Anatomic Course of Infection

• Inflammation Spreads from the Vagina or Cervix to the Upper Genital Tract, with Endometritis as an Intermediate Stage of Disease (NEJM, 2015) [MEDLINE]
  • Distribution of Sources
    • Approximately 85% of PID Cases are Caused by Sexually Transmitted Organisms or Bacterial Vaginosis-Associated Organisms
    • Approximately 15% of PID Cases are Caused by Other Organisms Which Have Colonized the Lower Genital Tract
  • Retrograde Menstruation and Sexual Intercourse May Be Involved in the Movement of Organisms from the Lower Genital Tract to the Upper Genital Tract (NEJM, 2015) [MEDLINE]
  • Infection of the Upper Genital Tract Results in Fibrinous/Suppurative Inflammatory Damage Along the Epithelial Surface of the Fallopian Tubes and Peritoneal Surface of the Fallopian Tubes and Ovaries (NEJM, 2015) [MEDLINE]
    • Results in Scarring, Adhesions, and Possibly Partial/Total Fallopian Tube Obstruction
  • Role of Multiple Organisms
    • In Patients with PID, Different Organisms Can Be Isolated from Various Levels of the Genital Tract (Am J Obstet Gynecol. 1979) [MEDLINE]
    • PID May Be a Polymicrobial/Mixed Infection (Involving Facultative, Anaerobic Organisms)
      • Studies Have Isolated Various Organisms in PID (Am J Obstet Gynecol, 1975) [MEDLINE] (NEJM, 1975) [MEDLINE] (Am J Obstet Gynecol, 1980) [MEDLINE]

Microbiology

Acute Pelvic Inflammatory Disease (≤30 Days in Duration)

• Sexually-Transmitted Cervical Pathogens
  • Neisseria Gonorrhoeae (Gonococci) (see Neisseria Gonorrhoeae, [[Neisseria Gonorrhoeae]])
  • Epidemiology
    • Genital Neisseria Gonorrhoeae Infection was the First Identified Etiology of PID
    • Genital Neisseria Gonorrhoeae Infection is Common in Sexually Active Pre-Menopausal Females
    • Approximately 15% of Endocervical Neisseria Gonorrhoeae Infections Progress to PID ( J Am Vener Dis Assoc, 1974) [MEDLINE] (Br J Vener Dis, 1978) [MEDLINE]
    • Gonococcal PID Has a Higher Risk of Hospitalization/Emergency Department Presentation for PID than Chlamydia Trachomatis PID (Clin Infect Dis, 2018) [MEDLINE]
  • Physiology
    • In Patients with Gonococcal PID, Other Organisms Have Been Isolated in 50% of Cases (Obstet Gynecol, 1981) [MEDLINE]
  • Chlamydia Trachomatis (se eChlamydia Trachomatis, [[Chlamydia Trachomatis]])
  • Epidemiology
    • Genital Chlamydia Trachomatis Infection is the Most Common Bacterial Sexually Transmitted Infection
    • In the US, Genital Chlamydia Trachomatis Infection is the Most Commonly Reported Infectious Disease
    • Genital Chlamydia Trachomatis is Common in Sexually Active Pre-Menopausal Females
    • Genital Chlamydia Trachomatis Infection Accounts for Approximately 33% of PID Cases
    • Approximately 15% of Untreated Endocervical Chlamydia Trachomatis Infections Progress to PID (NEJM, 2015) [MEDLINE]
  • Clinical
    • Asymptomatic or Subclinical Genital Chlamydia Trachomatis Infections are Common
  • Mycoplasma Genitalium (see Mycoplasma Genitalium, [[Mycoplasma Genitalium]])
  • Epidemiology
    • Likely to Be an Etiology of PID in Pre-Menopausal Females (Clin Infect Dis, 2015) [MEDLINE]
• Bacterial Vaginosis Pathogens
  • General Comments
    • Anaerobic, Facultative Organisms Which are Found in the Vaginal Flora are Present in Greater Numbers in Bacterial Vaginosis, Resulting in Decreased Vaginal Lactobacilli and Overgrowth of a More Complex Anaerobic Biofilm-Associated Microbiome (NEJM, 2015) [MEDLINE]
    • Bacterial Vaginosis is Associated with Local Enzyme Production Which Degrades the Cervical Mucus and Associated Antimicrobial Peptides, Disrupting the Cervical Barrier and Facilitating the Spread of Organisms to the Upper Genital Tract (NEJM, 2015) [MEDLINE]
  • Atopobium (see Atopobium, [[Atopobium]])
    • Has Been Isolated from the Fallopian Tubes of Patients with PID
  • Bacteroides (see Bacteroides, [[Bacteroides]])
  • Clostridium (see Clostridium, [[Clostridium]])
  • Leptotrichia (see Leptotrichia, [[Leptotrichia]])
    • Has Been Isolated from the Fallopian Tubes of Patients with PID
  • Mycoplasma Hominis (see Mycoplasma Hominis, [[Mycoplasma Hominis]])
  • Peptococcus (see Peptococcus, [[Peptococcus]])
  • Peptostreptococcus (see Peptostreptococcus, [[Peptostreptococcus]])
  • Sneathia (see Sneathia, [[Sneathia]])
    • Has Been Isolated from the Fallopian Tubes of Patients with PID
  • Ureaplasma Urealyticum (see Ureaplasma Urealyticum, [[Ureaplasma Urealyticum]])
• Enteric Pathogens
  • Bacteroides Fragilis (see Bacteroides Fragilis, [[Bacteroides Fragilis]])
  • Campylobacter (see Campylobacter, [[Campylobacter]])
  • Enterococcus (see Enterococcus, [[Enterococcus]])
    • Rare Etiology
  • Escherichia Coli (see Escherichia Coli, [[Escherichia Coli]])
    • May Be Associated with PID in in Postmenopausal Females
  • Prevotella (see Prevotella, [[Prevotella]])
  • Proteus Mirabilis (see Proteus Mirabilis, [[Proteus Mirabilis]])
  • Streptococcus Agalactiae (Group B Streptococcus) (see Streptococcus Agalactiae, [[Streptococcus Agalactiae]])
• Respiratory Pathogens
  • Haemophilus Influenzae (see Haemophilus Influenzae, [[Haemophilus Influenzae]])
    • Rare Etiology
  • Staphylococcus Aureus (see Staphylococcus Aureus, [[Staphylococcus Aureus]])
  • Streptococcus Pneumoniae (Pneumococcus) (see Streptococcus Pneumoniae, [[Streptococcus Pneumoniae]])
    • Rare Etiology
  • Streptococcus Pyogenes (Group A Streptococcus) (see Streptococcus Pyogenes, [[Streptococcus Pyogenes]])

Subclinical Pelvic Inflammatory Disease

• Cervical Pathogens
  • Neisseria Gonorrhoeae (Gonococci) (see Neisseria Gonorrhoeae, [[Neisseria Gonorrhoeae]])
  • Chlamydia Trachomatis (see Chlamydia Trachomatis, [[Chlamydia Trachomatis]])

Chronic Pelvic Inflammatory Disease (>30 Days in Duration)

• Actinomyces (see Actinomycosis, [[Actinomycosis]])
• Mycobacterium Tuberculosis (see Tuberculosis, [[Tuberculosis]])
• While Many of the Pathogens Below (Chlamydia Trachomatis, Neisseria Gonorrhoeae, Mycoplasma Genitalium, etc) May Be Involved in the Initiation of PID, PID Should Be Thought of as a Polymicrobial/Mixed Infection (Involving Facultative and Anaerobic Organisms)
  • Studies Have Isolated Various Organisms in PID (Am J Obstet Gynecol. 1975) [MEDLINE] (NEJM, 1975) [MEDLINE] (Am J Obstet Gynecol, 1980) [MEDLINE]
    • Actinomyces (seee Actinomycosis, [[Actinomycosis]])
      • Rare Etiology
    • Atopobium (see Atopobium, [[Atopobium]])
      • Has Been Isolated from the Fallopian Tubes of Patients with PID
    • Bacteroides (see Bacteroides, [[Bacteroides]])
    • Enterococcus (see Enterococcus, [[Enterococcus]])
      • Rare Etiology
    • Escherichia Coli (see Escherichia Coli, [[Escherichia Coli]])
      • May Be Associated with PID in in Postmenopausal Females
    • Haemophilus Influenzae (see Haemophilus Influenzae, [[Haemophilus Influenzae]])
      • Rare Etiology
    • Leptotrichia (see Leptotrichia, [[Leptotrichia]])
      • Has Been Isolated from the Fallopian Tubes of Patients with PID
    • Mycobacterium Tuberculosis (see Tuberculosis, [[Tuberculosis]])
      • Rare Etiology
    • Peptococcus (see Peptococcus, [[Peptococcus]])
    • Peptostreptococcus (see Peptostreptococcus, [[Peptostreptococcus]])
    • Prevotella (see Prevotella, [[Prevotella]])
    • Proteus Mirabilis (see Proteus Mirabilis, [[Proteus Mirabilis]])
    • Sneathia (see Sneathia, [[Sneathia]])
      • Has Been Isolated from the Fallopian Tubes of Patients with PID
    • Streptococcus Agalactiae (Group B Streptococcus) (see Streptococcus Agalactiae, [[Streptococcus Agalactiae]])
    • Streptococcus Pneumoniae (Pneumococcus) (see Streptococcus Pneumoniae, [[Streptococcus Pneumoniae]])
      • Rare Etiology
    • Streptococcus Pyogenes (Group A Streptococcus) (see Streptococcus Pyogenes, [[Streptococcus Pyogenes]])

Recommended Testing

• Complete Blood Count (CBC) (see Complete Blood Count, [[Complete Blood Count]])
  • Recommended for Patients with Fever and More Severe Clinical Presentations
• C-Reactive Protein (CRP) (see C-Reactive Protein, [[C-Reactive Protein]])
  • Suggested for Patients with Fever and More Severe Clinical Presentations
• Elevated Erythrocyte Sedimentation Rate (ESR) (see Erythrocyte Sedimentation Rate, [[Erythrocyte Sedimentation Rate]])
  • Suggested for Patients with Fever and More Severe Clinical Presentations
• Pregnancy Test (see Pregnancy Test, [[Pregnancy Test]])
  • Recommended to Rule Out Ectopic Pregnancy (see Ectopic Pregnancy, [[Ectopic Pregnancy]])
  • Recommended to Rule Out Complication of a Intrauterine Pregnancy (see Pregnancy, [[Pregnancy]])
• Vaginal Discharge Microscopy
  • Saline Microscopy of Vaginal Discharge with Examination for Increased White Blood Cells is Sensitive for the Diagnosis of PID, But Not Specific
  • Saline Microscopy Can Also Identify Coexisting Bacterial Vaginosis and Trichomoniasis
• Gram Stain of Cervical Discharge
  • If the Cervical Discharge Gram Stain is Positive for Gram-Negative Intracellular Diplococci (Suggestive of Neisseria Gonorrhoeae) When Interpreted by an Experienced Microscopist, this Significantly Increases the Probability of PID (Int J STD AIDS, 2014) [MEDLINE] (MMWR Recomm Rep, 2015) [MEDLINE]
  • A Negative Cervical Discharge Gram Stain is of Limited Value Because Most Cases of PID are Not Caused by Gonorrhoea, and the Sensitivity of Microscopy is Only 60%
• Nucleic Acid Amplification Tests (NAAT) for Chlamydia Trachomatis and Neisseria Gonorrhoeae (see xxxx, [[xxxx]])
  • Recommended to Evaluate for Chlamydia and Gonococcal Infections, But Negative Testing Does Not Rule Out the Diagnosis of PID
• Nucleic Acid Amplification Tests (NAAT) for Mycoplasma Genitalium (see xxxx, [[xxxx]])
  • Recommended to Evaluate for Mycoplasma Genitalium Infection, But Negative Testing Does Not Rule Out the Diagnosis of PID
  • Testing for Mycoplasma Genitalium is Also Recommended to Guide Antibiotic Therapy (Int J STD AIDS, 2018) [MEDLINE]
• Human Immunodeficiency Virus (HIV) Test (see Human Immunodeficiency Virus Test, [[Human Immunodeficiency Virus Test]]) Recommended to Evaluate for Coexistent HIV Infection
• Serologic Testing for Syphilis (see xxxx, [[xxxx]])
  • Recommended to Evaluate for Coexistent Syphilis Infection
• Urinalysis and Urine Culture (see Urinalysis, [[Urinalysis]] and Urine Culture, [[Urine Culture]])
  • Recommended for Cases with Urinary Symptoms

Acute Symptomatic Pelvic Inflammatory Disease

General Comments

• Sensitivity of Clinical Diagnosis of PID is 65-90% (Am J Obstet Gynecol, 1969) [MEDLINE] (Am J Obstet Gynecol, 1992) [MEDLINE] (Am J Obstet Gynecol, 1992) [MEDLINE] (Infect Dis Obstet Gynecol, 1997) [MEDLINE]
  • Since the Reproductive Consequences of PID are High, Treatment with Antibiotics is Often Made Based Upon a Presumptive Diagnosis
  • Adding Diagnostic Criteria Increases the Specificity, But Decreases the Sensitivity of the Diagnosis (MMWR Recomm Rep, 2015) [MEDLINE]
    • Fever >101°F (>38.3°C)
    • Abnormal Vaginal/Cervical Mucopurulent Discharge or Cervical Friability
    • Presence of Abundant White Blood Cells (>15-20 Per High Power Field or White Blood Cells > Epithelial Cells) on Saline Microscopy of Vaginal Secretions
    • Evidence of Cervical Infection with Neisseria Gonorrhoeae or Chlamydia Trachomatis

Hematologic Manifestations

• Leukocytosis (see Leukocytosis, [[Leukocytosis]])
  • Occurs in Only a Minority of PID Cases (NEJM, 1975) [MEDLINE]
• Elevated Erythrocyte Sedimentation Rate (ESR) (see Elevated Erythrocyte Sedimentation Rate, [[Elevated Erythrocyte Sedimentation Rate]])
  • Low Sensitivity/Specificity in the Diagnosis of PID (Am J Obstet Gynecol, 1993) [MEDLINE]
    • Patients with Severe PID Have Higher ESR and CRP Levels than Did Those with Mild Disease
    • In Detecting Severe PID with an ESR ≥40 mm/hr and CRP ≥60 mg/L Had a Sensitivity of 97%, Specificity of 61%, Negative Predictive Value of 96%, and a Positive Predictive Value of 70%
    • All Patients with Tubo-Ovarian Abscess or Perihepatitis and 86% of Patients Who Had Anaerobic Bacteria Isolated from the Fallopian Tubes Tested Positive with These Cutoff Levels
• Elevated C-Reactive Protein (CRP) (see Elevated C-Reactive Protein, [[Elevated C-Reactive Protein]])
  • Low Sensitivity/Specificity in the Diagnosis of PID (Am J Obstet Gynecol, 1993) [MEDLINE]
    • Patients with Severe PID Have Higher ESR and CRP Levels than Did Those with Mild Disease
    • In Detecting Severe PID with an ESR ≥40 mm/hr and CRP ≥60 mg/L Had a Sensitivity of 97%, Specificity of 61%, Negative Predictive Value of 96%, and a Positive Predictive Value of 70%
    • All Patients with Tubo-Ovarian Abscess or Perihepatitis and 86% of Patients Who Had Anaerobic Bacteria Isolated from the Fallopian Tubes Tested Positive with These Cutoff Levels

Infectious Manifestations

• Fever (see Fever, [[Fever]])
  • More Commonly Occurs in Cases with Peritonitis and/or Pelvic Abscess
• Sepsis (see Sepsis, [[Sepsis]])
  • May Occur in Some Cases

Reproductive Manifestations

• General Comments
  • Anatomic Sites of Infection
    • Endometritis
    • Salpingitis
      • Inflammation of Fallopian Tubes and Adjacent Structures
    • Tubo-Ovarian Abscess (see Tubo-Ovarian Abscess, [[Tubo-Ovarian Abscess]])
      • inflammatory Mass Involving the Fallopian Tube, Ovary, and Occasionally Other Adjacent Structures
      • Presents with a Palpable Adnexal Mass
    • Pelvic Abscess (see Abdominal Abscess, [[Abdominal Abscess]]): occurs in only a small percentage of cases
    • Peritonitis (see Peritonitis, [[Peritonitis]]): occurs in only a small percentage of cases
    • Perihepatitis (Fitz-Hugh Curtis Syndrome)
      • Inflammation of the Liver Capsule and Peritoneal Surfaces of the Anterior Right Upper Quadrant (with Minimal Hepatic Parenchymal Involvement)
      • Occurs in 10% of Patients with Acute PID (Associated with Both Neisseria Gonorrhoeae and Chlamydia Trachomatis Infections) (Am J Obstet Gynecol, 1980) [MEDLINE]
      • Clinically Presents with RUQ Abdominal Pain (and Tenderness) with Pleuritic Component (Which May Be Referred to the Right Shoulder in Some Cases)
      • May Be Misdiagnosed as Cholecystitis (J Gynecol Obstet Biol Reprod-Paris), 1990) [MEDLINE]
      • Minimal Transaminitis May Be Observed (JAMA, 1978) [MEDLINE] (Br Med Bull, 1983) [MEDLINE]
      • Laparoscopic Findings Include Patchy Fibrinous/Purulent Exudate (“Violin String Adhesions”), Predominantly Involving the Anterior Liver Surface (But Not the Liver Parenchyma)
  • Severity of Infection
    • Most Patients Present with Mild-Moderate Disease
• Lower Abdominal Pain/Tenderness (see Abdominal Pain, [[Abdominal Pain]])
  • Lower Abdominal Pain in PID Has Been Classically Described as Severe and Abrupt in Onset During or Shortly After Menstruation (Am J Obstet Gynecol, 1998) [MEDLINE] (NEJM, 2015) [MEDLINE]
    • However, in the Era of Decreasing Incidence of Neisseria Gonorrhoeae infections, the Presentation is Frequently Less Well-Defined and More Variable
    • Pain May Be Subtle and Worsening During Intercourse or with Jarring Movement May Be the Presenting Symptom in Some Cases
    • Pain is Generally More Severe in Cases with Peritonitis and/or Pelvic Abscess
  • Pain is Rarely >2 wks in Duration (MMWR Recomm Rep, 2015) [MEDLINE]
  • Abdominal Pain/Tenderness is Usually Bilateral, But May Be Asymmetric in Some Cases
  • Consideration of Alternative Diagnoses of Lower Abdominal Pain
    • Sudden Onset of Severe Abdominal Pain Suggests the Diagnosis of Ovarian Cyst Rupture or Ovarian Torsion
    • Abdominal Pain Localized to the Right Iliac Fossa Suggests the Diagnosis of Appendicitis
    • Abdominal Pain Associated with Bowel Symptoms in an Older Female Suggests the Diagnosis of Diverticulitis
• Abnormal Uterine Bleeding (Menorrhagia, Post-Coital Bleeding, Inter-Menstrual Bleeding) (see xxxx, [[xxxx]])
  • Occurs in >33% of Cases (Sex Transm Dis, 2005) [MEDLINE]
• Vaginal Discharge (see Vaginal Discharge, [[Vaginal Discharge]])
  • Common
• Endocervical Discharge
  • Common
• Urinary Frequency (see Urinary Frequency, [[Urinary Frequency]])
  • Occurs in Some Cases
• Rebound Tenderness
  • May Occur in More Severe Cases with Peritonitis and/or Pelvic Abscess
• Decreased Bowel Sounds
  • May Occur in More Severe Cases with Peritonitis and/or Pelvic Abscess
• Cervical Motion/Uterine/Adnexal Tenderness
  • Classical Findings in PID (Am J Obstet Gynecol, 2001) [MEDLINE] (Sex Transm Dis, 2005) [MEDLINE]
  • Significant Lateralization of Adnexal Tenderness is Uncommon in PID
  • Adnexal Tenderness is the Exam Finding Which Correlates Best with the Presence of Endometritis on Endometrial Biopsy (Am J Obstet Gynecol, 2001) [MEDLINE]

Subclinical Pelvic Inflammatory Disease

• Epidemiology
  • Associated with Specific Pathogens
    • Neisseria Gonorrhoeae (Gonococci) (see Neisseria Gonorrhoeae, [[Neisseria Gonorrhoeae]])
    • Chlamydia Trachomatis (see Chlamydia Trachomatis, [[Chlamydia Trachomatis]])
  • Subclinical PID is Common (Sex Transm Dis, 2005) [MEDLINE]
  • Subclinical PID is More Common in Patients with Lower Genital Tract Infection (with Gonorrhea, Chlamydia, or Bacterial Vaginosis) (Obstet Gynecol, 2002)
  • Subclinical PID Occurs More Commonly in Orla Contraceptive Users (JAMA, 1985) [MEDLINE] (Am J Obstet Gynecol, 1997) [MEDLINE]
  • Patients with Tubal Factor Infertility Due to Probable PID Frequently Do Not Give a History of PID
    • Approximately 30.6% of Patients with Adhesions/Distal Tubal Occlusion Have a History of PID, But 80.6% of These Patients Have a History of Lower Abdominal Pain (Obstet Gynecol, 1995) [MEDLINE]
    • Only 11% of Patients with Adhesions/Distal Tubal Occlusion Have No History of PID or Lower Abdominal Pain (or Laparoscopic Evidence of Endometriosis), Suggesting This Subset Could Be Classified as Having Silent PID (Obstet Gynecol, 1995) [MEDLINE]
• Diagnosis
  • Previously Undiagnosed PID Has Been Identified in Patients with a History of Only Mild Symptoms, But an Endometrial Biopsy Demonstrating Neutrophilia and Plasma Cells Consistent with PID
    • In Patients at Risk for PID But without Clinical Findings of PID, 13% Have Endometritis on Endometrial Biopsy (and Rates of Cervical Chlamydia Trachomatis Isolation were Similar to Women with Clinically Diagnosed PID) (Sex Transm Dis, 2005) [MEDLINE]
• Clinical
  • Symptoms May Be Subtle Enough for Patient Not to Seek Medical Attention
  • Infertility

Chronic Pelvic Inflammatory Disease

• Epidemiology
  • Associated with Specific Pathogens
    • Actinomyces (see Actinomycosis, [[Actinomycosis]])
      • IUD Use May Be a Risk Factor
    • Mycobacterium Tuberculosis (see Tuberculosis, [[Tuberculosis]])
• Clinical
  • Indolent Presentation
    • Abdominal Pain (see Abdominal Pain, [[Abdominal Pain]])
    • Low-Grade Fever (see Fever, [[Fever]])
    • Weight Loss (see Weight Loss, [[Weight Loss]])