Myasthenia Gravis: Other associations

Thymoma

• Most common anterior mediastinal mass in adults (50%)
• Paraneoplastic syndromes
• Myasthenia gravis
• Isaac's syndrome
• Pure red cell aplasia
• Acquired hypogammaglobulinemia
• Cushing syndrome
• Alopecia
• Pseudo-obstruction
• Rx pyridostigmine
• Antibody vs 66 kDa rat brain antigen (CV2)
• Autonomic neuropathy
• Hypercalcemia
• Pemphigus
• Encephalopathy
• Types:
• Noninvasive thymoma
• Almost all are > 25 years old
• Most common: 5th to 6th decade
• Calcification in 5-20%
• Invasive thymoma
• Metastasis to pleura and lungs (6%); rarely extrathoracic
• Thymic tumors & MG
• Frequency
• 10% to 15% of MG patients
• Mostly in patients > 30 years
• Anti-AChR antibodies
• 95% to 100% in patients with MG
• Increased incidence with thymoma without MG
• Clinical implications. A computed tomography scan of the thorax should be performed to look for a thymoma in MG patients aged 20 and above. MRI examinations of the chest are more expensive and not clearly superior. Thymic hyperplasia may be present in up to 80 percent of MG patients, most prominently in younger age groups. This association has therapeutic implications as thymectomy may promote long-term clinical improvement of MG in patients under 50 - 55.

Anti-striational antibodies

• MG - adult-onset
• Age related
• All MG patients: 30%
• < 20 years: Rare; Association with graft-versus-host disease
• > 60 years: 55%
• Thymoma and MG: 75% to 80%
• Thymoma without MG: 24%; Rise in titer may suggest tumor recurrence
• Progressive rise in titer: May indicate thymoma recurrence
• Other disorders
• Thymoma without MG: 24%
• Autoimmune liver disorders
• Target antigens: Varied
• Titin : Antibodies vs. 30 kD fragment
• 70 % sensitive for thymoma
• Almost 100% specific for thymoma
• Actinin
• Ryanodine receptor

Other antibodies

• Anti-nuclear antibodies: ? more common in MG patients with thymoma.
• Anti-thyroid (microsomal & thyroglobulin) and anti-parietal cell antibodies
• Not clearly associated with thymoma
• More common in ocular MG

Systemic disorders

• Thyroid: Disorders in ~ 15% of MG patients
• Hyperthyroidism more common than hypothyroidism
• Both can exacerbate MG
• Thyroid testing: Always indicated in MG workup
• Other autoimmune disorders: Increased incidence
• Rheumatoid arthritis
• Lupus erythematosus
• Polymyositis
• Pernicious anemia
• Laboratory screening: As indicated by signs in individual patients

Genetic Associations¹, ²

Acetylcholine receptor

• AChR a subunit: HB*14
• Dinucleotide CA-repeat
• Located in 1st intron of gene
• Present in ~ 20% of antibody + MG patients
• Stronger association when HLA: DQA1*0101 ± DQA1*0501

HLA

• DR3
• + MG; female; Early onset; Thymic hyperplasia
• DQA1 Domain 1: - All MG
• DQB1 Domain 2: - Early onset; Thymic hyperplasia
• DQB1 Domain 3: + All MG
• DQB1: Position 57 amino acids
• Alanine
• +: Early MG onset
• Valine
• -: Early onset & thymic hyperplasia
• +: Thymoma
• Asparagine & Serine: No associations

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9/4/97

1. J Neuroimmunol 1996;65:125-131
2. J Autoimmunity 1997;10:407-413