Cutaneous changes in leprosy

Leprosy (leprosy, Hansen's disease) is a chronic infectious disease caused by mycobacterium leprae. The causative agent is mycobacterium leprae. Not all people are equally susceptible to them. It is no coincidence that before the discovery of the causative agent, the main hypothesis for the development of the disease was hereditary. Men get sick more often. Blacks are more prone to leprosy, but the disease is milder for them. The disease is most common in India, Naples, and African countries. Most often, leprosy is contracted at the age of 10-20 years.

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Causes and pathogenesis of leprosy

The causative agent of the disease is the leprosy bacillus - mycobacterium leprae. It is straight or slightly curved, acid-resistant, 5 µm long, 0.5 µm thick. It does not grow in a nutrient medium or in cell culture. The main reservoir is a person, in addition, there may be some wild animals: armadillos, a number of monkeys, chimpanzees.

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Histogenesis of leprosy

In the development of the disease, great importance is attached to the violation of the state of cellular immunity and non-specific defense factors against the background of pronounced hypersensitivity to mycobacteria of leprosy, detected using the lepromin test. The presence of genetic predisposition to susceptibility (resistance) to the disease is evidenced by such data as a significantly higher concordance of monozygotic twins compared to dizygotic twins, interracial differences in the manifestations of leprosy, different susceptibility of relatives of patients with a similar probability of getting sick. An association of the disease with certain tissue compatibility antigens (mainly HLA-B8, DR2, HLA-BW21) has been found, which can affect the nature of the immune response and, accordingly, the features of the clinical picture. A defect in macrophages has been identified in patients with leprosy, resulting in their inability to convert mycobacterial antigens into immunogenic ones; an imbalance of immunoregulatory cells, which is different in different forms of the disease. In the lepromatous type of leprosy, a subpopulation of lymphocytes with a suppressor-cytotoxic function predominates, there may be a defect in T-helpers, and cell-mediated delayed-type hypersensitivity is practically not realized (the lepromin test is negative). Hyperactivity of B-cells and a high level of antibodies are detected, but without a protective role in relation to the leprosy mycobacterium. A.A. Yarilin (1999) draws attention to the dependence of the development of a particular form of leprosy on the pathway by which the formation of immunity will take place - humoral Th2-dependent (in lepromatosis) or Th1-dependent (in tuberculoid). In patients with tuberculoid leprosy, a subpopulation of T-helpers is predominantly detected, the lepromin test is positive, and antigens to the leprosy mycobacterium are not detected. In the mechanisms of damage to the peripheral nervous system, importance is attached to autoimmune reactions caused by the antigenic commonality of the leprosy mycobacterium and nervous tissue.

Symptoms of Leprosy

Only humans can get leprosy. In most cases, leprosy is contracted from a person with leprosy. Infection occurs through airborne droplets, through the mucous membrane of the upper respiratory tract, damaged skin, and possibly through the consumption of contaminated food and water. The incubation period is several years. Risk factors include:

• living in an endemic area;
• presence of sick relatives;
• contact with infected armadillos. Armadillos are used to cultivate the pathogen: they develop leprosy granulomas (lepromas).

The development of the disease depends on the state of specific cellular immunity. Leprosy pathogens multiply in peripheral nerves. In addition, they are found in many organs, where they remain for a long time in endothelial cells and phagocytes. Only 20% of infected people get sick, which is explained by the weakness of cellular immunity.

Currently, several clinical types of leprosy are distinguished: lepromatous, tuberculoid, indeterminate and dimorphic. The lepromatous type is the most severe and contagious type of leprosy, since there are a large number of pathogens in the lesions.

The disease is characterized by damage to the skin, mucous membranes, eyes, lymph nodes, peripheral nerve trunks, as well as the endocrine system and some internal organs, where granulomas and lepromatous infiltrates with a high content of lepra mycobacteria are formed.

Skin manifestations are located on the skin of the face, auricles, extensor surfaces of the limbs, buttocks, where erythematous, erythematous-pigmented spots of various shapes and sizes appear, without clear contours. Over time, the spots infiltrate, protruding above the skin surface, and increase in size. Tubercles and nodes (lepromas) also appear on the skin both in the infiltration zone and outside it, ranging in size from a few millimeters to 2 cm, of a dense elastic consistency, bluish-brown or reddish-rusty color. Diffuse infiltration and lepromas, located on the face (supraorbital arches, cheeks, nose, chin), disfigure the patient, giving his face the appearance of a lion's muzzle (facies leonina).

The eyebrow hair falls out, starting from the outer side. In the affected areas, the skin becomes tense, its pattern is smoothed out, the hair falls out. Then, specific bilateral and symmetrical damage to the peripheral nerves is noted, which leads to the disappearance of temperature, pain and tactile sensitivity. The ulnar, median, peroneal, large auricular nerves, and the upper branch of the facial nerve are often affected. In this case, the nerve trunks are thickened, dense, and smooth. Trophic and motor disorders gradually develop (lagophthalmos, paresis of the masticatory and facial muscles, amyotrophy, contractures, trophic ulcers).

Ulceration of leprosy is observed. Ulcers usually have steep, sometimes undermined infiltrated edges, they can merge, forming extensive ulcerative defects, slowly healing with an uneven scar. Simultaneously with skin changes, damage to the mucous membranes of the nose, larynx, and oral cavity is noted. Often the first signs of leprosy are difficulty in nasal breathing and nosebleeds. The mucous membrane of the nose is hyperemic, edematous, there are multiple small erosions on the surface (lepromatous rhinitis).

Over time, atrophy of the mucous membrane develops and individual lepromas and infiltrations appear, mainly in the cartilaginous part of the nasal septum. Lepromas of various shapes and sizes are pale pink in color and often ulcerate, which leads to deformation of the nasal septum, making nasal breathing difficult ("flat-depressed", "trunk-shaped", "lornette" nose, bulldog nose).

In severe cases, the mucous membranes of the lips, soft and hard palate, larynx, back of the tongue, etc. are affected.

Tuberculoid type

The tuberculoid type is characterized by lesions of the skin and peripheral nerves and is characterized by a benign course. In the lesions, pathogens are difficult to detect or, more often, are absent. This type is characterized by the appearance of a few erythematous spots of varying shape and size on the skin, as well as papular elements, which are the main manifestation of the disease. They are often located on the face, neck, flexor surfaces of the limbs, back, buttocks. The nodules are usually small, flat, reddish-bluish, polygonal, tend to merge into plaques with a sharply defined ridge-shaped raised rounded or polycyclic edge and to peripheral growth. Over time, atrophy, hypopigmentation, peeling are noted in the central part of the plaques, andan erythematous border of a few millimeters to 2-3 cm or more in width is preserved at the edge - a figured tuberculoid. The elements leave behind hypopigmentation or atrophy. With this type, damage to the peripheral nerve trunks is detected very early, sometimes before skin manifestations.

The ulnar, radial and peroneal nerves are most often affected, which manifests itself in their diffuse or bead-like thickening and soreness. This gradually leads to the development of paresis, paralysis, contractures of the fingers, atrophy of small muscles, skin, nails, mutilation of the hands and feet ("seal paw", "drooping hand", "monkey paw", "falling foot", etc.). There is a violation of temperature, pain and tactile sensitivity. Tendon reflexes are reduced. In the affected areas, sebum and sweating are impaired, vellus hair is absent.

Pathomorphology

Typical tuberculoid granulomas in the dermis are characteristic, isolated or merging, forming a tuberculoid infiltrate located mainly in the upper part of the dermis, directly under the epidermis, sometimes with its involvement in the process. Granulomas consist of epithelioid cells surrounded by a small number of lymphoid elements, among which giant Pirogov-Langhans cells can be seen. Elastic network with destructive phenomena. In this type of leprosy, destruction of small and larger nerve trunks occurs, running along the vessels infiltrated by epithelioid and lymphoid elements. Significant hypertrophy of the cutaneous nerves, usually surrounded by lymphocytes, is characteristic. Mycobacteria are very few or not found at all in this type of leprosy, but the lepromin test is positive. Skin appendages are almost completely destroyed or undergo atrophy with subsequent replacement by fibrous tissue.

Undefined type

The indefinite type is manifested by the appearance of only spotted rashes on the skin (hypochromic, erythematous, mixed, with geographic outlines). In the initial period, there is no damage to the peripheral nerves, and then a specific polyneuritis gradually develops, leading to sensitivity disorders in the distal parts of the extremities, amyotrophy of small muscles, contractures of the fingers, trophic ulcers, etc.

Dimorphic type

In the dimorphic type, there are rashes on the skin and mucous membranes, characteristic of the lepromatous type, and a disturbance of sensitivity, as in the tuberculoid type of leprosy.

In the development of all types of leprosy, progressive, stationary, regressive and residual stages are distinguished. In clinical practice, the transition of one type of leprosy to another is noted, for example, tuberculoid to lepromatous type with the formation of borderline forms.

In all types of leprosy, but more often in lepromatous leprosy, internal organs are affected (liver, spleen, adrenal glands, testicles), metabolic disorders (visceral amyloidosis), trophic ulcers are observed. Some patients have damage to the skeletal system (bone lepromas, ossifying periostitis of the tibia, elbow and other bones, resorption of the distal phalanges of the fingers and toes).

With leprosy, damage to the organs of vision is observed (episcleritis, keratitis, iritis, photophobia, lacrimation).

The lepromin test (Mitsuda test) has diagnostic, prognostic and epidemiological value. In the lepromatous type, this test is negative, in the tuberculoid type (as in healthy individuals) it is positive, and in dimorphic or undifferentiated leprosy it can be either positive or negative.

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Undifferentiated type of leprosy

The undifferentiated type of leprosy is characterized by the presence of several hypochromic or erythematous lesions with decreased sensitivity on various areas of the skin, in addition to large folds.

Pathomorphology. Lymphoid infiltration of the reticular layer of the dermis is found in the dermis, mainly perivascular, perifollicular and along the nerve trunks with phenomena of intensive proliferation of neurolemmocytes. In addition to lymphocytes, the infiltrate contains histiocytes, pdasmocytes and eosinophilic granulocytes. Infiltrates, gradually being replaced by fibrous tissue, compress and partially destroy skin appendages, nerve endings and nerve trunks.

Such changes, as they develop, can develop into lepromatous or tuberculoid leprosy.

Lepromatous type of leprosy

The lepromatous type of leprosy is characterized by clinical polymorphism: erythematous spots, plaque-infiltrative lesions and lepromas. The spots are asymptomatic, multiple, symmetrically located mainly on the face, extensor surfaces of the limbs, and buttocks. They can merge, occupying almost the entire skin (the so-called confluent spotted leprosy). The spots exist for a long time, then disappear or infiltration or lepromas develop in their area. Infiltrative lesions can have the appearance of limited plaques or diffuse lesions with unclear boundaries, a characteristic brownish-bluish color. With diffuse changes on the face, a picture similar to a lion's muzzle (facies leonina) appears. There are scleroderma-like, erysipelas-like, pellagroid changes, rashes resembling psoriasiform, seborrheides, sometimes bullous rashes like pemphigus, herpetiform dermatitis. Lepromas (leprous tubercle, node) can be cutaneous and subcutaneous. They are hemispherical, to varying degrees elevated above the skin level. With the natural course of the disease, two outcomes are possible - resorption or superficial ulceration with the formation of atrophic hyperpigmented foci or scars, respectively. Characteristic of the lepromatous type of leprosy is damage to the mucous membrane of the oral cavity, nose, larynx, the development of leprosy neuritis. During periods of exacerbation of the disease (reactive phases), polymorphic rashes can be observed. The most characteristic of them is erythema nodosum (can ulcerate). Special variants of the lepromatous type of leprosy include Lucio's leprosy and histioid leprosy. In Lucio's leprosy, the entire skin is diffusely altered and hyperemic. Multiple telangiectasias are noted, and there may be slight hyperpigmentation. Due to edema and infiltration, the skin becomes scleroderma-like and shiny. There may be extensive ulcerations. The diagnosis of histoid leprosy is based on histological examination (the presence of spindle-shaped histiocytes containing a large number of leprosy mycobacteria), clinical signs - sharply defined plaques with steep edges, peeling, and point depressions on their surface in the center.

Pathomorphology

The histological picture of the lepromatous type of leprosy is quite characteristic, granulomas are formed from histiocytes in various stages of development, with the formation of classic leprosy foamy Virchow cells, the cytoplasm of which contains a large number of leprosy mycobacteria and lipids, revealed by Sudan III staining. Among these cells are exudate cells - lymphocytes and plasma cells. Depending on the nature of the skin lesion, granulomas occupy different volumes of the dermis, located in islets or narrow strands in superficial lesions and diffusely in deeper infiltrates and lepromas. Giant Touton cells, including phospholipids, are sometimes found between the infiltrate cells. Russell bodies, formed as a result of the destruction of nuclei, can be detected in leprosy cells. Mycobacteria are located inside leprosy cells in the form of bundles and globules, as well as around small vessels and in the secretion of sebaceous and sweat glands. The epidermis is usually flattened and atrophic, epidermal outgrowths are smoothed out as a result of pressure from the infiltrate. A strip of unchanged collagen can often be seen under the epidermis, separating it from the granulomatous infiltrate.

The vessels and nerves of the skin are involved in the process. The vessel walls are infiltrated by macrophage elements, endotheliocytes swell, proliferate, and sometimes turn into leprosy cells. They usually contain many leprosy mycobacteria, sometimes in the form of globules. The nerves become angular due to the stratification of the perineurium, and contain a significant number of mycobacteria in all structures.

In diffuse lepromatous leprosy (Lucio phenomenon), in addition to the picture described above, necrobiotic changes in the epidermis, new formation of vessels in the dermis and significant infiltration of the subcutaneous fat with inflammatory elements, especially around large vessels, are observed.

Subsequently, capillary necrosis with secondary skin necrosis and ulceration may develop. Mycobacterium leprae invade the walls of blood vessels and even penetrate their lumen.

In addition, lepromatous erythema nodosum is distinguished as a reactive form, clinically similar to ordinary erythema nodosum, which is based on leprous panniculitis. Acute inflammatory infiltration of not only the dermis, but also the subcutaneous tissue with leprous cells with an admixture of lymphocytes, neutrophilic granulocytes and plasma cells is characteristic. Neutrophilic leukoclastic vasculitis with eosinophilia, fibrinoid changes in the vessel walls with subsequent hyalinosis are characteristic of this type of lepromatosis. Small leprous granulomas containing leprosy mycobacteria are found in the dermis and subcutaneous tissue.

Borderline type

The borderline group of leprosy is characterized by signs of polar types with a predominance of eruptive elements of tuberculoid or lepromatous leprosy. The clinical feature of borderline ("dimorphic") leprosy proper is the presence of "punched" or "stamped" spots and plaques, border foci that arise as a result of uneven regression of the process in different areas of the eruptive elements. Multiple asymmetric neuritis is common.

Pathomorphology

Along with foci of tuberculoid structure, clusters of a significant number of histiocytes with pronounced signs of leprosy cells are noted, located diffusely in the upper part of the dermis, but not penetrating the epidermis. In the reticular layer, the infiltrate is localized mainly near the skin appendages; destruction and infiltration of the muscles that raise the hair can be observed, as in the lepromatous type of leprosy. Cutaneous nerves are destroyed to a lesser extent, but their number is reduced, and the revealed bundles are thickened and infiltrated. As a rule, large nerve trunks are affected, in which infiltrate cells are found, mainly lymphocytes, as well as leprosy mycobacteria in the form of bundles or globules.

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Differential diagnosis of leprosy

Differential diagnosis is carried out with syphilis, vitiligo, toxicoderma, tuberculous lupus, etc.

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Treatment of leprosy

The treatment is complex and is carried out in leprosariums. Specific, general strengthening therapy is recommended. Vitamins A, C, and B vitamins, pyrogenic drugs, antioxidants, methyluracil, etc. are used as general tonics. Anti-leprosy drugs include dapsone (in tablets or powders, 50-200 mg per day or an oil suspension intramuscularly 1-2 times a week), 50% solution of solusulfone sulfetron (intramuscularly 2 times a week, starting with 0.5 ml and gradually increasing the single dose to 3.5 ml), siba-1906 (tablets from 0.5 to 2 g per day or as an oil suspension intramuscularly from 2 to 6 ml once a week), prothionamide (0.25 g 1-3 times a day), lampren - 100 mg (1 capsule) daily, rifampicin (300-600 mg or 2-4 capsules). Diucifon and dimocifon are also prescribed.