Pelvic Inflammatory Disease

Etiology

Pelvic inflammatory disease is caused by an ascending infection from the cervix. In 85% of cases, the infection is caused by sexually transmitted bacteria or microbes associated with bacterial vaginosis.[2] Of the offending agents, N gonorrhoeae and C trachomatis are the most common pathogens. Approximately 10% to 15% of women with endocervical N gonorrhoeae or C trachomatis develop pelvic inflammatory disease.[2] Typically, gonorrheal pelvic inflammatory disease is more severe than pelvic inflammatory disease caused by other pathogens. In contrast, pelvic inflammatory disease due to chlamydia is less likely to cause symptoms and, therefore, more likely to result in subclinical pelvic inflammatory disease.[2] Subclinical pelvic inflammatory disease can produce little to no symptoms but can still have significant long-term complications.

Other cervical microbes, including Mycoplasma genitalium, also cause the disease. In addition, pathogens responsible for bacterial vaginosis, such as Peptostreptococcus species and Bacteroides species; respiratory pathogens, such as Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus; and enteric pathogens, such as Escherichia coli, Bacteroides fragilis, and group B Streptococci, have been implicated in acute pelvic inflammatory disease.[7] Collectively, these organisms account for approximately 15% of cases.[2][8][9][10] In rare cases, pelvic actinomycosis or tuberculosis can cause a chronic, indolent form of pelvic inflammatory disease.[2]

Epidemiology

Pelvic inflammatory disease occurs most frequently in females aged 15 to 25. In 2001, there were more than 750,000 cases of pelvic inflammatory disease in the United States. Over the past decade, the rates of pelvic inflammatory disease have been decreasing, but it is still commonly observed in both outpatient clinics and emergency department settings.

Pathophysiology

Cervical infections disrupt the normal cervical barrier, including the mucosal innate immune system, between the vagina and upper genital tract, leading to infection of these typically sterile organs.[11] Organisms associated with bacterial vaginosis, which is common in patients with pelvic inflammatory disease, also interfere with the host defenses and introduce additional pathogenic microorganisms that can ascend into the upper tracts.[11][7] These organisms can produce local enzymes that degrade the antimicrobial peptides within the cervical mucus.

Infection of the upper female genital tract leads to inflammatory damage, resulting in scarring, adhesions, and partial or total obstruction of the fallopian tubes. This damage can result in the loss of ciliated epithelial cells along the inner lining of the fallopian tube, impairing ovum transport and an increased risk of infertility and ectopic pregnancy.[2] In addition, adhesions can lead to chronic pelvic pain.[12]

History and Physical

As pelvic inflammatory disease is primarily a clinical diagnosis, a thorough history and physical examination are crucial. Pelvic inflammatory disease may present with lower abdominal or pelvic pain, vaginal discharge, dyspareunia, and abnormal vaginal bleeding.[11][1][2] Clarification of the onset and character of the pain should be obtained while also exploring possible alternative diagnoses. With pelvic inflammatory disease, the pain is often bilateral and can range from mild to severe.[1] However, patients may also be entirely asymptomatic or have only subtle symptoms, such as pain only during intercourse or menses. Urinary symptoms, such as dysuria and frequency, are also possible.[1] Risk factors for pelvic inflammatory disease are similar to those for other STIs and include being younger than 25, having multiple sex partners, having a partner with STIs or symptoms, starting sexual activity at a young age, a prior history of STIs, inconsistent use of barrier contraception, and the presence of bacterial vaginosis.[1][7][11][13] In addition, the risk of pelvic inflammatory disease is increased in the first 3 weeks following the insertion of an intrauterine device; however, beyond this initial time period, the presence of an intrauterine device does not significantly increase the risk.[1]

Patients with suspected pelvic inflammatory disease should undergo a comprehensive evaluation, including abdominal, speculum, and bimanual pelvic examination.[1][3] Pelvic inflammatory disease is classically characterized by cervical motion, uterine, and adnexal tenderness on bimanual examination. Purulent vaginal discharge, cervical friability, and fever are also common findings.[1][3] An adnexal mass in pelvic inflammatory disease suggests a tubo-ovarian abscess. Purulent cervical discharge and abnormal vaginal discharge are also common. If the inflammation extends to the liver capsule, patients can develop a perihepatitis, known as Fitz-Hugh-Curtis syndrome, which can cause pleuritic pain in the right upper quadrant that radiates to the right shoulder.[1][2]

Evaluation

The diagnosis of pelvic inflammatory disease is primarily clinical.[1][2][3] Laboratory evaluation should include a pregnancy test to exclude the possibility of an ectopic pregnancy as an alternate etiology of pelvic pain. In addition, endocervical samples should be obtained for nucleic acid amplification testing for C trachomatis and N gonorrhoeae; if available, nucleic acid amplification testing for M genitalium should also be performed. Microscopy should also be performed to assess for the presence of bacterial vaginosis; abundant white blood cells are common with pelvic inflammatory disease. Although these tests may help confirm the diagnosis, negative results do not exclude pelvic inflammatory disease.[1][2][3] Testing for other STIs, including HIV and Treponema pallidum (syphilis), is also indicated. General blood tests, including a complete blood count, erythrocyte sedimentation rate, and C-reactive protein, may provide nonspecific evidence of disease and are primarily used to assess the severity of the illness.[3]

Pelvic ultrasound is typically appropriate in patients with acute pelvic pain; imaging is indicated if an adnexal mass is palpable to evaluate for a possible tubo-ovarian abscess.[1][14][15] Findings consistent with pelvic inflammatory disease include dilated, fluid-filled fallopian tubes, a cogwheel appearance on the cross-section of the tube, gas or fluid within the endometrial canal, and a complex, multiloculated adnexal mass.[3] However, the absence of imaging findings suggestive of pelvic inflammatory disease does not exclude the diagnosis. 

Treatment / Management

Due to the risk of potential long-term sequelae, treatment should not be delayed while awaiting the results of nucleic acid amplification testing. Clinicians should maintain a low threshold of suspicion for pelvic inflammatory disease, and early treatment should be initiated based on appropriate clinical suspicion.[16][17][18]

Indications for hospitalization include pregnancy; failed outpatient treatment; severe clinical illness, including patients with nausea, vomiting, and temperature >38.5 °C; pelvic inflammatory disease with pelvic abscess; or the possible need for surgical intervention.[3][1] Outpatient treatment is appropriate for patients with mild-to-moderate disease.[19](A1)

The 2021 United States Centers for Disease Control and Prevention (CDC) STI Treatment Guidelines recommend the following empiric regimen for pelvic inflammatory disease in the inpatient setting:

• Ceftriaxone 1 g intravenous (IV) every 24 hours plus doxycycline 100 mg by mouth or IV every 12 hours plus metronidazole 500 mg IV or by mouth every 12 hours or
• Cefotetan 2 g IV every 12 hours plus doxycycline 100 mg by mouth or IV every 12 hours or
• Cefoxitin 2 g IV every 6 hours plus doxycycline 100 mg by mouth or IV every 12 hours or
• Clindamycin 900 mg IV every 8 hours plus gentamicin 3 to 5 mg/kg IV once daily [13]

Supportive care, including fluid management, antiemetics, and analgesics, is also indicated. Surgical management may be appropriate for patients with a tubo-ovarian abscess that is associated with severe disease or is not responding to antibiotics. After 24 to 48 hours of clinical improvement, patients can be transitioned to an oral regimen consisting of doxycycline 100 mg twice daily plus metronidazole 500 mg twice daily to complete a total antibiotic course of 14 days. 

For patients being treated entirely as an outpatient, the preferred CDC regimen is as follows:

• A third-generation parenteral cephalosporin plus doxycycline 100 mg by mouth twice daily for 14 days plus metronidazole 500 mg by mouth twice daily for 14 days [13]

Appropriate cephalosporins to be used as part of an outpatient treatment regimen include:

• Ceftriaxone 500 mg IM once (or 1 g for individuals weighing >150 kg)
• Cefoxitin 2 g IM once plus probenecid 1 g by mouth once (concurrent with cefoxitin) 
• Others: Ceftizoxime and cefotaxime [13]

Metronidazole provides additional anaerobic coverage and is now recommended as a routine component of outpatient regimens due to evidence demonstrating improved long-term outcomes with its use. The sex partners of patients with STI-associated pelvic inflammatory disease should be evaluated and treated to prevent reinfection.

Patients with a tubo-ovarian abscess may require surgical drainage, especially if the abscess is greater than or equal to 8 cm, ruptures, or the patient becomes septic.[13]

Differential Diagnosis

Alternative conditions that should be considered when evaluating a patient with symptoms suggestive of pelvic inflammatory disease include:

• Ectopic pregnancy
• Ruptured ovarian cyst
• Adnexal torsion
• Endometriosis
• Urinary tract infection (cystitis and pyelonephritis)
• Appendicitis
• Diverticulitis
• Irritable bowel syndrome
• Traumatic injury [1][3][13][3]

Prognosis

The prognosis for pelvic inflammatory disease is favorable; however, there is a significant risk for long-term complications, which are discussed below.[13]

Complications

Acute complications of pelvic inflammatory disease include the development of a tubo-ovarian abscess and perihepatitis, also known as Fitz-Hugh-Curtis syndrome. Tubo-ovarian abscess develops in 15% to 35% of patients with pelvic inflammatory disease and may require surgical intervention in addition to standard antibiotic regimens.[13] With Fitz-Hugh-Curtis syndrome, the liver capsule and right upper quadrant peritoneal surfaces become inflamed, which can lead to severe right upper quadrant pain. The liver parenchyma is generally not involved, and aminotransferases are typically normal.

Delayed treatment of pelvic inflammatory disease has a strong association with worse outcomes and long-term complications. However, even with timely treatment, long-term complications can occur. A study estimated that for females with pelvic inflammatory disease aged 20 to 24, 18% developed chronic pain, 8.5% developed ectopic pregnancies, and 16.8% struggled with infertility.[20][21][22]

Chronic pelvic pain is observed in as many as one-third of women with pelvic inflammatory disease. The pain is thought to be related to inflammation, scarring, and adhesions from the infectious process. The strongest predictor of developing chronic pelvic pain related to pelvic inflammatory disease is recurrent pelvic inflammatory disease.

Pelvic inflammatory disease can lead to infertility, regardless of whether the disease is symptomatic or asymptomatic. The infection can cause severe damage to the fallopian tubes, including loss of the tubal ciliary epithelial cells and occlusion of the tube.[23] Studies have shown that women with a history of pelvic inflammatory disease have up to a 5-fold increased risk of infertility. Infertility related to pelvic inflammatory disease is more likely to occur if C trachomatis is the infectious cause, if there is a delay in treatment for pelvic inflammatory disease, if the patient has recurrent episodes of pelvic inflammatory disease, or if the case of pelvic inflammatory disease is more severe.[24]

The increased risk of ectopic pregnancy following pelvic inflammatory disease is also related to tubal damage. An older Swedish study involving 1844 women demonstrated that the rate of ectopic pregnancy following pelvic inflammatory disease is approximately 9% compared to a rate of 1.4% among patients with no history of pelvic inflammatory disease.[23]