Rheumatology (5-10%) Complete Flashcards
Synovial fluid analysis for arthritis:
1. White Cell count in non-inflammatory arthritis?
- White Cell count in inflammatory/crystal?
- White Cell count in Septic arthritis?
- Less than or equal to 2000
- 10,000 to 100,000
- If greater than 50,000 keep septic arthritis high on the differential and treat it as septic arthritis until proven otherwise
Rheumatoid Arthritis
• Tender, swollen, ________ small joints (MCPs, PIPs, wrists)
• ________ weeks of arthritis
• Rheumatoid factor
Ø ________% RA are RF negative
Ø DDx – Other CTD, Hepatitis C/cryoglobulinemia, Endocarditis, Malignancy (B cell neoplasms most common), age, normal variation
• Anti-CCP
Ø ________ specificity, can precede arthritis, predicts ________
• Elevated ________, ________
• Do not need ________ or ________ for diagnosis, especially with early disease
Rheumatoid Arthritis
• Tender, swollen, symmetric small joints (MCPs, PIPs, wrists)
• >6 weeks of arthritis
• Rheumatoid factor
Ø 25% RA are RF negative
Ø DDx – Other CTD, Hepatitis C/cryoglobulinemia, Endocarditis, Malignancy (B cell neoplasms most common), age, normal variation
• Anti-CCP
Ø 95% specificity, can precede arthritis, predicts more erosive disease
• Elevated CRP, ESR
• Do not need serology or X-rays for diagnosis, especially with early disease
RA extra-articular manifestations MUST KNOW
Cardiac:
1. _______________
Lung
1. _______________
2. _______________• (rule out ______, can mimic _________)
Hematologic
1. _______________ syndrome = _______________ +
_______________ + _______________
Neurologic
1. _______________
2. _______________ = life-threatening
RA extra-articular manifestations
Cardiac
• Accelerated atherosclerosis
Lung
• Interstitial lung disease (NSIP, UIP)
• Pleural effusion (rule out infection, can mimic empyema)
Hematologic
• Felty’s syndrome = Seropositive RA + splenomegaly + neutropenia
Neurologic
• Carpal tunnel syndrome (one of the earliest signs of RA)
• C1-C2 instability/subluxation = life-threatening
(pre-op oral scenario)
RA Management: “Bridge” Therapy/Symptomatic Treatment (NOT disease modifying):
1. __________
2. __________
3. __________
- Steroids (PO, IM, IA) ≦ 3 months – use the lowest dose for the shortest possible time
- NSAIDs
- Analgesics
RA Management: Long-Term Therapy (Disease modifying)
• Step 1: ______________
• Low disease activity: ______________
• Moderate to high disease activity: ______________
• Step 2: ______________
• Use when failed ______________
• Usually start with ______________ and continue ______________
• Change medication classes to alternate ______________ if not at the target
• Dose can be reduced in patients with low disease activity or remission for ______________ months
• Step 1: Conventional DMARD
• Low disease activity: Hydroxychloroquine
• Moderate to high disease activity: MTX monotherapy (oral > subcut)
• 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
• 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
Conventional DMARD side-effects and monitoring:
- Hydroxychloroquine?
Common side effects for Methotrexate (MTX), Leflunomide?, Sulfasalazine?
Other side effects for Methotrexate (MTX), Leflunomide?, Sulfasalazine?
- Hydroxychloroquine: retinal toxicity due to accumulative dose over time. - Baseline and annual ophthalmologic exam
Common side effects for Methotrexate (MTX), Leflunomide?, Sulfasalazine?
- Infection risk (new and activation of latent infection)
- GI side effects (nausea, vomiting, diarrhea, occasionally dyspepsia)
Other side effects for Methotrexate (MTX), Leflunomide?, Sulfasalazine?
Sulfasalazine? Rash and sulfa allergy
Methotrexate (MTX) and Leflunomide?
- Hepato-toxicity
- Cytopenias
- Teratogenicity (need to be stopped prior to planned conception)
Methotrexate in addition? Hypersensitivity pneumonitis
Management of low-dose MTX toxicity:
- Nausea, vomiting, diarrhea? How to manage?
- Stomatitis? How to manage?
- Hepatotoxicity, Rash, and cytopenias? How to manage?
- Pneumonitis? How to manage?
- Nausea, vomiting, diarrhea? How to manage?:
- Split dose (eg 10mg bid once weekly instead of 20mg po weekly)
- change from oral to subcutaneous injection
- Increase the dose of folic acid or add folinic acid/Leucovorin rescue - Stomatitis? How to manage?
- Same as above - Hepatotoxicity, Rash, and cytopenias? How to manage?
- Dose reduction
- If severe hold the medication reintroduce it back at a lower dose - Pneumonitis? How to manage?
- stop methotrexate and DONOT restart
How long should you treat latent TB before starting biological therapy?
Complete at least one month of treatment
Non-live vaccines and Rheumatology and Musculoskeletal disease patients on immunosuppression
Safe to give only Methotrexate and Rituximab have to be adjusted
Live vaccines and Rheumatology and Musculoskeletal disease patients on immunosuppression
Usually avoid
Rheumatoid arthritis and pregnancy:
Avoid?
Safe to use?
Breastfeeding:
Avoid?
Safe to use?
Rheumatoid arthritis and pregnancy:
Avoid? Methotrexate (MTX) and Leflunomide
Safe to use? Hydroxychloroquine and sulfasalazine
Breastfeeding:
Avoid? Methotrexate (MTX) and Leflunomide
Safe to use? Hydroxychloroquine and sulfasalazine
Male Pre-Conception and Methotrexate (MTX)?
MTX can be continued (previously recommended to hold)
Seronegative Arthropathies’ common features
Clinical?
_____ joint/_____ involvement
_______ joint
_____, _____, _____, _____
Skin:
Imaging?
HLA?
Clinical?
SI joint/Axial involvement
Peripheral joints
Enthesitis, dactylitis, uveitis, conjunctivitis
Skin: Erythema nodosum, Pyoderma gangrenosum
(IBD), Psoriatic skin, hair, and nail changes
Imaging?
Erosions, ankylosis periosteal new bone formation, and the fusion of the bones.
Joints: Peripheral joints, SI joints, Spine (Syndesmophytes)
HLA?
Often HLA B27 is positive but not diagnostic
Management of Seronegative Spondyloarthropathies: Axial Disease:
_________ first-line therapy
If failed then use _________
“We strongly recommend AGAINST treatment with _________ ”
If failed again then: _________
– NSAIDs are first-line therapy
If failed then use a second NSAID
• “We strongly recommend AGAINST treatment with systemic glucocorticoids”
If failed again then: BIOLOGICS/SMALL MOLECULE
• 1st line = TNF-α inhibitors: Etanercept (Enbrel), Infliximab (Remicade), Adalimumab
(Humira), Certulizumab (Cimzia), Golimumab (Simponi) or biosimilars
– If primary non-response -> progress to IL-17
– If secondary non-response (relapse after the initial response) -> 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
_________ first-line therapy
If failed then _________?
If failed then _________?
NSAIDs first-line therapy
If failed then?
– CONVENTIONAL DMARDS: Methotrexate, Sulfasalazine, [Leflunomide, Cyclosporine, Apremilast in PsA]
CONVENTIONAL DMARDS Only in Peripheral disease
If failed then?
– BIOLOGICS/SMALL MOLECULES
Reactive Arthritis
• Occurs several days to ~4 weeks following __________ or __________
• Typically __________, mono- or oligoarthritis, __________ extremity predominant
• Can develop inflammatory back pain and sacroiliitis
• Causative agents: __________
• Eye (50-75%): __________, __________
• Reactive arthritis can recur/become chronic (>6mo)
Treatment:
• __________, __________
• Consider __________ in recurrent/chronic disease
• No role for __________
Reactive Arthritis
• 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:
Most common organism for both native and prosthetic joints?
__________ #1 in osteomyelitis and septic arthritis in Sickle Cell Disease
Definitive Management?
Dosage of Ceftriaxone in septic arthritis?
S. aureus #1 in both native and prosthetic joints
Salmonella #1 in osteomyelitis and septic arthritis in Sickle Cell Disease
Definitive management requires source control (Orthopedics joint washout and antibiotics)
Dosage of Ceftriaxone in septic arthritis? Ceftriaxone 2 g IV every 24 hours
Gonococcal Arthritis: Presentation
2 common syndromes:
1. Triad of __________, __________, __________ without
__________
- __________ without __________
2 common syndromes:
- Triad of tenosynovitis, vesiculopustular skin
lesions, migratory polyarthralgia without
purulent arthritis - Purulent arthritis without skin lesions –> requires
a longer course of antibiotics
Gonococcal Arthritis: 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
DO NOT ALWAYS CO-TREAT AS BEFORE: NEW GUIDELINES
Lyme Arthritis: Treatment?
Oral antibiotics x 28 days (doxycycline or Amoxil)
Post-antibiotic Lyme Arthritis: Treatment?
Referral to Rheumatology for consideration of DMARD or biologic therapy (repeated courses of IV antibiotics not recommended)
Calcium pyrophosphate dihydrate disease (CPPD, aka
Pseudogout)
_____________ - radiographic diagnosis
• _____________ shaped, _____________
birefringent (_____________ when parallel)
VERY IMPORTANT: ASSOCIATIONS? 7 conditions?
Calcium pyrophosphate dihydrate disease (CPPD, aka
Pseudogout)
• Chrondrocalcinosis- radiographic diagnosis
• Intra-articular rhomboid-shaped, positively
birefringent (blue parallel)
Associated with:
- OA
- hypothyroidism
- hypomagnesemia
- hypophosphatemia
- hemochromatosis (2nd, 3rd MCP and PIP joint arthritis)
- hyperparathyroidism
- Wilson’s (rarely)
Crystals:
GOUT CRYSTALS (- birefringence):
YELLOW when parallel to polarized light
Crystals:
CPPD CRYSTALS (+ birefringence)
BLUE when parallel to polarized light
Indications for urate-lowering therapy?
Definite indications:
1. Two or more (≧2) attacks/year
2. Tophaceous gout
3. Gouty arthropathy (i.e. erosions)
Conditional indications: 1 episode of acute gout +
1. CKD Stage 3+
2. Uric acid level > 535
3. Urolithiasis
Gout:
Allopurinol: up-titrate until reach
target uric acid level ________
Gout:
Allopurinol: up-titrate until reach
target uric acid level < 356
Gout:
Allopurinol: Consider testing __________ in Southeast Asian and African Canadian patients due to __________
Allopurinol: Consider testing HLA-B*5801 in Southeast Asian and African Canadian patients due to increased Risk of hypersensitivity syndrome: TEN/SJS, fever, eosinophilia, hepatic necrosis, nephritis, diarrhea
Gout:
While titering up the dose of Allopurinol or Febuxostat: Overlap with anti-inflammatory prophylaxis with either colchicine, NSAID, or low-dose GC for ___________ months
Gout:
While titering up the dose of Allopurinol or Febuxostat: Overlap with anti-inflammatory prophylaxis with either colchicine, NSAID, or low-dose GC for 3 to 6 months
SLE Classification Criteria:
Entry Criterion?
Entry Criterion: ANA titre ≧ 1:80
Lupus Labs: ENA (Extractable Nuclear Antigen Antibodies)
• Anti-Sm: Specific but not sensitive (30-40%)
• Anti-histone: _____________________
• Anti-RNP: Required for diagnosis of _____________________
• Anti-Ro (SSA): Risk of _____________________
• Anti-La (SSB): _____________________
• 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
Lupus Nephritis:
Class III: _______ LN (_____% of glomeruli)
Class IV: _______ LN (_____% of glomeruli)
Class V: ________ LN
Class III: Focal LN (<50% of glomeruli)
Class IV: Diffuse LN (≧50% of glomeruli)
Class V: Membranous LN
Lupus Renal Syndrome – SLE + TMA (Thrombotic microangiopathy)
Causes?
Workup?
Different causes:
- TTP
- SLE-APS (anti-phospholipid antibody syndrome)
- Complement mediated
Workup:
- Measure ADAMSTS if you suspect SLE-TMA
- Measure APLAS
- Experienced heme needed…Treat underlying cause (PLEX, steroids, anticoag, eculizumab, etc)
Lupus Nephritis:
Class III/Class IV:
Presentation?
Treatment:
Induction?
First _______ then _________ + _________
_______ for all
Maintenance?
The aggressive disease needs aggressive treatment
Presentation? Nephritic picture
Induction: IV pulse GC 250-500 mg/d x 3 days then Prednisone 0.6-1mg/kg/d + another agent (cyclophosphamide versus MMF)
Cyclophosphamide:
• Low-dose IV protocol preferred (500 mg q2 weeks x 6)
• Risks infertility (significant), infection, malignancies esp GU (++hydration), cytopenias
MMF (2-3g/day x 6 months)
• Preferred for pts with future fertility consideration
• Risks GI S/E, cytopenias, unsafe in pregnancy
HCQ for all (Mortality benefit and reduces flare)
ACEi for proteinuria
Maintenance?: HCQ + MMF 1-2 g/day +/- low dose prednisone (target <7.5mg/d by 3 months)
• Alternative to MMF: AZA (ie. If pregnancy plans or intolerant), Tacrolimus
Lupus Nephritis:
Class V:
Presentation?
Treatment:
Presentation? Nephrotic range proteinuria
Treatment:
KDIGO 2021:
- For all: RAAS blockade (ACE-I), BP control (<130/80)
- For all: Hydroxychloroquine
Nephrotic range proteinuria:
- Treating upfront with immunosuppression, if nephrotic range proteinuria
- Induction: Prednisone (0.5 mg/kg) + additional agent (MMF, Cyclophosphamide, CnI, Ritux, AZA)
Lupus Nephritis:
Class V: nephrotic syndrome and patient worsens all of a sudden think?
Next step?
R/O renal vein thrombosis
Get dopplers
SLE and Pregnancy
SLE
• Continue __________ during pregnancy
• Start __________ prior to __________ weeks gestation to reduce pre-eclampsia risk
Ro/La+
• __________
Positive aPL:
• No APS= __________
• OB APS= __________
• Thrombotic APS= __________
SLE and Pregnancy
SLE
• Continue HCQ during pregnancy
• Start ASA 81mg daily prior to 16 weeks gestation to reduce pre-eclampsia risk
Ro/La+
• increased risk of neonatal lupus, so serial fetal echoes are recommended
Positive aPL:
• No APS= ASA alone
• OB APS= ASA + prophylactic heparin until 6-12 weeks postpartum
• Thrombotic APS= ASA + therapeutic heparin during pregnancy and postpartum
Drug-induced lupus:
Drugs?
Serology?
• Common Causes: hydralazine, procainamide, TNF inhibitors, isoniazid
• Serology: ANA+, dsDNA -, anti-histone Ab+
Shrinking lung syndrome:
Rare complication of SLE related to ___________
Workup?
Shrinking lung syndrome:
rare complication of SLE related to diaphragmatic muscle weakness
• Lungs are clear on imaging but volume is decreased (CXR, MIP/MEPs).
- Check MIP/MEPs
Libman Sacks Endocarditis:
Associated with __________
Is it infectious or non-infectious?
• Can result in _______ phenomena
• Treated with _________
Libman Sacks Endocarditis (Non-infectious):
associated with APLAS
• Can result in embolic phenomena
• Treated with steroids and anticoagulation
The differential diagnosis for bilateral parotid gland enlargement:
- Sjogren’s
- Infectious – Mumps, TB, bacterial
- Sarcoidosis, IgG4 syndrome
- Lymphoma
- Alcoholism, Anorexia/bulimia
Sjogren’s Syndrome:
> 40X increased risk of ________
> 40X increased risk of B-cell lymphoma
Systemic Sclerosis (Scleroderma)
Diffuse?
- Sclerodactyly: where?
- Increased risk of ___ and ____
Limited Cutaneous/CREST syndrome?
- Sclerodactyly: where?
- Association
Serology?
Diffuse:
– Sclerodactyly proximal to elbows and proximal to
knees
– Internal organ involvement, including increased risk of ILD and renal crisis
Limited Cutaneous/CREST syndrome:
- Sclerodactyly distal to elbows and distal to
knees
- Calcinosis
– Raynaud’s phenomenon
– Esophageal dysfunction
– Sclerodactyly
– Telangiectasias
- Pulmonary hypertension
Serology? highly specific for scleroderma >98%
– Anti-centromere: Limited (CREST) 60%, Diffuse 15%
– Anti Scl-70/topo I: ~40% of scleroderma patients, mostly diffuse disease
– Neither useful for disease monitoring
Scleroderma renal crisis:
Treatment?
Scleroderma renal crisis
• Increased risk with prednisone, RNAP3 autoantibodies, and early disease
• Treatment: ACE inhibitor (Captopril)
Pulmonary hypertension and systemic sclerosis:
More common in _______
Monitor with _____
Pulmonary hypertension and systemic sclerosis:
• More common in LIMITED OR CREST
• Monitor with NT-proBNP, echo and PFTs for all SSc patients annually
Raynaud’s Phenomenon:
Treatment:
First line?
Others?
Treatment:
• Conservative measures
• 1st line - Calcium channel blockers - Amlodipine, nifedipine
• Can consider topical nitrates, PDE5 inhibitor
What are myositis-specific antibodies?
Seen in?
Seen in Dermatomyositis/Polymyositis (DM/PM)
- Anti-synthetase Syndrome = Anti-Jo1 Antibody
- Anti-Mi2 Antibodies
• Associated with the classic form of DM
• Highly responsive to treatment and carries a favorable prognosis - Anti-NXP2 and Anti-TIF1-ɣ Antibodies
• Highly associated with malignancy
High Yield Vasculitis Overview
Management of Large: Giant Cell Arteritis:
• Visual symptoms/loss or critical cranial ischemia?
• No visual symptoms/loss or critical cranial ischemia?
• Extracranial GCA?
• _____ only if critical/flow-limiting lesion of carotid/vertebral arteries
Management: DOSE IS IMPORTANT
• Visual symptoms/loss or critical cranial ischemia:
IV pulse steroids 1g x 3 days then Prednisone 1mg/kg daily + Tocilizumab (TCZ)
• No visual symptoms/loss or critical cranial ischemia:
Prednisone 1mg/kg daily + Tocilizumab
• Extracranial GCA: Prednisone 1mg/kg daily + (TCZ or MTX)
• ASA only if critical/flow-limiting lesion of carotid/vertebral arteries
• Treat with high dose steroids x 1 month then taper
Polyarteritis Nodosa (PAN):
Clinical presentation:
Constitutional Symptoms?
Cutaneous?
GU?
GI?
Is viral infection associated?
Constitutional Symptoms: Fever, Unexplained weight loss >4kg
• Cutaneous: Livedo reticularis
• Testicular pain or tenderness
• Abdominal pain (post-prandial)
• +/- Hepatitis B virus infection (HbSAg or HbCoreAb positive)
Non-pharmacological Management of Hand OA:
• 1st CMC orthosis
Rheumatologic Emergencies:
• Septic joint: ________________
• GCA with vision loss: ________________
• Pulmonary-renal syndrome
- If ANCA+ = ________________
- If anti-GBM+ =________________
• Scleroderma renal crisis: ________________
• Thrombotic microangiopathies (antiphospholipid syndrome, SLE) = _______________
• Systemic disease flare (RA, SLE, polymyositis, seronegative, vasculitis) =
Rheumatologic Emergencies:
• Septic joint = Antibiotics, Ortho for washout
- If can’t go to OR and large joint, daily aspirations with synovial WBC
• GCA with vision loss = Pulse steroids + Tocilizumab
• Pulmonary-renal syndrome
- If ANCA+ = Steroids + Rituximab (or Cyclophosphamide) (+PLEX? See notes on ANCA Slide)
- If anti-GBM+ = Definite PLEX, Steroids + Cyclophosphamide (preferred per Nephro)
• Scleroderma renal crisis = ACE inhibitors (esp. Captopril)
• Thrombotic microangiopathies (antiphospholipid syndrome, SLE) = Anticoagulation (caution if
hemorrhage component), tailor treatment to clinical presentation, and cause
• Systemic disease flare (RA, SLE, polymyositis, seronegative, vasculitis)
- Disease: Cardiac, pulmonary, renal, muscle, CNS/neurologic
- Treatment complications: cytopenias, pneumonitis, renal/hepatic dysfunction, allergy etc
Antibiotic summary
