DIAGNOSIS: Myasthenia Gravis - Outpatient Management
ICD-10: G70.00 (Myasthenia gravis without exacerbation), G70.01 (Myasthenia gravis with exacerbation)
SYNONYMS: MG, myasthenia, autoimmune myasthenia gravis, ocular myasthenia, generalized myasthenia, AChR-positive MG, MuSK myasthenia, seronegative myasthenia, MG chronic management, MG maintenance therapy
SCOPE: Outpatient diagnosis, management, and monitoring of myasthenia gravis in adults. Covers antibody-positive (AChR, MuSK, LRP4) and seronegative MG, ocular and generalized subtypes, pyridostigmine optimization, immunotherapy initiation and monitoring, thymectomy evaluation, and crisis prevention. Excludes myasthenic crisis (see "Myasthenia Gravis - Exacerbation/Crisis"), Lambert-Eaton myasthenic syndrome (LEMS), congenital myasthenic syndromes, and drug-induced myasthenia.
VERSION: 1.1
CREATED: January 27, 2026
REVISED: January 30, 2026
STATUS: Draft - Pending Review
KEY CLINICAL FEATURES:
- Fatigable weakness: Worsens with activity, improves with rest
- Ocular MG: Ptosis, diplopia; may remain ocular or generalize (50-80% generalize within 2 years)
- Generalized MG: Bulbar (dysarthria, dysphagia, facial weakness), limb (proximal > distal), respiratory
- Diurnal variation: Worse later in day, better in morning
- MuSK MG: Prominent bulbar, neck, respiratory weakness; less ocular; poor response to pyridostigmine
ANTIBODY SUBTYPES:
| Subtype | Frequency | Characteristics |
|---------|-----------|-----------------|
| AChR-positive | 85% of generalized, 50% of ocular | Typical MG; thymoma association; good pyridostigmine response |
| MuSK-positive | 40% of AChR-negative | Bulbar predominant; less ocular; poor pyridostigmine response; good rituximab response |
| LRP4-positive | ~2% of double-negative | Milder phenotype; overlap with AChR+ features |
| Seronegative | ~10-15% | May seroconvert; treat as AChR-positive; consider low-affinity antibodies |
PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting
CRISIS PREVENTION
Myasthenic crisis occurs in 15-20% of patients. Recognize warning signs (worsening bulbar/respiratory symptoms, declining FVC) and know medications to avoid. See Section 3E for medications that exacerbate MG.
THYMECTOMY CONSIDERATION
Thymectomy improves outcomes in non-thymomatous AChR+ generalized MG age 18-65. All patients need CT chest to evaluate for thymoma. See Section 4A for referral criteria.
First-line symptomatic treatment for all MG subtypes
30 mg :: PO :: TID :: Start 30 mg TID; increase by 30 mg/dose every 3-5 days as tolerated; usual maintenance 60 mg q4-6h (max 120 mg q4h); take 30-60 min before meals for swallowing
Mechanical bowel/bladder obstruction; known hypersensitivity
Cholinergic symptoms (SLUDGE: salivation, lacrimation, urination, defecation, GI distress, emesis); bradycardia; if symptoms occur, reduce dose
STAT
STAT
ROUTINE
STAT
Pyridostigmine SR (Mestinon Timespan)
PO
Nocturnal symptoms; morning weakness on awakening
180 mg :: PO :: qHS :: 180 mg at bedtime for nocturnal weakness; do NOT crush; erratic absorption limits daytime use; max 1 tablet daily
Mechanical bowel/bladder obstruction; known hypersensitivity
Cholinergic symptoms (SLUDGE); bradycardia
-
ROUTINE
ROUTINE
-
Glycopyrrolate
PO
Cholinergic side effects from pyridostigmine
1 mg :: PO :: BID :: 1-2 mg PO BID-TID for secretions, diarrhea, or cramping from pyridostigmine; does not cross BBB
PYRIDOSTIGMINE DOSING GUIDANCE:
- Start low: 30 mg TID to assess response and tolerability
- Titrate slowly: Increase by 30 mg/dose every 3-5 days
- Time meals: Take 30-60 minutes before meals if dysphagia present
- MuSK MG: Often poor response; may worsen with high doses; use cautiously
- Overcorrection: Cholinergic crisis (SLUDGE symptoms, weakness, fasciculations) if overdosed
Ocular or mild generalized MG; outpatient initiation
10 mg :: PO :: daily :: Start 10-20 mg daily; increase by 10 mg every 5-7 days to target 1 mg/kg/day (max 60-80 mg); LOW-DOSE START prevents transient worsening in outpatient setting
Active untreated infection; psychosis (relative); poorly controlled diabetes
Glucose weekly during titration; BP; weight; mood; bone density annually
-
ROUTINE
ROUTINE
-
Prednisone (high-dose)
PO
Hospital setting with crisis protection (post-IVIg/PLEX)
60 mg :: PO :: daily :: 60-80 mg or 1 mg/kg daily; only start high-dose after IVIg/PLEX coverage in hospital or if admitted for monitoring
Active infection (relative); NOT FOR OUTPATIENT INITIATION
Glucose q6h; BP; K+; monitor for transient worsening days 5-10
-
STAT
-
STAT
Prednisone (maintenance/taper)
PO
Chronic MG on stable steroids
Per taper :: PO :: per schedule :: Once stable on target dose x 2-4 weeks, begin slow taper: reduce by 10 mg q2-4 weeks until 20 mg, then by 5 mg q2-4 weeks until 10 mg, then by 2.5 mg q month; may need minimum maintenance dose indefinitely
Adrenal insufficiency risk with abrupt stop
Symptoms of adrenal insufficiency during taper; flare
-
ROUTINE
ROUTINE
-
STEROID WARNING: High-dose corticosteroids can cause transient worsening of MG (typically days 5-10).
- Outpatient initiation: ALWAYS start LOW (10-20 mg) and titrate slowly
- Hospital with IVIg/PLEX coverage: Can start high-dose since protected by immunotherapy
- Never stop steroids abruptly after >2 weeks of therapy (adrenal suppression)
50 mg :: PO :: daily :: Start 50 mg daily x 1-2 weeks; increase by 50 mg every 2-4 weeks to target 2-3 mg/kg/day (usually 150-200 mg/day); takes 6-12 months for full effect
TPMT genotype or enzyme activity; CBC; LFTs; hepatitis panel
CBC weekly x 4 weeks, then monthly x 3 months, then q3 months; LFTs monthly x 3 months, then q3 months; flu-like symptoms on initiation (hypersensitivity, discontinue)
-
ROUTINE
ROUTINE
-
Mycophenolate mofetil
PO
Steroid-sparing; alternative to azathioprine
500 mg :: PO :: BID :: Start 500 mg BID; increase to 1000 mg BID after 2 weeks; may increase to 1500 mg BID if needed; takes 3-6 months for effect
MuSK-positive MG (often first-line after steroids); refractory AChR+ MG
375 mg/m2 :: IV :: weekly :: Either 375 mg/m2 IV weekly x 4 weeks OR 1000 mg IV x 2 doses (2 weeks apart); premedicate with methylprednisolone 100 mg, acetaminophen, diphenhydramine; repeat courses as needed
Hepatitis B screening (HBsAg, anti-HBc); quantitative immunoglobulins; TB screen
Active hepatitis B; active severe infection; live vaccines within 4 weeks
1000 mg :: PO :: daily :: Calcium 500-600 mg BID with meals; Vitamin D 1000-2000 IU daily; target 25-OH Vitamin D >30 ng/mL
Hypercalcemia; kidney stones
Vitamin D level annually; calcium as needed
-
ROUTINE
ROUTINE
-
Alendronate
PO
Osteoporosis prevention/treatment on chronic steroids
70 mg :: PO :: weekly :: 70 mg PO weekly on empty stomach with full glass of water; remain upright 30 min; consider if steroids >3 months at prednisone >5 mg/day
GFR <30-35; esophageal disorders; inability to remain upright
DEXA at baseline and q1-2 years; jaw osteonecrosis rare
-
-
ROUTINE
-
Omeprazole
PO
GI protection during high-dose steroids
20 mg :: PO :: daily :: 20-40 mg PO daily while on high-dose prednisone; consider tapering off when steroids reduced
Long-term use increases C. diff risk
Limit duration; consider H2 blocker alternative
-
ROUTINE
ROUTINE
-
Trimethoprim-sulfamethoxazole
PO
PJP prophylaxis if on high-dose steroids + other immunosuppression
1 DS tablet :: PO :: 3x weekly :: 1 DS tablet (160/800 mg) PO Monday/Wednesday/Friday; or 1 SS tablet daily
Stable ocular or mild generalized MG; FVC >60% and stable; able to swallow safely; no respiratory symptoms; reliable follow-up
Admit to floor
Moderate-severe worsening not requiring ICU; initiation of high-dose steroids with IVIg/PLEX coverage; significant bulbar symptoms with aspiration risk; FVC 30-60% and declining; new diagnosis with moderate severity
Admit to ICU
FVC <30% or rapidly declining; NIF weaker than -30 cmH2O; impending respiratory failure; severe bulbar dysfunction with aspiration; need for intubation or BiPAP
Emergency evaluation
Acute worsening of weakness; new respiratory symptoms (dyspnea, orthopnea); difficulty swallowing or speaking; recent infection or medication change with weakness; FVC declining on outpatient checks
Transfer to MG center
Refractory MG not responding to standard therapy; thymectomy evaluation; clinical trial consideration; complex immunotherapy decisions
NEW DIAGNOSIS CONFIRMED
|
v
+------------------+
| Ocular MG only? |
+------------------+
| |
YES NO
| |
v v
Pyridostigmine Pyridostigmine + CT chest (thymoma screen)
| |
v v
Symptoms controlled? +-------------------+
| | | Thymoma present? |
YES NO +-------------------+
| | | |
v v YES NO
Monitor for Add | |
generalization prednisone v v
(low-dose Thymectomy Age 18-65, AChR+?
start) urgent Generalized?
| | | |
v v YES NO
If generalizes, Taper steroids; | |
treat as add steroid- v v
generalized sparing agent Consider Steroids +
(AZA or MMF) thymectomy steroid-sparing
| (skip surgery)
v
Stable on minimal steroids?
| |
YES NO
| |
v v
Continue Escalate:
monitoring Rituximab (esp MuSK+)
OR Complement inhibitor
OR FcRn inhibitor