MOSHOOD ABIOLA POLYTECNIC, OJERE, ABEOKUTA,

OGUN STATE

PELVIC IMMFLAMATORY DISEASES (P I D)

DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY

ADEBOYE FARIDAT ITUNUOLUWA

19/60/0269

Under The Guidance Of Mr Ijaola

September, 2021

Project Seminar Report Presentations

 TABLE OF CONTENTS

CHAPTER ONE

1.0 Pelvic Inflammatory Disease

1.1 Pathophysiology And Microbial Causes

CHAPTER TWO

2.0 Clinical Manifestations And Diagnosis

2.1 Treatment Of Pelvic Inflammatory Disease

CHAPTER THREE

3.0 Long-Term Reproductive Outcomes

3.1 Prevention Of Pelvic Inflammatory Disease

CHAPTER FOUR

4.0 SUMMARY

4.1 Conclusion
 CHAPTER ONE

1.0 Pelvic Inflammatory Disease

Pelvic inflammatory disease is an infection-induced inflammation of the female upper

reproductive tract (the endometrium, fallopian tubes, ovaries, or pelvic peritoneum); it has a wide

range of clinical manifestations.1 Inflammation spreads from the vagina or cervix to the upper

genital tract, with endometritis as an intermediate stage in the pathogenesis of disease.2 The

hallmark of the diagnosis is pelvic tenderness combined with inflammation of the lower genital

tract; women with pelvic inflammatory disease often have very subtle symptoms and signs.3

Many women have clinically silent spread of infection to the upper genital tract, which results in

subclinical pelvic inflammatory disease.

Pelvic inflammatory disease is a major concern because it can result in longterm reproductive

disability, including infertility, ectopic pregnancy, and chronic pelvic pain. After the introduction

of laparoscopy in the 1960s, research on pelvic inflammatory disease proliferated through the

1970s, 1980s, and 1990s, leading to major breakthroughs in the understanding of the microbial

causes of the disease and its relationship to reproductive disability, as well as enabling the

standardization of antimicrobial treatment. According to a national estimate, in 2001 more than

750,000 cases of pelvic inflammatory disease occurred in the United States.5 Over the past two

decades, the rates and severity of pelvic inflammatory disease have declined in North America

and western Europe.6-9 These declines have occurred in association with public health efforts to

control Chlamydia trachomatis and Neisseria gonorrhoeae infection.6,10,11 Despite progress,

however, pelvic inflammatory disease remains a problem because reproductive outcomes among
treated patients are still suboptimal, subclinical pelvic inflammatory disease remains poorly

controlled, and programs aimed at the prevention of pelvic inflammatory disease are not feasible

in much of the developing world.

From the Department of Medicine, University of British Columbia, Vancouver, Canada

(R.C.B.); the Department of Reproductive Health and Research, World Health Organization,

Geneva (S.L.G.); and the Department of Obstetrics and Gynecology, University of Helsinki,

Helsinki ( J.P.). Address reprint requests to Dr. Brunham at the Department of Medicine,

University of British Columbia, 655 West 12th Ave., Vancouver, BC V5Z 4R4, Canada, or at

Robert brunham@ bccdc.ca.

1.1 PATHOPHYSIOLOGY AND MICROBIAL CAUSES

Acute (≤30 days’ duration), clinically diagnosed pelvic inflammatory disease is caused by

spontaneous ascension of microbes from the cervix or vagina to the endometrium, fallopian

tubes, and adjacent structures. More than 85% of infections are due to sexually transmitted

cervical pathogens or bacterial vaginosis–associated microbes, and approximately 15% are due

to respiratory or enteric organisms that have colonized the lower genital tract (Table 1).

Subclinical pelvic inflammatory disease has causes similar to those of acute pelvic inflammatory

disease and may be twice as common.1,12 Chronic (>30 days’ duration) pelvic inflammatory

disease is defined as chronic infection due to Mycobacterium tuberculosis or actinomyces

species rather than as chronic recurrent pelvic pain, which remains common after the treatment

of acute pelvic inflammatory disease. This review focuses on acute and subclinical pelvic

inflammatory disease. Ascending infection from the cervix is often due to sexually acquired

infections with N. gonorrhoeae or C. trachomatis. Sexually transmitted Mycoplasma genitalium

has been identified as a likely cause of cervicitis, endometritis, salpingitis, and infertility, but the

evidence has been inconsistent. 13-15 The factors determining which cervical infections ascend

to the upper genital tract have not been completely elucidated, but data from prospective studies

suggest that about 15% of untreated chlamydial infections progress to clinically diagnosed pelvic

inflammatory disease.16-18 The risk of pelvic inflammatory disease after gonococcal infection

may be even higher. Sexual intercourse and retrograde menstruation may be particularly

important in the movement of organisms from the lower to the upper genital tract.

Anaerobic and facultative bacteria that are found in vaginal flora have been isolated alone or

with N. gonorrhoeae and C. trachomatis infection in the fallopian tubes of women with acute

pelvic inflammatory disease (Table 1).1,19-23 These organisms occur in greater concentrations

in association with bacterial vaginosis, a polymicrobial dysbiosis characterized by a reduction in

normal vaginal lactobacilli and overgrowth of a much more complex anaerobic biofilm-

associated microbiome. 24 Bacterial vaginosis is associated with local production of enzymes

that degrade cervical mucus and associated antimicrobial peptides.3,25,26 This degradation may
impair the cervical barrier to ascending infection and facilitate the spread of microorganisms to

the upper genital tract.27 Infection results in fibrinous or suppurative inflammatory damage

along the epithelial surface of the fallopian tubes and the peritoneal surface of the fallopian tubes

and ovaries, which leads to scarring, adhesions, and possibly partial or total obstruction of the

fallopian tubes. The adaptive immune response plays a role in the pathogenesis of pelvic

inflammatory disease because reinfection substantially increases the risk of tubalfactor infertility

(i.e., the inability to conceive because of structural or functional damage to the fallopian tubes).

Infection-induced selective loss of ciliated epithelial cells along the fallopian tube epithelium can

cause impaired ovum transport, resulting in tubal-factor infertility or ectopic pregnancy (Fig.

1).28 Peritoneal adhesions along the fallopian tubes may prevent pregnancy, and adhesions

within the pelvis are related to pelvic pain.

 CHAPTER TWO

2.0 CLINICAL MANIFESTATIONS AND DIAGNOSIS

Pelvic inflammatory disease is particularly common among sexually active young and adolescent

women, who are most often treated in ambulatory clinics, physician offices, or emergency

departments.9,29-31 The abrupt onset of severe lower abdominal pain during or shortly after

menses has been the classic symptom used to identify acute pelvic inflammatory disease,

although it is now well recognized that both the onset and severity of symptoms can be more ill-

defined and subtle. Atypical, milder clinical manifestations have become more common as rates

of N. gonorrhoeae infection have fallen.32,33 The symptoms associated with acute pelvic

inflammatory disease include pelvic or lower abdominal pain of varying severity, abnormal

vaginal discharge, intermenstrual or postcoital bleeding, dyspareunia, and dysuria.34 Fever can

occur, but systemic manifestations are not a prominent feature of pelvic inflammatory disease.

Occasionally, right-upperquadrant pain suggestive of inflammation and adhesion formation in

the liver capsule (perihepatitis or the Fitz-Hugh–Curtis syndrome) can accompany pelvic

inflammatory disease. A large body of evidence suggests that infection and inflammation in the

upper genital tract can occur and lead to long-term reproductive complications in the absence of

symptoms, a condition often called subclinical pelvic inflammatory disease.1,4,12

Asymptomatic infections of the upper genital tract have been well documented,35 and most

women with tubal-factor infertility do not have a history of clinically diagnosed pelvic

inflammatory disease, as has been observed in studies showing strong associations between

infertility and serologic evidence of previous C. trachomatis or N. gonorrhoeae infection.36,37

Among women with tubal-factor infertility, biopsy specimens show similar pathologic tubal

damage in women who have a history of pelvic inflammatory disease and those who do not.28

However, of note, in one study involving infertile women without a history of diagnosed pelvic

inflammatory disease, 60% of the women with tubal-factor infertility, as compared with only

19% of those without tubal-factor infertility, reported health care visits for abdominal pain38;

this suggests that many cases of pelvic inflammatory disease are missed and that clinicians

should have a low threshold for considering the diagnosis. The clinical diagnosis of pelvic

inflammatory disease is based on the finding of pelvic organ tenderness, as indicated by cervical

motion tenderness, adnexal tenderness, or uterine compression tenderness on bimanual

examination, in conjunction with signs of lower genital tract inflammation. Signs of lower

nclude cervical mucopus, which is visible as an exudate from the endocervix or as yellow or

green mucus on a cotton-tipped swab placed gently into the cervical os (positive “swab test”);

cervical friability (easily induced columnar epithelial bleeding); or increased numbers of white

cells observed on saline microscopic examination of vaginal secretions (wet mount) (Fig.

2).39,40 Pelvic tenderness of any kind has high sensitivity (>95%) for pelvic inflammatory

disease, but it has poor specificity. Findings of lower genital tract inflammation increase the

specificity of the diagnosis.41 Figure S1 in the Supplementary Appendix, available with the full

text of this article at NEJM.org, shows a simplified algorithmfor guiding the clinical diagnosis of

pelvic inflammatory disease. Unfortunately, the clinical diagnosis of pelvic inflammatory disease

is imprecise. Only about

Figure 1.
Pathologic Changes in the Epithelial Surface of the Fallopian Tube after Pelvic Inflammatory

Disease. Scanning electron micrographs show normal human fallopian tube epithelia (Panel A)

and the epithelial surface after pelvic inflammatory disease (Panel B). Pelvic inflammatory

disease causes a selective loss of ciliated epithelial cells, which interferes with intratubal ovum

transport, resulting in infertility or ectopic pregnancy. Images courtesy of Dorothy L. Patton,

University of Washington,

Figure 2. Diagnosis of Pelvic Inflammatory Disease. The clinical diagnosis of pelvic

inflammatory disease is based on the findings of pelvic tenderness on bimanual vaginal

examination and of lower genital tract inflammation on speculum examination. Panel A shows

mucopurulent endocervical discharge as seen on speculum examination. An area of endocervical

columnar epithelium (ectopy) is seen on the face of the cervix. The epithelium is edematous and
erythematous and bleeds easily when touched (friability). Panel B shows mucopurulent

endocervical discharge as a yellow–green exudate on the tip of a Dacron swab (a positive swab

test).38 Panels C and D show high-power microscopic examination of vaginal fluid, with clue

cells typical of bacterial vaginosis (Panel C) and increased numbers of white cells (≥1 per

vaginal epithelial cell) (Panel D).

75% of women who have received a clinical diagnosis of pelvic inflammatory disease that is

based on symptoms of pelvic tenderness and inflammation of the lower genital tract have

laparoscopic confirmation of salpingitis (visualization of tubal and uterine inflammation,

exudate, adhesions, or abscess).42 Although laparoscopy has been considered the standard for
the diagnosis of pelvic inflammatory disease, it has high interobserver variability43 and might

not detect endometritis or early tubal inflammation.44 In addition, it is an invasive surgical

procedure that is not readily available in many settings and is not routinely performed, especially

in women with mild-to-moderate symptoms. Transcervical endometrial aspiration with

histopathological findings of increased numbers of plasma cells and neutrophils is more

commonly used to confirm the diagnosis of pelvic inflammatory disease, and these findings are

often seen in association with laparoscopically confirmed salpingitis.2 However, endometrial

biopsy is somewhat invasive, requires skill for the pathological interpretation of the sample, and

results in a delayed diagnosis.45 Transvaginal ultrasonography and magnetic resonance imaging

(MRI) revealing thickened, fluidfilled tubes are available during the diagnostic workup and are

highly specific for salpingitis.46,47 However, the sensitivity of ultrasonography is only fair, and

although MRI has high sensitivity, it is expensive and not typically available in resource-poor

settings. Power Doppler studies showing increased fallopian-tube blood flow are highly

suggestive of infection.46,48 Imaging studies may also be useful in making an alternative

diagnosis, such as ovarian cyst, endometriosis, ectopic pregnancy, or acute appendicitis; these

conditions can be found in 10 to 25% of women who are thought to have acute pelvic

inflammatory disease. All patients with suspected pelvic inflammatory disease should undergo

cervical or vaginal nucleic acid amplification tests for N. gonorrhoeaeand C. trachomatis

infection; if the results are positive, the probability that pelvic inflammatory disease is present

increases substantially.Molecular tests for M. genitalium are not yet commercially available.

Vaginal fluid should be evaluated for increased numbers of white cells (more than one neutrophil

per epithelial cell) and signs of bacterial vaginosis, including vaginal epithelial cells that have

their cell margins obscured by attached bacteria (i.e., clue cells), an elevated pH, and an amine
odor on addition of potassium hydroxide (positive “whiff” test).40 Normally, bacterial vaginosis

is a noninflammatory condition, and if white cells accompany clue cells, this suggests pelvic

inflammatory disease. A pregnancy test should be routinely requested to help rule out ectopic

pregnancy. Serologic testing for human immunodeficiency virus (HIV) should be performed;

HIV increases the risk of a tuboovarian abscess.49 An elevated erythrocyte sedimentation rate or

C-reactive protein level can increase the specificity of a pelvic inflammatory disease diagnosis.

2.1 TREATMENT OF PELVIC INFLAMMATORY DISEASE

Guidelines for the treatment of pelvic inflammatory disease have been developed by the Centers

for Disease Control and Prevention (CDC) on the basis of the results of clinical trials and the

consensus recommendations of expert clinicians (Table 2).33 The treatment of pelvic

inflammatory disease is empirical and involves the use of broadspectrum combination regimens

of antimicrobial agents to cover likely pathogens. Treatment should cover the principal

pathogens, N. gonorrhoeae and C. trachomatis, regardless of the results of testing. The need to

cover anaerobes has not been definitely established in randomized clinical trials, but because

bacterial vaginosis is commonly found in women with pelvic inflammatory disease and

anaerobes are often recovered from upper genital tract samples, antimicrobials with anaerobic

coverage are recommended. Reliable coverage of M. genitalium is problematic, because the

majority of strains are resistant to doxycycline. Moxifloxacin reliably eradicates M.

genitalium13; however, N. gonorrhoeae has acquired quinolone resistance, and quinolone

monotherapy for pelvic inflammatory disease is no longer routinely recommended. 50

Substitution of azithromycin for doxycycline covers M. genitalium and simplifies dosing.

However, in a recent trial of treatment for nongonococcal urethritis,51 azithromycin was found

to be less reliable than doxycycline for the eradication of C. trachomatis, so it remains an

alternative regimen.The Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH)

study showed that among women with mild-to-moderate pelvic inflammatory disease, the

doxycycline therapy, with respect to both shortterm and long-term complications, was similar in

inpatient and outpatient settings.52 The same held true for adolescents. The reasons for

hospitalization for pelvic inflammatory disease currently include pregnancy, an inability to rule

out competing diagnoses, severe illness combined with an inability to take oral medications, or

tubal abscess. Most patients are successfully treated as outpatients with single-dose

intramuscular ceftriaxone, cefoxitin plus probenicid, or another third-generation cephalosporin

(cefotaxime or ceftizoxime), followed by oral doxycycline with or without metronidazole for 2

weeks (Table 2). For hospitalized patients, therapy with cefotetan or cefoxitin (administered

parenterally until 24 to 48 hours after clinical improvement) together with doxycycline and

followed by doxycycline with or without metronidazole to complete 2 weeks of treatment is

recommended. A regimen of clindamycin and an aminoglycoside may be particularly

appropriate for patients with a tubo-ovarian abscess. Adjunctive nonsteroidal anti-inflammatory

drugs do not improve the clinical outcome.53 Removal of an intrauterine device (IUD) does not

hasten clinical resolution (and may delay it), and in most cases the IUD is left in place.
 CHAPTER THREE

3.0 LONG-TERM REPRODUCTIVE OUTCOMES

Although more than 90% of patients with pelvic inflammatory disease will have a clinical

response to CDC-recommended treatment, the long-term outcome of treatment is still

suboptimal. In classic studies conducted between 1960 and 1984, Westrom and colleagues

followed 2501 Swedish women for several years after the women underwent laparoscopy and

treatment for clinically suspected pelvic inflammatory disease; 1844 of the women (74%) had

confirmed salpingitis Infertility (i.e., an inability to conceive after 1 year of attempting to

become pregnant) developed, overall, in 16% of the women with laparoscopically confirmed

salpingitis, as compared with 2.7% of the women with clinically suspected pelvic inflammatory

disease but no salpingitis. In addition, 9% of women with salpingitis had a subsequent ectopic

pregnancy. The PEACH study provides more modern-day estimates of the risk of reproductive

sequelae among 831 urban American women treated with cefoxitin and doxycycline for mild-to-

moderate, clinically diagnosed pelvic inflammatory disease between 1996 and 1999.52 After 3

years of follow-up, approximately 18% of the women reported infertility, 0.6% had an ectopic

pregnancy, and 29% had chronic pelvic pain (pain reported at two or more consecutive visits 3 to

4 months apart during a period of 2 to 5 years); 15% of the women had recurrent pelvic

inflammatory disease.55 Both of these studies indicate that repeated episodes of pelvic

inflammatory disease markedly worsen the reproductive outcomes. Of note, delayed care for

pelvic inflammatory disease has also been strongly associated with worse long-term outcomes.56

It remains unclear why the long-term outcome of pelvic inflammatory disease remains so dismal,

given the high rates of clinical response. Perhaps infection-induced damage to the fallopian tubes

has occurred by the time treatment is firs . This observation, together with the of subclinical
pelvic inflammatory disease, have highlighted the importance of recognizing prevention of

pelvic inflammatory disease as a major public heath priority.

3.1 PREVENTION OF PELVIC INFLAMMATORY DISEASE

The most important public health measure for the prevention of pelvic inflammatory disease is

the prevention and control of sexually transmitted infections with C. trachomatis or N.

gonorrhoeae. Many high-income countries have implemented programs to screen and treat

women for asymptomatic C. trachomatis infection, on the basis of evidence from randomized

controlled trials indicating that screening for and treating cervical C. trachomatis infection can

reduce a woman’s risk of pelvic inflammatory disease by approximately 30 to 50% over 1

year.17,57,58 The U.S. Preventive Task Force, CDC, and other professional organizations

recommend annual C. trachomatis screening for all sexually active women younger than 25 years

of age and older women at increased risk for infection (e.g., women with multiple or new sex

partners).33,59 These groups also recommend testing for N. gonorrhoeae among women at

increased risk for infection (e.g., women with multiple sex partners or previous gonorrhea

infection and women living in communities with a high prevalence of disease). Comprehensive

sex education, promotion of the use of condoms, and provision of condoms are cornerstones of

the prevention of sexually transmitted infection globally and also have benefits for the

prevention of pelvic inflammatory disease. Data from the PEACH study showed that persistent

condom use during follow-up was associated with reduced risks of recurrent pelvic inflammatory

disease, chronic pelvic pain, and infertility.60 In women with pelvic inflammatory disease due to

N. gonorrhoeae or C. trachomatis, reinfection and repeat pelvic inflammatory disease are

common. Thus, prompt evaluation and empirical treatment of male sex partners of women with

pelvic inflammatory disease or cervical infection are essential. If sex partners cannot be linked to
care, expedited treatment of the partner (e.g., providing prescriptions or medications to a patient

to take to her partner, without the clinician examining the partner) is a useful approach and has

been shown to reduce the risk of reinfection.

 CHAPTER FOUR

4.0 SUMMARY

Pelvic inflammatory disease is an infection of the upper genital tract involving all or either of the

following structures: cervix, uterus, fallopian tubes, ovaries, and its surrounding structures.1-3

There are several risks factors associated with this condition among which are multiple sexual

partners, unsafe termination of pregnancies, uterine instrumentation, no previous pregnancy, non

use of barrier contraceptive method, intrauterine contraceptive device, early coitache, past

history of pelvic inflammatory disease and tobacco smoking, previous stillbirths, and multiple

sexual partners.[4-7] Its improper diagnosis and treatment is a cause of medical and

socioeconomic sequelae: It constitutes about 2% of gynaecological consultations of young

women to their primary care physician in England and Wales.[8] Adolescents and young adults

account for nearly half of the 780,000 cases of PID reported annually in the United States with

250,000 women hospitalized annually and 18/10,000 hospital discharges.

4.1 CONCLUSION

Based on the nonspecific nature of several clinical diagnostic criteria and low predictive value

for pelvic inflammatory, the use of laparoscopy in the diagnosis of this clinical condition

appeared justified. Its use will facilitate the identification of life-threatening gynecological

conditions that may be missed and also permit carrying interventional therapy for patients having

tubovarian masses and abscess as part of the spectrum of disease entity.

 REFERENCES

1. Paavonen J, Westrom L, Eschenbach D. Pelvic inflammatory disease. In: Holmes KK,

Sparling PF, Stamm WE, et al., eds. Sexually transmitted diseases. 4th ed. New York: McGraw-

Hill, 2008.

2. Kiviat NB, Wølner-Hanssen P, Eschenbach DA, et al. Endometrial histopathology in patients

with culture-proved upper genital tract infection and laparoscopically diagnosed acute

salpingitis. Am J Surg Pathol 1990; 14: 167-75.

3. Soper DE. Pelvic inflammatory disease. Obstet Gynecol 2010; 116: 419-28.

4. Wiesenfeld HC, Hillier SL, Meyn LA, Amortegui AJ, Sweet RL. Subclinical pelvic

inflammatory disease and infertility. Obstet Gynecol 2012; 120: 37-43.

5. Sutton MY, Sternberg M, Zaidi A, St Louis ME, Markowitz LE. Trends in pelvic

inflammatory disease hospital discharges and ambulatory visits, United States.