What is the recommended treatment for a patient with Myasthenia Gravis (MG), a chronic autoimmune disorder?

Myasthenia Gravis Treatment

Start pyridostigmine immediately at 30 mg orally three times daily and titrate upward based on clinical response to a maximum of 120 mg four times daily, escalating to corticosteroids if symptoms persist or interfere with daily activities. 1

Initial Symptomatic Management

• Begin pyridostigmine 30 mg orally three times daily and gradually increase based on clinical response and tolerability to a maximum of 120 mg orally four times daily. 1, 2
• Pyridostigmine may be sufficient as monotherapy in mild disease (Grade 1-2 with ocular symptoms only). 1
• For patients unable to take oral medications, 30 mg oral pyridostigmine corresponds to 1 mg IV pyridostigmine or 0.75 mg neostigmine intramuscularly. 3

Escalation to Immunosuppressive Therapy

• Add corticosteroids directly if pyridostigmine provides insufficient control for Grade 2 symptoms (some interference with activities of daily living). 1
• Initiate prednisone at 1-1.5 mg/kg orally daily, with approximately 66-85% of patients showing positive response. 1, 4
• Taper corticosteroids gradually based on symptom improvement. 1
• Consider azathioprine as a third-line steroid-sparing agent for patients with moderate to severe disease. 4

Management of Severe Disease and Myasthenic Crisis (Grade 3-4)

• Immediately hospitalize patients with myasthenic crisis presenting with respiratory compromise, severe generalized weakness, dysphagia, or rapidly progressive symptoms, and initiate acute immunotherapy. 1
• Permanently discontinue any causative immune checkpoint inhibitors. 1
• Administer IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) OR plasmapheresis for 5 days as first-line acute treatment. 1
• Continue corticosteroids (methylprednisolone 1-2 mg/kg daily) concurrently during IVIG or plasmapheresis. 1
• Sequential therapy (plasmapheresis followed by IVIG) is no more effective than either treatment alone and should be avoided. 3
• IVIG may be preferred in pregnant women due to fewer monitoring requirements compared to plasmapheresis. 3

Critical Medications to Avoid

• Strictly avoid medications that worsen myasthenic symptoms through interference with neuromuscular transmission, including β-blockers, intravenous magnesium, fluoroquinolone antibiotics, aminoglycoside antibiotics, macrolide antibiotics, metoclopramide, and barbiturate-containing medications. 1, 3
• Administration of contraindicated medications can lead to worsening muscle weakness, potential progression to myasthenic crisis with respiratory failure, and need for intensive care unit admission and mechanical ventilation. 3

Diagnostic Confirmation Requirements

• Measure acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies in blood as first-line serologic testing. 1, 4
• If AChR antibodies are negative (occurs in 20-60% of ocular MG), test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies. 1, 4
• Perform electrodiagnostic studies including repetitive nerve stimulation and/or single-fiber EMG with jitter studies (>90% sensitivity for ocular myasthenia). 3, 4
• Obtain pulmonary function testing with negative inspiratory force and vital capacity. 1
• The ice test (applying ice pack over closed eyes for 2 minutes) is highly specific for myasthenia gravis, particularly for ocular symptoms. 4

Important Clinical Pitfalls

• Do NOT use IVIG for chronic maintenance therapy - it should be reserved only for acute exacerbations or crisis situations. 1, 3
• Pupils are characteristically NOT affected in myasthenia gravis - pupillary involvement should prompt immediate evaluation for third nerve palsy or other etiologies. 1, 4
• Approximately 50-80% of patients with initial ocular symptoms will develop generalized myasthenia within a few years, requiring vigilant monitoring. 1, 4
• Failure to show clinical improvement may reflect underdosage, but can also indicate overdosage leading to cholinergic crisis, characterized by increasing muscle weakness that may lead to respiratory failure and death. 2
• Differentiate myasthenic crisis (needs more anticholinesterase therapy) from cholinergic crisis (requires prompt withdrawal of all anticholinesterase drugs and atropine administration). 2

Disease Classification and Treatment Algorithm

• Grade 1 (ocular symptoms only): Pyridostigmine 30 mg three times daily, titrate to maximum 120 mg four times daily; hold immune checkpoint inhibitors temporarily and may resume only if symptoms completely resolve. 3
• Grade 2 (mild generalized weakness with some ADL interference): Pyridostigmine plus add corticosteroids if inadequate response; hold immune checkpoint inhibitors temporarily and may resume only if symptoms resolve to Grade 1 or less. 3, 4
• Grade 3 (severe weakness limiting self-care ADLs): Permanently discontinue immune checkpoint inhibitors; high-dose corticosteroids, IVIG, or plasmapheresis; frequent pulmonary function assessment. 3
• Grade 4 (life-threatening respiratory failure): Permanently discontinue immune checkpoint inhibitors; high-dose IV corticosteroids, IVIG, or plasmapheresis; immediate intubation if respiratory arrest or inability to protect airway. 3

Monitoring and Follow-Up

• Plan regular neurology consultation to adjust treatment as needed. 1
• Teach patients to monitor for and report worsening symptoms including changes in speech/swallowing (bulbar symptoms), respiratory difficulties, and diplopia. 1, 3
• Instruct patients to seek immediate medical attention for significant increase in muscle weakness. 1, 3
• Regular pulmonary function assessment is crucial, especially for patients with generalized disease. 1, 3
• Advise patients to plan activities around medication timing for optimal strength. 3
• Do NOT use noninvasive positive-pressure ventilation (NIPPV) for preventive purposes in stable patients, as studies show increased mortality with prophylactic nocturnal ventilation. 3

Special Considerations

• Approximately 30-50% of patients with thymomas have myasthenia gravis, and all patients suspected of having thymomas should have serum anti-acetylcholine receptor antibody levels measured before any surgical procedure to avoid respiratory failure during anesthesia. 4
• Consider thymectomy in selected patients, particularly those with thymoma or early-onset generalized MG. 5, 6
• For treatment-refractory disease, medications such as rituximab, high-dose cyclophosphamide, and eculizumab may be used. 5
• The safety of pyridostigmine during pregnancy or lactation has not been established; use requires weighing potential benefits against possible hazards to mother and child. 2