Oct. 09, 2026
Patients with connective tissue disease (CTD), such as rheumatoid arthritis, can develop interstitial lung disease (ILD).
According to a review in Mayo Clinic Proceedings, ILD is present in approximately 40% of patients with CTD, although prevalence varies widely by the underlying CTD.
CTD-ILD can progress slowly over several years or rapidly over a short period. It is one of the leading causes of morbidity and mortality in people with CTD.
For example, the same review reports that five-year mortality is three times higher in patients with rheumatoid arthritis and scleroderma who also have ILD. These findings underscore the importance of early recognition, continuous monitoring and timely referral when disease progresses.
Early diagnosis and appropriate treatment of CTD-ILD are essential to improving long-term outcomes. Management starts with identifying which CTD is driving the lung disease.
"There are many different types of connective tissue disease, each of which can have very different treatment implications," says Eva M. Carmona Porquera, M.D., Ph.D., a pulmonologist specializing in ILD and director of the ILD and Familial Pulmonary Fibrosis Clinic at Mayo Clinic in Rochester, Minnesota.
ILD can develop in the following CTDs:
- Idiopathic inflammatory myositis.
- Mixed connective tissue disease.
- Rheumatoid arthritis.
- Scleroderma.
- Sjogren syndrome.
- Systemic lupus erythematosus.
- Systemic vasculitis.
Multidisciplinary evaluation when autoimmune features are subtle
In some patients, the diagnosis is straightforward: A patient presents with an established CTD and classic clinical symptoms and imaging. Other times, patients present with lung symptoms but no classic symptoms of autoimmune disease.
When classic features are absent, patients at Mayo Clinic undergo a thorough evaluation that includes:
- Assessment to rule out other causes of lung damage or autoimmune disease.
- High-resolution chest CT scan to define ILD pattern.
- Serological testing to identify autoimmune biomarkers.
A multidisciplinary team of experts from pulmonary, pathology, rheumatology and radiology interprets the results. The team determines the proper diagnosis, treatment approach and monitoring plan.
Treatment options are highly variable and depend primarily on the underlying CTD. Monitoring is very important and may include follow-up pulmonary function testing and imaging when clinically indicated.
These cases often hinge on subtle distinctions that can be difficult to resolve in isolation. "Multidisciplinary review allows us to integrate the clinical, radiologic, pathologic and rheumatologic findings and arrive at the most accurate diagnosis and treatment approach," Dr. Carmona Porquera says.
Some patients present with autoimmune features but do not meet the criteria for a specific CTD. They are often diagnosed with interstitial pneumonia with autoimmune features (IPAF). This classification describes an overlap between idiopathic interstitial pneumonia and CTD. Currently, its optimal management remains unclear.
In some cases, familial pulmonary fibrosis (FPF) masquerades as IPAF or even CTD. Patients may have some positive antibodies but not the full clinical spectrum of a rheumatologic disease.
A patient mistakenly diagnosed with CTD or IPAF may receive immunosuppressants for an autoimmune process the patient doesn't have. At the same time, the patient is unaware of the cancer risks, comorbidities, familial implications and transplant considerations associated with FPF.
"The only way to know is by suspecting it and testing," Dr. Carmona Porquera says. In these cases, patients follow the same referral path described earlier: referral to the Genetic Testing and Counseling (GTAC) Unit for telomere length and genetic testing.
When referral changes CTD-ILD management
Mayo Clinic's multidisciplinary team specializes in differentiating CTD-ILD from other diagnoses. Experienced clinicians can help referring physicians evaluate and manage patients with suspected CTD-ILD.
Dr. Carmona Porquera recommends referral for patients with CTD-ILD, particularly when the disease is progressing, is not responding to treatment or is severe.
"The most challenging cases require collaboration," Dr. Carmona Porquera says. "Our referring physicians are essential partners — not only in helping us deliver the best care for individual patients but also in advancing our understanding and treatment of these diseases."
For more information
Mira-Avendano I, et al. Interstitial lung disease and other pulmonary manifestations in connective tissue diseases. Mayo Clinic Proceedings. 2019;94:309.
Refer a patient to Mayo Clinic.