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Beryllium Disease

(Berylliosis)

by Lee S. Newman, MD, MA

Acute beryllium disease 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 by formation of granulomas throughout the body, especially in the lungs, intrathoracic lymph nodes, and skin. Chronic beryllium disease causes progressive dyspnea, cough, and fatigue. Diagnosis is by history, beryllium lymphocyte proliferation test, and biopsy. Treatment is with corticosteroids.

Etiology

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, aircraft, automotive, aerospace, and metal scrap, 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

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 lymphocytes by antigen-presenting cells, principally in HLA-DP molecules. T lymphocytes in the blood, lungs, or other organs, in turn, recognize the beryllium, proliferate, and form T-lymphocyte clones. These clones then release proinflammatory cytokines, such as tumor necrosis factor-α, IL-2, and interferon- γ. 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 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 secretaries and security guards, also develop sensitization and disease but at lower rates. The typical pathologic consequence is a diffuse pulmonary, hilar, and mediastinal lymph node granulomatous reaction that is histologically indistinguishable from sarcoidosis. Early granuloma formation with mononuclear and giant cells can also occur. Many lymphocytes are found when cells are washed from the lungs (bronchoalveolar lavage [BAL]) during bronchoscopy. These T lymphocytes proliferate when exposed to beryllium in vitro, much as the blood cells do (a test called beryllium lymphocyte proliferation test [BeLPT]).

Symptoms and Signs

Patients with chronic beryllium disease often have dyspnea, cough, 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 > 40 yr after exposure has ceased. Some people remain asymptomatic.

Diagnosis

  • Beryllium lymphocyte proliferation test (using blood or bronchoalveolar lavage cells)

  • Chest x-ray or CT

Diagnosis depends on a history of exposure, the appropriate clinical manifestations, and an abnormal blood or BAL BeLPT or both. BAL BeLPT is highly sensitive and specific, helping to distinguish chronic beryllium disease from sarcoidosis and other forms of diffuse pulmonary disease. 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.

Prognosis

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 ABG at rest and during exercise testing. Decreased diffusing capacity for carbon monoxide (DL co ) and restriction appear later. Pulmonary hypertension and right ventricular failure develop in about 10% of cases, with death due to cor pulmonale. Beryllium sensitization progresses to chronic beryllium disease at a rate of about 6%/yr after initial detection through workplace medical surveillance programs. Subcutaneous granulomatous nodules caused by inoculation with beryllium splinters or dust usually persist until excised.

Treatment

  • Corticosteroids

  • In acute beryllium disease, sometimes mechanical ventilation

  • In chronic beryllium disease, sometimes supplemental O 2 , pulmonary rehabilitation, and treatment for right ventricular failure

  • In end-stage chronic beryllium disease, sometimes lung transplantation

In acute disease, the lungs often become edematous and hemorrhagic. Mechanical ventilation is necessary in severely affected patients.

Some patients with chronic beryllium disease 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. In symptomatic patients with abnormal pulmonary function, prednisone 40 to 60 mg po once/day or every other day is given for 3 to 6 mo. 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 10 to 15 mg po once/day or every other day). Lifelong treatment with corticosteroids is usually required. There is anecdotal evidence that the addition of methotrexate (10 to 25 mg po once/wk) reduces the need for corticosteroids as it does in sarcoidosis.

Spontaneous remission of chronic beryllium disease is rare. In patients with end-stage disease, lung transplantation can be lifesaving. Other supportive measures, such as supplemental O 2 therapy, pulmonary rehabilitation, and drugs for treatment of right ventricular failure, are used as needed.

Prevention

Industrial dust suppression is the basis for preventing beryllium exposure. Exposures must be reduced to levels that are as low as reasonably achievable—preferably more than 50-fold below current Occupational Safety and Health Administration (OSHA) standards—to reduce the risk of sensitization and chronic beryllium disease. 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.

Key Points

  • 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.

Drugs Mentioned In This Article

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  • OTREXUP
  • RAYOS

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