| What is rheumatoid arthritis (RA)? | It is the most common inflammatory rheumatic disease (causes classic rheumatism)
The prototype of auto-immune disease, typically affects small and medium sized joints symmetrically
It is a chronic destructive disorder, treated to avoid destruction and inflammation. |
| How is the pathogenesis of RA? | It causes cartilage breakdown, bony erosion and loss of function ultimately in some joints.
Primary lesion is synovitis, the leading to the formation of inflammatory pannus.
Causes systemic manifestations and reduces life expectancy |
| How is the epidemiology of RA? | 1-3 % of europians, regional variation (acc to genetics and environment)
Women are three times more likely to get it.
Variable course of action (execerbation and remission vary from one person to another) |
| What are the auto-antibodies seen in RA? | Rheumatoid Factor (RF): targets Fc of IgG, not very specific but sensitive (60-70%)
Anti-Citrullinated Peptide Ab (ACPA/ Anti CCP): Attacks citrullinated aa at peptides (arginine), occurs in lungs due to smoking and causes RA, These Ab are highly specific for RA only and is as sensitive as RF.
Can be detected pre clinical RA, confirms RA |
| How is the pathobiology of RA? | Genetic predisposition (HLA) with environmental factors (smoking Increase ACPA, RF, TB) to give pre RA seen by elevated ACPA, then a trigger occurs (trauma, infection...) that leads to an inflammatory response triggering RA to start |
| What are the risk factors that give RA? | Genetics (60% heritability, ACPA + or HLADR4/DR1, it is a polygenic disease)
Smoking (most common factor, more difficult, erosive and severe RA, induces protein citrullation)
Periodontal disease (oral flora imp to take care of oral hygiene)
Other factors (coffee, mineral oils, silica dust, alcohol, pregnancy) |
| How is the physiopathology of RA? | APCs present ACPA, then go to T cells and stimulates formation of ACPA Ab, activating inflammatory cytokines
Another mechanism is by Ag-Ab complexes accumulating in the joint increasing synovitis
In addition, increased cytokines start inflammation, angiogenesis and osteoclastic stimulation thus increasing bone resorption systematically |
| What are the anti-inflammatory cytokines? | TGF-beta, IL10 |
| What are the clinical aspects of RA? | Articular Manifestations: swelling of polyarticular small joints (PIP, MCP, wrist, MTP, TMJ but never DIP)
To test swelling, touch all joints squeeze them and touch lateral edges see consistency
Extra Articular manifestations (fever, chills, fatigue, anorexia, weight loss, Sicca syndrome (dry eyes and mouth), carpal tunnel syndrome (due to compression on median nerve by ACPA), pericarditis and pleural effusion)
Most important is lung and eye involvement |
| What are lab manifestations of RA? | CBC (leukocytosis with high CRP/Erythrocyte sedimentation rate (ESR) and thrombocytosis)
High RF and ACPA (the higher the more severe)
reduced hemoglobin is common (called anemia of chronic disease) |
| What are image findings in RA? | X ray (gold std for diagnosing damage in RA, 1st sign is soft tissue swelling, perarticular osteopenia, erosions joint space narrowing (which is diagnostic even if negative labs). Erosions occur rapidly 50% first year and 70% 5 years, important to know that first erosion is at MTP5, MTP before MCP. But X ray is limited since it needs 2 years to be visible)
US (of hands and feet, earlier detection of erosion, shows joint, inflammation, tendon, angiogenesis, synovium, early detection subclinical synovitis, important to know common presentation is extensor carpi ulnaris tenosynovitis which is pathogneumonic)
Others (MRI for early dx and staging not routinely used) |
| How are classifications of RA? and differential diagnosis? | Use ACR/EULAR classifications, not for diagnosis usually, score>6.
differential (Osteoarthritis, peripheral SPA, viral arthritis (parvo), Lyme, acute sarcoid (Lofgren), Connective tissue disease (SLE, myositis, Sjogren), crystal, polymyalgia) |
| What are prognostic factors of RA? | Prediction of future structural damage (ACPA, erosive, female gender, acute phase reactants, RF , TNF and IL6, genetic markers (HLADR4), HAQ score, MRI)
Prediction of increased mortalitiy (age, education, physical status, RF, comorbidities, infection, extra-articular manifestations, increased HAQ, poor health, glucocorticoud use) |
| How are the clinical aspects of chronic RA? | When we have long lasting inflammation (chronic RA), we will get deformities (Boutonniere, Z shape, A swan neck, ulnar drift, volar subluxation) mainly in MCP, PIP and DIP.
We get involvement of C1-C2 (antlantoaxial subluxation) due to synovial mmb between C1 and C2, this is rare and severe life threat, we get persistent synovitis produce erosion at dens and transverse ligament lead to instability, which is risk of rupture and anterior displacement of the dens compressing the spine which may lead to death.
As for lower limbs we should check for deformities in MTPs, malate, hallus valgus, subluxation of foot arch, pennus nodules on extensors (rheumatic nodules in seropositive disease).
Other joints shoulder elbows TMJ cricoarythenoid, see bursitis or flexor tenosynovitis) |
| What are extra articular manifestations of RA? | Hematology (Anemia, thrombocytosis, Felty's syndrome [splenomegaly w/leukopenia and thrombocytopenia])
Ocular (keratoconjuctivitis sicca, scleritis/episcleritis)
Hepatic abnormality, Pulmonary (Pleural effusion, intersitial fibrosis, nodules, alveolitis, dilatation, pneumoconiosis, pulmonary HTN, bronchiolitis)
Skin (SC nodules, pyoderma gangrenosum, vasculitis rash, leg ulcer, amyloidosis)
Vasculitis (nail fold, systemic)
Cardiac (pericarditis, pericardial effusion, valvular heart disease, conduction defects)
Neurological (nerve entrapment, cervical myelopathy, neuropathy peripheral or mononeuritis)
Infection, Osteoporosis, Muscle wasting, Cancer, Secondary Sjogren, Atherosclerosis, Mortality.
Functional disability and consequences (pain and joint destruction, lead to loss of mobility, psychosocial functioning, mental distress, depression and fatigue |
