Inflammatory Myositis 6.5%

Question 1

What are the Bohan and Peter Criteria for dermatomyositis?

Answer 1

REQUIRED: Pathognomonic rash (heliotrope rash, Gottron papules)

Features:

• proximal muscle weakness
• elevated muscle enzymes
• EMG changes of chronic inflammatory myositis
• histopathological changes of inflammatory myositis

DEFINITE JDM: 3/4 features present
PROBABLE JDM: 2/4 features present

Question 2

What is on the differential diagnosis for a child who develops inflammatory myositis after receiving routine vaccines?

Answer 2

Macrophagic myofasciitis: predominantly macrophagic infiltration with focal myositis in deltoids or quads at injection site of vaccine containing aluminum

Question 3

What is the classic pattern of muscle weakness in JDM?

Answer 3

Symmetric, proximal muscle weakness
Gower sign
Trendelenburg sign - indication of weak hip abductors

Question 4

A 7 year old female presents with fatigue, difficulty climbing stairs, and violaceous hue to her eye lids. Her muscle enzymes are elevated. She answers questions in a quiet voice, and you notice that she coughs occasionally while eating her breakfast.

What muscle groups are involved that could explain her voice and cough? What additional work-up is indicated?

Answer 4

Involvement of palatopharyngeal muscles may result in difficulty swallowing and increase risk of aspiration. Dysphonia, weak/gurgling voice, nasal speech are other frequent signs.

In up to 80% of patients, subtle or even asymptomatic dysfunctional swallowing can be demonstrated by barium swallow test, which does not necessarily correlate with weakness or other measures of disease activity. Thus, all children with JDM should undergo evaluation for swallowing dysfunction.

Question 5

What are other MSK manifestations of JDM other that muscle weakness?

Answer 5

Arthralgias
Arthritis (transient, nondeforming) may be present in 26-67% of JDM patients
Tenosynovitis or flexor nodules
Flexion contractures – knees, hips, shoulders, elbows, ankles, wrists due to myofascial inflammation

Question 6

What are classic skin findings in JDM?

Answer 6

Heliotrope rash
Gottron papules
Malar rash - less discrete than in lupus, spares nasolabial folds
Periungal erythema and capillaropathy
Gingival capillaropathy
Photosensitive rash - malar rash, facial erythema, shawl/V sign, linear exnesor erythema - in up to 50%
“Tear drop” erythema near inner canthi

Scalp dermatitis - up to 25%
Panniculitis
Anasarca in severe disease
Overlying SQ tissue may be edematous and indurated, including periorbital area

Question 7

What is the implications of skin ulcers in JDM?

Answer 7

Patients with generalized rash and cutaneous ulcers may have severe and prolonged disease, but this is not observed universally.

Question 8

What myositis specific antibody is seen with increased frequency in patients with JDM and generalized lipodystrophy?

Answer 8

Anti-TIF-1 (anti-p155/140)

Question 9

What are the two most. common autoimmune rheumatologic diseases associated with lipodystrophy?

Answer 9

1. JDM

2. JIA

Question 10

What are risk factors associated with the development of lipodystrophy?

Answer 10

Features of severe disease:

Calcinosis
Muscle atrophy
Joint contractures
Facial rash
Greater skin disease activity
Decreased density of periungal nailfold capillaries

Question 11

What is calcinosis?

Answer 11

Dystrophic calcification that typically occurs after onset of symptomatic myositis

May occur in SQ plaques or nodules, as large deposits in muscle groups, as calcification within fascial planes, bridging joints, or as extensive SQ exoskeleton

Question 12

What are the risk factors for the development of calcinosis?

Answer 12

Delay to diagnosis
Duration of untreated disease
Duration of active disease
Inadequate therapy
Underlying cardiac or pulmonary disease
Male
Older at onset
Prolonged persistent disease activity after dx
Need for steroid-sparing immunosuppression that indicates severe disease activity

Question 13

What are myositis-specific antibodies associated with the development of calcinosis?

Answer 13

Anti-NXP-2 (anti-MJ)
Anti-PM-Scl

Bonus: Proinflammatory cytokine polymorphisms of TNFa and IL-1a also a/w risk of development of calcinosis

Question 14

For JDM, What is persistently decreased nailfold capillary density related to?

Answer 14

More severe, chronic disease course; cutaneous ulceration; development of calcinosis

Question 15

What are complications of calcinosis

Answer 15

Cellulitis
Flexion contractures – calcinosis crosses joint margins
Severe pain – if calcinosis entraps nerves
May slowly resolve with recurrent extrusion of small flecks of calcium or development of liquid Ca salts that resorb. The latter occurs with aggressive anti-inflammatory and demineralizing treatments
Exoskeleton – SQ Ca deposition along fascial planes and within muscle. Results in severe disability

Question 16

What is a potential emergency in JDM patients?

Answer 16

GI tract vasculitis

Presents as diffuse, severe, progressive abdominal pain, pancreatitis, melena, and hematemesis, which represents vasculopathy of the GI mucosa with tissue ischemia or acute mesenteric infarction

Rare, usually occurs soon after onset of sx, can occur later, poor prognosis

Can rapidly lead to death

Perforation – seen as free air on XR; multiple perforations of duodenum are difficult to see and can recur

Question 17

What myositis-specific antibodies are associated with interstitial pneumonitis in JDM?

Answer 17

Anti-Jo-1 and other antisynthetase Ab

Anti-MDA-5

Question 18

What are early markers of ILD in JDM?

Answer 18

KL-6 and ferritin

Question 19

What type of lung involvement can be seen in moderate-severe JDM?

Answer 19

Symptomatic, restrictive lung disease

Look for decreased TLC or DLCO

Question 20

What is the incidence of JDM?

Answer 20

3.2 per million

Question 21

What is the age of onset of dermatomyositis?

Answer 21

Bimodal
Age 5-14 then
Age 45-64

Median age of onset 7 years

Question 22

What is the sex ratio of JDM?

Answer 22

2 female : 1 male

Question 23

True of false: There is an increased risk of malignancy in children with JDM.

Answer 23

False

Question 24

A 7 year old male develops calf pain and tenderness 1 week after flu-like symptoms. He has no rash. His ESR is slightly elevated. He has a moderate leukopenia. His CK and AST are elevated. What is the diagnosis?

Answer 24

Viral myositis due to influenza

Question 25

A 13-year-old female with SLE and class IV LN receiving IV methylprednisolone pulsing x 3 doses/week weekly, mycophenolate mofetil, and Plaquenil. She has demonstrated clinical improvement. She reports new fatigue, myalgias, difficulty climbing the stairs. Her muscle enzymes are elevated. What is on the differential for her new muscle weakness

Answer 25

Steroid-induced myopathy Plaquenil-induced myopathy Underlying SLE

Question 26

A 6-year-old male presents for evaluation of muscle weakness and markedly elevated CK in the 10,000s. On exam, he has no rashes. He has prominent calf muscles. His mother reports she has had similar symptoms. What is the diagnosis?

Answer 26

Duchenne muscular dystrophy

Question 27

A 15-year-old female presents with fatigue, hair thinning, proximal muscle weakness, and muscle cramping and enlargement in her calves. Her CK is elevated, and she has lab signs of rhabdomyolysis. What endocrinopathy is on the differential and how could we initially evaluate for it?

Answer 27

Hypothyroid myopathy TSH, FT4

Question 28

What features may help distinguish juvenile polymyositis from JDM?

Answer 28

Age of onset: preteen-teen (median 12.1 years) More severe illness, higher CK, more frequent falling as a sign of distal weakness, myalgias, Raynaud phenomenon, weight loss, pulmonary disease, cardiac abnormalities Calcinosis infrequent Need muscle biopsy to exclude other myopathies

Question 29

What features may help distinguish overlap myositis from JDM/JPM?

Answer 29

More frequent Raynaud phenomenon, ILD, arthritis, sclerodactyly, periungal capillary abnormalities Mortality is highest for overlap compared to JDM or JPM

Question 30

What are the differences between malar rash in SLE vs JDM?

Answer 30

JDM malar rash lacks well-defined borders and does NOT spare nasolabial folds

Question 31

What histopathologic muscle biopsy findings are seen in chronic arthritis, acute rheumatic fever, SLE, and scleroderma?

Answer 31

focal accumulation of lymphocytes, patchy fiber atrophy, and increased interstitial connective tissue but no significant vasculopthy

Question 32

What histopathologic muscle biopsy findings are seen in Sjogren?

Answer 32

muscle fiber degeneration and atrophy, sarcoplasmic degeneration, and microcyst formation

Question 33

What histopathologic muscle biopsy findings are seen in polyarteritis nodosa?

Answer 33

necrotizing vasculitis with muscle fiber degeneration and neurogenic atrophy

Question 34

What is the condition that results in painful muscle and fascial swelling followed by fibrosis, calcification, and ossification? Classic early finding is short great toes with hallux valgus.

Answer 34

Fibrodysplasia ossificans progressiva Rare AD inflammatory disorder Patients may present with spontaneous joint contracture or pre-osseous soft tissue lesions. Hard to diagnose until calcification occurs. Biopsy may look like malignant sarcoma. Common sites include back of neck and posterior trunk with tumorlike swellings followed by limbs. Palmar and plantar fascia may be affected. The great toes are congenitally malformed, usually short with hallux valgus. The thumbs are sometimes involved. The toe deformity is an early clinical sign to diagnosis, even before ossification. May also have cranial skeleton deformities. There is no therapy for prevention or treatment.

Question 35

What condition is associated with higher frequency of homozygosity at HLA-DQA1?

Answer 35

Multiplex myositis

Question 36

What percentage of patients will have elevated muscle enzymes?

Answer 36

80-96% Muscle enzymes can be normal despite active disease. Degree of muscle enzyme elevation does NOT correlate with disease outcome

Question 37

What are 2 proposed biomarkers for JDM disease activity to distinguish active disease from remission and may be elevated months prior to a flare or CK elevation?

Answer 37

Galectin-9, CXCL-10

Question 38

What is the percentage of patients with JDM who have a positive ANA?

Answer 38

76%

Question 39

What is the percentage of patients with JIIMs who have an MSA?

Answer 39

40-60%

Question 40

What are classic findings on EMG for JDM?

Answer 40

Increased spontaneous and insertional activity (as evidenced by fibrillation potentials and positive sharp waves); low-amplitude short duration, polyphasic motor unit action potentials; and early recruitment

Question 41

What type of muscle (striated vs smooth) is affected in JDM?

Answer 41

Striated skeletal muscle

Question 42

What are some classic muscle biopsy findings for JDM?

Answer 42

Muscle fibers demonstrate perifascicular atrophy or necrosis, which is a/w noninflammatory capillaropathy Variations in myofiber size due to degeneration and regeneration Focal necrosis replaced by interstitial proliferation of connective tissue Inflammatory exudate often present Inflammatory cells include lymphocytes and mononuclear cells, located in perimysium and perivascularly around septae or fascicles – nondiagnostic because this can be seen in muscular dystrophies too. Also macrophages, plasma cells, mast cells, and – rarely – eos or basos Nonspecific changes: disruption of myofibrils and tubular systems, central nuclear migration, prominent nuclei and basophilia Immunohistochemistry shows that pDCs are one of the primary infiltrating immunophenotypes

Question 43

There are tubuloreticular inclusions seen on EM of muscle biopsy obtained from a patient with presentation suspicious for JDM. What does this signify?

Answer 43

Increased Type I interferon

Question 44

What is a predictor of a chronic course on muscle histopathology of a patient with JDM?

Answer 44

Extensive myopathic changes: uscle degeneration and vacuolation Sarcoplasmic pallor and necrosis Central nuclei without basophilia Muscle infarction correlates with chronic course, GI ulceration, and death

Question 45

What are classic findings on MRI w/wo contrast in JDM?

Answer 45

T1 weighted detects muscle atrophy and fatty infiltration with chronic disease Subcutaneous fat signal intensity change is associated with more aggressive chronic disease and may signify increased likelihood to develop calcinosis in the future T2 weighted imaging and fat suppression shows soft tissue edema with active disease STIR - increased signal intensity reflects edema Whole body MRI can even identify distal muscle edema even if the patient is asymptomatic

Question 46

What physical examination finding may suggest decreased bioavailability of oral prednisone in JDM and suggest that the patient may respond better to IV methylprednisolone?

Answer 46

Loss of nailfold capillary end-row loops

Question 47

What is the first line treatment for JDM?

Answer 47

Corticosteroids | Methotrexate

Question 48

What symptoms/signs of JDM tend to respond well to IVIG?

Answer 48

IVIG is good for persistent skin manifestations despite improvement in muscle disease Dose: 2 grams/kg/infusion (max 70 grams)

Question 49

When would you consider addition of cyclosporine to the treatment of a patient with JDM?

Answer 49

May be used in refractory skin disease Textbook authors reserve its use in secondary MAS

Question 50

What are some indications for cyclophosphamide use in JDM?

Answer 50

Used in severe or refractory disease: skin ulceration, severe muscle disease with dysphonia/dysphagia, GI involvement, ILD

Question 51

What are some indications for addition of mycophenolate mofetil to the treatment of a patient with JDM?

Answer 51

May be used in persistent skin disease but could be good for muscle disease too Demonstrated improvement in both skin and muscle disease at 12 months in one study and improvement in muscle strength and decrease in steroid use at 3 months in another study Textbook authors use in patient who don’t tolerate methotrexate

Question 52

What are some indications for the addition of Plaquenil to the treatment of a patient with JDM?

Answer 52

May be used in skin predominant disease Textbook authors use sparingly, mostly for overlap patients because Plaquenil does not appear to have marked effect on skin rash or myositis in JDM

Question 53

What are some indications for the use of rituximab in the treatment of JDM?

Answer 53

Textbook authors use for necrotizing myopathy (anti-SRP or anti-HMGCR-positive patients) and sometimes for ILD Rituximab in Myositis (RIM) trial - multicenter, randomized, double-blind, placebo-phase trial comparing rituximab at week 0 and 1 to rituximab at week 8 and 9 83% of patients responded to rituximab and decreased their steroid doses by week 44 No difference in time to response between early (week 0 and 1) and late (week 8 and 9) treatment arms Presence of antisynthetase (particularly anti-Jo-1) and anti-Mi-2, juvenile onset, and lower disease damage predicted better efficacy Reported improvement in skin disease too No improvement in calcinosis

Question 54

What is an indication for the use of TNFi in the treatment of JDM?

Answer 54

Adalimumab, infliximab used in UK as second-line for calcinosis Etanercept not effective and some patients got worse

Question 55

What are some indications for the use of abatacept in the treatment of JDM?

Answer 55

Refractory skin ulcers, progressive calcinosis There is an ongoing clinical trial in refractory JDM Bonus: Abatacept is a soluble fusion protein made of CTLA-4 and Fc portion of IgG

Question 56

What has tofacitinib been used for in the treatment of JDM?

Answer 56

Refractory skin disease and inflammatory arthropathy - case series Amylopathic dermatomyositis intersititial lung disease - case report

Question 57

What are some non-pharmacologic treatments that should be discussed with patients with a new diagnosis of JDM?

Answer 57

Sunscreen (UVA and UVB protection, at least SPF 30) Calcium and Vitamin D supplementation given chronic steroid use PT, OT

Question 58

What are some complications of lipodystrophy seen in JDM?

Answer 58

Insulin resistance Diabetes Hypertriglyceridemia

Question 59

What fraction of patients with JDM have a monocyclic course?

Answer 59

1/3 of patients with JDM have a monocyclic course

Question 60

What fraction of patients with JDM have a polycyclic course?

Answer 60

3-30%

Question 61

In JDM, which clinical features improve faster: skin disease or muscle disease?

Answer 61

Muscle disease

Question 62

What are predictors of a longer time to remission in JDM?

Answer 62

Gottron papules at 3 months | Abnormal nailfold capillaries and rash at 6 months

Question 63

What are some common causes of death in patients with JDM?

Answer 63

``` GI vasculitis leading to GI bleed or GI perforation Progressive pulmonary disease Progressive myositis Progressive CV disease Super infections ```

Question 64

What symptoms or distinguishing features are seen more in juvenile polymyositis (JPM) compared to JDM?

Answer 64

``` more severe disease illness onset and higher CK levels More frequent falling episodes as a sign of distal weakness Myalgias Raynaud phenomenon Weight loss Pulmonary disease Cardiac abnormalities Abnormal nail fold capillary pattern Calcinosis occurs infrequently Anasarca ```

Question 65

What is the incidence of JPM as a percentage of all JIIM?

Answer 65

2% of all JIIMs are JPM 22% of all JIIMs are JDM

Question 66

What are some pulmonary manifestations of JDM?

Answer 66

Aspiration pneumonia Alveolar hypoventilation Interstitial lung disease

Question 67

What are additional diagnostic studies useful in evaluation of pulmonary involvement in a patient with JDM?

Answer 67

PFTs - including DLCO (carbon monoxide diffusion capacity) - can see restrictive ventilatory defects and decreased DLCO HRCT chest - confirmatory testing since PFTs can show restrictive pattern from respiratory muscle weakness alone You can see the following findings on HRCT chest: - Consolidation - Reticulonodular infiltration - Ground glass opacities - Peribronchovascular thickening - Bilateral lesions, mostly lower lobe

Question 68

What myositis specific antibodies are associated with an increased risk of developing calcinosis in JDM?

Answer 68

Anti-NXP-2 (anti-MJ) | Anti-PM-Scl

Question 69

What is an indication for bisphophanate use in a patient with JDM?

Answer 69

Treatment of calcinosis

Question 70

What are some complications of calcinosis in JDM?

Answer 70

Cellulitis Flexion contractures – calcinosis crosses joint margins Severe pain – if calcinosis entraps nerves May slowly resolve with recurrent extrusion of small flecks of calcium or development of liquid Ca salts that resorb. The latter occurs with aggressive anti-inflammatory and demineralizing treatments Exoskeleton – SQ Ca deposition along fascial planes and within muscle. Results in severe disability

Question 71

A 4 year old male presents with fatigue, diffuse arthralgias and myalgis, difficulty walking up the stairs. He is otherwise healthy and received his 4 year old vaccines recently. His CK is elevated. MRI reveals mostly unilateral proximal muscle edema in his left thigh. Muscle biopsy of his affected quad reveals a predominantly macrophagic infiltration with focal myositis with aluminum intracytoplasmic inclusions. What is the diagnosis? What is the trigger?

Answer 71

Macrophagic myofasciitis triggered by vaccine containing aluminum

Question 72

A school age male develops acute onset severe proximal calf pain and tenderness. He is otherwise healthy except for he has been out sick for a few days last week with fever, headache, and body aches. His labs look pretty good except mildly elevated ESR, moderate leukopenia, and elevated CK and AST. What is the diagnosis and treatment?

Answer 72

Post influenza myositis. Occurs 3-14 days after flu. Lasts days to weeks. Treatment supportive.

Question 73

What infection has a syndrome that mimics DM?

Answer 73

Toxoplasmosis

Question 74

What does the muscle biopsy of juvenile polymyositis (JPM) look like?

Answer 74

endomysial inflammatory infiltrate scattered throughout the muscle fascicle (in contrast to juvenile dermatomyositis [JDM], in which affected muscle fibers are typically grouped in one portion of the fascicle). In JPM, muscle fiber size is variable, and there are usually no signs of vasculopathy. Scattered necrotic muscle fibers may be present.

Question 75

What disease has these findings on muscle biopsy? scattered endomysial inflammatory infiltrate with little evidence of vasculopathy

Answer 75

juvenile polymyositis (JPM)

Question 76

What disease has these findings on muscle biopsy? Rounded, hypercontracted myofibers with areas of fatty replacement

Answer 76

congenital myopathies like Duchenne muscular dystrophy Although not specific, histologic findings in Duchenne muscular dystrophy are more likely to demonstrate “opaque” hypertrophic fibers, rounded hypercontracted myofibers, and significant replacement of muscle by fat.