Sarcoidosis: causes, symptoms, diagnosis, treatment

Sarcoidosis (synonyms: Benier-Beck-Schaumann disease, benign sarcoidosis, Beck's disease) is a systemic disease of unknown etiology that affects a wide variety of organs and tissues, the pathomorphological basis of which is an epithelial cell granuloma without signs of caseous necrosis.

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

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What causes sarcoidosis?

The causes and pathogenesis of sarcoidosis are not clear. For several decades, the theory of tuberculous origin of sarcoidosis was dominant, i.e., it was believed that sarcoidosis is a special form of tuberculous infection. Genetic factors play an important role in the development of the disease, as indicated by the higher concordance of monozygotic twins for this disease compared to dizygotic ones, the unequal association of sarcoidosis with some tissue compatibility antigens (e.g., HLA-B8, DR3) in populations, and racial differences in morbidity.

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

Summarizing all views on the etiology and pathogenesis of sarcoidosis, we can come to the conclusion that it is a polyetiological syndrome.

Histopathology of sarcoidosis

All forms of sarcoidosis show similar changes. In the middle and deep parts of the dermis, granulomas are found consisting of epithelioid histiocytes with an admixture of lymphocytes, single giant cells of the Langhans type, or foreign bodies. Unlike tuberculosis, caseous necrosis is usually absent. In the resolution stage, granulomatous islets are replaced by connective tissue.

Pathomorphology of sarcoidosis

Typically, there are numerous uniformly constructed, sharply delimited granulomas consisting mainly of histiocytic elements. Necrosis is not characteristic. In the center of individual granulomas, giant cells of the Pirogov-Langhans type can be seen; foreign body cells are also encountered. Crystalloid inclusions and Schaumann asteroid bodies are often found in the cytoplasm of these cells; however, they are not specific for sarcoidosis. The peripheral rim of lymphoid elements at this stage is small or completely absent. Typical for these granulomas is the presence of concentrically located collagen fibers around them, which are stained red with picrofuchsin and give a weak PAS-positive reaction. Impregnation with silver nitrate using the Fuga method reveals reticulin fibers both around the granuloma and inside it. At the stage of fibrous changes, the granuloma cells become mixed with fibroblastic elements, and the reticulin fibers turn into collagen fibers.

In Beck-Schaumann sarcoidosis, epithelioid islets are localized in the upper third of the dermis, closer to the epidermis, while in Darier-Roussy sarcoidosis, they are mainly located in the subcutaneous fat layer. Lupus pernio differs from Beck-Schaumann sarcoidosis only by the presence of sharply dilated capillaries in the upper part of the dermis. In the erythrodermic form, the infiltrate consists of small foci of epithelioid cells and a certain number of histiocytes and lymphocytes located around the superficial capillaries.

Sarcoidosis should be differentiated from tuberculous lupus, which also has tubercles of epithelioid structure. In the presence of caseous granulomas and a significant number of lymphoid elements, it is very difficult to distinguish sarcoidosis from tuberculosis. However, in tuberculosis, the granulomatous infiltrate closely adheres to the epidermis, often destroying it, while in sarcoidosis, the infiltrate is separated from the epidermis by a strip of unchanged collagen. In sarcoidosis, granulomas usually have very few lymphoid cells, necrosis is absent or very weakly expressed, the epidermis is of normal thickness or atrophic. In tuberculous lupus, acanthosis is often noted, sometimes ulceration with pseudo-epitheliomatous hyperplasia. Bacteriological examination is of great importance. It is difficult to differentiate sarcoidosis from the tuberculoid type of leprosy, since mycobacteria of leprosy are detected in only 7% of cases. However, granulomas in leprosy are located mainly around and along the skin nerves. As a result, they have an irregular shape, and necrosis is often visible in their center.

Histogenesis is unclear. Currently, sarcoidosis is considered a polyetiological disease, mainly of immunopathological genesis. There is a decrease in the number of T-lymphocytes, an imbalance in their main populations; a reduced response of T-cells to mitogens; weakened reactions of delayed-type hypersensitivity; 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. At the stage of granuloma formation, T-helpers dominate in them with a relative increase in the number of circulating T-suppressors.

In the development of sarcoid granuloma of the skin, K.A. Makarova and N.A. Shapiro (1973) distinguish three stages: hyperplastic, granulomatous, and the stage of fibrous-hyalinous changes. In the hyperplastic stage, proliferation of cells of the mononuclear-macrophage system is observed, among which epithelioid elements then appear. The forming granulomas, as a rule, are still not clearly defined. Multinuclear cells are usually absent at this stage of the process. It is believed that the hyperplastic and granulomatous stages are an expression of increasing tension of cellular immunity, and fibrous-hyalinous changes are a morphological sign of the onset of the phase of immunological exhaustion. Electron microscopic examination showed that round cells located on the periphery of the granuloma, considered lymphocytes, have lysosomes, which contain acid phosphatase and other lysosomal enzymes. They are blood monocytes that later form epithelioid cells. There is no evidence of bacterial fragments in epithelioid cells, although they contain electron-dense and electron-light lysosomes, several autophagic vacuoles and a complex of residual bodies. Giant cells are formed from epithelioid cells, Schaumann bodies are formed from residual lysosome gels. Asteroid bodies consist of collagen lumps with a typical (64 to 70 nm) periodicity. This is due to the fact that collagen appears between epithelioid cells at the time of formation of giant corpuscles from them. Immunomorphological examination in some cases showed the deposition of IgM in the zone of the dermal-epidermal border and in the walls of blood vessels, as well as IgG in the granulomas themselves and in the surrounding dermis.

Symptoms of sarcoidosis

Less than 50% of patients have skin lesions, they can be polymorphic (like erythema nodosum, spotted-erythematous lesions), but more often there are tuberculous elements of various sizes, the peculiarity of which is the basis for distinguishing such clinical variants as Beck's cutaneous sarcoid, Broca-Pautrier's angiolupoid, Besnier-Tennesson's lupus erythematosus, and Darier-Roussy's subcutaneous sarcoids. Beck's sarcoid can manifest itself in the form of small-tuberculous, including lichenoid, large-nodular and diffuse-plaque rashes. In rare cases, the process can occupy the entire skin (erythrodermic form of sarcoidosis). The color of the tubercles is characteristic: cyanotic, yellowish-brown, with diascopy yellowish-brown spots appear. In case of lupus erythematosus with chills of Besnier-Tennessee, changes are observed mainly on the skin of the nose and adjacent areas of the cheeks in the form of diffuse-plaque foci of a bluish-red color; in case of subcutaneous sarcoidosis of Darier-Ruesi, hypodermal nodes are found, the skin above which becomes pinkish-bluish. Rare (atypical) variants of sarcoidosis are encountered: erythematous (spotted), erythrodermic, lichenoid (clinically similar to lichen planus), prurigo-like, warty-papillomatous, annular, figured (circinate), erosive-ulcerative. ulcerative-gangrenous, papulonecritical, scleroderma-like, post-traumatic (scarring), elephantiatic, clinically similar to the tuberculoid form of leprosy, lupoid necrobiosis, erythematous-squamous (ichthyosis- and psoriasis-like), atrophic, angiomatous, etc., which can resemble a wide variety of dermatoses, including such unique clinical manifestations as eczema.

Sarcoidosis is more common in women and is characterized by greater clinical polymorphism. Skin rashes may be nonspecific or specific. The latter are detected by histological examination of the affected skin.

Depending on the manifestation of the dermatosis, typical (small-nodular, large-nodular, diffuse-infiltrative, nodular sarcoid, chill lupus of Besnier-Tenesson) and atypical forms of sarcoidosis are distinguished.

The small-nodular form is the most common and is characterized by a rash of numerous pink-red spots, which over time turn into nodules of a dense elastic consistency of a brownish-bluish color, from a pinhead to a pea in size, hemispherical in shape, with clear boundaries and a smooth surface, rising above the surrounding skin. The elements are often localized on the face and upper limbs. Diascopy reveals tiny yellowish-brownish spots ("specks" or dust phenomenon). With regression, hyperpigmentation or superficial atrophy, telangiectasia remain in place of the nodules.

The macronodular form of sarcoidosis manifests itself as single or multiple, sharply delimited and clearly protruding above the level of the surrounding skin, hemispherical flat nodes of a violet-brown or bluish-brown color, the size of a 10- to 20-kopeck coin or more. The elements have a dense consistency, a smooth surface, are sometimes covered with telangiectasias, large nodes can ulcerate. During diascopy, a dusty phenomenon is observed.

Diffuse-infiltrative sarcoid is most often localized on the face, rarely on the neck, scalp and is manifested by the development of plaques of a dense consistency, brownish or brownish-blue in color, with a smooth surface, not sharply delimited and slightly protruding above the skin level. The surface may be covered with a network of capillaries. Diascopy reveals a yellowish-brown color (the "speck" symptom).

Broca-Pottier angiolupoids usually develop on the nose, cheeks and, very rarely, on other parts of the body. At the onset of the disease, round, painless spots the size of a bean or a coin, medium in size, red or purple-red in color appear. Gradually, they transform into slightly protruding, rounded plaques with clear boundaries, acquiring a brown or rusty tint, with a smooth surface. Rarely, a slight compaction of the spot can be felt by palpation, and brownish dots can be seen during diascopy (the "apple jelly" symptom). Sometimes telangiectasias are visible on the surface of the elements. The plaques persist for a long time.

Lupus erythematosus besnier-Tenneson. Small erythematous infiltrated lesions appear on the skin of the cheeks, nose, chin, back of the fingers and forehead. As a result of the growth and fusion of elements, purple-red nodes or plaques are formed, which have fairly clear boundaries. Enlarged openings of the sebaceous glands and hair follicles are observed. The process worsens in the cold season. Some patients have lesions of the lungs, bones, joints, and enlarged lymph nodes. Yellowish dots-spots are revealed during diascopy.

Nodular sarcoid (subcutaneous sarcoid of Derrieu-Roussy) is clinically characterized by the formation of subcutaneous nodes on the skin of the trunk, thighs and lower abdomen, measuring from 1 to 3 cm in diameter. They are usually few in number, painless, mobile on palpation and when merging form large plaque infiltrates, resembling an orange peel. The skin over the nodes has a normal or slightly bluish color, while the skin covering the lesions is dull pink.

Atypical forms of sarcoidosis. Several atypical forms are encountered in clinical practice: ulcerative, maculopapular, psoriasiform, ichthyosiform, scleroderma-like, scofuloderma-like, paillomatous, angiomatous, similar to basalioma, lupus erythematosus, etc.

Patients with sarcoidosis experience damage to various organs and systems. In this regard, patients are recommended to undergo chest X-rays and tomography, bones, and an ophthalmological examination.

Among non-specific skin lesions in sarcoidosis, nodular erythema is noted, clinically manifested in the form of dense pink-red nodes, localized most often on the anterior surface of the shin. In this case, patients have high temperature, bone pain, uveitis, increased ESR, bilateral, hilar lymphadenopathy.

Differential diagnosis

The disease should be differentiated from tuberculous lupus, reticulosis of the skin, eosinophilic granuloma of the face, lichen planus, and tuberculous leishmaniasis of the skin.

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Treatment of sarcoidosis

Monotherapy or combination therapy with the following agents is recommended: corticosteroids (prednisolone 30-40 mg per day for several months), antimalarial drugs (delagyl, resoquin), cytostatics (prospidin, cyclophosphamide). A good effect is observed with the use of cyclosporine A, thalidomide, etc. In the case of acute non-specific lesions, specific treatment is not carried out, since spontaneous recovery occurs in most cases. It is advisable to send patients to resorts with mineral springs.