although immune or hypersensitivity responses are also possible. Acute beryllium disease has been reported only rarely in the last several decades.
CBD, however, despite substantial reductions in beryllium respiratory exposures, continues to occur in exposed workers. The pathogenesis of CBD involves a lymphocyte-mediated immune response (delayed hypersensitivity) to beryllium that leads to noncaseating granulomatous lesions. CBD affects primarily the lungs, although granulomas can occur in other organs, such as skin, liver, and spleen. BeS precedes the development of CBD and since the late 1980s has been detected by in vitro challenge of lymphocytes with beryllium salts in the beryllium lymphocyte proliferation test (BeLPT). In the older literature, patients with CBD typically presented with respiratory symptoms, fatigue, and chest-radiographic and lung-function abnormalities. Since the BeLPT has been available, screening of workers with it has enabled diagnosis of CBD often when they have minimal or no symptoms. That has shifted the clinical spectrum of CBD toward less severe cases. The recent epidemiologic literature on BeS and CBD and their clinical presentation, diagnosis, and management are reviewed below.
In the United States, acute beryllium disease was first reported in the early 1940s by Van Ordstrand et al. (1943); the first reports of CBD were by Hardy and Tabershaw (1946). Cases were observed in industrial plants that were refining and manufacturing beryllium metal and beryllium alloys and in plants manufacturing fluorescent light bulbs. By 1948, the known cases totaled more than 400, and the basic clinical features of the disease were understood. It was established that the risk of disease among beryllium workers was variable and generally rose with the intensity of airborne exposure (Machle et al. 1948; see Chapter 2 for more information). From the late 1940s into the 1960s, clusters of CBD cases were identified around beryllium refineries in Ohio and Pennsylvania, and outbreaks in family members of beryllium-factory workers were presumably from exposure to contaminated clothing (Hardy 1980). Although there was a relationship between the air concentration of beryllium and the risk of CBD in areas close to the factories, the disease rates outside the plants were higher than expected and not very different from the rate of CBD in the workforce (Eisenbud et al. 1949; Lieben and Metzner 1959).
The prevalence of CBD in workers exposed during the 1940s and 1950s has been estimated at 1-10% (Eisenbud and Lisson 1983) although there is considerable uncertainty because most of the studies in that era did not use well-defined cohorts, modern diagnostic methods, or have adequate followup.
Sterner and Eisenbud (1951) first proposed an immunologic mechanism of CBD in 1951. Their evidence was largely circumstantial, but their inference was correct. They based their hypothesis on several pieces of evidence: the highly variable incidence in different groups of workers, the surprising occurrence in neighborhoods whose exposure appeared to be low, the sometimes rapid onset of disease after exposure, and the failure to observe an association between the amount of beryllium in lung autopsy specimens and the extent of lung damage.