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Toussirot E, et al. Pulmonary nodulosis and aseptic granulomatous lung disease occurring in patients with rheumatoid arthritis receiving tumor necrosis factoralpha-blocking agent: a case series. Journal of Rheumatology 36: 2421-7, No. 11, Nov 2009 - France 803007550

Pulmonary nodulosis and aseptic granulomatous lung disease: 11 case reports Eleven patients developed pulmonary nodulosis or aseptic granulomatous lung disease during treatment with adalimumab, etanercept or infliximab for rheumatoid arthritis. [See table for patient characteristics.]

Patient characteristics Pt/sex/ age (y)

Druga

Time to onset (m)

Action

Outcome

1/M/70

Infliximab

48

Continued

2/M/57 3/M/74

Adalimumab Infliximab

12 48

Withdrawn Withdrawn

4/F/70 5/M/54 6/F/45

Etanercept Etanercept Etanercept

9 6 24

Withdrawn Withdrawn Continued

7/M/56

Etanercept

13

Withdrawn

8/F/45

Adalimumab

12

Continued

9/M/52

Etanercept

36

Continued

10/M/54

Etanercept

31

Withdrawn

11/M/42

Adalimumab

17

Withdrawn but later restarted

No progression Resolved No progression Resolved Resolved No progression No progression No progression No progression No progression New lesions on rechallenge

a

dosages not stated

Three patients had a history of pulmonary lesions before initiation of anti-TNFα therapy, one patient had a history of pulmonary fibrosis and one patient had vasculitis. Concomitant therapies included methotrexate (patients 3, 5, 10), leflunomide (1, 2, 4, 8, 11), and prednisolone (all patients). Five patients reported asthenia (2, 5), cough (5, 6, 8), dyspnoea (8) or chest pain (7) during anti-TNFα therapy. X-ray or CT scans revealed multiple nodules in ten patients, and hilar adenopathies in patient 7; patients 2 and 10 had cavitated lesions and patient 6 had conflating predominantly apical nodular lesions. Lung biopsies were not performed in patients 2, 8 and 9. However, characteristic rheumatoid nodules were evident in patients 1, 3, 6 and 11, a chronic and granulomatous inflammatory lesion was noted in patient 4, and patients 5 and 10 exhibited granulomatous lesions with central fibrinoid necrosis; in patient 7, a lung biopsy showed noncaseating granulomatous lesion with silica particles. Anti-TNF-α therapy was discontinued in six patients, and maintained in the other five. In most patients, lung nodules did not progress over 2 years of follow-up, and spontaneous resolution of the nodule was observed in patient 2. Nodules resolved in patients 4 and 5 following rituximab therapy. In patient 11, adalimumab was restarted after 6 months and new nodular lung lesions developed [outcome not stated]. Author comment: "We conclude that aseptic and inflammatory pulmonary nodules may appear in patients receiving anti-TNF-agents, and that they correspond to rheumatoid nodules or granulomatous inflammation. These lesions are mainly observed during etanercept therapy, particularly in cases of granulomatous inflammatory disease."

0114-9954/10/1292-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved

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