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ICD-10 J63.2
ICD-9 503

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Synonyms and Keywords: Chronic beryllium disorder; CBD


Berylliosis or chronic beryllium disorder (CBD) is an occupational lung disease. It is a chronic allergic-type lung response and chronic lung disease caused by exposure to beryllium and its compounds. The condition is incurable but symptoms can be treated.

Historical Perspective

  • Berylliosis was first discovered by Dr. Harriet Hardy, an American pathologist, in 1945 following an outbreak of respiratory illnesses affecting nearby factory workers.[1][2]
  • In 1946, Hardy established the National Beryllium Registry at the Massachusetts General Hospital.[2]


  • There is no formal classification system established for berylliosis.
  • Berylliosis may be classified as a rare disorder and an occupational disease.[3][4]


  • Exposure to beryllium can cause cell mediated immunity .
  • which can cause sensitize the T cells to beryllium
  • In each subsequent exposure macrophage and CD4+ helper T - lymphocytes accumulation in the lungs.
  • As a result macrophages, CD4+ T lymphocyte and plasma cell accumulate to form noncaseating granulomas that cause fibrosis.[5]
  • Beryllium is presented to CD4+ T cell by antigen presenting cells,principally in HLA-DP molecules. T cell in the blood lungs or other organs in turn recognize the beryllium, proliferate and form T cell clones.These colnes the release proinflammatory cytokines. such as tumor necrosis factor alpha , IL-2 and interferon gamma.These cytokines amplify the immune response, as result formation of mononuclear cell infiltrates and noncaseating granulomas in target organs where beryllium has deposited.
  • on average about 2 to 6 % of beryllium exposed people develop beryllium sensitized ( defined by positive blood lymphocyte proliferation salt in vitro ) with most progressing to disease.In certain high risk groups such as beryllium metal and alloy machinists, chronic beryllium disease prevalence is > 17 % workers with bystander exposures, such as secretaries and security guards, also develop sensitization and disease but at lower rates.The typical pathologic consequence is a diffuse pulmonary, hilar and mediastinal lymph node granulomatous reaction that is histologically indistinguishable from sarcoidosis.
  • Early granuloma formation with mononuclear and giant cells can also occur.
  • Many lymphocytes are found when cell are washed from the lungs ( bronchoalveolar lavage BAL during bronchoscopy.
  • These T cells proliferate when exposed to beryllium in vitro , much as the blood cells do ( a test called beryllium lymphocyte proliferation test BeLPT ).


  • Chronic exposure to beryllium
  • Genetic predisposition ( Mutation at the HL-A DPB1 Glu69 position increase the prevalence of beryllium sensitization.[6]

Differentiating Berylliosis from other Diseases

Granulomas are seen in other chronic diseases, such as tuberculosis, sarcoidosis, and it can occasionally be hard to distinguish berylliosis from these disorders.

Risk Factors

  • Extended exposure with berylium
  • Genetic predisposition ( Mutation at the HL-A DPB1 Glu69 position increase the prevalence of beryllium sensitization.

Natural History, Complications, and Prognosis

Natural History

Patients with chronic beryllium disease often have dyspnea , cough , weight loss and a variable chest X-ray pattern, typically showing nodular opacities in the mid and upper lung zones, frequently with hilar and mediastinal adenopathy.

patients complain of insidious and progressive exertional dyspnea , cough , chest pain , weight loss , night sweats and fatigue. Symptoms may develop within months of first exposure or more than 30 years after exposure and some people remain asymptomatic.

Acute beryllium disease is distinguished from chronic disease based on history of very high level of exposure followed by acute onset of dry cough and progressive dyspnea on exertion in addition to systemic sign and symptoms ( conjunctivitis , dermatitis,laryngotracheobronchitis ).

Further radiographic finding occur with 1 to 3 weeks of exposure. In chronic beryllium disease the sign and symptoms are present for at least a year and clinical presentation can be varied from asymptomatic to dry cough, progressive dyspnea, fatigue and night sweats.BAl BeLPT is highly sensitive and specific, helping to distinguish chronic beryllium disease from sarcoidosis and other form of diffuse pulmonary disease.

Ultimately, this process leads to restrictive lung disease, a decreased diffusion capacity.


Rarely, one can get granulomas in other organs including the liver.


Acute beryllium disease can be fetal but prognosis is usually excellent unless progression to chronic beryllium disease occurs. Chronic beryllium disease often results in progressive loss of respiratory function. Early abnormalities include airflow obstruction and decreased oxygenation on ABG at rest and during exercise testing.Decreased diffusing capacity for carbon monoxide ( DLco) and restriction appear later pulmonary hypertension and right ventricular failure develop in about 10 % case , which death due to cor pulmonale.

Mortality rates range from 6 to 35 percent.The variability of mortality depend duration of beryllium exposure after development of chronic beryllium disorder disease, individual variation and duration of follow up.[7][8]

History and Symptoms

  • History of beryllium exposure
  • Positive blood or bronchoalveolar lavage ( beryllium lymphocyte proliferation test BeLPT
  • Cough
  • Shortness of breath
  • Chest pain
  • Arthralgia
  • Weight loss
  • Fever
  • The onset of symptoms can range from weeks up to tens of years from the initial exposure. In some individuals a single exposure can cause berylliosis.

Laboratory Test

  • Blood beryllium lymphocyte proliferation test ( BeLPT )[9]
  • High resolution computed tomography ( HRCT )
  • Bronchoalveolar lavage
  • Tissue biopsy
  • Pulmonary function test
  • Chest X ray[10]
  • chest X- ray may be normal or show diffuse infiltrate that can be nodular,reticular or have a hazy ground - glass appearance, often with hilar adenopathy resembling the pattern seen in sarcoidosis.
  • A miliary pattern also occur in high resolution CT is more sensitive than X-ray.
  • Biopsy proven disease occurrence even in people with normal imaging test result.


  • There is no cure for CBD the goal is reducing symptoms and slow progression of disease.
  • All patient with CBD should be removed from further exposure to beryllium decrease the progression of the disease.[11]
  • There is no specific treatment for CBD but drug of choice is glucocorticoid therapy.
  • Initial dose is 0.5 to 0.6 mg/k of prednisone for 6 to 12 week.
  • Methotrexate is also used if patient not respond to glucocorticoid or has severe side effects from glucocorticoid.
  • Once diagnosed and successfully treated, patients with CBD need long term followed-up with pulmonologist to monitor lung function.[12]
  • In acute beryllium disease patient put on mechanical ventilation.
  • In chronic beryllium disease, supplemental oxygen,pulmonary rehabilitation and treatment for right ventricular failure.
  • In end stage chronic beryllium disease sometime lung transplantation.


  • Industrial dust suppression is the basis for preventing beryllium exposure.Exposure must be limited to level that are as low as reasonably achievable 0.2 micrograms per cubic meter of air.
  • Average over 8 hours and limited short term exposure to 2 micrograms per cubic meter of air over a 15 minutes sampling period.
  • Medical surveillance, using blood BeLPT and chest X-ray is recommended for all exposed workers including those indirect contact. Both acute and chronic disease must be promptly recognized and affected workers removed from further beryllium exposure.


  1. HARDY HL, TABERSHAW IR (1946). "Delayed chemical pneumonitis occurring in workers exposed to beryllium compounds". J Ind Hyg Toxicol. 28: 197–211. PMID 21000285.
  2. 2.0 2.1 Oakes EH. Encyclopedia of World Scientists. Infobase Publishing; 2007.
  3. Berylliosis. National Organization for Rare Diseases (2009). Accessed on January 24, 2017.
  4. United States Department of Labor. Occupational Safety and Health Administration. Accessed on January 24, 2017.
  5. Gossman WG, Bhimji SS. PMID 29261866. Missing or empty |title= (help)
  6. Li L, Silveira LJ, Hamzeh N, Gillespie M, Mroz PM, Mayer AS, Fingerlin TE, Maier LA (June 2016). "Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis". Eur. Respir. J. 47 (6): 1797–808. doi:10.1183/13993003.01469-2015. PMC 5134922. PMID 27103383.
  7. Boffetta P, Fordyce TA, Mandel JS (December 2016). "A mortality study of beryllium workers". Cancer Med. 5 (12): 3596–3605. doi:10.1002/cam4.918. PMC 5224864. PMID 27766788.
  8. Boffetta P, Fordyce TA, Mandel JS (December 2016). "A mortality study of beryllium workers". Cancer Med. 5 (12): 3596–3605. doi:10.1002/cam4.918. PMC 5224864. PMID 27766788.
  9. Harber P, Su J, Alongi G (August 2014). "Beryllium BioBank: 2. Lymphocyte proliferation testing". J. Occup. Environ. Med. 56 (8): 857–60. doi:10.1097/JOM.0000000000000199. PMID 25099413.
  10. Mayer A, Hamzeh N (March 2015). "Beryllium and other metal-induced lung disease". Curr Opin Pulm Med. 21 (2): 178–84. doi:10.1097/MCP.0000000000000140. PMID 25602804.
  11. Balmes JR, Abraham JL, Dweik RA, Fireman E, Fontenot AP, Maier LA, Muller-Quernheim J, Ostiguy G, Pepper LD, Saltini C, Schuler CR, Takaro TK, Wambach PF (November 2014). "An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease". Am. J. Respir. Crit. Care Med. 190 (10): e34–59. doi:10.1164/rccm.201409-1722ST. PMID 25398119.
  12. Thomas CA, Deubner DC, Stanton ML, Kreiss K, Schuler CR (July 2013). "Long-term efficacy of a program to prevent beryllium disease". Am. J. Ind. Med. 56 (7): 733–41. doi:10.1002/ajim.22175. PMID 23450749.