Oct. 09, 2026
Interstitial lung disease (ILD) presents diagnostic and treatment challenges for pulmonologists. The same radiographic pattern can result from very different underlying diseases.
For example, a fibrotic pattern may be seen in autoimmune disease, genetic disease, environmental exposure, drug toxicity or idiopathic pulmonary fibrosis. A granulomatous pattern may be associated with infection, sarcoidosis, granulomatous-lymphocytic interstitial lung disease (GLILD) and other conditions.
"All of these diseases can be very tricky to diagnose," 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. "You have to consider the whole clinical picture — the patient, their symptoms, environmental exposures, comorbidities and other relevant factors. This helps guide the right diagnostic testing, understand both the nature and severity of the disease, and ultimately answers the question: Is this really fibrosis?"
An incorrect or incomplete diagnosis can lead to inappropriate treatment, missed extrapulmonary disease and unrecognized hereditary risk. Because the stakes are high, Mayo Clinic pulmonologists perform a comprehensive assessment of every patient and partner with referring physicians to ensure continuity of care.
While the ILD landscape is broad, Mayo Clinic pulmonologists highlight three areas where the field is advancing: sarcoidosis, precision medicine in ILD diagnostics and antifibrotic therapy, and connective tissue disease-associated interstitial lung disease (CTD-ILD).
Diagnosing sarcoidosis: Looking beyond the lungs
Sarcoidosis is a rare inflammatory disease that causes granulomas to accumulate in different parts of the body. Because it frequently affects the lungs and lymph nodes in the chest, doctors classify sarcoidosis as ILD.
The disease can mimic metastatic cancer on imaging. "A PET-CT scan tends to show very extensive lymphadenopathy, and that can be confused for malignancy," Dr. Carmona Porquera says.
A biopsy that reveals granulomatous inflammation typically prompts a diagnosis of sarcoidosis.
However, that finding should prompt a broader differential diagnosis.
"Just because you find granulomas, it doesn't always mean the diagnosis is sarcoidosis," Dr. Carmona Porquera says. It could possibly be disseminated tuberculosis, histoplasmosis or another infection. Clinicians should exclude these other possibilities before establishing a diagnosis of sarcoidosis.
Even after establishing a sarcoidosis diagnosis, the evaluation should not stop at the lungs. Because sarcoidosis is a systemic disease, clinicians should assess for involvement of other organs, particularly when extrapulmonary disease could have important implications for treatment or prognosis. Some organ involvement may be clinically silent yet still carry a risk of significant complications, making systematic assessment important even in the absence of symptoms.
Dr. Carmona Porquera recalls the case of a young woman who presented for preoperative evaluation for a heart valve that needed to be replaced. She had an established sarcoidosis diagnosis in the lungs that did not require treatment.
During her evaluation at Mayo Clinic, Dr. Carmona Porquera identified recurring eye symptoms indicative of ocular sarcoidosis and palpitations concerning heart involvement.
"Sarcoidosis in the eye can lead to blindness, and this was a patient in her 20s," she says. Recognizing the urgency behind the symptoms, Dr. Carmona Porquera immediately consulted her ophthalmology colleagues and scheduled a same-day ophthalmology appointment.
The patient also was evaluated for cardiac sarcoidosis and directed to the cardiac sarcoidosis clinic to complete her evaluation and treatment before her valve replacement surgery.
Deciding when sarcoidosis needs treatment
Diagnosis is only the first step. Determining whether to treat sarcoidosis is another challenge.
For many asymptomatic patients, monitoring for disease progression or complications is preferable to immediate treatment. "Steroids and other treatments have side effects, and sometimes the side effects can be worse than the disease itself," Dr. Carmona Porquera says.
Clinicians should consider treatment when sarcoidosis causes symptoms, such as:
- Heart palpitations or arrhythmia.
- Facial palsy or other neurological concerns, such as headaches or seizures.
- Progressive shortness of breath, severe coughing, wheezing or other respiratory issues.
- Renal failure.
- Severe muscle and joint pain.
- Skin problems such as lupus pernio, characterized by bluish-red or violet lesions of the nose, cheeks and ears.
- Syncope or presyncope.
- Vision problems.
Dr. Carmona Porquera also cautions against overtreatment, particularly when fatigue is a prominent symptom. Although fatigue can be a manifestation of sarcoidosis, it does not necessarily indicate active disease that requires escalation of steroids or other immunosuppressive therapy.
"Sometimes, patients with sarcoidosis are very fatigued, and there may be a tendency to treat with steroids because of concern for active disease. But steroids can make the patient even more fatigued and deconditioned," she says.
Before initiating or increasing treatment, Mayo Clinic pulmonologists evaluate for other potential contributors to fatigue. For example, while sarcoidosis can cause fatigue, the patient may have an untreated underlying health condition, such as sleep apnea, depression or anemia.
In some patients, acknowledging fatigue as part of the sarcoidosis experience, providing reassurance and addressing deconditioning — including referral to pulmonary rehabilitation when appropriate — may be more beneficial than escalating steroid therapy.
"Regardless of whether it's sarcoidosis or something else, if the patient is not doing well, I always ask myself: Is it due to the disease? Is it a complication of the disease or its treatment? Or do I have the right diagnosis?" Dr. Carmona Porquera says.
Referral is especially helpful when:
- Infection or malignancy remains in the differential.
- Sarcoidosis is suspected in the lung and outside the lungs.
- Symptoms and imaging do not align.
- Treatment escalation is being considered.
For more information
Refer a patient to Mayo Clinic.