The urethral smear as a tool in diagnosing adenovirus-induced urethritis

Introduction

Non-gonococcal urethritis (NGU) is defined as the finding of five or more polymorphonuclear cells per high power field (HPF) of a stained smear from the anterior urethra in the absence of gonorrhoea.

Adenovirus has been implicated as one of the aetiological agents for NGU, and clinical suspicion should be heightened in the additional presence of meatitis and conjunctivitis. Although several studies have looked at other indicators of adenovirus as the causal pathogen in NGU, there is little in the literature about supporting microscopy findings. ¹

Case report

A middle-aged, Caucasian heterosexual man presented to our clinic on his return from a two-month holiday in the Philippines. He had a four-day history of dysuria and a three-day history of sore, red watery eyes.

He admitted to insertive oral sex with a regular female partner in the Philippines two days prior to onset of symptoms. He had been prescribed 1.5 g azithromycin empirically four weeks previously in the Philippines, because of a yellow penile discharge which subsequently resolved and was considered unrelated to his current symptoms.

On examination, the patient had bilateral conjunctivitis with clear discharge; he denied visual disturbances (Figure 1). OPEN IN VIEWER

Genital inspection revealed a meatitis with serous urethral discharge. A urethral smear was taken using a metal spatula, and stained with methylene blue. Methylene blue is a rapid one-step procedure routinely used for staining urethral smears in Norway. One-step staining methods have been found to have comparable sensitivity and specificity to Gram stain in diagnosing gonococcal urethritis. ² Microscopy revealed an NGU with >30 leukocytes per HPF, which were almost exclusively mononuclear cells (Figures 2 and 3). OPEN IN VIEWER

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Figure 3.

Mononuclear cell urethritis.

As a result of these findings, viral swabs for HSV and adenovirus were taken from both eyes and the urethra together with a first void urine sample for Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium. HIV and syphilis serology was requested.

Although the patient’s symptoms and clinical findings were highly indicative of a viral aetiology, he was given empirical treatment with oral doxycycline 200 mg daily for seven days as a bacterial cause could not be excluded at this stage.

The patient was reviewed one week later. He had not experienced any improvement in symptoms by day 4 of doxycycline, and consequently self-discontinued the antibiotics. On day 5, his dysuria had disappeared. He had been examined by his primary care physician, and was prescribed chloramphenicol eye-drops.

On examination in clinic, he still had conjunctival injection, but reported that his eyes were less sore. A new urethral smear revealed complete resolution of the urethritis.

Microbiological results showed positive adenovirus (in-house PCR) type 8, from both eyes and urethra, Herpes simplex I & II (in-house PCR) was negative. First void urine was negative for C. trachomatis (Roche COBAS Taq Man CT test v2. 0), N. gonorrhoeae (Por A gene PCR) and M. genitalium (in-house PCR). HIV and syphilis serology was negative.

Discussion

Adenovirus described as an aetiological agent of NGU is often associated with oral sex and concomitant conjunctivitis. ³ O’Mahony ⁴ described a similar case report emphasising the importance of considering adenovirus as a causal agent when the constellation of dysuria, conjunctivitis, meatitis and NGU is observed.

This case report highlights the usefulness of microscopy in the diagnostic work-up of viral urethritis. There is remarkably little described in the published literature on the subject. However, Azariah and Reid allude ⁵ to the finding of mononuclear cell response on a urethral smear as a possible indication of viral aetiology in their article on adenovirus-induced urethritis.

The clinical findings of conjunctivitis, meatitis and serous penile discharge alone aroused the suspicion of a viral aetiology. With the additional finding of abundant monocytosis in the urethral smear, this strengthened the theory. A similar microscopic picture might be seen with HSV urethritis, but our patient had neither herpetic lesions nor inguinal lymphadenopathy to suggest this, ⁶ and PCR for HSV-1 and HSV-2 was negative.

Adenovirus type 8 is a known cause of seasonal keratoconjunctivitis. This man’s genital symptoms preceded his conjunctivitis, and it is not unreasonable to assume that he was initially infected genitally via oral sex, and thereafter self-inoculated his eyes.

Microscopy and interpretation of the urethral smear is one of the cornerstones of a venereologist’s practice. Although there is a clear division between gonococcal urethritis and NGU, other nuances in the urethral smear findings are less well described. The advent of modern day laboratory diagnostics has revolutionised venereology and decreased reliance on the urethral smear. However, a renaissance in appreciating the finer points of this diagnostic tool is not out of place.

When microscopy is used routinely in the assessment of patients with symptoms of urethritis, finding an obviously mononuclear cell urethritis can increase the suspicion of a viral aetiology. It also allows reassurance with regard to its self-limiting nature. Patients should be counselled accordingly in relation to infection control measures, especially in households with children.

Written consent for the publication of this case report and images has been obtained from the patient.