A 15-year-old boy presents to your clinic with a 3-day history of a sore on his penis. He denies urinary frequency, change in urine appearance, or penile discharge. He reports no significant past medical history. He is sexually active and infrequently uses condoms. His examination is normal, other than a shallow, nontender ulcer approximately 1 cm in diameter on the dorsal aspect of the penile shaft. There is no lesion discharge or bleeding, but slight induration around the ulcer is noted. His urinalysis is normal.
What is the most likely diagnosis?
What is the next step in evaluation?
ANSWERS TO CASE 32: Primary Syphilis
Summary: A sexually active adolescent with a penile chancre.
• Most likely diagnosis: Primary syphilis.
• Next step in evaluation:Obtain a thorough history and review of systems, focusing on sexual history and symptoms consistent with sexually transmitted disease (STD) and possible extragenital infection. Perform a focused examination for oropharyngeal, abdominal, genitourinary (GU), joint, or skin abnormalities. Test for syphilis, and testing for concomitant STDs (gonorrhea, chlamydia, HIV) is always considered.
1. Describe the workup and treatment of primary syphilis.
2. Understand the various stages of untreated syphilis.
3. Describe select ulcerative GU lesions and adolescent STDs.
This adolescent with a painless penile ulcer represents a typical presentation for primary syphilis. Presenting symptoms and examination findings may permit narrowing the list of possible STD pathogens, but the causative agents frequently coexist and physical signs often overlap. An accurate diagnosis without testing is difficult. Considerations include sending blood, urine, urethral secretions, or a lesion aspirate or scraping for specific infections based on symptoms and examination findings. For instance dark field microscopy of an ulcer scraping may occasionally be used to diagnose syphilis while a urine chlamydia probe might be useful for a patient with dysuria, clear urethral discharge, and leukocyte esterase on urinalysis. HIV and hepatitis B screening is always considered whenever an STD is suspected.
The Adolescent with Primary Syphilis
CHANCRE:Painless ulcer with indurated base usually caused by Treponema pallidum.
CHANCROID: Painful ulcer with exudate caused by Haemophilus ducreyi.
VENEREAL DISEASE RESEARCH LABORATORY (VDRL) AND RAPID PLASMA REAGIN (RPR):Rapid screening assays; referred to as nontreponemal testing; measure antibody to cells affected by Treponema pallidum; may be false positive (related to viral infection, malignancy, or autoimmune disease) or false negative (up to 25% seroreversion [SR] possible); often used to monitor treatment response (four-fold titer decrease) or define reactivation (four-fold titer increase).
FLUORESCENT TREPONEMAL ANTIBODY ABSORPTION (FTA-ABS) AND TREPONEMA PALLIDUM PARTICLE AGGLUTINATION (TP-PA):Organism-specific quantitative assays; referred to as treponemal testing; measures specific antibody to Treponema pallidum; typically used to verify infection, or repudiate nontreponemal assay false positives or negatives (seroconversion may not occur for weeks after initial infection).
The timing and constellation of GU signs and symptoms consistent with STD can be helpful in narrowing the differential diagnosis and prompting appropriate laboratory studies and treatment. Questions should include whether dysuria, frequency, discharge, or changes in urine appearance have been noted. One should inquire about lesions on the genitalia, around the anus, or on the skin of the lower abdomen, groin, or inner thighs. Rashes elsewhere on the body also should be investigated; the transient, pustular rash associated with disseminated gonococcal infection or the macular rash on the palms of patients with secondary syphilis could be identified. In both sexes, typical GU infections may present atypically; gonorrhea may not present with a purulent urethral discharge, and herpes infection could be associated with mucoid urethral discharge.
Evaluation of the adolescent witha penile lesion should commence with a sexual and GU history of both the patient and sexual partner(s), if known. Multiple partners, early sexual activity, inconsistent condom use, and use of drugs and alcohol are known STD risk factors. A penile chancre in an otherwise healthy, sexually active male should raise suspicion for syphilis. Urinary tract findings of dysuria and penile discharge are not typical for syphilis, but may be encountered. Inguinal lymphadenopathy also is possible.
Prevalence of syphilis in the adolescent population has been steadily increasing over the past few years, with both sexes and all racial and ethnic groups demonstrating an approximately 20% to 25% increase.
Primary syphilis is characterized by a painless ulceration that usually erupts on the genitalia or perianal region (oropharyngeal ulcer also possible) within 2 to 3 weeks of transmission, and spontaneously resolves over 4 to 6 weeks (Figure 32-1). If untreated, secondary syphilis may develop within 2 to 3 months, with malaise, fever, lymphadenopathy, and a stereotypical rash (macular to papular lesions often found on the palms and soles), or nondescript rash that may mimic an allergic dermatitis or a viral exanthem. Tertiary syphilis occurs in approximately 15% of untreated patients often a decade or more after infection, and may involve the skin (gummas), cardiovascular system (aortic aneurysm), or central nervous system (neurosyphilis with possible meningitis, seizures, or musculosensory deficits).
Figure 32-1. Early chancre presenting as a flat, eroded papule with raised, indurated borders and a smooth, clean base. (Reproduced, with permission, from Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York, NY: McGraw-Hill, 2007. Figure 200-2.)
Other genital ulcer diseases appearing similar to the primary syphilitic chancre include the typically painful chancroid associated with Haemophilus ducreyi and denuded, coalesced herpes simplex virus (HSV) lesions. Chancroid is usually characterized by an exudative and friable, but nonindurated, genital ulcer. Tender inguinal lymphadenopathy also may be noted. HSV lesions may start with localized pruritus, not typically seen with other STDs.
Initial evaluation of a patient with suspected syphilis usually involves obtaining a serum VDRL or RPR assay. If diagnostic suspicion is high, one might consider foregoing a screening assay and proceed with MHA-TP or TP-PA testing. Any neurologic symptoms or findings in the patient with suspected syphilis warrants a lumbar puncture for cell counts and VDRL or FTA-ABS testing of cerebrospinal fluid to exclude neurosyphilis.
Treatment for syphilis in the adolescent patient is dependent upon infection classification, with primary and secondary syphilis treated with one to three weekly intramuscular penicillin G injection(s), dependent on duration (unknown or greater than 1 year warrants three weekly injections). Tertiary syphilis requires a minimum of 10 days of intravenous penicillin G. Tetracycline group antibiotics (doxycycline) are an alternative therapy consideration in the penicillin-allergic teen. Some advocate desensitizing allergic patients to and treating with penicillin, rather than using another potentially less efficacious antibiotic.
Adequate screening, timely treatment, and appropriate follow-up in syphilis are important, since a prolonged asymptomatic carrier state subsequent to the primary eruption is possible. Ultimately, a thorough history and examination, including focus on any past or present signs or symptoms consistent with GU infection, are paramount to the proper diagnosis and appropriate treatment of any STD.
32.1 A 16-year-old girl presents with a 1-day history of stabbing left groin pain, and white vaginal discharge and mild dysuria for the past week. There has been no abnormal vaginal bleeding, with her last menses approximately 3 weeks ago. She reports one urinary tract infection (UTI) since menarche, but no STDs. She has been sexually active for the past year and takes an oral contraceptive. Her partners irregularly use condoms. She is afebrile, but has left lower quadrant and suprapubic abdominal pain on deep palpation and minimal guarding. Which of the following is the most appropriate next step?
A. Request emergent surgery consultation.
B. Perform urinalysis and urine pregnancy testing.
C. Order pelvic ultrasonography.
D. Perform pelvic examination and Pap smear.
E. Order follicle-stimulating hormone and luteinizing hormone levels.
32.2 Over the past 2 days, a 14-year-old sexually active boy has been complaining of slight burning on urination. He has not had frequency or change in urine appearance. His past medical history is unremarkable. He is uncircumcised, and has a 1.5-cm ulcer with raised margins on his glans penis. There is no urethral erythema or discharge. The rest of his exam and a urinalysis are unremarkable. Which of the following is the next most appropriate test to perform to diagnose his probable condition?
A. Urine culture
C. HSV immunoglobulin G (IgG)
E. Urine GC/chlamydia probe
32.3 A 17-year-old girl presents with severe pain in the right upper quadrant and has some pain in her right shoulder. She has nausea, fever, and chills. The abdominal pain increases with movement or Valsalva activities. On physical examination, you confirm pain over the gallbladder, but also notice that she has right lower quadrant abdominal pain. Her pelvic examination is significant for discharge from the cervical os and pain upon cervical motion. Which of the following is consistent with the most likely diagnosis?
B. Ectopic pregnancy
C. Fitz-Hugh-Curtis syndrome
D. Gallbladder disease
E. Right lower quadrant pneumonia
32.4 A 15-year-old girl has burning on urination, but no fever, urinary frequency, hematuria, vaginal discharge, GU lesions, or abdominal pain. She has regular cycles. Her abdominal examination is normal. Her GU examination reveals erythema surrounding the vaginal introitus, but no vaginal discharge, tenderness, or masses during the pelvic examination. Her urinalysis is benign. Which of the following is the most important historical clue to be gathered?
A. Miscarried last year
B. Douching twice daily over the past month
C. Treated for UTI last year
D. Treated for chlamydia last year
E. Receiving contraceptive injections quarterly
32.1 B. STD is a concern in this patient with pyuria and abdominal pain; a surgical evaluation at this time does not seem necessary. In addition to pelvic inflammatory disease (PID), possible etiologies include UTI, ovarian torsion, ovarian cyst, and ectopic pregnancy. The first step in evaluation should be urinalysis and pregnancy testing. A pelvic examination and testing for GC and chlamydia should be included in the evaluation of this sexually active female, but a Pap smear is not likely to identify the etiology of her symptoms. Pelvic ultra-sonography may be required if the physical examination proves equivocal.
32.2 D. This scenario is typical for primary syphilis. A screening urinalysis is reasonable (white blood cells or leukocyte esterase may be seen), and may help guide additional STD testing, but a urine culture is not likely to result in the correct diagnosis. Urine GC/chlamydia testing is a reasonable consideration for detecting often asymptomatic chlamydial infection, as is ordering an HIV assay whenever an STD is suspected, but initial efforts should be directed toward excluding syphilis. Finally, this case scenario is not consistent with HSV; immunoglobulin testing for HSV remains controversial with unclear diagnostic yield.
32.3 C. This girl likely has Fitz-Hugh-Curtis syndrome. This disease can be seen in both genders, but is more prevalent in girls and is usually (but not always) associated with evidence of acute PID. The right upper quadrant pain results from ascending pelvic infection and inflammation of the liver capsule and diaphragm. It can mimic other abdominal emergencies and must be considered in sexually active adolescents as a diagnosis of exclusion. This condition was once thought to be caused only by Neisseria gonorrhoeae; Chlamydia trachomatis infection probably is more common. The acute phase is described above and in the question; a chronic phase of persistent right upper quadrant pain or complete resolution of symptoms can also be seen.
32.4 B. Chemical urethritis as a result of frequent douching is likely in this patient. Other possible etiologies for this benign urethritis include chemical irritants (soaps), fabrics (rayon), and drying agents (powders). Past pregnancy and a history of GU disorder are important, but have less relevance in this case, especially given her benign pelvic examination and urinalysis. Treatment typically entails eliminating the offending agent and waiting for symptoms to subside.
The goals of evaluating GU complaints are to diagnose and treat infections that can threaten the viability of reproductive organs or cause extragenital or systemic infection.
Typical STDs may present atypically or in combination, making patient and partner history, focused examination, and case-specific testing important tools.
American Academy of Pediatrics. Syphilis. In: Pickering LK, ed. Red Book: Report of the Committee on Infectious Disease. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:638-651.
Burstein GR. Sexually transmitted diseases. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics, 19th ed. Philadelphia: WB Saunders, 2011:705-714.
Hwang LY, Mosicki, A-B, Shafer, M-A. Sexually transmitted infections. In: Rudolph CD, Rudolph AM, Lister GE, First, LR, Gershon AA, eds. Rudolph’s Pediatrics, 22nd ed. New York: McGraw-Hill, 2011: 923-933.