SLE Flashcards
SLE - ARA criteria? (11)
4/11 of followings
- Malar rash
- Discoid rash (indurated/erythematous/scaly plaques)
- Photosensitive rash
- Neuropsychiatric (wide variety of symptoms): seizures & psychosis (not related to drugs/metabolic), dementia, neuropathy, optic neuritis, stroke, MS-like
- Oral/Apthous ulcers
- Serositis: pericardial/pleural effusion/pericarditis
- Lupus nephritis (proteinuria >500mg/24h or RBC casts)
- Haematological: haemolytic anaemia, cytopaenia, ITP
- ANA (>1:160)
- Immunological: Anti-dsDNA, anti-smith, antiphospholipid Abs
- Arthritis
SLE - PRICMCP
P: ask main presenting symptoms: ARA 11 criteria + constitutional symptoms (malaise [100%], weight loss [60%], Fever [77%]) + thrombosis (arterial/venous) / recurrent miscarriages/fetal death
Note if renal biopsy proven lupus, do not need other criteria.
R: FH, Sex (F>M), Age (15-45), ethnicity (non-white), Drugs
I: how was Dx established - clinical, serological +/- renal biopsy
C: of disease (taken at the same time as P) - focus on vascular disease [MI, Stroke, VTE], lupus nephritis, CNS lupus, debilitating arthritis, recurrent miscarriages/fetal death in utero;
M: how does the patient protect themself from sun-exposure?, NSAIDs, current drug regime, whether it had made any difference. Previous regime + why stopped.
Complications of drugs: [HCQ] VF defect, retinal toxicity, Steroids [DM/Lipids/infection/OP], ImmSx [BM/Infection/Hepatotoxicity/Pancreatitis - Aza/Haemorrhagic cystitis/Ototox - Cyclo]
C: impact - reduced ADL? work? is the disease active? frequency of F/U?
P: patient’s understanding of this incurable/chronic disease/prognosis.
What are the symptoms of SLE that are not in ARA criteria? (3)
Sicca (dry eyes/dry mouth)
Raynaud’s
Alopecia
Causes of Drug-induced lupus? (5)
The Lupus PhIMP
Procainamide
Hydralazine
Isoniazid
Methyldopa
Penicillamine/Phenytoin
What would be your advise to young women with SLE with regards to contraception?
Contraception is recommended - pregnancy is risky if the disease is active.
Progesterone or Low-dose Oestrogen contraception (given prothrombotic risk with usual OCPs)
SLE - examination
In short…
Steroids (Cushingoid/prox myopathy) - Rheum (symmetrical/deforming/reducible polyarthropathy) - Skin (Alopecia + Rash) - Cardiac (pericarditis/murmur [LSE]) - Lung (fibrosis/effusion) - Abdo (HSM), Neuro (cerebellar/MNM)
In long…
Cushingoid/Ecchymoses/Anaemia/Alopecia
Hands: symmetric polyarthritis/rash/vasculitis (?gangrene, nail-fold infarct)
Arm: BP (HTN in lupus nephritis)
Malar/Discoid Rash
Eye: keratoconjunctivitis sicca, fundi - Cystoid lesions (hard-exudates due to vasculitis)
Apthous ulcers
Cervical LN
Heart: no pericardial rub/muffling
Lung: pleural effusion, ILD, pleurisy
Abdo: no renal angle tenderness/splenomegaly
MSK: tenderness in… / no evidence of active synovitis/effusion
Neuro: evidence of cerebellar ataxia, mononeuritis multiplex
Legs: thrombophlebitis/leg ulceration
Would like to check urine for haematuria/proteinuria, temperature
What are you looking for in Fundi in a patient with SLE? (1)
Cystoid lesions - hard exudates secondary to vasculitis
What are the differentials for murmur in patient with SLE? (2)
Standard murmurs like AS/MR
Libman Sacks endocarditis
The most specific Ab for SLE?
Best Ab for disease monitoring of activity?
- Anti-Smith
- Anti-dsDNA
Other ABs associated with SLE? (except ANA, dsDNA, Anti-smith) - 3
Anti-Ro/SSA (neonatal lupus, congenital heart block, cutaneous), also Sjogren’s
Anti-La/SSB (neonatal lupus, cutaneous)
Anti-U1RNP (MCTD with myositis)
Can you have ANA -ve lupus?
Yes - Cutaneous Lupus with positive Anti-Ro/SSA: classic annular rash with central clearing (Sub-acute cutaneous lupus)
What are lung involvement of the SLE? (6)
ILD
Pleuritis
Pleurisy
PE
Pulmonary haemorrhage
Pulmonary HTN
Cardiac manifestations of SLE? (4)
Pericarditis/Serotitis
Conduction block
Accelerated atherosclerosis (2-5 x mortality), exacerbated by prednisolone
Libman Sack’s endocarditis
What are the criteria for biopsy-ing the kidney in Lupus nephritis? (3)
Increasing Cr without other cause
Proteinuria 1g
Proteinuria 500mg + Haematuria (>5 RBCs / HPU) or Cellular casts
What are the indications for treating Lupus nephritis?
Depending on the class, based on renal biopsy: I-II (ACEi), III-IV (treat), VI (no point)
Basically treat the proliferative GN.
Class 1: minimal mesangial = normal LM, no Rx, ACE for proteinuria
Class 2: mesangioproliferative, no Rx, ACE
Class 3: focal prolif <50% Glomeruli, Rx indicated
Class 4: diffuse prolif >50% glomeruli, Rx indicated
Class 5: membranous, Rx if in nephrotic range
Class 6: advanced sclerosed –> >90% glomeruli sclerosed, no Rx, burnt out
What are the commonest neurological syndrome/symptoms in Lupus/SLE? (5)
- Cognitive impairment (most common)
- Headache
- Mood disorder
- Seizures
- CVA
What do you look for in Brain MRI in patients with suspected CNS lupus? (2) Most useful serology for CNS lupus?
Atrophy is the most common finding.
Look for increased signal intensity in both grey + white matter, in conjunction with positive APL + Anti-Ribosomal P10
Significance of triple positive antiphospholipid syndrome? (anticardiolipin, lupus anticoagulant, b2m +ve)
Lots and lots of thrombosis. Very High Risk.
Significance of positive Ab to Anti-Ro/SSA in female of reproductive age?
Significant risk of congenital - heart block (2-3%) where 60% req pacemaker, 20% mortality.
3 specific Abs for SLE?
Anti-dsDNA (97% specific)
Anti-Smith (highly specific)
Anti-Ribosomal P (99% specificity, poor sensitivity): a/w depression, psychosis from CNS lupus.
How would you investigate this patient with SLE?
T: ANA, dsDNA, Anti-smith, antiphospholipid Abs, anti-Ribosomal P (CNS lupus) + as per ARA criteria (FBC + DAT - ACD, low PLT, WCC, EUC + UA to look for casts/RBCs/proteinuria (lupus nephritis).
If criteria met, renal biopsy.
E: Anti SSA/SSB (Ro/La - Scleroderma), U1-RNP (MCTD), anti-Histone (drug-induced)
S: dsDNA, C3/C4 (+CH50 - total haemolytic complement), ESR - are markers of disease activity. CRP (serositis only), WCC (leukopaenia)
T: Baseline FBC, LFTs, EUCs prior to commencing ImmSx. Coags (PT raised)
S: Guided by symptoms - ECG (ischaemic changes, conduction disease), TTE (if murmur - LSE, RWMA suggestive of IHD), CXR (obvious fibrotic changes/effusion), PFT (DLCO/restrictive pattern), XR joints affected, work-up for CNS lupus (dep on PC: EEG if seizure, CTB+COW if stroke, LP/MRIB (LP - anti-DNA Abs, IgG, oligoclonal bands are increased or normal, MRIB to look for white matter lesions)
What is the prognosis of SLE? 4 major causes of death?
Generally good - 90% 10y survival. Lupus nephritis is associated with poor prognosis.
Major causes of death are: infections, renal failure, lymphoma, MI.
What are typical findings of renal biopsy in lupus nephritis and which histopathology are associated with the best and worst prognosis?
Best = Mesangial proliferation.
Worst = Diffuse proliferation (need aggressive tx with high-dose pulse steroids + cyclophosphamide)
Mediaum = focal GN, membranous prolierative.
What are the general non-pharmacological Mx of SLE? (5)
Avoid sun exposures/sunscreens
Stop smoking + aggressive CV risk factor Mx
Osteoporosis: fall prevention, Calcium , Vit D, bisphosphonate (if long term steroids likely)
Infection prevention + vaccination
Malignancy screening: Lymphoma***, cervical dysplasia (offer HPV vaccine***)
+
Education relating to complications of disease and importance of surveillance (e.g. ocular toxicity with HCQ)
Support groups (e.g. Lupus Australia)
Pharmacological Mx of lupus/SLE? (many!) what do you know about the pharmacological Mx of Lupus? (5 principles)
Involve Rheumatology early to help guide management. General principles are;
- HCQ for all
- Steroids for initial control of inflammation
- Cyclophosphamide for end-organ damage (NEJM 2012: MMF + steroids was not inferior with fewer side effects)
- Azathioprine or MMF for maintenance
-
Specific organ-disease Mx
- APS: life-long anticoagulation (Warfarin)
- Arthritis/Serositis: MTX
- Mucocutaneous: topical steroids +/- MTX/Steroids
- Raynauds: avoid cold, amlodipine, topical nitrates (GTN 5-10mg/d), PG infusions
For resistant disease
- Belimumab or Rituximab.
What are the risk of pregnancy in patients with Lupus? (4)
Maternal:
- High risk of flare (60%)
- High-risk of thrombosis (if APS)
- Significant risk of pre-eclampsia
Foetal:
- Neonatal lupus
What is your approach in managing this patient planning ongoing pregnancy who is on treatment for SLE and APS?
This is a complex management problem: involve Rheumatologist + Obstetrician early.
-
Educate: about the risk of flare, pre-eclampsia, pre-term birth, neonatal lupus, fetal loss, congenital CHB (SSA/SSB+ve)
- Advise discontinuation of meds increases Lupus flare and pregnancy-related complications
- Defer conception for 6 months before getting pregnant, especially lupus nephritis (highest risk) -
Assess the activity: aim free of active disease for 6 months
- Activity at the time of conception: single important RF for adversity.
- Test Anti-Ro/La (SSA/SSB) - CHB, ds DNA, C3/4, CH50, other routine bloods - If the disease is active: Aim to induce remission and take precautions to avoid conception
- Continue HCQ (if mild), pred+AZA (if severe/nephritis), MTX can be used if not pregnant yet (better than Cyclo). Once pregnant, MTX, Cyclophosphamide, MMF, Leflunomide - all CI’ed.
Although currently evidence is lacking, given that IgG does not cross placenta until week 12, we continue Rituximab or Belimumab, if they were already on these
Tacrolimus can be used - discuss with renal physician - so MMF can be switched to either AZA or TAC
They also need Aspirin, regardless of APS status, starting in 12 weeks gestation (to reduce risk of pre-eclampsia, and IUGR)
Cease ARB/ACEi - switch to Methyldopa, Labetolol, Nifedipine or Hydralazine
** HCQ is class D drug but still used in pregnancy as benefit outweighs the risk of flare.
What is your approach to managing APS in pregnancy?
What about if patient develop thrombosis whilst INR therapeutic at 2-3?
Switch to Heparin + Aspirin during pregnancy.
Aim higher INR (3-4) or remain same INR (2-3) then add Aspirin.
Pharmacological Mx option for those who failed standard therapy in SLE? (2 agents to consider?)
Rituximab
Belimumab (BlyS blocker) - evidence accumulating.
Is steroids safe in pregnancy?
Yes, except for Dex, which crosses placenta.
Antiphospholipid syndrome History?
P: when dx, where was the clot - venous, arterial?
R: SLE or any other AI conditions, FH
I: how was dx confirmed - bloods, clinical or both. If was on bloods one-off?
C: Arterial (stroke, MI) or Venous (e.g. axilla), Bleeding (thrombocytopaenia), pregnancy-related problems: pre-eclampsia, recurrent unexplained abortion.
Ask: did the patient have Addison’s (adrenal vein thrombosis), bowel ischaemia, (renal failure renal vein trhombosis)
M: Warfarin vs. Observation (e.g. +ve Cardiolipin but no clinical features), INR target, is patient also on aspirin (could be added on due to TE whilst on therapeutic Warfarin)
C/P: current issues, interval of F/U
APS investigations? (4)
Anticardiolipin IgG (diagnostic if high titre + correct clinical context)
Lupus anticoagulant: if detected, higher risk of thrombosis/pregnancy related complications
Beta-2-glycoprotein-1
PT (raised), PLT, Other autoimmune profiles
