Sarcoidosis

Sarcoidosis involves inflammation that produces tiny lumps of cells in various organs in the body. The lumps are called granulomas because they look like grains of sugar or sand. They are very small and can be seen only with a microscope. These tiny granulomas can grow and clump together, making many large and small groups of lumps. If many granulomas form in an organ, they can affect how the organ works. This causes the symptoms of sarcoidosis. The course of the disease varies greatly among people. However, two phases are always present. In the active phase, the granulomas form and grow, symptoms develop, and scar tissue forms. In the nonactive phase, the inflammation settles down, and the granulomas stay the same size or shrink. The scars may remain and cause symptoms.

Organs Affected

Sarcoidosis can affect almost any part of the body and almost always occurs in more than one organ. Some organs are moiré susceptible to sarcoidosis than others. Usually sarcoidosis starts in the Lungs or lymph nodes (especially those in the chest cavity). Other organs frequently involved include the following:

• Skin
• Eyes
• Liver

Sarcoidosis infrequently affects the following organs:

• Spleen
• Brain
• Nerves
• Heart
• Tear glands
• Salivary glands
• Bones and joints

The thyroid glands, breasts, kidneys, and reproductive organs are rarely involved.

This graph shows the average number of cases of sarcoidosis that occurred in specific organs in participants in a large clinical study in the United States in the late 1990s. It shows, for example, that among every 100 of these patients, 95 had sarcoidosis in their lungs.^[1]

Signs and Symptoms

Many people who have sarcoidosis have no symptoms. Often, the condition is discovered by accident only because a person has a chest x-ray for another reason. Symptoms that do occur are often dependent on which organs are involved.

Sarcoidosis usually does not cause sudden illness, and the changes in sarcoidosis usually occur slowly (e.g., over months). However, arthritis in the ankles, eye and heart problems could occur suddenly. In some serious cases in which vital organs are affected, sarcoidosis can result in death.

Lung

Below are some of the more frequent signs of sarcoidosis in the lungs:

• Shortness of breath
• Dry cough that doesn't bring up phlegm, or mucus
• Wheezing
• Pain in the middle of the chest that gets worse while breathing deeply or coughing (rare)

Lymph node

Sarcoidosis can cause the lymph nodes to enlarge and become painful. Nodes in the neck and chest are affected most often, and those under the chin, arm pits, or in the groin are affected infrequently.

Skin

Erythema Nodosum. Source: Wikimedia Commons

Various types of bumps, ulcers, or, rarely, flat areas of discolored skin can appear. Most often these conditions occur near the nose, eyes, back, arms, legs, and scalp. These bumps usually itch but aren't painful. They usually last a long time. Sometimes painful bumps appear on the ankles and shins. These can be warm, tender, red or purple-to-red in color, and slightly raised. This is called erythema nodosum There may be fever and swollen ankles and joint pain along with the bumps. The bumps often are an early sign of sarcoidosis, but they occur in other diseases too. The bumps usually go away in weeks to months, even without treatment.

Disfiguring skin sores that may affect the nose, nasal passages, cheeks, ears, eyelids, and fingers have also been reported. This is called lupus pernio. The sores tend to be ongoing and can return after treatment is over.

Eye

Sarcoidosis can have many affects on the eyes:

• Burning, itching, tearing, pain
• Red eye
• Sensitivity to light
• Dryness
• Floaters (i.e., seeing black spots)
• Blurred vision
• Reduced color vision
• Reduced visual clearness
• Blindness (in rare cases)

Heart

Below are signs of heart involvement:

• Shortness of breath
• Swelling in the legs
• Wheezing
• Coughing
• Irregular heartbeat, including palpitations (a fluttering feeling of rapid heartbeats) and skipped beats
• Sudden loss of consciousness
• Sudden death

Joint and Muscle

Signs of joint involvement include joint stiffness, swelling, or pain. Usually stiffness affects the hands, ankles, and feet. Muscle involvement is signified by muscle pain, aches, weakness, or development of a mass.

Symptoms of painful or painless arthritis can develop. Symptoms in the ankles can develop because of erythema nodosum.

Bone

Sometimes sarcoidosis causes lesions on bones or swelling (especially in fingers), both of which are painless. Anemia can result from granulomas affecting the bone marrow.

Liver

Signs of liver involvement include the following:

• Fever
• Fatigue
• Itching
• Pain in the upper right part of the abdomen, under the right ribs
• Enlarged liver

Parotid and other salivary gland

Swelling, which makes the cheeks look puffy, and Excessive mouth and throat dryness are sometimes reported.

Blood, urinary tract, and kidney

Kidney involvement increases the amount of calcium in the blood and urine. This increases the risk of kidney stones. Impaired kidney function can also cause confusion and increased urination.

Nervous system

Signs of nervous system involvement include the following:

• Headaches
• Vision problems
• Weakness or numbness of an arm or leg
• Coma (rare).
• Drooping of one side of the face that results from sarcoidosis affecting a facial nerve.
• Paralysis of the arms or legs
• Weakness, pain, or a "stinging needles" sensation

Pituitary gland

Rarely, sarcoidosis affects the pituitary gland, which is an area of the brain that releases hormones. Headaches, vision problems, and weakness or numbness of an arm or leg, or coma can result from pituitary gland involvement.

Other symptoms

Below are some other signs of sarcoidosis, many of which are general and do not necessarily signify the condition:

• Nasal obstruction or frequent bouts of inflammation of the sinuses called sinusitis.
• Enlarged spleen, which leads to a decrease in platelets in the blood and pain in the upper left abdomen.
• Uneasiness, feeling sick (malaise), an overall feeling of ill health
• Tiredness, fatigue, weakness
• Loss of appetite or weight
• Fever
• Night sweats
• Sleep problems

Causes

Sarcoidosis may have several causes, which are under investigation. Scientists think that sarcoidosis develops when the immune system responds to something in the environment (e.g., bacteria, viruses, dust, chemicals) or perhaps to the bodies own tissue (autoimmunity).

Normally, the immune system defends the body against things that it sees as foreign and harmful. This defense involves mobilization of special cells to the affected organs. These cells release chemicals that produce inflammation around the foreign substance or substances to isolate and destroy them. In sarcoidosis, the inflammation never subsides, even after the foreign substances have disappeared. Eventually the inflammation causes granulomas or lumps.

Scientists have not yet identified the initial trigger of the immune attack. They also think that sarcoidosis develops only if someone has inherited a certain combination of genes.

Diagnosis

Doctors use medical histories, physical exams, and diagnostic tests to diagnose sarcoidosis. The tests are designed to find granulomas and rule out other causes of the symptoms. They can also determine the amount of damage and if treatment is necessary.

Medical history

Medical histories take into account a family history of sarcoidosis and the types of jobs that were held over the years. Exposure to inhaled beryllium metal, which is used in aircraft and weapons manufacture, or organic dust from birds or hay produce granulomas in the lungs. However, these are not signs of sarcoidosis.

Physical exam

Physical exams are used to look for symptoms of the condition. Red bumps on the skin, swollen lymph nodes, an enlarged liver, spleen, or salivary gland(s), or redness in the eyes are some of the symptoms detected in this exam. Abnormal lung or heart sounds could also signify sarcoidosis.

Diagnostic tests

No one test can diagnose sarcoidosis. It is harder to make a diagnosis in some organs (e.g., heart, nervous system) than in others.

Chest x-ray

A chest x-ray takes a picture of the heart and lungs. It may show granulomas or enlarged lymph nodes in the chest. About 95% of people with sarcoidosis have an abnormal chest x-ray. Doctors usually use a staging system to help determine the severity of the condition:

• Stage 0: Normal chest x-ray
• Stage 1: enlarged lymph nodes but otherwise clear lungs
• Stage 2: enlarged lymph nodes and shadows in the lungs
• Stage 3: shadows in the lungs, but the lymph nodes are not enlarged
• Stage 4: scars in the lung tissue

In general, lung symptoms and function worsen as the stage increases. Stages 0, 1, 2, or 3, may not show symptoms and may not need treatment.

Blood Tests

Blood tests can show the number and type of cells in the blood. They also show whether calcium levels are increased and changes in the liver, kidney, and bone marrow.

Lung function tests

In one lung function test, the amount and speed of air exhaled from the lungs after taking a deep breath is measured with a spirometer. If there is a lot of inflammation and/or scarring in the lungs, it may be difficult to move normal amounts of air in and out.

Another test measures how much air the lungs can hold. Sarcoidosis can cause the lungs to shrink, and they will not be able to hold as much air as healthy lungs.

Electrocardiogram (EKG)

An electrocardiogram is used to detect signs of heart involvement.

Blood gases

A couple of tests can be used to determine the oxygenation of the blood. The amount of oxygen in the blood is a measure of lung function. Pulse Oximetry uses a small clip attached to the fingertip to determine how well the heart and lungs are moving oxygen into the blood. In the arterial Blood Gas Test, blood taken from an artery is used for analysis of carbon dioxide and oxygen levels. This test is more accurate than pulse oximetry.

Fiberoptic bronchoscopy

In a bronchoscopy, a doctor inserts a long, narrow, flexible tube with a light on the end through the nose or mouth into the lungs to look at the airways. This tube is called a bronchoscope. Sometimes during this procedure a doctor injects a small amount of salt water (saline) through the bronchoscope into the lungs. This bronchoalveolar Lavage washes the lungs and helps bring up cells and other material from the air sacs deep in the lungs where the inflammation usually starts to develop. The cells and fluid are then examined for signs of inflammation.

Biopsy

In a biopsy, a doctor takes a small sample of tissue from one of the affected organs. For example, when breathing tests or chest x-rays show signs of sarcoidosis in the lungs, a fiberoptic bronchoscopy biopsy may be performed. Biopsies of the skin, liver, or other organs are sometimes done to detect granulomas.

Imaging tests

A computerized Tomography scan (CT scan) provides a computer-generated image of organs in much more detail than does an x-ray. CT scans are used for several reasons:

• Obtain more information about how much of the lung is affected by sarcoidosis
• Detect sarcoidosis in the liver. A CT scan of the abdomen shows enlargement of the liver.

Magnetic Resonance imaging(MRI) uses powerful magnets and radio waves to map organs that cannot be biopsied. Thallium and gallium scans are often done to see if sarcoidosis is affecting the heart. Thallium and gallium are radioactive elements that collect at places in the body where there is inflammation. Finally, positron emission tomography (PET) are often used often used. This test also uses radioactive injections. It may be more sensitive than gallium in detecting areas of inflammation.

Treatment

Treatment has several goals:

• Improve how the organs affected by sarcoidosis work
• Relieve symptoms
• Shrink the granulomas

Treatment depends on the severity of the symptoms as well as the organs involved and the nature of the damage. Treatment may shrink the granulomas and even cause them to disappear, but this may take many months. Some organs must be treated, regardless of symptoms. Others may not need to be treated. Usually, if there are no symptoms, then treatment is not needed.

In many people, sarcoidosis is mild. The inflammation that causes the granulomas may get better on its own. The granulomas may stop growing or shrink. Symptoms may go away within a few years. In other people, the inflammation remains but doesn't get worse. Sometimes the disease may flare-up and treatment is needed. In the worst cases, the condition slowly progresses to cause extensive organ damage and death.

Although treatment is often effective, scar tissue can develop in affected tissue. The scar tissue can affect how the organs work. Treatment usually does not affect scar tissue and the scars can be a source of ongoing symptoms.

Medications

The main treatment for sarcoidosis is corticosteroids, especially prednisone. Prednisone is a corticosteroid, or anti-inflammatory drug. Sometimes it is used with other drugs.

Other drugs

Other drugs are sometimes necessary to treat sarcoidosis either because the prednisone is ineffective or produces intolerable side effects. Most of these other drugs are immune system suppressants.

Drugs used for sarcoidosis can either be local or, like prednisone, systemic. Local therapy is the safest way to treat sarcoidosis. The drug is applied directly to the affected area. As a result, only small amounts of the drug reach other parts of the body. Eye drops, inhaled drugs, and skin creams are some examples of local drugs used for sarcoidosis. Systemic drugs act throughout the body and can affect many organs and body systems. Some examples of systemic medications for sarcoidosis are listed below:

• hydroxychloroquine–This drug is used to treat the skin or help people who have high levels of calcium in their blood.
• Methotrexate–This is an immunosuppressant commonly used to treat arthritis.
• Azathioprine–This drug may work in about half of the people who have sarcoidosis.
• Cyclophosphamide–This is a very toxic drug usually used to treat cancer and reserved for only the most serious forms of sarcoidosis.

Treatment of specific organs

• Eyes. Sarcoidosis in the eyes almost always responds to treatment. Often the only treatment needed is eye drops containing corticosteroids.
• Spleen. Sarcoidosis can cause enlargement of the spleen. This can reduce the number of red blood cells, white blood cells, or platelets in the blood. This, in turn, increases the risk of infection and blood clotting disorders. Treatment is usually given to increase the number of blood cells and ease pain. In rare cases, the spleen may need to be removed.
• Liver. Sarcoidosis rarely causes permanent liver damage, and treatment is rarely needed. Drugs, and in severe cases transplantation, have been used to treat the liver.
• Nervous system. Sarcoidosis in the nervous system (neurosarcoidosis) usually needs treatment. Nerve tissue heals slowly, so treatment often takes a long time.
• Erythema nodosum. These painful bumps on the shins often go away in weeks to months without treatment. Acetylslicylic acid (Aspirin) or ibuprofen can be used to relieve pain.
• Heart. Steroids are usually used to treat sarcoidosis in the heart. Other drugs may be used to improve the pumping ability of the heart, or to correct a disturbed heart rhythm. For the latter, devices such as a cardiac pacemaker may need to be implanted.
• Lupus Pernio. This is a rash on the face, especially the cheeks and nose. It commonly occurs with a loss of the sense of smell, nasal stuffiness, and sinus infections. Skin creams, oral medications (e.g., prednisone), or injections of steroids.

Prevention

The development of sarcoidosis cannot be prevented.

Research

Scientists worldwide are trying to learn more about sarcoidosis and how to improve its diagnosis and treatment. Some avenues of research include the following:

• The causative agent or agents
• Why sarcoidosis seems to act differently in people of different races
• Why sarcoidosis appears in some families
• How genes, passed from one generation to another, may make some people more likely than others to develop sarcoidosis
• How cells act and communicate with each other to cause sarcoidosis symptoms.

Drugs

Many drugs are under investigation for their potential use in sarcoidosis. Etanercept (Enbrel) and infliximab (Remicade) are immunosuppressant’s that need to be injected. They are currently used for many autoimmune diseases. Pentoxifylline (Trental) is another immunosuppressant that has been shown to reduce sarcoidosis in the lungs. The cancer drug thalidomide (Thalomid) is effective against other conditions that involve granulomas of the skin. Finally, the tetracycline antibiotics have been shown effective for treatment of the skin in small studies.

Living With Sarcoidosis

Many support groups exist for people with sarcoidosis. Often talking to others with sarcoidosis can provide coping tips.

Pregnancy

Many women give birth to healthy babies while being treated for sarcoidosis. Pregnancy usually doesn't affect the course of sarcoidosis, corticosteroid treatment can be continued through the pregnancy. None of the other drugs are recommended for use during pregnancy. Sometimes sarcoidosis gets worse after delivery of a baby. Women with severe sarcoidosis, especially if they are older, may have trouble becoming pregnant.

Epidemiology

Sarcoidosis was once thought to be an uncommon condition. It's now known to affect tens of thousands of people throughout the United States. Because many people who have sarcoidosis have no symptoms, it's hard to know how many people have the condition.

Sarcoidosis affects people of all ages and races worldwide, but some people are at higher risk:

• Adults between the ages of 20 years and 40 years
• African Americans (especially women)
• People of Asian, German, Irish, Puerto Rican, and Scandinavian origin.
• Health care workers
• Nonsmokers
• Elementary and secondary school teachers
• People exposed to agricultural dust, insecticides, pesticides, or mold
• Firefighters
• Brothers and sisters, parents, and children of people who have sarcoidosis

In the United States, sarcoidosis affects African Americans somewhat more often and more severely than Caucasians.

Studies have shown that sarcoidosis is more likely to affect certain organs in certain populations:

• Sarcoidosis of the heart and eye appears to be more common in Japan.
• Painful skin lumps on the legs occur more often in people from Northern Europe.

Clinical Trials

• Sarcoidosis Clinical Trials
• Current Research (National Institutes of Health)
• Current Research (NHLBI)

References

1. ↑ Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1885-9. Abstract | Full Text

External Links

National Heart, Lung, and Blood Institute (NHLBI)

Lung Diseases Information for the Public

The Foundation for Sarcoidosis Research

National Sarcoidosis Resources Center

Sarcoidosis Networking

sisresearch.org/ Sarcoidosis Research Institute