The role of lung ultrasound B-lines and serum KL-6 in the screening and follow-up of rheumatoid arthritis patients for an identification of interstitial lung disease: review of the literature, proposal for a preliminary algorithm, and clinical application to cases

Abstract

Screening and follow-up of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) is a challenge in clinical practice. In fact, the majority of RA-ILD patients are asymptomatic and optimal tools for early screening and regular follow-up are lacking. Furthermore, some patients may remain oligosymptomatic despite significant radiological abnormalities. In RA-ILD, usual interstitial pneumonia (UIP) is the most frequent radiological and pathological pattern, associated with a poor prognosis and a high risk to develop acute exacerbations and infections. If RA-ILD can be identified early, there may be an opportunity for an early treatment and close follow-up that might delay ILD progression and improve the long-term outcome.In connective tissue disease–associated interstitial lung disease (CTD-ILD), lung ultrasound (LUS) with the assessment of B-lines and serum Krebs von den Lungen-6 antigen (KL-6) has been recognized as sensitive biomarkers for the early detection of ILD. B-line number and serum KL-6 level were found to correlate with high-resolution computed tomography (HRCT), pulmonary function tests (PFTs), and other clinical parameters in systemic sclerosis–associated ILD (SSc-ILD). Recently, the significant correlation between B-lines and KL-6, two non-ionizing and non-invasive biomarkers, was demonstrated. Hence, the combined use of LUS and KL-6 to screen and follow up ILD in RA patients might be useful in clinical practice in addition to existing tools. Herein, we review relevant literature to support this concept, propose a preliminary screening algorithm, and present 2 cases where the algorithm was used.

Novel Biomarkers, Diagnostic and Therapeutic Approach in Rheumatoid Arthritis Interstitial Lung Disease—A Narrative Review

“…KL-6 might be used as a diagnostic marker in CTD-ILD. According to Oguz et al in a study conducted on 113 CTD patients and 45 healthy controls, median KL-6 readings were significantly higher in the CTD-ILD group [ 44 , 45 , 46 , 47 , 48 ].…”

Serum B-cell activating factor and lung ultrasound B-lines in connective tissue disease related interstitial lung disease

“…Multiple B-lines were a sensitive sign of ILD, even in the subclinical and very early stages (21,24), more B-lines were an indicator of more severe ILD as well (17). LUS's non-invasive, inexpensive, relatively feasible nature make it a tempting target as a screening tool (24,46) or as a tool for follow-up of specific patients (47,48). It could also be used in conjunction with other measurements (e g., with anti-MDA-5 antibody) for prognostic functions in patients with IIM-ILD (20,(49)(50)(51) or to support other measurements such as PFT or HRCT.…”

Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond

“…MUC1 protein levels were elevated on T cells isolated from the joint fluid of a patient with RA ( 352 ). The combination of lung ultrasound and serum MUC1 levels, in addition to current markers, was proposed for screening and following patients with ILD associated with RA ( 353 ). A greater number of RA patients expressed MUC3 protein in synovial lining cells and synovial macrophages compared with normal controls ( 354 ).…”