Mystery

Sarcoidosis was first identified over 100 years ago by two dermatologists working independently Dr. Jonathan Hutchinson in England and Dr. Caesar Boeck in Norway. Sarcoidosis was originally called Hutchinsons disease or Boecks disease. Dr. Boeck went on to fashion todays name for the disease from the Greek words sark and oid, meaning flesh-like. The term describes the skin eruptions that are frequently caused by the illness. Sarcoidosis ranks among the top misdiagnosed illnesses and is one of the least understood. It is an inflammatuous disease that can appear in almost any body organ, but most often it starts in the lungs or lymph nodes. The disease can appear suddenly and disappear just as fast. It can also develop gradually and go on to produce symptoms that come and go, sometimes for a lifetime. No one yet knows what causes sarcoidosis.

As sarcoidosis progresses, small lumps (granulomas) appear in the affected tissues. In the majority of cases, these granulomas clear up, either with or without treatment. In cases where the granulomas do not heal and disappear, the tissues tend to remain inflamed and become scarred (fibrotic). Originally, scientists thought that sarcoidosis was caused by an acquired state of immunological inertness (anergy). This notion was revised a few years ago, when the technique of bronchoalveolar lavage provided access to a vast array of cells and cell-derived mediators operating in the lungs of patients with sarcoidosis. Sarcoidosis is now believed to be associated with a complex mix of immunological disturbances involving simultaneous activation, as well as depression of certain immunological functions. Immunological studies on patients with sarcoidosis show that many of the immune functions associated with thymus-derived white blood cells, called T-lymphocytes or T-cells, are depressed. The depression of this cellular component of systemic immune response is expressed in the inability of the patients to evoke a delayed hypersensitivity skin reaction (a positive skin test), when tested by the appropriate foreign substance, or antigen. In addition, the blood of patients with sarcoidosis contains a reduced number of T-cells. These T-cells do not seem capable of responding normally when treated with substances known to stimulate the growth of laboratory-cultured T-cells. Neither do they produce their normal complement of immunological mediators, cytokines, through which the cells modify the behavior of other cells.

There are many unanswered questions about sarcoidosis. Identifying the agent that causes the illness, along with the inflammatory mechanisms that set the stage for the alveolitis, granuloma formation, and fibrosis that characterize the disease, is the major aim of the National Heart, Lung, and Blood Institutes program on sarcoidosis. Development of reliable methods of diagnosis, treatment, and eventually, the prevention of sarcoidosis is the ultimate goal.

Who gets sarcoidosis?
Sarcoidosis was once considered a rare disease. We now know that it is a common chronic illness that appears all over the world. Indeed, it is the most common of the fibrotic lung disorders, and occurs often enough in the United States for Congress to have declared a national Sarcoidosis Awareness Day in 1990. Anyone can get sarcoidosis, and it occurs in all races and in both sexes. Nevertheless, the risk is greater if you are a young black adult, especially a black woman, or of Scandinavian, German, Irish, or Puerto Rican origin.

Because sarcoidosis can escape diagnosis or be mistaken for several other diseases, we can only guess at how many people are affected. The best estimate today is that about 5 in 100,000 whites in the United States have sarcoidosis. In blacks, it occurs more frequently, in probably 40 out of 100,000 people. Sarcoidosis mainly affects people between 20 to 40 years of age. White women are just as likely as white men to get sarcoidosis, but black females get sarcoidosis twice as often as black males. Overall, there appear to be 20 cases per 100,000 in cities on the east coast and somewhat fewer in rural locations. Some scientists, however, believe that these figures greatly underestimate the percentage of the U.S. population with sarcoidosis.

Course of the disease
In general, sarcoidosis appears briefly and heals naturally in 60 to 70 percent of the cases, often without the patient knowing or doing anything about it. From 20 to 30 percent of patients with sarcoidosis are left with some permanent lung damage. In 10 to 15 percent of the patients, sarcoidosis can become chronic. When either the granulomas or fibrosis seriously affect the function of a vital organ�the lungs, heart, nervous system, liver, or kidneys, for example�sarcoidosis can be fatal. This occurs 5 to 10 percent of the time. No one can predict how sarcoidosis will progress in an individual patient. But the symptoms the patient experiences, the doctors findings, and the patients race can give some clues.

For example, a sudden onset of general symptoms such as weight loss or feeling poorly are usually taken to mean that the course of sarcoidosis will be relatively short and mild. Dyspnea often indicate that the course of sarcoidosis will be more chronic and severe. White patients are more likely to develop the milder form of the disease. Black people tend to develop the more chronic and severe form. Sarcoidosis rarely develops before the age of 10 or after the age of 60. However, the illness�with or without symptoms�has been reported in younger as well as in older people. Symptoms that appear in these age groups are tiredness, sluggishness, coughing, and a general feeling of ill health.

Signs and symptoms
In addition to the lungs and lymph nodes, the body organs more likely to be affected by sarcoidosis are the liver, skin, heart, nervous system, and kidneys, in that order of frequency. Patients can have symptoms related to the specific organ affected, they can have only general symptoms, or they can be without any symptoms whatsoever. Symptoms also can vary according to how long the illness has been under way, where the granulomas are forming, how much tissue has become affected, and whether the granulomatous process is still active.

Even when there are no symptoms, a doctor can sometimes pick up signs of sarcoidosis during a routine examination, usually a chest x-ray, or when checking other complaints. The patients age and race or ethnic group can raise an additional red flag that a sign or symptom could be related to sarcoidosis. Enlargement of the salivary or tear glands and cysts in bone tissue may also be caused by sarcoidosis.

Laboratory Tests
No single test can be relied on for a correct diagnosis of sarcoidosis. X-rays and blood tests are usually the first procedures the doctor will order. Pulmonary function tests often provide clues to diagnosis. Other tests that the doctor uses to help diagnose sarcoidosis or follow the progress of the disease include bronchoalveolar lavage, biopsy, gallium screening, Kveim test, and slit-lamp examination.

Management
Fortunately, many patients with sarcoidosis require no treatment. When therapy is recommended, the main goal is to keep the lungs and other affected body organs working and to relieve symptoms. The disease is considered inactive once the symptoms fade. Corticosteroids remain the primary treatment for inflammation and granuloma formation. Prednisone is probably the corticosteroid most often prescribed today. There is no treatment at present to reverse the fibrosis that might be present in advanced sarcoidosis. Occasionally, a blood test will show a high blood level of calcium accompanying sarcoidosis. The reasons for this are not clear. Some scientists believe that this condition is not common. When it does occur, the patient may be advised to avoid calcium-rich foods, vitamin D, or sunlight, or to take prednisone; this corticosteroid quickly reverses the condition.

Because sarcoidosis can disappear even without therapy, doctors sometimes disagree on when to start the treatment, what dose to prescribe, and how long to continue the medicine. The doctors decision depends on the organ systems involved and how far the inflammation has progressed. If the disease appears to be severe�especially in the lungs, eyes, heart, nervous system, spleen, or kidneys�the doctor may prescribe corticosteroids.

The NHLBI and sarcoidosis
The NHLBI is supporting a number of research projects examining the causes and treatment of sarcoidosis. Researchers supported by the National Heart, Lung, and Blood Institute are trying to answer the following research questions:

What is sarcoidosis?
Is it produced by a single agent or several?
In which body organ does sarcoidosis actually start?
How does sarcoidosis spread from one part of the body to another?
Do heredity, environment, and lifestyle play any role in the appearance, severity, or length of the disease?
Is the abnormal immune response seen in patients a cause or an effect of the disease?
How can sarcoidosis be prevented?
In 1995, the National Heart, Lung, and Blood Institute started a multi-center case control study of the etiology of sarcoidosis. The investigation is planned to last six years and is collecting information and specimens for use in investigation of environmental, occupational, lifestyle, and genetic risk factors for sarcoidosis. Examination of the natural history of sarcoidosis is underway in patients at early and late stages of the disease. Such information should improve our understanding of the cause(s) of sarcoidosis and provide insight into how to better prevent and treat the disease.

Another clinical trial supported by the NHLBI is the Treatment of Pulmonary Sarcoidosis with Pentoxifylline (POF), a xanthine derivative used for many years in the treatment of peripheral vascular disease. This is a randomized, double-blind, placebo-controlled trial with POF in patients with pulmonary sarcoidosis on corticosteroid therapy. The primary objective of this study is to determine whether POF treatment can be beneficial as an adjunct to corticosteroid therapy in patients with pulmonary sarcoidosis.

Programs focusing on sarcoidosis in Blacks
A trial the NHLBI started in 1995, A Case-Controlled Etiologic Study of Sarcoidosis (ACCESS), is directed at understanding the disproportionate prevalence of sarcoidosis among blacks and women. The major objective of this multi-center case-control study in a predominately black population is to assess the role of environmental and familial factors in the etiology of the disease. One of the investigator-initiated studies aims to determine whether hereditary susceptibility predisposes blacks to sarcoidosis and to identify sarcoidosis susceptibility genes in blacks.

Another project is elucidating the mechanisms involved in the immunologic and inflammatory processes that ultimately lead to end-stage fibrosis in progressive pulmonary sarcoidosis; 50 percent of the participants are black. The protocols in all studies include comprehensive clinical characterization and examination of markers of immune responsiveness as well as banking of blood components for further studies.