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SEXUALLY TRANSMITTED DISEASES

Work-up for a penile ulcer

When presented with a penile ulcer of recent onset, the classic sexually transmitted diseases (STDs) should be considered (i.e. herpes simplex, syphilis, chancroid, lymphogranuloma venereum, and granuloma inguinale). It should also be remembered that, occasionally, two organisms are found in one genital ulcer or that the patient may have other, non-ulcerative STD(s). Effective and early treatment of genital ulceration is important not only in its own right, but also as a part of any strategy to control the spread of HIV infection. This stems from the fact that genital ulceration has been associated with increased transmission of HIV infection in several cross-sectional and longitudinal studies.

Figure 20.37 Herpes genitalis in a male patient. (Courtesy of Michael O. Murphy, M.D.)

    The work-up for a penile ulcer should include the following (summarized in Tables 20.2 and 20.3).

    A detailed sexual history should be taken, which would include number and characteristics of sexual partners as well as HIV status or risk factors.

    The physical examination should look for characteristics of the ulcer, such as odor and exudate. Lymphadenopathy, hair loss, perianal lesions, oral lesions, etc. may all be relevant.

    Multiple slides should be made from the ulcer: first, use a cotton-tipped applicator rolled over the ulcer and then on to the slide; second, use a blade to scrape the edge of the ulcer and then smear on the slide. The slides may be then sent for Gram stain and Wright stain.

    To detect syphilis, dark-field microscopy or DIF should be used if available, and blood should be taken for serologic tests for syphilis, such as a rapid plasma reagin (RPR) test. '

Figure 20.38 Primary syphilis: chancre. In primary syphilis, solitary or multiple, painless ulcers or erosions called chancres occur. (Courtesy of the Department of Dermatology, University of California, San Diego.)

    Testing for herpes simplex can be by culture or DIF.

    To exclude chancroid, a swab for culture should be sent, alerting the laboratory to culture for H. ducreyi .

    Testing for HIV is important; a genital ulcer increases the likelihood of HIV infection, plus there are implications for treatment.

    Regarding other infections, complement fixation may be helpful in diagnosing lymphogranuloma venereum. Less common infectious causes of genital ulcers include leishmaniasis and amebiasis.

    Before all results are back, the best guess as to diagnosis should be made and appropriate treatment given. If test results alter the diagnosis, the therapy can then be modified. Rarely, a biopsy is needed for diagnosis, and some non-infectious causes may need to be considered (Table 20.4). Non-infectious causes that need to be considered include Behçet disease, Crohn disease, a factitial cause, and neoplasia.

PRACTICE POINTS

Herpes genitalis

Pain or burning may precede by several hours the eruption of grouped vesicles on an erythematous base in herpes genitalis. Primary infection is more severe than recurrences (see Ch.25; Fig. 20.37).

Primary syphilis

Etiology and pathogenesis

Syphilis is an STD caused by Treponema pallidum . There has been a major increase recently in the number of cases in many countries of the world, with many of the affected patients being men who have sex with men. This resurgence reflects in part the relapse toward high-risk activity
such as unprotected oral sex. There is a strong correlation between HIV positivity and syphilis.

    If untreated, this infection will develop in three phases. In primary syphilis, an ulcer develops on the genitalia. Approximately 6 weeks later, the secondary phase develops, in which various changes occur throughout the integument (discussed later). Years later, tertiary syphilis appears as indolent and potentially mutilating ulcers as well as annular lesions. In terms of diagnosis, the RPR blood test is positive 2–3 weeks after the appearance of the chancre, so dark-field microscopy of either serous exudate from a lesion or aspirate from an involved lymph node is the best approach to early diagnosis. However, this technique requires skill and experience. Non-treponemal blood tests include the venereal disease research laboratory (VDRL), RPR, and ART. These tests usually become negative after several years. Treponema tests include FTA-ABS and MHA-TP. These remain positive for the life of the patient.

Clinical

In primary syphilis, solitary or multiple, painless ulcers or erosions called chancres occur (Fig.20.38).They tend to remain superficial but may become quite indurated. In women, the chancre may occur in the vagina or on the cervix and go unnoticed. Chancres may occur at other sites of inoculation (e.g. the anus in a homosexual man or the mouth after oral sex). Inguinal lymphadenopathy may occur.

Figure 20.39 Secondary syphilis: (a) papulosquamous lesions of the soles, (b) lesions on the palms, (c) lesions on the penis, (d) papulosquamous lesions on the palms. (Panels a–c courtesy of Michael O. Murphy, M.D.; panel d courtesy of Steven Goldberg, M.D.)

Figure 20.40 Secondary syphilis: alopecia of the eyebrows. This patient presented to the dermatologist with the sole complaint of loss of eyebrow hair.

Differential diagnosis

See Table 20.4.

Treatment

Treatment should follow the current public health service recommendations. In the past, for primary, secondary, or early latent disease, one dose of benzathine penicillin intramuscularly, 2.4 million units, has been sufficient. In the case of penicillin allergy, tetracycline (500mg four times a day for 15 days) or doxycycline (100mg orally, twice a day for 2 weeks) has been used. The RPR or VDRL titer should be followed to ensure adequate treatment (look for at least a fourfold drop).

Secondary syphilis

Clinical

A widespread eruption of ham- to copper-hued lesions with a predilection for the palms and soles is characteristic (Fig.20.39). Scale, when present, tends to be located at the periphery. Necrotic or nodular forms occur. Constitutional symptoms include sore throat, fever, headache, myalgia, and weight loss. Other cutaneous signs include loss of eyebrow hair (Fig.20.40), condyloma lata (Fig.20.41), mucous patches (see earlier oral mucosa section), and alopecia of the scalp (Fig.20.42). RPR and MHA-TP are positive in over 95% of patients with secondary syphilis.

Figure 20.41 Secondary syphilis. (a) Perianal condyloma lata: these lesions are teeming with Treponema pallidum. (b) Perianal condyloma lata. (Panel a courtesy of Michael O. Murphy, M.D.)

Figure 20.42 Secondary syphilis: moth-eaten alopecia, which affects the scalp, eyebrows, eyelashes, and beard. (Courtesy of Stacy Smith, M.D.)

Figure 20.43 Tertiary syphilis. An annular lesion in a darker-skinned patient. (Courtesy of the Department of Dermatology, University of California, San Diego.)

Figure 20.44 Chancroid. (a) A painful, solitary, foul-smelling ulcer. (b) Multiple ulcers of chancroid. (Courtesy of Michael O. Murphy, M.D.)

Figure 20.45 Granuloma inguinale. (Courtesy of Michael O. Murphy, M.D.)

Treatment

The current recommendations for treatment should be checked. Benzathine penicillin (2.4 million units intramuscularly, repeated in a week) has been used in the past. A febrile reaction (Jarisch–Herxheimer) that commonly occurs with treatment may be avoided by pretreatment with prednisone or indomethacin.

Figure 20.46 (a–c) Vulvar intraepithelial neoplasia III. Erythematous or pigmented, smooth or papillomatous papules, sometimes coalescent into nodules, are characteristic. Human papillomavirus, especially type 16, has been found in a signicant percentage of lesions, and therefore the patient should be monitored for atypia of the uterine cervix. (Courtesy of Paul Koonings, M.D.)

Tertiary syphilis

The cutaneous lesions of tertiary syphilis (gummas) are often polycyclic or serpiginous with central ulceration or clearing. These granulomatous lesions are usually painless but may be locally destructive. Gummatous lesions may develop internally as well. The color is often a coppery red (Fig. 20.43). Treatment is with penicillin.

Chancroid

Etiology and pathogenesis

Chancroid is an infectious disease caused by Haemophilus ducreyi , a gram-negative bacillus that on smear has a school of fish appearance. Individual bacilli appear like a closed safety pin because of bipolar staining. Diagnosis may be made based on clinical findings and by the elimination of other STDs. A smear from the edge of an ulcer or from an aspirate of an enlarged node can confirm the diagnosis by showing the characteristic appearance. Various media allow for culture of the organism. Some laboratories offer polymerase chain reaction (PCR) tests. The incubation period is 4–7 days.

Clinical

This STD occurs worldwide but is most common in poor, urban, seaport populations. The male:female ratio is 10:1. The initial lesion is a papule, which becomes a pustule and finally a painful, solitary, genital ulcer that may be foul-smelling (Fig.20.44). Autoinoculation can result in multiple lesions. Painful, unilateral, inguinal adenopathy often occurs and may suppurate.

Figure 20.47 Condyloma acuminatum. (a) Scattered, flesh-colored or hyperpigmented, smooth or verrucous papules or erythematous macules along the shaft of the penis, scrotum, and perianal area are characteristic. The term bowenoid papulosis is used when the histologic picture of a lesion resembles Bowen disease. (b) Perianal condyloma acuminatum. The viral particles causing perianal condyloma may have originated from warts elsewhere on the body and been transmitted via the patient’s own hands, or they may have been contracted during anal sex. (c) Condyloma acuminatum. Multiple lesions on the shaft of the penis.

Differential diagnosis

See Table 20.4.

Treatment

The most recent public health recommendations should be sought. As of this writing, the following are recommended: azithromycin 1g orally in a single dose, or ceftriaxone 250mg intramuscularly in a single dose, or ciprofloxacin 500mg orally twice a day for 3 days, or erythromycin base 500mg orally three times a day for 7 days. Patients who are uncircumcised and patients with HIV infection do not respond as well to treatment and may need longer courses. Patients should be retested for syphilis and for HIV 3 months after the diagnosis of chancroid if the initial test results were negative.

PRACTICE POINTS

Granuloma inguinale

Granuloma inguinale, also known as donovanosis, is caused by Calymmatobacterium granulomatis . Phylogenetic analysis confirms close similarities with the genus Klebsiella , and a proposal has been made that C. granulomatis be reclassified as K. granulomatis . It is endemic in Papua New Guinea , the Caribbean , southern India , South Africa , South-East Asia , Australia , and Brazil , but is uncommon in the USA and even less frequent in the UK . Giemsa or Wright stain of a tissue smear or skin biopsy specimen shows intracytoplasmic inclusion bodies (Donovan bodies) within histiocytes. A beefy yet asymptomatic ulcer with exuberant granulation tissue occurs on the penis (Fig. 20.45).

    The appropriate public health guidelines should be followed. Azithromycin has emerged as the treatment of choice among many experts. Other antibiotics reported to be useful include tetracycline, erythromycin, trimethoprim–sulfamethoxazole, streptomycin, gentamicin, chloramphenicol and ceftriaxone, and ofloxacin (400mg twice a day).

Lymphogranuloma venereum

Etiology and pathogenesis

Lymphogranuloma venereum (LGV) is an STD caused by Chlamydia trachomatis . Diagnosis is made by the appropriate history and clinical findings, plus a fourfold or greater rise in the LGV complement xation test.

Clinical

After a 3–30-day incubation period, a papulovesicle progresses to a small and often unnoticed erosion. Firm lymphadenopathy, which may suppurate, occurs 1–2 weeks later. The classic ‘groove sign' is created by enlarged inguinal and femoral nodes (known as buboes) separated by the Poupart ligament. Later, lymphatic obstruction may lead to elephantiasis of the genitalia. Unilateral inguinal adenitis may be the presenting sign, especially in men. Proctitis and periproctitis may occur in the rectal syndrome, which tends to affect women. Destructive vulvar ulceration, bridging and tunneling, fistulas (e.g. rectovaginal), and strictures (e.g. urethra, vaginal, and rectal) may occur in women.

Differential diagnosis

See Table 20.4.

Treatment

The appropriate public health guidelines should be followed. In the past, the following antibiotics have been given for 3 weeks: doxycycline (100mg twice a day) or erythromycin (500mg four times a day). Fluctuant buboes may be aspirated.

Condyloma acuminatum (genital warts)

Etiology and pathogenesis

Condyloma acuminatum is an STD caused by human papillomavirus (HPV). In the male genitalia, condyloma acuminatum, Bowen disease, and bowenoid papulosis are sometimes grouped under the term penile intraepithelial neoplasia, with the amount of atypia graded I–III. In the female genitalia, condyloma acuminatum, Bowen disease, and bowenoid papulosis are sometimes grouped under the term vulvar intraepithelial neoplasia, with the amount of atypia graded I–III (Fig. 20.46).

Figure 20.48 Bowenoid papulosis, or penile intraepithelial neoplasia, presents as red-brown papules and plaques.

Figure 20.49 Molluscum contagiosum. (a) Lesions of molluscum on the lower abdomen and groin of adults are often transmitted during sexual contact. In contrast, genital lesions in children are obtained innocently in most cases (see Ch. 25). (b) Molluscum on the shaft of the penis (see Ch. 25).

Figure 20.50 Pearly penile papules. These papules may be mistaken for warts but are not infectious

Figure 20.51 Ectopic sebaceous glands. These lesions may be confused with condyloma. Note their uniform appearance and distribution. (Courtesy of Clifford M. Lawrence, M.D.)

    More than 30 different types of HPV may infect the genitalia. Many of these infections are subclinical and unbeknown to the patient. Visible lesions are usually caused by HPV types 6 and 11. Certain HPV types (e.g. 16 and 18) have been associated with dysplasia or malignancy of the uterine cervix.

Clinical

In women, genital warts may affect any part of the vulval or perineal skin, and also occur within the introitus, in the vagina, and on the cervix. Associated cervical dysplasia may be present. In men, scattered, flesh-colored, smooth or verrucous papules or erythematous macules along the penile shaft, scrotum, and perianal area are characteristic (Fig.20.47). Acetowhitening is sometimes used clinically, but both false positive and false negative results lessen the value of this procedure.

Differential diagnosis

Various papules on the genitalia may be confused with warts, including the following.

Figure 20.52 Candidal balanitis.

Figure 20.53 Allergic contact dermatitis. The Rhus allergen is carried to the penis by the fingers when the man urinates. (Courtesy of Michael O. Murphy, M.D.)

Treatment

Current evidence suggests that eliminating visible lesions may reduce infectivity but not eliminate it. Furthermore, untreated lesions may regress spontaneously, therapy may be costly, and side effects may occur. Therefore observation is a reasonable alternative to intervention in patients with condyloma. If therapy is attempted, the goal should be to provide the patient with disease-free periods without promising cure. Sexual partners should be examined, and female patients with HPV should have regular cervical smears, as they have an increased incidence of cervical cancer.

    A variety of provider-performed or applied measures are available, including cryotherapy, podophyllin resin 10–25% (washed off by the patient in 6h) or podophyllotoxin (an easier agent to use at home), trichloroacetic acid (TCA), or bichloroacetic acid (BCA) 80–90%. Each of these should be applied every 2–3 weeks until the warts are cleared. Waiting too long between treatments allows for recurrence. Topical imiquimod is a newer agent for genital warts, that works by augmenting local immunity rather than by the destructive mechanism of most older treatments. Finally, for resistant warts, surgical excision with or without electrocautery, intralesional interferon, or laser surgery may be employed.

Figure 20.54 Psoriasis.

Figure 20.55 Lichen planus. The penis is a typical site for the annular variant.

    Several patient-applied treatments may be prescribed. For external genital or perianal warts, the patient may apply 0.5% podophyllotoxin solution or gel twice daily for 3 days per week or imiquimod 5% cream on Monday, Wednesday, and Friday each week. Look for clearing in 4–8 weeks.

    Urethral meatus condylomata may be treated by cryotherapy or podophyllin as described earlier. Alternatively, 5% 5-fluorouracil cream may be applied after each voiding for 2–3 weeks. The procedure is to dry the urethral opening with one end of a Q-tip and to apply the cream with the other end. The opening is then pressed closed and the excess wiped off. Painful urination and discharge may occur in the later part of therapy. Vaginal warts may be treated with cryotherapy, TCA, BCA, or podophyllin in a manner similar to that discussed earlier.

    Perianal condyloma acuminata is an important problem that may need special attention. The possibility of abuse must always be considered, especially in children 3 years of age or older (in younger children, warts may have been acquired from the maternal birth canal or innocently from hands). The presence of any other STD strongly suggests abuse in children. Topical podophyllin resin or imiquimod may be applied. Imiquimod has been reported effective in hyperproliferative cases of condyloma in children when applied every other day for 3 weeks.

Bowenoid papulosis

In bowenoid papulosis, papular growths of the genitalia histologically show features of Bowen disease. HPV-16 has been found in a significant percentage of cases. One significant concern is that HPV-16 has also been related to the development of cervical carcinoma. Red-brown papules occur on the glans and shaft of the penis in men (Fig.20.48) and on the labia majora, labia minora, and perianal area in women.

    Sexual partners should be examined and women observed for cervical neoplasia. Conservative destruction with cryotherapy, electrocautery,
CO2 laser, or simple shave or scissors excision is appropriate. Five percent 5-fluorouracil cream twice daily for 1 month can be tried.

Figure 20.56 Penile melanosis.

Figure 20.57 Balanitis xerotica obliterans (BXO). (a) Note the dramatic scarring, white color, and telangiectasias. (b) BXO forming a circumferential ring. Painful phimosis may result. (c) Purpuric lesions in BXO.

Molluscum contagiosum

Grouped, pink to flesh-colored, smooth papules with a central dell—the central depression being most visible during cryotherapy—are characteristic. In children, they may occur anywhere. In an adult, the lower abdomen, groin, or penis is characteristic (Fig.20.49), and sexual transmission should be suspected.

Figure 20.58 Erythroplasia of Queyrat

Figure 20.59 Zoon balanitis. A moist, shiny, erythematous, well-demarcated plaque on the glans penis in an older uncircumcised man is characteristic of Zoon balanitis, also known as balanitis plasmocellularis. The condition is benign.

Figure 20.60 Verrucous carcinoma of the penis. This variant of a squamous cell carcinoma is typically slow-growing.

    For the adult with molluscum in the genital area, cryotherapy every 2–3 weeks until clear is very effective.

White/Cox: Diseases of the Skin, 2ed.(c) 2006, Elsevier Inc. All rights reserved.