Dermatovenerology diagnostic and treatment for syphilis
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Diagnostics and treatment of syphilis
Laboratory diagnostics direct methods indirect methods
Direct research methods (used for establishing the final diagnosis) Direct identification of the causative agent of the disease - T. pallidum - is absolute criterion for the diagnosis of syphilis I • Microscopy in the dark field of the microscope , • Direct immunofluorescence, • Nucleic acid amplification (NAA) methods such as polymerase chain reaction (PCR).
Dark - field microscopy The material for dark-field microscopy is serous discharge from the surface of erosion, ulcers, macerated or excoriated, eroded papules or plaques There are several methods for obtaining interstitial fluid: 1 - Method of irritation . The test object is thoroughly cleaned with a cotton swab or swab moistened with a sterile saline. With a sterile Volkmann spoon or loop produce careful not to cause bleeding, stroking the surface element. After a while, the surface becomes shiny as a result leakage of tissue fluid. It is transparent or slightly opalescent. If bleeding starts, it should be stopped by pressing a cotton swab to the surface of element, and then continue stroking. A small admixture of blood to the serum acceptable.
2-Compression method . After cleaning, erosion or ulcer is squeezed from the sides with your fingers wearing gloves or tweezers, while stimulating the release of serous exudate, which is taken from the surface with a bacteriological loop or by a neat applying a cover glass to the erosion / ulcer surface. Received serous discharge is mixed on a glass slide with an equal amount of isotonic solution, covered with a cover glass and the resulting native preparation is examined under the microscope.
3-Scarification method . It is used in the examination of dry elements (roseola, lenticular papules, epithelialized erosions). The surface of the examined element scarified, while capillary bleeding inevitably appears, which stop, and by the method of irritation of the scarified surface get serous fluid. This method is significantly inferior in efficiency to the previous ones. The study may give a falsely negative result due to the use by the patient local antiseptics, antibiotics, or when a secondary infection is attached. In this case, lotions with saline are prescribed, after which (for the next day) the study is repeated
In some cases, material for microscopic diagnostics is taken from an enlarged regional lymph node, often inguinal. Punctured dense, mobile lymph node without signs of inflammation. The puncture site is treated with iodine, the knot is fixed with two fingers of the left hand, and the right a needle is inserted into the knot connected to a syringe containing a small amount sterile saline solution. The puncture is made at one of the poles of the gland and push the needle in the direction of the long axis to the opposite pole, while releasing the saline in the syringe. Then the needle is slowly withdrawn from the assembly while pulling the plunger out of the syringe. Correct puncture production confirmed by the presence of lymphocytes in the punctate.
Preparation of preparations The material obtained from the lesion site on the skin and mucous membrane is mixed with a drop saline on a glass slide at room temperature Cover with a cover slip and examine under a microscope. The lymph node puncture is not mixed with a drop saline. When examined in a dark field, the pale spirochete looks like a very delicate mobile spiral, faintly luminous with a silvery sheen. The entire field of vision is in the preparation littered with a mass of tiny luminous points in a chaotic Brownian movement
Direct Immunofluorescence (DIF) Method Direct immunofluorescence method provides direct detection of T. pallidum in the sample when processing the material with specific monoclonal antibodies. When setting the test, the same consumables are used as for the dark-field microscopy. Additionally used: • acetone or methanol as fixatives, • monoclonal antibodies to pathogenic treponema pale, combined with FITC, • fluorescent microscope, • mounting liquid for preparations
Preparations are examined using a fluorescent microscope at magnification x200, x400 and x1000. In this case, the cells are stained red-orange or yellow, pale treponema fluoresces bright green, retaining all morphological signs of a spirochete. Note: This method is not yet widely used due to the lack of industrial production. and certification of relevant ingredients, in particular monoclonal antibodies to pathogenic treponema pallidum labeled with FITC.
Nucleic acid amplification methods (NAA) Nucleic acid amplification (NAA) techniques, e.g. polymerase chain reaction (PCR), allow you to detect a single DNA molecule of the pathogen among millions of other molecules. As an object of research by the PCR method can be used: Scrapings from chancroid and other rashes (papules, wide condylomitis ), spinal, amniotic liquid, blood serum.
Indirect research methods (used for establishing a preliminary diagnosis) Non- treponemal tests This type of diagnosis is based on the determination of antibodies that the patient's body produces in response to lipids, which are areas of the treponemas membrane. These antibodies can appear in the body 1-2 weeks after the chancre has formed on the skin, which corresponds to 4-5 weeks after the entry of the microorganism into the internal environment. The method is screening, that is, express diagnostics, which does not require much time and money. This is like the primary determination of the need for further diagnosis, and not confirmation of syphilis.
As an antigen in non- treponemal tests, a mixture of cardiolipin , lecithin and cholesterol. These tests are based on flocculation (the reaction product precipitates in the form of flakes). These tests detect IgG and IgM antibodies to lipids of the cell wall of treponema pallidum, which appear in the blood about 1 week after forming a hard chancre Reaction of microprecipitation (RMP) Rapid plasma reagin (RPR) test VDRL test(Venereal Disease Research Laboratory Test ) TRUST(Toluidine red unheated serum test) RST( Reagin Screen Test)
Sensitivity and specificity of non- treponemal serological diagnosis of syphilis
Non- treponemal tests are not strictly specific responses to syphilis, since the determination of the presence of anticardiolipin antibodies is carried out. In serum of human blood reaginic antibodies can be transiently detected with systemic lesions of parenchymal organs (liver, kidneys, lungs), with myocarditis, atherosclerosis, acute viral infections, including hepatitis, chickenpox and measles, with malaria, after vaccination and during pregnancy. Number of false positives results are increased when examining blood samples from older people. With low positive titers of non- treponemal tests (<1: 8) requires specific treponemal tests, such as RIF-abs, ELISA, RPHA or treponema immobilization reaction (RIT).
The technique is based on the same principle as the previous one. The difference lies in the fact that the antigen in this case is treponema . An inactivated pathogen, purified or ultrasonic, is taken for analysis. The technique is more costly and time-consuming to use. There are modifications: immunofluorescence, agglutination, enzyme immunoassay, immunoblotting. This type of research is more accurate than the previous group of tests. They are used to confirm the diagnosis , but there are also some that give a false result. Treponemal tests
Treponemal reactions include: Enzyme immunoassay (ELISA), Reaction of passive hemagglutination (RPHA) or its variant - the method of microhemagglutination T. pallidum (MGA-TP), as well as the reaction of immobilization of pale treponemas (RIT or RIPT), immunofluorescence reaction (RIF), as well as the method of immunoblotting and a new test with using chromatographic strips (point-of-care)
Treatment
Antibacterial drugs recommended for the treatment of syphilis. Penicillins : - durant : bicillin-1 ( dibenzylethylenediamine salt of benzylpenicillin , otherwise - benzathine benzylpenicillin ), combined: bicillin-5 ( dibenzylethylenediamine and novocaine and sodium salts of penicillin in a ratio of 4: 1); medium durability: benzylpenicillin novocaine salt; water-soluble: crystalline benzylpenicillin sodium salt; semi-synthetic: ampicillin sodium salt, oxacillin sodium salt. Tetracyclines : doxycycline. Macrolides: erythromycin. Cephalosporins : ceftriaxone. The drug of choice for treating syphilis is benzylpenicillin .
Preventive treatment ■ Bicillin-5, 1.5 mln Units / intramuscularly 2 times / Week No. 2 or ■ benzylpenicillin novocaine salt, 600 thousand units / intramuscularly 2 times / Day. daily for 7 days. A single administration of durant penicillin ( benzathine benzylpenicillin ) is preferred: no treatment failure is described, while at the same time, he has the greatest compliance.
Treatment of patients with primary syphilis ■ Bicillin-1, 2.4 million units intramuscularly 1 time in 5 days No. 3, or ■ Bicillin-5, 1.5 million units intramuscularly 2 times / week No. 5, or ■ benzylpenicillin novocaine salt, 600 thousand units intramuscularly 2 times / day daily for 20 days, or benzylpenicillin sodium salt crystalline, 1 million units intramuscularly every 4 hours (6 times / day) daily for 20 days.
Treatment of patients with secondary and early latent syphilis ■ Benzylpenicillin novocaine salt 600 thousand units intramuscularly 2 times / day every day for 20 days, or ■ benzylpenicillin sodium salt, crystalline 1 million units intramuscularly every 4 hours (6 times / day) daily for 28 days, or ■ Bicillin-1, 2.4 million units intramuscularly 1 time in 5 days № 6. In patients with a disease more than 6 months old, it is recommended to use benzylpenicillin novocaine salt, benzylpenicillin crystalline sodium salt.
Treatment of patients with tertiary, late latent and latent unspecified syphilis ■ Benzylpenicillin sodium salt, crystalline 1 million U intramuscularly every 4 hours (6 times / day) daily for 28 days, after 2 weeks - the second course of treatment with benzylpenicillin sodium salt crystalline in similar doses or one of the drugs of "medium" durability ( benzylpenicillin novocaine salt) or ■ benzylpenicillin novocaine salt, 600 thousand units intramuscularly 2 times / day daily for 28 days, after 2 weeks the second course of benzylpenicillin novocaine salt in a similar dose for 14 days.
Treatment of patients with visceral syphilis is recommended in a hospital setting - dermatovenerological or therapeutic / cardiological , taking into account the severity of the lesion. Treatment is carried out by dermatovenerologist prescribing specific treatment, together with a therapist / cardiologist recommending concomitant and symptomatic therapy. Treatment of patients with early visceral syphilis ■ Crystalline benzylpenicillin sodium salt, 1 mln U / intramusculary every 4 hours (6 times / day) daily for 28 days or ■ benzylpenicillin novocaine salt, 600 thousand units / intramusculary 2 times / day daily for 20 days.
Treatment of patients with late visceral syphilis Treatment begins with a 2-week wide spectrum antibiotic preparation (doxycycline, erythromycin). Then they switch to penicillin therapy. ■ Benzylpenicillin sodium salt, crystalline 400 thousand units / intramusculary every 3 hours (8 times / day) daily for 28 days, after 2 weeks the second course of benzylpenicillin sodium salt crystalline in a similar dose within 14 days or ■ benzylpenicillin novocaine salt, 600 thousand units / intramusculary 2 times / day daily for 28 days, after 2 weeks a second course of benzylpenicillin novocaine salt in a similar dose for 14 days.
Treatment of patients with early neurosyphilis ■ Benzylpenicillin sodium salt, crystalline, 12 million units intravenously drip 2 times / day daily for 20 days. A single dose of the antibiotic is diluted in 400 ml of isotonic sodium chloride solution and injected intravenously for 1.5-2 hours. Solutions are used immediately after preparation, or ■ benzylpenicillin sodium salt, crystalline 4 million units intravenously jet 6 times / day daily for 20 days. A single dose of the antibiotic is diluted in 10 ml of isotonic sodium chloride solution and administered intravenously slowly for 3-5 minutes into the ulnar vein.
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 90-60-30 mg, respectively (once in the morning). Treatment of patients with late neurosyphilis ■ Crystalline benzylpenicillin sodium salt, 12 million units intravenously drip 2 times / day daily for 20 days, after 2 weeks the second a course of benzylpenicillin sodium salt crystalline in a similar dose for 20 days, or ■ benzylpenicillin sodium salt, crystalline, 2-4 million units intravenously jet 6 times / day daily for 20 days, after 2 weeks the second course benzylpenicillin sodium salt crystalline in a similar dose within 20 days.
Side effects and complications of anti-syphilitic therapy 1. Exacerbation reaction ( Jarisch-Herxheimer ) In most patients, clinical manifestations begin 2–4 hours after the first administration of the antibiotic, reaching maximum severity in 5-7 hours, within 12-24 hours, the condition returns to normal. The main clinical symptoms are chills and a sharp increase in body temperature (up to 39 ° C, sometimes higher). Other reactions symptoms are general malaise, headache, pain in muscles, joints, tachycardia, rapid breathing, lowering blood pressure, leukocytosis. With secondary syphilis, roseolous and papular rashes become more numerous, bright, edematous, sometimes elements merge due to the abundance
2. Reaction to intramuscular administration of prolonged penicillin preparations (Hine syndrome). May occur after any injection of the drug. It is characterized by dizziness, tinnitus, fear of death, pallor, paresthesias , visual impairment, high blood pressure, short-term loss of consciousness, hallucinations or convulsions may occur immediately after the injection. Lasts within 20 minutes. Symptoms can be expressed in different degrees - from mild to severe. Differentiate with anaphylactic shock, in which blood pressure drops. Treatment: 1) complete rest, silence, horizontal position of the patient's body; 2) prednisolone 60–90 mg or dexamethasone 4–8 mg i / v or i / m; 3) suprastin or diphenhydramine 1 ml 1% solution in / m, 4) with high blood pressure - papaverine 2 ml 2% solution and dibazol 2 ml 1% solution in / m. If necessary, consult a psychiatrist and use sedatives and antipsychotics
3. Nicolaou's syndrome - a symptom complex of complications after intra-arterial injection durant drugs of penicillin or other drugs with a crystalline structure: Sudden ischemia at the injection site, the development of painful cyanotic irregular spots (livedo) with subsequent blistering and skin necrosis, in some cases flaccid paralysis of the limb in which the drug was injected, in rare cases - transverse paralysis. 4. Neurotoxicity - convulsions (more often in children), when using high doses of penicillin, especially in renal failure. Electrolyte imbalance - in patients with heart failure with large doses of benzylpenicillin sodium salt possible increased edema (1 million units of the drug contains 2.0 mmol sodium).
5. Allergic reactions - toxicoderma , urticaria , Quincke's edema, headache, fever, joint pain, eosinophilia - when administered penicillin occurs in 5 to 10% of patients. The most dangerous complication is anaphylactic shock, which gives up to 10% mortality. 6. Anaphylactic shock is characterized by the fear of impending death, feeling of heat throughout the body, loss of consciousness, pale skin, cold clammy sweat, pointed facial features, frequent shallow breathing, threadlike pulse, low blood pressure Treatment: 1) inject epinephrine 0.5 ml of 0.1% solution into the injection site of the drug; 2) epinephrine 0.5 ml 0.1% solution in / v or in / m; 3) prednisolone 60-90 mg or dexamethasone 4–8 mg IV or IM; 4) suprastin or diphenhydramine 1 ml 1% solution in / m; 5) calcium gluconate 10 ml 10% solution in / m, in case of difficulty respiration - aminophylline 10 ml 2.4% solution intravenously slowly
Contraindications to the administration of drugs of the penicillin group: ■ Intolerance to benzylpenicillin , its prolonged-release drugs and semi-synthetic derivatives; ■ Prolonged-release penicillin preparations should be prescribed with caution with severe hypertension, previous myocardial infarction, with diseases of the endocrine glands, with acute gastrointestinal diseases, active tuberculosis, with diseases of the hematopoietic system.
SPECIAL SITUATIONS Treatment of pregnant women The doctor's role is to provide timely adequate treatment (started before the 32nd week of pregnancy and carried out with penicillin preparations of medium durability, penicillin sodium salt, semi-synthetic penicillins , or ceftriaxone) and providing psychological support to the pregnant woman. Specific treatment for pregnant women regardless of gestational age carry out benzylpenicillin with crystalline sodium salt or drugs of medium durance ( benzylpenicillin novocaine salt)as well as treatment of non-pregnant women, according to one of the proposed recommendations of techniques, in accordance with the established diagnosis
Prophylactic treatment of pregnant women is carried out starting from the 20th week of pregnancy, but if specific treatment is started late - immediately after it. Preparations, single doses and frequency of administration correspond to those for specific treatment. Duration of therapy is 10 days. If, in the presence of indications for preventive treatment of pregnant women, there is information about the inferiority of the specific treatment, then preventive treatment should continue for 20 days (as additional)
Treatment of syphilis with indication of intolerance to penicillin drugs When indicating the presence of allergic reactions to penicillin, reserve drugs are used: ■ ceftriaxone 1.0 g IM 1 time / day daily No. 5 for preventive treatment and No. 10 for the treatment of primary syphilis; 1.0 g IM 1 time / day daily No. 20 for the treatment of secondary and early latent; 2.0 g IM 1 time / Day daily No. 20 for the treatment of early neurosyphilis in heavy cases (syphilitic meningoencephalitis, acute generalized meningitis), it is possible to use the drug intravenously and increase the daily doses up to 4 g; 1.0 g IM 1 time / day daily No. 20, after 2 weeks the second course of the drug in the same dose daily No. 10 for the treatment of late forms of syphilis.
■ doxycycline 0.1 g orally 2 times a day daily for 10 days for preventive treatment, 20 days for primary treatment and 30 days for treatment of secondary and early latent syphilis; ■ erythromycin 0.5 g orally 4 times / day daily for 10 days for preventive treatment, 20 days for primary treatment and 30 days for treatment of secondary and early latent syphilis; ■ oxacillin sodium salt or ampicillin sodium salt 1mln U IM 4 times/ day (every 6 hours) daily for 10 days for preventive treatment, 20 days for primary treatment and 28 days for treatment of secondary and early latent syphilis.
Maintaining contact persons Persons who have had sexual or close household contact with patients with early forms of syphilis, who have passed since the moment of contact no more than 2 months, preventive treatment is shown using one of the above methods. For persons who have passed from 2 to 4 months from the moment of contact with a patient with early syphilis, a double clinical and serological examination is carried out with an interval of 2 months; if more than 4 months, a single clinical and serological examination is performed.