RA Flashcards
RA Etiology:
- Genetic
- Enviro
- Antibodies
Genetic: MHC region for HLA-DR genes, SNPs of STAT4, PTPN22, TRAF1
Enviro: smoking, silica, pollution, viruses, bacteria
Antibodies to citrullinated/ carbamylated proteins –> immune complex, complement activation, inflammation, NETosis, osteoclast-genesis/activation, adaptive immune system
RA Classification Criteria
2010: ACR/EULAR: 6 or more
- Swollen/tender joint
* One medium to large joint (shoulders, elbows, hips, knees, ankles) = 0
* 2–10 medium to large joints = 1
* 1–3 small joints (MCP, PIP, 2–5 MTP, or wrist with or without large joint involvement) = 2
* 4–10 small joints (with or without large joint involvement) = 4
* >10 joints (at least one small joint involved) = 5 - Serology
* -RF and -ACPA = 0
* Low +RF or low +ACPA (<=3 x ULN) = 2
* High +RF or high +ACPA (>3 x ULN) = 3 - Acute-phase reactants
* Normal CRP and normal ESR = 0
* Abnormal CRP or abnormal ESR = 1 - Duration of self-reported symptoms
* <6 weeks = 0
* ≥6 weeks = 1
DDx RA
- Seroneg (PEAR)
- Crystal (CPPD, polyarticular gout)
- CTD (SLE, SSc, PM, Vasc, MCTD, PMR)
- Infectious (EBV, HIV, Parvo, rubella, Hep C)
- FM, OA
Uncommon:
- Infectious: endocarditis, rheumatic fever, Lyme
- Metabolic: hypothyroid, hemochromatosis, hyperlipoproteinemias (types II, IV), amyloid arthropathy
- Infiltrative: sarcoidosis,
- Vascular: hemoglobinopathies (sickle cell disease)
- Malignant: malignancy, paraneoplastic syndrome, hypertrophic osteoarthropathy,
- Inflamm: Behçet’s disease, Relapsing polychondritis, R3SPE, FMF, SAPHO
RA Epidemiology (race, age, prevalence)
All races (higher in Native Americans)
Age: 40-60 in F, older in M
1% of US
RA Patterns
- Insidious (55%–65%): Arthritis over weeks to months.
- Subacute (15%–20%): Similar to insidious onset but more systemic symptoms.
- Acute (10%): Severe onset, some have fever.
b) Variant patterns of onset (10% of patients)
* Palindromic (episodic) pattern: Usually <5 joints and resolves within several days.- Tx: HCQ may decrease frequency of attacks and progression to RA.
* Insidious onset of elderly (>65 years): Pain/stiffness of limb girdle joints often with swelling of UE (difficult to differentiate from PMR & RS3PE)
* Arthritis robustus: Typically seen in men: bulky, proliferative synovitis –> erosions/ deformities with little pain or disability.
* Rheumatoid nodulosis: recurrent joint pain/swelling in, subcutaneous nodules, and subchondral bone cysts on XR.
RA Hand/Wrist deformities
Wrist:
- Volar subluxation (due to articular cartilage degradation and ligamentous laxity)
- Radial deviation (extensor carpi ulnaris tendon weakness = unopposed radial)
- Piano key ulnar head (radioulnar ligament damage –> floating ulnar styloid)
-Vaughan-Jackson deformity
MCPs:
- Subluxation (metacarpal head dorsally, prox phalanx head volar)
- Ulnar deviation
Fingers
- Ulnar drift (with wrist radial deviation, finger tendons pull fingers ulnarly)
- Fusiform swelling—PIP synovitis (spindle-shaped)
- Boutonnière
- Swan-neck
- Hitchhiker thumb (Z thumb)
Opera glass hands - bone resorption/shortening
RA XR findings
A—Alignment, abnormal; no ankylosis
B—Bones—periarticular (juxtaarticular) osteopenia; no periostitis or osteophytes
C—Cartilage—uniform (symmetric) joint space loss in weight-bearing joints; no cartilage or soft tissue
calcification
D—Deformities (swan neck, ulnar deviation, boutonnière) with symmetrical distribution
E—Erosions, marginal
S—Soft-tissue swelling; nodules without calcification.
RA C spine involvement
- subluxation
- impaction
- which joints
- neurologic manifestations
- C1–C2 atlantoaxial subluxation (60%–65%) –> anterior: C1 arch and C2 odontoid gap >3mm 2/2 synovial proliferation around odontoid –> stretch/rupture of transverse/alar ligaments; >9mm anterior atlantodontoid interval or <14mm posterior atlantodontoid interval risks spinal cord compression
- C1–C2 impaction: superior migration of odontoid from destroyed occipitoatlantal and atlantoaxial joint articulations between C1 and C2 –> impinge brainstem if moves into foramen magnum (worst neuro prognosis = odontoid ≥5 mm above Ranawat’s line)
- Subaxial involvement: involves C2–C3 and C3–C4 facets and intervertebral disks –> “stair-stepping” vertebrae (important if >3.5mm)
Manifestations:
-neck pain to occiput
-painless sensory loss (hands/feet)
- syncope/death
- cerebral ischemia w vertebral insufficiency
Rheumatoid Nodules
- Histology / Layers
- Inner: Central area of fibrinoid necrosis
- Middle: Palisading macrophages and histiocytes
- Outer: Monocytes and cellular connective tissue
RA Ocular Manifestations
- MOST COMMON: Sicca
- Episcleritis (painless)
- Scleritis –> scleromalacia perforans
- Choroid and retinal nodules,
- Ulcerative keratitis (corneal melt)
RA Pulmonary Manifestations
- Pleura: thickening, pleuritis, exudative effusion
- Interstitium: IPF/UIP >NSIP, COP, nodules, pneumoconiosis (Caplan’s syndrome), apical fibrobullous dz, lymphocytic interstitial PNA (LIP)
- Airway: criocoarytenoid arthritis, dysphagia, hoarseness, stridor, bronchiolitis (proliferative and obstructive), bronchiectasis
- Vascular: PH, vasculitis
- Other: infection, drug related, amyloid
RA Cardiac Manifestations
- Pericarditis: constriction, effusion, tamponade
- Myocarditis: CHF, afib
- Coronary: CAD, arteritis, vasculitis
- Nodules on valves: valvulopathy, conduction, endocarditis
RA Neuro Manifestations
- Entrapment neuropathy: median nerve (carpal tunnel), posterior tibial nerve (tarsal tunnel), ulnar nerve (cubital tunnel), and posterior interosseous branch of the radial nerve
- Peripheral neuropathy
- Mononeuritis multiplex
- CNS vasculitis
- C1/C2 subluxation or impaction
- Subaxial subluxation (C2/C3 and C3/C4)
RA Heme Manifestations
- Felty’s syndrome (leukopenia, splenomegaly, RA)
- Lymphomas
- Large granular lymphocyte syndrome: neutropenia, splenomegaly, susceptibility to infections
RA Other manifestations
- Sjögren’s syndrome
- Amyloidosis
- Osteoporosis
- Ossicles of ear: tinnitus and decreased hearing.
RA Derm Manifestations
- Palmar erythema,
- Subcutaneous nodules,
- Vasculitis
Tx of Felty
- If RA and infxn: MTX –> +Ritux –> +Steroids as needed (unless infxn). TNF not effective.
- G-CSF if severe infxn (risk of arthritis/vasculitis)
- Splenectomy (for severe infxns and nonhealing ulcers)
- Others: LEF, CNI, CYC, Abatacept > TNF
DC SSZ (neutropenia)
RA Disease activity measures
DAS28
SDAI
CDAI
RAPID3
RA Markers of poor prognosis
- Poor functional status (HAQ >1) at presentation
- Long dz duration prior to tx
- Low education level (<gr 11)
- Male
- Smokers
- Polyarthritis (small and large) >13
- Erosions within 2 years of onset
- Extraarticular dz: nodules, vasculitis
- HLA-DR4 genetic marker
- RF & CCP +
- ANA + (if also RF+)
- Persistently elevated ESR or CRP
RA Treatment targets
-how soon treatment
-activity level
Therapy within 3-6 mo of synovitis
Aim for LDAS or remission
SDAI calculation
Simplified disease activity index: TJC (0–28) + SJC (0–28) + PtGA (0–10) + PhGA (0–10) + CRP (mg/dL)
i.e. CDAI + CRP
CDAI calculation
Clinical disease activity index: TJC (0–28) + SJC (0–28) + PtGA (0–10) + PhGA (0–10)
RAPID calculation and cutoffs
Routine assessment of patient index data: MDHAQ (0–10) + patient pain (0–10) + PtGA (0–10)
Cutoff: <1, 1.3-2, 2.3-4, 4.3-10
RA Mortality causes
CV
Infection: PNA
Cancer: lymphoma, leukemia, lung, melanoma
Renal: amyloid
GI bleed: NSAID