Urethritis is the most common genitourinary syndrome in sexually active men younger than 50 years old.1 The most frequent symptoms include mucoid, mucopurulent, or purulent urethral discharge (60% up to 90%), dysuria (50% up to 80%), increased urinary frequency (6%), or itching (5%); urethritis, however, can run asymptomatic.2

Cervicitis results from the inflammation of the cervix, and the most common symptoms are purulent or mucopurulent endocervical discharge visible in the endocervical canal or in an endocervical swab sample. Some women may report abnormal vaginal discharge, intermenstrual vaginal bleeding (e.g., postcoital), suprapubic abdominal pain, or dyspareunia; although it is often asymptomatic.3

Sexually transmitted infections (STIs) affecting the anus, rectum, colon, and small intestine consist of acute or subacute inflammatory processes caused by microorganisms that can be transmitted through various sexual practices such as receptive anal sex, use of contaminated sex toys, fisting, or oro-anal sex. The incidence of these infections is increasing, with most being diagnosed in men who have sex with men (MSM), with a higher prevalence in people living with HIV (PLHIV).4–6

In proctitis, there is inflammation of the rectum, often accompanied by rectal tenesmus, anorectal or suprapubic pain, mucous or purulent anal discharge, rectal bleeding, a sensation of incomplete evacuation, or constipation. Proctitis can also be associated with fever and/or general malaise, ulcers or vesicles, edema, and erythema of the rectal mucosa; a high percentage of proctitis cases, though, are asymptomatic.

In proctocolitis, the inflammation extends beyond the rectum, and in enteritis, it affects the colon and/or small intestine. Proctocolitis can present with proctitis symptoms, colicky abdominal pain (especially in the hypogastric area), diarrhea (often with blood), and general symptoms (fever, chills, myalgias, vomiting). A person with enteritis may experience nausea and vomiting, diarrhea, colicky abdominal pain, abdominal distension, or fever, but without proctitis or proctocolitis symptoms.5

Urethritis can have multifactorial causes (Table 1),7–12 but in most cases, it is sexually acquired. When sexually acquired, urethritis is described as gonococcal urethritis (GU) if Neisseria gonorrhoeae (NG) is detected, or as non-gonococcal urethritis (NGU) if it is not. Its etiology varies according to the local prevalence of infectious agents. NG can account for 10% up to 20% of urethritis cases, Chlamydia trachomatis (CT) for 15% up to 40% of NGU cases, and Mycoplasma genitalium (MG) for 15% up to 25% of NGU cases.13

Ureaplasma urealyticum is inconsistently associated with NGU and is probably not a cause unless present with a high bacterial load. In Western Europe, Trichomonas vaginalis (TV) as a cause of male urethritis is uncommon. Adenoviruses may account for 2% up to 4%, and herpes simplex virus (HSV) is an uncommon cause of NGU, although they can cause urethritis in the absence of typical genital ulcers. Neisseria meningitidis, Haemophilus spp., Candida spp., and others have been reported in a small proportion of NGU cases.

Of note that polymicrobial infections can be identified in up to 20% of men, and in 20% up to 30% of urethritis cases, no known pathogens are detected.13

CT or NG is the most common etiology of cervicitis,13 although TV, MG, and HSV—mainly HSV-2, although HSV-1 is increasingly common—have also been reported.14–17 However, in many cases of cervicitis, no microorganism is isolated, especially among women with relatively low risk of contracting STIs (e.g., women older than 30 years). Limited data suggest that bacterial vaginosis and frequent douching may cause cervicitis.18 Available data do not suggest that there is an association between group B streptococcal colonization and cervicitis, nor is there specific evidence of a role for Ureaplasma parvum or Ureaplasma urealyticum in cervicitis.19

Although proctitis can be multifactorial, in most cases, it is sexually acquired.13 The main etiological agents of sexually transmitted proctitis are NG and CT. Rectal infection with MG alone is rarer and causes fewer symptoms than NG or CT.20,21 In 30% up to 40% of cases, no microorganism is identified, and in 10% of cases, more than 1 microorganism is involved.22

In the differential diagnosis of proctitis, non-infectious causes should be considered, such as medical radiation, inflammatory bowel disease, drug-related adverse effects or associated with topical products. Some traumas may occur in a sexual context (e.g., fisting practices, enemas, sex toys, drug insertion) and/or among chemsex users (substances like methamphetamines, mephedrone, or gamma-hydroxybutyrate-gamma-butyrolactone).23,24 Conversely, proctocolitis and enteritis are not always sexually acquired. The main etiology of these sexually acquired entities is shown in Table 2.

To identify the cause, it is necessary to conduct a clinical history, a physical examination, and a few additional tests.

Additional testsIn patients with symptoms of urethritis

For symptomatic patients and those with visible discharge, experts recommend confirming urethritis in the clinic as a guide for immediate treatment, without waiting for the lab test results (Fig. 1) (level of evidence 2a, grade of recommendation C). Urethritis is confirmed if a urethral sample—stained with methylene blue or Gram stain—contains, at least, 5 polymorphonuclear leukocytes per high-power field.2,13 However, this study is often unavailable in most centers, is not recommended to rule out asymptomatic urethritis—contact tracing or screening—may cause inter/intra-observer differences, and its sensitivity depends on how the sample is obtained.

Figure 1.

Algorithm on the management of suspected urethritis cases due to STIs. CT: Chlamydia trachomatis; MG: Mycoplasma genitalium; NAAT: nucleic acid amplification test; NG: Neisseria gonorrhoeae.

(0.39MB).

What tests should we perform?

• 1.

  Nucleic acid amplification test (NAAT) to detect NG and CT in the first void urine or urethral sample (level of evidence 1b, grade of recommendation A).29 Both samples have the same sensitivity if taken correctly. It is also strongly recommended to test for MG, preferably with macrolide resistance detection.

  • •

    The first void urine should not contain more than 10mL, as a larger volume will reduce sensitivity, and the post-urination interval should extend for, at least, 2hours.

  • •

    If a urethral sample is taken instead2: retract the foreskin, clean the meatus with saline, and gently insert the swab into the urethra to collect the sample. If urethral discharge is present, it can be collected without inserting the swab into the meatus (level of evidence 4, grade of recommendation C).

• 2.

  Another urethral or discharge sample for bacterial culture to perform an antibiogram if necessary. This sample can be self-collected by the patient (level of evidence 4, grade of recommendation C).30

• 3.

  Additionally, NAAT is recommended to detect NG and CT at any potentially exposed site depending on sexual activity (rectal and/or pharyngeal swabs). With appropriate instructions, self-collection of rectal and/or pharyngeal swabs by the patient for NG and CT detection has proven to be a valid and acceptable option (level of evidence 2a, grade of recommendation B).31,32

What tests should we avoid?

Routine testing or treatment of asymptomatic or symptomatic men for M. hominis, U. urealyticum, and U. parvum is ill-advised.2 Asymptomatic colonization by these bacteria is common, and most individuals do not develop disease. Although U. urealyticum has been associated with urethritis in men, most infected/colonized men do not develop disease. Therefore, other causes (NG, CT, MG, and TV in men who have sex with women) should be excluded before testing for U. urealyticum in symptomatic men. Lastly, it is advised to treat only men with a high bacterial load (> 1000 copies/mL of U. urealyticum in first void urine).2

In patients with symptoms of cervicitis

What tests should we perform?

Since cervicitis can be a sign of upper genital tract infection (e.g., endometritis), women should be evaluated for signs of pelvic inflammatory disease and tested for CT and NG using NAAT on vaginal, cervical, or urine samples13 (level of evidence 2a, grade of recommendation B). Vaginal sampling can be performed by the physician or through self-collection. Women with cervicitis should also be evaluated for bacterial vaginosis and trichomoniasis. Since the sensitivity of microscopy for detecting T. vaginalis is relatively low (approximately 50%), symptomatic women with cervicitis and negative microscopy for trichomonas should undergo further testing (mainly NAAT). Testing for MG using NAAT should also be considered. Although HSV infection has been associated with cervicitis, testing should only be performed if the patient presents with symptoms compatible with genital herpes.

Additionally, it is important for patients to undergo testing for CT and NG at any potentially exposed site based on the type of sexual activity (rectal and/or pharyngeal swabs) (level of evidence 2b, grade of recommendation B).

What tests should we avoid?

Testing for U. parvum, U. urealyticum, Mycoplasma hominis, or genital culture for group B streptococcus is ill-advised.

In patients with symptoms of proctitis

Samples should be collected to confirm the suspected microbiological diagnosis (by inserting a swab through the anal canal or visualizing through anoscopy/proctoscopy) (Fig. 2):

• 1.

  Gram stain of rectal secretions (if available).

• 2.

  Culture of rectal secretions to perform an antibiogram if necessary (level of evidence 3a, grade of recommendation C).33,34

• 3.

  NAAT of rectal secretions to detect NG and CT (serovars D-K and L1-L3) (level of evidence 2a, grade of recommendation B).35 Althought this is the test of choice, the study can be expanded to other pathogens such as T. pallidum (TP),36 HSV,37 and/or Mpox, in the presence of clinical suspicion. Any positive rectal NAAT for CT should be typed to rule out lymphogranuloma venereum (LGV) (level of evidence 2a, grade of recommendation B).38 Initially, specific NAAT for MG is not recommended, but if positive and available, a macrolide resistance test is suggested (level of evidence 3b, grade of recommendation C).39

• 4.

  In the presence of ulcerated lesions in the rectum or perianal area, an exudate sample can be taken for dark-field microscopy and TP and/or HSV detection by NAAT.

• 5.

  In cases of suspected cytomegalovirus (CMV) infection, useful tests include CMV IgM/IgG serology, NAAT, and immunohistochemistry of biopsies.40

Figure 2.

Algorithm on the management of suspected proctitis cases due to STIs. CT: Chlamydia trachomatis; LGV: Lymphogranuloma venereum; NAAT: nucleic acid amplification test; NG: Neisseria gonorrhoeae; TP: Treponema pallidum; HSV: herpes simplex virus.

(0.55MB).

Self-collection of a rectal swab for dual NAAT for CT and NG in high-risk asymptomatic patients (e.g., those taking pre-exposure prophylaxis [PEP], people living with HIV [PLWH] with multiple partners, MSM engaging in unprotected receptive anal sex in the last 6 months) is a valid option (level of evidence 2a, grade of recommendation B).41

In patients with symptoms of proctocolitis or enteritis

In patients with symptoms of proctocolitis or enteritis, especially if they present with a > 7-day history of diarrhea and fever, it is recommended to assess stool culture, NAAT for bacteria and parasites in stool, rectosigmoidoscopy or upper and lower GI endoscopy, among other additional tests depending on clinical presentation and availability.

CT-LGV proctitis can clinically and even histopathologically mimic other proctocolitis syndromes; therefore, it should be considered in MSM with suspected chronic inflammatory bowel disease (level of evidence 4, grade of recommendation C).42

Empirical treatment for cervicitis should include antibiotics that cover CT:

• •

  Doxycycline 100mg orally, twice a day for 7 days (level of evidence 1b, grade of recommendation A).

Treatment to cover NG should be added in women at higher risk (e.g., age < 25 years, new sexual partner, a sexual partner with concurrent partners, having an STI or risk of gonorrhea, or living in a community with high gonorrhea prevalence).13 Trichomoniasis and bacterial vaginosis (BV) should only be treated if detected.

For women at low risk of STIs, treatment may be postponed until diagnostic test results are available.

In cases of suspected acute proctitis with clinical symptoms, empirical treatment should begin without having to wait for the test results (level of evidence 2a, grade of recommendation B).34

• •

  Ceftriaxone 500mg or 1g IM/single dose + doxycycline 100mg orally, twice a day for 7 days (extended to 21 days in the case of LGV) (level of evidence 3a, grade of recommendation B).34,37

• •

  In cases of painful ulcerative proctitis suggestive of herpes simplex, especially in MSM and PLWH, add treatment for herpes simplex (level of evidence 4, grade of recommendation C).

Initially, supportive measures and rehydration are necessary, and empirical antibiotic treatment is generally not required (level of evidence 1b, grade of recommendation B).47 Empirical treatment may be considered based on local epidemiology if associated with severe symptoms, sepsis, or need for hospitalization (due to severe dehydration, intractable vomiting, severe diarrhea, acute renal failure, or comorbidities).

All patients diagnosed with gonorrhea should be recommended to return for TOC, especially in the presence of:

• 1.

  Persistent symptoms or signs

• 2.

  Pharyngeal infection

• 3.

  Treated with any regimen other than first-line therapy, or

• 4.

  The infection was acquired in the Asia-Pacific region

If symptoms persist, a culture should be performed 3 to 7 days after treatment. For all other cases, a sample for NAAT should be taken 2 weeks after treatment. If NAAT tests positive, an effort should be made for culture confirmation before retreatment. All positive cultures from TOC should undergo antimicrobial susceptibility testing.

M. genitalium32,52: TOC should be considered for all patients due to the high prevalence of resistance, especially in the presence of:

• 1.

  Persistent urethritis, or

• 2.

  Cervicitis, or

• 3.

  PID, or

• 4.

  A regimen including azithromycin was used without a macrolide resistance test

TOC samples should be collected 4-5 weeks (and not earlier than 3 weeks to avoid false negatives) after the start of treatment to ensure microbiological cure and help identify emerging resistance.

C. trachomatis53–55: Routine TOC is not recommended in patients treated with the recommended first-line regimens but should be performed in the presence of:

• 1.

  Pregnancy

• 2.

  Complicated infections

• 3.

  Persistent symptoms

• 4.

  Second or third-line regimens were used

• 5.

  Treatment noncompliance, or

• 6.

  Detection of rectal CT but no LGV test has been conducted

TOC should be postponed for, at least, 3 weeks after therapy ends because NAAT can detect residual non-viable chlamydia DNA for 3 to 5 weeks after treatment.

T. vaginalis and bacterial vaginosis56: TOC is only recommended in women with persistent symptoms or during pregnancy, 4 to 5 weeks after treatment.

This article used the levels of evidence from the Oxford Centre for Evidence-Based Medicine (CEBM).72–74Annex 4d of the supplementary data explains how these levels of evidence are classified.