Case 12

GYNECOLOGY CASE 12 Trinidad Vinluan. Joseph David Villegas, Jose Bernabe Wong, Deo Adiel Yague, Glenn Yang, Caprice

Dr.

A 24 year old G4P1 (1030) complained of fever and moderate hypogastric pain which has been increasing in severity since yesterday. LMP- August 17-20, 2007. PE: BP-110/70 PR-94,full RR-19 T-38.9C. There was direct tenderness over the hypogastric and both iliac areas without rebound tenderness. On speculum examination, the cervix was congested, with moderate muco-purulent discharge from the os. On IE, the cervix was long, firm, and closed, with minimal tenderness on motion. The uterus was normal in size, movable retroflexed, and slightly tender. There was bilateral adnexal tenderness but no masses were appreciated; fornices were deep. 1) What additional information should be inquired about? Initially, we should inquire about the patient’s menstrual, sexual, and gynecological history. In the menstrual history, it is important to ask about the Last Menstrual Period to rule out pregnancy especially since our patient is in the reproductive age group. In the sexual history, it is important to ask whether the patient has been diagnosed with sexually- transmitted diseases (STDs) or with Pelvic Inflammatory Disease (PID) or had experienced symptoms of the two like unusual discharges or intense pruritus for the former and pelvic pain, cervical motion tenderness (pain felt during a bimanual examination due to stretching of the inflamed peritoneum), and adnexal masses accompanied with fever for the latter. A past history of STDs, PID, bacterial vaginosis, or salpingitis should also be inquired. Recurrent cervical infection with Neisseria gonorrhoea and Chlamydia trachomatis have been associated with increased risk of developing PID. Bacterial vaginosis is also linked to PID because organisms isolated from the upper genital tract of women with PID are often similar to those found in bacterial vaginosis. Infertility, ectopic pregnancy, peritubal adhesions, chronic pelvic pain, and recurrent PID are more common after an episode of salpingitis. Aside from the questions mentioned under the sexual history, the patient’s age of first sexual intercourse, number of partners, and sexual practices. Women with multiple sexual partners and those who engage in unusual sexual practices are prone to myriad of sexually transmitted diseases. A recent sexual exposure to a male with symptoms of urethritis or any STD should be asked. This should be done to identify and cure the potentially infected partner and prevent recurrence of the infection. We should ask about the her occupation, if it involves any sexual activities that could place her at risk for STDs.

The patient should be asked about recent intrauterine procedures like use of intrauterine device (IUD), dilatation and curettage, surgical abortion, cesarean section, or hysterosalpingography. The presence of a recently fitted IUD ( <3 months) increases the risk of developing PID by three- to five- fold ( Danakas GT, 1999), because insertion facilitates the upward migration of cervical and vaginal bacteria. The onset of IUDassociated PID typicall is gradual and may be preceded by a malodorous vaginal diacharge. There is also an increased risk of ascending infection after D & C, surgical abortion, hysterosalpingography, or cesarean section. It is also pertinent to ask if the patient uses vaginal douching. In a study done by Scholes et al in 1998, he found that women aged 18 to 34 years old who douched were at increased risk for acquiring a cervical chlamydial infection. This risk was even greater for those who douched four or more times per month. Vaginal douching alters the vaginal pH and hence affecting the normal vaginal flora making the patient prone to infection. Any accompanying symptoms should also be asked such as, anorexia, nausea, or vomiting, unilateral pain limited to the right lower quadrant suggests acute appendicitis. Missed periods, morning sickness, unilateral pelvic pain is suggestive of ectopic pregnancy. Unilateral pain with signs and symptoms of peritonitis suggests ruptured ovarian cyst. Presence of dysuria and an abnormal urinalysis result suggest urinary tract infection. Constant pain that begins a week before menses suggests endometriosis. Severe unilateral pain and hematuria is suggestive of renal calculus. Adnexal torsion and hemorrhaging corpus luteum both present with unilateral pain. Proctocolitis presents with anorectal pain, tenesmus, rectal discharge or bleeding. Any co-morbid illnesses and medications (steroids and antibiotics), in particular those that cause an immunocompromised state, should be determined since this could affect treatment or may be putting her on further risk of infection. 2. What is the probable diagnosis? The patient complained of fever and moderate hypogastric pain with increasing severity and on physical exam there was direct tenderness over the hypogastric and both iliac areas without rebound tenderness; on internal exam, IE, the cervix was long, firm, and closed, with minimal tenderness on motion. The patient may be suffering from pelvic inflammatory disease (PID). It is an infection of the female upper genital tract that encompasses a broad category of diseases, including endometritis, salpingitis, salpingo-oophoritis, tubo-ovarian abscess (TOA), and pelvic peritonitis. Prompt diagnosis and treatment of this condition are critical because the complications of PID can be life and fertility threatening. Traditionally, the diagnosis of PID has been based on a triad of symptoms and signs, including pelvic pain, cervical motion and adnexal tenderness, and the presence of fever. It is now recognized that there is wide variation in many symptoms and signs among women with this condition, which makes the diagnosis of acute PID difficult.

PID most commonly occurs as a result of Chlamydia trachomatis or Neisseria gonorrhoeae infection of the cervix or vagina that then spreads into the endometrium, fallopian tubes, ovaries, and adjacent structures. Less commonly, direct spread from a nearby infection such as appendicitis or diverticulitis may occur. Hematogenous infection is a rare cause of PID except in cases of tuberculous PID. At least 4 factors could contribute to the ascent of these bacteria and/or be associated with the pathogenesis of upper-genital- tract infection. First, uterine instrumentation (e.g., the insertion of an intrauterine device facilitates upward spread of vaginal and cervical bacteria. Second, the hormonal changes during menses, as well as menstruation, leads to cervical alterations that may result in loss of a mechanical barrier preventing ascent. Also, the bacteriostatic effect of cervical mucus is lowest at the onset of menses. Third, retrograde menstruation may favor ascent to the tubes and peritoneum. Finally, individual organisms may have potential virulence factors associated with the pathogenesis of acute chlamydial and gonococcal PID. Platt et al.found evidence of adnexal involvement in about half of women who had recently been infected with N. gonorrhoeae. Similarly, Stamm et al. noted evidence of upper genital tract infection in 6 of 20 women (30 percent) infected with both gonococci and chlamydiae who were treated with antibiotics active only against N. gonorrhoeae. Risk factors include young age, multiple sexual partners, and certain methods of contraception. Sexually experienced teenagers are three times more likely to have pelvic inflammatory disease than sexually experienced women who are 25 to 29 years of age. Women with multiple sexual partners are at increased risk of acquiring causative organisms such as N. gonorrhoeae and C. trachomatis. Barrier methods of contraception (condoms and diaphragms) and oral contraceptive agents, protect against upper genital tract infection. Most studies have implicated intrauterine devices as a predisposing factor, especially for nongonococcal, nonchlamydial pelvic inflammatory disease. Most of the increased risk occurs during the first few months after the insertion of the device. Recent studies have suggested that vaginal douching may be a predisposing factor. Cigarette smoking has also been implicated and may be an indication of risk-taking behavior. Lower abdominal pain, usually bilateral, is the most common presenting symptom. Pain may be associated with an abnormal vaginal discharge, abnormal uterine bleeding, dysuria, dyspareunia, nausea, vomiting, fever, or other constitutional symptoms. Gonococcal pelvic inflammatory disease tends to have a more abrupt onset and more dramatic symptoms of fever and peritoneal irritation than nongonococcal disease. Both gonococcal and chlamydial disease are more likely to begin during the first half of the menstrual cycle than later in the cycle. Tubal damage and scarring result in important long-term complications, such as recurrent disease, chronic pelvic pain, ectopic pregnancy, and infertility. In a prospective study by Westrom et. al, chronic pelvic pain was found in about 18 percent of women after pelvic inflammatory disease had resolved. Similarly, ectopic pregnancy occurred about six times more often among women who had had the disease than among comparable women who had not.

3. Give the differential diagnosis The following are entities that may present clinically similar to PID: a. Ectopic pregnancy- the classic clinical triad of ectopic pregnancy is pain, amenorrhea, and vaginal bleeding; only 50% of present typically. Patients may present with other symptoms common to early pregnancy, including nausea, breast fullness, fatigue, low abdominal pain, heavy cramping, shoulder pain, and recent dyspareunia. High index of suspicion for ectopic pregnancy in any woman who presents with these symptoms and who presents with physical findings of pelvic tenderness, enlarged uterus, adnexal mass, or tenderness. b. Appendicitis- the most common symptom of appendicitis is abdominal pain. Typically, symptoms begin as periumbilical or epigastric pain migrating to the right lower quadrant (RLQ) of the abdomen. Later, there is worsening progressive pain along with vomiting, nausea, and anorexia. Usually, patients are lying down, flexing their hips, and drawing their knees up to reduce movements and to avoid worsening the pain. Tenderness on palpation in the RLQ over the McBurney point is the most important sign in these patients. Additional signs such as increasing pain with cough (ie, Dunphy sign), rebound tenderness related to peritoneal irritation elicited by deep palpation with quick release (ie, Blumberg sign), and guarding may or may not be present. The obturator sign is present when the internal rotation of the thigh elicits pain (ie, pelvic appendicitis), and the psoas sign is present when the extension of the right thigh elicits pain (ie, retroperitoneal or retrocecal appendicitis). c. Endometriosis- is the presence of endometrial tissue (stroma and glands) outside the uterus, usually the pelvic viscera and the peritoneum. Endometrial foci are under the influence of ovarian hormones and therefore undergo cyclic menstrual changes with periodic bleeding. The pain that occurs with endometriosis begins usually begins 2 to 3 days before menses and worsens during menstruation. The pain may be due to local peritoneal inflammation, deep infiltration with tissue damage, adhesion formation, fibrotic thickening, and collection of shed menstrual blood in endometriotic implants, producing pain whenever tissues are moved. Aside from dysmenorrhea, there may also be dyspareunia and pain on defacation although endometriosis can be asymptomatic. Tender nodules along the uterosacral ligament (which in this case was found in the patient during the rectal examination), a posteriorly fixed uterus, and enlarged cystic ovaries are characteristic findings. d. Torsion of the Adnexa- results in ischemia and rapid onset of acute pelvic pain. The onset of the torsion and the symptoms of abdominal pain frequently coincide with lifting, exercise, or intercourse. Autonomic reflexes such as nausea, emesis, and apprehension are usually present. On examination, there is the presence of large pelvic mass, the abdomen is very tender, and localized rebound tenderness in the lower quadrants. Mild temperature elevation and leukocytosis may accompany the infarction. 4. What diagnostic procedures are necessary?

Initially, a pregnancy test should be performed to rule out ectopic pregnancy Approximately 4% of those admitted to the hospital with a diagnosis of acute PID have an ectopic pregnancy. All women with suspected PID should have an immediate urine or serum pregnancy test to exclude ectopic pregnancy. Cervical, urethral, and rectal specimens should be obtained as indicated by history and physical examination. Anaerobic cultures are not helpful in determining PID etiology, since many anaerobes are normal cervical flora. Rapid enzyme tests are available for office use for the diagnosis of chlamydial and gonococcal infections. A Gram stain of the endocervical secretions for inflammatory cells can be helpful. The presence of gram-negative intracellular diplococci implicates N. gonorrhoeae as the causative agent. Although finding evidence of gonococcal or chlamydial infection on a Gram-stain is helpful, it is not a prerequisite for diagnosis. Laparoscopy or laparotomy provides immediate and accurate diagnosis. Laparoscopy offers the chance to inspect the tubes directly, to assess the severity of the inflammatory reaction, and to obtain biopsy and culture specimens. Laparoscopy may also be indicated in a patient being appropriately treated for acute PID who fails to respond to medical therapy. Laparoscopy is the most specific method for diagnosis of acute salpingitis. The primary and uncontested value of laparoscopy in women with lower abdominal pain is for the exclusion of other surgical problems. Some of the most common or serious problems that may be confused with salpingitis (e.g., acute appendicitis, ectopic pregnancy, corpus luteum bleeding, ovarian tumor) are unilateral. Laparoscopic criteria used for the diagnosis of salpingitis include (1) erythema of the fallopian tube, (2) edema of the fallopian tube, and (3) seropurulent exudate or fresh, easily lysed adhesions at the fimbriated end or on the serosal surface of a fallopian tube.

Laparoscopic View of Normal and Inflamed Fallopian Tubes. Figure A shows a normal right fallopian tube over the posterior peritoneum. The fimbriae -- the branched, finger-like projections at the distal end of each fallopian tube -- are pale. The tube is not congested and is of normal caliber. Figure B shows fallopian tubes with acute, mild pelvic inflammatory disease. The fimbriae of the right fallopian tube are red, edematous, and covered by a white exudate. The inflamed left fallopian tube extends into the cul-de-sac, which contains a purulent serosanguineous exudate.

A white blood cell count and erythrocyte sedimentation rate are neither sensitive nor specific for diagnosis of PID. Fewer than 50% of women with documented acute PID have an elevated white blood cell count, although this is included as a subcriterion for diagnosis. A normal erythrocyte sedimentation rate (<15 mm/hr) was found in 24% of women with laparoscopically proven PID. While pelvic ultrasound is not used in the routine diagnosis of uncomplicated PID, it is a valuable adjunct in the diagnosis of tuboovarian abscess. This imagery also can help diagnose other entities on the differential, including ovarian cyst and ovarian torsion. Endometrial biopsy is relatively sensitive and specific for the diagnosis of endometritis when the endometrial changes described above are found, and the presence of endometritis correlates well with the presence of salpingitis. Endometritis is found in at least three-fourths of women with laparoscopically confirmed salpingitis and is not found in women without PID. Culdocentesis is occasionally helpful in the evaluation of acute pelvic pain. Culdocentesis is a safe and quick technique, but should not be performed if there is a mass in the cul-de-sac or if the uterus is markedly retroflexed. Peritoneal fluid that contains more than 30,000 white blood cells per milliliter supports the diagnosis of acute PID. The aspiration of nonclotting bloody fluid strongly suggests ectopic pregnancy. When clear serious fluid is found on culdocentesis, a diagnosis of ruptured ovarian cyst should be considered. All fluids obtained at culdocentesis should be cultured. Magnetic resonance imaging (MRI) can be useful for the identification of tuboovarian or pelvic abscess. MRI or intravaginal ultrasound assessment of the tubes has been reported to show increased tubal diameter, intratubal fluid, or tubal wall thickening in cases of salpingitis.

5. What is the treatment? PID can be alleviated with the use of numerous types of antibiotics. However, antibiotics do not reverse any damage that has already occurred to the reproductive organs. Speedy antibiotic treatment can prevent severe damage to reproductive organs. The longer a woman delays treatment for PID, the more likely she is to become infertile or to have a future ectopic pregnancy because of damage to the fallopian tubes. Because of the difficulty in identifying organisms infecting the internal reproductive organs and because more than one organism may be responsible for an episode of PID, PID is usually treated with at least two antibiotics that are effective against a wide range of infectious agents. These antibiotics can be given by mouth or by injection. The symptoms may go away before the infection is cured. Even if symptoms go away, the woman should finish taking all of the prescribed medicine. This will help prevent the infection from returning. Women being treated for PID should be reevaluated two to three days after starting treatment to be sure the antibiotics are working to cure the infection. In addition, a woman's sex partner(s) should be treated to decrease the risk of re-infection, even if the partner(s) has no symptoms.

For women with PID of mild or moderate severity, parenteral and oral therapy appears to have similar clinical efficacy. Many randomized trials have demonstrated the efficacy of both parenteral and oral regimens. In the majority of clinical trials, parenteral treatment for at least 48 hours has been used after the patient has demonstrated substantial clinical improvement. The majority of clinicians recommend at least 24 hours of direct inpatient observation for patients who have tubo-ovarian abscesses. Recommended Parenteral Regimens Regimen A • Cefotetan 2 g IV every 12 hours • Cefoxitin 2 g IV every 6 hours PLUS 12 hours

Doxycycline 100 mg orally or IV every

Regimen B • Clindamycin 900 mg IV every 8 hours PLUS Gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily dosing may be substituted. Alternative Parenteral Regimens • Levofloxacin 500 mg IV once daily* WITH OR WITHOUT Metronidazole 500 mg IV every 8 hours • Ofloxacin 400 mg IV every 12 hours* WITH OR WITHOUT Metronidazole 500 mg IV every 8 hours • Ampicillin/Sulbactam 3 g IV every 6 hours PLUS Doxycycline 100 mg orally or IV every 12 hours * Quinolones should not be used in persons with a history of recent foreign travel or partners’ travel, infections acquired in California or Hawaii, or infections acquired in other areas with increased Quinolone-Resistant N. gonorrheae (QRNG)prevalence. Oral therapy can be considered for women with mild-to-moderately severe acute PID, as the clinical outcomes among women treated with oral therapy are similar to those treated with parenteral therapy. The following regimens provide coverage against the frequent etiologic agents of PID. Patients who do not respond to oral therapy within 72 hours should be reevaluated to confirm the diagnosis and should be administered parenteral therapy on either an outpatient or in-patient basis. Recommended Oral Regimens Regimen A • Levofloxacin 500 mg orally once daily for 14 days* • Ofloxacin 400 mg orally twice daily for 14 days* WITH OR WITHOUT Metronidazole 500 mg orally twice a day for 14 days * Quinolones should not be used in persons with a history of recent foreign travel or partners’ travel, infections acquired in California or Hawaii, or infections acquired in other areas with increased QRNG prevalence. Regimen B

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Ceftriaxone 250 mg IM in a single dose PLUS Doxycycline 100 mg orally twice a day for 14 days WITH OR WITHOUT Metronidazole 500 mg orally twice a day for 14 days Cefoxitin 2 g IM in a single dose and Probenecid, 1 g orally administered concurrently in a single dose PLUS Doxycycline 100 mg orally twice a day for 14 days WITH OR WITHOUT Metronidazole 500 mg orally twice a day for 14 days Other parenteral third-generation cephalosporin (e.g., ceftizoxime or cefotaxime) PLUS Doxycycline 100 mg orally twice a day for 14 days WITH OR WITHOUT Metronidazole 500 mg orally twice a day for 14 days

Alternative Oral Regimen One other regimen has undergone at least one clinical trial and has broad spectrum coverage. Amoxicillin/clavulanic acid and doxycycline was effective in obtaining short-term clinical response in a single clinical trial; however, gastrointestinal symptoms might limit compliance with this regimen.

Reference: Novak’s Gynecology 14th ed. Current Medical Diagnosis and Treatment 2006 www.newenglandjournalofmedicine.com http://www.cdc.gov/std/treatment/2006/pid.htm#pid2