SLE Flashcards
List some DDx for a presentation of:
- 34yo F
- 3 week hx joint pain, fever, facial rash, alopecia
- intermittent ankle and knee joint paint
PDx. SLE
DDx.
• AI disease
o SLE (anti-DsDNA)
o Drug induced SLE- hydralazine, procainamide, isoniazid, chlorpromazine, methyldopa, quinidine
o Scleroderma (CREST mnemonic)- calcinosis, Raynaud’s, esophageal dysmotolity, sclerodactyly
o RA (RF, anti-CCP)- symmetrical small joint polyarthritis, DIP sparring, erosive x-ray
o Sjogren’s syndrome- dry mouth/eyes, joint pain
o Mixed CT disease (anti-RNP)
• Myopathies- polymyositis, dermatomyositis
• Seronegative spondyloarthropathies (PAIR mnemonic)- psoriatic arthritis, ankylosing spondylitis, IBD, reactive (chlamydia, shigella, salmonella, campylobacter)
• Vasculitides
• Anti-phospholipid syndrome
• Infection- HBV, HCV, HIV, CMV, viral illness
• Dermatology causes- light sensitivity, allergy
• Other arthritis
o Septic arthritis (monoarthritis)
o Crystalline arthropathies- gout, pseudogout
How is SLE diagnosed?
Diagnostic criteria (American College of Rheumatologists): need 4/11 (Mnemonic MD SOAP Brain) Clinical criteria (7): M- malar rash D- discoid rash S- serositis O- oral/nasopharyngeal ulcers A- arthritis P- photosensitivity Neuro- headache, seizures, psychosis, concentration, memory Lab criteria (4): B- blood (haemolytic anaemia, reticulocytosis, leukopenia, thrombocytopenia, antiphospholipid syndrome) R- renal problems (lupus nephritis) A- ANA positive I- immunological features (anti-dsDNA, anti-Smith, anti-phospholipid) N- neuro (as in clinical)
What investigations would you do?
Diagnostic: - ANA panel (immunofluorescence or enzyme-linked immunosorbent assay): anti-dsDNA, anti-histone - anti-phospholipid antibodies (lupus anticoag and anticardiolipin Abs) Bedside - urinalysis - ECG - echo Bloods - full AI panel (anti-dsDNA, anti-histone, anti-smith, anti-Ro, anti-RNP, Sc-70 - FBC - EUC - ESR/CRP - CK- myositis - serology HBV, HCV, EBV- septic/reactive arthritis - blood and urine cultures - coag panel (raised aPTT in anti-phospholipid syndrome) - complement Imaging: - X-ray joints (non-erosive_ - CXR (pericardial, pleural effusions) - ECG - Renal US (biopsy)
Explain the significance of antinuclear antibodies?
- Def: auto-antibodies that bind to the contents of the cell nucleus
- Indication: ANA- serological hallmarks of AI disease (sensitive), useful for diagnosis and estimation of disease progression
- Various ANA subtypes bind to different proteins in the nucleus
List the differing ANA subtypes and their relevant conditions?
ANA- SLE (90-100%), drug-induced SLE (95%), RA (45%), scleroderma (95%), Sjogren’s syndrome (60%), mixed CT (100%)
• Anti double-stranded DNA (anti-dsDNA)- SLE (poor prognosis, renal disease) (most sensitive for SLE 70%)
• Anti-Smith- SLE (most specific for SLE)
• Anti-histone- drug-induced lupus
• Anti-phospholipid- SLE (anti-cardolipin, lupus anticoagulant)
• Anti-Scl-70, anti-centromere- Scleroderma
• Anti-SSA, anti-SSB- Sjogren
How is ANA measured?
Method: immunofluorescence and enzyme-linked immunosorbent assay (ELISA)
o HELA cells (do not die after set number of divisions) used as substrate to detect antibodies
o Cells visualized w microscopy and UV
o If antibodies present, they will bind to antigens on these cells -> ANAs with bind to the nucleus
o Visualized by adding fluorescent tagged anti-human antibody (which binds to these antibodies)
o Depending on the antibody present, distinct patterns seen on the HELA cells
o In immunofluorescence, the level of autoantibodies is reported as a titre (highest dilution of the serum at which autoantibodies still detectable)
- Positive autoantibody titres at a dilution > 1:160 clinically significant
Why does she have a malar rash?
- Malar rash- butterfly shaped macular rash on nasal bridge, red/purple, scaly
- Caused by photosensitivity: UV -> apoptosis of cells w exposure of DNA to autoantibodies -> deposition of immune complexes in sun-exposed areas of skin (type 3 hypersensitivity) -> inflammatory response
What are some of the connective tissue diseases you know of?
Autoimmune: o SLE o RA o Scleroderma o Sjogren’s syndrome o Mixed CT disease o Polymyositis o Dermatomyositis Genetic: o Marfan’s syndrome o Ehlers-Danlos syndrome o Osteogenesis imperfecta (poor quality collagen -> brittle bones)
What would be the significant if the woman had previous miscarriages?
Previous miscarriages would suggest antiphospholipid syndrome
• Path: auto-antibodies (anti-cardiolipidin and lupus anticoagulant) bind to platelets and monocytes
⇒ Creates microthrombi -> lodge in placenta vasculature
⇒ Auto-antibodies can also cross the placenta → miscarriages and obstetric complications
• Clinical (CLOT mnemonic)
C- coag defect
L- levido reticularis (mottled vascular pattern)
O- obstetric complications
T- thrombocytopenia
• Diagnosis
- Clinical: thrombotic event, spontaneous miscarriage
- OR blood: lupus anticoag, anticardiolipin
What is lupus anticoagulant?
• Def: immunoglobulin that binds to phospholipids and proteins on the cell membranes of platelets and monocytes
⇒ creates microthrombi by binding to phospholipids on platelets (prothrombotic agent)(thus misnomer, as not an “anticoagulant”, but does raise PTT in vitro)
• Indication for testing: prolonged clotting times on routine plasma test
How do you test for lupus anticoagulant?
Method:
1) Mixing test
• Pt plasma is mixed with normal pooled plasma, clotting reassessed
• If clotting inhibitor (e.g. LA) present, it will interact w normal pooled plasma -> give abnormal PTT
• Diagnosis (LA) excluded if clotting time of mixed plasma corrects towards normal -> more likely a deficient clotting factor
2) Phospholipid-sensitive clotting test (e.g. Russel’s viper venom time)- to confirm LA diagnosis
What type of renal disease can be caused by SLE?
1) Lupus nephritis - immune complex deposition -> inflamed glomerulus
- class I: minimal mesangial lupus nephritis
- class II: mesangial proliferative lupus nephritis
- class III: focal lupus nephritis (50% glomeruli affected)
- class IV: diffuse lupus nephritis (>50% glomeruli affected)
- class V: lupus membranous nephropathy
- class VI: advanced sclerosing lupus nephritis (>90% glomeruli affected)
2) tubulointerstitial nephritis
- interstitial infiltrate
- tubular injury
3) vascular disease
- immune complex deposition
- immunoglobulin microvascular thrombi
- thrombotic microangiopathy
- vasculitis
- atheroembolic disease
- atherosclerosis
Describe the principles fo SLE treatment?
- ensure LTM survival
- achieve low disease activity
- prevent organ damage
- minimize drug toxicity
- improve QOL
- educate pts
Describe the treatment of SLE?
Non-pharm: avoid sun exposure
Pharm:
- mild: hydroxychloroquine LTM + prednisolone low dose STM + NSAID
- moderate: hydroxychloroquine LTM + prednisolone medium dose STM + NSAID
- severe: immunosuppressive (cyclophosphamide, rituximab) + prednisolone high dose STM
Monitor: renal function, BP, eye exam
Describe the MA and SE of hydroxychloroquine?
Hydroxychoroquine:
o Indication- LTM Rx for constitutional, cutaneous and articular manifestations, continued as preveter after symptom resolution
o MA: Anti-malarial- interfers w digestive vacuole function in malarial parasites. Immunosuppressive- inhibits chemotaxis of neutrophils and eosinophils, impairs complement-dependent antigen-antibody reactions
o SE: retinal toxicity
