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How to Recognize the
Top Three STDs in Women
Elusive and often misleading, these infections can have serious consequences if not caught in time. Here’s how to diagnose and treat them.
By Bisan Salhi, MD
We don’t know the true incidence and prevalence of most sexually transmitted diseases (STDs). Many aren’t reportable, and many patients have no obvious symptoms. What we do know is that STDs are exceedingly common diagnoses in emergency departments and urgent care centers. We also know that they cause a variety of long-term adverse health effects and psychological distress.
More than 25 STDs have been identified to date. The three most commonly diagnosed in women in the United States are genital herpes, cervicitis, and pelvic inflammatory disease (PID). This article will focus on how to identify often misleading symptoms of these diseases, treat primary and recurrent infection, and counsel patients on what can be a stressful, even life-altering illness.
Herpes Simplex virus
Genital herpes is the most prevalent STD in the United States, infecting more than 50 million people over age 12. Prevalence has jumped 30% since the late 1970s, particularly among young adults. More women are infected than men. Herpes infection is also more common as people age.
It was previously thought that genital herpes was caused exclusively by herpes simplex virus (HSV) 2. It is now known that HSV-1, like HSV-2, can be spread via contact with infected bodily fluids. Although the majority of genital herpes infections are still caused by HSV-2, HSV-1 genital infections are becoming increasingly common. The two strains are clinically indistinguishable, but HSV-1 tends to cause less severe outbreaks with fewer recurrences than HSV-2. Also, HSV-1 has a lower rate of vertical transmission during childbirth.
Appropriate, timely diagnosis of symptoms is crucial. Approximately 90% of infected patients are unaware of their disease, either because they are asymptomatic or because they attribute subtle signs and symptoms to other conditions. But the virus can be shed even in the absence of obvious symptoms. If left undiagnosed, women may unwittingly pass the virus to sexual partners or transmit it to the fetus during vaginal delivery.
PATIENT PRESENTATION
Primary infection is defined as a genital ulceration with negative HSV-1 or HSV-2 serology. Patients classically present with nonspecific flu-like symptoms, such as fever, headache, and malaise. Some patients report a prodrome of genital itching, pain, or paresthesias, followed by swelling and painful, “burning” lesions in the cervix, vaginal vault, labia, or anal region. The lesions become pustular before crusting over and healing, usually within two to four weeks. Recurrent outbreaks are usually less severe and shorter than the initial infection. Patients who are immunocompromised or have HIV have longer outbreaks and more severe manifestations.
It is important to obtain a careful sexual history and perform a pelvic examination, because most women with genital herpes do not present classically. They may have no symptoms or there may be subclinical symptoms, such as dyspareunia, vaginitis, vaginal dryness, or a disproportionate sensitivity to feminine products (such as tampons or vaginal cleansing products). They may also mistake their symptoms for those of vulvovaginal candidiasis, hemorrhoids, or other common conditions and may not report them unless specifically asked.
CONFIRMING THE DIAGNOSIS
Whether the patient is infected with HSV-1 or HSV-2 influences long-term prognosis, so it’s important to order diagnostic tests that can distinguish between the two strains. Although the sensitivity is low, isolation of HSV in a cell culture is the recommended virologic test for patients with genital ulcers and suspected genital herpes. When available, type-specific serologic tests for HSV-1 and HSV-2 antibodies should also be drawn to confirm the diagnosis and distinguish between primary and recurrent infections.
A positive cell culture with negative HSV antibodies defines primary infection, but interpretation of HSV serologies can sometimes be more difficult. Because almost all HSV-2 infections are acquired sexually, the presence of HSV-2 antibody implies anogenital infection. Conversely, HSV-1 antibodies may be present with oral infection alone and must be interpreted in the context of clinical history and in conjunction with the results of cell culture. When the cell culture is negative and the patient’s serologies are only positive for HSV-1, assume that the patient has HSV-1 anogenital infection and counsel and treat accordingly.
ANTIVIRAL THERAPY
The mainstay of therapy for genital herpes is systemic antiviral drugs, including acyclovir, valacyclovir, and famcyclovir. Of these, acyclovir has been studied the most and has the best-documented safety profile. It is also the least expensive, but has a less convenient dosing schedule than famcyclovir or valacyclovir.
Antiviral drugs are used to relieve symptoms and speed healing. They may be given at any point during active infection but are more effective when given within 48 hours of symptom onset. Occasionally, the treatment course may need to be lengthened if sores don’t heal in the expected amount of time.
Antivirals may also be used to reduce recurrences in patients who have had frequent (more than six to eight) outbreaks per year. Suppressive therapy can reduce recurrences by 70% to 80% in these patients. It also reduces, but does not eradicate, asymptomatic viral shedding or partner transmission. The efficacy of suppressive therapy in HIV-infected patients is unknown, but it is still recommended in selected patients.
Women infected with HIV require a different treatment regimen than do immunocompetent women (see table above). It is generally accepted that acyclovir is safe to use in pregnancy, but it isn’t yet known whether the same is true of famciclovir and valacyclovir.
WHAT TO TELL THE PATIENT
Genital herpes is a chronic, incurable disease that can be extremely distressing. Counsel the patient about how to recognize the prodrome and outbreaks for what they are. Encourage her to be proactive by adhering to the treatment regimen and practicing safe sex to reduce transmission. Explain that infection with one serotype does not provide immunity to the other, regardless of the infection site. Let her know that she may need to return for repeat cell cultures if the symptoms recur.
It is important to provide a clear picture of the prognosis and to emphasize that genital herpes is an incurable disease that can be transmitted to others even when the patient is asymptomatic. Encourage her to inform current and future sexual partners and her physicians of her diagnosis, especially while pregnant, to ensure adequate treatment and prophylaxis.
CERVICITIS: INCREASINGLY COMMON
Cervicitis is an increasingly common clinical diagnosis that disproportionately affects women 15 to 25 years old. Multiple endothelia in the vagina and cervix have different host characteristics and vulnerability to infection, which makes for a long list of potentially infective organisms, including Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, HSV-1 and HSV-2, and Gardnerella vaginalis. Many patients are coinfected with a combination of these.
Chlamydia trachomatis is the most commonly reported infectious disease in the United States, followed by N. gonorrhoeae. Mycoplasma genitalium has recently emerged as a potentially important sexually transmissible cause of cervicitis and acute endometritis, although its role is not yet fully understood. However, in as many as 40% of patients, no etiology for cervicitis is identified, and the infection may persist despite multiple courses of antibiotics.
If not appropriately treated, cervicitis can spread to the upper genital tract, progress to systemic infection, and cause adverse pregnancy and fetal outcomes (such as endometritis, PID in pregnancy, and premature labor and delivery), and infertility. Cervicitis also makes women more susceptible to HIV infection.
NO CONSENSUS ON DEFINITION
Although cervicitis is seen and diagnosed in a wide variety of patients and clinical settings, there is no clear consensus on its definition or diagnostic hallmarks, and our understanding of the disease process overall is still evolving.
Cervicitis is characterized by a clear or purulent vaginal discharge and cervical friability (easily induced cervical bleeding by passage of a cotton swab through the cervical os). Women with uncomplicated cervicitis may present with discharge, irregular vaginal bleeding, or bleeding after sexual intercourse. However, many women with documented infections are asymptomatic and show no evidence of cervicitis.
Trichomoniasis is often signaled by a yellow or green malodorous vaginal discharge with or without vulvar irritation, but again, many patients with trichomoniasis have few or no symptoms. Patients should also be assessed for signs of subacute PID, such as mild abdominal pain, low-grade fever, malaise, and abnormal vaginal discharge.
CONFIRMING THE DIAGNOSIS
Microscopic evaluation will likely show an increased number of white blood cells (WBCs) per high-power field (HPF), although the exact number required for diagnosis is unclear. Various authors have advocated using anywhere between 10 to 30 WBCs per HPF as the cutoff. In deciding the appropriate cutoff point, consider pretest probability, patient presentation, risk factors for STDs, and infection prevalence.
Nucleic acid amplification tests (NAATs) are the mainstay of diagnosis for C. trachomatis and N. gonorrhoeae. They are highly sensitive and specific and can be performed on cervical or vaginal swabs. They may also be performed on urine specimens when the clinical setting precludes a pelvic examination, without sacrificing sensitivity, specificity, or diagnostic utility.
Diagnosis of T. vaginalis is usually confirmed when mobile, flagellated protozoa are visualized on wet-mount microscopy. However, this test is only approximately 60% sensitive and sometimes not immediately available. When trichomonads are not visualized on the wet mount, cultures for T. vaginalis, in addition to C. trachomatis and N. gonorrhoeae, should be sent for further diagnosis. Multiple point-of-care tests approved by the Food and Drug Administration are commercially available, with results available within 10 to 45 minutes, depending on the test. They are more sensitive than vaginal wet preparations, but may yield false positives if used in communities with low prevalence of trichomoniasis. The gold standard for the diagnosis of trichomoniasis is vaginal culture, which should be sent with other cultures or NAATs for testing.
TREATMENT STRATEGIES
Empiric antibiotic treatment for cervicitis is aimed at C. trachomatis, N. gonorrhoeae, and T. vaginalis (see table below). The primary treatment for C. trachomatis, azithromycin 1 gm, is a single oral dose, which improves compliance and can be given easily in a clinical setting. Alternatively, patients can be treated with doxycycline, erythromycin, ofloxacin, or levofloxacin orally for one week. Bear in mind, however, that doxycycline, ofloxacin, and levofloxacin are contraindicated in pregnancy; amoxicillin is an alternative treatment for chlamydial infection in pregnant women.
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Because quinolone-resistant N. gonorrhoeae is becoming so widespread, the Centers for Disease Control and Prevention (CDC) has recently advised that quinolones no longer be used to treat gonococcal infections. Recommended treatments now include cephalosporins, especially ceftriaxone 125 mg IM in a single dose, which enhances compliance while maintaining high bactericidal systemic levels. Cefixime, given in a single 400-mg oral dose, has an antimicrobial spectrum similar to that of ceftriaxone but has a slightly lower cure rate. It’s also subject to shortages because of inventory problems.
If the patient is allergic to cephalosporins, spectinomycin can be administered in a single 2-gm IM dose. If gonococcal pharyngitis is suspected, however, this should be avoided. Azithromycin 2 gm in a single oral dose is effective in treating uncomplicated gonococcal infections, but it is not generally recommended due to cost, gastrointestinal side effects, and concerns about resistance.
The decision about which patients to treat empirically is complicated and depends on a number of clinical factors, including the patient’s age, availability for follow up, prior history of STD, and individual STD risk assessment, as well as community prevalence of infection. Keep a low threshold to treat empirically for C. trachomatis. Women who live in communities with a high (5% or higher) prevalence of gonococcal infection, have a likelihood of infection, or may be lost to follow-up should be treated empirically for N. gonorrhoeae coinfection before test results are available. If found, concomitant bacterial vaginosis and trichomoniasis should also be treated.
Topical agents are ineffective in the treatment of T. vaginalis. The recommended treatment is a single 2-gm dose of metronidazole. However, metronidazole resistance has been identified in up to 10% of patients. When a single metronidazole dose is ineffective and reinfection has been excluded, alternative treatments include higher doses of metronidazole or oral tinidazole. Counsel the patient against drinking alcohol for 24 hours after finishing the course of metronidazole or 72 hours after the course of tinidazole.
Infection with T. vaginalis in pregnant patients has been associated with a higher risk of perinatal morbidity, include preterm labor and complications associated with prematurity. While the CDC recommends metronidazole for pregnant patients with cervicitis, the drug has not been shown to reduce the risk of poor outcomes.
Routine testing and treatment for M. genitalium is not available or recommended at this time.
REFERRAL FOR FOLLOW-UP
Patients treated for cervicitis should be referred for follow-up on test results and re-evaluation. Pregnant women should be specifically retested three to four weeks after treatment to ensure adequate response. Advise patients to abstain from sexual intercourse for seven days after single-dose treatment or for seven days after the completion of a longer course of antibiotics.
Let the patient know that, because no specific infectious cause for the cervicitis may be identified, she may need more than one course of antibiotics—and even that may not help. If the infection persists, and if reinfection can reliably be excluded, her treatment choices are unclear. These patients should be referred to a gynecologic specialist for further treatment and evaluation.
PELVIC INFLAMMATORY DISEASE
Annually, more than 1.5 million women contract PID, an infection of the upper genital tract. Pelvic inflammatory disease is a polymicrobial STD that can affect the uterus, fallopian tubes, ovaries, and peritoneal cavity. It is commonly caused by C. trachomatis and N. gonorrhoeae. Organisms found in normal vaginal flora have also been implicated.
Risk factors for infection include sexual intercourse at an early age, a history of previous STDs (especially C. trachomatis and N. gonorrhoeae), multiple sex partners, and older sex partners.
It is important to identify this disease early and to initiate appropriate treatment to prevent complications, which include tubo-ovarian abscess (TOA), chronic pelvic pain, and infertility. Patients may also suffer psychological complications from the chronic pain, potential infertility, and the stigma of the diagnosis.
CLASSIC SYMPTOMS
The classic symptoms of acute PID are low abdominal pain, fever, and vaginal discharge. In reality, however, patients present with a wide variety of signs and symptoms, including back pain, dyspareunia, nausea and vomiting, and abnormal vaginal bleeding. Pelvic peritonitis and sepsis are also possible. Patients with subacute PID may present with chronic abdominal pain and low-grade fever.
In pregnant patients, PID has a similar presentation to that of nonpregnant patients. However, PID is exceedingly rare after the first trimester.
Pelvic inflammatory disease is difficult to diagnose. No single clinical, laboratory, or radiologic finding can reliably diagnose or exclude it. Therefore, PID is diagnosed clinically in patients with lower abdominal pain, tenderness, abnormal vaginal discharge, cervical motion tenderness, adnexal tenderness (suggesting TOA), and fever. A sexual history is suggestive but not fully reliable.
Laboratory testing and further imaging are generally reserved for patients with more severe illness or when other diagnoses are considered (such as appendicitis, ectopic pregnancy, or ovarian torsion). Laboratory testing may show leukocytosis, a high number of WBCs on wet mount, WBCs in the urine, elevated erythrocyte sedimentation rate (ESR), or elevated C-reactive protein (CRP). While none of these studies is diagnostic, there is evidence to suggest that PID can be reliably excluded if the vaginal WBC and serum WBC, ESR, and CRP are all normal. Health care providers should still maintain a high index of suspicion and a low threshold for treating PID to avoid delayed diagnosis and the sequelae of a missed diagnosis.
Vaginal cultures, NAATs, and wet mount aid in the diagnosis. The patient should also be given a pregnancy test. Ultrasonography should be obtained to exclude TOA, which can complicate up to 40% of cases of PID but may be present in isolation.
BROAD-SPECTRUM ANTIBIOTICS
First-line treatment for PID is broad-spectrum antibiotics, again aimed at treating C. trachomatis and N. gonorrhoeae (see table below). Most patients can be treated on an outpatient basis with close follow-up for re-examination, but a small subset of patients will require hospitalization for parenteral antibiotics. The CDC recommends admission when the patient cannot tolerate oral antibiotics, has signs of severe illness, has not responded to antibiotics, has concomitant TOA, or can’t follow an outpatient regimen, or when surgical emergencies cannot be excluded. Some experts advocate admission for adolescents or nulliparous women who wish to become pregnant in the future, but this has not been shown to reduce complication rates or improve long-term outcomes.
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Patients should be counseled that their sex partners should be tested and that they need to inform future health care providers of the diagnosis. They should also be counseled about safe sex practices, HIV testing if available, and the need for follow-up with a gynecologist.
The table above provides a guide to the differential diagnosis of genital herpes, cervicitis, and PID.
SLOWING THE SPREAD OF STDs
Sexually transmitted diseases are very common but very elusive and difficult to diagnose, and because of the many possible etiologies they are often difficult to treat. It is important, therefore, to take a detailed history, to perform a directed physical exam whenever possible, and to maintain a high index of suspicion even when patients do not present classically.
Sensitive counseling is an important adjunct to pharmacologic treatment. Every patient with an STD also presents an important window of opportunity for education about future safe sex practices and HIV testing (see box below ). It is imperative to talk with patients about partner testing and treatment, when appropriate.
Some STDs are curable, but even when they are, they can be disruptive at best and dangerous at worst. Candid conversations with your patients can help make them aware of what’s “normal” and what isn’t, as well as help protect them, their partners, and their future children from the effects of an untreated STD.
Suggested Reading
Centers for Disease Control and Prevention: Updated recommended treatment regimens for gonococcal infections and associated conditions—United States, April 2007. Available at: www.cdc.gov/std/treatment/2006/updated-regimens.htm. Accessed May 12, 2008.
Centers for Disease Control and Prevention; Workowski KA and Berman SM: Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 55(RR-11):1, 2006.
Crossman SH: The challenge of pelvic inflammatory disease. Am Fam Physician 73(5):859, 2006.
Gupta R, et al.: Genital herpes. Lancet 370(9605):2127, 2007.
Marrazzo JM and Martin DH: Management of women with cervicitis. Clin Infect Dis 44(Suppl 3):S102, 2007.
Sen P and Barton SE: Genital herpes and its management. BMJ 334(7602):1048, 2007.
Steben M: Genital herpes simplex virus infection. Clin Obstet Gynecol 48(4):838, 2005.
Sulak PJ: Sexually transmitted diseases. Semin Reprod Med 21(4):399, 2003. |
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