Syphilis of the urogenital organs

Syphilis of the urino-genital organs is a chronic infectious disease caused by pale treponema, transmitted predominantly through the sexual way, and also vertically (from mother to the fetus). Without treatment for syphilis, a prolonged course characterized by periodic damping (remissions) and exacerbations, which are accompanied by the formation of foci of specific inflammation in all organs and tissues.

The natural course of syphilis can vary greatly.

ICD-10 codes

• A51. Early syphilis.
• A52. Late syphilis.
• A50. Congenital syphilis.
• A53. Other and unspecified forms of syphilis.

Epidemiology of genitourinary syphilis

The last decade of the XX century. Was characterized by an extremely high incidence of this infection in Russia and Eastern Europe. According to WHO, during the year around 12 million cases of syphilis are registered in the world. In view of the incomplete registration of syphilis of the genitourinary organs, the actual rates of its incidence are several times higher than those of official statistics.

[1], [2], [3], [4], [5], [6], [7],

What causes syphilis of the urino-genital organs?

The causative agent of syphilis of urogenital organs is pale treponema (Treponema pallidum). It refers to the order of Spirochaetales, the family Spirochaetaceae, the genus Treponema, the species Treponema pallidum. Under a light microscope, the spirochete varies from 0.10 to 0.18 nm in diameter and from 6 to 20 nm in length. Visualization of the microorganism is possible through darkfield or phase-contrast microscopy, as well as impregnation with silver.

The main way to transfer syphilis of the urino-genital organs is sexual contact. A kiss, a blood transfusion, infection of the fetus, a household way of transmission are no less important today. Most children with congenital syphilis were infected in utero, but the newborn could also become infected by contact with infected generic pathways during labor. Infectious contamination (with cuts of the skin of the hands) has been described in medical workers when contacting a patient without using gloves.

The time from infection to the manifestation of primary syphilis is called an incubation period, the duration of which is on average 3-4 weeks. The average incubation period (3 weeks) is provided by the introduction of 500-1000 microorganisms. However, it can reach 4-6 months due to the uncontrolled use of antibiotics for various diseases, as well as under the influence of several other factors.

Symptoms of syphilis of the urino-genital organs

The first clinical sign of the disease is hard chancre, appears on average 3-4 weeks after infection on the spot, where pale treponema penetrated the body. From this moment the primary period of syphilis begins, which lasts until the appearance of multiple syphilitic eruptions on the skin and mucous membranes and lasts 7-8 weeks.

At first, the primary affect develops as a painless sealed papule. Then its surface is necrotic with the formation of erosion or ulcers with clear boundaries containing treponema. Histopathologically, chancre is characterized by perivascular infiltration by plasma cells, lymphocytes, histiocytes, endothelial proliferation of capillaries with outcome in obliterating endarteritis. Pale treponema is located in inter-epithelial spaces, in invaginations of phagocytes of endothelial cells, fibroblasts, plasma cells and endothelial cells of small capillaries, inside lymphatic canals and regional lymph nodes. The second characteristic symptom of this stage of syphilis is regional lymphadenitis. Serous fluid from the lesions contains treponema. The diagnosis can be confirmed n) the detection in a dark field or the PCR method.

The primary period of genitourinary syphilis is divided into primary seronegative (standard serological reactions are still negative) and primary seropositive (standard serological reactions become positive, which occurs 3-4 weeks after the onset of primary syphiloma).

After 7-8 weeks after the appearance of primary syphiloma or 10-12 weeks after infection, a secondary period of syphilis occurs. Secondary syphilis of the genitourinary organs is a stage of dissemination of the disease and is caused by the proliferation and spread of spirochetes in the body, with treponema found in most organs and tissues, despite the presence of anti-treponemal antibodies in high concentrations. Clinically, the secondary period of syphilis is characterized by manifestations on the skin and mucous membranes of rosaceous, papular pustular eruptions, lesions of internal organs, nervous and bone systems. Nonspecific symptoms of secondary syphilis include fever headache, sore throat, arthralgia, anorexia, generalized lymphadenopathy. Eruptions of the secondary period after a few weeks independently disappear, and the latent period of the disease sets in. After a while, relapse occurs, the skin and mucous membranes again appear rashes, characteristic of the secondary period, after which the latent period of the disease may again occur. The secondary period of genitourinary syphilis without treatment can last 3-4 years.

In the secondary period of the disease, with rare exceptions, all serological tests for urogenital syphilis are positive. Pale treponema is found in the separated syphilis.

Syphilitic lesions can develop in any internal organ. They have an inflammatory or dystrophic character, occur asymptomatically or with various functional disorders, less often acquire a clinically pronounced character. Early lesions of syphilis of internal organs are not always diagnosed, as in a routine clinical examination, as a rule, they can not be identified. The clinical picture of diseases of internal organs affected by syphilitic infection by any specific symptoms is not manifested. Diagnosis is established based on the detection of lesions of the skin and mucous membranes and positive serological reactions in the blood. In the vast majority of observations, visceral syphilis responds well to antisyphilitic treatment.

The defeat of the kidneys, as a rule, is revealed at the beginning of the secondary fresh syphilis. It manifests itself in the form of asymptomatic renal dysfunction, determined by the results of radionuclide renography, benign proteinuria, syphilitic lipoid nephrosis and glomerulonephritis. The only symptom of benign proteinuria is the presence of protein in the urine (0.1-0.3 g / l).

Syphilitic lipoid nephrosis is observed in two versions: acute and latent. In acute lipoid nephrosis, the patient's skin is pale, swollen. Urine is turbid, excreted in small amounts, has a high relative density (up to 1.040 and above): the amount of protein in the urine usually exceeds 2-3 g / l. The sediment contains cylinders, leukocytes, epithelium, fat drops: erythrocytes - rarely in small amounts, arterial pressure is not increased, the fundus is normal. The latent nephrosis develops slowly, sometimes after a considerable time after infection, is manifested by moderate albuminuria and minor edema.

Specific nephritis is diagnosed as membrane tubulopathy and infectious glomerulonephritis. At the heart of kidney damage is the primary lesion of small vessels, the gradual death of the glomeruli and the progressive shrinking of the kidney. Syphilitic glomerulonephritis is due to its disease immune complexes. These complexes include treponemal antigen, anti-gonadal IgG antibodies and the third complement component (C3).

Immune complexes are deposited in the subepithelial basement membrane zone. Specific treatment of late syphilis of the kidneys is very effective. It prevents the development of chronic nephrosis and kidney failure. One-third of patients (if they do not receive proper treatment) after 10-20 years and earlier (3-6 years) there comes the tertiary period of syphilis of urogenital organs, which is characterized by the formation of tertiary syphilis (tubercles and hum).

Syphilis can be single and multiple and vary in the exchange from microscopic defects to large tumor-like formations in which a small amount of treponemus is usually present. Late forms of syphilis of the urogenital organs.

• Nervous system (neurosyphilis) - dorsal, progressive paralysis
• Internal organs (viscerosyphilis) meso-aortitis, aortic aneurysm, liver and stomach damage.

In this period, the course of syphilis is also wavy, the phases of active manifestations can be replaced by phases of latent syphilis.

In the tertiary period of syphilis of the urogenital organs, limited gums or gummy infiltrations may appear in all internal organs, as well as various dystrophic processes and metabolic disorders. Most often, late syphilis affects the cardiovascular system (90-94%), less often the liver (4-6%) and other organs - lungs, kidneys, stomach, intestines, testicles (1-2%).

Kidney damage can be in the form of amyloid nephrosis, nephrosclerosis and gummy processes (limited nodes or diffuse gummy infiltration). The two first forms are clinically no different from similar lesions of another etiology, the diagnosis is established only on the basis of concomitant manifestations of urogenital syphilis, anamnesis and positive serological responses. Limited gummy nodes occur under the guise of tumors and are difficult to recognize. Thus there are edemas, in the urine they detect blood, protein, cylinders. The disease is sometimes accompanied by paroxysmal pain in the lower back. When the breakdown of gum and the breakthrough of the contents in the pelvis, a thick turbid brown urine with abundant sediment from erythrocytes, leukocytes, and cellular detritus is released. Sclerotic process in the kidney leads to an increase in blood pressure, hypertrophy of the left ventricle of the heart.

The defeat of the testicle is characterized by the appearance of limited gummy nodes or diffuse infiltrate in the parenchyma of the organ. The affected testicle increases, becomes dense, heavy. With limited shape, the testis surface is tuberous, with a diffuse smooth, even surface. Palpation is painless. Disturbing the feeling of heaviness as a result of stretching the spermatic cord. Limited gums can be opened through the skin of the scrotum. The resolution of a diffuse gummy infiltrate leads to testicular atrophy.

Diagnosis of late visceral syphilis is very difficult. In patients, as a rule, several organs and the nervous system are affected. Syphilitic damage to one organ often leads to a pathogenetically related disorder of the function of other organs. These secondary diseases can hide the syphilitic nature of the main process. It is difficult to diagnose the absence in the anamnesis of 75-80% of patients of the indication of syphilis of urogenital organs in the past. Standard serological reactions of blood are positive in 50-80% of patients, the reaction of immobilization of pale treponemes (RIT) and the reaction of immunofluorescence - in 94-100%. In addition, in patients with active visceral syphilis, serological reactions, including RIT and immunofluorescence, may be negative. In doubtful cases, a diagnostic therapy should be used as a diagnostic technique.

Tertiary period of infection is considered to be non-contagious. The basis for the diagnosis is usually the positive results of treponemal reactions. Treponema can be detected in gammas or organ biopsy with direct microscopy.

The traditional staged course of syphilis of the urogenital organs occurs in a significant number of patients. However, in recent years, patients with an asymptomatic course of the disease are increasingly diagnosed, diagnosed only serologically.

In a number of patients, there is no infection at all, or cases of self-healing are observed, which can be explained by the peculiarities of the patient's organism, in particular, by the presence of normal immobilizins possessing treponemacid and treponemastatic properties.

Immunity with syphilis of the genitourinary organs is contagious and exists as long as there is an agent in the body. It is generally accepted that people infected with syphilis have a certain immunity to exogenous reinfection (the so-called chancroid immunity). Unsuccessful attempts to create an antisyphilitic vaccine are due to the fact that this microorganism is not cultivated on nutrient media.

Natural barriers that prevent the penetration of the pathogen into the human body:

• undamaged skin due to its integrity and the presence of fatty acids and lactic acid (the products of vital activity of sweat and sebaceous glands) that create low acidity (pH), harmful to microorganisms;
• mucus secreted by the cells of the genital tract, due to the viscosity creates an obstacle to the penetration of microorganisms;
• bactericidal components of the body - spermine and zinc of male sperm, lysozyme (saliva, tears), bactericidal proteolytic enzymes;
• normal bactericidal flora (eg, Dodderlein sticks in the vagina). Acting on the principle of competition with the microbe.
• phagocytosis.

Diagnosis of urogenital syphilis

To establish the diagnosis, in addition to the history and objective examination of the patient, laboratory methods of investigation are necessary: bacterioscopy, serological examination of blood, examination of cerebrospinal fluid.

Sensitivity and specificity of various methods of diagnosis of urogenital syphilis

Method	Sensitivity	Specificity
Darkfield microscopy	70%	100%
PCR	70-90%	99%
MP (RMP) and its variants	70%	80%
The complement fixation reaction	80%	98%
Immunofluorescence reaction	84-99%	97-99%
RIT	79-94%	99%
ELISA	98-100%	96-100%
Passive hemagglutination reaction	93-98%	98%

At the first clinical signs of syphilis of the urogenital organs and the appearance of a solid chancre, the diagnosis can be confirmed by positive results of darkfield microscopy and PCR from the separated syphilis and punctate regional lymph nodes, as well as RIFabs, the earliest and sensitive treponemal reaction, and ELISA that detects the total (IgM- IgG) antibodies, sometimes a direct hemagglutination reaction and a complement fixation reaction with treponemal antigen. After 2-3 weeks after the appearance of a hard chancre or 5-6 weeks from the moment of infection, i.e. At the stage of primary syphilis (seropositive according to the old classification), 60-87% of patients undergo positivisation of the so-called non-treponemal tests that detect antibodies to non-treponemal antigen (AH), which is usually a cardiolipine-lecithin-cholesterol complex.

This is the complement fixation reaction with the cardiolipin antigen, or the Wasserman reaction itself, the microreaction of precipitation and its domestic (LUES test) and foreign analogues (RPR, VDRL TRUST and other tests). At the same stage of infection, as a rule, immunofluorescence reactions, ELISA, direct hemagglutination reaction in 80-88% of cases, in a smaller number of patients - RIT (30-50%) are usually positive. The diagnosis can be confirmed by positive results of dark-field microscopy and PCR when taking material from solid chancre and regional lymph nodes.

During the height of the infection, in the secondary stage of the disease almost all patients have positive both non-treponemal and treponemal tests, including one of the most "late" reactions that records the appearance of antibodies-immobilizines-RIT, as well as the direct hemagglutination reaction. A high degree of positivity of these reactions in the latent and further in the Tertiary period of infection. As a rule, is preserved, which often serves as the basis for a retrospective diagnosis in the asymptomatic course of syphilitic infection. The number of positive results of non-treponemal tests, on the contrary, falls with the progression of latency and the transition to late syphilis of the genito-urinary organs (up to 50-70%).

The most spontaneously or under the influence of treatment, the most labile antibodies determined in MP (RMP) and complement binding reactions with cardiolipin antigen are eliminated first, either spontaneously or under the influence of treatment, then in the complement binding reaction with treponemal antigen, as well as IgM antibodies. The indicators of activity of the infectious process. Long-term seropositivity, especially with respect to treponemospecific IgM antibodies, is highly likely to indicate foci of persistent infection. Positive results of such tests as RIT, immunofluorescence reaction, ELISA (IgG or total antibodies), direct hemagglutination reaction, can persist for a long time, sometimes the rest of their lives, testifying about the previous syphilis of urogenital organs. Confirmation of the diagnosis in the secondary stage of the infection is facilitated by positive results of darkfield microscopy and PCR of the separated syphilides, as well as PCR in whole blood, puncture of lymph nodes, cerebrospinal fluid and cells of the phagocytic system.

In the late stages of syphilis of the urogenital organs, the probability of detection of treponema and the products of its decay by the PCR method falls, however, the source of its detection can serve as biopsy specimens of internal organs (liver, stomach), contents of gummy infiltrates and spinal fluid.

Due to its high sensitivity, specificity and reproducibility, ELISA is practically a universal method of examination and can be used for prophylactic examination of the population for syphilis of urogenital organs, with a preventive examination for syphilis in patients with eye, psychoneurological, cardiological hospitals and pregnant women, for donor examination, for diagnosing all forms of syphilis and recognition of false positive results.

In syphilological practice, an indirect variant of ELISA is used, which is one of the most modern and promising methods of syphilis serodiagnosis. This is defined as its high sensitivity (95-99%) and specificity (98-100%) with syphilis, and simplicity, position. Reproducibility, the possibility of using both a diagnostic (treponemal test), and a selection method, as well as a criterion for the cure of the disease and the reference test when taking patients off the register.

PCR is a good method for diagnosing syphilis of urogenital organs with a small amount of treponem in the material under study, although the results can still be considered preliminary. It is highly specific, sensitive, reproducible, universal. With competent conduct and preparation of samples is reliable. However, it should be noted that the method is very sensitive to the quality of reagents (especially to the choice of primers) and requires a special room. It should be noted that in Russia at the moment there is not one officially registered PCR test system and not one standard that allows to evaluate the quality of the proposed kits. Given the complexity of the immune response in syphilis, a comprehensive diagnosis is still required, involving at least two methods: non-treponemal and treponemal. One of the options for an adequate replacement of the conventional serological response is the combination of ELISA and RMP. The undoubted advantage of the combination of ELISA and RMP is due to the possibility of screening and confirming the diagnosis, as well as the quantitative analysis of antibodies, which is especially important in controlling the effectiveness of treatment.

[8], [9], [10], [11]

Treatment of syphilis of the urino-genital organs

Specific treatment of syphilis of urogenital organs is prescribed to a patient with syphilis after confirmation of the diagnosis. The diagnosis is established on the basis of the corresponding clinical manifestations, the detection of the pathogen and the results of the serological examination of the patient (serological reaction complex, immunofluorescence reaction). The investigation of cerebrospinal fluid is performed for diagnostic purposes in patients with clinical symptoms of nervous system damage. It is also suitable for latent and late forms of syphilis of the urogenital organs. Anti-syphilitic drugs without confirmation of the presence of syphilitic infection are prescribed only with preventive treatment, treatment of pregnant women and children, during trial treatment.

Preventive treatment is carried out to prevent syphilis of urogenital organs to persons who were in sexual and intimate contact with patients with early stages of syphilis.

Preventive treatment of genitourinary syphilis is also performed by patients with gonorrhea with an unclear source of infection if it is not possible to establish follow-up care for them.

Preventive treatment is not prescribed for persons who were in sexual or intimate contact with patients with tertiary, late latent, syphilis of internal organs, nervous system. Do not also carry out preventive treatment for persons who have been in sexual contact with patients who have been given preventive treatment (ie, second-order contacts). When detecting syphilis patients in a children's team, preventive treatment is prescribed for those children who can not exclude close household contact with patients.

Trial treatment of genitourinary syphilis can be prescribed for suspected specific lesions of internal organs, nervous system, sensory organs, musculoskeletal system in those cases when the diagnosis can not be confirmed by laboratory data, and the clinical picture does not exclude the possibility of syphilitic infection.

Treatment of syphilis of urogenital organs should be prescribed early, immediately after diagnosis (with early active forms in the first 24 hours). The earlier treatment is started, the more effective and better the prognosis.

Treatment should be full and energetic. Medicinal preparations should be applied in sufficient doses with observance of single and course doses of certain terms.

Treatment of syphilis of urogenital organs should be maximally individualized taking into account the age and physical condition of the patient, the stage and form of syphilitic infection, the presence of intercurrent diseases, the tolerability of drugs. Specific treatment should be more prolonged, and the total doses of antisyphilitic drugs are higher the longer the time has passed since the moment of infection with syphilis.

Treatment of syphilis of the urino-genital organs should be combined. Specific therapy must be combined with methods of nonspecific stimulating therapy, since the results of treatment largely depend on the overall condition of the patient's nature of reactivity and the susceptibility of his organism. Combination treatment is especially indicated in the late stages of syphilis of the urogenital organs, with sero-resistant lesions of the nervous system.

Syphilis of urogenital organs is treated under careful monitoring of the general condition of the patient with the tolerability of the drugs used. Once in 10 days they make a general analysis of blood and urine, measure blood pressure; once in 10 days, and with primary seronegative syphilis and preventive treatment - every 5 days - a complex of serological reactions. With a sharply positive Wasserman reaction in the course of treatment and subsequent observation, it must be repeated, applying various dilutions of the serum and determining the titer of the reactants.

Currently, as antisyphilitic drugs (ie possessing treponemocidal or treponemostic properties), mainly use benzylpenicillin and its durant preparations and bismuth salts.