https://orcid.org/0009-0007-7313-5773
Abstract
Myasthenia gravis (MG) is a rare autoimmune neuromuscular disorder characterised by varying degrees of skeletal muscle weakness. Diagnosing MG represents a challenge for clinicians due to the diversity of disease manifestations. We present an unusual case of this disease in an older gentleman in which the patient reported swollen tongue and lips which was incorrectly diagnosed and treated as angioedema. Months later, he developed progressive dysphagia, dysarthria and weight loss. The diagnosis was further delayed by the identification of a hiatal hernia and Zenker’s diverticulum after extensive investigation for dysphagia. A total of 15 months on prompted by persistent symptoms, the patient was found to have MG by positive antibody test and Electromyogram. Treatment was initiated which led to a rapid and significant relief of his symptoms.
Key Points
Because of the variability in symptoms, a high index of clinical suspicion is required to make the diagnosis of MG.
MG can present with tongue and lip swelling in the setting of bulbar and facial weakness.
Delayed diagnosis of MG can have severe implications with an increased likelihood of deterioration and risk of myasthenic crises.
MG can cause significant morbidity, especially in older people, but treatment carries a good prognosis which underscores the importance of prompt diagnoses.
In new onset bulbar weakness, neuromuscular causes such as MG should be considered early as a differential diagnosis.
Case report
A 72-year-old male patient was admitted to the emergency department (ED) with symptoms of tongue and lip swelling, dysphagia and slurred speech for over 1 year. The patient symptoms started 15 months before presentation with lip and tongue swelling suspected to be allergy related or angioedema. Patient had no urticaria, previous allergies or identifiable triggers. He was treated with multiple courses of steroids and antihistamines with no improvement in symptoms. Patient was referred to allergy clinic, and investigations for angioedema were all negative. C1 esterase inhibitor activity (C1 INH) 0.35 g/l (normal 0.19–0.39), complement C4 0.32 g/l (normal 0.14–0.54) and mast cell tryptase 6 ng/ml (normal 2–14).
In addition to the ongoing symptoms, 4 months later he developed a combination of dysphagia and dysarthria. First, he had difficulty swallowing solids, which later progressed to liquids. For evaluation of dysphagia, he was referred to Gastroenterologist and ear, nose and throat (ENT) specialist. Oesophagogastroduodenoscopy (OGD) and 2 barium swallows were performed which diagnosed incidental hiatal hernia and Zenker’s diverticulum. He also had oesophageal dilatation for the latter. Over a 6-month period, he had gone to the ED on two occasions, despite the presence of dysphagia, treated as angioedema with Intravenous steroids and antihistamine. His symptoms persisted and were progressive which necessitated his last admission.
His medical history is of prostatic hypertrophy, hypertension, osteoarthritis, obstructive sleep apnoea and a 3-year history of a squint in his left eye. On direct questioning, he reports difficulty with closing his eyes fully. He has not otherwise had issues with dyspnoea, limb weakness or gait abnormality. The review of other systems was not significant. On examination, the patient had swollen lower lip (Figure 1), partial left ptosis, divergent squint on the left eye, bilateral facial weakness with reduced eye and lip closure, reduced tongue strength but no obvious tongue swelling. His speech is slurred, with nasal voice quality. Further neurological examination was consistent with normal motor, sensory and cerebellar functions.
Clinical Photography (A) demonstrating swelling of the lower lip (B) demonstrating resolution of the lower lip swelling after treatment.
CT scan of the brain was normal. Following a neurology review, diagnosis of Myasthenia gravis (MG) was made and commenced on Pyridostigmine 60 mg four times a day and prednisolone gradually up titrated to 35 mg daily. The patient showed a drastic improvement after 1 day of commencing pyridostigmine. Repetitive nerve stimulation of a right median nerve, right accessory nerve, left facial nerve showed significant decrement consistent with neuromuscular junction defect. Acetylcholine receptor antibodies were found to be strongly positive 12.73 nmol/l (normal < 5). CT Thorax was done, which demonstrated no evidence of thymoma.
On discharge, dysphagia has improved significantly. He was able to tolerate a normal diet. Lower lip swelling, left eye ptosis and bilateral facial weakness all improved. On follow-up 7 months post discharge, his symptoms have not worsened and no recurrence of lip swelling. He was able to commence steroid sparing agents Azathioprine.
Discussions
MG has a wide spectrum of manifestations, from mild extraocular muscle weakness to life-threatening generalised weakness, which possess a challenge in reaching a diagnosis. It is especially more difficult in older people with co-morbid illnesses, non-specific symptoms that are easily missed such as voice change, ocular symptoms and when these symptoms are identified there is a long list of differentials [1]. Misdiagnosis of MG could lead to unnecessary diagnostic and therapeutic interventions [2]. Our patient had a total of five primary care visits, two ENT visits, two Gastroenterology visits, three ED visits, one allergy specialist visit, one OGD, two Barium swallows and one oesophageal dilatation.
Bulbar weakness is a recognized entity of MG seen in ~20%. Tongue swelling subjective/objective has been previously documented as a feature of MG usually associated with bulbar weakness [3, 4]. But this is the first case where patient has persistent lip swelling in the setting of MG. This could be because of concurrent lower facial weakness leading to a protrusion of the lower lip. On the other hand, we also considered whether the presence of the lip swelling was due to a co-morbid pathology. In the first instance common causes of angioedema were excluded such as medication induced, hereditary angioedema (normal C4 and C1 INH). It is possible to have idiopathic acquired angioedema (AAE) in association with other autoimmune disorders, however AAE is not expected to present for the first time at this age group [5]. Moreover, patient did not show any response to initial steroid or antihistamine treatment. Sustained improvement in symptoms occurred only after commencing anticholinesterase where both weakness and angioedema resolved.
Declaration of Conflicts of Interest
None.
Declaration of Sources of Funding
None.
Declaration of Consent
Written informed consent for publication of clinical details and images was obtained from the patient.
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