Pelvic Inflammatory Disease 

Pelvic inflammatory disease (PID) is an infectious and inflammatory disorder of the upper female reproductive tract, including the uterus, fallopian tubes, and adjacent pelvic structures.

Pelvic inflammatory disease (PID) is initiated by infection that ascends from the vagina and cervix. Chlamydia trachomatis is the predominant sexually transmitted organism causing PID. Newer, more accurate, laparoscopic studies have shown that PID may often be polymicrobial in nature (30-40%). Other organisms that have been implicated in the pathogenesis of PID include Neisseria gonorrhoeae, Gardnerella vaginalis, Haemophilus influenzae, and anaerobes, such as Peptococcus and Bacteroides species. (see Etiology).

At presentation, women with PID may range from asymptomatic to seriously ill. The most common presenting complaint is lower abdominal pain. Many women also exhibit an abnormal vaginal discharge. The diagnosis of acute PID is primarily based on historical and clinical findings, but many patients may exhibit only a few or no symptoms. (See Clinical Presentation.)

The classic high-risk patient is a menstruating woman younger than 25 years who has multiple sex partners, does not use contraception, and lives in an area with a high prevalence of sexually transmitted disease (STD).

The differential diagnosis includes appendicitis, cervicitis, urinary tract infection, endometriosis, and adnexal tumors. PID is the most common incorrect diagnosis in cases of ectopic pregnancy. A pregnancy test is required in all women of childbearing age. A delay in diagnosis or treatment of PID can result in long-term sequelae, such as chronic pelvic pain and tubal infertility. (See Differentials.)

PID may produce tubo-ovarian abscess (TOA) and extend to produce pelvic peritonitis and Fitz-Hugh-Curtis syndrome (perihepatitis), as shown in the image below.

Laparoscopy is the current criterion standard for the diagnosis of PID. No single test is highly specific or sensitive for the disease, but certain laboratory studies that can be used to support the diagnosis include the erythrocyte sedimentation rate, C-reactive protein, and chlamydial and gonococcal DNA probes and cultures. Imaging studies, such as ultrasound, computed tomography, and magnetic resonance imaging may also prove helpful in unclear cases. (See Workup.)

Empirical treatment is suggested by the Centers for Disease Control and Prevention (CDC) Sexually Transmitted Disease Management Guidelines in patients with uterine or adnexal tenderness and cervical motion tenderness, if no other etiology explains the findings. All antibiotic regimens must be effective against C trachomatis and N gonorrhoeae, as well as against gram-negative facultative organisms, anaerobes, and streptococci . Most patients are now treated in an outpatient setting, but physicians should consider hospitalization in selected cases. (See Treatment and Management.)

Pelvic inflammatory disease may extend from infection of the lower female reproductive tract, including the vagina and cervix. Pelvic inflammatory disease (PID) is an infectious and inflammatory disorder of the upper female reproductive tract, including the uterus and fallopian tubes. Infection and inflammation may spread to adjacent pelvic structures in the pelvis and abdomen, including perihepatic structures (Fitz-Hugh Curtis syndrome).

Most cases of pelvic inflammatory disease (PID) are presumed to occur in 2 stages. The first stage is acquisition of a vaginal or cervical infection; this infection is often sexually transmitted and may be asymptomatic. The second stage is direct ascent of microorganisms from the vagina or cervix to the upper genital tract, with infection and inflammation of these structures.

The exact mechanism of ascent of microorganisms from the vagina and cervix is unknown. However, studies have suggested that a number of factors may be involved. Although cervical mucus provides a functional barrier against upward spread, the efficacy of this mechanism may be decreased by hormonal changes that occur during ovulation and menstruation.

Alterations in the cervicovaginal microenvironment may also result from antibiotic treatment and sexually transmitted infections that can disrupt the balance of endogenous flora, causing normally nonpathogenic organisms to overgrow and ascend. Opening of the cervix during menstruation with retrograde menstrual flow may also facilitate ascent of microorganisms.

Intercourse may contribute to the ascent of infection due to rhythmic mechanical uterine contractions. Bacteria may be carried along with sperm into the uterus and tubes

It has also been suggested that genetic polymorphisms of PID pathogens affect the likelihood that a lower tract infection will progress to frank PID. Chlamydial heat shock protein 60 (CHSP60) antigen expression in C trachomatis^[1] and P9Opa(b) protein expression in N gonorrhoeae^[2] are examples of specific bacterial genes implicated in the pathology of PID.

In the upper tract, a number of microbial and host factors appear to play a role in the degree of host inflammation and resultant scarring. Tubal infection initially affects the mucosa, but acute, complement-mediated transmural inflammation may develop rapidly and increase in intensity with subsequent infections.

Inflammation may extend to uninfected parametrial structures, including the bowel. Infection may extend by spillage of purulent materials from the fallopian tubes or via lymphatic spread beyond the pelvis to produce acute peritonitis and acute perihepatitis (Fitz-Hugh Curtis syndrome).

Pregnancy-related factors

Pregnancy decreases the risk of PID once the cervical os is protected by the mucous plug. PID rarely occurs in pregnancy; however, the disease can occur in the first 12 weeks of gestation, before the mucous plug solidifies and seals off the uterus from ascending bacteria; fetal loss may result. Concurrent pregnancy influences the choice of antibiotic therapy for PID and demands that an alternative diagnosis of ectopic pregnancy be excluded. Uterine infection is usually limited to the endometrium but may be more invasive in a gravid or postpartum uterus.

Genetics

Den Hartog et al found a possible contributing role of 5 single-nucleoside polymorphisms (SNPs) in 4 genes encoding pattern recognition receptors in local tubal cells and circulating immune cells (eg, macrophages). The presence of 2 or more SNPs in patients appeared to correlate with increased laparoscopically identifiable tubal pathology.^[3]

Infecting organisms

The organisms most commonly isolated in many, if not most, cases of acute PID are Neisseria gonorrhoeae and Chlamydia trachomatis.^[4] C trachomatis, an intracellular bacterial pathogen, is the predominant sexually transmitted organism causing PID, In the United States, the role of N gonorrhoeae as the primary cause of PID has decreased; however, it remains the second most frequently reported sexually transmitted infection after Chlamydia. C linically, infection may be asymptomatic or manifest similarly to Chlamydia. An estimated 10-20% of untreated chlamydial or gonorrheal infections progress to PID.

However, newer studies using more sensitive and specific laparoscopic cultures have found acute PID to be polymicrobial in up to 30-40% of cases. N gonorrhoeae and C trachomatis may be instrumental in the initial infection of the upper tract, with anaerobes, facultative anaerobes, and other bacteria increasingly isolated as inflammation increases and abscesses form. Organisms involved include the following:

• Gardnerella vaginalis
• Mycoplasma hominis
• Mycoplasma genitalium^[5]
• Ureaplasma urealyticum
• Herpes simplex virus–2 (HSV-2)
• Trichomonas vaginalis
• Cytomegalovirus
• Haemophilus influenza
• Streptococcus agalactiae
• Enteric gram-negative rods (Escherichia coli)
• Peptococcus species
• Anaerobes

In addition, cytomegalovirus (CMV) has been found in the upper genital tracts of women with PID, suggesting a potential role of CMV in PID. In iatrogenically induced infections, the endogenous microflora of the vagina predominate. Bacteroides fragilis can cause tubal and epithelial destruction. N gonorrhoeae and C trachomatis may be instrumental in the initial infection of the upper tract, with anaerobes, facultative anaerobes, and other bacteria increasingly isolated as inflammation increases and abscesses form.

The microbiology of PID has also been found to reflect the predominant sexually transmitted infections (STIs) prevalent within a specific population and also less-common organisms seen in that population. Bacterial vaginosis (BV) is suggested to play a role in the initiation of ascending infection in a subset of women with heavy growth of BV-associated organisms, such as G vaginalis, more than 2 recent sexual partners, and especially after recent abortion or gynecologic surgery.^{[6, 7]} In less-developed countries, PID may be due to a granulomatous salpingitis caused by Mycobacterium tuberculosis or Schistosoma species.^[8]

Patients infected with T vaginalis demonstrated a 4-fold increase in the histologic evidence of acute endometritis in a 2006 cross-sectional study of 736 women with PID. Co-infection of HSV-2 with N gonorrhoeae, C trachomatis, and BV was also associated with histologic evidence of acute endometritis. HSV-2 was demonstrated to be associated with fallopian tube inflammation and lower tract ulcerations that may contribute to disruption of the endocervical canal mucus barrier.^[9]

Human immunodeficiency virus (HIV) infection has been found to be associated with an increased incidence of C trachomatis infection, Candida, and human papillomavirus. Women with HIV infection also have an increased risk of progression to PID and tubo-ovarian abscess.^[10]

Microbial virulence appears to play a significant role in PID. Bjartling et al studied different chlamydial strains recovered from patients with PID and found less symptomatic disease in infection produced by a less virulent variant strain.^[11]

Risk factors

Risk factors for PID include multiple sexual partners, a history of prior STIs, and a history of sexual abuse.^[12] Frequent vaginal douching has also been implicated. Frequent vaginal douching has been considered a risk factor for PID,^[13] but studies reveal no clear association.^[14]

Younger age has been found to be associated with increased risk, suggested to be due to some combination of increased cervical mucosal permeability, a larger zone of cervical ectopy, a lower prevalence of protective chlamydial antibodies, and increased risk-taking behaviors. Surgical procedures, such as endometrial biopsy, curettage, and hysteroscopies break the cervical barrier, predisposing women to ascending infections.

The microbiology of PID has also been found to reflect the predominant STIs prevalent within a specific population and also less-common organisms seen in that population. Bacterial vaginosis (BV) is suggested to play a role in the initiation of ascending infection in a subset of women with heavy growth of BV-associated organisms, such as G vaginalis, more than 2 recent sexual partners, and especially after recent abortion or gynecologic surgery.^{[6, 7]} PID may result from Mycobacterium tuberculosis in endemic areas.^[8]

Contraception

Different forms of contraception may affect PID incidence and severity. Appropriately used barrier contraception has clearly been shown to decrease the acquisition of most STIs.

The CDC recommends that spermicides and condoms containing nonoxynol-9 should be avoided, as a number of African studies have demonstrated that nonoxynol-9 can cause vaginal lesions and may increase the risk of HIV transmission. While the level of nonoxynol-9 in condoms is lower than the level associated with vaginal lesions, these are also not recommended because they are more expensive, have a shorter shelf life, and have been associated with urinary tract infections.^[15]

Studies of oral contraceptive pills (OCPs) have found differing effects on PID risks. On the one hand, OCPs are thought to increase the risk of endocervical infection, probably by increasing the zone of cervical ectopy. On the other hand, evidence has indicated that OCPs can decrease the risk of symptomatic PID, possibly by increasing cervical mucus viscosity, decreasing menstrual anterograde and retrograde flow, and modifying local immune responses. Still other data have suggested that OCPs may not have any effect on PID incidence.^[15]

Intrauterine-device (IUD) use has been associated with a 2- to 9-fold increased risk for PID, but data suggest that the risk with current IUDs may be significantly less.^[16] Kelly et al found a rate of 9.6 cases of PID per 1,000 IUD insertions, with the most significant risk in the first 20 days.^[17] Meirik et al validated early risk of PID within the first month after insertion and also found that the risk appears to be modified by the patient’s number of sexual partners, patient’s age, and the community prevalence of STIs.^[18]

Actinomycete species have been identified almost exclusively in patients with IUDs.^[19]

Bilateral tubal ligation (BTL) has not been found to provide protection against PID; however, patients with BTL may have delayed or milder forms of PID.^[20]

From 1995-2001, 769,859 cases of PID were reported in the United States annually.^[21] The true incidence was probably much higher; cases likely went unreported due to incomplete and untimely conventional, nonelectronic reporting methods and because many cases of silent and smoldering PID occur and are discovered only when the patient develops chronic complications.

The CDC has estimated that more than 1 million women experience an episode of PID every year. The disease leads to approximately 2.5 million office visits and 125,000-150,000 hospitalizations yearly.^{[22, 23]}

International statistics

While no specific international data are available for PID incidence worldwide, the World Health Organization (WHO) estimated in 1999 that approximately 340 million new cases of curable STIs occur annually in individuals aged 15-49 years.^[24] Factors contributing to the difficulty in determining the actual worldwide incidence and prevalence of PID include lack of patient recognition of disease, difficulties in access to care, the often subjective method of disease diagnosis, lack of diagnostics and laboratory facilities in many developing countries, and underfunded and overstretched public health systems.^[25]

Worldwide, WHO has determined that STIs rank in the top 5 disease categories for which adults seek care. Women in resource-poor countries, especially those in sub-Saharan Africa and Southeast Asia, experience an increased rate of complications and sequelae.

The annual rate of PID in high-GNP countries has been reported to be as high as 10-20 per 1000 women of reproductive age. Public health efforts implemented in Scandinavia to decrease the prevalence of STIs have been quite effective.

Chronic pelvic pain occurs in approximately 25% of patients with a history of pelvic inflammatory disease (PID). This pain is thought to be related to cyclic menstrual changes, but it also may be the result of adhesions or hydrosalpinx.

Impaired fertility is a major concern in women with a history of PID. Infection and inflammation can lead to scarring and adhesions within tubal lumens. Of women with tubal factor infertility (TFI), 50% have no history of PID but have scarring of the fallopian tubes and exhibit antibodies to C trachomatis. The rate of infertility increases with the number of episodes of infection. The risk of ectopic pregnancy is increased 15-50% in women with a history of PID. Ectopic pregnancy is a direct result of damage to the fallopian tube.

PID may produce tubo-ovarian abscess (TOA) and extend to produce pelvic peritonitis and Fitz-Hugh Curtis syndrome (perihepatitis), as shown in the image below. TOA is reported in up to one third of women hospitalized for PID.

Approximately 125,000-150,000 hospitalizations occur yearly because of PID.^[22] Women in resource-poor countries, especially those in sub-Saharan Africa and Southeast Asia, experience an increased rate of complications and sequelae.

Asking women about high-risk sexual behavior is very important. Encourage screening tests for those at risk. Additionally, ensure that male sex partners are evaluated and treated.

Patient education should focus on methods of preventing PID and STIs, including reducing the number of sexual partners, avoiding unsafe sexual practices, and routinely using appropriate barrier protection. Adolescents should be advised to delay the onset of sexual activity until age 16 years or older, as they are at an increased risk for PID.

After treatment, women should be counseled to abstain from sexual activity or be educated to strictly and appropriately use barrier protection until their symptoms have fully abated and they have completed their antibiotic regimen and their partner(s) have been treated.

For patient education information, see the Women's Health Center, Sexually Transmitted Diseases Center, and Pregnancy and Reproduction Center, as well as Pelvic Inflammatory Disease, Ectopic Pregnancy, Birth Control Overview, Birth Control FAQs, and Female Sexual Problems.