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Case history

image A 62-year-old woman was referred by her GP with an abnormal chest X-ray performed for non-productive cough that failed to resolve following antibiotic treatment. She was an ex-smoker (30 pack-year history) and had a medical history of eczema and hypertension. Medication included ramipril 2.5 mg/day and hydrocortisone 1% cream. A CT scan revealed a right upper lobe lung cancer with metastases in the left lung, liver and adrenals. Bronchoscopy confirmed adenocarcinoma; epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS-1 receptor tyrosine kinase were all negative; 40% of cells demonstrated programmed death-ligand 1 (PD-L1) positivity. Her WHO performance status was 1. Treatment with palliative pembrolizumab, pemetrexed and carboplatin was begun on the basis of evidence from the KEYNOTE-189 trial (ClinicalTrials.gov NCT02578680), which demonstrated improved progression-free and 1 year overall survival with the addition of the programmed cell death protein 1 (PD-1) antibody pembrolizumab to chemotherapy in patients with non-squamous cell lung cancer.

During the first four cycles her only side effect was fatigue, her cough resolved and a CT scan showed a good response to treatment. On cycle 5, day 15, she contacted the oncology hotline complaining of increased shortness of breath and diarrhoea. She was immediately brought to the oncology day unit for assessment. Her diarrhoea had settled spontaneously, having occurred for a 24 h period after eating a takeaway. She was now struggling to climb one flight of stairs and had developed a productive cough. Observations showed reduced oxygen saturation (89%) and low-grade pyrexia (37.7°C). Chest X-ray showed increased opacification in the right lower lobe and reduction in the right upper lobe mass. Blood tests showed increased inflammatory markers (white blood cell count 15 × 109/l, C-reactive protein [CRP] 1142.9 nmol/l) and incidental hyponatraemia (125 mmol/l).

She was admitted for treatment with intravenous amoxicillin and further investigation. The next day her oxygen saturation was normal and repeat blood tests showed resolution of the inflammatory markers. Her sodium level was now 118 mmol/l, with a stage 1 acute kidney injury (AKI) (urea 15 mmol/l, creatinine 150 μmol/l). Clinically she was euvolaemic. Repeat measurement of osmotic concentration showed a decrease in serum concentration from 290 to 240 mmol/kg, an increase in urine concentration from 380 to 500 mmol/kg and a normal random cortisol value. The tests indicated syndrome of inappropriate antidiuresis (SIAD), rather than hypoadrenalism. Fluid restriction led to an increase in her sodium levels by 2–3 mmol/l per day.

Two days later she developed sudden shortness of breath and her oxygen saturation dropped to 80%. A CT pulmonary angiogram showed no pulmonary embolus but bibasal pulmonary fibrosis. She was started on methylprednisolone 2 mg/kg per day and transferred to intensive care but was too unwell for a bronchoscopy. On day 2 of intensive care, her oxygen requirement continued to increase: her steroids were continued and she was given infliximab 5 mg/kg per day. Despite the increase in immunosuppressant therapy she died of respiratory arrest 24 h ...

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