Sarcoidosis

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Sarcoidosis is a chronic granulomatous disease of unknown cause, in which many tissues are
infiltrated by non-caseating granuloma.
It is slightly more common in women than in men, and most patients present before the age of 40 years old.
The organs and systems that are most commonly involved clinically are the lymphoreticular system, the lungs, skin, eyes and the brain, although histological examination in sarcoidosis shows asymptomatic granulomas in many other organs and tissues, such as the heart, skeletal muscle, lacrimal glands and gastrointestinal tract.

As so many systems and organs are involved, the clinical presentation patterns are wide and varied; there are also marked differences in the clinical expression of the disease on a geographical and racial basis.
The aetiology and pathogenesis are completely unknown, although numerous immunological abnormalities can be detected in patients with sarcoidosis; however, these may be an effect of the disease rather than the cause.
Nevertheless, in lung involvement particularly, it is thought that one important factor is
an enhanced cell-mediated immune response.
The granulomatous infiltrate of sarcoidosis may be seen in most tissues.
Lymphoreticular involvement in sarcoidosis is manifest as enlarged lymph nodes
The lymph nodes that are most commonly enlarged in sarcoidosis are the intrathoracic lymph
nodes at the hilum of the lung. The enlargement of these nodes is invariably bilateral and
almost symmetrical, and can be associated with diffuse pulmonary infiltration. Sarcoid
enlargement of peripheral nodes, such as the axillary or cervical nodes, is less common.
The spleen is histologically involved in many patients, but the enlargement of the spleen
is clinically manifest in only about 5% of cases in Caucasians; it is more common in Afro-Caribbeans,
probably being manifest in about 15% of cases.
Massive splenomegaly may be associated with secondary haematological features such as pancytopenia.
Lung involvement in sarcoidosis is common, and is responsible for much of the morbidity
In addition to the bilateral hilar lymphadenopathy, there is frequently a diffuse pulmonary
infiltration which leads to a restrictive ventilatory defect and reduced gas transfer.
The lung shows interstitial infiltration by typical sarcoid granulomas in the early stages,
but these eventually heal by fibrosis.
Much of the permanent pulmonary damage, whether structural or functional, is the result
of progressive pulmonary interstitial fibrosis.

Skin lesions in association with sarcoidosis are very common.
Skin manifestations occur in sarcoidosis in about one-quarter to one-third of all cases.
There are two main patterns of involvement:
1 Erythema nodosum presents characteristic, tender, red or purple
subcutaneous lumps, usually on the shins and thighs, sometimes accompanied by fever and
malaise, and frequently by associated arthralgia. It is an nflammatory lesion
of the subcutaneous fat, usually associated with inflammation of a large vein. Although
occasional giant cells are seen in relation to necrotic fat, true sarcoid
granulomas are not seen. This pattern is particularly associated with the
bilateral hilar lymphadenopathy pattern in the thorax, and is said to have a good prognosis.
2 Sarcoid granulomas in the skin may have several clinical manifestations, including brown papules
(sometimes associated with hair follicles, leading to hair loss),
reddish/brown fixed nodules and plaques, and a characteristic pattern called
lupus pernio. In this pattern, which is associated with severe systemic involvement
(including the nasal passages, lung and eye), there are persistent,
rubbery, purple shiny plaques on the face, the tip of the nose
and the ends of fingers and ears.
Eye involvement in sarcoidosis is a common presenting symptom, particularly in women
The most common type of ophthalmic involvement in sarcoidosis is an acute uveitis.
This is often transient and mild, and is particularly associated with erythema nodosum
and bilateral hilar lymph node enlargement.
It is probable that uveitis occurs in over a quarter of all cases of sarcoidosis,
but is subclinical in the majority.
More severe eye involvement occurs in chronic uveitis, which is persistent and
is more likely to lead to permanent impairment of vision. It is usually associated with more
severe sarcoidosis, e.g. with extensive pulmonary infiltration and fibrosis,
or with cutaneous lupus pernio.
Involvement of the central and peripheral nervous system in sarcoidosis is important
and often underdiagnosed
Neurological involvement occurs in at least 10% of patients with sarcoidosis,
and is particularly common in patients with diffuse pulmonary infiltration and eye lesions.
Sarcoid granulomas that are developing and proliferating in the nervous system can produce
a wide range of clinical effects, which are dependent on their location;
some of the more common are:
Chronic meningitis with cerebrospinal fluid abnormalities and non-caseating granulomas in the meninges.
Cranial nerve lesions, often as a result of chronic sarcoid meningeal inflammation at the base of the brain.
Space-occupying lesions in the cerebral hemispheres, pituitary or hypothalamus.
'Mononeuritis multiplex', due to the involvement of many peripheral nerves.
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