Sarcoidosis: causes, symptoms, diagnosis, treatment

Sarcoidosis (synonyms: Benjet-Beck-Shauman disease, benign sarcoidosis, Beck's disease) is a systemic disease of unknown etiology that affects a variety of organs and tissues, the pathomorphological basis of which is epithelioid-cell granuloma without evidence of caseous necrosis.

The disease of sarcoidosis was first described by the Norwegian dermatologist Bek (1899).

[1], [2], [3], [4]

What causes sarcoidosis?

The causes and pathogenesis of sarcoidosis have not been elucidated. For several decades, the theory of tuberculous origin of sarcoidosis dominated, ie, they believed that sarcoidosis is a special form of tuberculosis infection. In the development of the disease, the role of genetic factors is important, as indicated by the greater concordance of monozygotic twins for this disease in comparison with dizygotic, the association of sarcoidosis with some tissue antigen antigens (for example, HLA-B8, DR3), racial differences in incidence is not the same in populations.

The presence of family cases, the defeat of mono- and heterozygous twins confirms the genetic predisposition to granulomatous inflammation. Some authors believe that imbalance in the immunity system plays an important role in the development of sarcoidosis.

Summarizing all the views on the etiology and pathogenesis of sarcoidosis, it can be concluded that it is a poly-emotional syndrome.

Histopathology of sarcoidosis

With all forms of sarcoidosis, the same type of changes are noted. In the middle and deep sections of the dermis are found granulomas, consisting of epithelioid histiocytes with an admixture of lymphocytes, single giant cells such as Langhans or foreign bodies. In contrast to tuberculosis, cheesy necrosis, as a rule, is absent. At the resolution stage, replacement of granulomatous islets with a connective tissue is noted.

Pathomorphology of sarcoidosis

Typically the presence of numerous monotypically constructed sharply limited granulomas, consisting mainly of histiocytic elements. Necrosis is not typical. In the center of individual granules, one can see giant cells of the Pirogov-Langhans type, and cells of foreign bodies are also found. In the cytoplasm of these cells, crystalloid inclusions and Shaumann asteroids are often found, which, however, are not specific for sarcoidosis. The peripheral rim of the lymphoid elements in this stage is small or completely absent. Characteristic for these granulomas is the presence around them of concentrically arranged collagen fibers stained with picrofuxine in red and giving a weak Schick-positive reaction. Impregnation with silver nitrate according to Fug's method reveals reticulin fibers both around the granuloma and inside it. In the stage of fibrotic changes, granuloma cells are replaced by fibroblastic elements, the reticulin fibers are converted into collagen ones.

With the Beka-Shaumann sarcoid epithedioid islets are localized in the upper third of the dermis, closer to the epidermis, with the Darje-Russi sarcoid - mainly in the subcutaneous fat layer. Lumbar lupus differs from the Bek-Shaumann sarcoma only by the presence of sharply dilated capillaries in the upper part of the dermis. In erythrodermic form, the infiltrate consists of small foci of epithelioid cells and a certain number of histiocytes and lymphocytes located around the surface capillaries.

Sarcoidosis must be differentiated from tuberculous lupus, in which also the tubercles of the epithelioid structure are also observed. If granulomas of caseosis and a significant number of lymphoid elements are present, it is very difficult to distinguish sarcoidosis from tuberculosis. However, with tuberculosis, the granulomatous infiltrate closely adjoins the epidermis, often destroying it, that as with sarcoidosis, the infiltrate is separated from the epidermis by a strip of unaltered collagen. With sarcoidosis in granulomas, as a rule, very few lymphoid cells, there is no or very weakly expressed necrosis, the epidermis is normal thickness or atrophic. With tuberculosis same lupus often acanthosis, sometimes ulceration with pseudoepithelioma hyperplasia. Bacteriological research is of great importance. It is difficult to differentiate sarcoidosis from tuberculoid type leprosy, since mycobacteria leprosy with this peak are detected only in 7% of cases. However, granulomas in leprosy are located mainly around and along the skin nerves. As a result of which they are irregular in shape, necrosis is often seen in their center.

Histogenesis is not clear. Currently, sarcoidosis is considered as a polyethological disease, mainly immunopathological genesis. There is a decrease in the number of T-lymphocytes, an imbalance in their main populations; reduced response of T cells to mitogens; weakened delayed-type hypersensitivity reactions; an increase in the number and hyperactivation of B-lymphocytes with nonspecific polyclonal hypergammaglobulinemia, an increased level of circulating antibodies, especially in the presence of erythema nodosum. In the stage of granuloma formation, T-helpers predominate in them with a relative increase in the number of circulating T suppressors.

In the development of sarcoid granuloma skin KA. Makarov and N.A. Shapiro (1973) distinguishes three stages: hyperplastic, granulomatous and the stage of fibrous-hyaline changes. In the hyperplastic stage proliferation of cells of the mononuclear-macrophage system is observed, among which then appear epithelioid elements. Forming granulomas, as a rule, are still indistinct opranichey. Multinucleate cells are usually absent in this stage of the process. It is believed that the hyperplastic and granulomatous stages are an expression of the increase in the intensity of cellular immunity, and fibrotic-hyaline changes are a morphological sign of the onset of the phase of immunological exhaustion. An electron microscopic study showed that round cells located on the periphery of the granuloma, considered to be lymphocytes, have lysosomes in which acidic phosphatase and other lysosomal enzymes are present. They are monocytes of blood, from which epithelioid cells are then formed. There is no evidence of the presence of bacterial fragments in epithelioid cells, although they contain electron-dense and electron-bright lysosomes, several autophagic vacuoles, and a complex of residual bodies. Giant cells are formed from epithelioid, Shaumann's Taurus are formed from residual gels of lysosomes. Asteroid bodies consist of clumps of collagen, having a typical (from 64 to 70 them) periodicity. This is due to the fact that the collagen is between the epithelioid cells at the time of the formation of giant ktst of them. Immunomorphological examination in some cases shows the deposition of IgM in the zone of the dermo-epidermal boundary and in the walls of the vessels, as well as IgG in the granulomas themselves and in the surrounding dermis.

Symptoms of sarcoidosis

Skin lesion is observed in less than 50% of patients, it can be polymorphous (such as erythema nodosum, spotted erythematous foci), but more often there are various tuberous elements, the origin of which is the basis for isolating such clinical variants as Beck's cutaneous sarcoid, Broca's angiolyupoid -Potrius, refreshed lupus Bénie-Tennesona, subcutaneous sarcoids Daria-Russi. The Beck sarcoid can manifest itself in the form of small-tubercle, including lichenoid, coarse-grained and diffusive-plaque eruptions. In rare cases, the process can occupy the entire skin (erythrodermic form of sarcoidosis). The color of tubercles is characteristic: cyanotic, yellowish-brown, with yellowish-brown specks appear during a diascopy. With refreshed lupus Bienier-Tenneson, changes are observed mainly on the skin of the nose and adjacent areas of the cheeks in the form of diffuse-plaque foci of cyanotic red color; with subcutaneous sarcoid Darje-Rousi find hypodermal nodes, the skin over which becomes pinkish-cyanotic. There are rare (atypical) variants of sarcoidosis: erythematous (spotted), erythrodermic, lichenoid (clinically similar to red planar lichen), prurigopodobny, verruko-papillomatous, ring-shaped, figured (zircinarny), erosive-ulcerative. Ulcerative-gangrenous, papulonecritic, scleroderm-like, posttraumatic (cicatricial), elephantiatic, clinically similar to tuberculoid leprosy, lupoid necrobiosis, erythematous squamous (ichthyoso- and psoriasis-like), atrophic, angiomatous, etc., which can resemble a wide variety of dermatoses in including such peculiar in clinical manifestations, as eczema.

Sarcoidosis is more common in women and is manifested by a large clinical polymorphism. Skin rashes can be nonspecific or specific. The latter are found in the histological examination of the affected skin.

Depending on the manifestation of dermatosis, there are typical (small-node, large-node, diffuse-infilpyrtive, nodular sarcoid, refractory lupus Bienier-Tenesson) and atypical forms of sarcoidosis.

The small-scaled form is found most often and is characterized by the precipitation of numerous pink-red spots, which eventually turn into nodules of a dense elastic consistence of brownish-cyanotic color, from pinhead to pea, hemispherical, with clear boundaries and smooth surface, rising above the surrounding skin. Elements are often localized on the face and upper limbs. With a diascopy, tiny yellowish-brownish spots appear ("dust particles," or the phenomenon of dustiness). With regression on the site of the nodules, there remain hyperpigmentation or superficial atrophy, telangiectasia.

Large-node form of sarcoidosis manifests itself as single or multiple, sharply delimited and distinctly protruding above the level of the surrounding skin with hemispherical flat knots of violet-brown or cyanotic-brownish color, ranging in size from 10 to 20-penny coins and more. Elements have a dense consistency, a smooth surface, sometimes covered with telangiectasia, large nodes may ulcerate. At a diascopy the phenomenon of dust is observed.

The diffuse-infiltrative sarcoid is more often localized on the face, rarely on the neck, the scalp and is manifested by the development of plaques of a dense consistence of brownish or brownish-blue color, with a smooth surface, not clearly delineated and slightly protruding above the skin level. The surface can be covered with a network of capillaries. With a diascopy, a yellowish-brown color is found (a symptom of a "speck of dust").

Angioleukoid Broca-Potry usually develops on the nose, cheeks and, exceptionally rarely, on other parts of the body. At the beginning of the disease, there are round, painless spots the size of beans or coins, of medium size, red or violet-red. Gradually they are transformed into slightly protruding plaques of rounded shape with distinct boundaries, acquiring a brown or rusty hue, with a smooth surface. Rarely palpation, one can feel an easy compaction of the spot, and with diascopy see brownish points (a symptom of "apple jelly"). Sometimes telangiectasias are seen on the surface of the elements. Plaques persist for a long time.

Biliary-Tenneson's lupus erythematosus. On the skin of the cheeks, nose, chin, back surface of the fingers and forehead there are small erythema-tosic infiltrated lesions. As a result of the growth and fusion of elements, purple-red knots or plaques with rather distinct boundaries are formed. Extended openings of the sebaceous glands and hair follicles are observed. The process deteriorates during the cold season. In some patients, lesions of the lungs, bones, joints, enlarged lymph nodes are detected. At a diascopy yellow spots-specks come to light.

Nodular sarcoid (subcutaneous sarcoid of Derye-Russi) is clinically characterized by the formation on the skin of the trunk, thighs and lower abdomen of subcutaneous nodules measuring from 1 to 3 cm in diameter. As a rule, they are few, painless, mobile at palpation and when merged form plaque infiltrates of large size, resembling an orange peel. The skin above the nodes has a normal or slightly cyanotic color, covering the foci, a dull pink.

Atypical forms of sarcoidosis. In clinical practice, there are several atypical forms: ulcerative, spotty-papular, psoriasis, ichthyosiformes, scleroderm-like, scofulo-dermic, paiillomatous, angiomatous, similar to basal cell, lupus erythematosus, etc.

In patients with sarcoidosis, various organs and systems are affected. In connection with this, patients are advised to make a radiograph and tomography of the chest, bone and ophthalmological examination.

Of nonspecific lesions of the skin in sarcoidosis, nodosum erythema is noted, clinically manifested as dense pink-red nodes, localized most often on the anterior surface of the shin. In this case, patients have high fever, bone pain, uveitis, increased ESR, bilateral, basal lymphadenopathy.

Differential diagnosis

Differentiate the disease with tuberculous lupus, skin reticulum, eosinophilic granuloma of the face, red planar lichen, tuberculous leishmaniasis of the skin.

[5], [6], [7]

Treatment of sarcoidosis

Recommended monotherapy or combined treatment with the following means: corticosteroid drugs (prednisolone 30-40 mg per day for several months), antimalarial drugs (delagil, resichin), cytostatics (prospidin, cyclophosphamide). A good effect is observed when using cyclosporine A, thalidomide, etc. In the case of the appearance of acute nonspecific lesion, no specific treatment is performed, as in most cases spontaneous cure occurs. It is advisable to refer patients to resorts with mineral springs.