Rheum Flashcards
Inflammatory Arthritis- description
- Cardinal features of inflammation:
- Morning stiffness (typically >60min)
- Worse with rest, better with activity
- Night pain (esp. latter half of night)
- Swelling
- Joint number:
- Mono-arthritis: 1 joint
- Oligo-arthritis: 2-4 joints
- Poly-arthritis: 5 or more joints
- Acute: < 6 weeks duration vs Chronic: > 6 weeks
- Extra-articular features
- Synovial Fluid Analysis
Sero-negative arthritis
PEAR
Psoriatic Arthritis (PsA)
Enteropathic (IBD) arthritis
Ankylosing Spondylitis (AS)
Reactive Arthritis
Undifferentiated
Rheumatoid Arthritis- dx
Symmetric small joint polyarthritis of synovial joints (MCPs, PIPs,
wrists)
* ≥6 weeks of arthritis
* Serology: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP)
Ø 25% RA are RF negative (RF is not diagnostic)
Ø Anti-CCP: 95% specificity, can precede arthritis, predicts
more erosive disease (in association with smoking = major RF)
Ø Elevated CRP, ESR
- XR – periarticular osteopenia, joint space narrowing, marginal erosions
- Do not need serology or X-rays for diagnosis, especially with early disease
RA Extra-articular Manifestations
Cardiac
* Pericarditis (+/- effusion), myocarditis
* Coronary artery disease àRA is independent
RF for developing CAD due to accelerated
atherosclerosis
Lung
* Interstitial lung disease (NSIP, UIP) – usually
anti-CCP positive
* Pleural effusion (sterile exudate with low glucose)
* Pulmonary nodules
* Bronchiolitis obliterans
Hematologic
* Anemia, reactive thrombocytosis
* Felty’s syndrome (rare) = Seropositive RA +
splenomegaly + neutropenia
* Lymphoproliferative conditions
Neurologic
* Carpal tunnel syndrome (one of the
earliest signs of RAà know for oral)
- C1-C2 instability/subluxation = life-
threatening (pre-op oral scenario)
Other
* Rheumatoid nodules
* Vasculitis – variable vessel involvement
* Often occurs in “burnt out” disease
* Secondary Amyloidosis
* Scleritis/Episcleritis, corneal melt
* Sicca symptoms (dry eyes, dry mouth)
* Raynaud’s phenomenon
* Sweet’s syndrome
* Neutrophilic dermatosis
RA Management: Overview of DMARD
Conventional synthetic DMARD (csDMARD)
* Methotrexate (MTX)
* Hydroxychloroquine (HCQ, PLQ)
* Sulfasalazine (SSZ)
* Leflunomide (LEF)
Biologic DMARD (bDMARD)
* TNF Inhibitors – Adalimumab, infliximab, certolizumab,
etanercept, golimumab
* Tocilizumab (IL-6)
* Abatacept (T cell inhibitor)
* Rituximab (anti-CD20)
Small molecules/targeted synthetic DMARD (tsDMARD)
* Tofacitinib* (Xeljanz)
* Baricitinib* (Olumiant)
* Upadacitinib* (Rinvoq)
* Apremilast (Otezla)
* JAKi – significantly increased risk of HZ
RA Management- general concepts
- “Bridge” Therapy/Symptomatic Treatment (NOT disease modifying)
- Steroids (PO, IM, IA) ≦ 3 months – use lowest dose for shortest possible time
- NSAIDs, Analgesics
- Long Term Therapy (Disease modifying)
- Step 1: Conventional DMARD
- Low disease activity: Hydroxychloroquine
- Moderate to high disease activity: MTX monotherapy
- Note: Triple therapy (MTX + PLQ + SFZ) no longer recommended as a preferred strategy
- Step 2: Biologic or Small Molecule
- Use when failed MTX monotherapy (preferred over triple therapy)
- Usually start with TNF inhibitor and continue MTX
- MTX is used for synergistic effects but also to prevent formation of anti-drug Ab
- Change medication classes to alternate biologic or small molecule if not at target
- Dose can be reduced in patients with low disease activity or remission for >6 months
RA Management: Special Considerations
Pulmonary disease : Screen at baseline with PFTs and High Resolution CT [not CXR – new- ACR 2023]
* MTX can cause pneumonitis (rare complication)
* If patient has at baseline parenchymal lung disease that is incidental/mild/stable then can still use MTX over
other DMARDs for arthritis particularly if moderate to severe RA disease activity
- Heart Failure
- Don’t start TNFi if history of NYHA Class III or IV heart failure
- If patient develops heart failure on TNFi switch to another agent (non-TNF biologic)
- Lymphoproliferative Disorder
- Use rituximab first line if patient has moderate to severe disease activity and a lymphoproliferative disorder
in which rituximab is indicated - Hepatitis B
- If Hep B core Ab Positive, SAg + à prophylactic antiviral therapy while starting all biologic dMARD.
- If starting rituximab à prophylactic antiviral therapy even if surface antigen neg if core Ab +
- Metabolic-dysfunction associated steatotic liver disease (formerly NAFLD): Can still use MTX if liver enzymes
normal, liver function tests normal, no advanced liver fibrosis, and patient has moderate to severe disease activity,
with more frequent (q4-8wk) monitoring of LFTs - MTX can be hepatotoxic
Conventional DMARD- SE
Methotrexate (MTX)
Hepatotoxicity, nausea, pancytopenia,
pulmonary (hypersensitivity pneumonitis,
fibrosis), oral ulcers, alopecia, teratogenic
Prescribe with folic acid to reduce s/e
-Baseline CXR, HCV, HBV, CBC, LFTs, Cr
-Initial CBC, LFTs, Cr q2-4 weeks, then
q12 weeks after 3 months
- ESR and CRP for disease monitoring
Hydroxychloroquine
Retinal toxicity, rash, photosensitivity,
myotoxicity (rare), cardiotoxicity (rare)
- Baseline and annual ophthalmologic
exam (retinal toxicity)
Leflunomide
GI (nausea, GI pain, dyspepsia, diarrhea),
hepatotoxicity, HTN, myelosuppression
(rare), peripheral neuropathy, teratogenic
-Baseline CBC, LFTs, Cr, HBV, HCV
-Initial CBC, LFTs, Cr q2-4 weeks, then
q12 weeks after 3 months
Sulfasalazine
GI toxicity, headache, rash
-Initial CBC, LFTs, Cr q2-4 weeks, then
q12 weeks after 3 months
Biologics Key Points
- Risks of Biologics: Infection (new or reactivation), drug induced SLE/antibodies (get baseline ANA),
local skin reactions, malignancy risk - Baseline Testing (prior to starting biologic):
- Hepatitis B surface Ag, Surface Ab, Core Ab, Hepatitis C serology (treat concurrently if positive)
- TB skin test, IGRA, and/or CXR as appropriate (see algorithm slide)
- Special Situations/Controversial to use if:
- NYHA Class III or IV heart failure (TNFi can worsen CHF)
- Active hepatitis (start hepatitis treatment first, consult GI)
- Prior lymphoproliferative malignancy – use Rituximab
- Prior solid organ malignancy – consult Oncologist prior to starting
- Prior skin cancer – csDMARDs preferred (avoid TNFi as increased risk nonmelanoma skin ca)
- Prior serious infection – considering using csDMARDs if serious infection w/i 12 months
- If flare, modify frequency rather than dose first
Management of RA during Pregnancy
Pre-Pregnancy: Ideal if in remission
* Stabilize disease on medication that is safe to take in pregnancy
* Discontinue MTX at least 1-3 months prior to conception
* Ideally avoid leflunomide in patients with the possibility of pregnancy; if on leflunomide,
measure leflunomide levels and treat with cholestyramine washout if detectable
* Taper prednisone to <20mg/day
* Pregnancy: Often patients with RA go into remission intra-partum
* Hydroxychloroquine, SSZ, and biologics are safe during pregnancy, and can be continued
* Certolizumab (Cimzia) marketed as larger molecule that can’t cross placental barrier
* Avoid NSAIDs (especially in third trimester), low dose (<20mg/day) glucocorticoids can be used
* Post-partum: Higher risk of flare
* Sulfasalazine can be used during breast-feeding (theoretical risk of kernicterus)
* Avoid MTX and leflunomide during breast-feeding, biologics safe
* Male Pre-Conception:
* MTX can be continued (previously recommended to hold)
* Avoid Cyclophosphamide and Thalidomide
RA Mimics
EORA: elderly onset RA (65y+)
* M=F, usually more drastic initial
presentation
* May have “PMR like presentation” –
symptoms may be drastically similar early
on in presentation
* More large joint, less likely seropositive
Viral Arthritis
* Often, acute self-limited polyarthritis with
viral symptoms
* Parvo B19: often associated reticular rash,
childcare worker
* Others: EBV, HBV, HCV
RS3PE: Remitting seronegative symmetrical
synovitis with pitting edema
* Acute onset, symmetrical polyarthritis
with profound pitting edema
* Most common in older M
* Very responsive to prednisone
* May be paraneoplastic
Hemochromatosis Arthropathy
* Chronic arthropathy, RA-like distribution
* Concurrent CPPD deposition
* Hooked osteophytes at MCPs
Seronegative Arthropathies
Clinical Features
* SI joint/Axial involvement
* Peripheral joints
* Asymmetric, large joint: AS, PsA,
Reactive, IBD Type 1 (oligo, usually
large joints, correlates with bowel
activity)
* Symmetric, small joint: PsA (DIP), IBD
Type 2 (polyarthritis, independent of
bowel)
*Strongly suggestive clinical features: IBD, psoriasis,
uveitis
Other clinical features: Enthesitis, inflammatory
back pain, response to NSAIDs, skin involvement
Imaging Features
* Peripheral X-rays: Erosions, periosteal new
bone formation, ankylosis
* Spine X-ray: Syndesmophytes
* SI Joint X-ray: sclerosis, erosions, ankylosis
* Can be symmetric in AS, asymmetric in PsA/IBD
* SI Joint MRI: Bone marrow edema
No role for bone scan, PET too expensive, may
consider low dose CT
HLA-B27 not diagnostic!
AS, IBD associated,
PsA, Reactive
Arthritis
*Many skin manifestations! Erythema nodosum,
Pyoderma gangrenosum (IBD), keratoderma
blennorrhagicum, circinate balanitis (Reactive), Psoriatic skin and nail changes (Psoriasis)
Management of Seronegative
Spondyloarthropathies: Axial Disease
Non-pharmacologic: physiotherapy, exercise, smoking cessation
Pharmacologic:
– NSAIDs are first-line therapy; conditional recommendation for continuous use > on-demand
– “We strongly recommend AGAINST treatment with systemic glucocorticoids”
Step up therapy to BIOLOGICS/SMALL MOLECULE if:
– No response or intolerance to at least 2 different NSAIDs at maximal doses over 1 month or incomplete
response to at least 2 NSAIDS over 2 months
* 1st line = TNF-α inhibitors: Etanercept (Enbrel), Infliximab (Remicade), Adalimumab (Humira),
Certolizumab (Cimzia), Golimumab (Simponi) or biosimilars*
NO preference over which TNFi is used
– If primary non-response à progress to IL-17
– If secondary non-response (relapse after initial response) à change to alternate anti-TNF
* 2nd line = IL-17 inhibitors: Secukinumab (Cosentyx), Ixekizumab (Taltz)
* 3rd line = JAK inhibitor: Tofacitinib (Xeljanz)
Management of Seronegative
Spondyloarthropathies: Peripheral Disease
- Non-pharmacologic: PT, OT, smoking cessation, weight loss, exercise
- Pharmacologic
– NSAIDS: - 1st line for peripheral arthritis related to AS or Reactive Arthritis
- IBD: Use with caution, should be discussed with GI, do not use if gut is flaring
- PsA: For symptoms only
– GLUCOCORTICOIDS: Systemic GCs should be avoided; injections can be used for mono/oligo-arthritis
– DMARDS: Methotrexate, Sulfasalazine, [Leflunomide, Cyclosporine, Apremilast in PsA]
– BIOLOGICS/SMALL MOLECULES:
Reactive Arthritis- dx and tx
- Occurs several days to ~4 weeks following gastroenteritis or urethritis
- Typically asymmetric, mono- or oligoarthritis, lower extremity predominant
- Can develop inflammatory back pain and sacroiliitis
- Causative agents: C. trachomatis, Yersinia, Salmonella, Shigella & Campylobacter
- Eye (50-75%): Uveitis, conjunctivitis
- Reactive arthritis can recur / become chronic (>6mo)
- Treatment:
- NSAIDs, intra-articular corticosteroids
- Consider DMARDs in recurrent/chronic disease, e.g. MTX, sulfasalazine;
rarely TNFi - No role for antibiotics (unless evidence of active infection)
Septic Arthritis-dx and tx
- Most commonly monoarthritis of hip or knee
- S. aureus #1 in both native and prosthetic joints
- Salmonella #1 in osteomyelitis and septic arthritis in Sickle Cell Disease
- Crystal arthritis can co-exist with infection – don’t be fooled!
- Definitive management requires source control (i.e. ortho consult for washout)
(see abx chart)
Gonococcal Arthritis-dx and tx
2 common syndromes:
1. Triad of tenosynovitis, vesiculopustular skin
lesions, migratory polyarthralgias without
purulent arthritis
2. Purulent arthritis without skin lesions à requires
longer course of antibiotics
* Occurs in <5% of gonococcal STDs
- Treatment:
– Ceftriaxone
– Check Urine NAAT for Chlamydia and treat if
positive (or tx empirically if delays to diagnosis
or concern of compliance with follow-up) - Doxycycline 100mg po bid x 7 d, or single dose
azithromycin
Lyme Arthritis- dx and tx
- Clinical Picture
- Acute Infection: Arthralgias and myalgias
- Lyme Arthritis: Late onset (>6 months post infection), oligoarthritis with synovitis and swelling
most commonly affecting the knee. Symptoms can fluctuate – swelling and erythema without
significant pain. Synovial fluid inflammatory. - Diagnosis
- Lyme Serology + Clinical Picture
- Where diagnosis needs confirmation, PCR of synovial fluid or tissue
- Treatment
- Oral antibiotics x 28 days (doxycycline or amoxicillin)
- Treatment failure with objective severe synovitis – ceftriaxone 2-4 weeks IV if other
diagnoses excluded - Post-antibiotic Lyme Arthritis: Referral to Rheumatology for consideration of DMARD or
biologic therapy (repeated courses of IV antibiotics not recommended)
Crystal Arthritis: Gout dx and tx
Gout
* Monosodium urate crystals (needle shaped, negatively birefringent)
* Acute self limited inflammatory arthritis (mono>oligo>poly)
* Gold standard – arthrocentesis with SF demonstrating MSU crystals
* Presence of crystals on arthrocentesis does NOT rule out septic arthritis
Risk Factors:
* Hyperuricemia – may be increased production (purine rich
diet, TLS, hemolysis, polycythemia) or reduced clearance
(renal insufficiency, diuretics)
* Meds: thiazides, low dose ASA, allopurinol, pyrazinamide
* Diet: beer, red meat, seafood
* Demographics: male, post-menopausal females, obesity
* Estrogen has protective effect (so not in young healthy females!)
- Monoarticular in ~80% of initial attacks
with predilection to lower extremities,
most commonly 1st MTP or knee
Uric acid level is not diagnostic but is a
target for therapy - Look for tophi on cool extremities
(especially helix/elbows)
Crystal Arthritis: Pseudogout
Calcium pyrophosphate dihydrate disease (CPPD, aka pseudogout)
* Various presentations:
* Pseudogout –acute mono/oligo-arthritis
* “RA-like” – chronic inflammatory arthritis
* OA with CPPD – atypical OA distribution (lateral knees, wrists,
elbows)
- Chondrocalcinosis is radiographic diagnosis (may be asx)
- CPPD crystals = rhomboid shaped, positively birefringent
- If present on synovial fluid, then patient has CPPD
- Secondary Causes: hypothyroidism, hypomagnesemia,
hypophosphatemia, hemochromatosis (2nd, 3rd MCP arthritis
with hooked osteophytes), hyperparathyroidism, Wilson’s (rare)
Calcific Tendinitis / Milwaukee Shoulder (basic calcium phosphate/hydroxyapatite
crystals)
* Older female patients
* Acute onset, destructive shoulder arthropathy
Treatment of Gout: Acute
NSAIDs
Colchicine
* 1.2mg load then 0.6mg an hour later then 0.6mg BID until
symptoms resolve
– Requires dose reduction for CKD – CrCl <30 start 0.3mg per
day
- Risks: diarrhea, nausea, vomiting, (myopathy for long term use)
- OD is life-threatening and is non dialyzable with no anti-dote
Glucocorticoids (IA / PO) - IA if mono/oligo-arthritis, oral if polyarthritis (or C/I to above
meds)
IL-1 blocker (Anakinra) - Consider only in patients with frequent flares and
contraindications to colchicine, NSAIDs & corticosteroids
Notes on Allopurinol
Frequently asked Allopurinol/ULT Facts:
* If patient is already on chronic
allopurinol/ULT therapy you do NOT
need to stop it during an acute flare
* Common concern is ↑ in gout attacks
during initiation of ULT thus must add
prophylaxis
* Do NOT use ULT with AZA = risk of bone
marrow failure
* If develop allopurinol hypersensitivity
reaction (rash, fever, ↓ platelets, ↑
liver enzymes) STOP and never take
again
Treatment of Gout: Chronic
Non-pharmacologic: dietary changes, alcohol reduction, med review
Pharmacologic: Urate lowering therapy
Definite indications: * Two or more (≧2) attacks/yr
* Tophaceous gout * Gouty arthropathy (erosions)
Conditional indications: 1 episode
acute gout + RF:
* CKD Stage 3+
* Uric acid level > 535
-stones
ULT Treatment Options:
1) Allopurinol: 1st line
* Start at 100mg/d (or 50mg if CKD 4) and up-titrate until reach target uric acid level < 356umol/L or <300umol/L if
tophi
* Can start in addition to colchicine during flare/continue if on tx
– Risk of hypersensitivity syndrome: TEN/SJS, fever, eosinophilia, hepatic necrosis, nephritis, diarrhea
– Consider testing HLA-B*5801 in Southeast Asian and African Canadian patients at increased risk
2) Febuxostat
* Use if cannot tolerate allopurinol or high risk for allopurinol hypersensitivity, not approved for dialysis patients
* Risk of rash, diarrhea, ?cardiovascular risk*
Overlap with anti-inflammatory prophylaxis with either colchicine, NSAID or low-dose GC for 3-6 months
2019 SLE Classification Criteria
Entry Criterion: ANA titre ≧ 1:80
If present, apply additive criteria
Weighted score based classification
requiring 1 clinical criteria + ≧ 10
points
Lupus Labs
ANA:
* Sensitive (95%), but not specific
* DDx of positive ANA
* Rheum: SLE, scleroderma, MCTD, drug-induced lupus, polymyositis/
dermatomyositis, rheumatoid arthritis
* Thyroid disease, autoimmune hepatitis, PBC, IBD, IPF
* Infection: hepatitis C, parvovirus, TB
* Family history of any of above
* Healthy (healthy titres: 1/40 = 20%, 1/80 = 10%, >1/160 = 5%)
* Not used to follow disease activity (do not repeat over time)
Anti-dsDNA
* Specific (97-98%), but not sensitive (present in 60-80% of SLE patients)
* Associated with lupus nephritis
* Can be used for monitoring disease activity, along with serum complements (C3, C4)
in concordant individuals
– Concordance = When flare, high anti-dsDNA, low complements
– Discordance = When flare, above pattern doesn’t apply
- Anti-Sm: Specific but not sensitive (30-40%)
- Anti-histone: Drug-induced lupus; SLE (50-70%)
- Anti-RNP: Required for diagnosis of MCTD; SLE (30-40%)
- Anti-Ro (SSA): Risk of congenital heart block and neonatal
cutaneous lupus; also seen in Sjogren’s syndrome - Anti-La (SSB): seen in Sjogren’s syndrome
