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  • Author: Raed A Dweik, MD, FACP, FRCPC, FCCP, FCCM, FAHA; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
Updated: Dec 31, 2015


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.



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]

A study by Van Dyke et al found that a genetic factor, a glutamic acid at position 69 (E69), and exposure to beryllium contribute to the odds of developing chronic beryllium disease and beryllium sensitization.[2]

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.




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.


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.


Although strong evidence of genetic susceptibility exists, no racial preference has been shown.


Males and females are affected equally.


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.

Contributor Information and Disclosures

Raed A Dweik, MD, FACP, FRCPC, FCCP, FCCM, FAHA Professor of Medicine, Cleveland Clinic Lerner College of Medicine; Director, Pulmonary Vascular Program, Respiratory Institute, Cleveland Clinic

Raed A Dweik, MD, FACP, FRCPC, FCCP, FCCM, FAHA is a member of the following medical societies: American Heart Association, American College of Chest Physicians, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Thoracic Society, Royal College of Physicians and Surgeons of Canada, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.


Gregg T Anders, DO Medical Director, Great Plains Regional Medical Command , Brooke Army Medical Center; Clinical Associate Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Science Center at San Antonio

Disclosure: Nothing to disclose.

Oleh Wasyl Hnatiuk, MD Program Director, National Capital Consortium, Pulmonary and Critical Care, Walter Reed Army Medical Center; Associate Professor, Department of Medicine, Uniformed Services University of Health Sciences

Oleh Wasyl Hnatiuk, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

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A high-resolution CT scan of the chest showing the typical ground glass appearance in a patient with chronic beryllium disease, or berylliosis.
A histopathology slide (hematosin and eosin stain) showing the typical well-formed granuloma of chronic beryllium disease, or berylliosis.
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