Amyloidosis of the skin

Amyloidosis of the skin is a metabolic disorder in which the amyloid deposits in the skin.

Studies have shown that amyloid is a protein glycoprotein. The deposition of this protein leads to disruption of the vital activity of tissues and organs.

[1], [2], [3]

Causes and pathogenesis of skin amyloidosis

The causes and pathogenesis of amyloidosis are not fully understood. According to some authors, the underlying cause of the disease is a mutation that leads to the formation of a clone of cells of mesenchymal origin - amyloidoblast, synthesizing fibrillar protein amyloid.

Amyloidosis is mesenchymal dysproteinosis, accompanied by the appearance in the tissues of an abnormal fibrillar protein with the formation of a complex substance in the interstitial tissue - amyloid.

VV Serov and GN Tikhonov (1976), L.N. Kapinus (1978) showed that the amyloid substance is a glucoprotein, the main component of which is the fibrillar protein (F-component). Electron microscopy revealed that amyloid fibrils have a diameter of 7.5 nm and a length of 800 nm, devoid of transverse striation. Fibrillar protein is synthesized by mesenchymal cells - amyloidoblast (fibroblasts, reticular cells). In tissue, it combines with proteins and polysaccharides of the blood plasma, which are its second mandatory component (P-component), in the electron microscope it looks like rod-shaped structures 10 nm in diameter and 400 nm in length, consisting of pentagonal formations. Amyloid fibrils and the plasma component enter into connections with glycosaminoglycans of the tissue, and fibrin and immune complexes join the resulting complex. Fibrillar and plasma components have antigenic properties. GG Glenner (1972) believes that the amyloid can arise from monoclonal light chains and immunoglobulins that are part of amyloid fibrils, regardless of the clinical classification of amyloid in both primary and secondary amyloidosis. G. Husby et al. (1974), along with this describe the occurrence of amyloid masses from a non-immunoglobulin-protein (amyloid A). Both types of amyloid, as a rule, occur together.

Morphogenesis of amyloidosis, according to V.V. Serov and GN. Tikhonova (1976), V.V. Serov and I.A. Shamova (1977), consists of the following links:

1. transformation of elements of the macrophage-histiocyte system with the appearance of a clone of cells capable of synthesizing the fibrillar component of amyloid;
2. synthesis of fibrillar protein by these cells;
3. aggregation of fibrils with the formation of the "skeleton" of the amyloid substance and
4. compounds of the fibrillar component with proteins and plasma glucoproteins, as well as glycosaminoglycan tissues.

The formation of amyloid occurs outside the cells in close connection with fibers of connective tissue (reticulin and collagen), which gives grounds to distinguish two types of amyloid - perioretiklarnogo and pericollagen. Perioreticular amyloidosis occurs mainly in lesions of the spleen, liver and kidneys, adrenal glands, intestines, intimal vessels, and pericollagen is characteristic of amyloidosis of the adventitia of vessels, myocardium, striated and smooth muscle tissue, nerves and skin.

Amyloid masses when stained with hematoxylin and eosin are dyed in pale pink, according to Van Gyzon's method, yellow. Specific color - Congo red color it red. A special method for detecting amyloid is also reactions with thioflavin T followed by immunofluorescence microscopy.

Depending on the causative factor, according to the classification of V.V. Serov and I.A. Shamova (1977). Amyloidosis is divided into the following forms: idiopathic (primary), hereditary, acquired (secondary), senile, local (tumor).

The skin is most often affected by primary localized, then by primary systemic amyloidosis. In family forms of amyloidosis, skin changes are less frequent than in systemic forms. Skin changes with systemic amyloid are polymorphic. Hemorrhagic eruptions are more common, but more characteristic are asymptomatic, yellowish nodular-nodular elements, located mainly on the face, neck, chest, and also in the oral cavity, often accompanied by macroglossia. There may be spotted, scleroderm-like, plaque foci, changes. Similar to kaantomatous and myxedematous lesions, in rare cases - bullous reactions, alopecia. Secondary systemic amyloid occurs, as a rule, without skin changes. Secondary local amyloidosis of the skin develops against a background of a variety of skin diseases, mainly in the foci of red flat lichen and neurodermatitis.

[4], [5], [6], [7], [8]

Pathomorphology of skin amyloidosis

With localized papular amyloidosis in the lesions, amyloid masses are detected, usually in the papillate layer of the dermis. In the new lesions, small aggregates are observed in the reduced papillae of the skin or directly under the epidermis. These deposits are often localized perikapillyarno, and around them are located a number of reticulin fibers, a moderate number of fibroblasts, in some cases - chronic inflammatory infiltrates.

In large amyloid masses, melanin-suppressed macrophages, fibroblasts, histiocytes, and sometimes lymphocytes are seen. Occasionally, thick deposits of amyloid can be observed in the thickened epidermis. Appendages of the skin are mostly intact.

The histogenesis of amyloid lichen has not been fully elucidated. There is evidence of epidermal origin of amyloid due to focal damage to epithelial cells, converting them into fibrillar masses, and then into amyloid. The participation of keratin in the formation of amyloid is indicated by the reaction of amyloid fibrils with antibodies against human keratin, the presence of disulfide bonds in the amyloid, and also the indirectly positive effect of the use of derivatives of retinoic acid.

Primary spotted cutaneous amyloidosis

Primary spotted cutaneous amyloidosis is characterized by the appearance of significantly itchy spots 2-3 cm in diameter, brown or brown, which are localized on the trunk, but most often in the upper part of the back, the interblade area. The case of the appearance of pigment amyloidosis around the eyes is described. Spots are prone to fusion and form hyperpigmented areas. Mesh hyperpigmentation is a characteristic feature of spotted amyloidosis. Simultaneously with hyperpigmentation, hypopigmented foci may occur, which resembles poikilodermia. Patients complain of itching of varying intensity. In 18% of cases, itching may be absent. Simultaneously with spotted rashes appear small nodules (nodular amyloidosis).

In pathomorphological research, amyloid is found in the papillary layer of the dermis. The development of spotted-papular amyloidosis in a patient with Epstein Barr virus is described. After treatment with acyclovir and interferon, patchy-papular rashes were significantly observed, which confirms the role of viruses in the deposition of amyloid in tissues. The spotted form of amyloidosis occurs in adults, men and women suffer the same. The disease is often found in Asia and the Middle East, rarely in Europe and North America.

Nodular-plaque form of skin amyloidosis

Knot-plaque form is a rare variant of primary cutaneous amyloidosis. Mostly sick women. Single or multiple nodules and plaques are more often localized on the lower legs, sometimes on the trunk and extremities. On the front surface of both shins, numerous, as large as a pinhead to a pea, are spherical, shiny nodules that closely adjoin each other but do not merge, and are separated by narrow furrows of healthy skin. Some lesions have the character of warty formations with horny stratifications and scales on the surface. Rashes are accompanied by a painful itch, visualized the foci of scratching and lichenification of the skin. In most patients, the level of a- and y-globulins in serum is elevated. Combinations of nodular-plaque amyloidosis with diabetes, Sjogren's syndrome and the transition of this form of amyloidosis to the systemic with the involvement of internal organs in the pathological process are described.

Detect significant deposition of amyloid in the dermis, subcutaneous fat layer, in the walls of blood vessels, the basement membrane of the sweat glands and around the fat cells. Amyloid masses can be found among the cells of a chronic inflammatory infiltrate, in which plasmocytes are detected, as well as giant cells of foreign bodies. In biochemical analysis, peptides with a molecular weight of 29,000 have been found in amyloid fibrils; 20 000 and 17 000. Immunoblotting revealed the staining of a peptide with a molecular weight of 29 000 antibodies to the a chain of immunoglobulin. There are data on a combination of deposits of light χ- and λ-chains of immunoglobulins. These materials indicate the immunoglobulin nature of amyloid in this form of amyloidosis. It is assumed that in the centers there is an accumulation of plasma cells secreting the L-chains of immunoglobulins that are phagocytosed by macrophages and converted to amyloid fibrils. As with nolular amyloidosis, amyloidosis requires amyloidosis to be excluded from bullous amyloidosis. A peculiar form of bullous amyloidosis was described by T. Ruzieka et al. (1985) Clinically, it resembles atypical herpetiform dermatitis due to itching erythema urticaria and bullous rash, spotty hyper- and depigmentation. There are also foci of lichenification and ichthyosiform hyperkeratosis. In a histological study, amyloid deposition is found in the upper layers of the dermis. According to electron microscopy, the blisters are located in the region of the light plate of the basal membrane. Immunohistochemical studies using antisera against various proteins of amyloid fibrils and monoclonal antibodies against IgA gave a negative result.

Secondary systemic amyloidosis

Secondary systemic amyloidosis in the skin can develop mainly with various chronic suppuration in patients with myeloma and plasmacytoma. Clinical changes on the skin are rare, but histologically when the color of the alkaline Congo red it can reveal amyloid masses, which in the polarization microscope look green. In these cases, they can be seen around the sweat glands, sometimes around the sacs of hair and fat cells.

Secondary localized amyloidosis

Secondary localized amyloidosis can develop against a background of a variety of chronic dermatoses, such as red lichen planus, neurodermatitis, as well as some skin tumors: seborrheic wart, Bowen's disease and basal cell disease. With spotty amyloidosis, amyloid lichen, in the circumference of the kerat or epithelium, with chronic eczema, so-called amyloid bodies (amyloid clumps, amyloid bunches) are often observed. They are more often localized in the papillate layer of the dermis, while being located in the form of large groups. Sometimes the individual papillae are completely filled with homogeneous masses, but they can also be observed in the deeper parts of the dermis more often in the form of clots. They are eosinophilic, Schick-positive, specifically stained Congo red, in a polarizing microscope of a yellowish green color, fluoresce with thioflavin T and give an immune response with specific antisera. Amyloid bodies are often surrounded by numerous connective tissue cells, the processes of which are associated with them, and some authors believe that these masses are produced by fibroblasts.

Family (hereditary) amyloidosis

Family (hereditary) amyloidosis is described with both familial and localized cutaneous amyloidosis. A family is described, the affected members of which had hyperpigmentation and severe itching. It is believed that the disease is inherited by an autosomal dominant pathway. Primary! Cutaneous amyloidosis was found in identical twins, which in addition to amyloidosis suffered various congenital anomalies. In the literature, cases of combination of cutaneous amyloidosis with congenital pachyonichia, congenital dyskeratosis, palmar-plantar keratoderma, multiple endocrine dysplasia, etc. Have been described.

[9], [10], [11], [12], [13], [14]

Histopathology

When the pathomorphological study reveals the diffuse deposition of amyloid in the skin and subcutaneous fat in the walls of the vessels, the membranes of the sweat glands and fat cells.

Symptoms of amyloidosis of the skin

At present, amyloidosis is classified into the following forms:

1. Systemic amyloidosis
   • primary (myeloma-associated) systemic amyloidosis
   • secondary systemic amyloidosis
2. Cutaneous amyloidosis
   • primary cutaneous amyloidosis
   • primary amyloidosis
   • mottled amyloidosis
   • nodular amyloidosis
   • knotty-plaque amyloidosis
   • secondary (tumor-associated) cutaneous amyloidosis
3. Family (hereditary) amyloidosis or a combination of amyloidosis with family syndromes.

Primary systemic amyloidosis

Primary systemic amyloidosis occurs without a previous disease. In this case, organs of mesenchymal origin are affected: tongue, heart, GIT and skin. Myelosolated amyloidosis is also included in the primary systemic amyloidosis. In primary systemic amyloidosis, skin rashes occur in 40% of cases, which are polymorphic and manifest as petechia, purple, nodules, plaques, nodes, tumors, poikiloderma, blisters, scleroderm-like changes. Elements tend to merge. The most common are purpura (in 15-20% of patients). Purples appear around the eyes .. On the limbs, in the mouth after trauma, overexertion, physical activity, vomiting, severe cough, as there is an increase in pressure in the vessels that are surrounded by amyloid.

Glossitis and macroglossia occur in 20% of cases, often are early symptoms of primary systemic amyloidosis and can lead to dysphagia. The tongue increases in size and becomes grooved, the impressions from the teeth are visible. Sometimes on the tongue there are papules or knots with hemorrhages. Bubble rashes are described, which are very rare. Bubbles with hemorrhagic contents appear in the places of the greatest traumatism (arms, legs) and are clinically very similar to blisters in congenital bullous epidermolysis and late cutaneous porphyria.

At a primary systemic amyloidosis also diffuse and focal alopecia are described, scleroderm-like and scleromixedemoid rashes.

Amyloid cystosis

A peculiar form of systemic amyloidosis is amyloidic zlastoz, clinically manifested by nodular-nodular eruptions, and histologically - amyloid deposition around the elastic fibers of the skin and subcutaneous tissue, serous membranes, the walls of the blood vessels of the muscular type. Previously, it was shown that the amyloid component of P, associated with microfibrils of normal elastic fibers, can participate in the deposition of amyloid fibrils.

With spotty amyloidosis, the skin shows slight deposits of amyloid in the papillae of the dermis. They can be detected, though not always, only by special staining. Amyloid masses with this variety of amyloidosis can be in the form of globules or homogeneous masses, located directly under the epidermis and partly in its basal cells. As a result, there may be incontinence of the pigment, which often occurs in the melanophages of the papillary layer of the dermis, which is usually accompanied by an inflammatory reaction. Clinically spotted amyloidosis is manifested by hyperpigmented spots of various sizes, mainly located on the skin of the back, or by mesh foci. Along with the spots, one can also detect nodular eruptions, similar to those observed with amyloid lichen. It was shown that in cases of spotted amyloidosis caused by contact with nylon, the main component of amyloid is the altered keratin.

[15], [16], [17], [18], [19], [20], [21], [22]

Secondary systemic amyloidosis

Secondary systemic amyloidosis develops in people with chronic diseases, such as tuberculosis, lepromatous leprosy, Hodgkin's disease, rheumatoid arthritis, Behcst disease, ulcerative colitis. In this case the parenchymal organs are affected, but the skin does not suffer.

Primary localized skin amyloidosis

The primary localized amyloidosis in the skin is most often manifested as papular amyloidosis. Less often - nodular-plaque, spotted and bullous.

Papular amyloidosis develops more often on the skin of the legs, but it can also occur in other places. There are family cases. The lesions are represented by itching dense hemispherical flat or conical papules closely adjacent to each other. Fusing, they form large plaques with a verruxial surface.

Differential diagnosis

Amyloidosis should be distinguished from myxedema lichen, red flat lichen, knotty prurigo.

[23], [24], [25]

Treatment of amyloidosis of the skin

With an easy flow of primary localized cutaneous amyloidosis, local local glucocorticosteroids are effective. In Ecuador, where there were many cases of primary cutaneous amyloidosis, a good effect was observed from topical application of 10% dimethylsulfoxide (DMSO). With a nodular form, retinitis is effective enough, however, after discontinuation of the drug, the disease often recurs. Cyclophosphamide (50 mg per day) significantly reduces itching and resolves papules with nodular form of cutaneous amyloidosis.

Some authors recommend the treatment of amyloidosis of the skin with resorchin (delagil), for a long time, 0.5 g per day, laser therapy, 5% -unithiolomium - intramuscularly.