Myasthenia gravis: GP diagnosis and shared care

A condition defined by fatigability

Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder of the neuromuscular junction with an Australian prevalence of approximately 250 per million. The clinical hallmark — fatigable skeletal muscle weakness that worsens with sustained activity and improves with rest — distinguishes MG from most other neurological conditions. Recognition in general practice depends on identifying this diurnal pattern: symptoms worsen as the day progresses and partially recover after rest.

Antibodies target post-synaptic junction proteins: acetylcholine receptor (AChR) antibodies in 80–85% of generalised disease, muscle-specific kinase (MuSK) antibodies in ~5–8%, and LRP4 antibodies in ~1–3%. Antibody sub-type determines prognosis and treatment approach, particularly the role of thymectomy and response to pyridostigmine.

The GP role is two-fold: early recognition with appropriate initial workup and prompt neurology referral, and ongoing shared care including monitoring, immunosuppressant oversight, safety-netting, and crisis recognition. MG Australia is the national patient support and clinical resource body.

A. Core clinical — the AU general-practice framework

Who to consider MG in

MG has a bimodal age distribution: young women aged 20–30 years and older men aged 60–80 years. Overall female-to-male ratio is approximately 3:2. Thymoma is present in 10–15% of cases. Associated autoimmune conditions — thyroid disease (Graves’, Hashimoto’s), type 1 diabetes, systemic lupus erythematosus, Sjögren’s syndrome — occur in ~15% of patients.

Consider MG in any patient presenting with:

• Ptosis (drooping eyelid), often asymmetric, worsening through the day
• Diplopia that is binocular and variable across the day
• Bulbar symptoms — slurred speech that deteriorates with sustained talking, nasal voice, difficulty chewing a full meal, dysphagia with solids or liquids
• Proximal limb weakness — difficulty rising from a chair, climbing stairs, lifting arms above shoulder height
• Respiratory breathlessness, particularly with exercise or when speaking continuously
• Any pattern of muscle weakness that fluctuates and partially recovers after a period of rest

The critical history question is: “Is the weakness worse in the evening than the morning, and better after resting?” Affirmative answers in combination with the above features carry high clinical probability for MG.

Examination findings

The ice pack test is a useful bedside procedure for suspected ptosis: apply a pack of ice wrapped in a thin cloth or gauze over the closed eyelid for 2 minutes; improvement in ptosis ≥2 mm has sensitivity ~80% and high specificity for MG. This is far more practical in an outpatient setting than the historical edrophonium (Tensilon) test.

Further examination:

• Neck flexion strength: weakness of neck flexors is an early and sensitive sign — ask the patient to lift the head off the examination table against mild resistance
• Single breath count: ask the patient to count aloud steadily from one on a single breath; a count below 20 suggests significant respiratory muscle involvement
• Sustained upgaze: increasing ptosis over 60–90 seconds on sustained upward gaze is highly suggestive
• Limb assessment: test proximal power — shoulder abduction, hip flexion — and ask the patient to perform repeated chair rises; reflexes are preserved in early MG

Initial workup

Per eTG Neurology and AMH, GP-initiated investigations for suspected MG:

• AChR-IgG antibody (binding antibody) — first-line; arrange with neurology referral so results are available at the specialist review
• TSH, FBC, electrolytes, CK, vitamin D, B12, HbA1c — exclude contributing comorbidities and screen for associated thyroid disease
• Spirometry (FVC) if any respiratory or bulbar symptoms — MBS item 11506
• Neurology referral for: MuSK and LRP4 antibody testing (if AChR negative), electrophysiology (repetitive nerve stimulation and single-fibre EMG), and CT thymus with contrast (mandatory in all newly diagnosed MG to exclude thymoma)

Urgent same-day review is required if the patient has respiratory distress, a falling breath count, or cannot handle their secretions safely.

Drug history — review at every consultation

The following drug classes can precipitate life-threatening exacerbation and must be avoided or used only with specialist input:

• Aminoglycosides (gentamicin, tobramycin, amikacin) — potentiate neuromuscular blockade
• Fluoroquinolones (ciprofloxacin, moxifloxacin) — commonly prescribed in general practice for urinary tract infections and respiratory infections; check MG status before prescribing
• Beta-blockers (oral and eye drops)
• IV magnesium — including for obstetric eclampsia
• Neuromuscular blocking agents (used in anaesthesia)
• Telithromycin (macrolide antibiotic)
• Botulinum toxin — contraindicated including cosmetic use
• Checkpoint inhibitor immunotherapy (pembrolizumab, nivolumab) — can induce immune-related MG; increasing presentation in oncology patients

Flag this list in the patient’s electronic health record and My Health Record. Alert the dispensing pharmacy to add an alert. Discuss the list directly with patients at diagnosis and at reviews.

B. Treatment and recent advances

Management aligns with international consensus (Sanders Neurology 2021) and eTG Neurology:

Symptomatic therapy: pyridostigmine

Pyridostigmine (Mestinon) 60 mg orally three to four times daily, titrated to effect; maximum ~120 mg per dose. Onset ~30 minutes, duration ~4 hours. Muscarinic side effects — abdominal cramps, diarrhoea, excessive salivation — can be managed with hyoscine butylbromide or loperamide. Pyridostigmine addresses the symptom but does not modify the underlying immune process.

Important: in MuSK antibody-positive MG, pyridostigmine frequently worsens symptoms — titrating upwards if the patient is not improving risks cholinergic toxicity. MuSK MG requires prompt escalation to immunotherapy as the primary treatment.

Cholinergic crisis from pyridostigmine overdose presents with weakness (indistinguishable from myasthenic crisis), miosis, excess salivation, diarrhoea, bradycardia, and fasciculations. If uncertain in a deteriorating patient, withhold pyridostigmine for 24 hours and reassess.

Immunotherapy: corticosteroids

Prednisolone is the cornerstone of disease-modifying treatment. To avoid steroid-induced paradoxical early exacerbation (occurs in ~50% with rapid dose escalation), eTG recommends a gradual introduction: begin at 5–10 mg daily and increase by 5 mg every 3–5 days toward a target of 1 mg/kg alternate-day. Once stable, taper slowly — 5 mg reductions every 2–4 weeks until below 20 mg, then 1–2.5 mg reductions every 4–8 weeks.

Bone protection is mandatory: calcium 1000–1300 mg daily, vitamin D supplementation, baseline DEXA, and bisphosphonate if indicated — see the osteoporosis article. Glycaemic monitoring and mood screening are required throughout.

Steroid-sparing immunosuppressants

Co-initiation of azathioprine (2–3 mg/kg/day) with prednisolone is recommended for generalised MG given the expected prolonged steroid requirement (Palace J Neurol Sci 1998). Check TPMT enzyme activity before starting — low activity predicts haematological toxicity. Monitor FBC and liver function weekly for four weeks then three-monthly. Clinical benefit takes 6–12 months to manifest, so co-initiation with prednisolone is rational from the outset. Mycophenolate mofetil (1 g twice daily) is an alternative with faster onset (~3–6 months).

PBS-funded biologics for refractory disease

Two transformative treatments are now PBS-funded in Australia:

Efgartigimod (Vyvgart) is an FcRn antagonist that reduces circulating IgG including pathogenic AChR antibodies. Given as intravenous infusion weekly × 4 in cycles. The ADAPT trial (Howard NEJM 2022) demonstrated significant improvement in MG activities of daily living score. PBS Authority Section 100 since 2023 for AChR+ generalised MG; eligibility criteria include MGFA class II–IV, documented AChR antibody positivity, and prior failure of conventional immunotherapy.

Eculizumab (Soliris) is a complement C5 inhibitor given intravenously fortnightly. The REGAIN trial (Howard NEJM 2017) demonstrated clinically meaningful improvement in refractory AChR+ generalised MG. PBS Authority Section 100 (Highly Specialised Drugs) since 2019; meningococcal vaccination is mandatory before initiation.

Rituximab (anti-CD20) is first-line treatment for refractory MuSK antibody-positive MG, with dramatic and durable responses documented in the RINOMAX trial (Piehl JAMA Neurol 2022) and multiple case series. For AChR+ MG rituximab is less reliably effective. PBS listing for MG is not formally established — hospital-funded or compassionate access is typically required.

Thymectomy

The MGTX trial (Wolfe NEJM 2016) demonstrated that extended transsternal thymectomy in AChR+ non-thymomatous MG patients aged under 65 significantly improved MGFA status and reduced steroid burden at 3 and 5 years compared with immunotherapy alone. Thymoma requires surgical removal regardless of MG severity. Thymectomy is not indicated for MuSK or seronegative MG. VATS and robotic-assisted thoracoscopic approaches are now standard in major Australian centres.

C. Monitoring and shared care

The GP’s ongoing role in MG is substantial even after neurology initiates treatment:

Routine monitoring:

• GP review 4–8-weekly when initiating or adjusting treatment; 3–6-monthly when stable
• Neurology: 6–12-monthly when stable; sooner if breakthrough symptoms
• Bloods on azathioprine: FBC + LFT weekly × 4, then three-monthly
• Spirometry annually or whenever bulbar or respiratory symptoms change
• DEXA every 2 years on chronic prednisolone
• Annual influenza and COVID-19 vaccination per ATAGI — live vaccines contraindicated during immunosuppression; see immunocompromised patient care
• Mood screen at every review — depression is common given chronic illness and the mood effects of corticosteroids

At every GP consultation:

1. Review the contraindicated drug list before prescribing anything new
2. Confirm MedicAlert bracelet and drug warning card are current
3. Ensure drug-warning documentation is in My Health Record
4. Ask about recent infections, heat exposure, missed medication, or new prescribed medicines
5. Single breath count or brief spirometry if any new respiratory symptoms

GPCCMP care planning: MG qualifies as a chronic neurological condition for the GPCCMP (items 965/967), facilitating direct allied-health referrals — physiotherapy (titrated exercise, respiratory conditioning), speech pathology (bulbar swallow and voice management), occupational therapy (energy conservation, assistive technology, workplace modification), psychology (mood and adjustment disorder), and dietitian (swallow-safe diet for bulbar disease).

Mental Health Care Plan (items 2715/2717): depression and adjustment disorder are common in MG — screen routinely and initiate a plan when indicated.

Driving fitness: ptosis affecting visual fields, diplopia, or significant fatigue affecting reaction time require assessment against Austroads Assessing Fitness to Drive 2022 standards. Refer for a formal occupational therapy driving assessment if uncertain.

D. Australian operations

MBS items:

• GP consultation: 23 / 36 / 44
• AChR antibody (binding): 73529 (neurology-requested)
• EMG / single-fibre EMG: 11018 and related neurophysiology items (specialist)
• Spirometry: 11506
• CT thymus with contrast: 56407
• Case conferencing: 132/133
• Telehealth (existing-relationship rule met by shared care): 91790/91891

PBS (specialist-initiated, GP-continued):

• Pyridostigmine (Mestinon) — Authority Required (Streamlined) for MG
• Prednisolone — General Schedule
• Azathioprine — Authority Required for autoimmune indications
• Mycophenolate mofetil — Authority Required
• Eculizumab — Authority Section 100 Highly Specialised Drugs (2019)
• Efgartigimod (Vyvgart) — Authority Section 100 (2023)
• IVIg — Section 100 BloodSafe via National Blood Authority criteria

NDIS (under 65): significant functional impairment in mobility, communication, or self-care qualifies; neurology and occupational therapy assessments support applications.

Workers’ compensation: employment-impact letters for reasonable adjustments — temperature control (heat worsens MG), rest breaks, voice-rest for bulbar-affected workers — under Fair Work Act and Disability Discrimination Act provisions.

E. Special populations

Pregnancy: MG generally remains stable through pregnancy though exacerbations occur in some patients, particularly in the first trimester and postpartum. Pyridostigmine and low-dose prednisolone are safe throughout pregnancy and during breastfeeding. Azathioprine is used under specialist guidance. Mycophenolate and methotrexate are teratogenic — cease ≥3 months before planned conception and switch to azathioprine with specialist input. IVIg is safe in pregnancy and breastfeeding. Magnesium sulphate — used for obstetric eclampsia — is contraindicated in MG and causes severe neuromuscular blockade; alternative agents are used when eclampsia management is required. Neonatal MG: 10–20% of infants born to mothers with active MG develop transient neonatal MG from transplacental passage of antibodies — feeding and respiratory difficulties in the first 2–4 weeks of life; alert neonatology at delivery planning.

Older adults: older men (60–80 year peak) are more likely to present with thymoma. Polypharmacy risk is amplified — a systematic medicine review at diagnosis and annually screens for aminoglycosides, fluoroquinolones, and beta-blockers. Steroid-related complications (osteoporosis, hyperglycaemia, increased infection risk) require active co-management.

Oncology patients: checkpoint inhibitors (pembrolizumab, nivolumab, atezolizumab) can induce immune-related MG — a clinically distinct entity with potentially more rapid and severe presentation. New ptosis, dysarthria, or limb weakness in a patient on checkpoint inhibitor therapy requires urgent oncology and neurology communication. Arrange same-day review if any respiratory symptoms are present.

Children and adolescents: juvenile MG before puberty is less common; diagnosis and management are specialist-led with paediatric neurology.

When to escalate

Arrange emergency care (call 000) immediately for:

• Respiratory distress at rest, single breath count below 20, FVC falling rapidly
• Bulbar failure — unable to swallow secretions or saliva safely
• Rapid onset or worsening of generalised weakness over hours to days (suspected myasthenic crisis)

Urgent neurology referral within days:

• Newly suspected MG — for antibody confirmation, CT thymus, and electrophysiology
• Breakthrough exacerbation on established immunotherapy
• New prescription of a potentially dangerous drug in an MG patient (if any uncertainty about safety)
• Pre-conception planning in a patient with MG

Routine:

• Annual neurology review for stable shared-care patients
• Immunosuppressant initiation (neurology to prescribe first course)
• Telehealth monitoring reviews for blood results and stable symptom checks

What this article is and is not

This is general health information drawn from eTG Complete Neurology, AMH, MG Australia, the AAN 2020 practice advisory, and the landmark clinical trials cited throughout. It is not personal medical advice and does not create a clinician–patient relationship. Specific management decisions — including immunosuppressant selection, biologic eligibility, and thymectomy — require specialist neurology assessment.

For patient information: HealthDirect — Myasthenia gravis, Better Health Channel, MG Australia.

For life-threatening emergencies, call Triple Zero (000) immediately.

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Sources cited

1. Therapeutic Guidelines (eTG) — Neurology: Myasthenia gravis
2. Australian Medicines Handbook (AMH) — Neurology and immunosuppressant chapters
3. Sanders DB et al. — International consensus guidance for MG: 2020 update (Neurology 2021)
4. AAN — Myasthenia gravis practice advisory 2020
5. Wolfe GI et al. — MGTX randomised trial of thymectomy in MG (NEJM 2016)
6. Howard JF et al. — REGAIN trial: eculizumab in refractory AChR+ MG (NEJM 2017)
7. Howard JF et al. — ADAPT trial: efgartigimod in generalised MG (NEJM 2022)
8. Piehl F et al. — RINOMAX trial: rituximab in MuSK MG (JAMA Neurol 2022)
9. Gajdos P et al. — Plasma exchange for MG (Cochrane 2012)
10. Palace J et al. — Prednisolone + azathioprine vs prednisolone alone in MG (J Neurol Sci 1998)
11. MG Australia — clinical resources
12. National Blood Authority — IVIg criteria for MG
13. ATAGI — Australian Immunisation Handbook
14. Austroads — Assessing Fitness to Drive 2022
15. HealthDirect — Myasthenia gravis
16. Better Health Channel — Myasthenia gravis