Right question resolves teen’s pain dilemma

The Case

A 16-year-old girl presents to an emergency department (ED) accompanied by her boyfriend to report a 24-hour history of right lower quadrant pain. The pain is associated with midline lower back pain and light vaginal bleeding (1 to 2 tampons per day). She has experienced some nausea but no vomiting. Review of systems is negative for fever, diarrhea, constipation, dysuria, abnormal vaginal discharge, blood in her stool, or blood in her urine. 

History and examination

Vaginal bleeding suggests a gynecologic cause, which may be divided into pregnancy-related conditions (the most life-threatening of which is ectopic pregnancy) and non–pregnancy-related conditions. Gastrointestinal causes (of which acute appendicitis would be most life-threatening), urinary system causes, musculoskeletal pain, and intra-abdominal lymphadenitis are also common conditions to consider.

History and physical examination include a full review of systems and a confidential sexual history. The emergency medicine physician speaks to the patient alone without her boyfriend present. She tells the doctor that she is worried she might be pregnant. She thinks that her last menstrual period was 4 to 5 weeks earlier but she is having difficulty remembering. She regularly has unprotected sex with her boyfriend and is not on any contraception. Her last unprotected sexual activity was 10 days ago. She tested negative for chlamydia and gonorrhea at a public health clinic 2 weeks earlier. Her boyfriend is the only sexual partner she has had for several months.

On physical examination, the patient appears well and is in no acute distress. Her blood pressure (BP) is 124/79 mm Hg and her heart rate is 110 beats per minute (bpm). Her temperature is 99.6° F. Examination of her eyes, ears, nose, and throat is unremarkable. No head or neck lymphadenopathy is detected. She has no respiratory distress and she has clear and equal breath sounds bilaterally. Her cardiovascular examination is normal except for mild tachycardia. Upon abdominal examination, she has tenderness to palpation in the left lower quadrant, suprapubic region, and right lower quadrant; the worst pain is in the right lower quadrant. She does not exhibit guarding or rebound tenderness. No other physical examination is performed.

Urinalysis demonstrates 3+ leukocytes and 1+ blood. Urine beta-human chorionic gonadotropin (β-HCG) test is negative. An ultrasound is performed that shows a normal appendix, normal ovaries, and no evidence of an intrauterine or ectopic pregnancy. No other laboratory studies are obtained.

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The patient is diagnosed with a presumed urinary cystitis. Her urine is sent for culture and she is discharged with a course of oral cephalexin.

It is worth noting that although urinary cystitis may present with suprapubic pain, it is unusual for it to cause right or left lower quadrant tenderness. It also does not explain the patient’s vaginal bleeding. The patient’s tachycardia may be related to anxiety, but it also may be related to a disease process more invasive than an ordinary urinary cystitis.

Although the patient had a negative urine β-HCG, the patient reports that her last unprotected sexual activity was only 10 days ago, and urine β-HCG may not be sensitive enough to detect a pregnancy conceived less than 2 weeks earlier. Therefore, at this stage, one cannot be sure that the patient is not pregnant.

Second presentation

The patient’s boyfriend brings her back to the ED 3 days later because her right lower quadrant pain and back pain are worse, and she has now developed fever and dysuria for 24 hours. She continues to have light vaginal bleeding. She felt too unwell to take oral medication so she never started the cephalexin that was prescribed to her. She has not engaged in sexual activity since she was last discharged from the ED.

On physical examination, her BP is 106/54 mm Hg and her heart rate is 78 bpm. She is febrile (100.8° F) and appears more unwell. Head and neck, cardiovascular, respiratory, and abdominal examination are repeated and are essentially unchanged, but she continues to demonstrate discomfort with lower abdominal palpation and is particularly tender in the right lower quadrant.

A renal and pelvic ultrasound is repeated and continues to show a normal appendix, no ovarian pathology, no intrauterine or ectopic pregnancy, no abscess, and no evidence of urinary obstruction. Urine β-HCG remains negative, but this time a serum β-HCG is obtained and is also negative. Her complete blood count (CBC) shows an elevation in white blood cells (20,100 cells/µL) with 20% bandemia; hemoglobin and platelets are normal; and C-reactive protein (CRP) is elevated (24.4 mg/dL). Serum electrolytes, blood urea nitrogen, and creatinine are normal. Urinalysis demonstrates 1+ leukocytes and 3+ blood. The urine culture that was sent when she presented 3 days earlier is now positive for Staphylococcus saprophyticus (>100,000 organisms/mL).

The patient is tentatively diagnosed with pyelonephritis. She receives intravenous (IV) fluids and is started on IV clindamycin. She is kept for observation overnight. By morning, she is afebrile and is able to tolerate oral clindamycin, but her abdominal pain, back pain, vaginal bleeding, and dysuria have not improved. She is discharged on oral clindamycin with instructions to see her primary care physician within 48 hours. When she asks why she is being discharged even though she still feels sick, she is told that her symptoms are “probably related to her pyelonephritis” and should resolve if she completes her antibiotics.

The providers effectively ruled out pregnancy-related causes by documenting a negative serum β-HCG and urine β-HCG about 2 weeks after the patient’s last sexual intercourse. Her blood work (which demonstrates leukocytosis, a left shift, and an elevated CRP) in combination with her fever and unwell appearance are highly suggestive of an inflammatory or invasive infectious cause. Although back pain, fever, dysuria, urine leukocytes, and a positive urine culture may be consistent with pyelonephritis, vaginal bleeding is out of keeping with pyelonephritis and should prompt consideration of a gynecologic diagnosis, which also can present with dysuria and urine leukocytes if urethritis is present.

Third presentation

The patient sees her regular pediatrician the following day. Since leaving the ED, she has been taking her oral clindamycin and has remained afebrile, but still has had no improvement in her right lower quadrant pain, back pain, vaginal bleeding, or dysuria. She continues to feel very unwell and is frustrated that “nobody is helping me.”

The pediatrician asks the patient why she has not had sex with her boyfriend in more than 2 weeks, even though they were previously engaging in frequent sexual activity. Specifically, the pediatrician asks if sex has become painful. No provider has asked her this question until now. The girl replies that sex has indeed become too painful; in fact, even inserting a tampon is very painful.

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On physical examination, the patient’s temperature is 97.9° F but she still appears unwell. Abdominal examination continues to show tenderness throughout the lower abdomen, worst in the right lower quadrant. Although the patient reports vague midline low back pain, back examination reveals no costovertebral angle tenderness, no flank pain, and no pain with palpation of the spinous processes. The pediatrician performs a bimanual examination that demonstrates significant cervical motion tenderness, uterine tenderness, and adnexal tenderness that is worse on the right than the left. Of note, the patient reports that no previous providers had performed a bimanual examination or examined her back.

Differential diagnosis

The differential diagnosis of lower abdominal or pelvic pain in an adolescent female is broad (Table).

In any adolescent presenting with right lower quadrant pain, appendicitis is a life-threatening diagnosis that must be considered. However, visualization of a normal appendix on this patient’s ultrasound made this unlikely. The patient’s urine leukocytes, dysuria, fever, and back pain were suggestive of pyelonephritis, and indeed the patient’s urine culture was positive for a significant colony count of S saprophyticus (a common cause of urinary tract infection [UTI] in young women). However, vaginal bleeding is not a feature of pyelonephritis or cystitis, and this symptom should have made her providers suspicious of a gynecologic diagnosis.

Gynecologic infections such as pelvic inflammatory disease (PID) or cervicitis are often accompanied by urethritis, resulting in dysuria and urine leukocytes. Gynecologic infections and UTIs frequently occur concurrently, so a positive urine culture does not exclude a gynecologic infection.

The gynecologic differential diagnoses may be subdivided into pregnancy-related and non–pregnancy-related causes. Had the patient been pregnant, ectopic pregnancy would have been the most life-threatening diagnosis to exclude, although the differential diagnosis would have included threatened spontaneous miscarriage, molar pregnancy, placental abruption, or endometritis. However, a negative urine pregnancy test at least 2 weeks after the patient’s last unprotected sexual intercourse effectively ruled out pregnancy-related causes.

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Once it was established that the patient was not pregnant, the most important gynecologic disorder to exclude was PID because it is associated with the greatest risk of long-term morbidity if not treated early. Other common conditions might include a ruptured or hemorrhagic ovarian cyst or gynecologic trauma. If the symptoms of dyspareunia, lower abdominal pain, and irregular vaginal bleeding were chronic rather than acute, endometriosis (which is more common in adolescents than previously believed) should be considered. A fibroid-related cause is possible but uncommon in adolescence. Ovarian torsion and mittelschmertz can cause significant lower abdominal pain but are unlikely to present with vaginal bleeding.

Diagnostic discussion

The patient in this case presented with fever, dysuria, vaginal bleeding, abdominal pain, and back pain. A more thorough history earlier in her presentation would have elicited that she had dyspareunia (pain with sexual intercourse), a symptom highly suggestive of gynecologic pathology. Providers often forget to ask patients about dyspareunia, which may be the sole presenting symptom of PID. Of critical importance, all sexually active patients reporting abdominal pain, pelvic pain, dyspareunia, or back pain must have a bimanual examination performed to rule out PID, as these are the historical features distinguishing PID from cervicitis.

Providers may be hesitant to perform bimanual examinations on adolescents, but PID is a clinical diagnosis that cannot be made without this essential examination. Providers must remember that the sequelae of missed PID are far greater than the risks of performing a bimanual examination. Bimanual examination, if performed earlier, would have resulted in earlier empiric treatment and lower risk of long-term sequelae for this patient.

Patients with back pain should receive a back examination. This patient did not have the flank pain or costovertebral angle tenderness typical for pyelonephritis; rather, she had vague and diffuse pain more characteristic of PID.

What is PID?

This teenager has PID. Approximately 5% of sexually active women will experience PID in their lifetime¹; the highest age-specific rates occur in adolescents.² Pelvic inflammatory disease includes any combination of endometritis, salpingitis, oopheritis, peritonitis, and/or a tubo-ovarian abscess. Any sexually active female presenting with abdominal or pelvic pain who has adnexal tenderness, uterine tenderness, or cervical motion tenderness on bimanual examination should be clinically diagnosed with PID and presumptively treated in the absence of another clear cause of illness.³

Clinical indicators that increase the likelihood of PID include fever; elevated erythrocyte sedimentation rate or CRP; >10 white blood cells per high-powered field on microscopic examination of vaginal discharge; and cervical friability or mucopurulent cervical discharge on speculum examination (although speculum examination is not required for diagnosis).³

Delayed treatment of PID may have devastating consequences including chronic pelvic pain associated with decreased quality of life, decreased fertility, and ectopic pregnancy.^4-7 One study found that 7 years after a single mild to moderate PID infection, the prevalence of infertility was 16.7% and increased to 26.2% if the PID recurred. The prevalence of chronic pelvic pain was 35.3% after 1 infection and almost 70% if the PID recurred. Even subclinical PID without significant symptoms is associated with significantly reduced fertility.⁶ Unfortunately, studies show that providers frequently fail to diagnose PID, and frequently provide incorrect antibiotic treatment even if PID is diagnosed (most often erroneously treating with a single dose of antibiotics, which is sufficient for treating cervicitis but inadequately covers PID).^8-10

Fewer than 50% of women with acute PID test positive for chlamydia or gonorrhea.^11-13 This may be because available tests (eg, urine testing; vaginal or cervical swabs) only sample the lower genital tract while PID by definition affects the upper genital tract. Furthermore, PID is frequently polymicrobial and may be associated with other vaginal flora including anaerobes. Providers should empirically treat clinical PID regardless of chlamydia/gonorrhea test results.

Most patients with PID may be treated as outpatients, but inpatient treatment is indicated for patients who are pregnant; who have a tubo-ovarian abscess; who cannot adhere to or tolerate oral medication; who have severe illness (eg, high fever, intractable vomiting); who may have an alternative surgical emergency that still needs to be ruled out (eg, appendicitis); or who do not show clear improvement within 72 hours of initiating antibiotics.³

The Centers for Disease Control and Prevention has published several acceptable regimens for treating PID.³ Inpatient regimens include intravenous cefoxitin and oral doxycycline or intravenous clindamycin and gentamicin. Inpatients usually can be transitioned to oral therapy after demonstrating 24 to 48 hours of clinical improvement. Preferred outpatient treatment is a single intramuscular (IM) dose of ceftriaxone 250 mg with doxycycline 100 mg orally twice a day for 14 days. The provider should consider adding clindamycin or metronidazole if anaerobic involvement is suspected (eg, if chlamydia/gonorrhea tests are negative or if an abscess is present). Outpatients should have a repeat bimanual exam performed within 72 hours to ensure response to treatment. All women with PID should be tested for human immunodeficiency virus (HIV).

All sexual partners from 60 days prior to the onset of symptoms (or the most recent partner, if it has been more than 60 days since last intercourse) should be presumptively treated for both chlamydia and gonorrhea, even if their test results are negative.³ Patients must complete their 14-day treatment and ensure partners are treated before resuming sexual intercourse.

Patient outcome

The patient is clinically diagnosed with PID on the basis of her bimanual examination. She receives ceftriaxone 250 mg IM in the clinic and is started on doxycycline 100 mg twice a day for 14 days. She is instructed to complete the oral clindamycin that she already had been prescribed to provide anaerobic coverage.

A rapid oral HIV test is performed in the clinic and is negative. The patient’s boyfriend is treated with a single dose each of ceftriaxone 250 mg IM and azithromycin 1 gram orally. They are instructed to abstain from sex until the patient has completed 14 days of antibiotics.

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The patient is reassessed within 72 hours. She now appears well and reports complete resolution of her vaginal bleeding and dysuria. Also, her abdominal pain and back pain are almost gone. Abdominal examination is now normal and she has no discomfort with repeat bimanual examination.

She is counseled that her risk of tubal pregnancy, infertility, and chronic pelvic pain will increase substantially with every subsequent episode of PID. She is encouraged to protect herself by using condoms for all future sexual encounters.

REFERENCES

1. Leichliter JS, Chandra A, Aral SO. Correlates of self-reported pelvic inflammatory disease treatment in sexually experienced reproductive-aged women in the United States, 1995 and 2006-2010. Sex Transm Dis. 2013;40(5):413-418.

2. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2014. Atlanta, GA: US Department of Health and Human Services; 2015.

3. Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137. Erratum in: MMWR Recomm Rep. 2015;64(33):924.

4. Pavletic AJ, Wölner-Hanssen P, Paavonen J, Hawes SE, Eschenbach DA. Infertility following pelvic inflammatory disease. Infect Dis Obstet Gynecol. 1999;7(3):145-152.

5. Trent M, Bass D, Ness RB, Haggerty C. Recurrent PID, subsequent STI, and reproductive health outcomes: findings from the PID evaluation and clinical health (PEACH) study. Sex Transm Dis. 2011;38(9):879-881.

6. Wiesenfeld HC, Hillier SL, Meyn LA, Amortegui AJ, Sweet RL. Subclinical pelvic inflammatory disease and infertility. Obstet Gynecol. 2012;120(1):37-43.

7. Haggerty CL, Schulz R, Ness RB; PID Evaluation and Clinical Health Study Investigators. Lower quality of life among women with chronic pelvic pain after pelvic inflammatory disease. Obstet Gynecol. 2003;102(5 pt 1):934-939.

8. Shih TY, Gaydos CA, Rothman RE, Hsieh YH. Poor provider adherence to the Centers for Disease Control and Prevention treatment guidelines in US emergency department visits with a diagnosis of pelvic inflammatory disease. Sex Transm Dis. 2011;38(4):299-305.

9. Woods JL, Scurlock AM, Hensel DJ. Pelvic inflammatory disease in the adolescent: understanding diagnosis and treatment as a health care provider. Pediatr Emerg Care. 2013;29(6):720-725.

10. Kane BG, Degutis LC, Sayward HK, D'Onofrio G. Compliance with the Centers for Disease Control and Prevention recommendations for the diagnosis and treatment of sexually transmitted diseases. Acad Emerg Med. 2004;11(4):371-377.

11. Burnett AM, Anderson CP, Zwank MD. Laboratory-confirmed gonorrhea and/or chlamydia rates in clinically diagnosed pelvic inflammatory disease and cervicitis. Am J Emerg Med. 2012;30(7):1114-1117.

12. Llata E, Bernstein KT, Kerani RP, et al. Management of pelvic inflammatory disease in selected US sexually transmitted disease clinics: Sexually Transmitted Disease Surveillance Network, January 2010-December 2011. Sex Transm Dis. 2015;42(8):429-433.

13. Goller JL, De Livera AM, Fairley CK, et al. Characteristics of pelvic inflammatory disease where no sexually transmitted infection is identified: a cross-sectional analysis of routinely collected sexual health clinic data. Sex Transm Infect. 2017;93(1):68-70.