Genitourinary syphilis

Syphilis of the genitourinary organs is a chronic infectious disease caused by pale treponema, transmitted mainly sexually, as well as vertically (from mother to fetus). Without treatment, syphilis is characterized by a long course with periodic attenuations (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 considerably.

ICD-10 codes

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

Epidemiology of urogenital syphilis

The last decade of the 20th century was characterized by an extremely high incidence of this infection in Russia and Eastern European countries. According to WHO, approximately 12 million cases of syphilis are registered worldwide each year. Due to incomplete registration of urogenital syphilis, the actual incidence rates are several times higher than official statistics.

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

What causes genitourinary syphilis?

The causative agent of urogenital syphilis is pale treponema (Treponema pallidum). It belongs to the order Spirochaetales, family Spirochaetaceae, genus Treponema, 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 using dark-field or phase-contrast microscopy, as well as silver impregnation.

The main method of transmission of urogenital syphilis is sexual contact. Kissing, blood transfusion, infection of the fetus, and household transmission are no less important today. Most children with congenital syphilis were infected in utero, but a newborn could also become infected through contact with infected birth canal during childbirth. Asexual infection (through cuts on the skin of the hands) has been described in health workers through contact with a patient without using gloves.

The time from infection to the manifestation of primary syphiloma is called the 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 some other factors.

Symptoms of syphilis of the genitourinary organs

The first clinical sign of the disease is a hard chancre, which appears on average 3-4 weeks after infection at the site where the pale treponema entered the body. From this moment, the primary period of syphilis begins, which continues until multiple syphilitic rashes appear on the skin and mucous membranes and lasts 7-8 weeks.

Initially, the primary affect develops as a painless, compacted papule. Then its surface necrotizes with the formation of an erosion or ulcer with clear boundaries containing treponemas. Histopathologically, the chancre is characterized by perivascular infiltration by plasma cells, lymphocytes, histiocytes, proliferation of the capillary endothelium with an outcome in obliterating endarteritis. Pale treponema is located in the interepithelial spaces, in invaginations of phagosomes of endothelial cells, fibroblasts, plasma cells and endothelial cells of small capillaries, inside the lymphatic channels and regional lymph nodes. The second characteristic symptom of this stage of syphilis is regional lymphadenitis. Serous fluid from the lesions contains treponemas. The diagnosis can be confirmed by dark field detection or PCR.

The primary period of syphilis of the genitourinary organs 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 syphilis).

The secondary period of syphilis begins 7-8 weeks after the appearance of the primary syphiloma or 10-12 weeks after infection. Secondary syphilis of the genitourinary organs is the stage of dissemination of the disease and is caused by the reproduction and spread of spirochetes in the body, while treponemes are found in most organs and tissues, despite the presence of antitreponemal antibodies in high concentrations. Clinically, the secondary period of syphilis is characterized by manifestations on the skin and mucous membranes of roseolous, papular pustular rashes, damage to internal organs, the nervous and skeletal systems. Non-specific symptoms of secondary syphilis include fever, headache, sore throat, arthralgia, anorexia, generalized lymphadenopathy. The rashes of the secondary period disappear on their own after a few weeks, and a latent period of the disease begins. After some time, the disease relapses, rashes characteristic of the secondary period appear on the skin and mucous membranes again, after which the latent period of the disease may set in again. The secondary period of urogenital 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. Treponema pallidum is found in the discharge of syphilides.

Syphilitic lesions can develop in any internal organ. They have an inflammatory or dystrophic nature, are asymptomatic or with various functional disorders, and less often acquire a clinically expressed character. Early syphilitic lesions of internal organs are not always diagnosed, since they usually cannot be detected during a routine clinical examination. The clinical picture of diseases of internal organs affected by syphilitic infection does not manifest any specific symptoms. The diagnosis is established based on the detection of lesions of the skin and mucous membranes and positive serological reactions in the blood. In the overwhelming majority of cases, visceral syphilis responds well to antisyphilitic treatment.

Kidney damage is usually detected at the onset of secondary fresh syphilis. It manifests itself as 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 variants: acute and latent. In acute lipoid nephrosis, the patient's skin is pale and edematous. Urine is turbid, excreted in small quantities, has a high relative density (up to 1.040 and higher): the amount of protein in urine usually exceeds 2-3 g/l. The sediment contains cylinders, leukocytes, epithelium, fat droplets: erythrocytes - rarely in small quantities, arterial pressure is not elevated, the fundus is normal. Latent nephrosis develops slowly, sometimes after a significant time after infection, manifests itself as moderate albuminuria and minor edema.

Specific nephritis is diagnosed as membranous tubulopathy and infectious glomerulonephritis. The basis of kidney damage is the primary damage to small vessels, gradual death of glomeruli and progressive shrinkage of the kidney. Syphilitic glomerulonephritis is a disease of immune complexes. These complexes include treponemal antigen, anti-treponemal antibodies IgG and the third component of complement (C3).

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

Syphilides can be single or multiple and vary in size from microscopic defects to large tumor-like formations, which usually contain a small number of treponemes. Late forms of syphilis of the genitourinary organs.

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

During this period, the course of syphilis is also wave-like; phases of active manifestations can be replaced by phases of latent syphilis.

In the tertiary period of urogenital syphilis, limited gummas or gummatous infiltrations may occur in all internal organs, and various dystrophic processes and metabolic disorders are also observed. Most often, in late syphilis, the cardiovascular system is affected (90-94%), less often the liver (4-6%) and other organs - lungs, kidneys, stomach, intestines, testicles (1-2%).

Kidney damage may be in the form of amyloid nephrosis, nephrosclerosis and gummatous processes (limited nodes or diffuse gummatous infiltration). The first two forms are clinically no different from similar lesions of other etiologies, the diagnosis is established only on the basis of concomitant manifestations of syphilis of the genitourinary organs, anamnesis data and positive serological reactions. Limited gummatous nodes occur under the guise of tumors and are difficult to recognize. In this case, edema appears, blood, protein, and cylinders are found in the urine. The disease is sometimes accompanied by paroxysmal pain in the lower back. When the gumma disintegrates and the contents break through into the pelvis, thick, cloudy, brown urine with abundant sediment of erythrocytes, leukocytes, and cellular detritus is released. The sclerotic process in the kidney leads to an increase in blood pressure and hypertrophy of the left ventricle of the heart.

The testicular lesion is characterized by the appearance of limited gummatous nodes or diffuse infiltrate in the organ parenchyma. The affected testicle increases in size, becomes dense and heavy. In the limited form, the surface of the testicle is bumpy, while in the diffuse form it is smooth and even. Palpation is painless. The feeling of heaviness as a result of stretching of the spermatic cord is disturbing. Limited gummas can be opened through the skin of the scrotum. Resolution of the diffuse gummatous infiltrate leads to testicular atrophy.

Diagnosis of late visceral syphilis is very difficult. Patients usually have lesions of several organs and the nervous system. Syphilitic lesions of one organ often lead to pathogenetically related dysfunction of other organs. These secondary diseases may conceal the syphilitic nature of the primary process. The absence of any history of urogenital syphilis in 75-80% of patients complicates diagnosis. Standard serological blood tests are positive in 50-80% of patients, and the pale treponema immobilization test (PTT) and immunofluorescence test are positive in 94-100%. In addition, serological tests, including PTT and immunofluorescence test, may be negative in patients with active visceral syphilis. In doubtful cases, trial therapy should be used as a diagnostic measure.

The tertiary period of infection is considered non-infectious. The basis for diagnosis is usually positive results of treponemal reactions. Treponemes can be detected in gummas or organ biopsies under direct microscopy.

The traditional staged course of urogenital syphilis occurs in a significant number of patients. However, in recent years, patients with an asymptomatic course of the disease, which is diagnosed only serologically, have been increasingly identified.

In a number of patients, infection does not occur at all or self-healing cases are observed, which can be explained by the characteristics of the patient's body, in particular, the presence of normal immobilizins with treponemacidal and treponematic properties.

Immunity in urogenital syphilis is infectious and exists as long as the pathogen is present in the body. It is generally recognized that people infected with syphilis have a certain immunity to exogenous reinfection (the so-called schanker immunity). Unsuccessful attempts to create an anti-syphilitic vaccine are due to the fact that this microorganism is not cultivated on nutrient media.

Natural barriers that prevent the pathogen from entering the human body:

• intact skin due to its integrity and the presence of fatty acids and lactic acid (waste products of sweat and sebaceous glands), which create low acidity (pH), which is harmful to microorganisms;
• mucus secreted by the cells of the genital tract, due to its 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 (for example, Doderlein bacilli in the vagina), acting on the principle of competition with the microbe.
• phagocytosis.

Diagnosis of syphilis of the genitourinary organs

To establish a diagnosis, in addition to the anamnesis data and objective examination of the patient, laboratory research methods are necessary: bacterioscopic examination, serological blood test, examination of cerebrospinal fluid.

Sensitivity and specificity of various diagnostic methods for urogenital syphilis

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

At the first clinical signs of urogenital syphilis and the appearance of a hard chancre, the diagnosis can be confirmed by positive results of dark-field microscopy and PCR from the discharge of syphilides and punctates of regional lymph nodes, as well as RIFABS - the earliest and most sensitive treponemal reaction, and the ELISA method, which detects total (IgM-IgG) antibodies, sometimes the direct hemagglutination reaction and the 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 (seropositive according to the old classification) syphilis, 60-87% of patients show positivity of the so-called non-treponemal tests, which detect antibodies to the non-treponemal antigen (AG), which is usually the cardiolipinlecithin-cholesterol complex.

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

During the peak of infection, in the secondary stage of the disease, almost all patients have positive non-treponemal and treponemal tests, including one of the most "late" reactions, registering the appearance of immobilizin antibodies - RIT, as well as the direct hemagglutination reaction. The high degree of positivity of these reactions in the latent and then in the tertiary period of infection, as a rule, remains, 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 genitourinary organs (up to 50-70%).

In this case, the most labile antibodies, determined in MP (RMP) and the complement fixation reaction with cardiolipin antigen, are eliminated first, either spontaneously or under the influence of treatment, then in the complement fixation reaction with treponemal antigen, as well as IgM antibodies. serving as an indicator of the activity of the infectious process. Long-term seropositivity, especially with respect to treponema-specific IgM antibodies, with a high probability indicates the preservation of 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 for the rest of life, indicating a history of syphilis of the genitourinary organs. Confirmation of the diagnosis in the secondary stage of infection is facilitated by positive results of dark-field microscopy and PCR of syphilid secretions, as well as PCR in whole blood, lymph node punctures, cerebrospinal fluid and cells of the phagocytic system.

In the late stages of urogenital syphilis, the probability of detecting treponema and its decay products by PCR decreases; however, biopsies of internal organs (liver, stomach), the contents of gummatous infiltrates and cerebrospinal fluid can serve as a source of its detection.

Due to its high sensitivity, specificity and reproducibility, ELISA is a virtually universal examination method and can be used in preventive examination of the population for syphilis of the genitourinary organs, in preventive examination of patients in eye, psychoneurological, cardiology hospitals and pregnant women for syphilis, in examination of donors, for the diagnosis of all forms of syphilis and recognition of false positive results.

In syphilidological practice, the indirect version of ELISA is mainly used, which is one of the most modern and promising methods of serodiagnosis of syphilis. This is determined by its high sensitivity (95-99%) and specificity (98-100%) for syphilis, as well as simplicity, reliability, reproducibility, the possibility of using both a diagnostic (treponemal test) and a selection method, as well as a criterion for cure of the disease and a reference test when removing patients from the register.

PCR is a good method for diagnosing urogenital syphilis with a small number of treponemes in the test material, although the results can still be considered preliminary. It is highly specific, sensitive, reproducible, and universal. If carried out correctly and samples are prepared, it 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 a single officially registered PCR test system and not a single standard that allows assessing the quality of the proposed kits. Given the complexity of the immune response to syphilis, comprehensive diagnostics are still necessary, involving the use of at least two methods: non-treponemal and treponemal. One of the options for an adequate replacement for the generally accepted complex of serological reactions is a combination of ELISA and RMP. The undoubted advantage of the combination of ELISA and RMP is due to the ability to screen and confirm the diagnosis, as well as quantitative analysis of antibodies, which is especially important when monitoring the effectiveness of treatment.

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Treatment of syphilis of the genitourinary organs

Specific treatment of urogenital syphilis is prescribed to a patient with syphilis after confirmation of the diagnosis. The diagnosis is established based on the corresponding clinical manifestations, detection of the pathogen and the results of serological examination of the patient (a complex of serological reactions, immunofluorescence reaction). A study of the cerebrospinal fluid is carried out for diagnostic purposes in patients with clinical symptoms of damage to the nervous system. It is also advisable for latent and late forms of urogenital syphilis. Antisyphilitic drugs without confirmation of the presence of syphilitic infection are prescribed only for preventive treatment, treatment of pregnant women and children, and trial treatment.

Preventive treatment is carried out to prevent syphilis of the genitourinary organs in persons who have been in sexual and close household contact with patients with early stages of syphilis.

Preventive treatment of syphilis of the genitourinary organs is also carried out for patients with gonorrhea with an unknown source of infection if it is impossible to establish dispensary observation for them.

Preventive treatment is not prescribed to persons who have had sexual or close household contact with patients with tertiary, late latent, internal organs, or nervous system syphilis. Preventive treatment is also not administered to persons who have had sexual contact with patients who have been prescribed preventive treatment (i.e., second-order contacts). When syphilis patients are identified in a group of children, preventive treatment is prescribed to those children for whom close household contact with patients cannot be ruled out.

Trial treatment of urogenital syphilis may be prescribed if there is a suspicion of specific lesions of the internal organs, nervous system, sensory organs, musculoskeletal system in cases where the diagnosis cannot be confirmed by laboratory data, and the clinical picture does not allow us to exclude the possibility of syphilitic infection.

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

Treatment should be complete and vigorous. Medicines should be used in sufficient doses, observing single and course doses of certain periods.

Treatment of urogenital syphilis 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, and drug tolerance. Specific treatment should be longer and the total doses of antisyphilitic drugs should be higher, the more time has passed since the moment of syphilis infection.

Treatment of urogenital syphilis should be combined. Specific therapy should be combined with methods of non-specific stimulating therapy, since the results of treatment largely depend on the general condition of the patient, the nature of the reactivity and susceptibility of his body. Combined treatment is especially indicated in the late stages of urogenital syphilis, with seroresistance and lesions of the nervous system.

Syphilis of the genitourinary organs should be treated under careful control of the patient's general condition and tolerance of the drugs used. Once every 10 days, a general blood and urine test is done, blood pressure is measured; once every 10 days, and in primary seronegative syphilis and preventive treatment - every 5 days - a set of serological reactions. In case of a sharply positive Wasserman reaction during treatment and subsequent observation, it is necessarily repeated, using various dilutions of serum and determining the titer of reagins.

Currently, benzylpenicillin and its durant preparations and bismuth salts are mainly used as antisyphilitic drugs (i.e. those with treponemocidal or treponemostatic properties).