16: Dysuria

Dysuria is pain or burning with or after urination. Most patients with dysuria have a urinary tract infection (UTI). When considering this symptom, pivotal points are history and physical exam findings that suggest more serious or complicated etiologies. Important historical features include vaginal or penile discharge, flank pain, rectal/perineal pain, nausea or vomiting, fever, hematuria, urinary hesitancy, urinary urgency, nocturia, and urinary frequency. On the physical exam, vital signs including temperature and sometimes orthostatics are important as are abdominal and costovertebral-angle (CVA) tenderness. A pelvic exam should be performed in any woman with discharge. A prostate exam should be performed in any man in whom cystitis is suspected, especially those with symptoms of nocturia, hesitancy, or rectal pain. When approaching the differential diagnosis for dysuria, an anatomic approach to the genitourinary tract is helpful for organization.

1. Skin: rash causing irritation with urination

   1. Herpes

   2. Irritant contact dermatitis

   3. Syphilitic chancre

   4. Erosive lichen planus

2. Urethra (urethritis from sexually transmitted infections [STIs])

   1. Gonorrhea

   2. Chlamydia

   3. Trichomoniasis

3. Male genital structures

   1. Epididymis: epididymitis

   2. Testes: orchitis

   3. Prostate

      1. Benign prostatic hypertrophy (BPH)

      2. Acute prostatitis

      3. Chronic prostatitis

4. Female genital structures

   1. Vagina

      1. Trichomoniasis

      2. Bacterial vaginosis

      3. Candidal infections

      4. Atrophic vaginitis

   2. Uterine/bladder prolapse

   3. Cervix

      1. Neisseria gonorrhoeae infection

      2. Chlamydia trachomatis infection

5. Bladder

   1. Acute cystitis

      1. Uncomplicated (healthy women with no urinary tract abnormality)

      2. Complicated (men or patients with any of the following: urinary obstruction; pregnancy; neurogenic bladder; concurrent kidney stone; immunosuppression; indwelling Foley catheter; systemic infection, such as bacteremia or sepsis)

   2. Interstitial cystitis

6. Kidney: pyelonephritis

Ms. D is a healthy young woman with symptoms consistent with cystitis. The pivotal points in this case are the absence of flank pain, vaginal discharge, nausea, vomiting, or fever. Vaginitis is a common disease that can cause similar symptoms, and pyelonephritis is a must not miss diagnosis. These diagnoses must be explored as part of the limited differential diagnosis (Table 16-1).

Leading Hypothesis: Cystitis

Textbook Presentation

Cystitis typically presents with dysuria or suprapubic pain or both. Often, there is associated urinary frequency, urgency, or hematuria. There is usually no penile or vaginal discharge, CVA tenderness, nausea, vomiting, or fever.

Disease Highlights

1. Cystitis is an infection of the bladder.

2. Most common bacterial pathogens include enteric flora such as:

   1. Gram negatives: Escherichia coli (75–95%), Klebsiella pneumoniae, and Proteus mirabilis.

   2. Gram positives: Staphylococcus saprophyticus, Enterococcus faecalis, and group B streptococcus.

3. Risk factors for cystitis

   1. Sexual intercourse

   2. Use of spermicides

   3. Previous UTI

   4. A new sexual partner in the past year

4. Cystitis in the elderly

   1. Elderly patients often have atypical presentations of cystitis; many have chronic symptoms of frequency and incontinence.

   2. Delirium, functional decline, or acute confusion may be the presenting symptoms of cystitis in elderly patients.

      Cystitis frequently presents in atypical ways in the elderly. UTIs should be on the differential for delirium or functional decline.

Evidence-Based Diagnosis

1. History

   1. Dysuria or suprapubic pain with or without frequency, hematuria, or urgency.

   2. The symptoms of vaginal discharge (LR- 0.3) or vaginal irritation (LR- 0.2) decrease the probability of cystitis in a woman.

   3. The probability of cystitis is over 90% in women with dysuria and frequency without vaginal discharge or irritation.

2. Laboratory testing

   1. Women with classic uncomplicated cystitis (dysuria with or without frequency and without vaginal discharge) may be treated without any testing.

   2. Urinalysis or urine dipstick findings suggestive of cystitis

      1. Leukocyte esterase is an enzyme released by leukocytes and signifies pyuria. LR+ 12.3-48

      2. The presence of nitrites indicates the presence of bacteria that convert urinary nitrates to nitrites.

      3. White blood cells on urine microscopy

      4. Hematuria demonstrated by positive blood on dipstick or RBCs on microscopy

      5. Table 16-2 shows the sensitivity, specificity, and LRs of urinalysis and microscopy findings.

      6. The negative likelihood ratio of leukocyte esterase and urine nitrite is only 0.3. Absence of these findings does not rule out cystitis.

         The diagnosis of cystitis should not be ruled out by a urinalysis that is negative for both leukocyte esterase and nitrites in the presence of a convincing clinical presentation.

   3. Urine culture

      1. Used as a confirmatory test in the setting of diagnostic uncertainty or the need to identify a specific bacterial pathogen and the antimicrobial susceptibility (such as in the setting of recurrent cystitis).

      2. The definition of a positive urine culture is > 10⁵ colony-forming units (CFU) of bacteria per milliliter.

      3. Women with clinical symptoms of cystitis and lower concentrations of bacteria may still have cystitis. One study demonstrated 30-50% of women with cystitis had CFU counts of 10² to 10⁴.

Treatment

1. Prevention

   1. Factors that have not been found to be associated with cystitis

      1. Precoital or postcoital voiding patterns

      2. Daily beverage consumption

      3. Tampon use

      4. Douching

      5. Hot tub use

      6. Underwear type

      7. Body mass index

      8. Wiping patterns

   2. There are no data supporting that changing the above factors prevents recurrent cystitis.

2. Antibiotics

   1. Antibiotic choice is empiric, covering enteric organisms.

   2. First-line options include nitrofurantoin and trimethoprim-sulfamethoxazole (TMP-SMX).

   3. Other options include ciprofloxacin, levofloxacin, amoxicillin-clavulanate, and other beta-lactams.

   4. There is increasing resistance of E coli to TMP-SMX and fluoroquinolones. Once resistance in a treatment region exceeds 20% that antibiotic is no longer recommended.

      A urine culture is unnecessary in a patient with uncomplicated cystitis and no history of recurrent infections or recent treatment failure.

3. Treatment duration is based on whether the patient has uncomplicated or complicated cystitis.

   1. Uncomplicated cystitis is defined as cystitis in healthy women with no urinary tract abnormalities.

   2. Complicated cystitis is defined as cystitis occurring in:

      1. Pregnant women

      2. Men

      3. Patients with urinary tract abnormalities (such as obstruction, neurogenic bladder, kidney stones), or an indwelling Foley catheter

      4. Patients with immunosuppression or chronic kidney disease

   3. In uncomplicated cystitis, a shorter duration of antibiotics (1-5 days) is effective and recommended.

   4. In complicated cystitis, a longer duration of antibiotics (7-10 days) is recommended.

   5. In patients with complicated cystitis and previous or recurrent cystitis, it is helpful to review old cultures for previous resistance patterns when choosing empiric therapy.

4. Work-up for secondary causes

   1. Imaging (pre- and post-contrast CT) should be considered in women with multiple episodes of cystitis with the same pathogen.

   2. Patients with hematuria during cystitis should have repeat urinalysis after resolution to determine whether hematuria persists and further work-up is warranted.

   3. Men without a clear predisposition for cystitis (ie, Foley catheter, known BPH) should be considered for further urologic evaluation.

5. Recurrent cystitis

   1. If symptoms continue or return within 2 weeks after treatment for cystitis, relapse or antimicrobial resistance is likely. Antibiotics should be broadened and urine culture performed.

   2. If cystitis recurs beyond 1 month after successful treatment, then standard treatment may be used.

   3. Antimicrobial prophylaxis (continuous or postcoital) may reduce the risk of recurrence by 95% for women with 3 or more infections in 12 months.

The results of the urine dipstick fit with the diagnosis of uncomplicated cystitis. The patient has neither discharge to suggest vaginitis nor flank pain, fever, nausea, or vomiting to suggest pyelonephritis.

Alternative Diagnosis: Vaginitis

Textbook Presentation

Vaginitis typically presents with abnormal vaginal discharge, odor, irritation, itching, dysuria, or dyspareunia.

Disease Highlights

1. Common infectious causes of vaginitis are bacterial vaginosis, trichomoniasis, and candidiasis.

2. Bacterial vaginosis occurs when the normal flora of the vagina are replaced with anaerobic bacteria most commonly, Gardnerella vaginalis.

3. Trichomoniasis is an STI caused by the flagellated protozoan, Trichomonas vaginalis. It can also infect men, causing urethritis or silent infection.

4. Vulvovaginal candidiasis is caused by various Candida species. It often occurs when changes in the vaginal environment precipitate pathologic activity, such as, high estrogen states (menses, pregnancy), antibiotic use, immunosuppression, uncontrolled diabetes.

5. Atrophic vaginitis occurs because of estrogen deficiency (most often postmenopausal) when the vaginal mucosa thins and becomes dry. In addition to being symptomatic itself, it may increase the risk of recurrent cystitis and treatment may be helpful.

6. Cervical infections often present with vaginal discharge. Although the discharge originates from the cervical os, the presentations may be similar. These infections are discussed later in the chapter.

Evidence-Based Diagnosis

1. The primary diagnostic test for vaginitis is examination of the discharge. The test characteristics for many of the tests are discussed in Table 16-3.

   1. pH testing is done of discharge from the vaginal sidewall.

   2. Saline wet mount viewed at high and low power through a microscope looking for clue cells, candida, or trichomonads.

   3. The whiff test (performed by adding 10% potassium hydroxide (KOH) to the discharge and sniffing the sample for a fishy amine odor).

   4. A KOH wet mount should be performed to look for findings of candidiasis.

2. Bacterial vaginosis

   1. Presents with malodorous (typically fishy) white or gray discharge without pain or itching.

   2. Bacterial vaginosis is diagnosed by the Amsel criteria (see Table 16-3).

3. Trichomoniasis

   1. Presents with thin yellow or green frothy discharge, irritation, dysuria, and dyspareunia

   2. May be asymptomatic

   3. On physical exam punctate hemorrhages may be present on the cervix (strawberry cervix) or vaginal walls.

   4. Diagnosis usually made by seeing motile trichomonads on saline wet mount.

   5. Visualization of leukocytes being more prevalent than epithelial cells on wet mount also suggests trichomoniasis.

   6. The whiff test may also be positive with trichomoniasis.

4. Vulvovaginal candidiasis

   1. Presents with itching, irritation, dysuria, dyspareunia and thick white “curd-like” discharge without odor. Lack of itching argues against the disease.

   2. Women are effective at self-diagnosis. Clinicians whose patients report “I have another yeast infection” can usually rely that it is an accurate diagnosis.

   3. On exam, inflammation of the vulva and lack of odor increases the likelihood of candidiasis. A thick, curdy, white discharge argues for candidiasis while a watery discharge argues against it.

   4. The presence of budding yeast or branching mycelia on KOH preparation of discharge is highly suggestive.

5. Atrophic vaginitis

   1. Dryness is the most common symptom

   2. Other symptoms that may occur include pruritus, irritation, discharge, dysuria and dyspareunia.

   3. On exam, vaginal mucosa is thin and dry, and inflammation may be present.

   4. Diagnosis is based on presentation and exam and lack of findings suggestive of infection.

6. Inconclusive evaluation

   1. About 30% of women with vaginal complaints do not have a clear diagnosis after a complete evaluation.

   2. Options include

      1. Empiric treatment for the most likely cause

      2. Further testing with culture or rapid diagnostic tests

      3. Testing for cervical infection

      4. Observation

Treatment

1. Bacterial vaginosis in nonpregnant women is treated with oral metronidazole or intravaginal metronidazole or clindamycin.

2. The recommended treatment for trichomoniasis in nonpregnant women is tinidazole or metronidazole. Treatment of sexual partners is necessary and sexual intercourse should not be resumed until both partners are treated and symptoms resolve.

3. The recommended treatment for uncomplicated vulvovaginal candidiasis is a short course of topical over-the-counter antifungals or a single dose of oral fluconazole.

4. Complicated infection (immunosuppression, pregnancy, diabetes, severe infection, 4 or more annual episodes) should be treated with longer durations of topical or oral therapies.

5. Atrophic vaginitis is treated with intravaginal estrogen.

Alternative Diagnosis: Pyelonephritis

Textbook Presentation

Pyelonephritis typically presents with dysuria and flank or back pain, fever, chills, malaise, nausea and vomiting.

Disease Highlights

1. Pyelonephritis is an upper UTI affecting the parenchyma of the kidney.

2. Bacterial pathogens are the same as those for cystitis.

3. Uncomplicated pyelonephritis occurs in immunocompetent women with normal urinary tracts and without reduced kidney function.

4. Complicated pyelonephritis is present if the patient is male, pregnant, or immunosuppressed or has urinary obstruction, nephrolithiasis, foreign-body/catheters, or kidney dysfunction.

Evidence-Based Diagnosis

1. History often includes symptoms of cystitis with flank or back pain, fever, chills, malaise, and nausea or vomiting.

2. CVA tenderness on physical exam suggests pyelonephritis but is surprisingly nondiagnostic (LR+ 1.1-2.5 and LR- 0.78-0.96).

3. Urinalysis or urine dipstick testing also aids diagnosis with the same findings as cystitis.

4. Urine culture is indicated for all patients with suspected pyelonephritis. Urine culture is positive in 90% of patients with pyelonephritis.

5. Imaging (CT or ultrasound) is indicated if there is concern for concomitant nephrolithiasis or obstruction or if the diagnosis is uncertain.

Treatment

1. Many patients with pyelonephritis can be treated as outpatients.

2. Indications for admission include the following:

   1. Unstable vital signs

   2. Inability to tolerate oral medications

   3. Concern for nonadherence

   4. Pregnancy

   5. Immunocompromised state

   6. Concern for urinary tract obstruction or nephrolithiasis

3. Outpatient management

   1. The first-line empiric therapy is a fluoroquinolone (if local E coli resistance does not exceed 20%).

   2. A single IV dose of ceftriaxone or a long-acting aminoglycoside is recommended before outpatient therapy if fluoroquinolone resistance exceeds 10%.

   3. Treatment should be adjusted once antimicrobial susceptibility results are available.

   4. Duration of antibiotic therapy

      1. 7–10 days for uncomplicated pyelonephritis

      2. 14 days for complicated pyelonephritis

   5. Follow-up

      1. Patients should be seen in 24–72 hours to ensure clinical improvement.

      2. If fever persists beyond 48–72 hours of appropriate antibiotics or illness worsens, the patient should be admitted for IV antibiotics and further evaluation.

4. Inpatient management

   1. Patients who are admitted for treatment should be given IV antibiotics (a fluoroquinolone, ceftriaxone, or an aminoglycoside with or without ampicillin).

   2. Treatment duration should be for 14 days.

   3. If fever, pain, or vomiting has not improved in 48–72 hours of appropriate therapy, the following 2 options should be considered:

      1. Obtain imaging (CT scan or ultrasound) to evaluate for complications such as a perinephric abscess, kidney stone, or obstruction.

      2. Broaden antibiotic coverage to cover for resistant organisms if susceptibility data has not returned.

It is important to know local E coli resistance patterns when prescribing empiric antibiotics for cystitis because resistance to fluoroquinolones and TMP-SMX is not uncommon.

Mr. C is a man experiencing dysuria with radiation to the perineum and associated urinary hesitancy. His gender and the radiation of the pain are pivotal points in this history suggesting possible acute prostatitis. Acute prostatitis is a life-threatening cause of dysuria in a male and must be considered. Urosepsis is another must not miss diagnosis given the systemic symptoms and orthostasis. The absence of penile discharge is important in limiting the list of diagnoses. Other common but less dangerous alternatives include urethritis from an STI and complicated cystitis. Pyelonephritis should also be considered. Table 16-4 lists the differential diagnosis.

Leading Hypothesis: Acute Prostatitis

Textbook Presentation

Acute prostatitis typically presents with dysuria, low back pain, perineal pain or ejaculatory pain with fever, chills, and myalgias. Patients often have associated urinary symptoms including frequency, urgency, or obstruction.

Disease Highlights

1. Acute bacterial prostatitis is an infection of the prostate gland that occurs from an ascending urethral infection or through reflux of infected urine into the prostate through the ejaculatory or prostatic ducts.

2. Frequent pathogens include gram-negative coliform bacteria, Klebsiella, Proteus, enterococci, and Pseudomonas.

3. Sexually transmitted bacteria, such as Chlamydia, may also be the cause.

Evidence-Based Diagnosis

1. Although prostatitis may present with classic symptoms of low back pain, dysuria, and perineal pain, the disease may also present with nonspecific symptoms such as myalgias, malaise, or nausea and vomiting.

2. On physical exam, the prostate gland may be tender, warm, swollen, or firm.

3. Theoretically, infection may be induced or worsened by rigorous digital rectal exam so this is not recommended if acute bacterial prostatitis is suspected.

4. Prostate massage

   1. Traditionally, prostatic massage to examine prostatic secretions for white blood cells and bacteria has been advocated.

   2. This test has not been validated, and it is not recommended because it is difficult to perform, painful, and may worsen infection.

5. Urinalysis or urine dipstick

   1. May show signs consistent with cystitis (eg, leukocyte esterase, nitrites or white blood cells)

   2. May also be normal

6. Often the pathogen will be identified by urine culture; however, urine culture can be negative in acute prostatitis.

7. A urine sample should be sent for PCR testing for gonorrhea and chlamydia if a sexually transmitted pathogen is suspected.

8. Renal function should be assessed in patients who may have obstruction.

9. Diagnosis is made based on a combination of the history, physical exam, and urine studies. No single test is diagnostic for acute prostatitis.

Treatment

1. First-line antibiotics include a fluoroquinolone or TMP-SMX. If an STI is likely, treatment for Chlamydia should also be given.

2. While nitrofurantoin is used to treat cystitis, it is ineffective in prostatitis because it does not have good prostate penetration.

3. The duration of antibiotics is at least 3–4 weeks.

4. Supportive treatment for pain and stool softeners are also helpful.

5. Patients with severe infection or medically complex patients should be admitted for IV antibiotic therapy.

6. Patients who do not respond to treatment should be evaluated for a prostatic abscess. Although a prostatic abscess may be palpable on exam, it requires imaging by CT, MRI, or transrectal ultrasound to confirm diagnosis. Drainage or resection can be necessary.

7. Prostatitis will elevate prostate-specific antigen (PSA) levels.

The findings on urinalysis together with the tender prostate on physical exam support the presumed diagnosis of acute prostatitis as opposed to complicated cystitis or urethritis. Urosepsis is less likely given the reassuring vital signs and absence of systemic inflammatory response syndrome (SIRS) criteria (presence of 2 of the following: WBC > 12,000 K/mcL, WBC < 4000 K/mcL, fever > 38.0°C, hypothermia < 36.0°C, tachycardia > 90 bpm, or tachypnea > 20 breaths per minute). Diagnosis could be confirmed by culture of prostatic fluid but rigorous examination in the patient would be contraindicated because it could increase the severity of infection. Urine culture and GC PCR testing helps identify the bacterial pathogen.

Alternative Diagnosis: Urethritis from STIs (Cervicitis in Women)

Textbook Presentation

Urethritis in men typically presents with dysuria, urethral pruritus, and penile discharge. Patients may also have dyspareunia, abdominal pain, or testicular pain. Women with cervicitis typically have cervical discharge, dysuria, and dyspareunia. They may also have spontaneous or postcoital vaginal bleeding.

Disease Highlights

1. Urethritis and cervicitis are usually due to an STI.

2. The 2 main sexually transmitted pathogens causing cervicitis and urethritis are N gonorrhoeae and C trachomatis.

3. Other less common causes include Mycoplasma genitalium, Trichomonas, herpes simplex virus, and adenovirus. Herpes simplex virus may also cause cervicitis.

Evidence-Based Diagnosis

1. Urethritis can be diagnosed based on the following:

   1. Discharge on physical exam

   2. Microscopy of discharge showing > 5 WBCs per oil immersion field (sensitivity, 26%; specificity, 95%; LR+, 2.7)

   3. Positive leukocyte esterase on first-void urine

   4. Microscopy of first-void urine showing > 10 WBCs per high power field

   5. Gram stain of discharge or urine culture that identifies organisms

2. Cervicitis can be diagnosed based on mucopurulent endocervical discharge on pelvic exam. Sustained cervical bleeding caused by gentle passage of a swab in the cervical os may also be seen.

3. PCR

   1. To confirm the diagnosis of urethritis or cervicitis, an endocervical, vaginal, urine or urethral sample should be sent for PCR testing for gonorrhea and chlamydia.

   2. Urine PCR is the preferred test for males (sensitivity and specificity 90–100% and 97–100% respectively).

   3. Although urine testing may be equivalent, vaginal swabs are preferred for women (sensitivity and specificity of 96% and 99%, respectively).

Treatment

1. Patients should be treated empirically prior to confirmation of a pathogen.

2. The first-line treatment for chlamydia is a 1-time dose of 1 g of oral azithromycin or a 1-week course of 100 mg of doxycycline given twice daily.

3. Concurrent treatment for gonorrhea should be given if clinical suspicion or gonorrhea prevalence in the patient population is high.

4. The first-line treatment for gonorrhea is a 1-time injection of ceftriaxone 125 mg intramuscularly.

5. Given the high incidence of coinfection with chlamydia, patients treated for gonorrhea should always be treated for coexisting chlamydia infection unless testing for it is negative.

6. Patients should abstain from intercourse until 1 week after a single-dose treatment or until completion of a 1-week regimen (assuming symptoms have also resolved).

7. Partners

   1. Sexual partners of all patients infected with an STI should be evaluated and treated.

   2. If partners are unable to be seen at a health practice, the CDC recommends expedited partner treatment (the physician gives the patient a prescription for their partner). The laws regarding this practice vary by state.

8. Repeat testing to establish cure is not necessary unless symptoms persist or reinfection or nonadherence is suspected.

9. Due to the high risk of repeat infections, it is recommended all patients be re-tested 3–12 months after initial infection.

Alternative Diagnosis: Urosepsis

Textbook Presentation

Sepsis is covered extensively in Chapter 25, Hypotension. This section will focus on urosepsis specifically. Urosepsis typically presents with fever, chills, and lethargy or altered mental status. Symptoms of the underlying infection, such as dysuria or flank pain, are often present.

Disease Highlights

1. Sepsis is defined as a suspected or proven infection with the presence of the SIRS criteria.

2. Severe sepsis occurs when there is target organ dysfunction, such as hypotension, hypoxemia, oliguria, metabolic acidosis, thrombocytopenia, or obtundation.

3. Urosepsis occurs when the infectious source of sepsis is an infection of the urinary or male genital tract.

4. It is estimated one-quarter of sepsis cases are due to a urogenital infection.

Evidence-Based Diagnosis

Diagnosis is made based on SIRS criteria (see above) and the confirmation of a genitourinary infection.

Treatment

1. All patients with suspected urosepsis should be hospitalized. Admission to the ICU is often necessary.

2. Early empiric IV antibiotics and aggressive volume resuscitation with IV fluids should be initiated to prevent worsening sepsis.