Berylliosis

Acute and chronic berylliosis are caused by inhalation of dust or vapors of beryllium compounds and products. Acute berylliosis is now rare; chronic berylliosis is characterized by the formation of granulomas throughout the body, especially in the lungs, intrathoracic lymph nodes, and skin. Chronic berylliosis causes progressive dyspnea, cough, and malaise. Diagnosis is made by comparing the anamnesis, beryllium lymphocyte proliferation test, and biopsy. Treatment of berylliosis is with glucocorticoids.

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Causes of berylliosis

Beryllium exposure is a common but unrecognized cause of illness in many industries, including beryllium exploration and mining, alloy manufacturing, metal alloy processing, electronics, telecommunications, nuclear weapons, defense, aviation, automotive, aerospace, and electronics and computer recycling.

Acute beryllium disease is a chemical pneumonitis causing diffuse parenchymatous inflammatory infiltrates and nonspecific intraalveolar edema. Other tissues (eg, skin and conjunctiva) may also be affected. Acute beryllium disease is now rare because most industries have reduced exposure levels, but cases were common in the 1940s–1970s, and many progressed from acute to chronic beryllium disease.

Chronic beryllium disease remains common in industries that use beryllium and beryllium alloy. The disease differs from most pneumoconioses in that it is a cellular hypersensitivity reaction. Beryllium is presented to CD4+ T cells by antigen-presenting cells, primarily in the context of HLA-DP molecules. T cells in the blood, lung, or other organs in turn recognize the beryllium, proliferate, and form T cell clones. These clones then produce proinflammatory cytokines such as tumor necrosis factor-α, IL-2, and interferon-gamma. These enhance the immune response, leading to the formation of mononuclear infiltrates and noncaseating granulomas in target organs where beryllium is deposited. On average, 2–6% of people exposed to beryllium develop beryllium sensitization (defined as positive blood lymphocyte proliferation to a beryllium salt in vitro), most of whom develop disease. Certain high-risk groups, such as workers in beryllium metals and alloys, have a prevalence of chronic beryllium disease greater than 17%. Indirectly exposed workers, such as secretaries and security guards, are also prone to develop sensitization and disease, but less frequently. Typical pathological changes are a diffuse granulomatous reaction of the pulmonary, hilar, and mediastinal lymph nodes, histologically indistinguishable from sarcoidosis. Early granuloma formation with mononuclear and giant cells may also occur. If cells are washed out of the lungs during bronchoscopy, large numbers of lymphocytes are found (bronchoalveolar lavage [BAL]). These T lymphocytes proliferate when exposed to beryllium in vitro to a greater extent than blood cells (beryllium lymphocyte proliferation test [BLPT]).

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Symptoms of berylliosis

Patients with chronic beryllium disease often present with dyspnea, cough, weight loss, and a highly variable chest radiographic appearance, usually characterized by diffuse interstitial consolidation. Patients present with sudden and progressive dyspnea on exertion, cough, chest pain, weight loss, night sweats, and fatigue. Symptoms of beryllium disease may develop within months of initial exposure or more than 40 years after exposure has ceased. Some individuals remain asymptomatic. Chest radiography may be normal or show scattered infiltrates that may be focal, reticular, or have a ground-glass appearance, often with hilar adenopathy, resembling the changes seen in sarcoidosis. A miliary pattern also occurs. High-resolution chest radiography is more sensitive than plain radiography, although cases of biopsy-proven disease occur even in patients with normal imaging findings.

Diagnosis of berylliosis

Diagnosis depends on the history of exposure, adequate clinical manifestations, and abnormal blood tests and/or BAL BTPL. BAL BTPL is very sensitive and specific, helping to differentiate chronic beryllium disease from sarcoidosis and other forms of diffuse lung disease.

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Treatment of berylliosis

Some patients with chronic beryllium disease never require treatment because of the relatively slow progression of the disease. Treatment is with glucocorticoids, which result in symptomatic recovery and improved oxygenation. Treatment of beryllium disease is usually initiated only in patients who have significant symptoms and signs of impaired gas exchange or a rapid decline in lung function or oxygenation. Symptomatic patients with impaired lung function are given prednisolone 40 to 60 mg orally once daily or every other day for 3 to 6 months, after which pulmonary physiology and gas exchange are re-evaluated to document response to therapy. The dose is then gradually tapered to the lowest dose that maintains symptomatic and objective recovery (usually approximately 10 to 15 mg once daily or every other day). Lifelong glucocorticoid therapy is usually required. There is a surprising indication that the addition of methotrexate (orally 10-25 mg once a week) allows for a reduction in glucocorticoid doses in chronic beryllium disease, similar to that seen in sarcoidosis.

Acute berylliosis often causes edema and hemorrhages in the lungs. In severe cases, artificial ventilation is necessary.

Unlike many cases of sarcoidosis, spontaneous recovery from chronic beryllium disease is rare. In patients with terminal chronic beryllium disease, lung transplantation may be lifesaving. Other supportive measures, such as supplemental oxygen, pulmonary rehabilitation, and drugs to treat right ventricular failure, are used as needed.

How to prevent berylliosis?

Industrial dust control is the primary means of preventing beryllium exposure. Exposures should be reduced to levels as low as reasonably practicable, preferably more than 10 times lower than current OSHA standards, to reduce the risk of sensitization and chronic beryllium disease. Medical surveillance with blood BTPL testing and chest radiography is recommended for all exposed workers, including those with direct or indirect contact. Beryllium disease (both acute and chronic) should be promptly recognized, and sensitized workers removed from further exposure to beryllium.

What is the prognosis for berylliosis?

Acute beryllium disease can be fatal, but the prognosis is usually good unless patients progress to chronic beryllium disease. Chronic beryllium disease often results in progressive loss of respiratory function. Early findings include obstructive respiratory failure and decreased oxygenation on resting and exercise blood gas measurements. Decreased diffusing capacity for carbon monoxide (DL^) and restriction occur later. Pulmonary hypertension and right ventricular failure develop in about 10% of cases, leading to death from cor pulmonale. Beryllium sensitization progresses to chronic beryllium disease in about 8% of medically sensitized patients per year. Subcutaneous granulomatous nodules caused by encapsulated beryllium dust or splinters usually persist until excision.