eMedicine Specialties > Pulmonology > Occupational Lung Diseases

Berylliosis: Differential Diagnoses & Workup

Author: Raed A Dweik, MD, FACP, FCCP, FRCPC, Associate Professor of Medicine; The Cleveland Clinic, Lerner College of Medicine; Director, Pulmonary Vascular Program, Respiratory Institute, The Cleveland Clinic Foundation
Contributor Information and Disclosures

Updated: Nov 19, 2008

Differential Diagnoses

Hypersensitivity Pneumonitis
Pulmonary Fibrosis, Idiopathic
Sarcoidosis
Tuberculosis

Other Problems to Be Considered

Mycobacterial infections (other than tuberculosis)
Granulomatous disease caused by other metals such as aluminum or titanium

Workup

Laboratory Studies

  • Blood BeLPT currently is the test of choice to identify beryllium workers who develop beryllium sensitization or chronic beryllium disease (CBD).4,5,6 Blood BeLPT has an integral role in reaching a diagnosis of CBD. The test involves exposing peripheral blood mononuclear cells in vitro to beryllium salts at varying concentrations for variable time intervals. Cell proliferation in the presence of beryllium indicates a positive test result. BeLPT is only performed in selected specialized laboratories, including the following:
    • Center for Epidemiologic Research
      Oak Ridge Institute for Science and Education
      Former Beryllium Worker Medical Surveillance Program
      ORISE/CER, P.O. Box 117
      Oak Ridge, TN 27831-0117
      (865) 576-3115
      (865) 241-6152
      FAX (865) 241-2923
    • Cleveland Clinic Foundation
      9500 Euclid Avenue
      Cleveland, OH 44195-0001
      (216) 444-2200
      (216) 444-8844
      (800) CCF-CARE (223-2273) ext 48844 or 55763
    • Hospital of the University of Pennsylvania
      Pulmonary Immunology Laboratory
      815 East Gates Building, 4300 Spruce Street
      Philadelphia, PA 19104-4283
    • National Jewish Center for Immunology and Respiratory Medicine
      Cellular Immunology Tests
      Pulmonary Division and Occupational/Environmental Medicine Division
      1400 Jackson Street
      Denver, CO 80206
      (303) 388-4461
    • Specialty Laboratories, Inc.
      OncQuest
      2211 Michigan Avenue
      Santa Monica, CA 90404-3900
      (310) 828-6543 or (800) 421-4449

Imaging Studies

  • Findings on chest radiograph are normal in about half of the patients with documented chronic beryllium disease (CBD). Abnormal findings include hilar adenopathy and/or increased interstitial markings.
  • High-resolution CT (HRCT) scan of the chest is more sensitive than the chest radiograph.7
    • Typical findings on HRCT scan are ground glass opacification (see Media File 1), parenchymal nodules, or septal lines.
    • Findings on HRCT scan are negative in 25% of patients with documented CBD.

Other Tests

  • Pulmonary function tests include the following:
    • Spirometry
    • Lung volumes
    • Diffusing capacity of lung for carbon monoxide (DLCO)
    • Arterial blood gases
    • Cardiopulmonary exercise
  • With disease progression, spirometry may show evidence of obstruction, restriction, or both. In an early study in 40 patients with advanced CBD, an obstructive pattern was observed in 39% of patients, a restrictive pattern in 20%, and a low DLCO in 36%.
  • The DLCO declines over the course of the disease.
  • The most sensitive test is abnormalities in gas exchange during exercise.
  • Laser microprobe mass spectrographic (LAMMS) analysis can be used to detect beryllium in histologic sections from lung biopsy specimens. This test is not necessary for the diagnosis and is not widely available.

Procedures

  • Flexible fiberoptic bronchoscopy with BAL and transbronchial biopsies (TBBX) usually is the first invasive step necessary to confirm a suspected diagnosis of CBD.
    • Patients with CBD usually have BAL lymphocytosis (>20% lymphocytes).
    • The BeLPT test also can be performed on BAL cells.
    • Transbronchial biopsies are sent for histology. A minimum of 6 high-quality biopsies should be obtained to optimize the yield. If TBBX results are negative but the suspicion for CBD remains high (eg, a positive result on BeLPT and/or a high percentage of lymphocytes in the BAL specimens), consider repeat bronchoscopy.
  • Open lung biopsy may need to be performed if repeat bronchoscopy findings still are negative.

Histologic Findings

The hallmark of CBD is the presence of nonnecrotizing granulomas on lung biopsy (see Media File 2). These granulomas are histopathologically indistinguishable from sarcoid granulomas.

More on Berylliosis

Overview: Berylliosis
Differential Diagnoses & Workup: Berylliosis
Treatment & Medication: Berylliosis
Follow-up: Berylliosis
Multimedia: Berylliosis
References
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References

  1. Saltini C, Winestock K, Kirby M, Pinkston P, Crystal RG. Maintenance of alveolitis in patients with chronic beryllium disease by beryllium-specific helper T cells. N Engl J Med. Apr 27 1989;320(17):1103-9. [Medline].

  2. Berlin JM, Taylor JS, Sigel JE, Bergfeld WF, Dweik RA. Beryllium dermatitis. J Am Acad Dermatol. Nov 2003;49(5):939-41. [Medline].

  3. Richeldi L, Sorrentino R, Saltini C. HLA-DPB1 glutamate 69: a genetic marker of beryllium disease. Science. Oct 8 1993;262(5131):242-4. [Medline].

  4. Barna BP, Culver DA, Yen-Lieberman B, Dweik RA, Thomassen MJ. Clinical application of beryllium lymphocyte proliferation testing. Clin Diagn Lab Immunol. Nov 2003;10(6):990-4. [Medline].

  5. Newman LS. Significance of the blood beryllium lymphocyte proliferation test. Environ Health Perspect. Oct 1996;104 Suppl 5:953-6. [Medline].

  6. Rossman MD, Kern JA, Elias JA, Cullen MR, Epstein PE, Preuss OP, et al. Proliferative response of bronchoalveolar lymphocytes to beryllium. A test for chronic beryllium disease. Ann Intern Med. May 1988;108(5):687-93. [Medline].

  7. Newman LS, Buschman DL, Newell JD Jr, Lynch DA. Beryllium disease: assessment with CT. Radiology. Mar 1994;190(3):835-40. [Medline].

  8. Kreiss K, Mroz MM, Newman LS, Martyny J, Zhen B. Machining risk of beryllium disease and sensitization with median exposures below 2 micrograms/m3. Am J Ind Med. Jul 1996;30(1):16-25. [Medline].

  9. Amicosante M, Berretta F, Franchi A, Rogliani P, Dotti C, Losi M, et al. HLA-DP-unrestricted TNF-alpha release in beryllium-stimulated peripheral blood mononuclear cells. Eur Respir J. Nov 2002;20(5):1174-8. [Medline].

  10. Culver DA, Dweik RA. Chronic beryllium disease. Clin Pulm Med. 2003;10:72-9.

  11. Kreiss K, Miller F, Newman LS, Ojo-Amaize EA, Rossman MD, Saltini C. Chronic beryllium disease--from the workplace to cellular immunology, molecular immunogenetics, and back. Clin Immunol Immunopathol. May 1994;71(2):123-9. [Medline].

  12. Kreiss K, Mroz MM, Zhen B, Wiedemann H, Barna B. Risks of beryllium disease related to work processes at a metal, alloy, and oxide production plant. Occup Environ Med. Aug 1997;54(8):605-12. [Medline].

  13. Kreiss K, Newman LS, Mroz MM, Campbell PA. Screening blood test identifies subclinical beryllium disease. J Occup Med. Jul 1989;31(7):603-8. [Medline].

  14. Kriebel D, Brain JD, Sprince NL, Kazemi H. The pulmonary toxicity of beryllium. Am Rev Respir Dis. Feb 1988;137(2):464-73. [Medline].

  15. Meyer KC. Beryllium and lung disease. Chest. Sep 1994;106(3):942-6. [Medline].

  16. MOSBY'S GENRx-The Complete Reference For Generic And Brand Drugs. 9th ed. St. Louis, Mo: Mosby-Year Book; 1999.

  17. Müller-Quernheim J, Gaede KI, Fireman E, Zissel G. Diagnoses of chronic beryllium disease within cohorts of sarcoidosis patients. Eur Respir J. Jun 2006;27(6):1190-5. [Medline].

  18. Newman LS. Immunology, genetics, and epidemiology of beryllium disease. Chest. Mar 1996;109(3 Suppl):40S-43S. [Medline].

  19. Newman LS, Kreiss K, King TE Jr, Seay S, Campbell PA. Pathologic and immunologic alterations in early stages of beryllium disease. Re-examination of disease definition and natural history. Am Rev Respir Dis. Jun 1989;139(6):1479-86. [Medline].

  20. Newman LS, Lloyd J, Daniloff E. The natural history of beryllium sensitization and chronic beryllium disease. Environ Health Perspect. Oct 1996;104 Suppl 5:937-43. [Medline].

  21. 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. Jan 1 2005;171(1):54-60. [Medline].

  22. Pappas GP, Newman LS. Early pulmonary physiologic abnormalities in beryllium disease. Am Rev Respir Dis. Sep 1993;148(3):661-6. [Medline].

  23. Saber W, Dweik RA. A 65-year-old factory worker with dyspnea on exertion and a normal chest x-ray. Cleve Clin J Med. Nov 2000;67(11):791-2, 794, 797-8, 800. [Medline].

  24. Stokes RF, Rossman MD. Blood cell proliferation response to beryllium: analysis by receiver-operating characteristics. J Occup Med. Jan 1991;33(1):23-8. [Medline].

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Further Reading

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Keywords

berylliosis, beryllium, Be, chronic beryllium disease, CBD, acute beryllium disease, acute chemical pneumonitis

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Contributor Information and Disclosures

Author

Raed A Dweik, MD, FACP, FCCP, FRCPC, Associate Professor of Medicine; The Cleveland Clinic, Lerner College of Medicine; Director, Pulmonary Vascular Program, Respiratory Institute, The Cleveland Clinic Foundation
Raed A Dweik, MD, FACP, FCCP, FRCPC is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Medical Research, American Medical Association, American Thoracic Society, Royal College of Physicians and Surgeons of Canada, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

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