Family doctor

What is it and what causes it?

Sarcoidosis is a disease in which unusual tissue formations called granulomas are deposited in organs throughout the body. Granulomas are collections of immune and inflammatory cells surround by fibrous tissue, which develop as an immune response to a trigger of some description. Their presence results in distortion and inflammation of the normal tissue in which they are deposited.

 Granulomas occur in many conditions for which the triggers can be identified, including infections (e.g. tuberculosis, brucellosis), occupational diseases (e.g. beryllium disease), autoimmune diseases (e.g. primary biliary cirrhosis) and cancer (e.g. lymphoma) &endash; to name a few examples. In sarcoidosis, however, the precise trigger remains as yet unknown.

 Many studies have looked at the particular triggers that may be the cause of sarcoidosis, and various possible factors have been identified, including:

• environmental triggers (numerous cases of sarcoidosis occurred in a group of fire-fighters who lived together)
• infectious causes (sarcoidosis has been transmitted by heart and bone marrow transplants)
• genetic factors (sarcoidosis occurs in 5% of family members of a white person with the disease &endash; a much higher rate than normal).

 Who gets sarcoidosis?

Sarcoidosis occurs throughout the world, but is more common in certain races &endash; especially African Americans. Amongst white races, it is found more frequently in Scandinavians. It is rare in Asians. Women are more commonly affected than men, and although the disease can occur at the extremes of age, it is most typical in those aged 20-40 years.

 How do I know I have it?

Patients with asymptomatic sarcoidosis are usually diagnosed incidentally after a chest x-ray demonstrates disease in the lymph glands or lungs. However, most people with sarcoidosis present to their doctors with non-specific, generalised symptoms, including fatigue, loss of appetite, weigh loss and fever. Other symptoms relate to the organs involved, with over 50% of patients presenting with ongoing respiratory symptoms.

 In general, the symptoms relate to the organs that are affected by granulomas. Some of the symptoms that may occur depending on the organs involved are shown in the table.

How is sarcoidosis diagnosed?

Because sarcoidosis can affect so many different organs and cause a variety of symptoms in different patients, it has to be distinguished from other diseases that may cause similar effects. Consequently, when a patient presents with a constellation of symptoms, a variety of tests may be ordered to help make a diagnosis. Sarcoidosis may only sometimes be considered in the first instance (for example, if there are specific findings on a chest x-ray). More often it is diagnosed after a number of other possible diseases have been excluded (especially as the cause of sarcoidosis remains unknown).

 There are no specific blood tests, skin tests, or x-ray studies to confirm the diagnosis of sarcoidosis, which can only be proven by a biopsy of an area with granulomas. Nowadays biopsies are taken from sites that are easily accessible, such as the skin and the lungs (via bronchoscopy &endash; i.e. direct examination of the airways using a special tube inserted down the breathing tube). The biopsy specimen is then examined microscopically, to determine that it contains granulomas; if found, various other tests should be conducted to exclude other causes of these lesions.

 The examination and tests that are recommended as part of the initial evaluation in sarcoidosis are as follows:

• complete medical history, and history of possible occupational and environmental exposure
• full physical examination, with emphasis on lung, skin, eye, liver and heart
• chest x-rays (to determine severity of lung involvement)
• testing of lung function
• ECG (electrical tracing of heart)
• eye examination using a 'slit lamp'
• blood tests of liver and kidney function; measurement of serum calcium
• other tests depending on organs involved.

 How is it sarcoidosis treated?

Patients with sarcoidosis require regular monitoring of their disease to determine if it is progressing. Assessment by specialists is often indicated. Patients may be advised to follow a low-calcium diet, and to avoid sunlight and vitamin D supplements (as these can compound hypercalcaemia).

 Patients without severe disease should be managed by observation in the first instance, because many of them will recover spontaneously. However, oral corticosteroids such as prednisone are necessary to treat those with severe sarcoidosis affecting the eyes, nerves, heart, or lungs, or those with excessively raised calcium levels.

 Corticosteroids can suppress the disease, causing a decrease in the number of granulomas and improvement in the function of affected organs. Corticosteroids may be necessary long-term, as many patients relapse after stopping them. Occasionally, steroid therapy may be given by injection (e.g. into skin or eye lesions).

 'Cytotoxic drugs' are the other agents used to treat sarcoidosis. These drugs affect specific immune cells (an integral part of granulomas) and although they are generally used for other conditions such as cancer, some have been tried in sarcoidosis. Methotrexate is particularly useful for those sarcoidosis patients who have not responded well to corticosteroids (such as those with disease of the musculoskeletal system). Cyclosporine is another cytotoxic agent that has been tried for sarcoidosis, although with less benefit that hoped.

 Treatment for complications of sarcoidosis depends on the organ affected; for example, those with cardiac sarcoidosis may require medications to control heart failure if it develops as a consequence of the disease.

 Occasionally, patients with sarcoidosis require organ transplantation to improve their survival and quality of life; examples include liver, lungs and heart.

 What is the course of sarcoidosis?

Sarcoidosis may cause no symptoms (i.e. it is 'asymptomatic), acute disease (i.e. it causes symptoms over a short period of time) or chronic disease (i.e. it causes symptoms over a long period of time). The disease may affect many different organs or only one at a time, and the symptoms may be mild or severe. Around two-thirds of patients demonstrate spontaneous recovery (in which the granulomas disappear), while others require constant medications to control their symptoms or slow disease progression. In 15-20% of patients, symptoms may recur after they have apparently disappeared or been controlled.

 Around one third of patients develop chronic disease, and of them, up to 25% may die from lung disease. (If granulomas are deposited in the lungs or heart, these organs may begin to dysfunction, eventually resulting in the death of the patient.) Overall, 5% of patients with sarcoidosis die of their disease, most commonly from lung or heart involvement.

 Many tests have been investigated to see if they can predict the course of sarcoidosis; as yet, few have proved to be particularly useful.

 The course of the disease differs according to race, with white persons usually having asymptomatic or chronic disease. In blacks, the disease is usually more acute and more severe.