title: Exacerbation of myasthenia gravis with voriconazole.
abstract: BACKGROUND
  We describe a patient with stable generalized myasthenia gravis who presented with new onset severe ophthalmoplegia and ptosis after initiation of voriconazole for aspergillosis.
  
  
  METHODS
  Ligand-protein docking software was used to simulate the interaction of voriconazole with the acetylcholine receptor (AChR). We tested voriconazole binding to AChR in comparison to high affinity and neutral compounds.
  
  
  RESULTS
  There was no clinical improvement after intravenous immunoglobulin infusion and plasmapheresis. However, the patient improved slowly after withdrawal of voriconazole. Based on our results, voriconazole binds favorably to AChR and may putatively block muscle nicotinic AChRs. Other theoretical explanations include blocking potassium channels and reducing their intracellular trafficking.
  
  
  CONCLUSIONS
  The mechanisms involved in ocular exacerbation may be multi-factorial, reflecting the intricate dynamics of the neuromuscular junction. It is important to consider medications that harbor pyridine or pyrimidine moieties as potential causes of exacerbation in myasthenic patients, especially those who present with ocular symptoms.
authors.affiliation: Neuromuscular Center, Department of Neurology and Neurological Institute, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, Ohio 44106-5098, USA.
authors.forename: Raed
authors.initials: R
authors.lastname: Azzam
authors.forename: Aasef G
authors.initials: AG
authors.lastname: Shaikh
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serra
authors.forename: Bashar
authors.initials: B
authors.lastname: Katirji
mesh_terms: D000935:Antifungal Agents / Q000009:adverse effects*; D001228:Aspergillosis / Q000188:drug therapy; D001763:Blepharoptosis / Q000139:chemically induced* / Q000150:complications; D003198:Computer Simulation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000150:complications*; D009886:Ophthalmoplegia / Q000139:chemically induced* / Q000150:complications; D011743:Pyrimidines / Q000009:adverse effects*; D014230:Triazoles / Q000009:adverse effects*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole