IIM

Question 1

What are IIM

Answer 1

An acquired group of autoimmune disorders characterized by inflammatory cell infiltration in skeletal muscle, leading to:
Myalgia
Fatigue
Progressive muscle weakness
Functional disability

Question 2

What are 3 types of acquired IIM

Answer 2

Polymyositis
Dermatomyositis
Inclusion body myositis

Question 3

What is the most common inherited muscle dystrophy

Answer 3

DMD

Question 4

Muscle biopsy of IIM shows infiltration of which cells

Answer 4

CD8⁺ T-cells

CD4⁺ T-cells

B-cells

Macrophages

Question 5

Which IIM has acute (rapid onset of symptoms)

Answer 5

Polymyositis
Dermamyositis

weeks to months

Question 6

Which IIM has insidious (gradual, slow) onset

Answer 6

Inclusion body myositis

very slow progression over years

Question 7

Are IIM chronic

Answer 7

typically chronic but fluctuate

Metabolic myopathies - gets worse with activities

Question 8

Do mysotitis cause proximal (shoulders) or distal (feet)

Answer 8

Proximal > Distal
Daily activities like standing, sitting, and lifting use proximal muscles, so weakness here is more noticeable.

Question 9

Example of proximal and distal weakness

Answer 9

Proximal - difficulty rising from a chair (hip muscles) or combing hair (shoulders)

Distal - Difficulty standing on toes or hands grip

Question 10

Which ones are symmetric (Both sides of the body affected equally)

Answer 10

Polymyositis
Dermamyositis

Question 11

Which one is asymmetric

Answer 11

IBM- one side is weaker that the others

Question 12

What does focal (affecting one limb) symptoms and sensory loss are indicative of?

Answer 12

Not myositis
Indicated neurological cause

Question 13

What are some symptoms of myositis

Answer 13

Difficulty swallowing
Respiratory muscle weakness
Pulmonary artery hypertension
Arthritis
Rash
fever, fatigue

Question 14

What are 5 things needed for diagnosis

What is needed for definitive diagnosis of PM
Definite diagnosis of DM

Answer 14

1- Symmetrical proximal weakness of muscles (shoulders, hips, neck)
2- Muscle biospy showing inflammation
3- Elevation of serum creatine kinase (marker of muscle damage)
4- EMG (electromyography) results showing myopathy
5- Typical rash including helitrope (purple rash under eyes) and gottron’s papules (raised scaly lesions)

1- 4
5 plus any 3 from (1-4)

Question 15

Where should the biopsy be taken from

Answer 15

Deltoid or vastus lateralis (proximal)
Avoid distal muscle (gastrocnemius)

Question 16

Histopathology of DM

Answer 16

• Inflammatory infiltrate
• perifasicular (The perifasicular area refers to the region surrounding muscle fascicles in muscle tissue) infiltrate
• perifasicular atrophy
• CD4 cells
• Increased expression of MHC-1 (localised to fibres which undergo atrophy)

Question 17

Hitopathology of PM

Answer 17

Cellular infiltrate within fascile with inflammatory cells invading individual muscle fibre
Cytotoxic T Cells

Question 18

What is different in each myopathy

Answer 18

inflammation
atrophy
fatty replacement

Question 19

What are uses of mri in myositis

Answer 19

Treatment response
to show active disease vs damage
targets for biopsy

Question 20

Features of IBM

Answer 20

BM should be considered when polymyositis is unresponsive to standard immunosuppressive therapy. IBM is often misdiagnosed as polymyositis, but it does not respond well to steroids or immunosuppressants

Most common in males and people over 50

Has insidous onset

Causes distal weakness and asymentric involvement

Dysphagia (difficulty swallowing)

Has characteristics of early muscle atrophy (forearm, quadriceps)

Question 21

Hallmarks of IBM

Answer 21

Low levels of PCK compared to PM and DM
EMG - shows both neuropathic and myopathic findings
Histology is distinctive e.g endomysial inflammation, congo red deposits and rimmed vacuoles seen

Question 22

What plays a role in myositis development

Answer 22

Overlap of Genes and environment

Question 23

Which antibody is associated with anti-synthesa syndrome

Answer 23

Anti- Jo- 1

Question 24

Antibody assocoated with myositis/scleroderma overlap

Answer 24

anti-PM- Scl

Question 25

Treatments of myositis

Answer 25

Immuno-supressant drugs : methotraxate, cyclophosphamide Corticosteroids are the strongest drugs available for reducing inflammation, however, they have serious side effects at high doses ~ their use may worsen infection resistance, high blood pressure, heart failure, diabetes, peptic ulcers, and osteoporosis

Question 26

Does endurance exercise mediate positive adaptive responses in muscle?

Answer 26

Yes

Question 27

Is there a poor correlation between weakness and inflammatory cell load? Why?

Answer 27

Yes In myositis patients, significant muscle weakness may persist even when inflammatory markers are low. In genetically engineered mice to overexpress MHC class I molecules, the mice become weaker before any immune cells even infiltrate the muscle. Thereofre suggests that non-immune cell mediated mechanisms must also contribute to muscle weakness in IIM.

Question 28

Myopathy in absence of adaptive immunity

Answer 28

Scientists used special mice (Rag2-/-) that have no T cells or B cells . They made these mice overproduce MHC Class I in their muscle cells Even though these mice don’t have any immune cells, they still got muscle weakness and damage. Too much MHC Class I in the muscle cell causes Stress inside ER, leading to muscle weakness

Question 29

Which chromosome shows a major mhc-1 signal

Answer 29

6

Question 30

Function of ER

Answer 30

where newly made proteins are folded via a process called thiol-disulphide If proteins don’t fold properly, they can: Clump together (aggregate) Become toxic to the cell- To deal with this, the ER has a built-in quality control system called the: 🛡️ Unfolded Protein Response (UPR): When misfolded proteins pile up, the UPR: Slows down new protein production — to reduce the workload Increases chaperone proteins — which help fold or refold proteins Promotes degradation of irreversibly misfolded proteins If stress continues, it may trigger cell death to protect the body.

Question 31

Do patients display elevated levels of ER stress marker

Answer 31

In myositis, too much MHC I is produced in muscle cells. That overloads the ER, leading to: Misfolded proteins ER stress Activation of the UPR This contributes to muscle damage, even without immune cells. Yes, Biopsy tissue from myositis patients displays elevated levels of ER stress maker Grp78. This suggests ER stress and high GRP78 may contribute directly to muscle weakness and damage, not just be a side effect.