When used to treat severe psoriasis and other autoimmune diseases, infliximab is known to cause pulmonary complications, such as increased risk of infection from tuberculosis. Interstitial lung disease (ILD) has also been reported as a complication of antitumor necrosis factor-alpha (anti-TNFα), although the connection is less understood. Moreover, most published reports are about patients with rheumatoid arthritis and preexisting ILD, not psoriasis.
Researchers from Evangelismos General Hospital of Athens in Greece reported on a case of ILD in a patient with psoriasis who was treated with infliximab and who had no history of pulmonary disease.
The patient, a 64-year-old man, presented to the emergency department (ED) with general malaise, fever, persistent dry cough, and progressive exertional dyspnea for 1 week. He had been diagnosed with psoriasis a year earlier and had been treated for depression for the past 2 years. He was started on corticosteroids and cyclosporine for the psoriasis but was switched to 2 weekly intravenous (IV) doses of methotrexate (MTX). The MTX was discontinued due to ineffectiveness, and the infliximab was started. Nine days after the patient’s last MTX dose, the patient received his first IV infusion of infliximab 5 mg/kg. A second infusion of the same dose was given 2 weeks later. One week after that, the patient came to the ED and was admitted to the pulmonary clinic.
On admission, the patient had a respiratory rate of 36 breaths per minute; an arterial blood gas analysis revealed severe hypoxemia and hypocapnia. A chest examination revealed diffuse, inspiratory fine and coarse rales bilaterally. His blood chemistry was significant for increased inflammatory markers, and there were brightly erythematous psoriatic plaques on his trunk, arms, and lower legs. The rest of his physical examination was normal.
Based on the recent infliximab treatment, the low-grade fever, and elevated inflammatory markers, the patient was given broad-spectrum IV antibiotics as well as bronchodilators and furosemide. However, treatment failed to relieve his respiratory condition. The results of an extensive microbiology and immunologic workup were negative. A second thoracic computed tomography (CT) showed the ILD had progressed; a bronchoscopy was performed. Because bronchoalveolar lavage and other testing were negative for malignant cells, common pathogens, Pneumocystis carinii, fungi, and tuberculosis, the clinical team suspected infliximab-induced ILD.
Oral corticosteroid treatment (prednisone 50 mg/d) rapidly improved the patient’s oxygenation, and his symptoms resolved within a few days. One week later, a chest X-ray showed marked improvement. He was discharged on a tapering dose of prednisone. The authors note that in all 4 of the reported cases of infliximab-induced ILD in patients with psoriasis, the patients responded well to corticosteroids.
In the case of infliximab-induced ILD, the symptoms usually appear between 6 weeks and 3 months after infliximab is started, and follow the third infusion. However, the researchers note that ILD has been reported even 1 week after anti-TNFα therapy in other clinical settings, usually after the second or third infusion. In their patient, ILD symptoms appeared only 3 weeks after the first dose. The patient was a smoker, and the authors say possible undiagnosed lung disease should not be ruled out.
Similarly, the researchers say MTX may have played a role. Pulmonary toxicity attributed to anti-TNFα inhibitor usually occurs when the treatment coincides with or follows a course of MTX, which is widely known to cause acute interstitial pneumonitis. This progression has led to the hypothesis that infliximab may exacerbate the pulmonary toxicity of MTX. However, the authors note that a number of cases of anti-TNF-induced ILD have been in patients without MTX treatment. Although there was a strong temporal relationship between their patient’s symptoms and the introduction of infliximab, and the MTX course had been short, they acknowledge that only 9 days elapsed between the last MTX dose and the first dose of infliximab. Involvement of MTX can’t be ruled out in their patient, they add, “because MTX lung toxicity is both unpredictable and poorly understood.”
Infliximab is a wonder drug for patients with plaque psoriasis and psoriatic arthritis when symptoms don’t respond to traditional regimens. However, some patients are at higher risk for ILD, the authors say. Older age, smoking, systemic disease, and concomitant immunosuppressive therapy are all risk factors. Their patient had 3 of those. When deciding whether to start a patient on infliximab, they advise screening for these risk factors. When subclinical ILD is suspected, they advise an initial high-resolution chest CT and pulmonary function tests before starting anti-TNF therapy. Finally, they suggest, instruct patients on infliximab to report any new pulmonary symptoms without delay.