In 2014, the Venereology Group of the Dermatological and Venereal Diseases Committee of the Chinese Society of Integrative Medicine organized experts to discuss the serum fixation of syphilis, and finally formed an expert consensus on the clinical management of syphilis serum fixation for clinical reference.
Syphilis is a sexually transmitted disease that seriously endangers human health, and the incidence of syphilis has been increasing year by year in recent years, with 419,000 syphilis cases reported nationwide in 2014. The incidence of serofixation reaction (syphilis serofast reaction) or sero-resistance in syphilis patients after treatment is high, and the incidence by syphilis stage is 3.80% ~ 15.20% for stage I syphilis, 11.64% ~ 35.80% for stage II syphilis, 45.02% ~ 45.90% for stage III syphilis, and latent syphilis 27.41% ~ 40.50%. Serum fixation has become a thorny issue in the clinical management of syphilis.
I. Definition
There is no clear definition of syphilis serum fixation, and the views of domestic and foreign experts are summarized as follows.
① syphilis patients after anti-syphilis treatment, non-syphilis spirochete serological test [such as rapid plasma reactin ring card test (RPR)] can mostly turn negative, but there are a few patients serologic reaction titer gradually decreased to a certain extent that no longer fall, long-term maintenance in low titer, that is, the phenomenon of serum fixation or known as serum resistance, the criteria are generally considered early syphilis 2 years after treatment, late syphilis 2 years after treatment those whose seropositivity remains positive above.
②Patients with syphilis who have not been converted to negative non-syphilis spirochete antigen serologic test within 1 ~ 2 years after adequate anti-syphilis treatment, or whose titer does not decrease.
(iii) Patients with early syphilis who have been followed up for a prescribed period of time after anti-syphilis treatment and whose serum still does not turn negative are referred to as serum fixation; 1 year after early syphilis treatment or 2 years after late syphilis treatment when the serum reactin test has not turned negative is serum fixation.
④After regular syphilis treatment and adequate follow-up (1 year for stage I syphilis, 2 years for stage II syphilis and 3 years for late stage syphilis), RPR is maintained at a low titer for a long time, even accompanied by lifelong non-turning negative.
⑤ 6 months after the standardized syphilis treatment, some patients’ serum reactin test has not yet turned negative, but the antibody titer still has a decreasing trend, which should not be judged as serum fixation prematurely at this time, and the serum reactin antibody titer to a certain level no longer decreasing for more than 3 months can be regarded as serum fixation.
(6) Patients with syphilis whose clinical manifestations have disappeared after standardized syphilis treatment, and whose serum reactin test still does not turn negative after 6 months of early syphilis and 12 months of late syphilis.
(7) Patients with syphilis who have undergone standardized anti-syphilis treatment and adequate follow-up (generally 6 to 12 months) and whose non-syphilis spirochete antigen serologic test [e.g., RPR, toluidine red unheated serologic test (TRUST)] titer only decreases by less than 2 dilutions or remains positive but is not a treatment failure (treatment failure is defined as a 4-fold or more increase in non-syphilis spirochete antigen serologic test titer after treatment) .
The main disagreement between the above definitions is the varying duration of follow-up after standardized treatment, ranging from six months, one year to two years. In our opinion, serological fixation of syphilis can be defined as a patient with syphilis who has undergone standardized anti-syphilis treatment and adequate follow-up (1 year for stage I syphilis, 2 years for stage II syphilis, and 3 years for advanced syphilis), and whose non-syphilis spirochete serological test has remained at a certain titer (generally 1:8 or less, but not infrequently more than 1:8) for more than 3 months, excluding reinfection, neurosyphilis, cardiovascular syphilis, and biological false The serofixation of syphilis is defined as a false positive.
It is generally accepted that serum fixation and serum resistance are conceptually compatible, but serum fixation is more commonly used.
II. Mechanism of formation
The mechanism by which serum fixation of syphilis occurs is not fully understood. There are many factors that may influence the serologic response of patients after treatment, such as younger, earlier staging, fewer sexual partners, higher baseline titers, and better recovery of serologic response in patients with Jarisch-Herxheimer reaction after initial treatment, and vice versa. It may also be related to the type and dose of the initial treatment and the route of administration.
It is believed that the possible mechanisms of syphilis serum fixation include: alteration of syphilis spirochete membrane peptide antigens, lipoproteins and genes, resulting in failure to be cleared by the body’s immunity, abnormalities in the body’s immunity, including immune imbalance and immunosuppression, and disorders of T-cell subsets, natural killer (NK) cells and cytokine secretion.
Third, the harm and regression
There is insufficient evidence to assess the harms of syphilis serofixation, and it is uncertain whether syphilis serofixation increases the risk of relapse or progression to advanced syphilis, and whether additional penicillin therapy is beneficial. Persistent positive syphilis serology has mainly psychological and psychiatric effects on patients, who may suffer from depression, anxiety and other adverse psychological states due to concerns about prognosis and transmission, social discrimination, etc.
IV. Treatment
Due to the high incidence of syphilis serum fixation, the management of such patients has become a difficult clinical problem. Early diagnosis and timely standardized treatment are important measures to prevent syphilis serum fixation. At the time of initial treatment of syphilis, a detailed medical history should be obtained, including the history of sexual contact (time of infection, syphilis infection status of sexual partners, recent risky sexual behavior, etc.), history of previous treatment (time of starting treatment, type of drugs used, course of treatment, dosage, follow-up, etc.), so that the post-treatment serologic response of patients can be predicted. During follow-up, cerebrospinal fluid testing is recommended for those identified with syphilis serofixation to exclude neurosyphilis, with repeated testing if necessary. HIV testing should also be performed to rule out HIV infection. Cardiovascular syphilis and other visceral syphilis also need to be ruled out by appropriate tests. False-positive syphilis serology should also be excluded.
Patients with serofixed syphilis need to be analyzed and counseled. Patients who have received adequate anti-syphilis treatment and adequate follow-up, if there is no recurrence of clinical symptoms, neurological examination, cerebrospinal fluid examination and other relevant tests to exclude neurological and other visceral systemic damage, and if the non-syphilis spirochete serology test is maintained at a low titer of 1:8 for a long time, treatment is not necessary, but regular follow-up (usually every 6 months) is required. It is recommended to add syphilis spirochete-specific IgM antibody testing at follow-up if available, which can be used as a marker for syphilis recurrence and reinfection. A 4-fold or higher increase in the titer of the non-syphilis spirochete serologic test during follow-up indicates recurrence or reinfection and requires re-treatment.
Patients with syphilis serofixation need to weigh the pros and cons of pregnancy, and if pregnant need to be followed up regularly and, if necessary, considered for prophylactic treatment, i.e., treated according to the syphilis in pregnancy protocol during pregnancy. Studies have shown that treatment of pregnant syphilis patients with a standardized anti-syphilis regimen can block congenital syphilis in 98.5% to 100% of cases.
Chinese medicine can be used as an adjunctive treatment for patients with serum fixation of syphilis. According to TCM, the etiology of syphilis serum fixation is mainly due to the deficiency of positive qi, the presence of evil toxins, and the deficiency of positive evil. The principle of treatment is to tonify the spleen and benefit the qi, and detoxify the dampness. Astragalus membranaceus, Rhizoma Atractylodis Macrocephalae, Radix et Rhizoma Ganoderma lucidum, Poria tulipifera, Rhizoma Inulae, Rhizoma Polygonati, Radix et Rhizoma Glycyrrhizae can be used for treatment.
V. Conclusion
This time, the Venereology Group of the Dermatological and Venereal Diseases Committee of the Chinese Society of Integrative Medicine has formed a preliminary expert consensus on the definition, mechanism of occurrence, hazards and clinical management of syphilis serum fixation for clinical reference. Future research on syphilis serofixation should be strengthened. This consensus will be revised and updated with future advances in basic and clinical research on syphilis serofixation.
This article is extracted from the Chinese Journal of Dermatology