Berylliosis is an occupational disease with a predominant lesion of the respiratory system resulting from the harmful effects of beryllium compounds on the body. Acute berylliosis occurs as bronchitis or pneumonia. The chronic process is characterized by a gradually increasing cough, shortness of breath, severe asthenization and signs of intoxication. Diagnosis is based on anamnesis data, chest radiography and CT, skin and serological tests, examination of biopsy material. Treatment with corticosteroids, antihistamines and antitussive drugs is prescribed.
Berylliosis (beryllium lung disease) develops when inhaling beryllium vapors and dust. Exceeding the maximum permissible concentrations of soluble metal compounds in the environment (more than 0.001 mg per m3) leads to acute berylliosis. Currently, this pathology is rare. Insoluble and insoluble beryllium compounds, entering the human body, cause a chronic form of the disease in 1-16% of people who have come into contact with beryllium alloys. Chronic berylliosis occurs at any age. The incidence of this form of occupational pathology does not depend on the concentration of the substance in the air and the exposure time. Women suffer more often.
Pathology belongs to the category of occupational diseases. It occurs among beryllium miners, foundry workers and employees of enterprises using this metal or its compounds in production. Beryllium is widely used in aircraft construction, space research, nuclear power and other industries. Its vapors and dust usually enter the respiratory tract when inhaled. With skin contact with very high concentrations of beryllium compounds, a transdermal pathway of penetration of harmful substances into internal organs and systems is possible. Beryllium present in a woman’s body overcomes fetoplacental and lactation barriers.
The element is highly toxic. When inhaling air with a high content of acidic beryllium salts, acute severe chemical pneumonitis occurs. Permissible concentrations of compounds of this metal cause chronic berylliosis, to which genetically predisposed individuals are susceptible. There is no correlation between the prevalence of this form of the disease and the amount of metal in the external environment and the time of its exposure. If there is a predisposition, not only patients who are in direct contact with beryllium and its alloys become ill, but also people who work or live in neighboring premises.
The pathogenesis of berylliosis has not been fully studied. In the course of scientific research in the field of pulmonology and occupational pathology, it has been established that there are certain alleles of genes encoding a predisposition to the occurrence of chronic beryllium disease. When inhaling the vapors of beryllium compounds, metal particles enter the airways, accumulate in the lungs and intra-thoracic lymph nodes. Very slowly and gradually, other organs are involved in the pathological process. In patients genetically predisposed to this pathology, beryllium is recognized as an antigen. A cellular immune response is formed. During the reaction, cytokines are released that damage their own tissues.
Numerous epithelioid cell granulomas without caseosis are formed in the lungs. They are localized in interstitial tissue, surround vascular bundles, bronchioles and small bronchi. At the same time, the interalveolar partitions thicken, gas exchange suffers. In the future, there is an expansion of the bronchioles, the appearance of air bulls, a gross violation of the architectonics of the acinus – the formation of a cellular lung. Gas exchange deteriorates even more. Severe respiratory failure develops. Soluble beryllium compounds, when ingested into the respiratory system, cause a pronounced exudative inflammatory reaction and pulmonary interstitial edema.
Despite the fact that some authors consider acute beryllium intoxication to be a variant of metal fever, most pulmonologists and occupational pathologists divide berylliosis into acute and chronic. There are acute lesions of the upper (laryngitis, tracheitis, bronchitis) and lower (bronchiolitis, alveolitis) respiratory tract. Changes in the radiation examination of the lungs reflect the following stages of a chronically occurring disease:
- Stage I. There are mainly interstitial changes, intra-thoracic lymphadenopathy. Single small granulomas are detected.
- Stage II. Against the background of the strengthening of the pulmonary pattern, widespread fine-point shadows are revealed. The lungs on the X-ray resemble sandpaper.
- Stage III. The vascular pattern is roughly deformed. Multiple granulomas, air bulls, pleurodiaphragmatic and pleuropericardial adhesions are determined.
The clinical picture of acute beryllium intoxication usually consists of symptoms of irritation of the upper respiratory tract and conjunctiva. The disease is manifested by lacrimation, photophobia and redness of the mucous membranes of the eyes. The patient is concerned about nasal congestion or, conversely, abundant light mucous discharge. The voice changes – hoarseness or hoarseness appears, a superficial barking cough joins. There are pains and tickling in the throat, burning behind the sternum. This form of the disease is usually stopped independently within a few days after the cessation of contact with a harmful agent, less often complicated by severe beryllium pneumopathy.
Acute berylliosis with alveolar tissue damage is severe. It is characterized by an increase in body temperature to febrile and hyperthermic values, accompanied by chills. The patient complains of a sharp headache, shortness of breath, painful dry or unproductive cough. There may be an admixture of blood in the sputum. Myocardiodystrophy develops, manifested by various cardiac arrhythmias, tachycardia and a decrease in blood pressure. The disease is usually protracted, lasts 2-3 months. Temporary improvement of the condition is periodically replaced by deterioration.
Chronic berylliosis develops 1-30 years after contact with dust, smoke or vapors of beryllium compounds. The onset of the disease is gradual. General weakness and fatigue are slowly increasing. The patient loses weight dramatically, body weight loss can reach 20 kg within 3-6 months. Dyspnea is steadily progressing, it is accompanied by a constant dry cough, chest pains of varying intensity and localization. The distal phalanges of the fingers of the extremities are deformed by the type of drumsticks, the nails take the form of watch glasses. The patient is worried about tachycardia. Due to the enlargement of the liver, pain appears in the right hypochondrium. The patient’s condition worsens during the period of exacerbation. An increase in cough, shortness of breath and weakness is often accompanied by an increase in temperature.
Acute berylliosis with timely adequate treatment often proceeds favorably, however, cases of death of patients from acute pulmonary heart failure are known. Chronic berylliosis in 10% of cases is complicated by severe respiratory failure and early formation of a chronic pulmonary heart with subsequent disability and death of the patient. Spontaneous pneumothorax on the background of a chronic variant of beryllium lung disease are rare. In 11% of patients, recurrent hemoptysis is observed.
If berylliosis is suspected, it is of great diagnostic importance to establish contact of the patient with beryllium vapors or dust in the anamnesis. On examination, attention is drawn to acrocyanosis or diffuse cyanosis of the skin. Sometimes subcutaneous granulomas are found. Breathing is rapid, shortness of breath increases with little physical exertion and conversation. Distal hypertrophic osteoarthropathy is observed. Enlarged lymph nodes are palpated. A characteristic feature of berylliosis is an increase in the ulnar lymph nodes to the size of a pea. For the final confirmation of the diagnosis, the following are performed:
- Physical examination. Percussion reveals boxed sound from both sides. During auscultation, scattered crepitating or moist small-bubbly wheezes are usually heard, localized mainly in the projection of the basal parts of the lungs. Sometimes the wheezing is dry, the noise of pleural friction is heard. The heart tones are usually muted, the emphasis of the II tone on the pulmonary artery is determined.
- Radiography, CT of the lungs. Interstitial and granulomatous changes are observed. The X-ray images show the strengthening and deformation of the pulmonary pattern, single or multiple miliary shadows, bullous emphysema, pleural fusion. In the terminal stage of the disease, the lungs resemble a honeycomb (honeycomb lung).
- Functional diagnostics. The study of the function of external respiration makes it possible to identify restrictive disorders. ECG shows signs of hypertrophy of the right heart, tachycardia, arrhythmias. During pulse oximetry, a decrease in blood oxygen saturation is determined.
- Laboratory tests. Are auxiliary methods. In the acute process and during the exacerbation of the chronic form, leukocytosis and acceleration of ESR are observed in the analysis of peripheral blood. A biochemical blood test reveals hypoalbuminemia and hypergammaglobulinemia. Beryllium can be found in urine, pleural fluid, and bronchial lavage waters.
- Skin and serological tests. The appearance of erythema as a result of cutaneous application of beryllium chloride solution with a high degree of probability indicates the presence of beryllium disease. To confirm sensitization to beryllium, a number of serological tests (RPGA, RTML, RPL and others) with blood serum are performed.
Chronic berylliosis is differentiated with disseminated tuberculosis, Beck’s sarcoidosis, metastatic lesions of the respiratory organs, and other pneumoconioses. According to the indications, consultations of a phthisiologist and an oncologist are prescribed, immunodiagnostic tests are carried out (Mantoux test, Diaskintest), sputum is examined for BC. In unclear cases, a lung biopsy is performed with further histological examination of the obtained material.
It is necessary to immediately exclude any contact with the pathogenic agent. In case of acute poisoning, systemic corticosteroids, antihistamines and antitussive medications, alkaline inhalations are prescribed. When a secondary bacterial infection is attached, antibiotics are recommended. Acute beryllium pneumonitis is an indication for oxygen therapy. If necessary, artificial ventilation of the lungs is performed, cardioprotectors are used.
Corticosteroid hormones are the drug of choice for the implementation of the basic therapy of the chronic process. If corticosteroid treatment is ineffective, methotrexate is sometimes prescribed. Basic treatment is carried out in two stages. First, hormones of systemic action are applied. To prevent the development of possible side effects, gastro- and angioprotectors, calcium and potassium preparations are used together with them. At the second stage, the patient receives inhaled corticosteroids through a nebulizer or in the form of a dosed aerosol. Respiratory gymnastics and physical therapy for the patient. In the last stage of the disease, heart and lung transplantation is possible.
Prognosis and prevention
Acute berylliosis usually proceeds favorably. Fatal outcomes or chronization are rare. The prognosis for the chronic course of the disease depends on the timeliness of detection and the start of basic therapy. The use of corticosteroids in the early stages of the disease leads to prolonged persistent remission and compensation of respiratory functions. If berylliosis is detected in the late stage, the outcome is unfavorable. Patients need a heart-lung complex transplant.
For the primary prevention of this occupational disease, it is necessary to use personal protective equipment when working with beryllium compounds. All persons working in harmful conditions are subject to regular preventive examinations with the use of X-ray examination of the thoracic cavity and determination of hypersensitivity to beryllium.
- Balmes JR, Abraham JL, Dweik RA, Fireman E, Fontenot AP, Maier LA, Muller-Quernheim J, Ostiguy G, Pepper LD, Saltini C, Schuler CR, Takaro TK, Wambach PF, ATS Ad Hoc Committee on Beryllium Sensitivity and Chronic Beryllium Disease An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease. Am J Respir Crit Care Med. 2014 Nov 15;190(10):e34-59. – link
- Boffetta P, Fordyce TA, Mandel JS. A mortality study of beryllium workers. Cancer Med. 2016 Dec;5(12):3596-3605. link
- Occupational Safety and Health Administration (OSHA), Department of Labor. Occupational Exposure to Beryllium. Final rule. Fed Regist. 2017 Jan 09;82(5):2470-757. – link
- Kreiss K, Fechter-Leggett ED, McCanlies EC, Schuler CR, Weston A. Research to Practice Implications of High-Risk Genotypes for Beryllium Sensitization and Disease. J Occup Environ Med. 2016 Sep;58(9):855-60. link
- Mayer A, Hamzeh N. Beryllium and other metal-induced lung disease. Curr Opin Pulm Med. 2015 Mar;21(2):178-84. – link