Methotrexate

Author Information

An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 48-year-old woman developed COVID-19 respiratory infection while receiving methotrexate for rheumatoid arthritis. Additionally, she experienced rebound effect in the form of anti-neutrophil cytoplasmic antibodies (ANCA) associated-vasculitis following discontinuation of methotrexate.

The woman, who had a history of rheumatoid arthritis, hypertension developed Covid-19 infection while receiving methotrexate 15mg every week treatment [route not stated] along with unspecified Janus kinase inhibitor for rheumatoid arthritis.

Hence, the woman's methotrexate treatment was discontinued on her positive covid-19 test results. Her COVID-19 respiratory infection presentation included non-specific symptoms of dry eyes. Six weeks later, she presented to hospital with shortness of breath, troubled speaking due to rapid breathing, dry cough, body aches and diarrhoea. Five weeks after stopping immunosuppression, she was treated with azithromycin and amoxicillin/clavulanic acid for community-acquired pneumonia, acute kidney injury and keratoconjunctivitis, which thought to be the early manifestation of vasculitis. On admission, physical examination revealed tachycardia and respiratory distress with a respiratory rate of 40–50 breaths/min, and non-invasive positive pressure ventilation (NPPV) by biphasic positive airway pressure bi-level positive airway at 80% FiO2 was required. Chest X- ray revealed diffuse bilateral pulmonary airspace disease concerning for severe pulmonary oedema with a possibility of COVID-19 respiratory infection. CT angiogram of the chest confirmed severe bilateral airspace opacities with air bronchograms, findings concerning for severe pulmonary oedema, with superimposed pneumonia and/or acute respiratory distress syndrome. Her respiratory acidosis worsened on NPPV, and she was intubated and transferred to intensive care unit. This time her nasal swab for SARS-CoV-2 was negative. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) confirmed diffuse alveolar haemorrhage (DAH). Serology screening confirmed perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) titre of 1:320 with anti-myeloperoxidase (MPO) antibody level of 81.5 U/mL. Initially, sepsis due to pneumonia, COVID-19 relapse, vasculitis and overlap syndrome were suspected, but microbial screening results were negative. She was initiated on unspecified glucocorticoid therapy for DAH, and continuous renal replacement therapy for anuric acute kidney injury with refractory acidosis. Renal biopsy, which revealed pauci-immune glomerulonephritis, confirmed diagnosis of microscopic polyangiitis (MPA). Based on her vasculitis disease activity, she was then continued with steroids, and initiated on plasma exchange therapy, rituximab and regular haemodialysis. During a follow-up visit after discharge, she showed gradual improvement in her conditions with remission in vasculitis disease activity, and her rheumatoid arthritis was also managed well.