What is the initial treatment for Myasthenia gravis?

Initial Treatment for Myasthenia Gravis

Begin with pyridostigmine 30 mg orally three times daily as first-line symptomatic therapy, titrating gradually to a maximum of 120 mg four times daily based on clinical response. 1, 2, 3

Diagnostic Confirmation Before Treatment

Before initiating therapy, 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 1, 2
• Pulmonary function testing with negative inspiratory force and vital capacity to establish baseline respiratory status 1, 2
• Electrodiagnostic studies including repetitive nerve stimulation and/or single-fiber EMG with jitter studies to confirm neuromuscular junction dysfunction 1, 4

Stepwise Treatment Algorithm

Grade 2 Disease (Mild Generalized Weakness, Ocular Symptoms)

• Start pyridostigmine 30 mg orally three times daily, increasing gradually as tolerated based on symptom response 1, 2, 3
• Add corticosteroids directly (prednisone 1-1.5 mg/kg orally daily) if pyridostigmine provides insufficient control after adequate trial 1, 2
• Hold immune checkpoint inhibitors if this is immune-related myasthenia gravis, and may resume only if symptoms completely resolve 1
• Consult neurology for all patients at this stage 1, 2

Grade 3-4 Disease (Severe Weakness, Dysphagia, Respiratory Compromise)

• Permanently discontinue immune checkpoint inhibitors if applicable 1
• Admit to hospital with ICU-level monitoring capability for close respiratory surveillance 1, 2
• Initiate IVIG 2 g/kg total dose over 5 days (0.4 g/kg/day for 5 consecutive days) OR plasmapheresis for 5 days 1, 2
• Continue or initiate corticosteroids (methylprednisolone 1-2 mg/kg daily or prednisone 1-1.5 mg/kg daily) concurrently with IVIG/plasmapheresis 1, 2
• Maintain pyridostigmine throughout acute treatment 2
• Perform frequent pulmonary function assessments with negative inspiratory force and vital capacity monitoring 1, 2
• Conduct daily neurologic evaluations to assess progression or improvement 1, 2

Critical Medications to Avoid

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

• β-blockers (all formulations, especially intravenous) 1, 2, 5
• Intravenous magnesium 1, 2, 5
• Fluoroquinolone antibiotics (ciprofloxacin, levofloxacin, moxifloxacin) 1, 2, 5
• Aminoglycoside antibiotics (gentamicin, tobramycin, amikacin) 1, 2, 5
• Macrolide antibiotics (azithromycin, erythromycin, clarithromycin) 1, 2, 5
• Barbiturate-containing medications like Fioricet (butalbital/acetaminophen) 2, 5

Important Clinical Pitfalls

• Approximately 50-80% of patients with isolated ocular symptoms will progress to generalized myasthenia within a few years, making early diagnosis and treatment critical to prevent respiratory failure 4
• Corticosteroids can paradoxically worsen symptoms when first initiated, particularly at high doses, requiring close monitoring during the first 1-2 weeks 5
• IVIG should NOT be used for chronic maintenance therapy in myasthenia gravis—it is reserved exclusively for acute exacerbations or crisis situations 2
• Pupils are characteristically spared in myasthenia gravis—if pupillary abnormalities are present, immediately consider alternative diagnoses such as third nerve palsy 4

Monitoring and Patient Education

• Teach patients to monitor for worsening bulbar symptoms (dysphagia, dysarthria), respiratory difficulties, and diplopia, with instructions to seek immediate medical attention for significant weakness progression 2
• Plan activities around medication timing for optimal strength, as pyridostigmine has a predictable time-action profile 2
• Arrange regular neurologic follow-up to adjust immunosuppressive therapy and taper corticosteroids based on symptom improvement 1, 2