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
