What exactly is IPAF?

IPAF, or Interstitial Pneumonia with Autoimmune Features, is a condition where individuals show Interstitial Lung Disease (ILD) alongside signs of autoimmunity. Unlike Connective Tissue Disease-related ILDs (CTD-ILDs), IPAF patients do not meet all the criteria for a definite Connective Tissue Disease (CTD). This means while they show lung disease and autoimmune markers, they are not easily classified into existing CTD categories.

How is IPAF diagnosed?

The 2015 classification, established by the American Thoracic Society and the European Respiratory Society, defined IPAF. To be diagnosed with IPAF, a patient must meet specific criteria: they must show ILD on imaging or biopsy, all other causes of ILD must be excluded, they must not meet the criteria for a defined CTD, and they must have at least one feature from two of these domains: clinical, biological, or morphologic.

Why is IPAF significant?

IPAF is important because it represents a specific group of patients with overlapping lung and autoimmune issues who don't fit neatly into established diagnostic categories like CTD-ILDs. Recognizing IPAF helps physicians create tailored treatment plans, which are essential as CTD-ILDs have a more favorable prognosis than conditions like Idiopathic Pulmonary Fibrosis (IPF). The importance lies in accurate classification for better patient care and outcomes.

What are the different domains used in diagnosing IPAF?

The clinical domain looks at the physical signs and symptoms, such as Raynaud's phenomenon or arthritis. The biological domain evaluates the patient's blood work, specifically focusing on autoimmune markers like antinuclear antibodies (ANA). The morphologic domain assesses the patterns of lung damage seen on imaging, such as CT scans, or histological analysis from a lung biopsy, looking for features like Nonspecific Interstitial Pneumonia (NSIP), Organizing Pneumonia (OP), or Lymphoid Interstitial Pneumonia (LIP).

What is the future of IPAF?

While the IPAF classification is a crucial step forward, research continues to refine the criteria and understand the long-term impacts of this condition. Some clinicians suggest that additional clinical signs should be included. The prognostic implications of IPAF are still under investigation. The ongoing research and personalized care are aimed at better understanding the disease and improving treatment strategies for patients with this complex condition.

Lungs intertwined with autoimmune symbols, representing IPAF.

Decoding IPAF: When Lung Disease Mimics Autoimmunity

Beau Callahan in Health & Wellness December 2025 • 3 min read.

"Understanding Interstitial Pneumonia with Autoimmune Features (IPAF) for Better Diagnosis and Care"

Interstitial lung diseases (ILDs), also known as diffuse parenchymal lung diseases (DPLDs), can sometimes overlap with autoimmune conditions, creating diagnostic challenges. One such overlap is seen in Interstitial Pneumonia with Autoimmune Features (IPAF), where patients exhibit lung disease alongside autoimmune markers but don't meet the criteria for a defined connective tissue disease (CTD). This article unpacks the concept of IPAF, its diagnostic criteria, and what it means for treatment.

Recognizing a potential connective tissue disease in ILD cases is crucial because the prognosis and treatment approaches differ significantly. Connective tissue disease-related ILDs (CTD-ILDs) often have a more favorable prognosis compared to idiopathic pulmonary fibrosis (IPF), and treatment typically involves corticosteroids and immunosuppressants.

Sometimes, lung involvement is the first sign of an underlying CTD, highlighting the importance of thorough clinical evaluation for autoimmune features in ILD patients. These features are more commonly found in women under 50. Imaging and histological findings, such as nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), or lymphoid interstitial pneumonia (LIP), can also suggest an underlying CTD.

What Defines IPAF? The 2015 Classification

Lungs intertwined with autoimmune symbols, representing IPAF.

In 2015, the American Thoracic Society and the European Respiratory Society proposed new criteria to standardize the definition of IPAF. This was an attempt to better characterize this patient group and facilitate research into their long-term prognosis.

The diagnosis of IPAF requires:

Presence of ILD on imaging (CT scan) or surgical lung biopsy.
Exclusion of other known causes of ILD after careful evaluation.
Absence of sufficient criteria for a defined connective tissue disease.
Presence of at least one feature from two of the following domains: clinical, biological, or morphologic.

Let's break down these domains:

The Future of IPAF: Research and Personalized Care

While the IPAF classification is a step forward, questions remain about the exhaustiveness and relevance of the criteria. Some clinicians argue that other clinical signs, such as esophageal dysmotility or muscle weakness, should be included. Additionally, the prognostic implications of IPAF are still being studied.

Current treatment for IPAF is not standardized and is tailored to the individual patient, considering clinical, imaging, biological, and histopathological findings. Multidisciplinary discussion is essential to determine the best approach.

Ultimately, the IPAF classification helps standardize the definition of a distinct entity from IPF and CTD-related ILDs. Further research is needed to refine the criteria, evaluate long-term prognosis, and guide therapeutic interventions, leading to more personalized and effective care for patients with IPAF.