The Myopathies: Pattern, Biopsy, and the CK

The Pattern: Distribution Names the Disease

Run the distribution reflex before you touch a lab value: proximal, distal plus finger flexors, ocular, or facial-scapular. The pattern shortlists the myopathy, and the CK and biopsy finish the job.

Every myopathy announces itself through which muscles fail. Proximal symmetric weakness (rising from chairs, climbing stairs, reaching overhead, combing hair) is the floor shared by polymyositis, dermatomyositis, and steroid myopathy. Deep finger flexor plus quadriceps weakness with dysphagia in a patient over 50 is inclusion body myositis, the inflammatory myopathy that ignores steroids. Ptosis and ophthalmoplegia point to mitochondrial disease (chronic progressive external ophthalmoplegia), especially with no fluctuation and no response to an ice pack. Facial and scapular weakness names facioscapulohumeral dystrophy, and large calves with proximal weakness in a boy names the dystrophinopathies.

The EMG reads the pattern at the motor-unit level: myopathic units are small-amplitude, short-duration, and polyphasic with early recruitment, because each motor unit loses muscle fibers. That is the opposite of neurogenic units, which are large and fire slowly. The CK then grades the injury: it climbs high in inflammatory myopathy and Duchenne, stays quiet in steroid myopathy, and runs normal to mildly elevated in inclusion body myositis, where the story matters more than the number.

Which distribution names the disease?

The Skin Is the Split: Dermatomyositis vs Polymyositis

Same proximal weakness, same climbing CK, one wearing the diagnosis on the skin. Dermatomyositis is complement-mediated and paraneoplastic; polymyositis is T-cell mediated and rash-free. The skin decides, and the antibodies follow.

Dermatomyositis carries pathognomonic skin findings: Gottron papules, scaly violaceous papules exactly over the metacarpophalangeal and interphalangeal joints, the most specific finding in the disease; the heliotrope rash, violaceous eyelid discoloration with periorbital edema; and the shawl sign, photodistributed erythema across the shoulders and upper back with the V sign on the chest. The muscle attack is complement-mediated microangiopathy, and the biopsy shows perifascicular atrophy. Anti-Mi-2 is the classic DM antibody; anti-MDA5 tracks a rapidly progressive interstitial lung disease.

Polymyositis has no skin findings by definition: T cells invade the muscle, the CK climbs, and the biopsy shows endomysial CD8 inflammation. Its signature antibody is anti-Jo-1 (histidyl-tRNA synthetase), the antisynthetase antibody that pairs proximal weakness with interstitial lung disease, mechanic's hands, arthritis, and fever. Both respond to corticosteroids; DM in an adult demands malignancy screening (ovary, lung, pancreas, GI, lymphoma) alongside treatment, and juvenile DM adds the pediatric clue of dystrophic calcinosis cutis.

Flip between the two inflammatory myopathies.

Tap each letter of the DM skin trio.

The Biopsy Atlas: Five Slides That Close the Case

When distribution and CK leave doubt, the biopsy settles it, and every slide carries its own treatment consequence. Tap each finding on the muscle section.

The biopsy is the tiebreaker boards grade last because it is the most specific. Perifascicular atrophy, small fibers clustered at the edge of each fascicle, is dermatomyositis: complement injures the capillaries at the periphery first. Rimmed vacuoles with endomysial inflammation are inclusion body myositis, and they explain why the patient with IBM "failed steroids." Ragged red fibers on modified Gomori trichrome, coarse red granular material at the fiber edge, are subsarcolemmal mitochondrial accumulations: mitochondrial myopathy. Type II fiber atrophy without inflammation is steroid myopathy, atrophy without necrosis, which is why the CK stays normal. Absent dystrophin staining at the sarcolemma is Duchenne muscular dystrophy, and the same stain with patchy, reduced dystrophin is Becker.

Hold the consequence with each slide: perifascicular atrophy means steroids plus cancer screening; rimmed vacuoles mean stop escalating immunosuppression and protect the swallow; ragged red fibers mean supportive care; type II atrophy means taper the steroid; and absent dystrophin means cardiac surveillance, because cardiomyopathy is what kills these patients.

Tap each finding on the muscle section.

The Toxic and Metabolic Myopathies: Steroids, Statins, McArdle, Mitochondria

Not every myopathy is autoimmune or dystrophic. Some are poisoned, some run out of fuel, and some lose their power plants. Each has one board fingerprint: a quiet CK, a drug interaction, a second wind, or ragged red fibers.

Steroid myopathy punishes the reflex that weakness means a high CK. Chronic glucocorticoids cause preferential type II fiber atrophy, so the weakness is proximal, legs first, and the CK is normal or near normal: this is atrophy, not necrosis. The fix is tapering to the lowest effective dose plus physical therapy, never escalating immunosuppression. Statin myopathy is the opposite: myalgia with a climbing CK, and the rhabdomyolysis trap is the combination of a statin with gemfibrozil, another fibrate, or niacin. A mild asymptomatic CK elevation does not require stopping the statin, and coenzyme Q10 is not proven to prevent or treat the myopathy.

McArdle disease is myophosphorylase deficiency (glycogen storage disease type V): muscle cannot break down glycogen in the first minutes of exercise, so cramps, fatigue, and myoglobinuria strike at the start. After a few minutes the muscle switches to free fatty acids and blood glucose, symptoms clear, and exercise becomes possible: the second wind. The ischemic forearm test shows no lactate rise, the diagnostic fingerprint. Mitochondrial myopathy shows ragged red fibers and gives chronic progressive external ophthalmoplegia: symmetric ptosis and ophthalmoplegia with no fluctuation, no ice-test response, and no anti-acetylcholine receptor antibodies, the fixed-eye story that is not myasthenia. The periodic paralyses are channelopathies: hypokalemic episodes after carbohydrate-heavy meals with thyrotoxicosis, hyperkalemic episodes after rest, and the rule that you measure the potassium during the attack before you replace anything.

Which door does the weak patient walk through?

The Dystrophies: Duchenne and Becker, the Dystrophin Pair

X-linked diseases of the dystrophin gene: the protein that anchors the cytoskeleton to the extracellular matrix. The split between Duchenne and Becker is the split between absent and partially functional dystrophin.

Duchenne muscular dystrophy comes from frameshift or nonsense mutations that leave dystrophin absent. The boy is weak before age 5: frequent falls, trouble rising, and the Gowers sign, climbing up his own legs to stand. The calves look big, but that is pseudohypertrophy, fat and fibrosis replacing muscle. The CK is massively elevated in the preschool years, often above 10,000 U/L, and falls as muscle mass is lost. The disease does not stop at the limb muscles: dilated cardiomyopathy is the leading cause of death, and respiratory failure closes the story in the 20s to 30s. Corticosteroids slow the decline, and cardiac surveillance is mandatory.

Becker muscular dystrophy is the milder sibling: non-frameshift deletions leave partially functional dystrophin, onset is later, ambulation continues into adulthood, and survival is longer, but the cardiomyopathy still demands surveillance. When the genetics are unclear, the biopsy answers: absent dystrophin staining is Duchenne, patchy reduced staining is Becker. The one-screen rule: a boy with a Gowers sign, big calves, and a sky-high CK is Duchenne until proven otherwise, and the pedigree is X-linked, so the mother is the carrier.

Put the Duchenne timeline in order.

Myotonic Dystrophy and the Rest: The Face, the Repeat, and the Girdle

Myotonic dystrophy wears its genetics on its face and its fingers, with a trinucleotide repeat that grows across generations. Facioscapulohumeral and limb-girdle fill in the other patterns by distribution.

Myotonic dystrophy type 1 is an autosomal dominant CTG trinucleotide repeat expansion in DMPK on chromosome 19. The hallmarks: myotonia, an inability to relax after contraction, so the patient cannot release a handshake or let go of a doorknob, with percussion myotonia of the thenar eminence; the hatchet face of temporal wasting, ptosis, frontal balding, and wasted sternocleidomastoids; and early posterior subcapsular cataracts, often the only clue in a mildly affected parent. The repeat count grows with each generation, so onset gets earlier and disease gets severer in descendants: anticipation. Cardiac conduction defects and the congenital form with hypotonia and an open-mouth face round out the board portrait.

Facioscapulohumeral dystrophy is the face-and-scapula pattern: inability to whistle or bury the eyelashes, scapular winging, and later foot dorsiflexor weakness, usually autosomal dominant. Limb-girdle muscular dystrophy is the heterogeneous proximal bucket: shoulder and hip girdle weakness with an elevated CK, no facial predominance, no myotonia, and genetic panels that sort the subtypes. The treatment ladder below is the same reflex the boards grade: which myopathy gets steroids, which one is refractory, and which one never sees immunosuppression.

Open each rung of the treatment ladder.

The Rhabdo Emergency: Myoglobin, Potassium, and the Calcium Flip

Muscle breaks down faster than the body can clear it: myoglobin darkens the urine, potassium pours out of the lysed cells, and the kidney clogs with casts. The treatment is fluids, fluids, fluids.

Rhabdomyolysis is the CK storm: creatine kinase far above 10,000 U/L, often in the hundreds of thousands. The urine turns cola-colored with myoglobinuria, and the bedside proof is the heme-positive dipstick with no red cells on microscopy, because the dipstick cannot tell myoglobin from hemoglobin. The potassium pours out with the myocyte contents: hyperkalemia is the first lethal threat, worse when the kidneys fail. Calcium does a flip: hypocalcemia early, as calcium binds the damaged muscle and the released phosphate, then hypercalcemia in recovery as it washes back out. The trap is treating the early hypocalcemia; it rebounds on its own, and aggressive calcium can overshoot.

The kidney is saved by volume: aggressive isotonic intravenous fluids with urine output monitoring dilute the myoglobin and flush the tubules. Hyperkalemia is treated emergently (intravenous calcium for ECG changes, insulin-glucose to shift potassium into cells), and dialysis waits for refractory hyperkalemia, severe acidosis, or fluid overload, never the first move. Dantrolene belongs only to malignant hyperthermia. The causes are the history: statin plus gemfibrozil or another fibrate, seizures, alcohol, crush injury, neuroleptic malignant syndrome, malignant hyperthermia, and snake venom.

Score the CK story, then hold the consequence.

Walkthrough: race the pattern reflex

Original practice scenarios, one at a time. Choose an answer, then open any option to work its reasoning.