Pelvic inflammatory disease

Pelvic inflammatory disease (PID) is a general term for infection of the upper female genital tract, including the uterus, Fallopian tubes, and ovaries.

PID usually results from ascending infection from the cervix. It is a common and serious complication of some sexually transmitted infections, especially chlamydia and gonorrhoea. It can damage the Fallopian tubes and tissues in and near the uterus and ovaries. Untreated PID can lead to serious complications, including infertility, ectopic pregnancy, abscess formation and chronic pelvic pain.

Epidemiology¹

The exact prevalence of PID is unknown as it is under-diagnosed and it is also often asymptomatic² .

Public Health England (PHE) reported rates of PID in GP settings in England in 2011 as follows:

• Overall rate of definite/probable PID diagnoses among women aged 15-44 years was 176 diagnoses per 100,000 person-years.

• Rates of PID diagnoses were highest among woman aged 20-24 years.

• Rates of PID diagnoses showed a declining trend between 2000 and 2011.

The decline in PID diagnosis rates may reflect reducing risk of PID in age groups eligible for chlamydia screening via the National Chlamydia Screening Programme, as well as increases in chlamydia testing in genitourinary medicine (GUM) clinics and other settings.

Aetiology

• Pelvic infections are often polymicrobial. PID can be caused by genital mycoplasmas, endogenous vaginal flora (anaerobic and aerobic bacteria), aerobic streptococci, Mycobacterium tuberculosis, and sexually transmitted infections such as Chlamydia trachomatis or Neisseria gonorrhoeae³ .

• Genital chlamydial infection is currently the most common sexually transmitted infection diagnosed in genitourinary medicine (GUM) clinics in the UK.

• The incidence of gonorrhoea is increasing and therefore becoming a more common cause of PID.

• Other organisms implicated in PID include those commonly associated with bacterial vaginosis - eg, Gardnerella vaginalis, Mycoplasma hominis, Mobiluncus spp. and other anaerobes. Actinomycetes are part of the normal vaginal flora and a rare cause of PID.

Risk factors

• Risk factors for acquiring sexually transmitted infections - eg, young age, new sexual partner, multiple sexual partners, lack of barrier contraception, lower socio-economic group.

• There may be an increased risk in those women who have had an intrauterine contraceptive device (IUCD), but only if inserted in the previous 20 days³ .

• Termination of pregnancy.

Presentation

Diagnosis of acute PID made only on clinical signs and positive swab results is 65-90% as accurate when compared to laparoscopic diagnosis. Many episodes of PID go unrecognised, as women often have absent, mild, or atypical symptoms.

There is no combination of symptoms and signs to make a clinical diagnosis of PID so it is very important to have a high index of suspicion for PID.

Symptoms

The following features are suggestive of PID:

• Bilateral lower abdominal pain.

• Deep dyspareunia.

• Abnormal vaginal bleeding (postcoital, intermenstrual or menorrhagia).

• Vaginal or cervical discharge that is purulent.

Signs

• Lower abdominal tenderness (usually bilateral).

• Mucopurulent cervical discharge and cervicitis seen on speculum examination.

• Cervical motion tenderness and adnexal tenderness on bimanual vaginal examination.

• Fever above 38°C (but may be apyrexial).

Other symptoms and signs include nausea or vomiting, urinary symptoms, proctitis and an adnexal mass.

Differential diagnosis

• Other causes of abdominal pain - eg, appendicitis (nausea and vomiting are seen more often than PID), ectopic pregnancy.

• Other causes of abnormal vaginal bleeding.

• Other causes of vaginal discharge - eg, foreign body.

• Other causes of dyspareunia - eg, endometriosis.

Investigations

• Pregnancy test (pregnant women with PID should be admitted; ectopic pregnancy may be confused with PID).

• Cervical swabs for chlamydia and gonorrhoea: a positive result supports the diagnosis of PID; however, a negative result does not exclude PID² .

• Endocervical swabs for C. trachomatis and N. gonorrhoeae, using nucleic acid amplification tests where available, are recommended in all patients with suspected PID.

• An elevated ESR or CRP may also support a diagnosis of PID; however, these are nonspecific tests.

• Endometrial biopsy and ultrasound scanning may also be helpful.

• Laparoscopy with direct visualisation of the Fallopian tubes is the best single diagnostic test, but is an invasive procedure and obviously not appropriate in routine clinical practice.

• Urinalysis and urine culture to exclude urinary tract infection.

• Ultrasound scans may be useful in excluding other conditions² .

Management¹

• Mild or moderate disease can be managed in primary care or outpatients, whereas clinically severe disease requires hospital admission for intravenous (IV) antibiotics.

• Provide adequate pain relief.

• The evidence for whether an IUCD should be left in situ or removed is limited. Removal of the IUCD may be associated with better short-term clinical outcomes. The decision to remove the IUCD needs to be balanced against the risk of pregnancy in those who have had otherwise unprotected intercourse in the preceding seven days.

• Consider referral to a GUM clinic, for a full sexually transmitted infection screen (HIV, etc), contact tracing and treatment of sexual partners.

Antibiotic treatment

• Do not delay antibiotic treatment while waiting for the results of tests if PID is clinically suspected.

• Delayed treatment increases the risk of long-term complications, such as ectopic pregnancy, infertility and pelvic pain.

• Negative swabs do not exclude PID and therefore should not influence the decision to treat.

• Emphasise the importance of completing the course of antibiotics to reduce the risk of long-term complications.

• The choice of an appropriate treatment regimen may be influenced by local guidelines, cost, patient preference and severity of disease.

• Broad-spectrum antibiotic treatment to cover C. trachomatis, N. gonorrhoeae and anaerobic infection is recommended.

• In those who fail to respond to treatment, laparoscopy is essential to confirm the diagnosis or to make an alternative diagnosis.

The British Association for Sexual Health and HIV (BASHH) recommends⁴ :

Outpatient regimens
First-line therapy:

• Intramuscular ceftriaxone 1 g single dose, followed by oral doxycycline 100 mg twice daily plus metronidazole 400 mg twice daily for 14 days.

Second-line therapy:

• Oral ofloxacin 400 mg twice daily plus oral metronidazole 400 mg twice daily for 14 days.

• Oral moxifloxacin 400 mg once daily for 14 days.

Metronidazole is included in some regimens to improve coverage for anaerobic bacteria. Anaerobes are of relatively greater importance in patients with severe PID and metronidazole may be discontinued in those patients with mild or moderate PID who are unable to tolerate it.

Ofloxacin and moxifloxacin should be avoided in patients who are at high risk of gonococcal PID (eg, when the patient's partner has gonorrhoea, in clinically severe disease, following sexual contact abroad) because of high levels of quinolone resistance.

Levofloxacin has the advantage of once daily dosing (500 mg once daily for 14 days). It may be used as a more convenient alternative to ofloxacin.

Ofloxacin, levofloxacin and moxifloxacin are effective for the treatment of C. trachomatis.

Quinolones (ofloxacin, levofloxacin and moxifloxacin) can cause disabling and potentially permanent side-effects involving tendons. muscles, joints and the nervous system, and are therefore only recommended as second-line therapy except for the treatment of M. genitalium-associated PID where no alternative therapy is available. Quinolones are not licensed for use in patients aged under 18 years.

Alternative regimens

• Intramuscular ceftriaxone 1 g immediately, followed by azithromycin 1 g/week for two weeks.

Inpatient regimens

• IV ceftriaxone 2 g daily plus IV doxycycline 100 mg twice daily (oral doxycycline may be used if tolerated) followed by oral doxycycline 100 mg twice daily plus oral metronidazole 400 mg twice daily for a total of 14 days.

• Intravenous clindamycin 900 mg three times daily plus IV gentamicin (2 mg/kg loading dose) followed by 1.5 mg/kg three times daily [a single daily dose of 7 mg/kg may be substituted]) followed by either oral clindamycin 450 mg four times daily or oral doxycycline 100 mg twice daily plus oral metronidazole 400 mg twice daily to complete 14 days.

IV therapy should be continued until 24 hours after clinical improvement and then switched to oral.

Alternative regimens

• Intravenous ofloxacin 400 mg twice daily plus IV metronidazole 500 mg three times daily for 14 days.

• Intravenous ciprofloxacin 200 mg twice daily plus IV (or oral) doxycycline 100 mg twice daily plus IV metronidazole 500 mg three times daily for 14 days.

Management of sexual partners

• Patients should be advised to avoid unprotected intercourse until they and their partner(s) have completed treatment and follow-up.

• Screen for other sexually transmitted infections, ideally at a GUM clinic. All sexual partners within the previous six months (or the most recent sexual partner if there have been no sexual contacts within the previous six months) should be notified and offered screening for sexually transmitted infections.

• Sexual partners should be treated for chlamydial infection even if this is not identified on testing.

• Treatment for gonorrhoea only needs to be offered if N. gonorrhoeae is identified in the woman with PID or in her partner.

• Empirical treatment for chlamydial infection and gonorrhoea should be given to partners who are unwilling to be screened.

• As many cases of PID are not associated with gonorrhoea or chlamydia, broad-spectrum empirical therapy should also be offered to male partners - eg, azithromycin 1 g single dose.

• BASHH recommends that doxycycline be used as empirical treatment for male partners of women with PID to reduce exposure to macrolide antibiotics which has been associated with increased resistance in M. genitalium⁴ .

Referral

Admission to secondary care (for IV antibiotics and/or further investigation) should be considered in the following situations:

• Diagnostic uncertainty - eg, where appendicitis or ectopic pregnancy cannot be excluded.

• Severe symptoms or signs.

• Deteriorating clinical condition.

• Clinical failure with oral treatment, ie failure to show substantial improvement within three days.

• Inability to tolerate oral treatment - eg, due to nausea and vomiting.

• Presence of a tubo-ovarian abscess.

• Pregnancy.

• Immunodeficiency - eg, HIV infection, immunosuppression therapy.

Complications

Studies have shown that delaying treatment by as little as two or three days increases the risk of infertility² . Prompt treatment for cases of suspected PID is therefore very important. Complications include:

• Infertility: the risk of infertility following PID is related to the number of episodes of PID and their severity.

• Ectopic pregnancy.

• Chronic pelvic pain.

• Perihepatitis (Fitz-Hugh Curtis syndrome): causes right upper quadrant pain.

• Tubo-ovarian abscess.

• Reactive arthritis.

• In pregnancy: PID is associated with an increase in preterm delivery, and maternal and fetal morbidity.

• Neonatal: perinatal transmission of C. trachomatis or N. gonorrhoeae can cause ophthalmia neonatorum. Chlamydial pneumonitis may also occur.

Prevention

• Use of barrier contraception significantly reduces the risk of PID.

• Limited evidence suggests that screening for chlamydia and treating identified infection prior to IUCD insertion reduce the risk of PID. Routine prophylactic antibiotics prior to IUCD insertion are not recommended.

• The English National Chlamydia Screening Programme (NCSP) recommends that all sexually active men and women under the age of 25 be tested for chlamydia annually or on change of sexual partner⁵ .

• Highly sensitive and specific tests - nucleic acid amplification tests (NAATs) - for chlamydia are widely available, and used for all chlamydia tests performed through this screening programme. These tests can be performed on non-invasive samples (urine in men, self-taken vulvovaginal swabs or urine for women).

• Testing for gonorrhoea is recommended within specialist sexual health clinics targeting higher-risk populations or where clinically indicated⁶ . However, there is no evidence to support widespread opportunistic screening for gonorrhoea in community-based settings, and the evidence for selected screening in UK community-based settings is sparse⁷ .