UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Chronic beryllium disease (berylliosis)

Authors
Lee S Newman, MD, MA, FCCP, FACOEM
Lisa A Maier, MD
Section Editor
Talmadge E King, Jr, MD
Deputy Editor
Helen Hollingsworth, MD

INTRODUCTION

Chronic beryllium disease (CBD), also called berylliosis, is a granulomatous disease caused by exposure to beryllium. Beryllium is an alkaline earth metal that is used in a number of different industrial applications. CBD shares many clinical and histopathological features with sarcoidosis and was first described in 1946 when 17 fluorescent lamp workers presented with a syndrome of advanced pulmonary granulomatous disease [1-3].

The pathogenesis, sources of exposure, clinical and laboratory findings, diagnosis, and treatment of CBD will be reviewed here. The evaluation of the adult with interstitial lung disease and the clinical manifestations and diagnosis of sarcoidosis are discussed separately. (See "Approach to the adult with interstitial lung disease: Clinical evaluation" and "Approach to the adult with interstitial lung disease: Diagnostic testing" and "Clinical manifestations and diagnosis of pulmonary sarcoidosis".)

DEFINITIONS

A patient is considered to have chronic beryllium disease (CBD) if all of the following are present [4]:

A history of any beryllium exposure

A positive blood or bronchoalveolar lavage (BAL) beryllium lymphocyte proliferation test (BeLPT) (see 'Beryllium lymphocyte proliferation test' below)

                          

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Thu Feb 25 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. HARDY HL, TABERSHAW IR. Delayed chemical pneumonitis occurring in workers exposed to beryllium compounds. J Ind Hyg Toxicol 1946; 28:197.
  2. Fireman E, Haimsky E, Noiderfer M, et al. Misdiagnosis of sarcoidosis in patients with chronic beryllium disease. Sarcoidosis Vasc Diffuse Lung Dis 2003; 20:144.
  3. Rossman MD, Kreider ME. Is chronic beryllium disease sarcoidosis of known etiology? Sarcoidosis Vasc Diffuse Lung Dis 2003; 20:104.
  4. 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:e34.
  5. Kolanz ME. Introduction to beryllium: uses, regulatory history, and disease. Appl Occup Environ Hyg 2001; 16:559.
  6. Taylor TP, Ding M, Ehler DS, et al. Beryllium in the environment: a review. J Environ Sci Health A Tox Hazard Subst Environ Eng 2003; 38:439.
  7. Infante PF, Newman LS. Beryllium exposure and chronic beryllium disease. Lancet 2004; 363:415.
  8. Kreiss K, Wasserman S, Mroz MM, Newman LS. Beryllium disease screening in the ceramics industry. Blood lymphocyte test performance and exposure-disease relations. J Occup Med 1993; 35:267.
  9. Kreiss K, Mroz MM, Zhen B, et al. Epidemiology of beryllium sensitization and disease in nuclear workers. Am Rev Respir Dis 1993; 148:985.
  10. Kreiss K, Mroz MM, Newman LS, et al. Machining risk of beryllium disease and sensitization with median exposures below 2 micrograms/m3. Am J Ind Med 1996; 30:16.
  11. Schuler CR, Kent MS, Deubner DC, et al. Process-related risk of beryllium sensitization and disease in a copper-beryllium alloy facility. Am J Ind Med 2005; 47:195.
  12. Henneberger PK, Cumro D, Deubner DD, et al. Beryllium sensitization and disease among long-term and short-term workers in a beryllium ceramics plant. Int Arch Occup Environ Health 2001; 74:167.
  13. Stange AW, Hilmas DE, Furman FJ, Gatliffe TR. Beryllium sensitization and chronic beryllium disease at a former nuclear weapons facility. Appl Occup Environ Hyg 2001; 16:405.
  14. Kelleher PC, Martyny JW, Mroz MM, et al. Beryllium particulate exposure and disease relations in a beryllium machining plant. J Occup Environ Med 2001; 43:238.
  15. Newman LS, Mroz MM, Maier LA, et al. Efficacy of serial medical surveillance for chronic beryllium disease in a beryllium machining plant. J Occup Environ Med 2001; 43:231.
  16. Sackett HM, Maier LA, Silveira LJ, et al. Beryllium medical surveillance at a former nuclear weapons facility during cleanup operations. J Occup Environ Med 2004; 46:953.
  17. Stanton ML, Henneberger PK, Kent MS, et al. Sensitization and chronic beryllium disease among workers in copper-beryllium distribution centers. J Occup Environ Med 2006; 48:204.
  18. Cummings KJ, Deubner DC, Day GA, et al. Enhanced preventive programme at a beryllium oxide ceramics facility reduces beryllium sensitisation among new workers. Occup Environ Med 2007; 64:134.
  19. Rosenman K, Hertzberg V, Rice C, et al. Chronic beryllium disease and sensitization at a beryllium processing facility. Environ Health Perspect 2005; 113:1366.
  20. Welch L, Ringen K, Bingham E, et al. Screening for beryllium disease among construction trade workers at Department of Energy nuclear sites. Am J Ind Med 2004; 46:207.
  21. Stange AW, Furman FJ, Hilmas DE. Rocky Flats Beryllium Health Surveillance. Environ Health Perspect 1996; 104 Suppl 5:981.
  22. Henneberger PK, Goe SK, Miller WE, et al. Industries in the United States with airborne beryllium exposure and estimates of the number of current workers potentially exposed. J Occup Environ Hyg 2004; 1:648.
  23. Maier LA, Martyny JW, Liang J, Rossman MD. Recent chronic beryllium disease in residents surrounding a beryllium facility. Am J Respir Crit Care Med 2008; 177:1012.
  24. CURTIS GH. Cutaneous hypersensitivity due to beryllium; a study of thirteen cases. AMA Arch Derm Syphilol 1951; 64:470.
  25. Saltini C, Amicosante M, Franchi A, et al. Immunogenetic basis of environmental lung disease: lessons from the berylliosis model. Eur Respir J 1998; 12:1463.
  26. Fontenot AP, Maier LA. Genetic susceptibility and immune-mediated destruction in beryllium-induced disease. Trends Immunol 2005; 26:543.
  27. Hanifin JM, Epstein WL, Cline MJ. In vitro studies on granulomatous hypersensitivity to beryllium. J Invest Dermatol 1970; 55:284.
  28. Kreiss K, Miller F, Newman LS, et al. Chronic beryllium disease--from the workplace to cellular immunology, molecular immunogenetics, and back. Clin Immunol Immunopathol 1994; 71:123.
  29. Falta MT, Pinilla C, Mack DG, et al. Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease. J Exp Med 2013; 210:1403.
  30. Sawyer RT, Day BJ, Fadok VA, et al. Beryllium-ferritin: lymphocyte proliferation and macrophage apoptosis in chronic beryllium disease. Am J Respir Cell Mol Biol 2004; 31:470.
  31. Fontenot AP, Canavera SJ, Gharavi L, et al. Target organ localization of memory CD4(+) T cells in patients with chronic beryllium disease. J Clin Invest 2002; 110:1473.
  32. Tinkle SS, Kittle LA, Schumacher BA, Newman LS. Beryllium induces IL-2 and IFN-gamma in berylliosis. J Immunol 1997; 158:518.
  33. Tinkle SS, Newman LS. Beryllium-stimulated release of tumor necrosis factor-alpha, interleukin-6, and their soluble receptors in chronic beryllium disease. Am J Respir Crit Care Med 1997; 156:1884.
  34. Bost TW, Riches DW, Schumacher B, et al. Alveolar macrophages from patients with beryllium disease and sarcoidosis express increased levels of mRNA for tumor necrosis factor-alpha and interleukin-6 but not interleukin-1 beta. Am J Respir Cell Mol Biol 1994; 10:506.
  35. Sawyer RT, Abraham JL, Daniloff E, Newman LS. Secondary ion mass spectroscopy demonstrates retention of beryllium in chronic beryllium disease granulomas. J Occup Environ Med 2005; 47:1218.
  36. Sawyer RT, Dobis DR, Goldstein M, et al. Beryllium-stimulated reactive oxygen species and macrophage apoptosis. Free Radic Biol Med 2005; 38:928.
  37. Marchand-Adam S, El Khatib A, Guillon F, et al. Short- and long-term response to corticosteroid therapy in chronic beryllium disease. Eur Respir J 2008; 32:687.
  38. Dai S, Murphy GA, Crawford F, et al. Crystal structure of HLA-DP2 and implications for chronic beryllium disease. Proc Natl Acad Sci U S A 2010; 107:7425.
  39. Maier LA. Genetic and exposure risks for chronic beryllium disease. Clin Chest Med 2002; 23:827.
  40. Maier LA, McGrath DS, Sato H, et al. Influence of MHC class II in susceptibility to beryllium sensitization and chronic beryllium disease. J Immunol 2003; 171:6910.
  41. Richeldi L, Sorrentino R, Saltini C. HLA-DPB1 glutamate 69: a genetic marker of beryllium disease. Science 1993; 262:242.
  42. McCanlies EC, Ensey JS, Schuler CR, et al. The association between HLA-DPB1Glu69 and chronic beryllium disease and beryllium sensitization. Am J Ind Med 2004; 46:95.
  43. Weston A, Snyder J, McCanlies EC, et al. Immunogenetic factors in beryllium sensitization and chronic beryllium disease. Mutat Res 2005; 592:68.
  44. Van Dyke MV, Martyny JW, Mroz MM, et al. Risk of chronic beryllium disease by HLA-DPB1 E69 genotype and beryllium exposure in nuclear workers. Am J Respir Crit Care Med 2011; 183:1680.
  45. Silveira LJ, McCanlies EC, Fingerlin TE, et al. Chronic beryllium disease, HLA-DPB1, and the DP peptide binding groove. J Immunol 2012; 189:4014.
  46. Newman LS. To Be2+ or not to Be2+: immunogenetics and occupational exposure. Science 1993; 262:197.
  47. McCanlies EC, Kreiss K, Andrew M, Weston A. HLA-DPB1 and chronic beryllium disease: a HuGE review. Am J Epidemiol 2003; 157:388.
  48. Maier LA, Sawyer RT, Bauer RA, et al. High beryllium-stimulated TNF-alpha is associated with the -308 TNF-alpha promoter polymorphism and with clinical severity in chronic beryllium disease. Am J Respir Crit Care Med 2001; 164:1192.
  49. Sato H, Silveira L, Fingerlin T, et al. TNF polymorphism and bronchoalveolar lavage cell TNF-alpha levels in chronic beryllium disease and beryllium sensitization. J Allergy Clin Immunol 2007; 119:687.
  50. McCanlies EC, Schuler CR, Kreiss K, et al. TNF-alpha polymorphisms in chronic beryllium disease and beryllium sensitization. J Occup Environ Med 2007; 49:446.
  51. Stoeckle JD, Hardy HL, Weber AL. Chronic beryllium disease. Long-term follow-up of sixty cases and selective review of the literature. Am J Med 1969; 46:545.
  52. Newman LS, Orton R, Kreiss K. Serum angiotensin converting enzyme activity in chronic beryllium disease. Am Rev Respir Dis 1992; 146:39.
  53. Newman LS, Buschman DL, Newell JD Jr, Lynch DA. Beryllium disease: assessment with CT. Radiology 1994; 190:835.
  54. Naccache JM, Marchand-Adam S, Kambouchner M, et al. Ground-glass computed tomography pattern in chronic beryllium disease: pathologic substratum and evolution. J Comput Assist Tomogr 2003; 27:496.
  55. Handa T, Nagai S, Kitaichi M, et al. Long-term complications and prognosis of chronic beryllium disease. Sarcoidosis Vasc Diffuse Lung Dis 2009; 26:24.
  56. Pappas GP, Newman LS. Early pulmonary physiologic abnormalities in beryllium disease. Am Rev Respir Dis 1993; 148:661.
  57. Newman LS. Beryllium disease and sarcoidosis: clinical and laboratory links. Sarcoidosis 1995; 12:7.
  58. Newman LS, Kreiss K. Nonoccupational beryllium disease masquerading as sarcoidosis: identification by blood lymphocyte proliferative response to beryllium. Am Rev Respir Dis 1992; 145:1212.
  59. Middleton DC, Lewin MD, Kowalski PJ, et al. The BeLPT: algorithms and implications. Am J Ind Med 2006; 49:36.
  60. Middleton D, Kowalski P. Advances in identifying beryllium sensitization and disease. Int J Environ Res Public Health 2010; 7:115.
  61. Saltini C, Winestock K, Kirby M, et al. Maintenance of alveolitis in patients with chronic beryllium disease by beryllium-specific helper T cells. N Engl J Med 1989; 320:1103.
  62. Newman LS, Kreiss K, King TE Jr, et al. Pathologic and immunologic alterations in early stages of beryllium disease. Re-examination of disease definition and natural history. Am Rev Respir Dis 1989; 139:1479.
  63. Stange AW, Furman FJ, Hilmas DE. The beryllium lymphocyte proliferation test: Relevant issues in beryllium health surveillance. Am J Ind Med 2004; 46:453.
  64. Kreiss K, Mroz MM, Zhen B, et al. Risks of beryllium disease related to work processes at a metal, alloy, and oxide production plant. Occup Environ Med 1997; 54:605.
  65. Arjomandi M, Seward J, Gotway MB, et al. Low prevalence of chronic beryllium disease among workers at a nuclear weapons research and development facility. J Occup Environ Med 2010; 52:647.
  66. Farris GM, Newman LS, Frome EL, et al. Detection of beryllium sensitivity using a flow cytometric lymphocyte proliferation test: the Immuno-Be-LPT. Toxicology 2000; 143:125.
  67. Milovanova TN, Popma SH, Cherian S, et al. Flow cytometric test for beryllium sensitivity. Cytometry B Clin Cytom 2004; 60:23.
  68. Maier LA, Kittle LA, Mroz MM, Newman LS. Beryllium-stimulated neopterin as a diagnostic adjunct in chronic beryllium disease. Am J Ind Med 2003; 43:592.
  69. Pott GB, Palmer BE, Sullivan AK, et al. Frequency of beryllium-specific, TH1-type cytokine-expressing CD4+ T cells in patients with beryllium-induced disease. J Allergy Clin Immunol 2005; 115:1036.
  70. Fontenot AP, Palmer BE, Sullivan AK, et al. Frequency of beryllium-specific, central memory CD4+ T cells in blood determines proliferative response. J Clin Invest 2005; 115:2886.
  71. Martin AK, Mack DG, Falta MT, et al. Beryllium-specific CD4+ T cells in blood as a biomarker of disease progression. J Allergy Clin Immunol 2011; 128:1100.
  72. Mroz MM, Kreiss K, Lezotte DC, et al. Reexamination of the blood lymphocyte transformation test in the diagnosis of chronic beryllium disease. J Allergy Clin Immunol 1991; 88:54.
  73. Newman LS, Mroz MM, Balkissoon R, Maier LA. Beryllium sensitization progresses to chronic beryllium disease: a longitudinal study of disease risk. Am J Respir Crit Care Med 2005; 171:54.
  74. Shorr AF, Torrington KG, Hnatiuk OW. Endobronchial biopsy for sarcoidosis: a prospective study. Chest 2001; 120:109.
  75. Newman LS, Maier LA. Beryllium Disease. In: Interstitial lung disease, 5th ed, Schwarz MI, King TE (Eds), People's Medical Publishing House-USA, Shelton, CT 2011.
  76. Williams WJ. United Kingdom Beryllium Registry: mortality and autopsy study. Environ Health Perspect 1996; 104 Suppl 5:949.
  77. Bronchoalveolar lavage constituents in healthy individuals, idiopathic pulmonary fibrosis, and selected comparison groups. The BAL Cooperative Group Steering Committee. Am Rev Respir Dis 1990; 141:S169.
  78. Sood A. Current treatment of chronic beryllium disease. J Occup Environ Hyg 2009; 6:762.
  79. Sood A, Beckett WS, Cullen MR. Variable response to long-term corticosteroid therapy in chronic beryllium disease. Chest 2004; 126:2000.
  80. FERRIS BG Jr. Chronic beryllium intoxication treated with corticosteroids and corticotropin. Am Rev Respir Dis 1962; 85:583.
  81. Case studies in environmental medicine: Beryllium toxicity. http://www.atsdr.cdc.gov/csem/beryllium/index.html (Accessed on July 20, 2010).
  82. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001; 44:1496.
  83. Müller-Quernheim J, Kienast K, Held M, et al. Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen. Eur Respir J 1999; 14:1117.
  84. Maier LA, Barkes BQ, Mroz M, et al. Infliximab therapy modulates an antigen-specific immune response in chronic beryllium disease. Respir Med 2012; 106:1810.
  85. PEYTON MF, WORCESTER J. Exposure data and epidemiology of the beryllium case registry, 1958. AMA Arch Ind Health 1959; 19:94.
  86. Mroz MM, Maier LA, Strand M, et al. Beryllium lymphocyte proliferation test surveillance identifies clinically significant beryllium disease. Am J Ind Med 2009; 52:762.
  87. Newman LS, Bobka C, Schumacher B, et al. Compartmentalized immune response reflects clinical severity of beryllium disease. Am J Respir Crit Care Med 1994; 150:135.
  88. Beryllium and beryllium compounds. IARC Monogr Eval Carcinog Risks Hum 1993; 58:41.
  89. MacMahon B. The epidemiological evidence on the carcinogenicity of beryllium in humans. J Occup Med 1994; 36:15.
  90. Levy PS, Roth HD, Hwang PM, Powers TE. Beryllium and lung cancer: a reanalysis of a NIOSH cohort mortality study. Inhal Toxicol 2002; 14:1003.
  91. Hollins DM, McKinley MA, Williams C, et al. Beryllium and lung cancer: a weight of evidence evaluation of the toxicological and epidemiological literature. Crit Rev Toxicol 2009; 39 Suppl 1:1.
  92. Ward E, Okun A, Ruder A, et al. A mortality study of workers at seven beryllium processing plants. Am J Ind Med 1992; 22:885.
  93. Madl AK, Unice K, Brown JL, et al. Exposure-response analysis for beryllium sensitization and chronic beryllium disease among workers in a beryllium metal machining plant. J Occup Environ Hyg 2007; 4:448.
  94. Cullen MR, Kominsky JR, Rossman MD, et al. Chronic beryllium disease in a precious metal refinery. Clinical epidemiologic and immunologic evidence for continuing risk from exposure to low level beryllium fume. Am Rev Respir Dis 1987; 135:201.
  95. Tinkle SS, Antonini JM, Rich BA, et al. Skin as a route of exposure and sensitization in chronic beryllium disease. Environ Health Perspect 2003; 111:1202.
  96. Day GA, Stefaniak AB, Weston A, Tinkle SS. Beryllium exposure: dermal and immunological considerations. Int Arch Occup Environ Health 2006; 79:161.