[STDs] Atlas of Pelvic Inflammatory Disease

Atlas of Pelvic Inflammatory Disease. EPIDEMIOLOGY, HISTORY, LABORATORY DIAGNOSIS, DIAGNOSTIC CRITERIA, TREATMENT, PARTNER MANAGEMENT AND PREVENTION

OVERVIEW

Pelvic inflammatory disease (PID) is the most common serious STD complication, apart from AIDS. PID is defined as salpingitis, usually accompanied by endometritis and sometimes pelvic peritonitis, that results from ascending genital infection unrelated to childbirth or invasive procedures of the genital tract. At least 90% of first episodes of PID meeting these criteria are sexually acquired, but a few cases are attributed to nonsexually transmitted pathogens. The frequency of symptomatic PID appears to have declined in the United States and the United Kingdom since the 1990s, perhaps due in part to expanded chlamydia screening.

The main sequelae of PID are infertility and ectopic pregnancy that result from tubal scarring, and chronic pelvic pain. The risk of infertility following symptomatic PID was estimated in the 1980s to be 15–20%, but this varies with the causative agent, the severity of PID as documented by laparoscopy, and the number of PID episodes. More recent estimates suggest a lower risk of infertility, perhaps the result of earlier diagnosis and improved recognition of mild cases. Each occurrence of PID enhances the risk of subsequent episodes, probably because scarring impairs normal tubal clearance mechanisms. PID is sometimes clinically severe, accompanied by fever, tubo-ovarian abscess, peritonitis, and other systemic manifestations, but most cases are mild. Indeed, subclinical salpingitis is estimated to account for 60% of all cases, and most women with tubal factor infertility or ectopic pregnancy have no past history of PID or unexplained abdominal pain. “Chronic” PID is an indistinct entity; the term sometimes is used inappropriately for pelvic adhesions and unexplained pelvic pain, without evidence of active infection or inflammation.

Chlamydia trachomatis is the most common cause of acute PID in industrialized countries and the likely etiology of most subclinical cases. Neisseria gonorrhoeae remains a major cause in populations and geographic settings where gonorrhea is common. Mycoplasma genitalium may have an etiologic role in 10–20% of cases, but conflicting results have been reported and its contribution to PID is uncertain, although caution dictates coverage for M. genitalium in treatment. Numerous other bacteria contribute to PID, including M. hominis and various aerobic and anaerobic components of the vaginal flora, and most women with acute PID have bacterial vaginosis (BV). It is probable that any of several cervical infections—gonorrhea, chlamydial infection, perhaps M. genitalium, and perhaps cervicitis associated  with BV—result in ascending endometrial and tubal infection with the primary pathogen, vaginal bacteria, or both. No sexually transmitted pathogen can be isolated in most cases of recurrent PID. Occasionally a nonsexually transmitted pathogen such as Haemophilus influenzae is isolated in pure culture from the fallopian tubes or culdocentesis aspirate in women with primary PID. The specific bacteria contributing to salpingitis usually are not known in individual patients, and antibiotic treatment should cover C. trachomatis, N. gonorrhoeae, M. genitalium, and mixed aerobic and anaerobic flora 

EPIDEMIOLOGY

Incidence and Prevalence

• Diagnosed in 1–5% of women in STD clinics in the United States

• Declining rates in the United States and United Kingdom since 1990s

° In the United Kingdom, the rate of PID in general practices declined 10% per year from 2000 to

2008, especially in women age 16-19 years.

° In the United States, estimated annual rate declined 25% in women with private health insurance,

from 317 cases per 100,000 in 2001 to 336 per 100,000 in 2005

° Perhaps due in part to improved prevention of chlamydial infections and gonorrhea; probably also

influenced by changing definitions and diagnostic standards

• Overt or subclinical PID is the most common cause of ectopic pregnancy and tubal infertility

Transmission

• As for C. trachomatis and N. gonorrhoeae

• Uncommon in sexually inactive women, but nonsexually acquired cases occur, especially in recurrent PID

Age

• Markedly elevated risk in sexually active teens, probably due to both behavioral and physiologic factors

that may enhance susceptibility to C. trachomatis and perhaps N. gonorrhoeae (e.g., cervical ectopy)

Sexual Orientation

• Probably uncommon in WSW with exclusively female sex partners, but few data exist

Other Risk Factors

• Behavioral markers of STD risk

• Some intrauterine contraceptive devices (especially older designs) probably increase risk

• Previous PID

• Vaginal douching

• Repeat chlamydial infection may elevate PID risk compared to initial infection

HISTORY

Incubation Period

• Varies from 1–2 days to several months following acquisition of  C. trachomatis or N. gonorrhoeae 

Symptoms

• Most cases mild or subclinical

• Low abdominal pain is nearly universal in symptomatic cases

• Most patients have increased vaginal discharge or other symptoms of MPC or BV

• Often dyspareunia, menorrhagia, intermenstrual bleeding

• Right upper quadrant abdominal pain (Fitz-Hugh–Curtis syndrome)

• Fever, chills, malaise, nausea, and vomiting in severe cases

PHYSICAL EXAMINATION

• Pelvic adnexal tenderness, usually bilateral; variable severity

• Uterine fundal and cervical motion tenderness

• Signs of MPC or BV

• Fever is common but often absent

• Lower quadrant abdominal tenderness, sometimes with rebound tenderness or other peritoneal

inflammatory signs; usually bilateral

• Adnexal mass sometimes present on bimanual examination

• Right upper quadrant tenderness may be elicited, due to perihepatitis (Fitz-Hugh-Curtis syndrome),

especially with chlamydial PID

LABORATORY DIAGNOSIS

Lower Genital Tract Infection and Microbiology

• Laboratory evidence of MPC, BV, or both usually is present

• NAAT or culture for N. gonorrhoeae and C. trachomatis

• If laparoscopy done, test tubal aspirate or peritoneal exudate for N. gonorrhoeae and C. trachomatis

and culture for aerobic and anaerobic bacteria

Other Tests

• Leukocyte count and either erythrocyte sedimentation rate (ESR) or assay for C-reactive protein (CRP) should be performed; normal results do not exclude PID, but elevated levels are associated with increased severity

• Pelvic ultrasound examination

• Laparoscopy indicated if diagnosis is uncertain, in severe cases, or when initial response to antibiotics is inadequate

• Endometrial biopsy can be helpful in documenting endometritis, a surrogate marker of salpingitis 

DIAGNOSTIC CRITERIA

• In sexually active women, low abdominal pain plus adnexal or cervical motion tenderness indicate

sufficient likelihood of PID to warrant presumptive treatment

• Ancillary criteria enhance specificity of the diagnosis

° Fever (≥101°F or 38.0°C)

° Mucopurulent cervicitis

° Purulent vaginal discharge

° Abundant PMNs in cervical or vaginal discharge

° Elevated ESR or CRP

° Cervical infection with C. trachomatis or N. gonorrhoeae

• Laparoscopy may be helpful, but only ~70% of patients with clinically diagnosed PID have laparoscopic evidence of salpingitis

TREATMENT

Principles

• Treat all suspected cases while awaiting diagnostic confirmation

• Routinely cover N. gonorrhoeae, C. trachomatis, and mixed aerobic and anaerobic bacteria, regardless of pathogens identified in patient or sex partner and regardless of apparent clinical severity

• All recommended antibiotic regimens have similar short-term clinical efficacy

• No comparative data are available on long-term outcomes, i.e., prevention of infertility, ectopic pregnancy, or recurrent PID

• Indications for hospitalization and parenteral therapy

° Inability to reliably exclude surgical emergency (e.g., appendicitis)

° Suspected tubo-ovarian abscess

° Pregnancy

° Severe clinical manifestations such as nausea, vomiting, high fever, or peritonitis

° Low likelihood of adherence to oral antibiotic therapy

° Poor clinical response to initial oral antibiotics

Recommended Regimens

Inpatient Treatment

For patients with PID of sufficient severity to require hospitalization, many experts recommend Regimen A

for probable chlamydial or gonococcal PID and Regimen B when predominant aerobic and anaerobic infection is likely (e.g., recurrent PID or suspected tubo-ovarian abscess).

• Regimen A

° Doxycycline 100 mg IV or PO∗ every 12 hours 

plus

° Cefotetan 2.0 g IV every 12 hours OR cefoxitin 2.0 g IV every 6 hours for minimum 48 hours, or longer until clinical improvement observed

followed by

° Doxycycline 100 mg PO bid to complete 14 days total therapy

• Regimen B

° Clindamycin 900 mg IV every 8 hours for minimum 48 hours or until improved

plus

° Gentamicin 2.0 mg/kg body weight (loading dose) IV or IM, then 1.5 mg/kg IV or IM every 8 hours for a minimum of 48 hours, until improved

followed by

° Doxycycline 100 mg PO bid to complete 14 days total therapy; or

° Clindamycin 450 mg PO qid to complete 14 days total therapy; or

° Both doxycycline and clindamycin to complete 14 days total therapy

• Alternative parenteral regimens, providing coverage for all likely pathogens but less well studied

° Ampicillin/sulbactam 3 g IV every 6 hours plus doxycycline 100 mg IV or PO every 12 hours for >48 hours, then oral doxycycline to complete 14 days total therapy

or

° Azithromycin 500 mg IV, followed by azithromycin 250 mg PO once daily for 5–6 days, optionally combined with metronidazole 500 mg PO bid for 14 days

Outpatient Treatment

• Initial single dose cephalosporin

° Ceftriaxone 250 mg IM (single dose)

or

° Cefoxitin 2.0 g IM or IV (single dose) with probenecid 1.0 g PO (single dose)

plus

° Doxycycline 100 mg PO bid for 14 days

° Optionally add metronidazole 500 mg PO bid for 14 days

Supportive Therapy

• If IUD present, consider removal

• Bed rest may speed subjective improvement in severe cases

• Analgesics as needed

• Advise sexual abstention for at least 2 weeks

Follow-up

• Reexamine every 1–3 days until improved

• Clinical progression at any time or failure to improve within 3–4 days is an indication for laparoscopic diagnosis and parenteral therapy

• After improvement begins, reexamine weekly until clinically resolved 

Partner Management

• Examine all partners, even when sexual acquisition of PID seems unlikely

• Treat partners for presumptive gonorrhea and chlamydial infection, unless sexual acquisition is excluded with certainty

Counseling

• Counsel patient about sexually transmitted nature of PID and risks of tubal infertility and ectopic

pregnancy

° Avoid nonspecific terms that deemphasize the sexually transmitted nature of PID (e.g., “infected

ovarian cyst”)

PARTNER MANAGEMENT AND PREVENTION

• Depending on suspected or documented cause, manage partners as described for gonorrhea, chlamydial infection, or NGU

• General STD prevention measures (partner selection, condoms)

• Screen sexually active young women for C. trachomatis and N. gonorrhoeae

20–1. Laparoscopic view of pelvic structures in acute PID, showing normal uterus being retracted anteriorly by probe; left fallopian tube (left side of figure) has slight edema with reddened, agglutinated fimbria; right tube is moderately swollen; erythematous; purulent exudate is seen deep in cul-de-sac. 

CASE 1

Patient Profile Age 18, grocery clerk

History Increased vaginal discharge for 10 days; mild low abdominal pain for 4 days, exacerbated during intercourse; severe pain for 1 day; no fever or chills; monogamous with current boyfriend for 3 months

Examination Afebrile; bilateral lower quadrant abdominal tenderness, without rebound; external genitals normal; edematous cervical ectopy and mucopurulent cervical exudate; homogeneous white vaginal fluid; moderate cervical motion, fundal and adnexal tenderness bilaterally; left adnexal fullness without overt mass

Differential Diagnosis Pelvic inflammatory disease, ectopic pregnancy, endometriosis, appendicitis,

urinary tract infection (UTI), colitis

Laboratory Findings of BV and MPC by microscopy, pH, and amine odor test WBC 8,600 per mm3 with normal differential; ESR 35 mm/h; endocervical NAATs for C. trachomatis (positive) and N. gonorrhoeae (negative); RPR and HIV serology negative

Diagnosis PID due to C. trachomatis

Treatment Ceftriaxone 250 mg IM (single dose), followed by doxycycline 100 mg PO bid and metronidazole 500 mg PO bid for 14 days

Partner Management Advised to refer partner for examination and treatment; he was found to have

asymptomatic urethral chlamydial infection; treated with azithromycin 1.0 g PO, single dose

Follow-up Reexamined 2 days later; pain improved, with reduced abdominal and adnexal tenderness;

counseled regarding STD prevention and future risks of infertility and ectopic pregnancy; scheduled to be rescreened for C. trachomatis 3 months later.

20–2. Tubo-ovarian abscess in severe PID: bilobed pyosalpinx/abscess, which was
adherent to uterine fundus (above center), purulent exudate at the site where the
uterus and pyosalpinx adhered.  

CASE

Patient Profile Age 32, married schoolteacher

History Intermittent, mild low abdominal pain and vaginal discharge since IUD inserted 4 months earlier; severe abdominal pain, fever, chills, nausea, and vomiting for 1 day; denied extramarital sex

partners

Examination Temperature 39.2°C; bilateral lower quadrant direct and rebound abdominal tenderness; profuse mucopurulent cervical discharge; IUD string observed; marked bilateral pelvic tenderness, with suggestion of right adnexal mass (examination compromised by tenderness and guarding)

Differential Diagnosis PID, appendicitis, ectopic pregnancy, severe endometriosis

Laboratory Pelvic ultrasound showed 6 × 8-cm fluid-filled mass with internal echoes, plus small effusion in cul-de-sac; WBC 14,700 per mm3 with 80% PMNs; ESR 50 mm/h; Gram-stained smear of cervical exudate and vaginal saline mount showed many PMNs and clue cells, without trichomonads or yeasts; vaginal pH 5.0, KOH amine odor positive; negative cultures for N. gonorrhoeae and C. trachomatis; 2 blood cultures sent (negative); VDRL and HIV serology negative

Diagnosis Acute PID with tubo-ovarian abscess, following IUD insertion; bacterial vaginosis

Treatment Patient hospitalized; IUD removed; treated with clindamycin and gentamicin IV for 4 days until improvement began, then clindamycin 450 mg PO qid to complete 14 days treatment 

Partner Management Husband referred for examination; denied other sex partners, examination normal; negative urine NAATs for C. trachomatis and N. gonorrhoeae (negative); not treated 

20–3. Bilateral pyosalpinx in severe PID; pus is seen exuding from both tubes at sites of
needle aspiration for culture. 

20–4. Pelvic ultrasound examination in acute PID with pyosalpinx  

20–5. Adhesions between liver (below) and parietal peritoneum in a woman with acute perihepatitis (FitzHugh–Curtis syndrome) due to C. trachomatis  

REFERENCES

H. Hunter Handsfield, MD, Color Atlas & Synopsis of Sexually Transmitted Diseases, Third Edition.