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Pelvic Inflammatory Disease
Fozia Akhtar Ali, MD
Paula A. Shelton, MD
image BASICS
DESCRIPTION
  • Pelvic inflammatory disease (PID) is an infectious and inflammatory disorder of the upper female genital tract, including the uterus, fallopian tubes, ovaries, and adjacent pelvic structures. It is community acquired from sexually transmitted organisms (1).
  • Salpingitis is the most important component due to its impact on future fertility.
  • Diagnosis may be challenging and incorrect in up to 1/3 of cases. No set of criteria is both sensitive and specific for the disease.
  • System(s) affected: reproductive
EPIDEMIOLOGY
  • Predominant age: 15 to 25 years; this number has remained constant since early 1900s.
  • Predominant sex: female only (1)
Incidence
Over 770,000 cases of acute PID are diagnosed annually in the United States. Incidence decreased from 1885 to 2001. 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, 200,000 hospitalizations, and 100,000 surgical procedures yearly. The cost of PID is approximately $2 billion annually; however, costs have decreased over the past decade (2).
ETIOLOGY AND PATHOPHYSIOLOGY
Multiple organisms may be etiologic agents in PID. Most cases are polymicrobial.
  • Chlamydia trachomatis, Neisseria gonorrhoeae, genital tract mycoplasmas (particularly Mycoplasma genitalium), aerobic and anaerobic (Bacteroides fragilis), and vaginal flora (e.g., Prevotella, Peptostreptococci, Gardnerella vaginalis, Escherichia coli, Haemophilus influenzae) are recognized as etiologic agents (1,3,4).
  • Many nongonococcal, nonchlamydial microorganisms recovered from upper genital tract in acute PID are associated with bacterial vaginosis (especially Prevotella bivius, Prevotella disiens, and Prevotella capillosus) (2).
  • The precise mechanism by which microorganisms ascend from the lower genital tract is unclear. Possible mechanisms include the following: (i) travel from cervix to endometrium to salpinx to peritoneal cavity; (ii) lymphatic spread via infection of the parametrium (from an IUD); and (iii) hematogenous route, although this is rare.
  • Of cases, 75% occur within 7 days of menses, when cervical mucus favors ascent of organisms.
RISK FACTORS
  • Sexually active and age <25 years (5)
  • First sexual activity at young age (<15 years)
  • New/multiple sexual partners
  • Nonbarrier contraceptive methods (i.e., oral contraceptive pills)
  • Previous history of PID; 20-25% will have a recurrence.
  • Cervical ectopy
  • History of C. trachomatis; 10-40% will develop PID.
  • History of gonococcal cervicitis; 10-20% will develop PID.
  • Gynecologic procedures such as endometrial biopsy, curettage, and hysteroscopy break the cervical barrier, predisposing women to ascending infections.
GENERAL PREVENTION
  • Educational programs about safer sex practices such as barrier contraceptives, especially condoms and spermicidal creams or sponges, provide some protection (5).
  • The U.S. Preventive Services Task Force recommends screening for chlamydia in all sexually active women <25 years and in those 25 years and older at increased risk (new sex partner/multiple sex partners).
  • Routine STI screening in pregnancy
  • Early medical care with occurrence of genital lesions or abnormal discharge
COMMONLY ASSOCIATED CONDITIONS
  • If PID is suspected in a patient with an IUD and a pelvic abscess is present; an Actinomyces infection requiring penicillin treatment may be present.
  • Rupture of an adnexal abscess is rare but life-threatening. Early surgical exploration is mandatory (3).
  • Chlamydial or gonococcal perihepatitis may occur with PID. This combination is called Fitz-Hugh-Curtis (FHC) syndrome and is characterized by severe pleuritic right upper quadrant pain. FHC syndrome complicates 10% of PID cases.
  • Plasma cell endometritis has also been seen in the majority of females with PID; the density of plasma cell infiltration has been related to severity of symptoms (3).
image DIAGNOSIS
  • The diagnosis of PID is based primarily on clinical evaluation. Clinical diagnosis alone is 87% sensitive and 50% specific.
  • Physicians must consider PID in the differential diagnosis in women 15 to 44 years of age who present with lower abdominal or pelvic pain and cervical motion or pelvic tenderness, even if these symptoms are mild.
  • The CDC recommends empiric treatment for PID if ≥1 of the following minimum criteria are present on pelvic exam in an at-risk patient: cervical motion tenderness, uterine tenderness, and adnexal tenderness in the presence of lower abdominal or pelvic pain.
  • Additional criteria used to enhance specificity: fever >101°F, new/abnormal vaginal discharge, presence of abundant numbers of WBCs on wet prep, elevated ESR, and laboratory documentation of cervical infection with N. gonorrhoeae or C. trachomatis (1,6)
  • Most specific criteria for diagnosing PID: Endometrial biopsy reveals endometritis/plasma cells; transvaginal ultrasound showing thickened, fluid-filled salpinges; and laparoscopic abnormalities consistent with PID (1).
PHYSICAL EXAM
  • Fever
  • Lower abdominal pain and particularly cervical motion tenderness
  • Findings of cervicitis with/without vaginal discharge (1)
DIFFERENTIAL DIAGNOSIS
  • Appendicitis
  • Constipation
  • Gastroenteritis
  • Ectopic pregnancy
  • Ovarian tumor/torsion
  • Hemorrhagic/ruptured ovarian cyst
  • Endometriosis/dysmenorrhea
  • Functional pelvic pain
  • Inflammatory bowel disease
  • Diverticulitis
  • UTI/pyelonephritis
  • Nephrolithiasis (1)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Pregnancy test must be performed to rule out ectopic pregnancy and complications of an intrauterine pregnancy.
  • Specific testing for chlamydia and gonorrhea (usually nucleic acid amplification test [NAAT] and/or ligase chain reaction)
  • Urinalysis (3,4)
  • Saline microscopy of vaginal fluid (for WBC)
  • Consider CBC: WBC count ≥10,500/mm3, although ≤50% of PID cases present with leukocytosis
  • CRP (optional)
  • Consider transvaginal ultrasound: not necessary for diagnosis; may show thickened, fluid-filled tubes (hydrosalpinges) ± free fluid, or tubo-ovarian abscess (TOA)
Follow-Up Tests & Special Considerations
  • ESR >15 mm/hr or elevated C-reactive protein used in some diagnostic criteria
  • Consider HIV testing in patients with PID.
  • Follow-up ultrasound as outpatient for resolution of adnexal abscess.
Diagnostic Procedures/Other
  • Culdocentesis with culture is rarely necessary.
  • Laparoscopy is best used for confirming, as opposed to making, the diagnosis of PID and should be reserved for the following situations:
    • Ill patient with competing diagnosis (e.g., appendicitis)
    • Ill patient who has failed outpatient treatment.
    • Any patient not improving after 72 hours of inpatient treatment
  • Endometrial biopsy (rarely indicated): reveals endometritis/plasma cells (3)
P.775

image TREATMENT
  • Outpatient treatment, if appropriate
  • Criteria for hospitalization and parenteral treatment are described below.
GENERAL MEASURES
Avoid intercourse until treatment is completed (7)[C]. IUD removal is NOT required for mild PID.
MEDICATION
First Line
  • Several antibiotic regimens are highly effective, with no single regimen of choice (3)[A].
  • Outpatient treatment regimen
    • Ceftriaxone 250 mg IM single dose plus
    • Doxycycline 100 mg PO BID for 14 days ±
    • Metronidazole 500 mg PO BID for 14 days
  • On the basis of the recent emergence of fluoroquinolone-resistant gonococci, the CDC no longer recommends the use of fluoroquinolones for the treatment of gonococcal infections and associated conditions such as PID.
  • Metronidazole should be considered in cases where risk of infection with anaerobic organisms is considered high.
Second Line
  • Because of emerging resistance in gonococcus, resistance testing and confirmation of treatment success is advisable (3).
  • Outpatient treatment regimen
    • Cefoxitin 2 g IM single dose and probenecid 1 g PO administered concurrently in single dose plus
    • Doxycycline 100 mg PO BID for 14 days +/−
    • Metronidazole 500 mg PO BID for 14 days
  • In persons with documented severe allergic reactions to penicillin or cephalosporins, azithromycin or spectinomycin might be an option for therapy of uncomplicated gonococcal infections.
  • Special consideration
    • Refer sex partners for appropriate evaluation and treatment if they had sexual contact with patient during preceding 60 days or most recent sexual contact. Partners should be treated, irrespective of evaluation, with regimens effective against chlamydia and gonorrhea (3).
SURGERY/OTHER PROCEDURES
Reserved for failures of medical treatment and for suspected ruptured adnexal abscess with resulting acute surgical abdomen
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • Hospitalization recommended in the following (3)[C]:
    • Surgical emergencies (e.g., appendicitis)
    • Suspected pelvic abscess
    • Pregnancy
    • Severe illness, nausea, vomiting, or high fever
    • Intolerance/inability to adhere to outpatient regimen
    • Failure to respond to outpatient therapy
  • For inpatient treatment of PID, the CDC also lists two currently accepted treatment regimens (6):
    • Parenteral regimen A
      • Cefotetan 2 g IV q12h or cefoxitin 2 g IV q6h + doxycycline 100 mg PO or IV q12h (6)[A]
      • Parenteral therapy for 24 hours after clinical improvement (6)[C]. Continue doxycycline for a total of 14 days.
    • Parenteral regimen B
      • Clindamycin 900 mg IV q8h + gentamicin loading dose IV or IM (2 mg/kg of body weight) followed by a maintenance dose (1.5 mg/kg) q8h (6)[A]
      • Parenteral therapy for 24 hours after clinical improvement; continue doxycycline as aforementioned or clindamycin 450 mg PO QID for a total of 14 days.
  • During pregnancy: PID is rare in pregnant patients; however, may appear prior to 12 weeks' gestation before mucous plug appears. Change doxycycline to azithromycin + second-generation cephalosporin (6).
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Review at 72 hours is recommended particularly for patients with moderate or severe clinical presentation (8)[C].
  • Close observation of clinical status, particularly for fever, symptoms, degree of peritonitis, serum WBC
  • Retest for gonorrhea and chlamydia in 3 to 6 months. The likelihood of reinfection is high.
  • Follow adnexal abscess size and position with serial ultrasound (6).
PATIENT EDUCATION
  • Abstinence from any type of sexual contact until treatment of patient/partner (if necessary) is complete.
  • Consistent and correct condom use should be enforced.
  • Hepatitis B and human papilloma virus (HPV) vaccines should be given to patients who meet criteria.
  • Advise comprehensive STI screening (6).
PROGNOSIS
  • Wide variation with good prognosis if early effective therapy is instituted and further infection is avoided.
  • Poor prognosis related to late therapy and continued high-risk sexual behavior
  • Nongonococcal, nonchlamydial PID is more often associated with severe PID and with worse prognosis for future fertility (2).
REFERENCES
1. Gradison M. Pelvic inflammatory disease. Am Fam Physician. 2012;85(8):791-796.
2. Lareau SM, Beigi RH. Pelvic inflammatory disease and tubo-ovarian abscess. Infect Dis Clin North Am. 2008;22(4):693-708, vii.
3. Judlin P. Current concepts in managing pelvic inflammatory disease. Curr Opin Infect Dis. 2010;23(1):83-87.
4. Weinstein SA, Stiles BG. A review of the epidemiology, diagnosis and evidence-based management of Mycoplasma genitalium. Sex Health. 2011;8(2):143-158.
5. Sweet RL. Treatment of acute pelvic inflammatory disease. Infect Dis Obstet Gynecol. 2011;2011: 561909.
6. Workowski KA, Berman S; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59(RR-12):1-110.
7. Brookoff D. Compliance with doxycycline therapy for outpatient treatment of pelvic inflammatory disease. South Med J. 1994;87(11):1088-1091.
8. Thompson SE, Brooks C, Eschenbach DA, et al. High failure rates in outpatient treatment of salpingitis with either tetracycline alone or penicillin/ampicillin combination. Am J Obstet Gynecol. 1985;152(6, Pt 1):635-641.
9. Camus E, Poncelet C, Goffinet F, et al. Pregnancy rates after in-vitro fertilization in cases of tubal infertility with and without hydrosalpinx: a metaanalysis of published comparative studies. Hum Reprod. 1999;14(5):1243-1249.
Codes
&NA;
ICD10
  • N73.9 Female pelvic inflammatory disease, unspecified
  • N73.0 Acute parametritis and pelvic cellulitis
  • N70.93 Salpingitis and oophoritis, unspecified
Clinical Pearls
&NA;
  • Most often, PID starts with gonorrhea or chlamydia infection, but it can be polymicrobial.
  • Physicians should treat on the basis of clinical judgment without waiting for confirmation from laboratory or imaging tests. PID is a common cause of infertility.
  • Complications include hydrosalpinx, adhesions, pelvic pain, and 10-fold increased risk of ectopic pregnancy.
  • Three major predictors of preserved post-PID fertility: (i) short duration of symptoms (<72 hours) prior to initiation of treatment, (ii) first episode of PID, and (iii) nongonococcal PID.