Syphilis: Primary, Secondary, Latent, Tertiary - Sexually Transmitted Diseases

The causative organism of syphilis is Treponema pallidum, a spirochete.
Syphilis is usually acquired by sexual contact with infected mucous membranes or cutaneous lesions, although on rare occasions it can be acquired by nonsexual personal contact, accidental inoculation, or blood transfusion.

Clinical presentation

The clinical presentation of syphilis is varied, with progression through multiple stages possible in untreated or inadequately treat patients (Table Presentation of Syphilis Infections).

Primary Syphilis

Primary syphilis is characterized by the appearance of a chancre on cutaneous or mucocutaneous tissue. Chancres persist only for 1 to 8 weeks before spontaneously disappearing.

TABLE. Treatment of Gonorrhea

Type of Infection	Recommended Regimens^a	Alternative Regimens^b
Uncomplicated infections of the cervix, urethra, and rectum in adults^c^,d	Ceftriaxone 125 mg intramuscularly once^e; or ciprofloxacin 500 mg orally once^e; or cefixime 400 mg orally once^f; or ofloxacin 400 mg orally once^eplus	Spectinomycin 2 g intramuscularly once; or ceftizoxime 500 mg intramuscularly once; or cefotaxime 500 mg intramuscularly once; or cefotetan 1 g intramuscularly once; or cefoxitin
	A treatment regimen for presumptive C. trachomatis coinfection	2 g intramuscularly once with probenecid 1 g orally once; or lomefloxacin 400 mg orally once; or enoxacin 400 mg orally once; or norfloxacin 800 mg orally once plus A treatment regimen for presumptive C. trachomatis coinfection
Gonococcal infections in pregnancy	Ceftriaxone 125 mg intramuscularly once^g^,hplus A recommended treatment regimen for presumptive C. trachomatis infection during pregnancy^h	Spectinomycin 2 g intramuscularly once plus a recommended treatment regimen for presumptive C. trachomatis infection during pregnancy^h
Disseminated gonococcal infection in adults (>45 kg)^h^,i,j,k	Ceftriaxone 1 g intramuscularly or intravenous every 24 h^l	Ceftizoxime 1 g intravenous every 8 h^l or Cefotaxime 1 g intravenous every 8 h^l
Uncomplicated infections of the cervix, urethra, and rectum in children (<45 kg)	Ceftriaxone 125 mg intramuscularly once^m	Spectinomycin 40 mg/kg intramuscularly once (not to exceed 2 g)
Gonococcal conjunctivitis in adults	Ceftriaxone 1 g intramuscularly onceⁿ
Ophthalmia neonatorum	Ceftriaxone 25-50 mg/kg intravenous or intramuscularly once (not to exceed 125 mg)
Infants born to mothers with gonococcal infection (prophylaxis)	Ceftriaxone 25-50 mg/kg intravenous or intramuscularly once (not to exceed 125 mg)
^aRecommendations are those of the Centers for Disease Control. ^bA number of other antimicrobials have demonstrated efficacy in treating uncomplicated gonorrhea but are not included in the Centers for Disease Control guidelines. ^cTreatment failures are usually due to reinfection and necessitate patient education and sex-partner referral; additional treatment regimens for gonorrhea and chlamydia infections should be administered. Epididymitis should be treated for 10 days (see Table 44-8). ^dPatients allergic to β- lactams should receive a quinolone. Persons unable to tolerate a β- lactam (penicillin or cephalosporin) or a quinolone should receive spectinomycin. ^eAlso recommended for the treatment of uncomplicated infections of the pharynx in combination with a treatment regimen for presumptive C. trachomatis infection; fluoroquinolones are not recommended for treating infections in MSM or infections acquired in Hqwaii, California, or other parts of the world where high-level resistance to fluoroquinolones is reported. ^fIn July, 2002, Wyeth Pharmaceutical discontinued manufacturing cefixime; at the time of publication, there were no generic manufacturers of cefixime. ^gAnother recommended intramuscularly or orally cephalosporin also may be used. ^hThe fluoroquinolones, doxycycline, and erythromycin ethylsuccinate are contraindicated during pregnancy. ⁱPatients treated with one of the recommended regimens should be treated with doxycycline or azithromycin for possible coexistent chlamydial infection. ^jPatients with gonococcal meningitis should be treated for 10-14 days and those with endocarditis for at least 4 wk with ceftriaxone 1-2 g intravenous every 12 h. ^kAll treatment regimens should be continued for 24-48 h after improvement begins; at this time therapy can be switched to one of the following oral regimens to complete a 7-day course of treatment: cefixime 400 mg orally 2 times daily, or ciprofloxacin 500 mg orally 2 times daily, or ofloxacin 400 mg orally 2 time daily. ^lAll regimens should be continued for 24-48 h after improvement begins; at this time therapy can be switched to one of the following oral regimens to complete a 7-day course of treatment: cefixime 400 mg orally 2 times daily or ciprofloxacin 500 mg orally 2 times daily or ofloxacin 400 mg orally 2 times daily. ^mPatients with bacteremia or arthritis should receive ceftriaxone 50 mg/kg (maximum 1 g) intramuscularly or intravenous once daily for 7 days. ⁿThe eye should be lavaged 1 time with saline solution.

TABLE. Presentation of Syphilis Infections

General
Primary	Incubation period 10-90 days (mean 21 days)
Secondary	Develops 2-8 wk after initial infection in untreated or inadequately treated individuals
Latent	Develops 4-10 wk after secondary stage in untreated or inadequately treated individuals
Tertiary	Develops in approximately 30% of untreated or inadequately treated individuals 10-30 yr after initial infection
Site of Infection
Primary	External genitalia, perianal region, mouth, and throat
Secondary	Multisystem involvement secondary to hematogenous and lymphatic spread
Latent	Potentially multisystem involvement (dormant)
Tertiary	central nervous system, heart, eyes, bones, and joints
Signs and Symptoms
Primary	Single, painless, indurated lesion (chancre) that erodes, ulcerates, and eventually heals (typical); regional lymphadenopathy is common; multiple, painful, purulent lesions possible but uncommon
Secondary	Pruritic or nonpruritic rash, mucocutaneous lesions, flulike symptoms, lymphadenopathy
Latent	Asymptomatic
Tertiary	Cardiovascular syphilis (aoritits or aortic insufficiency), neurosyphilis (meningitis, general paresis, dementia, tabes dorsalis, eighth cranial nerve deafness, blindness), gummatous lesions involving any organ or tissue

Secondary Syphilis

The secondary stage of syphilis is characterized by a variety of mucocutaneous eruptions, resulting from widespread hematogenous and lymphatic spread of T. pallidum.
Signs and symptoms of secondary syphilis disappear in 4 to 10 weeks; however, in untreated patients, lesions may recur at any time within 4 years.

Latent Syphilis

Persons with a positive serologic test for syphilis but with no other evidence of disease have latent syphilis.
Most untreated patients with latent syphilis have no further sequelae; however, approximately 25% to 30% progress to either neurosyphilis or late syphilis with clinical manifestations other than neurosyphilis.

Tertiary Syphilis and Neurosyphilis

Forty percent of patients with primary or secondary syphilis exhibit central nervous system (central nervous system) infection.

Diagnosis

Because T. pallidum is difficult to culture in vitro, diagnosis is based primarily on dark-field or direct fluorescent antibody microscopic examination of serous material from a suspected syphilitic lesion or on results from serologic testing.
Serologic tests are the mainstay in the diagnosis of syphilis and are categorized as nontreponemal or treponemal. Commonly used nontreponemal tests include the Venereal Disease Research Laboratory slide test, the rapid plasma reagin card test, the unheated serum regain test, and the tuluidine red unheated serum test
Treponemal tests are more sensitive than nontreponemal tests and are used to confirm the diagnosis (i.e., the fluorescent treponemal antibody absorption [FTA-ABS]).

Treatment

Treatment recommendations from the Centers for Disease Control for syphilis are presented in Table Drug Therapy and Follow-up of Syphilis. Parenteral penicillin G is the treatment of choice for all stages of syphilis. Benzathine penicillin G is the only penicillin effective for single-dose therapy.
Patients with abnormal cerebrospinal fluid findings should be treated as having neurosyphilis.
For pregnant patients, penicillin is the treatment of choice at the dosage recommended for that particular stage of syphilis. To ensure treatment success and prevent transmission to the fetus, some experts advocate an additional intramuscular dose of benzathine penicillin G, 2.4 million units, 1 week after completion of the recommended regimen.
The majority of patients treated for primary and secondary syphilis experience the Jarisch-Herxheimer reaction after treatment, characterized by flulike symptoms such as transient headache, fever, chills, malaise, arthralgia, myalgia, tachypnea, peripheral vasodilation, and aggravation of syphilitic lesions.
The Jarisch-Herxheimer reaction should not be confused with penicillin allergy. Most reactions can be managed symptomatically with analgesics, antipyretics, and rest.

Evaluation of therapeutic outcomes

Centers for Disease Control recommendations for serologic follow-up of patients treated for syphilis are given in Table Drug Therapy and Follow-up of Syphilis. Quantitative nontreponemal tests should be performed at 6 and 12 months in all patients treated for primary and secondary syphilis and at 6, 12, and 24 months for early and late latent disease.
For women treated during pregnancy, monthly quantitative nontreponemal tests are recommended in those at high risk of reinfection.