Pelvic inflammatory disease is an infectious process involving a woman’s upper genital tract. While the infection may be limited to the uterus, fallopian tubes, and/or ovaries, it may also become extensive and involve the neighboring pelvic organs.

Pelvic inflammatory disease (PID) is the most frequent gynecologic cause of emergency department visits, approaching 350,000 per year.¹ Complications of untreated PID are devastating and include ectopic pregnancy, infertility, and chronic pelvic pain.

Therefore, it is necessary for emergency physicians to diagnose and initiate appropriate antibiotic therapy in patients with PID in order to achieve optimal patient outcomes.

Pathogenesis

PID affects the female upper genital tract, with infection leading to endometritis, salpingitis, oophritis, pelvic peritonitis, and perihepatits.²

The dominant organism in a healthy woman’s vaginal flora is Lactobacillus acidophilus, though species of streptococci, staphylococci, and enterobacteriaceae are also present.³

While the endocervical canal typically functions as a barrier between the potentially pathogenic vaginal bacteria and the sterile female upper reproductive tract, PID results from a disruption of both the vaginal flora and the endocervical canal.

Risk factors for the development of PID include a prior episode of PID,⁴ a high number of sexual partners,⁵ use of nonbarrier contraception,⁶ and earlier age at first intercourse.⁷

Microbiology

Epidemiologic studies suggest that sexually transmitted diseases are the cause of community-acquired PID.

The most common initiating pathogens are Neisseria gonorrhoeae and Chlamydia trachomatis, although a specific inciting organism is not determined in approximately 20% of PID cases.⁸

N. gonorrhoeae was the first identified cause of PID and currently accounts for approximately 40% of PID cases overall, though there is considerable geographic variance.⁹ C. trachomatis was first recognized as an organism responsible for PID in the mid-1970s and is identified in 50% of cases.¹⁰

While the vast majority of gonorrheal and chlamydial infections are asymptomatic, it is estimated that approximately 15% of cervical infections from these organisms ultimately result in PID.¹¹

Diagnosis

PID represents a spectrum of infection, ranging from patients who are minimally symptomatic to those who are toxic with fever, vomiting, and severe pain at the time of presentation.

As a result, the diagnosis of PID often presents a challenge for the emergency physician because of the nonspecific nature of the most common presenting signs and symptoms.

However, while there is no gold standard for the diagnosis of PID, information garnered from the history and physical exam will certainly aid in diagnosis.

More than 90% of patients diagnosed with PID present with bilateral lower abdominal pain.¹² The onset of this pain during or shortly after menses is particularly suggestive, as up to 75% of cases occur within the first 7 days of menses, when the quality of the cervical mucus favors the ascension of vaginal bacteria.¹³

New vaginal discharge is also present in up to 75% of cases but is neither sensitive nor specific for the diagnosis.¹⁴ Abnormal uterine bleeding occurs in one-third of patients.14

More than 90% of patients with PID will have a tender lower abdomen, but only half of all patients exhibit fever.¹⁵

The pelvic examination is unequivocally the most useful component of the physical exam to aid in the diagnosis of PID. Mucopurulent endocervical discharge, cervical motion tenderness, and bilateral adnexal tenderness are all highly suggestive of PID.¹⁵ Endocervical cultures for N. gonorrhoeae and C. trachomatis should be obtained in all cases of presumed PID.

There is no single test or combination of tests that is sensitive and specific for the diagnosis of PID. Additional criteria used to enhance specificity for the diagnosis include oral temperature higher than 101° F, abnormal cervical or vaginal mucopurulent discharge, presence of abundant numbers of white blood cells on saline microscopy of vaginal secretions, elevated ESR, elevated CRP, and laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis.¹⁵

All patients with presumed PID should have a pregnancy test, as PID in pregnancy is an indication for hospitalization, and ectopic pregnancy and septic abortion are in the differential diagnosis of PID.

A urinalysis is helpful to exclude urinary tract infection.

Of note, an elevated WBC count is not a CDC criterion for diagnosis, because fewer than two-thirds of women with PID have a WBC count of more than 10,000 cells/mcL.¹⁶

As the clinical diagnosis of PID is imprecise due to the nonspecific nature of the presenting signs and symptoms, the Centers for Disease Control and Prevention recommends that health care providers maintain a low threshold for diagnosis and empiric treatment for patients with presumed PID.

Recent guidelines recommend treatment for any patient who has lower abdominal tenderness on palpation, adnexal tenderness, and cervical motion tenderness in the absence of an established cause other than PID.¹⁵

Treatment

While PID was originally considered an indication for hospital admission and parenteral therapy, there is now a dominant trend toward outpatient treatment.

Currently, just 10%–25% of women diagnosed with PID are hospitalized.¹⁷ The CDC has established these criteria as indications for hospitalization:

pregnancy, lack of response to or intolerance of oral medications, nonadherence to therapy, severe clinical illness, pelvic abscess, or possible need for surgical intervention.¹⁸

Because the efficacy both of oral and parenteral therapies has been supported by randomized clinical trials, decisions concerning appropriate antimicrobial therapy are influenced instead by cost, allergy history, and resistance patterns.¹⁹

Regardless of whether oral or parenteral therapy is used, the CDC recommends a 14-day course of antibiotics.¹⁵

Recommended outpatient regimens include:¹⁵

• Ceftriaxone (250 mg IM) plus doxycycline (100 mg p.o. b.i.d. for 14 days).
• Cefoxitin (2 g IM) with probenicid (1 gram p.o. once) plus doxycycline (100 mg p.o. b.i.d. for 14 days).
• Any other third-generation cephalosporin in a single IM dose combined with doxycycline for 14 days.

The decision of whether to add metronidazole to the treatment regimen is addressed in the controversies section.

As of 2007, the CDC no longer recommends the use of fluoroquinolones as first-line therapy for PID, given increasingly high rates of gonorrheal resistance.¹⁵ Thus, outpatient therapy in the truly cephalosporin-allergic patient is very limited.

Depending on the severity of illness, the most effective treatment regimen is admission for parenteral therapy with clindamycin plus gentamicin.

In well-appearing patients, an alternate therapy includes levofloxacin (500 mg orally daily for 14 days), but these patients require close follow-up to determine if symptoms are improving, as well as a test of cure at the conclusion of therapy.

Inpatient treatment regimens closely follow outpatient recommendations. The CDC recommends one of these two regimens:

• Cefoxitin (2 g IV every 6 hours) or cefotetan (2 g IV every 12 hours) plus doxycycline (100 mg IV or p.o. every 12 hours).
• Clindamycin (900 mg IV every 8 hours) plus gentamicin loading dose (2 mg/kg) followed by a maintenance dose (1.5 mg/kg every 8 hours). Either regimen results in a clinical cure in more than 90% of cases.¹⁸

Many patients initially admitted for parenteral therapy can be transitioned to oral therapy to complete the course; this transition typically occurs 24 hours after sustained clinical improvement.¹⁵

the cdc recommends that health care providers maintain a low threshold for diagnosis and empiric treatment of presumed PID.

Complications

Even with prompt diagnosis and appropriate treatment of PID, complications are frequent, resulting from the scarring and adhesion formation that develop while the infected organs heal.

Immediate complications include tubo-ovarian abscess and Fitz-Hugh-Curtis syndrome, while the longterm complications include chronic pelvic pain, infertility, and ectopic pregnancy.

Tubo-ovarian abscess (TOA) is one of the most immediate and life-threatening complications of PID. Up to one-third of patients may experience this complication, which occurs when purulent material gains access to the ovary via the fallopian tube.

TOA is a polymicrobial infection that leads to worsening abdominal pain with unilateral adnexal tenderness and fever. Patients with TOA should be hospitalized until they begin to improve, as abscess rupture is a surgical emergency and can rapidly lead to sepsis, shock, and death.

Fitz-Hugh-Curtis syndrome refers to a perihepatitis resulting from peritoneal dissemination of PID. Inflammation and swelling of the liver capsule lead to pleuritic right upper quadrant pain.

Fitz-Hugh-Curtis syndrome affects up to a quarter of women diagnosed with PID, and in chronic cases, the formation of adhesions can lead to persistent pain.²⁰

Chronic pelvic pain, defined as infraumbilical pain of at least 6 months’ duration that is severe enough to cause functional disability, is one of the causes of long-term morbidity following a case of PID.

Chronic pelvic pain occurs in up to one-third of women who are diagnosed with PID, and there is currently no cure. Recurrent episodes of PID are the strongest predictor in the development of chronic pelvic pain.²¹

Infection of the fallopian tubes leads to two of the most devastating consequences of PID: infertility and ectopic pregnancy.

Infection in the fallopian tubes causes a vigorous inflammatory reaction, and a combination of bacteria and white blood cells fills the tubes.

The presence of this inflammatory reaction leads to permanent scarring. This scar tissue may lead to partial or complete blockage of the tube, thereby affecting future fertility.

A study by Westrom demonstrated a 16% infertility rate after a single episode of PID.²² Risk factors associated with the development of tubal infertility include increasing numbers of PID episodes, delay in seeking care, severity of infection, and Chlamydia infection.⁴

In addition to infertility, the risk of ectopic pregnancy increases with the number of episodes and severity of disease, and is 6 to 10 times as common in women with a history of PID, compared with those patients without a history.⁴

To prevent recurrent episodes of PID and its long-term complications, patients should be counseled about the nature of the disease at the time of diagnosis.

Patients should be informed that PID is a sexually transmitted disease, educated about safe sex practices, and offered follow-up for HIV and syphilis testing.

In addition, male sex partners within the preceding 60 days of a woman’s diagnosis with PID should undergo evaluation for treatment.

PID is the most frequent gynecologic cause of emergency department visits, approaching 350,000 per year.

Controversies

Because there is no single diagnostic gold standard for PID, the question as to the utility of adjunct imaging studies is often discussed.

The utility of transvaginal ultrasound to aid in diagnosis is particularly debated.

Acute PID produces notable changes on ultrasound, including tubal wall thickness greater than 5 mm, incomplete septae within the tube, fluid in the cul-de-sac, and a “cogwheel” appearance to the tube on cross-sectional view.

However, the utility of ultrasound for diagnosis remains limited, as the absence of these findings should not diminish one’s clinical suspicion for PID.

One study of 55 women with histologically-confirmed PID who underwent transvaginal ultrasound found sensitivities of 32%-42% for findings consistent with PID.²³

As a result of these low sensitivities, transvaginal ultrasound cannot be used to rule out PID. Its use should be limited to acutely ill patients with clinically diagnosed PID in whom the diagnosis of TOA is suspected (sensitivity 93%, specificity 98%).²⁴

Laparoscopy, once considered the diagnostic gold standard for PID, is now thought to lack sufficient sensitivity for the diagnosis.²⁵

In a study by Gaitain comparing various means of diagnosing PID, conclusions were that clinical diagnosis has an 87% sensitivity, while laparoscopy has 81% sensitivity and 100% specificity.26

Therefore, given the invasiveness of laparoscopy, it is now utilized as a diagnostic means only for those patients who follow an atypical course and fail to respond to aggressive inpatient parenteral therapy.

The decision of whether to add metronidazole to cover bacterial vaginosis and other anaerobic organisms is also widely debated.

While any patient with concomitant bacterial vaginosis or trichomonas infection should be treated with a course of metronidazole, the addition of this therapy in other patients is based on their risk of infection with an anaerobic organism.

Those at risk include patients with a pelvic abscess and those with a history of gynecological instrumentation in the 3 weeks preceding infection.¹⁵

Adherence to the 14-day antibiotic regimen is difficult for many patients, and research has focused on how to achieve better compliance with the antibiotic regimen.

One double-blind, randomized, control study compared the efficacy of combining a single dose of IM ceftriaxone followed by 14-days of either twice daily doxycycline or once a day azithromycin. In this study, once daily azithromycin proved superior, with a cure rate of 90%, compared with 72% in twice daily doxycycline.²⁷ The results are attributed in part to the fact that fewer than 70% of patients completed the doxycycline course as prescribed.

However, the CDC has not yet added azithromycin to its recommended regimens, as more studies are first needed to confirm this finding.

Conclusion

Pelvic inflammatory disease affects hundreds of thousands of women each year and is a leading cause of abdominal pain in women presenting to the emergency department.

The diagnosis is largely a clinical one, and practitioners must maintain a low threshold for diagnosing and treating PID, as empiric therapy will lessen the serious complications related to untreated disease.

References

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