User:Alan.taylor2013/sandbox

My name is Alan Taylor and I am and Occupational Medicine resident in an occupational epidemiology course. As part of this course I will be working on Berylliosis page. I am planning on adding and claryifying to the signs and symptoms section and diagnosis. I will add an epidemiology and screening section and possibly a section on pathophisiology

Berylliosis, or chronic beryllium disease (CBD), is a chronic allergic-type lung response and chronic lung disease caused by exposure to beryllium and its compounds, a form of beryllium poisoning. As an occupational lung disease, it is most classically associated with aerospace manufacturing, beryllium mining or manufacturing of fluorescent light bulbs (which once contained beryllium compounds in their internal phosphor coating).

The condition is incurable, but symptoms can be treated.

Signs and symptoms
With single or prolonged exposure by inhalation the lungs may become sensitized to beryllium. Continued exposure causes the development of small inflammatory nodules, called granulomas. Of note, the authors of a 2006 study suggested that beryllium inhalation was not the only form of exposure and perhaps skin exposure was also a cause, as they found that a reduction in beryllium inhalation did not result in a reduction in CBD or beryllium sensitization.

Granulomas are seen in other chronic diseases, such as tuberculosis and sarcoidosis, and it can occasionally be hard to distinguish berylliosis from these disorders. Note, however, that the granulomas of CBD will typically be non-caseating, i.e. not characterized by necrosis and therefore not exhibiting a cheese-like appearance grossly.

Ultimately, this process leads to restrictive lung disease (a decrease in diffusion capacity).

Clinically, patients experience cough and shortness of breath. Other symptoms include chest pain, joint aches, weight loss, and fever.

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

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.

Pathogenesis
In susceptible persons, beryllium exposure can lead to a cell-mediated immune response. The T-cells become sensitized to the beryllium. Each subsequent exposure leads to an immune response involving CD4+ helper T-lymphocytes and macrophages accumulating in the lungs. As this response continues macrophages, CD+4 T-lymphocytes and plasma cells aggregate together to form the noncaseating granulomas. Eventually, the final outcome is fibrosis of the lung.

Several studies have shown that there is a genetic component to beryllium sensitivity. Specifically, those beryllium exposed workers with a mutation at the the HLA-DPB1 Glu69 position have increased prevelance of beryllium sensitization and CBD. The HLA-DPB1 gene is important for MCH class II molecule function on antigen presenting cells.

Epidemiology
The number of workers in the United States exposed to beryllium vary but has been estimated to be as high as 800,000 during the 1960s and 1970s. A more recent study estimated the number of exposed workers in the United States from in 1996 to be around 134,000.

The rate of workers becoming sensitized to Beryllium varies based on genetics and exposure levels. In one study they found the prevalence of beryllium sensitization to range from 9 - 19% depending on the industry. Many workers who are found to be sensitive to beryllium also meet the diagnostic criteria for CBD. In one study of nuclear workers, among those who were sensitized to beryllium, 66% were found to have CBD as well. The rate of progression from beryllium sensitization to CBD has been estimated yo be approximately 6-8% per year. Stopping exposure to beryllium in those sensitized has not been definitively shown to stop the progression to CBD.

The overall prevalence of CBD among workers exposed to beryllium has ranged from 1 - 5% depending on industy and time period of study.

Diagnosis
The differential diagnosis for berylliosis includes: Of these possibilities, berylliosis presents most similarly to sarcoidosis. Some studies suggest that up to 6% of all cases of sarcoidosis are actually berylliosis.
 * Sarcoidosis
 * Granulomatous lung diseases
 * Tuberculosis
 * Fungal infections
 * Granulomatosis with polyangiitis
 * Idiopathic pulmonary fibrosis
 * Hypersensitivity pneumonitis
 * Asthma

Definitive diagnosis of berylliosis is based on history of beryllium exposures, documented beryllium sensitivity and granulomatous inflammation on lung biopsy. Given the invasive nature of a lung biopsy diagnosis can also be based on clinical history consistent with berylliosis, abnormal chest x-ray or CT scan findings, an abnormalities in pulmonary function tests.

Establishing beryllium sensitivity is the first step in diagnosis. The beryllium lymphocyte proliferation test (BeLPT) is the standard way of determining sensitivity to beryllium. The test is performed by acquiring either, peripheral blood or fluid from a bronchial alveolar lavage, and lymphocytes are cultured with beryllium sulfate. Cells are then counted and those with elevated number of cells are considered abnormal. Those exposed persons with two abnormal BeLPT tested with peripheral blood, or one abnormal and one borderline result, are considered beryllium sensitized. Also, those with with one abnormal BeLPT tested with fluid from a bronchial alveolar lavage are considered sensitized.

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 also not specific to 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, intersitial pulmonary fibrosis and plueral thickening.

Treatment
Although the evidence that stopping exposure to beryllium decreases progression of the disease, it is still considered to be the an accepted approach to treatment in any stage of disease. In those with early stages of disease, without lung function abnormalities or clinical symptoms, periodic monitoring with physical exam, pulmonary function testing and radiography is the mainstay of treatment. Once clinical symptoms or significant abnormalities in pulmonary function testing appear the first choice of treatment are oral corticosteriods. Individuals are started at higher doses for 3 to 6 months, and the tapered down to the lowest effective dose.

Other treatment modalities include methotrexate and azathioprine but niether have been studied extensively.

There is no cure for berylliosis the goals of treatment or to reduce symptoms and slow the progression of disease.

History
Cases of bronchitis and pneumonia-like symptoms were reported in Germany and Russia in the 1930s, among workers mining and refining beryllium. By 1946, a cluster of cases associated with fluorescent lamp manufacturers were apparent in the United States, and the lamp industry stopped using beryllium in 1949. The level of reaction of individuals varies greatly, with some not developing symptoms until years after exposure within industrial plants, but other workers only exposed to traces of dust became affected as well. A study found 1% of people living within 3/4 of a mile of a beryllium plant in Lorain, Ohio, had berylliosis after exposure to concentrations estimated to be less than 1 milligram per cubic metre of air. In the United States the Beryllium Case Registry contained 900 records, early cases relating to extraction and fluorescent lamp manufacture, later ones coming from the aerospace, ceramics and metallurgical industries.