Rheumat Flashcards
ACR 1997 Classification criteria for SLE
*American College of Rheumatology
4 out of 11
SOAP BRAIN MD
- Serositis (Pleurisy, pericarditis)
- Oral ulcers
- Arthritis
- Photosensitivity
- Blood disorders (Leukopenia, Lymphopenia, Thrombocytopenia, Hemolytic anemia)
- Renal disorders
- ANA (High titre = >1/160)
- Immunological disorders (Anti-dsDNA, Anti-Smith Ab, Anti-phospholipid Ab)
- Neurological disorders
- Malar rash
- Discoid lupus erythematosus
Anti-dsDNA antibodies
Anti-double stranded DNA
(for SLE)
A group of ANA, target antigen is double stranded DNA Can detect by ELISA and immunofluorescence
Highly diagnostic of SLE
Implicated in the pathogenesis of lupus nephritis
ELISA
Enzyme-linked immunosorbent assay
酵素結合免疫吸附分析法
Temporal patterns of joint involvement in polyarthritis
- Migratory (rheumatic fever, GC arthritis)
- Remit, then reappear in other joints - Additive (RA, SLE)
- Progressively worsen - Intermittent (RA, polyarticular gout, palindromic rheumatism)
- Complete remission in btn attacks
Ix for Chronic polyarticular Sx
- CBC
- ESR, CRP
- L/RFT
- Serum uric acid
- Urinalysis
- Synovial fluid analysis
- Relevant serological tests, e.g. ANA, RF, Anti-CCP
- Relevant radiological studies
Rheumatoid factor
IgM, an autoAb against IgG
Not very sensitive (70% positive in RA)
Not specific
High level = poor RA prognosis
Anti-CCP
Anti-cyclic citrullinated peptide Abs
- Specific for RA (>90%)
- Predictive of progressive and erosive disease
- Allow early Dx
- Not sensitive (60%)
- Sensitivity better if screened tgt with RF
- 100% sensitivity + specificity for RF + Anti-CCP tgt
Ankylosing spondylitis associations
HLA-B27 SI joints, spine Reactive arthritis (Reiter's syndrome), psoriasis, IBD
Pharm tx for RA
- Pain relief
- Panadol / NSAID / COX-2 inhibitor
- DMARDs (Disease-modifying anti-rheumatic drugs)
- Start within 3m if poor result with NSAIDs
1. Hydroxychloroquine
2. Methotrexate
3. Sulfazalazine
4. Leflunomide
5. Parenteral gold
6. Penicillamine
7. Azathioprine
8. Cyclosporine A
- Start within 3m if poor result with NSAIDs
- Biologics
- TNF alpha blockers
Etanercept (Enbrel)
Infliximab (Remicade)
Adalimumab (Humira)
Golimumab
Certolizumab pegol - IL-1 receptor blocker
Anakinra - Anti-CD 20 Ab
Rituximab (MabThera) - IL-6-receptor blocker
Tocilizumab (Actemra) - T-cell co-stimulation blocker
Abatacept (Orencia)
- TNF alpha blockers
- Corticosteroids (local or systemic)
Allopurinol SE
Toxic epidermal necrolysis and vasculitis
Pseudo-gout
aka Calcium pyrophosphate deposition disease (CPPD)
Affect knees
Acute attack tx same as gout
FK-506
Tacrolimus
Calcineurin inhibitor –> decrease IL-2
SE: New onset DM, nephrotoxicity
Drugs that induce lupus
Procainamide
Hydralazine
Drugs that exacerbate SLE
Sulphonamide
OCP
Joint function history taking
RB
- Dressing
- Washing unaided
- Working in kitchen
- Climbing stairs
- Get in and out of car
Dermatomyositis classical signs
RB
- Heliotrope rash
- Periorbital edema
- Photosensitive rash on sun exposed areas, e.g. V neck sign
- Gottron’s patches: scaly, violaceous rash on dorsal MCPJ and PIPJ
- Signs of underlying malignancy
Sjogren’s syndrome classical signs
RB
Wiki: Long-term AI disease in affecting moisture-producing glands
- Dry eyes, gritty sensation, may be cx by infection
- Positive Schimer’s test: sterile strip of filter paper hooked onto temporal side of lower eyelid; positive if mositure extends <5mm in 5 mins
- Dry mouth
- Synovitis of MCPJ and PIPJ
- Lymphadenopathy
- Post-auricular mass, parotid and submandibular swelling
- Raynaud’s phenomenon
- RA in 50% patients
- May transform into lymphoma
Ix findings for Sjogren’s syndrome
RB
- CBC (low WBC, low lymphocyte)
- Increase ESR
- Electrolytes, e.g. HypoK due to secondary renal tubular acidosis (type 1; distal)
- Increase serum globulin, IgG
- Immune markers: ANA, Anti-Ro, Anti-La, RF
- Abnormal salivary duct scintigraphy, biopsy
- FNAC parotid/submandibular mass
Ix for SLE
- ANA (Anti-dsDNA, ENA, Antiphospholipid only when ANA is positive or highly suspect)
- RF (to rule out RA/Sjogren)
- Complements
- CBC w/ D
- RFT, including urine exam
- Serum albumin, globulin
CREST syndrome
- Calcinosis cutis
- Raynaud’s phenomenon
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia
Asso w/ Anti-centromere Ab
Spare kidneys
Sjogren Abs
Ro(SS-A) and La(SS-B)
Female (9:1)
Xanthine oxidase inhibitor
- Allopurinol
2. Febuxostat
SE of Febuxostat
wiki
Nausea Diarrhea Arthralgia Headache Elevated LFT Rash
CI: Azathioprine at same time
New criteria for RA
ACR/EULAR 2010
> =6 out of 10 = positive
Joint involvement 1 large --> 0 2-10 large --> 1 1-3 small --> 2 4-10 small --> 3 >10 (at least 1 small) --> 5
Serology
RF and ACPA (Anti-Citrullinated protein Ab) normal –> 0
Any low positive (1-3x ULN) –> 2
Any high positive (>3x ULN) –> 3
Duration
<6wk –> 0
>= 6wk –> 1
Acute phase reactant
ESR/CRP normal –> 0
Any abnormal –> 1
Joints: exclude DIP, 1st MTP, 1st CMC
Small joints: MCP, PIP, MTP 2-5, thumb IP, wrist
Old criteria for RA
ACR 1987
4 out of 7
- Morning stiffness >1h
- Arthritis >= 3 joints
- Arthritis of hand joints
- Symmetrical arthritis
- Rheumatoid nodule
- RF
- Radiological changes suggestive of joint erosion
Poor prognostic factor for RA
What to do?
HH
- High disease activity at onset (>= 18 joints)
- High baseline joint damage (erosive disease)
- Persistent high CRP
- Positive IgM RF or Anti-CCP
- Positive FH of RA
- Nodular disease
- Extra-articular manifestations
==> Early aggressive use of DMARDs
Extra-articular manifestation of RA
ESNMHLHK
(Ed suc nip in MH Les HK)
- Eye: Scleritis, keratoconjunctivitis (secondary Sjogren)
- Skin: thinning, ulceration, Rheumatoid nodules
- Nerve: Peripheral neuropathy, CTS
- Muscle: wasting
- Hemat: anemia (of chronic disease, PU due to NSAID/steroid), thrombocytopenia, lymphadenopathy, splenomegaly
- Lung: Fibrosis, pleurisy, pleural effusion
- Heart: Pericardial effusion/pericarditis
- Kidney: AA amyloidosis
Rheumatoid nodules
- Non-tender, firm, SC nodules
- Usu over bony prominence (but can be everywhere)
- Usu on extensor surface, pressure areas (ulnar border of elbow/forearm, knuckles)
- May have ulceration –> infection
Pre-Tx Ix and screening for RA
- CBC
- LRFT
- CXR
- Viral hepatitis serology
- Comorbidities
- Extra-articular manifestations
- Infections (TB, hepatitis)
- Vaccination status
- Pregnancy and lactation
Tx algorithm for RA
Dx, Pre-Tx Ix and screening
–> Check for poor prognostic factors
Yes –> start combination DMARD +/- steroid
No –> MTX monotherapy
If poor response after 6m after combination –> MTX + Biologic or Triple therapy
If still poor –> taper and stop steroid; then stop biologics; titrate to lowest possible dose of DMARD
RA drug classes
- Analgesics
- Conventional DMARDs (HCQ, MTX, Sulfasalazine, Leflunomide)
- Biologics (TNF alpha blocker, IL-1/6 blocker, Anti-CD20, T cell co-stimulation blocker)
- Corticosteroids
SE of Methotrexate MTX
Antimetabolite, folic acid analog
- Pneumonitis (can lead to fibrosis)
- Mucositis
- Intestinal
- Hepatotoxicity (cirrhosis)
- BM suppression
- Lymphoma
- Alopecia
- Teratogenicity, not safe for BF
SE of Hydroxychloroquine
Anti-malarial; also for RA, SLE
- Bull’s eye maculopathy
- Corneal deposition
- Skin pigmentation esp exposed to sunlight
- Peripheral neuropathy
- Proximal myopathy
- Cardiomyopathy
Sero-negative Spondyloarthropathy
Inflammatory back pain
- Young (<40y)
- Insidious onset
- Nocturnal pain
- Improve with exercise
Type [PEAR]
- Ankylosing spondylitis
- Psoriatic arthritis
- Reactive arthritis / Reiter’s syndrome
- Enteropathic arthropathy asso w/ IBD (UC>CD)
Ankylosing spondylitis
- Chronic, inflammatory disorder of axial skeleton, affect SIJ and spine
- Strong genetic asso w/ HLA-B27
- Usu ascending involvement
Psoriatic arthritis
- DIP, peripheral arthritis, spondyloarthritis
- 5 patterns
- Distal arthritis
- Asymmetrical oligoarthritis
- Symmetrical polyarthritis (RA-like) - most common in HK
- Spondyloarthritis (AS-like)
- Arthritis mutilans (rare)
- Seronegative (RF, ACPA neg)
- Phase 1: Pain relief: NSAID, local steroid injection
- Phase 2: 1st line DMARD, i.e. MTX
- Phase 3: Anti-TNF or another DMARD (avoid HCQ)
- Phase 4: Biologics
Gout
- Dx by urate crystals in synovial fluid / tophus
- M; 30-60y/o
- Precipitated by Thiazides
- Asymptomatic hyperuricemia –> acute gouty arthritis –> chronic gouty arthritis
RF for Gout
- Hyperuricemia
- FH
- Male
- PM women
- Obesity
- Alcohol
- High purine diet
- Drugs, e.g. Thiazide, Loop diuretic, Pyrazinamide, Cy A
- Hyper-TG
Tx of Gout
Asymptomatic hyperuricemia
- Drug not indicated
Acute attack
- Mild/Moderate: Monotherapy with Oral NSAID or oral colchicine or IA/systemic steroid
- Severe polyarticular: combination of NSAID/Steroid + Colchicine
- NSAID: Indomethacin; avoid Aspirin
If repeated acute attacks (>=2 in 1y), tophus, renal disease, need to take diuretics –> start urate lowering drugs (XOI, Uricosuric) *1-2wk after acute attack subsided
- XOI: Allupurinol, Febuxostat
- Uricosuric: Probenecid
SE of Colchicine
- Acute: GI upset, esp diarrhea
2. Chronic: Myelosuppression, renal impairment
SLICC Classification criteria 2012 for SLE
AC ON SSRN HLT
> =4 (at least 1 clinical, 1 immunologic)
Clinical x11
- Acute/subacute cutaneous lupus
- Chronic cutaneous lupus
- Oral/nasal ulcers
- Non-scarring alopecia
- Synovitis (>=2 joints)
- Serositis
- Renal
- Neurologic
- Hemolytic anemia
- Leukopenia
- Thrombocytopenia
Immunologic x6
- ANA
- Anti-dsDNA
- Anti-Smith Ab
- Anti-phospholipid Ab
- Low complement (C3/C4/CH50)
- Direct Coombs’ test (in absence of hemolytic anemia)
Tx for SLE
- NSAID, Anti-pyrexial drugs
- Anti-malarials: Chloroquine, Hydroxychloroquine
- Useful for arthritis, cutaneous manifestations, constitutional symptoms
- May reduce systemic complications
- Retinopathy is rare but irreversible
- Corneal deposition is more common and reversible - Steroids
- Very useful but numerous SE for long term use
- Variable doses for different manifestations
- Small dose for skin rashes, arthritis, serositis
- Moderate dose for resistant serositis, hematological abnormalities and class 5 GN
- High dose for severe/resistant hematologic changes, diffuse GN, major organ involvement
- Whenever steroid is indicated, consider a steroid sparing agent (including anti-malarial agents) or an immunosuppressive drug - Immunosuppressives
- Azathioprine (hepatotoxicity)
- Cyclophosphamide (infertility, hemorrhagic cystitis)
- Cy A (renal toxicity)
- MTX (hepatotoxicity)
- Leflunomide (hepatotoxicity)
- MMF (GI related SE, e.g. abd pain, better tolerated)
- Tacrolimus [FK-506]
* All can cause BM suppression, immunosuppression; potentially carcinogenic, teratogenic - Biologic agents
- Rituximab (Anti-CD20 monoclonal Ab – off label use)
- Belimumab (Anti-BAFF *B cell activating factor)
Cause of SOB in SLE
- RS
- Pleural effusion, infective pneumonia (esp on steroid/immunosuppressants), ILD, BOOP, Shrinking lung syndrome (rising diaph, neuromuscular, myopathy) - CVS
- Pericardial effusion, myocarditis, HT heart disease (HT due to uremia/steroid), IHD (arteritis of coronary a.) - Vascular
- PE (antiphospholipid syndrome, NS, immobility), pul HT, fluid retention - Anemia
- Due to chronic disease, part of SLE pancytopenia, hemolytic anemia, due to uremia, GIB due to steroid/NSAID, BM suppression due to immunosuppressants (e.g. Aza)
High CRP in SLE
Suspect infection
Could also be: active arthritis, serositis, vasculitis
Specific tx strategy for SLE
Conservative
- for MSS Sx, Cutaneous lupus, systemic upset, serositis
- MSS: NSAID, HCQ, Low dose prednisolone
- Cutaneous: Avoid sunlight, topical steroid, HCQ
Aggressive
- for life-threatening Cx, major organ involvement
- Ind: Lupus nephritis, Cerebral lupus, Transverse myelitis, peripheral neuropathy, pneumonitis/pul hemorrhage, severe and refractory serositis, severe hemolysis
- Start with high dose steroid, then cytotoxic agents
e. g. high dose IV steroid, then oral steroid for maintenance and rapidly tapered - Lupus nephritis now use MMF (instead of Aza)
- Cyclophosphamide for more severe and life threatening Cx
Poor prognostic factors for SLE
- Race (Black)
- Late disease onset
- Socio-economic status
- Time btn onset and Dx of SLE
- Acute disease at presentation
- Major organ involvement (renal, cerebral)
- Severe thrombocytopenia
Sulfasalazine
For RA, IBD
Breaks into 5-ASA (Mesalazine)
Biologics SE
- Infection: Reactivation of HBV, Latent TB (Etanercept has Lower risk of TB Reactivation)
- Malignancy
- Others: Eg. Injection site reaction, Infusion reaction
TNF Blockade: Infection, Neutropenia, Demyelinating disease, HF, Malignancy, AI disease
Behçet’s disease
Classical triad: Mouth ulcer, genital ulcer, uveitis
Young (20-40y); affect BVs of all sizes
Dx: at least 3 episodes of mouth sores in a year together with at least 2 of: genital sores, eye inflammation, skin sores, a positive skin prick test (Pathergy test)
Pathergy test
Behçet’s disease
Gout and Polycythemia vera
Related due to increase RBC breakdown
RA radiological features
Rev
Soft tissue swelling Periarticular osteopenia Joint space narrowing Periarticular bony erosions Chronic deformities
SE of Biologics (anti-TNF)
Rev
Infections, particularly mycobacterial, fungal, viral
Reactivation and de novo infection
Tumors
Non-melanotic skin cancer
Heart failure
Autoimmunity
Development of anti-drug Abs