Inflammatory Myopathies and Polyarthragia Rheumatica Flashcards
What drugs may induce symptoms that mimick Myositis disorders?
- HMG-CoA reducatase inhibitors => statins
- Note: these drugs may even lead to the formation of antibodies that bind HMG-COA reductase
ALSO, proliferating muscle has been shown to express HMG-CoA reductase, this may be why antibodies against HMG-CoA reductase cause RHABDOMYOLYSIS
What pattern of muscle involvment do you expect to see in inflammatory myopathies?
•what muscles are affected (generally)?
Mostly striated (skeletal) muscles are affected in Dermatomyositis and Polymyositis. Muscle involvment in these diseases is typically symmetric and PROXIMAL.
Specifically, what muscles often become weak in myositis?
• Neck
• Abdominal Mm.
• Upper 1/3 of Esophagus
• Diaphragm/Thoracic Muscles
• Problems with sphincter ani causing urinary incontinence.
What is the major differentiating factor between polymyositis and dermatomyositis?
• SKIN INVOLVMENT
Aside from diaphragmatic weakness, what pulmonary complications should patients with Polymyositis and Dermatomyositis be warned of?
70% of patients may present with interstitial lung disease of varying degrees but still very similar to ideopathic interstitial lung disease (remember this dz? honeycomb lung, 3-5 yrs to live, pattern of involvment from exterior of lung towards the inside)
***Clearly this is a bad px***
What symptoms should you start looking for in a patient with Polymyositis or Dermatomyositis that is positive for anti-Jo-1 antibodies?
• what are anti-Jo-1 antibodies directed against?
• What is this called?
• How often is this seen?
Arthritis and Mechanics Hands are associated with myositis that is accompanied by anti-Jo-1 antibodies, this is called ANTISYNTHETASE SYNDROME. 20% of patients with DERMATO- or POLYMYOSITIS will have this.
• Abs. Directed against histidyl-tRNA synthetase (and other anti-synthetase abs are associated with the developement of arthritis as well)
Is the heart involved in Polymyositis and Dermatomyositis?
• Yes you can see heart involvment with conduction abnormalities, and arrythmias, myocarditis, and CAD.
What is a common GI complaint of someone with a myositis?
Difficulty swallowing
Note: GI problems in patients are most commonly related to weakness of the tongue, pharyngeal muscles, and sometimes lower esophagus, diarrhea, constipation, stomach pain all secondary to disturbed motility.Vasculitisof GI vessels resulting in bleeding can happen but israre.
Note: GI problems in patients are most commonly related to weakness of the tongue, pharyngeal muscles, and sometimes lower esophagus, diarrhea, constipation, stomach pain all secondary to disturbed motility. Vasculitis of GI vessels resulting in bleeding can happen but is rare.
Aside from dermatomyositis and polymyositis, what are 4 other types of inflammatory myopathies?
• Antisynthetase Syndrome (anti-Jo-1 antibodies)
• Amyopathic Dermatomyositis
• Juvenile Dermatomyositis
• Inclusion Body Myositis
Differentialte dermatomyositis and Amyopathic Dermatomyositis?
• What are some complications of amyopathic dermatomyositis?
Amyopathic Dermatomyositis is dermatomyositis without the myositis. Clearly these people are at a high risk of developing dermatomyositis especially later in dz.
RISKS:
• HIGH risk of IPF (interstitial pulmonary fibrosis)
****Because this disease often goes undiagnosed IPF is typically in late (honeycomb) stages before anyone catches it*****
What changes are seen in the joints of someone with antisynthetase syndrome?
- These patients get symmetric polyarthritis of small joints
- This arthritis is NON-EROSIVE (imp for ddx with RA)
What age groups experience the highest incidence of Juvenile Dermatomyositis?
• what additional features are seen in this disease that are not seen in the adult form?
Highest Incidence between 6 and 11 years old. These kids have all the same symptoms of adult dermatomyositis.
30-70% have additional symptoms of:
• Calcinosis
• Cutaneous Ulceration
• Lipodystrophy (calcification of fat)
What are the KEY features of inclusion body myositis?
• who presents with this disease and how do they present?
• what should you key in on when taking history?
• what can you tell this pt. about there outcome after treatment is initiated?
IBM (inclusion body myositis) typically presents with a 50 year old man with an insideous onset of muscle weakness (months -> years) that is localized primarily to his thigh muscles and fingers.
Inclusion body myositis can be familial or sporadic so he may have a positive family history of this disease.
We can give this guy glucocorticoids but it probably won’t do much for him.
The following pictures are symptoms of what disease?
• name what you see in each picture.
DERMATOMYOSITIS is shown
A. Gottron’s Papules
B. Heliotrope rash
C. Gottron’s Sign on the knee
D. Gottron’s Sign on the elbow
Lupus involves the formation of a heliotrope rash as well as rashes on the hands etc. On the basis of physical findings alone how can you differentiate dermatomyositis from lupus?
A key difference is the pattern of the rash seen on the hands:
• in Dermatomyositis Redness overlies JOINTS
• in Lupus Redness SKIPS JOINTS
What is shown here?
Evidence of Capillary damage near the nailbed is a common feature of this disease is Raynaud’s which when severe enough may cause damage in the capillary beds
Name each of these signs associated with Dermatomyositis.
• what antibodies are likely to be positive on this person’s panel?
A. Linear Erythema
B. Scalp Rash
C. V-like sign
D. Shawl Sign
A, C, D are all associated with Anti-Mi-2 antibodies diffectes against nuclear helicase
A guy that is 55 y.o. presents to you with a history that includes increasing hip and shoulder pain. No cutaneous abnormalities are noticed on physical exam. He shows you his hands and they look like the picture shown below.
• What might this guy have?
• How could you nail down the dx?
Looks like this guy has polymyositis accompanied by Anti-synthetase syndrome which is why he is presenting with mechanic’s hands. Anti-Jo-1 antibodies would help assure you that this is PM + Anti-synthetase syndrome
Differentiate Polymyositis, Dermatomyositis, and Inclusion body myositis with respect to the patient that’s likely to present with it.
Polymyositis:
• is typically seen in females in their LATE teen or older with average age of onset being 50-60 y/o.
Dermatomyositis:
• BIMODAL with females 5-15 or 45-65 being most likey to get this disease.
Inclusion Body Dermatitis:
• Almost always 50 and up and is more common in males.
Do inflammatory myopathies ever occur in the setting of other autoimmune diseases?
YES, 11-40% of patients with other autoimmune diseases with get one. Typically htose with Connective Tissue autoimmune diseases are at the highest risk.
(e.g. systemic sclerosis, SLE, RA, Sjorgren’s, polyarteritis nodosa, Sarcoidosis)
A 59 year old woman presents to your office with Gottron’s nodules on her hands and a shawl rash. She has had increasing fatigue and has experienced stiffness in her shoulder and hip.
• What is the likely diagnosis?
• What should you do immediately after making this diagnosis?
This woman has Dermatomyositis. You should send her for cancer screens because 12% of patients with myositis present with cancer (typically breast adenocarcinoma) in the 1st year of diagnosis.
81% of the time the myositis is DM, the other 19% if PM
What conditions might you suspect if patients are positive for the following antibodies on their panel:
• anti-tRNA synthetases
• anti-Mi-2
Anti-tRNA synthetase abs.:
• Interstitial lung diseases
Anti-Mi-2 abs. (anti-nuclear helicase):
• Gottron’s Papules
• V sign
• Shawl sign
What are PM-scl antibodies associated with?
• features of this disease?
PM-scl antibodies are frequently associated with a POLYMYOSITIS (PM) - SCLERODERMA (Scl) cross over syndrome characterized by:
- mild muscle disease
- Prominent Arthritis
- Limited Skin Sclerosis
***Responsive to therapy***
T or F: PM and DM are both involve at least some aspect of both humoral and cell mediated immune response.
True, certain antibodies like anti-tRNA and anti-Mi-2 abs are associated with pulmonary fibrosis and skin rash, but its also been shown that PM and DM involve CD8 and CD4 t-cells.
What evidence of Cell Mediated Response is there in Dermatomyositis?
CD4+ cells form perivascular infiltrates, often in perimysial areas and is made of:
• Macrophages
• Dendrititic Cells
• B-cells (makes sense b/c of the effector T cell activation required to make a plasma cell and humoral response seems to be a bit more pronouced in DM due to things like anti-Mi-2 and anti-tRNA antibodies that are involved in IPF and cutaneous aspects of this disease)
What evidence of Cell-mediate immune response is there in Polymyositis?
CD8+ cells and macrophages for ENDOMYSIAL infiltrates with mononuclear cells surrounding and sometimes invading necrotic muscle fibers.
What evidence of Cell-mediate immune response is there in Inclusion Body Myositis?
CD8+ cells and macrophages for ENDOMYSIAL infiltrates with mononuclear cells surrounding and sometimes invading necrotic muscle fibers.
**Note: same cells involved as PM
Why does it make sense that in PM and IBM you would see actual invasion of muscle fibers by mononuclear cells?
in PM and IBM the mononuclear cells are predominantly CD8+ which can recognize MHC class I that is present on all tissue. In these diseases CD8+ cells recognize something on the MHC class I cells of muscle that they don’t like and they kill it.
***NOTE: MONOCLONAL proliferations of CD8+ cells in PM and IBM is not uncommon***
Review of Fas Ligand Cell death pathway used by CD8+ cells
What is the mechanism of cell death caused by polymyositis?
Where is muscle weakness located in Inclusion body myositis?
• Proixmal Muscle weakness in the lower extremities with distal muscle supplying upper extremities
What findings do you expect to see in the inflammatory myopathies for:
• Serum Muscle Enzymes
• Electromyograms
Serum Muscle Enzymes:
• Elevated
Electomyograms:
• Abnormal
How do you expect your typical patient with PMR to present?
• what standard lab value is elevated?
Patient is most likely to be 50 years or older and have stiffness and pain in her shoulder and hip musculature. Pain causes patients to stop using these muscles so you often see profound muscle atrophy in muscles.
• ESR is often elevated
What is a huge tip off that you’re dealing with a patient that has Polymyalgia Rheumatica and not someone with osteoarthritis?
• SHOULDER involvment with NO OCCUPATIONAL HISTORY that would lead you to think that osteoarthritis was the cause
When a 50 year old woman presents to you with pain in here shoulder and muscle atrophy with an elevated ESR what TWO conditions should you start thinking about?
Polymyalgia Rheumatica often presents like this and is many times accompanied by Temporal (Giant Cell) Arteritis.
When shoud you become suspecious of a patient with PMR of having Giant cell arteritis?
- Patients OVER 70
- Headache or Jaw Claudication
- Clinically abnormal temporal arteries
What are some key findings that you might see on an MRI in polymyalgia Rheumatica?
- *• Inflammation of Tendon Sheaths** (tenosynovitis)
- *• Bursitis** (Subacromial and Subdeltoid)
What is a complication related to PMR induced tenosynovitis occuring in 10-14% of patients?
Carpal Tunnel Syndrome
T or F: Polymyalgia Rheumatica is associated with swelling, pitting edema over the hands, wrists, ankles, and top of the feet.
True, not that common that you see this though
What is the definination of Giant Cell/Temporal Arteritis?
Necrotizing inflammation of large sized arteries originating from the arch of the aorta.
What is the pathophysiology of Temporal Arteritis?
T or F: about half of the people with polymyalgia rheumatica also have temporal cell arteritis, but only about 15% of the people with TCA have PMR.
False, 50% of ppl. with TSA will get dx. with PMR but only about 15% of ppl. with PMR get temporal cell arteritis
What are the symptoms of Temporal Arteritis?
What is one of the most severe complications of Temporal Cell Arteritis?
• how can we screen for it?
• what key finding would you see if the screeing were positive?
THORACIC aortic aneurysm may occur as a result of damage done to the aorta in progression of the disease. We can monitor this by CXR. Mediastinal widening would be the key CXR finding
Note: 10% of pts with GCA may present with upper respiratory symptoms (non-productive cough, severely sore throat). It is not uncommon to see AST increased as a result of glucocorticoid therapy.
Note: 10% of pts with GCA may present with upper respiratory symptoms (non-productive cough, severely sore throat). It is not uncommon to see AST increased as a result of glucocorticoid therapy.
What does ESR measure?
• what is it an indirect measure of?
Note: CRP is a more sensitive measure than ESR
Do you expect there to be changes in the ESR in patients with Temporal Arteritis?
YES ITS OFTEN MARKEDLY INCREASED
• normal ESR is 0-20 in most people
• ESR in TCA is like 60 or more
On a biopsy of a patient with Giant Cell Arteritis, where is inflammation the greatest?
• Inflammation in Temporal Arteritis is typically concentrated around the ELASTIC MEMBRANE
How do you treat PMR?
How should you treat Temporal Arteritis?
What is shown here?
• what are the key features?
Inclusion Body Myositis
• notice Purple Inclusion bodies
**Compare this muscle tissue to the tissue below**
What is shown here?
• key features?
H and E stain of Inclusion Body Myositis - notice the marked variation in cell size
One more pic of IBM trichrome stain.
• what causes the purple inclusions?
• who are we most likely to see this in?
Myeloid Bodies and Amyloid Deposition
Typically a MAN over 50 that has quad and finger pain
This is a picture of normal muscle. What changes do you expect to see in dermatomyositis?
• what late changes might you expect?
Myositis with muscle fiber necrosis in a perifasicular pattern
LATE:
• Muscle fiber atrophy
• Fatty change
• Fibrosis
What is shown here?
What is shown here?
• key features?
Polymyositis because its ENDOMYSIAL inflammation, the actual muscle cell is being invaded
Why are mutations in the dystrophin gene so common?
Its the longest gene in the genome
What cells mediate temporal cell arteritis?
• who is typically affected?
- Likely T cells
- Disease of White Females over 50
What is shown here?
TEMPORAL CELL ARTERITIS WITH TRANSMURAL INFLAMMATION**
