Bronchiolar disorders in systemic autoimmune rheumatic diseases

Abstract

Pulmonary manifestations of systemic autoimmune rheumatic diseases (SARDs) may involve the large and small airways, lung parenchyma, pleura, respiratory muscles and thoracic cage. Bronchiolar disorders (BDs) or small airways disease (SAD) are common and may sometimes be the dominant presentation in patients with SARDs. We conducted a literature review using search terms "bronchiolitis," "small airway diseases" and the names of individual SARDs and collated relevant articles published between January 1977 and April 2024. A summary of the incidence/prevalence, clinical manifestations, pathogenetic mechanisms, pulmonary function testing, chest imaging, histopathology and treatment options for BDs associated with SARDs is provided in this review. BDs associated with Sjögren syndrome, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, idiopathic inflammatory myositis, mixed connective tissue disease and ankylosing spondylitis are specifically highlighted.

FIGURE 1

Literature search and review methodology. A literature review was conducted using two electronic databases (PubMed and Scopus) as outlined in the flow diagram. Search terms included: ((“small airway* disease*” OR “small airway* dysfunction*” OR “small airway* disorder*”) OR (“bronchiolar disease*” OR “bronchiolar dysfunction*” OR “bronchiolar disorder*” OR “bronchiolitis”)) AND (“connective tissue disease*”) OR (“systemic autoimmune rheumatic disease*”). Search terms for individual connective tissue diseases (CTDs) were “Sjögren's syndrome” OR “SS,” “rheumatoid arthritis” OR “RA,” “systemic lupus erythematosus” OR “SLE,” “idiopathic inflammatory myositis” OR “IIM,” “mixed connective tissue disease” OR “MCTD,” “ankylosing spondylitis” OR “AS” were also applied. We captured relevant articles published between January 1977 and April 2024. Titles and abstracts of screened papers were assessed for data relevant to our topic. To be eligible for inclusion, articles were English language, available for full-text access and focused on bronchiolar disorders involving any of the systemic rheumatologic diseases. A full-text review of eligible publications and their bibliography was performed, with additional references retrieved.

FIGURE 2

Transbronchial biopsy demonstrating histopathology of constrictive bronchiolitis (as shown in a) and follicular bronchiolitis (as shown in b and c). a) Constrictive bronchiolitis is characterised by peribronchiolar fibrosis (arrow), with fibroblast proliferation beneath obliterated respiratory epithelium. The interstitium surrounding alveoli are infiltrated by chronic inflammatory cells and scattered fibroblasts (arrowhead). b) Follicular bronchiolitis is characterised by lymphoid aggregates surrounding small airways (arrow) with extension to local alveoli (arrowhead). c) Lymphoid follicles in follicular bronchiolitis surround an alveolus causing architectural distortion without significant fibrosis.

FIGURE 3

a) 77-year-old female, diagnosed with rheumatoid arthritis-associated bronchiolitis. High-resolution computed tomography demonstrates bronchial thickening (white arrow) and diffused centrilobular nodules with tree-in-bud pattern (black arrows), as shown in a) and c). Centrilobular nodules are better emphasised on maximum intensity projection images at the same level as shown in b) and d).

FIGURE 4

A 68-year-old female, diagnosed with systemic sclerosis-associated bronchiolitis. Chest computed tomography demonstrates mosaic attenuation (white arrowheads) and diffuse centrilobular nodules (black arrows), as shown in a) and d). Mosaic attenuation is more pronounced on expiratory phase images at the same level (b and e). Centrilobular nodules are better emphasised by maximum intensity projection (c and f).