Syphilis (syphilis) is a chronic, systemic sexually transmitted disease caused by the pale spirochete. It can be divided into acquired syphilis and fetal syphilis (congenital syphilis). Acquired syphilis is further divided into early and late syphilis. Early syphilis refers to infection with the syphilis spirochete within 2 years, including stage I, stage II and early recessive syphilis, and stage I and II syphilis can also overlap. Late syphilis has a duration of more than 2 years and includes stage III syphilis, cardiovascular syphilis, and late recessive syphilis. Neurosyphilis can occur in both the early and late stages of syphilis. Fetal syphilis is further divided into early stage (onset within 2 years after birth) and late stage (onset after 2 years of birth).
Diagnosis of syphilis
1. Phase I syphilis.
(1) Epidemiological history: history of unsafe sex, multiple sexual partners or sexual partner infection.
(2) Clinical manifestations.
(1) Hard chancre: The incubation period is usually 2 to 4 weeks. It is often single, but can also be multiple. The first nodule is a corn-sized nodule above the skin surface, and later develops into a round or oval shallow ulcer with a diameter of about 1 to 2 cm. The typical nodule is well-defined, with slightly elevated margins and a flat, clean wound; the infiltrate is obvious on palpation and is cartilage-like in hardness; there is no obvious pain or mild tenderness. It is usually found in the external genital area;
(2) Inguinal or affected near-guard lymph nodes enlargement: can be unilateral or bilateral, painless, isolated from each other without adhesions, medium quality, not septic rupture, its surface skin without redness, swelling and heat.
(3) Laboratory examination.
(1) Dark-field microscopy or silver-plated microscopy can be used to detect syphilis spirochetes by taking the exudate of sclerosing chancre or lymph node puncture fluid, but the detection rate is low;
(2) Positive serological test for non-syphilis spirochetes. If the infection is less than 2 to 3 weeks, the test may be negative and should be repeated after 4 weeks of infection;
(3) Positive serological test for syphilis spirochetes, which can be negative at very early stage.
(4) Diagnostic classification.
①Suspected case: should be consistent with both clinical manifestations and laboratory tests in ②, may or may not have epidemiological history; or consistent with both clinical manifestations and laboratory tests in ③, may or may not have epidemiological history;
② confirmed cases: should meet both the requirements of suspected cases and laboratory tests in ①, or both the requirements of suspected cases and both types of syphilis serological tests are positive.
2, phase II syphilis.
(1) Epidemiological history.
History of unsafe sex, multiple sexual partners or sexual partner infection, or history of blood transfusion (the blood donor is a patient with early syphilis).
(2) Clinical manifestations: There may be a history of stage I syphilis (often appearing 4-6 weeks after the onset of sclerosing chancre), and the disease period is within 2 years.
(1) Skin and mucous membrane damage: The types of lesions are diverse, including macules, maculopapular rash, papules, scaly lesions, follicular rash and pustular rash, etc. They are distributed on the body and extremities, and are often generalized and symmetrical. Dark erythematous and desquamative macules on the palms and plantars, and eczema or flat warts on the vulva and perianal area are the characteristic damages. The rash is usually not pruritic. Oral mucosal plaques and worm-like alopecia may be present. The number of second-stage recurrent syphilis lesions is small, and the lesions are peculiarly shaped, often in the form of rings or arcs or arcs;
(2) The superficial lymph nodes may be enlarged;
(3) Syphilitic bone and joint, eye, visceral and neurological damage may occur.
(3) Laboratory tests.
① dark-field microscopy or silver-plated staining microscopy method, take the second-stage lesions, especially flat warts, wet papules, town to find syphilis spirochetes. el cavity mucosal spots because it is not easy to distinguish from other spirochetes in the oral cavity, so do not use this method of examination;
② Positive serological test for non-syphilis spirochetes;
(3) positive serological test for syphilis spirochetes.
(4) Diagnostic classification.
① suspected cases should be consistent with both clinical manifestations and laboratory tests in ②, may or may not have an epidemiological history;
② confirmed cases should meet both the requirements of suspected cases and laboratory tests in ①, or both the requirements of suspected cases and both types of syphilis serological tests are positive.
3.Stage III syphilis.
(1) Epidemiological history: history of unsafe sex, multiple sexual partners or sexual partner infection, or history of blood transfusion.
(2) Clinical manifestations: there may be a history of stage I or II syphilis with a disease duration of more than 2 years.
(1) Late syphilis: a. Skin and mucous membrane damage: nodular syphilis rash on the head, face and extremities, proximal joint nodules near large joints, dendritic swelling of the skin, mouth, tongue and throat, mucous membrane dendritic swelling of the palate and nasal septum can lead to perforation of the palate and septum and saddle nose. b. Bone syphilis, ocular syphilis, other visceral syphilis involving the respiratory tract, gastrointestinal tract, liver and spleen, genitourinary system, endocrine glands and skeletal muscles, etc;
(2) cardiovascular syphilis, which can occur as simple aortitis, aortic atresia, aortic aneurysm, etc.
(3) Laboratory tests.
① positive serological test for non-syphilis spirochetes, very few advanced syphilis can be negative; ② positive serological test for syphilis spirochetes.
(4) Diagnostic classification.
① suspected cases should be consistent with both clinical manifestations and laboratory tests in ①, may or may not have an epidemiological history;
② confirmed cases should meet both the requirements of suspected cases and positive serological tests for both types of syphilis.
4. Neurosyphilis.
(1) Epidemiological history: history of unsafe sex, multiple sexual partners or sexual partner infection, or history of blood transfusion.
(2) Clinical manifestations.
① Asymptomatic neurosyphilis: no obvious neurological symptoms and signs;
(2) Meningeal neurosyphilis: fever, headache, nausea, vomiting, cervical ankylosis, optic papillary edema, etc;
③Meningeal vascular syphilis: manifestation of occlusive cerebrovascular syndrome, such as hemiplegia, paraplegia, aphasia, epileptiform seizures, etc;
(iv) cerebral parenchymal syphilis: psychiatric symptoms may appear, such as paralytic dementia, inattention, mood changes, delusions, as well as mental retardation, judgment and memory, personality changes, etc.; neurological symptoms may appear, such as tremor, speech and writing disorders, ataxia, muscle weakness, seizures, tetraplegia and incontinence. If the spinal cord is damaged by syphilis spirochetes, the disease is called spinal consumption. Lightning-like pain, abnormal sensation, tactile pain and temperature perception disorders; hyperalgesia and loss of deep sensation; position and vibration perception disorders, etc. may occur.
(3) Laboratory tests.
① Positive serological test for non-syphilis spirochetes, very few patients with advanced disease can be negative;
(2) Positive syphilis spirochete serology test;
③Cerebrospinal fluid examination: white blood cell count ≥5×106 several, protein amount >500mg/L, and no other causes of abnormalities. Positive cerebrospinal fluid fluorescent spirochete antibody absorption test (FrA-ABS) and/or venereal disease research laboratory (VDRL) test. In the absence of conditions for FFA-ABS and VDRL, the syphilis spirochete gelatin agglutination test (TPPA) and rapid plasma reactin ring card test (RPR)/toluidine red unheated serological test (TRUST) may be used instead.
(4) Diagnostic classification.
①Suspected cases: should be consistent with both clinical manifestations, laboratory tests ①, ②, ③ in the routine examination of cerebrospinal fluid abnormal (exclude other causes of abnormalities), may or may not have an epidemiological history ;
② confirmed cases: should meet the requirements of both suspected cases and laboratory tests ③ in the cerebrospinal fluid syphilis serology test positive.
5, latent syphilis (latent syphilis).
(1) Epidemiological history: history of unsafe sex, multiple sexual partners or sexual partner infection, or history of blood transfusion.
(1) Early latent syphilis: disease duration <2 years: a. A clear history of high-risk sexual behavior within the past 2 years, and no history of high-risk sexual behavior 2 years ago. b. Clinical manifestations consistent with stage I or II syphilis within the past 2 years, but not diagnosed and treated. c. A clear history of syphilis infection in sexual partners within the past 2 years;
②Late stage occult syphilis: duration of disease > 2 years. Those who cannot determine the duration of the disease are treated as advanced late-stage occult|biogenic syphilis.
(2) Clinical manifestations: no clinical symptoms and signs.
(3) Laboratory tests.
① positive non-syphilis spirochete serology test, a few late stage cryptosporidium can be negative;
(2) Positive syphilis spirochete serology test;
(3) No significant abnormalities in cerebrospinal fluid examination.
(4) Diagnostic classification.
①Suspected cases: should also meet the laboratory tests in ①, no previous history of syphilis diagnosis and treatment, no clinical manifestations;
②Confirmed cases: meet the requirements of suspected cases and both types of syphilis serological tests are positive. If conditions are feasible cerebrospinal fluid examination to exclude asymptomatic neurosyphilis.
6, fetal syphilis.
(1) epidemiological history: the birth mother is a syphilis patient.
(2) Clinical manifestations.
(1) early fetal syphilis: generally <2 years of age, similar to acquired stage II syphilis, dysplasia, lesions are often erythema, papules, flat warts, blisters a blister; syphilitic rhinitis and laryngitis; osteomyelitis, osteochondritis and periostitis; may have generalized lymph node enlargement, hepatosplenomegaly, anemia, etc.;
②Late stage fetal syphilis: generally >2 years old onset, similar to acquired stage III syphilis. Inflammatory damage (interstitial keratitis, neurogenic deafness, nasal or palatal dendritis, kleaton joint, tibial periostitis, etc.) or marked damage (rounded forehead, saddle nose, peyote shin, osteochondral hypertrophy of the clavicothoracic joint, Hechin’s teeth, radiolucency of the skin around the mouth, etc.) are present;
(3) Occult fetal syphilis: that is, untreated fetal syphilis, no clinical symptoms, positive syphilis serology test, normal cerebrospinal fluid examination, age <2 years old for early occult fetal syphilis, >2 years old for late occult fetal syphilis.
(3) Laboratory examination: microscopic examination: using dark-field microscopy or silver-plated staining microscopy, take the skin mucosal damage or placenta specimens of children with early fetal syphilis, syphilis spirochetes can be detected; positive serological test for non-syphilis spirochetes, their antibody titers ≥ 2 dilutions of the mother, or the titers show an increasing trend in follow-up for 3 months has a confirmatory significance; positive serological test for syphilis spirochetes, their IgM antibody test positive has a confirmatory significance, negative cannot exclude fetal syphilis.
(4) Diagnostic classification.
Suspected cases: all infants born to mothers with syphilis who have not been effectively treated, or cases of stillbirth, stillbirth, or miscarriage that have occurred, where the evidence is not yet sufficient to confirm the diagnosis of fetal syphilis.
Confirmed cases: laboratory tests and follow-up findings consistent with any of the following.
(i) Dark-field microscopy, or silver-plated staining for syphilis spirochetes in skin/mucosal damage and tissue specimens from early congenital syphilis, or positive nucleic acid test for syphilis spirochetes;
② Positive serum IgM antibody test for syphilis spirochetes in infants;
(iii) The infant was born with a non-syphilis spirochete serological test titer ≥ 4 times the mother’s titer, and a positive syphilis spirochete serological test;
(4) The infant was born with a negative non-syphilis spirochete serology test or with a titer that was less than 4 times the mother’s titer, but was found to change from negative to positive during subsequent follow-up, or with a titer that increased with clinical symptoms, and with a positive syphilis spirochete serology test;
(5) Infants born to mothers with syphilis have continued to test positive for the syphilis spirochete antigen until 18 months of age.
Treatment of syphilis
1. General principles.
① Early detection, timely formal treatment, the earlier the treatment effect is better;
② adequate dose, the course of treatment rules. Irregular treatment may increase recurrence and promote the early occurrence of late stage damage;
③After treatment, we should follow up for enough time;
④Check and treat all sexual partners at the same time.
2.Treatment program.
(1) Early syphilis (including stage I, stage II and latent syphilis of <2 years duration) Recommended regimen.
Procaine penicillin G 800,000 u/d, intramuscular injection for 15 d; or benzathine penicillin 2.4 million u, divided into bilateral intramuscular injections in the buttocks, once a week for 2 times Alternative regimen: ceftriaxone 0.5-1 g, once a day, intramuscular injection or intravenous administration for 10 d.
Allergy to penicillin with the following drugs: doxycycline 100 mg twice daily for 15 d; or tetracycline hydrochloride 500 mg four times daily for 15 d (prohibited in hepatic and renal insufficiency).
(2) Recommended regimen for advanced syphilis (stage III skin, mucous membrane, bone syphilis, advanced latent syphilis or latent syphilis in which the stage cannot be determined) and stage II recurrent syphilis.
Procaine penicillin G, 800,000 u/d, intramuscularly, for 20 d for 1 course, or consider giving a 2nd course with 2 weeks of discontinuation between courses or benzathine penicillin 2.4 million u, divided into bilateral gluteal intramuscular injections, once a week for 3 times.
Allergy to penicillin with the following drugs: doxycycline 100 mg twice daily for 30 d; or tetracycline hydrochloride 500 mg four times daily for 30 d (prohibited in hepatic and renal insufficiency).
(3) Recommended regimen for cardiovascular syphilis.
If there is heart failure, treat heart failure first, when the heart function can be compensated, inject penicillin, need to start with small dose to avoid Jihai reaction, causing aggravation or death. Aqueous penicillin G, day 1 100,000 U, 1 intramuscular injection; day 2 lO million u, 2 daily intramuscular injections; day 3 200,000 u, 2 daily intramuscular injections; from day 4 onwards, treatment according to the following protocol: procaine penicillin G, 800,000 U/d, intramuscular injection, 20 d for a course of treatment, a total of 2 courses (or more), stopping between courses of treatment for 2 weeks; or benzathine penicillin 2.4 million u, divided into bilateral gluteal intramuscular injection, once a week, a total of 3 times.
For those allergic to penicillin, use the following drugs: doxycycline 100 mg twice daily for 30 d; or tetracycline hydrochloride 500 mg four times daily for 30 d (prohibited for those with hepatic or renal insufficiency).
(4) Recommended regimen for neurosyphilis and ocular syphilis.
Aqueous penicillin G 18 million. 24 million u intravenously (3 million to 4 million u every 4 hours) for 10-14 d. If necessary, followed by benzathine penicillin G 2.4 million u intramuscularly once a week for 3 times. Or procaine penicillin G, 2.4 million U/d, 1 intramuscular injection, together with oral propofol, 0.5 g each time, 4 times per Et for 10-14 d. If necessary, followed by benzathine penicillin G 2.4 million U, 1 intramuscular injection once a week for 3 times.
Alternative regimen: Ceftriaxone 2 g, administered intravenously once daily for 10-14 d. For those allergic to penicillin, use the following drugs: doxycycline 100 mg twice daily for 30 d; or tetracycline hydrochloride 500 mg four times daily for 30 d (contraindicated in hepatic and renal insufficiency).
(5) Recommended regimen for early fetal syphilis (<2 years old).
For abnormal cerebrospinal fluid: aqueous penicillin G, 100,000 to 150,000 u/kg-1・d~, for newborns within 7 d after birth, at 50,000 U/kg each time, intravenously every 12 h, and every 8 h thereafter, until a total course of 10-14 d. Or procaine penicillin G, 50,000 u/kg. 1・d~, intramuscularly, once daily for 10-14 d.
If the cerebrospinal fluid is normal: benzathine penicillin G, 50,000 U,’kg, 1 intramuscular injection in both buttocks. If there is no condition to check the cerebrospinal fluid, it can be treated as the abnormal cerebrospinal fluid. For those who are allergic to penicillin, there is no evidence that using other treatment options is effective, erythromycin treatment can be tried.
(6) Recommended regimen for late fetal syphilis (>2 years old).
Aqueous penicillin G, 150,000 u・kg’1・d a, divided intravenous drip for 10-14 d, or procaine penicillin G, 50,000 U/kg daily, intramuscular injection for 10 d as a course of treatment (penicillin dosage for older children should not exceed the treatment for adult patients of the same period). For normal cerebrospinal fluid: benzathine penicillin G, 50,000 U/kg, 1 injection in both gluteal muscles.
Alternative regimen: for those who are allergic to penicillin and have used cephalosporin antibiotics in the past without allergy under close observation: Ceftriaxone 250mg, 1 time daily, intramuscular injection for 10-14 d. Tetracycline is prohibited in children <8 years old.
(7) Syphilis in pregnancy.
Pregnant women with newly diagnosed syphilis during pregnancy should be treated according to the appropriate syphilis staging. Treatment principles are the same as for non-pregnant patients, but tetracycline and doxycycline are prohibited, and quantitative non-syphilis spirochete serology tests are performed once a month after treatment to observe for recurrence and reinfection. A course of anti-syphilis treatment is recommended for patients with syphilis in pregnancy in the early 3 months of pregnancy and 1 course in the last 3 months of pregnancy.
For those who are allergic to penicillin and cephalosporins, due to pregnancy and lactation, tetracyclines cannot be used, macrolides can be used instead: erythromycin 500 mg 4 times daily for 15 days for early syphilis
Erythromycin has poor efficacy in the treatment of syphilis and should be followed up clinically and serologically after treatment. After cessation of breastfeeding, retreatment with doxycycline is required.
(8) Management of syphilis patients with co-infection with HIV.
① All HIV-infected patients should be screened for syphilis serology; all syphilis patients should be screened for HIV antibodies;
② conventional syphilis serological examination can not determine the diagnosis, skin lesion biopsy, immunofluorescent staining or silver staining to find syphilis spirochetes;
③All syphilis patients with HIV co-infection should be considered for lumbar puncture examination of cerebrospinal fluid to exclude neurosyphilis;
④Whether syphilis patients with co-infection of HIV should increase the dose or course of treatment for syphilis is still unclear, for stage I, stage II and occult syphilis it is recommended to check the cerebrospinal fluid to exclude neurosyphilis, if this cannot be achieved, it is recommended to treat with neurosyphilis treatment protocol;
⑤ Close monitoring and regular follow-up of patients.