Introduction
Background
Inhalation of beryllium (Be) has been associated with 2 pulmonary syndromes, which are an acute chemical pneumonitis and a granulomatous lung disease known as chronic beryllium disease (CBD), or berylliosis.
In acute beryllium disease, the metal acts as a direct chemical irritant, causing a nonspecific inflammatory reaction (acute chemical pneumonitis). Due to improved industrial hygiene measures, acute beryllium disease virtually has disappeared and is not discussed in this article.
CBD continues to occur in industries where beryllium is manufactured and processed and workers are exposed to beryllium fumes or dust. It is clinically similar to other granulomatous diseases such as sarcoidosis.
To make the diagnosis of CBD, the following criteria need to be satisfied: (1) evidence of sensitization to beryllium by positive findings on blood or bronchoalveolar lavage (BAL) beryllium lymphocyte proliferation test (BeLPT) (see Workup) and (2) the presence of compatible lung pathology (usually nonnecrotizing granulomas on lung biopsy).
Patients with a positive finding on blood BeLPT but no lung pathology are considered sensitized to beryllium, but they do not have CBD.
In patients with unclear or uncertain history of exposure to beryllium, a positive finding on BeLPT can be used as evidence of prior exposure.
Pathophysiology
The key to the pathogenesis of chronic beryllium disease (CBD) is a delayed-type hypersensitivity reaction in which beryllium most likely functions as a hapten and acts as a class II restricted antigen, stimulating local proliferation and accumulation in the lung of beryllium-specific T cells.
Beryllium exposure occurs primarily by inhalation of beryllium fumes or dust and contact through broken skin.
Most beryllium is excreted in the urine, and the pulmonary half-life ranges from several weeks to 6 months. Relatively insoluble chemical forms of beryllium may be retained for years.
Following inhalation of beryllium, large numbers of CD4+ lymphocytes accumulate in the lungs. These helper T cells demonstrate a marked proliferative response on exposure to beryllium.1
Beryllium not only has antigen-specific effects but also acts in nonspecific inflammatory ways to promote the cellular events leading to granuloma formation. It may induce changes in lung permeability and production of proinflammatory cytokines and growth factors that lead to granuloma formation and maintenance.
As the disease progresses, the granulomas become organized and eventually form small, fibrous nodules; progressive impairment of pulmonary function occurs.
Frequency
United States
A small percentage of exposed persons (1-10%) develop beryllium hypersensitivity and a portion of those go on to develop chronic disease.
Attack rates can be as high as 16% in selected worker populations with higher exposures. Usually the attack rate is highest in areas of highest exposure.
The disease also has been reported in populations with very low exposure, such as secretaries, who are not involved in the manufacturing process.
Mortality/Morbidity
- A wide spectrum of morbidity exists with CBD. Some patients may be completely asymptomatic while others may progress to disabling lung dysfunction and death. The factors that determine progression of the disease are not clear.
- The lung is the primary organ involved in CBD, and, as the disease progresses, granulomas become organized and eventually form small fibrous nodules that lead to progressive impairment of pulmonary function.
- Inhaled beryllium is solubilized in the lungs and distributed primarily to bone, liver, and kidneys. However, other organs can be involved, including extrapulmonary lymph nodes, skin, salivary glands, myocardium, and skeletal muscle.
Race
Although strong evidence of genetic susceptibility exists, no racial preference has been shown.
Sex
Males and females are affected equally.
Age
CBD is reported in all age groups, from children (due to secondary exposure) to elderly people. Because this is mostly an occupationally acquired disease, the most commonly affected age group is adults.
Clinical
History
- The most significant exposure to beryllium occurs in the occupational setting. Obtaining a good occupational history is critical to effective diagnosis.
- Occupations with the highest potential for exposure to beryllium are those involved with primary production, metal machining, and reclaiming scrap alloys. Other high-exposure occupations are in the nuclear power, aerospace, and electronics industries. Some of the modern day uses of beryllium include the following:
- Nuclear reactors and weapons
- Inertial guidance systems
- X-ray tube windows
- Turbine rotor blades
- Spark plugs
- Laser tubes
- Electrical components
- Rocket engine liners
- Ceramic applications
- Springs, gears, aircraft brakes, aircraft engines, landing gear, and bearings
- Oil and gas industries
- Injection and blow mold tooling
- Welding electrodes
- Electrical contacts
- Computer electronics
- Automotive electronics
- The number of industries that use beryllium is continuously expanding and the above list should not be viewed as exclusive. Beryllium has been used in a wide variety of products, including some bicycles and golf clubs.
- Individuals using end products that contain beryllium, however, are not currently considered at risk for sensitization or disease. Only if the beryllium component is handled in a way that generates beryllium dust or particles (eg, sanding) would there be a risk.
- With the use of the BeLPT, establishing the diagnosis of CBD before any symptoms develop now is common.
- Dyspnea, usually of insidious onset, is the most common symptom. Other symptoms include the following:
- Cough
- Chest pain
- Arthralgia
- Fatigue
- Weight loss
Physical
- Making the diagnosis of CBD before any physical signs can be detected now is common.
- Physical signs include the following:
- Inspiratory crackles on pulmonary auscultation
- Lymphadenopathy
- Skin rash (dermatitis)2
- Hepatosplenomegaly
Causes
Chronic beryllium disease (CBD), or berylliosis, is an occupationally acquired lung disease caused by exposure to beryllium, primarily by inhalation and contact through broken skin.
- Genetic predisposition seems to have a major role in the development of CBD.
- A variant of the major histocompatibility complex HLA-DPb1(Glu 69) was found in 97% of patients with CBD and only in 30% of controls. In this genetic variant, glutamine is expressed instead of lysine at position 69 of the beta region of class II of the major histocompatibility complex.3
- This genotype is a marker for susceptibility to CBD, but it is not useful as a screening test due to its high prevalence in the general population (>30%).
More on Berylliosis |
 Overview: Berylliosis |
| Differential Diagnoses & Workup: Berylliosis |
| Treatment & Medication: Berylliosis |
| Follow-up: Berylliosis |
| Multimedia: Berylliosis |
| References |
| Next Page » |
References
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Further Reading
Keywords
berylliosis, beryllium, Be, chronic beryllium disease, CBD, acute beryllium disease, acute chemical pneumonitis
