Rheumatoid arthritis (RA) is a systemic, autoinﬂammatory disorder deﬁned by its characteristic attack on the diarthroidal joints. It affects approximately 1% of the adult U.S. population, with a two-to-one female pre-dominance. When compared with the general population, overall mortality is increased, with the median survival decreased by 1 decade. A signiﬁcant portion of the clinical impact of the disease is attributable to its extraarticular manifestations (ExRAs). ExRAs are common, the prevalence of clinically “severe” ExRA ranging up to 40%, and are dominated by cardiac, vascular, and pulmonary disorders.
Up to one-third of RA patients have respiratory symptoms, and up to two-thirds have chest imaging changes. Physiologic impairment occurs less frequently, but when present, it is a poor prognostic sign. Because the medications used to treat RA have been described to cause both direct pulmonary toxicity as well as increase the risk of infectious complications, both respiratory infection and drug-induced lung disease should always be considered in patients with new respiratory symptoms or signs. A large group of direct RA complications is also well recognized. These complications can be approached anatomically because they can affect all the compartments of the chest both in isolation or collectively.
RA can cause upper, lower, and distal airway disease. Arthritis of the cricoarytenoid joints, rheumatoid nodules of the upper airway, and vocal cord paresis all occur. Radiographic bronchiectasis has been described in up to one-third of patients, but clinically important disease appears much less frequently. Small airway disease with physiologic obstruction is common and presents with dyspnea, a nonproductive cough, or wheezing. Imaging with high-resolution computed tomography (HRCT) demonstrates centrilobular nodules, hyperinﬂation, and heterogeneous air trap- ping. Pathologically, both ﬁbrosing (obliterative or constrictive bronchiolitis) and cellular (lymphocytic, follicular, and diffuse panbronchiolitis) types of small airways disease can be seen. Pleurisy, pleuritis, and effusions occur in approximately 5% of patients and may be the most common symptomatic intrathoracic manifestation of the disease. The effusions may precede, accompany, or follow the onset of joint involvement. Despite the preponderance of women with this disease, rheumatoid pleural effusions are more prevalent in men. They tend to be small and asymmetric and to wax and wane. Pleural ﬂuid analysis generally reveals a low glucose level (<50 mg/dL), low pH (<7.30), high lactate dehydrogenase (LDH) level (>1000 IU/L), and high rheumatoid factor. When identiﬁed, effusions should not be assumed to be RA associated; empyema, sterile empyema, chylothorax, and congestive heart failure are all seen, but a ﬁbrothorax with its physiologic restriction and trapped lung are rare. Isolated, pulmonary hypertension caused by a primary vasculopathy is exceedingly rare, but capillaritis or alveolar hemorrhage can occur. Rheumatoid (necrobiotic) nodules are found in up to 20% of patients, typically range from millimeters to centimeters in size, are usually asymptomatic, and can ﬂuctuate in size over time. However, they can cavitate and be complicated by pneumothorax, hydropneumothorax, sterile empyema, and hemoptysis. Nodules identiﬁed on high-resolution computed tomography (HRCT) must be distinguished from malignant and infectious lesions. Caplan syndrome refers to conglomerations of nodules seen in patients with RA and pneumoconiosis.
Symptomatic interstitial lung disease (ILD) has been described in 10% of subjects, but prospective studies using HRCT have shown speciﬁc features of ILD in up to two-thirds. Similar to what is seen with pleural disease, ILD may precede, accompany, or follow the onset of joint involvement. Although all of the pathologic patterns described in the idiopathic interstitial pneumonias (usual interstitial pneumonia [UIP], nonspeciﬁc interstitial pneumonia [NSIP], organizing pneumonia, diffuse alveolar damage [DAD]) have been described in RA, unlike most other connective tissue diseases, on surgical lung biopsy a UIP pattern is more common than the NSIP pattern. The DAD pattern (i.e., Hamman-Rich syndrome), is quite uncommon but is impressive with its presentation as rapid and progressive respiratory failure that frequently results in death.