Genitourinary Skin and Mucous Membrane Infections and Inguinal Lymphadenopathy


In children and adolescents, inguinal lymphadenopathy often occurs as part of generalized lymphadenopathy caused by systemic disease. In contrast, isolated inguinal lymphadenopathy commonly results from localized infections of the groin, buttocks, lower abdominal wall, or lower extremities. Firm or fixed nodes should always raise suspicion for malignancy.

Inguinal Lymphadenopathy with Genital Ulcers

Genital ulcer disease (GUD) frequently manifests as unilateral or bilateral inguinal lymphadenopathy, even when ulcers are not identified clinically. Although GUD can have infectious or noninfectious origins, most cases are caused by sexually transmitted infections (STIs). Prompt diagnosis and treatment of GUD is important to minimize sequelae and decrease transmission of STIs. For example, GUD increases the risk of human immunodeficiency virus (HIV) acquisition and transmission. The diagnosis and management of GUD can be challenging because of many possible causes, diverse clinical presentations, and various diagnostic requirements and treatments. , ,

Etiologic Agents

The most common infectious causes of GUD are herpes simplex viruses (i.e., HSV-2 and HSV-1) and Treponema pallidum (i.e., syphilis). Although both are STIs, HSV-1 and HSV-2 also can be spread by nonsexual transmission or from autoinoculation. , Other STIs that cause GUD include Haemophilus ducreyi (i.e., chancroid); Chlamydia trachomatis serovars L1, L2, and L3 (i.e., lymphogranuloma venereum [LGV]); and Klebsiella granulomatis (i.e., donovanosis or granuloma inguinale). With any GUD, regional lymph nodes can become involved and lead to femoral or inguinal adenopathy or ulceration. Infrequently, scabies and pubic lice can cause GUD.

Non-STI infectious GUD causes include varicella-zoster and Epstein-Barr virus infections, tuberculosis, HIV/AIDS, leishmaniasis, secondary bacterial infections, pyoderma, and infections with Candida species , Capnocytophaga species, Histoplasma capsulatum, Francisella tularensis , Yersinia enterocolitica, or Entamoeba histolytica . GUD also can be associated with noninfectious conditions, including fixed drug eruptions, pyoderma gangrenosum, psoriasis, Behçet syndrome, lichen planus, malignancies, aphthae, Lipschütz vulvar ulcers, and Crohn’s disease. ,

Epidemiology of Genital Ulcer Disease Caused by Sexually Transmitted Infections

In the US, most young, sexually active people with genital, anal, or perianal ulcers have genital herpes or syphilis. Their frequencies vary by geographic area and population. However, genital herpes is more prevalent and is the leading cause of GUD worldwide. ,

HSV infections are lifelong, often asymptomatic, and cause intermittent viral shedding in the genital tract. Most HSV infections are transmitted by people unaware that they are infected. In 2018, an estimated 1.3 million HSV-2 infections occurred among US people between the ages of 18 and 24 years. The majority of cases of recurrent genital herpes are caused by HSV-2 and 11.9% of persons 14–49 years of age are estimated to be infected in the US. HSV-1, which typically causes orolabial herpes, is increasingly the cause of genital herpes. The growing numbers of adolescents who lack HSV-1 antibodies at sexual debut likely contributes to the percentage of genital herpes (50%–80%) due to HSV-1 in some populations of young women.

Syphilis remains a major US health problem, particularly among men who have sex with men (MSM). , Primary and secondary syphilis rates have increased over the past decade, with 53% of cases occurring among MSM in 2018. Between 2014 and 2018, the primary and secondary syphilis rate among women increased 173%. Of the 7758 primary and secondary syphilis cases among US persons between the ages of 15 and 24 years in 2018, 80% occurred in males.

The US prevalence of chancroid has declined with only 3 cases reported in 2018, and it has declined in countries where it was previously endemic. , However, due to the difficulty in detecting H. ducreyi in the laboratory, chancroid may be underreported. Chancroid infections in the US are usually associated with sporadic outbreaks.

LGV is endemic in parts of Africa, Southeast Asia, Latin America, and the Caribbean. Since 2003, LGV proctocolitis has also been reported among MSM in the US, Europe, and Australia; LGV proctocolitis outbreaks have been reported among MSM with high rates of HIV co-infection. , Granuloma inguinale occurs rarely in the US but sporadic cases have been described in parts of India, South Africa, and South America. , ,

Clinical Manifestations and Differential Diagnosis

Determining the cause of GUD is challenging based solely on clinical presentation. GUD in children and adolescents requires a thorough history and physical examination to exclude underlying systemic conditions, recent illnesses, or medications, and to identify associated factors such as sexual activity or abuse. Frequently, specialized testing is required to establish the cause.

Classic clinical features of GUD are described in Table 50.1 . In practice, the etiologic diagnosis may be indistinguishable because of coexisting infections, atypical presentations, medication effects, or immunocompromising conditions. Careful examination of the entire genital region, including the perineum and anus, and areas of lymphadenopathy which is facilitated by a good light source and magnifying lens, may improve clinical assessments and guide the choice of diagnostic tests. Anoscopic examinations can identify asymptomatic anorectal manifestations potentially overlooked by the patient and clinician and improve GUD diagnosis and treatment.

TABLE 50.1
Clinical Features of Sexually Transmitted Genital Ulcer Disease Syndromes
Feature Herpes Simplex Virus (Herpes) Treponema pallidum (Syphilis) Haemophilus ducreyi (Chancroid) Chlamydia trachomatis (Lymphogranuloma Venereum) Klebsiella granulomatis (Granuloma Inguinale)
Estimated incubation period 2–7 days 10–90 days 1–14 days 3–42 days 8–80 days
Site
Male Glans, prepuce, penis, buttocks, legs, anus, rectum At site of inoculation At site of inoculation At site of inoculation (urethral or rectal) 90% involve genitalia
Female Cervix, vulva, perineum, buttocks, legs, anus, rectum At site of inoculation At site of inoculation At site of inoculation (urethral or rectal) 90% involve genitalia
Typical primary lesion Vesicle (depends on lesion duration, host immune status) Papule (ulcerates) Papule or pustule Papule, vesicle, vesiculopustular lesion Papule or subcutaneous nodules (pseudobuboes) that ulcerate; may be hypertrophic or verrucous
Number of lesions Usually multiple; can coalesce, especially in immunocompromised host Usually single, can be multiple Often multiple; can coalesce Usually single Single or multiple
Ulcer appearance Small, superficial, smooth; with erythematous edge, circular Superficial, medium size, well demarcated with elevated edge, circular/oval Deep, small to large; undermined, with ragged edge, irregular shape Variable depth, small to medium size; elevated edge, round or oval Small to large lesions with elevated edge and beefy base; irregular shape
Induration None Firm Soft Occasionally firm Firm
Pain Typically painful; can be painless Typically painless; can be painful Varies Varies Typically painless
Inguinal lymphadenopathy Firm, tender, often bilateral Firm, nontender, bilateral Tender, typically unilateral; can suppurate; secondary superinfection may occur Large, tender, unilateral; can suppurate Pseudobuboes; usually without regional lymphadenopathy; superinfection may occur
Treatment Acyclovir, valacyclovir, famciclovir, or other acyclovir analogues Penicillin (dose and duration depend on clinical stage) Azithromycin, ceftriaxone, ciprofloxacin, or erythromycin Doxycycline (alternative: azithromycin or erythromycin) Azithromycin (alternatives: doxycycline, erythromycin, trimethoprim-sulfamethoxazole)

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