Pelvic Inflammatory Disease: Current Concepts in Pathogenesis, Diagnosis and Treatment

Key points

Pelvic inflammatory disease (PID) is characterized by infection

Epidemiology

In the United States in 2000, there were an estimated 1.2 million medical visits for PID,¹ a number that has been decreasing since 1985.2, 3, 4 This decrease is attributed in part to widespread adoption of screening for Chlamydia trachomatis, the goal of which is to identify and treat asymptomatic cases of cervicitis before they can progress to PID.⁵ Estimated direct medical costs associated with PID and its sequelae (ectopic pregnancy, chronic pelvic pain, and tubal infertility) were as high

Etiology

In early studies of PID, N gonorrhoeae was the most commonly isolated pathogen, and is still more likely than other pathogens to cause severe symptoms.13, 17, 18, 19 However, as the prevalence of gonorrhea has decreased, its importance as a causal agent for PID has diminished.20, 21 C trachomatis remains a significant pathogen associated with PID, detected in up to 60% of women with confirmed salpingitis or endometritis.22, 23, 24 Mycoplasma genitalium has been independently associated with

Pathogenesis

Mathematical modeling based on epidemiologic and microbiologic studies suggests that 8% to 10% of women with C trachomatis infection will develop PID if not treated,³⁰ although in studies that followed women with chlamydial endocervical infection without treatment, the rate was even lower.31, 32 When both the lower and upper genital tract are sampled there is a clear gradient of infections, with a higher proportion of women testing positive at the vagina and/or cervix, fewer in the endometrium,

Clinical evaluation and differential diagnosis

In practical terms, when a sexually active woman presents to the clinic or emergency department with lower abdominal or pelvic pain, PID must be considered in the differential diagnosis, which also includes appendicitis, ectopic pregnancy, ovarian torsion, intrapelvic bleeding, rupture of an adnexal mass, endometriosis, and gastroenteritis.⁴⁵ Key components of the physical examination include:

• 1.

  Abdominal examination, including palpation of the right upper quadrant

• 2.

  Vaginal speculum examination,

Sensitivity and specificity of CDC diagnostic criteria

The clinical diagnosis of PID is based on recommendations from the Centers for Disease Control and Prevention (CDC). Minimum diagnostic criteria (Box 1) have been set with a high sensitivity and low specificity in order to detect as many cases of clinical disease as possible, thus potentially avoiding the long-term reproductive sequelae and economic costs associated with delayed diagnosis and lack of treatment.

In a cohort of patients with suspected PID who underwent laparoscopy in Lund, Sweden,

Laboratory testing

Because PID is a clinical diagnosis, laboratory data or imaging studies are not usually necessary, but can be helpful in establishing the diagnosis or in defining its severity.⁵¹ In the PEACH trial, which enrolled women with abdominal pain, pelvic tenderness, and evidence of lower genital tract inflammation, an elevated leukocyte count (≥10,000 cells/mL) had 41% sensitivity and 76% specificity for the presence of endometritis.⁵² The presence of 1 or more neutrophils per 1000× field saline wet

Imaging studies

Ultrasonography can also be used to aid in the diagnosis of PID and its direct treatment. A finding of thickened, fluid-filled tubes has 85% sensitivity and 100% specificity for endometritis among women with clinically diagnosed PID.⁵⁵ Timor-Tritsch and colleagues⁵⁶ detailed the various transvaginal sonographic markers of acute tubal inflammatory disease, including dilated tubal shape, abnormal wall structure, increased wall thickness (≥5 mm), and presence of pelvic peritoneal fluid (free fluid

Inpatient versus outpatient management

The therapeutic goal for the treatment of PID is 2-fold: short-term microbiologic and clinical cure; and long-term prevention of sequelae, namely tubal infertility, ectopic pregnancy, and chronic pelvic pain. Since the 1980s, PID therapy has shifted from the inpatient to the outpatient setting, with a 68% decline in hospitalization⁴ attributable in part to several studies showing equivalent short-term outcomes with outpatient versus inpatient therapy for mild to moderate PID.59, 60 Between 1995

CDC recommendations for antimicrobial therapy

Current recommendations for antimicrobial treatment regimens in PID were published in 2010 (Table 4), and are scheduled for update in 2014.⁶⁷ A guiding principle for selection of antimicrobial therapy for PID is that the regimen should cover N gonorrhoeae and C trachomatis, regardless of results of diagnostic testing for these pathogens. Therapy for gonorrhea, and therefore PID, shifted away from fluoroquinolone-based regimens between the 2006 and 2010 iterations of the CDC Treatment

Alternative antimicrobial regimens

Although not part of the CDC recommendations, newer data suggest that parenteral followed by oral azithromycin, either as monotherapy or in combination with doxycycline and metronidazole, produces clinical cure rates of 97% to 98% at 2 weeks after initiation of treatment, and microbiologic cure rates of 90% to 94% at 6 weeks posttreatment.⁷⁰ The azithromycin-based regimens were compared with third-generation cephalosporin-based regimens or parenteral amoxicillin-based regimens and showed no

Anaerobes: to cover or not?

There is little clarity on the need for empiric coverage for anaerobic bacteria when PID is diagnosed, in part because there is a lack of clear understanding of the contribution of anaerobes to pathogenesis in PID. Several studies have shown that BV is associated with PID, with BV-associated anaerobic bacteria present in endometritis, but that BV may not actually cause acute PID.16, 61, 74 However, other data have not shown any long-term reproductive sequelae of histologically diagnosed

Additional treatment considerations

Among patients who qualified for outpatient therapy, reevaluation of clinical status should occur within 72 hours, or sooner if indicated. If no meaningful clinical response is detected, patients with PID may require inpatient hospitalization, transition to parenteral antibiotics, further diagnostic tests including additional laboratory studies and imaging to evaluate for possible TOA, and possible surgical intervention.

Empiric treatment of gonorrhea and chlamydia is recommended for all male

Tubo-ovarian abscess

Although the presenting signs and symptoms of a TOA are not often distinct from those with salpingitis/endometritis, there are often more objective signs of infection and inflammation. A large series of patients with ultrasonographically or surgically confirmed TOA found that 60% had a temperature higher than 37.8°C, 68% had leukocytosis (>10,000 cells/mL), 26% had nausea, and 19% had chronic abdominopelvic pain.⁷⁷ In women with PID, palpation of an adnexal mass on physical examination,

Special populations: HIV-infected women

The presenting signs and symptoms of PID generally do not differ significantly by HIV infection status,81, 82 although some studies have demonstrated an increased odds of fever, higher clinical severity scores, and higher likelihood of having a TOA among HIV-infected women.83, 84, 85 Clinical severity has been found to correlate with immunosuppression among HIV-infected women with laparoscopically confirmed PID.⁸³

Treatment of PID or TOA has been shown to be as effective in HIV-infected women as

Special populations: postmenopausal women

Although rare, postmenopausal women can develop PID, presenting most commonly with lower abdominal pain and postmenopausal bleeding, as well as fever, nausea, and altered bowel habits; they are considerably more likely to have TOAs.87, 88 Among 20 postmenopausal women with TOAs in one case series, although only 20% of patients were febrile, 45% had elevated WBC counts, 55% had a palpable pelvic mass, and 90% had a TOA on surgical exploration.⁸⁹ In several small case series, pathologic analysis

Special populations: intrauterine devices

In the 1970s the Dalkon Shield intrauterine device (IUD) was associated with increased rates of PID, and led to significant concerns about the safety of IUDs in women at risk for STIs.⁹¹ Modern IUDs, including the levonorgestrel IUD (Mirena) and the copper IUD (Paraguard), have not been associated with an increased risk of PID over the long term.⁹² There does appear to be a slightly increased rate of PID in the 20 days after insertion: in one study the rate of PID during this time was 9.66 per

Sequelae

Women with PID have an increased risk of ectopic pregnancy, infertility, and chronic pelvic pain caused by tubal scarring and damage from inflammation. In the PEACH trial, 36% of participants reported chronic pelvic pain; women with 2 or more episodes of PID were at highest risk.⁹⁸ In a cohort study of women with laparoscopically confirmed salpingitis in Sweden, followed for a mean of 94 months, the infertility rate was 16%, 67% of which was attributable to tubal factor infertility, compared

Prevention

As gonorrhea and chlamydia contribute more than half to three-quarters of PID, screening for and treating these infections should decrease the incidence and sequelae. Four randomized trials have examined whether this strategy is effective. The earliest was conducted between 1990 and 1992 in Seattle, Washington. More than 1000 women in a managed care organization were randomized to receive an invitation for chlamydia screening, then followed for a year and compared with approximately 1600 women

Summary

PID is associated with significant reproductive morbidity, which appears to be reduced with prompt, proactive treatment of cervicitis and lower genital tract infections. It is a clinical diagnosis, and providers should maintain a high index of suspicion when presented with a woman of reproductive age complaining of abdominal and pelvic pain. STIs are commonly associated with PID, but vaginal anaerobes also seem to be involved, and antibiotic coverage for these pathogens should be considered