Autoimmune Disorders Flashcards
What is the immune system?
The immune system is a host defence system made up of organs, tissues, cells and molecules comprising many biological structures and processes within an organism that protects against disease.
- Defence system of our body
- To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism’s own healthy tissue
The various subsystems and functions
o Innate immune system vs adaptive immune system
- A fundamental feature of the immune system is to protect the host from pathogens. This function depends upon the innate immune system’s capacity to coordinate cell migration for surveillance and to recognize and respond to invading microorganisms
o Humoral vs cell mediated
o Barriers (blood–brain barrier, blood–cerebrospinal fluid barrier, other fluid–brain barriers)
- In humans, the blood–brain barrier, blood–cerebrospinal fluid barrier, and similar fluid–brain barriers separate the peripheral immune system from the neuroimmune system, which protects the brain. Whether or not an antigenic substance is to be treated as foreign is learned by the immune system (usually at birth). If the distinction between ‘foreign’ and ‘self’ breaks down, the results is an autoimmune disease, a condition in which the organism produces antibodies to its own proteins
o Compliment system
- Part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens
- Part of the innate immune system
- Consists of a number of small proteins (over 30)
- Synthesized in liver, normally circulating as inactive precursors (pre proteins)
- When simulated specific proteins cleaved to release cytokines = initiate amplifying cascade of further cleavages
- = activation of cell-killing membrane attack complex
o Lympatic system etc.
What are the changes in pregnancy
- In pregnancy, the human decidua contains a high number of immune cells, such as macrophages, natural killer (NK) cells and regulatory T cells The immune system at the implantation site is not suppressed, on the contrary it is active, functional and is carefully controlled
- Progesterone and Oestrogens are natural immune suppressor, in pregnancy
- Rise in glucocorticoids, shown to play a role in the development and homeostasis of T lymphocytes
- Decrease in T cell mediated immunity
- Reversed postnatally (prolactin) with postpartum flares and exacerbations.
Connective tissue disorders
- Rheumatoid arthritis
- Systemic Lupus Erythematosus
- Antiphospholipid syndrome
- Raynaud’s Syndrome
- Sjögren’s syndrome
- Mixed Connective Tissue disease
- Systemic sclerosis/scleroderma
- Primary Biliary Cirrhosis
- Ehlers Danlos Syndrome (hypermobility) etc.
Rheumatoid arthritis
- Systemic disorder; Chronic inflammatory disease
- Results from IgM autoantibodies activating the complement system to inflame the synovial membranes of joints, tendons and bursae
- T4 lymphocytes initiate an immune response (inc Rheumatoid Factor) causing synovial membrane to thicken (hyperplasia) and to be thrown into folds (pannus)- abnormal layer of fibrovascular tissue or granulation tissue with a subsequent increase in synovial fluid causing painful swelling and restriction of joint movement
Diagnostic tests
- Clinical examination
- X ray
- RF
- anti-cyclic citrullinated peptide (CCP) antibodies
- ANA (antinuclear antibody)
- Anti-Phospolipid antibodies
- Full blood count (anaemia, WBC)
- ESR (erythrocyte sedimentation rate)
- CRP
Risk factors
- Genetic predisposition
- Adverse pregnancy outcome
- Smoking
- Obesity
- Recent infection
- COC may actually offer protection or delay onset
- Nutrition (Gluten, Dairy, Soya etc)? Gut flora?
Complications
- Wasting of small muscles of the hand
- Diminished movement of affected joints
- Swelling of soft tissue around the joints
- Ruptured tendons or joints (Baker’s cysts)
- Spinal cord compression
- Neuropathy
- Infection (secondary to steroids)
- Secondary anaemia
- Anaemia
- Sjőgren’s syndrome (dry eyes)
- Secondary Raynaud’s phenomenon
- Scleroderma (sclero = hardening, Derma = skin)
- Lungs develop pleural effusion and nodules
- Heart develops asymptomatic pericarditis
- Reduced life expectancy from cardiac complications
- Psychosocial complexities
- Financial impact
Treatments of Rheumatoid arthritis
Treatments
- Disease-modifying anti-rheumatic Drugs (DMARDs) to modify disease
- Non pregnancy treatment
o Drugs which suppress disease process- Gold, Penicillamine
o Drugs which affect the immune process:Leflunoamide, Azathioprine
o TNF (Tumor necrosis factor) inhibitors: to supress the immune response
o Steroids: to reduce inflammation
- NSAIDS- to control symptoms
o Risk of oligohydramnious
o Infertility
o Increased risk of neonatal haemorrhage (reduced platelet function)
o Premature closure of the ductus arteriosus
- Physiotherapy
o Re-education with provision of aids to assist mobility
o Exercises to improve an maintain joint function and muscle power
o Hydrotherapy
o Splints to rest joints during flare-up or for doing every-day tasks
o Footwear
Pregnancy care for Rheumatoid arthritis
Pre-conception
- Vital as drugs, especially DMARDs, contraindicated in pregnancy
- Modern therapy has improved health, fertility and sex life and increased risk of unplanned pregnancies
- Replace with NSAIDs or steroids
- Leflunomide (Drugs which affect the immune process) should be stopped, with contraceptive cover, for two years prior to conception
- Folic acid 0.4mg important as folate deficiency common from long term DMARD usage (folate antagonists)
Pregnancy
- 75% of women experience improvement or remission (16% remission) and 25% disability
- Regular NSAIDs use in third trimester associated with fetal ductus ateriosus constriction, impaired renal function
- Existing complications of anaemia or infection can be exacerbated
- Screen for Anti Ro and Anti La (risk of neonatal lupus; book specialist cardiac fetal scans; inform NICU)
- Rheumatic joints become unstable due to joint loosening and altered weight distribution
- Risk of subluxation (impairment of rotation of the neck) of cervical vertebrae esp C1 and C2: refer to anaesthetic for review
- Pyscho-social issues
Labour
- Mobility issues and theoretical risk of DVT for immobile mothers
- Abduction of hips – lithotomy
- Potential problem for IV cannulation especially if scleroderma
- Atlanto-axial subluxation: rare anaesthetic complication (CS)
Postnatal
- In majority of cases risk of acute and severe return of symptoms – can lead to depression
- May have an effect on BF as would delay return to pre-pregnancy drug regime
- Physical restrictions may affect handling and feeding of baby
- Poor mobility = ↑risk of VTE
- Good contraceptive advice
Raynaud’s Syndrome
- Congestion of peripheral circulation due to arteriolar spasm under autoimmune nervous control on exposure to cold temperature and/or stress
- Exact aetiology unknown
- Ischaemic type pain in peripheries esp ears, tip of nose, toes and middle fingers of each hand
Classic triphasic colour changes
- White and very painful due to ischaemia
- Blue and numb due to cynosis
- Red and painful when reperfusion occurs
Primary
- Usually benign
- Mild symptoms
- Usually managed by GP with advice usually without drug treatment
Secondary
- Usually presents later in life arising from another medical condition such as:-
- Schleroderma
- Rheumatoid arthritis
- Systemic lupus erythematosous (SLE)
- Sjögren’s syndrome (dry eyes and mouth) - Other connective tissue diseases (5%)
- Repetitive vibration injuries (white finger)
- Schleroderma
Complications
- Most at risk in secondary
- Migraine
- Ischaemic pain in body extremities
- Chilblains
- Skin and mouth ulceration
- Skin rashes
- Joint inflammation and pain
Diagnosis/Treatment
- Nailform capillary test with an opthalmoscope
- Blood tests for FBC, ESR, autoantibody screen
- Advised to:
o Cease smoking and minimise caffeine intake
o Avoid extremes of temperature
o Care with COC as sometimes contraindicated
o Should not take beta-adrenoceptor antagonists or vasoconstrictor drugs
Pregnancy and treatment of Raynaud’s Syndrome
Pregnancy
- Symptoms may actually improve due to vasodilation from progesterone, haemadilution, rise in maternal core temperature
- Can attack nipple causing severe throbbing pain (can be misdiagnosed as thrush, nipple vasospasms that are due to poor latch only)
Treatments in pregnancy:
- Treatment in pregnancy:
- Vitamin B6 supplements can reduce milk supply in some breastfeeding women.
- Nifedipine (calcium channel blockers) is generally considered safe for breastfeeding women, but it is not generally prescribed for pregnant women.
- Nitroglycerin ointments or sprays are unsuitable for pregnant or breastfeeding mothers
Systematic Lupus Erythematosus
- Body produces autoantibodies against its own connective tissue. Two main types:
o Discoid Lupus Erythematous (DLE): skin alone affected, with defined, red scaly patches on face and neck and alopecia leading to scarring on the scalp, both aggravated by sunlight
o Systemic Lupus Erythematosus (SLE): extends beyond skin to organs, with enlarged lymph glands and various other manifestations: can be fatal, especially if kidneys involved
Diagnosis
- Clinical criteria and investigations (American Pheumatic Association)
- Skin biopsy to detect SLE autoantibodies
- Usually +ve for antinuclear antibody (ANA) and DNA antibodies (Sm)
- Raised ESR common (high immunoglobulin levels)
- +ve rheumatoid factor (25%)
- False +ve for syphilis (33%)
- Some have antiphospholipid antibodies – screen all women with SLE for APS (anticardiolipin Ab)
Complications
- Fatigue and myalgia (muscle pain)
- N&V and diarrhoea
- Photosensitivity
- Arthritis (morning stiffness)
- Secondary Raynaud’s
- Sjögren’s syndrome (dry eyes/mouth)
- Alopecia
- Ulceration of mouth nose and vagina
- Acute and chronic infection
- Renal disease
- Jaccoud’s arthropathy (deformed joints due to lax ligaments)
- Pleurisy (often asymptomatic)
- Pericarditis (often asymp)
- Ischaemic heart disease
- Pulmonary hypertension
- Leucopenia (Reduced leucocyte count)
- Thrombocytopenia
- Anaemia – result of chronic inf
- Neuro-psychiatric states i.e. CVA, migraine, epilepsy, depressive or manic symptoms and dementia
Advice
- Avoid sunlight and use sunblock
- Avoid infection if possible
- Avoid unplanned pregnancy
- Avoid stress and get adequate rest
- Use analgesics as needed
- Protect against cold if Raynaud’s occurs
- Eat a well-balanced diet
- Positive self-image (e.g. camouflage make-up)
Treatment
- Corticosteroids for disease flare e.g. prednisolone
- NSAIDs for pain, fever and arthritis
- Antimalarial drugs (e.g. hydroxchloroquine) for skin disease, fatigue and arthralgia (joint pain)
- DMARDs to arrest disease progression
- methotrextrate, cyclophosphamide, azathioprine, mycophenolate
- Artificial tears for Sjögren’s
Monitor
- Regular BP
- Urinalysis for blood and protein (indicates renal disease)
- Blood tests for FBC, ESR, WBC, U&E, creatinine, C3 and C4 complement and anti-DNA titre
- LFT if taking azathioprine
- Long term steroid use - Screening for diabetes and osteoporosis
- Investigations for antiphospholipid (Hughes) syndrome
Pregnancy and Systematic Lupus Erythematosus
Pre-conception
- High risk of fetal loss if conception occurs during disease flare
- Refer to rheumatologist for screening of organ involvement and risk-benefit drug assessment
- Knowledge of AntiRo, La, aPLs, renal and BP to predict risks
- Avoid COC
- DMARDs usually replaced by NSAIDs or steroids
Pregnancy Issues
- With modern Rx fetal loss reduced from 50% to 20%
- However still increase of IUGR, pre-term labour, IUFD, Miscarriage, congenital abnormalities (drug related)
- 40-60% chance of lupus flare in pregnancy or PN
- Changes of pregnancy make it difficult to diagnose mildly active lupus
- Flare associated with premature delivery (30% with LN)
- Flares difficult to predict; prophylaxis for flares not recommened
- Pre-existing renal disease may worsen (active nephritis a factor for fetal loss; lupus nephritis can appear for first time in pregnancy)
- Increase risk of PIH, pre-eclampsia
- All hazards reduced if lupus is mild or stable
Antenatal care
- ASA-aspirin for women with Ln and/ or APLs
- Baseline values of blood tests and proteinuria and subsequent serial measurements
- MDT approach with regular monitoring of disease activity, fetal growth, Dopplers, specialist cardiac fetal assessment if Anti Ro/La
- Flares early awareness
- Actively manage the flares: steroids as first agent
- Appropriate medication (similar to RA); no need to stop hydroxychloroquine: can induce flares
- Control of hypertension/ dD from PET
Intrapartum
- Aim for SVD in absence of obstetric complications or flare
- May require additional steroids to cover delivery
- Continuous EFM
- If lupus flare and PET cannot be differentiated beyond 24-28w when the fetus is viable, delivery may be the most appropriate course, if the mother or the fetus is at risk.
Postnatal
- 5% neonates born to anti-Ro or anti-La +ve mothers risk neonatal lupus = discoid, facial “owl eyes”, 2% risk of congenital heart block
- May require prompt return to pre-pregnancy drug regimen
- Drugs excreted in breast milk, BF may exacerbate maternal fatigue
- Prolactin release may exacerbate condition
- Neuro-psychiatric state may be wrongly identified as PN depression
