Sexually Transmitted Diseases

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[edit] Sexually Transmitted Diseases

Robin R. Ingalls

Peter A. Rice

Sexually transmitted diseases (STDs) are a continuing public health problem, and the “traditional” venereal diseases, including syphilis, gonorrhea, chancroid, lymphogranuloma venereum, and granuloma inguinale, account for only a part of STDs in industrialized societies. Whether the measure of the problem is the number of infections and accompanying physical and psychologic morbidity or the resulting complications such as pelvic inflammatory disease (PID), infertility, and perinatal morbidity, most infections are caused by microorganisms outside the traditional sphere of venereology. Primary care physicians and other health care providers must understand the increased scope of the etiology, epidemiology, prevention, and pathogenesis of STDs if these conditions are to be recognized and managed in individual patients and controlled in populations. Although a syndromic approach may serve as a useful initial guide to a differential diagnosis, most STDs have overlapping modes of presentation, and individual infections may produce several complaints. Further evaluation, including physical and laboratory examinations, is usually necessary to make a specific diagnosis and to formulate a plan for management.

This chapter focuses primarily on men; Chapter 46 discusses vaginitis, mucopurulent cervicitis, and PID.

[edit] EVALUATION

Any person who engages in unprotected sexual activity is at risk for acquiring an STD, so screening is sound preventive medicine. Although the optimal frequency of STD screening visits is not well established, we recommend annual visits. In high-risk groups, such as sexually active adolescent females, testing for STDs should be offered twice a year.^[1][2] Indications for more frequent testing include a new partner and a history of sexually acquired infections.

[edit] Patient History.

A detailed sexual history is necessary, although time may be limited in a screening setting because of the extensive agenda. The physician should inquire about any history of sexual intercourse (frequency, last occurrence), gender preference, contraceptive or condom use, number of sexual partners within past 30 to 60 days and over patient's lifetime, and route of penetration (i.e., penile-vaginal, penile-anal, oral-genital). The normal review of systems should include asking about any symptoms of pain, discharge, dysuria, pruritus, or skin rashes. Female patients should describe their menstrual cycle, including timing of last menstrual period and symptoms of dysmenorrhea, amenorrhea, and spotting.

[edit] Physical Examination.

A routine examination should include inspection of the external genitalia and a general skin examination. The patient at risk for STDs should have a complete physical and genital examination.

The male examination should include inspection of the inguinal region, pubic hair, scrotum, and penile shaft for any skin lesions. The testes in the scrotal sac should be palpated for a mass or tenderness, and the patient should be taught testicular self-examination. A rectal examination should be done if the patient reports any symptoms or a history of receptive anal intercourse. A urethral swab for Gram's stain and specific testing for Chlamydia and gonorrhea should be obtained if history or examination warrants.

Females should have a breast examination, inspection of pubic hair and inguinal area, external genital assessment for discharge or lesions, and bimanual examination for evaluation of uterine size, cervical motion tenderness, and adnexal swelling or tenderness. At least once a year, sexually active females should have a speculum examination with a Papanicolaou (Pap) smear. The cervix should be examined for friability and discharge, and if warranted by history, endocervical specimens should be tested for gonorrhea and Chlamydia at least once a year, even in the absence of symptoms.

[edit] Laboratory Examination.

Clinical data alone are inaccurate predictors of most STDs, so diagnostic testing is routinely used to confirm any clinical suspicion. In addition to diagnostic testing, laboratory screening is especially useful when used to diagnose infections associated with few or no symptoms. Screening implies that a diagnostic test in an asymptomatic person will lead to early diagnosis of a disease and will improve the outcome, as with Pap smear screening of cervical cancer and early diagnosis of Chlamydia to prevent the complications of PID. A useful screening tool has been the development of an inexpensive, highly sensitive urine-based test for Chlamydia based on detection of plasmid deoxyribonucleic acid (DNA) by the polymerase chain reaction (PCR) or ligase chain reaction (LCR). Infections with generally asymptomatic pathogens, such as Chlamydia, syphilis, hepatitis B, and human immunodeficiency virus (HIV), are all useful targets for screening purposes.

[edit] Counseling and Contact Tracing.

All sexually active persons need to be educated about reducing risk factors for STDs and HIV infection. If an STD is diagnosed, sexual partners must be identified and treated as part of the patient's management. Because many infections are not reportable to the Centers for Disease Control and Prevention (CDC), the provider cannot rely on the partners being contacted by public health authorities. Voluntary notification of all partners must be judiciously emphasized to the patient as a mature and necessary action. In most states the health department will assist in partner notification, allowing the index case to remain anonymous; the patient is usually interviewed by a trained staff member, who obtains the names and location of sexual partners. Sexual partners at least should be brought to medical attention for examination. Treatment is often administered, even without symptoms or confirmatory laboratory tests, especially when the diagnosis of a treatable STD appears likely. Syphilis, gonorrhea, and acquired immunodeficiency syndrome (AIDS) are reportable diseases throughout the United States. The requirement for reporting other STDs, such as Chlamydia infection, varies from state to state.

[edit] MALE URETHRITIS

Urethritis, or inflammation of the urethra, is the most frequent STD found in men in developed countries. It is caused by an infection that leads to the discharge of mucopurulent or purulent material from the urethra and burning during urination. The only bacterial pathogens of proven clinical importance in men with urethritis are Neisseria gonorrhoeae and Chlamydia trachomatis.^[3]Ureaplasma urealyticum has also been associated with some cases of urethritis. Currently in the United States, most cases of sexually acquired urethritis do not have an established etiology. Although most of these have an epidemiologic pattern that is consistent with a recently acquired STD, they may have a waxing and waning course, and not all cases will respond to antibiotic therapy.

N. gonorrhoeae is a small, gram-negative diplococcus. During the course of infection in males, invasion of urethral epithelial cells by gonococci has been documented, thus explaining the usual clinical manifestation of acute anterior urethritis.^[4] Typically the incubation period is 2 to 5 days, followed by rapid onset of dysuria and purulent urethral discharge.^[5] Compared with other causes of urethritis discussed next, gonorrhea usually has a shorter incubation period and produces more intense symptoms of dysuria and discharge (Fig. 29-1, A). Although more than 95% of men infected with gonorrhea will develop overt urethritis and come to medical attention, a small proportion may remain asymptomatic.^[6] In the general population an estimated 2% to 10% of infected men never become symptomatic, accumulate in number over time, and constitute about two thirds of all infected men at any point in time.

Figure 29-1 Urethritis in men. A, Gonococcal urethritis classically produces profuse, purulent discharge. B, Nongonococcal urethritis (NGU) more often results in scant, mucoid discharge.

Nongonococcal urethritis (NGU) includes all cases from which N. gonorrhoeae is not isolated. Many organisms have been associated with NGU, but the only clinically important bacterial pathogen in men with urethritis is C. trachomatis. Chlamydia is an obligate intracellular organism estimated to account for 23% to 55% of NGU cases in men.^[3] Many men infected with gonorrhea are also coinfected with Chlamydia. NGU is now the most common bacterial STD in industrialized countries, and asymptomatic urethral carriage in men may be an even more important epidemiologic problem than urethritis with N. gonorrhoeae. The symptoms of NGU are similar to those of gonorrhea but are less intense and develop more slowly after a longer incubation period. Dysuria and urethral discharge occur in only about a third of men with NGU, and NGU is more likely to present with a single symptom than is gonococcal urethritis.^[7] When present, the discharge in NGU usually appears only after penile stripping. In contrast to gonococcal urethritis, NGU discharge is sparse, with a mucoid rather than a purulent appearance (Fig. 29-1, B).

[edit] Evaluation of History and Symptoms.

The symptoms of urethral infection in men may vary from vague discomfort to dysuria, or urinary frequency without a discharge to frank dysuria accompanied by a thick purulent discharge. The major historic features to be elicited from the patient are (1) recent sexual exposure; (2) estimate of the incubation period, if possible (i.e., last sexual contact); (3) recently acquired and treated STD, since the current event may represent a treatment failure or a reinfection with an untreated sexual partner; (4) drug allergies, particularly to penicillin; and (5) identification of sexual contacts. Urethritis may occur in association with urinary tract infections, bacterial prostatitis, urethral stricture, and phimosis and secondary to catheterization or other instrumentation of the urethra.

[edit] Physical and Laboratory Examinations.

If the patient is not circumcised, the foreskin should be retracted to examine the glans completely. Inability to retract the foreskin may indicate adhesion to the glans or phimosis. Edema of the foreskin may result from vigorous sexual activity or infection. For example, balanitis can occur from urethral discharge being trapped, resulting in an inflammatory reaction of the glans and the overlying foreskin. Hypospadias, or displacement of the urethral meatus to the underside of the shaft, is common and usually causes no problem. The examiner should carefully inspect for the presence and characteristics of a urethral discharge, which may be seen only as staining of the underwear. Unfortunately, the presence of a visibly clear urethral discharge or even small amounts of mucoid discharge does not always indicate urethritis. Other lesions on the penile shaft and at the base of the shaft and the presence or absence of inguinal lymphadenopathy should also be determined.

If a discharge is not present, the penis should be milked or stripped by applying gentle pressure over the ventral and dorsal surfaces of the base and moving the fingers toward the meatus to bring forward small amounts of discharge. Gonococcal urethritis usually results in a profuse and purulent discharge, in contrast to NGU, which is more often associated with a scant mucoid discharge (see Fig. 29-1). A dacron or rayon swab mounted on wire (not the routine wooden or nylon cotton swab) should be inserted 2 cm into the urethra to obtain a specimen for microscopic examination and culture. If sufficient moist material is obtained, the swab first is rolled on a glass slide for Gram's stain. If facilities are available for culture of gonorrhea, the remaining sample should then be transferred onto a modified Thayer-Martin plate for culture by rolling the swab in a large Z pattern. Because N. gonorrhoeae grows best in relatively anaerobic conditions, culture plates should be incubated at 37° C in a 2% to 10% carbon dioxide (CO₂) environment within 30 minutes of being plated. A candle jar is a simple and convenient way to achieve a CO₂ environment for growing gonorrhea. Culture media transport systems are also available if longer holding periods are required.

Although culture is considered the gold standard, it is not always practical. Alternate testing methods include a DNA probe, which can test for both gonorrhea and Chlamydia infection. PCR and LCR, which have become the mainstay of Chlamydia testing, are also available for diagnosis of gonorrhea. In a review of 21 studies on two nucleic acid–based tests, Gen-Probe and Amplicor LCR, for the diagnosis of gonorrhea, sensitivity was 85% and 98% and specificity 95% and 99%, respectively. When the proficient performance of culture is available, these tests offer no advantage over culture.^[8]

For diagnosis of Chlamydia infection, a second swab should be obtained, with particular attention paid to rolling the swab against the walls of the urethra so as to obtain sloughing cells where the Chlamydia organisms reside intracellularly. Obtaining discharge alone is not sufficient either for C. trachomatis antigen detection assays or for culture. In many settings, culture is impractical because Chlamydia must be grown intracellularly in a tissue culture facility. Rapid antigen tests are available (e.g., DFA, EIA), but most lack sufficient sensitivity and specificity, especially in asymptomatic men. The techniques of PCR and LCR have become the new gold standard of Chlamydia testing. They are highly sensitive and specific and can also be done with urine samples if urethral (or cervical) samples cannot be obtained (Box 29-1). Thus they are quite useful for screening populations at risk, such as adolescents. A recent study compared the cost-effectiveness of pelvic examination and culture with urine testing by LCR to prevent PID in sexually active, asymptomatic adolescent females.^[9] Urine-based LCR screening was the most cost-effective strategy to detect chlamydial and gonococcal infections in this population, and given the ease of implementation, it would likely prevent the greatest number of PID cases.

Gram's stain is often overlooked for diagnosis of STDs but is a sensitive test for the diagnosis of gonococcal urethritis in symptomatic men. We recommend that a Gram's stain be performed on any discharge and the stained smear examined under oil-immersion microscopy for polymorphonuclear neutrophils (PMNs) as well as for gram-negative intracellular diplococci (Fig. 29-2). The examiner should record exactly what is seen on the slide. To avoid counting superimposed cells, an area of the slide consisting of a monolayer of separate cells should be found. The presence of five or more white blood cells (WBCs) per field in five oil-immersion fields indicates an inflammatory discharge in a male. These criteria are analogous to those employed in men without apparent urethral discharge who are undergoing evaluation for signs and symptoms of urethritis.

Figure 29-2 Gram's stain of urethral discharge from patient with gonococcal urethritis. Note extensive number of neutrophils in discharge, as well as gram-negative intracellular diplococci in center of field.

The urinary dipstick leukocyte esterase test (LET) is also used to predict culture-verified urethral infections with C. trachomatis and N. gonorrhoeae in men.^[10] Although the sensitivity of this test varies with the status of clinical symptoms and the overall prevalence of infections in the population being tested, the specificity for either of these infections may be greater than 90%. Unfortunately, some men will have N. gonorrhoeae or C. trachomatis isolated when the urethral Gram's stain and first-voided urine sediment do not contain PMNs or when the LET is negative.

[edit] Confirmation of Urethritis.

According to the CDC guidelines, physicians should document that urethritis is present before treatment by any of the following signs: (1) mucopurulent or purulent discharge, (2) positive Gram's stain of urethral secretions demonstrating five or more WBCs per oil-immersion field, or (3) positive LET on first-voided urine, or microscopic examination of first-voided urine demonstrating 10 or more WBCs per high-power field. If none of these criteria is present, treatment should be deferred pending documentation of N. gonorrhoeae or C. trachomatis or appropriate clinical follow-up.^[3]

[edit] Treatment.

The following treatment recommendations are based on 1998 CDC guidelines.^[3] Options for the treatment of gonococcal urethritis include ceftriaxone, 125 mg intramuscularly (IM) in a single dose, or cefixime, 400 mg orally as a single dose. The spectra of activity for cefixime and ceftriaxone are quite similar, but ceftriaxone provides a higher and more sustained level of drug and is slightly better than cefixime (99.1% vs. 97.1%) in clinical trials.^[3] Other single-dose regimens include ciprofloxacin, 500 mg, or ofloxacin, 400 mg. For patients who cannot tolerate cephalosporins or quinolones, spectinomycin, 2 gm IM in a single dose, is an option. Because coinfection with C. trachomatis occurs in about 40% of patients with gonorrhea, treatment for Chlamydia is also recommended.

For treatment of NGU or chlamydial infection, two options are available: azithromycin, 1 gm orally as a single dose, or doxycycline, 100 mg orally twice a day for 7 days. Although some formulations are more expensive than doxycycline, azithromycin is the preferred agent because of patient compliance. For patients who cannot tolerate either regimen or for whom the drugs are contraindicated, erythromycin base, 500 mg four times a day for 7 days, is an alternative. Although single-dose therapy with 2 gm of azithromycin is effective against both gonorrhea and Chlamydia, it is generally not used because this increased dose is associated with significant gastrointestinal distress.

[edit] Follow-up.

Patients should be instructed to abstain from sexual intercourse until therapy is completed. All sexual partners within the previous 2 months should be referred for evaluation and treatment. Sexual contacts of symptomatic patients should be treated if their last sexual contact was within 30 days of the onset of symptoms; if the patient was asymptomatic, contacts should be treated if they were within 60 days. In the case of gonorrhea, partners should also be treated for Chlamydia infection.

Medical follow-up for urethritis is not routinely recommended. Increasingly, however, repeat DNA amplification assays performed 1 month after treatment in persons at high risk for STDs have resulted in a 10% positive (relapse or reinfection) rate. Patients should be instructed to return for evaluation if symptoms persist or recur after completion of therapy. Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, or suspicions of reinfection are not sufficient cause for re-treatment.

[edit] Recurrent or Persistent Urethritis

The management of persistent or recurrent symptoms of dysuria and discharge can be challenging. The physician must look for objective signs of urethritis before initiating another course of antimicrobial therapy. Because effective regimens have not been identified for treating patients with persistent symptoms or frequent recurrences after initial treatment, no set guidelines exist.

The evaluation should include a wet-mount examination and culture of an intraurethral swab specimen for Trichomonas vaginalis. Urologic examinations usually do not reveal a specific etiology. The simple cases show clear evidence of noncompliance or reexposure, and re-treatment should be offered. Often, re-treatment is attempted with the opposite drug than originally chosen (i.e., azithromycin or doxycycline), but it is not necessary to change agents. For the remainder of the cases, the differential diagnosis of dysuria should be expanded to include trichomoniasis or herpes simplex virus. Reiter's syndrome should also be considered.

If the patient was compliant with the initial regimen and reexposure can be excluded, the following regimen is recommended by the CDC.^[3] Metronidazole, 2 gm orally in a single dose, plus erythromycin base, 500 mg orally four times a day for 7 days, or erythromycin ethylsuccinate, 800 mg orally four times a day for 7 days.

[edit] EPIDIDYMITIS

Acute epididymitis is characterized by pain and swelling of the epididymis. Among sexually active men under age 35, epididymitis is most often caused by a C. trachomatis or N. gonorrhoeae. Epididymitis caused by sexually transmitted Escherichia coli infection can also occur among homosexual men who are the insertive partners during anal intercourse. Sexually transmitted epididymitis is usually accompanied by asymptomatic urethritis. Nonsexually transmitted epididymitis associated with urinary tract infections caused by gram-negative enteric organisms occurs more frequently among men over 35 years old, men who have recently undergone urinary tract instrumentation or surgery, and men with anatomic abnormalities.

The treatment for epididymitis is similar to that outlined earlier for urethritis, except doxycycline should be administered for 10 days, not 7; single-dose azithromycin is not recommended. For epididymitis most likely caused by enteric organisms or for patients allergic to cephalosporins or tetracyclines, the recommendation is for ofloxacin, 300 mg orally twice a day for 10 days. Although most patients can be treated on an outpatient basis, hospitalization should be considered when severe pain suggests other diagnoses (e.g., torsion, testicular infarction, abscess) or when patients are febrile or might be noncompliant with an antimicrobial regimen. Epididymitis is often associated with urethritis.

[edit] Follow-up.

Most patients should be reexamined 2 to 4 days after starting therapy. Failure to improve should prompt reconsideration of the diagnosis. The differential diagnosis includes tumor, abscess, infarction, testicular cancer, and tuberculous or fungal epididymitis. Partners should be treated for possible gonorrhea and chlamydial infection.

[edit] EVALUATION OF GENITAL SKIN LESIONS

Genital skin lesions can be classified broadly as ulcerative or nonulcerative. They may or may not have an infectious etiology, and not all infections are sexually transmitted. Numerous lesions are related to trauma; some are secondary to a dermatologic disorder or a neoplastic process. Even when all available tests are used by experienced physicians, as many as 40% of ulcerative lesions do not yield a specific diagnosis.

[edit] Evaluation of History and Symptoms.

Initially the patient should be questioned to determine if trauma is the cause of the genital lesion, particularly with an ulcerative lesion. If trauma is implicated, the onset of the lesion should have been noted shortly after the trauma, and the traumatic event should have been noticeably painful at the time. The patient should provide a complete history of sexual activity and uncommon sexual exposure. A history of vesicular lesions in a patient with genital erosion, particularly if the lesions are recurrent, suggests herpes simplex infection. Patients infected with pediculosis pubis or scabies may complain of significant pruritus, and erosions may be secondary to excoriation.

[edit] Physical and Laboratory Examinations.

In the assessment of patients with genital lesions, simple and careful clinical observations are essential in evaluating potential causes and in establishing priorities for the implementation of laboratory methods to assist and confirm the clinical impression. More than one STD may coexist, and thus ulcerative and nonulcerative patterns may be mixed. Clinical findings are sometimes diagnostic (e.g., herpetic vesicles) and with epidemiologic considerations may help guide initial therapy. Many genital ulcerations, however, cannot be diagnosed on examination alone. Syphilis must be excluded by appropriate serology in all patients. When possible, darkfield or direct immunofluorescent microscopy should be performed by experienced technologists on lesions that suggest primary (usually ulcerative) or secondary (usually nonulcerative) syphilis.

[edit] ULCERATIVE GENITAL LESIONS

The infectious causes of genital ulcers include HSV, Treponema pallidum, Haemophilus ducreyi, three specific serotypes of C. trachomatis, and Calymmatobacterium granulomatis. The incidence and etiology of sexually transmitted infectious causes of genital ulceration vary according to geographic area. In certain parts of Asia and Africa, genital ulceration is the usual reason for a patient to attend a clinic, and both syphilis and chancroid are very common. In Western industrial societies, urethritis and vaginitis are much more frequent reasons to visit clinics, herpes simplex infection is the most common form of ulceration, followed by syphilis and chancroid. Lymphogranuloma venereum and granuloma inguinale (formerly known as donovanosis) are rare causes of genital infections in the United States but are endemic in parts of Africa, South America, Asia, the Caribbean, Australia, and New Guinea. Thus it is important to obtain a travel history along with a sexual history, since casual sexual encounters during overseas travel may result in unusual causes of genital ulceration.

[edit] Patient Evaluation.

Although clinical features can often help differentiate between the various causes of genital ulcers, a diagnosis based only on the history and physical examination often is inaccurate. Therefore the evaluation of all patients with genital ulcers should include a serologic test for syphilis and an evaluation for herpes. Table 29-1 broadly classifies the differential diagnosis of genital ulcer disease, and Table 29-2 describes laboratory procedures that assist in the diagnosis of ulcerative lesions.

Table 29-1 Genital Ulcers

Table 29-2 Laboratory Procedures for Diagnosis of Sexually Acquired Genital Ulcerative Lesions

[edit] Genital Herpes

Genital herpes is caused by herpes simplex virus (HSV), a DNA virus with two serotypes. Type 1 is usually found in oral lesions but also causes 10% to 20% of genital herpes. In contrast, type 2 occurs predominantly in genital infections. The two types can be distinguished by various laboratory techniques, including differing cytopathic effects, neutralization, and immunofluorescence. In general, genital infection with HSV-1 is associated with less severe disease and fewer recurrences than with HSV-2.

[edit] Clinical Manifestations.

After skin inoculation, HSV replicates locally, producing the characteristic thin-walled vesicle on an inflammatory base. The incubation period of primary genital herpes is typically 3 to 5 days but can range from 2 to 7 days. At the onset, prodromal burning of the skin occurs, usually followed by the appearance of grouped vesicles. These vesicles rupture to form multiple shallow painful ulcers, which may coalesce into one or more larger ulcers (Fig. 29-3). In men, herpetic lesions typically occur on the glans, prepuce, or shaft of the penis; in women the labia minora and majora and the fourchette are often affected. In 90% of women with primary genital herpes, HSV can be recovered from the cervix, even without clinically apparent lesions. Homosexual men often have perianal herpetic lesions, making defecation intensely painful.

Figure 29-3 Genital ulcerative lesions in men. A, Primary syphilis is associated with solitary, round ulcers that are usually superficial with raised edges. B, Chancre associated with chancroid may be multiple, with irregular shape, rough surface, and undermined edges. C, Herpetic ulcers initially appear as vesicles that evolve into multiple, painful, superficial ulcers. (A and C from Meheus A, Ursi JP: Sexually transmitted diseases, Kalamazoo, Mich, 1982, Upjohn.)

The predominant symptom in primary HSV is pain. In addition, tender bilateral inguinal lymphadenopathy, dysuria, and constitutional symptoms (e.g., malaise, fever, headache) are also common. Complications include the development of extragenital lesions, which may occur in up to 20% of patients, and aseptic meningitis. In some patients, HSV may cause a sacral radiculitis, leading to constipation, urinary retention, and perigenital anesthesia.^[11] Without bacterial superinfection the course is usually self-limited, and healing occurs in 1 to 3 weeks. Concurrent HIV infection, however, may lead to a more severe, prolonged course of disease.

In recurrent genital herpes the ulceration is often milder, and the associated constitutional symptoms are slight or absent. A prodrome of itching, burning, or tingling often precedes the appearance of lesions. Lesions are usually less painful and fewer in number than with the primary episode and heal in 6 to 10 days. Viral shedding is possible between recurrences, and even without visible lesions, viral transmission can occur. In addition, autoinoculation from genital to extragenital sites (or vice versa) can occur, and patients should be cautioned about developing genital herpes from an oral lesion.

[edit] Diagnosis.

At present the most sensitive laboratory method for HSV diagnosis is tissue culture isolation. Recovery of virus is easier from an intact vesicle or early ulcer than from a late ulcer and is easier from primary than recurrent lesions. The sample should be collected in virus transport medium, held at 4° C, and sent to the laboratory within 12 hours. Although smear tests (immunofluorescence, immunoperoxidase, Pap) are specific for HSV, their sensitivity may be as low as 50%.^[3] The serology test demonstrates a fourfold rise in titer of antibodies to HSV, as detected by complement fixation or neutralization tests; however, the difficulties in collecting acute and convalescent sera and the delay in obtaining results make this an inferior method of diagnosis.

[edit] Treatment.

For the treatment of first clinical episodes of genital herpes, several options are available: acyclovir, 400 mg orally three times a day for 7 to 10 days; acyclovir, 200 mg orally five times a day for 7 to 10 days; famciclovir, 250 mg orally three times a day for 7 to 10 days; or valacyclovir, 1 gm orally twice a day for 7 to 10 days.^[3] The treatment can be extended if healing is incomplete after 10 days of therapy. Treatment of initial episodes of genital herpes generally prevents development of new lesions, hastens the period of crusting and healing, and shortens the time of viral shedding.

The physician must discuss the natural history of herpes infection with the patient during the initial episode, especially the potential for recurrent episodes, and the risk of sexual transmission during asymptomatic viral shedding. Patients should be encouraged to inform their sex partners that they have genital herpes and should be advised to abstain from sexual activity when lesions or prodromal symptoms are present. Condoms should be used during all sexual exposures with new or uninfected sex partners. The risk for neonatal infection should be explained to all patients, including men.

Because most patients with genital herpes will experience recurrent lesions, episodic or suppressive therapy should be discussed. If treatment can be instituted during the prodrome or within the first day of onset, episodic therapy can be beneficial. If patients experience frequent recurrences (e.g., more than six episodes per year), however, daily suppressive therapy may be preferable.

Treatment for recurrent episodes includes acyclovir, 400 mg orally three times a day for 5 days, 200 mg orally five times a day for 5 days, or 800 mg orally twice a day for 5 days; famciclovir, 125 mg orally twice a day for 5 days; or valacyclovir, 500 mg orally twice a day for 5 days.^[3]

For patients with frequent or severe recurrences, daily suppressive therapy is an option. The original studies done with acyclovir found the drug to be well tolerated and effective.^[12][13] Development of resistant virus while receiving long-term therapy, even after 6 years, has not been encountered, at least in immunocompetent individuals.^[14][15] Although suppressive therapy will reduce viral shedding, it will not eliminate it completely, and patients should be encouraged to discuss this with their sexual partners. Suppressive regimens include acyclovir, 400 mg orally twice a day; famciclovir, 250 mg orally twice a day; valacyclovir, 250 mg orally twice a day; or valacyclovir, 500 or 1000 mg orally once a day.^[3]

[edit] Syphilis

Syphilis is a systemic infection caused by T. pallidum subspecies pallidum, a slender, close-coiled, spiral organism that is motile and multiplies by binary fission every 30 hours. Although too slender to be seen by ordinary light microscopy, it is visible by darkfield or direct immunofluorescent microscopy. It has never been propagated in artificial media or in tissue culture but will grow in rabbit testicle tissue. The recent sequencing of the T. pallidum genome has disproved earlier reports that the organism contained endotoxin or lipopolysaccharide in the outer membrane.^[3]

[edit] Clinical Manifestations.

Clinically, syphilis can be divided into five stages: incubating, primary, secondary, latent, and late (or tertiary) syphilis. Incubating syphilis refers to the period between exposure and onset of symptoms. Primary syphilis has an incubation period of 9 to 90 days and is characterized by an ulcer or chancre at the site of inoculation (see Fig. 29-3). In men the primary chancre develops at the frenulum, coronal sulcus, urinary meatus, or shaft of the penis. In women primary chancres occur on the labia, at the fourchette, near the clitoris, or sometimes on the cervix. In anoreceptive homosexual men, chancres may appear at the anus or in the anal canal, although they may easily escape diagnosis because they are often inconspicuous.

A primary chancre first appears as a papule that soon becomes eroded, forming a well-defined, hardened ulcer with a sloughing or granulating floor. Although slow to heal, the ulcer is painless, unless it becomes secondarily infected. This is in contrast to HSV ulcers, which are typically painful. Primary chancres are usually single, but about 15% of patients have multiple chancres. Within a week or so of chancre appearance, inguinal lymphadenopathy, either unilateral or bilateral, develops in most patients. The nodes are discrete, rubbery in consistency, and usually painless.

After infection with T. pallidum, the organism enters the bloodstream and disseminates throughout the body; any organ can be invaded. This marks the beginning of secondary syphilis, usually 2 to 8 weeks after the appearance of the chancre. Secondary syphilis has many manifestations, but the classic and most common presentation is a rash. The appearance can be macular, papular, maculopapular, and pustular. Except for congenital syphilis, however, the rash is never vesicular. The location is typically the truncal and proximal extremities, but any site can be involved. Other skin manifestations include papular cutaneous lesions on the genitals or near the anus, which may erode to form shallow ulcers, and mucous patches that may appear on the oral or genital mucosa. In addition, diffuse or patchy alopecia can occur, as well as the loss of eyelashes and lateral eyebrows.

Because the rash of secondary syphilis can mimic almost any dermatologic condition, it is often prudent to obtain a sexual history from a patient with a rash and send tests when appropriate. Patients with secondary syphilis often have other systemic signs and symptoms, including lymphadenopathy, constitutional symptoms (e.g., fever, malaise, pharyngitis), and central nervous system symptoms (e.g., headache, meningismus). Hepatitis, glomerulonephritis, and arthritis have also been reported. Because of the variety of presentations, secondary syphilis has been called “the great imitator.”

Latent syphilis is defined as the stage at which the serologic test is positive but the patient has no clinical manifestations. Latent syphilis is termed early latent syphilis during the period when clinical relapses resembling secondary syphilis occur, usually within the first 1 to 2 years after primary infection; beyond this period all other cases of latent syphilis are either late latent syphilis or syphilis of unknown duration. In theory the treatment for late latent syphilis, as well as tertiary syphilis, requires a longer duration of therapy because organisms are dividing more slowly, but this has never been proved.

Late syphilis, or tertiary syphilis, is a slowly progressive disease that can affect any organ system in the body and produce illness years after the initial infection. Depending on the site involved, it is referred to as neurosyphilis, cardiovascular syphilis, or gummatous syphilis.

[edit] Diagnosis.

The following recommendations are based on current CDC guidelines.^[3] The definitive diagnosis of early syphilis requires the detection of T. pallidum, usually by darkfield or direct immunofluorescent microscopy, in fluid obtained from lesions or from aspirated lymph nodes. This technique requires a specialized microscope and experienced reader. PCR has recently been studied to detect T. pallidum in ulcer swabs, and a multiplex-PCR reaction is available that can simultaneously amplify for H. ducreyi, T. pallidum, and HSV-1 and HSV-2.^[16] A presumptive diagnosis of syphilis can be made using serologic tests, although serology is less reliable in early disease (i.e., when the patient presents with an ulcer), and should be repeated a week later when serologic tests are negative and a diagnosis of primary syphilis is suspected.

The two types of serologic tests for syphilis are (1) nontreponemal, Venereal Disease Research Laboratories (VDRL), or rapid plasma reagin (RPR) tests and (2) specific treponemal tests; fluorescent treponemal antigen-absorbed (FTA-ABS) or microhemagglutination assay (MHA-TP). Both tests are clinically useful, and together they are used to plan diagnosis and treatment. The nontreponemal tests are usually obtained first as a screening test. Because false-positive nontreponemal test results can occasionally occur, usually secondary to concurrent medical conditions, all positive nontreponemal tests must be confirmed with one of the specific tests (Box 29-2). Nontreponemal tests should be reported quantitatively, as a titer, which usually correlates with disease activity and should be used to assess response to therapy. Because of test variability, a fourfold change in titer, equivalent to a change of two dilutions (e.g., from 1:16 to 1:4 or from 1:8 to 1:32), is considered a clinically significant difference between two test results. Nontreponemal tests should become negative following therapy, although in some patients the test can remain positive with a low titer. In these cases the patients are considered serofast, and the test will remain positive for the remainder of their lives, regardless of treatment or disease activity.

The diagnosis of neurosyphilis can be more complicated (see Chapter 165 ).

[edit] Treatment.

The CDC^[3] recommends the following therapies for syphilis in nonimmunocompromised patients.^[3] Penicillin G is the drug of choice for treatment of all stages of syphilis. The tetracyclines are also effective and can be used in nonpregnant, penicillin-allergic patients. Penicillin is the only therapy with documented efficacy for neurosyphilis. The Jarisch-Herxheimer reaction may occur within the first 24 hours after therapy for syphilis. This reaction consists of an acute febrile illness accompanied by headache and myalgias. Patients should be warned about this acute illness, and antipyretics may be used as needed.

For cure, serum levels of penicillin must reach at least 0.03 μg/ml for a minimum of 7 days. The treatment for primary and secondary syphilis, 2.4 million U of benzathine penicillin G administered IM in a single dose, will ensure that these levels are reached. Patients who are allergic to penicillin should be treated for 2 weeks with oral doxycycline, 100 mg twice a day, or tetracycline, 500 mg four times a day. With no proven alternatives to penicillin, the pregnant woman with penicillin allergy should be treated with penicillin after undergoing desensitization. Erythromycin should not be used because it does not reliably cure an infected fetus. Some physicians treat secondary syphilis with longer regimens, reasoning that the duration of therapy must increase as the disease progresses. Such prolonged regimens include a second injection of benzathine penicillin G, 2.4 million U administered 1 week after the first. Some physicians prescribe the second dose of benzathine penicillin G for primary syphilis as well.

Patients who have latent syphilis should be evaluated for evidence of tertiary disease. If no evidence of neurosyphilis is found on cerebrospinal fluid (CSF) examination, treatment consists of benzathine penicillin G, 7.2 million U total, administered IM as three doses of 2.4 million U at 1-week intervals. Patients with neurosyphilis or syphilitic eye disease should be treated with 18 to 24 million U of aqueous penicillin G, administered as 3 to 4 million U IV every 4 hours for 10 to 14 days.

[edit] Follow-up.

Response to therapy should be monitored by clinical examination and a quantitative reagin test (VDRL or RPR) at 3 and 6 months after treatment. Patients being treated for neurosyphilis should also have CSF examination repeated every 6 months until it is normal. Successful treatment of seropositive early syphilis reduces the reagin titer. The FTA-ABS test often remains reactive indefinitely and is therefore not useful for follow-up. Persistent or recurrent symptoms and a sustained fourfold rise in the nontreponemal test titer suggest treatment failure or reinfection. If the titer does not decline by fourfold at 3 months, the patient also is at risk for treatment failure. In a pregnant woman this titer should decrease at 1 month, and if not, she should be re-treated. After 1 year, all adequately treated patients with seropositive primary syphilis have become seronegative; after 2 years, 95% to 100% of patients with secondary syphilis are seronegative. If, after 2 years, reagin tests are either negative or stabilized at a low titer, further follow-up is not needed. Homosexual men and members of other high-risk groups, however, should be urged to undergo serologic testing every 6 months indefinitely.

Sexual transmission of T. pallidum occurs only when mucocutaneous syphilitic lesions are present, but persons exposed sexually to a patient with syphilis in any stage should be evaluated clinically and serologically. Again, persons who were exposed within the 90 days preceding the diagnosis of primary, secondary, or early latent syphilis in a sex partner might be infected even if seronegative.

[edit] Human Immunodeficiency Virus and Syphilis.

Concurrent HIV disease is a special situation that requires rather close patient follow-up. First, HIV-infected patients can have abnormal serologic test results (i.e., unusually high, unusually low, and fluctuating titers), making it difficult to determine response to therapy. Second, minor CSF abnormalities are not uncommon in HIV disease even without other central nervous system infections. Often this leads to confusion about the diagnosis of possible neurosyphilis. Thus it is important that HIV-infected patients be evaluated clinically and serologically for treatment failure at 3, 6, 9, 12, and 24 months after therapy. Although unproved, many experts also recommend a CSF examination after therapy (i.e., at 6 months). HIV-infected patients who meet the criteria for treatment failure should be managed the same as those without concurrent HIV. Also, penicillin regimens should be used to treat all stages of syphilis in HIV-infected patients; those with penicillin allergy should be considered candidates for desensitization, especially if being treated for latent syphilis.

[edit] Chancroid

The etiologic agent of chancroid is Haemophilus ducreyi, a short, gram-negative rod with rounded ends. In stained clinical specimens it is usually obscured by other organisms. H. ducreyi is fastidious, requiring special enriched media for culture. Improved culture techniques have shown that chancroid is a more common cause of genital ulcer disease than previously thought. A recent study found the prevalence of chancroid in genital ulcers on culture to range from 12% in Chicago to 20% in Memphis.^[17] In addition, coinfection with HIV, T. pallidum, or HSV may occur.

[edit] Clinical Manifestations.

The incubation period of chancroid is 1 to 5 days. The lesions are papular at first but soon form superficial ulcers that are multiple, ragged, and painful, but not indurated (see Fig. 29-3). The granulation tissue at the ulcer base may be covered with a necrotic exudate and easily bleeds with manipulation. In men, ulcers occur at the meatus (where they may cause phimosis or paraphimosis) or on the glans or shaft of the penis. Homosexual men often develop perineal or anal ulceration. In women, ulcers often affect the introitus, labia, and vagina; perianal ulcers in women are often small and may not be painful. Thus a careful examination is important in recognizing these lesions. Genital and perianal chancroid heals slowly. More than 50% of patients develop regional inguinal lymphadenopathy. Lymph nodes become painful and tender, and suppuration may cause a fluctuant inguinal abscess (see Table 29-1).

[edit] Diagnosis.

A definitive diagnosis of chancroid requires identification of H. ducreyi on special culture media not widely available commercially. If culture is an option, a swab from the ulcer should be plated directly onto enriched chocolate agar, which is then incubated in a 5% to 10% CO₂ environment at 33° C. Colonies may not appear for a week or longer. Even with the appropriate media, sensitivity is 80% or less. In areas with infrequent cases, results of culture are correspondingly less satisfactory. PCR has recently emerged as a sensitive diagnostic assay for chancroid.^[18] Also, multiplex-PCR reaction can simultaneously amplify for H. ducreyi, T. pallidum, and HSV-1 and HSV-2.^[16] No reliable serologic test exists for chancroid. Thus the diagnosis is most often a clinical one. The combination of a painful ulcer and tender inguinal adenopathy, which occurs among one third of patients, suggests chancroid; when accompanied by suppurative inguinal adenopathy, these signs are almost pathognomonic. According to CDC guidelines,^[3] probable diagnosis, for both clinical and surveillance purposes, may be made if certain criteria are met (Box 29-3).

[edit] Treatment.

The CDC currently recommends three regimens for treatment of chancroid: (1) single-dose therapy with azithromycin, 1 g orally, or ceftriaxone, 250 mg IM; (2) ciprofloxacin, 500 mg orally twice a day for 3 days; or (3) erythromycin base, 500 mg orally four times a day for 7 days. Because its safety has not been established, azithromycin should not be administered to pregnant or lactating women. Ciprofloxacin is contraindicated in pregnancy. Patients should be reexamined 3 to 7 days after starting therapy. If there is no clinical improvement, the physician should reconsider the diagnosis or the patient's compliance.

After successful treatment, prolonged follow-up of chancroid is not necessary. However, if nontreponemicidal drugs were used in the treatment, the patient should undergo a final serologic test for syphilis 3 months after the original exposure to infection.

[edit] Lymphogranuloma Venereum

Lymphogranuloma venereum (LGV) is a rare disease in the United States caused by C. trachomatis serovars L1, L2, and L3. These strains are immunologically distinct from the C. trachomatis strains associated with ocular disease and urethritis/cervicitis.

[edit] Clinical Manifestations.

The incubation period of LGV is typically less than a week. The initial lesion, a small papule or painless herpetiform ulcer, is transient and inconspicuous. The patient and physician often fail to notice these lesions, which may be seen in women; in men they appear on the glans or shaft of the penis. The most prominent feature of early LGV is inguinal adenitis, which follows the primary lesion by a few days to several weeks. Both inguinal and femoral lymph nodes may be affected. Large, tender masses of nodes appear, sometimes grooved by the inguinal ligament. Lymphadenopathy may be unilateral or bilateral. Abscesses form, causing fluctuant swellings that can discharge spontaneously. Women and homosexual men may have proctocolitis or inflammatory involvement of perirectal or perianal lymphatic tissues, which can result in fistulas and strictures. The inflammation is chronic, with extensive fibrosis, and clinically may be confused with anal carcinomas. Recovery from lymphadenitis is slow, especially without prompt treatment.

[edit] Diagnosis.

The diagnosis usually is made serologically and by exclusion of other causes of inguinal lymphadenopathy and genital ulcers, such as syphilis, herpes, chancroid, bacterial lymphadenitis, and lymphoproliferative disorders. The most common diagnostic test is a complement fixation test, which uses either LGV or psittacosis antigens; a microimmunofluorescence test is somewhat less widely available. In a patient with LGV the complement fixation test becomes positive a week or two after the infection is acquired, usually with a titer of 1:64 or higher. It is usually impractical to demonstrate a rising titer of antibodies, since in clinical practice, serology is often limited to a single test.

If chlamydial culture facilities are available, LGV may be conclusively diagnosed by isolation of the agent from aspirated buboes. Although the Chlamydia detection can probably be accomplished with PCR, the use of this test on aspirated pus has not been rigorously studied.

[edit] Treatment.

The preferred agent for treatment of LGV is doxycycline, 100 mg by mouth twice a day for 3 weeks. Erythromycin base, 500 mg orally four times a day, is an alternative. Pregnant women should be treated with erythromycin. Azithromycin may be effective in multiple doses over 2 to 3 weeks, but clinical data are lacking.^[3] Patients should have follow-up until symptoms have resolved. If the chosen regimen has not resulted in a good clinical response, it may need to be repeated. The stage of the disease when treatment is begun appears to be the most important predictor of success. Inguinal abscesses should undergo aspiration rather than incision.

[edit] Granuloma Inguinale

Granuloma inguinale is a poorly understood disease caused by the intracellular gram-negative bacterium, Calymmatobacterium granulomatis. A rare disease in the United States, it is endemic in certain tropical and developing areas, including India, Papua New Guinea, central Australia, and southern Africa. The causative organism cannot be cultured on standard microbiologic media, and diagnosis requires visualization on tissue crush preparation or biopsy of dark-staining C. granulomatis (Donovan bodies) within the cytoplasm of macrophages. Because this organism cannot be readily cultured and has not been thoroughly characterized, the Koch's postulates have not been fulfilled.

[edit] Clinical Manifestations.

Granuloma inguinale presents clinically as painless papules on the genitals. These lesions ulcerate and slowly develop into granulation tissue, which spreads over large areas of the genitals without regional lymphadenopathy. The lesions are highly vascular (i.e., beefy red in appearance) and bleed easily on contact. Although inguinal adenitis does not occur, pseudobuboes (subcutaneous granulations in the inguinal region) may appear. In anoreceptive homosexuals, granulating lesions develop at the anus and may spread to surrounding areas.

[edit] Diagnosis.

Microscopy of lesion specimens can confirm a clinical diagnosis. The examiner removes a small fragment of granulomatous tissue from the lesion's edge and smears the undersurface on a glass slide. The specimen is then dried, fixed with methanol, and stained with Wright-Giemsa. Microscopic viewing reveals Donovan bodies within large mononuclear tissue cells; these pink, ovoid bodies are surrounded by two capsules and exhibit bipolar staining. This may be the only aid to diagnosis; culture for C. granulomatis is not routinely available, and no serologic test exists.

[edit] Treatment.

Treatment recommendations include trimethoprim-sulfamethoxazole, one double-strength tablet twice a day for 3 weeks, or doxycycline, 100 mg twice a day for 3 weeks. Patients should be seen for monthly follow-ups until all lesions are healed.^[3]

[edit] NONULCERATIVE GENITAL LESIONS

Nonulcerative lesions may also appear on the genital surfaces. Some may be infected but not sexually acquired; others are caused by STDs. With the exception of syphilis, the diagnosis of nonulcerative genital lesions is predominantly clinical. However, this clinical diagnosis must be supplemented by biopsy if the diagnosis is unclear or if a premalignant condition is suspected. Genital warts are the most common nonulcerative genital lesion seen, and their appearance is familiar but varied. Condylomata acuminata, genital warts, must be distinguished from warts seen in secondary syphilis, condylomata lata. Often this is only possible with darkfield analysis and serologic testing for syphilis. Again, the two diseases may coexist, so inclusion of one does not always exclude the other. The presence of a smooth rounded umbilicated papule varying in size from barely visible to 3 to 4 mm in diameter suggests a diagnosis of molluscum contagiosum. Sexually transmitted pruritic lesions are usually caused by either scabies or crab lice. Specific diagnostic features, including laboratory investigations, are described later under each condition.

Biopsy for anogenital warts is problematic. Although most are benign, malignancy does develop in some; warts that fail to respond to treatment or that are atypical in any way should be excised for histopathologic examination. Previous podophyllin therapy may make the histology difficult to interpret.

Pruritic lesions should be evaluated for scabies or crab lice. Some nonulcerative genital or anal lesions are caused by STDs. Others are infective but are caused by organisms not sexually transmitted. Others are noninfective, but since they enter into the differential diagnosis of STDs, the physician needs to be familiar with them.

[edit] Anogenital Warts

Human papillomavirus (HPV) is the etiologic agent of genital warts. Infection with HPV has increased tenfold over the past 15 years, making anogenital warts the most frequently diagnosed STD in the United States. More than 30 types of HPV infect the anogenital skin and mucosa, causing condylomata and intraepithelial neoplasia of varying severity. HPV types 6 and 11 are associated most often with anogenital warts. HPV types 16, 18, and 45 are distinguished from the others by their strong association with high-grade intraepithelial neoplasia and anogenital malignancy. The oncogenic activity of HPV appears to be related to the expression of three proteins, E6, E7, and E5, which disrupt the normal control of the cell cycle.^[19]

HPV has a specific cell tropism and infects the basal layer of squamous or transitional epithelium. As a result of HPV infection, epithelial cells are stimulated to grow, producing hyperplastic proliferation of the epidermis (acanthosis) often associated with increased superficial keratin (hyperkeratosis). The host response to HPV infection is poorly understood, but an intact immune system is clearly important in the control of infection. Patients with immune deficiencies, such as HIV infection or transplant recipients, have much more frequent and severe disease.

[edit] Clinical Manifestations.

Genital warts often result from intercourse with individuals who already have warts. The incubation period is 2 to 3 months. On moist surfaces these lesions appear as sessile or pedunculated exophytic lesions, known as condylomata acuminata. Condylomata begin as minute swellings, rapidly growing into fleshy exophytic lesions with pointed surfaces and sometimes fusing into large, irregular masses. In men, condylomata often develop on the glans penis, prepuce, coronal sulcus, or within the urethral meatus (Fig. 29-4, B). Typical sites in women include the labia, vaginal introitus, and perianal region. Condylomata may also occur internally on the cervix or vagina and should be suspected in women with vulvar warts.

Figure 29-4 Nonulcerative genital lesions. A, Molluscum contagiosum of suprapubic area. Note flesh-colored papules with central umbilication. B, Typical condylomata of penile warts, most often associated with human papillomavirus type 6 or 11. (A from Holmes KK et al, editors: Sexually transmitted diseases, New York, 1984, McGraw-Hill; B, from Bingham JS: Pocket picture guides: sexually transmitted diseases, London, 1994, Gower.)

Other clinical manifestations of HPV infection include papular warts, which are usually small, multiple, keratotic, and less papillary. These usually occur on nonmucosal surfaces such as the penile shaft in men or the labia majora in women. More often, however, HPV infection is subclinical.

[edit] Diagnosis.

The diagnosis of genital warts is usually clinical. For subclinical infections with HPV, detection can be accomplished only by soaking the area with 3% to 5% acetic acid for 2 to 5 minutes and examining either directly or under magnification for shiny, aceto-whitened areas. Aceto-whitening is not specific for HPV, however, and false-positive tests are common. Colposcopy has been the traditional method of detecting HPV infection in women, but it has recently been advocated for use in male patients as well.

Cytologic and histopathologic examination is helpful in establishing a diagnosis of HPV infection, but its accuracy is difficult to determine without a gold standard for comparison. The classic cytologic findings of HPV infection include squamous cells with hyperchromatic nuclei surrounded by a perinuclear clear zone (koilocytes), multinucleated giant cells, acanthosis, and papillomatosis. Newer methods of detecting HPV infection include nucleic acid hybridization techniques, Southern blot analysis, immunohistochemical techniques, and PCR. The accuracy of Pap smears is variable and depends on the sampling method and the pathologic criteria used. About 10% or more of tissue specimens from women with normal Pap smears may contain HPV DNA, as determined by these other methods, but the clinical significance of this viral DNA is unclear.

[edit] Treatment.

HPV infection is treated for a variety of reasons, including cosmetic purposes, symptomatic improvement, reduction of viral transmission, and prevention of neoplasia. No current data, however, prove that treatment affects either the transmission or the natural history of the disease. The usual treatment for warts is cytotoxic therapy or ablative therapy.

For provider-administered treatment, several options are available.^[3] Cryotherapy with liquid nitrogen or cryoprobe can be applied every 1 to 2 weeks. Podophyllin resin (10% to 25%), an antimitotic agent, can also be applied to the lesions once or twice a week. A single application should not exceed 0.5 ml of a 25% solution because of the risk of absorption and ensuing toxic symptoms. Podophyllin should remain in contact with the lesions for 4 hours before being washed off. Trichloroacetic acid (TCA) or bichloroacetic acid (BCA) 80% to 90% can also be applied weekly. Finally, surgical removal is an option for large warts.

For patient-applied treatment, two options are recommended: podofilox 0.5% solution or imiquimod 5% cream. Patients apply podofilox daily for 3 days, followed by 4 days of no therapy, and repeat this cycle three more times if necessary. Imiquimod cream should be applied at bedtime three times a week for as long as 6 weeks.

The CDC currently recommends cryotherapy as first-line management for anogenital warts. Early studies on BCA and TCA cryotherapy are promising. Unlike podophyllin, TCA can be used in pregnant women and for cervical warts. Liquid nitrogen cryotherapy usually can be swabbed or sprayed onto a lesion. Each individual lesion is frozen down to its base with some adjacent epithelium. Unfortunately, depth of tissue destruction cannot be controlled, and cervical lesions extending into the endocervical canal cannot be reached. Ablative therapy can also be done by specialists with surgical excision, electrocautery/electrodissection, CO₂ laser therapy, and the loop electroexcisional procedure. Although laser therapy does not seem to impart any significant advantage over electrocautery and is costly, cautery is more effective than topical therapies, with recurrence rates of about 25%. Cautery and laser fumes, however, contain bioactive HPV particles, which can contaminate the mucous membranes of the surgical team.

Immunotherapy is probably based more on humoral responses than cell-mediated mechanisms. The direct injection of interferon-α into condylomata has been approved for refractory lesions, although it may have systemic side effects. Immunotherapy is probably most efficacious in an adjuvant setting. For example, trials have demonstrated significantly decreased recurrence rates of condylomata among patients treated with surgical ablation plus intralesional interferon compared with those treated with surgery alone.

All women with external anogenital warts or contacts of patients with anogenital warts should have a Pap smear. Any evidence of atypical cervical cytology is an indication for colposcopy. Patients with condylomata on the urethral meatus or perianal area should also undergo urethroscopic or proctoscopic examination, respectively. In the absence of coexisting dysplasia, treatment of subclinical HPV infection, as detected by Pap smear, colposcopy, biopsy, acetowhitening, or nucleic acid detection, is not recommended (see Chapter 46 ).

[edit] Genital Molluscum Contagiosum

Genital molluscum contagiosum is caused by a poxvirus that has not yet been cultured in vitro. Thus virologic techniques are not used for diagnosis. Although lesions can occur anywhere on the body, in adults they are particularly common on the genitals. The incubation period lasts from 2 to 8 weeks, after which lesions appear. These are raised, flesh-colored, umbilicated papules, 2 to 5 mm in diameter, each with a central depression containing a white plug made up of degenerated epithelial cells and viral inclusion bodies (Fig. 29-4, A). The lesions are found on the penis or scrotum in men, on the labia majora in women, and on the inner thighs and pubic area of both sexes.

The lesions are benign and usually resolve spontaneously without significant associated symptoms. In patients coinfected with HIV, however, molluscum can have a severe and unremitting course and may be found in areas outside the genital tract (see Chapter 32 ).

[edit] Scabies

Scabies are caused by the itch mite. The adult female, a round-bodied, eight-legged mite measuring 400 μm in length, travels across human skin at the rate of 2.5 cm (1 inch) per minute. The mite chooses a suitable location and burrows into the horny layer to the boundary of the stratum granulosum, remaining there for the rest of its approximately 30-day life. Within hours of burrowing it begins laying huge eggs, which develop into adult mites in 10 days. The average infested patient hosts about 11 adult female mites.

[edit] Clinical Manifestations.

The mites tend to settle in specific areas, especially the hands and wrists. Because the eruption is partially caused by immature stages of the mite and by sensitization, the distribution of scabietic lesions does not correspond to that of the adult females. In primary infestation, itching and eruption occur only after sensitization, which takes several weeks. Itching characteristically occurs at night.

The hands are frequently the first areas infested; the lesions, often eczematous, appear primarily on the finger webs and the sides of the digits. Lesions often develop on the flexor surfaces of the wrists, as well as on the extensor surfaces of the elbows (where lesions may be nodular but are usually dry and eczematous) and the anterior axillary folds. In women, eczematic lesions may develop on the breasts. Papular lesions often occur on the abdomen, frequently arranged in a spokelike pattern around the umbilicus. The penis is typically involved; here the lesions may take the form of nodules, pyoderma, or chancriform changes. The infestation may spread to the crease where the buttocks join the upper part of the thighs, causing impetiginous crusting in this area. In adults the palms, soles, scalp, face, neck, and upper back are usually not involved.

The pathognomonic burrow is a short wavy line, dirty in appearance, which often crosses skin lines. It appears most frequently on the finger webs, volar wrists, elbows, and penis. Most infested areas have small, erythematous, often excoriated papules, many of which are larval sites. Secondary eczematization and infection may obscure other features and make diagnosis more difficult. In general, scabies causes polymorphic lesions, although occasionally a patient has urticaria as the only cutaneous feature.

[edit] Diagnosis.

Diagnosis of scabies requires a specimen from freshly developed, unexcoriated papules or burrows; these can be located with the aid of a hand lens or head loupe. The physician places mineral oil on a sterile scalpel blade and allows the oil to trickle onto the lesions. Six or seven vigorous scrapes of the scalpel remove the surface of the burrows or papules, along with the oil. The specimen is placed on a glass slide, covered by a coverslip, and viewed under the microscope. The presence of any stage of the mite, or the more numerous fecal pellets, confirms the diagnosis.

[edit] Treatment.

The CDC-recommended treatment is 5% permethrin cream (Elimite), applied to all areas of the body from the neck down and washed off after 8 to 14 hours.^[3] Alternatives include 1% lindane (Kwell) lotion (1 oz) or cream (30 gm), applied thinly from the neck down and washed off thoroughly after 8 hours, or 6% sulfur ointment, applied nightly for 3 nights with thorough washing after the third night. Lindane should not be used after a bath, and it is not recommended for persons with extensive dermatitis, pregnant or lactating women, and children under 2 years of age. An alternative is pyrethrins with piperonyl butoxide, applied and washed off after 10 minutes. Bedding and clothing should be decontaminated as well, but decontamination of the living areas is not necessary. Pruritus can persist for several weeks, but some experts recommend re-treatment if patients are still symptomatic after 1 week. Sexual and close household contacts should be evaluated and treated if necessary.

[edit] Pediculosis Pubis (Pubic Lice)

Lice are wingless insects that are obligate parasites. Two species parasitize humans: pediculus humanus (which is subdivided into two populations, the head louse and the body louse) and Phthirus pubis, the pubic or crab louse, which causes pediculosis pubis. The pubic louse ranges from 0.8 to 1.2 mm in length and is broader than it is long. Powerful claws on the second and third pairs of legs enable the louse to latch onto the pubic hair. From egg to egg, the life cycle of the pubic louse is about 25 days.

[edit] Clinical Manifestations.

The pubic area is the most common site of infestation. Although the lice tend to remain at the initial site of contact, they occasionally spread to the hairs of the thighs and trunk, especially in hairy individuals, and even to the beard and mustache. Involvement of the eyelashes and periphery of the scalp occurs mainly in children and is probably acquired by close contact with an infested mother.

Pruritus, the most common symptom, begins about 30 days after exposure. Initiated by the louse inserting its mouthparts into a cutaneous cavity and sucking blood, the itching may be immunologic rather than mechanical. Excoriations may lead to pyoderma, which may obscure the organisms. Lymphadenitis and febrile episodes may ensue, although these secondary symptoms are probably less common in developed countries because of early diagnosis and prompt, effective therapy.

[edit] Diagnosis.

Although not common, the maculae ceruleae are characteristic of pubic lice infestation. These asymptomatic, bluish or slate-colored macules appear on the trunk and thighs and fade shortly thereafter. Two likely causes of the macules are hemoglobin breakdown products of the host and secretions from the parasite's salivary gland.

Involvement of areas other than the pubic region may complicate the diagnosis. Any pruritic eruption of a hairy area should suggest crab lice. In some cases, examination of other areas (e.g., axillae) may be more readily diagnostic, since the patient may have already eradicated the pubic infestation by self-treatment. Eyelash infestation is especially troublesome to diagnose because it may simulate seborrheic, infectious, or eczematous blepharitis; however, careful examination shows that the crusts consist of the parasites.

Pediculosis pubis is rare among STDs in that it can be diagnosed by physical examination alone. The adult lice can be identified with a magnifying lens, especially after feeding, when they become rust colored. Particles of rust-colored excreta may be visible at sites of infestation. Usually, however, the disease is diagnosed by recognizing the numerous nits or ova, which the parasites attach to the pubic hair with a cementlike secretion. Since the nits are initially affixed to the hair at skin level, then grow out with the hair, the length of the infestation can be estimated by the distance of the nits from the skin surface. Although the nits are visible to the naked eye, they can be confused with kinks and knots in the hair or flakes of seborrheic dermatitis. The diagnosis should be confirmed by plucking the hair and identifying the nit under the microscope.

[edit] Treatment.

The two CDC-recommended regimens are 1% permethrin cream rinse (Elimite), applied to all body areas from the neck down and washed off after 8 to 14 hours, or 1% lindane (Kwell) shampoo, applied thinly from the neck down and washed off thoroughly after 8 hours.^[3] Lindane should not be used after a bath, and it is not recommended for persons with extensive dermatitis, pregnant or lactating women, and children under 2 years of age. An alternative is pyrethrins with piperonyl butoxide, applied and washed off after 10 minutes. Bedding and clothing should be decontaminated as well, but decontamination of the living areas is unnecessary. Although pruritus can persist for several weeks, some experts recommend re-treatment if patients are still symptomatic after 1 week. Although corticosteroids may reduce the pruritus associated with pediculosis, they should be avoided. If used before diagnosis, corticosteroids potentiate the infestation, allowing it to become generalized.

Sexual contacts of pediculosis patients should be treated simultaneously to prevent reinfection; other noninfested household members need not be treated. Once the parasites have been eradicated, the patients and sexual partners should wash and dry all used underwear, pajamas, sheets, and pillowcases by machine (hot cycle) or have them dry-cleaned.

[edit] REFERENCES