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Case report
Persistent type 2 respiratory failure on background of advanced thymoma with lung metastases
  1. Abrar Munir,
  2. Mohsin Ijaz Khan and
  3. Jason Kah Chun Cheong
  1. Acute Internal Medicine, North Manchester General Hospital, Manchester, UK
  1. Correspondence to Dr Abrar Munir; drabrar786{at}gmail.com

Abstract

We report a patient in her 60s with history of end-stage thymoma with bilateral lung metastases on palliative chemotherapy presented to the hospital with sudden shortness of breath initially treated for probable pulmonary embolism (PE) pending CT of the pulmonary arteries which was subsequently negative for PE. During this admission, she developed transient right-sided facial droop and slurred speech which resolved spontaneously; however, the patient became unresponsive and desaturated with severe decompensated type 2 respiratory failure. Patient was supported with non-invasive ventilation (biphasic positive airway pressure) for few days. Myasthenia gravis was suspected due to clinical features and confirmed by the high titre of acetylcholine receptor antibody titre.

  • respiratory system
  • resuscitation
  • ethics
  • neuromuscular disease
  • endocrine cancer

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Background

Respiratory failure is a significant complication of myasthenia gravis reported frequently during the course of the disease but the first presentation of myasthenic crisis with severe type 2 respiratory failure is sparsley reported in the literature. There is a strong association of thymoma with the myasthenia gravis which is a relatively uncommon disease with an estimated prevalence of 15 per 100,000 populations.1 Although the disease is overall more common in females; however, it has bimodal peaks to the age of onset, the first peak is in the second and third decade with female predominance and a second peak in the sixth to seventh decade with male predominance. Additionally, estimated 30%–50% of patients with thymoma have a concurrent diagnosis of myasthenia gravis.2 It is important to detect the condition early due to the availability of specific treatments for the type of disease including anticholinesterase drugs, immune modulatory/immunosuppressive agents and thymectomy which can improve patient’s quality of life and prognosis.

Case presentation

Patient in her 60s, WHO performance status of 3, body mass index 23, non-smoker, background history of end-stage thymoma, bilateral lung metastases, haemolytic anaemia and aortic stenosis presented to the acute medical unit with increasing shortness of breath. Patient was started on palliative chemotherapy recently and had received one cycle prior to this admission. There were no risk factors associated with pulmonary embolism (PE) except malignancy. Relevant clinical examination including neurological examination was unremarkable except for the requirement of 2 L of oxygen via nasal cannula to maintain oxygen saturations above 94%. Other vital signs were unremarkable.

Patient was initially treated for PE with low-molecular weight heparin pending CT of the pulmonary artery (CTPA). However, CTPA was negative for PE but showed mixed response of lung metastases to palliative chemotherapy. During this admission to the hospital, patient developed acute confusion, transient right-sided facial droop and slurred speech which resolved spontaneously. CT scan of the head was immediately performed for the possibility of stroke; however, it did not show any significant findings.

Subsequently, patient’s condition was deteriorated overnight and showed a low oxygen saturation of 60% on air. Patient was initially started on 15 L of oxygen via non-rebreather mask. Arterial blood gas showed severe type 2 respiratory failure so was switched to non-invasive ventilation (NIV)–biphasic positive airway pressure and was deemed not suitable for intensive care (level 3) due to end-stage cancer on palliative chemotherapy. She was continued on NIV due to persistent type 2 respiratory failure with acidosis for few days.

Investigations

Baseline haematological and biochemical investigations were unremarkable and D-dimer was also negative.

Initial arterial blood gas on admission demonstrated, pH 7.38, pO2 8.8 kPa and pCO2 6.3 kPa on 2 L of oxygen via nasal cannula. Latest chest X-ray showed resolved left lower zone consolidation in comparison to previous chest X-ray (figure 1). ECG showed sinus tachycardia with no acute changes.

Figure 1

Chest X-ray on admission indicating resolving left lower zone consolidation.

CTPA was negative for PE (figure 2) and CT head showed no acute intracranial event or pathology.

Figure 2

CTPA showing no signs of embolism; however, multiple lymph nodes indicative of metastatic disease and an anterior mediastinal mass. CTPA, CT of the pulmonary artery.

Chronologically, serial arterial blood gases during deterioration was as following:

  1. pH 6.94, pCO2 20 kPa, pO2 19.3 kPa, lactate 2.9–15 L oxygen on non-rebreathe mask.

    • Severe respiratory acidosis and type 2 respiratory failure observed so started on NIV.

  2. pH 7.07, pCO2 14.5 kPa, pO2 11.5 kPa, lactate 1.2—after 1 hour on NIV.

  3. pH 7.20, pCO2 11.3 kPa, pO2 9.4 kPa, lactate 1.1—after 2 hours on NIV.

  4. pH 7.37, pCO2 7.4 kPa, pO2 12.5 kPa, lactate 0.9—after 7 hours of NIV.

    • Respiratory acidosis and type 2 respiratory failure improving after starting on NIV, weaning from NIV considered after 24 hours of improvement with following results.

  5. pH 7.20, pCO2 11.3 kPa, pO2 9.4 kPa—after off NIV for 3 hours.

  6. pH 7.27, pCO2 9.6 kPa, pO2 14.8 kPa, lactate 0.7—after restarting NIV for 2 hours.

Patient redeveloped respiratory acidosis and type 2 respiratory failures after attempting weaning off NIV. This pattern persisted for a few days during admission. Patient had frequent episodes of sudden acute type 2 respiratory failures after being weaned off NIV which was suggestive of respiratory muscles weakness leading to the suspicion of myasthenia gravis associated with thymoma.

Antibodies for acetylcholine receptor antibodies, muscle-specific tyrosine kinase (MUSK) antibodies and anti-voltage-gated calcium channel (anti-VGCC) antibodies were also requested considering the suspicion of paraneoplastic syndrome or myasthenia gravis.

The patient was offered the biopsy of lungs lesions and Positron Emission Tomogram (PET) scan but she refused to have any more interventions including PET scan so radiological diagnosis of metastasis was accepted.

Differential diagnosis

Patient was initially treated for PE with low molecular weight heparin. This was based on the history of thymoma, lung metastases, recent chemotherapy, sudden shortness of breath with hypoxia and tachycardia.

Patient’s Well’s score was also 5.5, which was considered moderate risk.

However, D-dimer was negative which has good negative predictive value for PE. However, considering the clinical probability CTPA was requested which was also negative for PE but showed mixed response of lung metastases to chemotherapy

Subsequent differential diagnosis was symptomatic aortic stenosis due to acute shortness of breath with mild bilateral leg swelling. This could indicate early onset heart failure.

Myasthenia gravis was only considered as a differential diagnosis after observing persistent type 2 respiratory failure and respiratory acidosis with patient having a background of thymoma. Neurophysiological studies were not conducted during admission due to patient refusing further investigations despite adequate explanation and consequences. Patient was clearly showing mental capacity to make informed decisions for herself.

Lambert-Eaton myasthenic syndrome was considered due to respiratory failure with neuromuscular weakness but there was evidence of lung metastasis from thymoma on the basis of expert radiological review rather primary small cell lung cancer which has association with Lambert-Eaton myasthenic syndrome. Moreover, MUSK antibodies and anti-VGCC antibodies were negative.

Treatment

Patient was initially given therapeutic dose of low-molecular weight heparin due to clinical probability of PE but was eventually ceased due to negative PE on imaging.

Patient was given oxygen therapy, initially via nasal cannula but was escalated to non-rebreather mask during deterioration. Patient was also started on NIV as above due to persistent type 2 respiratory failure and respiratory acidosis. Patient was decided not for escalation to high-dependency unit (HDU) or intensive care unit (ICU) for intubation and ventilation due to comorbidities, patient’s wishes and a do not attempt cardiopulmonary resuscitation order which was in place for the patient. Patient was also not given empirical treatment for myasthenia gravis, such as steroids or acetylcholinesterase inhibitors due to lack of the confirmation of the diagnosis of on presentation, as advised by the neurologist.

Outcome and follow-up

Discussions with neurologist were carried out during admission due to unclear cause of persistent type 2 respiratory failure. Patient was reviewed by a neurologist during admission while waiting discharge planning, which showed no signs of fatigability and focal neurology. Hence, the neurologist recommended further investigations including nerve conduction studies with repetitive stimulation, to confirm the diagnosis of myasthenia gravis. The risk–benefit was explained and patient eventually decided not to be investigated due to long-term outcome, considering the comorbidities and disturbance in the quality of life.

The complexity of the case was discussed in the multidisciplinary team meeting and considering the frailty, advanced malignancy and poor physiological reserve decided that repeated NIV will not improve patient’s quality of life and only resulted in patient being uncomfortable wearing NIV for long duration. This was discussed with the patient and patient agreed for symptom relief with controlled home oxygen. Subsequent discussions were also made with oncologist that chemotherapy would be discontinued if patient’s performance status declines and would be discussed in future outpatient clinic. Patient was then discharged home with home oxygen and no further follow-up.

The result of the antibodies was not known till few weeks postdischarge due to sample being assayed in a specialised laboratory unit. Acetylcholine receptor antibodies were found to be positive at 6.58 nmol/L (normal range <0.44 nmol/L) with MUSK antibodies and anti-VGCC antibodies being negative.

The results were related to the patient postdischarge. Discussion was again made whether patient would still consider further investigations and management of myasthenia gravis. Patient decided once again not to undergo further investigations and additional treatment. She would prefer to preserve her current quality of life.

Discussion

Myasthenia gravis is an autoimmune condition characterised by the production of autoantibodies which affect the neuromuscular junction, causing muscle fatigability.3 Myasthenia gravis can generally be classified into ocular or generalised, type of antibody specificity, age of onset and whether the thymus is affected.4 Ocular myasthenia gravis only affects the ocular muscles, causing subsequent ptosis and diplopia without other further motor symptoms whereas generalised myasthenia gravis can potentially affect any skeletal muscles of the body.

Most patients generally develop ocular symptoms initially before progressing to generalised myasthenia gravis. However, our patient did not complain of any visual or ocular symptoms. There was only a single spontaneously resolved episode of slurred speech and facial droop prior to isolated type 2 respiratory failure. There have been previously few reports of isolated type 2 respiratory failures as the initial presentation of myasthenia gravis.5–9 Myasthenia gravis was then suspected due to unexplained type 2 respiratory failure with background of metastatic malignant thymoma. As mentioned above, 30%–50% of patients with thymoma can present with symptoms and signs of myasthenia gravis at any point in time.

The most lethal complication of myasthenia gravis is weakness of muscles of ventilation, such as the intercostal muscles. This would reduce patient’s respiratory effort and lead to type 2 respiratory failure. Ideally, patient’s vital capacity and tidal volume should be monitored with spirometry to indicate potential myasthenia crisis, whereby worsening muscle weakness leading to intubation and ventilation.10 However, our patient was not for escalation to HDU/ICU and only for ward-based care.

Acetylcholine receptor antibodies have been proven to be first-line investigation for myasthenia gravis.11 It has shown to have a sensitivity of 80%–90% in patients with proven myasthenia gravis. Other antibodies can be measured such as MUSK antibodies for seronegative myasthenia gravis or anti-VGCC for Lambert-Eaton myasthenic syndrome to rule out paraneoplastic syndromes. Nerve conduction studies with repetitive stimulation are able to assist in diagnosis.

Anticholinesterases and immunosuppressant therapies such as steroids and disease-modifying antirheumatic drugs are generally used first-line for generalised myasthenia gravis to relieve symptoms of weakness.12 Intravenous immunoglobulins and plasma exchange are only used in emergency situations such as myasthenic crisis. Thymectomy is also recommended for patients who are below the age of 45 years and acetylcholine receptor antibodies positive due to association of thymus pathology with myasthenia gravis.11

Our patient was not suitable for thymectomy due to comorbidities and metastatic disease. Patient was undergoing palliative chemotherapy for symptom relief and delay in disease progression. Our patient was also not started on any medical treatment for myasthenia gravis due to patient refusing further investigations and management. However, patient is highly suspected of the disease due to clinical features, investigations and exclusion of other potential common causes.

Learning points

  • Always consider and think about neuromuscular diseases in patients with persistent type 2 respiratory failure.

  • Myasthenia gravis can present as isolated type 2 respiratory failure without ocular symptoms or other muscle weakness.

  • Myasthenia gravis can present in patients with thymus pathology, such as thymoma, thymus aplasia or atrophy.

  • Always involve the patient in discussions regarding their own condition and allow the patient to decide on further investigations and treatment.

References

Footnotes

  • Contributors AM and MIK worked for the planning and conduct of the case report. MIK and AM worked for the reporting and JKCC for the conception of the design of case report. MK and JKCC worked for the acquisition of the data and AM has done the critical analysis of the data interpretation and reporting.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.