Pulmonary rheumatoid nodules (PRN) occur in 20%−25% of rheumatoid arthritis (RA) patients and can lead to complications.1 Disease-modifying antirheumatic drugs (leflunomide, methotrexate) and antitumour necrosis factor α (anti-TNFα) have been implicated in their development.2,–,4 The immunopathological characteristics of PRN are quite distinct from those of subcutaneous nodules with the presence of B lymphocytes expressing CD20 in the periphery.5 We therefore decided to assess the efficacy of rituximab (RTX) in patients with PRN using data from the French AutoImmunity and Rituximab/Rheumatoid Arthritis registry.6 Of the 10 patients studied, all but one (n 8) were positive for rheumatoid factors and anticitrullinated protein antibodies (anti-CCP). Five patients had a history of smoking: two were active smokers (n 2, 3), and three past smokers (n 5, 7, 9). All patients had previously received anti-TNF and been screened for tuberculosis according to French recommendations.7 When PRN were discovered, diagnosis was made in six patients by histological examination. In the other four, tuberculosis had been ruled out by bronchoalveolar lavage and tuberculosis spot. However, one patient was treated as having pulmonary tuberculosis without improvement of PRN. In all patients, RTX was started because RA was active (disease activity score 5.6±1.91). Six patients also had active lung involvement under TNF blockers (discovery of PRN n=4, worsening n=2). Infusion of 1 g of RTX on days 1 and 14 was performed. All patients had a CT scan before (1.6±1.4 months) and after (11.5±8.2 months) the first infusion of RTX. Rereading of the scans was carried out centrally (AR) and the number and size (long axis in millimetres) of the nodules were determined (concordance correlation coefficient of the reader 0.998 and reproducibility SD<0.001).

After a mean follow-up of 12.8±9.3 months, 19 PRN were observed versus 26 before treatment (table 1, figure 1). No new nodule appeared while patients were receiving RTX. The decrease in mean size of the nodules (15.04±8.05 mm vs 9.8±10.02 mm) was highly significant in the whole group (p<0.001) and remained so after the exclusion of a patient (patient 8) in whom the PRN had disappeared (14.7±8.9 vs 12.69±9.65 mm; p<0.04). In this patient (n 8), who had had an rheumatoid factors and anti-CCP negative RA for 10 years, anti-TNF therapy had been interrupted 18 months before RTX. There was an improvement in RA activity in six of the seven assessable patients in whom there was an improvement in PRN nodules.

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Figure 1

Outcome after three cycles of rituximab (RTX) (patient 7).

All patients in the study had been treated previously with anti-TNF, which in six patients was associated with the appearance of PRN or an increase in their size. Nineteen cases of increased size or appearance of PRN under TNF-blockers have been reported.4 In five cases, TNF blocker was continued without any progression of the nodules. TNF blocker was discontinued in 14 patients, and in the 12 assessable cases the nodules disappeared in three patients, regressed in one and remained stable in eight. Six of these 14 patients had RTX treatment with subsequent disappearance or improvement of the nodules.2 ,8 ,9 RTX was also successful in one patient who had never received TNF blocker.10 In our study, time from anti-TNF discontinuation until the first RTX infusion was 2.6±1.6 months. It is possible that the favourable evolution in our observation was due to withdrawal of anti-TNF treatment. However, this hypothesis seems improbable since 70% of our patients improved whereas only 30% of patients reported in the literature had a favourable evolution after stopping anti-TNF.2 The probable efficacy of RTX is supported by the presence of B lymphocytes in the periphery of the PRN, which suggests the role of B cells in this RA-related extra-articular involvement.