What are the signs of a myasthenia gravis flare?

Identifying a Myasthenia Gravis Flare

A myasthenia gravis flare is identified by worsening or new-onset fatigable muscle weakness, particularly affecting ocular, bulbar, or respiratory muscles, with symptoms that fluctuate throughout the day and worsen with activity. 1, 2

Key Clinical Features to Monitor

Ocular Manifestations

• Progressive or worsening ptosis (eyelid drooping) that worsens as the day progresses or with sustained upgaze 1, 2
• New or worsening diplopia (double vision) from extraocular muscle weakness, typically asymmetric 2, 3
• Ophthalmoplegia (impaired eye movements) that may progress from partial to complete 1, 4

Bulbar Symptoms (Critical Warning Signs)

• Dysarthria (slurred speech) that worsens with prolonged talking 1, 3
• Dysphagia (difficulty swallowing) - a particularly concerning sign requiring immediate assessment 1, 2
• Facial muscle weakness including difficulty with facial expressions 1, 3
• Drooling from facial and bulbar involvement 2

Generalized Weakness Patterns

• Proximal muscle weakness more than distal (difficulty climbing stairs, rising from chairs, lifting arms overhead) 2, 3
• Neck weakness including difficulty holding head up 1, 3
• Fatigability - weakness that worsens with repetitive activity and improves with rest 5, 6

Respiratory Compromise (Medical Emergency)

• Shortness of breath with light activity or at rest 2
• Respiratory muscle weakness leading to respiratory insufficiency 1, 3
• Reduced vital capacity (VC) and negative inspiratory force (NIF) on pulmonary function testing 1, 3

Immediate Assessment Protocol

Clinical Evaluation

• Assess respiratory function immediately in any patient with generalized symptoms - measure VC and NIF 1, 3
• Evaluate bulbar function by testing swallowing ability and speech clarity 1, 2
• Document the pattern of weakness - fluctuating throughout the day, worsening with activity, improving with rest 5, 6

Laboratory and Diagnostic Testing

• Check creatine phosphokinase (CPK), aldolase, ESR, CRP to evaluate for concurrent myositis 1
• Obtain troponin T and perform ECG/echocardiography if respiratory insufficiency or elevated CPK present, as myocarditis may coexist 1
• Consider repeat antibody testing (AChR, antistriated muscle antibodies) if previously negative 1, 2

Bedside Testing

• Ice pack test - apply ice over closed eyes for 2 minutes; improvement in ptosis is highly specific for MG flare 2
• Edrophonium chloride test may show unequivocal improvement in strength during acute exacerbation 6, 7

Grading Severity of Flare

The MGFA classification helps determine urgency 3:

• Class I: Ocular symptoms only - hold or adjust medications, may resume treatment if symptoms resolve 1
• Class II: Mild generalized weakness interfering with activities of daily living 1, 3
• Class III: Moderate generalized weakness 3
• Class IV: Severe generalized weakness requiring hospitalization 3
• Class V: Myasthenic crisis requiring intubation - this is a medical emergency 3

Critical Distinction: Myasthenic Crisis vs. Cholinergic Crisis

This differentiation is extremely important as treatment differs radically 8:

Myasthenic Crisis (Undertreated)

• Progressive weakness despite current medication 8
• Requires increased anticholinesterase therapy or immunotherapy 8
• Respiratory compromise from disease progression 1

Cholinergic Crisis (Overtreated)

• Increasing muscle weakness from overdosage of pyridostigmine or other cholinergic drugs 8
• May include muscarinic symptoms: excessive salivation, lacrimation, sweating, abdominal cramping 8
• Requires prompt withdrawal of all anticholinesterase drugs and immediate atropine administration 8
• Can lead to death through respiratory muscle involvement 8

Use edrophonium chloride testing and clinical judgment to distinguish between these two conditions 8

Common Pitfalls to Avoid

• Do not assume stable disease means no monitoring needed - 50-80% of patients with initial ocular symptoms progress to generalized MG, often within 2-3 years 2, 3
• Avoid medications that worsen MG: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 2, 3
• Do not delay respiratory assessment - respiratory compromise can develop rapidly and requires immediate intervention 1, 3
• Recognize that failure to improve on pyridostigmine may indicate either underdosage OR overdosage - increasing the dose blindly can precipitate cholinergic crisis 8

When to Escalate Care Immediately

All grades of MG flare warrant work-up and intervention given the potential for progressive disease leading to respiratory compromise 1:

• Any new or worsening respiratory symptoms 1, 3
• Bulbar symptoms affecting swallowing (aspiration risk) 1, 2
• Grade 3-4 symptoms requiring IVIG (2 g/kg over 5 days) or plasmapheresis 2, 3
• Suspected cholinergic crisis 8