Muscle Pathology

Question 1

What is dermatomyositis? What may be associated with this condition? How do patients usually present?

Answer 1

• inflammatory disorder of skin and skeletal muscle of unkown etiology; inflammation of the perimysium via CD4+ T cells
• possible association with carcinoma, so make sure to check these patients for cancer!
• patients (most common in children) present with bilateral proximal weakness (progresses to distal), heliotrope rash (rash of upper eyelids), and red papules on elbows, knuckles, knees
• a malor rash (the butterfly rash) may also be see
• “can’t climb the stairs or comb my hair”

Question 2

How do we diagnose dermatomyositis? How do we treat it?

Answer 2

• diagnose with clinical signs, elevated creatine kinase (because of muscle damage), positive ANA, and presence of the anti-Jo-1 antibody
• treat with corticosteroids

Question 3

What is polymyositis?

Answer 3

• inflammation of skeletal muscle; inflammation of the endomysium via CD8+ T cells
• patients present with bilateral proximal weakness; treat with corticosteroids
• (unlike dermatomyositis, there is no skin involvement and the inflammation is of the endomysium instead of the perimysium)

Question 4

What is X-linked muscular dystrophy? What is it also known as? How do patients classically present? Explain the pathophysiology.

Answer 4

• degenerative disorder of muscle with wasting
• AKA Duchenne’s muscular dystrophy
• deletions of dystrophin gene (the protein anchors the muscle to the ECM) result in proximal muscle weakness (progression to distal) at 1 year of age
• inability to use muscle leads to atrophy and replacement with adipose tissue
• look for calf pseudohypertrophy (calf muscles increase from starting to walk, but eventually get replaced by fat) and elevated creatine kinase (note that this will eventually decrease once muscle mass is lost)
• patients usually die by early adulthood from cardiac or respiratory failure, as these muscles are also involved

Question 5

What is Becker’s muscular dystrophy?

Answer 5

• this is the same as X-linked (Duchenne’s) muscular dystrophy, but a more mild version
• it is more mild (presenting later and more slowly) because it involves a mutated dysrophin gene rather than a fully deleted gene; unfortunately, it is LESS common than Duchenne’s

Question 6

What is myasthenia gravis? How do patients classically present? How can we treat the disease?

Answer 6

• autoimmune (women) reaction with antibodies against the POST-synaptic ACh receptors on skeletal muscle resulting in competitive inhibition
• patients present with ptosis, diplopia, and muscle weakness that significantly WORSENS with use (initial contractions will be OK, but ACh levels get less and less, allowing more antibodies to inhibit the receptors)
• can’t treat the disease, but symptoms are significantly improved with anti-cholinesterase agents (inhibiting ACh esterase will increase amount of ACh available)
• also associated with thymic hyperplasia and thymoma (removing the thymus in these cases is somewhat curative)

Question 7

What is Lambert-Eaton syndrome? How do patients classically present? How can we treat the disease?

Answer 7

• a paraneoplastic syndrome (commonly due to small cell carcinoma) resulting in generation of antibodies against the PRE-synaptic Ca2+ channels, preventing ACh release into the NMJ
• usually affects the proximal muscles and tends to spare the eyes; weakness IMPROVES with use (because increased use results in increased pressure to open more Ca2+ channels, overpowering the antibodies)
• these will NOT respond to anti-cholinesterase agents (as ACh can’t even get out into the NMJ)
• treat by removing the tumor

Question 8

What is rhabdomyolysis? What are the classic findings? How do we diagnose it?

Answer 8

• the breakdown of skeletal muscle resulting in the subsequent release of intracellular skeletal muscle contents into the circulation
• classic findings: muscle weakness, aches, general feeling of malaise, tea-colored urine (because of myoglobin release; remember skeletal muscle has myoglobin to store excess O2 when needed)
• only real lab finding is a raised creatine kinase (and urine myoglobin)

Question 9

What are the major causes of rhabdomyolysis? How do we treat it?

Answer 9

• MANY causes, usually all result in a loss of ATP in muscle cell, causing calcium inflow into the cytoplasm and activation of enzymes to cause degeneration of the cell
• illicit drugs, alcohol abuse, trauma (crush syndrome), prolonged immobility and excess exercise, infection, drugs (ex: statins)
• treat with prompt and aggressive fluid resuscitation, eliminate the cause, and prevent/manage any complications

Question 10

What are the major complications of rhabdomyloysis? How do we prevent/manage these?

Answer 10

• hyperkalemia due to releaseof intracellular contents (risk of arrhythmia): treat with insulin and glucose
• renal failure due to myoglobin clots in renal tubules: this is the most serious issue; prevent with aggressive IV fluids/hydration or with dialysis if necessary
• compartment syndrome due to the ischemia and edema increasing the pressure: treat with fasciotomy
• other complications: acidosis (bicarb is NOT recommended to treat, as it can generate an even worse alkalosis), hypovalemia, and DIC (treat with platelets and vitamin K)

Question 11

Where is the dystrophin gene located? What is unique about it that may explain the relatively common mutations that occur here?

Answer 11

• (this is the gene involved in Duchenne’s and Becker’s muscular dystrophies)
• located on the short arm of the X chromosome (Xp21)
• this is the largest gene in the body! it is therefore more likely to gain a mutation here and there