Myasthenia Gravis - Outpatient Management¶
DIAGNOSIS: Myasthenia Gravis - Outpatient Management ICD-10: G70.00 (Myasthenia gravis without exacerbation), G70.01 (Myasthenia gravis with exacerbation)
CPT CODES: 86235 (AChR binding antibody), 86255 (Anti-striated muscle antibody), 84443 (TSH), 85025 (CBC with differential), 80053 (CMP), 81401 (TPMT genotype), 87340 (Hepatitis B surface antigen), 86803 (Hepatitis C antibody), 82784 (Quantitative immunoglobulins: IgG, IgA, IgM), 86701 (HIV antibody), 86480 (QuantiFERON-Gold), 82947 (Fasting glucose), 82306 (Vitamin D, 25-OH), 84439 (Free T4), 82533 (Cortisol, AM), 80400 (ACTH stimulation test), 82523 (Bone densitometry markers: CTX), 71260 (CT chest with contrast), 71250 (CT chest without contrast), 95937 (Repetitive nerve stimulation), 94010 (Pulmonary function tests: FVC), 95872 (Single-fiber EMG), 71551 (MRI chest), 78816 (PET-CT), 74230 (Video swallow study), 77080 (DEXA scan), 95857 (Edrophonium (Tensilon) test), 95810 (Sleep study, polysomnography), 75557 (Cardiac MRI) 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: Approved
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.
SECTION A: ACTION ITEMS¶
1. LABORATORY WORKUP¶
1A. Essential/Core Labs - Diagnostic Workup¶
| Test (CPT) | ED | HOSP | OPD | ICU | Rationale | Target Finding |
|---|---|---|---|---|---|---|
| AChR binding antibody (CPT 86235) | URGENT | STAT | ROUTINE | STAT | Primary diagnostic test; positive in 85% generalized, 50% ocular MG | Positive confirms diagnosis |
| AChR modulating antibody (CPT 86235) | - | ROUTINE | ROUTINE | - | Increases sensitivity when combined with binding antibody | Positive supports diagnosis |
| AChR blocking antibody (CPT 86235) | - | ROUTINE | ROUTINE | - | Additional AChR antibody; may be positive when binding negative | Positive supports diagnosis |
| MuSK antibody (CPT 86235) | - | ROUTINE | ROUTINE | - | Order if AChR negative; positive in ~40% of AChR-negative patients | Positive confirms MuSK MG |
| LRP4 antibody (CPT 86235) | - | EXT | EXT | - | Order if AChR and MuSK negative; available at specialized labs | Positive confirms LRP4 MG |
| Anti-striated muscle antibody (CPT 86255) | - | ROUTINE | ROUTINE | - | Thymoma association; if positive, high likelihood of thymoma | Positive warrants urgent CT chest |
| TSH (CPT 84443) | - | ROUTINE | ROUTINE | - | Autoimmune thyroid disease common comorbidity (10-15%) | Normal |
| CBC with differential (CPT 85025) | STAT | STAT | ROUTINE | STAT | Baseline before immunotherapy; infection assessment | Normal |
| CMP (CPT 80053) | STAT | STAT | ROUTINE | STAT | Baseline renal/hepatic function; electrolytes | Normal |
1B. Extended Workup (Second-line)¶
| Test (CPT) | ED | HOSP | OPD | ICU | Rationale | Target Finding |
|---|---|---|---|---|---|---|
| TPMT genotype (CPT 81401) | - | ROUTINE | ROUTINE | - | Required before azathioprine initiation; low activity increases toxicity risk | Normal or intermediate activity |
| Hepatitis B surface antigen (CPT 87340), core antibody (CPT 86704) | - | ROUTINE | ROUTINE | - | Before rituximab or other B-cell depleting therapy | Negative |
| Hepatitis C antibody (CPT 86803) | - | ROUTINE | ROUTINE | - | Before immunosuppressive therapy | Negative |
| Quantitative immunoglobulins: IgG, IgA, IgM (CPT 82784) | - | ROUTINE | ROUTINE | - | Baseline before IVIg or rituximab; IgA deficiency is IVIg contraindication | Normal; IgA >7 mg/dL |
| HIV antibody (CPT 86701) | - | ROUTINE | ROUTINE | - | Before immunosuppressive therapy | Negative |
| QuantiFERON-Gold (CPT 86480) | - | ROUTINE | ROUTINE | - | Before chronic immunosuppression | Negative |
| Fasting glucose (CPT 82947), HbA1c (CPT 83036) | - | ROUTINE | ROUTINE | - | Baseline before chronic steroid therapy | Normal |
| Vitamin D, 25-OH (CPT 82306) | - | ROUTINE | ROUTINE | - | Steroid-induced osteoporosis prevention | >30 ng/mL |
| Free T4 (CPT 84439) | - | ROUTINE | ROUTINE | - | If TSH abnormal; autoimmune thyroid disease | Normal |
1C. Rare/Specialized (Refractory or Atypical)¶
| Test (CPT) | ED | HOSP | OPD | ICU | Rationale | Target Finding |
|---|---|---|---|---|---|---|
| Clustered AChR antibody assay (CPT 86235) | - | - | EXT | - | Seronegative MG; may detect low-affinity antibodies not seen on standard assay | Positive supports diagnosis in seronegative cases |
| Paraneoplastic panel (CPT 86255) | - | EXT | EXT | - | Occult malignancy concern; particularly if anti-striated muscle positive | Negative |
| Cortisol, AM (CPT 82533) | - | ROUTINE | ROUTINE | - | Adrenal insufficiency if on chronic steroids being tapered | Normal stress response |
| ACTH stimulation test (CPT 80400) | - | EXT | EXT | - | Suspected secondary adrenal insufficiency from steroid withdrawal | Normal cortisol response |
| Bone densitometry markers: CTX (CPT 82523), P1NP (CPT 83519) | - | - | EXT | - | Osteoporosis risk on chronic steroids | Normal |
2. DIAGNOSTIC IMAGING & STUDIES¶
2A. Essential/First-line¶
| Study (CPT) | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications |
|---|---|---|---|---|---|---|---|
| CT chest with contrast (CPT 71260) | URGENT | URGENT | ROUTINE | URGENT | At diagnosis; exclude thymoma | No thymoma or thymic hyperplasia (or if present, surgical planning) | Contrast allergy, renal impairment (CrCl <30) |
| CT chest without contrast (CPT 71250) | URGENT | URGENT | ROUTINE | URGENT | If contrast contraindicated | Thymic abnormality assessment | None |
| Repetitive nerve stimulation (CPT 95937) | - | ROUTINE | ROUTINE | - | Diagnostic confirmation; if antibodies negative or for monitoring | Decremental response >10% at 3 Hz (positive) | None |
| Pulmonary function tests: FVC (CPT 94010), NIF (CPT 94150) | URGENT | URGENT | ROUTINE | URGENT | Baseline respiratory function; symptom correlation | FVC >80% predicted; NIF more negative than -60 cmH2O | Facial weakness limiting seal |
2B. Extended¶
| Study (CPT) | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications |
|---|---|---|---|---|---|---|---|
| Single-fiber EMG (CPT 95872) | - | EXT | ROUTINE | - | Most sensitive test; if RNS and antibodies negative | Increased jitter and blocking | None |
| MRI chest (CPT 71551) | - | ROUTINE | ROUTINE | - | If CT indeterminate for thymoma; cystic thymic lesions | Characterize thymic mass | Pacemaker, severe claustrophobia |
| PET-CT (CPT 78816) | - | EXT | EXT | - | Suspected thymoma malignancy or metastasis | No FDG-avid lesions | Pregnancy; hemodynamic instability |
| Ice pack test | STAT | STAT | ROUTINE | STAT | Bedside diagnostic for ptosis; cooling improves neuromuscular transmission | Improvement in ptosis after 2 minutes of ice application | None |
| Video swallow study (CPT 74230) | - | URGENT | ROUTINE | - | Dysphagia symptoms; aspiration risk assessment | Safe swallow; define texture modifications | None |
| DEXA scan (CPT 77080) | - | - | ROUTINE | - | Chronic steroid exposure; osteoporosis screening | T-score >-2.5 | None |
2C. Rare/Specialized¶
| Study (CPT) | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications |
|---|---|---|---|---|---|---|---|
| Edrophonium (Tensilon) test (CPT 95857) | - | EXT | EXT | - | Rarely used now; if diagnostic uncertainty and other tests unavailable | Improvement in weakness within 30-60 seconds | Cardiac arrhythmia, asthma (relative) |
| Sleep study, polysomnography (CPT 95810) | - | - | EXT | - | Sleep-disordered breathing; respiratory weakness; fatigue | AHI <5/hour; no nocturnal desaturation | None |
| Cardiac MRI (CPT 75557) | - | - | EXT | - | Suspected cardiac involvement (rare) | Normal | Pacemaker |
3. TREATMENT¶
3A. Cholinesterase Inhibitors (Symptomatic Treatment)¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Pyridostigmine | PO | 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 | Glaucoma; severe cardiac disease; GI obstruction | Dry mouth; urinary retention; constipation; tachycardia | - | ROUTINE | ROUTINE | - |
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
3B. Corticosteroids¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Prednisone (low-dose start) | PO | 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)
3C. Steroid-Sparing Immunosuppressants (Disease-Modifying)¶
| Treatment | Route | Indication | Dosing | Pre-Treatment Requirements | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|---|
| Azathioprine | PO | Steroid-sparing; first-line maintenance immunosuppressant | 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 | TPMT deficiency (intermediate requires 50% dose reduction); pregnancy; concurrent allopurinol (75% dose reduction required) | 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 | CBC; LFTs; hepatitis panel; pregnancy test | Pregnancy (teratogenic); breastfeeding; hypersensitivity | CBC every 2 weeks x 2 months, then monthly x 4 months, then q3 months; LFTs q3 months; GI side effects common | - | ROUTINE | ROUTINE | - |
| Mycophenolate sodium (Myfortic) | PO | Alternative formulation with less GI side effects | 360 mg :: PO :: BID :: Start 360 mg BID; increase to 720 mg BID; 720 mg = 1000 mg mycophenolate mofetil | CBC; LFTs; hepatitis panel; pregnancy test | Pregnancy (teratogenic); breastfeeding; hypersensitivity | CBC every 2 weeks x 2 months, then monthly x 4 months, then q3 months; LFTs q3 months; GI side effects common | - | ROUTINE | ROUTINE | - |
| Tacrolimus | PO | Steroid-sparing; faster onset than azathioprine (3-6 months) | 3 mg :: PO :: daily :: Start 3 mg daily; adjust to trough level 5-10 ng/mL; usual dose 3 mg BID; faster onset than azathioprine | Renal function; glucose; BP; drug interaction review | Renal impairment; uncontrolled hypertension; concurrent potassium-sparing diuretics | Tacrolimus trough level monthly; renal function monthly; glucose; BP; tremor; headache | - | ROUTINE | ROUTINE | - |
| Cyclosporine | PO | Alternative to tacrolimus; similar efficacy | 3 mg/kg :: PO :: BID :: 3-5 mg/kg/day divided BID; adjust to trough 100-200 ng/mL | Renal function; BP; lipids | Renal impairment; uncontrolled hypertension; concurrent nephrotoxins | Cyclosporine trough monthly; renal function monthly; BP; lipids; gingival hyperplasia; hirsutism | - | - | ROUTINE | - |
3D. Biologic and Targeted Immunotherapies¶
| Treatment | Route | Indication | Dosing | Pre-Treatment Requirements | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|---|
| Rituximab | IV | 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 | Infusion reactions; CD19/CD20 B-cell count q3-6 months; immunoglobulins annually; infection monitoring | - | URGENT | ROUTINE | - |
| Eculizumab (Soliris) | IV | AChR+ refractory generalized MG; FDA approved | 900 mg :: IV :: weekly :: 900 mg IV weekly x 4 weeks (induction), then 1200 mg IV every 2 weeks (maintenance); infuse over 35 min | Meningococcal vaccination (MenACWY and MenB) at least 2 weeks before; REMS enrollment | Unresolved Neisseria meningitidis infection; not current with meningococcal vaccines | Meningococcal infection risk (BLACK BOX); infusion reactions; headache; URI | - | ROUTINE | ROUTINE | - |
| Ravulizumab (Ultomiris) | IV | AChR+ refractory generalized MG; longer dosing interval | 2700 mg :: IV :: q8wk :: Load: 40-60 kg: 2400 mg; 60-100 kg: 2700 mg; >100 kg: 3000 mg; Maintenance q8 weeks: 40-60 kg: 3000 mg; 60-100 kg: 3300 mg; >100 kg: 3600 mg | Meningococcal vaccination; REMS enrollment | Unresolved Neisseria meningitidis infection; not current with meningococcal vaccines | Meningococcal infection risk (BLACK BOX); infusion reactions; less frequent infusions | - | ROUTINE | ROUTINE | - |
| Efgartigimod (Vyvgart) | IV | AChR+ generalized MG; FcRn inhibitor; lowers IgG | 10 mg/kg :: IV :: weekly :: 10 mg/kg IV infusion over 1 hour weekly x 4 weeks per treatment cycle; repeat cycles as needed based on clinical response | Baseline immunoglobulins; infection screening | Active serious infection; IgG <2 g/L (relative) | IgG levels; infection; infusion reactions; headache | - | ROUTINE | ROUTINE | - |
| Efgartigimod-fvhp + hyaluronidase (Vyvgart Hytrulo) | SC | AChR+ generalized MG; subcutaneous administration | 1008 mg :: SC :: weekly :: 1008 mg SC injection weekly x 4 weeks per treatment cycle; self-administered at home after training | Baseline immunoglobulins; infection screening | Active serious infection; IgG <2 g/L (relative) | IgG levels; infection; injection site reactions; headache | - | - | ROUTINE | - |
| Rozanolixizumab (Rystiggo) | SC | AChR+ generalized MG; FcRn inhibitor | 420 mg :: SC :: weekly :: 420 mg SC injection weekly x 6 weeks per treatment cycle; repeat cycles as needed | Baseline immunoglobulins; infection screening | Active serious infection | IgG levels; infection; pyrexia; headache; diarrhea | - | - | ROUTINE | - |
| Zilucoplan (Zilbrysq) | SC | AChR+ generalized MG; C5 complement inhibitor; daily SC | 0.3 mg/kg :: SC :: daily :: 0.3 mg/kg SC daily; self-administered; meningococcal vaccination required | Meningococcal vaccination (MenACWY and MenB); REMS enrollment | Unresolved Neisseria infection | Meningococcal infection risk; injection site reactions; diarrhea; URI | - | - | ROUTINE | - |
3E. Medications to AVOID in Myasthenia Gravis¶
CRITICAL: These medications can worsen MG and precipitate crisis. Review all prescriptions before initiating.
| Category | Medications to AVOID | Safer Alternatives |
|---|---|---|
| Antibiotics | Aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin); Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin); Macrolides (azithromycin, erythromycin, clarithromycin); Telithromycin (absolute contraindication) | Penicillins; Cephalosporins; Carbapenems; Sulfonamides; Vancomycin |
| Cardiac medications | Beta-blockers (propranolol, metoprolol, atenolol, carvedilol - ALL); Calcium channel blockers (verapamil, diltiazem); Class Ia antiarrhythmics (procainamide, quinidine, disopyramide); Lidocaine IV | ACE inhibitors; ARBs; Dihydropyridine CCBs (amlodipine, nifedipine) with caution |
| Neuromuscular blockers | Succinylcholine (prolonged paralysis); Non-depolarizing agents (prolonged effect) | If essential: reduced-dose rocuronium with sugammadex reversal available |
| Psychiatric medications | Lithium; Chlorpromazine and other phenothiazines; High-dose benzodiazepines | SSRIs (sertraline, escitalopram); Bupropion; Low-dose benzodiazepines with caution |
| Anticonvulsants | Phenytoin; Gabapentin (rare reports); Pregabalin (rare reports) | Levetiracetam; Valproate; Lamotrigine |
| Magnesium | IV magnesium sulfate (high dose); Magnesium-containing antacids (high dose) | If eclampsia: use with monitoring and intubation preparedness |
| Other | D-penicillamine (can induce MG); Botulinum toxin (any formulation); Quinine; Chloroquine/hydroxychloroquine; Iodinated contrast (use with caution); Checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab) | Document MG on chart; consult neurology before new medications |
3F. Supportive Care and Comorbidities¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Calcium + Vitamin D | PO | Bone protection on chronic steroids | 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 | Sulfa allergy; G6PD deficiency | CBC periodically; rash | - | ROUTINE | ROUTINE | - |
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Neuromuscular specialist/MG center for diagnosis confirmation, treatment optimization, and clinical trial consideration | - | ROUTINE | ROUTINE | - |
| Thoracic surgery consult for thymectomy evaluation in AChR+ generalized MG age 18-65 years without thymoma, or any patient with thymoma | - | ROUTINE | ROUTINE | - |
| Pulmonology consult for baseline pulmonary function testing and ongoing respiratory monitoring in patients with respiratory symptoms | - | URGENT | ROUTINE | URGENT |
| Neuro-ophthalmology for diplopia management, prism prescription, or ptosis surgery evaluation in stable ocular MG | - | - | ROUTINE | - |
| Speech therapy for swallow evaluation given bulbar symptoms and aspiration risk assessment | - | URGENT | ROUTINE | URGENT |
| Physical therapy for generalized weakness to maintain function and prevent deconditioning | - | ROUTINE | ROUTINE | - |
| Occupational therapy for ADL assessment and energy conservation strategies given fatigable weakness | - | ROUTINE | ROUTINE | - |
| Rheumatology if concurrent autoimmune disease suspected (thyroid, lupus, rheumatoid arthritis) | - | ROUTINE | ROUTINE | - |
| Infusion center for IVIg, rituximab, eculizumab, or other IV immunotherapy administration | - | ROUTINE | ROUTINE | - |
| High-risk OB for pregnancy planning in women with MG given medication adjustments and delivery planning | - | - | ROUTINE | - |
| Endocrinology for steroid-induced diabetes, osteoporosis, or adrenal insufficiency management | - | ROUTINE | ROUTINE | - |
| Social work for disability planning, MG Foundation resources, and insurance navigation for expensive biologics | - | ROUTINE | ROUTINE | - |
| Psychiatry for depression or anxiety related to chronic illness or steroid side effects | - | ROUTINE | ROUTINE | - |
4B. Patient Instructions¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Return immediately if worsening weakness, breathing difficulty, or difficulty swallowing develops (may indicate crisis requiring hospitalization) | STAT | STAT | ROUTINE |
| Carry MG medical alert card or bracelet listing diagnosis and medications to avoid (aminoglycosides, fluoroquinolones, beta-blockers, magnesium) | STAT | STAT | ROUTINE |
| Do not stop prednisone or immunosuppressants abruptly; sudden discontinuation may trigger exacerbation or adrenal crisis | STAT | STAT | ROUTINE |
| Take pyridostigmine 30-60 minutes before meals to improve swallowing and reduce choking risk during eating | - | ROUTINE | ROUTINE |
| Report fever or signs of infection promptly as immunosuppression increases infection risk and infection can trigger MG exacerbation | STAT | STAT | ROUTINE |
| Avoid extreme heat as high temperatures worsen neuromuscular transmission and increase weakness | - | ROUTINE | ROUTINE |
| Do not drive if diplopia or ptosis impairs vision; symptoms may fluctuate throughout the day | STAT | STAT | ROUTINE |
| Avoid overexertion; pace activities throughout the day with rest periods to manage fatigable weakness | - | ROUTINE | ROUTINE |
| Report new medications (including over-the-counter) to neurologist before taking, as many common drugs worsen MG | STAT | STAT | ROUTINE |
| Women: Discuss pregnancy plans with MG specialist in advance as medication adjustments are needed before conception | - | - | ROUTINE |
| Contact Myasthenia Gravis Foundation of America (www.myasthenia.org) for patient support, educational resources, and community | - | ROUTINE | ROUTINE |
| Report symptoms of cholinergic overdose: excessive secretions, diarrhea, cramping, muscle twitching, bradycardia (reduce pyridostigmine dose) | STAT | STAT | ROUTINE |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Medication reconciliation before any new prescription to avoid MG-exacerbating drugs; bring medication list to all appointments | STAT | STAT | ROUTINE |
| Avoid live vaccines while on immunosuppression (azathioprine, mycophenolate, rituximab, high-dose steroids); inactivated vaccines are safe | - | ROUTINE | ROUTINE |
| Annual influenza vaccine (inactivated) to prevent respiratory infections that can trigger exacerbation | - | ROUTINE | ROUTINE |
| Pneumococcal vaccination (PCV15 or PCV20 + PPSV23) before starting immunosuppression | - | ROUTINE | ROUTINE |
| Aspiration precautions including upright positioning during and after meals, small bites, and avoiding mixed textures if bulbar symptoms present | STAT | STAT | ROUTINE |
| Energy conservation techniques including pacing activities, scheduled rest periods, and prioritizing important tasks for morning | - | ROUTINE | ROUTINE |
| Avoid smoking as respiratory infections worsen MG and smoking reduces treatment efficacy | ROUTINE | ROUTINE | ROUTINE |
| Limit alcohol intake as it can worsen weakness and interact with medications | - | ROUTINE | ROUTINE |
| Stress management as psychological stress can trigger MG exacerbations | - | ROUTINE | ROUTINE |
| Good sleep hygiene as fatigue and sleep deprivation worsen MG symptoms | - | ROUTINE | ROUTINE |
| Wear medical alert identification listing MG diagnosis and medications to avoid in emergencies | STAT | STAT | ROUTINE |
| Weight management to reduce respiratory load and minimize steroid side effects | - | ROUTINE | ROUTINE |
SECTION B: REFERENCE¶
5. DIFFERENTIAL DIAGNOSIS¶
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| Lambert-Eaton myasthenic syndrome (LEMS) | Proximal weakness improves with exercise; autonomic symptoms (dry mouth); SCLC association; areflexia | VGCC antibody; EMG with incremental response; CT chest for malignancy |
| Botulism | Descending paralysis; fixed dilated pupils; GI symptoms; recent wound or food exposure | Stool/serum toxin assay; EMG (incremental response); clinical history |
| Oculopharyngeal muscular dystrophy | Ptosis, dysphagia; slowly progressive; no fluctuation; onset >45 years; family history | Genetic testing (GCN repeat in PABPN1); muscle biopsy |
| Thyroid eye disease | Proptosis; lid retraction (not ptosis); restrictive ophthalmopathy; thyroid dysfunction | TSH, free T4; orbital CT/MRI (extraocular muscle enlargement) |
| Chronic progressive external ophthalmoplegia (CPEO) | Slowly progressive ptosis and ophthalmoparesis; no fluctuation; may have systemic features | Muscle biopsy; mitochondrial DNA analysis; lactate |
| Miller Fisher syndrome | Ataxia, areflexia, ophthalmoplegia; post-infectious; acute onset | Anti-GQ1b antibody; CSF (albuminocytologic dissociation) |
| Brainstem lesion (stroke, tumor, MS) | Cranial nerve palsies; other brainstem signs; no fatigability | MRI brain with contrast |
| Guillain-Barre syndrome | Ascending weakness; areflexia; no fluctuation; sensory symptoms | CSF (elevated protein); EMG/NCS (demyelinating pattern) |
| Amyotrophic lateral sclerosis (ALS) | Upper and lower motor neuron signs; fasciculations; no fatigability; progressive | EMG (denervation); no antibodies; clinical criteria |
| Drug-induced myasthenia | Temporal relationship to D-penicillamine, checkpoint inhibitors, aminoglycosides | Medication history; may have positive AChR antibodies |
6. MONITORING PARAMETERS¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| CLINICAL | |||||||
| MG composite or QMG score | Every visit | Stable or improved | Escalate therapy if worsening | - | ROUTINE | ROUTINE | - |
| Forced vital capacity (FVC) | Baseline; q3-6 months if respiratory symptoms; urgent if symptoms worsen | >80% predicted; >15 mL/kg | If FVC declining: hospitalize, consider IVIg/PLEX | STAT | STAT | ROUTINE | STAT |
| Negative inspiratory force (NIF) | With FVC; if respiratory symptoms | More negative than -60 cmH2O | If NIF >-20 cmH2O: crisis, intubate | STAT | STAT | ROUTINE | STAT |
| Swallow function | Each visit if bulbar symptoms | Safe swallow | Modified diet; speech therapy; consider PEG if severe | - | URGENT | ROUTINE | URGENT |
| Weight | Each visit | Stable | Monitor steroid side effects; nutritional assessment if losing | - | ROUTINE | ROUTINE | - |
| LABORATORY | |||||||
| CBC with differential | Weekly x 4 then monthly x 3 then q3 months (azathioprine/MMF) | WBC >3000; ALC >500; Plt >100K | Hold immunosuppressant if low; may resume at lower dose | - | ROUTINE | ROUTINE | - |
| LFTs | Monthly x 3 then q3 months | AST/ALT <3x ULN | Reduce dose or discontinue if >3x with symptoms | - | ROUTINE | ROUTINE | - |
| Glucose | Weekly during steroid titration; q3 months on maintenance | Fasting <126; random <200 | Initiate diabetes treatment if elevated | - | ROUTINE | ROUTINE | - |
| Blood pressure | Each visit | <130/80 mmHg (steroid hypertension) | Antihypertensive if elevated | - | ROUTINE | ROUTINE | - |
| TPMT level/genotype | Once before azathioprine | Normal activity | Reduce dose 50% if intermediate; avoid if deficient | - | - | ROUTINE | - |
| Tacrolimus trough | Monthly if on tacrolimus | 5-10 ng/mL | Dose adjustment | - | ROUTINE | ROUTINE | - |
| Immunoglobulins (IgG, IgA, IgM) | Baseline; annually on rituximab or anti-CD20 | IgG >400 mg/dL | Consider IVIG replacement if low and recurrent infections | - | ROUTINE | ROUTINE | - |
| B-cell count (CD19/CD20) | q3-6 months on rituximab | Depleted initially; document recovery | Guide re-dosing | - | ROUTINE | ROUTINE | - |
| BONE HEALTH | |||||||
| DEXA scan | Baseline; q1-2 years if on chronic steroids | T-score >-2.5 | Bisphosphonate if osteopenia/osteoporosis | - | - | ROUTINE | - |
| Vitamin D, 25-OH | Baseline; annually | >30 ng/mL | Supplement if low | - | ROUTINE | ROUTINE | - |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| Manage outpatient | 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 |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| Pyridostigmine for symptomatic treatment of MG | Class I, Level A | Mehndiratta MM et al. Cochrane 2014 |
| Thymectomy improves outcomes in AChR+ generalized MG age 18-65 | Class I, Level B | Wolfe GI et al. NEJM 2016 (MGTX Trial) |
| Corticosteroids effective for MG | Class II, Level B | Schneider-Gold C et al. Cochrane 2005 |
| Azathioprine as steroid-sparing agent | Class I, Level B | Palace J et al. NEJM 1998 |
| Mycophenolate mofetil in MG (mixed evidence) | Class II, Level B | Sanders DB et al. Muscle Nerve 2016 |
| Rituximab effective in MuSK-positive MG | Class II, Level B | Nowak RJ et al. Neurology 2022 |
| Rituximab in refractory AChR+ MG | Class II, Level C | Tandan R et al. Muscle Nerve 2017 |
| Eculizumab for refractory generalized AChR+ MG | Class I, Level A | Howard JF et al. Lancet Neurol 2017 (REGAIN) |
| Efgartigimod for generalized AChR+ MG | Class I, Level A | Howard JF et al. Lancet Neurol 2021 (ADAPT) |
| Medications that exacerbate MG | Class III, Level C | Juel VC. Semin Neurol 2004 |
| AAN/MGFA guidelines for MG management | Expert consensus | Sanders DB et al. Neurology 2016 |
| Ocular MG: 50-80% generalize within 2 years | Class II, Level B | Kupersmith MJ et al. Arch Neurol 2003 |
| Low-dose steroid initiation prevents worsening | Class II, Level B | Pascuzzi RM. Semin Neurol 2003 |
| Anti-striated muscle antibody and thymoma association | Class II, Level B | Romi F et al. Arch Neurol 2005 |
| Ravulizumab for generalized AChR+ MG | Class I, Level A | Vu T et al. NEJM 2022 (CHAMPION-MG) |
| Rozanolixizumab for generalized AChR+ MG | Class I, Level A | Bril V et al. Lancet Neurol 2023 |
| Zilucoplan for generalized AChR+ MG | Class I, Level A | Howard JF et al. Lancet Neurol 2023 (RAISE) |
CHANGE LOG¶
v1.1 (January 30, 2026)
- Standardized lab tables (1A/1B/1C) to Test (CPT) | ED | HOSP | OPD | ICU | Rationale | Target Finding format
- Standardized imaging tables (2A/2B/2C) to Study (CPT) | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications format
- Added inline CPT codes to all laboratory and imaging studies
- Fixed structured dosing first fields across all treatment sections (3A/3B/3C/3D/3F)
- Expanded "Same as mycophenolate mofetil" cross-references in mycophenolate sodium (Pre-Treatment, Contraindications, Monitoring)
- Expanded "Same as IV efgartigimod" cross-references in efgartigimod SC (Pre-Treatment, Contraindications, Monitoring)
- Expanded "Same as eculizumab" cross-references in ravulizumab (Contraindications, Monitoring)
- Reorganized header block for consistency
- Added REVISED date
v1.0 (January 27, 2026) - Initial template creation for MG outpatient management - Comprehensive antibody subtype overview (AChR, MuSK, LRP4, seronegative) - Pyridostigmine dosing with structured format for order sentences - Corticosteroid initiation protocols (low-dose outpatient vs high-dose inpatient) - Steroid-sparing agents with pre-treatment and monitoring requirements - All FDA-approved MG biologics (eculizumab, ravulizumab, efgartigimod, rozanolixizumab, zilucoplan) - Comprehensive medications to avoid list - Thymectomy indications and referral criteria - Crisis prevention and warning signs - PubMed citations verified for all evidence statements
APPENDIX A: MGFA Clinical Classification¶
| Class | Description |
|---|---|
| I | Ocular weakness only (ptosis, diplopia) |
| II | Mild generalized weakness +/- ocular |
| IIa | Predominantly limb/axial |
| IIb | Predominantly oropharyngeal/respiratory |
| III | Moderate generalized weakness +/- ocular |
| IIIa | Predominantly limb/axial |
| IIIb | Predominantly oropharyngeal/respiratory |
| IV | Severe generalized weakness +/- ocular |
| IVa | Predominantly limb/axial |
| IVb | Predominantly oropharyngeal/respiratory |
| V | Intubation required (with or without mechanical ventilation) |
Clinical Use: Document at diagnosis and follow changes. Class IIb, IIIb, IVb (bulbar predominant) have higher aspiration and crisis risk.
APPENDIX B: Thymectomy Decision Guide¶
| Factor | Favors Thymectomy | Against/Defer |
|---|---|---|
| Antibody status | AChR-positive | MuSK-positive (poor evidence); seronegative (limited data) |
| Age | 18-65 years (MGTX data) | <18 or >65 (less evidence, still consider) |
| MG type | Generalized MG | Ocular MG (controversial; consider if not responding to treatment or generalizing) |
| Thymoma | ALL thymomas require resection regardless of MG severity | N/A |
| Disease stability | Stable enough for surgery | Actively worsening; optimize with IVIg/PLEX first |
| Comorbidities | Good surgical candidate | Poor surgical risk |
MGTX Trial Key Findings: - Thymectomy + prednisone superior to prednisone alone over 3 years - Lower prednisone requirements - Fewer immunosuppressants needed - Fewer exacerbations - Benefits persist at 5-year follow-up
APPENDIX C: Treatment Algorithm¶
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
APPENDIX D: Crisis Warning Signs - Patient Handout¶
SEEK IMMEDIATE MEDICAL ATTENTION IF YOU EXPERIENCE:
- Difficulty breathing or feeling short of breath
- Trouble swallowing or choking on food/liquids/pills
- Difficulty speaking (slurred or nasal speech) that is new or worsening
- Weakness that is rapidly getting worse
- Fever or signs of infection (infections can trigger crisis)
- Recent exposure to medications on the "avoid" list
WARNING SIGNS OF IMPENDING CRISIS:
- Increasing difficulty breathing when lying flat
- Needing more pillows to sleep
- Waking up short of breath at night
- Feeling you can't take a deep breath
- Voice becoming weaker or more nasal
- Difficulty clearing throat or coughing effectively
- Meals taking much longer due to swallowing difficulty
- Choking episodes increasing
- Needing to use neck muscles to breathe
WHAT TO DO:
- Go to emergency department immediately (do not wait for clinic appointment)
- Bring your medication list and MG card
- Tell staff you have myasthenia gravis
- Ask them to contact your neurologist
- Request they avoid medications on your avoid list