Lymphogranuloma venereum mimicking rectal cancer (T3 N2) and causing a rectovesical fistula

Introduction

According to their particular aetiology, various causes for the development of proctitis and proctocolitis are well known, including infections, autoimmune disorders (especially inflammatory bowel disease), trauma or lymphoma, among several others. ¹ Typical clinical signs of a distinct proctitis encompass tenesmus, painful defecation, and bloody or mucopurulent discharge. In the case of proctocolitis, a diarrhoea can additionally often be observed. ¹

Case report

A 66-year-old bisexual man presented due to repetitive painful defecation and bloody discharge for the period of the last two months at an endoscopic surgeon. The performance of a procto-sigmoideoscopy revealed ulcerative rectal alterations as well as a rectovesical fistula. An equally conducted magnetic resonance imaging (MRI) showed transmural rectal thickening (4 × 2 cm), stranding of the mesorectal fascia and enlarged lymph nodes in the mesorectal area, suggesting diagnosis of rectal cancer stage T3 N2 (Figure 1(a)). Several biopsies were taken. However, a thorough histopathologic evaluation of all specimens showed no hints for any malignancy at all, but an active proctocolitis and suspected inflammatory bowel disease with granulomatous plasmocellular changes. The performance of polymerase chain reaction (PCR) for treponema pallidum emerged negative. Laboratory values, including relevant tumor-related parameters [carcinoembryonic antigen (CEA), alpha-1-fetoprotein (AFP), carbohydrate antigen 19–9 (CA19-9), cancer antigen 72–4 (CA72-4) and prostate specific antigen (PSA)] were inconspicuous. After these examinations the patient was referred to our department at a tertiary academic center. After recording the patient’s detailed sexual history (bisexual behaviour for years, occasional condomless receptive anal sex with casual partners), we suspected LGV. A multiplex PCR (EuroArray STI11; Euroimmun® Lübeck, Germany) searching for relevant sexually transmitted pathogens (including Neisseria gonorrhoeae, Treponema pallidum, Mycoplasma genitalium, Haemophilus ducreyi, Herpes genitalis and Chlamydia trachomatis (CT) among others) was performed at the patient’s oral, rectal and urethral regions. Chlamydia trachomatis could be detected in rectal swabs; a consecutive subtyping using a specific protocol ² confirmed the diagnosis of lymphogranuloma venereum (LGV) due to CT L2. Consecutively, doxycycline 100 mg BID was prescribed orally for 21 days. In addition, a late onset latent syphilis was verified according to laboratory values (RPR 1:2; TPPA positive, TMPA positive, TMPA IgM negative). Due to the patient’s negative treatment history, a specific pharmacological therapy was performed according to Austrian national guidelines with three injections of benzathine penicillin 2.4 MIE per week. HIV, HBV and HCV could be excluded. General information concerning STIs was provided, and due to his negative HIV status, the patient was advised of PREP availability. The patient’s clinical symptoms faded completely within days after starting doxycycline treatment. A control MRI after three months demonstrated a complete regression of previously present pathogenic features (Figure 1(b)). The patient gave oral and written informed consent for publishing this case.

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Figure 1.

(a) Initial MRI of the rectum: Axial T1-weighted MR image shows irregular circumferentially thickened rectal wall (red arrow) with soft tissue infiltration of the mesorectum and multiple pathological mesorectal lymph nodes (yellow arrow). Obliteration of the mesorectal fat tissue between rectum and seminal vesicles (green arrow). (b) Control MRI of the rectum: Axial T2-weighted MR image shows normal thickness of the rectal wall (red arrow). Normal appearance of the mesorectal fat (green arrow) with no signs of the lymphadenopathy (yellow arrow).

Discussion

Lymphogranuloma venereum represents a serious sexually transmitted infection caused by invasive L1-3 CT serovars, with a global incidence on the rise.^3,4 Until 2003, LGV was uncommon in the Western world, when first reports emerged about an increasing incidence in men who have sex with men (MSM), thus LGV is now stated to represent an endemic disease.^3,4 As described above, proctitis or proctocolitis are the most typical clinical presentations, being often accompanied by systemic symptoms like fever, chills, lymphangitis or lymphadenitis.^3,4 Anorectal LGV is often mistaken with other diseases, like inflammatory bowel disease (IBD), or other infectious reactions of the anorectal region. Due to the similarity of symptoms, particularly in patients suffering from IBD, LGV might often be misdiagnosed or diagnosed with a significant delay, resulting in an unnecessary increase of morbidity.^5,6 Recently, a group from Israel focused on delayed diagnosis of colorectal STIs, including NG, CT and syphilis, as symptoms were misinterpreted as IBD. ⁶ The authors urged that at least testing of syphilis and anal Chlamydia should be offered in MSM who have symptoms of procto(colitis). ⁶ Moreover, it is inevitable that patients are adequately interviewed for their history regarding sexual health, of any medical professional working in the field of anorectal complaints, including gastroenterologists, endoscopic surgeons, dermatovenerologists, and specialists for infectious diseases. An accurate physical examination with a conventional anoscope increases the suspicion and facilitates the early start of treatment, reducing the complications and the diagnostic tests required.

Lymphogranuloma venereum represents a disease of three stages, starting from a papule/pustule that might transform to an ulcer (stage I), to painful (typically unilateral) lymphadenopathy (stage II), followed by the appearance of buboes and residues like fistulas, strictures and irreversible lymphedema (stage III).^3,4 However, asymptomatic infections are possible in up to a fourth of all patients. ⁴ In the respective patient the occurrence of a rectovesical fistula is of particular interest, since those are very uncommon in the context of LGV.^7,8 The patient showed no significant urinary symptoms or signs of a urinary tract infection. Nevertheless, the respective fistula was confirmed by two independent endoscopic surgeons due to the loss of urine into the rectum and was visualized during endoscopy, whereas the fistula was not detected on MRI. It has to be emphasized that this fistula was not detectable in a later control endoscopy anymore and its exact origin remains elusive.

Laboratory analyses are essential for a correct diagnosis of LGV, moreover, a subtyping of CT is highly recommended in all MSM patients who have a positive CT result at the anorectal region, but this is unfortunately not available everywhere and it seems that a significant and systematic under-diagnosis might take place in the real-life setting.^4,5 Current guidelines recommend oral treatment regimen with doxycycline 100 mg BID for 21 days as first line therapy; alternative treatment options include azithromycin or erythromycin. ⁴ All sexual partners of the last three months should be mandatorily informed and testing to these should be offered. ⁴ Moreover, due to LGVs ulcerative pathology, the transmission of infections like HIV or hepatitis may be facilitated. Therefore, those STIs should be monitored very closely, according to their diagnostic window and depending on a patient’s sexual behaviour. Moreover in HIV negative patients, PREP should be advised. A test of cure should be performed up to six weeks after the ending of antibiotics, if other drugs than doxycycline were used. ⁴

Conclusion

This case report describes the rare event of a LGV mimicking rectal cancer at a significant stage of the disease. Many LGV cases are believed to be misdiagnosed due to sometimes unspecific symptoms, asymptomatic courses or low detection/testing possibilities. ⁵ However, all medical specialists working in the large and complex field of infectious diseases should be aware of the potentially significant morbidity of LGV, which undoubtedly represents an important and under-diagnosed disease.^4,5