Introduction to Sarcoidosis

An introduction to the disease with a short history, detailed explanation, etiology, epidemiology and basic treatment, by the late Dr. Om P. Sharma.

More than a century ago, Jonathan Hutchinson, a surgeon-dermatologist, identified the first case of sarcoidosis at King's College, London, U.K. The disease is now commonplace. Although no organ in the body is immune to sarcoidosis, the disease most frequently involves the lungs, liver spleen, skin, eyes, myocardium, central nervous system, joints, and bones.

Sarcoidosis is common in Scandinavian countries, the United Kingdom, Ireland, the United States, and Japan; it appears less frequently in Central and South America, China, Korea, India, Southeast Asia, and Africa. In the United States, sarcoidosis shows a prevalence rate of 10 to 40 per 100,000 population, with a predilection for African Americans (12:1 black: white ratio). Women outnumber men 2:1 in black patients, whereas, sex distribution is even among Caucasian patients. Its presentation and severity varies in different ethnic and racial groups. Sarcoidosis in blacks is more extensive and symptomatic, whereas in whites it tends to be asymptomatic and limited. Acute uveitis and erythema nodosum are more common in Scandinavians, Puerto Ricans, and the Irish; lupus pernio is more frequent in American blacks; cardiac and ocular sarcoidosis is more common in the Japanese. A number of studies have noted seasonal, geographic, occupational, and familial clustering of sarcoidosis. The disease has been reported to occur in healthcare workers, particularly nurses, more frequently than in controls. Three cases of sarcoidosis occurred in a group of 57 firefighters who worked together in the same environment. Familial sarcoidosis tends to occur more among blacks than whites. Such clustering of the disease is significant because it points toward an environmental agent that preys on the genetically susceptible host.

The cause of sarcoidosis is not known. No infective or inflammatory agent has been consistently isolated from patients with sarcoidosis. Early studies that examined the role of meteorology, soil, plants, pine pollen, proximity to woods and forests, and exposure to pets and farm animals have proven to be of no avail. The disease most likely represents an inflammatory response to one or many agents (bacteria, fungi, virus, chemicals) occurring in a person with either an inherited or acquired predisposition.

The basic lesion in sarcoidosis is a compact, noncaseating granuloma made up of radically arranged epithelioid cells with pale nuclei, a few giant cells, and lymphocytes. Caseation is absent; occasionally, a small area of necrosis may be present. Granuloma may resolve spontaneously, leaving no scar; may persist for a long time with little or no fibrosis; or may undergo complete and fibrosis, resulting in loss of tissue architecture.

The first step in the development of sarcoidosis involves the interaction of an unknown antigen or antigens and alveolar macrophages bearing increased expression of major histocompatbility complex (MHC) class II molecules. These macrophages engulf, process, and present the putative antigen(s) to T-Iymphocyte cells of Th-1 type. These activated T-cells release a number of cytokines, including interleukin-2, monocyte chemotactic factor, macrophage migration inhibition factor, and leukocyte inhibitory factor. Interleukin-2 activates and expands various clones of T-Iymphocytes; monocyte chemotactic factor attracts monocytes from blood into the lungs; macrophage migration inhibitory factor influences the trapped monocytes that are ready to transform into epithelioid cells and modulate the formation of a granuloma. The granuloma formation and associated helper (CD4+) T-lymphocyte alveolitis may lead to substantial lung injury. At this time, when the lung is the site of tremendous outpouring of lymphocytes, the peripheral circulation shows a CD4+ T-cell reduction resulting in depression of cutaneous delayed hypersensitivity reactions. Simultaneously, the B-cell function is increased. It is manifested by hyperglobulinemia; increased antibodies to Epstein-Barr, herpes simplex, and other viruses, and the presence of circulating immune complexes. Activated macrophages manufacture and release a number of chemicals mediators, including fibronectin, cytokines, and growth factors responsible for causing fibrosis.

Untreated sarcoidosis eventually subsides in most of the patients, but it may worsen in others. The outlook is better in patients with erythema nodosum. The patients who experience spontaneous remission rarely relapse. If pulmonary infiltration persists for more than 2 years, it is unlikely to remit without therapy. Devastating complications are due to the irreversible scarring of the lungs, the heart, the eyes, the kidneys, and the neuro-muscular system. The prognosis is poor in American blacks, particularly women, and especially those, who at the time of the initial discovery, have pulmonary infiltration and disease involving more than three organ systems.

Corticosteriods are effective drug against sarcoidosis and its complications. Other drugs, such as chloroquine, hydroxychloroquine, methotrexate, azathioprine, pentoxyphylline,and thalidomide have been used with varying success. These drugs are of particular value in patients who cannot tolerate corticosteriods or their side effects. Lung or heart transplantation may be necessary in cases of severe pulmonary or heart failure.