Approach to the Male Patient with Urethritis

John D. Goodson

A penile discharge or urethral discomfort may be the presenting manifestation of a sexually transmitted disease (STD) and, as such, requires prompt attention. Nongonococcal urethritis (NGU), most often the result of chlamydial infection, has surpassed gonorrhea as the principal cause of urethral symptoms in men and has reached epidemic proportions in sexually active adolescents and college-age persons. It can occur as an isolated infection or in conjunction with gonorrhea or other STDs.

Because NGU is the most common STD among heterosexuals in the United States and is a potential source of female infertility and infant morbidity, prompt and focused efforts by the primary physician concerning diagnosis, treatment, and prevention have important benefits for both patients and public health. This chapter focuses on urethritis in men; urethritis in women is covered separately elsewhere (see Chapters 117, 125, and 133).

PATHOPHYSIOLOGY, CLINICAL PRESENTATION, AND COURSE (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12)

Most penile discharges are a consequence of urethral infection or inflammation. In older men, a discharge may result from an inflamed prostate gland or, in rare instances, a tumor. Numerous bacterial and nonbacterial organisms can invade its mucosal lining. Organisms causing NGU are characterized by their low levels of tissue invasiveness.

Clinical presentations of urethritis range from prominent mucopurulent or purulent penile discharge with dysuria to watery discharge with little or no other symptoms; many patients are entirely asymptomatic. The hallmark of urethritis on microscopic Gram stain examination of the discharge is five or more WBC per high-power (oil immersion) field. Characteristic findings on a firstvoid urine sample include a positive leukocyte esterase test and, on microscopic examination, 10 or more WBC per high-power field.

Most etiologies are infectious, ranging from gonococcal disease to infections with Chlamydia, Ureaplasma, Mycoplasma, or Trichomonas species; autoimmune mechanisms are purported in some instances. Causes are usually categorized as gonococcal and nongonococcal.

Gonococcal Urethritis

The typical presentation of symptomatic gonococcal disease is a 2- to 4-day history of significant dysuria and a thick and purulent penile discharge. The gram stain reveals polymorphonuclear leukocytes and Gram-negative intracellular diplococci. Systemic gonococcemia develops in approximately 3% of patients, manifested by rash, fever, and polyarthritis (see Chapter 137). Mixed infections, involving both gonococci and chlamydiae, occur in up to 20% of patients presenting with gonococcal urethritis. Such patients complain of persistence of symptoms after being effectively treated only for gonorrhea.

Gonococcal urethritis (GU) responds well to proper antibiotic therapy, with resolution of symptoms and no sequelae. In men, even untreated disease may resolve spontaneously within few weeks. An asymptomatic carrier state may ensue, or a chronic low-grade discharge may remain. Stricture is a possible consequence of untreated disease.

Nongonococcal Urethritis

NGU tends to be an indolent illness of longer duration (e.g., 3 to 4 weeks). Dysuria, if present, is not as severe, and the discharge is less purulent, mucoid, sometimes scanty, or even absent. Most men with NGU due to chlamydial infection are asymptomatic. The urethral gram stain shows neutrophils (by definition more than five cells per high-power field) and, at most, a few mixed extracellular pleomorphic organisms, features that help to distinguish NGU from gonococcal infection. Only 20% of ambiguous Gram stains (rare extracellular Gram-negative diplococci) are shown by subsequent culture to represent gonococcal infection. Infectious etiologies predominate, most notably Chlamydia trachomatis, but also Ureaplasma urealyticum, Mycoplasma genitalium, and Trichomonas vaginalis. Of the noninfectious causes, Reiter syndrome (reactive arthritis) stands out.

Chlamydia trachomatis

Chlamydia trachomatis infections of the urogenital tract have reached epidemic proportions, with 20% to 50% penetration of some populations. It accounts for upward of 40% of cases of NGU. Prevalence is greatest among sexually active adolescents and young adults, especially those younger than 25 years of age. Rates in nonwhite populations are nearly double. Among heterosexual men with NGU, the organism is recovered from the urethra in 35% to 60%; recovery rates are even higher in male partners of women with chlamydial infection. In heterosexual men, urethritis with penile discharge, dysuria, or both is the most common symptomatic clinical presentation, but 25% to 50% may manifest neither symptoms nor leukocytes on urethral swab. Chlamydial infection is increasingly prevalent in men who have sex with men (see Chapters 13 and 141).

In untreated cases, symptoms may wax and wane during several weeks; spontaneous resolutions do occur. Complications are rare, but ascending infection can lead to prostatitis and epididymitis in untreated or poorly treated cases. Fortunately, the epididymitis is not believed to result in serious long-term consequences, but about half of the cases of epididymitis in the United States are believed to be chlamydia related.

Female counterparts of chlamydial NGU have been identified, including mucopurulent cervicitis and urethritis (see Chapters 117, 125, and 133). The prevalence of chlamydial infection among female partners of men with chlamydial NGU is very high (almost 70%; see Chapter 125).

Other Organisms

In most cases of NGU that do not test positive for chlamydial infection, no organism is readily identified. However, evidence derived from research-based nucleic acid amplification techniques (NAATs) testing suggests etiologic roles for sexually transmitted NGU for M. genitalium, T. vaginalis, herpes simplex virus (HSV types 1 and 2), and adenoviruses. Enteric bacteria have been identified as an uncommon cause of NGU and might be associated with insertive anal intercourse. U. urealyticum has also been implicated, but evidence is inconsistent, and some view it as a nonpathogenic commensal.

Mycoplasma genitalium invades epithelial cells and has emerged as a common cause of NGU, especially in men who have sex with men, accounting for 15% to 25% of NGU cases
in the United States. The urethritis is indistinguishable clinically from NGU of other causes.

Trichomonas vaginalis infection is a common cause of vaginitis in women and also an important source of urethritis in men. A 22% urethral prevalence was found among male partners of women with known trichomonal infection and a 6% prevalence among heterosexuals attending a clinic for STDs. About 50% of patients are symptomatic and have a discharge on examination. Others have symptoms but no visible discharge. The odds ratio for trichomonal infection in patients with nongonococcal, nonchlamydial urethritis has been found to be 3.8. The condition should be suspected in patients with symptoms but little or no discharge on physical examination.

HSV infection resulting in NGU often presents with characteristic vesicular genital skin lesions, inflammation of the urethral meatus, and severe dysuria, but reports of more indolent disease in persons with no lesions have come from STD clinics where there is a high prevalence of HSV infection.

Reactive Arthritis (Reiter Syndrome)

The finding of genetic overlap between the histocompatibility antigen HLA-B27 (found in up to 96% of patients vs. 10% of controls) and certain Klebsiella and C. trachomatis antigens suggests that infection with such organisms in susceptible persons may play a role in the pathogenesis of this form of reactive arthritis. It usually presents as urethritis in conjunction with a host of other mucocutaneous and musculoskeletal symptoms. Various combinations of conjunctivitis, iritis, fever, acute asymmetric polyarthritis, nonarticular bony pain (e.g., of the heel), circinate balanitis, keratoderma blennorrhagicum, and mucosal ulcerations may be present at any one time (see Chapter 146). The most characteristic presentation is onset of mild dysuria and a mucopurulent urethral discharge about 2 to 4 weeks after a diarrheal illness or sexual contact. Many patients present first with the urethritis, although involvement of other organ systems is frequently present in subclinical form or develops within a few weeks. Most patients with this form of reactive arthritis experience a self-limited illness of 6 to 12 months’ duration, although a minority progress to chronic or recurrent symptoms in conjunction with bouts of arthritis.

Prostatitis

In sexually active men, penile discharge and symptoms suggestive of urethritis may also be a manifestation of chronic prostatitis complicating untreated sexually transmitted urethritis. Minor penile discharge may be noted, exacerbated by prostatic massage; in addition, symptoms of urinary outflow obstruction, perineal discomfort, and ejaculatory complaints may dominate the clinical picture (see Chapter 139). In older men, prostatic hyperplasia predisposes to obstruction and infection (see Chapter 138).

Persistence or recurrence of symptomatic urethritis after appropriate antibiotic treatment of NGU has been linked to antibiotic-resistant strains of responsible organisms; however, most recurrent NGU represents poor compliance or reinfection by an untreated sexual partner rather than antibiotic resistance.

DIFFERENTIAL DIAGNOSIS (3,6, 7 and 8)

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