Infectious proctitis: what every gastroenterologist needs to know

Laboratory studies

An anal swab for N. gonorrhoeae, C. trachomatis and HSV should be performed (Fig. 1A). Exclusion of other potential STIs, namely HIV, hepatitis B and C, as well as blood serology for syphilis must also be performed.

Figure 1 Anal swab for Neisseria gonorrhoeae, Chlamydia trachomatis and Herpes simplex virus (A), Dacron swab and a methanol-based fixative container (B) and disposable anoscope system with obturator (C)

Anal Pap test

The anal Pap test technique consists of blind insertion of a Dacron swab (Fig. 1B) into the anal canal (2-4 cm) and vigorous rotation through 360°. The sample is fixed in a specific container with methanol-based fixative (Fig. 1B), and is interpreted using the Bethesda System terminology (atypical squamous cells of undetermined significance, low- and high-grade squamous intraepithelial lesion).

Anoscopy

The proctological examination must include anoscopy (without bowel preparation) with recourse to an anoscope and a light source (Fig. 1C). After digital rectal examination with the aid of a lubricant, anoscopic examination should be performed to identify lesions, such as internal hemorrhoids, fissures, warts, abscesses or tumors, that are included in the differential diagnosis of IP.

Imaging studies

IP sigmoidoscopy may reveal an inflamed rectal mucosa with erythema, erosions, ulcers or vesicles (Fig. 2). Most endoscopic findings are non-specific and rectal biopsies should be performed mainly if a C. trachomatis test is positive, to rule out LGV using a PCR test. If there is suspicion of IBD, colonoscopy should be performed. Radiologic imaging is usually not necessary for the evaluation of anorectal symptoms, except if perianal abscess or anal cancer are suspected.

Figure 2 Endoscopic findings of the rectum of a patient with IP positive for 3 different agents: Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum. Hyperemic nodularities with “pseudotumoral” aspect were observed in the distal rectum

Empiric therapy

In acute proctitis with mild symptoms, empirical treatment should be avoided, considering antibiotic resistance. However, therapy can be initiated in patients with a severe clinical presentation pending results of microbiological investigation, especially if anorectal exudate is detected on examination, or polymorphonuclear leukocytes detected on a gram-stained smear of anorectal exudate or secretions. Empiric therapy should only be considered after a proctological examination and after exclusion of other diagnoses with similar symptoms, such as anal cancer.

European guidelines suggest single-dose administration of ceftriaxone 500 mg (or 1 g if weight ≥150 kg) plus doxycycline 100 mg b.i.d. for 7 days [9]. Alternatives to ceftriaxone include cefoxitin (2 g i.m. plus probenecid 1 g orally) and cefotaxime (500 mg i.m.). An extended course of doxycycline to 21 days is recommended if clinical suspicion of LGV is strong (Fig. 3). Empirical treatment of genital herpes should also be considered in cases of painful ulcers and among patients with HIV [4,7].

Figure 3 Flowchart for the management of acute infectious proctitis

¹Havrix® or Vaqta®: 2-dose series at 0 and 6-12 months

²Gardasil9® or Cervarix®: 2-dose vaccine schedule at 0 and 6-12 months for persons who initiate vaccination before their 15^th birthday. 3-dose vaccine schedule at 0, 1-2, and 6 months for immunocompromised persons

³If RPR is positive: penicillin G benzathine 2.4 million

⁴If not done within past 12 months

⁵For persons weighing ≥150 kg, 1 g of Ceftriaxone should be administered.

⁶If LGV genovar positive: Doxycycline 100 mg, bid for 3 weeks

⁷Especially in cases with severe pain and among people living with HIV

(a) Workowski K, et al, 2021, [4] (STIs treatment guidelines, CDC)

(b) de Vries HJC, et al, 2021, [7] (European guideline on the management of proctitis, proctocolitis and enteritis caused by sexually transmissible pathogens)

NG, Neisseria gonorrhoeae; LGV, lymphogranuloma venereum; HAV, hepatitis A virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HSV, Herpes simplex virus; RPR, rapid plasma regain

Specific therapy

To avoid antibiotic resistance, patients with mild symptoms could wait for microbiology results (anal swabs and rectal biopsies). After identifying the etiologic pathogen, a specific therapy should be initiated. In fact, this is a critically important component of therapy, because it prevents the emergence of antimicrobial resistance in the community and can reduce cost and toxicity of therapy.

However, if the microbiology results fail to detect a specific pathogen, empiric therapy could be initiated if the clinical suspicion for an infectious cause (based on history and physical examination) is high. In this scenario, an alternative etiology should also be considered, such as non-infectious processes (IBD, traumatic or radiation proctitis), or an infectious disease caused by non-sexually transmitted pathogens.

N. gonorrhoeae

Gonococcal infection is the second most common STI in the United States, with more than 1.5 million cases diagnosed each year [4]. The incidence of N. gonorrhoeae infection has been decreasing in the last decades of the 20^th century [8]. Nevertheless, the rate of this infection has been increasing in the last 2 decades [8,10].

N. gonorrhoeae is a gram-negative diplococcus capable of producing symptomatic infection at several anatomic locations, including the urethra (particularly in men), cervix (women), oropharynx, and rectum. Rectal infection occurs predominantly by receptive anal intercourse, being more common in women and MSM [4,11]. Women with gonococcal cervicitis often present with concomitant rectal infection, believed to be the result of contiguous spread [8,12].

N. gonorrhoeae is considered the most common cause of sexually transmitted proctitis, accounting for 30% of all patients presenting with clinical evidence of IP [5]. Anorectal involvement is frequently associated with concomitant infection at other locations (e.g., cervix and urethra). Indeed, only 4% of women with gonococcal infection will have exclusive anorectal involvement, whereas 40-50% of MSM with gonorrhea will have isolated rectal infection [8].

Asymptomatic gonococcal infection is common, particularly in women [13]. In fact, at least half of men and 95% of women with rectal infection by N. gonorrhoeae are asymptomatic [8]. Symptoms of rectal infection are non-specific and most frequently include mucopurulent or bloody discharge associated with anorectal symptoms such as tenesmus, anorectal pain or constipation [7,8,13].

Anoscopic and endoscopic findings include the presence of mucopurulent discharge over the rectal mucosa, most frequently extending no further than 10 cm from the anal verge. Mucosal lesions include loss of normal vascular pattern, mucosal edema, erythema and friability (Fig. 4). Ulceration is less common than other etiologies, namely rectal infection by C. trachomatis serovars associated with LGV and T. pallidum.

Figure 4 Endoscopic findings of Neisseria gonorrhoeae positive infectious proctitis with several superficial hyperemic ulcers (A, B)

Patients with suspected rectal gonococcal infection should undergo microbiological testing [4]. Gram stains, culture, and nucleic acid amplification tests (NAATs) can be used to diagnose infection by N. gonorrhoeae. The identification of intracellular gram-negative diplococci within polymorphonuclear leukocytes is highly sensitive and specific for the diagnosis of gonococcal infection in symptomatic patients. Nevertheless, gram stains should not be used to rule out gonococcal infection in asymptomatic patients, given their low sensitivity in this subset of patients [4]. The introduction of NAATs has simplified the diagnostic approach to these patients. The sensitivity of these tests has been shown to be superior to that of N. gonorrhoeae culture and they should be performed to confirm positive gram stains [4,8].

Over the last decades, significant concerns about an increasing prevalence of antibiotic-resistant N. gonorrhoeae have been raised in the medical literature [9,14]. Cultures should be obtained in cases of suspected or confirmed treatment failure [8].

Antibiotic treatment should be started upon diagnosis (Table 1). Ceftriaxone (a single intramuscular dose) is the standard of care for treatment of gonorrhea. Although the 2020 gonorrhea guideline recommends azithromycin 2 g combined with ceftriaxone, this is no longer recommended [15]. However, in IP, when N. gonorrhoeae is suspected, instead of azithromycin, doxycycline could be added, as it is superior against (suspected) C. trachomatis infections, and to avoid azithromycin resistance in undiagnosed coinfection with Mycoplasma genitalium (M. genitalium).

To promote treatment adherence and reduce transmission, empirical treatment covering N. gonorrhoeae and C. trachomatis should be offered, as previously described [4]. A test of cure is generally unnecessary in uncomplicated disease, except if poor treatment adherence or persisting infection is suspected [9]. Nevertheless, precise information should be given to the patient and a close follow up should be maintained.

C. trachomatis

Infection by C. trachomatis represents the most diagnosed STI worldwide, with over 100 million people infected each year [16]. The incidence of C. trachomatis infection has been rising over the last decades [10]. Anorectal infection is more common in young women and MSM [4]. Rectal infection occurs as a consequence of receptive anal intercourse, and symptoms occur after an incubation period of 7-10 days [11]. Like other STIs, women with chlamydial urethritis or cervicitis may present with simultaneous rectal infection due to direct spreading [12]. Rectal chlamydia infection has been shown to account for approximately 20% of all IP cases, frequently in association with other agents [5].

C. trachomatis is an intracellular bacterium presenting 15 different serovars. Serovars A-K are responsible for non-LGV infections, whereas L1-L3 serovars are responsible for LGV. This subtype of C. trachomatis infection is particularly prevalent in HIV-positive LGV patients and is often associated with other concomitant STIs [17,18].

Non-LGV serovars produce inflammation restricted to the epithelium and are often asymptomatic. Nevertheless, symptomatic patients may complain of anal pain, mucopurulent or bloody discharge and tenesmus [8,11].

LGV is an invasive and systemic infection, generating systemic symptoms more frequently compared to infection by non-LGV serovars. The clinical presentation of LGV is often divided into 3 stages. The first stage is characterized by the presence of anal and/or genital ulcers or papules at the site of inoculation. The appearance of the characteristic painful inguinal or femoral lymphadenopathy (buboes) is typical of the second stage of infection [11]. At this stage, anorectal ulcers may also appear. Symptoms at this stage may include mucopurulent or bloody discharge, anal pain, malaise, myalgia, and fever [8,11]. When untreated, the final stage may include the development of rectal abscesses, granulomas, fistulae, and strictures.

The proctoscopic and endoscopic appearance of rectal mucosa infected by non-LGV C. trachomatis is non-specific, including erythema and friability. In addition to these findings, infection by LGV specimens may lead to the presence of ulceration, granulomas and abscesses [8] (Fig. 5). Longstanding LGV, leading to granulomas, fistulae and structuring, can generate an endoscopic, radiologic, and even histological appearances resembling Crohn’s disease [6].

Figure 5 Endoscopic findings of Chlamydia trachomatis (C. trachomatis)-positive infectious proctitis. (A) An ulcer with well-defined borders present in proctosigmoidoscopy of non-Lymphogranuloma venereum (LGV) C. trachomatis infectious proctitis (IP). (B) Multiple hyperemic ulcers (some of them with deep ulcers) in the rectal mucosa of a patient diagnosed with LGV C. trachomatis-positive IP

Upon clinical suspicion, microbiologic testing should be performed to achieve a definite diagnosis. NAATs are the most sensitive tests for the diagnosis of C. trachomatis infection. Rectal specimens can be obtained by clinician-collected swabs or rectal tissue sampling [4]. NAATs are particularly important, as they enable the genotyping of C. trachomatis, thus allowing the identification of LGV serotypes [7]. The current guidelines from the Centers for Disease Control and Prevention (CDC) recommend annual screening for women under 25 and men who engage in receptive anorectal sexual activity [4].

Treatment should be provided for all patients with proven C. trachomatis infection. Oral doxycycline 100 mg b.i.d. for 7 days is the first-line treatment directed toward non-LGV C. trachomatis [4,16]. This therapeutic course should be extended to 21 days if an LGV serovar is diagnosed.

A test of cure is generally unnecessary, except in the case of complicated disease, pregnancy, suspected poor treatment compliance or need of treatment with second-line therapies. Nonetheless, information regarding the disease course, as well as partner notification and treatment should be given to the patient.

HSV

HSV infection manifests near the mucocutaneous junctions; therefore, proctitis due to HSV results in extension of the disease from the perianal region to the anal canal and rectum. Anorectal HSV infection is more common in an immunosuppressed population that practices receptive anal intercourse.

Both serotypes (HSV-1 and HSV-2) can be found in the anogenital area [8]. Although most cases of recurrent genital herpes are caused by HSV-2, an increased proportion of HSV-1 anogenital herpetic infections has been observed, especially in young women and MSM [4].

Symptoms described in HSV proctitis are anorectal pain, tenesmus, exudate, rectal bleeding, and sacral paresthesia. The presence of painful vesicular lesions or ulcers in the perianal area is a clue to the diagnosis (Fig. 6). Inguinal lymphadenopathies can also be present [12]. The endoscopic findings of rectal mucosa could be erythema, mucosal edema and ulcerations.

Figure 6 Perianal vesicles (A) and vesicular eruptions in the anal canal (B) in 2 immunosuppressed patients infected with Herpes simplex virus-2

People with symptoms of acute proctitis with painful perianal or mucosal ulcers detected on proctological examination should receive presumptive treatment for genital herpes [7]. The diagnosis of anorectal HSV infection can be performed using PCR, which has a higher sensitivity compared to the gold standard test (culture virus in rectal tissue) [19]. Treatment options are acyclovir 400 mg t.i.d., valganciclovir 500 mg b.i.d., or famciclovir 250 mg t.i.d., for 5-10 days [8,20]. Intravenous treatment must be considered only in cases of severe HSV, such as disseminated disease, pneumonitis, hepatitis, and meningoencephalitis (Table 2) [20].

Table 2 Summary of recommendations for the diagnosis and treatment of infectious proctitis

Ideally, therapy should be administered within the first 24 h of appearance of the lesion or during the prodrome (burning sensation or pain) to shorten the duration of injuries [7]. The healthcare provider should discuss the importance of abstaining from sexual activity with uninfected partners when lesions or prodromal symptoms are present [7].

T. pallidum

Syphilis is a chronic bacterial infection caused by a spirochete, T. pallidum, whose incidence has risen steadily in recent years in Western Europe and the Americas, mainly in the MSM population [21]. Patients may be completely asymptomatic, and diagnosis is made as a result of incidental screening. When patients are symptomatic, the signs or symptoms may vary according to the stage of the disease [22,23].

In primary syphilis that appears within 3 months (average 2-3 weeks) after direct contact with another person’s infectious skin lesions, an anogenital lesion is typically solitary, painless, ulcerative and indurated, with a clean base and discharge of serous fluid (chancre) [24,25]. Regional lymphadenopathy may also be present in the genitalia, mouth or rectum [24].

If not identified and properly treated, infection may progress to the secondary stage, typically in 6-12 weeks. In fact, secondary syphilis is the most common recognized clinical syndrome of syphilis, particularly among women or MSM. In this stage, a multisystem disease is described and can include several manifestations, such as maculopapular rash (typically palmoplantar), oral ulceration, proctitis and condylomata lata (wart-like papules commonly located in the perianal or genital area) [22,23]. Tertiary infection, which may occur several years after primary or secondary disease, can have major neurological or cardiovascular sequelae [22,23].

Syphilitic proctitis is rarely reported, but is being recognized more frequently because of the increasing incidence of syphilis among MSM. The signs and symptoms of proctitis are nonspecific, such as rectal bleeding, rectal pain, mucus and rectal fullness. The endoscopic appearance of the rectum may include edema, erythema, multiple friable erosions or ulcerations [26].

The presumptive diagnosis of syphilis is made using serologic tests that should include nontreponemal and treponemal tests (Table 2). For those without prior syphilis, either test can be used as the initial screening test. Confirmatory testing is necessary given the potential for false-positive screening test results (dark field microscopy/direct fluorescent antibody testing) or PCR of ulcer exudate, condylomata exudate or rectal biopsies [27].

First-line treatment of primary and secondary syphilis is penicillin G benzathine, 2.4 million units i.m. q.d. Second-line therapy with doxycycline or ceftriaxone can be considered (Table 2) [28].

M. genitalium

M. genitalium is a sexually transmitted pathogen that is a cause of non-chlamydial, non-gonococcal urogenital infections in men (10-35%) and genital tract infection in women, including pelvic inflammatory disease and associated female reproductive complications, such as spontaneous abortion, pre-term birth and infertility [29,30]. Proctitis when present is clinically less pronounced or asymptomatic [29,31,32].

The pathogenic role of M. genitalium in proctitis has been described, but not completely clearly and without a strong association [29-31,33]. Recently, an Australian study showed high rates of M. genitalium coinfection with C. trachomatis and N. gonorrhoeae in the rectum, with M. genitalium present in 13-14% of MSM [29].

There is no evidence that asymptomatic infection warrants treatment, and many patients will spontaneously clear the organism [30]. Therefore, asymptomatic screening is not recommended and testing for M. genitalium is only indicated in symptomatic proctitis after exclusion of other common etiologies. The detection of M. genitalium-specific nucleic acid in clinical specimens by NAATs is the best diagnosis method, which should be followed (if possible) with an assay for macrolide resistance mutations [34]. In M. genitalium infection, proctoscopy shows unspecific findings in rectal mucosae, similar to other infections (e.g., erythema, erosions and mucopurulent exudate).

Regarding therapy, only a few antimicrobial classes have activity against mycoplasma. Azithromycin has a cure rate of 85-95%; however, macrolide resistance is an urgent emerging problem worldwide [4]. The current guidelines recommend an extended course of azithromycin (500 mg on day 1, followed by 250 mg for 2-5 days) as primary choice of treatment for uncomplicated M. genitalium infection in the absence of macrolide resistance mutations or resistance testing [34]. Moxifloxacin is recommended as second-line treatment in case of macrolide resistance mutations or failure of azithromycin therapy, and as first option for complicated M. genitalium infection. There are few options for persistent M. genitalium infection after azithromycin and moxifloxacin (Table 2).

Pristinamycin is a streptogramin and the best evaluated third-line treatment (1 g q.i.d. for 10 days). Minocycline (100 mg b.i.d. for 14 days), or an extended doxycycline regimen, can be an alternative therapy in this scenario [4,34].

On the other hand, a resistance-guided sequential therapy is recommended if treatment is indicated before the results of microbiological investigation are available. This approach is based on doxycycline as initial empiric therapy (100 mg b.i.d. for 7 days), which reduces the organism load, followed by high-dose azithromycin (1 g on day 1, followed by 500 mg daily for 2-4 days), or moxifloxacin for macrolide resistance cases [4,34]. Two large studies achieved a microbial cure of 92-95% with resistance-guided sequential therapy supporting this strategy.

According to the European guidelines, a test of cure, 3 weeks after the completion of treatment, should be considered in all patients, given the high prevalence of resistance present either pre-treatment or developing during treatment, with the consequent risk of spread of resistance [34]. In contrast, CDC recommendations only suggest test of cure in patient with persistent symptoms and signs after treatment.

Monkeypox

Monkeypox is a zoonotic viral infection caused by an orthopoxvirus of the family Poxviridae. Until May 2022, it was an occasional, endemic disease, mainly from Central and West African countries, with small outbreaks described. Since the beginning of the recent outbreak, more than 83,500 cases have been reported worldwide. They are mainly linked to groups of MSM, suggesting an important role for sexual transmission [35].

Clinical manifestations usually appear after an incubation period of 5-24 days, characterized by biphasic pattern with a prodromal phase of fever, lethargy, myalgias, headache and lymphadenopathy, followed by skin eruption 2-4 days later. Skin lesions follow a typical pattern of evolution, starting as macules and progressing into papules, vesicles, pustules and ulcers [36,37]. New clinical presentations of monkeypox infection have been identified, including perianal lesions, severe rectal pain, proctitis, pharyngitis, and penile edema [37].

The incidence of proctitis and/or proctalgia in patients with monkeypox in different series ranged from 22-37% [34-36]. In a recent prospective observational study that included 181 patients with Monkeypox virus (MPXV) infection, 78% had lesions in the anogenital region and 43% in the oral and perioral region. About 39% of them had complications requiring treatment and 25% had proctitis, the most common complication. Patients reporting anal-receptive sex were more likely than others to have proctitis and early systemic symptoms before developing skin lesions [34].

The diagnosis of MPXV infection can be performed by PCR, with detection of MPXV DNA in the skin or an anorectal lesion. Additionally, small series showed a high detection of MPXV DNA in anorectal specimens, even in patients without rectal disease [38].

There is no specific treatment for monkeypox infections. However, monkeypox and smallpox viruses are genetically similar and consequently the antiviral drugs (e.g., tecovirimat, brincidofovir, cidofovir) and vaccines developed to protect against smallpox, may be used in severe illness or immunocompromised individuals.

Antiviral therapy is recommended for patients with or at risk for severe disease and those with infection in anatomic sites (e.g., mouth, pharynx, anogenital area) that may be associated with severe pain or result in sequelae (e.g., scarring, strictures). Currently, tecovirimat, also known as TPOXX, is the treatment of choice for pediatric and adult MPXV infection, and the only drug authorized in Europe [39,40]. Tecovirimat inhibits the activity of a protein called VP37, found on the surface of orthopoxviruses, which is required for the formation of an infectious virus particle. The dose of tecovirimat depends on body weight (Table 2) and it is given typically for 14 days, but should be individualized based on the clinical response and tolerability [39]. Most patients with monkeypox disease will have mild and self-limited disease, with supportive care [41].

HIV and hepatitis C infections

Testing for HIV infection is mandatory upon suspected diagnosis of IP [7]. The relationship between HIV status and the incidence of anorectal venereal infections is bidirectional: HIV-positive patients have a higher incidence of anorectal STIs and recurrence is more common in this subset of patients, while the inflamed mucosa in the setting of IP appears to increase HIV transmission 9-fold [42-44]. The patient should be offered treatment as soon as possible, and partners sharing risk factors with that patient should be encouraged to undergo evaluation [4]. In addition, it is important to perform serology for hepatitis C in MSM with a diagnosis of IP, as it is also considered a STI.

Hepatitis A serology and vaccination

Hepatitis A is a self-limited infection transmitted primarily by the fecal–oral route and sometimes results in epidemic outbreaks. Transmission of HAV can occur during sexual activity, probably due to fecal–oral contact. In MSM and patients living with HIV vaccination should be recommended, as they are considered risk groups for hepatitis A infection [41]. Prevaccination serologic testing for hepatitis A immunity before vaccination is not routinely recommended; however, it can be considered as a way to reduce costs.

Currently, there are 2 monovalent vaccines (Havrix^® and Vaqta^®), administered in a 2-dose series at 0 and 6-12 months [45]. A combined hepatitis A+B vaccine (Twinrix^®) has been developed as a 3-dose series for adults aged ≥18 years at risk for hepatitis A or B virus infections, administered in a 0, 1 and 6-month schedule [45].

HPV infection and related disorders

Although HPV does not cause symptomatic inflammation or a proctitis syndrome, it is important to consider this infection, mainly in the MSM population. As a matter of fact, MSM are at high risk for HPV-related disorders such as anal warts or dysplasia. In addition, anal cancer (generally of the squamous cell type) is more common in MSM than in the general population, and the risk increases dramatically among those who have HIV [46]. Moreover, the symptoms of anal cancer can also be similar to those present in an IP, such as bleeding and tenesmus. Therefore, anal Pap testing in all MSM with anorectal symptoms should be performed, if it has not been done within the past 12 months. There are only limited data to support general screening recommendations for anal Pap testing in MSM or other populations [4].

International recommendations for HPV vaccination include all adolescents at age 11 or 12 years and catch-up vaccination through age 26 years for those not previously vaccinated. MSM adults aged 26-45 years (not previously vaccinated) should be considered for HPV vaccination and clinical decision-making involving the patient and a clinician is recommended. Providers and patients should be aware that HPV vaccination after 26 years, at the data of writing of this protocol, is not covered by the public health system, and this may also affect the decision to vaccinate.

Currently, there are 2 vaccines available: Cervarix^® (targets high-risk genotypes 16 and 18) and Gardasil 9^® (targets genotypes 6, 11, 16, 18, 31, 33, 45, 52 and 58), of which the latter is the more recommended. A 2-dose vaccine schedule (at 0- and 6–12-month intervals) is recommended for persons who initiate vaccination before their 15^th birthday. A 3-dose vaccine schedule (at 0-, 1–2- and 6-month intervals) is recommended for immunocompromised persons, regardless the of age of initiation [47].

Differential diagnosis

The symptoms of IP, including rectal blood, mucous discharge and anorectal pain, may appear in other causes of proctitis, such as IBD. Indeed, the distinction between these diseases can be challenging in some cases, as IP and IBD share some overlapping endoscopic and histologic features [6,48]. According to symptoms, signs and physical examination, other differential diagnoses should be considered, such as traumatic proctitis due to the use of sex toys and douching, radiation proctitis, rectal malignancy, solitary rectal ulcer syndrome, diversion colitis, ischemia or Cytomegalovirus infections (particularly in severely immunocompromised patients or in the context of HIV infection with low CD4+ T-cell counts). Therefore, the differential diagnosis should be supported by a combination of clinical history and physical examination, as well as endoscopic, serologic, and microbiologic findings.

In terms of diagnosis, distinguishing between IBD and IP is the most challenging scenario. However, a prompt and correct diagnosis is crucial to ensure appropriate management and optimal outcomes for each clinical scenario.

Regarding clinical history, some authors conclude that a history of HIV-positive MSM, anal pain and anal discharge are discriminating features of infectious colitis [48]. If patients complain of abdominal cramping and diarrhea, it is important to distinguish proctitis from proctocolitis and enteritis. These infections, caused by Campylobacter, Shigella, Salmonella, Giardia, and Entamoeba histolytica, are not considered STIs, but sexual transmission can occur in MSM populations. Considering the histological findings, intense lymphohistiocytic infiltrate with prominent plasma cells, lymphoid aggregates and only minimal active chronic crypt centric damage, are more suggestive of IP than IBD [48].

Considering that both conditions can coexist and in order to reduce the cases of IP incorrectly diagnosed as IBD, some authors recommend HIV testing for every MSM patient with IBD suspicion. Moreover, all patients with IBD in the colorectal tract, even confirmed by endoscopy and histopathology, should be tested for STIs using molecular and serological methods [49]. Patients initially diagnosed with IBD not responding to standard therapy as expected, should also be tested for STIs.