Rheumatology Flashcards
Discuss antiphospholipid syndrome
-Types (3)
-Prevalence (5)
-Diagnosis (3)
- Types
-Primary - antiphospholipid antibodies are present, but Lupus anticoagulant is negative
-Secondary - associated with other conditions - mainly SLE
-Pregnancy outcomes are similar in both types
-Seronegative Lupus. Lab test negative but strong suggestive Hx. - Prevalence
-2-10% in normal population
-10-20% of women with recurrent miscarriage
-30% of patients with thrombosis
-30% of patients with severe early onset PET
-30-50% of patients with SLE - Diagnosis
-Best performed outside of pregnancy
-One laboratory test positive twice12 weeks apart (Lupus anticoagulatant, anti-cardiolipin antibodies, anti beta 2 glycoprotein 1 antibody)
-One clinical criteria Either Thrombosis related (arterial thrombsis, venous thrombosis, small vessel thrombosis) OR pregnancy related (Unexplained miscarriage >10 weeks, PTB before 34/40 due to PET/placental insufficiency, 3 or more unexplained early pregnancy losses)
Discuss the pathophysiology of anti-phospholidip syndrome
-What it is (1)
-Types of antibodies and how they are tested for(3)
-How it impacts thrombosis (2)
-How it impacts placental function (3)
- What is APLS
-A heterogenous group of antibodies directed against anionic phospholipids and phospholipid binding proteins - Types of antibodies
-Anti cardiolipin (ELISA - >99 centile for IgM and IgG)
-Anti beta2 glycoprotein (ELISA - >99 centile for IgM and IgG)
-Lupus anticoagulant - Prolonged APTT, prolonged dRVVT. (Correction of prolongation improves with addition of phospholipid) - How it impacts thrombosis
-Binding of Anti-phospholipid antibodies to Beta2 glycoproteins causes activation of inflammatory response and platelet plug formation on endothelia.
-inhibition of: fibrinolysis, protein C activity, tissue factor pathway inhibitor activity - How it impacts placental function
-Binding of anti-phospholipid antibodies causes infarction and thrombosis in the spiral arteries
-Anti phospholipid antibodies bind to trophoblasts causing impaired differentiation, proliferation and invasion on endometrium
-Complement is activated which results in trophoblast apoptosis
-Overall inflammatory mediated placental damage
-APL inhibit angiogenesis and endothelial growth factor.
Discuss APLS in pregnancy
-Impact of pregnancy on APLS (4)
-Impact of APLS on pregnancy (7)
-What factors predict risk of poor pregnancy outcomes (4)
- Impact of pregnancy on ALPS
-Risk of thrombosis is exacerbated 5-10% risk VTE
-Worsening thrombocytopenia
-Worsening haemolytic anaemia
-RARE - thromboembolic storm resulting multiorgan failure - Impact of APLS on pregnancy
-Increased risk of miscarriage
-FGR >30%
-PET 10% if previous recurrent loss, 30% if previous thrombosis
-PTB - 10% if previous recurrent loss, 30% if previous thrombosis
-Fetal distress in labour
-Fetal death - typically associated with oligo, FGR, PET
-HTN
-Abruption - What factors predict poor pregnancy outcomes
-Past obstetric history - greatest determinant
-Previous thrombosis or late fetal death
-Risk associated with antibody titre esp anticardiolipin
-Thrombosis more common in women with lupus anticoagulant cf anticardiolipin
How should antiphospholipid be managed
-Role of immunosuppression (1)
-Role of anticoagulation (3)
-Other considerations (3)
- Role of immunosuppression
-No role for immunosuppression or plasmapheresis - Role of anticoagulation
-Mainstay of treatment is anticoagulation.
-Previous VTE - lifelong anticoagulation - Warfarin
-Previous arterial thrombosis - aspirin - Other considerations
-Can consider hydroxychloroquin - safe in low doses in pregnancy
-Avoid COC
-Avoid smoking, encourage normal weight
-Thromboprophylaxis on long haul flights
Discuss management of APLS in pregnancy
-Pre-conception (3)
-Antenatal (6)
-Intrapartum (4)
-Postnatal (2)
Pre-conception
-Screen all women with a history of recurrent miscarriage, thrombosis, severe early onset PET/FGR or fetal death
-Commenced low dose aspirin
-Get baseline renal function and LFT
2. Antenatal
-MDT care
-Start LMWH (If previous thrombosis consider treatment dose)
-Regular BP and urinalysis
-Uterine artery dopplers at 20- 24/40
-Serial growth scans from 26/40
-Below knee compression stockings
3. Intrapartum care
-Aim VB
-IOL around 38/40 or earlier if other concerns
-Continuous fetal monitoring
-Discontinue anticoagulation in labour
4. Postpartum care
-Continue anticoagulation 6/52 PP - switch back to warfarin if already on this outside of pregnancy
-Avoid COC
Discuss Ehlers Danlos syndrome
-Pathophysiology (3)
-Types (4)
- Pathophysiology
-Autosomal dominant
-Heterogenous group of rare connective tissue disorders
-Syndrome is characterised by fragile skin and blood vessels, joint hypermobility, easy bruising - Types
-Type I - Classic High risk
-Type II - Mild
-Type III - Most common. Associated with joint hypermobility
-Type IV - Vascular. Highest risk. Maternal mortality 25%
Discuss Ehlers-Danlos syndrome
-Impact of EDS to pregnancy (12)
-Impact of pregnancy to EDS (2)
- Impact of EDS to pregnancy
-Most problems occur in those with Type I or IV
-Uterine rupture
-Damage to perinium and surrounding structures
-PTB
-PPROM
-Cervical incompetence
-Precipitous delivery
-Increased risk malpresentation
-Increased risk IUGR
-Severe PPH
-Uterine inversion
-Poor wound healing - Impact of pregnancy on EDS
-Pelvic instability
-Great vessel rupture and maternal death (Type IV)
Discuss management of Ehler’s-Danlos syndrome in pregnancy.
-Pre conception (2)
-Antenatally (4)
-Intrapartum (3)
- Preconception
-Advise against pregnancy for Type IV
-Refer to genetic counselors to get tested for type - Antenatal
-If Type IV should be cared for at tertiary centre
-Growth scans
-Anaesthetic review given difficult spinal and GA
-Monitor for cervical incompetence and consider cerclage - Intrapartum
-Consider preterm CS for type IV
-Active third stage
-Avoid FBS, instrumental and FSL if concern for affected fetus
Discuss safety of immunosuppressant drugs in first trimester, remaining pregnancy and breast feeding. Discuss if any associated fetal abnormalities known
-Methotrexate
-Leflunomide
-Hydroxychloroquine
-Sulfasalazine
-Azathioprine
-Mycophenalate
-Tacrolimus
-Ciclosporin
-IVIg
-Cyclophosphamide
-NSAIDS
-COX2
-Biologics
- Methotrexate
-Contra-indicated in all three categories
-Associated with NTD, Cardiodefects - Leflunomide
-contraindicated in all three categories - Hydroxychloroquine
-OK in all three categories
-In high doses can cause fetal retinopathy - Sulfasalazine
-Safe in all three categories - Azathioprine
-Safe in all three categories - Mycophenalate
-Contra-indicated in all 3 categories. Can use in third trimester for exceptional circumstances
-Cause cleft lip. microtia, microgathia, hypertelorism - Tacrolimus
-Safe in all three categories - Ciclopsporin
-Safe in all three categories - IVIg
-Safe in all three categories - Cyclophosphamide
-Contraindicated in all three categories
-Same class as methotrexate - NSAIDS
-Safe in first trimester and breastfeeding
-Stop at 32/40 or within 48hrs of delivery
-Not teratogenic
-Can cause neonatal haemorrhage at high doses
-Premature closure of ductus arteriosis
-Impaired fetal renal function - oligo. Reversible - Cox2
-Avoid in all 3 categories. Insufficient evidence - Biologics (Infliximab, adalumbumab
-OK in all three categories
-Consider stopping in 3rd trimester
-Delay live vaccines until 6 months
Discuss neonatal lupus syndromes
-What causes it
-Which mothers are at risk of delivering a baby with NLS (2)
-How is the fetus impacted (4)
- What causes neonatal lupus syndrome
-Anti-Ro and anti-La antibodies from the mother cross the placenta and affect the fetus - Which mothers are at risk…
-Mothers with Lupus, Sjorgens, Raynauds have increased risk of having Anti-Ro antibodies (30% in those with SLE)
-Can affect the fetus even the mother is asymptomatic - Impact to fetus
-Congenital heart block
-Erythematous rash
-Possible behavioural and learning difficulties
-Increase in autoimmune conditions
What are the risks of delivering a baby with neonatal Lupus syndrome
-If mother has SLE
-If mother has Anti-Ro antibodies
-If the mother has had a previously affected child (3)
-Correlation between maternal illness severity and likelihood child affected
- Risk if mother has SLE
-<5% - If mother has anti-Ro antibodies (30% of SLE women, 1% in general population)
-5% risk of neonatal cutaneous lupus
-2% risk of complete heart block - Risk if previous child affected
-2% if no affected child
-20% if one affected child
-50% if 2 affected children - Correlation between maternal illness severity and risk to neonate
-None
Discuss cutaneous neonatal lupus
-Risk of developing if mother has anti-Ro (1)
-Presentation (1)
-Onset and duration of symptoms (2)
-Management (2)
- Risk of developing cutaneous lupus if maternal anti Ro
-5% - Presentation
-Erythematous, scaling plaques on face and scalp
-Photosensitive - Onset and duration of symptoms
-Onset within 2 weeks of birth
-Duration about 6 months
-Permanent scarring is rare - Management
-Avoid sunlight
-May need small doses of hydrocortisone
Discuss cardiac neonatal lupus
-Risk of acquiring if mother is Anti-Ro + (1)
-When detected and diagnosis (3)
-Pathophysiology (4)
-Outcomes
- Risk of cardiac neonatal lupus in anti-Ro + women
-2% - When detected
-Occurs in utero. Usually detected between 18-28weeks
-Picked up with fetal bradycardia
-Feta echo shows AV dissociation with structurally normal heart - Pathophysiology
-Anti-Ro antibodies cause fibrosis of the conducting system in the heart
-Inflammation from the anti-Ro antibodies can also cause myocarditis, effusion, dilated cardiomyopathy
-Heart block can rapidly progress from first to second and third degree (Complete heart block).
-Complete heart block is irreversible but first and second degree maybe reversible. - Outcomes
-15-20% mortality in first 90 days of life
-60% will need pacemakers in early life or early teens
How should cardiac neonatal lupus be managed
- Maternal dexamethasone can reduce risk of progression to complete heart block
- Salbutamol if bradycardia is leading to fetal heart failure
- If diagnosed at term deliver
- In next pregnancy hydroxycholorquine prophylaxis can reduce risk
Discuss rheumatoid arthritis in pregnancy
-Impact of pregnancy on RA (4)
-Impact of RA on pregnancy (4)
- Impact of pregnancy on RA
-50% of women have improvement of symptoms
-Disease activity in previous pregnancy best indicator of how pregnancy will go
-Some may experience deterioration as off DMARDS
-90% have postpartum exacerbation within 4 months - Impact of RA on pregnancy
-No impact on fertility or miscarriage
-Increase in PTB and SGA
-If anti Ro positive neonate at risk of neonatal lupus syndromes
-Occasional joint stiffness limits vaginal birth
Discuss management of rheumatoid arthritis in pregnancy
-Pre-conception
-Antenatal care
-Postpartum
- Pre-pregnancy
-Review meds and stop methotrexate, mycophenalate, cyclophosphamide.
-Can continue other meds but give 5mg folic acid
-Screen for anti-Ro and anti La antibodies - Antenatal
-MDT with rheumatologist and obstetric anaesthenitist
-Assess ability to have vaginal birth
-Serial growth scans
-Continue meds - Postpartum
-Assess safety of med in breast feeding (safe in pregnancy = safe in breastfeeding)
Discuss scleroderma
-Pathogenesis (3)
-Impact of scleroderma on pregnancy (7)
-Impact of pregnancy on scleroderma (3)
- Pathogenesis
-Rare
-Progressive fibrosis involving just the skin if localised cutaneous form or multiorgans if the systemic form
-Part of CREST syndrome - Impact of scleroderma on pregnancy
-Good outcomes if localised cutaneous form of disease
-Pregnancy outcomes directly associated with disease state at conception
-Increased miscarriage rate
-PTD
-PET and FGR due to placental vasculopathy
-Difficult GA due to fibrosis of oral cavity
-If anti Ro or La consider neonatal lupus syndrome and heart block - Impact of pregnancy on scleroderma
-If systemic disease or renal involvement can rapidly deteriorate
-If pulmonary fibrosis - high risk for deterioration
-Pulmonary HTN and renal crisis = biggest risks in pregnancy
Discuss systemic lupus erythematosis
-Incidence (3)
-Pathophysiology (6)
- Incidence
-1:1000
-Average age dx 30.
-F:M 10:1 - Pathophysiology
-Idiopathic relapsing, remitting connective tissue disorder
-Affects multiple organ systems or a single organ system and has multiple presentations
-Caused by B cell activation and the formation of immune complexes which are deposited in tissue (blood vessels) resulting in inflammation.
-Caused by genetic and environmental components
-Characterised by antibodies to nuclear and cytoplasmic antigens (ANA+ in >95% of cases)
-Associated with other positive antibodies (Anti Ro and La, Anti cardiolipin and anti Beta2 glycoprotein - suggests link to other autoimmune diseases (sjorgens etc)
How is SLE diagnosed
-General overview of criteria (3 points)
-Laboratory features (6)
- Brief criteria
-Based on 11 criteria including immunological/Laboratory signs
-Represent symptoms from multi system involvement
-Need 4 of 11 for diagnosis - Laboratory features
-Lupus anticoagulant DRVVT
-ANA - 96%
-Anti Ds DNA - 80-90%
-APL antibodies - 40%
-Anti-smooth antibodies
-Test Anti Ro and anti La - 30%
Discuss SLE in pregnancy
-Risk of flares (3)
-Manifestation of flares (2)
-Predictors of flares (6)
-Methods to reduce risk of flares (2)
- Risk of flares
-Pregnancy can increase the risk of flares of SLE
-33% risk of flare in pregnancy or PP
-10% risk if disease quiescent in 6months prior to conception
-50-60% risk of flare if disease active in 6 months prior to conception - Manifestation of flares
-Flares same in pregnancy as outside of pregnancy
-Can be hard to spot as many sx same as in pregnancy (Palmar erythema, fatigue, hair loss, muscle aches, anaemia) - Predictors of flares
-Previous adverse outcome in pregnancy
-BMI >30
-Past nephritis or thrombosis
-High lupus anticoagulant
-Use of anti-hypertensives
-Thrombocytopenia - Methods to reduce flares
-Avoid pregnancy until 6 months of remission
-Hydrochloroquine at maintenance dose
Discuss the effect of SLE on pregnancy
-Factors that increase the risks in pregnancy (6)
-Factors that are protective against poor outcomes in pregnancy (1)
-Outcomes which are increased in pregnancy with SLE (6)
- Factors which increase poor outcomes in pregnancy
-Past obstetric hx with poor outcomes
-Renal involvement with or without active disease at time of conception
-Active disease within 6 months of conception
-Anti phospholipid antibodies
-HTN
-First presentation in pregnancy - Factors that are protective against poor outcomes
-Remission for 6 months prior to conception - Outcomes
-Miscarriage 20%
-FGR 10%
-Fetal loss
-PTB
-PET 15-30%
-Neonatal lupus 5%
Discuss management of SLE in pregnancy
-Preconception (6)
-Antenatal (8)
- Pre conception
-Avoid conception until remission 6 months
-Baseline renal function, inflammatory markers including C3
-Screen for APLS and anti Ro and anti La antibodies
-Consider renal Bx if concern for lupus nephritis
-Baseline blood pressure
-Discontinue/ switch cytotoxic drugs and delay pregnancy 3 months
-Switch ACEi to pregnancy safe antihypertensives - Antenatal
-MDT input
-Low dose aspirin
-Monitor maternal disease - C3, anti ds DNA, Urine PCR each trimester
-Monitor for PET - urinalysis and BP
-Manage HTN
-Uterine artery dopplers at 20-24 weeks
-Fetal echo if anti Ro/La antibodies
-Serial growth scans
Discuss management of an SLE flare in pregnancy
- Mild flare - PO prednisolone
- Severe flare - high dose prenisolone
- Severe flare with renal or CNS involvement
- IV methylpred
-Plasmapheresis or IVIg in severe recalcitrant flares - Lupus nephritis
- high dose prednisolone then azathioprine/rituximab in early pregnancy.
-Mycophenalate/cyclophosphamide in 2-3rd trimester
Discuss differentiation of Lupus nephritis and PET in pregnancy
-Shared features (4)
-Investigations for definitive differentiation (2)
-Factors more likely seen in Lupus flare (5)
-Factors more likely seen with PET (4)
-Very difficult to distinguish
-May be co-existent
1. Shared features - HTN, proteinuria, thrombocytopenia, renal impairment
2. Investigation for definitive differentiation
-Renal biopsy
-Do if pre-viable as it may allow for commencement of immunosuppressive therapy
3. Factors associated with Lupus flare
-Other sx associated with lupus flare
-Had active disease at conception
-Decreased complement level
-Raised anti ds DNA
-Leukopenia
4. Factors associated with PET
-New proteinuria (None at baseline tests)
-LFT derangement
-Elevated urate
-Antithrombin deficiency
What are the clinical manifestations of APLS
-Pregnancy related (3)
-Non pregnancy related
- Clinical manifestations in pregnancy
-Recurrent miscarriages >3
-Fetal loss after 10/40 of morphologically normal fetus
-Severe PET/IUGR - Clinical manifestations outside of pregnancy
-Renal failure / protienuria / HTN
-Unexplained thrombocytopenia
-Ischemic stroke
-TIA
-VTE - DVT/PE/Cerebral sinus thrombosus
-MI
-SLE
-Cutaneous changes - Livedo reticularis
-Cardiac valvular disease with nodules and vegetations
