Rheumatology

Question 1

What antibodies are associated with myocarditis in patients with an idiopathic inflammatory myopathy?

Answer 1

Anti signal recognition particle (SRP) Abs, anti-MDA-5, anti Jo-1, anti-SAE, anti-PL-12, anti-Ro, antimitochondiral Abs

Question 2

What is the association between dermatomyositis & malignancy?

Answer 2

8% patients with DM have malignancy, compared to 4% with PM
- highest risk in first 3 yrs post diagnosis
- risk factors for malignancy in patients with DM - absence of ILD, severe cutaneous disease, age > 65 yrs.
- common cancers = adenocarcinomas. Ovarian, pancreas, bladder, stomach, cervix, breast, colorectal, nasopharyngeal.
- Antibodies associated with increased risk of malignancy - anti NPX 2, anti TIF 1 gamma
- Antibodies associated with decreased risk of malignancy - anti RNP, anti PMScl, anti Ku, anti SRP, anti Mi2, anti-synthetase

Question 3

What antibody is associated with amyopathic dermatomyositis?

Answer 3

Anti-MDA-5 Abs

Represents 10-30% of DM
Associated with increased risk of malignancy

Question 4

What are the features of DM with positive anti-MDA-5 Ab? Melanoma differentiation associated gene 5 = MDA-5

Answer 4

• associated with amyopathic DM
• associated with an increased risk of ILD, including a rapidly progressive presentation with high mortality
• oral ulcers
• arthritis
• cutaneous ulcerations
• painful palmer macules & papules

Question 5

What antibodies are associated with ILD in patients with idiopathic inflammatory myositis?

Answer 5

Anti - Jo - 1
Anti-MDA-5

Anti-MDA-5 associated with rapidly progressive ILD

Question 6

What antibodies are associated with anti synthetase syndrome?

Answer 6

Antibodies against aminoacyl tRNA synthetase
1. Anti Jo - 1 Ab (main)
2. Anti PL7, anti PL 12, anti ks, anti DK - associated with ILD

Question 7

What is the pentad of symptoms in anti-synthetase syndrome?

Answer 7

1. Myositis > 90% (amyopathic 10%)
2. ILD - usual interstitial pneumonia pattern or bronchiolitis obliterans pattern)
3. Mechanic hands (dry, fissuring, cracking)
4. Raynaud’s phenomenon
5. Inflammatory arthritis - often mimics RA

Question 8

What is the most common cause of death in anti-synthetase syndrome?

Answer 8

Pulmonary fibrosis, followed by pulmonary hypertension

Question 9

What antibodies are associated with immune-mediated necrotising myopathy?

Answer 9

Anti SRP Abs - associated with myocarditis / cardiac involvement

Anti HMGCR Abs - strongly associated with MHC class II allele DRB1*11:01 , and also associated with exposure to statins

Question 10

What are the classical biopsy findings in IMNM?

Answer 10

Typical findings in an immune-mediated necrotising myopathy
- minimal or no inflammatory infiltrate
- scattered necrotic & regenerative fibres
- relative absence of lymphocyte infiltration
- abundance of macrophage infiltration
- significant muscle necrosis

Question 11

What is the most common acquired idiopathic inflammatory myopathy?

Answer 11

Inclusion body myositis

Question 12

What are the pathognomic cutaneous manifestations of dermatomyositis?

Answer 12

1. Gottron’s papules - erythema & scaling to DIP + PIP + MCP
2. Heliotrope rash - erythema on periorbital skin & eyelid oedema

Question 13

Presence of which antibody predicts severe motor, bulbar or respiratory involvement in inclusion body myositis?

Answer 13

Anti CN1A (cytosolic nucleotidase 1a) Ab
- present in 50% patients with IBM
- SPECIFIC (80-95%) but not sensitive
- associated with T cell large granular lymphocytic leukaemia
- predicts severe motor / bulbar / respiratory involvement

Question 14

Which malignancy is inclusion body myositis associated with?

Answer 14

T cell large granular lymphocytic leukaemia
- clonal expansion of CD8 + , CD 57 + cytotoxic cells
- In inclusion body myositis, clonal expansion of large granular lymphocytes that resemble T-LGLL

Question 15

What is the pattern of muscle involvement in inclusion body myositis?

Answer 15

• asymmetrical proximal lower limb & distal upper limb involvement
• cricothyroid muscle - dysphagia
• weakness of distal finger flexors is characteristic
  Flexor pollicis longus affected - thumb IP joint flexion
  Flexor digitorum profundus (DIP flexion) affected more than flexor digitorum superficialis (PIP flexion)
  Adductor pollicis & lumbricals preserved - MCP flexion normal
  Weakness & atrophy of quadriceps - vastus medialis & lateralis affected before rectus femoris which is responsible for hip flexion & knee extension
  Oculomotor muscles spared
  Muscles contrlling eye closure may be affected
  MARKED MUSCLE ATROPHY
  LOSS OF DEEP TENDON REFLEXES

Question 16

What is the leading cause of death in idiopathic inflammatory myositis?

Answer 16

CVD
Accelerated atherosclerosis
- 16 x risk of MI
- 32 x risk of MI in women

Question 17

What antibodies are associated with increased malignancy risk in inclusion body myositis?

Answer 17

Seronegative IBM is associated with highest malignancy risk (x 8 times)
Anti HMGCR - increased malignancy risk
Anti-SRP not associated with malignancy

Question 18

What are the biopsy findings in inclusion body myositis?

Answer 18

• mononuclear cell infiltrate in non-necrotic fibres - predominantly CD8+ T cells + macrophages
• rimmed vacuoles and inclusions
• Congo red or P62 + positive or tubulofilament filled inclusions on EM

Question 19

Steroid myopathy summary

Answer 19

Higher risk with fluorinated steroids e.g. dexamethasone vs non-fluorinated steroids (e.g. prednisolone)
Lower limb weakness more severe & early than UL

Question 20

What types of statins are more likely to cause muscle-related toxicity?

Answer 20

Lipophilic statins (rather than hydrophilic) - atorvastatin, simvastatin.
More likely to cause muscle related toxicity due to non-selective uptake into muscles
Also cross BBB more easily and can cause CNS Sx like insomnia and memory impairment
Metabolised by CYP3A4
CYP3A4 inhibitor e.g. diltiazmen incrase risk of myopathy

Hydrophilic statins - pravstatin, rosuvastatin, fluvastatin

Question 21

Risk factors for statin myopathy

Answer 21

• Statin type - lipophilic statins (atorvastatin, simvastatin)
• Hypothyroidism
• acute or chronic failure failure
• obstructive liver disease
• SLCO1B1 polymorphism - transporter that mediates hepatic uptake
• underlying neuromuscular disease (statins can worsen ALS)
• Concurrent use of other medications which can cause myopathy - glucocorticoids, cyclosporine, daptomycin, zidovudine, colchicine