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Beryllium Disease

(Berylliosis)

By

Carrie A. Redlich

, MD, MPH, Yale Occupational and Environmental Medicine Program Yale School of Medicine;


Efia S. James

, MD, MPH, Yale School of Medicine;


Brian Linde

, MD, MPH, Yale Occ and Env Medicine Program

Reviewed/Revised Oct 2023
View PATIENT EDUCATION

Acute 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 the formation of granulomas especially in the lungs and intrathoracic lymph nodes. The presentation of chronic beryllium disease is often similar to that of pulmonary sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more Sarcoidosis , with progressive dyspnea, cough, and fatigue, and can be misdiagnosed as sarcoidosis without a comprehensive occupational and environmental history. Diagnosis is made by history and diagnostic testing. Treatment is similar to pulmonary sarcoidosis.

Pathophysiology of Beryllium Disease

Acute beryllium disease is a chemical pneumonitis causing diffuse parenchymal inflammatory infiltrates and nonspecific intra-alveolar edema. Acute beryllium disease is now rare because most industries have reduced exposure levels.

Chronic beryllium disease continues to occur in industries that use beryllium and beryllium alloy. It differs from most pneumoconioses in that it is a cell-mediated hypersensitivity disease. T cells become sensitized to beryllium and then proliferate on re-exposure. This leads to the release of proinflammatory cytokines (such as tumor necrosis factor-alpha, interleukin-2, and interferon-gamma) and granulomatous inflammation. The proliferation of T cells from the lungs or blood when exposed to beryllium in vitro forms the basis of the beryllium lymphocyte proliferation test [BeLPT] test, which is used clinically to identify immune sensitization to beryllium.

The typical pathologic feature is a diffuse pulmonary, hilar, and/or mediastinal lymph node granulomatous reaction that is histologically indistinguishable from sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more Sarcoidosis .

The risk of progression from beryllium exposure to beryllium sensitization is multifactorial, including the dose of exposures, duration of exposures, and genetic factors.

Studies have shown that about 1% to 18% of beryllium-exposed workers develop beryllium sensitization (defined by positive blood lymphocyte proliferation to beryllium salts in vitro), with 6% to 8% of the workers progressing to chronic beryllium disease (1 Pathophysiology reference Acute 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... read more ). Workers with bystander exposures, such as administrative assistants and security guards, can also develop sensitization and disease at lower rates.

Pathophysiology reference

Etiology of Beryllium Disease

Beryllium exposure can occur in many industries, including beryllium mining and extraction, alloy production, metal alloy machining, electronics, telecommunications, nuclear weapon and defense industries, aerospace, and metal reclamation and recycling. Small amounts of beryllium may also be added to copper, aluminum, nickel, and other metals to make beryllium alloys. Given that beryllium is a sensitizer, relatively low level exposures can cause disease in susceptible individuals.

Symptoms and Signs of Beryllium Disease

Patients with chronic beryllium disease present with dyspnea, cough, night sweats, fatigue, and weight loss. Symptoms may develop within months of first exposure or > 30 years after exposure has ceased.

Symptoms and signs reference

Diagnosis of Beryllium Disease

  • Chest x-ray or CT

  • Beryllium sensitization, which is established with an abnormal beryllium lymphocyte proliferation test (BeLPT), using peripheral blood or bronchoalveolar lavage cells

  • Lung biopsy to document granulomatous inflammation

A chest x-ray may be normal or show diffuse infiltrates that can be nodular, reticular, or have a hazy ground-glass appearance in the upper lung zones, often with hilar and mediastinal adenopathy resembling the pattern seen in sarcoidosis. High-resolution chest CT is more sensitive than x-ray, although cases of biopsy-proven disease occur even in people with normal imaging test results.

The BeLPT, in which lymphocytes, obtained from a blood sample or from bronchoalveolar lavage fluid, are cultured with beryllium sulfate, is used to detect immune sensitization to beryllium. The BeLPT is recommended in all suspected cases of beryllium disease. It is also used to detect sensitization in workers exposed to beryllium.

Making the diagnosis of beryllium disease can be challenging because the BeLPT has limitations and is not widely available, and lung tissue cannot always be obtained. However, a diagnosis of probable beryllium disease can be made with differing combinations of the diagnostic criteria, including a history of exposure, chest imaging with findings consistent with sarcoidosis, abnormal pulmonary function test results, abnormal BeLPT results, bronchoalveolar lavage (BAL) lymphocytosis, and granulomatous inflammation on lung biopsy. It should be noted that certain findings, such as an abnormal BeLPT, provide greater diagnostic certainty than others, such as nonspecific radiographic changes.

Diagnosis reference

  • 1. Balmes JR, Abraham JL, Dweik RA, et al. An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease. Am J Respir Crit Care Med 2014;190(10):e34-e59. doi:10.1164/rccm.201409-1722ST

Treatment of Beryllium Disease

  • Discontinuation of exposure

  • Sometimes corticosteroids and immunosuppressants

Patients with chronic beryllium disease should be removed from further exposure to beryllium.

The natural history of chronic beryllium disease is variable, and some patients do not require treatment because the disease is stable or progresses relatively slowly. Otherwise, treatment is similar to that of pulmonary sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more Sarcoidosis .

Corticosteroids are usually started in patients with a combination of pulmonary symptoms and clinical evidence of disease progression (1, 2 Treatment references Acute 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... read more ). Prednisone is typically given for 3 to 6 months. Then, pulmonary physiology and gas exchange measures are repeated to document a response to therapy. The corticosteroid dose is gradually tapered to the lowest dose that maintains symptomatic and objective improvement. Corticosteroid-sparing therapy, such as with methotrexate (or infliximab), is selected based on a similar approach used in sarcoidosis.

Treatment references

Prognosis for Beryllium Disease

Similar to sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more Sarcoidosis , chronic beryllium disease has a variable clinical course. Disease can remain stable or progress slowly with loss of respiratory function over time. In a subset of cases, chronic beryllium disease can progress to end-stage lung disease. Notably, disease frequently progresses following elimination of exposure (1 Treatment references Acute 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... read more ).

Prognosis reference

Prevention of Beryllium Disease

Facilities that use beryllium-containing products should implement a control program to minimize exposure to beryllium. The United States Occupational Safety and Health Administration (OSHA) has set the permissible exposure limit (PEL) of beryllium to 0.2 micrograms per cubic meter of air, averaged over 8 hours (see OSHA Beryllium Standards). This standard is expected to reduce the number of cases but not entirely eliminate chronic beryllium disease, as cases can still develop at exposure levels below the OSHA standard. Efforts should also be made to minimize skin exposure, given the potential for sensitization following skin contact.

Medical surveillance, including blood BeLPT and pulmonary function tests, is recommended for exposed workers. Workers with a positive BeLPT result should undergo further evaluation with chest CT scan and possible bronchoscopy to determine whether they have chronic beryllium disease.

Key Points

  • Beryllium disease is under-recognized and affects workers in many industries.

  • Chronic beryllium disease should be considered in patients with presumed sarcoidosis given their similar clinical features.

  • High-resolution CT and beryllium lymphocyte proliferation test (BeLPT) using blood or bronchoalveolar lavage cells facilitate the diagnosis of chronic beryllium disease

  • Symptomatic patients with cough and dyspnea can be treated with corticosteroids and sometimes immunosuppressants.

  • Prevention involves minimizing exposure to beryllium dust and medical surveillance of exposed workers.

More Information

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

  • Balmes JR, Abraham JL, Dweik RA, et al. An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease. Am J Respir Crit Care Med 2014;190(10):e34-e59. doi:10.1164/rccm.201409-1722ST

Drugs Mentioned In This Article

Drug Name Select Trade
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
Jylamvo, Otrexup, Rasuvo, RediTrex, Rheumatrex, Trexall, Xatmep
AVSOLA, INFLECTRA, Remicade, RENFLEXIS, Zymfentra
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NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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