Oxford Handbook of Genitourinary Medicine, HIV, and Sexual
Health (2 edn)
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Introduction
Pelvic inflammatory disease (PID) refers to inflammation of the upper female genital tract (endometrium, fallopian tubes, and ovaries) and supporting structures (parametrium and pelvic peritoneum). It is usually a result of infection:
ascending from the endocervix
less commonly spread from other abdominal organs (e.g. appendicitis) or disseminated by blood.
Endometritis and endosalpingitis produce a purulent exudate that may escape into the rectovaginal pouch resulting in a pelvic abscess. Inflammation may spread to the ovaries (oophoritis), parametrium, and pelvic peritoneum (peritonitis).
Aetiology
Sexually transmitted infections
Neisseria gonorrhoeae in 5–75%: produces complement-mediated necrosis of ciliated epithelial cells.
Chlamydia trachomatis in 5–45%: induces Th-2 type immune response damaging tubal epithelium.
Worldwide data—wide ranges relate to variable infection rates and availability of reliable tests.
PID in 10–30% of untreated cervical chlamydial and gonococcal infections.
Other micro-organisms
Bacterial vaginosis (BV) associated organisms: anaerobic bacilli (e.g. Prevotella and Bacteroides spp), anaerobic cocci (e.g. Peptosreptococcus spp, Gardenerella vaginalis, Mycoplasma hominis, α and non-haemolytic streptococci). Recovered from fallopian tubes in up to 20% of ♀ with PID and 80% of endometrial samples in plasma cell endometritis (accompanying PID in ascending infection). Statistically significant association between BV and PID. Sialidase activity of Prevotella and Bacteroides spp, weakening cervical mucous barrier, possibly promotes ascending infection.
Other organisms have also been recovered from the fallopian tubes: viridans group streptococci, group A–D streptococci, Escherichia coli, Bacteroides fragilis, and coagulase −ve staphylococci).
Mycoplasma genitalium: cervical infection in ~15% ♀ with PID. Experimental evidence for PID in chimpanzees.
Actinomyces israelii and related species: occasionally cause a chronic pelvic abscess (<1 in 3000 cases of PID and 3% of all human actinomyces infections) usually in association with plastic intra-uterine devices (IUDs) and anaerobic co-infection.
Mycobacterium tuberculosis: haematogenously disseminated; an important cause in areas of high prevalence.
Salmonella spp: rarely as a result of abdominal spread from an intestinal focus of infection in typhoid and paratyphoid.
Factors facilitating ascending infection
Physiological
Uterine contractions: ↑ in the follicular phase until ovulation.
Loss of cervical mucus plug (formed in the luteal phase) and retrograde flow during menstruation.
Possible carriage of bacteria by spermatozoa.
Iatrogenic
Uterine instrumentation.
Epidemiology
Estimated annual incidence in industrialized countries ~1 in 1000 in ♀ aged 15–34 years (1.5–2/1000 if 15–24) with wide geographical and temporal variations. Sexual transmission is the major aetiological factor.
Young age: peak incidence in age group 15–24 years
Multiple partners
New partner within previous 3 months
Frequency of sexual intercourse
Past history of STI (patient or partner)
Past history of PID
Uterine instrumentation:
termination of pregnancy
insertion of IUD within the previous 6 weeks—not a high risk alone (overall incidence of PID only 0.15%) but concomitant cervical chlamydial/gonococcal infection ↑ risk to 3–5%
hysterosalpingography/hysteroscopy
endometrial biopsy, curettage, and ablation
in vitro fertilization procedure
Postpartum endometritis
Vaginal douching
Cigarette smoking
Hormonal contraception especially progesterone-only preparations (production of a ‘luteal-type’ cervical mucus plug and reduction in the tubal inflammatory response)
Consistent use of condom or diaphragm
Spermicide
Pregnancy: PID is uncommon because of thickened cervical mucus plug and is limited to the 1st trimester (protection afforded by the amniotic sac filling the uterine cavity is absent)
Clinical features
Acute PID (symptoms for <3 weeks)
Onset within 7 days of the 1st day of menstruation correlates with gonococcal/chlamydial infection. Symptoms and signs tend to be more acute/intense in gonococcal than chlamydial PID.
Symptoms
Lower abdominal pain; usually subacute if mild and acute if severe
Deep dyspareunia, common
Menstrual irregularity in ~40%
Abnormal bleeding
Dysmenorrhoea
Vaginal discharge
Nausea ± vomiting if severe
Signs
Lower abdominal tenderness with guarding; rebound if severe
Adnexal and cervical motion (excitation) tenderness
Fever (>38°C) in ~50%; more likely in severe or gonococcal PID
Adnexal mass in 50% of ♀ with gonococcal PID
Abdominal distension due to paralytic ileus if very severe (~1%)
Chronic PID (‘silent PID’)
May be asymptomatic and discovered only on investigation of infertility. Symptoms include constant or intermittent pain/discomfort in lower abdomen, groin or back, dyspareunia, malaise, and frequent/heavy menstrual periods. Usually no appreciable signs, but thickening of tubes and/or fixed retroverted uterus may be palpable.
Complications and sequelae
Tubo-ovarian and pelvic abscess
Late complication, likely to be associated with anaerobic bacteria.
Peri-appendicitis
Direct spread of infection from the right fallopian tube to the appendiceal serosa may produce external inflammation (serositis) without mucosal involvement. Tubo-appendiceal mass develops. 2–10% of acute appendicitis in ♀ may be due to peri-appendicitis, 25–50% of which may be linked to tubal inflammation.
Infertility
Occurs in 8%, 20%, and 40% after 1, 2, and 3 episodes of PID, respectively. Due to tubal occlusion and peritubal adhesions. The more severe the episode the higher the incidence of infertility. Conflicting evidence on risk ↓ with treatment of PID.
Ectopic gestation
Sevenfold ↑ in risk of ectopic gestation (9% compared with 1.3% in the absence of PID). Risk ↑ directly with PID severity and number of episodes.
Chronic pelvic pain
Incidence 12%, 33%, and 66% after 1, 2, and 3 episodes of PID, respectively. Due to pelvic adhesions that form after the initial or recurrent episodes. Affects psychosocial functioning and quality of life.
Perihepatitis (Fitz-Hugh–Curtis syndrome)
Inflammation of the hepatic capsule with ‘violin string’ adhesions between anterior surface of liver and abdominal wall. Results from peritoneal or lymphatic spread of pelvic gonococcal/chlamydial infection. Occurs in 10–20% with PID.
► Haematogenous spread possible (case reports in ♂ with gonorrhoea).
Symptoms and signs of PID are not always present but a past history of PID or lower genital infection may be obtained. Typical presentation is acute, often severe, with right upper quadrant pain radiating to the back and shoulder tip, made worse by deep inspiration and movement. Examination demonstrates tenderness and guarding in the right upper abdominal quadrant with Murphy’s sign (↑ pain on deep inspiration, examining hand just below the right costal margin). Hepatic rub may be heard on auscultation. Pyrexia in ~50%.
Differential diagnosis: acute cholecystitis, biliary colic, pleurisy, pneumonia, or pulmonary embolism.
Investigations
Routine
Swabs for N.gonorrhoeae and C.trachomatis.
Gram-stained smear of cervical material: may provide presumptive diagnosis of gonorrhoea. Polymorphonuclear leucocytes (PMNLs) are non-specific (positive predictive value only 17%) but useful for exclusion of PID (negative predictive value 95%).
Peripheral blood white blood cell (WBC) count: ↑ in ~50%.
Erythrocyte sedimentation rate (ESR)—↑ in ~75%.
C-reactive protein (CRP): ↑ in ~75%, level reflects severity.
Chlamydial antibody: only provides retrospective or inconclusive evidence, hence of limited value in acute PID. However, in ♀ investigated for infertility antibody, especially at high level, correlates closely with frequency and severity of tubal damage and adverse pregnancy outcome. Therefore useful as a screening test to determine the likelihood of tubal damage and need for early laparoscopy.
► Pregnancy test (urine or plasma β-hCG): essential for acute pelvic pain in all ♀ of childbearing age.
Urine analysis ± MSU if urinary tract infection is suspected.
Specialized
Endometrial histology/microbiology
Sensitivity ~70%, specificity ~90%.
Pelvic imaging
Abdominal ultrasound useful for detection of pelvic abscess. Transvaginal ultrasonography reported to have ~80% sensitivity and specificity (compared with laparoscopy/endometrial biopsy). May be necessary for differential diagnosis, particularly ectopic gestation.
Laparoscopy
Regarded as the gold standard but not routinely performed (time/cost/complication risk). Allows:
diagnosis of acute PID by identifying
pronounced hyperaemia of tubal surface
oedema of tubal wall
sticky exudate from fimbriae
collection of laboratory specimens from affected sites
identification of other causes (e.g. ectopic gestation, appendicitis, endometriosis) or complications (e.g. abscess, pelvic adhesions, ‘violin string adhesions’ of perihepatitis).
May fail to identify endosalpingitis/endometritis in early/mild infection.
Diagnosis
The presence of all main criteria plus one of the additional criteria is widely used for clinical diagnosis (Table 10.1). Positive predictive value of 65–90% compared with laporoscopy. In routine clinical practice a lower threshold is often applied for prompt antibiotic treatment.
| Main | Additional |
|---|---|
Low abdominal or pelvic pain | Temperature >38°C |
Abdominal ± rebound tenderness/adnexal tenderness | ↑ CRP/ESRWBC >10 × 109 |
Cervical motion (excitation) Tenderness | Adnexal massPMNLs in cervical/vaginal Gram-stained smears |
| Main | Additional |
|---|---|
Low abdominal or pelvic pain | Temperature >38°C |
Abdominal ± rebound tenderness/adnexal tenderness | ↑ CRP/ESRWBC >10 × 109 |
Cervical motion (excitation) Tenderness | Adnexal massPMNLs in cervical/vaginal Gram-stained smears |
Ectopic pregnancy: in ruptured ectopic pregnancy sudden onset of iliac fossa or hypogastric pain often associated with syncope. Vaginal spotting in early stages. Shoulder tip pain if blood tracked into abdominal cavity. Shock with intra-abdominal haemorrhage.
Acute appendicitis: initial peri-umbilical pain later localizing to right iliac fossa with pronounced nausea and vomiting.
Ruptured ovarian or endometriotic cyst: sudden onset of perimenstrual lower abdominal pain, usually afebrile.
Complications of ovarian neoplasms.
Acute pyelonephritis: pyrexia of sudden onset, rigors, loin/iliac fossa pain, urinary symptoms.
Mesenteric lymphadenitis, inflammatory bowel disease.
Adnexal torsion.
Other abdominal emergencies.
Endometriosis.
Pelvic congestion syndrome.
Ovarian cysts.
Ovarian and uterine neoplasms.
Interstitial cystitis.
Urethral syndrome.
Irritable bowel syndrome.
Inflammatory bowel disease.
Previous surgery, leading to pelvic adhesions or nerve entrapment.
Myofascial pain syndrome.
Psychosocial causes: depression, previous physical and sexual abuse/trauma, leading to somatization disorder.
Management
General principles
To minimize sequelae commence treatment promptly (even before definitive diagnosis). Hospital admission if:
systemic disturbance is severe
surgical/gynaecological emergency cannot be excluded
patient is pregnant or immunocompromised
tubo-ovarian or pelvic abscess is detected or suspected.
Rest and adequate analgesia. IUD removal is indicated only if severe PID, no improvement after 72 hours of treatment, actinomyces-like organisms present, or patient requests. Offer emergency contraception on removal if pregnancy risk within preceding 7 days. ► Advise avoidance of sexual intercourse until the patient and partner(s) have completed treatment.
Treatment regimens
When choosing antibiotic regimen consider:
severity and systemic disturbance—may need parenteral treatment
local prevalence of N.gonorrhoeae and antibiotic sensitivity
patient preference and likelihood of adherence.
Initial regimens (may need to be altered when antibiotic sensitivities are available)
Out-patient
Ceftriaxone 250mg IM single dose followed by doxycycline 100mg oral twice daily for 14 days plus metronidazole 400mg twice daily for 7–14 days (90–95% clinical cure rate).
Ofloxacin 400mg twice daily for 14 days plus metronidazole 400mg twice daily for 7–14 days (95% clinical cure rate).
Doxycycline 100mg twice daily for 14 days plus metronidazole 400mg twice daily for 7–14 days (70–81% clinical cure rate). Does not cover N. gonorrhoeae, viridans streptococci and coliforms.
Moxifloxacin 400 mg daily
for 14 days (no metronidazole) but because of
serious side-effects should only be used if no other
treatment is suitable. 
↑ risk
of life-threatening liver reactions, cardiac
arrhythmias with QTc prolongation, rhabdomyolysis
and tendon rupture.
In-patient
Cefoxitin 2g IV 4 times a day plus doxycycline 100mg orally (or IV if vomiting makes oral treatment intolerable) twice daily. Add metronidazole 500mg IV if pelvic or tubo-ovarian abscess develops.
Clindamycin IV 900mg 3 times a day plus gentamicin 2mg/kg IV or IM loading dose followed by 1.5mg/kg 3 times a day.
Ofloxacin 400mg IV infusion twice daily plus metronidazole 500mg IV 3 times a day.
Ampicillin/sulbactam IV infusion 3g 3 times a day plus doxycycline oral or IV 100mg twice daily.
Parenteral regimen is replaced after clinical improvement by one of the oral regimens and continued for a total of 14 days.
Treatment in pregnancy
Parenteral treatment advisable. Replace doxycycline with erythromycin (50mg/kg daily by continuous IV infusion).
Treatment of actinomycosis
Remove IUD. Benzylpenicillin 18–24MU (10.8–14.4g) IV daily as infusion (or 4 hourly injections) and metronidazole 500mg IV 8 hourly. Doxycycline, erythromycin, and clindamycin are alternatives to benzylpenicillin. Change to oral regimen after clinical improvement and continue for at least 4–6 weeks. Drainage of abscess relieves bowel or urinary tract compression. Salpingo-oophorectomy and hysterectomy may be necessary.
Partner notification
Sexual partner/s within a 6 month period of onset of symptoms should be contacted and offered screening for STIs and epidemiological treatment for chlamydia ± gonorrhoea taking into consideration the proven or probable aetiology.
Follow-up
Review diagnosis and management after 72 hours if acute symptoms and signs do not improve. Reassess after 2–4 weeks.
↓ production of interferon-G may ↑ susceptibility to PID
Tubo-ovarian abscess formation more likely if immunocompromised
Symptoms may be more severe but respond well to parenteral antibiotic therapy
