Infectious Genital Ulcers: No Single Scenario Fits All

I read with interest the case of lymphogranuloma venereum (LGV) featured in Dr Henry Schneiderman's recent "What's Your Diagnosis?" column (CONSULTANT, February 2007, page 187). As one who has had a career-long interest in sexually transmitted disease, I feel compelled to make a few remarks regarding this case.

First of all, Dr Schneiderman is to be heartily congratulated for making the correct diagnosis at an early stage in disease progression. The multiplicity of ulcerations and the absence of lymphadenopathy would certainly steer most clinicians away from this diagnosis. Although acquisition of LGV is suggested by epidemiological information (namely, unprotected intercourse that occurred in the Caribbean region), it is important to be aware that new cases may arise from exposures confined exclusively to the United States.¹ Also keep in mind that the vast majority of LGV cases reported in recent years in this country have been associated with HIV infection; thus, detection of the former should always prompt appropriate counseling and serological testing for the latter.

As Dr Schneiderman points out: "no single scenario fits all cases" of LGV. In fact, the same could be said of virtually all genital ulcer disease of infectious origin. Morphology, when considered apart from confirmatory laboratory testing (serology, culture, or DNA probe), may well lead to inaccurate diagnosis.

Multiplex polymerase chain reaction (PCR),² an old study which has been updated and streamlined,^3,4 may someday become the diagnostic tool of choice. One reason for the particular usefulness of the multiplex amplification technique in this setting is its ability to simultaneously detect many different infectious agents with both high sensitivity and rapid turnaround time. Genital lesions may be caused by concomitant infection with more than one organism. Thus, even though "laboratory testing confirmed the diagnosis" of LGV in this case (presumably by means of an LGV-complement fixation titer), it would not be unreasonable to suspect and search for simultaneous herpes, chancroid, or syphilis, especially given the somewhat atypical clinical presentation. Multiplex PCR has disclosed that between 1% and 8% of genital ulcers are caused by multiple primary infections in the same lesion.^5-7 Clinicians should always be vigilant for such multifactorial ulcerations.

- Ted Rosen, MD
  Professor of Dermatology
  Baylor College of Medicine
  Houston

REFERENCES:1. Ahdoot A, Kotler DP, Suh JS, et al. Lymphogranuloma venereum in human immunodeficiency virus-infected individuals in New YorkCity. J Clin Gastroenterol. 2006;40:385-390.
2. Orle KA, Gates CA, Martin DH, et al. Simultaneous PCR detection of Haemophilus ducreyi, Treponema pallidum, and herpes simplexvirus types 1 and 2 from genital ulcers. J Clin Microbiol. 1996;34:49-54.
3. Liu AY, Jiang MJ, Yin YP, et al. Detection of pathogens causing genital ulcer disease by multiplex polymerase chain reaction. ChinMed Sci J. 2005;20:273-275.
4. Mackay IM, Harnett G, Jeoffreys N, et al. Detection and discrimination of herpes simplex viruses, Haemophilus ducreyi, Treponemapallidum, and Calymmatobacterium (Klebsiella) granulomatis from genital ulcers. Clin Infect Dis. 2006;42:1431-1438 [Epub 2006 Apr 13].
5. Mertz KJ, Weiss JB, Webb RM, et al. An investigation of genital ulcers in Jackson, Mississippi, with use of a multiplex polymerasechain reaction assay: high prevalence of chancroid and human immunodeficiency virus infection. J Infect Dis. 1998;178:1060-1066.
6. Risbud A, Chan-Tack K, Gadkari D, et al. The etiology of genital ulcer disease by multiplex polymerase chain reaction and relationshipto HIV infection among patients attending sexually transmitted disease clinics in Lune, India. Sex Transm Dis. 1999;26:55-62.
7. Bruisten SM, Cairo I, Fennema H, et al. Diagnosing genital ulcer disease in a clinic for sexually transmitted diseases in Amsterdam,The Netherlands. J Clin Microbiol. 2001;39:601-605.

It is a pleasure to defer to Dr Rosen's incisive, lucid, and up-to-the-minute comments on and addenda to my column on LGV, which draw on his acknowledged expertise. They have enhanced my understanding of the condition. All of his points are well taken, including:

• The possibility of LGV in persons who have never been outside the United States.
• Its high prevalence among HIV-infected men who have sex with other men in Western Europe and in the United States.
• The pitfalls of diagnosis based on lesion morphology alone.
• The utility of multiplex PCR-based tests for diagnosis of this and other genital ulcer diseases.
• The possibility of coinfection with more than 1 organism in genital ulcers.

The possibility of concomitant infections in genital ulcers requires that we reset our diagnostic thinking: we cannot conclude that we have made the diagnosis when we find 1 positive test result, but must be alert to the possibility of polyinfection and consider further testing. If therapy targeting a pathogen that has been identified does not produce the desired resolution in a timely fashion, the need for additional testing for other pathogens will grow ever more urgent.

Lastly, I can't take any credit for making the diagnosis: another physician did so.

- Henry Schneiderman, MD
  Vice President, Medical Services/Physician-in-Chief
  Hebrew Health Care
  West Hartford, Conn
  Professor of Medicine (Geriatrics)
  Associate Professor of Pathology
  University of Connecticut
  Farmington