A 22-year-old man presented with complaints of painful lesions on his penis and swelling in the left groin that started 10 days ago. He denied fever, chills, night sweats, rashes, dysuria, discharge, testicular pain, or proctitis. His female partner had been diagnosed with chlamydia one year earlier but he has not undergone evaluation. Multiple small, nontender scabbed lesions are identified in the bilateral scrotal area and on the shaft of penis. The right inguinal lymph node was tender and swollen.
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The differential diagnoses for the presentation of the primary lesions in this case included lymphogranuloma venereum (LGV), herpes, chancroid, syphilis, pyoderma, or trauma.1 Since there was no scarring or history of ulceration(s), rashes, or trauma, LGV was suspected. Clinical guidelines recommend that clinicians consider LGV in the differential diagnosis when sexually active patients present with inguinal or femoral lymphadenopathy, buboes, or proctitis.2
The name “lymphogranuloma venereum” comes from Latin words that mean swelling of granular tissue in the lymph nodes resulting from sexual intercourse with an infected partner.3 LGV was considered rare before 2003; however, since that time large outbreaks have been reported in Western Europe and North America primarily in men having sex with men.4 LGV is acquired through sexual contact with contaminated exudates that contain an invasive form of Chlamydia trachomatis serovars L1, L2, and L3 from a person with active lesion(s).1 From an epidemiologic perspective, LGV has been seen in warm climates in parts of Africa, Asia, South America, and the Caribbean.5 HIV is recognized as a risk factor for LGV.6,7 Testing for HIV and other sexually transmitted infections (STIs) is essential for individuals with a diagnosis of LGV.
LGV is caused by C trachomatis bacteria penetrating tiny skin abrasions and mucous membrane tears.8 The bacteria spread to genital and rectal lymphatic tissue, causing marked inflammation, necrosis, buboes, abscesses on inguinal lymph nodes, and infection of surrounding tissues. After several weeks or months, healing and fibrosis results in scarring, which damages the lymph nodes and disrupts their function. The permanent lymphatic disruption can cause genital deformity and the lymph nodes can develop chronic swelling, hardening, and enlargement. C trachomatis can also spread systemically through the bloodstream and enter the central nervous system, thereby resulting in urogenital infections, trachoma, conjunctivitis, and pneumonia.
The incubation period of LGV is approximately 5 to 21 days. LGV occurs in 3 stages. The first stage, which is often unrecognized, involves the development of rapidly healing, painless genital papules or pustules.9 The genital lesions disappear while the infection spreads to lymph channels and lymph nodes of the genital and rectal areas.1 Lesions of LGV can be herpetiform ulcers with other various forms possible; the ulcer is usually asymptomatic, inconspicuous, and rapidly healing and leaves no scarring.8 The patient’s history may reveal a chancroid or ulcer at the site of inoculation. However, by the time the patient seeks medical attention the lesion has usually disappeared.10
The secondary or inguinal stage of LGV begins 2 to 6 weeks after onset of the primary lesion. It involves the inguinal syndrome, which manifests with constitutional symptoms (fever, malaise) associated with inguinal buboes.11 Severe local pain in buboes, as well as lower abdominal and back pain may be present.
The third stage of LGV manifests as anogenitorectal syndrome with anal pruritus, rectal discharge, fever, rectal pain, tenesmus, constipation, “pencil” stools, and weight loss.10,12 In both women and men, the tertiary stage of LGV can result in degeneration of the genitalia resulting in a condition called esthiomene (from the Greek, “eating away”); the area becomes swollen with ulceration.11 Esthiomene occurs 1 to 20 years after primary infection with LGV.13
In men, lesions occur most commonly on the penis or scrotum; in women, lesions are found on the vaginal wall, cervix, or labia.8 A large, tender lymphatic nodule or bubo, urethritis, and cervicitis are other signs of primary LGV. It has been observed that the most common clinical manifestation of LGV among heterosexuals is tender inguinal and/or regional lymphadenopathy that is typically unilateral.2 Bubo formation is most common in men and results in a distinctive inguinal swelling known as the “groove sign.”5 Since the path of pelvic lymph drainage is different in women, inguinal lymph node involvement characterize fewer than one-third of cases.8 In addition, approximately 30% of women typically have deep iliac or perirectal nodes and may present with nonspecific back and/or abdominal pain. In stages 2 and 3 of the disease, most women are not diagnosed because of the lack of inguinal lymphadenopathy.
Inflammation of the lymph nodes characterizes the secondary stage of untreated LGV in men. Initially the inguinal bubo is a firm, somewhat painful mass; as it steadily enlarges it becomes very painful, restricts mobility, and takes on a deep blue color.8 The color change is a signal of impending rupture of the bubo through the skin, although in some cases the bubo does not rupture but involutes and becomes firm. Thick yellow pus may drain from the site for weeks or months. Healing can be slow, resulting in scar formation. Systemic manifestation of secondary LGV may include meningitis, pneumonitis, and other major infections. Other reported conditions include arthritis, hepatitis, and ocular inflammatory disease.11
Anorectal LGV can be caused by direct inoculation or it may be a chronic or late manifestation of lymphatic spread from the inguinal area.8 Clinical manifestations of anorectal LGV include multiple ulcerations or chronic inflammation of the rectal mucosa, mucopurulent rectal discharge, and rectovaginal fistulae in women.8 Fever, rectal pain, and tenesmus may also be present.
Rectal strictures, perirectal abscesses, and fistulas represent the severe morbidity associated with LGV.8 In female patients or men who have sex with men, signs and symptoms of more invasive infection are typically present; these include proctolitis (including mucoid and or hemorrhagic rectal discharge), anal pain, constipation or painful bowel movements, fever, and/or ulcers and lymphadenopathy without proctitis.10,12 The fibrosis caused by chronic inflammation in the tertiary stage can lead to lymphatic obstruction and elephantitis of the genital area; this finding is usually seen in women.11
Case Patient Treatment and Follow-Up
Goals of treatment of LGV are to cure the disease and to prevent ongoing tissue scarring that may cause additional complications. It is also important to prevent further transmission of the disease in the community.
During the initial visit, the patient in the case presentation was treated with azithromycin 1 g coverage for the known exposure to chlamydia. Treatment for the probable herpetic lesions was not initiated as the lesions had been present for 10 days and were resolving. Laboratory assessment that was conducted during the visit included gonorrhea, chlamydia, herpes simplex virus type 1 (HSV-1), HSV-2, urinalysis, syphilis, HIV, and complete blood count. Patient education was initiated to identify and counsel on risky behaviors that are associated with STI exposure and transmission. Further direction included abstinence from sexual intercourse until further evaluation and treatment were completed. Anticipatory guidance regarding potential future exacerbation or flare-ups that would require medical evaluation and treatment at the onset of lesion eruption was provided. The patient was advised to return to the clinic in 1 week for follow-up examination and discussion of the laboratory results.
At the 1-week follow-up appointment, the patient stated that the previous genital lesions had resolved, but a new painful lesion was now on his penis. He denied fever or chills. Physical examination revealed continued tender swelling in the right groin area with a palpable lymph node that had increased in size without erythema or warmth. Multiple healing lesions were noted on inspection of the genitals. One new erythemic ulceration approximately was now located on the dorsal area of his penis. The penis was not swollen.
Laboratory results that were reviewed and discussed with the patient during the 1-week follow-up evaluation indicated positive chlamydia and HSV-1 tests. Complete blood count was negative for leukocytosis. Other negative laboratory testing included urinalysis, gonorrhea, syphilis, HIV, and HSV-2. The patient was diagnosed with LGV due to the clinical presentation and the positive chlamydial infection. The patient was started on a treatment regimen of doxycyline 100 mg twice daily for 21 days (the recommended treatment for LGV) and acyclovir 400 mg 3 times a day for 5 days (for the new HSV-1 lesion).2 The patient was provided with discharge instructions from the Centers for Disease Control and Prevention on STIs including LGV, herpes, and chlamydia; he was instructed to notify his partner of the multiple diagnoses. The patient was informed of mandatory reporting of STIs by health care providers to the state’s health department. The patient was instructed to return in 3 weeks for re-evaluation.
On his third and final visit after completion of treatment, the patient reported that he informed his partner and she had sought treatment. He denied sexual activity since his last visit to the clinic. Physical examination revealed that the genital lesions and the swollen right inguinal lymph node bubo had now resolved. The patient was instructed to delay sexual activity until his partner had finished her treatment. To exclude reinfections, a follow-up visit 3 months after the initial diagnosis with LGV was recommended.
Patients with LGV present with a wide range of symptoms indicative of other conditions and are frequently coinfected with other STIs.14 Clinicians presented with this situation in primary care need to be cognizant of the presentation of LGV in men and women, and recognize that assessment of sexual practices is crucial. As in this case description, treatment guidelines indicate that patients with clinical symptoms consistent with LGV including inguinal lymphadenopathy and genital ulcers need to be presumptively treated for LGV.2
Persons who have had sexual contact with an individual with LGV who is within 60 days of onset of symptoms should be examined and tested at the anatomic site of exposure. They should be presumptively treated with a chlamydia regimen (azithromycin 1 g orally single dose or doxycycline 100 mg orally twice a day for 7 days). Parra-Sánchez et al documented successful treatment of LGV with a single dose of azithromycin in 11 of 13 (84.6%) patients who received it.15 On the contrary, Oud et al found that azithromycin 1 g seemed insufficient to manage established infections with some cases of inguinal LGV requiring prolonged courses of doxycycline exceeding the currently advised 21-day regimen.16 Clinicians are to stress the importance of follow-up visits to reassess for complex comorbidities and/or until resolution of symptoms.
Further teaching is needed to educate patients on the potential for reinfection, risky behaviors, and potential complications due to delayed treatment. Although the infection is rare in industrialized countries, primary care clinicians should be aware of the clinical presentation of LGV and current treatment guidelines.
Alice O. Mwanda, DNP, FNP-C, and Rhonda Conner-Warren, PhD, RN, PNP-PC, are both assistant professors of health programs at Michigan State University College of Nursing, East Lansing, Michigan.
- Papadakis MA, McPhee SJ, Rabow MW. Current Medical Diagnosis & Treatment. 55th edition. New York: McGraw-Hill Medical; 2017.
- Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):33-34.
- Ceovic R, Gulin SJ. Lymphogranuloma venereum: diagnostic and treatment challenges. Infect Drug Resist. 2015;8:39-47.
- White JA. Manifestations and management of lymphogranuloma venereum. Curr Opin Infect Dis. 2009;22(1):57-66.
- Mabey D, Peeling RW. Lymphogranuloma venereum. Sex Transm Infect. 2002;78:90-92.
- Macdonald N, Sullivan AK, French P, et al. Risk factors for rectal lymphogranuloma venereum in gay men: results of a multicentre case-control study in the UK. Sex Transm Infect. 2014;90(4):262-268.
- Petrovay F, Balla E, Erdősi T. Emergence of the lymphogranuloma venereum L2c genovariant, Hungary, 2012 to 2016. Euro Surveill. 2017;22(5).
- McCance KL, Huether SE, Brashers VL, Rote NS, eds. (2014). Pathophysiology: The Biologic Basis for Diseases in Adults and Children. 7th edition. St. Louis, MO: Elsevier Mosby; 2014.
- Arsove P. Lymphogranuloma venereum (LGV). Available at: http://emedicine.medscape.com/article/220869-overview. Updated September 7, 2018. Accessed October 13, 2018.
- Centers for Disease Control and Prevention. Lymphogranuloma venereum (LGV). Available at: https://www.cdc.gov/std/tg2015/lgv.htm. Updated June 4, 2015. Accessed October 13, 2018.
- De Vries HJ, Zingon A, Kreuter A, Moi H, White JA. 2013 European guideline on the management of lymphogranuloma venereum. J Eur Acad Dermatol Venereol. 2015;29(1):1-6.
- Ward H Martin I, Alexander S, et al. Lymphogranuloma venereum in the United Kingdom. Clin Infect Dis. 2007;44(1):26-32.
- Gross G, Tyring SK. Sexually Transmitted Infections and Sexually Transmitted Diseases. Berlin, Heidelberg: Springer Berlin Heidelberg; 2011.
- Pallawela SNS, Sullivan AK, Macdonald N, et al. Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case-control study in the UK. Sex Transm Infect. 2014;90(4):269-274.
- Parra-Sánchez M, García-Rey S, Rodríguez IP, Fernández PV, Sánchez MJT, Folía JCP. Clinical and epidemiological characterisation of lymphogranuloma venereum in southwest Spain, 2013-2015. Sex Transm Infect. 2016;92(8):629-631.
- Oud EV, de Vrieze NHN, de Meij A, de Vries HJC. Pitfalls in the diagnosis and management of inguinal lymphogranuloma venereum: important lessons from a case series. Sex Transm Infect. 2014;90(4):279-282.