Leprosy [grech, lepra; synonym: Gansen's disease, ganseniaz, ganzenoz; outdated names: leprosy, elephantiasis graecorum, lepra arabum, lepra orientalis, Phoenician disease, satyriasis, leontiasis, mournful disease, grief, northern disease (Yakuts), the Crimean disease, krymka, black cannot, a fox scab, lazy death, Saint Lazar's disease etc.] — the chronic generalized infectious disease of the person caused by mycobacteria of a leprosy, which is characterized by damage of skin, mucous membranes, a peripheral nervous system, internals.
L. is among the most ancient of the known diseases of the person. There is an opinion that L. entered into group of the skin diseases described in books «Rigveda Samhita» and «Susiirutas Ayurvedas» (India, 1500 — 1000 to and. h.) under the general name "kushtha", in Ebers and Brugsh's papyrus (Egypt, 1300 — 1000 BC) — under the name «uchedu» and in the bible — under food of «zaraath» (leprosy). Rather complete descriptions skin and nevrol, manifestations of L. meet in literature of India and China relating to 8 — 5 centuries BC. Descriptions in the Indian book «Sushruta Samhita» (6 century BC) and in the Chinese book «Nei Ching Su Wen» (5 century BC) nodes, ulcerations, eyebrow sheddings, mutilations, damages of eyes, changes of a nose, disturbances of sensitivity, deformation of extremities and paralyzes testify to ability to diagnose late typical manifestations of L. K to the same period development of preventive manuals against distribution of L belongs., including divorce.
In the European countries of L. for the first time meets in 5 — 3 centuries BC, first of all in Greece and Italy where it was brought from Egypt, Phoenicia and the countries of Asia as a result of development of commercial relations, wars and other movements of the people. To distribution of L. in Europe its massive drift in 1 century BC the Roman soldiers of Pompey who were returned from long campaigns to the countries of Southeast Asia promoted. To South and Central America L. it was brought by Europeans in 16 — 18 centuries. In the first references of L. the European authors (Aristotle, 4 century BC) the disease was called satyriasis or leontia (leontiasis). Fullestly the wedge, symptoms of a disease are described in Europe in 2 century by doctors Aretaios and especially K. Galen, to-ry allocated six main signs of L.: inflammation knives, ulcers, thickening of the lower extremities, lion's face, hair loss and mutilations. The disease a long time appeared in Europe under the name «elephantiasis». Only in 3 century the Christian theologian Origen (apprx. 1 85 — 254) pointed that the name «elephantiasis» corresponds to the bible name «zaraath» and as 70 tolkovnik translating the bible in 3 century BC into Greek translated the term «zaraath» the word «lepra», it is necessary to call a disease «leprosy».
The first state legislations directed to restriction of distribution of L., appear in Europe in 5 — 8 centuries. Peak of an endemia of L. in Europe it falls on 10 — 13 centuries then gradual reduction of incidence and decrease in public interest in problem L is noted.
By the beginning of 19 century in various European countries, including and in Russia, there is a number of the special works devoted to the description a wedge, manifestations and to studying of distribution of L. The first thesis but L belongs to the same period., written in Russian by G. Plakhov in 1841. «About a nodular leprosy (elephantiasis graecorum) of Army of Donskoy called to Dona by leprosy, the Crimean disease and the Crimean leprosy». Especially the works of the famous Norwegian scientists of Danielssen which were published in 1847 were important (D. Page of Danielssen) and Beck (Page W. Boeck) «Om spedalskhed» and «Atlas Colorie de Spedalskhed», to-rye, according to R. Virkhov, laid the foundation for biological understanding L. Naiboley significant milestones in the history of development of the doctrine about L. are: opening of the activator L by G. Gansen., the offer Mitsuda (To. Mitsuda, 1919) leprominic test, establishment by Feydzhet (G. H. Faget, 19 43) antileprotic activity of drugs of a sulfonic row, development by Shepard (S. S. of Shepard, 1960) method of experimental infection of mice of L. person.
The important role in development of a leprology was played by the international congresses on L.: I - Germany (Berlin, 1897), II — Norway (Bergen, 1909), III — France (Strasbourg, 1923), IV — Egypt (Cairo, 1938), V — Cuba (Havana, 1948), VI — Spain (Madrid, 1953), VII — Japan (Tokyo, 1958), VIII — Brazil (Rio de Janeiro, 1963), IX — Great Britain (London, 1968), X — Norway (Bergen, 1973), XI — Mexico (Mexico City, 1 978). In 1931 the International association of leprologists, and in 1953 — Committee of WHO experts on L was created.
Danielssen and Beck (1847) allocated two kinds of L.: knotty and anestetichesky. At the end of 19 century idea of the mixed, makuloanestetichesky and secondary and nervous forms L appears. Questions of classification of a disease were discussed on most the international congresses on L. On the Cairo classification distinguished two types of a disease — lepromatous and nervous, allocating in the last three subtypes: neurospotty idle time, neurospotty tuberculoid and neuroanestetichesky. On the Havana classification allocated three types of a disease: lepromatous, tuberculoid and undifferentiated. In 1953 on the Madrid congress the first two ooze were recognized polar, and instead of undifferentiated type two groups are allocated: undifferentiated and boundary. The Madrid classification based as well as all previous, on a wedge, signs, was insufficiently informative, did not consider many features of leprose process and therefore could not satisfy leprologists. The X International congress on L. recommended to apply five-group classification of Ridley — Dzhoplinga which is further development of the Madrid classification taking into account the latest developments of immunology of L. Leprose process is considered as continuous immunol, process, at the same time tuberculoid and lepromatous types L. — as polar groups; besides, allocate three intermediate (boundary) groups. Thus, classification includes the following basic groups of L.: A TT — tuberculoid type (a synonym: polar tuberculoid, polar tuberculoid group); W — boundary and tuberculoid group (boundary tuberculoid); VV — boundary L. (boundary group); BL — boundary and lepromatous group (boundary lepromatoz); LL — lepromatous type L. (polar lepromatoz — polar lepromatous group). All five groups L. differ characteristic a wedge, manifestations, a current, the forecast, and also epidemiol, in the importance. Ridley's classification — Joplin hectare provides also two additional (not main) groups: subpolar lepromatoz (LLs) and undifferentiated L. Odnako such kinds of lepromatous type L do not keep within the specified classification., as Lucio's leprosy and gistoidny L.
Statistics and geographical distribution
According to WHO data, the number of the registered sick L. in the world in the 70th apprx. 3 million people, and true (settlement) number of patients, but this Bekelli and Martinez of Domínguez (L. M of Bechelli, V. Martinez Dominguez, 1973) and Committee of WHO experts on L., exceeded 10 million people. In Asia 1,3 million, in Africa — 1,3 million, in America — 0,2 million, Europe — 0,05 million sick L are registered. From the countries of Asia of L. meets more often in India, Indonesia, Burma, Thailand, South Korea where the number of patients hesitates from 3 to 30 for 1000 of the population. So, e.g., in India, in Big Bombay, at inspection of 50 697 school students at the age of 5 — 16 years 151 sick L were revealed. (2,97: 1000) and 100 children (1,87: 1000) with suspicion on L. V Afrike the highest incidence of the population of L. it was registered: in the People's republic of Congo (116,3 for 1000 of the population), Gabon, Upper Volta, Kenya, Cameroon, on Madagascar, in Mali, Guinea, Ivory Coast, Mozambique, Senegal, Tanzania, Uganda (from 20 to 55 for 1000 of the population). From the countries of South America of L. most often meets in Brazil (8,3 for 1000 of the population), Venezuela (4,7 for 1000), Colombia (3 for 1000). In Europe L. still remains in Spain, Portugal, Greece, and also in Turkey (from 0,8 to 3,0 for 1000 of the population). Incidence of men and women is identical, children at sick L. are born healthy.
Etiology and pathogeny
Activator L. the person it was described in 1874 by the Norwegian doctor Mr. Gansen. It revealed it in scraping from a cut surface of a node at knotty L. V patient with 1879 it. the microbiologist A. Neicer offered methods of coloring of bacteria of L. For this reason in literature sometimes the activator L. it is described as Gansen's mycobacterium — Neicer. In 1882 it was established acid - and a spirtoustoychivost of the activator L. In the first years after opening of the activator L. it was called by Bacillus leprae, Coccothrix leprae, Streptothrix leprae, diphtheroid, then it was included as an independent look in the sort Mycobacterium Lehmann et Neumann, 1896. Finally accessory of the activator L. to to mycobacteria (see) it was proved after detection by Dreyper (P. Draper, 1976) in its structure typical mikolevy to - you, and also works on studying of its antigenic structure. The most correct specific names of the activator L. Mycobacterium leprae, Mycobacterium leprae hominis, Mycobacterium Hanseni are. According to Berdzhi's classification the sort Mycobacterium enters into the Mycobacteriaceae family, an order of Actinomycetales, the class Schizomycetes.
Activator L., as a rule, has an appearance of a straight line or slightly curved stick with the rounded-off ends. The sizes of a mycobacterium vary: length is from 1,0 to 4,0 — 7,0 microns, to dia. 0,2 — 0,5 microns. In lepromas also granular, kokkovidny, threadlike, branchy, club-shaped, budding, gantelevidny forms of the activator meet. As well as other mycobacteria, mycobacteria of L. grampolozhitelna, are painted across Tsil — to Nelsen in red color; in cells of fabrics they come to light in the form of spherical dense accumulations (globa), in to-rykh separate bacteria are located in parallel each other that quite often compare to a look: cigarettes in packs («cigar packs»).
By electronic microscopic examinations it is established that the ultrastructure of the causative agent of the Leprosy essentially does not differ from a structure of other species of gram-positive bacteria. On a surface of mycobacteria of the Leprosy the uniform elektronnopronitsayemy (osmiofobny) layer 5 — 10 nanometers thick (an outside diffusion layer of a cell wall) comes to light. It is followed by the osmiofilny layer of a cell wall from 3 to 10 nanometers thick consisting of two very thin coats, skintight to each other. Directly the inner surface of a cell wall is adjoined by a periblast of the cytoplasmic membrane (fig. 1) representing as well as at other bacteria, a three-layered membrane 7,5 — 9 nanometers thick. In a bacterial cell 1 — 2 mesosom meet the expressed polymorphism (loop-shaped, vesicular, tubular, lamellar, uviform). In cytoplasm rather small amount of ribosomes, spherical electronic and dense inclusions of volutin to dia comes to light. 20 — 50 nanometers, the inclusions having an appearance of the vacuoles limited to a membrane (presumably lipoida), and homogeneous little bodies, the nature to-rykh remain to the unknown. The kernel has no certain form, is located in the center of a cell along its long axis, not limited to a membrane. Sometimes in the cells of mycobacteria of L lysing under the influence of chemotherapy. sporopodobny educations (fig. 2 and 3) come to light.
In the main way of reproduction of mycobacteria of L. division of a mother cell by growing of a cross partition is. Mycobacterium of L. is an obligate intracellular parasite of fabric macrophages or cells of reticuloendothelial system, shows the expressed tropism to skin and peripheral nerves, but at late stages of development of process meets also in many other cells and body tissues. In a fabric cell of a mycobacterium of L. breed only in cytoplasm (fig. 4); intranuclear parasitism for them is uncharacteristic. Mycobacteria in leprose cells are sometimes delimited from cytoplasm of a host cell by a fagosomny membrane. At late stages of an infection parasitizing of activators L. the person is followed by disturbance of a structure of an endoplasmic reticulum and mitochondrions of a host cell.
The activator L which got to an organism., having passed skin and mucous barriers, gets into nerve terminations, limf, and and slowly disseminates circulatory systems, without causing usually on site implementation of visible changes.
Numerous attempts to develop a method of cultivation of mycobacteria of L. in vitro did not yield a positive take. Small number and contradiction of the published data about biol, properties of mycobacteria of L is explained by it., and also difficulties in the solution of the major problems of a practical leprology (receiving a vaccine, testing of in vitro of new pharmaceuticals, definition of medicinal stability of the activator L., receiving diagnosticums etc.) . Still G. Gansen made attempts to infect L. various lab. animals, including monkeys. However neither he, nor his followers within 80 years managed to find susceptible to L. experimental animal. Since 1902 — 1903 as an approximate pilot model of L. the person it was used by L. rats (Stefansky's leprosy) which is an independent disease of rodents. In 1960 an amer. the researcher Shepard (S. S. of Shepard) developed a method of receiving local reproduction of mycobacteria of L. by their introduction to pulp of a sole of a pad of mice.
Despite shortcomings (duration of experience, labor input of calculation of mycobacteria of L. in suspensions of fabrics, rather small exit of the bred mycobacteria of L.), Shepard's method played a significant role in studying of L. also it is widely applied to experimental check of activity to lay down. and prophylactics.
Rice (R. J. W. Rees, 1966), Rees and Ueddell (R. J. W. Rees, A. G. Weddell, 1968) suggested to infect by Shepard's method previously timektomirovanny and subtotalno the irradiated mice. Such modification of a method allows to receive higher «harvest» of mycobacteria at the expense of their hematogenous dissimination on all organism. Gistol, changes in the struck fabrics at the same time are similar to the picture observed at the person, sick L. Similar results turn out also at infection by Shepard's method of other rodents (rats, hamsters). In 1971 an amer. researchers Kirkhkhaymer and Storrs (W. F. Kirchheimer, E. Storrs) reported about successful infection of L. nine-zone battleships (Dasypus novemcucinctus). In the next years this model was strenuously studied and improved. It is confirmed that at intravenous infection with high doses (to 108) mycobacteria of L. at 60% of battleships in 18 — 35 months develops generalized specific inf. process with existence of enormous quantity of mycobacteria of L. — to 6•10^12-13 in the struck fabrics (a liver, a spleen, limf. nodes). It opens opportunities for broader studying of biology of mycobacteria of L. and receiving diagnostic and vaccinal drugs in the conditions of lack of methods of cultivation of the activator L. Gistol, the picture of defeats of bodies at a battleship corresponds to the LL type L. at the person, however at a battleship in patol, process tissues of a lung are early involved that is uncharacteristic for L. person.
Abe (M. of Abe, 1970), conducting immunochemical researches of extract of a leproma, allocated two bacterial antigens of L., one of to-rykh is thermostable polysaccharide, and another — thermolabile protein, highly specific for mycobacteria of L. At immunization of rabbits large numbers of mycobacteria of L., the infected battleships allocated from fabrics, more than 20 antigenic components of mycobacteria, only one of to-rykh, according to G. Kronvall et al. are revealed (1977), is specific. Unique feature of antigenic properties of the activator L., in comparison with other mycobacteria, ability of the killed mycobacteria to strengthen cellular immune responses without addition of adjuvants is.
Prabhakaran (To. Prabhakaran, 1967, 1973) described L, specific to mycobacteria. enzyme to a 0-difenoloksidaz, to-ry, apparently, plays an important role in reproduction of mycobacteria of L. Identification of respiratory enzymes — peroxidases, cytochrome - with - oxidases, succinatedehydrogenases, dehydrogenases and others confirmed existence at mycobacteria of L. autonomous systems of aerobic breath.
Prevalence of L. the population of various countries also the dignity depends first of all on socio-economic factors, the material standard of living, the general. cultures.
The only tank and a source of a leprose infection is the sick person. At the end of 19 century Schäffer (I. Schaffer, 1898) established that a sick tuberous form L. at cough, sneezing and even at a conversation allocates in the large number of mycobacteria
of L. Bolshinstvo of researchers surrounding it space allow as an airborne way of transfer of L., and through skin. Data epidemiol, inspections confirm the prevailing value of an airborne way of transfer. Separate observations confirm a possibility of infection of L. and at penetration of the activator through the injured skin (e.g., cases of infection at a tattoo). The possibility of distribution of L is allowed. blood-sicking insects.
Also the opinion is expressed that L. a little contagious infection, probability of infection a cut is in direct dependence ©т duration and the nature of contact. From among persons, it is long (for several years) living together with patients, including also married couples, no more than 10 — 12% get sick, as a rule. A maximum of cases of the persons which had long family contact with patients with lepromatous type L. at extremely low level a dignity. culture and material security, was apprx. 36%.
On the basis of careful studying of incidence many researchers, in particular Kokrin (R. G. Cochrane, 1934), V. F. Choubin (1970), etc., came to conclusion that it is explained by high degree of resistance of the population to a leprose infection. Wedge, versions and stages of L. are not equivalent on the epidemiol, the importance. So, e.g., it is shown that the persons contacting to patients with lepromatous type L., are exposed for 70% to bigger risk of infection, than in case of contact with patients with tuberculoid type L. Because in the majority endemic on L. the countries regular treatment receives less than a half of the registered patients, the high level of incidence is supported. Extremely adverse epidemiol, an indicator is high incidence of L. children. In the dying-away centers of L. the greatest indicators of incidence are displaced on more senior age groups.
The pathological anatomy
Gistol, a research of biopsy material is important for establishment of the diagnosis and the forecast of a disease. Biopsies are exposed sites of the affected skin, occasionally — superficially located nerves. Morfol, changes at L. are shown in the form of granulomas of two polar types — lepromatous (LL) and tuberculoid (TT), and also three groups — boundary and tuberculoid (W), boundary (VV) and boundary and lepromatous (BL).
Histologically the lepromatous type is characterized by a lepromatous granuloma of skin, edges are represented by the infiltrate located in a mesh layer, separated from epidermis by not struck zone of collagenic fabric. The basic cellular elements of a lepromatous granuloma are leprose cells; besides, separate plasmatic, lymphoid cells, single fibroblasts, multinucleate foamy cells are observed (tsvetn. fig. 1 — 6). Leprose cells concern to macrophages, are characterized by a pale kernel and «foamy» cytoplasm (fig. 5) due to the maintenance of lipids. The leprose macrophage at early stages contains fat to - you, phospholipids, unsaturated lipids; at a stage of development of process neutral fats and acid lipids prevail. Most of researchers considers that the ground mass of lipids represents a product of metabolism and disintegration of mycobacteria L. Naiboley idiosyncrasy of a leprose macrophage — stay and reproduction in it a large number of mycobacteria of L., i.e. phenomenon of incomplete phagocytosis (see). In cytoplasm of a leprose cell the high level of oxidation-reduction enzymes, acid phosphatase, nonspecific esterase comes to light and activity of a lipase is not found. For gistol, pictures LL also existence of capillaries with considerable narrowing of their gleam due to proliferation and swelling of the endothelial cells containing a large number of a mycobacterium like «globa» is characteristic. Cutaneous nerves are penetrated by infiltrates from mikrobosoderzhashchy cells (tsvetn. fig. 7 and 10). Mycobacteria are found also in cells an endonevriya. In lepromatous defeats of big prescription partial or final fracture of appendages of skin is noted (follicles of hair, grease and sweat glands).
At gistoidny L. [the atypical option LL, is described by Wade (H. W. Wade, 1963)] infiltrate is presented by a set of the thin spindle-shaped cells forming the intertwining tyazh and "curls. The quantity of mycobacteria in these cells are more, than at usual lepromatous defeats; bacteria occupy almost all their cytoplasm. The combination of gistoidny H.p. elements of tuberculoid structures or usual lepromatous infiltrate is possible.
At tuberculoid type patol, process the created infiltrate can be massive, occupying all layers actually of skin, or to be located with the separate centers. Destruction of a subepidermal layer of collagenic fabric with an arrangement of a granuloma directly under epidermis with an erozirovaniye of the last is characteristic. The ground mass of a granuloma is made epithelial cells (see), located in the center and surrounded on the periphery with shaft from lymphoid cells (see. Lymphocytes ); huge multinucleate cells like Langkhans meet (see. Colossal cells ), in a small amount are found plasmocytes (see), mast cells (see), fibroblasts. In the period of an aggravation in a granuloma the abundance of polymorphonuclear is observed leukocytes (see). Cellular elements do not contain mycobacteria and lipids. The thickening of nervous trunks due to massive infiltration by epithelial cells is characteristic.
Morfol, the structures containing the elements characteristic of both types L. and being as if a transition phase between polar types, L are characteristic for boundary. At undifferentiated L. the picture banal hron is observed, inflammations (see) without specific changes. The main gistol, the criteria defining belonging to classification groups of Ridley — Dzhoplinga, is the following morfol, features of infiltrate.
1. Cellular structure of a granuloma. In an upper half of a range (a TT, W and B B) existence of epithelial cells is characteristic (tsvetn. fig. 8) and for a TT — multinucleate (huge) cells like Langkhans (tsvetn. fig. 9). At B B epithelial cells are often separated from each other by hypostasis. In the bottom of a range (BL and LL) epithelial cells give way to macrophages, cytoplasm to-rykh as approaching type LL becomes more dense, foamy and contains fat. 2. Density of populations of mycobacteria. The quantity of mycobacteria increases in proportion from an upper part of a range to lower. In numerical expression an indicator of a bacterial saturation of lepromatous infiltrate for a TT, W, BB, BL and LL makes 0/1; 0/2,5; 3/4,5; 4/5,5; 5/6,5 respectively. 3. Quantity and topography of lymphocytes in a granuloma. For a TT and W the high content of the lymphocytes located in the form of a dense border around the mass of epithelial cells is peculiar. At B B and the LL quantity of lymphocytes is more often reduced, they are disseminated through a granuloma and do not form a shaft. 4. Defeat of cutaneous nerves. The considerable thickening of a nerve at the expense of massive infiltrate (increase in the maximum diameter of a bunch is characteristic of a tuberculoid part of a range at TG). For B B and BL of a patognomonichna of change of a perineurium in the form of a bulbous peel (onion skin) due to stratification by its infiltrate from lymphocytes, plasmocytes (at B B) or bakteriosoderzhashchy macrophages (at BL). 5. Relation to epidermis. At a TT and W the granuloma is located directly under epidermis and can erode it. At BB, BL and LL between infiltrate and epidermis constantly there is not struck zone 30 — 75 microns thick — the so-called layer of Yip consisting of collagenic fabric.
The subpolar and lepromatous group (LLs) allocated in classification is located between BL and LL. In a granuloma lymphocytes and plasmocytes (cellular mosaicity), a large number of mycobacteria meet L. Penistost of cytoplasm of a macrophage at LLs is less expressed, than at LL. Nerve fibrils are thickened, without infiltration, stratification of a perineurium can be observed.
For L. defeat of a peripheral nervous system is characteristic. Mycobacteria are found practically in all sites of nerve fibrils. At lepromatous type infiltrate consists of foamy macrophages, at tuberculoid — of epithelial cells. More bystry development of an inflammation at tuberculoid type is noted, than early emergence nevrol, disturbances speaks. At lepromatous type L. there is gradual substitution of nerve fibril connecting fabric. Leprose neuritis, as a rule, has the ascending character. The most frequent defeat of sensory nerves and the expressed tropism of mycobacteria of L is noted. to lemmocytes (schwannian cells).
Damage of internals is most expressed at lepromatous type L. Specific changes in a type of granulomas from macrophages with the high content of mycobacteria are found in a liver (tsvetn. fig. 11), spleen, marrow, mucous membrane of upper respiratory tracts, testicles, adrenal glands, limf, nodes. In the material received at a puncture peripheral limf, nodes, mycobacteria of L are found.; in paracortical area accumulations of the undifferentiated macrophages containing a large number of mycobacteria come to light; I bury the germinal centers are developed, and brain tyazh are filled with plasmocytes.
As a result of deep disturbances of protein metabolism perhaps amyloid it is regenerated also about visceral bodies. In kidneys the phenomena of an amyloid and lipoid nephrosis are noted. Its emergence is promoted it is long the proceeding aggravations of L., and also quite often accompanying L. it is long not healing trophic ulcers and hron, osteomyelites.
At a tubercle it bottom type and boundary L. visceral defeats are less expressed. In endocrine organs, and also in a brain, kidneys, lungs, heart of a leproma do not develop.
Under natural conditions L. only the person is ill. From all studied animal species only at representatives of family of battleships to introduction of very high doses of mycobacteria of L. it was succeeded to get a generalized infection. Activity of cellular reactions of an immune response to mycobacteria of L. (but given to a blastogenic response, the test of braking of migration of leukocytes, leprominic test, etc.) gradually decreases from the tuberculoid type (TT) to lepromatous type (LL), reflecting, respectively, the most advanced and smallest stage immunol, resistance to a disease.
One of the first scientific achievements activating studying immunol, bases of a susceptibility to L., Mitsuda offered in 1919 by the Japanese researcher intracutaneous leprominic test was (a synonym Mitsuda's reaction).
Antigen for Mitsuda's reaction is lepromin (Mitsuda's antigen). Lepromin Mitsuda represents autoclaved suspension of mycobacteria of L., received by homogenization of a leproma and containing the remains of fabric cells; it is so-called integral lepromin. For standard it is taken lepromin, containing 160 million mycobacteria in i of ml of drug. Also other antigens were offered: the suspension of mycobacteria of L purified of the remains of fabric cells. — bacterial lepromin; nekoagulirovanny soluble proteins of mycobacteria of L. — leprolina; suspension of the fat-free and destroyed mycobacteria of L. — Dkharmendra's antigen. It is most often applied integral lepromin. Test is put by intradermal introduction of 0,1 ml of a lepromin and belongs to reactions of hypersensitivity slowed down ooze. Results of test are estimated on three to a plus scale. Distinguish early reaction on lepromin (Fernández's reaction), considered in 48 hours (a hyperemia, a small papule), and the late reaction (Mitsuda's reaction) developing in 2 — 4 weeks (a hillock, a node, sometimes with a necrosis). It is considered that Fernández's reaction is caused by action of water-soluble fraction of a lepromin, and Mitsuda's reaction is caused by corpuscular antigens of cells of mycobacteria of L. Positive reaction of Mi of a fife testifies to ability of an organism to development of response to introduction of mycobacteria of D., but not to its infection. It is established that Mitsuda's reaction can change in the course of transformation of types D., and also under the influence of treatment, vaccination p other factors.
Leprominic test has no diagnostic value. It characterizes a state immunobiol. reactivity of a macroorganism in relation to the activator L. and therefore the hl can be used for establishment of type D., and. obr. for the forecast.
It turned out that patients have the LL late leprominic reaction always negative, at sick TT, and also at the majority (80 — 98%) of healthy the L is crowded it positive, and at patients boundary. (VV) can be both positive, and negative. At sick TT during an aggravation leprominic test can temporarily yield a negative take or become steadily negative if there is a transformation towards LL.
Usually patients have the LL reaction to lei rum both and and to a disease negative. Considering that in population of the healthy population negative reaction of Mitsuda occurs approximately at 10%, sharp p the reobladaniye of number of patients with a TT is regarded as adverse! epidemiol, the indicator testimonial of the high infectiousness leading to a disease not only stuck, having predisposition to D., but also steadier against L. parts of the population. At newborns and in the first months of life Mitsuda's reaction negative. Approximately at 50% of children of 1 year up to 3 years reaction already slabopolozhitelny. During from 3 to 10 years intensity of positive reactions gradually increases and to 15-year age at the prevailing majority (80%) it reaches ++ or +++.
Direct dependence between the frequency of diseases of L is established. and indicators of reaction on lepromin at inhabitants endemic on L. districts.
Decisive factor of formation of type L. and an outcome of an infection tension of natural immunity against mycobacteria of L is., defined by leprominic test.
At people with positive reaction on lepromin relative natural immunity to L. it is characterized by rather high tension. At the majority of leprominopozitivny individuals the beginning process of a TT comes to an end with self-healing, at the few steady process of T T develops and only at an insignificant part of patients it can be transformed in boundary and tuberculoid (W) or a boundary (VV) leprosy. At persons, pe reacting on lepromin, the disease in the same conditions develops more often and mainly in forms LL, boundary and lepromatous (BL) or Centuries. Therefore, individuals with negative reaction of Mitsuda represent group of the increased risk of a disease
of L. Virulentnost of mycobacteria of L. does not make a little considerable impact on the nature of a disease. It is confirmed by the fact that in the same family in the presence of the same source and identical conditions at contact persons various types of H.p. various outcome can develop.
Immunity to L. is relative. At often repeating massive superinfection the disease in any form can arise also against the background of the existing natural and artificial immunity. On the other hand, in ecdemic but L. zones patients meet, for to-rykh a source of an infection it is not possible to establish in view of short duration and accident of contact and to-rye, therefore, shall be regarded as persons with the raised susceptibility to L.
Relative natural immunity can be increased in a certain measure by introduction of vaccine BTsZh, i.e. by creation of the acquired «infectious» antimikobakterialny immunity. On this basis it was suggested that the persons who transferred primary tubercular complex become less susceptible to a leprose infection.
At uncured patients with W, BB and BL process, as a rule, evolves in the LL direction that, apparently, demonstrates the oppressing action of mycobacteria on cellular immunity. Many associated diseases, especially virus, and also mental an overstrain, overcooling of an organism, malnutrition weaken tension of immunity to L. also can promote progressing of a disease, its transformation in the direction of type LL.
The range of all immunol, states does not keep within a framework from T T to LL. The persons who did not get sick with L. in case of close contact with the patient, and also the person, at to-rykh process the wedge, manifestations of a TT is limited to a subclinical stage of an infection or self-healing at sakhmy early stages, are considered as group with the most expressed immunity. Existence of such group demonstrates that sick TT also have a certain insufficiency of immunity to L.
Izuchayemye's mycobacteria immunol. point out by methods of feature of patients of LL insufficiency of reactions of cellular immunity to mycobacteria of L. Lymphocytes from patients of LL in the presence of mycobacteria L. do not give reaction of a blastotransformation, and at a TT it positive (see. Blastotransformation of lymphocytes ), macrophages do not activate and do not slow down their migration. Not activated macrophages do not limit spread of an infection since mycobacteria of L. breed in macrophages. The answer of lymphocytes from uncured patients of LL on phytohemagglutinin (FGA) is a little suppressed whereas lymphocytes of sick TT react normally. It is proved that at patients of LL and to a lesser extent at sick TT in comparison with healthy faces reaction of rejection of allotransplant is slowed down. On response to chemical sensitizers (dinitrobenzene chloride) and PPD (tuberculine), and also to the sick L prepared as a lepromin for a suspension of other mycobacteria. practically do not differ from the healthy population.
Thus, at patients of LL the anergy to mycobacteria of L comes to light., not followed by clear decrease in the general reactivity.
Most of researchers considers that an anergy to mycobacteria of L. it can be caused by existence of genetic defect or development of tolerance as a result of the previous contact with the cross reacting mycobacteria or with mycobacteria of L.
The reasons of specific decrease in the digesting ability of macrophages of patients of LL in relation to mycobacteria L. finally are not found out. Were most often suggested about absence or insufficiency of specific hydrolases in lysosomes of macrophages. However Konvit (J. Convit) et al. (1974) showed that macrophages of patients of LL have necessary euzymatic potential and that introduction of BTsZh it is possible to achieve activation of macrophages, to-rye
many attempts to connect a susceptibility to L begin to digest L. Predprinimalos's mycobacteria. and hl. obr. development of LL with certain immunogenetic indicators. Studying of genetic polymorphism of sick L was most widely carried out. on blood groups and studying of antigens of histocompatability and a research on twins.
Oppression of cellular reactions of immunity at LL is combined with high credits of humoral antibodys, including and antimikobakterialny, to-rye, according to most of authors, protective value is no. At a TT of an antibody to mycobacteria of L. are not found. Increase in fraction of immunoglobulins is caused by hl. obr. increase in number of IgA and IgM.
Along with immunoglobulins in serum of patients of LL various autoantibodies, including a rhematoid factor, anti-thyreoglobulins, antinuclear antibodies, cryoglobulins, cytotoxic and other antibodies come to light. Serums of patients of LL quite often give positive Wassermann reaction.
As a rule, the general content of serum proteins (is increased at decrease in amount of albumine), ROE can be accelerated, the caption of S-reactive protein is raised. These deviations in a reactive phase LL are especially expressed. At the same time any specific to L. serol, reaction does not exist. Reaction of an immunofluorescence with mycobacteria of L. for identification of anti-mycobacteria of L. in view of difficulty of receiving the mycobacteria of L cleared of fabrics. was not widely used.
Incubation interval at L. averages 3 — 7 years. Cases of lengthening of an incubation interval up to 15 — 20 and more years are known.
The Tuberculoid Type (TT) differs in a current, easier in comparison with lepromatous type (LL), will better respond to treatment. Skin and peripheral nerves are surprised, nek-ry internals are more rare. Mycobacteria of L. come to light at gistol, a research of the centers of defeat, and in scrapings of skin defeats and a mucous membrane of a nose are absent. Leprominic test positive.
Skin manifestations depending on a stage of a course of a disease have an appearance of single spots or papular rashes, plaques, bordyurny or sarkoidny elements. Spots at an early TT hypopigmental or slightly erythematic, with accurately outlined edges. Further on edge of spots small polygonal krasnovatosinyushny flat papules appear, they quickly merge in the continuous inflammatory plaques which are transformed then in bordyurny elements a little towering over the level of skin. The surface of plaques smooth, is sometimes shelled. The most typical, classical manifestation of the developed TT is the big erythematic plaque with the raised edge and tendency to peripheral growth which is sharply outlined valikoobrazno. In process of increase in a plaque its central part is flattened with the advent of an atrophy and hypopigmentation. It leads to emergence of the big ring-shaped merging bordyurny elements — figured tuberculoid (tsvetn. fig. 20). Width of a border can fluctuate from several millimeters to 2 — 3 cm and more. Its outer edge is raised, internal — is flattened. The sizes of plaques and bordyurny elements can be from 10 — 15 mm to the extensive centers taking the most part of a back, breast, waist. An arrangement of rashes usually asymmetric, on any body part.
One of kinds of damage of skin at this form L. sarkoidny (lupoid) formations from 2 — 3 mm to 2 — 3 cm in size of red-brown color with a clear boundary and a smooth surface, inclined to grouping, localized usually on a face and extremities are, is more rare on a trunk. At regress of all elements on their place there are hyponevus pigmentosus or sites atrophies of skin (see).
Defeat of a peripheral nervous system and touch, trophic and vasculomotor disturbances caused by it come to light very much early. In the centers of defeat frustration temperature, painful and tactile is noted sensitivity (see), loss of vellus hair, change of pigmentation, disturbance of sebaceous secretion, sweating (see), xeroderma, sometimes hyperkeratosis (see). The zone of disorder of temperature and painful sensitivity comes to 0,5 — 1,5 cm for visible borders of rashes, and disturbance of tactile sensitivity and sweating is registered only within vysypny elements. At an early stage dissociation of disturbances of sensitivity, in some cases perhaps short-term increase in all types of sensitivity is quite often noted (hyperesthesia), for the Crimea in the beginning decrease in sensitivity, and then full by all means follows anesthesia (see). In distal departments of extremities all types of sensitivity can be broken. Around plaques and spots it is possible to find a reinforced superficial branch of a cutaneous nerve that does not happen at LL. Defeat of nervous trunks is expressed in diffusion or their chetkoobrazny thickening, morbidity, and sometimes in development of a kollikvatsionny necrosis in places, most vulnerable for mycobacteria of L. (sites of a predilektion). Usually in the beginning the nervous trunk is surprised, in a zone of an innervation to-rogo plaques are located. Without treatment damage of nerves develops on type polyneuritis (see). As a result of defeat of large trunks of a peripheral nervous system paresis and paralyzes, trophic ulcers, contractures of fingers, an atrophy of small muscles, changes of nails, mutilations and other changes of brushes and feet develop (tsvetn. fig. 18 and 21). Often defeat of a facial nerve meets that is followed lagophthalmia (see) and paresis of face muscles (mask-like face). Other cranial nerves are involved in process seldom. In the started cases reflexes from calcaneal (Achilles) sinews and a sinew of a tricipital muscle can be broken. Proprioceptive sensitivity, as a rule, does not suffer.
The lepromatous type (LL) differs in a big variety a wedge, manifestations on skin (indistinct spots, infiltrates, plaques, nodes), in early involvement in process of mucous membranes, internals and later — a nervous system, will more difficultly respond to treatment. In all rashes enormous quantities of mycobacteria of L come to light. Leprominic reaction negative.
Enanthesis is more often presented numerous erythematic or erythematic nevus pigmentosus, characteristic signs to-rykh are the symmetric arrangement, the small sizes and lack of accurate contours. Most often spots are localized on a face, extensor surfaces of brushes, forearms and shins, and also on buttocks. Surface their smooth, brilliant. Over time initial red color of spots gets brown or yellowish (copper, rusty) a shade. Sensitivity and sweating within spots are not broken. For a long time (months, years) spots are left without changes, sometimes disappear, but are more often transformed to infiltrates or lepromas (tsvetn. fig. 15 and 16). At development of infiltrate of a spot take a form of limited plaques or considerable sites of superficial infiltration of skin without the clear boundary which is gradually passing into externally not changed skin. Development of paresis of vessels and a hemosiderosis causes brown or sinyushnobury color of infiltrate (tsvetn. fig. 13 and 14). Infiltration of skin is followed by strengthening of function of sebaceous glands therefore skin in places of defeats becomes fat, brilliant, shining. Expansion of follicles of vellus hair and output channels of sweat glands gives to skin a type of an orange-peel. Sweating in the field of infiltrates at first decreases, and in late stages — completely stops. At early stages of process growth of vellus hair is not broken, in later period (3 — 5 and more years) eyebrow shedding (since Outer sides) and eyelashes is observed, and also vellus hair on sites of infiltration of skin, the hair loss of a beard, moustaches is possible. At diffusion infiltration of face skin natural wrinkles and folds go deep, superciliary arches sharply act, is thickened Nov, cheeks, lips and a chin have a lobular appearance — «a lion's muzzle» (facies leonina, tsvetn. fig. 19). Pilar part of the head, interiors a century, axillary poles, elbow bends and popliteal spaces, as a rule, are not surprised (immune zones), but at widespread process in these zones come to light gistopato l. changes characteristic of LL. In the field of infiltrates often already at early stages there are single or multiple hillocks and nodes (lepromas), the sizes to-rykh vary from 1 — 2 mm to 2 — 3 cm. Lepromas are more often localized on a face (superciliary arches, a forehead, wings of a nose, a chin, cheeks), lobes of auricles, and also on brushes, forearms, shins, is more rare — on hips, buttocks, a back. They are sharply delimited from surrounding skin, are painless, in skarifikata from them at microscopic examination mycobacteria of L are found. (tsvetn. fig. 12).
Lepromas can be thermal or hypodermal. Hypodermal lepromas come to light palpatorno in the beginning, but further they reach a derma and become visible. Dermalny lepromas have an appearance of oval papules in the beginning, gradually turning into the hillocks of reddish and rusty color towering in the form of hemispheres over the level of skin. The surface their smooth, shines, is often speckled by teleangiectasias, is sometimes shelled. From plotnovato-elastic they become softer, and in rare instances of fibrous regeneration — very dense. Sometimes they are exposed to a rassasyvaniye, leaving behind the pigmented, a little sunk down spot. The most frequent outcome of a leproma in the absence of treatment is the ulceration. Process develops inertly, torpidno, without the expressed inflammatory phenomena and comes to an end with formation of a small hypopigmental hem. The bystry disintegration of lepromas beginning with a surface or the center of a node with formation of superficial is less often observed, it is long not healing ulcers, to-rye can merge, forming extensive ulcer surfaces. Edges of ulcers abrupt or subdug, infiltrirovanny, tower over surrounding skin a little, can be painful, afterwards become callused. The bottom of ulcers is covered with a grayish-yellow plaque. After healing there is equal, slightly sunk down, gipokhromichesky, sometimes a keloid cicatrix. In all cases mucous membranes of a nose, and in the started cases — mucous membranes of an oral cavity, a throat, and also a back of the tongue and a red border of lips are surprised. Rhinitis, nasal bleedings are quite often noted even before emergence of skin defeats. The mucous membrane of a nose is hyperemic, edematous, with small erosion; further there are lepromas, infiltration, massive crusts which are sharply complicating nasal breath. Disintegration of the lepromas located on a cartilage of a partition of a nose leads to its perforation and deformation of a nose. In the started cases the ulceration of lepromas on a mucous membrane of a soft palate is possible. Defeat of area of voice folds can lead to sharp narrowing of a glottis, an aphonia.
Specific defeats of an organ of sight before treatment by sulfonic drugs occurred approximately at 80% of sick L. At LL the front department of an eyeglobe and eyelids are surprised, episclerites most often meet (see. Sclerite ), a focal keratitis (see. Keratitis ), iridocyclites (see. Iridocyclitis ), cataract, and also conjunctivitis and blepharites. Development of episclerites begins with emergence in a limb of a cornea of a hyperemia, on site the cut is formed diffusion infiltrate or small (to dia. 2 — 4 mm) leproma. In uncured cases episkleralny lepromas increase, can burgeon in an iris and a ciliary body. A keratitis is characterized by emergence of small white (prosovidny) lepromas against the background of focal opacification of a cornea. Further lepromas increase, ulcerate, in a cornea there are vessels (a leprose pannus), the keratitis becomes diffusion, extends to all cornea. In the started cases defeat of an iris is possible (a hypertrophy of a pigmental pupillary rim, disintegration of a pigment, phenomenon of an iritis with a pericorneal injection of vessels, a photophobia, pains). Emergence of small lepromas and adjournment of fibrinous exudate in the form of white flakes and threads on a surface of an iris lead to deformation of a pupil and disturbance of accommodation. In the past hron, iridocyclites were the main reason for a blindness of sick L. On centuries diffusion infiltrates and lepromas can be localized that leads to loss of eyelashes. Feature of leprose conjunctivitis is absence separated and slight the phenomena of irritation.
At LL specific process often strikes a peripheral nervous system, limf, nodes, a liver, walls of the majority of blood vessels, testicles. Femoral, inguinal, Submandibular, axillary and others limf, nodes (except chest and mesenteric) are increased, a dense consistence.
Defeat of a peripheral nervous system is shown rather late and develops, as a rule, as a symmetric polyneuritis. Disturbances of sensitivity in a zone of skin rashes long time are absent, but over time they are always shown. Axial cylinders of nerves are rather steady against development in them leprose infiltrate, than quite long preservation of its function speaks. However infiltration by leprose cells of all diameter of a nervous trunk is observed further, in process of development the cut is lost sensitivity before full anesthesia. The struck nervous trunks are thickened, dense, smooth. At very late stages of neuritis, except disorders of sensitivity, various trophic and motive disturbances (a lagophthalmia, paresis of chewing and mimic muscles, amyotrophy, a contracture, the mutilations pro-butting and trophic ulcers of feet) develop. Deep types of sensitivity, and also tendon and periosteal jerks usually remain without disturbances.
Hron, hepatitises come to light early enough, they have tendency to aggravations, especially in the period of reactive phases. The liver can be increased, is sometimes painful, disturbances are noted various indistinctly expressed funkts (see. Hepatitis ), caused by existence of small prosovidny lepromas in paraortalny areas and segments of a liver.
Orchitis (see) and an orchiepididymitis are characterized hron. a current with the subsequent dysfunction of testicles (infantility and a gynecomastia). Sometimes at widespread LL are observed disturbances of a menstrual cycle.
At LL, as well as at other forms L., changes of nails are observed, they become the dim, grayish, reinforced, cut-up longitudinal grooves, fragile, easily exfoliate, crumble.
The erased and atypical forms of lepromatous type. Single spots, infiltrates and lepromas (an abortal current), and also very small lepromas which developed around follicles of vellus hair (follicular lepromas) concern to the first. From atypical manifestations ikhtioziformny, sklerodermoformny, pellagroidny, erizipeloidny, lichenoid, herpetiform, psoriasiform rashes, gistoidny are described by L. and Lucio's leprosy.
Gistoidny L. it is clinically characterized by the special clearness of borders and steep edges of elements (plaques and nodes), on to-rykh quite often there is a peeling, pointed impressions in the center.
Lucio's leprosy (synonym: Lucio's leprosy — Alvarado, diffusion LL, a diffusion leprosy of Lucio — Latapi, a spotty diffusion leprosy) is for the first time described in Mexico by Lucio and Alvarado (R. Lucio, I. Alvarado) in 1852 and Latapi is in detail studied (F. Latapi, 1938). It is extending to all body surface diffusion LL without separate spots, plaques and lepromas. Skin becomes brilliant and intense, as at a scleroderma. Indumentum sometimes is absent. Diffusion infiltration of the person (a crescent-shaped face), a hoarse voice, hypostases of legs remind a myxedema. Lucio's leprosy is characterized by poorly expressed inflammatory reaction and the vasculitis which is followed by thrombosis of skin blood vessels that leads to extensive ulcerations of skin. The vasculitis which is found at other forms L., usually is not followed by thrombosis. Lucio's leprosy accompanied with extensive ulcerations is called Saint Lazar's leprosy. At late stages of a leprosy of Lucio the ichthyosis develops.
Meets also so-called drain spotty LL, at a cut the scarcely noticeable hypopigmented or erythematic spots, quickly merging, form the uniform spot covering all skin except for immune zones. At these kinds of L. in diagnosis of a disease the bakterioskopichesky research of skarifikat of damages of skin is decisive: at LL in them a large number of mycobacteria of L is always found.
Boundary groups. In clinic of other groups of a leprosy (the W, Centuries of BL) to some extent expressed signs of both polar types (borderline cases).
Boundary and tuberculoid group (W). Skin rashes at W by outward, an arrangement and a condition of sensitivity very much remind manifestations of a TT. But at the same time spots and plaques of usually smaller sizes, multiple, meet elements indistinct borders (tsvetn. fig. 17). As a rule, there are thickenings of peripheral Nervous trunks, disturbances of sensitivity, sweating and growth of vellus hair, but in comparison with a TT all these manifestations are less expressed. Reaction on lepromin slabopolozhitelny or positive.
Boundary leprosy (VV). Skin manifestations, in addition to looking alike basic groups, are characterized by signs typical, not inherent in polar types: along with numerous asymmetric erythematic spots, often irregular shape, with indistinct borders or plaques with clear flat edge and more convex central part, as a rule, there are «punched», or «stamped», spots and plaques which received the name of holes of cheese. It is caused by emergence in the central part of rashes of accurately outlined sites of regress (subsiding) with skin, hypopigmented or normal on color. At plaques skin in sites of regress is flattened, the element at first takes a form of «the turned saucer», and then the roundish or polosovidny bordyurny elements towering over the level of skin with an accurate steep inner edge (unlike bordyurny elements at a TT where the internal specks are flattened). As a rule, such bordyurny manifestations get violet coloring. Near spotty and bordyurny elements clusters of small rashes — satellites usually come to light. Early enough multiple asymmetric defeats of peripheral nervous trunks develop. In rashes moderate disturbance of sensitivity comes to light. Sweating on rashes is usually not broken, vellus hair are partially kept. Leprominic test, as a rule, negative, is more rare slabopolozhitelny.
Boundary lepromatonaya group (BL). As well as at LL, basic elements of BL the spots which do not have clear borders, papules, plaques, diffusion infiltrates and nodes are. The main distinctiveness of BL is existence «punched», «stamped» a rash and roundish polosovidny bordyurny elements of a pla with the raised inner edge. Also existence of small impressions in the center of nek-ry papules and plaques is characteristic. Rashes are not so multiple as they at LL, quite often are located asymmetrically. On nek-ry elements already in an early stage decrease in sensitivity comes to light. Function of sweat glands does not suffer, also growth of vellus hair is not broken more often. As well as in case of boundary L., at BL the thickening of peripheral nervous trunks usually comes to light that, unlike LL, can precede emergence of an enanthesis.
Do not develop such typical for the LL manifestation as eyebrow shedding and eyelashes, deformation of a nose, damage of eyes, an ulceration of a mucous membrane of a nose, facies leonina. Reaction on lepromin always negative. At a bacterioscopy in all skin rashes in a large number L.
Techeniye's mycobacteria of a disease chronic come to light. At all kinds of L. can be observed acute or subacute activation of process (reaction, reactive phases, aggravations). Despite numerous attempts to unify descriptions of reactive states at L., their standard classification does not exist. Distinguish two types of reaction more often: the reactions which are followed by transition (transformation) of a disease to other classification group (so-called boundary reactions), and the reactions which are not followed by transformation of process. Boundary reactions can develop at sick TT, W, BB, BL and a subpolar lepromatoz (LLs), except LL, and share on ascending (the return, defensive, reverse), at to-rykh there is a transformation in the direction of the TT type, and on descending, followed by shifts in the direction LL. In the second group of reactions the aggravation like the leprose knotty erythema (LKE) met only at patients of LL and BL is allocated. Quite often reactions have character of an erysipelatous inflammation.
The main signs of development of boundary reaction are bystry modification of the nek-ry or all available skin rashes, (reddening, tension, gloss), local, and sometimes and the general temperature increase, morbidity of nervous trunks of a pla of a zone of an innervation of the affected nerve, swelled on a linden and extremities. Process extends also on limf, nodes, mucous membranes of a nose and an oral cavity, an eye, nek-ry internals. Later ulcerations of rashes, a necrosis of the struck nervous trunks can develop. Emergence of new vysylaniye testifies to the descending character of an aggravation more often. However the final conclusion can be drawn only on the basis gistol, researches. At reversivno ]] reactions come to light signs of strengthening of cellular immunity: increase in quantity of lymphocytes, epithelial and colossal cells and reduction of number of mycobacteria of L. (at the descending reaction — on the contrary). At a TT reverse reaction can lead to recovery. According to the direction of transformation at boundary reactions indicators of leprominic test change towards strengthening at reverse reactions and towards easing — at the descending reactions.
At an aggravation of LL there can be new rashes, puffiness of the person and extremities, neuritis, damages of eyes, limf arises or become aggravated, nodes and internals, old lepromas ulcerate. Sometimes in a reactive phase LL appear atypical (urtikarny, lichenoid, akneformny. ikhtioziformny, furunkuloidny, rozeolezny, pemfigoidny) rashes. Most often at the same time the aggravation like a leprose knotty erythema meets, at Krom the elements typical for a knotty erythema appear. The appeared bright red nodes and plaques can be painful, turn pale during the pressing, sometimes ulcerate, temperature in them is much higher, than in the skin surrounding them.
As a rule, aggravations of LL soprovozhdayuts I temperature increase. pains on the course of nervous trunks, in joints and bones, frustration of a dream. Emergence on rashes of a peeling testifies to the beginning of regress of reactions.
The aggravation at Lucio's leprosy is shown by emergence on skin of painful erythematic plaques, in the center to-rykh the necrosis develops (sometimes before it the bubble appears). Further the dark crust (scab) disappearing in several days forms. Ulcerations standing are especially expressed.
At the heart of reactive states at L. changes of tension of reaction of humoral and cellular immunity lie. The leprose knotty erythema and other reactions at LL and BL develop as Artyus's phenomenon (see. Artyusa phenomenon ). Existence in serum of patients of the LL large number of precipitant antibodies at high concentration in an organism of antigen leads to formation of cell-bound immune complexes antigen — an antibody. Being postponed in walls of vessels and in fabrics, they cause development of response allergic reaction. Quite often at the same time the glomerulonephritis of an immune origin, and in blood serum — deviations in the maintenance of a complement comes to light.
Aggravations at other types of L. (A TT, W and B B) changes in intensity of hypersensitivity of the slowed-down type reflect. With introduction of effective chemotherapy the number of reactions (aggravations) increased. The factors promoting development of reactive states are also associated diseases, especially infectious, mental an overstrain, surgeries, immunizations (especially against smallpox), pregnancy, childbirth, etc.
Early diagnosis of L. reduces probability of infection of people around, reduces terms of hospitalization of patients, promotes more successful medical and social rehabilitation of patients.
L, main for diagnosis. the wedge, symptomatology is. Diagnosis of late stages of L. (multiple lepromas, eyebrow shedding and eyelashes, paresis, paralyzes, mutilations, retraction of a nose, «a lion's muzzle») does not represent usually difficulties while early manifestations of leprose process are quite often difficult diagnosed as many manifestations of L. in this period can be erased and atypical.
Considering variety early Dermatolum, and nevrol, manifestations of leprose process, it is quite justified in all cases of the enanthesis (an erythema, hyper - or hypopigmentation, papules, infiltrates, hillocks, nodes) which is not regressing during the performing the standard therapy to conduct additional examination of the patient for the purpose of an exception of L. It is necessary to show vigilance also at decrease or disappearance of sensitivity on certain sites of an integument, emergence of paresthesias, unsharply expressed contractures V, IV and III fingers of hands, decrease in an animal force, the beginning atrophy of muscles, pastosity of brushes and feet, the permanent damages of a mucous membrane of a nose accompanied with nasal bleedings, existence of trophic ulcers, etc.
For the correct classification of process carefully study outward of defeats, their number, an arrangement, extent of disturbance of sensitivity and a condition of growth of vellus hair, existence in rashes and in scrapings from a mucous membrane of a nose of mycobacteria of L., and also results of reaction of a pas lepromin. Most precisely at a wedge, inspection of the patient it is diagnosed by LL. At establishment of other groups the final diagnosis is possible only on the basis of results gistol, researches. It is established that the changes revealed histologically immunol. reactivity advance changes in a wedge, a picture for weeks, months, and sometimes and for 1 — 2 years. At the same time careful studying nevrol, the status, including a state painful, tactile and a thermoesthesia, bakterioskopichesky, gistol is necessary., rentgenol, a research, statement funkts, tests (with a histamine, with nicotinic to - that, with a mustard plaster, on sweating, etc.).
Radiodiagnosis. At L. hl are surprised. obr. bones of distal departments of extremities. For lepromatous type (LL) the main rentgenol. signs are the single or multiple centers of specific inflammatory destruction (leproma) and neurotrophical changes which are characterized by an atrophy osteoporosis (see) and rassasyvaniye of a bone tissue; lepromas are more often localized in spongy substance, is more rare in cortical substance of phalanxes, metacarpal and plusnevy bones (fig. 6). At destruction of joint surfaces shift distally of the located bones to formation of an incomplete dislocation or dislocation happens by them.
At the tuberculoid type (TT) focal destruction of a bone tissue meets quite seldom. Phenomena ossifluence (see) as consequences of neurotrophical and vascular disorders are observed at all types L., followed by polyneurites. In the beginning these changes are shown by a smoothness of nail shoots, expansion of the channels feeding a bone, and in later stages — conduct to mutilation of phalanxes of brushes and feet. The concentric atrophy of phalanxes which is one of characteristic signs of L., causes a peculiar deformation of bones in the form of a chess pawn (fig. 7).
The resorption of bones can conduct to patol, to changes, incomplete dislocations, dislocations, an anchylosis, to partial or full rejection of bones (fig. 8). Changes in bones of feet are usually more expressed owing to accession of the osteomyelitis causing sequestration, destruction of bones and lead to deep disability of the patient. Also periostites and hyperostoses plusnevy, metacarpal meet, is more rare than long tubular bones of forearms and shins.
Functional trials. Pharmakodinamichesky tests help to reveal characteristic of L. very early defeats of a peripheral nervous system which are shown in addition to disturbances of superficial types of sensitivity, various vasculomotor, secretory and trophic frustration. Test with a histamine, morphine or dionine is most widely applied. On one drop of 0,1% of water solution of a histamine (or 1% of solution of morphine, 2% of solution of dionine) apply on the studied affected area and on externally not changed skin. Through drops make the easy, not reaching capillaries prick or do scratch. The limited erythema appearing in the place of a prick shall be replaced in 1 — 2 min. by a reflex erythema diameter in several centimeters, in the center the cut still is in a few minutes formed a blister or a papule. Completely all three phases of reaction (Lewis's triad) are observed at healthy people, on not affected skin at sick L. and on rashes of not leprose etiology. On defeats of a leprose origin, i.e. at defeat of nerve terminations, the reflex erythema developing by the principle axon reflex (see), is absent or it is expressed much more weakly.
For identification hardly noticeable, doubtful and even the manifestations of leprose process which are not seen even at usual survey apply test with nicotinic to - that, offered by N. F. Pavlov (1949). In 1 — 3 min. after intravenous administration of 5 — 8 ml of 1% of water solution nicotinic to - you appear gradually amplifying erythema of all integument, edges usually disappears in 10 — 15 min. On site defeats of a leprose etiology, including and invisible, there are sites of bright red color which are often towering in the form of blisters (the phenomenon of «ignition and hypostasis» of rashes caused by disturbance of adaptation ability of vazomotor).
In the presence of a hyponevus pigmentosus very valuable to identification of vasculomotor disturbances can be a test with a mustard plaster. The mustard plaster by a usual technique is imposed on border of the explored suspicious site and the surrounding not affected skin. At the same time on a spot of a leprose etiology the erythema does not develop or happens considerably less expressed, than on not affected skin surrounding it. The similar effect is observed also at radiation by an erythema dose of UV rays.
Characteristic of L. a sign is disturbance of sweating. The explored site of skin is greased with a reactant of the Minor (iodine of 2 g, castor oil of 15 g, alcohol of 98% to 100 ml) or just by 2 — 5% solution of iodine and after drying powder starch. For stimulation of sweating of the patient place in a sukhovozdushny bathtub or allow to drink hot to tea. On sites of skin with undisturbed sweating the dissolved iodine, connecting to starch, gives blue coloring whereas on sites of leprose defeats blue coloring does not appear.
Laboratory diagnosis consists in carrying out bakterioskopichesky and gistol, researches. The Bakterioskopichesky research has crucial importance for early diagnosis of L. only during the receiving positive takes and it is especially important at suspicion on LL or BL. At a TT, W of a mycobacterium can not come to light.
Usually for a bakterioskopichesky research take scraping from a mucous membrane of a nose and a skarifikata from an affected area of skin, and also skin of superciliary arches, lobes of auricles, a chin, distal departments of extremities. For capture of a skarifikat skin is clamped two fingers pleated, lengthways cover with a scalpel do a small section (depth of 1 — 2 mm) and transfer scraping from walls of a cut to a slide plate; smears paint across Tsil — to Nelsen. During the carrying out gistol, a part of cuts also paint researches on Tsil — to Nelsen for identification of mycobacteria.
The differential diagnosis should be carried out with many diseases of skin and a peripheral nervous system. Feyzel (P. Fasal, 1975) calls L. the «great simulator» capable to imitate many diseases of skin and a peripheral nervous system. From skin diseases, the wedge, manifestations to-rykh are similar to L., it must be kept in mind a grumous syphilide, syphilomas first of all (see. Syphilis ), toksikodermiya (see), a mnogoformny exudative erythema (see. Erythema exudative mnogoformny ), red flat deprive (see. Deprive red flat ), a tubercular lupus (see. Tuberculosis cutis ), sarcoidosis (see), scleroderma (see), vitiligo (see), fungoid mycosis (see. Mycosis fungoid ), reticuloses of skin (see), leushmaniosis (see), a knotty erythema (see. Erythema knotty ), the trophic and pro-butting ulcers of various etiology (see. Trophic ulcers ), I will give rise (see), pellagra (see), a pigmental small tortoiseshell (see. Mastocytosis ), etc.
In the countries of a tropical belt the differential diagnosis of L. it is necessary to carry out with such diseases as actinomycosis (see), sporotrichosis (see), zymonematosis (see), onchocercosis (see), pint (see), frambeziya (see).
Certain difficulties can meet at differentiation of L. and those defeats of a peripheral nervous system, at to-rykh there are disturbances of sensitivity, a contracture, amyotrophy, mutilation. Treat them myelosyringosis (see), traumatic neuritis (see), myelodisplasias, an acro-osteolysis, neural amyotrophy of Sharko — Mari (see. Amyotrophy ), hypertrophic neuritis of Dezherin — Sotta (see. Dezherina-Sotta hypertrophic neuritis ). At differentiation with these diseases it is necessary to take into account that at sick L. disturbances of superficial types of sensitivity whereas motive functions and deep sensitivity remain therefore they have no ataxy prevail. Defeats of sensitivity at L. never develop on segmented type. Also the atrophy of muscles of a shoulder girdle and proximal departments of extremities does not develop. C. N of page at L. is not surprised.
the Fixed antileprotic assets are drugs of a sulfonic row: diafenilsulfon (DDS, dapsone, avlosulfon), Solusulfonum (Sulfetronum), Diuciphonum, diacetyl-diamino-difenilsulfon, along with to-rymi apply rifampicin, lampren, Prothionamidum and Etioniamidum. Treatment of sick L. shall be complex, including use at the same time of two-three antileprotic drugs in a combination to the stimulating and fortifying means (gamma-globulin, pyrogenal, methyluracil, a hemotransfusion, vitamins, lipotropic substances). Diafenilsulfon apply inside in a daily dose from 50 to 200 mg. Oil suspension of dapsone in the corresponding dose is entered intramusculary 1 — 2 time a week. Diacetyl-diamino-difenilsulfon (DADDS) — sulphone of the prolonged action — is entered intramusculary 1 time in 72 days on 225 mg.
Solusulfonum in the form of 50% of solution 2 times a week in the maximum dose enter intramusculary 3,5 ml (the first injection — 1, ml, the second — 2 ml, the third — 3 ml, the fourth and the subsequent — 3,5 ml). Rifampicin (Rifadinum, Benemycinum) is appointed inside daily on 300 — 600 mg. Prothionamidum (Trevintixum) — on one tablet (0,25 g) from 1 to 3 times a day in 1 hour after food. Etioniamidum (Trecatorum) — on 0,25 g 2 — 3 times a day. Lampren (In 663, clofazimine) — inside daily on 100 mg (one capsule). The course of treatment antileprotic drugs proceeds 6 months. At their good tolerance treatment is carried out without breaks between courses. As a rule, include one of drugs of a sulfonic row and one-two drugs of other chemical structure in a complex of antileprotic means. For the purpose of increase in efficiency of treatment and the prevention of development of medicinal stability it is recommended to alternate drugs and their combinations through each 2 courses of treatment. Only a serious illness of internals can be a contraindication for performing the combined treatment.
At treatment of sick L. attempts to strengthen reactions of cellular immunity by use along with sulphones of various immune drugs were made. Repeated injections of BTsZh, purpose of levamisole, repeated introductions of leukocytic «transfer factor», and also suspension of allogenic leukocytes were the most effective. Goudel (T. Godal, 1978) considers all these methods perspective, but needing more careful argumentation, improvement and studying of possible side effects.
At treatment of L. quite often a wedge, displays of leprose neuritis accrue. It is explained by bystry substitution of granulomas in nerves cicatricial (fibrous) fabric that shall not be considered as a contraindication to continuation of treatment. For the purpose of the prevention of development or progressing of neuritis, amyotrophy and contractures in number to lay down. actions physiotherapeutic procedures from the very beginning shall join, lay down. gymnastics, mechanotherapy.
In the period of the reactive phases proceeding without the expressed disturbance of the general state, treatment should be continued, without reducing a dose, at heavy reactions — temporarily to cancel, appointing desensibiliz ruyushchy, fortifying and symptomatic means.
Efficiency of antileprotic treatment is estimated on the speed of regress a wedge. manifestations of L., by results of bakterioskopichesky control of dynamics of number of the activator in the centers of defeat and change of its morphology, and also by data gistol, researches.
For standardization, comparability and objectivity of assessment of results of bakterioskopichesky researches systems of their digital expressions — bakterioskopichesky indexes (BINS) are developed.
In the absence of effect of treatment and in cases of a recurrence of a disease it is necessary to exclude a possibility of development of resistance of mycobacteria of L. to the carried-out therapy. For this purpose use infection of mice by Shepard's method with the subsequent their treatment, and also well controlled treatment of the patient in the conditions of a hospital. In the latter case, if at the patient as a result of 3 — 6-month regular treatment is not observed regress a wedge., bakterioskopichesky and gistol, indicators, it is regarded as resistant to this antileprotic drug or a combination of drugs.
According to the V Committee of WHO experts (1976), at sulfonic monotherapy annually approximately at 3% of patients a recurrence of a disease is registered. Recurrence arises after the termination of treatment more often (i.e. are caused by persistent mycobacteria of L.), but are possible also against the background of a sulfonoterapiya (i.e. are caused by resistance of mycobacteria of L. or specific features of a macroorganism to metabolize drug).
Several methods of quantitative definition of sulphones in liquids and body tissues are developed for individual treatment and its control (colorimetric, flyuorometrichesky, gazokhromatografichesky, hromatodensitometrichesky, etc.). The only metabolite of dapsone in blood is monoacetyl-dapsone. Speed of acetylation of dapsone at certain patients is various and, according to Ellard (G. A. Ellard, 1974), fluctuates from 14 to 53 hour. To considerable fluctuations, depending on a phenotype, it is subject as well the speed of removal of sulphones from an organism of the patient. These indicators need to be considered at selection of the correct mode of treatment.
As Waters (M. of F. Waters, 1973) et al., even after many years of a sulfonoterapiya and full regress of skin manifestations of L established., viable mycobacteria of L. continue to come to light in peripheral nerves and cross-striped muscles though dapsone easily gets into these fabrics. Final explanation of such persistirovaniye of mycobacteria of L. it is not found, but is undoubted that it can be one of the main reasons for a recurrence of L. For this reason most of researchers considers that modern antileprotic means of sick L. (especially LL, BL and V B) should be treated throughout all their life. Treatment of sick TT shall continue not less than 3 — 5 years.
Achievements of chemotherapy, having caused e ample opportunities of use of dispensary methods of controlling L., gave special relevance to questions of physical and social rehabilitation of sick L. S the purpose of prevention of small injuries, attritions, burns, to-rye can lead to emergence of the hardly healing ulcers, contractures and other deformations, it is very important to train patients with disturbances of sensitivity of brushes and feet to use various devices during the performance of mechanical work and during the use of heating devices, it is correct to select footwear or to use orthopedic footwear, daily carefully to examine skin of brushes and feet, to treat timely any wound. Certain success in business of prevention of development of disability and elimination already developed physical is achieved. shortcomings (deformations of extremities, trophic ulcers, cosmetic defects, damage of eyes) methods of a plastic surgery and physical therapy.
Social and economic readaptation of sick L. includes overcoming a leprofobiya at a zdorovogoa of the population, psikhol, rehabilitation of the most sick, its employment and if it is required — professional reorientation that gives the chance to the patient to feel like the useful and full member of society.
the Forecast at L. depends on type of a disease, a stage of process at the time of an initiation of treatment and the correct selection of pharmaceuticals. Before use of drugs of a sulfonic row life expectancy of patients with lepromatous type L. (LL), according to various authors, averaged 12 — 15 years since emergence of the first a wedge, symptoms of a disease. The lethal outcome most often came from the asphyxia caused by obstruction of a trachea lepromas, intercurrent diseases, a leprose cachexia and also from the uraemia caused by an amyloidosis of kidneys. The patient becomes the deep disabled person by this time, at to-rogo mutilations and contractures of extremities, multiple trophic ulcers, paralyzes, a blindness, deformation of a nose, damage of internals are observed. At the same time separate cases when the diseased of LL lived 30 — 40 years are known. In extremely exceptional cases there occurred the self-healing of LL which was followed by the expressed disability. Patients with tuberculoid type L. (TT) and undifferentiated L. often lived to a ripe old age, and in a picture of disability effects of defeat of trunks of peripheral nerves prevailed (contractures, paralyzes, stir up l I tion).
After introduction to practice of chemotherapy of L., in particular drugs of a sulfonic row, rates of mortality of sick L. and average age of the dead approached indicators of the dead from other reasons.
In case of early diagnosis of L. (in 6 — 12 months after emergence of the first symptoms of a disease) and on condition of regular effective treatment can not remain with the patient any disabling effects of L. At later initiation of treatment (in 1 — 3 years after an onset of the illness) at sick L. there can be disturbances of sensitivity, amyotrophy, a contracture of fingers of hands, paresis that involves decrease in an animal force, restriction of working capacity.
Prevention at L. consists of individual and public (social) safety actions. Features of prevention at L. are caused by a long incubation interval, i.e. impossibility of use of measures, similar to a quarantine, and also lack of a vaccine and high-speed drugs. The extreme importance in prevention of L. has carrying out all-recreational and a dignity. - a gigabyte. actions: increase in living standards of the population, improvement of conditions of life, personal hygiene.
Individual prevention consists in the basic in observance of measures of personal hygiene.
Sick L. shall have a separate bed, separate ware, often and carefully to wash, to often make bandagings izjyazvivshikhsya lepromas and trophic ulcers, to be treated regularly. For members of the family of the patient as well as for the servicing medical staff, no special rules of conduct, in addition to respect for the standard standards of personal hygiene, are required. Medics should use gloves only at capture of biopsies and surgical interventions, and a mask — at inspection of upper respiratory tracts or at capture of scraping from a mucous membrane of a nose.
In the most ancient way of public prevention of L. in the conditions of lack of effective treatment full isolation of patients in specially intended for this place was — leper colonies (see). Establishment inf. nature of L. served as scientific justification of need of sanitary isolation of sick L. V the majority of the countries in specialized antileprotic institutions (leper colonies, antileprotic clinics of a pla sanatoria) only patients — bakteriovydelitel are hospitalized. In the nek-ry countries (e.g., in England, France, etc.) there are no specialized antileprotic institutions, and in case of need sick L. hospitalize in specialized departments or chambers in hospitals of tropical dermatology or in inf.-tsakh.
In the USSR the leader in fight against L. the dispensary method combining in itself a complex social, preventive is and to lay down. actions. Possibility of isolation of sick L. at home it was legalized by the resolution SNK in 1923. According to the existing «Instruction for fight against a leprosy» registration and the accounting of all patients with this disease are obligatory; treatment of again revealed patients is carried out as in antileprotic institutions, and is out-patient at the place of residence. In protpvoleprozny institutions hospitalize for carrying out the initial stage of treatment (before achievement of a bakterioskopichesky negativation) patients with «open» forms L.: 1) all patients with lepromatous, boundary and lepromatous and boundary forms L.; 2) patients with tuberculoid and boundary and tuberculoid forms if they have widespread skin rashes, results of a bacterioscopy positive and also if process is in a stage of an aggravation; 3) the patients who are on medical examination at emergence of a palindromia.
On an outpatient basis at the place of residence again revealed patients with the TT and W forms at limited skin manifestations and negative takes of a bacterioscopy of scrapings from a mucous membrane of a nose and skarifikat of affected areas of skin can be treated.
All patients discharged from leper colonies at emergence at them associated diseases (except for a recurrence of L.), demanding hospitalization, can be hospitalized in the general and any specialized to lay down. institutions without any restrictions.
In local but L. zones it is reasonable to inspect the healthy population by means of Mitsuda's reaction. Persons with an anergy to mycobacteria of L. it is necessary to include in the group of the increased risk of a disease needing constant observation, vaccination of BTsZh or preventive treatment.
A specific vaccine against L. no. Since 1974 under the direction of WHO within the special program for tropical diseases the program of scientific research but immunology of L is developed., the cut is an ultimate goal receiving a vaccine against L.
Strengthening of antileprotic immunity and transition of negative reaction on lepromin in positive can achieve vaccination of BTsZh therefore it can be used for prevention of L. However sufficient proofs of specific preventive action of BTsZh at L. it is not received since results of vaccination of BTsZh of inhabitants high-endemic on L. districts yield unequal results.
It is necessary to carry out preventive treatment of the persons which had long family contact with sick L., one of sulfonic drugs, a dosage and the scheme of introduction to-rogo same, as well as at sick L. Prodolzhitelnost' treatment preventive treatment — from 6 months to 3 years.
The «Instruction for preventive treatment at a leprosy» existing in the USSR provides performing chemoprophylaxis to persons aged from 2 up to 60 years. living in one family with sick H.p. forms LL, BL or Centuries. Antileprotic institutions are responsible for the organization and control of performing preventive treatment, and direct carrying out it is assigned both to antileprotic network, and to a skin venerol, clinics and local out-patient and polyclinic institutions.
As sick L. the paramount importance in prevention of L is the only source of a disease. has identification and treatment of patients in the earliest stage of a disease. Definition of group of people shall follow identification of the patient, the Crimea it could transmit an infection. For identification of patients in zones, local on L., routine maintenances shall be performed regularly. Members of families of sick L. put under dispensary observation. Medical examinations and, in case of need, lab. examinations are conducted quarterly or at least once a year. Duration of observation in various countries fluctuates from 3 to 10 years. If the prevalence reaches 1: 1000, L. for this area it is necessary to consider an important problem of public health care and it is recommended to conduct, in addition to regular inspection of contact persons, annual examinations of all school students and other groups of the organized population. At spread of a disease 5: All population is subject to 1000 annual inspections, and at a prevalence of L. 10: 1000 and more all inhabitants of this area are considered as contact.
In the majority of the countries sick L. are not allowed to work on the professions connected with direct service of people in child care and medical facilities at the food and utility enterprises, such as baths, hairdressing salons, etc. There are interstate agreements prohibiting entrance of sick L. to the nek-ry countries.
The children who were born at sick L. in antileprotic institutions, it is recognized possible to leave with mother for the period to 2 — 3-year age. If mother at the same time is accurately treated and observes necessary a dignity. - a gigabyte. norms, potentiality of a disease of the child practically comes down to zero. Moreover, it is established that with milk of mother a certain amount of sulphones is distinguished, and the child, therefore, receives preventive treatment. On reaching 3-year age the child as well as children of advanced age, for treatment of mother in antileprotic establishment it is transferred or to special orphanage for the children who were born from sick L. parents, or in orphanage of the general type. Any restrictions for the children who were born from sick L. there are no parents, in visit of school or other children's collectives. At the same time they, as well as other contact persons, shall be during an established period under constant medical observation. There are no restrictions in choice of profession by the persons who had long family contact with sick L. V the nek-ry countries of the children who were born from sick L also. parents, before the expiration of control overseeing by them do not call up for military service.
Dignity. - a gleam, work it has to be carried out differentially among sick L., members of their families and healthy population. In many countries there is a discriminatory treatment of sick L. and to members of their families. It quite often leads to concealment of patients, self-treatment. Giving the correct ideas of the nature, distribution and prevention of L., and also about importance of an early initiation of treatment of patients and a possibility of their treatment, a dignity. education promotes overcoming a leprofobiya and increase in efficiency of national programs of fight against L.
Bibliogr. Abdirov Ch. A., Dzhumanazarov A. D. and Podoplelov I. I. Blood groups and leprosy of the person, Nukus, 1977, bibliogr.; And l and m gifts Y. H. Some topical issues of a neuroleprology, Uchen. zap. Ying-that on studying of a leprosy, No. 9 (14), page 5, Astrakhan, L976, bibliogr.; B of e to e of l-l and L. and To m and N of of e since Century. The latest data on distribution of a leipa in the world, Bulletin WHO, t. 46, JNo 4, page 512, 1973; In and sh-N of e in e of c to and y F. E. Interpretation of data of a cytochemical research of a leprose cell in the light of modern ideas of a macrophage, Uchen. zap. Ying-that on studying of a leprosy, No. 9 (14), page 155, Astrakhan, 1976; E in with t r and t about in and V. A. Changes of bones at patients with a leprosy (X-ray inspection), Saturday. nauch. works on a leprosy, under the editorship of I. N. 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A phenomenon of «ignition and hypostasis» of spots after niacin at early diagnosis of a leprosy, Vestn, veins. and dermas., JSIa 5, page 45, 1949; Recognition and prevention of a leprosy, under the editorship of I. N. Pe-revodchikov and V. F. Choubin, M., 1957; Resheti of l of l about D. F. Leprosy, SPb., 1904; T about r with at e in N. A. The bibliographic index of works of domestic authors on a leprosy (till 1957 inclusive), Rostov N / D., 1959, 1964, 1968, 1974; it, Recognition and differential diagnosis of a leprosy, M., 1971, bibliogr.; T about r with at e in N. A. and the Log and - N about in V. K. Lepr of internals, Uchen. zap. Ying-that on studying of a leppa, No. 8 (13), page 7, Astrakhan, 1974; Choubin V. F. About use of system of epide-metric sizes in a leprology, in the same place, No. 5 (10), page 140, 1968, bibliogr.; Yu shch e of the Tax Code about And. 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A. A. Yushchenko; T. E. Vishnevetsky (stalemate. An.), V. A. Evstratova (rents.).