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
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
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
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.