What is the recommended treatment approach for a patient diagnosed with Myasthenia gravis?

Management of Myasthenia Gravis

Begin treatment with pyridostigmine 30 mg orally three times daily as first-line symptomatic therapy, titrating up to a maximum of 120 mg four times daily based on clinical response. 1, 2

Initial Diagnostic Workup

Before initiating treatment, confirm the diagnosis with:

• Acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies in blood; if AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 3, 4
• Electrodiagnostic studies including repetitive nerve stimulation and/or single-fiber EMG with jitter studies 3, 4
• Pulmonary function testing with negative inspiratory force and vital capacity to establish baseline respiratory function 3, 1
• Ice pack test for ocular symptoms (apply ice over closed eyes for 2 minutes)—highly specific for myasthenia gravis 4

Note that pupils are characteristically not affected in myasthenia gravis; pupillary involvement should prompt immediate evaluation for third nerve palsy or other diagnoses 4

Stepwise Treatment Algorithm

Mild Disease (Ocular or Minimal Symptoms)

• Start pyridostigmine 30 mg orally three times daily, gradually increasing based on symptom response 1, 2
• Maximum dose is 120 mg orally four times daily 3, 1
• Sustained-release formulations may improve quality of life and reduce dosing frequency 5
• Monitor for cholinergic side effects (diarrhea, abdominal cramping, excessive salivation) 1

Moderate Disease (Grade 2: Generalized Weakness)

If pyridostigmine provides insufficient control:

• Add prednisone 1-1.5 mg/kg orally daily 3, 1
• Taper corticosteroids gradually based on symptom improvement 3, 1
• Continue pyridostigmine at optimized dose 1
• Warning: Corticosteroids can paradoxically worsen symptoms when first initiated, particularly at high doses—monitor closely 6

Severe Disease (Grade 3-4: Myasthenic Crisis)

For respiratory compromise, severe dysphagia, or rapidly progressive weakness:

• Immediately hospitalize with ICU-level monitoring 3, 1
• Initiate IVIG 2 g/kg total dose over 5 days (0.4 g/kg/day × 5 days) OR plasmapheresis for 5 days 3, 1
• Continue corticosteroids concurrently 3, 1
• Perform frequent pulmonary function assessments with negative inspiratory force and vital capacity 3, 1
• Conduct daily neurologic evaluations 3, 1
• Pyridostigmine may be continued but should be discontinued if intubation is required 1

Critical distinction: IVIG should not be used for chronic maintenance therapy—it is reserved only for acute exacerbations or crisis situations 1. Sequential therapy (plasmapheresis followed by IVIG) is no more effective than either treatment alone and should be avoided 1.

Immunosuppressive Therapy for Refractory Disease

For patients requiring chronic immunosuppression beyond corticosteroids:

• Azathioprine as steroid-sparing agent for moderate to severe disease 4, 7
• Rituximab for treatment-refractory myasthenia gravis 7, 8
• Thymectomy should be considered in AChR antibody-positive generalized MG patients up to age 65 years 7

Critical Medications to Absolutely Avoid

Educate all patients to strictly avoid these medications that can precipitate myasthenic crisis:

• β-blockers (all formulations, especially IV) 3, 1, 6
• Intravenous magnesium 3, 1, 6
• Fluoroquinolone antibiotics (ciprofloxacin, levofloxacin, moxifloxacin) 3, 1, 6
• Aminoglycoside antibiotics (gentamicin, tobramycin, amikacin) 3, 1, 6
• Macrolide antibiotics (azithromycin, erythromycin, clarithromycin) 3, 1, 6
• Barbiturates (butalbital-containing medications like Fioricet) 1, 6
• Metoclopramide 1

Monitoring and Follow-up

• Regular neurology consultation to adjust treatment as needed 1
• Pulmonary function monitoring especially in generalized disease, as 50-80% of patients with initial ocular symptoms may develop generalized myasthenia within a few years 4
• Educate patients to immediately report worsening dysphagia, dysarthria, diplopia, or respiratory difficulties 1
• Plan activities around medication timing for optimal strength 1

Special Considerations

• Approximately 30-50% of patients with thymomas have myasthenia gravis; measure anti-AChR antibodies preoperatively in any patient requiring surgery to avoid respiratory failure during anesthesia 4
• In pregnant women, IVIG may be preferred over plasmapheresis due to fewer monitoring requirements 1
• Pyridostigmine-induced AV block can occur; if bradycardia develops, consider hyoscyamine (muscarinic antagonist) to block cardiac cholinergic effects without reducing neuromuscular efficacy 9