(See also Overview of Environmental Pulmonary Disease Overview of Environmental Pulmonary Disease Environmental pulmonary diseases result from inhalation of dusts, allergens, chemicals, gases, or environmental pollutants. The lungs are continually exposed to the external environment and... read more .)
Etiology of Beryllium Disease
Beryllium exposure is a common but underrecognized cause of illness in many industries, including beryllium mining and extraction, alloy production, metal alloy machining, electronics, telecommunications, nuclear weapon manufacture, defense industries, aircraft, automotive, aerospace, metal scrap, jewelry making, dental/alloy appliance, computer, and electronics recycling. Because small amounts of beryllium are toxic and are added to many copper, aluminum, nickel, and magnesium alloys, workers are often unaware of their exposure and its risks.
Pathophysiology of Beryllium Disease
Acute beryllium disease is a chemical pneumonitis causing diffuse parenchymal inflammatory infiltrates and nonspecific intra-alveolar edema. Other tissues (eg, skin, conjunctivae) may be affected. Acute beryllium disease is now rare because most industries have reduced exposure levels, but cases were common between 1940 and 1970, and many cases progressed from acute to chronic beryllium disease.
Chronic beryllium disease remains a common illness in industries that use beryllium and beryllium alloy. It differs from most pneumoconioses in that it is a cell-mediated hypersensitivity disease. Beryllium is presented to CD4+ T cells by antigen-presenting cells, principally in HLA-DP molecules. T cells in the blood, lungs, or other organs, in turn, recognize the beryllium, proliferate, and form T-cell clones. These clones then release proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-2, and interferon-gamma. These cytokines amplify the immune response, resulting in formation of mononuclear cell infiltrates and noncaseating granulomas in target organs where beryllium has deposited.
On average, about 2% to 6% of beryllium-exposed people develop beryllium sensitization (defined by positive blood lymphocyte proliferation to beryllium salts in vitro), with most sensitized people progressing to disease. In certain high-risk groups, such as beryllium metal and alloy machinists, chronic beryllium disease prevalence is > 17%. Workers with bystander exposures, such as administrative assistants and security guards, also develop sensitization and disease but at lower rates.
The typical pathologic consequence is
Diffuse pulmonary, hilar, and mediastinal lymph node granulomatous reaction that is histologically indistinguishable from sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more
Early granuloma formation with mononuclear and giant cells can also occur.
Many lymphocytes are found when cells are washed from the lungs (bronchoalveolar lavage) during bronchoscopy. These T cells proliferate when exposed to beryllium in vitro, much as the blood cells do (a test called beryllium lymphocyte proliferation test [BeLPT]).
Symptoms and Signs of Beryllium Disease
Patients with chronic beryllium disease often have dyspnea, cough, night sweats, fatigue, weight loss, and a variable chest x-ray pattern, typically showing nodular opacities in the mid and upper lung zones, frequently with hilar and mediastinal adenopathy. Patients complain of insidious and progressive exertional dyspnea, cough, chest pain, weight loss, night sweats, and fatigue. Symptoms may develop within months of first exposure or > 30 years after exposure has ceased. Some people remain asymptomatic.
Diagnosis of Beryllium Disease
Beryllium lymphocyte proliferation test ,using peripheral blood or bronchoalveolar lavage cells)
Chest x-ray or CT
Diagnosis of beryllium disease depends on a history of exposure, the appropriate clinical manifestations, and an abnormal beryllium lymphocyte proliferation test (BeLPT, in which lymphocytes are cultured with beryllium sulfate) done on blood, bronchoalveolar lavage fluid, or both. Diagnosis of beryllium disease requires 2 abnormal BeLPT results or one abnormal and one borderline result from peripheral blood, or a single abnormal BeLPT result from bronchoalveolar lavage cells.
Acute beryllium disease is distinguished from chronic disease based on history of a very high level of exposure followed by acute onset of dry cough and progressive dyspnea on exertion in addition to systematic signs and symptoms (conjunctivitis, dermatitis, pharyngitis, laryngotracheobronchitis). Further, radiographic findings occur within 1 to 3 weeks of exposure.
In chronic beryllium disease, the signs and symptoms are present for at least a year and the clinical presentation can be varied from asymptomatic to dry cough, progressive dyspnea, fatigue, and night sweats ( 1 Diagnosis references Acute and chronic beryllium disease are caused by inhalation of dust or fumes from beryllium compounds and products. Acute beryllium disease is now rare; chronic beryllium disease is characterized... read more ). BeLPT done on bronchoalveolar lavage cells is highly sensitive and specific, helping to distinguish chronic beryllium disease from sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more and other forms of diffuse pulmonary disease. Because serum angiotensin converting enzyme levels are not sensitive and, when positive, fail to distinguish between exposure and disease, these levels are not routinely measured ( 2 Diagnosis references Acute and chronic beryllium disease are caused by inhalation of dust or fumes from beryllium compounds and products. Acute beryllium disease is now rare; chronic beryllium disease is characterized... read more ).
Chest x-ray may be normal or show diffuse infiltrates that can be nodular, reticular, or have a hazy ground-glass appearance, often with hilar adenopathy resembling the pattern seen in sarcoidosis. A miliary pattern also occurs. High-resolution (thin-section) CT is more sensitive than x-ray, although cases of biopsy-proven disease occur even in people with normal imaging test results.
1. Stoeckle JD, Hardy HL, Weber AL: Chronic beryllium disease: Long-term follow-up of sixty cases and selective review of the literature. Am J Med 46 (4):545–561, 1969.
2. Newman LS, Orton R, Kreiss K: Serum angiotensin converting enzyme activity in chronic beryllium disease. Am Rev Respir Dis 146 (1):39–42, 1992.
Prognosis for Beryllium Disease
Acute beryllium disease can be fatal, but prognosis is usually excellent unless progression to chronic beryllium disease occurs. Chronic beryllium disease often results in progressive loss of respiratory function. Early abnormalities include air flow obstruction and decreased oxygenation on arterial blood gas (ABG) at rest and during exercise testing. Decreased diffusing capacity for carbon monoxide (DLCO) and restriction appear later. Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension is increased pressure in the pulmonary circulation. It has many secondary causes; some cases are idiopathic. In pulmonary hypertension, pulmonary vessels become constricted... read more and right ventricular failure develop in about 10% of cases, with death due to cor pulmonale Cor Pulmonale Cor pulmonale is right ventricular enlargement secondary to a lung disorder that causes pulmonary artery hypertension. Right ventricular failure follows. Findings include peripheral edema, neck... read more .
Beryllium sensitization progresses to chronic beryllium disease at a rate of about 6% per year after initial detection through workplace medical surveillance programs. Subcutaneous granulomatous nodules caused by inoculation with beryllium splinters or dust usually persist until excised.
Treatment of Beryllium Disease
In acute beryllium disease, sometimes mechanical ventilation
In chronic beryllium disease, sometimes supplemental oxygen, pulmonary rehabilitation, and treatment for right ventricular failure
In end-stage chronic beryllium disease, sometimes lung transplantation
In acute beryllium disease, the lungs often become edematous and hemorrhagic. Mechanical ventilation Overview of Mechanical Ventilation Mechanical ventilation can be Noninvasive, involving various types of face masks Invasive, involving endotracheal intubation Selection and use of appropriate techniques require an understanding... read more is necessary in severely affected patients.
In chronic beryllium disease, some patients never require treatment because the disease progresses relatively slowly. When needed, treatment is with corticosteroids, which decrease symptoms and improve oxygenation. Treatment is generally started only in patients with significant symptoms and evidence of abnormal gas exchange or evidence of an accelerated decline in lung function or oxygenation. The overall mortality rates reported are between 5 and 38% ( 1 Treatment references Acute and chronic beryllium disease are caused by inhalation of dust or fumes from beryllium compounds and products. Acute beryllium disease is now rare; chronic beryllium disease is characterized... read more ).
In symptomatic patients with abnormal pulmonary function, prednisone 40 to 60 mg orally once a day or every other day is given for 3 to 6 months. Then, measures of pulmonary physiology and gas exchange are repeated to document a response to therapy, and the dose is gradually tapered to the lowest dose that maintains symptomatic and objective improvement (usually about 5 to 10 mg orally once a day or every other day). Lifelong treatment with corticosteroids is usually required. Inhaled corticosteroids do not appear to improve lung function but can be considered for symptomatic relief of cough and dyspnea for patients who are not taking systemic corticosteroids ( 2 More Information Acute and chronic beryllium disease are caused by inhalation of dust or fumes from beryllium compounds and products. Acute beryllium disease is now rare; chronic beryllium disease is characterized... read more ). There is anecdotal evidence that the addition of methotrexate (10 to 25 mg orally once a week) reduces the need for corticosteroids as it does in sarcoidosis. Azathioprine, which is also used in sarcoidosis, has not been recommended in chronic beryllium disease.
Spontaneous remission of chronic beryllium disease is rare. In patients with end-stage disease, lung transplantation Lung and Heart-Lung Transplantation Lung or heart-lung transplantation is an option for patients who have respiratory insufficiency or failure and who remain at risk of death despite optimal medical treatment. The most common... read more can be lifesaving. Other supportive measures, such as supplemental oxygen therapy, pulmonary rehabilitation Pulmonary Rehabilitation Pulmonary rehabilitation is the use of supervised exercise, education, support, and behavioral intervention to improve functional capacity and enhance quality of life in patients with chronic... read more , and drugs for treatment of right ventricular failure Cor Pulmonale Cor pulmonale is right ventricular enlargement secondary to a lung disorder that causes pulmonary artery hypertension. Right ventricular failure follows. Findings include peripheral edema, neck... read more , are used as needed.
1. Newman LS, Lloyd J, Daniloff E: The natural history of beryllium sensitization and chronic beryllium disease. Environ Health Perspect 104 (Suppl 5):937–943, 1996.
2. Mroz MM, Ferguson JH, Faino AV, et al: Effect of inhaled corticosteroids on lung function in chronic beryllium disease. Respir Med 138S: S14–S19, 2018. doi: 10.1016/j.rmed.2018.01.009
Prevention of Beryllium Disease
Industrial dust suppression is the basis for preventing beryllium exposure. Exposure must be limited to levels that are as low as reasonably achievable; 0.2 micrograms per cubic meter of air, averaged over 8 hours and limited short-term exposure to 2.0 micrograms per cubic meter of air, over a 15-minute sampling period (see OSHA Final Rule to Protect Workers from Beryllium Exposure).
Medical surveillance, using blood BeLPT and chest x-ray, is recommended for all exposed workers, including those with indirect contact. Both acute and chronic disease must be promptly recognized and affected workers removed from further beryllium exposure. High-risk individuals should be screened for lung cancer using low-dose CT ( 1 Prevention reference Acute and chronic beryllium disease are caused by inhalation of dust or fumes from beryllium compounds and products. Acute beryllium disease is now rare; chronic beryllium disease is characterized... read more ).
1. Markowitz SB, Manowitz A, Miller JA, et al: Yield of low-dose computerized tomography screening for lung cancer in high-risk workers: The case of 7189 US nuclear weapons workers. Am J Public Health 108(10): 1296–1302, 2018.
Beryllium disease is under recognized and affects workers in many industries.
Consider high-resolution CT and beryllium lymphocyte proliferation test (using blood or bronchoalveolar lavage cells) to confirm the diagnosis.
Treat symptomatic patients with corticosteroids.
Prevention involves suppression of beryllium dust and surveillance of exposed workers.
Balmes JR, Abraham JL, Dwiek RA, et al: An official American Thoracic Society statement: Diagnosis and management of beryllium sensitivity and chronic beryllium disease. Am J Respir Crit Care Med 190(10):e34–e59, 2014. doi: 10.1164/rccm.201409-1722ST
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