Rheumatoid Arthritis and Lung Disease: From Mechanisms to a Practical Approach

Abstract

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease characterized by joint inflammation and, in a proportion of patients, extra-articular manifestations (EAM). Lung disease, either as an EAM of the disease, related to the drug therapy for RA, or related to comorbid conditions, is the second commonest cause of mortality. All areas of the lung including the pleura, airways, parenchyma, and vasculature may be involved, with interstitial and pleural disease and infection being the most common problems. High-resolution computed tomography of the chest forms the basis of investigation and when combined with clinical information and measures of physiology, a multidisciplinary team can frequently establish the diagnosis without the need for an invasive biopsy procedure. The most frequent patterns of interstitial lung disease (ILD) are usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), with some evidence for the prognosis being better than for the idiopathic equivalents. Risk factors depend on the type of disease but for ILD (mainly UIP and NSIP) include smoking, male gender, human leukocyte antigen haplotype, rheumatoid factor, and anticitrullinated protein antibodies (ACPAs). Citrullination of proteins in the lung, frequently thought to be incited by smoking, and the subsequent development of ACPA appear to play an important role in the development of lung and possibly joint disease. The biologic and nonbiological disease modifying antirheumatic drugs (DMARDs) have had a substantial impact on morbidity and mortality from RA, and although there multiple reports of drug-related lung toxicity and possible exacerbation of underlying ILD, overall these reactions are rare and should only preclude the use of DMARDs in a minority of patients. Common scenarios facing pulmonologists and rheumatologists are addressed using the current best evidence; these include screening the new patient; monitoring and choosing RA treatment in the presence of subclinical disease; treating deteriorating ILD; and establishing a diagnosis in a patient with an acute respiratory presentation.

Acute Respiratory Events in Connective Tissue Disorders

“…Indeed, there is considerable concern regarding the initiation of treatment for RA with biological, disease-modifying factors in case of an already established lung disease, especially in the case of ILD and bronchiectasis; several experts advise ‘careful counseling and patients' consent regarding the risks and benefits' [30]. The extreme spectrum of the abovementioned acute respiratory events, as well as the ‘vicious' coexistence of most of the aforementioned manifestations where specific treatment for one disease manifestation may be deleterious with regard to a coexistent respiratory manifestation, requires skills, specific diagnostic and therapeutic means, and most of all a multidisciplinary approach of adequately prepared and expert scientists [31]. …”

Pulmonary lymphangitic carcinomatosis with ground‐glass opacities as presentation of prostate cancer

“…Initially, it was difficult to determine the cause of the extensive GGOs because PLC seldom produces extensive, diffuse GGOs in both lungs, and various entities are possible in an immunocompromised rheumatoid arthritis patient, including opportunistic infection, drug‐induced pneumonitis, or rheumatoid arthritis‐associated interstitial pneumonia 5. However, specific abnormalities, such as a thickened interlobular septum and bronchovascular interstitium, suggested perilymphatic‐distributed disease and led to a definitive diagnosis of PLC from undiagnosed prostatic adenocarcinoma without delay, despite the rarity of this condition.…”

The 23-valent pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis: a double-blinded, randomized, placebo-controlled trial

“…Our data are consistent with these previous studies. Although the pathophysiologic mechanism for this finding has not been elucidated, decreased ciliary and respiratory epithelial function seen in patients with interstitial pneumonia may contribute to the higher frequency of pneumonia [30]. …”