Syphilis clinical guidelines. Latent early syphilis. Terms and Definitions

The causative agent of syphilis belongs to the order Spirochaetales, family Spirochaetaeceae, genus Treponema, species Treponema pallidum, subspecies pallidum (syn. Spirochaeta pallidum). Treponema pallidum is easily destroyed by external agents: drying, heating at 55 ° C for 15 minutes, exposure to a 50-56 ° solution ethyl alcohol. In the same time low temperatures promote the survival of Treponema pallidum. Treponema pallidum is a spiral-shaped microorganism; the number of revolutions of the spiral is from 8 to 12, its curls are uniform and have an identical structure. Performs characteristic types of movement: rotational, translational, wave-like and flexion. It reproduces primarily by transverse division into two or more segments, each of which then grows into an adult. The microorganism can also exist in the form of cysts and L-forms. The cyst is a form of survival of Treponema pallidum in unfavorable environmental conditions, is considered as a resting stage of T. pallidum and has antigenic activity. The L-form is a way for Treponema pallidum to survive and has weak antigenic activity.

According to official state statistical reporting, the epidemiological situation with syphilis is characterized by a gradual decrease in incidence in general Russian Federation(in 2009 - 53.3 cases per 100,000 population; in 2014 - 30.7 cases per 100,000 population). Against the background of a decrease in the overall incidence of syphilis, there is an increase in the number of registered cases of neurosyphilis with a predominance of its late forms (70.1%).

1. sexual (the most common and typical route of infection; infection occurs through damaged skin or mucous membranes);
2. transplacental (transmission of infection from a sick mother to the fetus through the placenta, leading to the development of congenital syphilis);
3. transfusion (with blood transfusion from a donor with syphilis at any stage);
4. contact-household (is rare; occurs mainly in children during everyday contact with parents who have syphilitic rashes on the skin and/or mucous membranes);
5. professional (infection of laboratory personnel working with infected experimental animals, as well as obstetricians-gynecologists, surgeons, dentists, pathologists, forensic experts when performing professional duties).
6. It is possible to infect infants with syphilis through the milk of nursing women with syphilis.
7. Also contagious biological fluids include saliva and semen of patients with syphilis with clinical manifestations of the corresponding localizations. Cases of infection through sweat and urine have been observed.

Currently used in Russia international classification diseases of the 10th revision (ICD-10), which does not always adequately reflect the clinical forms of the disease. Thus, A51.4 (other forms of secondary syphilis) includes early lesions nervous system, internal organs and musculoskeletal system. There is also no division of asymptomatic neurosyphilis into early and late, as a result of which all patients with asymptomatic neurosyphilis, regardless of the duration of the disease, are classified as late syphilis (A52.2). It should be noted that the ICD-10 code ending with the number 9 (A50.9; A51.9; A52.9 and A53.9), as well as A50.2 and A50.7, reflect forms of infection that have not been confirmed laboratory methods diagnostics, being “a basket into which incorrectly executed notices are dumped.”

A50 Congenital syphilis

A50.0 Early congenital syphilis with symptoms

1. Any congenital syphilitic condition specified as early on or occurring before the age of two years.
2. Early congenital syphilis: skin; skin and mucous membranes; visceral.
3. Early congenital syphilitic: laryngitis; oculopathy; osteochondropathy; pharyngitis; pneumonia; rhinitis.

A50.1 Early latent congenital syphilis

1. Congenital syphilis without clinical manifestations, with a positive serological reaction and a negative result in the study of cerebrospinal fluid, manifested before the age of two years.

A50.2 Early congenital syphilis, unspecified

1. Congenital syphilis NOS (not otherwise specified), manifested before the age of two years.

A50.3 Late congenital syphilitic eye damage

1. Late congenital syphilitic interstitial keratitis (H19.2).
2. Late congenital syphilitic oculopathy (H58.8).

A50.4 Late congenital neurosyphilis (juvenile neurosyphilis)

1. Dementia paralytic juvenile.
2. Juvenile: progressive paralysis; tabes dorsalis; taboparalysis.
3. Late congenital syphilitic: encephalitis (G05.0); meningitis (G01); polyneuropathy (G63.0).

A50.5 Other forms of late congenital syphilis with symptoms

1. Any congenital syphilitic condition specified as late or occurring two years or more after birth.
2. Clutton joints (M03.1).
3. Hutchinson: teeth; triad.
4. Late congenital: cardiovascular syphilis (198.);
5. syphilitic: arthropathy (M03.1); osteochondropathy (M90.2).
6. Syphilitic saddle nose.

A50.6 Late congenital syphilis latent. Congenital syphilis without clinical manifestations, with a positive serological reaction and negative test cerebrospinal fluid, manifested at the age of two or more years.

A50.7 Late congenital syphilis, unspecified/Congenital syphilis NOS, manifested at the age of two or more years.

A50.9 Congenital syphilis, unspecified

A51 Early syphilis

A51.0 Primary syphilis of the genital organs. Syphilitic chancre NOS.

A51.1 Primary syphilis of the anal area

A51.2 Primary syphilis of other localizations

A51.3 Secondary syphilis of the skin and mucous membranes

1. Condyloma lata.
2. Syphilitic(s): alopecia (L99.8); leukoderma (L99.8); lesions on the mucous membranes.

A51.4 Other forms of secondary syphilis

Secondary syphilitic: inflammatory disease of the female pelvic organs (N74.2); iridocyclitis (H22.0); lymphadenopathy; meningitis (G01); myositis (M63.0); oculopathy NEC (H58.8); periostitis ( M90.1).

A51.5 Early latent syphilis.

1. Syphilis (acquired) without clinical manifestations with a positive serological reaction and a negative sample of cerebrospinal fluid, less than two years after infection.

A51.9 Early syphilis, unspecified

A52 Late syphilis

A52.0 Syphilis of cardio-vascular system Cardiovascular syphilis NOS (198.0).

Syphilitic(s): aortic aneurysm (179.0); aortic insufficiency (139.1); aortitis (179.1); cerebral arteritis (168.1); endocarditis NOS (139.8); myocarditis (141.0); pericarditis (132.0); pulmonary insufficiency (139.3).

A52.1 Neurosyphilis with symptoms

1. Charcot arthropathy (M14.6).
2. Late syphilitic: acoustic neuritis (H49.0); encephalitis (G05.0); meningitis (G01); optic nerve atrophy (H48.0); polyneuropathy (G63.0); retrobulbar neuritis (H48.1) .
3. Syphilitic parkinsonism (G22).
4. Tabes dorsalis.

A52.2 Asymptomatic neurosyphilis

A52.3 Neurosyphilis, unspecified Gumma (syphilitic).

1. Syphilis (late) of the central nervous system NOS.
2. Syphiloma.

A52.7 Other symptoms of late syphilis

1. Syphilitic lesion of the renal glomeruli (N08.0).
2. Gumma (syphilitic) of any localization, except those classified in headings A52.0-A52.3.
3. Late or tertiary syphilis.
4. Late syphilitic: bursitis (M73.1); chorioretinitis (H32.0); episcleritis (H19.0); inflammatory disease of the female pelvic organs (N74.2); leukoderma (L99.8); oculopathy NCDR (H58. 8); peritonitis (K67.2).
5. Syphilis (without specifying the stage): bone (M90.2); liver (K77.0); lung (J99.8); muscle (M63.0); synovial (M68.0).

A52.8 Late latent syphilis

Syphilis (acquired) without clinical manifestations, with a positive serological reaction and a negative cerebrospinal fluid sample, two years or more after infection.

A52.9 Late syphilis, unspecified

A53 Other and unspecified forms of syphilis

A53.0 Latent syphilis, unspecified as early or late

1. Latent syphilis NOS.
2. Positive serological reaction to syphilis.

A53.9 Syphilis, unspecified

1. Treponema pallidum infestation, NOS. Syphilis (acquired)
2. Syphilis NOS causing death before the age of two years was excluded (A50.2).

The incubation period begins with the introduction of the syphilis pathogen through damaged skin or mucous membrane and ends with the appearance of the primary affect. Average duration incubation period ranges from 2 weeks to 2 months, this period can be shortened to 8 days or, conversely, extended to 190 days. A reduction in the incubation period is observed during reinfection and when the pathogen of syphilis is introduced into the body from several entrance gates, which accelerates the generalization of the infection and the development of immune changes in the body. An extension of the incubation period is observed as a result of the use of small doses of treponemocidal antibacterial drugs regarding intercurrent diseases.

Primary syphilis (A51.0-A51.2). At the site of introduction of pale treponema, a primary affect develops - erosion or ulcer with a diameter of 2-3 mm (dwarf chancre) to 1.5-2 cm or more (giant chancre), round in outline, with smooth edges, a smooth, shiny pink or red bottom , sometimes grayish-yellow in color, saucer-shaped (ulcer), with scanty serous discharge, painless on palpation; at the base of primary syphiloma there is a dense elastic infiltrate. Primary affect is accompanied by regional lymphadenitis, less often lymphangitis; can be typical (erosive, ulcerative) and atypical (indurative edema, chancre-felon and chancre-amygdalitis); single and multiple; genital, perigenital and extragenital; when a secondary infection occurs, it becomes complicated (impetiginization, balanoposthitis, vulvovaginitis, phimosis, paraphimosis, gangrenization, phagedenism). At the end of the primary period, polyadenitis and general infectious symptoms (intoxication syndrome) appear.

Secondary syphilis (A51.3). It is caused by hematogenous dissemination of infection against the background of the development of infectious immunity and is manifested by: rashes on the skin (roseolous (spotty), papular (nodular), papulopustular (pustular) and rarely vesicular) and/or mucous membranes (limited and confluent roseolous and papular syphilides) ; leukoderma, alopecia. Possible residual effects primary syphilis, damage to internal organs, the musculoskeletal system and the nervous system (A51.4).

Tertiary syphilis (A52.7). It can develop immediately after secondary syphilis, but in most cases there is a latent period between the secondary and tertiary periods. The appearance of symptoms of tertiary syphilis is possible many years after infection if the infection is asymptomatic. Manifests itself as rashes on the skin/mucous membranes (tubercular and gummous syphilides, tertiary roseola of Fournier), lesions of internal organs, the musculoskeletal system and the nervous system (A52.0-A52.7).

Hidden syphilis. There are early (A51.5) (up to 2 years from the moment of infection), late (A52.8) (more than 2 years from the moment of infection) and unspecified as early or late (A53.0) latent syphilis. Characterized by the absence of clinical manifestations. Patients with early latent syphilis should be considered dangerous in epidemic terms, since they may develop contagious manifestations of the disease. The diagnosis is established based on the results of a blood serum test using serological methods (non-treponemal and treponemal tests) and anamnestic data. In some cases, the diagnosis of syphilis is helped by objective examination data (scar at the site of the former primary syphiloma, enlarged lymph nodes), as well as the appearance of an exacerbation temperature reaction (Jarisch-Herxheimer reaction) after the start of specific treatment.

Congenital syphilis (A50) develops as a result of infection of the fetus during pregnancy. The only source of infection for the fetus is the mother with syphilis. There are early (manifests in the first 2 years of life) and late (manifests at a later age) congenital syphilis, occurring both with clinical manifestations (manifest) (A50.0; A50.3-A50.5) and without them (latent) (A50.1; A50.6).

Early congenital syphilis with symptoms (A50.0) is characterized by 3 groups of symptoms:

1. pathognomonic for congenital and not found in acquired syphilis (syphilitic pemphigoid, diffuse infiltration of Hochsinger’s skin, specific rhinitis - dry, catarrhal and ulcerative stages) and osteochondritis of the long tubular bones of Wegner (I, II and III degrees, detected by X-ray examination; I degree has no diagnostic value , since similar changes can be observed with rickets);
2. typical manifestations of syphilis, which occur not only with early congenital but also with acquired syphilis, are a papular rash on the limbs, buttocks, face, and sometimes throughout the body; in places of maceration - erosive papules and condylomas lata; roseola rash (rare), raucedo, alopecia, bone lesions in the form of periostitis, osteoporosis and osteosclerosis, bone gummas; damage to internal organs in the form of specific hepatitis, glomerulonephritis, myocarditis, endo- and pericarditis, etc., damage to the central nervous system in the form of specific meningitis, hydrocephalus, etc.;
3. general and local symptoms that also occur with other intrauterine infections: “senile appearance” of the newborn (skin is wrinkled, flabby, dirty yellow); small length and body weight with symptoms of malnutrition, up to cachexia; hypochromic anemia, leukocytosis, increased ESR, thrombocytopenia; hepatosplenomegaly; chorioretinitis (type IV); onychia and paronychia. The placenta in syphilis is enlarged and hypertrophied; its weight is 1/4-1/3 (normally 1/6-1/5) of the weight of the fetus.

Late congenital syphilis with symptoms (A50.3; A50.4) is characterized by reliable signs (Hutchinson’s triad: parenchymal keratitis, labyrinthine deafness, Hutchinson’s teeth), probable signs (saber shins, chorioretinitis, nasal deformities, radiating scars around the mouth, buttock-shaped skull, dental deformations, syphilitic gonitis, damage to the nervous system in the form of hemiparesis and hemiplegia, speech disorders, dementia, cerebral infantile paralysis and Jacksonian epilepsy) and dystrophies (thickening of the sternal end of the right clavicle, degeneration of the skull bones in the form of an “Olympic forehead”, high “Gothic” or “lancet” palate, absence of the xiphoid process of the sternum, infantile little finger, widely spaced upper incisors, tubercle on the chewing surface of the first maxillary molar). In addition, specific lesions on the skin and mucous membranes are characteristic in the form of tubercular and gummous syphilides of the skin, mucous membranes, damage to organs and systems, especially bone (periostitis, osteoperiostitis, gummous osteomyelitis, osteosclerosis), liver and spleen, cardiovascular, nervous and endocrine systems .

Neurosyphilis. There are asymptomatic and manifest neurosyphilis. Based on the time period from the moment of infection, neurosyphilis is conventionally divided into early (up to 5 years from the moment of infection) and late (more than 5 years from the moment of infection). This division does not completely define all aspects of the damage to the nervous system, since clinical manifestations neurosyphilis represent a single dynamic system with a combination of symptoms of early and late forms.

Asymptomatic neurosyphilis (A51.4; A52.2) is characterized by the absence of clinical manifestations. The diagnosis is based on pathological changes revealed by examining the cerebrospinal fluid.

Neurosyphilis with symptoms is manifested by any neurological or mental disorders that have an acute or subacute development and progress over several months or years. The most common early form of neurosyphilis (A51.4) is meningovascular syphilis, in clinical picture which is dominated by symptoms of damage to the membranes and blood vessels of the brain: syphilitic meningitis (acute convexital, acute basal, acute syphilitic hydrocephalus), syphilitic uveitis (chorioretinitis, iritis), vascular neurosyphilis (ischemic, less often hemorrhagic stroke), spinal meningovascular syphilis (syphilitic meningomyelitis). Late forms of neurosyphilis include progressive paralysis, tabes dorsalis, taboparalysis, atrophy optic nerves(A52.1) and gummous neurosyphilis (A52.3), the clinical picture of which is dominated by symptoms of damage to the brain parenchyma.

Syphilis of internal organs and musculoskeletal system Based on the time period from the moment of infection, they are conventionally divided into early (up to 2 years from the moment of infection) and late (more than 2 years from the moment of infection) forms. In early forms (A51.4), only functional disorders of the affected organs most often develop. The pathological process mainly involves the heart (early cardiovascular syphilis), liver (anicteric or icteric forms of hepatitis), stomach (transient gastropathy, acute gastritis, formation of specific ulcers and erosions), kidneys (asymptomatic renal dysfunction, benign proteinuria, syphilitic lipoid nephrosis, syphilitic glomerulonephritis). The earliest symptom of damage to the musculoskeletal system is night pain in long tubular bones limbs. The pain is not accompanied by any objective changes in the bones. Specific synovitis and osteoarthritis may be observed.
In late forms (A52.0; A52.7), destructive changes in internal organs are observed. Most often, specific lesions of the cardiovascular system are recorded (mesaortitis, aortic valve insufficiency, aortic aneurysm, myocarditis, gummous endo- and pericarditis), less often - late hepatitis (limited (focal) gummous, miliary gummous, chronic interstitial and chronic epithelial), even less often - other late visceral syphilitic lesions (A52.7). Late manifestations of pathology of the musculoskeletal system include tabetic arthropathy and gummous lesions of bones and joints (A52.7).

For laboratory diagnostics Direct and indirect methods are used to treat syphilis. Direct diagnostic methods identify the pathogen itself or its genetic material. Indirect methods for diagnosing syphilis include tests that detect antibodies to the causative agent of syphilis in blood serum and cerebrospinal fluid.

Absolute proof of the presence of the disease is the detection of treponema pallidum in samples obtained from lesions using dark-field microscopic examination, immunohistochemical studies using monoclonal or polyclonal antibodies, as well as detection of specific DNA and RNA of the pathogen using molecular biological methods using test systems allowed for medical use In Russian federation. Direct methods are used to diagnose early forms of the disease (primary and secondary syphilis) with clinical manifestations (erosive and ulcerative elements), to confirm congenital syphilis (umbilical cord tissue, placenta, fetal organs, discharge from the nasal mucosa, contents of blisters, discharge from the surface of papules) .

• Non-treponemal tests:

1. microprecipitation reaction (MPR) with plasma and inactivated serum or its analogues:
2. RPR (RPR) - rapid plasma reagin test (Rapid Plasma Reagins), or rapid plasma reagin test;
3. VDRL - Venereal disease Research Laboratory Test - test of the Research Laboratory of Venereal Diseases;
4. TRUST - test with toluidine red and unheated serum (Toluidin Red Unheated Serum Test);
5. USR - test for reagins with unheated serum (Unheated SerumReagins).

General characteristics of non-treponemal tests:

1. an antigen of non-treponemal origin is used (standardized cardiolipin antigen);
2. are positive 1-2 weeks after the formation of primary syphiloma;
3. have low sensitivity (up to 70-90% in early forms of syphilis and up to 30% in late forms), and can give false-positive results (3% or more).

Advantages of non-treponemal tests:

1. low cost;
2. technical ease of implementation;
3. speed of obtaining results.

1. screening the population for syphilis;
2. determining the activity of the infection (determining antibody titers);
3. monitoring the effectiveness of therapy (determining antibody titers).

Treponemal tests:

1. ELISA (enzyme-linked immunosorbent assay) is a highly sensitive and specific test. Sensitivity for primary and secondary syphilis is 98-100%, specificity is 96-100%. Enables differentiated and total determination of IgM and IgG antibodies to the causative agent of syphilis;
2. immunoblotting is a modification of ELISA. Sensitivity and specificity - 98-100%. Can be used to confirm the diagnosis, especially when the results of other treponemal tests are equivocal or inconsistent.

Methods for detecting treponeme-specific antibodies based on immunochemiluminescence (ICL) and immunochromatography (ICH) methods are relatively new for use in the Russian Federation.

1. ICL (immunochemiluminescence) method, which has high sensitivity and specificity (98-100%), makes it possible quantification level of antibodies to the causative agent of syphilis, can be used to confirm syphilitic infection and screening. Limitations of use: cannot be used to monitor the effectiveness of therapy, may give a false positive result.
2. PBT (simple rapid bedside tests, or immunochromatographic tests) allow for rapid determination of the content of treponeme-specific antibodies to the causative agent of syphilis in serum and whole blood samples without the use of special laboratory equipment and can be used in the provision of primary health care, including for epidemiological indications .Limitations of use: cannot be used to monitor the effectiveness of therapy, may give a false positive result.

RPHA (passive hemagglutination reaction) is a highly sensitive and specific test. The sensitivity of the method for primary syphilis is 76%, for secondary syphilis - 100%, for latent syphilis - 94-97%, specificity - 98-100%;

RIF (immunofluorescence reaction, including modifications RIFabs and RIF200) - is quite sensitive at all stages of syphilis (sensitivity for primary syphilis - 70-100%, secondary and late - 96-100%), specificity - 94-100%. RIF is used to differentiate latent forms of syphilis and false-positive test results for syphilis;

RIBT (RIT) (treponema pallidum immobilization reaction) is a classic test for identifying specific treponemal antibodies; sensitivity (total by stages of syphilis) is 87.7%; specificity - 100%. A labor-intensive and difficult test to perform, requiring significant funds for testing. The scope of application of RIBT is narrowing, but it retains its position as a “reaction arbiter” in the differential diagnosis of latent forms of syphilis with false-positive results of serological reactions to syphilis.

General characteristics of treponemal tests:

1. an antigen of treponemal origin is used;
2. sensitivity - 70-100% (depending on the type of test and stage of syphilis);
3. specificity - 94-100%.
4. RIF, ELISA, immunoblotting (IB) become positive from the 3rd week from the moment of infection and earlier, RPGA and RIBT - from the 7-8th.

Advantages of treponemal tests: high sensitivity and specificity.

Indications for the use of treponemal tests:

1. confirmation of positive results of non-treponemal tests;
2. confirmation in case of discrepancy between the results of a screening treponemal test and a subsequent non-treponemal test, as well as screening and confirmatory treponemal tests;
3. carrying out screening of certain categories of the population for syphilis using ELISA, RPGA, ICL, PBT methods (donors, pregnant women, patients in ophthalmological, neuropsychiatric, cardiological hospitals, HIV-infected).

Notes:

1. treponemal tests cannot be used to monitor the effectiveness of therapy, since antitreponemal antibodies circulate for a long time in the body of a patient who has had a syphilitic infection;
2. treponemal tests give positive results for non-venereal treponematoses and spirochetosis;
3. Treponemal tests can give false-positive reactions in patients with autoimmune diseases, leprosy, cancer, endocrine pathology and some other diseases.

Depending on the goals, serological screening of the population for syphilis is carried out using different methods:

False-positive serological reactions for syphilis (FPR)

False-positive, or nonspecific, are the positive results of serological reactions to syphilis in individuals who do not suffer from a syphilitic infection and have not had syphilis in the past.

Decision-makers may be due to technical errors during research and the characteristics of the body. Conventionally, DM is divided into acute (< 6 месяцев) и хронические (>6 months). Acute DMARDs can be observed during pregnancy and during menstruation, after vaccination, after recently suffered a heart attack myocardium, in many infectious diseases (leprosy, malaria, respiratory diseases, flu, chicken pox, viral hepatitis, HIV infection) and dermatoses; chronic drugs - with autoimmune diseases, systemic diseases connective tissue, oncological diseases, chronic pathology of the liver and biliary tract, with cardiovascular and endocrine pathologies, with blood diseases, with chronic lung diseases, injection drug use, in old age, etc.

False-positive reactions of treponemal and non-treponemal tests can be observed with endemic treponematoses (yaws, pinta, bejel), borreliosis, and leptospirosis. A patient with positive serological reactions for syphilis who arrived from a country with endemic treponematoses should be examined for syphilis and prescribed anti-syphilitic treatment if it has not previously been administered.

Chronic false-positive reactions can be preclinical manifestations of serious diseases. The number of DM increases with age. In the age group of 80-year-olds, the prevalence of PD is 10%.

False-negative serological tests for syphilis may be observed in secondary syphilis due to the prozone phenomenon when testing undiluted serum, as well as when examining immunocompromised individuals, such as HIV-infected patients.

The study of cerebrospinal fluid (CSF) plays a decisive role in the diagnosis of neurosyphilis.

Spinal puncture for CSF examination is indicated for patients with syphilis if they have clinical neurological symptoms (regardless of the stage of the disease); persons with latent, late forms of infection; patients with manifestations of secondary recurrent syphilis (in particular, with leukoderma, especially in combination with alopecia); suspected congenital syphilis in children; in the absence of negativity of non-treponemal serological tests in patients after complete specific treatment.

The diagnosis of neurosyphilis with symptoms is established on the basis of a combination of clinical manifestations with positive results of serological tests with CSF and changes in the composition of the latter (cell number and protein level), latent - on the basis of laboratory detection of pathological changes in CSF. Recommended methods for studying CSF include: cytological examination with counting the number of formed elements, determining the amount of protein, as well as serological tests to detect antibodies to T. pallidum: RMP, RIFc (RIF with whole cerebrospinal fluid), RPGA, ELISA, immunoblotting.

Pleocytosis and increased protein levels in the cerebrospinal fluid are not specific for neurosyphilis, but have important diagnostic value as criteria for development inflammatory processes membranes and organic lesions of the brain substance. The determination of more than 5 cells of the lymphocytic series in 1 mm3 of cerebrospinal fluid indicates the presence of pathological changes in the nervous system. The protein content in the cerebrospinal fluid of an adult is normally 0.16-0.45 g/l. The specificity of non-treponemal CSF tests is close to 100%, but their sensitivity is not high enough, and the frequency of negative results with various forms neurosyphilis varies from 30 to 70%. Treponemal tests, on the contrary, have high sensitivity (90-100%), but are not specific enough and can be positive with cerebrospinal fluid in forms of syphilis that are not accompanied by damage to the nervous system, but negative results of treponemal tests with CSF exclude neurosyphilis.

Currently, there is no universal test that would make it possible to unambiguously confirm or refute the diagnosis of neurosyphilis, as well as to distinguish antitreponemal antibodies that passively penetrate into the central nervous system from serum from locally synthesized ones. The diagnosis is established on the basis of a set of criteria.

To diagnose neurosyphilis, a reverse algorithm can be used, including the sequential use of modern laboratory diagnostic methods: ELISA/immunoblotting, RMP/RPR and RPGA. Testing using this algorithm includes persons suspected of having neurosyphilis, including patients with latent syphilis and persons who have had syphilis in the past, while maintaining positive non-treponemal serological blood tests. Testing begins with examination of the patient's cerebrospinal fluid using ELISA or immunoblotting methods. If the result is negative, with a high degree of probability it can be concluded that the patient does not have neurosyphilis. At positive result ELISA/IB research is carried out using one of the non-treponemal tests (RMP, RPR). If ELISA/IB and RMP/RPR give a positive result, the patient is diagnosed with neurosyphilis and further testing is stopped. If the RMP/RPR is negative, the cerebrospinal fluid is tested using a second highly sensitive and specific treponemal method - RPGA. If the RPGA result is positive, a conclusion is made about the presence of neurosyphilis in the patient. If the RPGA result is negative, it is concluded that the patient does not have neurosyphilis and the first treponemal test is a false-positive result. To diagnose neurosyphilis, they are additionally used instrumental methods: magnetic resonance and computed tomography, electroencephalography. The results of non-invasive neuroimaging studies for neurosyphilis are non-specific and are used to assess the extent of the lesion and topical diagnosis.

The diagnosis of neurosyphilis is considered confirmed if the patient has serologically proven syphilis, regardless of stage, and a positive result of RMP (RPR) with cerebrospinal fluid.

The diagnosis of neurosyphilis is considered probable when:

1. the patient has serologically proven syphilis, regardless of stage;
2. the presence of neurological/psychiatric/ophthalmological/otological symptoms that cannot be explained by other reasons;
3. negative result of RMP (RPR) with cerebrospinal fluid;
4. the presence of pleocytosis (more than 5 cells in 1 mm 3 of cerebrospinal fluid) and/or increased protein levels (more than 0.5 g/l), which cannot be caused by other diseases.

The diagnosis is established on the basis of the mother's medical history, clinical manifestations, X-ray data and the results of serological tests (RMP/RPR, ELISA, RPGA, RIBT, RIF).

According to WHO criteria (1999), a case of congenital syphilis is considered confirmed when Tr. pallidum by dark-field microscopy, PCR or IHC in material obtained from rash discharge, amniotic fluid, placental tissue, umbilical cord or autopsy specimens.

Stillbirth due to congenital syphilis is considered to be the death of a fetus that occurs after the 20th week of pregnancy or with a body weight of more than 500 grams, in the presence of untreated or inadequately treated syphilis in the mother.

Congenital syphilis is considered probable if:

1. the mother of the newborn did not receive treatment or received inadequate treatment (after the 32nd week of pregnancy or with reserve antibacterial drugs) during pregnancy (regardless of the presence of signs of the disease in the child);
2. with a positive TT result in a child and the presence of at least one of the following criteria: manifestations of congenital syphilis during a physical examination or radiography of long bones; positive RMP in the cerebrospinal fluid, pleocytosis or hyperproteinarchy (in the absence of other reasons); detection of 19S IgM in the RIF test - abs or RPGA, detection of IgM by ELISA or IB.

When diagnosing early congenital syphilis with symptoms, it should be borne in mind that grade I osteochondritis without other symptoms of congenital syphilis cannot serve as a sign of congenital syphilis, since similar changes can be observed in other diseases and even in healthy children.

Establishing a diagnosis of early congenital syphilis must be carried out taking into account the following main criteria:

1. detection of clinical manifestations of the disease in a child;
2. detection of Treponema pallidum using direct laboratory methods;
3. positive results of serological reactions in the child (blood is taken in parallel with the mother’s blood, examined in the same tests, RMP/RPR and RPGA - in a quantitative version);
4. the presence of pathological changes in the cerebrospinal fluid;
5. the presence of radiologically established changes in long tubular bones;
6. identifying macroscopic and pathomorphological signs of changes in the placenta, umbilical cord, internal organs;
7. detection of manifest or latent syphilis in the mother, confirmed by the results of direct and/or serological diagnostic methods.

It must be remembered that in newborns the level of antibodies in the serum is low, and even with obvious clinical signs of early congenital syphilis, some serological reactions may be negative. Serological reactions may remain negative for 4-12 weeks of life of the newborn if he became infected in late pregnancy. At the same time, positive results of serological reactions may be a consequence of passive transplacental transport of maternal antibodies. These antibodies disappear within 3-6 months after birth, and serological reactions gradually become negative.

If the titer of RMP/RPR with the newborn's serum is 4 or more times higher than the titer of these reactions with the mother's serum, or if during the first 3 months of the child's life there is at least a fourfold increase in the titer of RMP/RPR compared to the initial one, this is considered an indicator of congenital syphilis. However, this situation is observed only in 30% of children with early congenital syphilis, therefore, the absence of an NTT titer in a child four times higher than the maternal one does not exclude congenital syphilis. Specific antitreponemal IgM antibodies are detected by IgM-ELISA, IgM-IB, IgM-RIF-abs only in 75-80% of newborns with clinically manifest early congenital syphilis. Therefore, negative results of IgM tests also do not exclude congenital syphilis.

Late congenital syphilis can be diagnosed taking into account:

1. clinical manifestations of the disease: each of the manifestations included in Hutchinson’s triad has diagnostic significance; probable signs and dystrophies (stigmas of dysmorphogenesis) are taken into account in combination with reliable ones or in combination with serological examination data and anamnesis. Detection of only one dystrophy, without any other signs of syphilis, does not allow confirming the diagnosis, since dystrophy may be a manifestation of others chronic diseases and intoxication in parents (alcoholism, toxoplasmosis, endocrine diseases, etc.) and children (tuberculosis, rickets, etc.), as well as in practically healthy people.
2. positive results of serological reactions: NTT are positive in 70-80% of patients, TT - in 92-100%;
3. the mother has a late form of syphilis;
4. the mother’s medical history, including obstetrics, as well as the results of examination of the father and other children in the family.

Diagnostics syphilitic lesion internal organs and musculoskeletal system based on clinical manifestations, data from instrumental studies (x-ray, ultrasound, magnetic resonance imaging, computed tomography) And laboratory research(serological, pathomorphological).

Criteria for diagnosing early visceral syphilis:

1. detection during pathomorphological examination of a biopsy specimen of lymphohistioplasmacytic inflammatory infiltration and Treponema pallidum (using IHC and silvering methods) is evidence of the specific nature of the lesion;

Criteria for diagnosing late visceral syphilis:

1. the patient has serologically proven syphilis;
2. the presence of clinical symptoms of damage to the relevant organ;
3. detection of granulomatous inflammation during a pathomorphological examination of a biopsy specimen is evidence of the specific nature of the lesion;
4. positive dynamics of the process against the background of specific therapy.

Differential diagnosis is carried out:

Primary syphilis: with erosive balanoposthitis, genital herpes, trichomoniasis, chancriform pyoderma, skin cancer, soft chancroid, lymphogranuloma venereum, donovanosis, acute Chaplin-Lipschütz vulvar ulcer, fulminant gangrene of the genitals, thrombophlebitis and phlebolymphangitis of the genitals;

Secondary syphilis: spotted syphilides - with acute infections(rubella, measles, typhoid and typhus), toxicoderma, pityriasis versicolor, pityriasis versicolor, marbling of the skin, spots from insect bites; papular syphilides - with guttate parapsoriasis, lichen planus and psoriasis; when papules are localized on the palms and soles - with psoriasis, eczema, mycoses of the feet and hands; erosive papules of the genitals - with folliculitis, molluscum contagiosum; condylomas lata - with genital warts, pemphigus vegetans, hemorrhoids; papulopustular syphilides: acne - with vulgar (juvenile) acne, papulonecrotic tuberculosis of the skin, nodular allergic vasculitis, iodine or bromide acne, oil occupational folliculitis; smallpox - with chicken pox; impetigo-like - with vulgar impetigo; syphilitic ecthyma - with ecthyma vulgaris; syphilitic rupees - with psoriasis; vesicular syphilide - with herpetic rashes; damage to the mucous membranes - with lacunar angina, diphtheria of the pharynx, Plaut-Vincent angina, lichen planus, leukoplakia, lupus erythematosus, candidiasis, erythema multiforme, bullous pemphigoid, herpes, true pemphigus, aphthous stomatitis, exfoliative glossitis; syphilitic leucoderma - with pityriasis versicolor, leucoderma after resolution of other dermatoses (psoriasis, parapsoriasis, etc.), vitiligo; syphilitic alopecia - with diffuse alopecia nonspecific etiology, large-focal alopecia, seborrheic alopecia, cicatricial alopecia (Broca's pseudopelades), trichomycosis, discoid and disseminated lupus erythematosus, lichen planus;

Tertiary syphilis: tubercular syphilide - with tuberculous lupus, tuberculoid type of leprosy, conglobate acne, granuloma annulare, basal cell carcinoma, Besnier-Beck-Schaumann sarcoidosis, ecthyma vulgaris, varicose ulcers of the legs, cutaneous leishmaniasis, necrobiosis lipoidica, nodular necrotizing vasculitis, chronic i pyoderma, psoriasis; gumma - with scrofuloderma, indurative skin tuberculosis, vulgar ecthyma, chronic ulcerative pyoderma, spinocellular cancer, syphilitic ecthyma, ulcerated basalioma, lepromatous nodes, varicose ulcers, erythema nodosum, allergic nodular vasculitis, Weber-Christian nodular febrile panniculitis, skin leishmaniasis, tuberculosis lesions and neoplasms; tertiary roseola - with various erythemas (persistent figured erythema of Wende, chronic migratory erythema of Afzelius-Lipschütz, centrifugal annular erythema of Darier), as well as with macular rashes in leprosy;

Positive results of serological examination in latent forms of syphilis - with false-positive serological reactions to syphilis;

Neurosyphilis- with meningitis of any etiology, sensorineural hearing loss of various origins, hypertensive crisis, myelitis of other etiology, tumor spinal cord, thrombosis of spinal cord vessels, spinal form of multiple sclerosis; mental disorders with progressive paralysis - with neurasthenia, manic-depressive psychosis, schizophrenia, atherosclerosis, senile psychosis, brain tumor (especially frontal lobes); neurological disorders with tabes dorsalis - with trauma to the brain and spinal cord, acute infectious diseases with damage to the nervous system ( typhoid fever, flu), long-term chronic intoxication (arsenic, alcohol); primary tuberculous atrophy of the optic nerves - with atrophies of the optic nerves of another etiology, most often tuberculous; gummas - with neoplasms of the brain and spinal cord.

1. ophthalmologist, neurologist, otorhinolaryngologist - for children with suspected congenital syphilis;
2. an ophthalmologist and a neurologist - for all patients with acquired syphilis;
3. if a specific lesion of internal organs, the musculoskeletal system, etc. is suspected - consultation with specialists in accordance with complaints and/or pathological changes during instrumental examination.

Treatment Goals

Specific treatment is carried out with the aim of etiological cure of the patient by creating a treponemocidal concentration of the antimicrobial drug in the blood and tissues, and in the case of neurosyphilis - in the CSF.

Preventive treatment is carried out to prevent syphilis for persons who have had sexual and close household contact with patients with early forms of syphilis, if no more than 2 months have passed since the contact.

Prophylactic treatment is carried out to prevent congenital syphilis: a) pregnant women who were treated for syphilis before pregnancy, but who remain positive in non-treponemal serological tests; b) pregnant women who received specific treatment for syphilis during pregnancy; c) newborns born without manifestations of syphilis from an untreated or inadequately treated mother during pregnancy (specific treatment started after the 32nd week of pregnancy, violation or change in approved treatment regimens); d) newborns whose mothers, if indicated during pregnancy, did not receive preventive treatment.

Trial treatment (treatment ex juvantibus) in a specific volume is carried out if a specific lesion of internal organs, the nervous system and the musculoskeletal system is suspected, when the diagnosis cannot be confirmed by convincing serological and clinical data.

General notes on therapy

Penicillins:

1. durant: bicillin-1 (dibenzylethylenediamine salt of benzylpenicillin, otherwise - benzathine benzylpenicillin), combined: bicillin-5 (dibenzylethylenediamine and novocaine and sodium solipenicillin in a ratio of 4: 1);
2. medium duration: benzylpenicillin novocaine salt;
3. water-soluble: benzylpenicillin sodium salt crystalline;
4. semi-synthetic: ampicillin sodium salt, oxacillin sodium salt.

Tetracyclines: doxycycline.

Macrolides: erythromycin.

Cephalosporins: ceftriaxone.

The drug of choice for the treatment of syphilis is benzylpenicillin. Treatment of patients with visceral syphilis is recommended to be carried out in a hospital setting - dermatovenerological or therapeutic/cardiological, taking into account the severity of the lesion. Treatment is carried out by a dermatovenerologist, who prescribes specific treatment, together with a therapist/cardiologist, who recommends concomitant and symptomatic therapy.

Treatment of patients with clinically manifest forms of neurosyphilis is carried out in a neurological/psychiatric hospital due to the need for the active participation of a neurologist/psychiatrist in the treatment and observation of the patient, the severity of his condition and the likelihood of aggravation or appearance of neurological symptoms during antibacterial therapy. Specific treatment is prescribed by a dermatovenerologist.

Patients with asymptomatic forms of neurosyphilis can receive full medical care in a dermatovenerological hospital. The question of preparatory and symptomatic therapy is decided jointly by a dermatovenerologist, neurologist, psychiatrist and, if necessary, an ophthalmologist.

Indications for hospitalization

1. suspicion of the presence or established diagnosis of neurosyphilis;
2. suspicion of the presence or established diagnosis of cardiovascular syphilis and other visceral lesions;
3. syphilitic lesion of the musculoskeletal system;
4. late latent and unspecified syphilis;
5. tertiary syphilis;
6. syphilis in pregnant women;
7. congenital and acquired syphilis in children;
8. all forms of the disease that can be treated with water-soluble penicillin;
9. indication in the anamnesis of intolerance to antibacterial drugs; concomitant HIV infection;
10. workers of epidemiologically significant professions (listed in Order of the Ministry of Health and Social Development of the Russian Federation No. 302n dated April 12, 2011), which may be sources of the spread of syphilis due to the characteristics of production or the work (service) they perform;
11. all forms of the disease in the absence of the possibility of providing primary specialized health care in the patient’s territory of residence;
12. persons without a fixed place of residence.

Preventive treatment

1. bicillin-5 (B) 1.5 million units 2 times a week intramuscularly, 2 injections per course
2. benzylpenicillin novocaine salt (C) 600 thousand units 2 times a day intramuscularly for 7 days.
3. bicillin-1 (A) 2.4 million units intramuscularly once (the drug is injected at 1.2 million units into each gluteus maximus muscle, diluted with 1% lidocaine solution).

A single dose of durable penicillin (benzathine benzylpenicillin) is preferred: no treatment failures have been described, and at the same time it has the highest compliance.

Treatment of patients with primary syphilis

1. Bicillin-1 (A) 2.4 million units 1 time every 5 days intramuscularly, 3 injections per course
2. bicillin-5 (B) 1.5 million units 2 times a week intramuscularly, for a course of 5 injections
3. benzylpenicillin novocaine salt (C) 600 thousand units 2 times a day intramuscularly for 14 days
4. benzylpenicillin sodium salt crystalline (B) 1 million units every 4 hours (6 times a day) intramuscularly for 14 days.

The drug of choice is durant penicillin (benzathine benzylpenicillin), as it is the most convenient to use. Medium-duration drugs or water-soluble penicillin are used when it is necessary to treat a patient in a hospital (for complicated disease, somatically aggravated patients, etc.).

Treatment of patients with secondary and early latent syphilis

1. benzylpenicillin novocaine salt (C) 600 thousand units 2 times a day intramuscularly for 28 days
2. benzylpenicillin sodium salt crystalline (B) 1 million units every 4 hours (6 times a day) intramuscularly for 28 days,
3. Bicillin-1 (A) 2.4 million units 1 time in 5 days intramuscularly, for a course of 6 injections (for secondary syphilis).

In patients with a disease duration of more than 6 months, it is recommended to use benzylpenicillin novocaine salt or benzylpenicillin sodium crystalline salt.

Treatment of patients with tertiary, latent late and latent unspecified syphilis

1. benzylpenicillin sodium crystalline salt (B) 1 million units every 4 hours (6 times a day) intramuscularly for 28 days, after 2 weeks - a second course of treatment with benzylpenicillin sodium crystalline salt in similar doses for 14 days, or one of the “medium” drugs duration (benzylpenicillin novocaine salt)
2. benzylpenicillin novocaine salt (C) 600 thousand units 2 times a day intramuscularly for 28 days, after 2 weeks - a second course of treatment with benzylpenicillin novocaine salt in a similar dose for 14 days.

Treatment of patients with early visceral syphilis

1. benzylpenicillin sodium salt crystalline (B) 1 million units every 4 hours (6 times a day) intramuscularly for 28 days
2. benzylpenicillin novocaine salt (C) 600 thousand units 2 times a day intramuscularly for 28 days.

Treatment of patients with late visceral syphilis

Treatment begins with a 2-week preparation with antibacterial drugs wide range actions (doxycycline, erythromycin). Then they move on to penicillin therapy:

1. benzylpenicillin sodium crystalline salt (d) 1 million units every 4 hours (6 times a day) intramuscularly for 28 days, after 2 weeks - a second course of treatment with benzylpenicillin sodium crystalline salt in a similar dose for 14 days
2. benzylpenicillin novocaine salt (d) 600 thousand units 2 times a day intramuscularly for 28 days, after 2 weeks - a second course of treatment with benzylpenicillin novocaine salt in a similar dose for 14 days.

Treatment of patients with early neurosyphilis

1. benzylpenicillin sodium crystalline salt (d) 12 million units 2 times a day intravenously for 20 days. A single dose of the drug is diluted in 400 ml of isotonic sodium chloride solution and administered intravenously over 1.5-2 hours. Solutions are used immediately after preparation. Upon completion of the course intravenous injections- 1 injection of bicillin-1 at a dose of 2.4 million units
2. benzylpenicillin sodium salt crystalline (d) 4 million units 6 times a day intravenously in a stream for 20 days. A single dose of the drug is diluted in 10 ml of isotonic sodium chloride solution and administered intravenously slowly over 3-5 minutes into the cubital vein. At the end of the course of intravenous injections - 1 injection of bicillin-1 at a dose of 2.4 million units.

To prevent an exacerbation reaction (in the form of the appearance or worsening of neurological symptoms) in the first 3 days of penicillin therapy, it is recommended to take prednisolone in a decreasing dose. daily dose 90-60-30 mg (once in the morning).

Treatment of patients with late neurosyphilis

1. benzylpenicillin sodium crystalline salt (d) 12 million units 2 times a day intravenously for 20 days. At the end of a 20-day course of intravenous injections - 1 injection of bicillin-1 at a dose of 2.4 million units. 2 weeks after the injection of bicillin-1, a second course of treatment is carried out according to a similar scheme
2. benzylpenicillin sodium salt crystalline (d) 4 million units 6 times a day intravenously in a stream for 20 days. At the end of a 20-day course of intravenous injections - 1 injection of bicillin-1 at a dose of 2.4 million units once every 5 days. 2 weeks after the injection of bicillin-1, a second course of treatment is carried out according to a similar scheme.

In patients with progressive paralysis, to prevent exacerbation of psychotic symptoms against the background of specific treatment, the use of prednisolone in the doses indicated above is indicated at the beginning of therapy. For gummas of the brain and spinal cord, the use of prednisolone in parallel with penicillin therapy is recommended throughout the first course of treatment; use of prednisolone may precede the start by several days antibacterial therapy, which contributes to the regression of clinical symptoms of the disease.

Patients should be warned about possible reaction body for treatment. IN medical organizations Where therapy is carried out, there must be emergency aid facilities.

1. Exacerbation reaction (Jarisch-Herxheimer).

An exacerbation reaction is observed in 30% of patients with early syphilis. In most patients, clinical manifestations of the exacerbation reaction begin 2-4 hours after the first administration of the antibacterial drug, reach maximum severity after 5-7 hours, and the condition returns to normal within 12-24 hours. Main clinical symptoms are chills and a sharp increase in body temperature (up to 39 ° C, sometimes higher). Other symptoms of the reaction include general malaise, headache, nausea, pain in muscles, joints, tachycardia, increased breathing, decreased blood pressure, leukocytosis. With secondary syphilis, roseolous and papular rashes become more numerous, bright, swollen, sometimes the elements merge due to abundance (the so-called local exacerbation reaction). In some cases, against the background of an exacerbation reaction, secondary syphilides first appear in places where they were not present before treatment. Occasionally, patients may develop psychosis, stroke, convulsive syndrome, and liver failure. A rapidly transient exacerbation reaction usually does not require any special treatment. However, the development of a pronounced exacerbation reaction should be avoided:

1. when treating pregnant women, as it can provoke premature birth, fetal toxicity and stillbirth;
2. in patients with neurosyphilis, since an exacerbation reaction can provoke the progressive development of neurological symptoms;
3. in patients with damage to the organ of vision;
4. in patients with visceral syphilis, especially syphilitic mesaortitis.

High fever and severe intoxication syndrome can be dangerous in patients with chronic pathology cardiovascular system, severe somatic diseases in the stage of decompensation. To avoid an exacerbation reaction, it is recommended in the first 3 days of penicillin therapy to prescribe orally or intramuscularly prednisolone 60-90 mg per day (once in the morning) or in a decreasing dosage - 75-50-25 mg per day.

2. Reaction to intramuscular injection long-acting penicillin preparations (Hine's syndrome).

May occur after any injection of the drug. Characterized by dizziness, tinnitus, fear of death, pallor, paresthesia, blurred vision, high blood pressure, there may be a short-term loss of consciousness, hallucinations or convulsions immediately after the injection. Lasts within 20 minutes. Symptoms can be expressed to varying degrees - from mild to severe. The reaction is differentiated from anaphylactic shock, in which there is a sharp decline blood pressure.
Treatment: 1) complete rest, silence, horizontal position of the patient’s body; 2) prednisolone 60-90 mg or dexamethasone 4-8 mg intravenously or intramuscularly; 3) suprastin or diphenhydramine 1 ml of 1% solution intramuscularly; 4) for high blood pressure - papaverine 2 ml of 2% solution and dibazol 2 ml of 1% solution intramuscularly. If necessary, consultation with a psychiatrist and the use of sedatives and antipsychotics are indicated.

3. Nicolau syndrome

A symptom complex of complications after intra-arterial administration of durable drugs of penicillin or other drugs with a crystalline structure. It is characterized by sudden ischemia at the injection site, the development of painful bluish uneven spots (livedo) followed by the formation of blisters and necrosis of the skin, in some cases flaccid paralysis of the limb into which the artery was injected develops. the drug was introduced, in rare cases - transverse paralysis. Gross hematuria and bloody stools are observed as long-term complications. In the blood - leukocytosis. To date, cases have been reported only in pediatric practice.

4. Neurotoxicity- convulsions (more often in children), when used high doses penicillin, especially in renal failure.

5. Electrolyte imbalance- in patients with heart failure, when large doses of benzylpenicillin sodium salt are administered, edema may increase (1 million units of the drug contains 2.0 mmol of sodium).

6. Allergic reactions- toxicoderma, urticaria, Quincke's edema, headache, fever, joint pain, eosinophilia, etc. - when penicillin is administered, they occur in 5 to 10% of patients. Most dangerous complication is anaphylactic shock, which has a mortality rate of up to 10%.

7. Anaphylactic shock characterized by fear of impending death, a feeling of heat throughout the body, loss of consciousness, pale skin, cold sticky sweat, pointed facial features, frequent shallow breathing, thread-like pulse, low blood pressure. Treatment: 1) adrenaline 0.5 ml of 0.1% solution injected into the injection site of the drug; 2) adrenaline 0.5 ml 0.1% solution intravenously or intramuscularly; 3) prednisolone 60-90 mg or dexamethasone 4-8 mg intravenously or intramuscularly; 4) suprastin or diphenhydramine 1 ml 1% solution intramuscularly, 5) calcium gluconate 10 ml 10% solution intramuscularly, if breathing is difficult - aminophylline 10 ml 2.4% solution intravenously slowly.

1. 1. Intolerance to benzylpenicillin, its long-acting preparations and semi-synthetic derivatives.
2. 2. Long-acting penicillin preparations should be prescribed with caution to patients with severe forms hypertension who have suffered a myocardial infarction in the past, with disease of the endocrine glands, with acute gastrointestinal diseases, active tuberculosis, with diseases of the hematopoietic system.

Currently, due to the availability of effective and short-term treatment methods, detection of syphilis is not a medical indication for termination of pregnancy. The decision to continue or terminate the pregnancy is made by the woman. The role of the doctor is to provide timely adequate treatment (should be started before the 32nd week of pregnancy and carried out with medium-duration penicillin, sodium penicillin, semi-synthetic penicillins or ceftriaxone) and provide psychological support to the pregnant woman.

Specific treatment for pregnant women, regardless of gestational age, benzylpenicillin sodium crystalline salt or drugs of “medium” duration (benzylpenicillin novocaine salt) are carried out, as well as treatment of non-pregnant women, according to one of the methods proposed in these recommendations, in accordance with the established diagnosis.

Preventative treatment is carried out starting from the 20th week of pregnancy, but if specific treatment is started late - immediately after it. The drugs, single doses and frequency of administration correspond to those for specific treatment. The duration of preventive therapy is 10 days, and if there is information about the inadequacy of the specific treatment, then preventive treatment should last 20 days (as an additional one). If a pregnant woman is diagnosed with “late syphilis or syphilis unspecified as early or late”, a second course of specific treatment, which, as a rule, is carried out at 20 or more weeks of pregnancy, should be considered prophylactic treatment. In cases of complete adequate specific and preventive treatment, delivery can occur in a general maternity hospital at general principles. A child born without signs of congenital syphilis from a woman who has received full specific and preventive therapy does not need treatment.

Specific treatment of children with early congenital syphilis

benzylpenicillin sodium salt crystalline (d):

1. children under 1 month of age - 100 thousand units per kg of body weight per day, divided into 4 injections (every 6 hours), intramuscularly;
2. children aged 1 to 6 months - 100 thousand units per kg of body weight per day, divided into 6 injections (every 4 hours), intramuscularly;
3. children over 6 months of age - 75 thousand units per kg of body weight per day intramuscularly;
4. children over 1 year of age - 50 thousand units per kg of body weight per day intramuscularly:

within 20 days for latent early congenital syphilis; within 28 days - for manifest early congenital syphilis, including damage to the central nervous system, confirmed by positive serological reactions of the cerebrospinal fluid. If the mother refuses to perform a lumbar puncture for the child, the course of treatment should also be 28 days

benzylpenicillin novocaine salt (d) 50 thousand units per kg of body weight per day, divided into 2 injections (every 12 hours), intramuscularly: - for 20 days for latent early congenital syphilis - for 28 days - for manifest early congenital syphilis .

When indicating availability allergic reactions reserve drugs are used for penicillin:

1. Ceftriaxone (d) for children in the first two months of life is prescribed at a dose of 50 mg per kg of body weight per day in 2 administrations, for children from two months to 2 years - at a dose of 80 mg per kg of body weight per day in 2 administrations. The duration of treatment for latent early congenital syphilis is 20 days, for manifest early congenital syphilis, including with damage to the central nervous system, 28 days.
2. ampicillin sodium salt 100 thousand units per kg of body weight 2 times a day from 1 to 8 days of life, 3 times a day - from 9 to 30 days of life, 4 times a day - after 1 month of life. For latent forms of early congenital syphilis, the duration of treatment is 20 days, for manifest forms, including those with damage to the central nervous system, 28 days.

Specific treatment of children with late congenital syphilis

1. benzylpenicillin sodium crystalline salt (d) 50 thousand units per kg of body weight per day, divided into 6 injections (every 4 hours), intramuscularly for 28 days; after 2 weeks - a second course of treatment with benzylpenicillin crystalline sodium salt in a similar dose for 14 days.
2. benzylpenicillin novocaine salt (d) 50 thousand units per kg of body weight per day, divided into 2 injections (every 12 hours), intramuscularly for 28 days; after 2 weeks - a second course of treatment with benzylpenicillin with novocaine salt in a similar dose for 14 days.

When indicating the presence of allergic reactions to penicillin:

1. Ceftriaxone (d) for children aged 2 to 12 years is prescribed at a dose of 80 mg per kg of body weight per day in two doses, for children over 12 years old - at a dose of 1-2 g per day. For manifest or latent late congenital syphilis, the duration of the first course of treatment is 28 days; after 2 weeks, a second course of treatment with ceftriaxone is carried out at a similar dose for 14 days.

Specific treatment of acquired syphilis in children is carried out according to the method of treating adults in accordance with the diagnosis, based on age-specific doses of antibacterial drugs, taking into account the fact that domestic bicillins are contraindicated for children under 2 years of age, and tetracyclines for children under 8 years of age. The calculation of penicillin preparations for the treatment of children is carried out in accordance with the child’s body weight: at the age of up to 6 months, the sodium salt of penicillin is used at the rate of 100 thousand units per kg of body weight per day, at the age of over 6 months - at the rate of 75 thousand units per kg body weight body per day and over the age of 1 year - at the rate of 50 thousand units per kg of body weight per day.

The daily dose of novocaine salt of penicillin and a single dose of durant drugs are used at the rate of 50 thousand units per kg of body weight. The daily dose is divided into 6 equal single doses for water-soluble penicillin and into two doses for its novocaine salt.

Taking into account the anatomical and physiological characteristics of the urinary system in newborns and children in the first month of life, it is permissible to reduce the frequency of penicillin administration to 4 times a day. To avoid toxic reactions due to mass death Treponema pallidum after the first injections of penicillin (exacerbation of Herxheimer-Yarish-Lukashevich reaction) on the first day of treatment, a single dose of penicillin should not exceed 5000 units per injection. After each injection on the first day, control thermometry and monitoring of the child’s somatic condition are necessary.

Preventive treatment indicated for all children under 3 years of age. For older children, the issue of treatment is decided individually, taking into account the form of syphilis in the contact adult, the localization of the rash, the degree of contact of the child with the patient. It is carried out according to the method of preventive treatment of adults, based on age-specific doses of antibacterial drugs.

Preventive treatment is indicated for newborns born without manifestations of syphilis from an untreated or inadequately treated mother during pregnancy (specific treatment started after the 32nd week of pregnancy with a violation or change in approved treatment regimens), as well as newborns whose mother, if indicated, during pregnancy did not received preventive treatment.

The drugs, single doses and frequency of administration correspond to those for specific treatment.

The duration of therapy for newborns whose mother, if indicated during pregnancy, did not receive preventive treatment or received inadequate treatment is 10 days, newborns born without manifestations of syphilis from an untreated mother - 20 days.

Children born to mothers who received adequate specific treatment before pregnancy and preventive treatment during pregnancy, who at the time of birth remain positive for NTT with persistently low titers (RMP)<1:2, РПР <1:4), профилактическое лечение не показано, если НТТ у ребенка отрицательны, либо их титры не превышают титров НТТ у матери.

Adequate treatment of the mother should be considered documented therapy carried out in a medical institution in accordance with the clinical form and duration of syphilis, with strict adherence to single and course dosages and frequency of administration of antibacterial drugs.

When indicating the presence of allergic reactions to penicillin, reserve drugs are used:

1. ceftriaxone (C): for preventive treatment - 1.0 g 1 time per day intramuscularly daily for 5 days; for the treatment of primary syphilis - 1.0 g 1 time per day intramuscularly for 14 days; for the treatment of secondary and early latent syphilis - 1.0 g 1 time per day intramuscularly for 28 days; for the treatment of late forms of syphilis - 1.0 g 1 time per day intramuscularly for 28 days and after 2 weeks a second course of the drug in a similar dose for 14 days; for treatment early neurosyphilis - 2.0 g 1 time per day intramuscularly for 20 days, in severe cases (syphilitic meningoencephalitis, acute generalized meningitis), intravenous use of the drug and increasing the daily dose to 4 g are possible; for the treatment of late neurosyphilis, two courses of treatment are carried out in a similar manner regimen with an interval of 2 weeks between courses. Treatment regimens for syphilis with ceftriaxone were developed based on studying the pharmacokinetics of the original ceftriaxone. There have been no studies examining the effectiveness of most generic ceftriaxone preparations. There are no data on the equivalence (pharmaceutical, pharmacokinetic, therapeutic) of generic drugs ceftriaxone and the original drug, without studying which it is unacceptable to replace one drug with another,
2. doxycycline (C) 0.1 g 2 times a day orally for 10 days for preventive treatment; 0.1 g 2 times a day orally for 20 days - for the treatment of primary syphilis; 0.1 g 2 times a day orally for 28 days - for the treatment of secondary and early latent syphilis,
3. erythromycin (d) 0.5 g 4 times a day orally for 10 days for preventive treatment; 0.5 g 4 times a day orally for 20 days for the treatment of primary syphilis; 0.5 g 4 times a day orally for 28 days for the treatment of secondary and early latent syphilis,
4. oxacillin sodium salt or ampicillin sodium salt (d) 1 million units 4 times a day (every 6 hours) intramuscularly for 10 days for preventive treatment; 1 million units 4 times a day (every 6 hours) intramuscularly for 20 days - for the treatment of primary syphilis; 1 million units 4 times a day (every 6 hours) intramuscularly for 28 days for the treatment of secondary and early latent syphilis.

For pregnant women with intolerance to penicillin (including semisynthetic) and ceftriaxone, due to a contraindication to tetracycline drugs, it is recommended to prescribe erythromycin. However, the baby must be treated with penicillin after birth because erythromycin does not cross the placenta.

1. Negativity of nonspecific serological reactions - RMP (RPR, VdRL) - or a decrease in antibody titer by 4 or more times (by 2 serum dilutions) within 12 months after the end of specific therapy for early forms of syphilis.
2. Negativity of RIBT (usually no earlier than 2-3 years after the end of treatment).

Negativity of RIF, ELISA, and RPGA is extremely rare. The persistence of positive RIF, ELISA and RPGA with negative NTT in a person who has had syphilis is not considered a failure of therapy.

The criteria for the effectiveness of treatment of neurosyphilis are:

1. normalization of pleocytosis within 6 months after the end of therapy;
2. disappearance of specific IgM and antibodies to cardiolipins from the serum within 6-12 months after the end of therapy. Sometimes the production of these antibodies can continue for more than a year, then it is important to take into account the dynamics of the decrease in titers;
3. absence of new neurological symptoms and increase in existing neurological symptoms.

1. Persistence or recurrence of clinical manifestations (clinical relapse).
2. A sustained increase of 4 times or more compared to the initial values ​​of the titer of nonspecific serological reactions.
3. Repeated positivity of NTT after a period of temporary negativity in the absence of evidence of reinfection (serological relapse).
4. Persistent persistence of positive NTTs without a tendency to decrease antibody titers within 12 months after the end of specific therapy for early forms of syphilis (serological resistance).

If, within 12 months after the end of specific therapy for early forms of syphilis, the positivity of NTT and/or antibody titer gradually decreases (by at least 4 times), but complete negativity of NTT is not observed, delayed negativity of NTT is stated. Clinical and serological observation of such patients is extended to 2 years, after which the question of the advisability of prescribing additional treatment is decided.

Additional treatment is prescribed in the following cases:

1. if a year after full treatment of early forms of syphilis there has not been a 4-fold decrease in the titer of RMP/RPR;
2. if 1.5 years after full treatment of early forms of syphilis there is no tendency to further decrease in titers/degree of positivity of RMP/RPR;
3. if 2 years after full treatment of early forms of syphilis, complete negativity of RMP/RPR has not occurred;
4. if 6 months after full treatment of early congenital syphilis there has not been a 4-fold decrease in the titer of RMP/RPR.

Before additional treatment, a re-examination of patients by medical specialists (dermatovenerologist, ophthalmologist, neurologist, therapist, otorhinolaryngologist) and examination of the CSF are indicated, even in the absence of clinical neurological symptoms. If a specific pathology of the nervous system and internal organs is detected, a diagnosis of neuro- or visceral syphilis is established and appropriate specific treatment is carried out according to the methods of these forms.

In the absence of specific pathology of the nervous system and internal organs, additional treatment is usually carried out once/twice with the following drugs:

1. benzylpenicillin sodium salt crystalline (C) 1 million units 6 times a day (every 4 hours) intramuscularly for 28 days
2. benzylpenicillin sodium salt crystalline (B) 12 million units 2 times a day intravenously for 14 days. Due to the need to maintain the treponemocidal concentration of penicillin for at least 4 weeks, at the end of the course of therapy, 3 injections of bicillin-1 should be performed at a dose of 2.4 million units intramuscularly once every 5 days,
3. ceftriaxone (d) 1.0 g 2 times a day intramuscularly for 20 days.

Additional treatment in children is carried out according to the method of treating adults based on age-specific doses of antibacterial drugs.

Indications for an additional course of therapy after treatment of neurosyphilis:

1. the number of cells does not return to normal within 6 months or, having returned to normal, increases again;
2. within 1 year there is no decrease in the positivity of RMP/RPR in the CSF;
3. within 2 years there is no significant decrease in the protein content in the CSF.

Additional treatment in this case is carried out according to the methods of treating neurosyphilis.

Protein levels in the CSF change more slowly than cytosis and serological tests, and sometimes take up to 2 years to normalize. The persistence of an elevated but decreasing protein level with normal cytosis levels and negative results of serological tests is not an indication for an additional course of therapy.

Persons who have had sexual or close household contact with patients with early forms of syphilis, for whom no more than 2 months have passed since contact, are recommended to undergo preventive treatment using one of the above methods.

Persons for whom 2 to 4 months have passed since contact with a patient with early syphilis undergo a double clinical and serological examination with an interval of 2 months; if more than 4 months have passed since contact, a one-time clinical and serological examination is carried out.

Preventive treatment of a recipient who has received a blood transfusion from a patient with syphilis is carried out according to one of the methods recommended for the treatment of primary syphilis, if no more than 3 months have passed since the transfusion; if this period was from 3 to 6 months, then the recipient is subject to clinical and serological control twice with an interval of 2 months; If more than 6 months have passed since the blood transfusion, then a one-time clinical and serological examination is performed.

Adults and children who received preventive treatment after sexual or close household contact with patients with early forms of syphilis are subject to a single clinical and serological examination 3 months after the end of treatment.

Clinical serological control (CSC) after the end of specific treatment is carried out once every 3 months during the first year of observation and once every 6 months in subsequent years with non-treponemal tests, once a year - with the corresponding treponemal test, which was used for diagnosis of the disease.

Patients with early forms of syphilis who had positive results of RMP/RPR before treatment should be on CSC until serological non-treponemal tests are negative, and then for another 6-12 months (during which 2 examinations are necessary). The duration of CSC is determined individually depending on the results of treatment.

Patients with late forms of syphilis, in whom the results of non-treponemal tests often remain positive after treatment, should be on CSC for at least 3 years. The decision to deregister or extend control is made individually.

Patients with neurosyphilis, regardless of stage, should be on CSC for at least 3 years with mandatory monitoring of CSF composition once every 6-12 months. The persistence of pathological changes (taking into account non-treponemal tests) is an indication for additional treatment.

Persistent normalization of CSF composition, even if residual clinical manifestations persist, is an indication for deregistration.

Children born to seropositive mothers who did not have congenital syphilis, regardless of whether they received preventive treatment or not, are subject to observation for 1 year. The first clinical and serological examination is carried out at the age of 3 months and includes an examination by a pediatrician, consultations with a neurologist, ophthalmologist, otolaryngologist, and a comprehensive serological examination. If the results of the serological examination are negative and there are no clinical symptoms of the disease, the examination is repeated before deregistration at the age of 1 year. In other cases, the examination is carried out at 6, 9 and 12 months of age.

Children who received specific treatment are on CSC for 3 years.

If a clinical or serological relapse occurs, as well as in cases of persistent positivity or delayed negativity of serological reactions, consultations with a therapist, neurologist, ophthalmologist, otolaryngologist, spinal puncture, and clinical serological examination of the sexual partner are indicated. Treatment is carried out according to the methods specified in the “Additional treatment” section.

At the end of the observation period, a full clinical and serological examination is carried out, including RMP (or analogues), RPGA, ELISA, if necessary, RIBT, RIF and consultation with a therapist/pediatrician, neurologist, ophthalmologist, otolaryngologist.

Persons who have received a full course of specific treatment for syphilis, after regression of the clinical symptoms of the disease (in the presence of a manifest form of syphilis), are allowed to work in children's institutions and public catering establishments.

Children receiving specific treatment for syphilis can visit a child care facility after the disappearance of clinical manifestations and completion of the course of specific treatment.

Patients with positive results of non-treponemal tests can be removed from the register if the following conditions are met: 1) complete specific treatment; 2) KSK for at least 3 years; 2) favorable results of CSF examination before deregistration; 3) absence of specific clinical pathology upon consultation with specialists (neurologist, ophthalmologist, otolaryngologist, internist/pediatrician); 4) absence of suspicion of cardiovascular syphilis during ultrasound examination of the heart and aorta.

Prevention of syphilis includes: sanitary education; screening examination of certain population groups at increased risk of infection, or those groups in which the disease leads to dangerous social and medical consequences, as well as full-fledged specific treatment followed by clinical and serological observation.

Prevention of congenital syphilis is carried out antenatally and postnatally.

1. Antenatal prevention includes: working with healthy people, providing information about the possibility of intrauterine transmission of syphilis and the need for early prenatal care; three-time serological examination of pregnant women (when visiting an antenatal clinic, at 28-30 weeks and 2-3 weeks before birth); when syphilis is detected, adequate specific and preventive treatment is given.
2. Postnatal prevention of congenital syphilis consists of preventive treatment of children.

Individual prevention is ensured by the use of barrier methods of contraception (condoms). After accidental unprotected sexual intercourse, it can be carried out independently with the help of individual prophylactic agents (chlorhexidine bigluconate, miramistin).

Syphilis latent early

Profile: therapeutic, specialty - dermatovenerologist.
Treatment stage: hospital
Purpose of the stage: receiving a full course of specific treatment; prevention of late relapses.
Duration of treatment: Day 28

ICD codes: A51.5 Early latent syphilis.

Definition: Syphilis is an infectious disease characterized by immunological failure, caused by Treponema pallidum, transmitted predominantly sexually with a characteristic periodization of clinical symptoms, capable of affecting all organs and systems.
Latent early syphilis is a type of syphilis that takes a latent course from the moment of infection, without clinical signs of the disease, with positive serological reactions with a duration of infection of up to 2 years.

Classification:
1. Primary seronegative syphilis.
2. Primary seropositive syphilis.
3. Secondary fresh syphilis.
4. Secondary recurrent syphilis.
5. Latent early syphilis, lasting up to 2 years.
6. Serorecurrent syphilis.
7. Seroresistant syphilis.
8. Tertiary syphilis.
9. Late latent syphilis. Syphilis (acquired) without clinical manifestations with a positive serological reaction 2 years or more from the moment of infection.
10. Latent syphilis, unspecified. Cases with a positive serological reaction to syphilis when it is impossible to determine the timing of infection. This group includes persons who began treatment at a previously unknown stage of syphilis.
11. Early congenital syphilis. Congenital syphilis in infancy (up to 1 year) and early childhood (up to 2 years).
12. Late congenital syphilis more than 2 years old.
13. Latent congenital syphilis.
14. Syphilis of the nervous system: early - when the syphilitic infection is less than 2 years old; late - when the syphilitic infection has been more than 2 years old.
15. Tabes dorsalis.
16. Progressive paralysis.
17. Visceral syphilis indicating the affected organ.

Risk factors:
Promiscuous sexual intercourse, very rarely with indirect contact with a sick person through objects (toothbrushes, spoons, smoking pipes, etc.), intrauterine transmission from a sick mother to a child, with direct blood transfusion, through the milk of a sick nursing woman to a child. The risk of developing early latent syphilis: taking a large number of antibiotics for other diseases, self-medication, lack of awareness about sexually transmitted diseases.

Admission: planned.

Indications for hospitalization:
1. Socially unadapted people; minors delivered from the Center for Temporary Isolation for Adaptation of Rehabilitation of Minors with positive serological reactions.
2. Persons working in organized teams with positive serological reactions.

The required scope of examinations before planned hospitalization:
1. General blood test;
2. General urine analysis;
3. Feces on worm eggs;
4. Fluorography;
5. Wasserman reaction;
6. Blood test for HIV.

Diagnostic criteria:
1. Anamnesis data: taking antibiotics and other antibacterial drugs, blood transfusions, etc. in the last 2 years, presence in the past of eruptive elements-erosions, ulcers, as a rule, after casual sexual intercourse; results of external examination: secondary residual elements - scars, spots, enlarged regional lymph nodes.
2. Positive serological reactions (Wassermann reaction, immunofluorescence reaction, Treponema pallidum immobilization reaction, enzyme immunoassay, passive hemagglutination reaction) in the absence of clinical manifestations.
3. Herxheimer-Jarisch reaction (fever) after starting antibiotic therapy.
4. Relatively rapid negativity of serological reactions against the background of specific antisyphilitic treatment.

List of basic diagnostic services:
1. General blood test
2. General urine test
3. Blood test for HIV
4. ELISA-HBsAg
5. Enzyme-linked immunosorbent assay (ELISA)
6. Immunofluorescence reaction
7. Feces on me/worm
8. KSR.

List of additional diagnostic services:
1. Consultation with a therapist according to indications
2. Consultation with an ophthalmologist according to indications
3. Consultation with an otolaryngologist according to indications
4. Examination of smears for gonorrhea, trichomoniasis and yeast fungus
5. Chlamydia ELISA according to indications
6. Immunogram.

Treatment tactics:

Etiotropic therapy:
Method 1: Treatment is carried out with benzathine benzylpenicillin, 2.4 million units per injection, once a week, No. 3; or bicillin-1, 2.4 million units per injection, once every 5 days, No. 6.

Method 2: Treatment is carried out with bicillin-3, administered at a dose of 1.8 million units 2 times a week - No. 10; or bicillin-5 in a single dose of 1,500,000 units, administered 2 times a week - No. 10.

Method 3: Procaine-penicillin is used in a single dose of 1.2 million, daily for a course - No. 20, or novocaine salt of penicillin at 600,000 units 2 times a day - 20 days.

Method 4: Therapy is carried out with water-soluble penicillin, 1 million units every 6 hours, 4 times a day for 20 days.

Method 5:(used only for hypersensitivity to both penicillin and cephalosporin antibiotics):
Doxycycline is used 0.1 g every 8 hours 3 times a day for 30 days, 9 g per course; or tetracycline 0.5 g every 6 hours 4 times a day for 30 days, for a course of 60 g.
Erythromycin 0.5 g per dose 4 times a day, for 30 days, every 6 hours, for a course of 60 g.
Azithromycin 0.5 g every 12 hours 2 times a day for 3 weeks.

Method 6: Cefazolin 1.0 g every 4 hours 6 times a day for 28 days.

Method 7: Ceftriaxone 1.0 x 1 time per day every other day intramuscularly, course dose 10.0 g.

To prevent intestinal dysbiosis, antifungal therapy is prescribed: itraconazole oral solution 200 mg 2 times a day for 21 days or flucanozole 150 mg once every 3 days - 2-3 courses.

List of essential medications:
1. Benzylpenicillin. por d/i 1000000 units, fl
2. Cefazolin 1 g, fl
3. Ampicillin 1 g, fl
4. BenzathinebenzylpenicillinG 2.4 million units, fl
5. Benzylpenicillin novocaine salt 600,000 units, fl

List of additional medications:
4. Doxycycline 100 mg, tablet
1. Erythromycin 500 mg, tablet
2. Azithromycin 500 mg, tablet
3. Tetracycline 100 mg, 200 mg, tablet
4. Itraconazole oral solution 150 ml – 10 mg/ml
5. Flucanozole 150 mg, tablet
6. Ceftriaxone 1 g, fl
7. Vitamins B, C
8. Immunomodulators: methyluracil 500 mg tablet, cycloferon amp.
9. Biostimulants: aloe, vitreous body &

Criteria for transfer to the next stage: full course of specific treatment.
Patients who have received specific treatment are subject to clinical and serological monitoring for 3 years with the frequency of donating blood for the Wasserman reaction once every 3 months.

MANAGEMENT OF PATIENTSSYPHILIS

Moscow 2013

Personnel of the working group for the preparation of federal clinical recommendations in the profile "Dermatovenereology", section "Syphilis":

1. 
   Sokolovsky Evgeniy Vladislavovich - head of the department of dermatovenereology with the clinic of the First St. Petersburg State Medical University named after. Academician I.P. Pavlova, Doctor of Medical Sciences, Professor, St. Petersburg.
2. 
   Krasnoselskikh Tatyana Valerievna – Associate Professor of the Department of Dermatovenereology with the clinic of the First St. Petersburg State Medical University named after. Academician I.P. Pavlova, Candidate of Medical Sciences, St. Petersburg.
3. 
   Margarita Rafikovna Rakhmatulina – Deputy Director of the Federal State Budgetary Institution “State Scientific Center for Dermatovenereology and Cosmetology” of the Russian Ministry of Health for Medical Work, Doctor of Medical Sciences, Moscow.
4. 
   Frigo Natalya Vladislavovna– Deputy Director of the Federal State Budgetary Institution “State Scientific Center for Dermatovenereology and Cosmetology” of the Ministry of Health of Russia for scientific and educational work, Doctor of Medical Sciences, Moscow.
5. 
   Ivanov Andrey Mikhailovich - Head of the Department of Clinical Biochemistry and Laboratory Diagnostics Federal State Budgetary Educational Institution of Higher Professional Education "Military Medical Academy named after. CM. Kirov" of the Russian Ministry of Defense, chief laboratory assistant of the Russian Ministry of Defense, Professor, Doctor of Medical Sciences, St. Petersburg.
6. 
   Denis Vladimirovich Zaslavsky – Professor of the Department of Dermatovenereology of the State Budgetary Educational Institution of Higher Professional Education “St. Petersburg State Pediatric Medical University” of the Ministry of Health of Russia, Doctor of Medical Sciences, St. Petersburg.

METHODOLOGY

Methods used to collect/select evidence:

search in electronic databases.
Description of methods used to collect/select evidence:

• 
  Expert consensus;
• 
  Assessment of significance in accordance with the rating scheme (scheme attached).

Methods used to analyze evidence:

• 
  Reviews of published meta-analyses;
• 
  Systematic reviews with evidence tables.

Methods used to formulate recommendations:

Indicators of good practice (GoodPracticePoints – GPPs):

No cost analysis was performed and pharmacoeconomics publications were not reviewed.
Recommendation validation method:

• 
  External expert assessment;
• 
  Internal expert assessment.

Comments received from experts were systematized and discussed by members of the working group. The resulting changes to the recommendations were recorded. If changes were not made, then the reasons for refusing to make changes are recorded.
Consultation and expert assessment:

The preliminary version was posted for discussion on the website of the Federal State Budgetary Institution “State Scientific Center for Dermatovenereology and Cosmetology” of the Ministry of Health of Russia so that persons not involved in the development of recommendations had the opportunity to take part in the discussion and improvement of the recommendations.
Working group:

For final revision and quality control, the recommendations were re-reviewed by members of the working group.
Basic recommendations:

SYPHILIS

Code according to the International Classification of Diseases ICD-10

A 50, A51, A52, A53
DEFINITION

Syphilis is an infectious disease caused by Treponema pallidum ( Treponema pallidum), transmitted predominantly sexually, characterized by damage to the skin, mucous membranes, nervous system, internal organs and musculoskeletal system.
ETIOLOGY AND EPIDEMIOLOGY

The causative agent of syphilis belongs to the order Spirochaetales, family Spirochaetaeceae, family Treponema, mind Treponema pallidum, subspeciespallidum (syn. Spirochaeta pallidum). Treponema pallidum is easily destroyed under the influence of external agents: drying, heating at 55 ° C for 15 minutes, exposure to 50–56 O ethyl alcohol solution. At the same time, low temperatures promote the survival of Treponema pallidum.

Treponema pallidum is a spiral-shaped microorganism; the number of revolutions of the spiral is from 8 to 12, its curls are uniform and have an identical structure. Performs characteristic types of movement: rotational, translational, wave-like and flexion. It reproduces primarily by transverse division into two or more segments, each of which then grows into an adult.

The microorganism can also exist in the form of cysts and L-forms. The cyst is a form of survival of Treponema pallidum under unfavorable environmental conditions and is considered as a dormant stage T. Rallidum; has antigenic activity. L-form is a way of survival of Treponema pallidum and has weak antigenic activity.

According to official state statistical reporting, the epidemiological situation with syphilis is characterized by a gradual decrease in incidence in the Russian Federation as a whole (in 2009 - 53.3 cases per 100,000 population; in 2012 - 33.1 cases per 100,000 population).

Against the background of a decrease in the overall incidence of syphilis, there is an increase in the number of registered cases of neurosyphilis with a predominance of its late forms (70.1%). From 2000 to 2010, the incidence of neurosyphilis increased 7.2 times (from 120 to 862 cases).
ROUTES OF INFECTION

• 
  sexual (the most common and typical route of infection; infection occurs through damaged skin or mucous membranes);
• 
  transplacental (transmission of infection from a sick mother to the fetus through the placenta, leading to the development of congenital syphilis);
• 
  transfusion (with blood transfusion from a donor with syphilis at any stage);
• 
  contact-household (is rare; occurs mainly during everyday contact with children of parents who have rashes on the skin/mucous membranes);
• 
  professional (infection of laboratory personnel working with infected experimental animals, as well as obstetricians-gynecologists, surgeons, dentists, pathologists, forensic experts when performing professional duties);

Currently, Russia uses the International Classification of Diseases, 10th revision (ICD-10), which does not always adequately reflect the clinical forms of the disease. Thus, A51.4 (other forms of secondary syphilis) includes early damage to the nervous system, internal organs and musculoskeletal system. There is also no division of asymptomatic neurosyphilis into early and late, as a result of which all patients with asymptomatic neurosyphilis, regardless of the duration of the disease, are classified as late syphilis (A 52.2). It should be noted that the code ending with the number 9 (A 50.9; A 51.9, A 52.9 and A 53.9), as well as A50.2 and A50.7, reflect forms of infection that are not confirmed by laboratory diagnostic methods, being “a basket into which they are dumped incorrectly.” issued notices."

A 50 Congenital syphilis

A 50.0 Early congenital syphilis with symptoms

Any congenital syphilitic condition specified as early on or occurring before the age of two years.

Early congenital syphilis:

• 
  skin;
• 
  skin and mucous membranes;

• 
  visceral.

• 
  laryngitis;
• 
  oculopathy;
• 
  osteochondropathy;
• 
  pharyngitis;
• 
  pneumonia;
• 
  rhinitis.

Congenital syphilis without clinical manifestations, with a positive serological reaction and a negative cerebrospinal fluid test before the age of two years.

A50.2 Early congenital syphilis, unspecified

Congenital syphilis NOS, manifested before the age of two years.

A50.3 Late congenital syphilitic eye damage

Late congenital syphilitic interstitial keratitis (H19.2).

Late congenital syphilitic oculopathy (H58.8).

Hutchinson's triad (A50.5) is excluded.

A50.4 Late congenital neurosyphilis (juvenile neurosyphilis)

Dementia paralytic juvenile.

Juvenile:

• 
  progressive paralysis;
• 
  tabes dorsalis;
• 
  taboparalysis. Late congenital syphilitic(s):
• 
  encephalitis (G05.0);
• 
  meningitis (G01);
• 
  polyneuropathy (G63.0).

Excluded: Hutchinson's triad (A50.5).

A50.5 Other forms of late congenital syphilis with symptoms

Any congenital syphilitic condition specified as late or occurring two years or more after birth.

Clutton joints (M03.1).

Hutchinson:

• 
  teeth;
• 
  triad.

• 
  cardiovascular syphilis (198.);
• 
  syphilitic:

• 
  arthropathy (M03.1);
• 
  osteochondropathy (M90.2).

A50.6 Late congenital syphilis latent

Congenital syphilis without clinical manifestations, with a positive serological reaction and a negative cerebrospinal fluid test at the age of two or more years.

A50.7 Late congenital syphilis, unspecified

Congenital syphilis NOS at two or more years of age.

A50.9 Congenital syphilis, unspecified

A51 Early syphilis

A51.0 Primary syphilis of the genital organs Syphilitic chancre NOS.

A51.1 Primary syphilis of the anal area

A51.2 Primary syphilis of other localizations

A51.3 Secondary syphilis of the skin and mucous membranes Condyloma lata.

Syphilitic(s):

• 
  alopecia (L99.8);
• 
  leucoderma (L99.8);
• 
  lesions on mucous membranes.

Secondary syphilitic (s):

• 
  inflammatory disease of the female pelvic organs (N74.2);
• 
  iridocyclitis (H22.0);
• 
  lymphadenopathy;
• 
  meningitis (G01);
• 
  myositis (M63.0);
• 
  oculopathy NEC (H58.8);
• 
  periostitis (M90.1).

Syphilis (acquired) without clinical manifestations with a positive serological reaction and a negative sample of cerebrospinal fluid, less than two years after infection.

A51.9 Early syphilis, unspecified

3.2 Surgical treatment.

Early congenital syphilis:

■■ skin;

■■ skin and mucous membranes;

■■ visceral.

Early congenital syphilitic(s):

■■ laryngitis;

■■ oculopathy;

■■ osteochondropathy;

■■ pharyngitis;

■■ pneumonia;

■■ rhinitis.

A50.1 Early latent congenital syphilis

Congenital syphilis without clinical manifestations, with a positive serological reaction and a negative result in the study of cerebrospinal fluid, manifested before the age of two years.

A50.2 Early congenital syphilis, unspecified

Congenital syphilis NOS (not otherwise specified), manifested before the age of two years.

A50.3 Late congenital syphilitic eye damage

Late congenital syphilitic interstitial keratitis (H19.2).

Late congenital syphilitic oculopathy (H58.8). Hutchinson's triad (A50.5) is excluded.

A50.4 Late congenital neurosyphilis (juvenile neurosyphilis)

Dementia paralytic juvenile.

Juvenile:

■■ progressive paralysis;

■■ tabes dorsalis;

■■ taboparalysis.

Late congenital syphilitic(s):

■■ encephalitis (G05.0);

■■ meningitis (G01);

■■ polyneuropathy (G63.0).

If necessary, identify any related concern

Left mental disorder use an additional code. Hutchinson's triad (A50.5) is excluded.

A50.5 Other forms of late congenital syphilis with symptoms

Any congenital syphilitic condition specified as late or occurring two years or more after birth.

Clutton joints (M03.1).

Hutchinson:

■■ teeth;

■■ triad.

Late congenital:

■■ cardiovascular syphilis (198.);

■■ syphilitic:

- arthropathy (M03.1);

- osteochondropathy (M90.2). Syphilitic saddle nose.

A50.6 Late congenital syphilis latent

Congenital syphilis without clinical manifestations, with a positive serological reaction and a negative cerebrospinal fluid test, manifested at the age of two or more years.

A50.7 Late congenital syphilis, unspecified

Congenital syphilis NOS, manifested at the age of two or more years.

A50.9 Congenital syphilis, unspecified

A51 Early syphilis

A51.0 Primary syphilis of the genital organs

Syphilitic chancre NOS.

A51.1 Primary syphilis of the anal area A51.2 Primary syphilis of other localizations

A51.3 Secondary syphilis of the skin and mucous membranes

Condyloma lata. Syphilitic(s):

■■ alopecia (L99.8);

■■ leucoderma (L99.8);

■■ lesions on mucous membranes.

A51.4 Other forms of secondary syphilis

Secondary syphilitic(s):

■■ inflammatory disease of the female pelvic organs (N74.2);

■■ iridocyclitis (H22.0);

■■ lymphadenopathy;

■■ meningitis (G01);

■■ myositis (M63.0);

■■ oculopathy NEC (H58.8);

■■ periostitis (M90.1).

A51.5 Early latent syphilis

Syphilis (acquired) without clinical manifestations with a positive serological reaction and a negative sample of cerebrospinal fluid, less than two years after infection.

A51.9 Early syphilis, unspecified

A52 Late syphilis

A52.0 Syphilis of the cardiovascular system

Cardiovascular syphilis NOS (198.0). Syphilitic(s):

■■ aortic aneurysm (179.0);

■■ aortic insufficiency (139.1);

■■ aortitis (179.1);

■■ cerebral arteritis (168.1);

■■ endocarditis NOS (139.8);

■■ myocarditis (141.0);

■■ pericarditis (132.0);

■■ pulmonary failure (139.3).

A52.1 Neurosyphilis with symptoms

Charcot arthropathy (M14.6). Late syphilitic:

■■ acoustic neuritis (H49.0);

■■ encephalitis (G05.0);

■■ meningitis (G01);

■■ optic nerve atrophy (H48.0);

■■ polyneuropathy (G63.0);

■■ retrobulbar neuritis (H48.1). Syphilitic parkinsonism (G22). Tabes dorsalis.

A52.2 Asymptomatic neurosyphilis

A52.3 Neurosyphilis, unspecified

Gumma (syphilitic).

Syphilis (late) of the central nervous system NOS. Syphiloma.

A52.7 Other symptoms of late syphilis

Syphilitic lesion of the renal glomeruli (N08.0).

Gumma (syphilitic) of any localization, except those classified in headings A52.0–A52.3.

Sexually transmitted infections

Syphilis (without specifying the stage):

■■ bones (M90.2);

■■ liver (K77.0);

■■ lung (J99.8);

■■ muscles (M63.0);

■■ synovial (M68.0).

A52.8 Late latent syphilis

Syphilis (acquired) without clinical manifestations, with a positive serological reaction and a negative cerebrospinal fluid sample, two years or more after infection.

A52.9 Late syphilis, unspecified

A53 Other and unspecified forms of syphilis

A53.0 Latent syphilis, unspecified as early or late

Latent syphilis NOS.

Positive serological reaction to syphilis.

A53.9 Syphilis, unspecified

Infestation caused by Treponema pallidum, NOS. Syphilis (acquired) NOS.

Syphilis NOS causing death before the age of two years was excluded (A50.2).

ROUTES OF INFECTION

■■ sexual (the most common and typical route of infection; infection occurs through damaged skin or mucous membranes);

■■ transplacental (transmission of infection from a sick mother to the fetus through the placenta, leading to the development of congenital syphilis);

■■ transfusion (with blood transfusion from a donor with syphilis at any stage);

■■ contact-household(is rare; occurs mainly in children through everyday contact with parents who have syphilitic rashes on the skin and/or mucous membranes);

■■ professional (infection of laboratory personnel, working

dealing with infected experimental animals, as well as obstetricians-gynecologists, surgeons, dentists, pathologists, forensic experts in the performance of professional duties).

It is possible to infect infants with syphilis through the milk of nursing women with syphilis. Also contagious biological fluids include saliva and semen of patients with syphilis with clinical manifestations of the corresponding localizations. There were no cases of infection through sweat or urine.

CLINICAL PICTURE

Incubation period begins with the introduction of the causative agent of syphilis through damaged skin or mucous membrane and ends with the appearance of the primary affect. On average, the incubation period lasts from 2 weeks to 2 months; this period can be shortened to 8 days or, conversely, extended to 190 days. A reduction in the incubation period is observed during reinfection and when the pathogen of syphilis is introduced into the body from several entrance gates, which accelerates the generalization of the infection and the development of immune changes in the body. An extension of the incubation period is observed as a result of the use of small doses of treponemocidal antibacterial drugs for intercurrent diseases.

Primary syphilis(A51.0-A51.2). At the site of the introduction of pale treponema, a primary affect develops - erosion or ulcer with a diameter of 2–3 mm (dwarf chancre) to 1.5–2 cm or more (giant chancre), round in outline, with smooth edges, a smooth, shiny pink or red bottom , sometimes grayish-yellow in color, saucer-shaped (ulcer), with scanty serous discharge, painless on palpation; at the base of primary syphiloma there is a dense elastic infiltrate. Primary affect is accompanied by regional lymphadenitis, less often lymphangitis; can be typical (erosive, ulcerative) and atypical (indurative edema, chancre-felon and chancre-amygdalitis); single and multiple; genital, perigenital and extragenital; when a secondary infection is attached - complicated (impetiginization, balanoposthitis, vulvovaginitis, phimosis, paraphimosis, gangrenization, phagedenism). At the end of the primary period, polyadenitis and general infectious symptoms (intoxication syndrome) appear.

Secondary syphilis(A51.3). It is caused by hematogenous dissemination of infection against the background of the development of infectious immunity and is manifested by: rashes on the skin (roseolous (spotty), papular (nodular), papulopustular (pustular) and rarely vesicular) and/or mucous membranes (limited and confluent roseolous and papular syphilides) ; leukoderma, alopecia. Residual effects of primary syphilis, damage to internal organs, the musculoskeletal system and the nervous system are possible (A51.4).

Tertiary syphilis(A52.7). It can develop immediately after secondary syphilis, but in most cases there is a latent period between the secondary and tertiary periods. The appearance of symptoms of tertiary syphilis is possible many years after infection if the infection is asymptomatic. Manifested by rashes on the skin/mucous membranes (tubercular and gummous syphilides, Fournier tertiary roseola), lesions of internal organs, the musculoskeletal system and the nervous system (A52.0-A52.7).

shins, chorioretinitis, nasal deformities, radiating scars around the mouth, buttock-shaped skull, dental deformations, syphilitic gonitis, lesions of the nervous system in the form of hemiparesis and hemiplegia, speech disorders, weak intelligence, cerebral infantile palsy and Jacksonian epilepsy) and dystrophies (thickening of the sternal end of the right clavicle, dystrophy of the skull bones in the form of an “Olympic forehead”, high “Gothic” or “lancet” palate, absence of the xiphoid process of the sternum, infantile little finger, widely spaced upper incisors, tubercle on the chewing surface of the first molar of the upper jaw). In addition, specific lesions on the skin and mucous membranes are characteristic in the form of tubercular and gummous syphilides of the skin, mucous membranes, damage to organs and systems, especially bone (periostitis, osteoperiostitis, gummous osteomyelitis, osteosclerosis), liver and spleen, cardiovascular, nervous and endocrine systems.

Neurosyphilis. There are asymptomatic and manifest neurosyphilis. Based on the time period from the moment of infection, neurosyphilis is conventionally divided into early (up to 5 years from the moment of infection) and late (more than 5 years from the moment of infection). This division does not completely define all aspects of damage to the nervous system, since the clinical manifestations of neurosyphilis represent a single dynamic system with a combination of symptoms of early and late forms.

Asymptomatic neurosyphilis(A51.4; A52.2) is characterized by the absence of clinical manifestations. The diagnosis is based on pathological changes revealed by examining the cerebrospinal fluid.

Neurosyphilis with symptoms manifested by any neurological or mental disorders that have an acute or subacute development and progress over several months or years. The most common early form of neurosyphilis (A51.4) is meningovascular syphilis, the clinical picture of which is dominated by symptoms of damage to the membranes and blood vessels of the brain: syphilitic meningitis (acute convexital, acute basal, acute syphilitic hydrocephalus), syphilitic uveitis (chorioretinitis, iritis), vascular neurosyphilis (ischemic, less often hemorrhagic stroke), spinal meningovascular syphilis (syphilitic meningomyelitis). Late forms of neurosyphilis include progressive paralysis, tabes dorsalis, taboparalysis, optic nerve atrophy (A52.1) and gummous neurosyphilis (A52.3), the clinical picture of which is dominated by symptoms of damage to the brain parenchyma.

Syphilis of internal organs and musculoskeletal system Based on the time period from the moment of infection, they are conventionally divided into early (up to 2 years from the moment of infection) and late (more than 2 years from the moment of infection) forms. In early forms (A51.4), only functional disorders of the affected organs most often develop. The pathological process primarily involves the heart (early cardiovascular syphilis), liver (anicteric or icteric forms of hepatitis), stomach (transient gastropathy, acute gastritis, formation of specific ulcers and erosions),

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glasses (asymptomatic renal dysfunction, benign proteinuria, syphilitic lipoid nephrosis, syphilitic glomerulonephritis). The earliest symptom of damage to the musculoskeletal system is night pain in the long tubular bones of the limbs. The pain is not accompanied by any objective changes in the bones. Specific synovitis and osteoarthritis may be observed.

In late forms (A52.0; A52.7), destructive changes in internal organs are observed. Most often, specific lesions of the cardiovascular system are recorded (mesaortitis, aortic valve insufficiency, aortic aneurysm, myocarditis, gummous endo- and pericarditis), less often - late hepatitis (limited (focal) gummous, miliary gummous, chronic interstitial and chronic epithelial), and less often - other late visceral syphilitic lesions (A52.7).

Late manifestations of pathology of the musculoskeletal system include tabetic arthropathy and gummous lesions of bones and joints (A52.7).

DIAGNOSTICS

Direct and indirect methods are used for laboratory diagnosis of syphilis. Direct diagnostic methods identify the pathogen itself or its genetic material. Indirect methods for diagnosing syphilis include tests that detect antibodies to the causative agent of syphilis in blood serum and cerebrospinal fluid.

Absolute proof of the presence of the disease is the detection of treponema pallidum in samples obtained from lesions using dark-field microscopic examination, immunohistochemical studies using monoclonal or polyclonal antibodies, as well as detection of specific DNA and RNA of the pathogen using molecular biological methods using test systems approved for medical use in the Russian Federation. Direct methods are used to diagnose early forms of the disease (primary and secondary syphilis) with clinical manifestations (erosive and ulcerative elements), to confirm congenital syphilis (umbilical cord tissue, placenta, fetal organs, discharge from the nasal mucosa, contents of blisters, discharge from the surface of papules) .■ VDRL - Venereal Disease Research Laboratory test - test of the Research Laboratory of Venereal Diseases;

■ ■ TRUST - test with toluidine red and unheated serum (Toluidin Red Unheated Serum Test);

■ ■ USR - test for reagins with unheated serum (Unheated Serum Reagins).

General characteristics of non-treponemal tests:

■■ an antigen of non-treponemal origin is used (standardized cardiolipin antigen);

■■ are positive through 1-2 weeks after the formation of primary syphiloma;

■■ have low sensitivity (up to 70–90% in early forms of syphilis and up to 30% in late forms), can give false positive results (3% or more).

Advantages of non-treponemal tests:

■■ low cost;

■■ technical ease of implementation;

■■ speed of obtaining results.

Indications for the use of non-treponemal tests:

■■ screening the population for syphilis;

■■ determining the activity of the infection (determining antibody titers);

■■ monitoring the effectiveness of therapy (determining antibody titers).

Treponemal tests:

■ ■ ELISA (enzyme-linked immunosorbent assay) is a highly sensitive and specific test. Sensitivity for primary and secondary syphilis is 98-100%, specificity is 96-100%. Enables differentiated and total determination of IgM and IgG antibodies to the causative agent of syphilis;

■ ■ immunoblotting is a modification of ELISA. Sensitivity and specificity - 98-100%. Can be used to confirm the diagnosis, especially if the results of other treponemal tests are equivocal or inconsistent.

Methods for detecting treponeme-specific antibodies based on immunochemiluminescence (ICL) and immunochromatography (ICH) methods are relatively new for use in the Russian Federation.

■ ■ ICL (immunochemiluminescence) method with high sensitivity and specificity(98-100%), makes it possible to quantitatively determine the level of antibodies to the causative agent of syphilis,

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Can be used to confirm syphilitic infection and screen. Limitations of use: cannot be used to monitor the effectiveness of therapy and may give a false-positive result.

■ ■ PBT (simple rapid bedside tests, or immunochromatographic tests) allow for rapid determination of the content of treponeme-specific antibodies to the causative agent of syphilis in serum and whole blood samples without the use of special laboratory equipment and can be used in the provision of primary health care, including epidemiological indications. Limitations of use: cannot be used to monitor the effectiveness of therapy and may give a false-positive result.

■ ■ RPHA (passive hemagglutination reaction) is a highly sensitive and specific test. The sensitivity of the method for primary syphilis is 76%, for secondary syphilis - 100%, for latent syphilis - 94-97%, specificity - 98-100%;

■ ■ RIF (immunofluorescence reaction, including modifications RIFabs and RIF200) - quite sensitive at all stages of syphilis (sensitivity for primary syphilis - 70-100%, for secondary and late - 96-100%), specificity - 94-100 %. RIF is used to differentiate latent forms of syphilis and false-positive test results for syphilis;

■ ■ RIBT (RIT) (treponema pallidum immobilization reaction) is a classic test for identifying specific treponemal antibodies; sensitivity (total by stages of syphilis) is 87.7%; specificity - 100%. A labor-intensive and difficult test to perform, requiring significant funds for testing. The scope of application of RIBT is narrowing, but it retains its position as a “reaction-arbiter” in the differential diagnosis of latent forms of syphilis with false-positive results of serological reactions to syphilis.

General characteristics of treponemal tests:

■■ an antigen of treponemal origin is used;

■■ sensitivity - 70-100% (depending on the type of test and stage of syphilis);

■■ specificity - 94-100%.

RIF, ELISA, immunoblotting (IB) become positive from the 3rd week from the moment of infection and earlier, RPGA and RIBT - from the 7th–8th.

Advantages of treponemal tests:

high sensitivity and specificity.