Inclusion Disease in Childhood

It is well established that many viruses produce inclusion bodies in the nucleus or cytoplasm of an affected cell, and that the morphological appearance of such inclusions may be pathognomonic of a particular infection (Pinkerton, 1950). Similar bodies may also result from the toxic action of certain heavy metals (Lee, 1933; Blackman, 1936; Olitsky and Harford, 1937). They are occasionally found in cirrhotic livers, and Russell bodies are frequent in many non-specific inflammatory lesions. In view of these facts, Cowdry, Lucas, and Fox (1935) stated that the finding of inclusion bodies should be accepted with caution as evidence of viral infection. When they are conspicuous without the aid of oil immersion microscopy, are focal in distribution, and are related to marked lesions in the surrounding tissue, it is probable that they indicate a viral infection. Intranuclear inclusions are divided into two types (Cowdry, 1934). Type A inclusion bodies are represented by a mass of eosinophilic material in the centre of the nucleus with collections of basophilic substance near the nuclear membrane. Complete disintegration of the cell ultimately occurs, and such cells are accompanied by a noticeable reaction in the surrounding tissues. This variety is seen in herpes, yellow fever, varicella, etc. Type B inclusions show a similar acidophilic accumulation in the nucleus which pushes the other nuclear components towards the nuclear membrane. There is no extensive destruction and no severe tissue reaction. Both types, and particularly type B, have been found in a number of apparently healthy animals of various species (Cowdry et al., 1935). In 1920 Jackson observed inclusion bodies in the salivary glands of guinea-pigs. The affected cells were greatly enlarged and contained type A intranuclear inclusions and numerous small intracytoplasmic inclusion bodies. Cole and Kuttner (1926) first isolated a virus from affected guinea-pigs and, since then, the association of the salivary gland virus with the morphologically distinct inclusion cells has been firmly established (Markham, 1938, Rosenbusch and Lucas, 1939). Identical cells have been discovered in rats (Thompson, 1932), mice (Thompson, 1934), monkeys (Cowdry and Scott, 1935a and b), and mole (Rector and Rector, 1934). Efforts to transfer the infection from one species to another have failed, and it is now recognized that the virus is strictly species specific (Kuttner and Wang, 1934). Occasional reports of peculiar cells in human organs, almost invariably in infants and young children, have appeared in the literature since they were first described by Jesionek and Kiolemenoglou in 1904. These were regarded as representing protozoa until Goodpasture and Talbot (1921) recognized their similarity to the bodies described in the lesions of vaccinia (Tyzzer, 1906) and in the salivary glands of guinea-pigs (Jackson, 1920). It was later observed that these cells had the same morphology as those found in animals infected with a salivary gland virus. So far, however, attempts to isolate a virus from human material have failed (Kuttner and Wang, 1934). All affected cells are enlarged to a diameter of 20-40[L so that they are two to four times as large as unaffected cells (Fig. 1). Most authors point out that transitions from normal to abnormal cells are rarely if ever seen, although stages in the development of the inclusion bodies have been described (Cappell and McFarlane, 1947). Often there is a condensation of the cytoplasm to form a thick refractile cell membrane, a feature most prominent in those cells showing evidence of degeneration. The intranuclear inclusion bodies are two to three times as large as normal unaffected nuclei. Although usually round or oval, they may be reniform or distorted into bizarre shapes. They are acidophilic and often homogeneous, although sometimes they appear to be composed of numerous tiny particles. A clear halo invariably separates the inclusion from the nuclear membrane on which are small