1. Idiopathic Inflammatory Myositis
Pamela E. Prete MD, FACP, FACR
Section Chief Rheumatology
Long Beach Veterans Administration. Long Beach, CA
Professor of Medicine, Emeritus, recalled
University of California, Irvine

2. Idiopathic Inflammatory Myositis (IIM)
I Primary Idiopathic Polymyositis
II Primary Idiopathic Dermatomyositis
III Dermatomyositis or Polymyositis associated with Malignancy
IV Childhood Dermatomyositis or Polymyositis
V Dermatomyositis or Polymyositis associated with Connective Tissue Diseases
VI Inclusion Body myositis
VII Miscellaneous, Eosinophilic myositis, myositis ossificans, focal myositis, infectious myositis, giant cell myositis

3. REVIEW- Polymyositis and Dermatomyositis share many clinical features:
Symmetrical proximal muscle weakness- striated muscle
Elevated muscle enzymes
Characteristic EMG and Muscle BIOPSY
Can be associated with malignancies
Rare 1-8 per 106
2 females to 1 male
45-60 years of age
Rare in children
Black to white 5:1
Polymyositis with differences:
specific dermatologic manifestations
Some distinct muscle biopsy features
Seen in children
Black to white 3:1

4. Inclusion Body Disease- a different “animal”
Slowly progressive myopathy with characteristic biopsy features
Disease of older males > 50
Asymmetric distal weakness
Non responsive to therapy
Some Neurologic features
Weak knee extensors
Weak finger flexors
The pathogenesis of IBM is unknown. It may be autoimmune inflammatory myopathy or a primary degenerative myopathy with a secondary inflammatory. A prevailing theory is that there is an overproduction of β-amyloid precursor protein in muscle fibres that is somehow cleaved into abnormal β-amyloid, and the accumulation of the latter is somehow toxic to muscle fibres. However, there are many problems with this theory and more work needs to be done. Unfortunately, IBM is generally refractory to therapy. Further research into the pathogenesis, along with both preliminary small pilot trials and larger double blind, placebo controlled efficacy trials, are needed to make progress in our understanding and therapeutic approach for this disorders. 66‐year‐old man with weakness of the quadriceps muscles, bilateral foot‐drop, and severe loss of grip strength, progressing over nine years [081]. This shows the characteristic scooped‐out appearance of the volar forearms due to marked atrophy of the deep finger flexors. Dysphagia may be the first symptom of IBM [082] or may develop and worsen as the disease slowly progresses. The creatine phosphokinase may be only mildly elevated, so a misdiagnosis of motor neuron disease often occurs. Treatment for IBM is usually disappointing, although intravenous immunoglobulin has benefited a few cases [083].

5. Classic Symptoms of idiopathic Inflammatory myositis
Slowly progressive weakness 3-6months, muscle tenderness
(IBM may progress over years)
NO real precipitating event
Is symmetrical
Unable to rise from a chair, brushing hair
Other symptoms
Swallowing difficulty, dysphonia, diaphragmatic weakness, cardiac symptoms
Other diseases that cause insidious onset of muscle disease muscular dystrophy metabolic myopathies (glycogen and lipid disorders) endocrine myopathies Neuropathic diseases Amyotrophic lateral sclerosis myasthenia gravis acute onset suggest toxic or neuropathic or myopathic cause

6. history Thorough history
Illicit Drug history especially cocaine alcohol
Medications OTC drugs
Symptoms of endocrine disease
FAMILY history of muscular dystrophy or metabolic myopathies
Family history of autoimmune diseases

7. Meticulous skin exam… Skin Features of Dermatomyositis

8. Gottron’s Papules- Pathognomonic for Dermatomyositis
Pamela E. Prete, MD, Chief VA Rheumatology
re Pathognomonic

9. Dermatomyositis –common skin lesions

10. Capillary microscopy
Cuticular overgrowth

11. Autoimmune Pathogenesis: Distinct diseases on MUSCLE BIOPSY
Polymyositis—CD8 cell endomysial
Dermatomyositis B cell, perimysial perivascular
Polymyositis affects predominantly adults who present with subacute or chronic proximal weakness (without a rash) and elevated CK. The muscle biopsy shows endomysial mononuclear cells and myonecrosis. Polymyositis is a cell-mediated autoimmune disorder in which cytotoxic (CD8-positive) lymphocytes and macrophages invade and destroy myofibers expressing MHC-I antigens. The inflammatory cells are in the endomysium (between and around individual myofibers.) Inflammation may be focal and the MRI is useful in identifying affected areas for biopsy.
The pathology of dermatomyositis includes inflammation, vasculitis, and perifascicular atrophy. The inflammatory cells are predominantly B-cells (with smaller numbers of CD4-positive T-cells) and are found around blood vessels, in the septa between muscle fascicles, and in fibroadipose tissue around muscle. The key pathological change of dermatomyositis is a vasculitis, which involves endomysial and perimysial capillaries and arterioles. This vasculitis begins with endothelial swelling and is followed by endothelial necrosis and capillary loss. Tubuloreticular cytoplasmic inclusions are often seen in endothelial cells.

12. Myositis specific and Myositis associated Antibodies-a growing list

13. Most commonly used myositis antibodies
Anti-Jo
Anti-SRP
Anti Mi-2
Anti p155/140
cAMD-140
Anti PM-SCL
Anti U1 RNP
ILD, RP, Mechanic’s hands Arthritis
Severe necrotizing PM
Dermatomyositis
Cancer associated DM
Clinically amyopathic Dermatomyositis (ILD)
Overlap CT with PM and Scleroderma features
MCTD

14. Transfer RNA synthetase Syndromes
Specific amino acid Transfer RNA antibodies
Autoantibody
Autoantigen (tRNA synthetase)
Prevalence in IIM (%)
Jo-1
Histidyl
20-30
PL-7
Threonyl
<5
PL-12
Alanyl OJ
Isoleucyl EJ
Glycyl KS
Asparaginyl
<1
Tyr
Tyrosyl Zo
Phenylalanyl

16. Cancer associated Myositis (CAM)
Cancer rates are increased in DM>PM
DM, RR 2-4 fold increase, PM 1.5-2
The majority of cancers are diagnosed in 1 year
Before or after diagnosis
DM solid tumors, PM lymphomas, Asians, N-P cancers
Cancer risk returns to baseline after 5 years
WHO gets CAM?
older(>45 )
Men > women
Severe skin disease with Necrosis and ulcers
Rapid progressive weakness with dysphagia
64 AA female with cpk 380, rapid and
progressive weakness, later found to have
Endometrial cancer.

17. Myositis Markers for Malignancy
Lack of autoantibodies favors malignancy
Anti Synthetase antibodies are protective
Anti p-155/140 antibodies –associated with Cancer in DM
Several types TIF-1 alpha, TIF-1 beta, TIF -1 gamma
Regulate transcription, are involved in carcinogenesis
These autoantibodies are specific for DM, can occur in JDM
Meta- analysis of p-155 to diagnose CAM*
- PPV 58%, NPV 95%
* Trallero-Araguas et al, Arthritis Rheum 64(2):523-32, 2012

18. Remember this case (1)
33 year old woman is referred for shoulder and hip-girdle weakness
Mild dyspnea on exertion for 3 months.
Her medications are lisinopril 10mg po qd for mild HBP. Her sister has lupus.
ON PE she has low grade fever, proximal muscle weakness; 3/5 both shoulders and hips.
Swelling of the PIP’s and wrists (arthritis) with dry cracked finger tips

19. Case 1 Laboratory studies: Hgb 10.5g/dl ( 12-15g/dl)
ESR 30mm/hr (<20mm/hr)
AST U/L
ALT U/L
Creatinine normal
CPK ( normal U/L)
Anti-Jo-1 antibodies positive

20. Case1 --What is the next best step in management?
Computed tomography of the chest
Mammography
Ultrasonography of the liver
Magnetic resonance imaging of the thigh
ANA, SS-A, SS-B, ANTI -Sm, ANTI RNP

21. CASE1 Answer is A. Computed tomography of the chest
Anti synthetase syndrome
Interstitial lung disease
Mechanic’s hands, fever
Raynaud’s, arthritis
Transfer RNA antibodies
Anti Jo-1
PL 7
PL 12 EJ OJ
ILD
“mechanic’s hands”
Arthritis
Raynaud’s Phenomenon

22. Basic Workup for Idiopathic Inflammatory myositis
Creatine phosphokinase (CPK), aldolase,
Liver function tests
LDH is more sensitive to muscle necrosis
Myositis specific and associated antibodies, ANA
EMG
MRI -muscle inflammation vs atrophy. T2 weighted or STIR
Plain x-rays -cutaneous or muscle calcifications
Computerized tomography - ILD or cancer screen
Urinalysis and urine myoglobin -
Muscle biopsy (skin biopsy helpful)
Other tests:
pulmonary function studies,
electrocardiography (ECG),
esophageal manometry or barium swallow
Total body CT
. The EMG can help distinguish between myositis, myopathy and neuropathy that shows a myositis pattern with increased insertional and spontaneous activity, positive sharp waves, and low amplitude.

23. EMG findings in Idiopathic Inflammatory Myositis

24. Imaging in Polymyositis and Dermatomyositis
MRI
Ultrasound
46-year-old woman with suspected polymyositis. Whole-body turbo short tau inversion recovery (STIR) MR image (TR/TE, 4000/30; inversion time, 160 msec) shows gross symmetric inflammation or muscle edema in proximal upper (curved arrows) and lower limb girdle muscles. Note florid inflammation or muscle edema (straight arrow) in psoas muscles bilaterally. Edema is worse on right. The sensitivity of muscle ultrasound in detecting histopathologically proven disease (82.9%) was not significantly different from electromyography (92.4%) or serum creatine kinase activity (68.7%). The positive predictive value of ultrasound was 95.1%, the negative predictive value 89.2%, and the accuracy 91.3%. The different types of inflammatory myopathies presented with typical, but not specific ultrasound features. Polymyositis showed atrophy and increased echointensity predominantly of lower extremity muscles, whereas in dermatomyositis clear muscle atrophy was rare and echointensities were highest in forearm muscles. Echointensities were lower in dermatomyositis compared to poly- and granulomatous myositis. Granulomatous myositis was characterized by the highest echointensities and a tendency towards muscle hypertrophy. Severe muscle atrophy was the most impressive feature in the majority of patients with inclusion body myositis.

25. MRI inflammation vs atrophy

26. Keep in MIND other causes of myositis
Viral and bacterial causes
Systemic Vasculitis or CTD related elevations
Endocrine causes such Hypothyroidism or Diabetes or Cushing’s disease
Metabolic diseases
Electrolyte abnormalities
Inherited disorders of muscle MG or Dystrophies
Myotoxins, Alcohol, cocaine, malathion, cimetidine
Medication induced-- direct and immune mediated cpkemias- statins, colchicine,

27. Diagnostic clues to lead you away from Inflammatory myositis
Episodic weakness related to activity or fasting (MG or metabolic myopathies)
Asymmetric or unilateral weakness suggests neurologic disorder
Facial or ocular weakness occurs in MG rarely IIM
Hypertrophy or early muscle atrophy
Neuropathy or fasciculations or cramping
Family history of muscle disorder
No Family history of autoimmunity
NO fever, rashes, arthritis or other CTD symptoms, no capillary nail bed changes
No myositis specific antibodies
Enzymes <2x or >100x normal
MRI normal or only atrophic
No response to therapy

28. Another Case (2) An Air Force Colonel curbsides about a 18 y o recruit
Good athlete but noted dark urine after games
CPK is measures at 132,000 ALT is 1240 LDH is 6412
Recruit is hydrated and returns to normal
Further find out
Recruit has no weakness, has not been ill, has no delays in development and denies drugs
Musculoskeletal exam normal
But CPK is 402 (<350), AST, ALT, LDH normal
Urine no myoglobin

29. Case (2) YOUR advice is… A. Discharge from the military
B. See a neurologist or rheumatologist
C. Get a muscle biopsy
D. Try to reproduce the rhabdomyolysis again

30. CASE 2 ANSWER is D. Try to reproduce the rhabdomyolysis again
Forearm ischemic exercise test
Exercise the forearm and measure the ammonia and lactate
Normal --ammonia and lactate rise
IF only the ammonia rises, the patient lacks the enzyme myophosphorylase
McArdle’s Disease – Myophosphorylase deficiency
Valuable tool in the diagnosis of metabolic myopathies
Glycogen storage diseases
Myodenylate deaminase deficiency
Clinical muscle examination may be un-revealing
Muscle strength is often normal
Muscle enzymes may only be elevated during symptomatic periods
Electromyograms are frequently normal or demonstrate unspecific changes
Immunohistochemistry, biochemical assays, and molecular analysis will allow a definitive diagnosis

31. McArdle’s disease -glycogen storage V
Most common - Autosomal recessive (PYGM gene)
1 in (remember PM-DM is 1 per million)
Usually presents in teen years with sx after exercise
“Second wind “ phenomenon
CAN PRESENT LATER IN LIFE
50% have myoglobinuria
Muscle biopsy will lack the enzyme
Renal failure from rhabdomyolysis
Avoid isometric exercise, B6 and sucrose
CONSIDER metabolic myopathies
The onset of this disease is usually noticed in childhood,[4] but often not diagnosed until the third or fourth decade of life. Symptoms include exercise intolerance with myalgia, early fatigue, painful cramps, weakness of exercising muscles and myoglobinuria. Myoglobinuria, the condition where myoglobin is present in urine, may result from serious damage to the muscles, or rhabdomyolysis, where muscle cells breakdown, sending their contents into the bloodstream.
Patients may exhibit a “second wind” phenomenon
C is McArdle’s showing no myophophorylase staining
F is control

32. Remember this case 3
An 80 woman with HBP, Hyperlipidemia is admitted to hospital for progressive SOB and weakness. Despite diuresis for her CHF, her SOB and weakness and muscle cramping progressed.
On PE her RR 20/min, pulse 120/min, BP 132/90 , lungs crackles, Skin normal, Muscle testing 3/5, neck flexors shoulder abductors/flexors, hip flexors.
Lab shows
cpk 3510 (<200 U/L)
AST 335 (<40 U/L)
Urine myoglobin 8620 (<40 mg/mL).

33. CASE 3 continued. ANTI Jo-1, SRP, ANA were negative.
An EMG showed myopathy but not myositis
Muscle biopsy shows:
Muscle necrosis
No inflammatory infiltrate
Statin-induced necrotizing myopathy has been linked to an antibody against the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) protein, which is up-regulated in regenerating fibers.5 In a study conducted by Christopher-Stine and associates,6 exposure to statin ther­apy preceded the development of muscle symptoms and persisted long after the myotoxin was discontinued in more than 60% of patients with a necrotizing myopathy. The researchers found that this association was strongest in older patients; almost 90% of patients 50 years or older had been exposed to statins.
Arrows show necrotic muscle fibers
But no inflammatory infiltrate

34. CASE 3 And the next step is…
A. Give prednisone 1mg/kg for Transfer RNA Synthetase syndrome
B. Stop Statin
C. Give IVIG for Inclusion Body Muscle disease
D. Give prednisone and Methotrexate for Polymyositis
E. Stop Statin and give prednisolone 1mg /kg

35. CASE 3 answer is …D. Stop Statin and give prednisolone
Diagnosis: Statin induced Necrotizing myositis –
Another and new form of immune mediated statin induced myopathy
Antibody against the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) protein, which is up-regulated in regenerating muscle fibers.
Stopping Statin alone for this form is not enough, must give prednisone or other immunosuppressive
People at risk for statin myopathy
Older
Muscle pain with statins, unexplained cramping
Simvastatin, Atorvastatin more likely
Average onset 6 months ( range 1week-4 years) less likely in patient on statins for years
People at an increased risk for myopathy include those with prior history of muscle pain with cholesterol-lowering drugs, unexplained cramps or an increase in creatine kinase levels (creatine kinase is an enzyme released in the blood when a muscle is damaged). Drugs like simvastatin and atorvastatin are more likely to cause myopathy. In a small retrospective study of 45 patients, the mean duration of statin therapy before onset of symptoms was 6.3 months (range 1 week to 4 years). In this study the mean duration of myalgia after stopping statin therapy was 2.3 months (range 1 week to 4 months). Muscle symptoms that develop in a patient who has been taking statins for several years are unlikely to have been caused by these drugs.
In a small retrospective study of 45 patients, the mean duration of statin therapy before onset of symptoms was 6.3 months (range 1 week to 4 years). In this study the mean duration of myalgia after stopping statin therapy was 2.3 months (range 1 week to 4 months). Muscle symptoms that develop in a patient who has been taking statins for several years are unlikely to have been caused by these drugs.
In a small retrospective study of 45 patients, the mean duration of statin therapy before onset of symptoms was 6.3 months (range 1 week to 4 years). In this study the mean duration of myalgia after stopping statin therapy was 2.3 months (range 1 week to 4 months). Muscle symptoms that develop in a patient who has been taking statins for several years are unlikely, An association has been established between statin induced myopathy and variations in the SLCO1B1 gene In a small retrospective study of 45 patients, the mean duration of statin therapy before onset of symptoms was 6.3 months (range 1 week to 4 years). In this study the mean duration of myalgia after stopping statin therapy was 2.3 months (range 1 week to 4 months). Muscle symptoms that develop in a patient who has been taking statins for several years are unlikely to h In a small retrospective study of 45 patients, the mean duration of statin therapy before onset of symptoms was 6.3 months (range 1 week to 4 years). In this study the mean duration of myalgia after stopping statin therapy was 2.3 months (range 1 week to 4 months). Muscle symptoms that develop in a patient who has been taking statins for several years are unlikely to have been caused by these drugs.

36. Reminder Drugs that cause myositis
Direct Toxic Myopathy
ALCOHOL
HYDROXYCHLOROQUINE
COLCHICINE
COCAINE-most common cause of illicit drug induced medical problems in ER
Retroviral drugs
Immune mediated myopathy/myositis
D–Penicillamine
Hydralazine
Procainamide
Dilantin
Ace inhibitors
Statins rhadomyolysis and severe muscle inflammation
Interferon alpha
Genetic associations are not for workup and are the general genetic associations with autoimmune disease
Cocaine use is now the most common cause of illicit drug-induced medical problems in the United States, including muscle disease. In one report, at least five percent of cocaine users presenting to one emergency department had evidence of muscle injury based upon CK elevation [20]. Muscle injury can occur after oral or intranasal cocaine use, but may be more common after intravenous use or after smoking the alkaloid free base (crack cocaine) because of the more rapid and higher blood levels of the drug achieved via those routes. Muscle injury can occur after a one time use of the drug or after repeated use. The onset of muscle involvement is usually within hours after drug administration
Antimalarial neuromyopathy is thought to be due to the accumulation of chloroquine or hydroxychloroquine in lysosomes and the subsequent inhibition of lysosomal enzymes. Phospholipid and glycogen then accumulate in the lysosomes, producing the characteristic myeloid and curvilinear bodies seen on biopsy (see below)

37. One interesting question --is how much workup for Cancer should be done in inflammatory Myositis
Conventional
Extensive*
H&P
CBC, CMP, ESR, UA
Fecal Occult blood
Chest xray
AGE appropriate cancer screening
CT-chest, abdomen, pelvis
Endoscopy/colonoscopy
Bronchoscopy
Bone Marrow
Serum tumor markers
PET imaging*
The performance of FDG-PET/CT, a single imaging study, for diagnosing occult malignant disease in patients with myositis was comparable to that of broad conventional screening, which includes multiple tests.
*Selva-O’Callaghan et al, AJM 2010;123(6):

38. Unusual Complaints for IIM
Episodic weakness, especially after exercise or prolonged use of the affected muscles, occurs in myasthenia gravis and metabolic myopathies
Asymmetric or unilateral weakness, muscle cramps, and fasciculations suggest a primary neurologic disorder
Facial and ocular muscle weakness rarely occurs in myositis but is frequent in myasthenia gravis
A family history of primary myopathy is common in heritable forms of muscle disease.
List of the patient's medications may uncover a cause myopathy.
Pamela E. Prete, MD, Chief VA Rheumatology

39. Goals of IIM Therapy Reducing muscle inflammation with medications
Decreasing weakness – rehabilitation*
Preventing muscle atrophy
Minimizing medication side effects such as steroid myopathy
Avoid the sun
* when cpk <1000

40. Treatments for Dermatomyositis and Polymyositis
Corticosteroids - only FDA approved drugs for Dermatomyositis
Limited clinical trials
Hydroxychloroquine
Methotrexate/azathioprine
Mycophenolate mofetil
IVIG- make sure no IgA deficiency exists
TNF inhibitors, rituximab, cyclosporine, tacrolimus and cyclophosphamide
Mycophenolate mofetil may be used for the interstitial lung disease but is contraindicated in pregnancy. The does used ranges from 500mg PO twice daily to 1500mg PO twice daily. Mycophenolate mofetil is also used for recalcitrant dermatomyositis related skin disease.
Intravenous immunoglobulin (IVIG) is also used for recalcitrant muscle disease, not helpful for lung involvement- Cyclophosphamide may be given for severe refractory pulmonary disease Rituximab, a chimeric monoclonal antibody directed against CD20 on B cells, has also been shown to be useful in adult and pediatric polymyositis and dermatomyositis patients

41. Summary
Idiopathic inflammatory myositis are rare autoimmune diseases –women 2:1, blacks 3-5:1
Insidious symmetric proximal muscle weakness including neck flexors but sparing facial and ocular muscles
Gottron’s papules are pathognomonic for Dermatomyositis
MSA denote subtypes of IIM
Transfer RNA synthetase, anti SRP, anti Mi-2

42. Summary Cancer is associated with PM and DM
Anti p155/140 antibody useful in DM signalling cancer
Keep looking for 3 years, less likely after 5 years
Amyopathic Dermatomyositis does occur
Not all CPK elevations are Idiopathic Inflammatory Myositis
Always consider metabolic, infectious, toxins, medications, and dystrophies
Statins –IM but non inflammatory necrotizing myopathy

43. Summary Do appropriate testing
CPK, aldolase, liver enzymes, EMG MRI ultrasound Biopsy
Use the myositis specific antibodies (Transfer RNA’s, Anti Mi-2, Anti-SRP)
Most IIM responds to therapy (exception is Inclusion Body Myositis)
Corticosteroids Methotrexate -Beware steroid myopathy
Keep in mind the GOALS of therapy
Use Consultants –Rheumatology Neurology Pathology Dermatology and Rehabilitation

44. Thank you for your attention! Any Questions?
Pamela E. Prete, MD, Chief VA Rheumatology
Denali (Mt. McKinley) 2011
Thank you for your attention! Any Questions?

45. CASE 4
75year old woman has 4 weeks of progressive weakness, arms and legs. She has history of gout on colchicine and allopurinol for gout. Significant she was admitted 6weeks ago for CHF that responded to increase in diuretic. She developed right knee swelling that was treated with increasing her colchicine from 06.mg OD to 0.6mg qid. She also takes fenofibrate, metoprolol, hydralazine and furosemide

46. Physical exam revealed marked weakness of shoulder abduction and hip flexion without pain and pain both knees but no swelling.
Laboratory studies:
ESR mm/hr
Serum K mEq/dl
Serum creatinine 2.8mg/dl
Serum uric acid 8.2mg/dl
ANA negative
CPK (<240 IU/L)

47. What is the answer ? Vote on key pad
Colchicine induced neuromyopathy
Drug induced lupus related to Hydralazine
Fenofibrate induced myopathy
Polyarticular gout involving the hips and shoulders
Polymyositis

48. Answer is …
Colchicine induced neuromyopathy

49. MYOSITIS-SPECIFIC AND MYOSITIS-ASSOCIATED AUTOANTIBODIES IN ADULT POLYMYOSITIS AND DERMATOMYOSITIS AND JDM
Autoantibody
Autoantigen
Clinical features
Jo-1
Histidyl tRNA synthetase
Fever, Raynaud phenomenon, mechanic's hands, myositis, polyarthritis, ILD
SRP
Signal recognition particle (cytoplasmic protein translocation)
Severe necrotizing myopathy; predominantly PM
Mi-2
Helicase
DM (adult > children); “shawl sign” and other DM rashes
PM-Scl
Nucleolar macromolecular complex
Overlap features of myositis and SSc (or either disease alone); mechanic's hands
U1RNP
Small nuclear ribonucleoprotein
Overlap syndromes (MCTD)
SUMO-1 (small ubiquitin-like modifier 1)
Small ubiquitin-like modifier enzyme (post-translational modification)
Adult DM, ILD
p155/140
Transcriptional intermediary factor 1-gamma (TIF1γ)
Cancer-associated myositis in adults; 20+% frequency in JDM cohorts; severe cutaneous disease in adult DM and JDM
Anti-p140 (also anti-MJ)
NXP-2 (SUMO target; possible role in SUMO-mediated transcriptional repression)
20-25% frequency in JDM cohorts; calcinosis; severe disease (atrophy/contractures)
cADM-140
RNA helicase
ADM; ILD
PMS1
PMS1 (DNA mismatch repair enzyme)
Myositis (specifics not known) Ku
70 and 80 kDa nuclear/nucleolar protein complex (DNA break repair and recombination)
UCTD and overlap syndromes (Raynaud phenomenon, ILD, myositis, arthritis)
Recently, the anti-CADM-140 antibody was reported to be found specifically in clinically amyopathic DM (C-ADM) patients and to be associated with acute interstitial lung disease (ILD). We assessed the clinical significance of the anti-CADM-140 antibody and then investigated the autoantigen recognized by the anti-CADM-140 antibody. The anti-CADM-140 antibody was a marker of DM and intractable ILD and recognized IFIH1/MDA5, which is involved in innate immunity. These findings may give a new insight into the pathogenesis of DM.

50. Clinical signs Workup
Proximal, and usually symmetric muscle weakness and myalgia
Weakness of neck flexors
No facial weakness
Characteristic rash in DM
Arthritis
ILD
Elevations of creatine phosphokinase, aldolase and liver associated enzymes
Gammaglobulinopathy or ANA
MAA and MSA
MRI thigh
EMG
MUSCLE BIOPSY