Connective tissue diseases Flashcards
What is systemic lupus erythematosus (SLE)?
- SLE = an autoimmune disease
What is the epidemiology for SLE and what are some triggers for flare-ups?
- more common in females
Triggers…
- oestrogen-containing contraception (oral contraceptive pill)
- overexposure to sunlight (UV-B light)
- infections
- stress
What are the clinical features of SLE (and what is the most common cause of lupus-related death)?
- general: systemic upset (fever, myalgia, fatigue, weight loss), joint and/or skin involvement
- dermatological: photosensitive malar rash (butterfly rash across cheeks), ulcers, discoid rash, palpable purpura, livedo reticularis
- joints: arthritis / arthralgia
- cardiovascular: Raynauds, pericarditis
- respiratory: pleural effusions, pneumonitis
- renal: lupus nephritis (most common cause of lupus-related death)
- neurological: seizures, migraines, peripheral neuropathies, psychosis/depression/anxiety
- haematological: anaemia of chronic disease, lymphopenia, haemolytic anaemia, thrombocytopenia, leukopenia
- GI problems
Classic ‘butterfly’ malar rash of SLE…
Discoid lupus lesions, seen in SLE…
What are some common secondary diseases to SLE?
- secondary Sjorgen’s syndrome
- secondary anti-phospholipid syndrome
- mixed connective tissue disease (features of SLE, systemic sclerosis, and poly/dermatomyositis)
How does drug-induced lupus differ from normal lupus?
- presents as a milder form of SLE
- triggered by chronic use of certain drugs (symptoms not present before starting drug and stop after discontinuing the drug)
- Bloods: +ve anti-histone, -ve anti-dsDNA and anti-Sm
- note: malar rash, renal disease, neurological involvement are rare
What investigations should be done for suspected SLE?
- FBC and clotting screen: anaemia of chronic disease, prolonged partial thromboplastin time (PTT) suggest lupus anticoagulant so prompts need for check of APLS antibodies
- U+Es: screen for renal involvement
- ESR / CRP: sugests active disease
- auto-antibodies: anti-dsDNA, anti-Sm
- complement lvls: low C3 and C4
What is the management for SLE?
- education: avoid triggers
- pharmacological: NSAIDs, hydroxychloroquine, corticosteroids (for acute flares), cyclophosphamide (if severe SLE)
What is antiphospholipid syndrome (APLS)?
- APLS = an autoimmune condition characterised by thrombosis (venous/arterial), fetal loss, and thrombocytopenia (associated with raised levels of antiphospholipid antibodies)
What are the clinical features of antiphospholipid syndrome (APLS)?
- Clots: venous thrombosis (eg. DVT or pulmonary), arterial thrombosis (eg. myocardial infarction or stroke)
- Livedo reticularis: a mottled appearance of skin on lower limbs
- Obstretic loss: recurrent miscarriages, premature births
- Thrombocytopenia:
What are the investigations for suspected APLS?
- antibodies: lupus anticoagulant and anticardiolipin
- FBC: thrombocytopenia
What is the management for APLS?
- Reduce risk factors for thromboembolism: avoid oral-contraceptive pill/HRT, long periods of immobility, smoking
- Treat hypertension: diuretics, ACE inhibitors
- Treatment of thrombosis: anticoagulant (eg. warfarin. DOACs)
- note: warfarin is teratogenic, use low molecular weight heparin during pregnancy
What is Sjorgen sydrome?
- Sjorgen syndrome = an autoimmune disease, characterised by decreased salivary and lacrimal gland secretion
- manifests as dry eyes and dry mouth
What is Sicca syndrome?
- the presence of dry eyes or mouth as a result of non-autoimmune disease (such as smoking or drugs)
What are the clinical features of Sjorgen syndrome?
- Occular: reduced tear secretion (dry, gritty eyes), bacterial conjunctivitis common
- Oral: dryness of mouth (xerostomia), can cause dysphagia
- Other: vaginal dryness, reduced GI mucus secretion
- Extraglandular features: systemic upset (fever, myalgia, malaise, fatigue), arthritis, Raynauds
What are the investigations for suspected Sjorgen syndrome?
- Bloods: ESR/CRP raised, Rf, anti-Ro/anti-La
- Schirmer’s test: shows reduction in tear production
Schirmer test…
- one end of a strip of filter paper is placed beneath the lower eyelid
- wetting the paper by less than 5mm in 5 minutes suggests reduced tear secretion
What is the management for Sjorgen syndrome?
- dry eyes: hypromellose eye drops
- dry mouth: artificial saliva, drink frequently
- note: treat other symptoms individually (eg. arthritis - hydroxychloroquine)
What are the clinical features of polymyositis and dermatomyositis?
- MSK features: bilateral, proximal (hip and shoulder girdle) muscle weakness, gradual/progressive onset
- note: difficulty rising from a chair or walking up stairs, also difficult to reach things above head height
- extra-MSK: systemic upset, pulmonary, Raynauds, underlying malignancy (10-15% of patients)
- later symptoms: respiratory muscles (poor ventilation), oesophageal muscles (dysphagia)
- dermatomyositis: heliotrope rash, Gottron’s papules, macular rash, ulcers
Gottron papules…
Heliotrope rash…
Macular erythematous rash…
What are the investigations for polymyositis and dermatomyositis?
- muscle enzymes (creatine kinase): elevated due to myositis
- muscle biopsy: most definitive diagnostic test
- MRI: can locate muscle oedema for biopsy
- autoantibodies: anit-Jo-1
What is the management for polymyositis and dermatomyositis?
- long-term corticosteroids with methotrexate or azathioprine as a steroid-sparing agent
- physiotherapy
- (cyclophosphamide: prescribed for patients with severe interstitial lung disease)
What is scleroderma and what is systemic sclerosis?
- scleroderma = hardening of the skin (cutaneous)
- systemic sclerosis = multi-system autoimmune disease (abnormalities of blood vessels and fibrosis of skin and organs)
What are the features of limited cutaneous system sclerosis (CREST syndrome)?
- Calcinosis
- Raynaud’s phenomenon
- oEsophageal dysmotility (dysphagia)
- Sclerodactyly (shiny/tight/swollen skin of hands/feet)
- Telangiectasia
- note: symptoms limited to hands/forearms, feet/legs, and head/neck
Microstomia (tightness of skin around mouth)…
Sclerodactyly (localised thickening and tightening of the skin around fingers)…
What are the features of diffuse systemic sclerosis (and what is the emergency condition involving renal function that can occur)?
- Fx of systemic sclerosis
- dermatological: skin fibrosis (loss of skin creases, shiny skin), sclerodactyly, telangiectasia, microstomia, calcinosis, flexion contractures at IPs due to skin changes
- cardiovascular: Raynaud’s phenomenon, pericarditis
- GI: oesophageal dysmotility, bowel hypomotility
- respiratory: pulmonary fibrosis, pulmonary hypertension
- renal: scleroderma renal crisis (monitor renal function)
What are the investigations for suspected systemic sclerosis?
- Bloods: anti-centromere (limited), anti-Scl-70 (diffuse)
- diagnosis is made clinically and confirmed with serology
Which type of systemic sclerosis (limited or diffuse) has a better prognosis?
- limited systemic sclerosis has a relatively good prognosis
- diffuse systemic sclerosis has a relatively poor prognosis
What is the management for systemic sclerosis?
- symptomatic treatment
What is the management for Raynaud phenomenon?
- Hand warmers (gloves)
- Vasodilators: calcium-channel blockers, IV prostacyclin (iloprost) for severe ischaemia
What is the management for scleroderma renal crisis (medical emergency)?
- Antihypertensives (give immediately): ACE inhibitors, calcium-channel blockers, (temporary dialysis may be required too)
What is vasculitis?
- Vasculitis = inflammation of blood vessels
- it can be primary or secondary (such as with RA or SLE)
What are the two severe consequences of vascular inflammation?
- vessel stenosis leading to occlusion and distal infarction (ischaemia)
- aneurysm formation can lead to rupture of vessels and haemorrhage
How are the vasculitides classified?
Large-vessel vasculitis:
- Giant cell (temporal) arteritis and polymyalgia rheumatica
- Takayasu arteritis
Medium-vessel vasculitis:
- Polyarteritis nodosa
- Kawasaki disease
Small-vessel vasculitis:
- Granulomatosis with polyangiitis (GPA, or Wegener granulomatosis)
- Eosinophilic granulomatosis with polyangiitis (EGPA, or Churg-Strauss syndrome)
- Microscopic polyangiitis
- Henoch-Schonlein purpura
- Essential cryoglobulinaemic vasculitis
What are the symptoms of giant cell arteritis (GCA)?
- severe unilateral headache (temporal headache) and scalp tenderness
- jaw claudication (pain on chewing food)
- the temporal artery is thickened and may be pulselessness
- visual change (optic artery ischaemia, blindness can occur)
- note: often occurs with PMR
What is the management of giant cell arteritis (GCA)?
- high dose corticosteroids urgently: to reduce the risk of blindness
- followed by 1-2 year gradual taper of corticosteroids
- note: give bisphosphonates with corticosteroids
What are the symptoms of polymyalgia rheumatica (PMR)?
- occurs exclusively in patients over 50 yrs
- shoulder/hip girdle stiffness and pain (EMS >1hr)
- examination: no muscle weakness
- note: polymyositis presents as weakness, not pain
What is the management of polymyalgia rheumatica?
- steroids
What investigations should be done for suspected GCA and PMR?
- temporal artery biopsy
- ESR: usually raised
- Doppler ultrasound
- FBC: anaemia common
What should be prescribed along with longer-term steroid doses?
- bisphosphonates and vitamin D / calcium supplements
- (to prevent osteoporosis)
What is Takayasu arteritis and what is the epidemiology, symptoms, and treatment?
- affects aorta and its main branches (vascular inflammation)
- most common in Asian women between 10 and 40 yrs
- symptoms: night sweats, arthritis/myalgia, visual defects, abnormalities in peripheral pulses
- treatment: steroids
What is polyarteritis nodosa and what are the symptoms / treatment?
- most common in men aged 40-60 yrs
- symptoms: renal failure, coronary (ischaemic heart disease, myocardial infarction), GI (abdo pain, nausea), MSK (arthritis, myalgia), CNS (eye and skin complaints)
- treatment: corticosteroids, cyclophosphamide (severe cases)
What is Kawasaki disease (mucocutaneous lymph node syndrome), epidemiology, symptoms, treatment?
- affects children under the age of 5yrs
- symptoms: desquamation of the skin of hands/feet, conjunctival congestion, cervical lymphadenopathy, strawberry tongue is characteristic finding
- treatment: IV immunoglobulin and low-dose aspirin
Strawberry tongue (characteristic finding in Kawasaki disease)…
What is the presentation of granulomatosis with polyangiitis (Wegener’s granulomatosis)?
Classic triad…
- upper respiratory tract involvement: chronic sinusitis, epistaxis, saddle-nose deformity
- lower respiratory tract involvement: cough, haemoptysis, pleuritis
- Glomerulonephritis: haematuria, proteinuria (frothy urine)
What is the treatment for granulomatosis with polyangiitis (Wegener granulomatosis)?
- milder: methotrexate and azathioprine
- severe: corticosteroids and cyclophosphamide
Saddle nose deformity (seen in GPA)…
What are the 3 stages seen in eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome)?
- Atopic phase: allergic rhinitis, adult-onset asthma
- Eosinophilic phase: abnormally high eosinophils in peripheral blood samples (weight loss, night sweats, diarrhoea, wheeze may be present)
- Vasculitis phase: rashes, peripheral neuropathy, renal failure, abdo pains
- (note: treatment is the same as it is for GPA)
What is microscopic polyangiitis (MPA)?
- one of the more common forms of arteritis affecting smaller arteries (p-ANCA +ve)
- symptoms: systemic upset, kidney inflamm (glomerulonephritis), skin lesions (palpable purpura), peripheral nerve damage, lung involvement
c-ANCA (binds to PR3) and p-ANCA (binds to MPO) antibodies…
- c-ANCA: associated with granulomatosis with polyangiitis (Wegener’s)
- p-ANCA: associated with eosinophilic granulomatosis with polyangiitis (Churg-Strauss), and microscopic polyangiitis
What is Henoch-Schonlein purpura (HSP)?
- typically presents with a palpable purupuric rash on the legs and buttocks in children and adolescents
- GI involvement (abdo pains)
- glomerulonephritis (occurs in about 40%): self-limiting
- treatment: supportive
What is the presentation of hypermobility syndrome, diagnosis, and treatment?
- Presentation: joint and ligament injuries, pain, fatigue, thin/stretchy skin, GI issues (diarrhoea or constipation)
- Diagnosis: Beighton score >4 (out of 9)
- Treatment: physio and OT (strengthening muscles can protect joints), avoid high-impact sports
What are the symptoms of Bechet’s disease and treatment?
- oral and genital ulceration
- uveitis
- erythema nodosum
- treatment: steroids
What is Marfan’s syndrome?
- an autosomal dominant CTD caused by mis-sense mutation of the fibrillin 1 gene
What are the features of Marfan’s syndrome?
- Physical appearance: tall and thin with long arms and legs, arachnodactyly, high arch palate
- cardiovascular features: mitral valve prolapse, aortic problems
- ophthalmic features: lens dislocation, glaucoma
- MSK features: hypermobility, contractures
What is the management for Marfan’s syndrome?
- conservative: education (avoid high-impact exercise)
- pharmacological: antihypertensives
