Abstract

BackgroundMethotrexate has been implicated in a variety of lung complications, one of which is hypersensitivity pneumonitis. Hypersensitivity pneumonitis most often occurs within the first year of starting low-dose orally administered methotrexate. We present a case of methotrexate-induced hypersensitivity pneumonitis after 30 years of methotrexate use, which is the first case to be reported so far.Case presentationA 77-year-old African American woman with a history of rheumatoid arthritis presented with progressively worsening shortness of breath and nonproductive cough. She was on a daily dose of 2.5 mg of methotrexate that had been orally administered for the last 30 years. A physical examination was significant for fever of 38.2 °C (100.8 °F), tachycardia, bilateral basal crackles, and oxygen saturation of 88% on room air. A laboratory work up was significant for normal white blood cell count, increased eosinophil count of 18.3%, and erythrocyte sedimentation rate of 111 mm/hour. Sputum cultures were negative for any bacterial pathogens including acid-fast bacilli. Influenza and respiratory syncytial viral infection were ruled out. A (1-3)-B-D-glucan assay (Fungitell®) was within normal limits. Pulmonary embolism was ruled out and echocardiography was normal. A chest X-ray showed hazy opacity with prominent reticulation within the upper lung fields bilaterally, right greater than the left with no pleural effusion. Lung computed tomography revealed nonspecific bilateral upper lung opacification. A pulmonary function test was significant for no obstruction, normal maximum voluntary ventilation, and no restriction, with mildly decreased diffusion. Methotrexate was stopped, and our patient was started on prednisone 60 mg orally administered daily with dramatic clinical and radiologic improvement.ConclusionsMethotrexate-induced hypersensitivity pneumonitis usually occurs in the initial few weeks to months of starting treatment with methotrexate; however, it can occur late during therapy too, and prompt diagnosis is crucial as it is a reversible condition when diagnosed early.

Highlights

  • Methotrexate has been implicated in a variety of lung complications, one of which is hypersensitivity pneumonitis

  • Methotrexate-induced hypersensitivity pneumonitis usually occurs in the initial few weeks to months of starting treatment with methotrexate; it can occur late during therapy too, and prompt diagnosis is crucial as it is a reversible condition when diagnosed early

  • Our patient presented with shortness of breath of less than 8 weeks’ duration associated with a nonproductive cough, an oxygen saturation of less than 90% on room air, with leukocyte count of less than 15,000, a positive radiographic finding, and negative initial blood and sputum cultures

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Summary

Conclusions

Our case report shows that hypersensitivity pneumonitis has been reported to occur after initial weeks or months of starting the medications, it can occur even after 30 years of use. Clinicians should be aware of this fact and keep hypersensitivity pneumonitis in their differential diagnosis as it is a reversible disease if diagnosed early. There are no definite diagnostic criteria for establishing the diagnosis of MTX-induced lung toxicity, the best approach would be to combine the clinical, laboratory, and radiologic findings together to have an appropriate management plan. This would include ruling out acute infections, a trial of MTX discontinuation, and treatment with high-dose steroids, especially when a patient is not severely sick. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

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