A group of international rheumatologists has urged caution over the use of  ‘preclinical’ or ‘subclinical’ to describe non-symptomatic interstitial lung disease in RA patients, saying the definitions fail to adequately convey the heightened risk of disease progression and mortality.

In fact, the group said it advocates that all patients with RA and an incidental ILD diagnosis should be monitored for ILD progression whether symptomatic or not, to ensure appropriate disease management while new guidelines are awaited.

As yet there is no consensus on the clinical meaning of preclinical or subclinical ILD in RA patients, and as such these terms are currently used to categorise patients who have early, mild or asymptotic forms of the disease.

“These varying definitions not only create semantic confusion but they also cultivate the misconception that preclinical or subclinical ILD is a non-worrisome feature of rheumatoid arthritis when, in fact, it is associated with a 3 times higher risk of mortality compared with people with normal lung imaging in a study among smokers with rheumatoid arthritis”, they wrote, in an article in The Lancet Rheumatology.

There are also key, inherent limitations to assessing ILD symptoms in RA patients, the authors point out.

These include variable symptoms related to interstitial changes, and also challenges in determining the presence of respiratory symptoms in patients when the extra-pulmonary manifestations of RA might themselves restrict exercise tolerance, thus making an underlying lung issue more difficult to detect.

“Unless careful probing of past and current physical activity is performed, physicians might erroneously label these patients as asymptomatic,” the authors noted.

RA patients can also falsely link their dyspnoea to deconditioning or mobility issues as opposed to lung disease, while ILD symptoms such as cough can be attributed to other causes such as reflux or post-nasal drip, they said.

Further adding to the complexities surrounding the appropriate management of these patients, it remains unclear whether the outcomes with ‘preclinical’ or ‘subclinical’ RA associated ILD differ significantly from those of clinical ILD related to RA.

Both RA and ILD activity have been identified as “independent predictors of survival in rheumatoid arthritis associated ILD”, while patients with less extensive ILD can still experience respiratory infections and acute exacerbations, which contribute to hospital admissions and mortality in patients with RA-associated ILD, they noted.

“It is therefore conceivable that some patients with rheumatoid arthritis diagnosed with preclinical or subclinical ILD could potentially have worse outcomes if both the rheumatoid arthritis and ILD are not monitored closely,” said the group, which included Professor Paul Emery, a Consultant Rheumatologist at The Leeds Teaching Hospitals NHS Trust.

As such, while new clinical practice guidelines on autoimmune ILD are being developed, and the outcome of ongoing clinical trials it the area are awaited, all patients with RA and ILD on high-resolution CT should undergo monitoring for disease progression with assessments on symptoms, physiology and radiological changes.

“There is undoubtedly a future for precision medicine in rheumatoid arthritis-associated ILD but, first, we must ensure that all patients with rheumatoid arthritis-associated ILD receive appropriate ILD management”, the authors stressed.