Myasthenia gravis screening

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Keanu Ngo[2]

Screening

Population-based screening for asymptomatic myasthenia gravis (MG) is not recommended. The clinically relevant screening performed after MG is diagnosed consists of evaluation for thymoma, associated autoimmune disease, and safety risks before immunosuppressive therapy.

Thymoma screening

Chest imaging to exclude thymoma is considered mandatory in all patients with confirmed MG, regardless of antibody status, age, or ocular versus generalized phenotype. This recommendation is based primarily on expert consensus and observational evidence rather than randomized trials.

Approximately 10–20% of patients with MG have a thymoma. Detection of thymoma changes management because thymoma generally requires surgical evaluation.

• Chest CT is the standard initial imaging study. Non-contrast CT is a reasonable initial approach because available evidence indicates comparable sensitivity for thymoma detection. Whether iodinated contrast exacerbates myasthenic weakness is controversial: one retrospective study reported more acute (within 1 day) exacerbations after contrast CT (6.3% vs 0.6%), whereas other data found no meaningful excess and attributed worsening to alternative causes. The American College of Radiology (ACR) does not consider MG a clear contraindication and advises against withholding contrast when it is clinically indicated. Because non-contrast CT has comparable sensitivity for thymoma, it is a reasonable initial study and conveniently avoids this uncertainty.
• MRI aids differentiation of thymic malignancy from thymic cyst or hyperplasia and may be preferred over CT for this purpose, potentially avoiding unnecessary thymectomy. Chemical-shift and diffusion-weighted techniques are particularly useful for equivocal thymic masses. MRI is also an appropriate alternative when iodinated contrast is undesirable.
• Thymoma is strongly associated with AChR-antibody-positive MG and is very uncommon in MuSK-positive or seronegative MG; nevertheless, chest imaging should not be omitted on the basis of antibody status.
• Imaging can identify a thymic mass but cannot reliably establish thymic hyperplasia as a histologic diagnosis. A radiologic report of "thymic hyperplasia" should therefore be interpreted cautiously.
• Thymic hyperplasia occurs in both MG and Graves disease and therefore should not be used by itself to distinguish the two conditions.
• Thymoma may be missed on initial imaging. In a patient who has not undergone thymectomy, new or worsening myasthenic symptoms should prompt consideration of repeat imaging when clinically appropriate.

Associated autoimmune disease

MG frequently coexists with other autoimmune disorders, particularly thyroid disease. Baseline thyroid function testing should be obtained at diagnosis. Thyroid autoimmunity is present in approximately 10% of patients with MG, overt thyroid dysfunction in approximately 7%, and thyroid antibodies in approximately 20–30%.

Thyroid dysfunction may contribute to or aggravate ocular and generalized symptoms. Thyroid function should be reassessed in a previously stable patient with unexplained clinical worsening, particularly when ocular findings change.

Additional autoimmune or paraneoplastic disorders should be evaluated according to the clinical context. Patients with thymoma-associated MG may warrant particular attention to associated autoimmune conditions and paraneoplastic syndromes.

Extrathymic malignancy screening

Emerging population-based data suggest an increased prevalence of extrathymic neoplasms among patients with MG, largely associated with thymoma rather than AChR antibodies alone.

There is currently no established guideline recommendation for routine extrathymic malignancy screening in all patients with MG. In higher-risk patients, particularly older males and those with thymoma, clinicians may consider heightened malignancy vigilance, including age-appropriate evaluation and clinically directed intrathoracic imaging, dermatologic examination, and CBC. Prospective validation is lacking.

Pre-immunotherapy safety screening

Before initiating corticosteroids or nonsteroidal immunosuppression, baseline testing should identify latent infections and factors that affect treatment safety and monitoring.

Recommended baseline assessment includes:

• CBC with differential, serum creatinine, and liver function tests for baseline assessment and subsequent treatment monitoring.
• Latent tuberculosis testing with a tuberculin skin test or interferon-gamma release assay before immunosuppression.
• Hepatitis B screening; patients with hepatitis B core antibody positivity receiving rituximab require appropriate viral monitoring.
• HIV testing in patients age 65 years or younger and in older patients with relevant risk exposures.
• Pregnancy testing when clinically applicable in people of childbearing potential.
• TPMT activity before azathioprine, when available. Absent TPMT activity is a contraindication to azathioprine, while reduced activity warrants dose reduction because of increased risk of severe myelotoxicity.
• Vaccination status review before immunosuppression.
• For anticipated long-term corticosteroid therapy, assess baseline metabolic and bone health, including glucose, blood pressure, and osteoporosis risk.

Screening summary

• Do not screen asymptomatic populations for MG.
• Obtain chest imaging in every patient with confirmed MG to evaluate for thymoma, regardless of antibody status or clinical phenotype.
• CT is an appropriate initial chest imaging study; non-contrast CT may be preferred when avoidance of iodinated contrast is desirable, while MRI can provide additional tissue characterization and may help avoid unnecessary thymectomy.
• Iodinated contrast is not a clear contraindication in MG; the relationship between contrast administration and MG exacerbation remains controversial.
• Check thyroid function at diagnosis and reassess thyroid function when previously stable patients develop unexplained worsening.
• Evaluate additional autoimmune disorders according to clinical context.
• Before immunosuppression, perform infection, hematologic, renal, hepatic, vaccination, and treatment-specific safety assessment.
• Consider heightened vigilance for extrathymic malignancy in selected higher-risk patients, but recognize that routine screening is not yet established.