PULMONARY BERYLLIOSIS

Presented by –
SHAN ALI
Group- Ma 1706’o
INTRODUCTON-
Berylliosis, is a granulomatous disease caused by exposure to beryllium.
chronic beryllium disease CBD has a variable clinical course with cough,
fever, night sweats, and fatigue being the most common symptoms. A
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. 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.
CBD is more likely to develop in individuals who work in industries that
manufacture and process beryllium. Overall, there is nothing unique about
berylliosis; it is similar to many other granulomatous lung disorders.
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.
 Beryllium exposure tends to occur via inhalation of beryllium fumes or dust,
but it can also be absorbed following skin exposure. The organic forms of
beryllium are rapidly excreted, but the insoluble inorganic particles can
remain in the body for many years.
EPIDEMIOLOGY-

 CBD is a hypersensitivity granulomatous disease that occurs in 2 to 5% of

beryllium-exposed workers. 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)
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.
HISTOLOGY-
 The key feature on histopathology is the nonnecrotizing granulomas in
the lung; which mimic those seen in sarcoidosis.
CLINICAL MANIFESTATION-
 The clinical manifestations of CBD are nonspecific. The latency period
between beryllium exposure and the onset of symptoms varies from three
months to 30 years. 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. 
 The physical exam may reveal lymphadenopathy, crackles, rash, and
hepatosplenomegaly.
EVALUATION-
 A 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
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.
RADIOLOGY FINDINGS-

ON X RAY

 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.
ON CT SCAN-
 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.
Other tests include:

 Arterial blood gas

Pulmonary function tests
Spirometry
DLCO levels
TREATMENT-

 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 appears in
pulmonary function testing, oxygen and oral corticosteroids are started as
well as other supportive therapy as required.
 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. Patients
who fail to respond to steroids are started on immunosuppressive agents
such as methotrexate and azathioprine. Oral methotrexate at a 7.5mg weekly
dose is given with folic acid 1 mg. 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.
DIFFERENTIAL DIAGNOSIS-

 Differential diagnosis includes sarcoidosis, idiopathic pulmonary fibrosis,

hypersensitivity pneumonitis, asthma, and other granulomatous lung diseases
such as histoplasmosis, tuberculosis, silicosis. It is estimated that 6 percent of
all patients diagnosed with sarcoidosis may have CBD.
PROGNOSIS-

 Patients with beryllium sensitization in the absence of CBD do not 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%. CBD has a variable clinical
course. A higher percentage of lymphocytes in the bronchoalveolar lavage
correlates with greater severity of illness. Disability is common in people with
preexisting lung disease and smokers. The granulomas lead to nodule
formation, which can impair lung function.
THANK YOU …