Rheumatoid Nodules and Lung

Among the pulmonary manifestations of rheumatoid arthritis (RA), rheumatoid nodules (RN) are frequent even if mostly asymptomatic. They are generally peripheral and different for sizes (up to 8 centimeter in diameter) and number (one or more). RN can be a consequence of RA or of the drugs used for RA. In the first case, they usually appear in patients with more aggressive and seropositive longstanding RA and are often associated with cutaneous RN. Methotrexate, leflunomide, azathioprine among the disease-modifying anti-rheumatic drugs (DMARDS) and etanercept among "biological" ones are the more frequent responsible drugs. RN induced by drugs are histologically identical to non-drugs-induced RN. In these cases, drug withdrawal is the first therapeutic choice. Differential diagnosis with other causes of pulmonary nodule is imperative, especially when RN is the first clinical manifestation of RA and serum levels of rheumatoid factor (RF) and/or anti-citrullinated peptides antigens (ACPA) are in the normal ranges. Cancer (primitive or metastatic) and infectious diseases represent the main diagnostic dilemma. The exclusion of neoplastic or infectious causes is particularly important in the course of immunosuppressive therapy for RA. As highlighted by some authors, bronchogenic carcinoma can grow on RN and RN can be associated with metastatic nodules or infectious nodules in the lung, but these are outstanding events. Percutaneous biopsy or thoracotomy remain the gold standard for diagnosis especially when high-resolution computed tomography (HRCT) or positron emission tomography (PET) -CT features and laboratory tests are not conclusive.