Rheumatoid Arthritis Flashcards
Rheumatoid arthritis is a chronic ____ disorder of __, as well as __. There is a set pattern of __, elevated __ (2).
Pathology begins with inflammation of __, proliferation causing __ that invades bone, cartilage and ligaments leading to __ and __.
Chronic systemic inflammatory disorder
Joints as well as extra-articular manifestation
Joint involvement, autoantibodies (RF, ACPA)
Synovium
Pannus
Damage and deformity
Model of natural pathogenesis of RA
Predisposing factors
1. Genetics - HLA-DR-B
2. Smoking (21 fold)
3. Bacterias and viruses
- Porphyromonos gingivalis, prevotella copri
- EBV, parvovirus B19
Preclinical RA: autoimmunity without synovitis
4. Autoantibodies: RF, ACPA
Clinical RA
5. Initiation
- Target citrullinated proteins in joints
- Immune complex deposition in synovial venules incite inflammation and complement activation
- Increased vascular permeability and influx of more inflammatory cells and antibodies
- Osteoclastogenesis, chondrocyte damage
- Perpetuation via adaptive immune activation
Differential diagnosis of RA
Common
1. Seronegative spondyloarthropathies
2. CPPD
3. CTD - SLE, scleroderma, polymyositis, vasculitis, MCTD, PMR
4. Osteoarthritis
5. Viral infection (EBV, HIV, Hep B, parvovirus, rubella, Hep C)
6. Polyarticular gout
7. Fibromyalgia
8. Reactive arthritis
Uncommon
1. Hypothyroidism
2. Relapsing polychondritis
3. Subacute bacterial endocarditis
4. Rheumatic fever
5. Haemochromatosis
6. Sarcoidosis
7. Hypertrophic osteoarthropathy
8. Lyme disease
9. Hyperliproproteinaemia
10. Amyloidosis
11. Sickle cell disease
12. Malignancy and paraneoplastic
13. Behcet’s disease
Rare
1. Familial Mediterranean fever
2. Whipple’s disease
3. Multicentric reticulohistiocytosis
4. Angioimmunoblastic lymphadenopathy
5. SAPHO - synovitis, acne, pustulosis, hyperostosis and osteitis
ACR-EULAR 2010 Criteria for Classification of RA
Score of 6 or more
- Joint involvement
- Large joints vs small joints - Serology
- Negative, low positive or high positive - Acute phase reactants
- Duration of symptoms - > 6 weeks
Epidemiology of RA
- All races, more in Native Americans
- Female > males (3:1)
- Middle age 40-60 years, prevalence increases with age
Patterns and variations of RA
Typical pattern
1. Insidious (65%) - onset with arthritic symptoms of pain, swelling and stiffness, increasing number of joints over weesk to months
2. Subacute (20%) - similar to insidious, but more systemic symptoms
3. Acute (10%) - severe onset, might even have fever
Atypcial pattern
4. Palindromic (episodic) - < 5 joitns, resolves with days, with recurrent flare and eventual evolvement into persistent pain and deformity
5. Insicious in elderly > 65 - severe pain and sitffness of limb girdle joints with diffuse swellling of hands, wrists, forearm. Difficult to differentiate from PMR, PS3PE
6. Arthritis robustus - in men, with bulky proliferative synovitis causing joint erosions and deformities, minimal pain or disability
7. Rheumatoid nodulosis - recurernt pain/swelling in different joints, subcutaneous nodules, subchondral bone cysts on radiography
Pattern and progression of RA joint involvement
What are the most/lesser commonly affected joints in RA?
What are the atypical joints to prompt alternative diagnosis?
- Small joints involvement first, then large joints
- Oligoarticualr onset, progressing into polyarticular and symmetrical distribution over weeks to months
Commonly affected joints
1. MCP (90-95%)
2. PIP (75-90%)
3. Wrist (75-80%)
4. Knee (60-80%)
5. Shoulder (50-70%)
6. MTP (50-60%)
Less commonly affected joints
7. Ankle/subtalar (50-60%)
8. Cervical spine (C1-C2) (40-50%)
9. Elbow (40-50%)
10. Hip (20-40%)
11. Temporomandibular (10-30%)
Atypical joints
1. Thoracolumbar - OA
2. Sacroiliac - seronegative spondyloarthritis
3. Hands DIPJ - OA, psoriatic arthritis
What are the clinical and laboratory findings to predict whether early undifferentiated arthritis (UA) will develop into RA?
- Higher ACR/EULAR 2010 score but not fulfilling criteria
- 42% with score of 5 develops RA (score 6 = RA)
- Number of involved joits, duration of symptoms, presence of autoantibodies, elevated inflammatory markers - Grey scale synovitis on ultrasound
Pannus is a _____
- Inflammatory infiltrates of (5) lead to organisational structure resembling __, triggering synovial lining cells to proliferate, becomes __, __ and ________
- _____ in pannus may invade __ and __ leading to __ of joint
Proliferative synovium
Infiltrates of: CD4+ T lymphocytes, macrophages, B cells, plasma cells, dendritic
Synovium inflamed and becomes thickened, boggy and oedematous/villous projections
Fibroblast-like synoviocytes in pannus invade bone and cartilage, leading to destruction of joints
Joint deformities in RA
A. Hand deformities
1. Fusiform swelling over PIPJ (synovitis - spindle shaped)
2. Boutonniere deformity - flexed PIPJ, hyperextended DIPJ (extrinsic extensor tendon weakening, palmar displacement of lateral bands)
3. Swan-neck deformity - flexed MCPJ, hyperextended PIPJ, flexed DIPJ (intrinsic muscle of MCPJ contracture)
4. Ulnar defiation of fingers with radial deviation of wrist (subluxation of MCPJ, weakened ECU)
5. Z-thumb/Hitchhiker thumb - hyperextended IP, felxed MCP, adducted metacarpus, unable to pinch
6. Piano key ulnar head - floating ulnar styloid (ulnar collateral ligament destruction)
B. Feet deformity
1. MTPJ squeeze test positive - synovitis
2. Claw toe or hammer toe - MTPJ inflammation, subluxation of MT heads
3. Callus and ulcer formation
- difficulty fitting toes into shoe, tops of toes rub onto shoe box
- MT heads not cushioned, inferior surface of foot calluses
- Feels like walking on pebbles or stones
4. Pes planus and hindfoot valgus deformity - tarsal and subtalar joint involvement
C. Spinal deformity
1. C1/C2 subluxation - anterior (commonest), lateral (rotary), posterior (least common) atlantoaxial subluxation
- Widened gap between arch of C1 and odontoid of C2 (>3mm) -> ruptured transverse and alar ligament
(highest risk of compression if gap anteriorly 9mm or more, posteriorly 14mm or more)
2. C1/C2 impaction - superior migration of odontoid into foramen magnum and impinges brainstem
(Odontoid 5mm or more above Ranawat’s line)
3. Subaxial involvement of C2/C3 and C3/C4 facets and intervertebral disc (stiar stepping) - vertebrae subluxed forward on lower vertebrae 3.5mm or more
Radiographic features of RA
(M: ABCDES)
What are the key differences in radiography of RA vs OA?
A: aligment abnormal, but no ankylosis
B: bone periarticular (juxtaarticular) osteoporosis, no periostitis or osteophytes
C: cartilage uniform/symmetric joint space loss in weight bearing joints, but no cartilage or soft tissue calcification
D: deformities - Swan neck, ulnar deviation, Boutonniere in symmetrical distribution
E: erosions marginal
S: soft tissue swelling, nodules without calcification
Describe the early and late radiological progression of RA
Early
1. Juxtaarticular osteopenia
2. Joint erosions at margins of small joints
(hands 2/3/5 MCPs, feet 1/5 MTPs)
Late
3. Diffuse osteopenia
4. Joint space narrowing
5. Fixed deformities
Extra-articular manifetations of RA
A. General - fever, lymphadenopathy, weight loss, fatigue
(Only in severely active RA disease activity)
B. Dermatologic
- Palmar erythema
- Subcutaneous nodules
- Vasculitis
- Pyoderma gangrenosum
C. Ocular
- Episcleritis and scleritis -> scleral thinning -> scleromalacia perforans and corneal melt (blinding!)
- Choroid and retinal nodules
- Sicca symptoms in coexisting SS
D. Pulmonary
- Pleuritis and pleural nodules (Caplan’s syndrome)
- Interstitial lung disease and fibrosis
- Obstructive lung disease - airway thickening, bronchiolitis, bronchiectasis
- Arteritis
- Pleural effusion
E. Cardiac
- Pericarditis, myocarditis
- Coronary vasculitis
- Valve nodules
F. Neuromuscular
- Entrapment neuropathy (median, ulnar, radial)
- Peripheral neuropathy
- Mononeuritis multiplex
G. Haematologic
- Anaemia
- Felty syndrome - RA, neutropenia, splenomegaly
- Large granular lymphocyte syndrome
- Lymphomas
H. Renal - nephrotic syndrome
- Membranous GN
- Mesangioproliferative GN
- Mesangiocapillary GN
- Chronic tubulointerstitial nephritis
- Renal amyloidosis
- Tubulointerstitial nephritis, papillary necrosis, MCD (from NSAIDs)
I. Others
- Sjogren’s syndrome
- Amyloidosis
- Osteoporosis
- Atherosclerosis
What are the risk factors for extra-articular RA manifestations?
- Dual-positive RF and ACPA
(ACPAs alone strongly associated with articular RA severity, but not strongly associated with extra-articular) - HLA-DR4 positive
- Males
What are rheumatoid nodules?
What are the differential diagnoses to consider?
Subcutaneous nodules with histology of central area of fibrinoid necrosis surroundewd by zone of palisades of elongated histiocytes and peripheral layer of cellular connective tissue
Occurs in 20-35% RA patients, RF positive, severe disease
Reversible - occurs in active disease, resolves when controlled
Rarely develop paradoxical methotrexate nodulosis (usually as small, multiple nodules over finger pads)
Sites:
1. Forearm extensors
2. Olecranon bursa
3. Joints and pressure points (sacrum, occiput, heel)
Differentials
1. Xanthoma (cholesterol)
2. Gouty tophi
3. SLE (rare)
4. Amyloidosis
5. Rheumatic fever and subcutaneous nodules
6. Sarcoidosis
7. Multicentric reticulohistiocytosis
8. Leprosy
9. Granuloma annulare (no arthritis, RF neg, common in children)
DMARDs in RA
