Notes
Dermatomyositis, Polymyositis, Polymyalgia Rheumatica
Sections
Idiopathic Inflammatory Myopathies & Polymyalgia Rheumatica
Overview
Here, we'll learn about the inflammatory myopathies (myositis), which are a rare group of autoimmune disorders that cause proximal muscle wasting and weakness, as well as a variety of other potential skin and systemic manifestations.
To start, let's divide the inflammatory myopathies into:
Dermatomyositis (DM), which notably manifests with myositis and skin changes (rash).
Polymyositis (PM), which we can now think of as an umbrella term for a variety of inflammatory myopathies. These include:
- Antisynthetase syndrome, which is best thought of as "classic polymyositis". It is notably anti Jo-1 antibody positive.
- Immune-mediated necrotizing myopathy (aka, autoimmune necrotizing myopathy (NM)), which is best remembered as a severe statin myopathy (HMGCoAR inhibitors).
- Overlap syndromes, meaning myositis as a part of other rheumatologic disorders.
Inclusion body myositis (IBM), which is a mixed inflammatory/degenerative disorder.
General Features
Let's closely look at the pattern of weakness (myositis, skin changes that occur in dermatomyositis, and potential systemic involvement in the various myopathies.
Weakness (Myositis)
First, let's draw out the pattern of proximal weakness for dermatomyositis and polymyositis.
Draw the shoulder girdle and indicate that patients struggle to raise their arms above their head, for instance to comb their hair.
Draw the pelvic girdle and indicate that patients struggle to stand from a chair or climb stairs.
In regards to laboratory testing, creatine phosphokinase (CPK) (aka, CK creatine kinase (CK)), is typically elevated (although may not be in ~ 25% of cases).
- Post muscle contraction, CK catalyzes the rephosphorylation of ADP back to ATP so the ATP is again available for the next muscle contraction. Generally, the greater the muscle damage, the higher the serum CK.
- The normal range in non-myopathic patients is from 50 to 300 U/L.
- In frank rhabdomyolysis (acute muscle injury), CK's are often up to 200x normal (~ 40,000 U/L).
- Within the inflammatory myopathies, it is most elevated in necrotizing myopathy, with a very rough estimation of 5,000 to 10,000 U/L (on average) and in the non-necrotizing myopathies a rough average of 500 to 5,000 U/L (on average). Essentially necrotic tissue produces more CPK elevation than inflamed muscle tissue. We indicate rough CPK estimates below.
Notably, the ESR and CRP can be elevated but not to the extent that it is in polymyalgia rheumatica (in which it's elevated ~ 80% of the time).
Various myositis-specific antibodies are available that can predict aspects of systemic involvement in DM.
- Discussion of these is beyond our scope, here, but notably antibody is anti-transcriptional intermediary factor 1-gamma (anti-TIF1 gamma): cancer-associated myositis, which suggests increased risk of malignancy in adults and severe cutaneous involvement in children.
Skin Changes (Dermatomyositis)
Draw the upper portion of a female figure (front and back) – dermatomyositis has a strong female predominance, and let's show the characteristic rashes:
Show that the heliotrope eyelid rash refers to inflammation of the face that manifests blue-violet (or violaceous) color (like a lilac, hence: heliotrope), which involves the eyelids (it includes varying degrees of periorbital edema).
Then, show a butterfly-shaped, malar erythematous rash (note that malar refers to its site: the cheek and butterfly refers to its shape). Indicate that it crosses the nasolabial folds because this distinguishes it from the malar rash of systemic lupus erythematosus, which spares the nasolabial folds.
Next, draw the shawl sign: an erythematous, photosensitive rash across shoulder, neck, and back of the head, where a shawl would sit.
Now, draw a pair of hands and on one, show Gottron's papules: small, swollen inflammatory lesions of red scaly areas over the knuckles.
On the other, show calcinosis cutis, which is aberrant calcium depositions in the skin and subcutaneous tissues, which cause yellowish or white dermal lesions and stiffening with finger joint immobility.
Dermatomyositis leads to the dystrophic calcinosis. Note that metastatic, iatrogenic, and idiopathic forms of calcinosis also exist.
Systemic Involvement
Now, let's address some of the other potential systemic findings in the inflammatory myopathies.
Draw a pharynx to represent the dysphagia that can occur from pharyngeal or esophageal involvement.
Draw a set of lungs with interstitial lung disease (ILD), which manifests with dyspnea; show the characteristic ground-glass radiographic appearance on chest imaging.
Draw a heart to highlight the congestive heart failure that can occur from myocarditis.
Indicate that there is an increased risk of malignancy in inflammatory myopathies (more-so in dermatomyositis than polymyositis).
Disease Specifics
Note that the CPKs listed below vary widely within individuals and within the published literature.
Dermatomyositis
Dermatomyositis involves myositis plus the aforementioned skin changes; it has a female predominance; and the highest risk of malignancy of the inflammatory myopathies.
Average CPK: 3,000 (U/L)
Antisynthetase Syndrome (Subtype of Polymyositis)
Antisynthetase syndrome is now a recognized subtype of polymyositis (or we can just think of it as classic polymyositis, as the term polymyositis is on its way out, entirely).
Indicate that it is anti Jo-1 antibody positive, referring to aminoacyl transfer ribonucleic acid (RNA) synthetase antibodies (hence: antisynthetase syndrome).
Patients have clinical findings of interstitial lung disease and mechanic's hands: hands with hyperkeratotic lesions (cracking and thickening) on both surfaces.
It can also manifest with arthritis and Raynaud's phenomenon, amongst other symptoms.
Average CPK: 1,500 (U/L)
Immune-mediated necrotizing myopathy
In immune-mediated necrotizing myopathy (aka autoimmune necrotizing myopathy), the weakness can develop rapidly and, as indicated earlier, the CPK can be much higher.
Toxins/Triggers include statins, which are HMG-CoA reductase inhibitors (eg, atorvastatin); HMG-CoA reductase stands for 3-hydroxy-3methylglutaryl coenzyme A reductase.
- The immune response in statin myopathy is believed to either stem from the increased expression of HMG-CoA reductase levels in muscle or a conformational change within the enzyme that's brought on by the statin drug. The onset of weakness can be delayed for almost a decade after the initiation of statin therapy and can continue for several months after discontinuation, which complicates the diagnosis of it.
Laboratory tests include:
- Anti-HMG-CoA reductase antibody
- Anti-SRP (signal recognition particle), which is its own clinical phenotype but similarly both produce a necrotizing myopathy and both respond to immune therapy to varying degrees.
Average CPK: 10,000 (U/L)
Inclusion Body Myositis (IBM)
Inclusion body myositis is a mixed inflammatory and degenerative disorder.
It involves distal musculature (show wasting of the forearm flexors, especially the deep ulnar finger flexors) as well as proximal lower extremity muscles (show wasting of the quadriceps and tibialis anterior muscles) often in asymmetric (rather than symmetric) pattern.
- Thus, as opposed to typical inflammatory myopathies, patients may complain of tripping and falling before complaining of climbing stairs and they may complain of trouble buttoning a shirt before complaining of raising their arms above their head.
IBM presents predominantly in men (rather than women) and in a chronic, insidious manner (meaning over years) rather than acutely/subacutely like the other disorders.
Dysphagia is common due to weakened pharyngeal muscles.
Average CPK: 1,000 (U/L)
Histopathology
Normal Muscle Fiber Histology
Dermatomyositis – Perifascicular atrophy
Draw normal myocytes and vessels and then show perifascicular atrophy: small, atrophic fibers, which is the hallmark pathological feature in DM.
- It's a specific but insensitive finding (only found in ~ 50% cases).
- There may be other findings as well, including perivascular inflammation: membrane attack complex deposition around small blood vessels, which is non-specific but common in DM.
Antisynthetase Syndrome (Polymyositis) – Endomysial Inflammation
Here, draw pronounced endomysial inflammation and invasion of non-necrotic muscle fibers: meaning inflammation invades the myocytes but they do not appear necrotic.
Immune-mediated necrotizing myopathy
Draw a few normal myocytes and then include many destroyed, necrotic muscle fibers with minimal inflammation (rather just some invading macrophages).
Inclusion body myositis
For the inflammatory part of the disorder, show endomysial inflammatory infiltrates.
Then, for the degenerative component, show the characteristic rimmed vacuoles (vacuolated muscle fibers) and inclusion bodies.
Other degenerative findings include cytomembranous whorls intermixed between normal-appearing myonuclei and sarcoplasmic aggregation and protein deposition.
Polymyalgia Rheumatica
Polymyalgia Rheumatica
Before we conclude, let's present polymyalgia rheumatica (PMR), which is roughly 10 – 20 times more common than the inflammatory myopathies ( ~ 1/1,000 vs 1/20,000).
Indicate that just like the inflammatory myopathies, most patients are adult women with limb-girdle weakness.
Disease Specifics
PMR patients are generally slightly older (70 y.o.) than inflammatory myopathies (50 y.o.) and in PMR.
PMR has a higher incidence in whites than in blacks.
Patients develop pain and stiffness rather than frank motor weakness (the weakness is a functional condition), because this is an inflammatory arthropathy NOT a myopathic process.
So, as we may be able to predict, the CPK should be normal (or relatively normal) and the ESR (erythrocyte sedimentation rate) is elevated (at least > 40) in 85% of cases. Note that other inflammatory markers, including CRP (C reactive protein) are also elevated.
And glucocorticoids (anti-inflammatories) can quickly reduce the arthropathy and unlock the functional weakness.
Additional, Select Causes of Toxic Myopathy
Other key forms of toxic myopathy include
Endocrine Myopathy
Key Causes:
- Diabetes mellitus
- Thyroid dysfunction (hypo- and hyperthyroidism)
- Parathyroid disease
- Adrenal disease
- Other pituitary-axis endocrinopathies, such as acromegaly and testosterone deficiency.
Drug-Induced Myopathy
Key Causes:
- Statin myopathy (addressed above)
- Rheumatologic agents, such as the antimalarials colchicine and hydroxychloroquine, which are known to cause glycogen accumulation in vacuoles.
- Immunosuppressants, such as the glucocorticoids (eg, prednisone), which are no longer believed to be the cause critical illness myopathy but still can induce an atrophic myopathy.
- HIV therapies, such as zidovudine, which is known to cause a mitochondrial myopathy.
- Antimicrotubular agents, such as cochicine (for gout) and vincristine (a chemotherapy), which are known to cause a myopathy with lysosomal accumulation.
- Antiarrhythmics, such as amiodarone, which is best known to cause tremor, ataxia, and peripheral neuropathy but can also cause a vacuolar myopathy.
- Alcohol myopathy, which can present as acute rhabdomyolysis but also a chronic myopathy, especially in the setting of deconditioning and nutritional deficiency.
Critical Illness Myopathy
This is a complex disorder that manifests with proximal weakness (limb-girdle) and may be accompanied by a peripheral neuropathy.
The pathophysiologic mechanism involves various causes of physiologic stress-induced myopathy, which manifest with various myopathic and neuropathic subtypes of disease.
References
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