Polymyositis/Dermatomyositis

Poly = manyMyo = muscleItis = inflammation

So, basically, polymyositis (PM) is inflammation of muscles. What it looks like is a person with weakness in proximal muscles (shoulders and hips). It can come on abruptly or gradually, probably gradually more than suddenly. There is some pain but mostly weakness. The classic sign is difficulty getting up from a chair. 

Patients with PM with skin disease are diagnosed as dermatomyositis. Though simply inflammation of muscles plus inflammation of skin, there are other differences in the 2 diseases. 

Diagnosis

Diagnosis of PM starts with lab then can proceed with electrical muscle testing or MRI scan and in some cases a biopsy of muscle. 

Diagnostic criteria

Bohan and Peter criteria 

Proximal weakness, with or without dysphagia, elevation muscle enzyme, EMG criteria, muscle biopsy. With rash, dermatomyositis

New criteria 

Lab

Muscle enzymes

CPK

Aldolase

Myoglobin

LDH

Transaminases

Association with Malignancy

One in four adults with myositis has cancer, either 3 years before or after a diagnosis of myositis. It’s one of the leading causes of death in these patients, and they’re overwhelmingly diagnosed at a late stage.[2]

Risk factors for malignancy: [2]

dermatomyositis subtype

older age

male sex

dysphagia

cutaneous ulceration

antitranscriptional intermediary factor-1 gamma (anti-TIF1-gamma) positivity 

Reduced risk for malignancy [2]

polymyositis 

clinically amyopathic dermatomyositis subtypes

Raynaud’s phenomenon

interstitial lung disease

very high serum creatine kinase or lactate dehydrogenase levels

positivity for anti-Jo1 or anti-EJ antibodies 

Recommendations for cancer screening (18 - 13 strong, 5 conditional)

(from N Osterwell. First Recommendations for Cancer Screening in Myositis Issued. Medscape Nov 12, 2022.)

Strong

All adult IIM patients should continue to participate in country/region-specific age and sex appropriate cancer screening programs

Patients with verified inclusion body myositis or juvenile-onset IIM do not require routine screening for myositis-associated cancer

all adults with new-onset IIM be tested for myositis-specific and myositis-associated autoantibodies to assist in stratifying patients by risk category

Adults with IIM who are determined to be at low risk for IIM-related cancer should have basic cancer screening

comprehensive history and physical exam

complete blood count

liver functions tests

erythrocyte sedimentation rates/plasma viscosity, 

serum protein electrophoresis

urinalysis, 

chest x-ray. 

 Adults with IIM who are determined to be at low risk for IIM-related cancer should have basic cancer screening at the time of IIM diagnosis.

Adults with intermediate risk should undergo both basic and enhanced screening at the time of IIM diagnosis

those with high risk should undergo enhanced screening at the time of myositis diagnosis, with basic screening annually for 3 years

Conditional 

PET/CT for adults at high risk for cancer when an underlying cancer has not been detected at the time of IIM diagnosis

"A single screening test for anti-TIF1-gamma positive dermatomyositis patients whose disease onset was after age 40 and who have at least one additional risk factor. 

Upper and lower gastrointestinal endoscopy for patients at high risk when an underlying cancer is not found at the time of IIM diagnosis

nasoendoscopy in geographical regions with elevated risk for nasopharyngeal cancers,

screening for all IIM patients with red-flag symptoms or clinical features of cancer, including unexplained weight loss, family history of cancer, smoking, unexplained fever, or night sweat

ILD is more common and severe in patients with anti-PL-7/anti-PL-12 antibodies when compared with anti Jo-1 patients. The prevalence of anti-MDA5 antibodies is higher in Asians (11-60%) than in whites (7-16%). Sixty-six percent of antisynthetase syndrome patients had 'chronic ILD' compared with the more rapidly progressive ILD (RP-ILD) seen in 69% of patients with anti-MDA5 antibodies. [6]

Myositis specific antibodies (MSA)

Myositis-specific autoantibodies are associated with particular clinical syndromes within the idiopathic inflammatory myopathy spectrum.

These tests are positive in 45 to 85 percent of patients with PM

A negative myositis panel does not rule out a diagnosis of dermato or polymyositis. 

Myositis autoantibody panels can determine what particular myositis phenotype may best fit the patient. 

In many clinical settings, serologic test panels for idiopathic inflammatory myopathy are available from reference laboratories, in an effort to eliminate the need to order the numerous autoantibody tests individually. However, the results are often not available for several weeks, and treatment decisions may need to be made before the specific serologic profile is known. In addition, many commercially available myositis panels have varying degrees of accuracy.[1]

   Antibody       Clinical features

    Synthetase abs       

ASS (Anti-synthetase syndrome) were defined by the presence of any three of 5 clinical features (fever, Raynaud's phenomenon, arthritis, ILD, mechanic's hand), and one of the ARS. Clinical ASSD was diagnosed when the clinical criteria were satisfied but ARS were not present. The anti-aminoacyl-tRNA synthetase (ARS) tested included antibodies against Jo1, EJ, OJ, KS, PL-7, PL-12, Ha, Zo. [5]

    Jo-1        Lung, Mechanics hands

PL-12 

    MDA5        Lung

    TIFF1        Cancer

    NXP2        Calcinosis

Synthetase syndrome

Jo-1

Myositis associated antibodies (MAA)

Myositis-associated autoantibodies are associated with particular clinical syndromes within the idiopathic inflammatory myopathy spectrum but also can be seen in other autoimmune disorders. 

These tests include SSA-52 and PM-Scl ab.

Anti-Pm/Scl was found with one each of anti-PL7 and anti-PL12 antibodies. MSAs were largely mutually exclusive, apart from anti-TIF1ɣ, seen with anti-MDA5 antibody in one and anti-Jo1 with anti PL-12 in another individual [5]

Treatment

IV Ig

Random controlled trial x 16 wks. Trial entry criteria = inadequate responders; tried 2 immune suppressives; 2 grams IV then q 4 weeks. Thromboembolism assoc with IVIg is rare. None in this trial. Primary endpoint = . Intention to treat. 96 completed dbl blind trial. All had weakness and DM rash. 92% had elevated CK. 50% had muscle biopsy. 88% pts on steroid. 35% of patients had significant improvement. Secondary endpoints TIS (total improvement score) >60 30% vs 8% placebo. 58% adverse events vs 30% placebo. Headaches (42%) most common. No VTE in initial trial but one in extension trial.  [3]

MDA5 disease is strongly assoc with lung. Treatment options include