Syphilitic Chancre Case File

Syphilitic Chancre Case File

Eugene C. Toy, MD, Patti Jayne Ross, MD, Benton Baker III, MD, John C. Jennings, MD

CASE 39

A 31-year-old woman comes in for a well-woman examination. Her last menstrual period was 2 weeks ago. She has no significant past medical or surgical history. She denies having been treated for sexually transmitted diseases. On examination, her blood pressure (BP) is 130/70 mm Hg, heart rate (HR) is 70 beats per minute, and she is afebrile. Her thyroid is normal on palpation. Her heart and lung examinations are within normal limits. The abdomen is nontender and without masses. Examination of the external genitalia reveals a nontender, firm, ulcerated lesion approximately 1 cm in diameter, with raised borders and an indurated base located on the right labia majora. Bilateral inguinal lymph nodes are also noted that are nontender. Her pregnancy test is negative.

» What is the most likely diagnosis?

» What is your next step in diagnosis?

» What is the best therapy for this condition?

ANSWER TO CASE 39:

Syphilitic Chancre                                           

Summary: A 31-year-old woman who comes in for a well-woman examination is noted to have a nontender, firm, 1-cm ulcerated lesion of the vulva; it has raised borders and an indurated base. She also has bilateral, nontender inguinal lymphadenopathy.

• Most likely diagnosis: Syphilis (primary chancre).
• Next step in diagnosis: Syphilis serology (rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL]) and, if negative, darkfield microscopy.
• Best therapy for this condition: Intramuscular penicillin.

ANALYSIS

Objectives

1. Know the classic appearance and presentation of the chancre lesion of primary syphilis.
2. Know that penicillin is the treatment of choice for syphilis.
3. Understand that the antibody tests (VDRL or RPR) may not yet turn positive with early syphilitic disease and that darkfield microscopy would then be the diagnostic test of choice.

Considerations

This 31-year-old woman came in for a well-woman examination. It was unexpected to find the lesion in the vulvar area. The patient denies any history of sexually transmitted diseases. Nevertheless, she has the classic lesion of primary syphilis, the painless chancre. It is typically a nontender reddish ulcer with clean-appearing edges, often accompanied by painless inguinal adenopathy. Painful ulcers are typically associated with herpes simplex virus (HSV). Because exam findings are variable, specific tests for evaluation of genital ulcers include (1) syphilis serology and darkfield examination, (2) culture for HSV orpolymerase chain reaction (PCR) testing for HSV, and (3) serologic testing for type-specific HSV antibody. Occasionally, the patient will have a negative nontreponemal test in the setting of primary syphilis. Primary syphilis usually manifests itself within 2 to 6 weeks after inoculation. The treatment for syphilis, that is less than 1-year duration, is one injection of long-acting penicillin. If this patient were older, for instance, in her postmenopausal years, squamous cell carcinoma of the vulva would be considered.

APPROACH TO:

Infectious Vulvar Ulcers                                             

DEFINITIONS

NONTREPONEMAL TESTS: Nonspecific antitreponemal antibody tests, such asVDRL or RPR tests. These titers will fall with effective treatment.

SPECIFIC SEROLOGIC TESTS: Antibody tests that are directed against the treponemal organism such as the TP-PA (Treponema pallidum particle agglutination assay), MHA-TP (micro hemagglutinin antibody against Treponema pallidum) and FTA-ABS (fluorescent-labeled treponemal antibody absorption) tests. These tests will remain positive for life after infection.

CLINICAL APPROACH

The two most common infectious causes of vulvar ulcers in the United States are herpes simplex virus and syphilis, with chancroid being much less common. However, the differential diagnosis is complicated and can include trauma, other viral infections such as human immunodeficiency virus (HIV) or primary Epstein Barr virus (EBV) infection. Systemic diseases such as Behcet’s disease, Candida infection, or vulvar neoplasms should also be considered. Biopsy of the lesion is often helpful. A careful history and physical queries about travel, contacts, prior STIs, drug use, possibly allergic reactions, and other systemic or autoimmune symptoms are important. If the clinical assessment is not revealing, then a reasonable diagnostic approach would be:

• Step 1: Assess for HSV (PCR or culture or lesion, and type-specific serology) and syphilis.
• Step 2: If negative, consider darkfield microscopy (biopsy may be needed).
• Step 3: If negative, assess for Candida, HIV, and EBV.
• Step 4: If negative, then reassess based on the wide differential diagnosis; biopsy may be helpful.

Herpes Simplex Virus

Genital herpes is a recurrent sexually transmitted infection (STI) for which there is no cure. It is the most prevalent STI in the United States. This organism is highly contagious, and it is thought that 20% of women in their child bearing years are infected. There are two types of herpes viruses, HSV type 1 and type 2. Approximately 50% of new genital infections, particularly in young women, are due to HSV-1. Recurrence is greater with HSV type 2. The primary episode is usually a systemic as well as local disease, with the woman often complaining of fever or general malaise. Local infection typically induces paresthesias before vesicles erupt on a red base. After the primary episode, the recurrent disease is local, with less severe symptoms. The recurrent herpes ulcers are small and superficial, and do not usually scar. The gold standard diagnostic test is viral culture, but polymerase chain reaction tests are increasingly used because they are more sensitive. Rarely, HSV infections may be severe enough to warrant hospitalization, such as those with encephalopathy or urinary retention. Oral acyclovir is effective in suppressing frequent recurrences.

Syphilis

Syphilis, caused by the bacteria T. pallidum, may induce a chronic infection. Infections occur rarely in the United States and tend to be concentrated in southern regions. The organism is extremely tightly wound, and too thin to be seen on light microscopy. The typical incubation period is 10 to 90 days. The disease can be divided into primary, secondary, latent, and tertiary stages. Primary syphilis classically presents as the indurated, nontender chancre. The ulcer usually arises 3 weeks after exposure and disappears spontaneously after 2 to 6 weeks without therapy. Nontreponemal tests (such as the RPR or VDRL) sometimes are not positive with the appearance of the chancre. Darkfield microscopy is an accepted diagnostic tool, but is limited in availability. Secondary syphilis is usually systemic, occurring about 9 weeks after the primary chancre. The classic macular papular rash may occur anywhere on the body, but usually on the palms and soles of the feet. Flat moist lesions called condylomatalata may be seen on the vulva (Figure 39– 1), and have a high concentration of spirochetes. Treponemal and nontreponemal serologic tests are positive at this stage. Because nontreponemal tests can be falsely positive, a positive treponemal test is required to make a serologic diagnosis.

Latency of varying duration occurs after secondary disease; latency is subdivided into early latent (<1 year in duration), or late latent (>1 year). If untreated, about one-third of women may progress to tertiary syphilis, which may affect the cardiovascular system or central nervous system. Optic atrophy, tabes dorsalis, and aortic aneurysms are some of the manifestations. Penicillin G is the treatment of choice for all stages of syphilis. Because of the long replication time, prolonged therapy is required. One injection of long-acting benzathine penicillin G 2.4 million units intramuscularly is standard treatment for early disease (primary, secondary, and latent up to 1 year of duration). Patients with late-latent syphilis (> 1 year) should be treated with a total of 7.2 million units intramuscularly divided as 2.4 million units every week for a total of three courses (Table 39– 1). In pregnancy, penicillin is the only known effective treatment to prevent or treat congenital syphilis. The effectiveness of alternatives to penicillin in the treatment of early and latent syphilis has not been well documented. Treatment of nonpregnant penicillin-allergic women with doxycycline or tetracycline may be considered.

Neurosyphilis requires more intensive therapy, usually intravenous penicillin. After therapy, clinical and serologic assessment should be performed at 6 and 12 months after treatment for early syphilis and additionally at 24 months after treating late latent or syphilis of unknown duration. An appropriate response is a four-fold fall in titers in 6 to 12 months, 12 to 24 months for late-latent syphilis. When the titer does not fall appropriately, one possible etiology is neurosyphilis, which may be diagnosed by lumbar puncture.

Figure 39–1. Genital condylomalata of secondary syphilis.(Reproduced with permission from Cunningham FG, et al. Williams Obstetrics. 21st ed. New York, NY:McGraw-Hill; 2001:1487.)

Chancroid

Chancroid is a sexually transmitted disease, usually manifesting a soft, painful ulcer of the vulva. Although common worldwide, it is very rare in the United States. It is more common in males than in females. The typical ulcer is tender, with ragged edges on a necrotic base. Tender lymphadenopathy may also coexist with these infections. The etiologic organism is Haemophilusducreyi, a small gram-negative rod. Gram stain usually reveals the classic “school of fish.” After ruling out syphilis and herpes, chancroid should be suspected. Biopsy and/ or culture help to establish the diagnosis. Treatment includes oral azithromycin or intramuscular ceftriaxone.

Lymphogranuloma Venereum

Lymphogranuloma Venereum (LGV) is caused by Chlamydia trachomatis subtypes L1, L2, or L3, and causes a painless papule or shallow ulceration/ erosion (primary LGV). After 10 to 30 days following exposure, secondary LGV may lead to buboes (grossly enlarged tender nodes), and can lead to the “groove sign,” separation of the lymph nodes by the inguinal ligament. The diagnosis is confirmed via culture although LGV titers can be helpful. The treatment is doxycycline.

Granuloma Inguinale (GI)

GI is a chronic bacterial infection characterized by intracellular inclusions in macrophages referred to as Donovan bodies. The organism is now called Klebsiellagranulomatis, a Gram-negative pleomorphic bacillus. Large painless ulcerative lesions of the mucus membranes is the typical presentation, usually without lymphadenopathy. The lesions are usually beefy red, and bleed easily. The diagnosis is confirmed with culture or smear for Donovan bodies.Treatment is by doxycycline or trimethroprim/ sulfa.

COMPREHENSION QUESTIONS

39.1 A 19-year-old woman is noted to have an RPR titer of 1:16, and the confirmatory (TP-PA) test is positive. She had no history of syphilis. She is treated with benzathine penicillin G 2.4 million units intramuscularly. Six months after therapy, she is noted to have an RPR titer of 1:2. At 12 months, the titer is 1:1. Two months later, the repeat RPR is noted to be 1:32. Which of the following is the most likely diagnosis?

A. Resistant organism

B. Inadequately treated syphilis

C. Laboratory error

D. Reinfection

E. Systemic lupus erythematosus

39.2 Which of the following statements about Tpallidum is correct?

A. It is a protozoan.

B. Gram stain is a very sensitive method of diagnosis.

C. The spirochete does not cross the placenta during pregnancy.

D. Penicillin G is the recommended treatment for all stages of syphilis in nonpregnant women.

39.3 An 18-year-old G1P0 at 14 weeks’ gestation is noted to have a positive RPR with a positive confirmatory MHA-TP test. The patient states that she is allergic to penicillin, with hives and swelling of the tongue and throat in the past. Which of the following is the most appropriate next step?

A. Desensitize and treat with penicillin

B. Oral erythromycin

C. Oral doxycycline

D. Pretreat with prednisone, then administer penicillin

E. Intramuscular ceftriaxone

39.4 A 29-year-old woman was diagnosed with syphilis. She is noted to have a persistently elevated RPR titer of 1:32, despite treatment with benzathine penicillin G 2.4 million units each week for a total of 3 weeks. She complains of slight dizziness and a clumsy gait of 6 months duration. Which of the following is the best test to diagnose neurosyphilis?

A. Plain x-ray films of the skull

B. Electroencephalograph (EEG)

C. CT scan of the head

D. Lumbar puncture

E. Psychiatric evaluation

39.5 A 35-year-old woman is seen for a “sore in the groin area” for an 8-day duration. On examination, she is noted to have atender fluctuant mass which appears above and below the right inguinal ligament. Which of the following is the best treatment?

A. Acyclovir

B. Ceftriaxone

C. Doxycycline

D. Trimethroprim/ sulfa

E. Penicillin

ANSWERS

39.1 D. When RPR titers fall in response to therapy and then suddenly rise, the most likely scenario is reinfection. It is not uncommon, for individuals with systemic lupus erythematosus to have a positive RPR, but they would not have a positive treponemal test without syphilis infection. Syphilis has not been noted to be resistant to penicillin.

39.2 D. Penicillin G is the recommended treatment for all stages of syphilis and data regarding effectiveness of alternatives to treatment for penicillinallergic patients are limited. Syphilis is a bacteria and not a protozoan. It is very thin and tightly wound and therefore not visible on light microscopy. Transplacental infection during pregnancy is an important cause of congenital syphilis.

39.3 A. Penicillin is the best treatment of syphilis in pregnancy. When a pregnant woman with syphilis is allergic to penicillin, she should undergo desensitization and receive penicillin. Penicillin is the only known effective treatment for preventing congenital syphilis. Doxycycline use may lead to discoloration of the child’s teeth, and erythromycin has not been shown to be an effective treatment in treating an infected fetus.

39.4 D. Typically, after a patient undergoes therapy for syphilis and their RPR titer does not fall appropriately, one possible etiology is neurosyphilis, which may be diagnosed by lumbar puncture. The classic examination of neurosyphilis is unsteady balance and Argyll Robertson pupils. Cerebrospinal fluid for RPR may point toward neurosyphilis, although there is no definitive test. Neurosyphilis requires more intensive therapy such as prolonged IV penicillin.

39.5. C. This is a description of the secondary stage of LGV, caused by Chlamydia trachomatis. The primary stage is a painless lesion (papule) which usually only appears for a few days, followed by unilateral painful inguinal adenopathy (secondary stage) usually occurring 30 to 60 days after infection. These can be fluctuant and even sometimes rupture. Because they grow cephalad and caudad to the inguinal ligament, there is the so called “groove sign” in which the inguinal ligament forms a groove in the lymphatic mass. The best treatment is doxycycline. Herpes is treated with acyclovir; gonorrhea is treated with ceftriaxone; and granuloma inguinale is treated with doxycycline or trimethroprim/ sulfa.

    CLINICAL PEARLS    

» Syphilis of less than 1-year duration can be treated with a single intramuscular course of penicillin G; infection of greater than 1-year duration is treated by three courses of penicillin G at 1-week intervals. » The nontender ulcer with indurated edges is typical of the chancre of primary syphilis. Darkfield examination and serologic testing is warranted. » The best treatment for syphilis in pregnancy is penicillin. » Pregnant women with syphilis and an allergy to penicillin should undergo penicillin desensitization and then receive penicillin. » The most common infectious vulvar ulcers in the United States are herpes simplex virus and syphilis, and much less common is chancroid.

REFERENCES

Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR 2010;59(RR-12):18-36. 

Eckert LO, Lentz GM. Infections of the lower genital tract. In: Katz VL, Lentz GM, Lobo RA, Gersenson DM, eds. Comprehensive Gynecology. 5th ed. St. Louis, MO: Mosby-Year Book; 2007:569-606. 

McGregor JA, Lench JB. Vulvovaginitis, sexually transmitted infections, and pelvic inflammatory disease sepsis. In: H acker NF, Gambone JC, Hobel CJ, eds. Essentials of Obstetrics and Gynecology. 5th ed. Philadelphia, PA: Saunders; 2009:265-275.

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