- Indian Rheumatology association
C Saranya MD, DM
Professor, Department of Rheumatology, Saveetha Medical College and Hospital, Chennai, Tamil Nadu, India.
Patients with interstitial lung disease (ILD) are often referred for rheumatological evaluation to rule out underlying connective tissue disease (CTD). Among them, a subset of ILD patients may have clinical features suggesting an underlying autoimmune process but do not meet established criteria for a defined CTD. These patients are classified as ‘Interstitial Pneumonia with autoimmune features’ (IPAF), a clinical research classification proposed by the European Respiratory Society (ERS) and the American Thoracic Society (ATS) in 2015. This nomenclature ‘IPAF’ has replaced the older terms ‘Undifferentiated CTD-associated ILD’ (UCTD-ILD), ‘lung dominant CTD,’ and ‘autoimmune-featured ILD.’ The concept of IPAF underscores the importance of a multidisciplinary approach, with the rheumatologist playing a central role in diagnosis, monitoring, and management.
The diagnosis of IPAF requires the following mandatory criteria: a) Presence of interstitial pneumonia (via HRCT or surgical lung biopsy); b) Exclusion of alternative etiologies; c) Not meeting the criteria for a defined CTD. Additionally, at least one feature from two of the following domains should be present: clinical, serological, and morphological. The clinical domain encompasses symptoms or signs of autoimmune diseases, including distal digital fissuring (also known as “mechanic hands”), distal digital tip ulceration, inflammatory arthritis, Raynaud’s phenomenon, palmar telangiectasia, unexplained digital oedema, and unexplained fixed rash on the digital extensor surfaces (Gottron’s sign). Rheumatologists play a critical role in identifying these subtle or early signs, which are included in the clinical domain. Many patients with IPAF may have one or more positive serological markers, including antinuclear antibodies (ANA), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), anti-Ro/SSA, anti-La/SSB, and/or myositis-specific antibodies. However, interpretation of these tests is limited by false positives or negatives, necessitating specialist opinion. The expertise of the rheumatologist will help interpret these serological markers in the appropriate clinical context.
Approximately 10–20% of IPAF patients may eventually develop a well-defined CTD. Therefore, once the diagnosis of IPAF is established, it is essential to monitor the disease progression of ILD and the associated autoimmune features. Rheumatologists play a significant role in long-term surveillance by periodically monitoring these patients for the progression of systemic symptoms and ensuring timely reclassification if a defined CTD emerges.
Due to the lack of randomized controlled trials specific to IPAF, treatment strategies are often extrapolated from CTD-ILD studies. Management typically necessitates a collaborative multidisciplinary approach, involving pulmonologists, radiologists, and pathologists, with rheumatologists at the forefront of guiding immunomodulatory therapy. Treatment options include immunosuppressants such as corticosteroids, mycophenolate mofetil, azathioprine, or biologics, especially for patients with predominant inflammatory or autoimmune features. Antifibrotics (e.g., nintedanib) are considered in patients with a usual interstitial pneumonia (UIP) pattern, particularly when they exhibit IPF-like behaviour. Rheumatologists play a crucial role in distinguishing between autoimmune-dominant and fibrotic-dominant ILD patterns, thereby guiding the development of appropriate therapeutic strategies. Additionally, by contributing to clinical research, they help enhance the understanding of this evolving entity.
Some non-specific features, such as alopecia, photosensitivity, oral ulcers, weight loss, sicca symptoms, myalgia, or arthralgia, are not included in the clinical domain. Although ANCA panel positivity has been reported in association with interstitial pneumonia (particularly the UIP pattern), these autoantibodies are not included in the serologic domain because they are typically associated with vasculitides rather than the CTD-ILD spectrum. Regarding the morphological domain, the presence of a radiologic UIP pattern alone is not given credit. Thus, to be considered as having IPAF, a patient with a UIP pattern on HRCT would need to have at least one feature from the other two domains (a clinical feature or a serologic feature) or another morphological feature. Despite the structured criteria for IPAF mentioned above, it is acknowledged that these criteria require validation in prospective studies. As these diseases evolve, this framework can be viewed as a starting point that can be applied uniformly and revisited in the future.
In summary, the role of a rheumatologist is pivotal in various dimensions of IPAF, from the initial diagnosis and comprehensive evaluation to crafting individualised therapeutic strategies and vigilant follow-up of these patients.
