Myositis and Muscle diseases

1. List the signs of Muscle Disease (4)

2. What is the difference between Myalgia vs Myositis

Signs of Muscle Disease:

• Fixed weakness (true muscle weakness)

• Premature fatigue/exercise intolerance

• Postexertional aches, cramps, myalgias

• Problems w/ ADLs

---

Myalgia is not Myositis

• Muscle diseases: weakness > pain

• Myalgia syndromes: pain > weakness

  • EX: Fibromyalgia, Polymyalgia Rheumatica, Regional/Diffuse Pain Syndromes

Cramps +painful sustained contractions + involuntary contractions often relate to?

Cramps +painful sustained contractions + involuntary contractions often relate to:

• Lower motor neuron disease, 

• Electrolyte disorders, 

• Circulatory disorders

1. List “ the cardinal symptom” of Muscle Weakness (4)

2. List the muscle affected and how presentation is different across varying diseases (3)

Weakness:“ the cardinal symptom”

• Difficulty w/ ADLs

  • (Getting up from chair, put on socks, Up/Down Stairs, etc)

• Knee Pain 

  • Common Complaint

  • Due to Muscle Weakness

• Head:

  • Ptosis, dysphagia, dysphonia, palate weakness

• Gower's sign and Trendelenburg gait

---

Muscles Affected:

• Most myopathic  = Prox. Muscle Groups

• Distal = Late presentation or inclusion bodies

• Asymmetric = neuropathic or infectious

List the Factors suggesting another diagnosis instead of Polymyositis or dermatomyositis

Factors suggesting another diagnosis instead of Polymyositis or dermatomyositis

• Asymmetric or distal weakness

• Intermittent symptoms

• Muscle pain without weakness

• Marked muscle atrophy

• Calf hypertrophy

• Scapular winging

• Family history of muscle disease

• Medications that can cause myopathy

• Neuropathic symptoms or findings

DDX of Myopathies (7)

Autoimmune /Inflammatory disorders but also

• Paraneoplastic or Neoplasm

• Drugs

• Infections

• Endocrinopathies

• Neuropathic disorders

• Inborn errors of metabolism/storage disorders

• Pain syndromes

List the myopathies associated w/ these age of onset:

• childhood - teen

• 18-50

• >50

List the myopathies associated w/ these time of onset:

• Months - Yrs

• Weeks - Months

• Days - Weeks

• Episodic

Age of onset:

• Childhood - teen: 

  • Duchenne Dystrophy

  • Juvenile dermatomyositis

• 18-50: 

  • inflammatory myopathy,

  • metabolic myopathies, 

  • Endocrinopathies,

  • various dystrophies

• – > 50: 

  • inclusion body disease,

  • inflammatory associated with cancer

---

Time to onset:

• Months – years: 

  • inclusion body,

  • dystrophy

• Weeks – months: 

  • Inflammatory, 

  • drug/toxic, 

  • Endocrinopathies

• Days – weeks: 

  • Infectious,

  • Dermatomyositis (rare), 

  • drug induce rhabdomyolysis,

• Episodic: 

  • periodic paralysis

1. For Myopathies; things to look for and Ask? (6)

2. DDX if:

   • Muscle Pain at rest:  (5)

   • Exercise intolerance: (1)

   • Cramps:  (2)

3. Non Muscular Findings and what they indicate (6)

Things to look for and ask

• Inability to lift head or swallow saliva:

  • poor prognostic sign.

• Movement abnormalities  ((dystonia, myokymia)

  • lower motor neuron disorders

• Muscle volume: unaffected.

• Atrophy

  • lower motor neuron disease,

  • long standing untreated myopathies.

• Family history

• Just how sick does this individual look

  • Inpatient vs. outpatient work up

  • “Severity categorization”

---

DDX if:

• Muscle Pain at rest: 

  • drug induced, 

  • Juvenile Dermatomyositis,

  • severe inflammatory (with necrosis),

  • infectious, 

  • myopathy with metabolic bone disease

• Exercise intolerance: 

  • Metabolic myopathies (esp. CPT deficiency)

• Cramps: 

  • dystrophies, 

  • metabolic myopathies

---

Non Muscular Findings

• Rash: 

  • Dermatomyositis, SLE, PSS

• Other Rheumatic disorders: 

  • Raynaud’s, sicca, interstitial lung changes

• Endocrine: 

  • delayed reflexes, exophthalmos

• Mitochondrial: 

  • seizures, stroke like phenomena, retinopathy, sensory neural hearing loss (MELAS)

• Rhabdomyolysis:

  • Extreme weakness and “coca cola” urine

• Myoglobinuria: 

  • drug induced rhabdomyolysis

    • (stimulants and opiates), 

  • CPT deficiency

1. If the pt presents w/ Shortness of breath with myositis or myopathy:

   • DDX (5)

   • Labs (2)

   • Generally?

2. What about Dysphagia + dysphonia: (3)

Shortness of breath with myositis or myopathy *

• DDX:

  • Inflammatory lung interstitial lung disease 

  • Acid maltase disorder

  • Carnitine deficiency.

  • deconditioning + poor exercise tolerance

  • Anti- Synthetase syndrome

• Labs

  • ANA +, anti-Jo-1 Antibody +, 

• It is generally not an early sign/symptom.

---

Dysphagia + dysphonia:

• Lower motor neuron disease, 

• ALS (primary bulbar) 

• Inflammatory myopathy.

Dermatomyositis: heliotrope rash involving eyelids

Dermatomyositis: Heliotrope rash on eyelids

Dermatomyositis: rash lower neck and chest

Childhood dermatomyositis:

rash elbows, knees

Dermatomyositis: macular rash and acanthosis nigricans

Dermatomyositis: Trash on extensor surface of PIP, MCP, DIP knuckles

Dermatomyositis: Mechanic’s Hand

Dermatomyositis, childhood: subcutaneous calcification, knees and lower extremity

1. Initial Labwork you should order? (6)

2. Other Studies? (3)

3. List the Muscle Related enzymes when damage or death (5)

Initial Labwork

• CBC, Chemistries

• ESR, CRP

• TSH, free T3 , Free T4 if TSH abnormal

• Glucose

• Muscle enzyme analysis

  • CK, Aldolase. Sometimes Myoglobin

• Carnitine:

  • If neg. biopsy or nonspecific toxic/meta changes

---

Other studies

• EKG 

  • if has cardiac history, findings, or symptoms

• PFTs 

  • if lung symptoms or prior history

• Malignancy work up

---

Muscle related enzymes 

• CK:

  • Types: CK-MM (90%); Also CK-MB

• AST, ALT 

  • AST >> ALT for muscles 

• LDH 

  • Type II fibers

• Aldolase

  • Also related to RBC lysis

• Myoglobin

  • [Urinary] does not correlate w/ serum

    • renal tubular resorption, water resorption, and proteolytic factors

  • More sensitive than CK

1. List the Autoantibodes present in Myopathy

2. List the overlap w/ other diseases (5)

Autoantibodies

• ANA and Myositis Specific Antibodies (MSA)

---

Overlap w/ other diseases:

• SSA/SSB with Sjogren’s

  • 90% Sjogren’s are ANA and/or RF positive

• RNP with MCTD

• ANA/dsDNA/Sm with SLE and overlap

• SCL-70 with PSS and overlap

• RF/CCP with RA and overlap

Describe EMG/NCV *

• Uses (3)

• Typical findings (3)

Describe Biopsy

• Uses

• Procedures

• Stains

EMG/NCV *

• Uses:

  • Differentiates 

    • neuropathic vs. myopathic disorders

    • weakness from poor effort.

  • Severity.

  • Helps localize site for biopsy: 

    • Biopsy opposite side.

• Typical inflammatory finding is:

  • Increased insertional activity, fibrillations, sharp waves

  • Spontaneous high frequency discharges

  • Low amplitude/short duration polyphasic motor unit potentials

---

Muscle Biopsy

• Uses:

  • Provides histology and generally more accurate diagnosis, prognosis and therapeutic options

• Procedure:

  • Select weakest muscle group that is not atrophic)

    • Proximal muscle site for most biopsies

    • Often Deltoid or Vastus Lateralis

    • Distal site if suspect Inclusion Body Myositis

  • Open biopsy: yes. (Needle biopsy often not advised)

• Stains:

  • H & E & “Special” Stains

    • Electron Microscopy

NOTE:

• • Inflammatory disorders may “skip” around, so blind biopsy may miss an inflamed area.

Type 2 fiber atrophy

• Causes

• What does it look like?

• Disuse

• Steroids

• Aging

• Malnutrition/

• cachexia

• Hypothyroid

• Alcohol

Increased Risk Factors for Malignancy?

Increased Risk Factors for Malignancy

• Older age at onset

• Severe skin disease, shawl sign, necrosis

• Resistance to treatment

• Prior malignancy with risk of relapse

• (Less risk if interstitial lung disease present)

Describe Imaging Studies:

• Types?

• Helpful for?

Imaging studies

• Types: Ultrasound, CT, and MRI

  • MRI w/ fat suppression or STIR = guide biopsy; but not diagnostic 

• Helpful for:

  • Infectious etiology

  • CT abdomen/pelvis for ovarian cancer

Treatments for Inflammatory Myopathies?

When to Hospitalize?

Treatments for Inflammatory Myopathies

• Prednisone

  • Taper slowly (-20%/month)

  • Watch CKS and strength

• If Severe: “pulse” Methylprednisolone  therapy

  • 250 mg Q 6 hours x 3 days then decrease to Prednisone 20 mg t.i.d.

    • Less CNS affect and less dysrhythmias

  • Check electrolytes Q 6-12 hours

    • Specifically looking for Hypokalemia

  • Glucose checks as required

  • Low dose anxiolytics as necessary

• DMARD therapy for steroid sparing effect

  • Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil

  • Rituximab IV, Cyclophosphamide,

  • Intravenous Immunoglobulin

  • Hydroxychloroquine for Dermatomyositis

---

When to hospitalize

• Extremely high CK: 10,000 or more

• Profound weakness and inability to perform basic hygiene/walk, falls, or falling risk.

• Dysphagia with aspiration.

• Loss of neck flexors

Describe Poly/Dermatomyositis hospital patient

• Complications to Consider:

• Hospital Location: (2)

• What to do: (4)

Poly/Dermatomyositis hospital patient

• Complications to Consider:

  • cardiac conduction abnormalities or CHF

• Hospital Location:

  • ICU/IMC

• What to do:

  • Elevate head of bed to 30 degrees at all times

  • Aspiration precautions

  • Get Swallowing studies

  • Bedside PFTs Q 2-4 hours:

    • if FVC decreases by 20% or at <50% expected, check ABGs and Pulmonary consult (elective intubation ?)

Describe IV IgG vs. Plasmapheresis

• Complications (2,2)

• Cost

List non-drug tx

IV IgG vs. Plasmapheresis

• Complications:

  • Plasmapheresis:

    • infection,

    • Hypotension

  • IVIG 

    • headache/meningismus

      • Infusion rate related

• Money:

  • IVIG = more expensive 

• NOTE: Watch for CP status

---

Non Drug Treatments

• Exercise

  • Can be done early on.

  • Bed rest generally only in rhabdomyolysis

  • PROM/AROM

  • Physical therapy

    • Gait evaluation and training

    • Swallowing evaluations

  • OMM

What to consider for pts w/ myositis, hyperlipidemia, and cardiovascular disease

Pt with myositis, hyperlipidemia, and cardiovascular disease

• Statins = relative CI

  • Recommend monitoring CK ~ every 1-2 months

• If CK 2x baseline: discharge/recheck

• If no change, consider repeat biopsy.

1. List the drugs that can induce myopathy

2. Presentation of neuropathic disorders?

Drug Induced Myopathy

• Alcohol

• Statins/fibrates, Gemfibrozil

• Amiodarone and simvastatin (Inhibit CYP3A4)

• Cocaine/stimulant drugs/heroin

• Colchicine

• Steroids

• Hydroxycholorquine (Plaquenil), D- Penicillamine

• Phenytoin, valproic acid

• Nicotinic acid

• Zidovudine

• Diuretics:

Neuropathic Disorders:

• Presentation:

  • Asymmetry, distal involvement

  • Cranial neuropathies

  • Ptosis

  • Atrophy

  • Abnormal DTr

• NOTE: Inclusion Body Myopathy = distal 

1. List the Endocrine disorders associated w/ myopathy

2. List the metabolism/storage disorders

Endocrine Disorders

• Acromegaly

• Cushing's syndrome

• Hypo/hyperthyroidim

• Hyperparathyroidism

• Diabetes:

  • Neurogenic atrophy, or as Diabetic muscle infarct

---

Inborn errors of metabolism/storage disorders

• Glycogenoses

• Lipid storage disorders

• Mitochondrial disease

• Carnitine Deficiency

Carnitine palmitoyltransferase deficiency Presentation (4)

Carnitine palmitoyltransferase deficiency

• Extremely high CK, rhabdomyolysis

• Early adult onset

• labor (sustained) intensive job provokes, but often tolerate short burst of exertional activity

• At risk from stimulant drug rhabdomyolysis