Management of AChR-Positive Myasthenia Gravis
Start pyridostigmine bromide 30 mg orally three times daily as first-line treatment, gradually increasing to a maximum of 120 mg four times daily, but be prepared to escalate to corticosteroids (prednisone 0.5 mg/kg daily) in approximately 50% of patients who show inadequate response, particularly those with Grade 2 or higher symptoms that interfere with daily activities. 1, 2
Initial Symptomatic Treatment
- Pyridostigmine bromide is the first-line agent for all AChR-positive MG patients, starting at 30 mg orally three times daily and titrating up based on symptom response 1, 2
- Maximum dosing is 120 mg orally four times daily as tolerated 1, 2
- Approximately 50% of patients, particularly those with ocular/strabismus manifestations, will show minimal response to pyridostigmine alone and require escalation 3, 1
- Critical warning: Overdosage can cause cholinergic crisis characterized by increasing muscle weakness and respiratory failure, which is difficult to distinguish from myasthenic crisis 4
Escalation to Immunosuppressive Therapy
Second-Line: Corticosteroids
- Corticosteroids demonstrate superior efficacy with 66-85% positive response rates compared to pyridostigmine's 50% response rate 3, 1, 2
- Initiate prednisone 0.5 mg/kg orally daily for Grade 2 disease (mild generalized weakness, MGFA class I-II) when symptoms interfere with activities of daily living 2
- Corticosteroids are particularly effective when ocular motility abnormalities persist despite pyridostigmine 2, 5
Third-Line: Steroid-Sparing Immunosuppressants
- Azathioprine is the established third-line agent for moderate to severe disease or when steroid-sparing therapy is needed 1, 2, 5
- Other options include mycophenolate mofetil, cyclosporine, and methotrexate for long-term immunosuppression 6
Acute/Severe Disease Management (Grade 3-4)
- For moderate to severe weakness (MGFA class III-V): Add IVIG 2 g/kg IV over 5 days (0.4 g/kg/day) OR plasmapheresis for 3-5 days 2
- ICU-level monitoring may be necessary for rapidly progressive symptoms or respiratory muscle weakness 2
- Daily neurologic review and frequent pulmonary function assessment (negative inspiratory force and vital capacity) are mandatory 2
Surgical Intervention: Thymectomy
- Thymectomy is indicated in AChR-positive generalized MG patients up to age 65 years based on clear evidence from the MGTX trial 5
- Always perform thymectomy when thymoma is present 3
- CT chest with contrast is essential after diagnosis confirmation to evaluate for thymoma, which occurs in 10-20% of AChR-positive patients 2
- Thymectomy may substantially reduce symptoms and should be evaluated in appropriate AChR-positive patients 3, 2
Novel Therapies for Refractory Disease
- Efgartigimod alfa-fcab is FDA-approved specifically for AChR-positive patients who are refractory to conventional therapy 3
- Rituximab can be considered for treatment-refractory cases 7, 6
Critical Medication Avoidance
Immediately review and discontinue medications that worsen myasthenia, including: 1, 2
- β-blockers
- IV magnesium
- Fluoroquinolones
- Aminoglycosides
- Macrolide antibiotics
Essential Monitoring and Workup
- Pulmonary function testing with NIF and vital capacity to assess respiratory muscle involvement, as 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years 1, 2
- CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis 2
- Troponin and ECG (consider echocardiogram or cardiac MRI) to rule out concomitant myocarditis 2
Management of Ocular Symptoms
- Ocular symptoms are highly variable and not readily remedied with prisms 3, 2
- Ice pack test (apply over closed eyes for 2-5 minutes) can temporarily reduce symptoms and aid diagnosis 3, 1, 2
- Strabismus surgery should only be considered after disease stabilization, typically requiring 2-3 years of medical treatment 3, 2
- Surgical management requires particular care with anesthetic agents given potential respiratory muscle weakness 3
Common Pitfalls to Avoid
- Failing to distinguish cholinergic crisis from myasthenic crisis: Both present with extreme muscle weakness, but cholinergic crisis requires immediate withdrawal of all anticholinesterase drugs and atropine administration 4
- Masking signs of overdosage by using atropine to control gastrointestinal side effects, which can lead to inadvertent cholinergic crisis 4
- Inadequate monitoring for disease progression from ocular to generalized MG 8
- Delaying corticosteroid initiation in patients with persistent symptoms despite adequate pyridostigmine dosing 1, 2