Hospital Medicine

Cervicitis and pelvic inflammatory disease

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Cervicitis and pelvic inflammatory disease

I. What every physician needs to know.

Cervicitis is an inflammation of the female genital tract characterized by purulent endocervical exudate and/or friability of the cervix. It may be asymptomatic or may present with discharge or irregular bleeding. Cervicitis is often caused by the sexually transmitted Neisseria gonorrhoeae and Chlamydia trachomatis, can be the result of other sexually transmitted or non-sexually transmitted infectious agents or can arise from non-infectious sources.

Pelvic inflammatory disease (PID) is a more serious infection of the upper femal genital tract, which can also be caused by N. gonorrhoeae or C. trachomatis though it is often polymicrobial. PID is usually an ascending infection from vaginal or cervical bacteria, but can rarely be the result of transperitoneal spread of bacteria for example as in the case of a ruptured appendix. In most cases ascending PID is sexually transmitted though it can also be the result of pelvic instrumentation such as endometrial biopsy or other procedures.

Cervicitis itself does not have serious long-term complications if treated early and not allowed to progress to PID. PID, though, can lead to scarring and subsequent ectopic pregnancy and even infertility. Prompt identification of both disorders is thus important.

II. Diagnostic Confirmation: Are you sure your patient has cervicitis and pelvic inflammatory disease?

Cervicitis is defined by the presence of mucopurulent endocervical exudate and/or cervical friability or easy bleeding on exam, generally without significant abdominal or cervical tenderness.

PID is an infectious inflammation of the upper female genital tract and includes endocervicitis, endometritis, salpingitis, peritonitis, and tubo-ovarian abscesses. It is a clinical diagnosis with no absolute diagnostic criteria, but may present with abdominal and/or lower back pain, irregular menstrual or postcoital bleeding, abnormal vaginal discharge, fever, nausea, vomiting, or dysuria.

The Centers for Disease Control and Prevention (CDC) suggest that the presence of cervical motion tenderness or tenderness of the uterus or adnexa on exam are the minimum diagnostic criteria.

The presence of one or more of the following will increase the specificity of the diagnosis:

  • Oral temperature greater than 101.0 F

  • Mucopurulent cervical or vaginal discharge

  • Abundance of white blood cells on vaginal fluid microscopy

  • Elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)

  • Laboratory confirmation of N. gonorrhoeaeor C. trachomatis

A. History Part I: Pattern Recognition:

Patients with cervicitis may present with abnormal discharge, intermenstrual bleeding or postcoital bleeding. Some women may have dysuria, dyspareunia, or pelvic or lower abdominal pain and some may be asymptomatic. In general, patients with cervicitis are not ill appearing.

The symptoms of PID are non-specific as listed above and a thorough sexual history is important to distinguish this condition from other abdominal and pelvic pathology. Patients with PID can also be well appearing, but a minority will be ill, sometimes with unstable vital signs.

B. History Part 2: Prevalence:

Infectious cervicitis is most likely to be present in sexually active women less than 25 years old, women who have had a previous sexually transmitted disease, or women of any age who have multiple sexual partners or a new partner.

PID affects a similar population as cervicitis and is diagnosed in an estimated 800,000 women per year in the United States. Of these women, approximately 10% will be ill enough to require hospitalization. PID is rare in non-menstruating, i.e. premenarchal, pregnant or post-menopausal women.

C. History Part 3: Competing diagnoses that can mimic cervicitis and pelvic inflammatory disease.

Cervicitis can be confused with vulvovaginitis or PID but may also be mistaken for other diseases of the lower female genital tract (see chapter for details). A physical exam can help to establish the diagnosis.

PID may be confused with cervicitis, but a physical exam should help to distinguish between the two conditions. PID can also be easily confused with other intra-abdominal diseases including appendicitis or pyelonephritis. Again, a physical exam along with a sexual history should help clarify the source of the patient's symptoms.

D. Physical Examination Findings.

A pelvic exam is essential for the diagnosis of cervicitis. The vulvar exam is usually normal unless herpes simplex virus is the cause of the cervicitis. Vaginal exam may reveal erosions. When examined with a speculum the cervix is typically edematous, erythematous and friable. Mucopurulent endocervical discharge may be present and when the cervical os is touched lightly with a swab it may bleed.

Vesicular lesions will be seen if herpes simplex virus (HSV) is the etiology and a strawberry cervix with punctate hemorrhages is present with Trichomonas. Cervical motion tenderness, adnexal or significant abdominal tenderness are signs of PID rather than cervicitis.

Patients with PID may or may not have a fever. Other signs of sepsis may be present in severe disease. Patients may or may not have external abdominal or pelvic tenderness. Right upper quadrant tenderness can be present in PID-associated perihepatitis (Fitz-Hugh-Curtis syndrome). On pelvic examination, the patient will likely have tenderness of the cervix (cervical motion tenderness), uterus or adnexa. The examiner should attempt to palpate any masses as may be present with a tubo-ovarian abscess. As in cervicitis, discharge may be present and the cervical os may be friable.

E. What diagnostic tests should be performed?

Cervicitis

The examiner can check the vaginal potential hydrogen (pH), which will usually be elevated (greater than 4.5) with infectious cervicitis, though it does not give a specific diagnosis. Microscopy of secretions may show leukorrhea with more than 10 white blood cells per high-powered field; this test has a high negative predictive value for N. gonorrhoeae or C. trachomatis cervicitis.

Gram staining of endocervical specimens for N. gonorrhoeae is not recommended as a diagnostic tool because of its low specificity. Bacterial vaginosis, which can also cause cervicitis, is diagnosed clinically with the presence of three out of four of Amsel's criteria:

  • Homogenous discharge

  • Positive whiff test, or fishy amine order with application of potassium hydroxide (KOH)

  • PH greater than 4.5

  • The presence of clue cells or bacterial stippling on wet preparation

Pelvic inflammatory disease

As with cervicitis, microscopy of vaginal secretions should be done. Lack of leukorrhea combined with a normal appearing cervix on exam has a high negative predictive value for PID. The flora of bacterial vaginosis has been implicated in some cases of PID and Amsel's criteria as listed above can be applied for its diagnosis.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

N. gonorrhoeae and C. trachomatis are the most common causes of cervicitis. Both sensitive and specific, nucleic acid amplification testing (NAAT) for these organisms on urine, endocervical or vaginal samples is an important starting point for the diagnosis of cervicitis. Of note, though, a urine sample or vaginal swab should not take the place of a full pelvic examination.

If NAAT is negative, or if another cause is more likely, there are other possible etiologies of cervicitis. Options for the diagnosis of trichomoniasis include microscopy of a wet preparation, which has a sensitivity of 60-70%, or culture for Trichomonas vaginalis, which has good sensitivity and specificity.

If herpes simplex is suspected and confirmatory testing is needed, polymerase chain reaction (PCR) is the test of choice over culture. Herpes simplex serology and cultures are not recommended. Organisms that cause bacterial vaginosis can also cause cervicitis. Amsel's criteria as described previously and/or gram staining can be used for its diagnosis. Mycoplasma genitalium may be an emerging cause of cervicitis but testing is not widely available.

In many cases, especially in women over the age of 30, no organism is isolated as the cause of the cervicitis. Non-infectious causes of cervicitis include foreign body trauma from pessaries or diaphragms, malignancy, radiation therapy, local irritation such as from douching, and Behcet's syndrome. The history rather than laboratory tests will help define these causes.

Patients with suspected PID should have testing for N. gonorrhoeae and C. trachomatis. M. genitalium may lead to PID in some women, but as above, there is no readily available test to diagnose this. Inflammatory markers including ESR or CRP may increase the specificity of the diagnosis. A white blood cell count is not helpful in most women, but could be used as a baseline to assess response to therapy in severe illness or in the presence of a tubo-ovarian abscess.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

There are no imaging studies indicated for the diagnosis of cervicitis.

Imaging is not necessary for women with suspected PID with some exceptions. When other diagnoses such as appendicitis are high on the differential, imaging may help the hospitalist arrive at the correct diagnosis. Pelvic ultrasound has a low sensitivity and specificity for the diagnosis of PID, but may visualize an adnexal or tubal mass, thickened, fluid-filled tubes, or hyperemia, which in the right clinical context may help confirm the presence of PID.

Ultrasound may also confirm a tubo-ovarian abscess when there is a palpable mass on exam, or in the case of more severe illness. Magnetic resonance imaging is specific for the diagnosis, but not widely used. Laparoscopy is specific in the presence of salpingitis, as is endometrial biopsy when endometritis is present. However, these procedures are not necessary in most women.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Cervicitis

There is no role for additional laboratory or imaging tests other than what has been described above.

Pelvic inflammatory disease

Because the diagnosis is largely clinical, most women do not need laboratory testing or imaging other than what has been mentioned above. Ultrasound should be reserved for severe illness or for women in whom a tubo-ovarian abscess is suspected.

III. Default Management.

Cervicitis

If the patient is at risk for being lost to follow-up then she should be treated empirically for C. trachomatis and N. gonorrhoeae. The Centers for Disease Control and Prevention (CDC) recommend azithromycin 1000mg once for C. trachomatis or doxycycline 100mg twice daily for seven days. Recommended treatment for N. gonorrhoeae is intramuscular (IM) ceftriaxone 250mg once or cefixime 400mg orally once.

In patients who cannot tolerate cephalosporins, azithromycin 2g orally once is an alternative to the above, though due to concerns of emerging gonococcal resistance this should be used sparingly. If being lost to follow-up is not an issue the hospitalist can wait for the results of the above lab testing and treat accordingly.

Pelvic inflammatory disease

Antibiotic therapy should cover N. gonorrhoeae and C. trachomatis, even with negative testing, with consideration also given to covering the anerobes of bacterial vaginosis and Bacteroides fragilis.

The CDC guidelines suggest, for patients who can take oral medications, doxycycline 500mg twice daily for 14 days and a parenteral third generation cephalosporin including ceftriaxone IM 250mg once or IM cefoxitin 2g once combined with probenecid 1g orally once. The physician can add metronidazole 500mg orally twice daily for 14 days if needed for the flora of bacterial vaginosis.

Most patients who are hospitalized with PID will require parenteral therapy. The CDC recommends intravenous (IV) cefotetan 2g every 12 hours or cefoxitin 2g IV every 6 hours (both have anerobic coverage) plus doxycycline 100mg IV or orally twice daily. The cephalosporins can be discontinued 24-48 hours after clinical improvement, but the doxycycline should be continued for a full 14-day course. If a tubo-ovarian abscess is present, upon discontinuing the cephalosporin, the patient should be treated with clindamycin or metronidazole for anaerobic coverage in addition to doxycycline.

For patients who cannot tolerate cephalosporins an alternative antibiotic regimen is IV clindamycin 900mg every 8 hours plus gentamicin dosed either 2mg/kg IV or IM once and then 1.5mg/kg IV or IM every 8 hours, or 3-5mg/kg daily. 24 hours after clinical improvement the patient can be treated with either clindamycin 450mg orally 4 times daily or doxycycline as above to complete a 14 day course.

A. Immediate management.

Cervicitis is not a medical emergency and should be treated as above. The goal of treatment is to eradicate the infection and thus prevent ascending infection (i.e. PID), which can ultimately lead to scarring and infertility.

Patients with severe PID should be hospitalized. Some criteria for hospitalization include the following:

  • Tubo-ovarian abscess

  • Nausea, vomiting and high fever

  • Unable to tolerate oral medications

  • No response to oral treatment after 72 hours

  • Pregnancy

  • Acute abdomen or other surgical emergencies

Most women with tubo-ovarian abscesses will respond to antibiotic treatment alone so the above regimens should be started quickly after the diagnosis is established. Some patients with PID will present with an acute abdomen or shock, often from a ruptured tubo-ovarian abscess. This requires immediate surgical intervention. Of note, gonococcal PID is more likely to cause severe disease than the other possible etiologies.

B. Physical Examination Tips to Guide Management.

There is no need for immediate physical exam follow-up of a patient with cervicitis.

Women with PID though should be monitored for response to therapy. Continued symptoms or exam findings should prompt escalation of therapy as described above, or in the case of a tubo-ovarian abscess, surgical drainage.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Cervicitis

Over the short course of a hospital stay there are no laboratory tests indicated to monitor uncomplicated cervicitis. Repeat NAAT should be initiated at 3 months after the initial episode of cervicitis due to the possibility of re-infection from an untreated partner.

Pelvic inflammatory disease

Patients with no response to antimicrobials and an increasing leukocytosis may need surgical evaluation for tubo-ovarian abscess. Patients who are responding appropriately to treatment by showing improvement over the course of 1-3 days do not need routine lab testing for follow-up.

D. Long-term management.

The long-term management of cervicitis should focus on prevention of infectious or non-infectious causes and is discussed in greater detail below. If symptoms persist or recur, the patient should be evaluated for re-exposure to sexually transmitted diseases. If this evaluation is negative, other causes of cervicitis should be explored.

Women with chlamydial or gonococcal PID have a high rate of re-infection over the subsequent 6 months. The CDC guidelines recommend repeat testing for both N. gonorrhoeae and C. trachomatis 3-6 months after the initial course of PID.

E. Common Pitfalls and Side-Effects of Management.

The biggest challenge for hospitalists is likely to be making the diagnosis of cervicitis or PID. In the hospitalized woman with abdominal pain PID is particularly important to consider in the differential diagnosis, especially in young women, or women who have had recent pelvic procedures. That the diagnosis is mainly clinical furthers the need to keep PID high on the differential diagnosis in the appropriate population. Once the diagnosis is made, its management is straightforward as described above.

IV. Management with Co-Morbidities.

The CDC recommends that all pregnant women be screened for C. trachomatis and that high risk women or women in areas of high prevalence should be screened for N. gonorrhoeae. Pregnant women with chlamydial cervicitis should be treated with azithromycin, and with gonorrheal cervicitis with cephalosporins as per the CDC guidelines outlined above. The goals of treatment are to prevent ascending infection and to prevent transmission to the newborn.

PID increases maternal morbidity and the risk of preterm labor in pregnant women. This population should be admitted to hospital for parenteral treatment. Doxycycline though is a pregnancy category D drug. The most recent CDC guidelines do not specifically address appropriate chlamydial treatment in pregnant women, and consultation with the patient's obstetrician is warranted. Of note, PID is less common in non-menstruating women, including pregnant women.

A. Renal Insufficiency.

Cefotetan, cefoxitin and gentamicin must be renally dosed according to creatinine clearance. There is no specific renal dosing for azithromycin but it should be used with caution in patients with renal insufficiency.

B. Liver Insufficiency.

Azithromycin, doxycycline, cefotetan, and metronidazole have no specific hepatic dosing, but should be used with caution in hepatic insufficiency.

C. Systolic and Diastolic Heart Failure.

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease.

Azithromycin may prolong the QT interval. Consider an alternative in patients at risk.

E. Diabetes or other Endocrine issues.

As with any infection, diabetics should watch their glucose closely and adjust medication regimens as needed.

F. Malignancy.

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc).

Treatment for cervicitis is the same in patients with human immunodeficiency virus (HIV). Of note, cervicitis can increase HIV shedding, so its treatment may reduce transmission of the virus.

Patients with HIV and PID are more likely to have tubo-ovarian abscesses than women not infected with HIV. However, symptoms and signs are otherwise similar across the two groups. The CDC recommends the same treatment regimens and indications for hospitalization for both groups, as there is insufficient data to suggest that women with HIV and PID need more aggressive treatment, and some data to show that HIV infected and non-infected women respond similarly to existing treatment protocols.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management.

I. Gastrointestinal or Nutrition Issues.

No change in standard management.

J. Hematologic or Coagulation Issues.

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment.

No change in standard management.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

The hospitalist should be aware that increasing abdominal pain in a patient with cervicitis may be a sign of ascending infection, which should be treated as mentioned above.

Patients with PID who have progression of pain, unstable vital signs and/or an acute abdomen may have a ruptured tubo-ovarian abscess. This is a surgical emergency and appropriate consultation, either surgical or gynecological, should be obtained without delay.

B. Anticipated Length of Stay.

Cervicitis can be treated as an outpatient and though it may be a secondary complaint in a hospitalized patient, it should not be the primary reason for admission or a barrier to discharge. As noted the hospitalist can initiate empiric treatment for cervicitis while laboratory confirmation is pending.

Inpatients with PID can transition to oral medications 24 hours after clinical improvement, which usually occurs within 72 hours of onset of therapy.

C. When is the Patient Ready for Discharge.

Patients with cervicitis can be treated empirically while waiting for results of laboratory tests and this should not be a reason to delay discharge.

Patients with PID should have improvement of their presenting symptoms and signs such that they can transition to oral antibiotics. They should be tolerating oral fluids and medications prior to discharge.

D. Arranging for Clinic Follow-up.

1. When should clinic follow up be arranged and with whom.

Women with cervicitis should see their primary care provider within 3 months for repeat NAAT. An appointment closer to the time of discharge would facilitate time-sensitive prevention counseling. Women with PID should be seen soon after discharge to ensure resolution of the presenting illness.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

The patient should have HIV testing, either as an inpatient or at the outpatient follow-up appointment.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

None

E. Placement Considerations.

None

F. Prognosis and Patient Counseling.

Women with cervicitis or PID should abstain from sexual intercourse until they have completed antibiotic therapy, their partners have been treated and both the patient and her partner are asymptomatic. The importance of prevention with safe sexual practices (fewer sexual partners, abstinence or the correct use of condoms) must be emphasized. Spermicides and microbicides are not recommended for the prevention of HIV and sexually transmitted disease transmission.

Patients with PID should be aware of long-term sequelae of the illness including infertility, ectopic pregnancy, chronic pelvic pain, and recurrent infection. Rates of infertility and ectopic pregnancy increase with increasing severity of illness and increasing number of PID episodes. Rates of infertility also increase when there is a delay in seeking initial treatment.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

There are no Joint Commission core measures applicable to cervicitis and PID.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

High risk women defined as younger than 25 years old, or those older than 25 with multiple sexual partners and/or a history of sexually transmitted diseases should be screened for C. trachomatis and N. gonorrhoeae at least yearly, though there is no data to support the ideal time frame for this. Disease prevention as mentioned above is also essential to limit recurrent disease and thus readmission.

VII. What's the evidence?

Blenning, CE, Muench, J, Judkns, DZ. "Which tests are the most useful for diagnosing PID". The Journal of Family Practice. vol. 56. 2007. pp. 216-218.

"CDC: Sexually Transmitted Disease Treatment Guidelines 2010". Morbidity and Mortality Weekly Report. vol. 59. 2010.

Cicchillo, LA, Hamper, UM, Scoutt, LM. "Ultrasound evaluation of gynecologic causes of pelvic pain". Obstetrics and Gynecology Clinics of North America. vol. 38. 2011. pp. 85-114.

Gaitan, H, Angel, E, Diaz, R, Parada, A, Sanchez, L, Vargas, C. "Accuracy of five different diagnostic techniques in mild to moderate pelvic inflammatory disease". Infectious Diseases in Obstetrics and Gynecology. vol. 10. 2002. pp. 171-180.

Gaydos, C, Maldeis, NE, Hardick, A, Hardick, J, Quinn, TC. "Mycoplasma genitaliaas a contributor to multiple etiologies of cervicitis in women attending sexually transmitted disease clinics". Sex Transm Dis. vol. 36. 2009. pp. 598-606.

Marrazo, JM, Martin, DH. "Management of women with cervicitis". Clinical Infectious Diseases. vol. 44. 2007. pp. 5102-10.

Short, VL, Totten, PA, Ness, RB, Astete, SG, Kelsey, SF, Haggerty, CL. "Clinical presentation of Mycoplasma genitalium infection versus Neisseria gonorrhoeae infection among women with pelvic inflammatory disease". Clinical Infectious Diseases. vol. 48. 2009. pp. 41-47.

Soper, DE. "Pelvic Inflammatory Disease". Obstetrics and Gynecology. vol. 116. 2010. pp. 419-428.

Vandermeer, FQ, Wong-You-Cheong, JJ. "Imaging of acute pelvic pain". Clinical Obstetrics and Gynecology. vol. 52. 2009. pp. 2-20.

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