Double trouble: clinical phenotype of a young patient with myasthenia gravis and positivity for both AChR and MuSK antibodies

Abstract

Case Presentation: A 26-year-old woman presented at age 15 with binocular diplopia, fluctuating bilateral ptosis, and dysphonia. Over the following 3-4 months, she developed progressive dysphagia with intermittent nasal regurgitation of liquids and weight loss. At age 20, she experienced a major event of pulmonary aspiration, complicated with pneumonia, facial weakness and acute respiratory failure, requiring orotracheal intubation and, due to difficult weaning from mechanical ventilation, a subsequent tracheostomy. Neurological exam demonstrated persistent right ptosis, bilateral ophthalmoparesis, and a triple-furrowed tongue, with no cervical or appendicular weakness. Treatment with pyridostigmine, prednisone and methotrexate was ineffective, while azathioprine induced an adverse cutaneous rash. Repeated serological assays confirmed simultaneous positivity for both muscle-specific tyrosine kinase antibody (anti-MuSK) and acetylcholine receptor antibody (anti-AChR) antibodies. Chest computed tomography showed no evidence of thymoma. Therapy with rituximab allowed corticosteroid weaning and significant symptomatic relief, reducing the Myasthenia Gravis Composite score from 8 to 0 points within 3 months of initiation. Discussion: Specific autoantibodies for myasthenia gravis (MG) not only define the diagnosis but also serve as biomarkers predicting expected clinical phenotypes and treatment responses. The patient developed prominent features of both anti-MuSK (e.g., bulbar weakness, tongue atrophy) and anti-AChR (ocular involvement) subtypes, with a relative preservation of other muscle groups. Her symptoms were refractory to standard therapies for anti-AChR MG, such as acetylcholinesterase inhibitors and corticosteroids, improving only after introduction of an anti-CD20 monoclonal antibody. This presentation aligns with other case reports suggesting double-positive MG patients predominantly exhibit an anti-MuSK clinical profile. It also highlights the relevance of adequate testing for both AChR and MuSK antibodies, when disease does not progress as expected for a specific autoantibody phenotype or does not respond to optimal treatment. Final Comments: The coexistence of AChR and MuSK antibodies in MG is a rare phenomenon, with distinct clinical features and a challenging treatment. Clinicians should suspect double-positivity when a patient has a previous positive serological assay for anti-AChR or anti-MuSK but does not exhibit a typical phenotype or becomes refractory to standard therapies, requiring a more comprehensive serum autoantibodies profiling.