Idiopathic Inflammatory Myopathies and Systemic Sclerosis

Question 1

Classification of epidemiology of inflammatory myopathies

Answer 1

Classification (4 types)

1. Polymyositis
2. Dermatomyositis including amyopathic DM
3. Inclusion body myositis → most common acquired idiopathic inflammatory myopathy in >50s
4. Immune-mediated necrotising myopathy
5. +/- overlap myositis

Characterised by proximal skeletal muscle weakness and evidence of immune mediated muscle inflammation and distinct clinical, serological, histopathological features

Question 2

Pathogenesis of idiopathy inflammatory myopathies

Answer 2

Question 3

Clinical features of dermatomyositis and polymyositis

Answer 3

• 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

Question 4

Other syndromes seen with dermatomyositis or polymyositis

Answer 4

Question 5

Investigations for idiopathic inflammatory myopathy

Answer 5

• 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

Question 6

Prediction of outcome in DM, PM, IMNM

Answer 6

• 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

Question 7

Treatment for DM, PM, IMNM

Answer 7

• 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

Question 8

Notes on inclusion body myositis

Answer 8

• 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

Question 9

Notes on inclusion body myositis and T-LGLL

Answer 9

• 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

Question 10

Notes on myositis-specific and myositis-associated autoantibodies and specific associations

Answer 10

• 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

Question 11

Notes on cardiac involvement in myositis

Answer 11

• 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

Question 12

Epidemiology of systemic sclerosis and subtypes

Answer 12

• 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

Question 13

Notes on serum antibodies in systemic sclerosis

Answer 13

Question 14

Disease burden systemic sclerosis

Answer 14

• Highest mortality among rheumatic diseases
• Reduced life expectancy approx. 25 years
• Cardiopulmonary maifestations leading cause of death

Question 15

General management principles of systemic sclerosis

Answer 15

• 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

Question 16

Notes on scleroderma (skin thickening) in systemic sclerosis

Answer 16

• Puffy fingers, proximal progression of skin thickening, joint contractures (+/- arthritis), reduced hand function
• Rx → physio, OT/splinting, social work

Question 17

Notes on ILD in systemic sclerosis - epidemiology, staging, features of worse prognosis

Answer 17

• 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%

Question 18

Screening and monitoring for ILD associated with systemic sclerosis

Answer 18

• 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

Question 19

Treatment of systemic sclerosis ILD

Answer 19

General principles

• Maximise therapy for GERD
• Smoking cessation
• Vaccinations
• Supplemental O2 to maintain SPO2 >88% during ambulation

Immunosuppression

• Mycophenolate or mycophenolic acid if intolerant
• If severe or progressive disease unresponsive to MMF → oral or IV cyclophosphamide for 6-12 months followed by MMF or AZA
• 2019 RCT → nintedanib (TKI - antifibrotic) vs placebo. Decline in FVC less in treatment group compared to placebo.

Question 20

Notes on pulmonary hypertension in systemic sclerosis

Answer 20

• Group 1 (angioproliferative vasculopathy affecting mainly small pulmonary arteries → pre-capillary) - prevalence 10% in SSc
• Risk factors
  
  • Vascular → severe Raynaud’s, digital ulceration, extensive telangiectasis, reduced nailfold capillaries
  • Antibodies → Anti U3 RNP, nurcleolar Ab
  • O2 desat w/ exercise, DLCO <60%,
  • Raised BNP, Peripcardial effusion, RBBB
  • Raised ESR, IgG
• Evidence that screening programmes reduce mortality

Question 21

ECHO features of pulmonary hypertension in systemic sclerosis limitations of echocardiography

Answer 21

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

Question 22

Screening algorithm for pulmonary arterial hypertension in systemic sclerosis

Answer 22

Question 23

Risk stratification in PAH

Answer 23

Question 24

Treatment algorithm for PAH

Answer 24

• 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

Question 25

Notes on scleroderma renal crisis - epidemiology and features

Answer 25

• Life threatening, hyper-renineic, rapidly progressive renal impairment, usually within 5 years of disease onset
• Features:
  
  • Abrupt onset moderate to severe HTN
  • Normal urine sediment or only mild proteinuria with few casts/cells
  • Progressive renal failure
• 10-20% diffuse, much less frequent in limited
• Other risk factors → RNA polymerase III Ab, tendon friction rubs
• Corticosteroids can be a trigger
• Signs of severe SRC
  
  • MAHA, thrombocytopaenia
  • HF, flast APO
  • Blurred vision (retinopathy)
  • Headache, fever, malaise
  • Encephalopathy
  • Pericardial effusion

Question 26

Treatment of scleroderma renal crisis

Answer 26

• 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
  *

Question 27

Outcomes in scleroderma renal crisis

Answer 27

• 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

Question 28

Therapies for Raynaud’s phenomenon

Answer 28

Question 29

Management of digital tip ulcers in systemic sclerosis

Answer 29

• 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

Question 30

Notes on oropharyngeal involvement in systemic sclerosis

Answer 30

• Rigidity facial muscles and tongue → difficulty chewing
• Reduced saliva production
• Incoordination of swallowing 25%
• Gastrooesophageal reflex → 90%
  
  • Soft food, water with meals
  • Avoid cigarettes, alcohol, opioids
  • PPI before morning and evening meals, high doses
  • Combination with prokinetics
  • Alginate (Gaviscon) after each meal and before bed
  • Consider partial fundoplication - may be best avoided
  • Endoscopy +/- dilatation of stricture
  • Barrett’s surveillance
  • Treat candidiasis

Question 31

Gastrointestinal manfestations (exclusing oropharngeal) manifestations of systemic sclerosis

Answer 31

• Bloating, distension
• Secondary anatomical abnormalities e.g. diverticulae
• SIBO - diarrhoea, bloating, weight loss
• Intussuception/volvulus
• Pneumatosis intestinalis
• Faecal incontinence

Question 32

Indications for autologous stem cell transplant in systemic sclerosis

Answer 32

• Non-smokers, non-responsive to standard treatment along with either:
  
  • dcSSc within first 4-5 years of diagnosis with mild to moderate organ involvement
  • lcSSc with progessive visceral involvement