In last week’s ILD conference, we discussed a patient with seropositive RA for whom RA-ILD was suspected.
First, a quick reminder of ILD patterns associated with rheumatoid arthritis (1) from July ILD Round Up:
Dr. Rishi Agrawal mentioned that this patient’s HRCT pattern was most consistent with UIP; however, given this patient’s history of connective tissue disease, “exuberant honeycombing” may be expected, and the lack of any honeycombing was somewhat atypical.
What characteristics are commonly associated with a UIP pattern in patients with CT-ILD, and how might they differ from UIP in a patient with IPF?
A 2018 study (2) looked at patients with UIP with either a diagnosis of IPF or CTD-ILD. Exuberant honeycombing was found in only 6% of IPF patients compared to 22% of patients with CTD-ILD.
While we’re on the subject…what is exuberant honeycombing?
Exuberant honeycombing (3) refers to extensive honeycomb-like cyst formation within the lungs comprising >70% of the fibrotic portions of the lungs.
Finally, we discussed the patient’s prior treatment regimen, which included methotrexate (MTX).
What is the likelihood of methotrexate-associated interstitial lung disease in patients with RA-ILD on methotrexate?
A case-control study (4) looking at the association between MTX exposure and ILD (n=1083 patients) found an inverse correlation between MTX exposure and RA-ILD (OR 0.46: 0.24-0.90, p=0.02). Another meta-analysis (5) of 30 studies with 15000 total patients found no association (RR 1.02: 0.73-1.44) for non-infectious adverse respiratory events with MTX use.
Dr. Carrie Richardson noted that many patients with more severe RA will have already failed therapy with methotrexate for their articular symptoms, which may confound anecdotal reports of ILD associated with MTX use.
Dr. Jane Dematte also mentioned the distinct entity of MTX associated hypersensitivity. This association is well-recognized, with frequency level 5 from Pneumotox profile corresponding to >200 reported cases in the literature.
The actual frequency of occurrence depends on definitional criteria (see figure below) but is likely <1%. Below, see the commonly used Carson Criteria for diagnosis of MTX associated pneumonitis (MTX-P).
Sources:
1. DOI: 10.1183/09059180.00008014 / PMID: 25726549
2. DOI: 10.2214/AJR.17.18384 / PMID: 29140119
3. DOI: 10.1016/j.ejro.2022.100419 / PMID: 35445144
4. DOI: 10.1183/13993003.00337-2020 / PMID: 32646919
5. DOI: 10.1093/rheumatology/kez337 / PMID: 31504978