Sarcoidosis
Sarcoidosis is a disease in which abnormal collections of inflammatory cells (granulomas) form in many organs of the body.
The cause of sarcoidosis is unknown. It may result from an infection or from an abnormal response of the immune system. Inherited factors may be important. Sarcoidosis develops predominantly between the ages of 20 and 40 and is most common among Swedes and American blacks, although it can occur in anyone.
Sarcoidosis is characterized by the presence of collections of inflammatory cells (granulomas). The disease is primarily one of the lungs, but granulomas also form in the lymph nodes, lungs, liver, eyes, and skin, and less often in the spleen, bones, joints, skeletal muscles, kidneys, heart, and nervous system. The granulomas may eventually disappear completely or become scar tissue.
Symptoms
Many people with sarcoidosis have no symptoms, and the disease is discovered during a chest x-ray that is taken for other reasons. Most people develop minor symptoms that do not progress. Serious symptoms are rare.
The symptoms of sarcoidosis vary greatly according to the site and extent of the disease. Fever, fatigue, vague chest pain, a feeling of illness (malaise), weight loss, and aching joints may be the first indications of a problem in about one third of people. Enlarged lymph nodes are common but do not often cause symptoms. Fever and night sweats may recur throughout the illness.
The organ most affected by sarcoidosis is the lung. Enlarged lymph nodes at the place where the lungs meet the heart or to the right of the windpipe (trachea) may be seen on a chest x-ray. Sarcoidosis produces inflammation in the lungs that may eventually lead to scarring and the formation of cysts, which can cause coughing and shortness of breath. Fortunately, such progressive scarring occurs infrequently. Severe lung disease can eventually weaken the right side of the heart (cor pulmonale (see Section 4, Chapter 54)).
The skin is frequently affected by sarcoidosis. In Europeans, sarcoidosis often starts as raised, tender, red lumps, usually on the shins (erythema nodosum (see Section 18, Chapter 203)), accompanied by a fever and joint pain, but this is less common in the United States. Prolonged sarcoidosis may lead to the formation of flat patches (plaques), raised patches, or lumps just under the skin with discoloration of the nose, cheeks, lips, and ears (lupus pernio). Lupus pernio is most common in black women.
About 70% of people with sarcoidosis have granulomas in their liver. These granulomas often produce no symptoms, and the liver seems to function normally. Fewer than 10% of people with sarcoidosis have an enlarged liver. Jaundice caused by liver malfunction is rare. The spleen also enlarges.
The eyes are affected in 15% of people with sarcoidosis. Inflammation of certain internal eye structures (uveitis) makes the eyes red and painful and interferes with vision. Inflammation that persists for a long time may block fluid from draining from the eye, causing glaucoma (see Section 20, Chapter 233), which can lead to blindness. Granulomas may form in the conjunctiva (the membrane over the eyeball and inside the eyelids). Such granulomas often do not cause symptoms, but the conjunctiva is an accessible site from which a doctor can take tissue samples for examination. Some people with sarcoidosis complain of dry, sore, and red eyes, probably caused by sluggish tear glands that have been affected by the disease and no longer produce enough tears to keep the eyes lubricated.
Granulomas that form in the heart may cause chest pain (angina) or heart failure. Those granulomas that form near the heart's electrical conducting system can trigger potentially fatal irregularities in the heartbeat.
Inflammation can cause widespread pain in the joints. The joints in the hands and feet are most commonly affected. Cysts form in the bones and can make nearby joints swollen and tender.
Sarcoidosis can affect the cranial nerves (nerves of the head), causing double vision and making one side of the face droop. If the pituitary gland or the bones surrounding it are affected, diabetes insipidus (see Section 13, Chapter 162) may result. The pituitary gland stops producing vasopressin, a hormone needed by the kidney to concentrate urine, causing frequent urination and excessive amounts of urine.
Sarcoidosis can cause high levels of calcium to accumulate in the blood and urine. These high levels occur because sarcoid granulomas produce activated vitamin D, which enhances calcium absorption from the intestine. High blood calcium levels lead to a loss of appetite, nausea, vomiting, thirst, and excessive urine production. If present for a long time, high blood calcium levels may lead to the formation of kidney stones or calcium deposits in the kidney and, eventually, to kidney failure.
Diagnosis
Doctors most often diagnose sarcoidosis by observing its distinctive changes, including enlarged lymph nodes and a hazy, ground-glass appearance of lung tissue on a chest x-ray or on computed tomography (CT). When further testing is necessary, microscopic examination of a tissue specimen showing inflammation and granulomas confirms the diagnosis. Bronchoscopy with transbronchial lung biopsy is the best procedure for most people. Other possible sources of tissue specimens are skin abnormalities, enlarged lymph nodes close to the skin, and granulomas on the conjunctiva. Examination of a specimen from one of these tissues is accurate in 87% of cases. A liver biopsy is rarely needed even if there is evidence that the liver is affected.
Tuberculosis can cause many changes similar to those caused by sarcoidosis. Therefore, a doctor also performs a tuberculin skin test (and sometimes a lung biopsy) to make sure the problem is not tuberculosis.
Other methods that can help a doctor diagnose sarcoidosis or assess its severity include measuring the level of angiotensin-converting enzyme (ACE) in the blood, irrigating the lungs and examining the fluid, and using a whole-body gallium scan. In many people with sarcoidosis, the level of angiotensin-converting enzyme in the blood is high. The washings from a lung with active sarcoidosis contain a large number of lymphocytes, but this is not unique to sarcoidosis. Because gallium scanning shows abnormal patterns in the lungs or lymph nodes of a person with sarcoidosis in those places, this test is sometimes used when the diagnosis is uncertain.
In people with lung scarring, pulmonary function tests may show that the amount of air the lung can hold is below normal. Blood tests may reveal a low number of white blood cells or platelets. Immunoglobulin levels are often high, especially in blacks. The levels of liver enzymes, particularly alkaline phosphatase, may be high if the liver is affected.
Prognosis
Sarcoidosis improves or clears up spontaneously in nearly two thirds of people with lung sarcoidosis. Even enlarged lymph nodes in the chest and extensive lung inflammation may disappear in a few months or years. The course can be chronic or progressive in 10 to 30% of people. Serious involvement outside of the chest (for example, of the heart, nervous system, eyes, or liver) occurs in 4 to 7% of people at the beginning of their illness; the chance of involvement outside of the chest increases if lung disease persists.
People who have sarcoidosis that has not spread beyond the chest do better than those who also have sarcoidosis elsewhere in the body. People with enlarged lymph nodes in the chest but no sign of lung disease have a very good prognosis. Those whose disease began with erythema nodosum have the best prognosis. About 50% of people who once had sarcoidosis have relapses.
About 10% of people with sarcoidosis develop a serious disability from damage to the eyes, respiratory system, or elsewhere. Lung scarring leading to respiratory failure, and cor pulmonale is the most common cause of death, followed by bleeding from lung infection caused by the fungus Aspergillus. This fungus tends to grow in the lung cysts that develop in patients with progressive, chronic lung sarcoidosis.
Treatment
Most people with sarcoidosis do not need treatment. Corticosteroids are given to suppress severe symptoms such as shortness of breath, joint pain, and fever. These drugs also are given if tests show high levels of calcium in the blood; if the heart, liver, or nervous system is affected; if the sarcoidosis causes disfiguring skin lesions or eye disease that corticosteroid eyedrops fail to cure; or if lung disease continues to worsen. People who have no symptoms should not take corticosteroids. Although corticosteroids control symptoms well, they do not prevent lung scarring over the years. About 10% of those who need treatment fail to respond to corticosteroids and are switched to chlorambucil or methotrexate, which may be very effective. Hydroxychloroquine is sometimes helpful in eliminating disfiguring skin lesions.
The success of treatment can be monitored with chest x-rays, CT, pulmonary function tests, and measurements of calcium or angiotensin-converting enzyme levels in the blood. These tests are repeated regularly to detect relapses after treatment stops.
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