Connective Tissue Diseases Flashcards
What are auto-antibodies?
antibodies generated by the immune system against the body’s own proteins
What is systemic lupus erythematosus?
Systemic autoimmune condition that mainly involves the skin, joints, kidneys, blood cells, and nervous system but can affect almost any organ system
What is the aetiology of SLE?
- Autoimmune
- Genetic predisposition - HLA genes
- Hormonal factors - ↑ oestrogen
- Environmental factors - UV light, bacterial/viral infection, some medications
What are the risk factors of SLE?
- Higher prevalence in women (9:1)
- Usually presents in childbearing years - 20-40
- More common and more severe in those of Afro-Caribbean, Hispanic American, Asian, and Chinese ethnicity
What is the pathophysiology of SLE?
- Immune system attacks cells and tissues resulting in inflammation and tissue damage, also involves the formation of immune complexes (type III hypersensitivity)
1. Loss of immune regulation results in increased and defective apoptosis
2. Necrotic cells release nuclear materials which act as auto-antigens
3. Auto-immunity results from exposure to nuclear and cellular auto-antigens
4. B and T cells stimulated and autoantibodies are produced
5. Auto-antigens and autoantibodies form immune complexes which circulate and become deposited in the basement membrane (type III hypersensitivity)
6. Activation of complement which attracts leukocytes which release cytokines
7. Cytokine release perpetuates inflammation which causes necrosis and scarring
What is the presentation of subacute cutaneous lupus?
- Small erythematous lesions on neck, shoulders, and forearms (spares the face)
- 10% of cases of SLE
What is the presentation of discoid lupus erythematosus?
- Non-cancerous chronic skin condition
- Erythematous raised scaling plaques with active inflammation, triggered by UV light exposure
- Affects face, neck and head
- Associated with increased risk of developing SLE (10-15% risk)
What is the presentation of SLE?
- Fever
- Fatigue
- Weight loss
- Photosensitive rash - can occur anywhere on the body but is typically seen on the face (malar rash)
- Non-scarring alopecia
- Oral/nasal ulcers
- Raynaud’s phenomenon
- Arthritis - synovitis or tenderness of at least 2 joints with >30 mins of early morning stiffness
- Unlike in RA, deformities are reducible and should not affect joint function (e.g. patient should be able to make a fist)
- Arthralgia
- Myalgia
- Jaccoud’s arthropathy - non-erosive reversible joint disorder that can occur after repeated bouts of arthritis, occurs in 10-35% of SLE patients
- Renal - lupus nephritis
- Neurological - seizures, psychiatric change (delirium, psychosis), headache, cranial nerve disorder
- Serositis - pleural or pericardial effusion, acute pericarditis
- Haematological - leukopenia, thrombocytopenia, haemolytic anaemia, lymphadenopathy
What are the investigations of SLE?
Diagnostic: ≳4 criteria (at least 1 clinical and 1 lab criteria) OR biopsy-proven lupus nephritis with positive ANA or anti-DNA
ANA is present in almost all SLE patients
Anti-dsDNA - present in 60& of lupus, titre correlates with disease activity
Bloods
- Leukopenia, thrombocytopenia, haemolytic anaemia
- Low complement levels - activation and consumption related to disease activity
- C3 and C4 - particular association with renal and haematological disease
Urine dip stick test
- Anti DNA antibodies are toxic to the kidney - should always do a urine dipstick in any patient with suspected SLE
- Proteinuria >0.5g in 24 hours indicates lupus nephritis, may also be blood present or red cell casts
- After positive urine dipstick perform biopsy to confirm nephritis
Imaging
- May be used to look for organ involvement e.g. chest for interstitial lung disease, MRI brain for cerebral vasculitis
What is the general management of SLE?
- Sun protection measures
- Minimize steroid use
- Monitor disease activity using SLEDAI score
What is the pharmacological management for SLE?
Mild-moderate disease - skin disease and arthralgia
- Hydroxychloroquine
- Short course of NSAIDs for symptomatic control
- Steroids - IA for arthritis, topical for cutaneous manifestations
Moderate-severe disease - inflammatory arthritis or organ involvement
- Hydroxychloroquine
- Acute flareups - immunosuppressants (e.g. azathioprine)/ oral steroids (short periods) to try and induce remission
- Treat organ complications appropriately
Severe organ disease
- e.g. in lupus nephritis or CNS lupus
- Treatment tends to involve IV steroids and cyclophosphamide
Unresponsive cases
- Other therapies such as IV immunoglobulin and rituximab may be necessary
What is done to monitor SLE?
- anti-dsDNA antibodies and complement levels should be checked regularly, as well as urinalysis for blood or protein
- BP and cholesterol should be monitored due to increased CVD risk
What are the complications of SLE?
Increased prevalence of avascular necrosis, usually of the femoral head, which may relate to steroid use
What is Sjogren’s syndrome?
Autoimmune condition that affects the exocrine glands, characterised by lymphocytic infiltrates
What is the aetiology of Sjogren’s Syndrome?
- Higher prevalence in females (9:1), occurs mainly in middle aged women
- Can be a primary condition or can occur secondary to other autoimmune conditions (RA, SLE)
What is the pathophysiology of Sjogren’s Syndrome?
As the immune system mainly attacks lacrimal and salivary glands, patients typically present with dry eyes and mouth
What is the presentation of Sjogren’s Syndrome?
- Dry eyes - gritty feeling
- Dry mouth
- May lead to fissured tongue
- Dry throat
- Vaginal dryness
- Joint pains
- Fatigue
- Bilateral parotid gland enlargement
- Unexplained increase in dental caries
What are the investigations of Sjogren’s Syndrome?
- Schirmer’s test - ocular dryness
- Bloods - positive anti-Ro and Anti-La antibodies
- May also have raised IgG and raised plasma viscosity/ESR
- Lymphocytic infiltrates on a lip gland biopsy
What is the management of Sjogren’s Syndrome?
- Symptom control
- Tear and salivary replacement for dryness
- Analgesia, exercise for pain and fatigue
- Hydroxychloroquine can sometimes help with arthralgia and fatigue
- Other immunosuppression would usually only be used in the context of organ involvement e.g. interstitial lung disease
What are the complications of Sjogren’s syndrome?
- Increased risk of lymphoma
- Peripheral neuropathy and interstitial lung disease can occur but Sjogren’s is less commonly associated with organ complications than other connective tissue diseases - surveillance not performed
What is systemic sclerosis?
Systemic connective tissue autoimmune disease characterised by vasculopathy, autoimmunity and fibrosi; categorized into limited SSc and diffuse SSc
What is the aetiology of systemic sclerosis?
- Higher incidence in females
- Peak incidence 30-50 years
- Genetic predisposition + environmental trigger
What is the pathophysiology of systemic sclerosis?
- Etiological agent + genetic predisposition
- Endothelial cell and vascular alterations
- Chronic inflammation
- Vascular damage (vasculopathy) and tissue fibrosis → skin involvement, organ damage
Describe limited systemic sclerosis?
- Skin involvement tends to be confined to the face, hands, forearms and feet
- In 90% of cases, Raynaud phenomenon precedes the onset of other symptoms
- Organ involvement tends to occur later
- Anti-centromere antibody (ACA) association
Describe diffuse systemic sclerosis?
- Skin changes develop more rapidly and can involve the trunk
- Raynaud phenomenon often coincides with or follows the onset of other symptoms
- Early significant organ involvement
- Anti-SCL-50 antibody and anti-RNA polymerase III association
What is the presentation of systemic sclerosis?
- Thickening and hardening of the skin
- Sclerodactyly - thickening of the skin of the fingers and hands which can cause loss of dexterity of hands
- Raynaud’s phenomenon
- The result of vascular spasms that reduce the blood supply to the fingers, usually when the hands get cold
- The fingers will go white (blanching), then blue (acrocyanosis), then as they warm up, or the episode passes, they will become red (reactive hyperaemia)
- Multiple, painful ischaemic digital ulcers (caused by Raynaud’s)
- Fatigue, weakness
- Joint stiffness/pain
- Calcinosis of the fingertips
- When the skin of the face is involved:
- Pinching of the skin of the nose - ‘beaking’
- Tightening of the skin around the mouth - small mouth with ‘puckered lips’
- Telangiectasia
- Lack of wrinkles
What other organ involvement is involved in systemic sclerosis?
Musculoskeletal
- Arthralgia and myalgia
GI tract
- Oesophageal dysmotility → dysphagia and reflux
- Small bowel dysmotility → bloating, gas, constipation, cramping
Pulmonary disease
- Pulmonary hypertension
- Interstitial lung disease - dyspnoea, bilateral fine inspiratory crackles, cough
Cardiac disease
- Fibrosis, myocarditis, pericarditis
- Pulmonary hypertension can cause right sided heart failure
Renal disease
- Non-specific progressive renal dysfunction - due to microvascular changes and fibrosis
- Scleroderma renal crisis
- Uncontrolled hypertension with proteinuria and rapidly worsening renal function
- Associated with anti RNA polymerase III antibody
- Usually early in disease (presenting feature)
- High dose of steroids puts people at risk (incidence decreasing as steroids are used less now)
What are the investigations for systemic sclerosis?
Autoantibodies
- ANA present in 90% of cases (but not very specific)
- Limited SSc: anti-centromere antibody (ACA) - associated with vasculopathy complications
- Diffuse SSc: anti-topoisomerase (SCL-7) (associated with fibrosis complications) and anti RNA polymerase III (associated with renal involvement)
Pulmonary complications
- SSc patients should be screened yearly for pulmonary complications
- Pulmonary arterial hypertension - echo
- Pulmonary fibrosis - PFTs
- If PFTs restrictive - high resolution CT (honeycombing = fibrosis)
What is the medical management for systemic sclerosis?
- Nifedipine can be used to treat symptoms of Raynaud’s phenomenon
- Anti acid medications (e.g. PPIs) and pro-motility medications (e.g. metoclopramide) for gastrointestinal symptoms
- Analgesia for joint pain
- Antibiotics for skin infections
- Antihypertensives can be used to treat hypertension (usually ACE inhibitors)
- Treatment of pulmonary artery hypertension
- Supportive management of pulmonary fibrosis
What is the non-medical management for systemic sclerosis?
- Avoid smoking
- Gentle skin stretching to maintain the range of motion
- Regular emollients
- Avoiding cold triggers for Raynaud’s
- Physiotherapy to maintain healthy joints
- Occupational therapy for adaptations to daily living to cope with limitations
What is mixed connective tissue disease?
Uncommon, specifically defined condition which features symptoms also seen in other connective tissue diseases
What is the presentation of mixed connective tissue disease?
- Raynaud’s
- Arthralgia/arthritis
- Myositis
- Sclerodactyly
- Pulmonary hypertension
- ILD
What are the investigations of mixed connective tissue disease?
Antibodies - associated with anti-RNP antibodies
What is the management of mixed connective tissue disease?
- Varies according to presentation
- CCBs may be helpful for Raynaud’s
- If there is significant muscle or lung disease immunosuppression may be required
- Monitoring - patients should be monitored for pulmonary hypertension (annual echo) and ILD (PFTs
What is anti-phospholipid syndrome?
Autoimmune disorder that manifests clinically as recurrent venous or arterial thrombosis and/or fetal loss
What is the aetiology of anti-phospholipid syndrome?
- Genetic predisposition
- More common in females
- Some patients with APS have no evidence of any definable associated disease (primary APS), while, in other patients, APS occurs in association with SLE or another rheumatic or autoimmune disorder (secondary APS)
What is the pathophysiology of anti-phospholipid syndrome?
Antiphospholipid antibodies react against proteins that bind to anionic phospholipids on plasma membranes
What is the presentation of anti-phospholipid syndrome?
- DVT/PE
- Recurrent pulmonary emboli or thrombosis can lead to life-threatening pulmonary hypertension
- Livedo reticularis - blood clots in capillaries lead to swelling of venules, resulting in a purplish, net-like discoloration of the skin
- May contribute to an increased frequency of stroke or MI, especially in younger individuals
- Strokes may develop secondary to in situ thrombosis or embolization that originates from the valvular lesions of Libman-Sacks (sterile) endocarditis, which may be seen in patients with APS
- Miscarriage
- Late spontaneous fetal loss (second or third trimester) is common; however, it can occur at any time during pregnancy
- Recurrent early fetal loss (< 10 weeks’ gestation) is also possible
- Many patients have migraine
What is catastrophic APS?
multiorgan infarctions over a period of days to weeks, often fatal
What are the investigations for anti-phospholipid syndrome?
Bloods
- Thrombocytopenia
- Prolongation of aPTT (partial thromboplastin time)
- Lupus anticoagulant, anti-cardiolipin antibodies and anti-beta 2 glycoprotein may be positive
What is the management of anti-phospholipid syndrome?
- Anticoagulation for those with an episode of thrombosis - acute LMWH then warfarin or aspirin prophylaxis
- Patients who are found to have positive antibodies but who have never had had an episode of thrombosis do not require anti-coagulation
- LMWH and aspirin used during pregnancy for patients with recurrent pregnancy loss
