Idiopathic Inflammatory Myopathies and Systemic Sclerosis Flashcards
1
Q
Classification of epidemiology of inflammatory myopathies
A
Classification (4 types)
- Polymyositis
- Dermatomyositis including amyopathic DM
- Inclusion body myositis → most common acquired idiopathic inflammatory myopathy in >50s
- Immune-mediated necrotising myopathy
- +/- overlap myositis
Characterised by proximal skeletal muscle weakness and evidence of immune mediated muscle inflammation and distinct clinical, serological, histopathological features
2
Q
Pathogenesis of idiopathy inflammatory myopathies
A
3
Q
Clinical features of dermatomyositis and polymyositis
A
- Symmetrical proximal muscle weakness >90% patients with myalgias and muscle tenderness in 25-50%
- Deltoids, hip flexors, neck flexors
- Diaphragmatic and intercostal muscles - hypoventilation, hypercapnic respiratory failure
- Weakness of the striated muscle of upper third of oesophagus - dysphagia/aspiration
- Rash → precedes muscle weakness in 40-50% of patients with DM
- Photosensitive areas
- Heliotrope rash
- Myocarditis, increased risk MI
- ILD in at least 10% of PM and DM
- Can also occur in amopathic disease
- Can be rapidly progessive with high mortality
- A/W Anti-synthetase antibodies, MDA5
4
Q
Other syndromes seen with dermatomyositis or polymyositis
A
5
Q
Investigations for idiopathic inflammatory myopathy
A
- Elevated muscle enzymes → CK, transaminases, LDH, aldolase (elevated troponin suggests myocardial involvement)
- ANA positive in 80%
- Myositis specific antibodies positive in 30-40%
- Myositis associated antobodies more likely in overlap syndromes
- EMG → distinguish myopathic weakness from neuropathic. Non-specific and normal in 10%
- Findings include increased insertional activity and spontaneous fibrillations, abnormal myoapthic low-amplitude, short duration polyphasic motor unit potential, complex repetitive discharges, early recruitment and abnormal spontaneous activity
- MRI ASIS to ankles
- Areas of muscle inflammation, oedema with active myositis, fibrosis and calcification;
- Non-specific: rhabdomyolysis, muscular dystrophy, metabolic myopathy
Invesigations for complications (DM, PM, IMNM)
- ECG and ECHO
- PFTs and HRCT
- Oesophageal motility studies
- Increased malignancy risk in DM
6
Q
Prediction of outcome in DM, PM, IMNM
A
- DM and overlap more responsive to steroids
- Myositis specific antibodies
- Jo-1, SRP worse prognosis
- Mi-2, overlap (ENP, PM-Scl, Ku) better prognosis
- Greater weakness at diagnosis, ILD, dysphagia, respiratory muscle weakness and cardiac involvement all worse outcomes
7
Q
Treatment for DM, PM, IMNM
A
- High does glucocorticoids tapering over 1 year (1mg/kg up to 80mg a day). IV methylpred x 3 days if severe
- Steroid sparing agents → aza, methotrexate, IVIG, rituximab, plasma exchange
- Monitoring: CK, muscle power, PFTs
- Other
- Monitor respiratory function, measures to reduce aspiration, exercise, photoprotection if skin disease, prevention of osteoporosis and infections
8
Q
Notes on inclusion body myositis
A
- Commonest acquired myopathies in > 50 years
- Pathogenesis → myodegeneration, rimmed vacuoles
- Insidious onset of asymmetric proximal leg weakness for up to 5 years
- Weakness of distal finger flexros muscles in 95%
- More muscle atrophy
- Dysphagia due to cricopharngeal muscle involvement in ⅓rd to ½
- CK elevated <10 x ULN (more in the others), not useful for monitoring disease
- ESR/CRP usually normal
- 15% have an autoimmune disease
- EMG, MRI and muscle biopsy for diagnosis
- Less responsive to immunosuppresive therapy - limited trial of glucocorticoids
- IgG anti-cNI1antibody - 90% specificity, 30-40% sensitivity
9
Q
Notes on inclusion body myositis and T-LGLL
A
- T cell large granular lymphocytic leukaemia → rare
- Clonal expansion of CD8/CD57 cytotoxic T cells seen in peripheral blood, BM, spleen
- Associated with autoimmune disorders
- Associated with IBM
10
Q
Notes on myositis-specific and myositis-associated autoantibodies and specific associations
A
- Anti TIF1 AND anti-NXP 2 → malignancy
- Anti-SRP → carditis (also nerotising myopathy)
- Anti-HMGCR → necrotising myopathy and prior statin use
- Anti MDA5 → amyopathic DM, ILD, poor prognosis
11
Q
Notes on cardiac involvement in myositis
A
- CVS disease leading cause of death → accelerated atherosclerosis, myocardial inflammation
- Myocarditis
- Severe/clinical Rare → subclinical in 60-75% on MRI
- Associated antibodies → SRP, MDA5, Jo-1, antimitochondrial antibodies
12
Q
Epidemiology of systemic sclerosis and subtypes
A
- F:M 3:1
- Peak onset age 40-60 years
- 2 subtypes - limited cutaneous: diffuse cutaneous 4:1
- Rare familial causes
- Genetic and environmental factors:
- HLA DRB1, STAT4, interferon
- Silica, organic solvents, cinyl chrloride
Diffuse cutaneous
- Raynaud’s short history
- Rapid onset skin changes → contractures, skin of trunk and proximal limbs
- Tendon friction rubs → poor prognosis and more likely to progess to organ involvement
- Constitutional symptoms
- Early onset internal organ involvement (ILD 40%, renal crisis 10%)
- Scl-70 antibodies (anti-topoisomerase) → ILD
- Anti-RNA polymerase I, III antibosies - renal crisis
- ANA with nucleolar pattern
Limited cutaneous
- Raynaud’s for years
- Gradual onset skin changes limited to upper limbs/face
- Calcinosis, telangiectasia
- Oesophageal dysmotility
- Clinically significant ILD less frequent (<20%), cardiac and renal disease rare
- Anti-centromere antibodies
- Lower incidence Scl-70
13
Q
Notes on serum antibodies in systemic sclerosis
A
14
Q
Disease burden systemic sclerosis
A
- Highest mortality among rheumatic diseases
- Reduced life expectancy approx. 25 years
- Cardiopulmonary maifestations leading cause of death
15
Q
General management principles of systemic sclerosis
A
- Assess for organ involvement
- Therapy:
- Often symptom relief only → Raynaud’s, GI
- Mostly organ specific e.g. lung, skin, PAH
- No overall disease modifying therapy: immunosuppressive therapies, vasodilators, anti-fibrotics
- Monitor for new organ involvement:
- Scleroderma renal crisis - first 5 years in diffuse
- ILD → first 5 years in diffuse
- Pulmonary hypertension any time in both groups
17
Q
Notes on ILD in systemic sclerosis - epidemiology, staging, features of worse prognosis
A
- PFTs abnormal in 70%, usually NSIP, then UIP
- Not all patients progress, clinically significant in 42% dcSSc and 22% lcSSc, may lead to PAH (worse prognosis)
- High risk phenotypes:
- Early dcSSc and Scl-70 antibodies
- Early dcSSc and elevated CRP
Features predictive of clinically significant SSc-ILD/disease progression
- Male gender, African-American
- dcSSc
- Biomarkers - Scl-70 Ab, Neucleolar pattern on ANA (indicates Anti Th/To, U3 RNP), CCL-2, CCL 18, IL 6 and CRP, CXCL-4, KL-6, surfactant protein D
- Baseline FVC >70%, Baseline DLCO <55%
- Imaging → HRCT fibrosis >20-25%, HRCT total lung involvement >20%
18
Q
Screening and monitoring for ILD associated with systemic sclerosis
A
- In majority in whom FVC declines <55% it occurs within first 5 years
- In early difuse SSc with ILD → spirometry and DLCO every 3-4 months for 3-5 years after disease onset, then yearly
- No advantage in serial HRCT scans if PFTs stable
21
Q
ECHO features of pulmonary hypertension in systemic sclerosis limitations of echocardiography
A
Limitations of ECHO
- Sensitivity 88%, specificity 83%
- SPAP not estimated in up to 40% due to absent TR jet
- Can be normal in early PAH
- Significant cost
22
Q
Screening algorithm for pulmonary arterial hypertension in systemic sclerosis
A
23
Q
Risk stratification in PAH
A
24
Q
Treatment algorithm for PAH
A
- Vasodilator challenge not performed at right heart catheter
- CCB monotherapy not effective for SSc-CTD
- RCTs included patients with CTD-PAH but effects of PAH specific therapues not as significant as for idiopathic PAH
- Note worse survival in iron deficient SSc-PAH
26
Q
Treatment of scleroderma renal crisis
A
- Untreated can progress to ESRD 1-2 months
- Mainstay is prompt BP control
- ACEi → most experience with captopril
- Non-ACEi therapy (not recommended as first line) → prostacylins, plasma exchange, bosentan
- CNS involvement → captopril and IV nitroprusside
*
27
Q
Outcomes in scleroderma renal crisis
A
- 20-50% progress to ESRF despite ACEi
- Dialysis more difficult compared to other forms of ESRD
- High mortality
- Limited experience with transplant
- Survival superior to those that remain on dialysis
- Recurs in 5% of patients with renal transplants
28
Q
Therapies for Raynaud’s phenomenon
A
29
Q
Management of digital tip ulcers in systemic sclerosis
A
- Cold avoidance and optimal vasodilator therapy
- Pain relief
- Dressing to remove dry eschar and allow healing
- Treat contributing causes e.g infection
Management of critical digital ischaemia
- Urgent admission
- Establish diagnosis and treat contributing cause
- Large proximal vessel disease, vasculitis, coagulopathy, thromboembolism, smoking
- IV prostaglandin/prostacyclin
- Optimise vasodilator theraoy, antiplatelet therapy or short term anticoagulation
- Consider statin, antibiotics
- Consider botox around the digital vessel or digital sympathectomy
- Surgical debridement only if significant necrotic tissue
31
Q
Gastrointestinal manfestations (exclusing oropharngeal) manifestations of systemic sclerosis
A
- Bloating, distension
- Secondary anatomical abnormalities e.g. diverticulae
- SIBO - diarrhoea, bloating, weight loss
- Intussuception/volvulus
- Pneumatosis intestinalis
- Faecal incontinence
