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Leflunomide-induced lung injury that developed after its withdrawal, coinciding with peripheral blood lymphocyte

Takeshi Otsuka¹, Takako Koyama, Ryoko Ohtani

¹Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. tootsuka@munakata-med-hp.gr.jp

Modern Rheumatology

|December 28, 2007

Summary

Leflunomide (LEF) can cause severe lung injury in elderly rheumatoid arthritis patients, even after discontinuation. Careful monitoring is crucial for at least one month post-treatment, especially in those with pre-existing lung conditions.

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Area of Science:

Rheumatology
Pulmonology
Pharmacology

Background:

Rheumatoid arthritis (RA) management often involves disease-modifying antirheumatic drugs (DMARDs).
Leflunomide (LEF) is an effective DMARD, but its safety profile requires careful consideration, particularly in specific patient populations.
Elderly patients with pre-existing conditions like lung fibrosis may face unique risks associated with LEF therapy.

Observation:

A 60-year-old female RA patient with lung fibrosis developed acute lung injury 25 days after a brief 12-day course of LEF.
Clinical presentation included fever, dyspnea, elevated C-reactive protein, and characteristic chest CT findings of ground-glass opacities and consolidations.
High plasma levels of A771726, the active LEF metabolite, persisted post-discontinuation, correlating with the lung injury.

Findings:

The patient's lung injury was directly linked to persistent high levels of leflunomide's active metabolite, A771726.
Treatment with pulsed steroids and cholestyramine successfully depleted A771726, leading to clinical recovery.
Peripheral blood lymphocyte counts and serum albumin levels showed dynamic changes consistent with the onset and recovery from drug-induced lung injury.

Implications:

Leflunomide poses a significant risk of severe lung injury in elderly patients with pre-existing interstitial lung disease.
Extended monitoring for at least one month after leflunomide withdrawal is essential in this high-risk group.
This case highlights the importance of considering drug metabolite kinetics and patient-specific factors in managing potential adverse drug reactions.