What is IPAF? Save

Janet Pope, MD, MPH, FRCPC

Sep 26, 2025 8:00 am

Idiopathic Interstitial Pneumonia with Autoimmune Features - or IPAF - describes patients with interstitial pneumonia with autoimmune features, but they don’t meet a diagnosis of a CTD.

Classification criteria (2015 ERS/ATS):

Interstitial pneumonia on HRCT or lung biopsy.
Exclusion of alternative diagnoses (drug side effect, environmental diagnosis, etc.).
Don’t have full criteria for a CTD.
At least one feature from ≥2 of 3 domains:

Clinical domain: extrathoracic features like Raynaud’s, arthritis, mechanic’s hands.
Serologic domain: positive autoantibodies, e.g., ANA ≥1:320, anti-CCP, anti-Ro, etc.
Morphologic domain: HRCT/biopsy patterns like NSIP, OP, LIP, or multi-compartment involvement.

IPAF:

Is not a disease, but a research framework
Has a heterogeneous prognosis – oOutcomes vary depending on ILD pattern:
- UIP pattern → like IPF it has a poor prognosis.
- NSIP/OP patterns → acts more like CTD-ILD (better prognosis, may respond to immunosuppression).
May become CTD-ILD –10–20% eventually have a CTD diagnosis
Therapeutic uncertainty – No standardized treatment, so Rx is often related to the pattern, severity and what the IPAF seems to behave like (ex dermatomyositis, SSc, etc)
There is debate on whether there should be a category called IPAF:

too broad/heterogeneous, diverse clinical trial population, can’t predict response to Rx, vs.
may help in understanding suspected autoimmune ILD and you can’t predict the response to Rx of even classifiable ILD, and most trials have diverse populations even within an established disease (ex. SSc)

IPAF vs CTD-ILD vs IPF

	CTD-ILD	IPAF	IPF
Underlying disease	Established connective tissue disease (RA, SSc, myositis, etc.)	No CTD dx, ≥2 domains suggest autoimmunity (clinical/serologic/morphologic)	None
Criteria	Meets ACR/EULAR classification criteria for CTD + ILD	2015 ERS/ATS IPAF classification (IP + ≥2 domains)	ATS/ERS IPF guidelines (UIP pattern, exclude other causes)
Autoantibodies	+Ab disease-specific (anti-Scl70, anti-Jo1, anti-CCP, etc.)	May be present, but no CTD dx	Usually absent
HRCT/histology	NSIP, OP >UIP, LIP	Any of NSIP, OP, UIP, LIP	UIP
Prognosis	Better than IPF Varies by CTD And pattern, extent	Intermediate: – UIP poor like IPF – NSIP/OP better (like CTD-ILD)	Poor, median survival ~3–5 years
Treatment	Immunosuppression (mycophenolate, cyclophosphamide, rituximab, etc.) Antifibrotics if Progressive pulmonary fibrosis	Depends on pattern NSIP – immune suppression UIP pattern Rx like IPF	Antifibrotics (nintedanib, pirfenidone) Nerandomilast (when approved)

Terms:

CTD-ILD autoimmune established CTD with lung involvement.
IPF = idiopathic fibrotic lung disease, UIP pattern only.
IPAF = autoimmune features but no defined CTD