What is the diagnosis and treatment for Myasthenia Gravis (MG) with acetylcholine receptor (AChR) antibodies or muscle-specific kinase (MuSK) antibodies?

Myasthenia Gravis Antibody Testing and Management

Diagnostic Antibody Testing

Test for anti-acetylcholine receptor (AChR) antibodies first, as they are present in approximately 80% of patients with generalized myasthenia gravis and confirm the diagnosis 1, 2.

Primary Antibody Testing Algorithm

• AChR antibodies should be the initial test, though sensitivity drops to only 50% in purely ocular myasthenia 1
• Anti-muscle-specific kinase (MuSK) antibodies must be tested when AChR antibodies are negative, as approximately one-third of seronegative patients will be MuSK-positive 1, 3
• Anti-striated muscle antibodies should be included in the initial workup 4, 2
• If both AChR and MuSK are negative, consider LRP4 antibodies, though absence of all antibodies does not rule out myasthenia gravis 4, 5

Critical Distinction Between Antibody Types

MuSK-positive myasthenia gravis represents an immunologically distinct disease from AChR-positive disease 3, 6. Key differences include:

• MuSK-MG predominantly affects neck, shoulder, facial and bulbar muscles with more focal involvement and muscle wasting 6
• MuSK antibodies are predominantly IgG4 subclass and strongly inhibit MuSK function at the neuromuscular junction 3, 6
• MuSK-MG occurs predominantly in females in their fourth decade and is highly associated with HLA DR14-DQ5 haplotype 6
• Rare cases of double positivity (both AChR and MuSK antibodies) have been reported and may indicate more severe, treatment-resistant disease 7

Confirmatory Diagnostic Testing

Beyond antibody testing, complete the diagnostic workup with:

• Single-fiber electromyography (SFEMG) is the gold standard with >90% sensitivity for ocular myasthenia 1
• Repetitive nerve stimulation is less sensitive (positive in only one-third of ocular cases) but more widely available 1
• Ice pack test is highly specific for myasthenia gravis, particularly for ocular symptoms—apply ice pack over closed eyes for 2 minutes and observe for symptom reduction 1, 2
• Edrophonium (Tensilon) test has 95% sensitivity for generalized MG and 86% for ocular MG, but requires experienced practitioners with atropine available due to muscarinic side effects 1

Essential Supplementary Workup

• CT chest with contrast after diagnosis confirmation to evaluate for thymoma, which occurs in 10-20% of AChR-positive patients 1
• Pulmonary function testing with negative inspiratory force (NIF) and vital capacity (VC) to assess respiratory muscle involvement 4, 1
• CPK, aldolase, ESR, and CRP to evaluate for concurrent myositis 4, 1
• Troponin and ECG (consider echocardiogram or cardiac MRI) to rule out concomitant myocarditis 4, 1

Treatment Based on Antibody Status and Severity

AChR-Positive Myasthenia Gravis

Start pyridostigmine at 30 mg orally three times daily and gradually increase to maximum 120 mg four times daily based on symptoms 4, 2.

• For Grade 2 disease (mild generalized weakness, MGFA class I-II): Pyridostigmine plus prednisone 0.5 mg/kg orally daily if symptoms interfere with activities of daily living 4
• For Grade 3-4 disease (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 4, 2
• Thymectomy should be evaluated in appropriate AChR-positive patients 2
• Approximately 66-85% of patients respond positively to corticosteroids 2

MuSK-Positive Myasthenia Gravis

MuSK-MG requires a fundamentally different treatment approach because standard therapies have limited effectiveness 6.

• Cholinesterase inhibitors (pyridostigmine) have limited effectiveness in MuSK-MG 6
• Thymectomy is not effective for MuSK-MG 6
• Corticosteroids remain the primary immunosuppression 6
• Rituximab (B cell depletion) produces especially good responses with long-term remissions and should be considered early, particularly when conventional treatment fails 7, 6
• IVIG or plasmapheresis for acute exacerbations 2

Treatment-Resistant Cases

For patients not responding to initial therapy or those with double-positive antibodies:

• Consider rituximab early, as these patients may experience myasthenic crisis despite standard therapy 7
• Azathioprine can be used as third-line immunosuppressive therapy for moderate to severe disease 2

Critical Medication Avoidance

Immediately review and stop medications that worsen myasthenia 4, 1, 2:

• β-blockers
• IV magnesium
• Fluoroquinolones
• Aminoglycosides
• Macrolide antibiotics

Monitoring and Crisis Management

• Daily neurologic review and frequent pulmonary function assessment for Grade 3-4 patients 4
• Distinguish myasthenic crisis from cholinergic crisis: Both present with extreme muscle weakness, but cholinergic crisis results from pyridostigmine overdosage and requires immediate withdrawal of all anticholinesterase drugs plus atropine 8
• ICU-level monitoring may be necessary for rapidly progressive symptoms or respiratory muscle weakness 4
• Regular assessment is crucial as 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years 2