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Question 1

Inflammatory myopathies are systemic diseases involving multiple organs. What are some types?

Answer 1

-Dermatomyositis-Antsynthetase Syndrome-Amyopathic Dermatomyositis-Juvenile Dermatomyositis-Inclusion Body Myositis

Question 2

What is antisynthetase syndrome?

Answer 2

As asyndrome, this condition is poorly defined. Diagnostic criteria require one or more antisynthetase antibodies (which targettRNA synthetase enzymes), and one or more of the following three clinical features: interstitial lung disease, inflammatory myopathy, and inflammatory polyarthritis affecting small joints symmetrically. Other supporting features may include fever, Raynaud’s phenomenon and “mechanics hands”-thick, cracked skin usually on the palms and radial surfaces of the digits.

Question 3

What isAmyopathic Dermatomyositis? What is a major risk in these patients?

Answer 3

disease in whichpatients have DM type rash confirmed by skin biopsy, BUT no myositis (CPK normal and muscle function normal)but may develop myositis late and are at risk for severe ILD

Question 4

What isJuvenile Dermatomyositis? Common triad? Cause?

Answer 4

rare disease with peak onset at age 6 and 11 years with features commonly seen in adult DM (except in JDM the rash pain is WAY more severe); 30% to 70% have calcinosis (below), cutaneous ulceration and lipodystrophy.The disease is usually triggered by a condition that causes immune system activity that does not stop as it should, but the trigger is almost certainly not the cause in most cases. Common triggers includeimmunizations,infections, injuries, andsunburn.

Question 5

What isInclusion Body Myositis? Patients?

Answer 5

IBM has sporadic and familial hereditary forms, characteristic histological features including sarcoplasmic and nuclear inclusions and rimmed vacuoles, and an insidious onset of muscle weakness over months to yearscommon in older men (50+)and localizes in thigh muscles and finger flexors (resistant to much treatment)

Question 6

The insidious onset of muscle weakness seen in IBM is confined to where?

Answer 6

localized predominantly to the thigh muscle and finger flexors but eventually is widespread and both proximal and distal

Question 7

T or F.IBM is resistantto glucocorticoid treatment

Answer 7

T. So if you are considering this and PM (which present very similarly, the lack of efficiacy of prednisone suggests this)

Question 8

Patient population for IBM?

Answer 8

occurs mostly in men over 50 yrs.

Question 9

What are somecharacteristic features of dermatomyositis skin changes?

Answer 9

-Gottron’s papules-Heliotrope rash-Gottron’s sign of knees and elbows

Question 10

How can SLE be differentiated from DM?

Answer 10

Erythematous rashes on the hand in dermatomyositis and systemic lupus erythematosus. A, Note the changes on the knuckles and dorsum of the hand in dermatomyositis (Gottron’s sign). B, Rash is absent on the knuckles but present on the phalanges in lupus. C, Capillary nail-fold changes in dermatomyositis.

Question 11

What are some other possible sign changes in DM?

Answer 11

A, Linear erythema. B, Scalp rash. C, V-like sign. D, Shawl sign.

Question 12

What do these images show?

Answer 12

Appearance of “Mechanics Hands”Anti-Synthetase SyndromeMechanic’s hands in a white (A) and a black (B) patient. Note the characteristic skin changes on the lateral side of the fingers.

Question 13

What is theannual incidence of all inflammatory myopathies [dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM)]?

Answer 13

estimated to be 10 per million individuals.

Question 14

When does PM present?

Answer 14

usually in late teens OR older with a mean age at onset being 50-60 years (biphasic)MOSTLY IN WOMEN LIKE DM

Question 15

When does DM present? IBM?

Answer 15

DM shows two peaks-5 to 15 years and 45-65 years; mostly in WOMEN (very common to present after pregnancy- could be an immune rxn to lingering fetal antigens)IBM is commonly seen in MALESolder than 50 years

Question 16

Inflammatory myopathies (from 11 to 40% of all myositis) can occur in association with other autoimmune connective tissue diseases. Name some

Answer 16

Scleroderma, SLE,rheumatoid arthritis, Sjogren’s syndrome, polyarteritis nodosa, and sarcoidosis.

Question 17

12% of myositis cases areassociated with what?

Answer 17

a malignancy (breast CA, adenocarcinoma) and detected in the first year of diagnosis of myositis; majority have DM (81%), PM is 19%.Thus, DM and PM are essentially paraneoplastic syndromes in these cases (if the cancer is pre-existent, removal of the cancer usually results in remission of the dermatomyositis)

Question 18

Diagnosis?

Answer 18

Dermatomyositis - a heliotrope rash is NOT seen in polymyositis or MCTDIn inclusion body myositis, there is both proximal AND distal muscle weakness (and is usually asymmtric)

Question 19

Dx?

Answer 19

Inclusion body myositis, dont see weak finger flexors in polymyositis or dermatomyositis

Question 20

What is a very common complication of IBM?

Answer 20

Dysphagiais a progressive condition in about 50-75% of patients with IBM and often leads to death fromaspiration pneumonia.

Question 21

Arthritis occurs commonly with inflammatory myopathies. What Abs is it commonly associated with?

Answer 21

anti-Jo-1 ABs against histidyl-tRNA synthetase

Question 22

Diarrhea is often a symptom of inflammatory myopathies. Why?

Answer 22

sphincter ani can be impaired (and other straited muscle)

Question 23

How can you distinguish PM vs. DM histo?

Answer 23

PM- endomysial inflammation (below)DM- perimysal inflammation

Question 24

tRNA synthetase Abs are associated with what?

Answer 24

may have arthritis in addition to myositis, fevers, ILD and the “mechanic’s hands” so named because of the thickening of the palms of the hand

Question 25

Mi-2 ABs are associated with what? HLA type?

Answer 25

DM with Gottron’s papules, heliotrope rash, V sign, and the shawl signDR7

Question 26

What HLA groups are assoicated with aminoacyl-tRNA synthetase ABs?

Answer 26

HLA-DQA1*0501

Question 27

What HLA groups are assoicated with anti-SRP ABs? Clinical associations?

Answer 27

DR5associated with severe muscle weakness that comes on very rapidly, muscle aches, and cardiac involvement.

Question 28

What HLA groups are assoicated with anti-PM/Scl?

Answer 28

DR3

Question 29

Note about the presence of anti-PM/Scl ABs

Answer 29

these patients typically have a characteristic overlap syndrome with features of limited scleroderma with mild muscle disease, and prominent arthritis,respond well to therapy

Question 30

The composition of cellular infiltrates can be a useful diagnostic in inflammatory myopathies. What are the infiltrates like in DM?

Answer 30

perivascular, often in perimysial areas and is made up of CD4 T cells, macrophages, and dendritic cells with B cells

Question 31

What are the infiltrates like in PM or IBM?

Answer 31

mostly CD8 T cells and macrophages and are surrounding predominantly endomysial with mononuclear inflammatory cells and often invade non-necrotic muscle fibersthe CD8 lymphocytes can recognize MHC class I muscle fibers and may mediate muscle fiber damage

Question 32

How muscle damaged in polymyositis?

Answer 32

probably mediated by complement, Ab activation, and cytokines that can endothelial damage leading to hypoxia, capillary loss and eventually loss of skeletal muscle fiber ANDcytokines and CD8 T cells binding to MHC class I and causing ER stress and myofiber damage leading to loss of muscle fibers

Question 33

Describe inclusion body myositis. Patient population?

Answer 33

1.Mostly proximal muscle weakness in lower extremities with also distal muscle supplying upper extremities.2.Poor response to corticosteroids3.Seen mostly in older men

Question 34

T or F. CPK should be elevated in inflammatory myopathies

Answer 34

T. Except amyopathicDMcan be huge increases!! up to 1000s and 10ks

Question 35

How are inflammatory myopathies treated?

Answer 35

start with high-dose prednisone quickly to subside weakness and drop CPK and then you want to add a steroid-sparing agent such as methotrexate or azathioprine or MMif no response, go to IVIG (IBM doesnt respond well to any therapy)

Question 36

Dx.

Answer 36

Polymyalgia rheumaticaSLE- cant be (ANA was negative)Rheumatoid Arthritis- cant be (RF neg)Osteoarthritis- really doesnt present in the shoulder

Question 37

What are some symptoms of giant cell arteritis that aren’t present in PMR?

Answer 37

jaw claudication, temporal artery tenderness, HA, visual loss, and evidence of noncranial ischemia such as arm claudicaiton or cerebral ischemiaPMR has a low yield of temporal artery biopsyconstitiutional symptoms (fever, fatigue, weight loss) will be present

Question 38

T or F. Patients under 70, with no headahce or jaw claudicaiton, and with normal temporaly arteries have a very low risk of vasculitis

Answer 38

T.

Question 39

Note about PMR vs. GCA

Answer 39

PMR occurs in about 50% of patients with GCA,while 15% of PMR patients develop GCA.

Question 40

How does PMR present? Suspected causes? HLA type?

Answer 40

PMR occurs in patients over age 50 and is characterized by stiffness and pain in shoulder and hip musculature (mostly in the morning).Patients often develop profound disuse atrophy of muscles and complain of weakness, giving rise to the suspicion of polymyositis.TheESRis often elevated.Infection:Thevirusesthought to be involved include theadenovirus, which causes respiratory infections; the humanparvovirus B19, an infection that affects children; and thehuman parainfluenza virusDR4

Question 41

MRI has confirmed that PMR involves what?

Answer 41

inflammation of extrarticular synovial structures. As an example, MRI of the hands and feet of those with PMR frequently demonstrate inflammation of the ten­don sheaths. In addition, shoulder MRI reveals subacromial and subdeltoid bursitis in almost all patients with active PMR.

Question 42

What is a common pathology that occurs in a subset (10-15%) of PMR patients?

Answer 42

Tenosynovitis may also cause carpal tunnel syndrome

Question 43

Another rare condition associated with PMR?

Answer 43

Some patients with PMR develop swelling and pitting edema over the hands, wrists, ankles, and top of the feet. The edema usually occurs with other signs of polymyalgia rheumatica but can be the presenting symptom. It appears to represent tenosynovitis and synovitis in regional structures. This syndrome represents a subset of patients with PMR.Typically, they do not evolve into rheumatoid arthritis.

Question 44

Dx.

Answer 44

Giant cell arteritis/temporal arteritisALT, AST, and ALP can be elevated (will return to normal with steroids)

Question 45

What is GCA/temporal arteritis?

Answer 45

·Necrotizing inflammation of large sized arteries originating from the arch of the aorta1.Is associated with granulomas2.Is not associated with a glomerulonephritis

Question 46

How does GSA/TA occur?

Answer 46

IFN-y production follows antigen recognition in the adventitia of a vessel, leading to specialization of macrophages, formation of giant cells, and subsequent production of MMPs, and growth and angiogenic factors.Tissue destruction and repair/modeling then promote matrix degradation (arterial wall destruction) and occlusive intimal hyperplasia, respectively.

Question 47

How can GCA/TA affect the lungs/URT?

Answer 47

About 10% of these patients can have upper respiratory symptoms including nonproductive cough and SEVERE sore throat. Repeat negative throat cultures and absence of infiltrate on CXR are consistent

Question 48

What is a potential, very serious complication of GCA?

Answer 48

aortic aneurysm, monitor closely.

Question 49

Why does/can aortic aneurysm occur with GCA?

Answer 49

one of two mechanisms:1) chronic or late recrduescent aortitis causing elastin and collagen disruption2) mechanical stress on an aortic wall that was weakened in the early active phase of the disease

Question 50

How can an aortic aneurysm be detected?

Answer 50

widening of the mediastinum on CXR

Question 51

What is an ESR (sed rate) test?

Answer 51

simple and cheap test that measures the rate at which RBC fall through plasma and is an indirect measure of fibrinogen levels (influenced by RBC properties)

Question 52

How is temporal arteritis diagnosed?

Answer 52

·Diagnosis is by temporal artery biopsy

Question 53

Pathology of temporal arteritis?

Answer 53

Pathology early in disease reveals collections of lymphocytes in region of internal or external elastic membrane or adventitia. Later there is necrosis of portions of the arterial wall and granuloma formation with multinucleated giant cells, histocytes, plasma cells and fibroblasts. Thrombosis may occur. The inflammation is most marked near the elastic membrane which is typically destroyed or interrupted

Question 54

How is PMR treated?

Answer 54

prednisone up to 20mg/day for 7 daysthen check response:if good, diagnosis supported and continue to monitor for GCAif bad, increase prednisone to 30mg/day for 7 daysthen check response,if bad,reject PMR diagnosis

Question 55

How is TA treated?

Answer 55

Corticosteroids in high doses (1mg/kg/day of prednisone or equivalent)It is critical to begin treatment with steroids as soon as diagnosis is suspected otherwise your patient may go blind permanently. One should treat and make arrangements for the temporal artery biopsy but do not wait for the biopsy to be done or results to be back before starting treatmentPrognosis is good with treatment. However, blindness is irreversible.

Question 56

What is this?

Answer 56

Inclusion body myositis

Question 57

Presentation of polymyositis

Answer 57

Diagnosis is fourfold, history and physical examination, elevation ofcreatine kinase,electromyograph(EMG) alteration, and a positive musclebiopsy.The hallmark clinical features of polymyositis is proximal muscle weakness, with less important findings being muscle pain and dysphagia. Cardiac and pulmonary findings will be present in approximately 25% of cases of patients with polymyositis.

Question 58

PMvs. IBM

Answer 58

Sporadicinclusion body myositis(sIBM): IBM is often confused with (misdiagnosed as) polymyositis or dermatomyositis that does not respond to treatment is likely IBM. sIBM comes on over months to years; polymyositis comes on over weeks to months. Polymyositis tends to respond well to treatment, at least initially; IBM does not.