Rheumatology / immunology Flashcards
Described immunology changes in pregnancy
Shift away from cell-mediated immunity (T-helper 1 response) to humoral immunity (Th 2 response)
- Cell-mediated = T-helper 1 + macrophages + cytotoxins / cytokines
- Humoral = T-helper 2 + plasma cells + B cells –> antibodies and immunoglobulins
This probably occurs to protect the fetus from immunological attack by the mother
Changes are reversed postpartum
Effect of pregnancy on RA
70-80% improve during pregnancy
If improved in previous pregnancy, likely to improve in subsequent pregnancies
Improvement usually begins in first trimester
Most will relapse in the postpartum period (90% within first 4/12) - may be related to resurgence of T cell-mediated immunity. PP flare exacerbated by breastfeeding
Worsening symptoms may be due to withdrawal of disease-modifying anti-rheumatic drugs (DMARDs) in pregnancy
Effect of RA on pregnancy
Pregnancy outcomes if well-controlled RA are comparable to general population
Increased risk of SGA and PTB
Infants of women who have anti-Ro antibodies are at risk of neonatal lupus
Atlanto-axial subluxation is a rare complication of a GA
Very rarely, limited hip abduction is severe enough to impede vaginal delivery
Main concerns relate to medication safety during pregnancy and lactation
Pre-pregnancy counselling for RA
Avoid pregnancy during active RA
Avoid NSAIDs
- May affect blastocyst implantation and miscarriage (cause or association unclear)
Use contraception when taking teratogenic drugs
- Discontinue methotrexate, cyclophosphamide, chlorambucil, penicillamine, gold salts for >3/12 prior to conception
Drugs contraindicated in pregnancy
Methotrexate cyclophosphamide chlorambucil penicillamine gold salts
Switch >3/12 prior
Leflunomide - stop >2y pre-pregnancy
Rutixamab - stop 6/12 pre
Corticosteroids in pregnancy
Safe
Preferable to NSAIDs
Give lowest possible dose
Increased risk of maternal HTN, PET, GDM, PTB and osteoporosis
Monitor BP and glucose levels regularly
Calcium and vitamin D supplements recommended
IV hydrocort in labour
Safe in pregnancy
Corticosteroids
Azathioprine (As fetal liver lacks enzyme to convert it)
Maybe NSAIDs (short courses in second trimester)
Sulfasalazine (given with folic acid 5mg)
Hydrochloroquine
Inflixamab (monoclonal antibody, stop in third trimester, crosses placenta but not teratogenic, no live vaccines for baby until >6/12, crosses breast milk but destroyed in fetal stomach)
Management of RA
Antenatal:
- Screen for anti-Ro and anti-La
- FBC (no benefit to monitoring ESR and RF)
- Assess ROM at neck and hips
Aim for vaginal birth
Hydrocortisone 100mg IM q6h if taking >7.5mg prednisolone for >2/52 in pregnancy
Pathogenesis of SLE
Environmental triggers - UV light, viral infection
There is polyclonal B-cell activation, impaired T-cell regulation of the immune response and failure to remove immune complexes
Circulating non-organ-specific autoantibodies
Deposition of immune complexes causes vasculitis
Incidence of SLE
UK incidence 1 in 1000 women
Affects women > men (9:1)
Particularly during the childbearing years (15:1)
Bloods in SLE
FBC - normochromic normocytic anaemia, neutropenic, thrombocytopenia
Raised ESR
Normal CRP
Anti-nuclear antibody (ANA) - 96%
Anti-double-stranded DNA (anti-dsDNA) - 80% (more likely to have renal GN)
Anti-Sm antibodies (30-40%)
Anti-Ro (30%) / anti-La (20%)
Anti-phospholipid antibodies (aPLs) - 40%
Effect of pregnancy on SLE
Pregnancy and especially the puerperium increase the likelihood of flare from ~40% to 60%
Flare is more likely if disease has been active within 6/12 of conception
Effect of pregnancy on lupus nephritis
Risk of renal flare is 30%
Risk is much higher if the lupus nephritis is not in remission or only partial remission at conception (50-60%)
Delay pregnancy until >6/12 after flare
Pregnancy outcome is particularly affected by renal disease
Even quiescent renal disease a/w increased risk of fetal loss (up to 36%), PET (25-30%) and FGR - especially if proteinuria and HTN
Risk of preterm birth and LBW is ~30%
Effect of SLE on pregnancy
Maternal risks: VTE PET (3x) Maternal death (20x) Risk of stroke
Fetal risks: Spontaneous miscarriage Fetal death Preterm delivery FGR (1 in 4) Neonatal lupus syndrome
In women in remission >6/12, without HTN, renal involvement, APS, risks are probably no higher than in the general population
Implication of anti-Ro and anti-La
Passively acquired autoimmunity
Autoantibodies cross the placenta –> immune damage to the fetus
Risk of transient neonatal cutaneous lupus is ~5%
Risk of congenital heart block is ~2%
Risk of neonatal lupus if previous child affected:
- 16-18% with one affected child
- 50% if two
- Subsequent infants tend to be affected in the same way as their siblings
Taking hydroxychloroquine reduces risk
Presentation of cutaneous neonatal lupus
Cutaneous neonatal lupus is the most common
Usually manifests in the first 2/52 of life
Typical erythematous geographical skin lesions
- Usually on face or scalp
- Photosensitive - appearing after exposure to sun or other UV light
Rash disappears spontaneously within 4-6 months
Scarring is unusual
Advise avoiding sunlight and phototherapy
Presentation and treatment of congenital heart block
Appears in utero
Permanent
15-20% mortality
In severe cases heart failure leads to hydrops fetalis and IUFD
Usually detected at 18-28/40 via fetal bradycardia, confirmed by detailed scanning showing atrioventricular dissociation with structurally normal heart
Maternal autoantibodies confirm neonatal lupus
Dexamethasone may reverse lesser degrees of heart block or prevent progression to complete heart block
Salbutamol to mother if bradycardia causing fetal heart failure
50-60% require pacemakers in early infancy
Preconception counselling SLE
Assess disease - activity and organ involvement
Baseline proteinuria, renal function, and BP help guide prediction of risk to pregnancy
Outcome is improved if conception occurs during disease remission
Knowledge of antibody status (anti-Ro/La, aPLs, anti-dsDNA, complement C3 and C4)
- Help predict risk / neonatal implications
Review meds
Often on azathioprine and hydrochloroquine
- Both safe
Folic acid 5mg OD if on sulfasalazine
Antenatal management of SLE
MDT
Low-dose aspirin from 12/40 if lupus nephritis, aPLs or vasculitis
Uterine artery Dopplers at 20-24/40 in at risk fetuses
Serial growth scans
Establish bloods baseline values with serial measurements with intervals depending on disease severity for:
- FBC, U&E, Cr, LFTs
- Anti-dsDNA and complement titres
- Quantify proteinuria
Hydroxychloroquine should be continue as stopping may precipitate flare
HTN management
SLE disease flare antenatally
Features suggesting disease flare:
- Symptoms - arthralgia, pleuritis pain, skin rash
- Rising anti-dsDNA antibody titre
- Red blood cells or cellular casts in urinary sediment
- Fall in complement levels may help differentiate PET from active lupus - >25% fall in C3 or C4 suggests active SLE
Disease flare management:
- Corticosteroids (first-line)
- Azathioprine, NSAIDs, aspirin, or tacrolimus
Features that suggest SLE flare over PET
Active disease within 6/12 conception, extreme fatigue, skin lesions, arthralgia, fever not due to infection
> 2x increase in PCR suggests worsening lupus nephritis or PET
PET
- Elevated serum urate
- Abnormal LFTs
- Low placenta growth factor
- Antithrombin deficiency
SLE
- Leukopenia
- Raised ds-DNA levels
- Reduced complement levels (C3 or C4)
What is Takayasu’s arteritis
Predominantly affects large arteries (including aorta and its major branches, pulmonary arteries)
Inflammation leads to fibrosis, stenosis and thrombosis
Aneurysms may also be a feature
Predominantly affects women (8:1) of childbearing age
Features: HTN, vascular bruit, fever, raised ESR/CRP
Pregnancy implications of Takayasu’s arteritis
Increased risk of:
- PET
- FGR
There is an association between disease severity and adverse pregnancy outcome
Management in pregnancy
Corticosteroids = first-line
Azathioprine
BP control is important
What is scleroderma?
Rare
More common in females (3:1), especially in childbearing year (15:1)
Autoimmune condition, causing fibrosis of skin +/- visceral organs and vasculopathy
Localised cutaneous form
Systemic sclerosis - Raynaud’s and organ involvement
CREST
- calcinosis, Raynauds, oesophageal involvement, sclerodactyly, telangiectasia
Effect of pregnancy of sclerodermia
Localised cutaneous form - good prognosis
Early disease systemic sclerosis and/or renal involvement - risk of rapid overall deterioration and renal crisis
Raynaud’s - tends to improve
Risk of rapid overall deterioration and renal crisis - high risk of PP deterioration
effect of scleroderma on pregnancy
Overall success rates: 70-80%
Increased risk of:
- Preterm delivery (25%)
- Miscarriage
- PET
- FGR
- Perinatal mortality
Venepuncture, venous access, BP measurement - may be difficult because of skin or blood vessel involvement
GA may be complicated by difficult intubation (partly from limited mouth opening)
Regional - may be difficult if skin involvement on back
Management of scleroderma in pregnancy
Women with early diffuse disease should be advised to delay pregnancy until the disease has stabilised
Pre-pregnancy:
- Lung function tests
- ECHO
Women with multiple or severe organ involvement (pulmonary HTN, severe pulmonary fibrosis, renal involvement) should be advised against pregnancy
MDT
BP monitoring
Monitoring of fetal wellbeing
Steroid treatment for fetal lung maturity should be avoided - may precipitate a renal crisis
Benefits of ACE inhibitors in scleroderma renal crisis outweigh the risks to the fetus, and therefore use is justified if needed
Anaesthetic review`
Why is sjogren’s syndrome important in pregnancy
70-80% have anti-Ro and anti-La
Risks of type IV Ehlers Danlos
IV - Ecchymotic or vascular
High risk
Maternal mortality as high 25%
Increased risk of aortic and visceral rupture
Risk of uterine rupture, preterm delivery, skin fragility and poor healing
Avoidance of pregnancy or TOP recommended
C/s advised preterm (34/40) to reduce risk of uterine and aortic rupture of those with vascular EDS
Refer to geneticist pre-pregnancy for categorisation
Risks of type III Ehlers-Danlos
Commonest form
May be a/w postural orthostatic tachycardia syndrome (but not a/w heart or aortic disease)
May have increased joint and back pain
Risk of preterm ROM, preterm cervical dilatation, precipitous labour, PPH, skin fragility and poor hearing
Prophylactic antibiotics in labour
Refer to geneticist pre-pregnancy for categorisation
NSAIDs and pregnancy
Usually avoided, especially in the third trimester (discontinue by 32-34/40 if used at all)
May be used, especially short courses prior to 28/40 for control of arthritic pain if relative contraindication to steroids
May lead to oligohydramnios (via effect of fetal kidney, can lead to pulmonary hypoplasia) - Reversible after discontinuation
Premature closure of the ductus arteriosus (as they are prostaglandin synthetase inhibitors)
Non-obstetric manifestations of APS
DVT Thrombocytopenia Livedo reticularis skin disorder Stroke Superficial thrombophlebitis PE TIA Haemolytic anaemia Cognitive dysfunction Renal disease or GIT disease, ocular disease, adrenal disease, osteonecrosis
