Infectious Diseases in Obstetrics and Gynecology 2:38-48 (I 994) (C) 1994 Wiley-Liss, Inc.

Diagnostic Evaluation of Pelvic Inflammatory Disease

Jeffrey F. Peipert and David E. Soper Department of Obstetrics and Gynecology, Women and lnfants' Hospital, Brown University School of Medicine, Providence, RI (J.F.P.), and Department of Obstetrics and Gynecology, Medical College of Virginia, Richmond, VA (D.E.S.)

ABSTRACT

Pelvic inflammatory disease (PID) is a serious public health and reproductive health problem in the United States. An early and accurate diagnosis of PID is extremely important for the effective management of the acute illness and for the prevention of long-term sequelae. The diagnosis of PID is difficult, with considerable numbers of false-positive and false-negative diagnoses. An abnormal or evidence of lower genital tract infection is an important and predictive finding that is often underemphasized and overlooked. This paper reviews the clinical diagnosis and sup- portive laboratory tests for the diagnosis of PID and outlines an appropriate diagnostic plan for the clinician and the researcher. (C) 1994 .Wiley-Liss, Inc.

KEY WORDS Pelvic inflammatory disease, , adnexitis

n early and accurate diagnosis of pelvic inflam- urination and abdominal discomfort. Symptoms of matory disease (PID) is of paramount impor- abdominal and pelvic discomfort and dysuria be- tance for the effective management of the acute gan 1-2 days prior to evaluation. The patient had illness and for the prevention of long-term sequelae never been pregnant, had no significant medical or such as , ectopic , chronic pel- surgical history or history of sexually transmitted vic pain, and recurrent PID. The diagnosis of diseases (STDs), used condoms for contraception, PID, however, is problematic as patients often and was in a monogomous relationship for the past present with minimal signs or symptoms and the 2-3 years. severity of clinical signs varies widely. The chang- The practitioner evaluating the patient noted white ing etiologic, epidemiologic, and clinical profile of blood cells (WBCs) in the clean-catch urinalysis the disease magnifies this difficulty. Patients with and abdominal tenderness on examination. No pel- PID may have minimal pain and atypical symp- vic examination or cultures were performed. The toms and remain undiagnosed, or they may be mis- patient was diagnosed with a urinary tract infection diagnosed as having gastrointestinal or noninfec- and was told she might also have PID. She was tious gynecologic illnesses. 1-s Undiagnosed PID given a prescription for ofloxacin, 300 mg b.i.d., results in failure to treat or delay of treatment, which she filled and started immediately. which has been associated with an increased risk of The patient followed-up with the student health long-term sequelae. 6-8 clinic and was seen by a nurse practitioner 2 days later. On pelvic examination, she was noted to have CASE ILLUSTRATION abdominal, cervical motion, and adnexal tender- A 20-year-old university undergraduate presented ness. She was told that her examination was consis- to a medical clinic for evaluation of burning with tent with PID, and her prescription was changed to

Address correspondence/reprint requests to Dr. Jeffrey F. Peipert, Department of Obstetrics and Gynecology, Women and Infants' Hospital, 101 Dudley Street, Providence, R102905. Received March 3, 1994 Review Article Accepted June 2, 1994 PID DIAGNOSIS PEIPERT AND SOPER ofloxacin, 400 mg b.i.d., and , 500 TABLE I. Differential diagnosis of PID mg b.i.d., for 14 days. Instructions were given to Acute appendicitis have her sexual partner evaluated and treated. Ectopic pregnancy Concerned with a 2-week course of therapy and the implication of an STD, the patient or tumor Hemorrhage sought consultation with a gynecologist, then 5 days Rupture after the onset of symptoms. By this time, her Torsion symptoms were almost resolved with the exception Peritonitis of mild vulvar On examination at this Pyelonephritis pruritus. Ruptured or perforated viscus evaluation, she had a cloudy-white discharge in the Intraperitoneal hemorrhage vaginal vault but no abdominal or pelvic tender- Generalized sepsis ness. The vaginal pH was 4.2. Microscopic evalu- Urinary tract infection Uterine myoma ation of the discharge revealed no WBCs, trich- Pelvic adhesions omonads, or clue cells; occasional pseudohyphae Chronic salpingitis were noted. She was given a prescription for can- Acute gastrointestinal Miscellaneous didal and was told to continue her course of for "presumed" PID. The patient had numerous questions regarding her diagnosis, prog- nosis, and therapy. pected PID. By using more stringent criteria for This case illustrates the difficulties encountered the diagnosis, such as the presence of fever or leu- in the routine diagnosis of PID. Many primary kocytosis; the specificity of the diagnosis can be practitioners are reluctant to perform a pelvic ex- increased. However, this increase in specificity will amination. In addition, the importance of evaluat- result in a marked reduction in sensitivity. 10,11 ing the vaginal discharge is illustrated in this exam- The limitations of the clinical diagnosis of PID ple. Was the urine contaminated with excess vaginal underscore the need for more accurate diagnostic WBCs secondary to a lower genital tract infection? techniques that are widely available and cost-effec- Was the pyuria the result of inflammation of the tive. 12 What follows is a critical review of the bladder due to infection of the pelvic organs adja- current techniques used in the clinical diagnosis of cent to the bladder? Or was the vaginal discharge PID, including historical risk factors, physical ex- normal and the patient had a case of urethritis and amination, laboratory testing, and more elaborate cystitis? A simple saline preparation of the vaginal tests such as endometrial biopsy, endovaginal ultra- discharge would add important diagnostic informa- sonography, and laparoscopy. As these data are re- tion. viewed, the reader should consider how the accu- rate diagnosis of PID can be made with concer.n for PROBLEMS WITH THE CLINICAL both patient and health-care costs. DIAGNOSIS OF PID The clinical diagnosis of PID based on a bimanual HISTORIC RISK FACTORS AND pelvic examination and traditional laboratory test- RISK MARKERS ing has serious limitations. 9'1 Both overdiagnosis From case-control studies in the United States of and underdiagnosis are quite common, and the list women with confirmed PID, the patients with PID of conditions that must be considered in the differ- were younger, more often nonwhite, single, unem- ential diagnosis of PID is extensive (Table 1). ployed, had less education, consumed more alco- Jacobson and Westrom3 noted that one-third of hol, were more likely to use tobacco, and were women with the clinical diagnosis of PID have more likely to douche than a sexually active control been misdiagnosed. Twelve percent were found to group without PID. 1, 14 They also initiated sexual have other pathology such as appendicitis, endo- activity earlier, reported a higher number of life- metriosis, hemorrhagic corpus luteum, or ectopic time sexual partners, had intercourse more fre- pregnancy; 23% were normal upon laparoscopic quently, had frequent change of sexual partners, evaluation. 3 Laparoscopic evaluation of patients and reported a history of Neisseria gonorrhoeae, with other clinical diagnoses can also reveal unsus- Chlamydia trachomatis, or PID more often than did

INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY 39 PID DIAGNOSIS PEIPERT AND SOPER controls. In addition, cases with proven PID were TABLE 2. Prevalence of symptoms in cases of less likely than control subjects to use any birth- laparoscopically proven PID 13 control method. Symptom Percent Health-care behavior impacts on the risk of ac- quiring PID. The risk of an upper genital tract Abnormal vaginal discharge 55-75 Reported elevated temperature 35-45 infection increases when there is late medical con- Irregular bleeding 30-35 sultation for the diagnosis and treatment of STDs, Urinary symptoms 15-20 when there is noncompliance with medical therapy, Chills 0-15 13 Nausea and 5-I 0 and when the sexual partner is not treated. vomiting Anorectal symptoms 5-I 0 Contraceptive history influences the occurrence Right upper-quadrant pain 5 of PID. Studies have shown that barrier methods may decrease the risk of PID, presumably by pro- tecting against cervical infection, is The intrauter- ine device (IUD) may be associated with an in- intense, and medical consultation is sought usually creased risk of PID, but his risk appears to be within a few days. In contrast, chlamydial PID is limited to the 1st several months after IUD inser- less intense, and the patient may wait a week or tion. 16-8 However, women at low risk of acquir- longer prior to seeking medical attention. In ing an STD have little increased risk of PID with "asymptomatic salpingitis," or "atypical PID," pain IUD use. 19 A tubal ligation markedly decreases the may not be present. risk of ascending infection from the lower genital Symptoms typically occur during tract. 2 The literature is unclear with regard to the or the proliferative phase, rather than the luteal effect of oral contraceptives on the risk of PID. It phase of the cycle. 9'1 Abnormal uterine bleeding, would appear that, while the use of oral contracep- including and menorrha- tives increases a woman's risk for chlamydial endo- gia, is correlated with histologic evidence of en- cervical infection, it decreases the risk of develop- dometritis. 2 These symptoms were reported by ing overt PID. In addition, women using oral one-third of laparoscopically proven cases of acute contraceptives with laparoscopically proven salpin- salpingitis. 3 Menorrhagic or intermenstrual gitis tend to have a milder stage of disease. It is bleeding is more common in chlamydial PID than unclear whether or not the oral contraceptives pre- in cases of gonorrhea-associated or non-STD-asso- vent "silent salpingitis." Numerous human and an- ciated PID. imal studies exist, 21-29 yet the impact of oral con- Among cases of women with proven salpingitis traceptives on PID remains unclear due to who recorded their temperature prior to consulting numerous confounding behavioral variables in this medical care, 40% reported febrile illness. 9 Chills complex relationship. Additional studies are needed were reported by 12%. A vaginal discharge has to sort out this association. been considered a hallmark of PID. Three- While epidemiologic risk factors and risk mark- fourths of women with laparoscopically verified ers may be helpful in determining who is at an PID gave a history of an abnormal vaginal dis- increased risk of PlD, these factors may play only a charge, and all women with salpingitis had an ab- small role in the diagnosis of an individual patient. normal discharge on physical examination. 3'4 In general, women at risk for contracting an STD Urinary symptoms, such as frequency or a burning are at risk to develop PID. sensation, were present in 15-20% of laparoscopi- cally verified PID. 9 Gastrointestinal symptoms are SYMPTOMS uncommon in mild or moderate salpingitis, but Numerous symptoms are associated with upper gen- nausea and vomiting are common complaints in ital tract infection. is one of the most severe PID. Symptoms of proctitis are infre- common complaints encountered in gynecology and quent; if present, these symptoms should raise a may represent PID. Pain associated with PID is suspicion of a cul-de-sac abscess or gonoccoccal most often described as dull, continuous, low ab- proctitis. 9 The frequency of various symptoms in dominal or bilateral pelvic in location, and gradual cases of laparoscopically proven PID is presented in onset. In gonococcal PID, the pain is often more in Table 2.

40 INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY PID DIAGNOSIS PEIPERT AND SOPER In summary, numerous genitourinary tract TABLE 3. Sensitivities and specificities of selected symptoms occur in patients with PID. Pain may or physical examination findings not Since no may be present. symptom has signifi- Sign Sensitivity (%) Specificity (%) cant specificity or sensitivity with respect to the of with Adnexal tenderness 2 95 74 diagnosis PID, patients any genitourinary 12 candidates Bilateral tenderness 58 92 symptoms should be considered for the Cervical motion tenderness a 82 72 diagnosis. Palpable mass a 48 75 Abdominal guarding 4 64 63 PHYSICAL EXAMINATION Clinical cervicitis4 75 93 Hagdu et al. 3s used multivariate logistic regression analysis to identify important predictors of PID. The most important predictor of PID was found to women with coexisting pelvic pain or pelvic organ be an abnormal vaginal discharge which was found tenderness. 9,4 in virtually all women with salpingitis. The impor- Kahn and colleagues 12 evaluated data on the di- tance of a careful assessment for mucopurulent cer- agnosis of PID and combined data from 14 studies vicitis and cervical inflammation and an evaluation for review. Adnexal tenderness had a high sensitiv- of the vaginal discharge cannot be overstated. ity (95%), but a low specificity (74%) in predicting also has been found to be an PID. Other sensitivities and specificities of physi- independent risk factor for PID. In a study of cal examination findings based on this review 12 and women with suspected PID, bacterial vaginosis was a recent study from a primary care setting4 are found in 9/31 women with proven PID and 0/14 presented in Table 3. without PID. 36 In a recent study of the microbio- Since the treatment of a tubo-ovarian abscess logic etiology of acute salpingitis, an abnormal vag- (TOA) requires hospitalization, the presence of a inal flora characterized by bacterial vaginosis or its palpable is an important clinical find- intermediate state was almost always present in pa- ing. The clinical diagnosis of a TOA is based on tients with acute salpingitis. The authors noted that, clinical criteria for PID in conjunction with a pal- other than N. gonorrhoeae and C. trachomatis, bac- pable adnexal complex. The predictive value of a terial vaginosis microorganisms were the most com- palpable mass, however, is low as this finding was mon group of microorganisms isolated from the reported by experienced examiners in 25 % of cases upper genital tract. 37 In contrast, Faro and col- with normal findings at laparoscopy. 9 Ultrasound leagues38 did not find this association in their study may be useful to further characterize the mass. of 41 women with clinically severe PID. Other signs, symptoms, and laboratory tests are not Leukorrhea is present when inflammatory cells helpful in the diagnosis of a TOA. [polymorphonuclear (PMN) leukocytes] are the predominant cells noted during microscopy of a LABORATORY TESTING vaginal saline preparation. Microscopic evaluation There is no one diagnostic test that is pathogno- of the vaginal secretion is a simple and rapid test monic for PID. Several new tests have been pro- that can provide valuable information in the diag- posed in the evaluation and diagnosis of women nosis of PID. 3s The proportion of inflammatory with suspected upper genital tract infection. These cells indicates the degree of host response. A nor- tests include C-reactive protein (CRP),'42-4s en- mal wet mount of the vaginal secretions, plus clear dometrial biopsy, 2'6'45-47 and endovaginal ultra- cervical mucus, is felt to reliably exclude upper sound. 48-52 It is clearly important to develop and to genital tract infection. 3 The presence of a mu- carefully evaluate these and other diagnostic tests copurulent cervical discharge is defined as endocer- that would improve and facilitate the diagnosis of vical mucopus or the presence of > 10 PMN leuko- PID. For the sake of brevity, only a few of the cytes per high power field ( 1,000) in Gram- more predictive laboratory tests will be reviewed. stained endocervical smears. 39 The presence of In 4 of 4 studies reviewed by Kahn et al., 12 an leukorrhea or mucopus is consistent with the diag- elevated CRP was found to be a significant predic- nosis of lower genital tract infection. Leukorrhea tor. Sensitivities ranged from 74 to 93%, and spec- or mucopurulent is suggestive of PID in ificitie ranged from 50 to 90%. 30,42-45 In addi-

INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY 41 PID DIAGNOSIS PEIPERT AND SOPER tion, levels of CRP appear to reflect the severity of recent studies have shown that the polymerase chain laparoscopically proven salpingitis. The ability of a reaction (PCR) assay may be a more sensitive microbial substance to stimulate the synthesis of method, sS's9 PCR is not only sensitive, but is hepatic acute-phase proteins such as CRP is a prom- highly specific. In a study evaluating 15 women inent pathophysiologic mechanism of PID. 3 with laparoscopically verified salpingitis, Witkin Westrom3 noted an elevated erythrocyte sedi- et al. 6 found 60% (9/15) had positive PCR testing mentation rate (ESR) >15 mm/h in 76% of pa- for chlamydia. Only 2 of these positive results had tients with visually diagnosed acute salpingitis, but positive cervical cultures. The authors6 concluded also in 53% of women with suspected salpingitis that PCR is a more sensitive and more rapid test for but normal findings at laparoscopy. A significant C. trachomatis in this population of women with association was noted between the ESR and the acute salpingitis. stage of salpingitis at laparoscopy and with chlamy- Evidence of lower genital tract infection, either dia-associated salpingitis. When comparing ESR by microbiologic testing or by evaluation of cervi- and CRP, Wasserheit et al. 4 found that an ele- cal Gram stain or vaginal discharge, is a hallmark vated CRP was a more sensitive and specific pre- of upper genital tract infection. In fact, the clinical dictor of PID than was ESR. diagnosis of PID is suspect in women who do not Despite widespread belief by clinicians, an ele- test positive for N. gonorrhoeae or C. trachomatis or vated WBC count is not a reliable predictor of who fail to show evidence of lower genital tract PID, nor does it correlate with the severity of tubal inflammation. inflammation or need for hospitalization. In fact, fewer than 60% of women with a laparoscopic diag- ENDOMETRIAL BIOPSY nosis of acute salpingitis have a WBC count An endometrial biopsy can be a useful alternative to > 10,000 cells/ml. 9 laparoscopy as an objective test in the diagnosis of Even though no one diagnostic test is pathogno- PID. 32'36'46'47 It is a simple office or outpatient monic for PID, it would appear that CRP has procedure that can be performed with or without a sufficient predictive value to be utilized in the di- paracervical anesthetic. Endometrial sampling can agnosis of PID. Additional studies are necessary to be obtained with a variety of devices. A Novak determine if CRP remains predictive in cases of curette, a VABRA (Berkeley Medevices, Inc., Ber- mild and atypical PID. keley, CA) endometrial suction curette, or a flexi- ble endometrial sampling device such as the Pipelle MICROBIOLOGIC TESTING (Unimar, Inc., Danbury, CT) or Gynosampler N. gonorrhoeae has been called the "classic" PID- (Gynopharma, Inc., Somerville, NJ) can be used. causing agent. 9 In studies from the United States The histopathologic diagnosis is usually available in and Canada, N. gonorrhoeae has been isolated from 3-4 days. If an endometrial biopsy is used for the lower genital tract in 44-70% of women with histologic evaluation and culture of the upper geni- acute PID, depending on diagnostic inclusion cri- tal tract in patients with suspected upper genital teria. 9 Isolation of gonococci from the upper geni- tract infection, antibiotics should be administered tal tract of patients with PID is usually between 10 immediately after the sample is obtained. and 54%. 37,53,54 Based on culture or serologic evi- The histologic features of the that dence, infection with C. trachomatis may be present are associated with infection of the upper genital in up to 38%ss of hospitalized cases and 52% of tract and laparoscopically proven salpingitis include women treated as outpatients for PID. s6,s7 the presence of PMN leukocytes in the endometrial Positive tests for N. gonorrhoeae or C. trachoma- surface epithelium, dense subepithelial stromal lym- t/s also have been found to be significant predictors phocytic infiltration, germinal centers containing of PID in 2 well-designed studies. s'4 Studies transformed lymphocytes, and plasma cells in the evaluating the identification of microorganisms and endometrial stroma. 41,55,61 the diagnosis of PID are often limited by the mi- Recent studies have shown a fair correlation be- crobiologic technique used for identification. While tween as demonstrated histologically culture has traditionally been the gold standard for and the laparoscopic diagnosis of PID. 6'47 En- the diagnosis of both gonorrhea and chlamydia, dometrial inflammation on biopsy has a good sensi-

42 INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY PID DIAGNOSIS PEIPERT AND SOPER tivity (70-92%) and specificity (67-89%) for the respectively. The authors52 concluded that trans- diagnosis of PID. 43'44'55 Using a definition of vaginal sonography can aid in the outpatient evalu- histologic endometritis of > plasma cell/ 120 ation of women with suspected PID. field in the endometrial stroma plus >5 PMN The findings of Cacciatore and colleaguess2 leukocytes/X400 field in the endometrial surface should be validated in other cohorts of women with gave the best prediction of laparoscopically proven both mild and severe cases of PID. As clinicians salpingitis. This combination of histologic findings gain more experience with transvaginal sonogra- gave a sensitivity of 92% and a specificity of 87%. 61 phy, this technique may become useful in evaluat- Sellors and colleagues41 demonstrated that an en- ing patients with the presumptive diagnosis of PID. dometrial biopsy was more than 90% specific in predicting histopathologic evidence of salpingitis. CLINICAL CRITERIA FOR PID Additional prospective studies are necessary in Clinical criteria for the diagnosis of PID have been women with classic PID (with pain) and atypical outlined on several occasions6s-68 and are listed in PID (without pain) to confirm the predictive val- Table 4. The Centers for Disease Control and Pre- ues of histopathologic criteria for endometritis in vention (CDC) has released revised clinical criteria diagnosing patients with suspected upper genital for PID which are summarized in Table 5. 68 tract infection. Jacobson and Westrom3 evaluated the accuracy An endometrial biopsy is also an indispensable of conventional signs and symptoms of PID as tool in evaluating the endometrium of patients un- assessed by visual confirmation of acute salpingitis. dergoing laparoscopy. If laparoscopic findings are Diagnostic accuracy could be improved by increas- not consistent with visual criteria for salpingitis, ing the number of positive parameters. They also acute or chronic endometritis may be the source of" noted that a marked increase in the number of the patient's symptoms. inflammatory cells in the wet smear of vaginal se- An endometrial evaluation with outpatient sam- cretions was found in women with PID. This test pling devices is an underutilized procedure in the could be used to exclude the possibility of PID in diagnosis of upper genital tract infection. Histo- women with abdominal pain. logic evidence of endometritis confirms the pres- Criteria endorsed by the Infectious Disease Soci- ence of upper genital tract inflammation and sup- ety for Obstetrics and Gynecology (IDSOG) have ports the diagnosis of PID. been outlined by Hager et al. 6s The IDSOG guide- lines eliminate the previously required chief com- ULTRASONOGRAPHY plaint of abdominal pain. This is an important Transabdominal ultrasonography is useful in iden- improvement if we are interested in patients with tifying complicated PID, e.g., TOA or inflamma- atypical PID who may not have abdominal pain. tory complex, but has not been very effective in Soper67 proposed a set of clinical criteria that distinguishing uncomplicated PID from other gy- was a compromise between the 2 previously pub- necologic conditions such as endometriosis or ova- lished guidelines. In these guidelines, the impor- rian cysts. 62-64 The use of endovaginal probes has tance of signs of lower genital tract infection is refined the imaging of the pelvic organs. 48'49 stressed. In addition, the endometrial biopsy is pro- Transvaginal ultrasonography is a relatively nonin- posed as an adjunct to confirm the clinician's suspi- vasive diagnostic modality that can be combined cion of upper genital tract infection. with the pelvic examination for evaluating gyneco- The CDC's minimum clinical criteria for PID logic disorders, including PID. s'sl include abdominal tenderness, cervical motion ten- In a recent prospective study of 51 women with derness, and adnexal tenderness. 68 Based on the suspected PID, Cacciatore et al. s2 demonstrated presence of all 3 of these findings, empiric treat- that a transvaginal sonogram suggestive of PID, ment of PID should be instituted in the absence of e.g., thickened, fluid-filled tubes, had a sensitivity an established cause other than PID. The additional of 85% and a specificity of 100% for the diagnosis criteria listed are proposed for patients with severe of plasma cell endometritis as determined by an clinical signs in whom incorrect diagnosis and man- endometrial biopsy. The positive and negative pre- agement may cause unnecessary morbidity. dictive values for the group were 100 and 95%, Unfortunately, the clinical criteria proposed have

INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY 43 PID DIAGNOSIS PEIPERT AND SOPER TABLE 4. Clinical criteria for the diagnosis of PID Hager et al.6s Swee[66 Soper67

Major Criteria (All Must Be Present) Abdominal tenderness Abdominal tenderness Adnexal tenderness Cervical motion tenderness Cervical motion tenderness Signs of lower genital tract infection Adnexal tenderness Adnexal tenderness

Minor Criteria (Additional Criteria Increase the Specificity of the Diagnosis)

Endocervical Gram stain positive for >5 WBCs/ 1000 fieldgram on Histologic evidence of endometritis N. gonorrhoeae gram stain of endocervix Elevated CRP or ESR Temperature > 38C Temperature > 38C Temperature 38C Leukocytosis (> I0,000) Leukocytosis (> 10,500) Leukocytosis (> 0,000) Purulent material by culdocentesis Purulent material by culdocentesis Positive test for C. trachomatis or or laparoscopy Pelvic complex by examination or N. gonorrhoeae sonography Pelvic abscess or inflammatory Evidence of N. gonorrhoeae or C. complex on bimanual examination trachomatis in endocervix or sonography (+Gram stain for N. gonorrhoeae or monoclonal antibody for C. trachomatis)

TABLE 5. Revised CDC criteria for the diagnosis women without visible salpingitis may have infec- of PID tion either within the tubal lumen or the endo- metrium and therefore may have a false-negative Minimum 2'37 Lower abdominal tenderness laparoscopy. At the time of diagnostic laparos- Adnexal tenderness copy, it is recommended that an endometrial biopsy Cervical motion tenderness be performed to rule out endometritis that has not Additional to acute Routine progressed salpingitis. Oral temperature >38.8C Three laparoscopic findings have been used as Abnormal cervical or vaginal discharge the minimal criteria for the visual confirmation of Elevated ESR acute salpingitis: pronounced hyperemia of the tu- Elevated CRP Laboratory documentation of cervical infection with bal surface; edema of the tubal wall; and sticky N. gonorrhoeae or C. trachomatis exudate on the tubal surface and from the fimbri- Elaborate ated ends of the fallopian tubes when patent. The Histopathologic evidence of endometritis on endometrial at corre- biopsy severity of disease laparoscopic evaluation TOA on sonography or other radiologic tests lates with the development of long-term sequelae. Laparoscopic abnormalities consistent with PID ATYPICAL PID The classic picture of acute PID with abdominal, never been adequately validated in large prospec- cervical motion, and abdominal tenderness may rep- tive studies. 12,68 When attempts have been made to resent a small proportion of the entire spectrum of validate clinical criteria, the imprecision of clinical cases of PID. In fact, a growing body of evidence diagnosis is clear. Approximately one-third of suggests that acute PID with lower abdominal pain women diagnosed with PID do not have PID when as the chief complaint may represent the "tip of the laparoscopic inspection is performed. 3 iceberg" and that large numbers of women with relatively or completely painless upper genital tract LAPAROSCOPY infections are undiagnosed. The majority of women It is believed that PID is best diagnosed visually by with have no history of signs laparoscopic evaluation of the pelvic organs. 3,69,70 or symptoms of PID. 7 -7 Wolner-Hanssen et al. However, a diagnostic laparoscopy is expensive and have estimated that there may be 4-6 cases of atyp- is not always readily available. In addition, many ical PID for every case of classic or typical PID.

44 INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY PID DIAGNOSIS PEIPERT AND SOPER These authors suggested that additional studies are TABLE 6. Effect of adjunctive clinical criteria on the necessary to determine the prevalence of histopatho- specificity of the clinical diagnosis of PIDa endometritis in women logic with mucopurulent Criteria Specificity (%) cervicitis and in women with menorrhagia. Although PID is believed to be associated with Major Lower abdominal abdominal of recent from pain pain onset, symptoms Signs of lower genital tract infection other organ systems may also be due to upper geni- Bilateral adnexal tenderness tal tract infection. Genital tract symptoms (mu- Minor copurulent cervicitis, vaginal discharge, abnormal Fever Palpable adnexal swelling uterine bleeding, , or ), Leukocytosis gastrointestinal symptoms (nausea, vomiting, or Elevated ESR or CRP proctitis), or urinary tract symptoms (dysuria, ur- Positive test for N. gonorrhoeae or C. trachomatis gency, or frequency) may all be associated with Major criteria (all three) 61 PID. Major + one minor 78 Most PID studies address only the classic pre- Major + two minor 90 Major + three minor 96 sentations of the disease and fail to evaluate women with more atypical forms of the disease. Cates et aAdapted from Mardh and Westrom. al. 74 have attempted to identify predictors of atypi- cal PID and found that women with atypical PID were demographically more like fertile control sub- The CDC suggests that the minimal criteria jects than were women with overt PID. Behavioral needed for the diagnosis of PID are abdominal, characteristics of the atypical PID group were mid- cervical motion, and adnexal tenderness. 68 The sen- way between those of the overt PID group and the sitivity and specificity of these criteria are unknown fertile control group. The authors74 concluded that at this time and await further validation. It is im- the clinical predictors of atypical PID remain elu- perative to evaluate the lower genital tract for evi- sive. Clinicians should consider PID in the differ- dence of infection. We believe that evidence of any ential diagnosis of women with mucopurulent cer- pelvic organ tenderness and the presence of lower vicitis and abdominal pain and in patients with genital tract inflammation can be used to make the unexplained uterine bleeding, dyspareunia, or atyp- diagnosis of PID. If there is no evidence of lower ical pelvic pain. Future prospective studies should genital tract infection (normal cervical mucus and address women with atypical as well as typical pre- no predominance of WBCs in the vaginal wet prep- sentations of upper genital tract infection. aration), the likelihood of PID is quite low. The likelihood of PID increases as the number DIAGNOSTIC APPROACH of positive findings increase. Adjunctive criteria For the clinician, the diagnosis of PID should be for the diagnosis of PID include elevated tempera- considered in any woman of reproductive age who ture, palpation of an adnexal complex, leukocyto- has any genitourinary symptoms, a Clinicians sis, elevated ESR or CRP, purulent material ob- should have a high index of suspicion and a low tained by culdocentesis, and/or a positive test for a threshold for initiating treatment because the po- lower genital tract infection with N. gonorrhoeae or tential for serious long-term reproductive sequelae C. trachomatis. The specificity of the clinical diag- is great, even if the patient's symptoms are mild. nosis of PID increases to greater than 90% when 2 A comprehensive diagnostic evaluation will in- or more adjunctive criteria are present with find- clude a careful history to illicit risk factors for ings of pain, adnexal tenderness, and leukorrhea PID, as well as a pelvic examination, and careful (Table 6). More elaborate indicators (endometrial assessment for lower genital tract infection, includ- biopsy or laparoscopy) should be employed when ing tests for N. gonorrhoeae and C. trachomatis, the diagnosis is uncertain, when symptoms are se- testing for mucopurulent cervicitis, and evaluation vere and misdiagnosis may result in serious mor- of the vaginal wet preparation for leukocytes. Ad- bidity, or when the diagnosis of salpingitis in the ditional laboratory tests that may be helpful include patient with a mild clinical presentation must be ESR, CRP, and endometrial biopsy. confirmed.

INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY 45 PID DIAGNOSIS PEIPERT AND SOPER

Patients should be informed of the level of un- pelvic inflammatory disease: Diagnostic and prognostic certainty in the clinical diagnosis of PID and should value of routine laparoscopy. Am J Obstet Gynecol 105: 1969. be given the option of more elaborate diagnostic 1088-1098, 4. Chaparro MY, Ghosh A, Nashed A, Poliak A: Laparos- evaluation. The label of "PID" as an STD should copy for the confirmation and prognostic evaluation of not be taken lightly by the clinician. This diagnosis pelvic inflammatory disease. Int J Gynaecol Obstet 15: often calls for a frank discussion between the pa- 307-309, 1978. tient and her sexual partner. Patients often choose 5. Patton DL, Moore DE, Spadoni LR, et al.: A compari- to have more invasive testing when given the op- son of the 's response to overt and silent salpingitis. Obstet Gynecol 73:622-630, 1989. tion in order to provide an accurate The diagnosis. 6. Alder MW, Belsey EH, O'Connor BH: Morbidity asso- clinician should provide the patient with the facts ciated with pelvic inflammatory disease. Br J Vener Dis and allow the patient to play an active role in deci- 58:151-157, 1982. sions concerning further diagnostic testing. 7. Sellors JW, Mahoney JB, Chernesky MA, Rath DJ: Tubal factor infertility: An association with primary chlamydial infection and asymptomatic salpingitis. Fertil CONCLUSIONS Steril 49:451-457, 1988. 8. Hillis SD, Riduian J, Marchbanks PA, Wasserheit JN, The accurate of PID is and the diagnosis difficult, Cates W, Westrom L: Delayed care of pelvic inflamma- ramifications of misdiagnosis may be quite serious. tory disease as a risk factor for impaired fertility. Am J A thorough evaluation for PID will include a care- Obstet Gynecol 168:1503-1509, 1993. ful history and physical examination with attention 9. Mardh P-A, Westrom L: Acute pelvic inflammatory dis- to evidence of lower genital tract infection based on ease. In Holmes KK, Mardh P-A, Sparling PF, Wiesner Cates W, Lemon SM, Stature WE Sexually inspection and vaginal wet preparation. Supportive PJ, (eds): Transmitted Diseases. 2nd ed. New York: McGraw-Hill, laboratory evaluation may include an elevated ESR, pp 593-613, 1990. CRP, and positive cultures from the lower genital 10. McCormick WM: Pelvic inflammatory disease. N Engl tract. When numerous positive criteria are noted, J Med 330:115-119, 1994. the diagnostic specificity is high and further sup- 11. Peipert JF, Sweeney PJ: Diagnostic testing in obstetrics portive evaluation may not be necessary. and gynecology: A clinician's guide. Obstet Gynecol 82: the of 619-623, 1993. Missing diagnosis PID (false negative) 12. Kahn JG, Walker C, Washington AE, Landers DV, usually has more detrimental results than a false- Sweet R: Diagnosing pelvic inflammatory disease. A com- positive diagnosis. 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