Sarcoidosis is a disease characterized by inflammatory lumps (granulomas) that form in multiple organs. It can be either short- or long-term and can affect any organ, most often the lungs and lymph nodes. The granulomas seem to form as an overreaction to an unknown threat to the body.

The cause of sarcoidosis is not known, but it appears that some patients have genetic factors that make them susceptible. It may also affect different races, ethnic groups and populations in varying ways. For example, Japanese people are more likely to be affected in the heart and eyes, whereas in Northern Europeans the skin is affected along with another organ, such as the lungs. The disease may be related to infections similar to tuberculosis. Environmental factors, such as exposure to potentially toxic substances, may increase the risk of developing it.

Sarcoidosis usually has minor symptoms or none at all. Symptoms depend greatly on which organs are affected and to what extent. General symptoms include fever, fatigue and an overall unwell feeling. Symptoms of sarcoidosis in the lungs include shortness of breath, cough and chest pain.

Sarcoidosis is often first detected by x-ray. A series of other tests, including a biopsy of affected tissue, confirm diagnosis. The criteria for diagnosis are detection of the characteristic symptoms and abnormalities, particularly on a chest x-ray, ruling out infections and finding sarcoidosis granulomas in biopsy.

Many cases of sarcoidosis do not need treatment, but the disease can be serious and sometimes even fatal when it affects vital organs. When treatment is required, corticosteroids are normally used. Relapse is much more common when the condition is serious enough that medical treatment is required. Tests (e.g., breathing tests) are performed for a few years to monitor the disease whether or not treatment is required.

Sarcoidosis is an inflammatory disease characterized by the presence of noncaseating granulomas (collections of inflammatory cells that do not issue pus) that form small lumps in multiple organs. Once thought rare, this condition is now known to be common. In fact, it is among the most common chronic scarring lung disorders.

Sarcoidosis can be either chronic (long-term) or acute (short-term). It nearly always affects more than one organ and can affect any organ in the body. The lungs and lymph nodes, especially those in the chest, are affected most often, with a lingering cough or shortness of breath as the most common symptoms. However, in some cases symptoms are not present.

The disease also frequently affects the skin, eyes and liver. Less commonly it affects the joints, bones, tear glands, salivary glands, spleen, heart, or the nerves or brain. When the disease affects the central nervous system, it is known as neurosarcoidosis, a serious complication. More rarely, sarcoidosis can affect the thyroid gland, kidneys, breasts or reproductive organs.

According to the National Institutes of Health, about 75 percent of sarcoidosis patients have the acute form of the disease and the remaining 25 percent have the chronic form. In about half of those with the acute form, the disease leaves no significant problems. Scar tissue is the most common long-lasting problem, particularly in chronic cases.

Although physicians and researchers do not know what causes sarcoidosis or even precisely what is going on in the bodies of these patients, it is believed that it may be caused by overreaction of the immune system in genetically susceptible individuals to an unidentified toxin, drug or pathogen. Some believe that this unknown factor may be a mycobacterium, a bacterium from the family that is linked to tuberculosis. This theory has not been substantiated with clinical research.

In normal circumstances, the immune system forms granulomas around particles, germs or other foreign substances to isolate and eliminate them. In patients with sarcoidosis, granulomas apparently form without a cause. There is no visible particle or germ enclosed by them. Many granulomas may clump together, forming small to large lumps. These lumps show up on x-rays as shadows and may affect organ function and cause symptoms.

Sarcoidosis affects men and women of all ages, races and ethnic groups worldwide. It typically develops between the ages of 20 and 40 years. It is rare in children and uncommon in adults over 50 years. People of African, Asian, German, Irish, Puerto Rican or Scandinavian descent are most commonly affected.

The cause of sarcoidosis is not known. Several underlying causes may be related to different patterns of the illness, such as the variances between short-term or long-term occurrence or between race and ethnicity.

Abnormalities in the immune system play a part in sarcoidosis. The formation of granulomas (collections of inflammatory cells) is a function of the immune system. Some studies have demonstrated abnormalities in certain cells (e.g., T cells, cytokines) involved in the immune response in some patients.

A genetic predisposition to sarcoidosis seems likely in at least some individuals. The disease has been known to occur in families. Certain genetic factors may also confer a susceptibility or resistance to sarcoidosis.

Racial and ethnic differences may affect the form of the disease and the organs affected. For example, among Japanese people, the heart and eyes are often affected, and in Northern Europeans the skin is commonly affected, although some other organ (e.g., lung) is also affected. Fever and joint pain typically accompany skin involvement.

In the United States, sarcoidosis affects black people slightly more often than white people. Black Americans are more likely to be affected for a short period of time but with more severe symptoms, including neurosarcoidosis (involvement of the central nervous system), and black women are affected much more than black men. White people have a more equal gender distribution of sarcoidosis, and the symptoms are milder. The cause of these differences is not known.

Various infectious agents, particularly bacteria, have been suspected of causing sarcoidosis. Some studies have reported the presence of bacteria in the blood of some sarcoidosis patients. There have been occasions of the transmission of the disease after heart and bone marrow transplants. However, clinical research has not conclusively demonstrated that infections play a role in sarcoidosis development.

Age may be a factor in the development of sarcoidosis. The disease typically affects young adults between the ages of 20 and 40. It rarely affects children and uncommonly occurs in older adults.

A recent multicenter study on the etiology (cause) of sarcoidosis found little evidence for dominant or common environmental or occupational exposures associated with an increased risk of developing sarcoidosis. For unknown reasons, the disease occurs more often in healthcare workers and more commonly in nonsmokers than smokers.

Sarcoidosis is usually a mild condition, and many patients have no symptoms. Most develop minor symptoms that do not get any worse. Serious symptoms are uncommon, but in rare cases sarcoidosis can be fatal. Although onset can occur suddenly with immediate symptoms, sarcoidosis usually develops slowly and produces symptoms only after it has been present for some time.

Symptoms vary greatly depending on the extent of the disease and which organs it affects. Sarcoidosis can occur in any organ and affects more than one.

The organs most commonly affected by sarcoidosis include:

• Lungs. Symptoms may include shortness of breath (dyspnea), lasting cough or chest pain. The lungs are the most commonly affected organ.  Chronic production of sputum and blood in sputum are common in advanced stages.
  
  
• Lymph nodes. Swelling of lymph nodes in the neck and chest may cause pain.
  
  
• Liver. Although the liver is commonly affected by sarcoidosis, the disease may produce no symptoms there or may involve some abdominal pain.
  
  
• Eyes. May produce eye pain, redness, dry eyes, light sensitivity, cataracts and seeing black spots. In some cases, sarcoidosis in the eyes may lead to glaucoma, a leading cause of blindness.
  
  

  

• Skin. The main symptom is warm, tender, red bumps or painful, purplish red, slightly raised bumps (erythema nodosum). These may be accompanied by fever, joint pain or skin lesions.  Disfiguring skin sores affecting the nose, cheek, ears and fingers can occur.

Sarcoidosis has an active and inactive phase.  In the active phase, the granulomas grow.  In the inactive phase, inflammation goes down and granulomas shrink in size, but scarring can persist and can cause symptoms to persist also.

Lofgran syndrome is acute sarcoidosis characterized by erythema nodosum, bilateral hilar lymphadenopathy (an infection and inflammation of lymph nodes in the lungs), polyarthritis and, commonly, uveitis (an eye inflammation).  It is common among Scandinavians and the Irish, especially women, but occurs in less than 5 percent of the African American population with sarcoidosis.

Several other organ systems are less commonly affected by sarcoidosis. These include:

• Joints and bones
• Skeletal muscle
• Spleen
• Heart 
• Nervous system
• Salivary glands (involvement may cause dry mouth)
• Tear glands
• Sinuses

Rarely, sarcoidosis affects the thyroid gland, kidneys, breasts or reproductive organs.

Despite the relative rarity of sarcoidosis in these systems, the disease may cause serious long-term effects there. For example, sarcoidosis in the heart may lead to heart failure, and sarcoidosis in the nervous system (neurosarcoidosis) may lead to paralysis or coma.

Regardless of where the disease occurs, calcium levels in the urine are likely to be elevated. Calcium levels may also be elevated in the blood. The granulomas (collections of inflammatory cells) associated with sarcoidosis produce activated vitamin D, which enhances calcium absorption from the intestine. If prolonged, this may lead to kidney stones and calcium deposits in the kidneys. In rare and severe cases, the kidneys become unable to function because of the high levels of calcium, and kidney failure may result. Other symptoms of this elevation in calcium include:

• Loss of appetite
• Nausea
• Vomiting
• Thirst
• Excessive production of urine (polyuria)

Other general symptoms that a patient may experience regardless of what organs are affected include:

• Recurring fever
• Fatigue
• Malaise (overall feeling of ill health)
• Night sweats

In about half of all sarcoidosis cases, the disease is detected by a routine chest x-ray before any symptoms develop. A general physician may refer patients to a specialist dealing in whichever organs are affected by the disease, such as a lung specialist (pulmonologist) for lung involvement.

The physical will review the medical history and perform a physical examination, which sometimes reveals swelling of salivary glands or lymph nodes in the neck. A series of laboratory tests and imaging tests may be ordered. Sarcoidosis is diagnosed only after other diseases with similar symptoms (e.g., rheumatoid arthritis, fungal infection, tuberculosis) have been ruled out.

The American Thoracic Society recommends a comprehensive initial evaluation, including:

• History, including occupational and environmental exposure
  
• Physical examination
  
• Chest x-ray
  
• Pulmonary function tests (breathing tests)
  
• Blood tests, including complete blood count and calcium and liver enzyme tests
  
• Urine tests
  
• Electrocardiogram (EKG)
  
• Eye examination
  
• Tuberculin skin test

Most physicians recognize the following criteria for a diagnosis of sarcoidosis:

• Spotting characteristic signs and symptoms of the disease and/or abnormalities in a chest x-ray.
  
  
• Ruling out infection, particularly tuberculosis and histoplasmosis (fungal infection usually seen in the lungs).
  
  
• Biopsy of granulomas (collections of inflammatory cells) that are not encasing foreign particles. A biopsy may not be performed if other findings are highly suggestive of sarcoidosis.

During a physical examination, a physician looks for symptoms of sarcoidosis and checks for other possible causes of the symptoms found. Laboratory and imaging tests typically follow. These tests include:

• Chest x-ray. Radiation is used to produce images of tissues inside the chest. According to the National Institutes of Health, about 90 percent of people with sarcoidosis will have an abnormal chest x-ray. Granulomas, which appear as distinctive shadowing in the lungs, and enlarged lymph nodes at the place where the lungs meet the heart or to the right of the trachea (windpipe) may be observed. When other characteristics of sarcoidosis, such as erythema nodosum (tender or painful discolored bumps on the shins), also appear, the chest x-ray may be all that is needed for diagnosis.  A staging system is used depending upon the extensiveness of the disease on chest x-ray.
  
  
• Biopsy. Tissue is removed for laboratory examination. A biopsy of affected tissue reveals granulomas without encased germs or particles, which is very accurate. The sample used for biopsy can come from any affected organ and only one sample is necessary. The most convenient sources for tissue samples are skin lesions, enlarged lymph nodes close to the skin and granulomas on the conjunctiva (membrane over the eye and below the eyelid). Samples may also be taken from the lungs, liver or muscles.
  
  
• Pulmonary function tests. A device called a spirometer is used to evaluate lung function. The patient inhales and exhales into a tube, which records certain lung capacities. These tests are safe and easy, and their results are typically compared over time to monitor the disease. Various factors are measured in these tests, including:
  
• • Lung strength. How much and how fast a person can blow air out of the lungs after taking a deep breath. Will be below normal if there is inflammation or scarring in the lung.
    
    
  • Lung volume. How much air the lungs can hold. In some patients with sarcoidosis, the lungs may shrink and lung volume will be smaller than normal.
    
    
  • Diffusing capacity. How well a gas moves into the bloodstream from the lungs. Sarcoidosis makes diffusion of oxygen from the lungs into the bloodstream more difficult.
    
    
  In addition, a painless sensor called a pulse oximeter can be placed on the finger to estimate the level of oxygen in the blood.
  
  
• Blood tests. Numerous blood tests may detect different factors involved in sarcoidosis. For example, one test can reveal an elevated level of the gamma globulin antibody, which is common in black Americans with sarcoidosis. Other blood tests performed include:
  
• • Complete blood count. Measures the numbers of red blood cells, white blood cells and platelets. Sarcoidosis often involves an insufficiency of white blood cells (leukopenia) and platelets (thrombocytopenia).
    
    
  • Sedimentation rate. Detects inflammation in the body, which may be elevated for sarcoidosis.
    
    
  • Enzyme tests. May test for several elevated enzymes, including angiotensin converting enzyme (ACE), which is produced in the granulomas. This test is positive in 60 percent of patients with sarcoidosis.  Enzyme tests may be repeated after treatment to monitor relapse. Some tests indicate the levels of certain enzymes in the liver.
    
    
  • Calcium test. Hypercalcemia (too much calcium in the blood) plays a larger role in deciding if treatment is needed because concentrations of calcium can build up and cause complications, particularly in the liver and kidneys. Prolonged hypercalcemia can also weaken bones and lead to osteoporosis. Calcium and other minerals can be measured in an electrolyte panel.
    
    
  • Rheumatoid factor test. May be positive for sarcoidosis patients.
    
    
  • Blood gases. Blood from an artery may measure levels of oxygen in the blood and help determine the level of lung function. Blood levels of carbon dioxide may also be tested.
    
    
• Urine tests. A urine analysis can detect hypercalciuria (too much calcium in the urine).
  
  
• Electrocardiogram (EKG). Measures electrical activity of the heart. An EKG may be used to detect arrhythmias (irregularities in heartbeat) that may occur if sarcoidosis affects the heart.
  
  
• Eye examinations. General physicians typically refer patients to an ophthalmologist (eye specialist) for eye tests even if there are no symptoms in the eyes. Ophthalmologists look into the eyes for abnormalities and test for color blindness and other vision troubles. Results can help in monitoring sarcoidosis and are likely to be repeated, particularly if certain drugs are being used.
  
  
• Tuberculin skin test. A skin test used to determine if tuberculosis is present. If it is, sarcoidosis can be ruled out.
  
  
• Bronchoscopy. A long, narrow, flexible tube (bronchoscope) is inserted into an airway of the lung. This allows physicians to examine the lung tissues and makes certain tests possible, including:
  
• • Bronchoscopy biopsy. A sample of lung tissue is removed for laboratory analysis during bronchoscopy. This may assist in diagnosis when pulmonary function tests and chest x-rays are abnormal and characteristic of sarcoidosis, but no more easily accessed organs seem to be affected. It is usually very safe and performed as an outpatient procedure, with the patient mildly sedated.
    
    
  • Bronchoalveolar lavage (lung wash). During bronchoscopy, saline (salt water) is injected into a region of lung and suction is used to remove it. The fluid contains washed-out cells and other materials from inside the lungs that are examined for signs of inflammation, such as a large number of white blood cells. However, these findings are not unique to sarcoidosis.
    
    
• Mediastinoscopy. A physician removes a sample of lymph nodes for biopsy from the mediastinum (space between the lungs) using one or more small incisions. Risks of this include bleeding, temporary hoarseness and an adverse reaction to the anesthetic.
  
  
• Other imaging tests. May be performed when a diagnosis is uncertain or an affected organ is difficult to reach with a biopsy. These tests include MRI, CAT scan and radionuclide imaging. An MRI can also detect early stages of cardiac damage caused by sarcoidosis, researchers have found.

• Kveim-Siltzbach test. A standardized preparation of sarcoidosis-affected tissue is injected into the skin. The test is positive if a lump forms and biopsy of the lump reveals granulomas. However, it is not always positive, even when sarcoidosis is present. This test is not readily available in the United States and is rarely performed.

Physicians will also check for certain other conditions that may cause symptoms similar to sarcoidosis. These conditions include:

• Tuberculosis
• Histoplasmosis
• Lymphoma (lymph cancer)
• rheumatoid arthritis
• Rheumatic fever
• Exposure to toxic substances, such as the metallic element beryllium

Because no causes of sarcoidosis are known, there are no known methods of prevention. However, many patients do not need treatment. In fact, according to the National Institutes of Health (NIH), up to 60 percent receive no treatment. When treatment is used, its goal is to control symptoms, improve the function of the affected organs and shrink the granulomas.

Sarcoidosis is typically treated only when symptoms are severe or if critical organs (e.g., heart, eyes, kidneys, central nervous system) are involved. Treatment is usually restricted to the most minimal forms that control symptoms and prevent serious complications. Even patients who require treatment can typically lead normal lives with no lasting disability. Treatment also depends on which organ system is involved.

In many cases, sarcoidosis improves or clears up spontaneously, with or without treatment. The granulomas (collections of inflammatory cells) go away, either disappearing or becoming scar tissue. In some cases, however, the scars may remain with or without treatment and symptoms may never go away. An affected organ may continue to function poorly. In rarer cases, symptoms continue to worsen and organ function continues to degrade.

The likelihood for full recovery is better when sarcoidosis has not spread beyond the chest, particularly if enlarged lymph nodes are present in the chest but there are no signs of lung disease. Chances are typically best when the disease begins with erythema nodosum (warm, tender, discolored bumps on the shins). Relapse occurs in about half of all sarcoidosis cases, both acute and chronic. Patients who experience spontaneous remissions (those without treatment) usually do not relapse. Patients whose remissions were induced by medications have a high rate of relapse. Spontaneous remission usually occurs within two to three years.

Very few instances of sarcoidosis lead to serious disability. When disability occurs, it is usually due to damage to the eyes (sometimes leading to blindness) or damage to the respiratory system. Damage elsewhere, such as in the heart or kidneys, can also cause serious problems. Fatalities are very rare, both in the acute and chronic forms of sarcoidosis. Lung scarring leading to respiratory failure is the most common cause of death, followed by bleeding caused by lung infections.

Sarcoidosis is typically actively monitored during and after treatment and when treatment is not required. Pulmonary function (breathing) tests are the most common method of monitoring the disease when it affects the lungs, but chest x-rays may also be used. Blood tests monitoring levels of calcium and enzyme tests measuring angiotensin-converting enzyme (ACE) are commonly used. Frequent eye tests are used to catch the possible development of sarcoidosis in the eyes and to monitor the disease when already present. These monitoring tests are also repeated regularly to detect relapses. Routine follow-up care typically lasts for two to three years.

Because most medications used for sarcoidosis suppress the immune system, patients may be more likely to get sick from an infection. Local therapy is typically the safest way to treat the disease because only the affected area is exposed to the drug. However, local therapy is possible only if the affected area can be easily reached. Drops and creams may be used for the eyes and skin. The eyes almost always respond well to treatment. Inhalers may be used to help with affected lung tissue but may not reach deep lung tissues.

Sarcoidosis typically does not increase chances of complications during pregnancy for the baby or the mother. The disease often improves during pregnancy and worsens after delivery.

When treatment is necessary, it is accomplished by means of medication. The medications that may be used include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs), sometimes including COX-2 inhibitors. May be used in acute, minor cases.
  
  
• Corticosteroids. The main treatment for sarcoidosis. These may be given to suppress severe symptoms (e.g., shortness of breath, joint pain) that may occur when there are high levels of calcium, the heart, liver or nervous system is affected, or lung disease continues to worsen. Patients without symptoms typically do not take corticosteroids. These drugs control symptoms well but do not prevent lung scarring in chronic disease. They almost always relieve symptoms due to inflammation. However, there are some rare cases where patients do not respond to corticosteroids.

Corticosteroid treatment cannot be suddenly halted and usually lasts for several months or even years in rare cases. Relapse is common but may depend on how quickly treatment was stopped. Longtime use of corticosteroids may have serious side effects, such as diabetes, glaucoma, cataracts or osteoporosis.

• Disease-modifying anti-rheumatic drugs (DMARDs). When corticosteroids are not effective, the patient may be switched to DMARDs, such as methotrexate. According to the National Institutes of Health, methotrexate works in 60 to 80 percent of patients with sarcoidosis. However, it is required for up to six months or more to relieve symptoms and may cause side effects, including an increased risk of infection, liver damage, and damage to fetuses. Another type of DMARD, hydroxychloroquine, is also effective in some patients with sarcoidosis. It is more likely to be effective if the disease has affected the skin or there is a high level of calcium in the blood. It may be helpful in eliminating skin lesions.

When sarcoidosis affects the heart, arrhythmia (irregularities in the heartbeat) may be present. Cardiac devices to regulate the heartbeat may be implanted under the skin. These include pacemakers and defibrillators.

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about sarcoidosis:

1. What tests do I need for sarcoidosis? What do they involve?
   
   
2. What organs are affected by my sarcoidosis?
   
   
3. Is my sarcoidosis likely to spread to any other organs?
   
   
4. Does my sarcoidosis appear to be long term or short term?
   
   
5. Do I have tissue scarring?
   
   
6. How serious are my symptoms likely to be?
   
   
7. How often should I come in for follow-up appointments?
   
   
8. Should I receive treatment for my sarcoidosis?
   
   
9. If so, what are my treatment options? What are the risks and benefits of corticosteroids or other recommended treatments?
   
   
10. How long is the therapy likely to last?