Critical to cinching the diagnosis is a strong occupational history providing the source for exposure to the chemical. Occupations with highest potential exposure are primary production, nuclear power, reclamation of scrap alloys, aerospace, electronics, and metal machining.

Workers working with spark plugs, laser tubes, turbine rotor blades, nuclear weapons, ceramic applications, electrical components, oil and gas industries, aircraft engines and gears, welding electrodes are all at high risk for exposure to beryllium due its heavy use in these industries.

First the person develops a cough followed by irritation of the throat and the oesophagus leading to pain and inflammation. Rhinitis and nasal discharge are a consequence of the irritation of the nasal mucus membranes.

Next to follow in line is a chemical pneumonitis which leads to progressive dyspnoea, inspiratory crackles, chest pain and lymphadenopathy. Dermatitis due to skin contact with beryllium and hepatosplenomegaly in the long run are common signs.

General signs like fatigue, weight loss and arthralgia are not rare.
The most characteristic sign of granuloma formation is a response of the lymphocytes and is seen surrounding the beryllium particles.

There is noticeable scarring and thickening of tissue seen over the lungs as well as the skin.

• Weight Loss

  Its symptoms include coughing, shortness of breath, fatigue, weight loss or loss of appetite, fever and sweating. [web.archive.org]

  Fever, anorexia, and weight loss are common. Skin lesions are the most common extrathoracic manifestation. Granulomatous hepatitis, hypercalcemia, and kidney stones can also occur. [doi.org]

  The symptoms seen are cough, rhinitis (inflammation of nasal mucus membrane), fever, pharyngitis (sore throat), fatigue, weight loss, dyspnoea (shortness of breath), loss of appetite etc. [symptoma.com]

• Fever

  Its symptoms include coughing, shortness of breath, fatigue, weight loss or loss of appetite, fever and sweating. [web.archive.org]

  Fever, anorexia, and weight loss are common. Skin lesions are the most common extrathoracic manifestation. Granulomatous hepatitis, hypercalcemia, and kidney stones can also occur. [doi.org]

  Common symptoms include shortness of breath, a cough, chest pain, joint aches, fever and possible weight loss. This can all culminate towards reduced lung capacity. Unfortunately, there is no cure for the condition although symptoms can be treated. [pneumoconiosis.org.uk]

• Fatigue

  Its symptoms include coughing, shortness of breath, fatigue, weight loss or loss of appetite, fever and sweating. [web.archive.org]

  The symptoms seen are cough, rhinitis (inflammation of nasal mucus membrane), fever, pharyngitis (sore throat), fatigue, weight loss, dyspnoea (shortness of breath), loss of appetite etc. [symptoma.com]

  BeS precedes the lung disease that may present with chronic dry cough, fatigue, weight loss, chest pain, and increasing dyspnea. [orpha.net]

• Asymptomatic

  Clinical description Patients with CBD can range from those who are asymptomatic to those with severe lung dysfunction. [orpha.net]

  Some people remain asymptomatic. [merckmanuals.com]

  There are several challenges of conducting systematic longitudinal follow-up of individuals who are asymptomatic: the need for high participation rates limits the possibility to conduct regular bronchoscopic examinations of asymptomatic individuals in [occmed.oxfordjournals.org]

• Lymphadenopathy

  Mediastinal or hilar lymphadenopathy was shown in three cases. CT clearly demonstrates the pattern and distribution of pulmonary and mediastinal involvement in chronic pulmonary berylliosis but the appearances are non-specific. [ncbi.nlm.nih.gov]

  Imaging studies X-rays are normal in about half the patients having berylliosis although findings include increased interstitial markings and hilar lymphadenopathy. [symptoma.com]

  There may be inspiratory rales on pulmonary auscultation, lymphadenopathy, cutaneous dermatitis or rash and hepatosplenomegaly. Other symptoms may include weight loss, chest pain, fever and joint aches. [lecturio.com]

  […] non-specific and include: pulmonary nodularity is considered relatively common 1,2,6 patterns consistent with upper lobe fibrosis 1 diffuse interstitial fibrosis pattern 1 traction bronchiectasis 2 interlobular septal thickening 2 Mediastinal and hilar lymphadenopathy [radiopaedia.org]

  […] industries Inhalation causes 2 pulmonary syndromes: Acute chemical pneumonitis and chronic granulomatous lung disease IMAGING FINDINGS General Features Best diagnostic clue Pattern identical to sarcoidosis; however Ground-glass opacities more common Lymphadenopathy [radiologykey.com]

• Cough

  Its symptoms include coughing, shortness of breath, fatigue, weight loss or loss of appetite, fever and sweating. [web.archive.org]

  The acute disease involves both skin and lungs, causing a burning rash, eye irritation, nasal discharge, a cough, and chest tightness. [britannica.com]

  Chronic beryllium disease causes progressive dyspnea, cough, and fatigue. Diagnosis is by history, beryllium lymphocyte proliferation test, and biopsy. Treatment is with corticosteroids. [merckmanuals.com]

• Dyspnea

  Chronic beryllium disease causes progressive dyspnea, cough, and fatigue. Diagnosis is by history, beryllium lymphocyte proliferation test, and biopsy. Treatment is with corticosteroids. [merckmanuals.com]

  Symptoms usually include dyspnea and cough. Fever, anorexia, and weight loss are common. Skin lesions are the most common extrathoracic manifestation. Granulomatous hepatitis, hypercalcemia, and kidney stones can also occur. [doi.org]

  Acute beryllium disease has a sudden, rapid onset and is characterized by severe inflammation of the lungs (pneumonitis), coughing, increasing breathlessness (dyspnea), and other associated symptoms and findings. [web.archive.org]

• Dry Cough

  In individuals with chronic beryllium disease, associated symptoms and findings often include dry coughing, fatigue, weight loss, chest pain, and increasing shortness of breath. [web.archive.org]

  BeS precedes the lung disease that may present with chronic dry cough, fatigue, weight loss, chest pain, and increasing dyspnea. [orpha.net]

  It generally causes shortness of breath, especially after exercise, exhaustion, and a dry cough and can produce a permanent, though moderate, disability. [britannica.com]

• Exertional Dyspnea

  職業歴と検査所見より慢性ベリリウム症と診断した. 24-year-old man was admitted to our hospital because of exertional dyspnea and abnormal shadows on chest X-ray film. He worked in a factory, where he was exposed to 1.8% beryllium-copper alloys. [ci.nii.ac.jp]

  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 > 30 years after exposure has ceased. [merckmanuals.com]

• Rales

  There may be inspiratory rales on pulmonary auscultation, lymphadenopathy, cutaneous dermatitis or rash and hepatosplenomegaly. Other symptoms may include weight loss, chest pain, fever and joint aches. [lecturio.com]

• Nausea

  Nausea, vomiting, and a metallic taste may occur [3]. Bronchitis and/or pneumonia may occur one to two days after exposure, causing pulmonary edema and death in severe cases [2]. [scribd.com]

• Chest Pain

  In individuals with chronic beryllium disease, associated symptoms and findings often include dry coughing, fatigue, weight loss, chest pain, and increasing shortness of breath. [web.archive.org]

  Pathol. beryllium poisoning, characterized by the formation of granulomas, primarily affecting the lungs and causing a cough, chest pain, and shortness of breath. [medicine.academic.ru]

  BeS precedes the lung disease that may present with chronic dry cough, fatigue, weight loss, chest pain, and increasing dyspnea. [orpha.net]

  Common symptoms include shortness of breath, a cough, chest pain, joint aches, fever and possible weight loss. This can all culminate towards reduced lung capacity. Unfortunately, there is no cure for the condition although symptoms can be treated. [pneumoconiosis.org.uk]

• Arthralgia

  You could experience any of these symptoms if afflicted with berylliosis: • Chest pain • Arthralgia (joint pain) • Cyanosis (bluish tint to the skin) • Dry cough • Fatigue • Dyspnoea (fast respiration rate) • Dermatitis (rashes) • Shortness of breath [empowher.com]

  General signs like fatigue, weight loss and arthralgia are not rare. The most characteristic sign of granuloma formation is a response of the lymphocytes and is seen surrounding the beryllium particles. [symptoma.com]

Diagnosis can be established by a combination of blood tests, radio imaging and other tests like spirometry and pulmonary function tests. Diagnostics aim at differentiation the granulomas from those of sarcoidosis and tuberculosis. Hypersensitivity pneumonitis and Idiopathic pulmonary fibrosis (IPF) are the two other differential diagnoses that need to be ruled out.

Laboratory studies

Beryllium lymphocyte proliferation test (BeLPT) is an advanced blood test to diagnose chronic beryllium disease. Peripheral blood sample is collected and mononuclear cells are exposed to beryllium salts for varying periods of time at different concentrations. Cell proliferation with the salts is considered as a positive response due to the sensitization to beryllium [4] [5]. The test is available at only very specific centres.

Imaging studies

X-rays are normal in about half the patients having berylliosis although findings include increased interstitial markings and hilar lymphadenopathy. High resolution CT (HRCT) scans will show a classic ground glass like appearance, septal lines or parenchymal nodules. CT scans are considered more sensitive than chest radiographs [6]. Even so, HRCT scans are negative in almost a quarter of the patients having documented berylliosis.

Other tests

Histologic studies show non-necrotizing granulomas, the hallmark of berylliosis. Spirometry and pulmonary function tests (PFT) are essentially done as they may confirm the restrictive lung pattern due to exposure to the chemical. A study demonstrated an obstructive breathing pattern in 39% patients, a restrictive breathing pattern in 20% cases and a low diffusing capacity of lungs for carbon monoxide (DLCO) in 36% patients. In certain individuals a lung biopsy might be necessary to check for granulations as well as beryllium deposits. Detecting abnormalities in gas exchange while doing exercise is probably the most sensitive index to determine prognosis.

Invasive procedures

Flexible fiberoptic bronchoscopy with bronchoalveolar lavage or a transbronchial biopsy are often the first necessary invasive procedure in a suspected case. The lavage shows >20% lymphocytes. 6 high-quality transbronchial biopsy samples should be collected to get a optimum result.

• Bilateral Hilar Adenopathy

  We report a case of a woman with a history of beryllium exposure who developed cough and progressive dyspnea, accompanied by bilateral hilar adenopathy and nodular parenchymal disease. [nature.com]

• Granulomatous Tissue

  Because of the distribution of the metal throughout the body, certain other biochemical changes and granulomatous tissue reactions in organs other than the lung, the term beryllium poisoning or berylliosis appeals to some observers. [vitrinelinguistique.oqlf.gouv.qc.ca]

Treatment options are very limited in these individuals as there is an irreversible damage to the lung tissues. Corticosteroids remain the main stay of medications. If certain individuals develop adverse reactions then they are switched over to a methotrexate regimen.

Follow-up pulmonary testing to record improvement on medications is highly recommended. Prevention of exposure for longer durations is the best option in persons who are susceptible.

Studies are suggesting that current prevention guidelines of average maximum permissible levels at 2mcg/m3 are too high [7]. Lung transplants are the last resort.

The prognosis is poor as patients eventually face shortage of oxygen supply due to the parenchymal restriction. Monitoring by a pulmonologist is essential to decide outcomes.

Respiratory failure requiring oxygen supplementation is often observed in the fulminant cases.

In earlier days, people working in the factories where fluorescent lamps were manufactured were seen to be suffering from a granulomatous lung disease and were later on identified to be as berylliosis sufferers.

The main cause of the disease is exposure to beryllium fumes via inhalation as well as skin contact with dust; any contact with the chemical leads to a delayed type of hypersensitivity reaction produced by the lungs to form granulomas.

Cases are also seen in aerospace and ceramic industries where beryllium is one of the chemicals used.

The disease is more frequently seen in the people who are working in industries where beryllium is used as the chemical agent.

Only about 1-10% of the people exposed to beryllium actually go on to develop a hypersensitivity to beryllium and an even smaller portion progresses towards a chronic disease.

It is seen to affect workers with greater exposure to beryllium more often than other people. The areas with the highest exposure have the highest attack rates.

Men and women are equally affected. No racial predilections have been observed for berylliosis. Strong evidence for genetic susceptibility does exist.

A study showed that 97% patients having berylliosis had a variant of the major histocompatibility complex HLA-DPb1 (Glu 69) [1]. The chronic beryllium disease has been reported in children, adults as well as elderly.

The exposure to beryllium occurs either by inhalation of fumes or dust and skin contact. Although most of the beryllium is excreted via urine, the half life for pulmonary clearance ranges between many weeks to six months. The more insoluble forms of the chemical might never get cleared too.

The chief pathogenetic reaction that occurs on exposure to beryllium is a delayed-type (type IV) hypersensitivity reaction. Beryllium functions as the hapten and stimulates the local production and accumulation of specific T cells.

Following fume inhalation, there is a large accumulation of CD4+ lymphocytes in the lung parenchyma. The helper T cells show a strong proliferative reaction on being exposed to beryllium [2]. In a study conducted by Van Dyke, it was found that the substitution of a glutamic acid at the position 69 in one HLA gene coupled with the chronic beryllium exposure resulted in increased chances of beryllium sensitization and berylliosis [3].

The chemical acts in other non-specific ways as well, promoting cellular events that ultimately lead to formation of granulomas. Inducing changes in the lung permeability and elaboration of pro-inflammatory cytokines, growth factors all probably lead to the manifestation of granulomas in berylliosis. With progressive disease, the granulomas become more organized and become fibrous nodules that cause restriction of pulmonary function.

Beryllium exposure occurs primarily by inhalation of beryllium fumes or dust and contact through broken skin.

Inhalation of the element beryllium (Be) leads to acute and chronic pulmonary affections called as berylliosis. Both acute and chronic diseases are harmful and irreversible in nature. As science progressed, the acute effects of this harmful chemical irritant were curbed and hence we see only the chronic effects of beryllium inhalation.

Berylliosis is also called as chronic beryllium disease (CBD) as the effects are seen after prolonged inhalation or exposure to the chemical. It mainly affects the pulmonary tissues to produce granuloma formation which eventually restricts the functions of the pulmonary tissue. Since it is a disease which affects people who are into this occupation it is also classified into an occupational disease.

People suffering from this disease have to consider changing their occupation as continued exposure will worsen the health status of the patient.

Berylliosis is a chronic disease caused due to the heightened sensitivity of the immune system of the individual after repeated exposures of beryllium fumes and dust.

The person who is exposed beryllium develops an exaggerated immune response to the beryllium particle. It treats the beryllium particle as foreign and also develops an allergic response to it. As this sensitizing in the immune system of the body takes time, one may develop symptoms after many years of exposure to the beryllium fumes or dust. The lymphocytes which are stimulated by beryllium particles form granuloma around the beryllium particles thus preventing it from further spreading.

This will lead to the characteristic presentation of granuloma formation all over the tissues of skin, lung, and lymph nodes.

The symptoms seen are cough, rhinitis (inflammation of nasal mucus membrane), fever, pharyngitis (sore throat), fatigue, weight loss, dyspnoea (shortness of breath), loss of appetite etc.

All the above symptoms are extremely common in sarcoidosis as well as tuberculosis but the most distinguishing test to confirm diagnosis is beryllium lymphocyte proliferation test. Other tests to support the diagnosis is spirometry, pulmonary function tests, High resolution CT scan, X-ray and finally biopsy of lung parenchyma.

The person can be treated symptomatically but long term treatment with corticosteroids is the main line of action. Despite use of drugs there is just maintenance of the disease at the same level as there is no cure for this disease. The granuloma formation allows permanent thickening and scarring of the tissues.

Prognosis of such individuals is extremely poor and hence one must prevent long exposures to beryllium.

1. Richeldi L, Sorrentino R, Saltini C. HLA-DPB1 glutamate 69: a genetic marker of beryllium disease. Science. Oct 8 1993;262(5131):242-4
2. 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.
3. 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. Mar 11 2011
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.
5. 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.
6. Newman LS, Buschman DL, Newell JD Jr, Lynch DA. Beryllium disease: assessment with CT. Radiology. Mar 1994;190(3):835-40
7. 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.