Standards for the treatment of syphilis
Protocols for the treatment of syphilis
Syphilis latent early
Profile: therapeutic, specialty - dermatovenerologist.
Stage of treatment: 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 pale treponema, transmitted mainly through sexual contact 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 an infection duration of up to 2 years.
Classification:
1. Primary seronegative syphilis.
2. Primary seropositive syphilis.
3. Secondary fresh syphilis.
4. Secondary recurrent syphilis.
5. Hidden early syphilis, lasting up to 2 years.
6. Sero-recurrent syphilis.
7. Seroresistant syphilis.
8. Tertiary syphilis.
9. Latent 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 establish the timing of infection. This group includes persons who started treatment at a previously undetermined stage of syphilis.
11. Early congenital syphilis. Congenital syphilis of infancy (up to 1 year) and early childhood (up to 2 years) age.
12. Late congenital syphilis more than 2 years old.
13. Hidden congenital syphilis.
14. Syphilis of the nervous system: early - with prescription of syphilitic infection up to 2 years; late - with prescription of a syphilitic infection over 2 years.
15. Dorsal tabes.
16. Progressive paralysis.
17. Visceral syphilis with an indication of the affected organ.
Risk factors:
Indiscriminate sexual intercourse, very rarely through 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. Risk of developing early latent syphilis: taking large amounts of antibiotics for other diseases, self-medication, ignorance of sexually transmitted diseases.
Receipt: planned.
Indications for hospitalization:
1. Socially maladapted people; minors delivered from the Center for temporary isolation of adaptation of the rehabilitation of minors with positive serological reactions.
2. Persons working in organized teams with positive serological reactions.
Necessary volume of examinations before planned hospitalization:
1. Complete blood count;
2. General analysis of urine;
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 in the last 2 years, blood transfusions, etc., the presence of eruptive erosion elements in the past, ulcers, as a rule, after casual sexual intercourse; results of external examination: secondary residual elements - scars, spots, enlargement of regional lymph nodes.
2. Positive serological tests (Wasserman test, immunofluorescence test, pale treponema immobilization test, enzyme immunoassay, passive hemagglutination test) in the absence of clinical manifestations.
3. Herxheimer-Jarish reaction (fever) after the start of antibiotic therapy.
4. Relatively fast negative serological reactions against the background of specific antisyphilitic treatment.
List of basic diagnostic services:
1. Complete blood count
2. Urinalysis
3. Blood test for HIV
4. ELISA-HBsAg
5. Enzyme immunoassay (ELISA)
6. Immunofluorescence reaction
7. Feces on i/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. Pap test for gonorrhea, trichomoniasis and yeast
5. ELISA for chlamydia 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, 1 time in 5 days, No. 6.
Method 2: Treatment is carried out by bicillin-3, administered at a dose of 1.8 million IU 2 times a week - No. 10; or bicillin-5 in a single dose of 1500000 IU, 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, 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, both to antibiotics of the penicillin and cephalosporin series):
Doxycycline is used at a dose of 0.1 g every 8 hours 3 times a day for 30 days, for a course of 9 g; 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, after 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.
For the prevention of intestinal dysbacteriosis, antifungal therapy is prescribed itraconazole oral solution 200 mg 2 times a day for 21 days or flucanozol 150 mg 1 time in 3 days - 2-3 courses.
List of essential medicines:
1. Benzylpenicillin. por d / i 1000000 U, fl
2. Cefazolin 1 g, vial
3. Ampicillin 1 g, vial
4. Benzathine benzylpenicillin G 2.4 million U, vial
5. Benzylpenicillin novocaine salt 600000 IU, vial
List of additional medicines:
4. Doxycycline 100 mg, tab.
1. Erythromycin 500 mg tab.
2. Azithromycin 500 mg tab.
3. Tetracycline 100 mg, 200 mg tab.
4. Itraconazole oral solution 150 ml - 10 mg / ml
5. Flucanosole 150 mg tab.
6. Ceftriaxone 1 g, vial
7. Vitamins of group B, C
8. Immunomodulators: methyluracil 500 mg tab., cycloferon amp.
9. Biostimulants: aloe, vitreous body amp.
Criteria for moving to the next stage: full course of specific treatment.
Patients who received specific treatment are subject to clinical and serological control for 3 years with a frequency of blood donation for the Wasserman reaction 1 time in 3 months.
MANAGEMENTsyphilis
Moscow 2013
The personal composition of the working group for the preparation of federal clinical guidelines for the profile "Dermatovenereology", section "Syphilis":
Sokolovsky Evgeniy Vladislavovich - Head of the Department of Dermatovenereology with the clinic of the First St. Petersburg State Medical University. Academician I.P. Pavlova, Doctor of Medical Sciences, Professor, St. Petersburg.
Krasnoselskikh Tatyana Valerievna - Associate Professor of the Department of Dermatovenereology with the clinic of the First St. Petersburg State Medical University named after I.I. Academician I.P. Pavlova, candidate of medical sciences, St. Petersburg.
Rakhmatulina Margarita Rafikovna - Deputy Director of the Federal State Budgetary Institution "State Scientific Center for Dermatovenereology and Cosmetology" of the Ministry of Health of Russia for medical work, Doctor of Medical Sciences, Moscow.
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.
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 A.I. CM. Kirov" of the Ministry of Defense of Russia, chief laboratory assistant of the Ministry of Defense of Russia, professor, doctor of medical sciences, St. Petersburg.
Zaslavsky Denis Vladimirovich - Professor of the Department of Dermatovenereology, 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 the methods used to collect/select evidence:
Expert consensus;
Significance assessment in accordance with the rating scheme (the scheme is attached).
| Levels of Evidence | Description |
| 1++ | High quality meta-analyses, systematic reviews of randomized controlled trials (RCTs), or RCTs with a very low risk of bias |
| 1+ | Well-conducted meta-analyses, systematic, or RCTs with low risk of bias |
| 1- | Meta-analyses, systematic, or RCTs with a high risk of bias |
| 2++ | High-quality systematic reviews of case-control or cohort studies. High-quality reviews of case-control or cohort studies with very low risk of confounding effects or bias and moderate likelihood of causation |
| 2+ | Well-conducted case-control or cohort studies with moderate risk of confounding effects or bias and moderate likelihood of causation |
| 2- | Case-control or cohort studies with a high risk of confounding effects or biases and an average likelihood of causation |
| 3 | Non-analytic studies (eg: case reports, case series) |
| 4 | Expert opinion |
Methods used to analyze the evidence:
Reviews of published meta-analyses;
Systematic reviews with tables of evidence.
Methods used to formulate recommendations:
| Strength | Description |
| BUT | At least one meta-analysis, systematic review, or RCT rated 1++ that is directly applicable to the target population and demonstrates robustness a body of evidence that includes results from studies rated as 1+ that are directly applicable to the target population and demonstrate overall consistency of results |
| AT | A body of evidence that includes results from studies rated as 2++ that are directly applicable to the target population and demonstrate overall consistency of results extrapolated evidence from studies rated 1++ or 1+ |
| FROM | A body of evidence that includes results from studies rated as 2+ that are directly applicable to the target population and demonstrate overall consistency of results; extrapolated evidence from studies rated 2++ |
| D | Level 3 or 4 evidence; extrapolated evidence from studies rated 2+ |
Good practice indicators (Goodpracticepoints – GPPs):
Cost analysis was not performed and publications on pharmacoeconomics were not analyzed.
Recommendation validation method:
External peer review;
Internal peer review.
Comments received from experts are systematized and discussed by members of the working group. Changes to recommendations made as a result of this were recorded. If the changes were not made, then the reasons for refusing to make changes are recorded.
Consultation and expert assessment:
The preliminary version was put up for discussion on the website of the State Scientific Center for Dermatovenereology and Cosmetology of the Ministry of Health of Russia so that persons who are not involved in the development of recommendations have the opportunity to participate in the discussion and improvement of the recommendations.
Working group:
For final editing and quality control, the recommendations were re-analyzed by members of the working group.
Key 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 the musculoskeletal system.
ETIOLOGY AND EPIDEMIOLOGY
The causative agent of syphilis belongs to the order Spirochaetales, family Spirochaetaeceae, kind Treponema, mean Treponema pallidum, subspeciespallidum (syn. Spirochaeta pallidum). Pale treponema is easily destroyed under the influence of external agents: drying, heating at 55 ° C for 15 minutes, exposure to 50–56 O ethanol solution. At the same time, low temperatures contribute to the survival of pale treponema.
Pale treponema is a spiral-shaped microorganism; the number of turns of the spiral is from 8 to 12, its curls are uniform, have an identical structure. Performs characteristic types of movement: rotational, translational, wavy and flexion. It reproduces mainly 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 pale treponema in adverse environmental conditions and is considered as a resting stage. T. Rallidum; has antigenic activity. L-form is a way of survival of pale treponema, has a weak antigenic activity.
According to official state statistical reporting, the epidemiological situation of syphilis is characterized by a gradual decrease in the 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 frequent 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 (when transfusing blood from a donor with syphilis at any stage);
contact-household (is a rarity; occurs mainly in household 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 obstetrician-gynecologists, surgeons, dentists, pathologists, forensic experts in the performance of professional duties);
CLASSIFICATION
Currently, Russia uses the international classification of diseases of the 10th revision (ICD-10), which does not always adequately reflect the clinical forms of the disease. So, A51.4 (other forms of secondary syphilis) includes early damage to the nervous system, internal organs and the 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 cipher ending in 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 incorrectly dump issued notices.
A 50 Congenital syphilis
A 50.0 Early symptomatic congenital syphilis
Any congenital syphilitic condition specified as early or onset 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, presenting before the age of 2 years.
A50.3 Late congenital syphilitic eye disease
Late congenital syphilitic interstitial keratitis (H19.2).
Late congenital syphilitic oculopathy (H58.8).
Hutchinson's triad has been excluded (A50.5).
A50.4 Late congenital neurosyphilis (juvenile neurosyphilis)
Dementia paralytic juvenile.
Juvenile (th):
progressive paralysis;
dorsal tabes;
taboparalysis. Late congenital syphilitic (th):
encephalitis (G05.0);
meningitis (G01);
polyneuropathy (G63.0).
Excludes: Hutchinson's triad (A50.5).
A50.5 Other symptomatic forms of late congenital syphilis
Any congenital syphilitic condition specified as late or onset two or more years after birth.
Clutton's joints (M03.1).
Getchinson:
teeth;
triad.
cardiovascular syphilis (198);
syphilitic:
arthropathy (M03.1);
osteochondropathy (M90.2).
A50.6 Latent late congenital syphilis
Congenital syphilis without clinical manifestations, with a positive serological reaction and a negative test of cerebrospinal fluid 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 genital syphilis Syphilitic chancre NOS.
A51.1 Primary anal syphilis
A51.2 Primary syphilis of other sites
A51.3 Secondary syphilis of skin and mucous membranes Wide condyloma.
Syphilitic(s):
alopecia (L99.8);
leukoderma (L99.8);
lesions on mucous membranes.
Secondary syphilitic (s) (s):
female pelvic inflammatory disease (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 test of cerebrospinal fluid, less than two years old after infection.
A51.9 Early syphilis, unspecified
Early congenital syphilis:
■■ leather;
■■ skin and mucous membranes;
■■ visceral.
Early congenital syphilitic(s):
■■ laryngitis;
■■ oculopathy;
■■ osteochondropathy;
■■ pharyngitis;
■■ pneumonia;
■■ rhinitis.
A50.1 Latent early congenital syphilis
Asymptomatic congenital syphilis, with a positive serological test and a negative cerebrospinal fluid test, onset before the age of 2 years.
A50.2 Early congenital syphilis, unspecified
Congenital syphilis NOS (not otherwise specified) with onset before the age of 2 years.
A50.3 Late congenital syphilitic eye disease
Late congenital syphilitic interstitial keratitis (H19.2).
Late congenital syphilitic oculopathy (H58.8). Hutchinson's triad has been excluded (A50.5).
A50.4 Late congenital neurosyphilis (juvenile neurosyphilis)
Dementia paralytic juvenile.
Juvenile(s):
■■ progressive paralysis;
■■ dorsal tabes;
■■ taboparalysis.
Late congenital syphilitic (th):
■■ encephalitis (G05.0);
■■ meningitis (G01);
■■ polyneuropathy (G63.0).
If necessary, identify any related concern
left mental disorder use an additional code. Hutchinson's triad has been excluded (A50.5).
A50.5 Other symptomatic forms of late congenital syphilis
Any congenital syphilitic condition specified as late or onset two or more years after birth.
Clutton's joints (M03.1).
Getchinson:
■■ teeth;
■■ triad.
Late congenital:
■■ cardiovascular syphilis (198);
■■ syphilitic:
- arthropathy (M03.1);
- osteochondropathy (M90.2). Syphilitic saddle nose.
A50.6 Latent late congenital syphilis
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 with onset at 2 years of age or older.
A50.9 Congenital syphilis, unspecified
A51 Early syphilis
A51.0 Primary genital syphilis
Syphilitic chancre NOS.
A51.1 Primary syphilis of the anal region A51.2 Primary syphilis of other sites
A51.3 Secondary syphilis of skin and mucous membranes
Wide condyloma. Syphilitic(s):
■■ alopecia (L99.8);
■■ leukoderma (L99.8);
■■ lesions on mucous membranes.
A51.4 Other forms of secondary syphilis
Secondary syphilitic(s):
■■ female pelvic inflammatory disease (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 test of cerebrospinal fluid, less than two years old 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);
■■ lung failure (139.3).
A52.1 Neurosyphilis with symptoms
Charcot arthropathy (M14.6). Late syphilitic (th):
■■ acoustic neuritis (H49.0);
■■ encephalitis (G05.0);
■■ meningitis (G01);
■■ optic nerve atrophy (H48.0);
■■ polyneuropathy (G63.0);
■■ retrobulbar neuritis (H48.1). Syphilitic parkinsonism (G22). Dorsal dryness.
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 affection of renal glomeruli (N08.0).
Gumma (syphilitic) of any site other than those classified in A52.0–A52.3.
Sexually transmitted infections
Syphilis (no stage specified):
■■ 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 test of cerebrospinal fluid, two years ago or more after infection.
A52.9 Late syphilis, unspecified
A53 Other and unspecified forms of syphilis
A53.0 Occult syphilis, unspecified as early or late
Latent syphilis NOS.
Positive serological test for syphilis.
A53.9 Syphilis, unspecified
Treponema pallidum infestation, NOS. Syphilis (acquired) NOS.
Excluded syphilis NOS, which caused death under two years of age (A50.2).
ROUTES OF INFECTION
■■ sexual (the most frequent 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 (when transfusing blood from a donor with syphilis at any stage);
■■ contact household(is a rarity; occurs mainly in children with household contact with parents who have syphilitic rashes on the skin and / or mucous membranes);
■■ professional (infection of laboratory personnel, work-
working with infected experimental animals, as well as obstetrician-gynecologists, surgeons, dentists, pathologists, forensic experts in the performance of their professional duties).
Infection with syphilis of infants through the milk of nursing women with syphilis is possible. Also infectious biological fluids include saliva and semen of patients with syphilis with clinical manifestations of the corresponding localizations. Cases of infection through sweat and urine were not observed.
CLINICAL PICTURE
Incubation period begins with the introduction of the causative agent of syphilis through damaged skin or mucous membranes and ends with the appearance of a primary affect. On average, the duration of the incubation period is from 2 weeks to 2 months, this period can be reduced to 8 days, or, conversely, extended to 190 days. A reduction in the incubation period is observed with reinfection and with the introduction of the causative agent of syphilis into the body from several entrance gates, which accelerates the generalization of the infection and the development of immune changes in the body. The lengthening 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 introduction of pale treponema, a primary affect develops - erosion or an ulcer with a diameter of 2-3 mm (pygmy chancre) to 1.5-2 cm or more (giant chancre), rounded outlines, with smooth edges, a smooth, shiny bottom of pink or red , sometimes grayish-yellow, saucer-shaped (ulcer), with scanty serous discharge, painless on palpation; at the base of the primary syphiloma there is a dense elastic infiltrate. The primary affect is accompanied by regional lymphadenitis, rarely lymphangitis; can be typical (erosive, ulcerative) and atypical (indurated edema, chancre-felon and chancre-amygdalite); single and multiple; genital, perigenital and extragenital; with the addition of a secondary infection - 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). Caused by hematogenous dissemination of infection against the background of the development of infectious immunity and manifests itself: rashes on the skin (roseolous (spotted), papular (nodular), papulo-pustular (pustular) and rarely vesicular) and / or mucous membranes (limited and confluent roseolous and papular syphilides) ; leukoderma, alopecia. There may be residual effects of primary syphilis, damage to internal organs, the musculoskeletal system and the nervous system (A51.4).
Tertiary syphilis(A52.7). May 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 with an asymptomatic infection. Manifested by rashes on the skin / mucous membranes (tubercular and gummous syphilis, tertiary Fournier roseola), lesions of internal organs, the musculoskeletal system and the nervous system (A52.0-A52.7).
Latent syphilis. There are early (A51.5) (up to 2 years from the moment of infection) |
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infection), late (A52.8) (more than 2 years from infection) and unspecified |
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defined as early or late (A53.0) latent syphilis. Characterized |
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absence of clinical manifestations. Patients with early latent syphilis |
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infectious manifestations of the disease occur. The diagnosis is established on |
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based on the results of a study of blood serum using serological |
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clinical methods (non-treponemal and treponemal tests) and anamnestic |
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data. In some cases, the diagnosis of syphilis is helped by these objects. |
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physical examination (a scar at the site of the former primary syphiloma, an increase |
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lymph nodes), as well as the appearance of a temperature reaction aggravated |
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nia (reaction Jarisch - Herksheimer) after the start of specific treatment. |
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congenital syphilis(A50) develops due to infection of the |
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yes during pregnancy. The source of infection of the fetus is only |
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mother with syphilis. Distinguish early (manifested in the first 2 years |
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life) and late (manifested at a later age) congenital sy- |
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philis, proceeding as with clinical manifestations (manifest) |
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(A50.0; A50.3-A50.5), and without them (hidden) (A50.1; A50.6). |
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Early congenital syphilis with symptoms (A50.0) is characterized by 3 groups |
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pami symptoms: 1) pathognomonic for congenital and non-occurring |
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with acquired syphilis (syphilitic pemphigoid, diffuse in- |
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Gochsinger skin filtration, specific rhinitis - dry, catarrhal |
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and ulcerative stage) and osteochondritis of Wegner's long bones (I, II |
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and III degree, detected by x-ray examination; I degree |
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has no diagnostic value, since similar changes can |
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also observed in rickets); 2) typical manifestations syphilis, meet- |
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which are not only with early congenital, but also with acquired syphi- |
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fox, - papular rash on the limbs, buttocks, face, sometimes all over |
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body; in places of maceration - erosive papules and wide warts; ro- |
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zeolous rash (rare), raucedo, alopecia, bone lesions |
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in the form of periostitis, osteoporosis and osteosclerosis, bone gums; defeat |
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internal organs in the form of specific hepatitis, glomerulonephritis, |
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myocarditis, endo- and pericarditis, etc., lesions of the central nervous |
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systems in the form of specific meningitis, hydrocephalus, etc.; 3) general |
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and local symptoms occurring in other intrauterine in- |
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transmitted |
feces: "senile appearance" of the newborn (skin wrinkled, flabby, |
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dirty yellow) small body length and weight with symptoms of malnutrition, |
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up to cachexia; hypochromic anemia, leukocytosis, increased ESR, |
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thrombocytopenia; hepatosplenomegaly; chorioretinitis (type IV); onychia |
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and paronychia. The placenta with syphilis is enlarged, hypertrophied; her |
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infections, |
the mass is 1/4–1/3 (normally 1/6–1/5) of the mass of the fetus. |
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Late congenital syphilis with symptoms (A50.3; A50.4) is characterized by |
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reliable signs(Hatchinson's triad: parenchymal keratitis, la- |
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birinthine deafness, Hutchinson's teeth), probable signs (saber |
shins, chorioretinitis, nasal deformities, radiant scars around the mouth, buttock-shaped skull, tooth deformities, syphilitic gonitis, lesions of the nervous system in the form of hemiparesis and hemiplegia, speech disorders, mental retardation, cerebral palsy and Jacksonian epilepsy) and dystrophies (thickening of the sternal end of the right clavicle, degeneration of the bones of the skull 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, a 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 tuberculous and gummous syphilides of the skin, mucous membranes, lesions of 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. According to the timing from the moment of infection, neurosyphilis is conditionally divided into early (up to 5 years from the moment of infection) and late (over 5 years from the moment of infection). Such a division does not completely determine all aspects of the nervous system damage, 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 detected by examination of the cerebrospinal fluid.
Neurosyphilis with symptoms It 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 of the early forms of neurosyphilis (A51.4) is meningovascular syphilis, the clinical picture of which is dominated by symptoms of lesions of the meninges and 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 of the optic nerves (A52.1) and gummous neurosyphilis (A52.3), the clinical picture of which is dominated by symptoms of brain parenchyma damage.
Syphilis of internal organs and musculoskeletal system according to the terms from the moment of infection, they are conditionally divided into early (up to 2 years from the moment of infection) and late (over 2 years from the moment of infection) forms. In early forms (A51.4), most often only functional disorders of the affected organs develop. The pathological process mainly involves the heart (early cardiovascular syphilis), the liver (anicteric or icteric forms of hepatitis), the stomach (transient gastropathy, acute gastritis, the formation of specific ulcers and erosions),
Sexually transmitted infections
kidneys (asymptomatic kidney dysfunction, benign proteinuria, syphilitic lipoid nephrosis, syphilitic glomerulonephritis). The earliest symptom of damage to the musculoskeletal system is night pain in the long bones of the extremities. 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 the 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), more less often, other late visceral syphilitic lesions (A52.7).
Late manifestations of musculoskeletal pathology include tabetic arthropathy and gummous lesions of bones and joints (A52.7).
DIAGNOSTICS
For laboratory diagnosis of syphilis, direct and indirect methods are used. 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 the blood serum and cerebrospinal fluid.
The absolute proof of the presence of the disease is the detection of treponema pallidum in samples obtained from lesions using microscopic examination in the dark field of vision, immunohistochemical studies using monoclonal or polyclonal antibodies, as well as the identification of specific DNA and RNA of the pathogen by 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 (tissue of the umbilical cord, placenta, fetal organs, nasal mucosal discharge, contents of blisters discharged from the surface of papules) .■ VDRL - Venereal Disease Research Laboratory test - test of the Venereal Disease Research Laboratory;
■ ■ TRUST - test with toluidine red and unheated serum (Toluidin Red Unheated Serum Test);
■ ■ USR - Unheated Serum Reagins test.
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 ones) can give false positive results (3% or more).
Benefits 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;
■■ determination of the activity of the course of infection (determination of antibody titers);
■■ monitoring the effectiveness of therapy (determination of 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%. May be used to confirm the diagnosis, especially when other treponemal tests are questionable or inconsistent.
Relatively new for use in the Russian Federation are methods for detecting treponema-specific antibodies based on the methods of immunochemiluminescence (ICL) and immunochromatography (ICG).
■ ■ ICL method (immunochemiluminescence) with high sensitivity and specificity(98-100%), makes it possible to quantify the level of antibodies to the causative agent of syphilis,
Sexually transmitted infections
Can be used for syphilitic infection confirmation and screening. Application restrictions: cannot be used to monitor the effectiveness of therapy, may give a false positive result.
■ ■ PBT (Simple Rapid Bedside Tests or Immunochromatographic Tests) allows rapid detection of treponemospecific 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 primary health care, including epidemiological evidence. Application restrictions: cannot be used to monitor the effectiveness of therapy, may give a false positive result.
■ ■ RPHA (passive haemagglutination test) is a highly sensitive and specific test. The sensitivity of the method for primary syphilis is 76%, for secondary syphilis - 100%, for latent - 94-97%, specificity - 98-100%;
■ ■ RIF (immunofluorescence reaction, including RIFabs and RIF200 modifications) - 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 results of studies on syphilis;
■ ■ RIBT (RIT) (treponema pallidum immobilization test) - a classic test for the detection of specific treponemal antibodies; sensitivity (total by stages of syphilis) is 87.7%; specificity - 100%. A time-consuming and difficult test to set up, requiring significant funds for testing. The scope 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 tests for syphilis.
General characteristics of treponemal tests:
■■ 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, TPHA and RIBT - from the 7th–8th.
Benefits of treponemal tests:
high sensitivity and specificity.
Treatment goals.Specific treatment is carried out with the aim of etiological cure of the patient by creating a treponemicidal concentration of an antimicrobial drug in the blood and tissues, and in case of neurosyphilis - in the CSF.
Preventive treatment is carried out in order to prevent syphilis to persons who have been in sexual and close household contact with patients with early forms of syphilis, if no more than 2 months have passed since the moment of contact.
Preventive 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 32 weeks 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 with suspicion of a specific lesion of the internal organs, nervous system and musculoskeletal system, when the diagnosis cannot be confirmed by convincing serological and clinical data.
General remarks on therapy.
Antibacterial drugs recommended for the treatment of syphilis are:
Penicillins:
durant: Dibenzylethylenediamine salt of benzylpenicillin, otherwise - benzathine benzylpenicillin * and dibenzylethylenediamine and novocaine salts of penicillin in a ratio of 4: 1;
medium duration: Benzylpenicillin novocaine salt;
water soluble: Benzylpenicillin sodium salt crystalline*;
semi-synthetic: Ampicillin*, Oxacillin*.
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 - dermatovenerological or therapeutic / cardiological, taking into account the severity of the lesion. Treatment is carried out by a dermatovenereologist who prescribes specific treatment, together with a general practitioner/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 monitoring of the patient, the severity of his condition and the likelihood of aggravation or the appearance of neurological symptoms against the background of antibiotic therapy. Specific treatment is prescribed by a dermatovenereologist.
Patients with asymptomatic forms of neurosyphilis can receive full medical care in a dermatovenerological hospital. The issue of preparatory and symptomatic therapy is decided jointly by a dermatovenereologist, a neuropathologist, a psychiatrist and, if necessary, an ophthalmologist.
Indications for hospitalization.
suspicion of the presence or established diagnosis of neurosyphilis;
suspicion of the presence or established diagnosis of cardiovascular syphilis and other visceral lesions;
syphilitic lesions of the musculoskeletal system;
late latent and unspecified syphilis;
tertiary syphilis;
syphilis in pregnant women;
congenital and acquired syphilis in children;
all forms of the disease to be treated with water-soluble penicillin;
a history of intolerance to antibacterial drugs;
concomitant HIV infection;
workers of epidemiologically significant professions (listed in the 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 peculiarities of production or the work (service) they perform;
all forms of the disease in the absence of the possibility of providing primary specialized health care in the territory of the patient's residence;
persons without a fixed place of residence.
Treatment regimens.
preventive treatment.
Benzathine benzylpenicillin + Benzylpenicillin procaine 1.5 million U 2 times a week intramuscularly, 2 injections per course. Level of persuasiveness of recommendations B (level of evidence 2++) .
Or.
benzylpenicillin novocaine salt 600 thousand units 2 times a day intramuscularly for 7 days.
Durant penicillin (benzathine benzylpenicillin) is the drug of choice. Single administration - treatment failures are not described, at the same time it has the highest compliance:
Benzathine benzylpenicillin 2.4 million units intramuscularly once (the drug is injected at 1.2 million units into each gluteus maximus muscle). Recommendation strength level A (level of evidence 1++) .
Treatment of patients with primary syphilis.
Benzathine benzylpenicillin 2.4 million units 1 time in 5 days intramuscularly, 3 injections per course. Recommendation strength level A (level of evidence 1++) .
Or.
Benzathine benzylpenicillin + Benzylpenicillin procaine 1.5 million U 2 times a week intramuscularly, for a course of 5 injections. Level of persuasiveness of recommendations B (level of evidence 2++) .
Or.
benzylpenicillin novocaine salt 600 thousand units 2 times a day intramuscularly for 14 days. Level of persuasiveness of recommendations C (level of evidence 2+) .
Or.
benzylpenicillin sodium salt crystalline (B) 1 million units every 4 hours (6 times a day) intramuscularly for 14 days. Level of persuasiveness of recommendations B (level of evidence 1++) .
Drug of choice. Durant penicillin (benzathine benzylpenicillin), as the most convenient to use. Preparations of medium duration or water-soluble penicillin are used if it is necessary to treat a patient in a hospital (with a complicated course of the disease, somatically burdened patients, etc.;).
Treatment of patients with secondary syphilis.
Level of persuasiveness of recommendations C (level of evidence 2+) .
Or.
Or.
Benzathine benzylpenicillin 2.4 million units 1 time in 5 days intramuscularly, for a course of 6 injections. Recommendation strength level A (level of evidence 1++) .
In patients with a disease duration of more than 6 months, the drugs of choice are benzylpenicillin novocaine salt or benzylpenicillin sodium crystalline salt.
Treatment of patients with early latent syphilis.
benzylpenicillin novocaine salt 600 thousand units 2 times a day intramuscularly for 28 days. Level of persuasiveness of recommendations C (level of evidence 2+) .
Or.
benzylpenicillin sodium salt crystalline 1 million units every 4 hours (6 times a day) intramuscularly for 28 days. Level of persuasiveness of recommendations B (level of evidence 1+) .
Treatment of patients with tertiary, latent latent and latent unspecified syphilis.
benzylpenicillin sodium salt crystalline 1 million units every 4 hours (6 times a day) intramuscularly for 28 days, after 2 weeks - the second course of treatment of benzylpenicillin sodium salt crystalline in similar doses for 14 days, or one of the drugs of "medium" duration (benzylpenicillin novocaine salt). Level of persuasiveness of recommendations B (level of evidence 2++) .
Or.
benzylpenicillin novocaine salt 600 thousand U 2 times a day intramuscularly for 28 days, after 2 weeks - the second course of treatment of benzylpenicillin novocaine salt in the same dose for 14 days.
Treatment of patients with early visceral syphilis.
benzylpenicillin sodium salt crystalline 1 million units every 4 hours (6 times a day) intramuscularly for 28 days. Level of persuasiveness of recommendations B (level of evidence 1+) .
Or.
benzylpenicillin novocaine salt 600 thousand units 2 times a day intramuscularly for 28 days. Level of persuasiveness of recommendations C (level of evidence 2+) .
Treatment of patients with late visceral syphilis.
Treatment begins with a 2-week preparation with broad-spectrum antibacterial drugs (doxycycline, erythromycin). Then they move on to penicillin therapy:
benzylpenicillin sodium salt crystalline 1 million U every 4 hours (6 times a day) intramuscularly for 28 days, after 2 weeks - the second course of treatment of benzylpenicillin sodium salt crystalline in the same dose for 14 days. Recommendation strength level D (level of evidence 2+) .
Or.
benzylpenicillin novocaine salt 600 thousand units 2 times a day intramuscularly for 28 days, after 2 weeks - the second course of treatment of benzylpenicillin novocaine salt in the same dose for 14 days. Recommendation grade D (level of evidence 3) .
Treatment of patients with early neurosyphilis.
benzylpenicillin sodium salt crystalline 12 million U 2 times a day intravenously drip 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. Immediately after the end of the course of intravenous administration of penicillin, an injection of bicillin-1 is given at a dose of 2.4 million units.
Or.
benzylpenicillin sodium salt crystalline 4 million units 6 times a day intravenously by stream for 20 days. A single dose of the drug is diluted in 10 ml of isotonic sodium chloride solution and injected slowly over 3-5 minutes into the cubital vein. Immediately after the end of the course of intravenous administration of penicillin, an injection of bicillin-1 is given at a dose of 2.4 million units. Strength of recommendation D (level of evidence 2+).
To prevent an exacerbation reaction (in the form of the appearance or aggravation of neurological symptoms) in the first 3 days of penicillin therapy, it is recommended to take prednisolone in a decreasing daily dose of 90–60–30 mg (once in the morning).
Treatment of patients with late neurosyphilis.
benzylpenicillin sodium salt crystalline 12 million U 2 times a day intravenously drip 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. Immediately after the end of the course of intravenous administration of penicillin, an injection of bicillin-1 is given 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. Strength of recommendation D (level of evidence 2+).
Or.
benzylpenicillin sodium salt crystalline 4 million units 6 times a day intravenously by stream for 20 days. A single dose of the drug is diluted in 10 ml of isotonic sodium chloride solution and injected slowly over 3-5 minutes into the cubital vein. Immediately after the end of the course of intravenous administration of penicillin, an injection of bicillin-1 is given 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. Strength of recommendation D (level of evidence 2+).
In patients with late forms of neurosyphilis, to prevent exacerbation of psychotic symptoms against the background of specific treatment, the use of prednisolone at the above doses is indicated at the beginning of therapy.
With gummas of the brain and spinal cord, the use of prednisolone is recommended in parallel with penicillin therapy during the entire first course of treatment; the use of prednisolone may precede the start of antibiotic therapy by several days, which contributes to the regression of the clinical symptoms of the disease.
Expected side effects and complications of antisyphilitic therapy.
Patients should be warned about the possible reaction of the body to treatment. In medical organizations where therapy is carried out, there should be facilities for emergency care.
Aggravation reaction (Yarish-Herxheimer).
An exacerbation reaction is observed in 30% of patients with early syphilis. In most patients, the clinical manifestations of the exacerbation reaction begin 2-4 hours after the first administration of the antibacterial drug, reach a maximum severity after 5-7 hours, and the condition returns to normal within 12-24 hours. The main clinical symptoms are chills and a sharp increase in body temperature (up to 39 ° C, sometimes higher). Other symptoms of the reaction are general malaise, headache, nausea, pain in muscles, joints, tachycardia, increased respiration, lowering 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 there before the start of treatment. Occasionally, patients may develop psychosis, stroke, seizures, liver failure.
A rapidly transient flare-up reaction usually does not require any special treatment. However, the development of a pronounced exacerbation reaction should be avoided:
in the treatment of pregnant women, as it can provoke premature birth, toxic disorders in the fetus and stillbirth;
in patients with neurosyphilis, since the exacerbation reaction can provoke the progressive development of neurological symptoms;
in patients with damage to the organ of vision;
in patients with visceral syphilis, especially syphilitic mesaortitis.
High fever and pronounced intoxication syndrome can be dangerous in patients with chronic pathology of the cardiovascular system, severe somatic diseases in the stage of decompensation. To avoid an exacerbation reaction, it is recommended to prescribe oral or intramuscular prednisolone 60-90 mg per day (once in the morning) or in a decreasing dosage - 75-50-25 mg per day in the first 3 days of penicillin therapy.
Reaction to intramuscular administration of prolonged penicillin preparations (Heine's syndrome, procaine psychosis).
May occur after any injection of the drug. It is 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 injection. Lasts within 20 minutes. Symptoms can range in severity from mild to severe.
The reaction is differentiated from anaphylactic shock, in which there is a sharp decrease in 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) with high blood pressure - papaverine 2 ml of a 2% solution and dibazol 2 ml of a 1% solution intramuscularly. If necessary, a psychiatric consultation and the use of sedatives and antipsychotics are indicated.
Nicolau's syndrome is a symptomatic complex of complications after intra-arterial administration of durant drugs of penicillin or other drugs with a crystalline structure.
It is characterized by sudden ischemia at the injection site, the development of painful cyanotic uneven spots (livedo), followed by the formation of blisters and skin necrosis, in some cases, flaccid paralysis of the limb, into the artery of which the drug was injected, develops, in rare cases - transverse paralysis. Gross hematuria and bloody stools are observed as long-term complications. In the blood - leukocytosis. So far, cases have been noted only in pediatric practice.
Neurotoxicity - seizures (more often in children), with the use of high doses of penicillin, especially in renal failure.
Electrolyte imbalance - in patients with heart failure, with the introduction of large doses of the sodium salt of benzylpenicillin, edema may increase (1 million units of the drug contains 2.0 mmol of sodium).
Allergic reactions - toxicoderma, urticaria, Quincke's edema, headache, fever, joint pain, eosinophilia, etc.; - with the introduction of penicillin occur in 5 to 10% of patients. The most dangerous complication is anaphylactic shock, which gives up to 10% mortality.
Anaphylactic shock is characterized by fear of impending death, a feeling of heat throughout the body, loss of consciousness, pale skin, cold clammy sweat, pointed facial features, rapid shallow breathing, thready pulse, low blood pressure.
Treatment: 1) epinephrine 0.5 ml 0.1% solution injected into the injection site of the drug; 2) epinephrine 0.5 ml 0.1% solution intravenously or intramuscularly; 3) prednisolone 60-90 mg or dexamethasone 4-8 mg intravenously or intramuscularly; 4) chloropyramine 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.
Contraindications to the appointment of drugs of the penicillin group:
intolerance to benzylpenicillin, its prolonged preparations and semi-synthetic derivatives;
prolonged preparations of penicillin should be prescribed with caution to patients with severe hypertension, who had a past myocardial infarction, with diseases of the endocrine glands, with acute gastrointestinal diseases, active tuberculosis, and diseases of the hematopoietic system.
special situations.
Treatment of pregnant women.
Currently, due to the availability of effective and short-term treatments, the detection of syphilis is not a medical indication for termination of pregnancy. The decision to maintain or terminate the pregnancy is made by the woman. The role of the doctor is to conduct timely adequate treatment (should be started before the 32nd week of pregnancy and carried out with medium duration penicillin, penicillin sodium, semi-synthetic penicillins or ceftriaxone) and provide psychological support to the pregnant woman.
Specific treatment of pregnant women, regardless of the timing of gestation, is carried out with benzylpenicillin sodium salt of crystalline or drugs of "medium" duration (benzylpenicillin novocaine salt) in the same way as the treatment of non-pregnant women, according to one of the methods proposed in these recommendations, in accordance with the established diagnosis.
Preventive treatment is carried out starting from the 20th week of pregnancy, but with a late start of specific treatment - immediately after it. Preparations, single doses and frequency of administration correspond to those for specific treatment. The duration of prophylactic therapy is 10 days, and if there is evidence of the inferiority of the specific treatment carried out, then prophylactic treatment should continue for 20 days (as an additional one).
When a pregnant woman is diagnosed with late syphilis or syphilis unspecified as early or late, the second course of specific treatment, which is usually carried out at 20 or more weeks of pregnancy, should be considered prophylactic treatment. In cases where adequate specific and preventive treatment is carried out in full, delivery can occur in a general maternity hospital on a common basis. A child born without signs of congenital syphilis from a woman who has received full-fledged specific and preventive therapy does not need treatment.
Treatment of children.
Specific treatment for children with early congenital syphilis:
benzylpenicillin sodium salt crystalline:
Children under the age of 1 month - 100 thousand units per kg of body weight per day, divided into 4 injections (every 6 hours), intramuscularly;
Children aged 1 to 6 months - 100 thousand units per kg of body weight per day, divided into 6 injections (every 4 hours), intramuscularly;
Children aged 6 to 12 months - 75 thousand units per kg of body weight per day intramuscularly;
Children over the age of 1 year - 50 thousand units per kg of body weight per day intramuscularly.
- within 28 days - with overt early congenital syphilis, including damage to the central nervous system, confirmed by positive cerebrospinal fluid serological reactions, and 20 days - with latent early congenital syphilis. If the mother refuses to perform a lumbar puncture to the child, the course of treatment for latent early congenital syphilis should also be 28 days. Strength of recommendation D (level of evidence 2+).
Or.
- benzylpenicillin novocaine salt 50 thousand units per kg of body weight per day, divided into 2 injections (every 12 hours) intramuscularly for 28 days with overt early congenital syphilis and 20 days - with latent early congenital syphilis. If the mother refuses to perform a lumbar puncture to the child, the course of treatment for latent early congenital syphilis should also be 28 days. Strength of recommendation D (level of evidence 2+).
When indicating the presence of allergic reactions to penicillin, reserve drugs are used:
- ceftriaxone for children of the first two months of life is prescribed at a dose of 50 mg per kg of body weight per day in 2 injections, for children from two months to 2 years - at a dose of 80 mg per kg of body weight per day in 2 injections. The duration of treatment is 28 days for overt early congenital syphilis (including those with CNS damage) and 20 days for latent early congenital syphilis. If the mother refuses to perform a lumbar puncture to the child, the course of treatment for latent early congenital syphilis should also be 28 days.
Or.
ampicillin 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. The duration of treatment is 28 days for overt early congenital syphilis (including those with CNS damage) and 20 days for latent early congenital syphilis. If the mother refuses to perform a lumbar puncture to the child, the course of treatment for latent early congenital syphilis should also be 28 days. Recommendation grade D (level of evidence 3).
Specific treatment of children with late congenital syphilis:
benzylpenicillin sodium salt crystalline 50 thousand units per kg of body weight per day, divided into 6 injections (every 4 hours) intramuscularly for 28 days; after 2 weeks - the second course of treatment of benzylpenicillin with crystalline sodium salt in a similar dose for 14 days. Recommendation strength level D (level of evidence 2+) .
Or.
benzylpenicillin novocaine salt 50 thousand units per kg of body weight per day, divided into 2 injections (every 12 hours) intramuscularly for 28 days; after 2 weeks - the second course of treatment of benzylpenicillin with novocaine salt in a similar dose for 14 days. Recommendation grade D (level of evidence 3) .
When indicating the presence of allergic reactions to penicillin:
ceftriaxone for children aged 2 to 12 years is prescribed at a dose of 80 mg per kg of body weight per day in two injections, for children over the age of 12 years - at a dose of 1-2 g per day. With overt 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 the same dose for 14 days. Recommendation grade D (level of evidence 3).
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 doses of antibacterial drugs, taking into account the fact that domestic penicillins are contraindicated in children under 2 years of age, and tetracyclines in children under 8 years of age. The calculation of penicillin preparations for the treatment of children is carried out in accordance with the body weight of the child: 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 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 preparations 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 two doses for its novocaine salt.
Taking into account the anatomical and physiological features of the urinary system in newborns and children of the first month of life, it is permissible to reduce the frequency of penicillin administration up to 4 times a day. In order to avoid a toxic reaction due to the mass death of pale treponemas after the first injections of penicillin (aggravation reaction of Herxheimer-Yarish-Lukashevich) on the first day of treatment, a single dose of penicillin should not exceed 5000 IU per injection. After each injection on the first day, control thermometry and monitoring of the somatic condition of the child are necessary.
Preventive treatment is 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 a 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 doses of antibacterial drugs.
Prophylactic treatment is indicated for newborns born without manifestations of syphilis from an untreated or inadequately treated mother during pregnancy (specific treatment started after 32 weeks of gestation, with a violation or change in approved treatment regimens), as well as newborns whose mother, if indicated, during pregnancy did not receive prophylactic treatment.
Preparations, 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 14 days, newborns born without manifestations of syphilis from an untreated mother - 28 days.
Children born to mothers who received adequate specific treatment before pregnancy and prophylactic treatment during pregnancy, who at the time of delivery retain positive non-treponemal tests with persistently low titers (RMP< 1:2, РПР лечение не показано, если нетрепонемные тесты у ребенка отрицательны, либо их титры не превышают титров 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 the frequency of administration of antibacterial drugs.
Treatment of syphilis in case of intolerance to penicillin preparations.
When indicating the presence of allergic reactions to penicillin, reserve drugs are used:
ceftriaxone.
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 latent, unspecified and tertiary syphilis - 1.0 g 1 time per day intramuscularly for 28 days and after 2 weeks the second course of the drug in the same dose for 14 days;
for the treatment of early neurosyphilis - 2.0 g once a day intramuscularly for 20 days, in severe cases (syphilitic meningoencephalitis, acute generalized meningitis), intravenous use of the drug and an increase in the daily dose to 4 g are possible.
For the treatment of late neurosyphilis, two courses of treatment are carried out according to a similar scheme with an interval between courses of 2 weeks.
Strength of recommendation C (level of evidence 2+).
Treatment regimens for syphilis with ceftriaxone were developed based on the study of the pharmacokinetics of the original ceftriaxone. Studies on the effectiveness of most generic drugs of ceftriaxone have not been conducted. There are no data on the equivalence (pharmaceutical, pharmacokinetic, therapeutic) of generic drugs of ceftriaxone and the originator drug, without which it is unacceptable to replace one drug with another.
Or.
doxycycline 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. Level of persuasiveness of recommendations C (level of evidence 2+) .
Or.
erythromycin 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. Recommendation grade D (level of evidence 3) .
Or.
oxacillin or ampicillin 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. Recommendation grade D (level of evidence 3) .
For pregnant women with intolerance to penicillin (including semi-synthetic) and ceftriaxone, due to a contraindication to tetracycline drugs, the appointment of erythromycin is recommended. However, the baby must be treated with penicillin after birth because erythromycin does not cross the placenta.
Treatment of patients with syphilis with concomitant HIV infection.
If antibodies to HIV are detected in a patient with syphilis, he is sent for further examination, treatment and constant monitoring to the regional Center for the Prevention and Control of AIDS with appropriate recommendations for the treatment of syphilis.
The treatment of syphilis, as well as the follow-up of HIV-infected persons, is carried out in accordance with the same algorithms and methods that are accepted for HIV-negative patients. Studies on large groups of patients did not reveal statistically significant differences in response to antibiotic therapy depending on HIV status.
It is preferable to use preparations of medium duration and sodium salt of benzylpenicillin. There are very few data on the effectiveness of second-line therapy and reserve antibiotics. Limited data support the efficacy of intravenous ceftriaxone 1–2 g/day for 10–14 days in the treatment of neurosyphilis in HIV-infected patients with penicillin intolerance.
Clinical and serological monitoring after treatment of HIV-positive patients should be especially careful.
Treatment of patients with syphilis with concomitant STIs.
If urogenital infections are detected in a patient with syphilis, their treatment is carried out in parallel with the treatment of syphilis.
Requirement for the results of treatment (serological criterion for the effectiveness of syphilis therapy): negativity of non-specific serological reactions - RMP (RPR, VDRL) - or a decrease in antibody titer by 4 or more times (by 2 dilutions of serum) within 12 months after the end of specific therapy for early forms of syphilis. Strength of recommendation C (level of evidence 4).
Negativity of RIF, ELISA, RPHA is extremely rare. The persistence of positive RIF, ELISA, and TPHA with negative non-treponemal tests in a person who has had syphilis is not considered a failure of therapy. Adequately treated patients with syphilis may experience negative RIBT, but this usually occurs no earlier than 2-3 years after the end of therapy.
The criteria for the effectiveness of the treatment of neurosyphilis are:
normalization of pleocytosis within 6 months and protein levels - within 1.5-2 years after the end of treatment;
the disappearance of antibodies from the serum, determined in the RPM and RPR tests, within 6-12 months after the end of therapy. Sometimes the production of these antibodies can last more than a year, then it is important to take into account the dynamics of the decrease in titers;
the absence of new neurological symptoms and the increase in existing neurological symptoms.
Criteria for the ineffectiveness of the treatment of syphilis:
Persistence or recurrence of clinical manifestations (clinical relapse).
Sustained increase of 4 times or more compared with the initial values of the titer of non-specific serological reactions.
Re-positivity of non-treponemal tests after a period of temporary negative in the absence of evidence for reinfection (serological relapse).
Persistence of positive non-treponemal tests without a tendency to decrease in 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 non-treponemal tests and / or antibody titer gradually decreases (at least 4 times), but complete negativity is not observed, a delayed negativity of non-treponemal serological reactions is noted. Clinical and serological monitoring of such patients is extended up to 2 years, after which the question of the advisability of prescribing additional treatment is decided.
Tactics in the absence of the effect of treatment:
exclusion of reinfection;
appointment of additional treatment.
Reinfection. With syphilis, infectious (non-sterile) immunity develops, due to the presence of Tr pallidum in the body and disappearing soon after its elimination as a result of treatment. In this regard, after the microbiological cure of syphilis, re-infection is possible - reinfection. Diagnosis of reinfection is based on a set of criteria, among which the first four are mandatory:
the fact of the primary disease is confirmed by medical documentation;
a full treatment was carried out for the primary disease, which is confirmed by medical documentation;
in the process of primary treatment, there was a timely resolution of rashes (if any);
within 12 months after the end of treatment for the primary disease, there was at least a fourfold decrease in titers, a decrease in the positivity or negativity of non-treponemal tests (RMP or its analogues);
with the reappearance of syphilitic rashes (if any), Treponema pallidum was detected in their discharge by dark-field microscopy;
there is a re-positification of previously negative NTT or at least a fourfold increase in their titer compared to the original;
A new source of infection has been identified, which has been proven to have an early form of syphilis.
Additional treatment.
Additional treatment is prescribed in the following cases:
if a year after the full treatment of early forms of syphilis, a fourfold decrease in the titer of RMP / RPR did not occur;
if, 1.5 years after the full treatment of early forms of syphilis, there is no tendency to further reduce the titers / degree of positivity of RMP / RPR;
if 2 years after the full treatment of early forms of syphilis, there was no complete negativity of RMP / RPR;
if 6 months after the full treatment of early congenital syphilis, a 4-fold decrease in the titer of RMP / RPR has not occurred;
in case of clinical or serological recurrence.
Before additional treatment, a repeated examination of patients by specialist doctors (dermatovenereologist, ophthalmologist, neurologist, internist, otorhinolaryngologist), CSF examination, even in the absence of clinical neurological symptoms, echocardiography (Echo-KG) and electrocardiography (ECG) and clinical and serological examination of the genital partner. 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 a specific pathology of the nervous system and internal organs, additional treatment is carried out, as a rule, once with the following drugs:
benzylpenicillin sodium salt crystalline 1 million units 6 times a day (every 4 hours) intramuscularly for 28 days. Level of persuasiveness of recommendations C (level of evidence 2+) .
Or.
benzylpenicillin sodium salt crystalline 12 million U 2 times a day intravenously drip for 14 days. Due to the need to maintain a treponemicidal concentration of penicillin for at least 4 weeks, at the end of the course of therapy, 3 injections of bicillin-1 at a dose of 2.4 million units intramuscularly should be performed once every 5 days. Recommendation strength level B (level of evidence 1+).
Or.
ceftriaxone 1.0 g 2 times a day intramuscularly for 20 days. Recommendation grade D (level of evidence 3) .
Additional treatment in children is carried out according to the method of treatment of adults, based on age doses of antibacterial drugs.
Indications for an additional course of therapy after treatment of neurosyphilis:
the number of cells does not return to normal within 6 months or, having returned to normal, increases again;
within 1 year there is no decrease in the positivity of RMP / RPR in the CSF;
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 treatment of neurosyphilis.
CSF protein levels change more slowly than cytosis and serology and sometimes take up to 2 years to normalize. Persistence of an elevated but declining protein level with normal cytosis and negative serological tests is not an indication for an additional course of therapy.
Maintaining contacts.
Persons who have been in sexual or close household contact with patients with early forms of syphilis, in whom no more than 2 months have passed since the moment of contact, are shown preventive treatment according to one of the above methods.
Persons who have passed from 2 to 4 months from the moment of contact with a patient with early syphilis are subjected to a double clinical and serological examination with an interval of 2 months; if more than 4 months have passed since the contact, a single clinical and serological examination is performed.
Preventive treatment of a recipient who has been transfused with the blood of 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 single clinical and serological examination is performed.
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