Epidemiology of sarcoidosis in the Isle of Man--1: A case controlled study.

A case controlled study of 96 cases of sarcoidosis has been carried out in the Isle of Man. Age and sex matched controls were selected at random from the pathology and radiology records, which cover 85% of the resident population, and a second control group was drawn from a tuberculosis register. Special efforts were made to achieve a high level of ascertainment. In this study most cases occurred in young adults. It affected the sexes equally and occurred more frequently in the indigenous Manx population. Thirty eight cases (39.6%) had been in contact with the disease before diagnosis, compared with two (1.2%) of the combined controls. These contacts included members of the same household, colleagues at work, and close friends. A bias may have been introduced as patients would inevitably be more aware of the disease and be more likely to mention previous contact than the controls. Nevertheless, the evidence is considered to support the view that sarcoidosis is a communicable disease.

Epidemiology of sarcoidosis in the Isle of Man--2: Evidence for space-time clustering.

The case-control test for space-time clustering developed by Pike and Smith was applied to 96 cases of sarcoidosis diagnosed in the Isle of Man from 1962 to 1983. There were significantly more links between cases separated by time intervals of less than 10 years and distances of less than 100 metres than between the others. Analysis of the type of links indicated that clusters consisted of pairs whose contact was by place of residence or work. More linked cases were diagnosed less than three years apart than would be expected by chance. These findings lend support to the idea that sarcoidosis is a communicable disease.

The nature and physical characteristics of a transmissible agent from human sarcoid tissue.

In controlled experiments normal and immunologically deficient CBA mice were inoculated in footpads, intraperitoneally, or intravenously with whole fresh, fresh supernatant, and fresh filtered supernatant (0.2 mu) or with each of these homogenates after autoclaving or their further exposure to 60Co irradiation (2.5 MR). As controls, mice were inoculated with identically prepared fresh nonsarcoid homogenates by these same routes. Epithelioid- and giant-cell granulomas were present in viscera of mice given each fresh sarcoid homogenate by any of these routes 15 months after inoculation, but were not present in mice given nonsarcoid autoclaved sarcoid, or 60Co-irradiated sarcoid homogenate. Successful passages were achieved following the inoculation of whole or filtered supernatant (0.2 mu) sarcoid mouse tissue homogenate into footpads, intraperitoneally, or intravenously. The epithelioid- and giant-cell granulomas evolved slowly over a period of many months following the inoculation of sarcoid tissue or passage homogenates and persisted thereafter in association with Kveim reactivity. The transmissible agent is inactivated when homogenate prepared from human sarcoid or mouse sarcoid tissue is autoclaved or 60Co-irradiated, can be repeatedly passaged, and has been shown to pass an 0.2-mu membrane filter. It is therefore presumably viable and must approximate to the size of a virus or be capable of being deformed so as to pass a filter of such a pore size (0.2mu), L forms.

Transmissibility of sarcoid-specific granulomas in the footpads of mice.

Homogenate of 30 sarcoid lymph nodes was injected into the footpads of mice and 42% of the mice showed epitheloid-cell granulomas in the sites. However, the control lymph-node homogenates obtained from nonsarcoid patients also provoked similar granulomatous changes, although the positive rate was somewhat lower. In the granulomas a small amount of dust pigment remained, but no polarizing crystals were found in the sites or in the homogenate of either groups. No acid-fast bacilli, fungi, or other aerobic organisms were cultivated from the homogenate. Granuloma-formation activity remained after the homogenate had been sterilized in several ways and it existed in sediments of centrifugation of less than 2200 x g, but not in the supernate. The results seem to indicate that the granuloma formed in the footpads were the result of a local immunological reaction to the degenerated heterogenic protein of the injected and persistent homogenate.

Sarcoid granulomas in CBA/J mice. Histologic response after inoculation with sarcoid and nonsarcoid tissue homogenates.

Homogenates of lymph node and skin biopsy specimens and lymphocyte suspensions from patients with sarcoidosis and control subjects were injected into the footpads of CBA/J mice; histologic response was examined at intervals of 15 to 360 days. Kveim tests and complete autopsies were performed on animals of each group. Granulomas or equivocal granulomas were observed in 14.8% of biopsy specimens from animals that received sarcoid tissue homogenates and in 14.8% of control animals. No granulomas were observed after injection of lymphocytes from patients with sarcoidosis or from control subjects. Kveim tests were negative in all animals and autopsies were unremarkable. These studies fail to confirm previous reports of a "transmissible agent" in sarcoidosis and demonstrate that by the use of these techniques, such an agent is not invariably present in sarcoid granulomas.