BERYLLIUM
Beryllium (Be) is a metal whose strength, light weight, and other properties make it particularly well suited for aerospace, defense, nuclear, electronic, and other fore-front technology applications. Lung diseases caused by beryllium were first publicized in the early 1940s among beryllium-oxide extraction workers in Ohio and fluorescent lamp manufacturing workers in Massachusetts. Both acute chemical pneumonitis and chronic beryllium disease (CBD) resembling sarcoidosis (“Salem sarcoid” in lamp workers) were observed. Industrial hygiene measures limited the high exposures that caused acute pneumonitis, but the continuing effects of very low-dose exposure after sensitization were more difficult to control. Beryllium is mined in the United States, China, Kazakhstan, Russia, and other countries. The ore is processed on site to beryllium hydroxide and then converted into beryllium metal, oxide, and alloys. Beryllium salts and metal can sensitize susceptible individuals to cause a chronic granulomatous lung disease berylliosis that closely resembles sarcoidosis. The disease occurs almost exclusively among workers involved in beryllium extraction and production of beryllium alloy products. Sensitizing exposure does not occur after the metal has been integrated into finished products. Beryllium lung disease may serve as a paradigm for diseases in which the mechanism involves the combination of a genetically determined immunologically susceptible population with exposure to a unique specific antigen.
CHRONIC BERYLLIUM DISEASE
CBD, or berylliosis, usually begins with the gradual
onset of shortness of breath and dry cough. As the disease worsens, systemic
symptoms of easy fatigue, weakness, anorexia, and weight loss may be seen.
Severe pulmonary involvement can produce dyspnea at rest, hypoxemia, and cor
pulmonale with edema. The radiographic features resemble sarcoidosis with small
reticulonodular opacities in a diffuse or patchy distribution and obscuration
of peripheral vasculature by adjacent ground-glass opacities; bullae, lung
distortion, or pleural thickening are uncommon. Symmetric bilateral hilar lymph
node enlargement is usually moderate rather than massive and is found in fewer
than 50% of cases. Progressive coalescence of opacities in an upper or mid-lung
distribution can be seen as the disease advances. Pulmonary function tests show
a restrictive impairment, diminished gas transfer (DLCO [diffusing capacity for
carbon monoxide]), and hypoxemia at rest that often worsens on exertion; a high
proportion of patients with CBD also evidence airflow obstruction.
The pathology of CBD shows epithelioid cell non-necrotizing granulomas in the lung parenchyma, the hilar and mediastinal lymph
nodes, and less commonly in the skin and other organs. The lesions show
macrophage-derived multinucleated epithelioid giant cells surrounded by smaller
macrophage or monocytes and both T and B lymphocytes. Schaumann bodies are
common. Fibroblasts and collagen infiltrate the centers of the granulomas as the
disease progresses. Beryllium usually cannot be detected within these lesions.
Other organ systems beyond the thorax can be involved in CBD, such as the skin,
liver, spleen, peripheral lymph nodes, and bone marrow. Clinicians and
pathologists agree that sarcoidosis and CBD cannot be distinguished reliably for individual cases.
PATHOGENESIS
The pathogenesis of CBD is driven by the accumulation
of beryllium-specific CD4 Th1-cells at disease sites. Genetic factors appear to
determine the efficacy of presentation of beryllium to T cells, the T-cell
response, and the cytokine production that influences the subsequent immune
inflammatory response. Lung and peripheral blood CD4 T lymphocytes from
sensitized individuals respond to beryllium in vitro by proliferating
vigorously (i.e., the beryllium lymphocyte proliferation test). Sensitization
alone is not sufficient to produce clinically evident lung disease because many
exposed workers develop sensitization without progression to disease.
Lymphocyte immune sensitivity to beryllium is found in 1% to 16% of exposed
workers, but only half of the sensitized workers evidence lung granulomas.
DIAGNOSIS
The diagnosis of CBD requires a compatible clinical
picture, an appropriate environmental exposure history, and the demonstration of
cell-mediated immunity (lymphocyte sensitivity in vitro) to beryllium antigen.
Clinical evidence of disease with noncaseating granulomas in tissue pathology
is essential because not all exposed or sensitized workers develop disease. A
clinical syndrome alone is not sufficient because sarcoidosis can present
identical features and is much more common. Workers suspected of CBD can be
referred to one of several national research centers that offer consultation
and specialized testing.
THERAPY
The therapy for berylliosis is similar to the
treatment for sarcoidosis but must include strict avoidance of beryllium
exposure. Patients with very mild or early disease may require no treatment if
avoidance of further antigen exposure is successful. Most patients can be
managed with relatively low doses of oral corticosteroids. Higher doses of
steroids and cytotoxic or steroid-sparing alternatives (methotrexate,
azathioprine, cyclophosphamide) are equired by more patients with more severe disease.
