Pelvic Inflammatory Disease

Aka: Pelvic Inflammatory Disease, PID, Tubo-Ovarian Inflammatory Disease, Salpingo-Oophoritis, Fitz-Hugh-Curtis Syndrome, Chlamydial Perihepatitis, Gonococcal Perihepatitis, Tubo-Ovarian Abscess, Tuboovarian Abscess

1. Epidemiology
   1. Incidence: 750,000 cases per year in United States
   2. Age: Peaks between ages 15 to 29 years
2. Pathophysiology
   1. Intra-abdominal spread
      1. Cervix to endometrium and via fallopian tubes to the peritoneal cavity
   2. Lymphatic spread
      1. Example: IUD related infection
   3. Hematogenous spread (rare)
      1. Example: Tuberculosis
3. Causes
   1. Sexually Transmitted Disease (most common initial causes of PID)
      1. Chlamydia trachomatis (15% of untreated cases progress to PID)
      2. NeisseriaGonorrhea
   2. Polymicrobial Bacteria including Gram Negative Bacteria and Anaerobic Bacteria (superinfect STD, esp. with abscess formation)
      1. Bacteroides fragilis
      2. Escherichia coli
      3. Klebsiella species
      4. Mycoplasma hominis
      5. Mycoplasma genitalium (associated with treatment failures, not covered by all antibiotic regimens)
      6. HaemophilusInfluenzae
      7. Ureaplasma urealyticum
      8. Facultative or anaerobic organisms
   3. Bacterial Vaginosis associated infections
      1. Anaerobic Bacterial Infection related to BV is associated with PID
4. Risk Factors
   1. Sexually Transmitted Disease (STD) history
      1. Chlamydia is asymptomatic in 80-90% of women
      2. Gonorrhea is asymptomatic in 10% of women
      3. Untreated Chlamydia or Gonorrhea is associated with a 10-20% risk of PID
   2. Age younger than 25 years
   3. Onset sexual intercourse at a young age (younger than 15 years old)
   4. Prior history of Pelvic Inflammatory Disease
   5. High number of sexual partners (or new sexual partner)
   6. Non-barrier Contraception (e.g. IUD, Oral Contraceptives)
5. Symptoms: Onset usually in first half of Menstrual Cycle
   1. Abdominal Pain or Pelvic Pain or cramping (varying intensity)
   2. Vaginal Discharge (new or abnormal)
   3. Fever or chills (fever may be high grade)
   4. Dyspareunia
   5. Dysuria
   6. Heavy or prolonged Menses or post-coital bleeding
   7. Pleuritic right upper quadrant pain (liver capsule inflammation in Fitz-High-Curtis Syndrome, Perihepatitis)
6. Exam
   1. Bimanual exam and speculum exam in all suspected cases
      1. Cervical motion tenderness
      2. Uterine tenderness
      3. Adnexal tenderness
   2. See Diagnosis below for signs
   3. Clinical diagnosis alone is accurate (when compared with imaging and laparoscopy)
      1. Test Sensitivity: 87%
      2. Test Specificity: 50%
      3. Positive Predictive Value: 65-90%
7. Diagnosis: 2002 CDC Criteria
   1. Major Criteria (Required)
      1. Uterine or Adnexal tenderness to palpation or
      2. Cervical motion tenderness
      3. No other apparent cause
   2. Minor Criteria (Supporting, but not required)
      1. Fever >101 F (38.3 C)
      2. Abnormal mucopurulent discharge per Cervix or vagina
      3. WBCs on Gram Stain or Saline of Cervix swab
      4. Gonorrhea or Chlamydia testing positive
      5. Increased Erythrocyte Sedimentation Rate or C-Reactive Protein
      6. PID findings on diagnostic study (see below)
   3. Most specific findings (not required and rarely indicated unless refractory to management or unclear diagnosis)
      1. Laparoscopy findings consistent with Pelvic Inflammatory Disease
      2. Endometrial Biopsy with histology suggestive of Endometritis
      3. Imaging (Transvaginal Ultrasound or MRI) with classic findings
         1. Thickened, fluid filled tubes
         2. Free pelvic fluid may be present
         3. Tubo-ovarian complex
         4. Tubal hyperemia on Doppler Ultrasound
8. Differential Diagnosis
   1. See Acute Pelvic Pain
   2. See Acute Pelvic Pain Causes
   3. Ruptured Ovarian Cyst
      1. Sudden onset of mid-cycle, unilateral Pelvic Pain
   4. Ectopic Pregnancy
      1. Unilateral pain
      2. Positive Pregnancy Test
      3. Afebrile
      4. White Blood Cell Count normal
      5. Hypotension or Anemia
   5. Appendicitis
      1. Periumbilical or Right Lower Quadrant Abdominal Pain
      2. Peritoneal signs
      3. Vomiting, Anorexia
   6. Urinary Tract Infection (including Pyelonephritis)
      1. Dysuria, frequency, urgency
      2. No Cervical Motion Tenderness or Vaginal Discharge
   7. Ovarian Torsion
      1. More localized, unilateral severe, sudden onset Pelvic Pain
      2. Afebrile
      3. White Blood Cell Count normal
   8. Endometriosis
      1. Dysmenorrhea
      2. Dyspareunia
   9. Endometritis
      1. Fever
      2. Pelvic Pain
      3. Vaginal Discharge
   10. Ureteral Stone
       1. Unilateral Flank Pain or Pelvic Pain
       2. Nausea, Vomiting
   11. Other common causes
       1. Nephrolithiasis
       2. Inflammatory Bowel Disease
9. Labs
   1. General
      1. Do not delay treatment while waiting for lab results
      2. Delayed antibiotics by 2-3 days increases Infertility and future Ectopic Pregnancy risk by 3 fold
   2. Inflammatory markers (if all normal, PID is very unlikely)
      1. Complete Blood Count (CBC)
      2. Elevated Erythrocyte Sedimentation Rate or C-Reactive Protein
      3. Vaginal secretion exam (saline wet prep)
         1. Vaginal PMNs (Negative Predictive Value 95%)
         2. Identifies Trichomonas vaginalis and Bacterial Vaginosis
   3. Sexually Transmitted Disease screening
      1. DNA probe PCR for Gonorrhea and Chlamydia
         1. Cervical specimen recommended over urine specimen
         2. Test Sensitivity and Test Specificity are high
      2. Rapid Plasma Reagin (RPR)
      3. Human Immunodeficiency Virus Test (HIV Test)
   4. Other initial labs
      1. Urine Pregnancy Test (all patients)
         1. Exclude Ectopic Pregnancy if positive
      2. Blood Cultures
      3. C-Reactive Protein (CRP)
         1. High CRP levels are associated with Tubo-Ovarian Abscess
10. Diagnostics
    1. Endometrial Biopsy: Endometritis
       1. Test Sensitivity: 74%
       2. Test Specificity: 84%
    2. Transvaginal pelvic Ultrasound
       1. Efficacy
          1. Test Sensitivity: 30%
          2. Test Specificity: 76%
       2. Pelvic free fluid in cul-de-sac
       3. Tubo-Ovarian Abscess may be present
       4. Doppler demonstrates tubal hyperemia
       5. Fallopian tube changes
          1. Thickened fallopian tube wall >5 mm
          2. Fluid filled fallopian tubes
          3. Incomplete septae in fallopian tube
             1. Cogwheel sign on tube cross-section view
    3. CT Pelvis
       1. Other imaging modalities are preferred for PID evaluation
       2. Pelvic floor fascial, Adnexal inflammation
       3. Uterosacral ligament thickening
       4. Pelvic free fluid
    4. MRI Pelvis
       1. Efficacy
          1. Test Sensitivity: 81-95%
          2. Test Specificity: 89-100%
       2. Tubo-Ovarian Abscess may be present
       3. Pelvic free fluid
       4. Fallopian tube changes
          1. Fluid filled fallopian tubes
          2. Ovaries have polycystic appearance
       5. References
          1. Tukeva (1999) Radiology 210:209-16 [PubMed]
    5. Laparoscopy
       1. Indicated for unclear diagnosis
       2. Pelvic Inflammatory Disease misdiagnosed 25% time
11. Management: General
    1. Intrauterine Device (IUD) removal is controversial
       1. IUD increases PID for only first 3 weeks following insertion
          1. Risks are similar between the Copper-T IUD and the Mirena IUD
       2. Historically, IUD has been removed at time of PID diagnosis
       3. No evidence supports removal of IUD in PID
       4. Close follow-up is critical for those who developed PID with IUD in place
       5. IUD may be left in place if improving by 48 to 72 hours
    2. Treat patient's sexual contacts within last 60 days
       1. Abstain from sexual intercourse until patient and partner have completed treatment
       2. Counsel on safe sex
       3. Consider Expedited Partner Treatment (esp. if sex partners do not have medical contact)
          1. Legality varies by U.S. State
    3. Start empiric therapy if minimal criteria present
       1. Do not delay treatment
       2. Delay >2-3 days increases ectopic and Infertility risk by 3 fold (see above)
    4. Antibiotics should cover Gonorrhea and Chlamydia
    5. Follow-up
       1. Within 48 to 72 hours of hospital discharge or start of outpatient management
       2. Repeat STD testing in 3 months (Gonorrhea and Chlamydia)
          1. Intended to test for new infection
       3. Discuss risk of PID complications (Ectopic Pregnancy, Infertility)
12. Management: Special Populations
    1. HIV positive women
       1. May be treated with same antibiotics and guidelines as non-HIV patients
       2. Higher risk of Tubo-Ovarian Abscess
       3. More likely to be infected with Mycoplasma genitalum or Streptococcus than with Gonorrhea or Chlamydia
          1. Consult infectious disease and consider antibiotic modification if not improving
    2. Pregnant women
       1. PID is less common in pregnancy, but can occur in first trimester before formation of mucous plug
       2. Pregnant women with PID have greater risk of complications including Preterm Labor and mortality
       3. Admit and initiate parenteral antibiotics for initial PID treatment in pregnancy
       4. Treat with Cefoxitin and Azithromycin one gram
    3. Antibiotic resistant cases
       1. Consider Mycoplasma genitalum
13. Management: Outpatient
    1. Indications
       1. Temperature <=38 C (100.4 F)
       2. White Blood Cell Count <11,000 mm3
       3. Minimal peritoneal findings
       4. Tolerating food and fluids
    2. Step 1: Initial Treatment at Diagnosis (with step 2)
       1. Ceftriaxone 250 mg IM for 1 dose or
       2. Cefoxitin 2g IM and Probenecid 1g PO or
       3. Other third generation Cephalosporin (e.g Cefotaxime, Ceftizoxime)
    3. Step 2: Outpatient 14 day antibiotic course
       1. Select general antibiotic coverage
          1. Doxycycline 100 mg PO every 12 hours for 14 days (75% cure, preferred agent) or
          2. Azithromycin 1 gram orally once weekly for 2 weeks (alternative option, not CDC guideline)
             1. Savaris (2007) Obstet Gynecol 110:53–60 [PubMed]
       2. Consider adding anaerobic coverage (if Trichomoniasis, BV, recent uterine instrumentation)
          1. Metronidazole 500 mg orally twice daily for 14 days (preferred) or
          2. Clindamycin 450 mg PO four times daily for 14 days
       3. Agents to avoid
          1. Fluoroquinolones are no longer recommended
             1. However may be considered as alternative agent in cases where Gonorrhea is unlikely
                1. Patient/community are low risk for GC, GC testing obtained, patient reliable for followup
             2. In these cases, Fluoroquinolones are combined WITH Metronidazole 500 mg every 12 hours:
                1. Ofloxacin 400 mg orally twice daily or
                2. Levofloxacin 500 mg orally daily or
                3. Moxifloxacin (Avelox) 400 mg orally daily
          2. Cohorts at highest risk for Fluoroquinolone resistance
             1. Homosexual men and any female sexual contacts
             2. Endemic areas
                1. Asia: China, Japan, Korea, Philippines, Vietnam
                2. Other: England, Wales, Australia
                3. US: California
14. Management: Inpatient
    1. Hospitalization Indications
       1. Severe illness
          1. Toxic appearance
          2. High fever
       2. Unable to take oral fluids or oral medications (intractable Nausea, Vomiting)
       3. Unclear diagnosis
          1. Appendicitis
          2. Ectopic Pregnancy
          3. Ovarian Torsion
       4. Pelvic abscess (Tubo-Ovarian Abscess)
          1. Requires at least 24 hours of parenteral therapy inpatient
       5. Pregnancy
       6. HIV positive
       7. Adolescents
       8. Outpatient treatment failure
       9. Unreliable patient
    2. Inpatient treatment Regimens
       1. General
          1. Treat for at least 48 hours IV or oral regimen tolerated, affebrile and decreasing Leukocytosis
       2. Regimen A (preferred)
          1. Cefoxitin 2g IV q6h OR Cefotetan 2g IV q12h AND
          2. Doxycycline 100 mg PO or IV q12h
       3. Regimen B (consider in Cephalosporin allergy)
          1. Clindamycin 900 mg IV q8h AND
          2. Gentamicin 2 mg/kg IV load, then 1.5 mg/kg IV q8h
             1. Alternative: Conversion to single daily dosing (at 3-5 mg/kg)
       4. Alternative
          1. Ampicillin/Sulbactam (Unasyn) 3g IV q6 hours AND
          2. Doxycycline 100 mg PO or IV q12 hours
       5. Other options that are not recommended (if Cephalosporin and Penicillin allergic)
          1. Regimen C (only used as alternative if low Gonorrhea criteria met as listed above)
             1. Ofloxacin 400 mg IV q12h or Levoquin 500 IV qd and
             2. Metronidazole 500 IV q8 hours
       6. Discharge Regimen (after IV antibiotics above)
          1. See Outpatient Management Step 2 above
          2. Discontinue 24 hours after clinical improvement and complete therapy with oral antibiotics
             1. Doxycycline 100 mg orally twice daily for 14 days or
             2. Clindamycin 450 mg PO qid for 14 days
15. Course
    1. Expect clinical symptom improvement within first 72 hours of treatment
    2. Lack of improvement after 72 hours requires additional evaluation
       1. Consider inpatient parenteral therapy
       2. Broaden antibiotic coverage
       3. Consider Ultrasound to assess for Tubo-Ovarian Abscess
16. Prevention
    1. Screen all sexually active women age <25 years for Chlamydia
    2. Re-screen for STD 3 months after PID episode (Gonorrhea and Chlamydia)
    3. Encourage barrier Contraception (Condom use)
    4. Prophylactic antibiotic indications for women with history of PID
       1. Hysterosalpingography
       2. Uterine evacuation for pregnancy loss
17. Complications: Acute
    1. Fitz-Hugh-Curtis Syndrome or Perihepatitis (5-10% of PID patients)
       1. Hematogenous or transperitoneal spread of Chlamydia or Gonorrhea to peri-hepatic region
       2. Presents with right upper quadrant pain and tenderness, as well as Pleuritic Chest Pain
       3. Liver Function Tests may be elevated
    2. Tubo-Ovarian Abscess (17-20% of PID patients)
       1. More common with delay in treatment
       2. Admit all patients with Tubo-Ovarian Abscess
       3. Empiric antibiotic coverage
          1. Clindamycin 900 mg IV every 8 hours or Metronidazole IV every 8 hours AND
          2. Choose inpatient regimen from above OR
             1. Ampicillin IV AND Gentamicin IV
       4. Management varies by abscess size
          1. Abscess 4-6 cm diameter resolve with antibiotics alone 85% of the time
          2. Abscess >10 cm typically require surgical management
    3. Refractory Infection
       1. Mycoplasma genitalium
          1. Consider if persistent findings at 7-10 days
          2. Treat with Moxifloxacin 400 mg orally daily for 14 days
18. Complications: Chronic
    1. Infertility associated with tubal scarring (20%)
    2. Chronic Pelvic Pain (18%)
    3. Tubal Pregnancy (9%)
19. Resources
    1. Munro (2018) Diagnosis and Management of Tubo-Ovarian Abscess, TOG, 20(1):11-9
       1. https://obgyn.onlinelibrary.wiley.com/doi/10.1111/tog.12447
20. References
    1. (2002) MMWR Recomm Rep 51(RR-6):1-78 [PubMed]
    2. Brunham (2015) N Engl J Med 372(21):2039-48 [PubMed]
    3. Crossman (2006) Am Fam Physician 73(5):859-64 [PubMed]
    4. Curry (2019) Am Fam Physician 100(6): 357-64 [PubMed]
    5. Gradison (2012) Am Fam Physician 85(8): 791-6 [PubMed]
    6. Miller (2003) Am Fam Physician 67(9):1915-22 [PubMed]
    7. Workowski (2010) MMWR Recomm Rep 59(RR-12): 1-110 [PubMed]
    8. Workowski (2015) MMWR Recomm Rep 64(RR-3):1-137 [PubMed]