Essentials of Diagnosis cervicitis symptom.

 Inflammatory condition of the cervix defined by the presence of mucopurulent endocervical discharge, easily induced endocervical friability, or edematous cervical ectopy.

 Most often a result of chlamydia, gonorrhea, trichomoniasis, or genital herpes infection.

 Associated with an increased risk of upper genital tract infection, adverse pregnancy outcomes, and HIV acquisition.

General Considerations

Cervicitis is typically the consequence of infection with sexually acquired pathogens, most commonly Chlamydia trachomatis or Neisseria gonorrhoeae and, occasionally, Trichomonas vaginalis or herpes simplex virus (HSV). The diagnosis is made when either mucopurulent discharge or easily induced bleeding (friability) is present at the endocervical os; more subtle signs include edema of the cervical ectropion (edematous ectopy). Recent data suggest that disruption of normal vaginal flora, most often manifesting as bacterial vaginosis, may also promote cervicitis. Although C trachomatis is probably the most common cause of cervicitis, and N gonorrhoeae is also implicated, the majority of women (80–90%) infected with these pathogens have no signs of cervicitis.

Pathogenesis

The cervix consists of an underlying connective tissue matrix overlaid by two types of distinct epithelium, each of which is vulnerable to infection by distinct pathogens. The endocervical canal and ectropion (cervical ectopy), if present, are lined by columnar epithelial cells. These cells, which line what is commonly called the endocervix, provide vulnerable targets for infections with C trachomatis and N gonorrhoeae. The ectocervix, in contrast, is lined by squamous epithelium that is contiguous with the vaginal mucosa. For this reason, the ectocervix is susceptible to T vaginalis, an agent more commonly associated with vaginitis.

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Estrogen, produced endogenously or administered exogenously, promotes the formation and maintenance of cervical ectopy, which is present in adolescents, pregnant women, and women who take estrogen-containing contraceptives. Estrogen is also needed to maintain adequate thickness of the squamous cervicovaginal epithelium (20 cell layers). This promotes sustenance of a healthy population of hydrogen peroxide-producing Lactobacillus species, which maintain normal (acidic) vaginal pH. The quality of endocervical mucous is also affected by these hormones. Relatively high levels of estrogen during the follicular phase leading up to ovulation thin the endocervical mucous; this can result in elaboration of so-called physiologic discharge. In the luteal phase of the cycle, progesterone increases the viscosity and reduces the volume of endocervical mucous.

Recently, some investigators have proposed a direct role for these hormones in modulating the balance of cell-mediated (Th1) and humoral (Th2) immune responses, with estrogen predominance promoting Th2 and progesterone augmenting Th1 responses. Because endocervical mucous possesses intrinsic antimicrobial activity by virtue of lactic acid, low pH, and antimicrobial peptides, these hormonal changes are potentially important in mediating susceptibility to and natural history of cervical infection. For example, it is not at all clear why only a subset of women develops inflammatory signs of cervicitis when infected by chlamydia, gonorrhea, or trichomoniasis.

Prevention

Acquisition of the sexually transmitted diseases (STDs) that cause cervicitis—in particular, chlamydia, gonorrhea, trichomoniasis, and genital herpes—is markedly reduced when condoms are used consistently and correctly. No data speak to the effect of condoms on cervicitis in which no microbiologic etiology is apparent.

Clinical Findings

History

A thorough sexual history—including assessment of number and gender of recent partners, specific sexual practices (oral, anal, vaginal sex), whether sex partners are symptomatic or have been recently diagnosed with an STD or STD-related syndrome, recent Papanicolaou (Pap) smear history, and use of condoms or other prevention methods—should be obtained from women who present with cervicitis.

Symptoms referent to the lower genital tract that should be elicited include dysuria, urinary hesitancy or frequency, and abnormal vaginal discharge. Elements of the history that might suggest upper genital tract involvement should be assessed, including lower abdominal or pelvic pain or cramping, right upper quadrant pain, and pain or bleeding with intercourse or other penetrative sex.

Patients should be specifically queried about a history of douching and any use of intravaginal products, including lubricants, over-the-counter therapeutic preparations (especially antifungal products), and so-called feminine deodorants, all of which can cause a chemical or allergic mucosal reaction. Information about these factors can help to narrow the differential diagnosis considerably and direct subsequent management.

Symptoms and Signs

Symptoms of cervicitis include abnormal vaginal discharge (increase in amount; change in color [often yellow, green, or brown] or odor [malodorous]), intermenstrual bleeding, and bleeding that occur after intercourse or other penetrative sexual contact. However, most women with cervicitis do not complain of symptoms, and even when symptoms are present, they are nonspecific and may indicate vaginitis without cervical involvement. If endometritis or other pelvic inflammatory disease (PID) accompanies cervicitis, lower abdominal pain or cramping, often exacerbated with intercourse, may be present.

Mucopurulent discharge issuing from the endocervical canal and easily induced bleeding are the most easily recognized signs of endocervicitis. Both may be present simultaneously. Edematous ectopy is a more subtle sign and is characterized by a swollen, irregular mucosal surface to the ectropion. Signs of infection affecting the ectocervix depend on the responsible pathogen. T vaginalis can cause an erosive inflammation of the ectocervical epithelium, classically manifest as "strawberry cervix" or colpitis macularis. This process may appear as a range of epithelial disruption, from small isolated petechiae to large punctuate hemorrhages with surrounding areas of pale mucosa.

Genital infection with HSV types 1 and 2 can cause cervicitis, particularly in the case of women who experience severe clinical manifestations of primary infection with HSV-2. Although most primary HSV-2 infections are asymptomatic, some women (15–20%) experience a severe primary infection that may include cervicitis. Cervicitis in this setting is characterized by diffuse erosive and hemorrhagic lesions, usually in the ectocervical epithelium, and often accompanied by frank ulceration. Other manifestations of primary HSV-2 genital infection are usually evident, including external herpetic lesions, neurologic manifestations (including aseptic meningitis, urinary retention, and lumbosacral radiculitis), fever, and inguinal lymphadenopathy. Cervicitis may recur with clinical recurrences of genital HSV-2; however, it is typically not severe. Subclinical shedding of HSV-2 does not appear to be directly related to cervicitis. HSV-1 may also cause cervicitis similar to that described for HSV-2; however, the manifestations are typically less severe, and usually occur only during the primary genital infection with HSV-1. As with genital herpes, other causes of genital ulcer disease can cause lesions on the cervix; these include the chancre of primary syphilis and ulcers of chancroid.

Mycoplasma genitalium has recently been implicated as a sexually transmissible cause of cervicitis, but its exact prevalence, incidence, and natural history are not known; prospective studies are underway. Various case reports have attributed cervicitis to infection with certain Streptococcus species—most notably, S agalactiae (group B streptococcus) and S pyogenes—but reliable estimates of how commonly this might occur, if a causal relationship exists, are not available, nor is the approach to treating these agents if they are suspected etiologies of cervicitis clear.

Apart from the previously noted infections, numerous noninfectious and infectious systemic inflammatory processes and local insults can precipitate cervical inflammation that may present clinically as apparent cervicitis. The former group includes Behçet syndrome, sarcoidosis, ligneous conjunctivitis, and tuberculosis. Substances that either erode the endocervical mucous plug or cause an irritant mucositis can also cause signs of cervicitis. Commonly used, commercially available douching and feminine deodorant preparations often include detergents that have surfactant properties, and many include various chemicals such as antihistamines and cornstarch. In one large study in which commercial sex workers were randomized to use vaginal sponges impregnated with 1 g of nonoxynol-9 (N-9), cervical erosions as assessed by colposcopy were seen more commonly among N-9 users, who were also more likely to acquire HIV infection during the course of the study than were nonusers. Because N-9 has shown no benefit in reducing acquisition of HIV and STDs, it is no longer recommended for this purpose.

Even seemingly obvious signs of endocervical inflammation may have variable precision for chlamydia and gonorrhea, because the predictive value of individual cervical findings suggestive of cervicitis may vary with patients' age and other STD-related risk factors. For example, the presence of easily induced endocervical bleeding in a 16-year-old girl who reports recent unprotected sex with a new male partner is highly predictive of chlamydial infection; the predictive value of this sign is much lower for chlamydia in a 35-year-old woman in a long-term, monogamous relationship.

Laboratory Findings

Gram Stain

Gram stain of a smear of endocervical secretions was used for many years to support a diagnosis of cervicitis; however, its independent value, especially in predicting chlamydial infection, has been variable, and its sensitivity for detection of N gonorrhoeae at the cervix is only 50%. If this test is used, clinicians should first use a large cotton-tipped swab to gently remove adherent vaginal secretions from the face of the cervix before inserting a small cotton- or Dacron-tipped swab approximately 2 cm into the endocervical canal, rotating once or twice, then removing and swabbing the material on a fresh glass slide for staining. High-power fields should be examined (at 1000 x magnification, oil immersion), specifically focusing on areas that have abundant endocervical mucous that appears pink under Gram stain.

Most clinic guidelines recommend a threshold level of 10–30 polymorphonuclear (PMN) leukocytes per high-power field, with PMN counts above this level supporting a diagnosis of cervicitis. The sensitivity of this test increases and specificity decreases as this threshold cutoff is decreased.

Pap Smear

Although inflammatory changes on Pap smear are associated with an increased likelihood of detection of several STDs, including chlamydia, gonorrhea, trichomoniasis, and human papillomavirus, this test is neither specific enough to direct empiric therapy for these pathogens nor practical in delineating immediate etiologies of cervicitis for empiric therapy. Thus, it is not recommended as a means of evaluating women for the presence of cervicitis.

Microscopy

A finding of PMNs (> 5–10 per high-power field) on saline microscopy of vaginal fluid has been associated with an increased risk of cervical chlamydia and gonorrhea; further data are needed.

Special Tests

Chlamydia Tests

Women with cervicitis should be tested for chlamydia and gonorrhea. One of the most sensitive diagnostic assays, a nucleic acid amplification test (NAAT), should be used if at all possible. NAATs include polymerase chain reaction (PCR), transcription-mediated amplification, and strand displacement amplification. Use of these techniques is particularly important for chlamydia, because the sensitivity of NAAT for C trachomatis is at least 20% higher than that of unamplified DNA probes, enzyme immunoassay, and direct fluorescent antibody assays. These tests perform equally well in the presence of blood, mucopus, or pregnancy, and exhibit excellent specificity (>98%). Chlamydial infection at the cervix can be detected using any of three patient specimens: cervical swab, first-catch urine, or vaginal fluid.

Cervical Swab Specimen

A swab can be obtained directly from the cervix; this approach may be useful if a pelvic examination is performed for other indications, such as a Pap smear or assessment for PID. However, in general, clinicians need not perform a speculum examination for the sole purpose of obtaining a cervical swab for NAAT, because the sensitivities of NAAT performed on either a urine specimen or a vaginal swab are also excellent.

First-Catch Urine Specimen

A first-catch urine specimen (defined as the first 10–15 mL of urine stream) can be obtained. This test not only has the advantage of not requiring a pelvic examination, but also will detect the minority of chlamydial infections that occur in the female urethra and not at the cervix (10–15% of all lower genital tract infections in women). Importantly, women should be instructed not to cleanse or wipe the periurethral area prior to voiding, and not to collect a midstream sample (sometimes familiar to them from previous experience with collection of urine culture for evaluation of cystitis).

Vaginal Fluid Specimen

Swabs of vaginal fluid can be used. These may be collected by the clinician performing the examination or, occasionally, by the patient; however, not all NAATs are currently FDA cleared for patient collection of vaginal swabs.

Gonorrhea Tests

Although NAATs may be used to diagnose gonococcal infection at the cervix, the sensitivity of traditional culture is relatively close to that of NAATs, which do not offer the same degree of enhanced sensitivity for this pathogen as for C trachomatis. Culture is especially appropriate if there are concerns about the possibility of fluoroquinolone-resistant N gonorrhoeae (eg, a woman being assessed in Hawaii or California, history of travel outside the United States during the time frame in which the infection may have been acquired, or sexual contact with a bisexual man). Notably, several NAATs offer combination assays for both chlamydia and gonorrhea with the use of a single specimen.

Other Tests

Examination of vaginal fluid should be performed to look for the presence of bacterial vaginosis, because treatment of concurrent infection might enhance the resolution of cervicitis. The presence of three of the four Amsel criteria establishes the diagnosis of bacterial vaginosis: (1) homogeneous vaginal discharge, (2) vaginal fluid pH higher than 4.5, (3) clue cells comprising more than 20% of total vaginal epithelial cells seen on 100 x magnification on saline microscopy, and (4) an amine (fishy) odor on addition of potassium hydroxide. If microscopy if not available, pH testing of vaginal fluid offers valuable information; abnormally high vaginal pH is the most sensitive of the four Amsel criteria in diagnosing bacterial vaginosis: a normal pH (< 4.5) makes bacterial vaginosis highly unlikely. Saline microscopy also offers the opportunity to look for motile trichomonads and for PMNs. Trichomonads may also be identified by newly available rapid antigen–based diagnostic tests for T vaginalis.

Further workup should be determined by the specific clinical scenario. For example, if ulcerations are present on the cervix, specific tests for HSV are indicated and may include direct (culture or antigen detection [PCR]) or serologic assays. If the sexual and social history suggests that the woman is at increased risk for syphilis (eg, having sex with a man who reports sex with other men, exchange of sex for drugs or money), serologic screening should be performed and, if available, direct darkfield microscopy of exudate from the lesion. No test for M genitalium is commercially available at the present time.

Special Examinations

All women with cervicitis require a pelvic examination to rule out PID, because the presence of cervicitis is associated with a considerably increased risk of both silent endometritis and symptomatic PID. PID should be diagnosed if either cervical motion tenderness or uterine or adnexal tenderness is present; if PID is suspected, women should be treated with appropriate antibiotic regimens (see Chapter 8). Importantly, the single-dose antibiotic regimens recommended for the treatment of cervicitis are not adequate in the treatment of PID.

Differential Diagnosis

Because cervicitis is a clinically determined syndrome, the differential diagnosis is based on etiology. As previously described, the cause can be infectious, with an STD predominating, or noninfectious.

Complications

Cervicitis is associated with three major consequences. First, it is a marker for the presence of inflammation, and potential infection, in the upper genital tract. This can occur either as overt PID or as silent inflammation of the uterine lining (endometritis). Second, the presence of cervicitis during pregnancy has been associated with an increased risk of adverse pregnancy outcomes even when no specific pathogen was detected. Third, cervicitis influences the dynamics of HIV transmission. It increases a woman's risk of infection with HIV, probably by recruiting vulnerable lymphocytes to the site of inflammation, and, among women already infected with HIV, increases the amount of HIV shed at the cervix. Concomitantly, treatment of cervicitis in HIV-infected women effects a reduction in the quantity of HIV shed at the cervix. This observation provides an especially compelling rationale for screening and treatment of this condition among HIV-infected women.

Cervicitis treatment.

Tables 10–1 and 10–2 outline the general approach to management of cervicitis, and treatment based on suspected or documented microbial etiology. Presumptive therapy directed at C trachomatis should be provided, because the prevalence of this common STD is high among young women in the United States. The approach involving possible infection with N gonorrhoeae is less clear. Women with cervicitis who fall into subgroups with high prior likelihood of gonococcal infection should be empirically treated; these subgroups include adolescents in many inner-city areas of the United States. Presumptive therapy for gonorrhea should also be considered if the likelihood of a woman's return for treatment based on a diagnostic test that turns out to be positive is judged to be low. Other considerations that should weigh toward empiric therapy include report of an STD-related risk behavior (especially report of new or multiple sex partners in the prior 60 days) and recent history of STD (especially chlamydial or gonococcal infection in the prior year). Recurrent infection with C trachomatis is very common among women, ranging from 8% to 25% in several studies, and probably relates predominantly to resumption of unprotected sex with untreated partners. Recurrence of gonorrhea is likely to be equally common. For this reason, it is imperative to treat sex partners of women for whatever infection was either detected or presumptively treated in the woman (typically, chlamydia and sometimes gonorrhea).

Appropriate treatment of cervicitis—especially if it is caused by C trachomatis or N gonorrhoeae—is especially important among HIV-infected women, because at least one small study demonstrated a decline in the amount of HIV-1 shed from the cervical mucosa after empiric treatment of cervicitis aimed at chlamydial and gonococcal infection. This is likely to reduce these women's risk of transmitting HIV-1 to sex partners.

M genitalium appears to be more sensitive to macrolide than tetracycline antibiotics, but further study is required to confirm the efficacy of these agents in curing lower genital tract infection with this organism. M genitalium is difficult to culture and, to date, clinical studies have relied on PCR assays to detect it. The implication of this for determining microbiologic cure in such studies is not yet clear.

The approach to treating cervicitis in which no identifiable STD is detected is unclear. Scant evidence suggests that women should be evaluated for bacterial vaginosis at the time they present with cervicitis, and the concurrent condition should be treated if present. Among 51 women with cervicitis and bacterial vaginosis who received doxycycline and ofloxacin as empiric treatment for chlamydia and gonorrhea and were then randomized to receive either intravaginal metronidazole or placebo, those who received metronidazole had a higher rate of resolution of cervicitis at 2 and 4 weeks post-treatment. Women whose bacterial vaginosis resolved were more likely to have resolution of cervicitis at 2 weeks, regardless of which regimen they received.

Further management of cervicitis for which neither an identifiable STD nor bacterial vaginosis plays a role is empiric, and substantiated by little rigorous evidence, because no published data have addressed this issue. Certainly, intravaginal use of products that could potentially damage cervicovaginal mucosa, including douches, spermicides, lubricants, and other products, should be discouraged. Therapeutic approaches used and anecdotally successful include more extended courses of broad-spectrum antibiotics or ablative therapy, but neither can be recommended on the basis of available evidence.

When to Refer to a Specialist

The vast majority of cervicitis cases are uncomplicated; the major concern in most clinical situations is assessing the affected patient for PID. However, a subset of women has cervicitis that persists after treatment aimed at chlamydia, gonorrhea, trichomoniasis, and bacterial vaginosis. Although data on this condition are very limited, an identifiable cause is usually not evident, and prolonged therapy with antibiotics are not indicated. When endocervical discharge is copious and women suffer consequent symptoms, some gynecologists have used cryotherapy for ablation of the affected area, especially if ectopy is present. Referral to a gynecologist in such cases should be considered.

Prognosis

Cervicitis associated with STD-related infections typically resolves completely when antibiotic therapy aimed at causative pathogens is provided. However, relatively few studies of the natural history of this condition are available, and persistent cervicitis occurs in a minority of affected women. The incidence of persistent cervicitis is unknown, but anecdotally, is probably 5% or less.

Practice Points

Clinicians need not perform a speculum examination for the sole purpose of obtaining a cervical swab for NAAT, because the sensitivities of NAAT performed on either a urine or a vaginal swab are also excellent.