Berylliosis is a form of metal poisoning caused by inhalation of beryllium dusts, vapors, or its compounds or implantation of the substance in the skin. The toxic effects of beryllium most commonly occur due to occupational exposure. Beryllium is a metallic element used in many industries, including electronics, high-technology ceramics, metals extraction, and dental alloy preparation.
There are two forms of beryllium-induced lung disease, acute and chronic. Acute berylliosis has a sudden, rapid onset and is characterized by severe inflammation of the lungs (pneumonitis), coughing, increasing breathlessness (dyspnea), and other associated symptoms and findings. In addition, in some individuals, the skin or the eyes may be affected. The more common, chronic form of the disease develops more slowly and, in some cases, may not become apparent for many years after initial beryllium exposure. Chronic berylliosis is characterized by the abnormal formation of inflammatory masses or nodules (granulomas) within certain tissues and organs and widespread scarring and thickening of deep lung tissues (interstitial pulmonary fibrosis). Although granuloma development primarily affects the lungs, it may also occur within other bodily tissues and organs, such as the skin and underlying (subcutaneous) tissues or the liver. In individuals with chronic berylliosis, associated symptoms and findings often include dry coughing, fatigue, weight loss, chest pain, and increasing shortness of breath.
Acute berylliosis is a rare condition that develops suddenly due to exposure to beryllium. The condition is primarily characterized by severe inflammation of the lungs (pneumonitis). Associated symptoms typically include an abrupt onset of coughing, and difficulties breathing (dyspnea). Some affected individuals may also develop a sore throat (pharyngitis); inflammation of the mucous membranes of the nose (rhinitis) and associated nasal discharge; and inflammation of the windpipe and air passages of the lungs (tracheobronchitis). In addition, in some cases, other areas of the body may be affected, such as the skin or eyes. Although most individuals with acute berylliosis have a complete recovery with no residual effects, potentially life-threatening complications may result without prompt, appropriate treatment. The severity of the condition may depend upon the duration of beryllium exposure, the concentration of the irritant, and/or other factors.
Chronic berylliosis is a systemic disease in which there is an abnormally exaggerated immune response (hypersensitivity) to beryllium. The onset of symptoms after initial beryllium exposure may be extremely variable, ranging from a few months to years or even decades. In those with chronic berylliosis, abnormal inflammatory nodules (granulomas) form in the lungs and, in some cases, within other bodily tissues. These may include the lymph nodes, liver, skin and underlying (subcutaneous) tissues, and/or other organs and tissues. Chronic berylliosis is also characterized by widespread scarring and thickening of deep lung tissues (interstitial pulmonary fibrosis). Symptoms and findings associated with the disorder may include dry coughing; increasing shortness of breath (dyspnea); chest pain; fatigue; fever; night sweats; lack of appetite (anorexia); weight loss; and enlargement of lymph nodes. Some may also develop reddened patches or small raised spots on the skin. As the disease progresses, affected individuals may have increasingly severe lung damage, resulting in labored breathing with the slightest exertion; liver damage; and potentially life-threatening complications.
Berylliosis is caused by inhalation of beryllium dusts, fumes, or its compounds or entrance of the substance through the skin. Beryllium is a natural metallic chemical element that forms strong, lightweight alloys with various metals. (Alloys are formed by the fusion of two or more metals.) Due to such properties, beryllium has numerous industrial uses including aerospace, electronic, and nuclear components; high-technology ceramics; and dental alloys. In addition, prior to the 1950s, beryllium was often used in the manufacture of fluorescent lights. The risk of beryllium exposure occurs in any setting in which beryllium or its compounds may become airborne in the form of vapors, fumes, small particles, or dust.
Chronic berylliosis, also known as chronic beryllium disease (CBD), is a progressive, systemic disease caused by an abnormally exaggerated immune response (delayed-type hypersensitivity reaction) in individuals who have become “sensitized” or allergic to beryllium (sensitizing antigen). (The immune system is responsible for defending the body against foreign agents, such as toxins and invading microorganisms, including bacteria and viruses.) Sensitization to beryllium may develop rapidly or several years after initial beryllium exposure, resulting in an increased risk of chronic berylliosis.
In those who develop CBD, inappropriately heightened immune reactions result in an abnormal activation of certain white blood cells (macrophages and lymphocytes). The function of macrophages is to surround and destroy foreign particles (phagocytosis). Lymphocyte proliferation in affected tissues results in the formation of the inflammatory masses or nodules (granulomas) characteristically associated with CBD. The granulomas that are formed due to these processes may affect the normal structure and functioning of affected organ(s). For example, granulomas may develop around beryllium particles that are present in the walls of tiny air sacs within the lungs (alveoli), resulting in or contributing to increasing difficulties breathing. (The alveoli contain minute blood vessels [capillaries] that enable the absorption of oxygen into the blood.)
According to reports in the medical literature, a relatively small percentage of employees exposed to beryllium (i.e., one to six percent) ultimately develop CBD. Researchers suggest that specific genetic variations may be associated with sensitization to beryllium and increased suspectibility to CBD. For example, in all individuals, certain genetic variations (i.e., of the major histocompatibility complex [MHC]) result in the production of specific “human leukocyte antigens” or HLAs. HLAs are proteins that stimulate the production of certain antibodies in response to foreign agents. Because the specific structures of HLAs are partially genetically determined, they may take a variety of forms. The results of genetic analysis demonstrate that most individuals with CBD have specific variations (alleles) of one of the major histocompatibility genes (HLA-DPB1 gene alleles with glutamate 69 marker). Researchers suggest that such genetic variations may result in increased susceptibility to CBD in beryllium-exposed individuals.
The toxic effects of beryllium most commonly affect individuals who work in occupational settings in which beryllium or its components may become airborne. As discussed above, beryllium is used in numerous industries, including electronics, high-technology ceramics, dental alloy preparation, and metals extraction.
According to reports in the medical literature, the incidence of acute berylliosis is now rare due to the introduction of protective measures designed to reduce occupational exposure to beryllium. However, chronic beryllium disease (CBD) continues to occur at about the same rate as when the condition was originally reported in the 1940s. Approximately one to six percent of beryllium-exposed employees develop CBD.
In addition, there is increasing evidence that even limited exposure to low concentrations of beryllium may lead to CBD in some individuals with increased susceptibility. For example, research indicates that some employees who work outside of beryllium work zones, such as clerical staff, have developed CBD. There have also been reports of the disorder in family members who were exposed to beryllium dust from an employee’s clothing and in individuals who reside in the vicinity of beryllium refineries.
Individuals with an unexplained cough, difficulties breathing, fatigue, weight loss, and/or rash should inform their physicians concerning any past beryllium exposure. Berylliosis may be diagnosed based upon a thorough clinical evaluation, detection of characteristic physical findings, a complete patient history, and specialized testing. During examination with a stethoscope, abnormal lung sounds may be heard. In addition, a series of procedures may be performed to evaluate the function of the lungs (pulmonary function tests) and chest x-rays are typically conducted. Although imaging studies may be abnormal, the changes are usually similar to those seen in individuals with other lung disorders, such as sarcoidosis. In many patients with CBD, imaging studies may even be normal at the time of their initial presentation. Diagnostic assessment may include the surgical removal (biopsy) and microscopic examination of lung tissue. In those with chronic berylliosis, lung biopsy typically reveals granuloma development (a finding that is also associated with sarcoidosis).
Diagnostic assessment may include additional, more specialized tests to help distinguish berylliosis from other lung disorders. For example, blood tests may be conducted to confirm sensitivity to beryllium (beryllium lymphocyte proliferation test [BeLPT]). When white blood cells (lymphocytes) from affected individuals are cultured in the presence of certain beryllium salts (in vitro), they begin to abnormally proliferate, demonstrating a positive immune reaction associated with beryllium sensitivity or chronic berylliosis. In some cases, the BeLPT may also be conducted on cells and fluid obtained from the tiny air sacs (alveoli) and airways (bronchioles) of the lungs (bronchoalveolar lavage).
Some workplaces have implemented voluntary screening programs using BeLPT blood tests to identify employees with beryllium sensitivity. The goal of such testing is to identify those who may have an increased risk of developing CBD and to reassign such workers away from high-exposure work areas. Evidence suggests that approximately 45 percent of those with positive BeLPT results for beryllium sensitivity go on to develop CBD. However, there is a great deal of controversy concerning the use of such workplace screening, since current tests are not yet considered highly specific predictors of disease. Therefore, many suggest that the implementation of such screening programs may raise ethical issues including concerns about privacy, potential genetic discrimination issues, and whether effective preventive steps or treatments will be available for individuals with positive results. A number of research teams are working on developing more specific diagnostic tests (such as potential genetic analysis) that may more reliably identify employees who are risk for developing CBD.
As discussed above, protective measures have been introduced to minimize beryllium exposure in the workplace. Employees should follow all workplace and safety guidelines and take any additional, appropriate steps to reduce their exposure to beryllium dust particles, fumes, and vapors. For example, it may be advised that, after completing their shifts, employees change out of their work clothing and shoes, shower, and change into street clothing. (This may help to reduce the risk of carrying residual beryllium to their vehicles and back to their residences [e.g., via their hands, clothing, and shoes].)
The treatment of individuals with acute berylliosis may include therapy with corticosteroid drugs, breathing support (such as the use of ventilators), and/or other supportive measures. With prompt, appropriate treatment, most affected individuals have a complete recovery with no residual effects.
If it is determined that individuals have become sensitized to beryllium yet have not developed chronic beryllium disease (CBD), treatment may not be required. However, such individuals should be regularly monitored by physicians to ensure early detection of CBD and prompt, appropriate treatment. Avoidance of further exposure to beryllium is recommended.
There is currently no cure for CBD. Thus, prevention and early recognition of individuals at risk are crucial. In individuals diagnosed with chronic berylliosis, corticosteroid therapy, such as with the medication prednisone, may be prescribed. It is possible that such therapy may help to alleviate certain symptoms in some cases. Other treatment is symptomatic and supportive.
Researchers are conducting clinical trials to determine the effectiveness of a drug called infliximab (Remicade) in chronic beryllium disease (CBD). This drug may reduce tumor necrosis factor-alpha (TNF-a), which is associated with more severe disease and inflammation in the lung. Receiving infliximab may help with symptoms, and may improve clinical testing data normally ordered by your doctor, such as breathing tests.
Investigators are studying the effectiveness of corticosteroid pulse therapy in individuals with chronic beryllium disease. In one case reported in the medical literature, this therapy improved pulmonary function tests and blood gases also improved. More research is necessary to determine the long-term safety and effectiveness of this treatment for individuals with chronic beryllium disease.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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FROM THE INTERNET
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