syndrome (associated with pneumoconiosis), Idiopathic pulmonary fibrosis

• Eyes- scleritis (most common ocular complication of RA), scleromalacia perforans)

• Nervous system- mononeuritis multiplex, compression syndromes such as median neuropathy

• Kidneys- amyloid deposition• Hematopoietic system- Felty's syndrome (anemia,

splenomegaly, and leukopenia)• Vasculitis: usually is a non necrotising arteritis of the small

terminal arterials, Skin lesions, leg ulcers, necrotizing arteritis of the viscera, digital infarctions, and fever

• Sjogren's syndrome: occurs in 15%; RA + keratoconjunctivitis sicca, xerostomia

Cervical Spine in RA• Cervical spine involvement is common in RA (upto

90%), more common with long standing disease and multiple joint involvement

Most common presentations:• Atlantoaxial subluxation: most common and may

occur in upto 40%• Atlantoaxial impaction / Basilar invagination• Lower cervical spine: Joints of Lushka & facet

joints are affected, subluxation may occur at multiple levels; more common in males, with steroid use, sero-+ RA, with RA nodules, & severe RA

• Presentation: neck pain, neurologic involvement, myelopathy, radiculopathy

• Investigation: Cross table lateral X-ray, MRI

Treatment: Indications for Surgery

• 1. Space available for the cord: spinal cord compression with < 14 mm of room either at upper or lower cervical spine or with basilar invagination

• 2. Atlas Dens Interval (ADI): Instability is present when 3.5 mm ADI difference on flex/ext views, 7 mm difference may imply disruption of the alar ligaments; difference of > 9 mm is assoc with increase in neurologic injury & will usually require posterior fusion and wiring.

• 3. Myelopathy: neurologic impairment and/or instability are indications for treatment;

• Surgical Options: posterior or anterior cervical fusion.

RHEUMATOID HAND & WRIST1. Palmar subluxation & Radial deviation of wrist • Ulnar carpal complex (UCC) is commonly first leading to rupture of the

triangular fibrocartilaginous complex (TFCC) distally -> DRUJ d/l causing prominent ulnar head “caput ulnar syndrome”-> rupture of EDC 4 and 5.

• Radioscaphocapitate (RSC) or sling ligament is second; joined by incompetence of the radioscapholunate (RSL) causing rotatory subluxation of the scaphoid / loss of radial carpal height; joined by radiolunatriquetral (RLT) and wrist subluxes into anterior position.

• Dorsal radiocarpal(DRC) ligament fails causing ulnar translocation of carpus• Triquetrohamitatocapitate (THC) can deteriorate causing volar intercalated

segment instability (VISI)• Mid-carpal joint is relatively spared usually

2. Extensor Tendon Rupture• EPL Rupture common, t/t: EIP transfer• Vaughn Jackson syndrome: Ulnar side of wrist is most

common site of extensor tendon ruptures (EDC to 4th & 5th digits) due to the attrition over the damaged ulnar head

• EDQ rupture (with intact little EDC) is diagnosed with the Texas long horn sign, in which the index and little finger are extended while the ring and little fingers are flexed; this requires intact extensor indicis and EDQ tendons.

3. Flexor Tendon Rupture FPL>FDP little> index>FDS ring>middle; two usual causes: attrition or direct

4. Ulnar translocation of carpus5. Ulnar drift of the fingers- with radial deviation of wrist,

cause Z deformity 6. Palmar subluxation of MCP

7.Swan neck deformity of fingers: Hyperextension of PIP joints with flexion of DIP joint

8. Boutonniere deformity of fingers: Hyperextension of DIP & MCP joints with flexion of PIP joints

9. Lateral dislocation of any of the IP joints

10. MP subluxation & dislocation11. Intrinsic contracture (as

determined by Bunnel Test)

Elbow:• Synovitis• Posterior subluxation of elbow• Compression neuropathy – ulnar & PINHip: • Protrusio acetabuli: often progressive Flexion deformity

Rheumatoid Foot

• Initially, RA involves the forefoot, then the midtarsal joints, and finally the hindfoot; forefoot is involved twice as often as the hindfoot

Rheumatoid forefoot• - Hyperpronation of rheumatoid foot• - Metatarsalgia• - Claw toesMidfoot:• - Talonavicular arthritis• - Midfoot hyperpronation • Hind foot: calcaneovalgus

LAB TEST• Rheumatoid Factor: Rose Waller test, present in most RA patients

(80 % of affected pts); associated w/ increased morbidity. 5% normal pts also +ve.

False +ve in- SLE, sarcoidosis, TB, syphilis, chronic liver disease • Anti CCP antibody (anti-cyclic citrullinated peptide antibodies): more specific

( 95%) than RA factor.• Synovial Fluid Analysis: joint fluid in RA is sterile & has pleocytosis

(usually PMN), incr protein, & decreased viscosity & decreased complement

• ESR: active RA – elevated; good indicator of response to medical therapy and the activity of the disease

• C Reactive Protein• Normocytic normochromic anaemia

X-ray

• Early changes are limited to the soft tissues w/ fusiform swelling and joint effusion

• Juxta-articular osteoporosis • Cartilage destruction produces

narrowing of the joint• Erosion of bone occurs

characteristically in the metaphyseal region underlying collateral ligament attachments

• Mal-alignment, displacement, and ankylosis of the joint mark end-stage

Differential diagnoses

• Crystal induced arthritis (gout, and pseudogout)• Osteoarthritis• Systemic lupus erythematosus (SLE)• One of the several types of psoriatic arthritis resembles RA• Lyme disease• Reactive arthritis (previously Reiter's disease)• Ankylosing spondylitis• Hepatitis C• Sarcoidosis• Amyloidosis,• Whipple's disease• Hemochromatosis • Acute rheumatic fever• Gonococcal arthritis

TREATMENT Medical Management: 1. NSAIDS 2. Oral Corticosteroids- used to alleviate intractable joint

inflammation or vasculitis 3. DMARDS• Methotrexate: anti folate, hepatic and pulmonary toxicity; first

choice DMARD• Antimalarials: stabilize lysosomal membranes and inhibit IL1,

hydroxychloroquine sulfate, major side effect is macular degeneration

• Sulfasalazine (anti folate activity)• Gold: gold salts (inhibit monocyte function), side effects-

thrombocytopenia, neutropenia, or proteinuria• D-Penicillamine (modulate lymphocyte function)

4. Anti-cytokine agents• Etanercept - TNF type II receptor fused to IgG1 • Infliximab- chimeric mouse/human monoclonal antibody to TNF• Adalimumab- human antibody to TNF • 5. Immunosuppressive agents• Azathioprine• Cyclophosphamide • Cyclosporin A• Leflunomide: inhibit dihydroorotate dehydrogenase, an

essential enzyme in the pyrimidine biosynthetic pathway. Its predominant action is to inhibit the proliferation of T lymphocytes.

Physical TherapySurgical treatment• Synovectomy• Arthroplasty- hip, knee, shoulder, elbow, wrist,

MCP• Arthrodesis- wrist, PIP, MCP• Tendon transfer & reconstuctve surgery of

hand

JUVENILE RHEUMATOID ARTHRITIS

ACR dignostic criteria• Age < 16• Arthritis of 1 or more joints• Symptoms of at least 6 weeks• An onset type after 6 months of observation –

pauciarticular, polyarticular or sysytemic• Exclusion of other forms of arthritis

Types: • Pauciarticular – less than 5 joints involved;

with ANA + iridocyclitis or HLA B 27 + spondylitis

• Polyarticular –5 or more joints affected; RA factor + or -

• Systemic (Still’s disease)• < 20% have progressive destructive disease;

mostly systemic

Pauciarticular:A. With ANA + iridocyclitis• F>M• Onset age < 5yr• Fewer joint involved• 30-35% have chronic iridocyclitis; complications- posterior

synechia, band shaped keratopathy, cataract, glaucoma, blindnessB. With HLA B 27 + spondylitis• M>F• Onset age- >8 years• Arthritis involve lower limbs• Radiographic sacroiliitis• Iridocyclitis, reiter’s seen

Polyarticular:A. Rh factor -ve• F>>M• Symmetrical polyarthritis of small joints of hand, feet, elbow, ankle, knee• Low grade extraarticular manifestation• Inv of temporomandibular joint & cervical spine common• 10-15% develop severe destructive arthritisB. Rh factor +ve• F>M• Onset: late in childhood• Childhood equivalent of adult RA• Symmetric small joint arthritis with rheumatoid nodules, Felty’s synd,

fibrosing pneumonitis• >50% develop destructive arthritis

Systemic (Still’s disease)• M>=F• Intermittent quotidian fever (>1030 F) with chill &

evanescent rash• During fever- myalgia, arthralgia, transient arthritis,

pleuritis, pericarditis, adenitis, abdominal pain• Hepatosplenomegaly• Multiple symmetric joint involvement• Recur in > 50% cases• No iridocyclitis• Inv: leucocytosis, anaemia

Complications:• Flexion deformity at hip, knee, elbow• Triple deformity in knee (Flexion, external

rotation, posterior subluxation; also seen in TB, Polio)

• Growth defects- short stature, tortional deformity in limbs, leg length discripancy

TREATMENT

• Salicylates- promptly relieve symp. Aspirin 100 mg/kg in 5 devided doses

• Steroids in severe systemic disease & iridocyclitis

• Deformity correction, physiotherapy• Synovectomy