Berylliosis (Chronic Beryllium Disease)


Article Author:
Omeed Sizar


Article Editor:
Raja Talati


Editors In Chief:
David Tauber


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Avais Raja
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Carrie Smith
Abdul Waheed
Khalid Alsayouri
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Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
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John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
5/18/2019 10:22:28 PM

Introduction

Berylliosis, also known as chronic beryllium disease (CBD), is a granulomatous disease caused by exposure to beryllium. CBD has a variable clinical course with cough, fever, night sweats, and fatigue being the most common symptoms. Definitive diagnosis of berylliosis is based on occupational history, positive blood or bronchoalveolar lavage (BAL) beryllium lymphocyte proliferation test (BeLPT), and granulomatous inflammation on lung biopsy[1]. The current Occupational Safety and Health Administration (OSHA) guidelines reduce the permissible exposure limit for beryllium to .2 mcg/m3 averaged over 8 hours or less than 2 mcg/m3 over a 15 minute period. It is an incurable occupational lung disease, but symptoms can be treated with glucocorticoids and immunosuppressive agents.[2][3][4]

Etiology

Exposure to beryllium is the underlying causative factor. Heavy beryllium-using industries include metal machine shops, electronics, defense industries, and beryllium extraction companies. Other industries include ceramic, automotive, aerospace, jewelry making, dental/alloy appliance, and computer. It appears that some people may have a genetic predisposition towards developing severe CBD.[5]

Epidemiology

CBD is a hypersensitivity granulomatous disease that occurs in 2 to 5% of beryllium-exposed workers[6]. Stopping exposure to beryllium has not been shown to stop the progression to CBD. Unless an individual lives very close to an industrial site, the general population is unlikely to develop acute or CBD because ambient air levels of beryllium are normally very low (< 0.03 ng/m3)[5].

Pathophysiology

Exposure to Beryllium can lead to a cell-mediated immune response where T-cells become sensitized to beryllium. Each subsequent exposure leads to an immune response involving macrophages and CD4+ helper T-lymphocytes accumulating in the lungs. As this response proceeds, macrophages, CD+4 T-lymphocytes, and plasma cells aggregate to form noncaseating granulomas that evolve to cause fibrosis of the lung. Studies have revealed there is a genetic component to beryllium sensitivity. Specifically, those beryllium-exposed workers with a mutation at the HLA-DPB1 Glu69 position have increased the prevalence of beryllium sensitization and CBD. The HLA-DPB1 gene is important for MCH class II molecule function on antigen-presenting cells. Beryllium and beryllium compounds are category 1 carcinogens and carcinogenic to both animals and humans.[7]

History and Physical

The clinical manifestations of CBD are nonspecific[8]. The latency period between beryllium exposure and the onset of symptoms varies from three months to 30 years[9]. Common symptoms include fever, night sweats, weight loss, dry cough, and fatigue. Continued exposure causes noncaseating inflammatory granulomas. They also see granulomas in other chronic diseases, such as tuberculosis and sarcoidosis. CBD leads to restrictive lung disease (a decrease in diffusion capacity). Rarely, granulomas occur in other organs, such as the liver. 

Evaluation

Definitive diagnosis of berylliosis is based on the history, positive blood or bronchoalveolar lavage (BAL) beryllium lymphocyte proliferation test (BeLPT), and granulomatous inflammation on lung biopsy[1]. Establishing beryllium sensitivity is the first step, and this is determined by the beryllium lymphocyte proliferation test (BeLPT). The test is performed by acquiring either peripheral blood or fluid from a bronchial alveolar lavage and culturing lymphocytes with beryllium sulfate. Cells are then counted, and they consider those with an elevated number of cells abnormal. Those exposed persons with two abnormal BeLPTs with peripheral blood or one abnormal and one borderline result are beryllium sensitized. Also, those with one abnormal BeLPT with fluid from a bronchial alveolar lavage is considered sensitized. For patients with positive BeLPT, bronchoscopy with a bronchoalveolar lavage (BAL) is performed to obtain cell counts[1]. Lastly, a tissue biopsy is obtained from bronchoscopy to fulfill the last criterion for CBD diagnosis. [10]

Chest radiography findings of berylliosis are non-specific. Early in the disease, radiography findings are usually normal. In later stages, interstitial fibrosis, pleural irregularities, hilar lymphadenopathy, and ground-glass opacities have been reported. Findings on CT are not specific for berylliosis. Findings that are common in CT scans of people with berylliosis include parenchymal nodules in early stages. One study found that ground-glass opacities were more commonly seen on CT scan in berylliosis than in sarcoidosis. In later stages hilar lymphadenopathy, interstitial pulmonary fibrosis, and pleural thickening are found.

Treatment / Management

The goals when treating berylliosis are to reduce symptoms and slow the progression of the disease as no cure is available. Although there is no evidence that stopping exposure to beryllium decreases the progression of the disease, they still consider it to be an accepted approach to treatment. People with early stages, without lung function abnormalities or clinical symptoms are periodically monitored, with physical exams, pulmonary function tests, and radiography. All patients require influenza and pneumococcal vaccination and smoking cessation counseling. After the appearance of clinical symptoms or significant abnormalities appear in pulmonary function testing, oxygen and oral corticosteroids are started as well as other supportive therapy as required.[1] 

The drugs of choice to treat chronic beryllium disease are corticosteroids. It usually requires a high starting dose and the treatment duration is often for several months before they see symptom resolution. Once symptoms subside, tapering of the steroids is necessary to prevent the adverse effects. They can treat patients who fail to respond to steroids on immunosuppressive agents such as methotrexate and azathioprine. They starts oral methotrexate at a 7.5mg weekly dose given with folic acid 1mg. Complete blood counts and liver function tests should be repeated 8 to 12 weeks at a time.

Once a diagnosis of CBD is made, the patient needs life-long follow up with serial arterial blood gases, chest x-ray, and pulmonary function tests.[11] 

Differential Diagnosis

Differential diagnosis includes sarcoidosis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, asthma, and other granulomatous lung diseases such as histoplasmosis, tuberculosis, silicosis. They estimate it that 6 percent of all patients diagnosed with sarcoidosis may have CBD[12].

Prognosis

Patients with beryllium sensitization in the absence of CBD don't require treatment but should undergo periodic evaluation. Among these patients, the risk of progression to CBD is increased compared with non-sensitized workers. Overall mortality rates are 5% to 38%[13]. CBD has a variable clinical course. A higher percentage of lymphocytes in the bronchoalveolar lavage correlates with a greater severity of illness[14].

Deterrence and Patient Education

Prevention is the key in the management of berylliosis. OSHA has recommendations for the workplace including requiring work practice controls such as ventilation or enclosure to limit exposure, provide protective equipment such as respirators, train workers on beryllium hazards, and requiring medical exams to monitor exposed workers. In 2000, a study found that new workers who went through a comprehensive preventive program had reduced beryllium sensitization compared with workers working in the past[15].

Pearls and Other Issues

A study of workers in a beryllium facility found that people developed CBD when exposed to above .2 mcg/m3[16]. The current United States Occupational Safety and Health Administration (OSHA) reduces the permissible exposure limit for beryllium to .2 mcg/m3 averaged over 8 hours or less than two mcg/m3 over a 15 minute period.

The American Conference of Governmental Industrial Hygienists (ACGIH) in 2005 issued a recommendation to reduce the threshold limit value (TLV) by 100 fold from 2 to .02 mcg/m3 over a 15 minute period. Although ACGIH carries no legal force like OSHA does, it is important to note the recommendation. Beryllium exposure is difficult to control in an industrial work environment, so methods that reduce the possibility of airborne and surface contamination are needed. These include minimal use of beryllium and beryllium-containing alloys and employee education about the possible hazards when the dust or fumes of beryllium are encountered in the workplace. 

Enhancing Healthcare Team Outcomes

Several guidelines have been developed to help prevent berylliosis in the workplace. However, an interprofessional approach is required to ensure that the diagnosis is not missed. Patients often present to the primary health care provider who may not be aware of the disorder, hence referral to a pulmonologist is recommended. The pharmacist should advise the patient to discontinue smoking, and the nurse should educate the patient and the family on the disease. A pulmonologist may help make the diagnosis and help monitor the disease. The pharmacist should discuss the potential side effects of antibiotics and monitor the patient for complications, reporting to the healthcare team. [17](Level V)

Outcomes

In the USA, berylliosis is declining, but outside North America, it is still a problem because of unregulated textile industries. A detailed work exposure, history, physical examination, radiography, pulmonary function test, selected lab studies and bronchoalveolar lavage fluid can be used to identify early stages of disease. [18] (Level V)


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Berylliosis (Chronic Beryllium Disease) - Questions

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A 49-year-old presents with a dry cough of 5 months duration. He denies smoking, but says he worked in the light bulb industry for more than 20 years. A chest x-ray shows small nodules, and biopsy reveals non-distinct granulomas. What is this patient's most likely condition?



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A 53-year-old male with no past medical history presents with a dry cough and night sweats for the past 10 years. The atient worked at an electronic shop for the past 20 years. CT of the chest shows granulomatous disease. Chest x-ray, arterial blood gas, and pulmonary function tests are normal. What is the next step in establishing the diagnosis?



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Berylliosis (Chronic Beryllium Disease) - References

References

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Occupational Exposure to Beryllium. Final rule. Federal register. 2017 Jan 9     [PubMed]
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Cummings KJ,Deubner DC,Day GA,Henneberger PK,Kitt MM,Kent MS,Kreiss K,Schuler CR, Enhanced preventive programme at a beryllium oxide ceramics facility reduces beryllium sensitisation among new workers. Occupational and environmental medicine. 2007 Feb     [PubMed]
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Fireman E,Haimsky E,Noiderfer M,Priel I,Lerman Y, Misdiagnosis of sarcoidosis in patients with chronic beryllium disease. Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG. 2003 Jun     [PubMed]
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