Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology, Seventh Edition


Sexually Transmitted Diseases


Human Papillomavirus: Anogenital Infections

ICD-9: 079.4 image ICD-10: B97.7 image

image Mucosal human papilloma virus (HPV) infections are the most common sexually transmitted infection (STIs) seen by the dermatologist. Only 1-2% of HPV-infected young, sexually active persons have any visibly detectable clinical lesion.

image HPV present in the birth canal can be transmitted to a newborn during vaginal delivery and can cause external genital warts (EGW) and respiratory papillomatosis.

image Warts. Barely visible papules to nodules to confluent masses occurring on anogenital skin or mucosa and oral mucosa. EGW: External genitalia, perineum. Cervix. Oropharynx.

image Dysplasia of anogenital and oral skin and mucosa ranging from mild to severe to squamous cell carcinoma (SCC) in situ (SCCIS). Invasive SCC can arise within SCCIS. Most commonly in cervix, anal canal

Etiology and Epidemiology

Etiology. HPV is DNA papovavirus that multiplies in the nuclei of infected epithelial cells (see Section 27). More than 20 types of HPV can infect the genital tract: types 6, 11 most commonly. Types 16, 18, 31, 33, and 35 are strongly associated with anogenital dysplasia and carcinoma. In persons with multiple sexual partners, subclinical infection with multiple HPV types is common.

Risk Factors for Acquiring HPV Infection. Number of sexual partners/frequency of sexual intercourse. Sexual partner with HPV anogenital infection. Infection with other STIs.

Transmission. Through sexual contact: genital-genital, oral-genital, genital-anal. Microabrasions occur on epithelial surface allowing virions from infected partner to gain access to basal cell layer of noninfected partner.

• During delivery, mothers with anogenital warts can transmit HPV to neonate, resulting in EGW and laryngeal papillomatosis in children.

Incidence. Most sexually active individuals are subclinically infected with HPV; most HPV infections are asymptomatic, subclinical, or unrecognized. 1% of sexually active adults (15-19 years of age) develop clinical lesions.

Pathogenesis. “Low-risk” and “high-risk” HPV types both cause anogenital infections. HPV infection may persist for years in a dormant state and becomes infectious intermittently. Exophytic warts are probably more infectious than subclinical infection. Immunosuppression may result in new extensive HPV lesions, poor response to treatment, increased multifocal intraepithelial neoplasia. All HPV types replicate exclusively in host’s cell nucleus. In benign HPV-associated lesions, HPV exists as a plasmid in cellular cytoplasm, replicating extrachromosomally. In malignant HPV-associated lesions, HPV integrates into host’s chromosome, following a break in the viral genome (around E1/E2 region). E1 and E2 function is deregulated, resulting in cellular transformation.

Genital Warts image

Clinical Manifestation

Usually asymptomatic, except for cosmetic appearance. Anxiety of having STI. Obstruction if large mass is uncommon.

Mucocutaneous Lesions. Four clinical types of genital warts occur:

Small papular (Fig. 30-1).


Figure 30-1. Papular warts: penis A 23-year-old male with penile lesions for 6 months. Multiple skin-colored papules on the penis and scrotum.

Condyloma acuminatum. Cauliflower-floret (acuminate or pointed) lesions (Figs. 30-2 to 30-5).


Figure 30-2. Condyloma acuminatum A 30-year-old male with cluster of warts at the base of the penis in pubis for 6 weeks. This is a common site for HPV infection; condom use does not protect against transmission from infected partner.


Figure 30-3. Condylomata acuminata: penis A 20-year-old male with Crohn disease treated with infliximab infusion. Condylomata on the distal foreskin resemble cauliflower floret-like papules.


Figure 30-4. Condylomata acuminata: vulva Multiple, pink-brown, soft papules on the labia.


Figure 30-5. Genital warts A 37-year-old male with history of heart-lung transplantation and immunosuppression. Large condylomata acuminata are seen on the anal and perineal area.

Keratotic warts (Fig. 30-6).


Figure 30-6. Keratotic external genital warts (EGW): male A 46-year-old male with lesion at the base of penis for several years. A keratotic tumor at the base of the penis adjacent to the scrotum. Lesional biopsy reported EGW ruling out verrucous carcinoma.

Flat-topped papules/plaques (most common on cervix) (Fig. 30-7).


Figure 30-7. Condylomata acuminata: uterine cervix Sharply demarcated, whitish, flat plaques becoming confluent around the cervix.

Skin-colored, pink, red, tan, brown. Solitary, scattered, and isolated, or form voluminous confluent masses. In immunocompromised individuals, lesions may be huge (Fig. 30-5).

Sites of predilection. Male: Frenulum, corona, glans penis, prepuce, shaft (Figs. 30-130-230-530-6), scrotum. Female: Labia, clitoris, periurethral area, perineum, vagina, cervix (flat lesions) (Fig. 30-7). Both sexes: Perineal, perianal (Fig. 30-5), anal canal, rectal; urethral meatus, urethra, bladder; oropharynx.

Laryngeal Papillomas

• Relatively uncommon; associated with HPV-6 and -11.

• Arise most commonly on true vocal cords of larynx.

• Age: children <5 years of age, adults >20 years of age.

• Risk of SCCIS and invasive SCC.

Differential Diagnosis

Papular/Nodular External Genital Lesions. Normal anatomy (e.g., sebaceous glands, pearly penile papules, vestibular papillae), squamous intraepithelial lesions (SILs), SCCIS, invasive SCC, benign neoplasms (moles, seborrheic keratoses, skin tags, pilar cyst, angiokeratoma), inflammatory dermatoses (lichen nitidus, lichen planus), molluscum contagiosum, condylomata lata, folliculitis, scabietic nodules.

Laboratory Examinations

Pap Smear. Encourage all women to have annual Pap smear since HPV is the major etiologic agent for cancer of the cervix. Anal Pap test with a cervical brush and fixative solution helps detect anal dysplasia.

Dermatopathology. Biopsy is indicated if diagnosis is uncertain; lesions do not respond to standard therapy and worsen during therapy; the patient is immunocompromised; warts are pigmented, indurated, fixed, and/or ulcerated. Indicated in some cases to confirm diagnosis and/or rule out SCCIS or invasive SCC.

Detection of HPV DNA. Presence of HPV DNA and specific HPV types determined on smears and lesional biopsy by in situ hybridization. Serology. Genital warts are markers of unsafe sexual practices. Serologic tests for syphilis should be obtained on all patients to rule out coinfection with Treponema pallidum, and all patients offered HIV/AIDS testing.


Clinical diagnosis, occasionally confirmed by biopsy.


HPV is highly infectious, with an incubation period of 3 weeks to 8 months. Most HPV-infected individuals who develop genital warts do so 2-3 months after becoming infected. If left untreated, genital warts may resolve on their own, remain unchanged, or grow. After regression, subclinical infection may persist for life. Recurrence may occur with normal immune function as well as in immunocompromised. Recurrences more commonly are reactivation of subclinical infection than reinfection. In pregnancy, genital warts may increase in size and number, show increased vaginal involvement, and have an increased rate of secondary bacterial infection. Children delivered vaginally of mothers with genital HPV infection are at risk for developing recurrent respiratory papillomatosis in later life.

HPV types 16, 18, 31, and 33 are the major etiologic factors for in situ and invasive SCC: Cervix; external genitalia (vulva and penis); anus and perineum (homosexual/bisexual males but not necessarily, females).


Prevention. Use of condoms reduces transmission. HPV vaccine protects against four strains of HPV.

Goal of Treatment. Removal of exophytic warts and reduction of signs and symptoms. No therapy has been shown to eradicate HPV or prevent cervical or anogenital cancer. Treatment more successful if warts are small and present for <1 year. Risk of transmission might be reduced by “debulking” genital warts.

Selection of Treatment. Guided by preference of patient—avoid expensive therapies, toxic therapies, and procedures that result in scarring. See Section 27.

Patient Applied Agents. Imiquimod 5% cream, podophylox 0.5% solution.

Clinician Administered Therapy. Cryosurgery, podophyllin 10-25%, trichloroacetic acid 8090%, surgical removal, electrodesiccation.

HPV: Squamous Cell Carcinoma in Situ (SCCIS)

and Invasive SCC of Anogenital Skin

image HPV infection of the anogenital epithelium can result in a spectrum of changes referred to as SILs, ranging from mild dysplasia to SCCIS.

image Over time, these lesions can regress, persist, progress, or recur, in some cases to invasive SCC.

image Clinically, lesions appear as multifocal macules, papules, and plaques on the external anogenital region.

image Lesions involving the cervix and anus have the highest risk for transformation to invasive SCC; however, lesions can transform at any site.

image Synonyms: Vulvar intraepithelial neoplasia, penile intraepithelial neoplasm, bowenoid papulosis.

Etiology and Epidemiology

The Bethesda System (National Cancer Institute) is currently used as terminology for “dysplastic” lesions caused by HPV on anogenital sites. The terminology applies to both cytologic (Pap test) and histologic assessments. Intraepithelial neoplasia are designated as cervical (CIN), vulvar (VIN), penile (PIN), and anal (AIN). VIN is classified as VIN1 (mild dysplasia), VIN2 (moderate dysplasia), VIN3 (severe dysplasia or carcinoma in situ), and VIN3 differentiated type.

Etiology. HPV types 16, 18, 31, and 33.

Transmission. HPV transmitted sexually. Autoinoculation. Rarely, HPV-16 transmitted from mother to newborn with subsequent development on penis.

Demography. Cervical SCC is the second most common female malignancy worldwide, second only to breast cancer. It is the most frequent malignancy in developing countries—500,000 new cases and 200,000 deaths worldwide attributed to it annually.

Risk Factors. Host defense defects and cigarette smoking are risk factors for more dysplastic lesions and invasive SCC.

Pathogenesis. HPV-16- and -18-infected cells may not be able to differentiate fully as a result of either: Functional interference of cell cycle-regulating proteins, caused by viral gene expression or overproduction of E5, E6, and E7. When this occurs, the host DNA synthesis continues unchecked and leads to rapidly dividing undifferentiated cells with morphologic characteristics of intraepithelial neoplasia. Accumulated chromosomal breakages, rearrangements, deletions, and other genomic mutations in these cells lead to cells with invasion capability and, ultimately, to cervical malignancy.

Clinical Manifestation

Prior history of condylomata acuminata. Female partners of males may have CIN.

Mucocutaneous Lesions

• Erythematous flat-topped papules.

• Lichenoid (flat-topped) or pigmented papules (called bowenoid papulosis) (Figs. 30-830-9).


Figure 30-8. HPV squamous cell carcinoma in situ A 48-year-old male with penile lesion for 2 years. Pink papules forming a 1-cm plaque on the shaft of the penis. Lesional biopsy reported SCCIS with HPV changes (koilocytosis).


Figure 30-9. HPV squamous cell carcinoma in situ A 33-year-old renal transplant recipient with anogenital lesions for several years. A large pink plaque on the perineum and multiple small papules on posterior vulva. Lesional biopsy was reported to show SCCIS with HPV changes (koilocytosis).

• May show confluence or form plaque(s).

• Leukoplakia-like plaque (Fig. 30-10). Surface usually smooth, velvety.


Figure 30-10. HPV squamous cell carcinoma in situ A 49-year-old male with HIV disease noted to have anal lesion for 1 month. A white firm nodule on the rim of the anus. Biopsy reported SCCIS with HPV changes. No lesions were detected on anal colposcopy.

Colors: Tan, brown, pink, red, violaceous, white. Nodule or ulceration in field of SIL suggests invasive SCC (Figs. 30-11 and 30-12).


Figure 30-11. HPV-induced in situ and invasive squamous cell carcinoma: vulva Several red nodules (invasive SCC) arising within a white plaque (SCCIS) on the left labium.


Figure 30-12. HPV-induced in situ and invasive squamous cell carcinoma: perineal/perianal A 38-year-old male with HIV disease aware of perianal lesions for several months; he had prior history of EGW. Brown perineal and perianal macules and papules (SCCIS) with a pink nodule arising at the anal verge. Excisional biopsy of the nodule reported invasive SCC arising within SCCIS.

Arrangement. Characteristically clusters, i.e., commonly multifocal. May be solitary.

Distribution. Males: glans penis, prepuce (75%) (flat lichenoid papules or erythematous macules); penile shaft (25%) (pigmented papules). Females: labia majora and minora, clitoris. Multicentric involvement of the cervix, vulva, perineum, and/or anus occurs not infrequently. Both sexes: inguinal folds, perineal/perianal skin. Oropharyngeal mucosa. Sites other than external genitalia may be associated with cervical dysplasia, CIN, cervical SCC; rarely, SCCIS of other sites, i.e., nail unit (periungual, nail bed); intraoral (Fig. 30-13).


Figure 30-13. Metastatic SCC of urethra A 38-year-old male with primary urethral squamous cell carcinoma metastatic to inguinal lymph nodes with lymphedema. Red nodules and plaques are cutaneous metastases. PCR of thigh metastasis detected HPV-16.

Differential Diagnosis

Multiple Skin-Colored Papules ± Hyperkeratosis. Genital warts, psoriasis vulgaris; lichen planus.

Pigmented Anogenital Macule(s)/Papule(s). Genital lentiginosis, melanoma (in situ or invasive), pigmented basal cell carcinoma, angiokeratomas.

Laboratory Examinations

Dermatopathology. Epidermal proliferation with numerous mitotic figures, abnormal mitoses, atypical pleomorphic cells with large hyperchromatic, often clumped nuclei, dyskeratotic cells; basal membrane intact. Koilocytosis. Recent application of podophyllin to condyloma acuminatum may cause changes similar to SCCIS.

Southern Blot Analysis. Identifies HPV type.

Pap Smear. Koilocytotic atypia.

Exfoliative Cytology. Cervical Pap smears have been recommended annually for women >50 years of age. Cytology of the anal canal may also be helpful in management of individuals with a history of anal HPV infection, especially if immunocompromised (HIV disease, renal transplant recipients). By the Bethesda System, these cytologic findings are reported as atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade (HSIL), and SCC.


Clinical suspicion, confirmed by biopsy of lesion.


Invasive SCC develops only through well-defined precursor lesions (Figs. 30-1130-12). Over time, these lesions can regress, persist, recur, or progress, in some cases to invasive SCC. Natural history of CIN is best studied: progression to invasive SCC occurs in 36% of cases over a 20-year period. Patients with intraepithelial neoplasias, which often occur in immunocompromised individuals, should be followed indefinitely, with monitoring by exfoliative cytology and lesional biopsy specimens.

Laboratory Findings


The most common indication for colposcopy is abnormal exfoliative cytology. Acetic acid, 3-5%, is applied to the cervix, which causes columnar and abnormal epithelium to become edematous. Abnormal (atypical) epithelium adopts a white or opaque appearance that can be distinguished from the normal pink epithelium. Abnormal epithelium is then biopsied. Colposcopy can also be performed on individuals with abnormal anal exfoliative cytology, and biopsy specimens obtained from abnormal site(s).


In cases of documented SIL or SCCIS, biopsy specimens should be obtained from rapidly enlarging lesions, areas of ulceration or bleeding, exuberant tissue with abnormal vascularity.


The only way of possibly reducing the potential risk of invasive SCC is diagnosis and eradication of intraepithelial disease. Because lesions are relatively uncommon, cases are often best managed by a dermatologist with clinical experience in the care of these patients, an oncologic gynecologist, or a colorectal surgeon. If lesion biopsy specimens do not show early invasion, lesions can be treated medically or surgically.

Medical Management

5-Fluorouracil cream has been used but is difficult to use because of erosions. Imiquimod cream 5% is also effective.

Surgical Management

Surgical excision, Mohs surgery, electrosurgery, laser vaporization, cryosurgery.

Herpes Simplex Virus: Genital Disease

ICD-9: 054.10 image ICD-10: A60 Image

Image Genital herpes (GH) is a chronic sexually transmitted viral disease, characterized by symptomatic and asymptomatic viral shedding.

Etiology and Epidemiology

Etiology. HSV-2 > HSV-1. See also Section 27.

Prevalence. Highly variable. Depends on many factors: country, region of residence, population subgroup, gender, and age. Greater among higher risk sexual behavior groups. Prevalence of HSV-2 seropositivity in general population: United States: 21%; Europe: 8-15%; Africa: 40-50% in 20-year-olds. Strongly associated with age, increasing from negligible levels in children <12 to as high as 80% among higher risk populations. In the United States, approximately one in five adults infected.

Transmission. Usually skin-to-skin contact. Seventy percent of transmission occurs during times of asymptomatic HSV shedding. Transmission rate in discordant couples (one partner infected, the other not) approximately 10% per year; 25% of females become infected, compared with only 4-6% of males. Prior HSV-1 infection is protective; in females with anti-HSV-1 antibodies, 15% become infected with HSV-2, but in those without anti-HSV-1 antibodies, 30% become infected with HSV-2.

Clinical Manifestation

Only 10% of HSV-2 seropositive individuals are aware that symptoms are those of GH. Ninety percent do not recognize symptoms of GH. Most clinical lesions are minor breaks in the mucocutaneous epithelium, presenting as erosion, “abrasions,” fissures. The “classically” described findings are uncommon. Symptoms of aseptic HSV-2 meningitis can occur with primary or recurrent GH.

Primary Genital Herpes. Most individuals with primary infection are asymptomatic. Those with symptoms report fever, headache, malaise, myalgia, peaking within the first 3-4 days after onset of lesions, resolving during the subsequent 3-4 days. Erythematous papules initially evolve to vesicles or pustules, which become eroded as the overlying epidermis sloughs (Figs. 30-1430-15). Primary infection occurs anywhere on the anogenital skin, cervix, and anorectal mucosa. Epithelial defects heal in 2-4 weeks, often with resulting postinflammatory hypo- or hyperpigmentation, uncommonly with scarring.


Figure 30-14. Genital herpes, primary Multiple, extremely painful, punched-out, confluent, shallow ulcers on the edematous vulva and perineum. Micturition is often very painful. Associated inguinal lymphadenopathy is common.


Figure 30-15. Genital herpes, primary A 48-year-old male with painful genital lesions for 4 days. Multiple erosions on the penis and scrotum.

With host defense defects, lesions tend to be more extensive and delayed in healing.

Recurrent Genital Herpes. New symptoms may result from old infections. Most individuals do not experience “classic” findings of grouped vesicles on erythematous base. Common symptoms are itching, burning, fissure, redness, and irritation prior to eruption of vesicles. Dysuria, sciatica, and rectal discomfort. Lesions may be similar to primary infection but on a reduced scale. Often a 1- to 2-cm erythematous plaque with vesicles (Figs. 30-16 to 30-21), which rupture with of erosions.


Figure 30-16. Genital herpes, recurrent Group of vesicles with early central crusting on a red base arising on the shaft of the penis. This “textbook” presentation, however, is much less common than small asymptomatic erosions or fissures.


Figure 30-17. Genital herpes, recurrent: vulva Large, painful erosions on the labia. Extensive lesions such as these are uncommon in recurrent genital herpes in an otherwise healthy individual.


Figure 30-18. Genital herpes, recurrent A 30-year-old male with HIV disease. Multiple, painful, sharply demarcated ulcers are seen on the anus and perineum.


Figure 30-19. Chronic herpetic ulcers A 32-year-old male with extensive painful erosions of perineum and anus. This was the presenting complaint that lead to HIV serotesting and diagnosis of HIV disease.


Figure 30-20. Genital herpes, recurrent A 80-year-old female with recurring lesions on buttock. She has polymyalgia rheumatic and is being treated with prednisone. Blisters and crusted erosions are seen on both buttocks.


Figure 30-21. Genital herpes, recurrent A 51-year-old female with recurrent vesicles and crusted erosions on buttock, nearly continually since acquisition 31 years before. Recurrent lesion of the buttock were followed by erythema multiforme minor.

Distribution. Males. Primary infection: glans, prepuce, shaft, sulcus, scrotum, thighs, buttocks. Recurrences: penile shaft, glans, buttocks. Females. Primary infection: labia majora/minora, perineum, inner thighs. Recurrences: labia majora/minora, buttocks.

Anorectal Infection. Occurs following anal intercourse; characterized by tenesmus, anal pain, proctitis, discharge, and ulcerations (Figs. 30-1830-19) as far as 10 cm into anal canal.

General Findings. Inguinal/femoral lymph nodes may be enlarged, tender with primary infection. Signs of aseptic meningitis. Fever, nuchal rigidity; can occur in the absence of GH. Pain along sciatic nerve.

Differential Diagnosis

Trauma, candidiasis, syphilitic chancre, fixed drug eruption, chancroid, gonococcal erosion.

Laboratory Studies

See Section 27 “Herpes Simplex Virus Disease.”


Diagnosis can be made on clinical finding. Confirmation by viral culture or direct fluorescent antibody (DFA) or serology may be indicated. Coinfection with another STD should be ruled out.


GH is a lifetime infection and recurrances are the rule. Seventy percent are asymptomatic. Recurrence rates are high in those with an extended first episode of infection, regardless of whether antiviral therapy is given. Chronic suppressive therapy reduces shedding. Treatment of first-episode infection prevents complications such as meningitis and radiculitis. Erythema multiforme may complicate recurrences, occurring 1-2 weeks after an outbreak.


Prevention. Advise patients to abstain from sexual activity while lesions are present and encourage use of condoms during all sexual activity.

First Episode. Oral antivirals. Acyclovir 400 mg 5 times daily for 10 days or until lesions resolve.

Recurrances. Oral antivirals. Acyclovir 400 mg 3 times daily for 5 days or 800 mg twice daily for 5 days, or 800 mg 3 times daily for 2 days. Valacyclovir 500 mg twice daily for three days or 1 mg twice daily for 3 days. Famciclovir 125 mg twice daily for 5 days or 1 g once a day for 5 days.

Maintenance Therapy. Oral antivirals: Daily suppressive therapy. Acyclovir 400 mg twice daily. Valcyclovir 500-1000 mg once daily. Famciclovier 250 mg once daily.

Severely Immunocompromised. IV acyclovir 5 mg/kg every 8h for 5-7 days or oral acyclovir 400 mg 5 times a day for 7-14 days.

Acyclovir Resistant. IV foscarnet 40 mg/kg every 8h for 14-21 days.

Neonates. see Section 27.

Neisseria Gonorrhoeae DiseaseImage

imageEtiology. N. gonorrhoeae, the gonococcus.

ImageColonize Mucosa. oropharynx, anogenital sites.

imageEpidemiology. STI. Shares clinical spectrum of Chlamydia trachomatis; symptoms are usually more severe with gonococcal infections.

Clinical Manifestation

Local Infection. Gonorrhea or “clap.” Gonococcus infects mucocutaneous surfaces of the lower genitourinary tract, anus, and rectum and the oropharynx.

Invasive infection: Pelvic inflammatory disease (PID).

Disseminated Infection. If untreated, disseminated gonococcal infection (DGI) may occur spreading to deeper structures with abscess formation. Colonizes oropharyngeal or anogenital mucosa from which gonococcus seeds blood.

Etiology and Epidemiology

Etiology. N. gonorrhoeae, the gonococcus (Fig. 30-22). Humans are the only natural reservoir of the organism. Strains that cause disseminated infection tend to cause minimal genital inflammation. In the United States, these strains have occurred infrequently during the past decade. Up to 40% of persons coinfected with C. trachomatis. Gonorrhea enhances transmission as well as acquisition of HIV/AIDS.


Figure 30-22.Neisseria gonorrhoeae: Gram stain Multiple, gram-negative diplococci within polymorphonuclear leukocytes as well as in the extracellular areas of a smear from a urethral discharge.

Incidence. Gonorrhea is the second most commonly reported notifiable disease in the United States: 310,000 cases reported in United States in 2010. Higher in developing countries.

Demography. Young, sexually active. Symptomatic infection more common in males. In the United States, highest incidence of gonorrhea is in blacks, lowest in those of Asian/Pacific Island descent. In Africa, median prevalence of gonorrhea in pregnant women is 10%.

Transmission. Sexually, from partner who either is asymptomatic or has minimal symptoms. Neonate exposed to infected secretions in birth canal. About 1% of patients with untreated mucosal gonococcal infection develop disseminated infection (see below). Gonorrhea may enhance HIV transmission.

Pathogenesis. Gonococcus has affinity for columnar epithelium; stratified and squamous epithelia are more resistant to attack. Gonococcus penetrates between epithelial cells, causing a submucosal inflammation with polymorphonuclear (PMN) leukocyte reaction with resultant purulent discharge. Strains of gonococcus that cause disseminated infection tend to cause little genital inflammation and thereby escape detection. Most signs and symptoms of disseminated infection are manifestations of immune complex formation and deposition. Multiple episodes of disseminated infection may be associated with abnormality of terminal complement component factors (see below).

Neisseria Gonorrhoeae: Gonorrhea

ICD-9: 098 image ICD-10: A54 Image

Image In men, the most common presentation is purulent urethral discharge.

Image Most infected women are asymptomatic and cervical infection is most common.

Image Most men (90%) develop symptoms of urethritis within 5 days.

image Most women are asymptomatic; when symptoms occur, it is usually > 14 days since exposure.

image If untreated, infection can spread to deeper structures with abscess formation and disseminated gonococcal infection (DGI)

Clinical Manifestations

Genitalia. Men: Urethral discharge ranging from scanty and clear to purulent and copious (Fig. 30-23)


Figure 30-23. Gonorrhea Purulent, creamy urethral discharge from the distal urethra.

Women: Periurethral edema, urethritis. Purulent discharge from cervix but no vaginitis. In prepubescent females, vulvovaginitis. Bartholin abscess.

Anorectum. Proctitis with pain and purulent discharge.

Pharynx. Pharyngitis with erythema occurs secondary to oral-genital sexual exposure. Always coexists with genital infection.

Neonate. Conjunctivitis, swollen eyelid, severe hyperemia, chemosis, profuse purulent discharge; rarely, corneal ulcer and perforation. Usually in absence of genital infection.


Figure 30-24. Disseminated gonococcal infection Hemorrhagic, painful pustules on erythematous bases on the palm and the finger of the other hand. These lesions occur at acral sites and are few in number.

Differential Diagnosis

Urethritis. GH with urethritis, C. trachomatis urethritis, Ureaplasma urealyticum urethritis, Trichomonas vaginalis urethritis, Reiter’s syndrome.

Cervicitis. C. trachomatis or HSV cervicitis.

Laboratory Examinations

Gram Stain: Gram-negative diplococci intracellularly in PMN leukocytes in exudate (Fig. 30-22).

Culture. Men: Urethra, rectum, oropharynx. Women: Cervix, rectum, oropharynx. DGI: Blood. Isolation on gonococcal-selective media, i.e., chocolatized blood agar, Martin-Lewis medium, Thayer-Martin medium. Antimicrobial susceptibility testing important due to resistant strains.


Clinical suspicion, confirmed by laboratory findings, (Fig. 30-22) and culture. Coinfection with other sexually pathogens should be ruled out.


Most infected men seek treatment due to symptoms early enough to prevent serious sequelae, but not to prevent transmission to others. Most infected women have no recognizable symptoms until complications such as PID, tubal scarring, infertility, or ectopic pregnancy occur. DGI more common in women with asymptomatic cervical, endometrial, or tubal infection, and homosexual men with asymptomatic rectal or pharyngeal gonorrhea.


Localized Uncomplicated Gonorrhea. Single dose intramuscular ceftriaxone 125 mg or oral cefixime 400 mg. Alternatives: intramuscular ceftizoxime 500 mg, or intramuscular cefotaxime 500 mg, or intramuscular cefoxitin 2 g with oral probenecid 1 g.

Penicillin Allergy. Intramuscular spectinomycin 2 mg.

Disseminated Gonococal Infection. Intramuscular or intravenous ceftriaxone 1 g every 24 hours. Alternatives: intravenous cefotaxime or ceftizoxime 1 g every 8 hours or intramuscular spectinomycin 2 g every 12 hours.

Syphilis ICD-9: 97.9 image ICD-10: A50-53 Image

Image Chronic systemic infection caused by the spirochete T. pallidum, transmitted through skin and mucosa, with manifestations in nearly every organ system.

Image Incidence is approximately 30,000 cases annually.

Image Primary infection: A painless ulcer or chancre on the mucocutaneous site of inoculation. Associated with regional lymphadenopathy (chancriform syndrome: distal ulcer associated with proximal lymphadenopathy).

Image Systemic infection: Shortly after inoculation, syphilis becomes a systemic infection with characteristic secondary and tertiary stages.

Image Course: Clinical course and response to standard therapy may be altered in HIV/AIDS.

Etiology and Epidemiology

Etiology. Venereal syphilis caused by T. pallidum. T. pallidum is a thin delicate spirochete with 6-14 spirals. Only natural host for T. pallidum is the human. Subspecies of T. pallidum cause the nonvenereal diseases endemic syphilis (bejel), yaws, and pinta.

Transmission. Sexual contact: Contact with infectious lesion (chancre, mucous patch, condyloma latum, cutaneous lesions of secondary syphilis). Sixty percent of contacts of persons with primary and secondary syphilis become infected. Congenital infection: In utero or perinatal transmission.

Pathogenesis. The spirochetes pass through intact mucous membrane and microscopic abrasion in skin, enter lymphatics and blood within a few hours, and produce systemic infection and metastatic foci before development of a primary lesion. Spirochetes divide locally, with resulting host inflammatory response and chancre formation, either a single lesion or, less commonly, multiple lesions. Cellular immunity is of major importance in healing of early lesions and control of infection (TH1 type). Primary syphilis is the most contagious stage of the disease. Later syphilis is essentially a vascular disease, lesions occurring secondary to obliterative endarteritis of terminal arterioles and small arteries and by the resulting inflammatory and necrotic changes.

Laboratory Examinations

Dark-Field Microscopy. Positive in primary chancre and papular lesions of secondary syphilis such as condylomata lata. Unreliable in oral cavity because of the presence of saprophytic spirochetes, and negative in patients treated systemically or topically with antibiotics. Regional lymph node aspirated and aspirate examined in the dark-field microscope.

Direct Fluorescent Antibody T. pallidum (DFATP) Test Fluorescent antibodies are used to detect T. pallidum in exudate from lesion, lymph node aspirate, or tissue.

Serologic Tests for Syphilis (STS). Positive in persons with any treponemal infection. Tests always positive in secondary syphilis.

Nontreponemal STS. Measures IgG and IgM directed against cardiolipin—lecithin—cholesterol antigen complex. Rapid plasma reagin (RPR) test (automated RPR: ART). VDRL slide test; nonreactive in 25% of patients with primary syphilis. In early syphilis: either do fluorescent treponemal antibody-absorbed (FTA-ABS) test or repeat VDRL in 1-2 weeks if initial VDRL negative. Prozone phenomenon: if antibody titer high, test may be negative; must dilute serum; becomes nonreactive or reactive in lower titers following therapy for early syphilis.

Treponemal STS FTA-ABS Test. Agglutination assays for antibodies to T. pallidum: Microhemagglutination assay (MHA-TP; Serodia TPPA test); T. pallidum hemagglutination test (TPHA). Often remain reactive after therapy; not helpful in determining infectious status of patient with past syphilis.

Dermatopathology. In primary and secondary syphilis, lesional skin biopsy shows central thinning or ulceration of epidermis. Lymphocytic and plasmacytic dermal infiltrate. Proliferation of capillaries and lymphatics with endarteritis; may have thrombosis and small areas of necrosis. Dieterle stain demonstrates spirochetes.


Even without treatment, chancre heals completely in 4-6 weeks: the infection either becoming latent or clinical manifestations of secondary syphilis appearing. Secondary syphilis usually manifests as macular exanthem initially; after weeks, lesions resolve spontaneously and recur as maculopapular or papular eruptions. In 20% of untreated cases, up to three to four such recurrences followed by periods of clinical remission may occur over a period of 1 year. Infection then enters a latent stage, in which there are no clinical signs or symptoms of the disease. After untreated syphilis has persisted for >4 years, it is rarely communicable, except in the case of pregnant women, who, if untreated, may transmit syphilis to their fetuses, regardless of the duration of their disease. One-third of patients with untreated latent syphilis developed clinically apparent tertiary disease. Gummas hardly ever heal spontaneously. Noduloulcerative syphilides undergo spontaneous partial healing, but new lesions appear at the periphery.


Antibiotics (see p. 747749 for specific doses). Educate patients and treat sex partners.

Primary Syphilis ICD-9: 91.2 image ICD-10: A51 Image

Clinical Manifestation

Genital or extragenital lesions occur at sites of inoculation. Ulcers are usually painless unless secondarily infected. Incubation period: 21 days (average); range, 10-90 days.

Chancre Button-like papule develops at the site of inoculation into a painless erosion and then ulcerates with raised border and scanty serous exudate (Figs. 30-25 to 30-27). Surface may be crusted. Lesions few millimeters to 1 or 2 cm in diameter. Usually single lesions; less commonly, few, multiple, or kissing lesions. Extragenital chancres occur at any site of inoculatlon; lesions on the fingers may be painful.


Figure 30-25. Primary syphilis: penile chancre A 28-year-old male with penile lesion for 7 days. Painless ulcer on distal penile shaft with smaller erosion on the glans. The ulcer is quite firm on palpation.


Figure 30-26. Primary syphilis: nodule on glans A 58-year-old male with penile lesion for 10 days. Red firm nodule on the glans; the lesion resolved without therapy and did not ulcerate. Biopsy reported inflammatory changes. The diagnosis was made in retrospect when STS obtained before marriage was positive.


Figure 30-27. Primary syphilis: chancre on scrotum A 25-year-old male with painful lesion on scrotum for 10 days. A 1.5-cm ulcer on the scrotum, firm on palpation.

Sites of Predilection. Genital sites are most common. Male: inner prepuce, coronal sulcus of the glans penis, shaft, base. Female: cervix, vagina, vulva, clitoris, breast; chancres observed less frequently in women. Extragenital chancres: anus or rectum, mouth, lips, tongue (Fig. 30-28A), tonsils, fingers (painful!), toes, breast, nipple.



Figure 30-28. Primary and secondary syphilis A 24-year-old male with painful lesion on the tongue and disseminated rash. (A) Extragenital primary on tongue. A large ulceration on the tip of the tongue. (B) A disseminated papulosquamous eruption, i.e., secondary syphilis, was present at the time of the examination.

Lymphadenopathy. Appears within 7 days. Nodes are discrete, firm, rubbery, nontender, and more commonly unilateral; may persist for months.

Differential Diagnosis

Genital Erosion/Ulcer. GH, traumatic ulcer, fixed drug eruption, chancroid, lymphogranuloma venereum (LGV).


Clinical suspicion, confirmed by dark-field microscopy or serologically.


Intramuscular benzathine penicillin G 2.4 million units in single dose or oral doxycycline 100 mg twice daily for 14 days.

Secondary Syphilis ICD-9: 91.3 image ICD-10: A51.3 Image

Clinical Manifestation

Appears 2-6 months after primary infection; 2-10 weeks after appearance of the primary chancre; 6-8 weeks after healing of chancre. Chancre may still be present when secondary lesions appear (15% of cases) (Fig. 30-28). Concomitant HIV infection may alter course of secondary syphilis.

Fever, sore throat, weight loss, malaise, anorexia, headache, meningismus. Mucocutaneous lesions are asymptomatic.

Skin Lesions of Secondary Syphilis. Macules and papules 0.5-1 cm, round to oval; pink brownish-red. First exanthem always macular and faint. Later eruptions may be papulosquamous (Figs. 30-2930-30), pustular, or acneiform. Vesiculobullous lesions occur only in neonatal congenital syphilis (palms and soles). On palpation, papules are firm; condylomata lata, soft. Lesions may be annular or polycyclic, especially on face in dark-skinned persons (Fig. 30-31). In relapsing secondary syphilis, arciform lesions. Always sharply defined except for macular exanthem. Lesions are scattered, tend to remain discrete, and usually symmetric. Condylomata lata (Fig. 30-32): most commonly in anogenital region and mouth; can be seen on any body surface where moisture can accumulate between intertriginous surfaces, i.e., axillae or toe webs.


Figure 30-29. Secondary syphilis: papulosquamous lesion Typical red keratotic papules on the palm. (A) Subtle solitary papule on one palm only. (B) Multiple keratotic papules on palm.


Figure 30-30. Secondary syphilis: papulosquamous lesions A 20-year-old female with hyperkeratotic, scaling plaques on the plantar aspects of both feet. Similar lesions were present on the palms.


Figure 30-31. Secondary syphilis: annular facial lesions Annular plaques merging on the face of a South African woman. (Courtesy of Jeffrey S. Dover, MD.)


Figure 30-32. Secondary syphilis: condylomata lata Soft, flat-topped, moist, pink-tan papules and nodules on the perineum and perianal area. The lesions are teeming with T. pallidum.

Hair. Diffuse hair loss, including temples and parietal scalp. Patchy, moth-eaten alopecia on the scalp and beard area. Loss of eyelashes, lateral third of eyebrows.

Mucous Membranes. Small, asymptomatic, round or oval, slightly elevated, flat-topped macules and papules 0.5-1 cm in diameter, covered by hyperkeratotic white to gray membrane, occurring on the oral or genital mucosa. Split papules at the angles of the mouth.

Generalized Lymphadenopathy. Cervical, suboccipital, inguinal, epitrochlear, axillary. Splenomegaly.

Associated Findings. Musculoskeletal involvement: periostitis of long bones, particularly tibia (nocturnal pain); arthralgia; hydrarthrosis of knees or ankles without x-ray changes. Eyes: acute bacterial iritis, optic neuritis, uveitis. Meningovascular reaction: CSF positive for inflammatory markers. Gastrointestinal (GI) involvement: diffuse pharyngitis, hypertrophic gastritis, hepatitis, patchy proctitis, ulcerative colitis, rectosigmoid mass). Genitourinary involvement: glomerulonephritis and nephrotic syndrome, cystitis, prostatitis.

Laboratory Examinations

Dermatopathology. Epidermal hyperkeratosis; capillary proliferation with endothelial swelling; perivascular infiltration by monocytes, plasma cells, lymphocytes. Spirochete is present in many tissues including skin, eye, CSF.

CSF. Abnormal in 40% of patients. Spirochetes in CSF in 30% of cases.

Liver Function. Elevated enzymes.

Renal Function. Immune complex-induced membranous glomerulonephritis.


Recurrent eruptions appear after month-long asymptomatic intervals. Initially a relatively faint exanthem, always macular, pink; lesions are ill defined. Later lesions of early syphilis are papular, brownish, and tend to be more localized. Symptoms may last 2-6 weeks (4 weeks average) and may recur in untreated or inadequately treated patients. Secondary lesions subside within 2-6 weeks, infection entering latent stage.

Differential Diagnosis

Exanthem. Adverse cutaneous drug eruption, pityriasis rosea, viral exanthem, infectious mononucleosis, tinea corporis, tinea versicolor, scabies, “id” reaction, condylomata acuminata, acute guttate psoriasis, lichen planus.


Clinical suspicion confirmed by lab tests. Dark-field is positive in all secondary syphilis lesions except for macular exanthem.


As for primary syphilis (see p. 747).

Latent Syphilis ICD-9: 97.1 image ICD-10: A53.0 Image

image Suspected on the basis of a history of primary or secondary lesions, history of exposure to syphilis, or delivery of an infant with congenital syphilis; can occur without prior recognized primary or secondary lesions.

imageTreatment: As for primary syphilis (see p. 747).

Clinical Manifestation

No clinical signs or symptoms of infection; STS positive; CSF is normal.

Course. A previous negative STS defines the duration of latency. Early latent syphilis (< 1 year) is distinguished from late latent disease (≥ year). Latent disease does not preclude infectiousness or the development of gummatous skin lesions, cardiovascular lesions, or neurosyphilis. Maternal-fetal transmission can occur. Seventy percent of untreated patients never develop clinically evident tertiary syphilis. The more sensitive treponemal antibody test rarely becomes negative without treatment.

Tertiary/Late Syphilis ICD-9: 95 image ICD-10: 52.9 Image

Clinical Manifestation

Gumma. Nodular or papulosquamous plaques that may ulcerate and form circles/arc (Fig. 30-33). May expand rapidly causing destruction. May be indolent and heal with scarring. Solitary. Skin: any site, especially on scalp, face, chest (sternoclavicular), calf. Internal: skeletal system (long bones of legs), oropharynx, upper respiratory tract (perforation of nasal septum, palate), larynx, liver, and stomach.

Asymptomatic Neurosyphilis. Occurs in 25% of patients with untreated late latent syphilis. Lack neurologic symptoms/signs and CSF abnormalities. Twenty percent of patients with asymptomatic neurosyphilis progress to clinical neurosyphilis in first 10 years; risk increases with time.

Meningeal Syphilis. Onset of symptoms <1 year after infection; headache, nausea/vomiting, stiff neck, cranial nerve palsies, seizures, changes in mental status. Meningovascular syphilis. Onset of symptoms 5-10 years after infection; subacute encephalitis prodrome followed by stroke syndrome, progressive vascular syndrome.

General Paresis. Onset of symptoms 20 years after infection. PARESIS: Paresis, Affect, Reflexes (hyperactive), Eye (Argyll Robertson pupils), Sensorium (illusions, delusions, hallucinations), Intellect (decrease in recent memory, orientation, calculations, judgment, insight), Speech.

Tabes Dorsalis. Onset of symptoms 25-30 years after infection; ataxic wide-based gait and foot slap, paresthesia, bladder disturbances, impotence, areflexia, loss of position, deep pain, temperature sensations (Charcot or neuropathic joints, foot ulcers), optic atrophy.

Cardiovascular Syphilis. Results from endarteritis obliterans of vasa vasorum. Occurs in 10% of late untreated syphilis, 10-40 years after infection. Uncomplicated aortitis, aortic regurgitation, saccular aneurysm, coronary ostial stenosis.

Differential Diagnosis

Plaque(s) ± ulceration ± granulomas: Cutaneous tuberculosis, cutaneous atypical mycobacterial infection, lymphoma, invasive fungal infections.


Clinical findings, confirmed by STS and lesional skin biopsy; dark-field examination always negative.


In untreated syphilis, 15% of patients develop late benign syphilis, mostly skin lesions. Tertiary syphilis is now rare. Previously, patients presenting with tertiary syphilis gave a history of lesions of 3-7 years’ duration (range, 2-60 years); gumma developing by 15th year. As noted, there are neurologic and cardiovascular complications of tertiary syphilis if left untreated. Consider neurosyphilis in differential diagnosis of neurologic disease in HIV disease.


Intramuscular benzathine penicillin 2.4 million units once a week for three weeks. Patients allergic to penicillin should be treated by an infectious disease specialist.

Neurosyphilis. Consult CDC guidelines.

Congenital Syphilis ICD-9: 90 image ICD-10: A50.9 Image

imageTransmission. During gestation or intrapartum. Risk of transmission: Early maternal syphilis, 75-95%; >2 years’ duration, 35%.

imagePathogenesis. Lesions usually develop after fourth month of gestation, associated with fetal immunologic competence. Pathogenesis depends on immune response of fetus. Adequate treatment of mother before 16th week of pregnancy prevents fetal damage. Untreated: fetal loss up to 40%.

Clinical Manifestation

Early Manifestations. Appear before 2 years of age, often at 2-10 weeks of age. Infectious. Resembles severe secondary syphilis in adult. Bullae, vesicles on palms and soles, superficial desquamation, petechiae, papulosquamous lesions. Rhinitis or snuffles (23%); mucous patches, condylomata latum. Bone changes: osteochondritis, osteitis, periostitis. Hepatosplenomegaly, jaundice, lymphadenopathy. Anemia, thrombocytopenia, leukocytosis.

Late Manifestations. Appear after 2 years of age. Noninfectious. Similar to late acquired syphilis in adult. Cardiovascular syphilis. Interstitial keratitis. Eighth nerve deafness. Recurrent arthropathy; bilateral knee effusions (Clutton joints). Gummatous periostitis results in destructive lesions of nasal septum/palate. Asymptomatic neurosyphilis in 33% of patients; clinical syphilis in 25%.

Residual Stigmata. Hutchinson teeth [centrally notched, widely spaced, peg-shaped upper central incisors; “mulberry” molars (multiple poorly developed cusps)]. Abnormal facies: frontal bossing, saddle nose, poorly developed maxillae, rhagades (linear scars at angles of mouth, caused by bacterial secondary infection of early facial eruption). Saber shins. Nerve deafness. Old chorioretinitis, optic atrophy, corneal opacities due to interstitial keratitis.


Consult CDC guidelines.

Lymphogranuloma Venereum ICD-9: 99.1 image ICD-10: A55 Image

Image Clinical manifestations depend on the site of entry of C. trachomatis (the sex contact site) and the stage of disease progression: inguinal syndrome, rectal syndrome, and pharyngeal syndrome.

Etiology and Epidemiology

Etiology. C. trachomatis, obligate intracellular bacteria. Major outer-membrane protein delineates >20 serovars (immunotypes): Trachoma: Serovars A, B, Ba, and C. Mucosal STDs: Serovars D-K (most common bacterial STDs). Invasive STDs: Serovars L1, L2, L3, (in United States, L2 most commonly).

Transmission. Sexual: C. trachomatis in purulent exudate is inoculated onto skin or mucosa of sexual partner and gains entry through minute lacerations and abrasions. Perinatal. Heterosexual men: acute infection presents as inguinal syndrome. Women/homosexual men (MSM): Anogenitorectal syndrome most common.

Prevalence. Chlamydial urethritis more common in heterosexual men and high socioeconomic status. Prevalence of cervical infection in the United States: 5% for asymptomatic college students; >10% in family planning clinics: >20% in STD clinics.

Pathogenesis. Primarily an infection of lymphatics and lymph nodes. Lymphangitis and lymphadenitis occur in drainage field of inoculation site with subsequent perilymphangitis and periadenitis. Necrosis occurs; loculated abscesses, fistulas, and sinus tracts develop. As the infection subsides, fibrosis replaces acute inflammation with resulting obliteration of lymphatic drainage, chronic edema, and stricture.

Clinical Manifestation

Acute Lymphogranuloma Venereum. Primary genital lesion noticed in less than one-third of men and rarely in women. In heterosexual men and women: small painless vesicle or nonindurated ulcer/papule on penis or labia/posterior vagina/fourchette; heals in a few days. With receptive anal intercourse, primary anal or rectal infection develops after receptive anal intercourse. Infection can spread from primary site of infection to regional lymphatics.

Papule, shallow erosion or ulcer, grouped small erosions or ulcers (herpetiform), or nonspecific urethritis. Cordlike lymphangitis of dorsal penis may follow. Lymphangial nodule (bubonulus) may rupture, resulting in sinuses and fistulas of urethra and deforming scars of penis. Multilocular suppurative lymphadenopathy. Cervicitis, perimetritis, salpingitis may occur. Receptive anal intercourse: Primary anal rectal infection (hemorrhagic proctitis with regional lymphadenitis).

Erythema nodosum in 10% of cases (see Section 7).

Inguinal Syndrome. Characterized by painful inguinal lymphadenopathy beginning 2-6 weeks after presumed exposure. Unilateral in two-thirds of cases; palpable iliac/femoral nodes often present on same side (Fig. 30-33). Initially, nodes are discrete, but progressive periadenitis results in a matted mass of nodes that may become fluctuant and suppurative. Overlying skin becomes fixed, inflamed, thin, and eventually develops multiple draining fistulas. Groove sign: Extensive enlargement of chains of inguinal nodes above and below the inguinal ligament (Fig. 30-33).


Figure 30-33. Lymphogranuloma venereum: Groove sign Striking tender lymphadenopathy occurring at the left femoral and inguinal lymph nodes separated by a groove made by Poupart ligament (groove sign).

Unilateral bubo in two-thirds of cases (most common presentation) (Fig. 30-33). Marked edema and erythema of skin overlying node. One-third of inguinal buboes rupture; two-thirds slowly involute. Seventy-five percent of cases have deep iliac node involvement with a pelvic mass that seldom suppurates.

Anogenitorectal syndrome associated with receptive anal intercourse, proctocolitis, hyperplasia of intestinal and perirectal lymphatic tissue. Resultant abscesses, fistulas, and rectal stricture. Overgrowth of lymphatic tissue results in lymphorrhoids (resembling hemorrhoids) or perianal condylomata.

Esthiomene. Elephantiasis of genitalia, usually females, which may ulcerate, occurring 1-20 years after primary infection.

Differential Diagnosis

Primary Stage. GH, primary syphilis, and chancroid.

Inguinal Syndrome. Incarcerated inguinal hernia, plague, tularemia, tuberculosis, GH, syphilis, chancroid, lymphoma.


Diagnosis is based on clinical findings. Exclude other causes of inguinal lymphadenopathy or genital ulcers.


Highly variable. Bacterial secondary infections may contribute to complications. Rectal stricture is late complication. Spontaneous remission is common.


Oral doxycycline 100 mg twice daily for 21 days or oral erythromycin base 500 mg four times daily for 21 days.

Chancroid ICD-9: 099.0 image ICD-10: A57 Image

image Etiology: Haemophilus ducreyi, a gram-negative streptobacillus.

Epidemiology and Etiology

Etiology. H. ducreyi, a gram-negative streptobacillus.

Demography. Uncommon in industrialized nations. Endemic in tropical and subtropical developing countries, especially in poor, urban, and seaport populations. Much more common in young males. Lymphadenitis more common in males.

Transmission. Most likely during sexual intercourse with partner who has H. ducreyi genital ulcer. Chancroid is a cofactor for HIV/AIDS transmission; high rates of HIV/AIDS infection among those who have chancroid. Ten percent of individuals with chancroid acquired in the United States are coinfected with T. pallidum and HSV.

Pathogenesis. Primary infection develops at the site of inoculation (break in epithelium), followed by lymphadenitis. The genital ulcer is characterized by perivascular and interstitial infiltrates of macrophages and of CD4+ and CD8+ lymphocytes, consistent with a delayed type hypersensitivity, cell-mediated immune response. CD4+ cells and macrophages in the ulcer may explain the facilitation of transmission of HIV/AIDS in patients with chancroid ulcers.

Clinical Manifestation

Incubation period is 4-7 days.

Primary Lesion. Tender papule with erythematous halo that evolves to pustule, erosion, and ulcer. Ulcer is usually quite tender or painful. Its borders are sharp, undermined, and not indurated (Figs. 30-3430-35). Base is friable with granulation tissue and covered with gray to yellow exudate. Edema of prepuce common. Ulcer may be singular or multiple, merging to form large or giant ulcers (>2 cm) with serpiginous shape.


Figure 30-34. Chancroid Painful ulcer with marked surrounding erythema and edema. (Courtesy of Prof. Alfred Eichmann, MD.)


Figure 30-35. Chancroid Multiple, painful, punched-out ulcers with undermined borders on the vulva occurring after autoinoculation.

Distribution. Male: prepuce, frenulum, coronal sulcus, glans penis, shaft. Female: external genitalia, vaginal wall by direct extension from introitus, cervix, perianal. Extragenital lesions: breast, fingers, thighs, oral mucosa. Bacterial superinfection of ulcers can occur. Multiple ulcers (Fig. 30-35) (Fig. 30-28) develop by autoinoculation.

Painful Inguinal Lymphadenitis. Usually unilateral, occurs in 50% of patients 7-21 days after primary lesion. Ulcer may heal before buboes occur. Buboes occur with overlying erythema and may drain spontaneously.

Painful ulcer at the site of inoculation, usually on the external genitalia.

Regional Lymph Nodes. Tender adenopathy. Suppurative adenopathy.

STI most strongly associated with increased risk for HIV/AIDS transmission.

Synonyms. Soft chancre, ulcus molle, chancre mou.

Differential Diagnosis

Genital Ulcer. GH, primary syphilis, LGV, traumatic lesions.

Tender Inguinal Mass. GH, secondary syphilis, LGV, incarcerated hernia, plague, tularemia.


Combination of painful ulcer with tender lymphadenopathy (one-third of patients) is suggestive of chancroid. A definitive diagnosis of chancroid requires the identification of H. ducreyi on special culture media. Rule out HIV, T. pallidum, and HSV coinfection.


The time required for complete healing is related to the size of the ulcer; large ulcers may require 14 days. Complete resolution of fluctuant lymphadenopathy is slower than that of ulcers and may require needle aspiration through adjacent intact skin—even during successful therapy.


Azithromycin 1 g in single dose. Ciprofloxacin 500 mg twice daily for 3 days (contraindicated in pregnancy). Erythromycin base 500 mg three times daily for 7 days. Intramuscular ceftriaxone in single dose. Resistance to ciprofloxacin and erythromycin has been reported.

Donovanosis ICD-9: 099.2 image ICD-10: A58 Image

Image STI caused by Klebsiella granulomatis, an encapsulated intracellular gram-negative rod. Rare in industrialized nations. Endemic foci in tropical and subtropical environments.

Clinical Manifestation

Painless, progressive, ulcerative lesions of anogenital areas. Highly vascular (i.e., a beefy red appearance) (Fig. 30-36) and bleed easily on contact. Spreads by continuity or by autoinoculation of approximated skin surfaces. Distribution. Males: prepuce or glans, penile shaft, scrotum. Females: labia minora, mons veneris, fourchette. Ulcerations then spread by direct extension or autoinoculation to inguinal and perineal skin. Extragenital lesions occur in mouth, lips, throat, face, GI tract, and bone.


Figure 30-36. Donovanosis: ulcerovegetative type Extensive granulation tissue formation, ulceration, and scarring of the perineum, scrotum, and penis.

Regional Lymph Nodes. Not enlarged. Large subcutaneous nodule may mimic a lymph node, i.e., pseudobubo.

Variant Types. Ulcerovegetative (Fig. 30-36); nodular; hypertrophic; sclerotic/cicatricial.

Complications. Deep ulcerations, chronic cicatricial lesions, phimosis, lymphedema (elephantiasis of penis, scrotum, vulva), exuberant epithelial proliferation that grossly resembles carcinoma.

Differential Diagnosis

Differential diagnosis in endemic areas, syphilitic chancre, chancroid, chronic herpetic ulcer, LGV, cutaneous tuberculosis, invasive SCC.


Visualize Donovan bodies (rod-shaped organisms seen in cytoplasm of mononuclear phagocytes) in tissue samples or touch or crush preparation or in lesional biopsy specimen. Rule out other or concurrent cause of genital ulcer disease.


Little tendency toward spontaneous healing. Heals with antibiotic treatment. Relapse may occur.


All antibiotic treatments should be given for at least three weeks or until all lesions have healed.

Recommended Regimen. Oral doxycycline twice daily.

Alternative Regimen. Oral azithromycin 1 g once a week. Ciprofloxacin 750 mg twice daily. Erythromycin base 500 mg four times daily. Trimethoprim-sulfamethoxazole double strength tablet (160 mg/800 mg) twice daily.