A 20-year-old woman who works as a secretary for a local insurance agency comes to her primary care clinic because she has been experiencing lower abdominal pain for two days. For the past four days, she has also noticed a yellowish vaginal discharge and dyspareunia, along with some dysuria. The yellowish discharge developed on the day following the last day of her most recent menstrual period. The woman's vital signs are normal except for a slight fever (38ºC). The physical examination reveals a yellowish mucopurulent discharge from the cervical os. Moderate left lower abdominal tenderness is present. The bimanual pelvic examination shows considerable cervical motion tenderness and adnexal tenderness that is more severe on the left than on the right. When asked about recent sexual activity, the patient indicates that she has had intercourse with two partners during the last month, including a new partner with whom she has been active for the past ten days. The woman uses an oral contraceptive, but neither she nor her partners take any other precautions.

Question 4.1: What is your preliminary diagnosis?

Some type of STD seems likely, given the patient's age and history of recent unprotected sexual activity. The yellowish discharge is indicative of a mucopurulent cervicitis, but this alone is not likely to account for all of the symptoms. The combination of mucopurulent discharge, abdominal pain, cervical motion tenderness, and adnexal tenderness suggests a case of pelvic inflammatory disease (PID). The fact that the symptoms began to appear shortly after the woman's most recent menstrual cycle is also suggestive of PID.

Question 4.2: How is the diagnosis confirmed?

Clinical diagnosis of PID is difficult and imprecise. No single historical, physical, or laboratory finding is both sensitive and specific for the diagnosis of PID. The CDC issued diagnostic criteria for PID in 1998. Empiric treatment is based on the presence of all of the following symptoms as minimum criteria for diagnosis of PID: (1) lower abdominal pain, (2) adenxal tenderness, and (3) cervical motion tenderness. Additional criteria that can increase the specificity of the diagnosis of PID in women with severe clinical signs include: oral temperature >38.3ºC, abnormal cervical or vaginal discharge, elevated ESR, elevated C-reactive protein, and laboratory documentation of cervical infection with Neisseria gonorrhoeae and/or Chlamydia trachomatis. More definitive diagnosis of PID depends on methods like laparoscopy, in which case one would look for: (1) erythema of the fallopian tube, (2) edema of the fallopian tube, and (3) a seropurulent exudate of fresh, easily lysed adhesions at the fimbriated end or on the serosal surface of a fallopian tube. However, routine laparoscopy to confirm suspected cases of PID is generally impractical.

In the present case, the attending physician felt that the symptoms were sufficiently suggestive to go with a preliminary diagnosis of PID and to begin appropriate treatment. To help substantiate the diagnosis, the physician ordered cultures for N. gonorrhoeae and C. trachomatis, along with a Gram stain of the endocervical exudate. Large numbers of PMNs were seen in the Gram stain, and the enzyme immunoassay for C. trachomatis was positive. The culture for N. gonorrhoeae was negative.

Question 4.3: What other agents cause this disease?

First episodes of PID are especially likely to be caused by the sexually transmitted pathogens C. trachomatis or N. gonorrhoeae. Gonococcal infections have a higher incidence rate in inner city populations, whereas chlamydial PID occurs more frequently in college students and more affluent populations. Other microbes have been implicated in PID, primarily in association with secondary episodes that can follow a primary episode caused by C. trachomatis or N. gonorrhoeae. Among these other microbes are mycoplasmas (Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium) and other aerobic and anaerobic bacteria, including those that are commonly associated with bacterial vaginosis (Gardnerella vaginalis, Prevotella, etc.). Mycobacterium tuberculosis is an important cause of PID in developing countries, but is rare elsewhere.

Question 4.4: How does this disease develop?

PID is typically an infection that ascends from the vagina or cervix to involve the endometrium, one or both fallopian tubes (salpingitis), and/or the ovaries. The events that lead to PID are not well understood. Certain anatomical features seem to be important in the pathogenesis of gonococcal or chlamydial PID. For example, cervical infection by these organisms may damage the endocervical canal, break down the mucus plug in the endocervix, and enable them (along with other vaginal bacteria) to ascend into the upper genital tract. In addition, an increase in the size of the zone of ectopy (extension of the columnar epithelium onto the ectocervix) might result in increased susceptibility to infection by gonococci or chlamydiae because the epithelial cells are the preferred sites of attachment for microbial invasion. Most cases of PID occur within 7 days of the onset of menses. Alterations of the cervical mucus plug caused by hormonal changes during the menstrual cycle might permit the passage of microbial pathogens. The reflux of infected blood during menstrual uterine contractions could also provide a route of entry into the fallopian tubes. Regardless of the mechanism by which ascending infection occurs, the manifestations of gonococcal and chlamydial infections appear to be the result of nonspecific and specific inflammatory responses to bacterial invasion that lead to tissue damage.

Question 4.5: What complications or sequelae are possible?

PID infections can extend beyond the reproductive tract to cause pelvic peritonitis, generalized peritonitis, perihepatitis, or pelvic abscesses. Infections by gonococci and chlamydiae typically cause scarring or other damage that can increase susceptibility to recurrences. The major complication of PID is infertility resulting from tubal occlusion. It has been estimated that approximately 8% of women become infertile after one episode of PID, 19.5% after two episodes, and 40% after 3 or more episodes. Other common complications of PID include ectopic pregnancy and chronic pelvic pain.

Question 4.6: What are the predisposing risk factors?

Multiple sexual partners, young age at first sexual intercourse, a high frequency of intercourse, and a high rate of acquiring new sexual partners all appear to be significant risk factors for PID. In addition, it has been shown repeatedly that vaginal douching is associated with PID. Certain contraceptive practices influence the occurrence of PID. Use of an IUD increases the risk of infection significantly, whereas combined estrogen/progesterone oral contraceptive drugs and barrier methods are slightly protective against PID. Several biological risk factors change with age, namely lower titers of protective antibody, larger zones of cervical ectopy that may facilitate the attachment of pathogens (see above), and easier penetrability of the cervical mucus plug.

Question 4.7: How significant is this disease?

PID is the most serious and costly common consequence of sexually transmitted diseases affecting women. 750,000 to 1,000,000 new cases are thought to occur each year in the U.S., and it is estimated that 10-15% of reproductive-age women in the U.S. have experienced at least one episode of the disease. The highest annual incidence is noted in sexually active females, who have about a 1-in-8 chance of developing PID. PID is also the most common cause of female infertility and ectopic pregnancy.

Question 4.8: How is this disease treated?

Women with PID can be treated as outpatients or inpatients. Outpatient treatment is often effective, but hospitalization should be considered if (1) severe illness, nausea, and vomiting preclude outpatient treatment, (2) the diagnosis is uncertain and surgical emergencies (e.g., appendicitis or ectopic pregnancy) cannot be excluded, (3) pelvic abscess is suspected, (4) the patient is infected with HIV, (5) the patient is assessed as unable to tolerate outpatient therapy or (6) the patient has not responded to outpatient therapy. Following are regimens for PID treatment that were recommended by the CDC in 1998:

Outpatient treatment:

Regimen A: Ofloxacin (400 mg PO bid x 14 days), plus...

Metronidazole (500 mg PO bid x 14 days)

Regimen B: Cefoxitin (2 g IM), plus...

Probenecid (1 g PO), ceftriaxone (250 mg IM), or equivalent cephalosporin, plus...

Doxycycline (100 mg PO bid x 10-14 days)

Inpatient treatment:

Regimen A: Cefoxitin (2 g IV q6h) or cefotetan (2 g IV q12h), plus...

Doxycycline (100 mg IV or PO q12h)...

Continue above for at least 24 hrs after substantial clinical improvement; then...

Doxycycline (100 mg PI bid for total of 14 days)

Regimen B: Clindamycin (900 mg IV q8h), plus...

Gentamicin loading dose IV or IM (2 mg/kg body weight), followed by...

Gentamicin maintenance dose (1.5 mg/kg q8h)...

Continue above for at least 24 hrs after substantial clinical improvement; then...

Doxycycline (100 mg PO bid) or clindamycin (450 mg PI qid), to complete total of 14 days of therapy

NOTE: Treatment should cover N. gonorrhoeae, C. trachomatis, Gram-negative facultative bacteria (especially E. coli and Haemophilus influenzae), vaginal anaerobes (Gardnerella, etc.), and group B streptococci. Outpatients should be clinically reevaluated within 72 hours.