Living with lung complications of sarcoidosis

Abstract

Sarcoidosis is an inflammatory condition that can affect any part of the body, but most commonly affects the lungs. Many people with lung (pulmonary) sarcoidosis have manageable disease that does not impact them in the long term. However, some patients with pulmonary sarcoidosis develop complications that cause long-term (chronic) symptoms, such as shortness of breath and cough. These symptoms impair quality of life and may impair a person's ability to complete everyday activities at work and at home. Complications of pulmonary sarcoidosis also worsen the outcome of the disease (prognosis). It is important for patients with sarcoidosis to be aware of the journey that they may face with the disease so that they can better understand their condition and be part of decisions about their care. This article, co-authored by an experienced clinician and a patient, provides information for patients living with pulmonary sarcoidosis.

Tweetable abstract

Sarcoidosis may lead to pulmonary complications, such as lung fibrosis, bronchiectasis or pulmonary hypertension. Understanding how these complications are diagnosed and treated helps patients be part of decisions about their case.

Executive summary

Objective

• This article provides information to help patients understand how pulmonary sarcoidosis is diagnosed and the journey that patients may have following its diagnosis.

What is sarcoidosis?

• Sarcoidosis is a rare disease involving the immune system that can affect multiple organs at the same time.

How is sarcoidosis diagnosed?

• Diagnosing sarcoidosis is complicated and requires several types of tests, which means that getting a diagnosis can take time.

How might sarcoidosis affect the lungs?

• The lung is the organ that is most commonly affected by sarcoidosis. The lung tissue, airways, lymph nodes, and rarely, the lining of the lungs may be affected.

What are the symptoms of pulmonary sarcoidosis?

• Some patients with pulmonary sarcoidosis have no symptoms, but others experience shortness of breath or cough.

What is the prognosis of pulmonary sarcoidosis?

• The course of pulmonary sarcoidosis is highly variable. Most people have mild disease that gets better with time or treatment, but a small group of patients have disease that worsens (progresses) over time.

What are the potential complications of pulmonary sarcoidosis?

• Potential complications of pulmonary sarcoidosis include scarring (fibrosis) of the lungs, dilation of the airways (bronchiectasis), narrowing of the airways (stenosis), fungal infections, and high pressure in the blood vessels of the lungs (pulmonary hypertension).

How is pulmonary sarcoidosis treated?

• The best treatment for pulmonary sarcoidosis depends on factors such as which part of the lungs are affected, how severe the symptoms are, and if the disease is stable or worsening.

Where can patients get reliable information?

• Patients with pulmonary sarcoidosis can obtain more information about their condition from their doctor or patient groups.

Future perspective

• The coming decades will provide greater understanding of how sarcoidosis develops and why it presents differently in individual patients. There are several trials underway looking at whether new drugs can help prevent or treat pulmonary sarcoidosis.

Keywords: :

• lung disease
• interstitial
• pulmonary fibrosis

Sarcoidosis is a rare disease that can affect any part of the body and can affect multiple organs at the same time. This article focuses on sarcoidosis affecting the lungs (pulmonary sarcoidosis). Our aim, as a clinician with experience in managing pulmonary sarcoidosis and as a patient living with this condition, is to help patients understand how pulmonary sarcoidosis is diagnosed and the journey that patients may have following its diagnosis.

What causes sarcoidosis?

The exact cause of sarcoidosis is unknown, but certain genes inherited from family play a role [1]. In the USA, sarcoidosis is more common in Black people, especially Black women [2]. People of Northern European ancestry also have higher rates of sarcoidosis than other groups.

Researchers suspect that sarcoidosis develops in people with genetic risk, who are exposed to something in the environment (an antigen) that stimulates their immune system to make granulomas [1]. Granulomas are tight clusters of immune cells, including T cells, histiocytes, and B cells. The type of granulomas that are seen in sarcoidosis are called ‘non-necrotizing’ or ‘non-caseating’. This means that the center of the granuloma contains living cells (Figure 1). Depending on the number and location of granulomas, they can impair the function of the organ in which they are found.

Figure 1. Cells included in a non-caseating granuloma seen in patients with sarcoidosis.

No single gene has been found to be the cause of sarcoidosis in all people with the disease. Instead, many genes have been associated with an increased risk. The most common genes thought to be associated with risk for sarcoidosis relate to a region on a type of immune cell called the macrophage.

Environmental exposures (antigens) in the place that someone works or lives have been implicated in causing sarcoidosis, but no single antigen has been found to be the culprit [1]. Some occupations have been associated with an increased risk of sarcoidosis, but other than the World Trade Center Disaster first responders, such as fire fighters and police officers [3], no definite causal exposure in the workplace has been identified. There is also evidence that exposure to certain bacteria and fungi (e.g., mold) could increase the risk of developing sarcoidosis [4].

How is sarcoidosis diagnosed?

Diagnosing sarcoidosis can take time and require several types of tests [1,5]. The reason for the difficulty in diagnosis is that no single test is definitive for sarcoidosis and the symptoms seen in patients with sarcoidosis are also seen in people with other lung conditions, such as asthma, chronic obstructive pulmonary disease (COPD), emphysema, pulmonary fibrosis or infections. A diagnosis of sarcoidosis often requires a biopsy, but a biopsy alone is not enough for a diagnosis to be made, as granulomas can be seen in other conditions, such as infections, inflammatory conditions and certain cancers. In rare cases, a diagnosis of sarcoidosis is made conditionally, which means that sarcoidosis is assumed to be the diagnosis, but there is still a possibility that the patient may have a different disease.

A diagnosis of sarcoidosis depends on the presence of three factors:

▪	The symptoms and physical exam findings fit what is expected for sarcoidosis.
▪	A biopsy shows non-caseating or non-necrotizing granulomas.
▪	Other conditions that can look similar to sarcoidosis are excluded.

Findings that help healthcare providers feel more confident about making a diagnosis of sarcoidosis include finding granulomas in more than one organ, lack of symptoms of infection or cancer, a family history of sarcoidosis, and a pattern of disease on imaging of the lungs that is typical of sarcoidosis.

Given the number of tests required, for many patients, the journey to getting a diagnosis can take a long time. Kathryn Washington describes her experience, “My journey to a sarcoidosis diagnosis was a prolonged and intricate process, taking over a decade. It started with subtle symptoms, such as persistent coughing and unexplained fatigue, which were initially mistaken for common respiratory issues. Despite numerous tests, including blood tests, chest x-rays, and CT scans, achieving a definitive diagnosis was challenging. The pivotal moment was a biopsy, revealing the presence of non-caseating granulomas. This exhaustive process highlighted the complexities of diagnosing such an elusive condition and the importance of persistence in seeking answers.”

What happens when someone develops sarcoidosis?

Sarcoidosis presents differently from person to person [1]. Some patients have symptoms for a few months to years, while others experience them for the rest of their lives. The severity of symptoms also varies. The inflammation caused by sarcoidosis can lead to organ dysfunction, which means that an organ does not work like it is supposed to.

How might sarcoidosis affect the lungs?

The lung (Figure 2) is the organ that is most commonly affected by sarcoidosis [6]. Approximately 95% of patients with sarcoidosis have evidence of the disease in their lungs. Sarcoidosis can impact any part of the lungs including the lung tissue, airways, lymph nodes, and rarely, the lining of the lungs. The upper parts of the respiratory system, such as the sinuses and vocal cords, can also be affected but this is uncommon. The most common presentations of pulmonary sarcoidosis include enlarged lymph nodes around the airways and nodules in the lung tissue, which form from a clump of granulomas, with inflammation around the airways (Figure 3).

Figure 2. The parts of the respiratory system.

Figure 3. The ways in which sarcoidosis most commonly occurs in the lungs.

Some patients with pulmonary sarcoidosis have no symptoms and the disease is found by chance when they are being tested for another medical problem. However, symptoms may include shortness of breath, coughing, and wheezing. Other general symptoms of sarcoidosis that some people experience include fatigue, pain in the chest or other parts of the body, depression, and anxiety. It is important to remember that these symptoms are seen in many conditions so if you have these symptoms, it does not necessarily mean you have sarcoidosis.

What is the prognosis of pulmonary sarcoidosis?

The course of pulmonary sarcoidosis is highly variable [5,7]. Most people with lung sarcoidosis have mild disease that gets better with time or treatment. Mild disease could come with no symptoms or some shortness of breath or cough with exercise or other strenuous activity. Some people have disease that stays stable over decades (with or without treatment). These patients are considered to have chronic disease. Patients with chronic but stable sarcoidosis often have long-term symptoms that can be bothersome like shortness of breath while doing chores. Most will need treatment for a period of time.

A small group of patients with pulmonary sarcoidosis have worsening (progressive) disease and their lung function and symptoms worsen over time [8]. These patients will likely need long-term treatment and may need to take a combination of treatments to try to slow down the worsening of the disease. Breathing issues could worsen if the patient develops the flu or pneumonia and this might lead to hospitalization. Treatments are not always effective and some patients may require evaluation for lung transplantation. As explained by Kathryn Washington, “Managing progressive pulmonary sarcoidosis requires an understanding of the disease and its treatments, which often involves a combination of medications. My journey has been marked by the need to try various treatments before finding the right combination. Navigating through the side effects of these medications, such as fatigue, depression, and physical discomfort, has significantly impacted my daily life and activities. I've learned the importance of patient advocacy and taking charge of one's health, which includes understanding medications, their side effects, and the critical role of medication adherence.”

The risk of dying (mortality) due to sarcoidosis is generally low. Non-Hispanic Black women have the highest rate of mortality. This is likely because Black women usually have more organs affected and more severe disease. The most common cause of death associated with sarcoidosis is lung fibrosis (scarring), with or without a complication like a severe lung infection, or high pressure in the blood vessels in the lungs (pulmonary hypertension) [6].

Complications of pulmonary sarcoidosis

Complications of pulmonary fibrosis can develop over time (Table 1) and can worsen patients' symptoms and put them at a higher risk of death.

Table 1. Symptoms and testing performed for pulmonary complications of sarcoidosis.

Complication of sarcoidosis	Symptoms	Tests
Lung fibrosis	Shortness of breath, dry cough	CT, PFTs
Bronchiectasis	Cough with mucus	Chest imaging and PFTs
Airway stenosis	Shortness of breath and wheezing	CT, PFTs, bronchoscopy
Chronic fungal infection	Cough with mucus or blood, shortness of breath	CT, blood and sputum tests, bronchoscopy
Pulmonary hypertension	Shortness of breath, swelling in the feet	Echocardiogram, right heart catheterization

CT: computed tomography (of the chest); PFT: pulmonary function test.

Fibrosis

The function of the lungs is to take in oxygen and transfer it to the blood cells so that it can be transported to all the organs in the body. Without adequate oxygen, the organs in the body can fail. The lungs also help get rid of carbon dioxide, which is a waste product that the body makes.

Scarring (fibrosis) of the lungs may develop because it is one way for the body to heal inflammation and injury. A common example of this is the injury that happens to the skin and soft tissue after a fall or trauma. Initially there is redness and swelling inflammation of the skin. Over time, the redness and swelling get better and a scab appears. Once the scab falls off, scarring is visible, which usually takes a long time to heal and sometimes does not heal completely. This process of injury and inflammation followed by scarring can also occur in the lungs.

People with lung fibrosis due to sarcoidosis have changes on chest imaging [9]. A chest x-ray is the simplest type of scan, but a more detailed test known as a CT scan may be needed. Some of the findings that may be seen on a CT scan are shown in Figure 4. Fibrosis usually occurs in the upper parts of the lungs, but a small group of people can have fibrosis in the lower parts of the lungs. Fibrosis in the lungs develops slowly, but ultimately prevents oxygen from traveling from the air sacs in the lungs to the blood vessels (Figure 5). This can cause shortness of breath and reduce a person's ability to work or complete everyday activities at home. A long-term cough may develop. Because of the low oxygen levels in the blood, some patients need to take oxygen by a nasal cannula.

Figure 4. CT findings in patients with pulmonary sarcoidosis.

The two scans in the first row show typical CT findings. The two scans in the bottom row show fibrosis and emphysema (dark areas). Provided by and reproduced with permission from Divya C Patel, Adjunct Clinical Associate Professor; Division of Pulmonary, Critical Care, and Sleep Medicine; University of Florida College of Medicine; Gainesville, FL, USA.

Figure 5. The air sacs in normal lungs and in lungs with fibrosis (scarring).

Unfortunately pulmonary fibrosis is not reversible or curable. The main goal of treatment is to help improve symptoms and prevent worsening of lung function [9]. The treatment options for sarcoidosis, including steroids (e.g. prednisone), methotrexate, azathioprine, mycophenolate, leflunomide and infliximab, may help improve lung function or symptoms [10]. However, in some patients, the usual medications for treatment of sarcoidosis do not work, as the granulomas no longer respond to treatment or there is too much scar tissue. The best way to know if treatment will help is to start therapy and follow any changes in symptoms and lung function (using breathing tests called pulmonary function tests or PFTs). In some cases, a doctor may order imaging or blood tests to see if the sarcoidosis is active and then decide on medications based on the results.

Medications called “antifibrotics” may help patients with pulmonary fibrosis that is getting worse. In a clinical trial involving patients who had worsening fibrosis in the lungs from a variety of causes, the antifibrotic drug nintedanib slowed down the decline in lung function [11]. This trial included 12 patients in whom sarcoidosis was the cause of the lung fibrosis. Based on the results of this trial, some doctors have suggested using nintedanib to treat patients with fibrotic lung sarcoidosis that is getting worse.

As explained by Kathryn Washington, “Effective communication with healthcare providers is crucial in managing sarcoidosis. Discussing treatment options that can relieve symptoms or slow the progression of lung fibrosis is essential. Patients should actively engage with their care team, share their experiences, and provide feedback on their treatment plans. This collaborative approach helps in tailoring the treatment to the patient's unique needs”.

Bronchiectasis

Bronchiectasis is a dilation of the air tubes or airways in the lungs [12]. In patients with sarcoidosis, bronchiectasis most commonly occurs when there is lung fibrosis, as the scar tissue pulls open the airways, but it can also occur without fibrosis. Symptoms of bronchiectasis include cough with mucus production over many months. The mucus may be green, yellow, or brown in color and can lead to bacterial infections that are difficult to clear.

There is no cure for bronchiectasis. Controlling symptoms involves keeping the lungs free of mucus using techniques such as inhalers, nebulizers, flutter valves, and vibrating (percussive) devices. Antibiotics are used to treat bacterial infections. These treatments reduce the risk of worsening shortness of breath and pneumonia.

Airway stenosis

Airway stenosis means narrowing of the airways [13]. This can happen in patients with or without other problems in their lungs from sarcoidosis. Narrowing of airways causes shortness of breath and sometimes wheezing. Airway stenosis occurs in a small group of patients with sarcoidosis who have inflammation in the airways that heals by making scar tissue. This scar tissue may partially block the airways and make it difficult to breath. The medicines typically used to treat sarcoidosis, or inhalers, may help to relieve the symptoms of airway stenosis. Doctors who specialize in airway problems can help by performing procedures to relieve some of the blockage. The procedure is known as a bronchoscopy. In this procedure, done in the outpatient setting, the patient is given medication, so they are asleep and a long tube with a camera and light is inserted into their lungs through the mouth or nose. Once the area with the stenosis is found, devices like balloons and medications are used to relieve the stenosis.

Chronic fungal infection

Patients with pulmonary fibrosis and bronchiectasis are at risk of getting fungal infections, particularly from a type of fungi called Aspergillus [14]. The air we breathe is filled with fungi. When a person with sarcoidosis inhales a fungus, rarely it may settle in the lungs and cause a chronic infection. The infection is slow, but over a long period of time, the fungus may invade the lung tissue and blood vessels.

Diagnosis of a fungal infection is based on CT scan images, blood tests, sputum tests, and bronchoscopy. In mild cases, antifungal medications can be used long term to control the infection. Most patients do not know that they have a fungal infection since it occurs slowly, but over time, they may develop a worse cough and in rare instances, cough up blood. If you are coughing up blood, it is important to tell your doctor right away. Coughing up large quantities of blood can be life-threatening and requires immediate admission to hospital. Physicians can perform a specialized procedure called embolization or sometimes surgery to help stop the bleeding.

Pulmonary hypertension

Pulmonary hypertension means high pressure in the blood vessels of the lungs, which, in some cases, can cause stress to the right side of the heart [15]. There are several mechanisms by which sarcoidosis may cause pulmonary hypertension. One is when lung fibrosis leads to low oxygen levels, which over time, can lead to high pressure in the blood vessels.

Screening for pulmonary hypertension involves a test called an echocardiogram or ECHO. This is an ultrasound of the heart. This test gives clues about whether there might be pulmonary hypertension. To confirm the diagnosis, another test, called a right heart catheterization, is used. The results of this test, imaging tests and PFTs are used in combination to determine the cause of the pulmonary hypertension. There are several treatment options for pulmonary hypertension, but none are specifically licensed for the treatment of pulmonary hypertension due to sarcoidosis. Patients with sarcoidosis and pulmonary hypertension should see a healthcare provider who is an expert in pulmonary hypertension, usually a pulmonologist or cardiologist. Looking for a clinic with a specialized program is helpful because the specialists can work together to find the most appropriate treatment regimen.

Further recommendations for patients with pulmonary sarcoidosis and its complications are given in Box 1. Resources that may be useful are listed in Box 2. As described by Kathryn Washington, “The journey for people with sarcoidosis involves balancing health needs with other life aspects, such as employment. Coordinating care with healthcare providers and caregivers, while managing work commitments and navigating privacy under HIPAA, presents additional challenges. Being informed about environmental factors like weather conditions and prevalent illnesses is crucial in decision-making related to health. The support of a caregiver is invaluable, both in managing daily living activities and providing insights during medical appointments, especially when dealing with memory difficulties”.

Box 1. Recommendations for patients.

• Keep a record of your medical history including any exposures in your home or workplace, family history, and symptoms.

• Keep a list of questions and concerns and review it with your doctor.

• Bring someone with you to appointments who can help you to remember information or take notes.

• Tell your doctor if you are experiencing mental health issues such as depression or anxiety.

• If you have pulmonary sarcoidosis and are not getting better with treatment or need oxygen therapy, talk to your specialist about the complications or seek out care at a Sarcoidosis Center of Excellence.

• Consider participation in a clinical trial if this is available to you.

• Join a patient support group in your area or on-line.

• Find out more information from reliable sources (see “Resources”).

Box 2. Resources.

A podcast of Dr Divya Patel discussing potential complications of pulmonary sarcoidosis is available at: https://www.usscicomms.com/respiratory/Patel/PulmonarySarcoidosis

Foundation for Sarcoidosis Research: www.stopsarcoidosis.org

American Thoracic Society: https://www.thoracic.org/patients/patient-resources/resources/what-is-sarcoidosis.pdf

American Lung Association: https://www.lung.org/lung-health-diseases/lung-disease-lookup/sarcoidosis/learn-about-sarcoidosis

Conclusion

For most patients with pulmonary sarcoidosis, the disease is manageable. However, for a small group of patients, the disease can lead to severe chronic symptoms including shortness of breath and cough with or without mucus. Complications such as pulmonary fibrosis, bronchiectasis, pulmonary hypertension, and fungal infections are important to be aware of, since they can impact quality of life and prognosis. A specialist in sarcoidosis or lung diseases (pulmonologist) can do tests to look for these complications and help to manage them.

Future perspective

The coming decades will provide greater understanding of how sarcoidosis develops and why it presents differently in individual patients. Many sarcoidosis specialists and researchers think that sarcoidosis is not one condition but many conditions. New scientific techniques will help investigate this theory. There are several clinical trials of new drugs underway to see if those drugs can help treat pulmonary sarcoidosis, or help prevent the development of complications in the lungs in patients with sarcoidosis.

Financial disclosures

D Patel is an employee of Boehringer Ingelheim Pharmaceuticals, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

Editorial support was provided by Wendy Morris of FleishmanHillard, London, UK, which was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc. Boehringer Ingelheim was given the opportunity to review the article for medical and scientific accuracy as well as intellectual property considerations.

Acknowledgments

The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive any payment for their work on this article. The scientific content of the article was controlled by Divya Patel. A patient's perspective was provided by Kathryn Washington.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.