Pelvic Inflammatory Disease

Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia trachomatis and Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria gonorrhoeae, as well as organisms associated with bacterial vaginosis, such as Gardnerella vaginalis. Common symptoms are lower abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, cervical discharge, and irregular vaginal bleeding. Complications of PID can include ectopic pregnancy Ectopic pregnancy Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy, chronic pelvic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, and infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility. Diagnosis is primarily clinical in addition to PCR testing of cervical specimens and sometimes imaging or laparoscopy Laparoscopy Laparoscopy is surgical exploration and interventions performed through small incisions with a camera and long instruments. Laparotomy and Laparoscopy. Due to its polymicrobial nature, PID treatment is with combination antibiotic regimens.

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Overview

Definition

Pelvic inflammatory disease (PID) is an acute upper genital tract infection in women that affects the uterus, oviducts, ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries, and possibly the adjacent pelvic organs.

Epidemiology

  • Approximately 90,000 outpatient cases per year in the United States, including emergency department visits
  • More common in women < 35 years old
  • PID is rare before menarche. 
  • Risk factors:
    • Unprotected sexual intercourse
    • Multiple sexual partners
    • History of STIs
    • Presence of bacterial vaginosis (depending on the bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview)
  • The overall incidence of sexually transmitted PID is decreasing because of Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia screening in young women.

Etiology

  • STIs (85%):
    • Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia trachomatis (most common bacterial STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections, which may be subacute and subclinical in presentation)
    • Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria gonorrhoeae
    • Mycoplasma Mycoplasma Mycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or "walking" pneumonia. Mycoplasma genitalium
  • Other isolated bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview
    • Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus influenzae
    • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus agalactiae
    • Enteric gram-negative bacilli
    • Ureaplasma species
  • Post-operative peritonitis
  • Instrumentation or trauma-related pelvic infection
Chlamydia trachomatis inclusion bodies

Photomicrograph showcasing McCoy cell monolayers with Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia trachomatis inclusion bodies

Image: “ Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia trachomatis inclusion bodies” by CDC/Dr. E. Arum. License: Public Domain

Pathophysiology

Normal pelvic protection

  • Endocervical canal serves as a barrier between the sterile upper genital tract and the vaginal canal, which contains different bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview.
  • Normal vaginal flora is predominantly Lactobacillus spp. mixed with a low amount of potentially harmful bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview.

Pelvic infection

  • Infection from STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections or vaginal microorganisms (may be asymptomatic) → disruption of mucosal barrier → spread of infection to upper genital tract (usually symptomatic) → spread of infection to peritoneal cavity
  • Infection sites:
    • Cervix: cervicitis
    • Uterus/endometrium: endometritis Endometritis Endometritis is an inflammation of the endometrium, the inner layer of the uterus. The most common subtype is postpartum endometritis, resulting from the ascension of normal vaginal flora to the previously aseptic uterus. Endometritis
    • Fallopian tube: salpingitis
    • Ovaries: oophoritis
    • Surrounding area/ peritoneum Peritoneum The peritoneum is a serous membrane lining the abdominopelvic cavity. This lining is formed by connective tissue and originates from the mesoderm. The membrane lines both the abdominal walls (as parietal peritoneum) and all of the visceral organs (as visceral peritoneum). Peritoneum and Retroperitoneum: peritonitis
  • Increased risk of PID from lower genital tract bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview occurs:
    • During menses  
    • With an intrauterine device (IUD)
    • Due to poorly understood genetic or immune factors (affecting bacterial load and thickness of cervical mucus)
Pid sites

Sites of infection in PID: cervix, endometrium/uterus, ovary, and fallopian tubes

Image: “PID-Sites” by BruceBlaus. License: Public Domain

Clinical Presentation

Signs and symptoms

  • Acute PID:
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever 
    • Nausea and/or vomiting
    • Lower abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
    • Purulent vaginal discharge
    • Abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding
    • Dyspareunia
    • Dysuria
  • Subclinical PID:
    • Signs and symptoms can be mild, especially if due to C. trachomatis or M. genitalium.
    • Some patients present with infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility (from adhesions and distal tube occlusion from PID).
  • Chronic PID:
    • Indolent onset of fever, abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, and weight loss
    • Noted in actinomycosis and tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis

Physical exam

  • Cervical discharge
  • Cervical motion tenderness
  • Guarding or rebound tenderness
  • Uterine and/or adnexal tenderness 
  • Adnexal mass

Complications

  • Tubo-ovarian abscess: presents as an adnexal mass
  • Ectopic pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
  • Infertility
  • Hydrosalpinx 
  • Fitz-Hugh-Curtis syndrome (peri-hepatitis or inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver capsule and peritoneal surfaces)

Diagnosis and Management

Diagnosis

Diagnosis is primarily clinical with a high index of suspicion.

Laboratory tests:

  • CBC shows leukocytosis in 50% of patients.
  • Elevated inflammatory markers such as erythrocyte sedimentation rate (ESR) or CRP
  • Presence of > 10 WBCs per high-power field in vaginal discharge
  • PCR detection of N. gonorrhoeae and C. trachomatis
  • Cultures for causative organisms for PID
  • Additional STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections tests: HIV, syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis
  • Pregnancy test (to rule out ectopic pregnancy Ectopic pregnancy Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy)

Imaging:

  • Transvaginal ultrasound if clinical and laboratory findings inconclusive or complications suspected
  • May show thickened fallopian tube, free pelvic fluid, or indistinct endometrial borders
  • In cases of tubo-ovarian abscess: complex adnexal collection with multiple fluid levels

Laparoscopic exploration:

  • Failed empiric treatment
  • History of PID with negative tests
  • Fitz-Hugh-Curtis syndrome
  • Tubo-ovarian abscess

Management

  • Often, empiric antibiotic therapy with both outpatient and inpatient regimens aimed to cover aerobic and anaerobic infection
  • Main targets: C. trachomatis and N. gonorrhoeae
  • Outpatient management:
    • Long-acting cephalosporin (IM) + oral doxycycline (ceftriaxone 250 mg IM + doxycycline 100 mg oral twice a day x 14 days)
    • Add metronidazole if with Trichomonas vaginalis or bacterial vaginosis.
  • Inpatient management:
    • Cefotetan + doxycycline
    • Cefoxitin + doxycycline
    • Inpatient management indications:
      • Failed oral therapy
      • High fevers
      • Pregnancy
      • Tubo-ovarian abscess
      • If appendicitis Appendicitis Appendicitis is the acute inflammation of the vermiform appendix and the most common abdominal surgical emergency globally. The condition has a lifetime risk of 8%. Characteristic features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. Appendicitis or alternate diagnosis cannot be ruled out
  • Surgical:
    • Drain abscesses.
    • Exploratory laparoscopy Laparoscopy Laparoscopy is surgical exploration and interventions performed through small incisions with a camera and long instruments. Laparotomy and Laparoscopy needed in some cases to establish diagnosis
  • Pelvic rest
  • Patient education regarding safe sex practices and possible complications
Diagnosis of pelvic inflammatory disease

Pelvic inflammatory disease: grayscale ultrasound (A) and color Doppler (B) showing increased vascularity in the uterus (consistent with PID). Laparoscopy (C) confirms PID (uterine and adnexal swelling).

Image: “Pelvic inflammatory disease” by Department of Medical, Surgical and Neuro Sciences, Section of Radiological Sciences, Siena, Italy. License: CC BY 2.0

Differential Diagnosis

  • Ectopic pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Careimplantation of fertilized egg outside of the uterus, often due to disruption in normal anatomy of the fallopian tube. Abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain is a common symptom as the developing embryo grows. Diagnosis can be made with ultrasound and lab tests. Treatment can be expectant, medical, or surgical. 
  • Appendicitis: acute inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the vermiform appendix. Classic symptoms are periumbilical pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain that migrates to the right lower quadrant, anorexia, fever, nausea, and vomiting. Clinical diagnosis shows pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain over McBurney’s point in the right lower quadrant. Ultrasound or CT can help establish the diagnosis. Treatment is surgical appendectomy Appendectomy Appendectomy is an invasive surgical procedure performed with the goal of resecting and extracting the vermiform appendix through either an open or a laparoscopic approach. The most common indication is acute appendicitis. Appendectomy but perforations, which can occur up to 20% of the time, may be managed nonoperatively with antibiotics.
  • Endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis: a common condition of implantation of endometrial tissue outside of the uterus, usually within the pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 "hip" bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis. Symptoms include pelvic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain that is worse around menses. The condition can lead to chronic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, adhesions, and infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility. Diagnosis is clinical. Treatment includes oral contraceptive pills with progestin to suppress the inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation. Surgery is sometimes needed to establish the diagnosis and remove implantations.
  • Ruptured ovarian cyst: most ovarian cysts Ovarian cysts Ovarian cysts are defined as collections of fluid or semiliquid material, often walled off by a membrane, located in the ovary. These cysts are broadly categorized as either functional or neoplastic. Neoplastic ovarian cysts are subcategorized as either benign or malignant. Ovarian Cysts are small and benign, but rupture can cause unilateral lower abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. Diagnosis is made by ultrasound. 
  • Nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis: urinary calculi (stones) lead to pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, nausea, vomiting, and, possibly, fever and chills with infection. Diagnosis is by urinalysis and CT. Treatment can include pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain relief, antibiotics, lithotripsy, and endoscopy.

References

  1. Goje, O. (2019). Pelvic Inflammatory Disease (PID). Retrieved February 1, 2021, from https://www.merckmanuals.com/professional/gynecology-and-obstetrics/vaginitis,-cervicitis,-and-pelvic-inflammatory-disease-pid/pelvic-inflammatory-disease-pid
  2. Ross, J., Chacko, M. (2020). Pelvic inflammatory disease: Clinical manifestations and diagnosis. Retrieved February 2, 2021, from https://www.uptodate.com/contents/pelvic-inflammatory-disease-clinical-manifestations-and-diagnosis
  3. Le T, Bhushan, V, Sochat, M, et al. (2020). First Aid for the USMLE 1, 30th ed.(p.185). McGraw-Hill.

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