second-stage syphilis



Overview.

Definition

Syphilis is a chronic infectious disease caused by syphilis spirochete infection, belongs to China’s Class B infectious diseases, the disease is harmful, can invade all tissues of the body.

Stage II syphilis is the second stage of syphilis infection, mainly due to the untreated or incomplete treatment of stage I syphilis, the syphilis pathogen (pallid spirochete) enters the blood circulation by the lymphatic system, and spreads and reproduces in different tissues, which is most commonly seen after 9 to 12 weeks of syphilis infection. It appears 4 to 6 weeks after the occurrence of the chancre, a typical symptom of stage I syphilis, or 3 to 4 weeks after it has subsided.

Stage II syphilis can cause systemic damage to the skin and mucous membranes and bones and joints, eyes and nerves, as well as generalized lymph node enlargement [1-3].

Morbidity

There is a relative lack of epidemiologic data related to stage II syphilis, and the overall incidence of syphilis is described below. The incidence of syphilis is still high from the current data, but the incidence of early syphilis, including stage I and II syphilis, is decreasing.

From 2014 to 2019, the reported incidence rate of syphilis increased from 30.93/100,000 to 38.37/100,000, with an average annual increase of 4.41%; among them, the reported incidence rate of Stage I and Stage II syphilis declined by an average of 10.95% per year [4].

From the perspective of some provinces and cities, in Zhejiang Province, one of the regions with high syphilis incidence in China, for example, the incidence rate of stage II syphilis decreased from 19.23/100,000 in 2010 to 4.85/100,000 in 2019, with an average annual decrease of 14.19%. The number of cases of stage II syphilis decreased from 9,963 cases to 2,785 cases [5].

According to the website of the National Health and Wellness Commission (NHSC), between January 1 and December 31, 2021, a total of 480,020 cases of syphilis infections were reported in the country, of which the number of stage II syphilis was unknown.

Etiology

Causes

Source of infection

The only infectious source of syphilis is the person with syphilis, in whom the syphilis spirochete is present in skin lesions, blood, semen, milk and saliva [1].

Routes of transmission

Sexual contact: About 95% of patients are infected by sexual contact through small breaks in the skin and mucous membranes [1-2].

Bloodborne: The blood of patients with syphilis is contagious and infection may occur when such blood is imported [1].

Mother-to-child transmission: A pregnant mother with untreated syphilis can transmit the infection to the fetus through the placenta.

Other routes: Some patients may become infected through medical routes, kissing, shaking hands, breastfeeding, or indirect contact with everyday items, such as clothing, of patients with infectious damage [2].

Susceptible people

People who are in close contact with patients with syphilis.

People with high-risk sexual behavior (same-sex behavior, sexually active, etc.), drug users, and people who share syringes.

People with HIV infection and other sexually transmitted diseases.

People with traumatic operations that are not properly sterilized (tooth extraction, ear pinning, etc.), history of high-risk blood transfusion (blood donor is a syphilitic patient).

Symptoms

Main Symptoms

Generalized skin symptoms

Syphilis rash

Trunk, limbs, palms, soles and other parts of the body can be seen generalized, symmetrically distributed, painless and itchy light red or dark red infiltrative erythema, papules, maculopapular rash, plaques, nodules, pustules, ulcers, etc., a small number of patients can be a slight itching sensation, and some of the typical patients can be seen in the palms or soles of the feet, copper-red infiltrative erythema accompanied by the surface of the collar ring-like desquamation.

Flat warts

Flat, broad-bottomed, soybean to peanut-sized reddish papules or plaques with a moist surface in the groin, perineum, anus, and vulvar genitalia.

Mucosal manifestations

There may be atypical manifestations such as syphilitic stomatitis, mucosal plaques in the throat, nodular lesions of the nasal mucosa, perforation of the nasal septum, and syphilitic sore throat. The damage manifests as one or more well-defined erythema, edema, and erosion, and the surface may be covered with grayish-white membranous material.

Syphilitic alopecia

After syphilis spirochetes invade the hair follicles of the scalp, it manifests as irregular distribution of scalp alopecia, limited or diffuse, and the symptom of hair loss like being bitten by a bug (entomophagous alopecia).

Enlarged lymph nodes

Patients with syphilis may present with painless enlargement of lymph nodes throughout the body.

Systemic damage

Bone and joint system involvement

Osteoarthritis is the most common, characterized by mild thickening of the periosteum, marked tenderness and nighttime aggravation; arthritis is common in the shoulders, elbows, knees, hips, and ankles, and is mostly symmetrical, characterized by joint swelling, tenderness, and pain, and the symptoms are more severe during the day than at night. Others include osteitis, osteomyelitis, tenosynovitis or bursitis.

Eye involvement

It can involve all the structures of the eye, usually occurring in both eyes at the same time, manifesting as drooping eyelids, limited eye movement, conjunctival congestion, visual field defects, distortion of vision, discoloration of vision, darkening of visual field, flashes of light in front of the eyes, floaters in front of the eyes, diplopia, loss of visual acuity, and blindness.

Neurosyphilis

Neurosyphilis is a continuous lesion that can occur at any stage of syphilis infection. It is usually asymptomatic in the early stage, and in the late stage, headache, mental behavioral abnormality, hemiparesis, aphasia, epilepsy, and incontinence may occur.

Involvement of internal organs

Some patients with stage 2 syphilis will have abnormal liver function, which may include jaundice, hepatomegaly, and in advanced stages, liver dendritic swelling.

Medical treatment

Department of Medicine

Department of Venereal Disease

Patients with high-risk sexual behavior and suspicious red papules, maculopapular rash, flat papules or plaques on the skin and mucous membranes are advised to consult dermatologists, venereologists or dermato-venereologists in a timely manner.

Infection medicine

Patients with a history of high-risk sexual behavior who develop enlarged lymph nodes, etc. are advised to seek prompt medical attention.

Neurology

Patients with unexplained headache, abnormal mental behavior, etc. are advised to seek medical treatment promptly.

Preparation for medical treatment

Preparation for medical consultation: registration, preparation of documents, and frequently asked questions

Tips for seeking medical treatment

If you have a headache or memory loss, please ask your family to accompany you to the doctor.

Preparation List

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

Are there any mucous membrane breaks, erythema, flat papules, etc. on the surface of the skin?

Are there painless enlargement of superficial lymph nodes?

Are there any swollen joints, pressure and pain? Are there any changes in vision?

Are there any symptoms such as headache?

Medical History Checklist

Is there any high-risk sexual activity, such as multiple sexual partners, same-sex sexual behavior, etc.?

Is the sexual partner infected with syphilis?

Any history of transfusion of syphilis-infected blood?

Any operation or treatment such as tattooing, eyebrow tattooing, ear piercing, tooth extraction, etc.?

Checklist

Test results in the last six months, which can be brought to the doctor’s office

Serum syphilis antibody, non-spirochete test test report (RPR, TRUST, etc.)

Diagnosis

Basis of diagnosis

Medical history

May have a previous diagnosis of stage 1 syphilis.

May have a history of high-risk sexual behavior

May have a history of traumatic manipulation such as tattooing, eyebrow tattooing, etc., which are not properly sterilized.

Clinical manifestations

Clinical manifestations include erythema, papules, maculopapular rash and other stage 2 syphilis rashes, and pink flat papules or plaques and other flat warts. There may also be limited or diffuse wormlike alopecia.

Erythema and edema of the mucous membranes of the mouth and throat may also be present. Other symptoms may include joint swelling, vision loss, and headache.

Laboratory Tests

Microscopic examination

The diagnosis of syphilis can be confirmed by direct observation of active spirochetes under a dark-field microscope after taking samples from skin lesions.

Oral mucosal spots are not easy to identify with other spirochetes in the oral cavity, so this method is not used.

The sensitivity is low, even if the microscopic examination is negative, but also need to refer to the serologic examination, not commonly used in the clinic.

Syphilis serologic test

Non-syphilis spirochete antigen serologic tests

These tests are commonly expressed as titers of antibodies, correlate with the degree of disease, and play an important role in screening and treatment evaluation.

The main screening tests commonly used are the rapid plasma reactin ring card test (RPR) and the toluidine red serum test without heat (TRUST).

A positive result and a clinical picture consistent with syphilis can lead to a preliminary diagnosis. This test has a high sensitivity but low specificity and can cause false positive results due to pregnancy, autoimmune diseases, vaccines, and anticardiolipin syndrome.

A 4-fold or greater reduction in the titer of the same test after antibiotic therapy is indicative of effective treatment.

Syphilis spirochete antigen serologic test

These tests are used for the specific diagnosis of syphilis. Commonly used methods include the syphilis spirochete hemagglutination test (TPHA) and the syphilis spirochete gelatin agglutination test (TPPA), which are highly specific.

A single infection, long-term maintenance of positive, as a means to confirm the diagnosis, qualitative means, not as the basis for observation of the efficacy of treatment.

Cerebrospinal fluid examination

Cerebrospinal fluid examination is required for those who are suspected of having neurosyphilis.

If a person with neurosyphilis has elevated quantitative white blood cells and proteins on routine cerebrospinal fluid examination, other causes of abnormality need to be ruled out.

Cerebrospinal fluid TPPA, RPR, and TRUST tests may assist in the diagnosis.

Differential Diagnosis

Psoriasis

Typical lesions of psoriasis are well-demarcated erythematous spots and papules with thick white scales on the surface, which gradually expand into brownish-red plaques with clear borders, and neighboring ones can be fused with each other. It occurs mostly on the scalp and the extensor surfaces of the limbs.

Viral Rash

Viral rashes are skin rashes caused by various viral infections, and there are many kinds of viral rashes, including measles, hand, foot and mouth rashes, roseola, chicken pox, etc. Most of the viral rashes have a precursor. Most viral rashes have prodromal symptoms, which may include varying degrees of fever, sore throat, and malaise, followed by a uniform symmetrical atypical maculopapular rash, which may include small papules or bruises. Laboratory tests for white blood cells are often below normal.

Lichen planus

Lichen planus is typically characterized by purplish-red polygonal flat papules or plaques, which may fuse to form scaly plaques, often accompanied by itching.

Tinea cruris

Tinea cruris occurs in the groin area, but also in the buttocks, unilateral or bilateral. Due to the poor permeability of the affected area, moisture, easy to friction, often make the lesion inflammation obvious, itching is significant.

Treatment

Aim of treatment: Use antibiotics to completely expel syphilis spirochetes from the body to avoid progression into advanced syphilis.

Treatment principles: early diagnosis, early and regular treatment; adequate dosage, regular course of treatment; simultaneous examination and treatment of sexual partners; sufficient time for follow-up observation after treatment [1-3,6-8].

Medication

Penicillin G remains the treatment of choice for all stages of syphilis, but treatment needs to achieve drug concentrations that effectively inhibit the spirochete.

Treatment options for stage II syphilis

Penicillins.

Commonly used drugs include benzylpenicillin intramuscularly, once or twice a week. Procaine penicillin, intramuscular injection for 15 days [1,6].

Penicillin can cause allergic reactions such as drug fever or drug rash, the most serious being anaphylaxis, which requires advance skin testing. Gihai reactions may also occur, and oral prednisone administered along with treatment for 2-3 consecutive days and then discontinued can help reduce the incidence of Gihai reactions [1-3].

Other drugs

Ceftriaxone is preferred for penicillin allergy. However, be aware of possible cross-allergic reactions between ceftriaxone sodium and penicillin.

Tetracyclines are also available, and commonly used drugs include doxycycline. This type of drugs can not be used by pregnant women because they affect the development of fetal bones and teeth.

Treatment options for neurosyphilis, ocular syphilis, etc.

Most patients with neurosyphilis have complex and serious clinical manifestations, so it is recommended to carry out multidisciplinary collaborative treatment, and multidisciplinary experts will formulate scientific, reasonable, standardized and personalized diagnosis and treatment plans for patients.

Penicillin is administered intravenously for 10 to 14 days; if necessary, it is followed by benzylpenicillin, which is injected intramuscularly three times a week. Or procaine penicillin, single intramuscular injection, along with oral probenecid 4 times daily for 10 to 14 days; if necessary, followed by benzylpenicillin, intramuscular injection 3 times weekly.

An alternative regimen is ceftriaxone, administered intravenously once daily for 10 to 14 days.

For those allergic to penicillin, use doxycycline twice daily for 30 days.

Surgery

Syphilis causes damage to the bone and joints, and localized bone defects may require orthopedic surgery.

Prognosis

Cure

Most patients can be cured with early and standardized treatment, but it is difficult to reverse the systemic damage that has been caused.

In a small number of patients with syphilis, after regular antiseptic treatment and adequate follow-up (1 year for stage I syphilis, 2 years for stage II syphilis, and 3 years for advanced syphilis), the serologic test for non-syphilis spirochete antigens remains at a certain titer for more than 3 months, and the titer is often fixed at less than 1:8, which is known as serofixation [1-3,6].

Hazards

Stage II syphilis is contagious and may cause psychological stress to the patient and those around them.

Untreated stage 2 syphilis will continue to progress, and when it progresses to advanced syphilis and neurosyphilis it can greatly affect the quality of life and even lead to death.

Daily

Daily Management

Daily management

If there are skin breaks, pay attention to keep dry, pay attention to hygiene and avoid combined skin bacterial infection.

Maintain regular and moderate physical exercise, the intensity of which should be such that you do not feel tired after exercise.

All sexual partners of syphilis patients should be examined and treated at the same time.

Psychological support

Receive health education, learn about syphilis, view syphilis correctly, and participate in diagnosis and treatment together with medical staff to enhance the sense of security and confidence in cure.

If you are emotionally unstable or psychologically depressed, talk to your friends and relatives or seek help from the medical staff, and seek psychological counseling if necessary, so as to prevent psychological problems from affecting the effectiveness of the treatment.

Follow-up and review

Serum syphilis antibody titer (RPR, TRUST), cardiac ultrasound and other items should be checked during and after treatment, once every three months in the first year and once every six months thereafter, usually for two to three years.

For serofixed patients, if there is no clinical manifestation of recurrence, and except neurological, cardiovascular and other visceral syphilis, as well as re-infection, no further treatment is necessary, but the serum reaction titer should be rechecked regularly, and the follow-up should be more than 3 years to judge whether to terminate the observation. If there are still skin and mucous membrane damage, lymph node enlargement and other discomforts, it is recommended to visit the hospital for timely review [6-10].

Prevention

Avoid high-risk sexual behaviors and have a regular partner.

Avoid going to informal medical institutions, beauty salons, tattoo parlors for invasive operations.

Medical personnel who are prone to contact with syphilis patients should do self-protection.