Guideline sources The following summarized guidelines for the evaluation and management of lymphogranuloma venereum (LGV) are prepared by our editorial team based on guidelines from the European Academy of Dermatology and Venereology (EADV 2019) and the British Association for Sexual Health and HIV (BASHH 2013). 1 2 Pathway Lymphogranuloma venereum Diagnosis and management Guidelines 1. Screening and diagnosis https://web.pathway.md/diseases/rec4I7AGkMT1BL6Xj 1/6 6/29/23, 5:56 AM Lymphogranuloma venereum Pathway Indications for testing: Obtain testing for LGV in the following patients: human immunodeficiency virus-positive MSM or in MSM eligible for human immunodeficiency virus pre-exposure prophylaxis A patients with other Chlamydia trachomatis positive sites - urethra/urine/pharynx - if symptoms persist despite receiving recommended treatment options B symptomatic patients with suspected LGV contacts of confirmed LGV index cases all MSM with a Chlamydia trachomatis positive anorectal sample irrespective of symptoms. Show 3 more Diagnosis: confirm the diagnosis of LGV by detecting genovar-specific Chlamydia trachomatis deoxyRNA. 2. Diagnostic investigations Initial diagnostic testing: obtain an NAAT to detect C. trachomatis nucleic acid in urethral, cervical, urine, rectal, and pharyngeal specimens. Specimen selection: Consider using the following specimens for the diagnosis of LGV: swab of ulcer base, or exudate from primary anogenital lesions rectal mucosal specimens (swabs or biopsies, ideally collected from the mucosal lining under proctoscopic vision, but also self-collected rectal swabs in asymptomatic MSM) lymph node or bubo aspirates using a 21-gauge needle after topical disinfection if LGV is suspected urethral swab or first-catch urine specimen if LGV is suspected pharyngeal swabs from MSM and women exposed at those sites. Nucleic amplification tests: As per EADV 2019 guidelines: Obtain a two-step procedure for sensitive and specific detection of LGV genovar (L1, L2 and L3, including subvariant)-specific Chlamydia trachomatis deoxyRNA: use commercially available NAAT to detect Chlamydia trachomatis deoxyRNA/RNA in suspected clinical samples obtain testing for LGV genovar-specific Chlamydia trachomatis deoxyRNA if Chlamydia trachomatis deoxyRNA/RNA is detected. B Obtain testing for LGV genovar in a timely manner (preferably within 1 week) for clinical management. As per BASHH 2013 guidelines: Obtain a PCR for LGV DNA in patients with a positive NAAT, in order to confirm the diagnosis. Confirm Chlamydia trachomatis-positive samples by real-time PCR for LGV-specific DNA in cases of suspected LGV, as only detection of LGV DNA confirms the diagnosis. https://web.pathway.md/diseases/rec4I7AGkMT1BL6Xj 2/6 6/29/23, 5:56 AM Lymphogranuloma venereum Pathway Serology: As per EADV 2019 guidelines, consider obtaining validated and quality-assured Chlamydia genus-specific serological assays for the presumptive diagnosis of LGV in the absence of LGV genovar-specific Chlamydia trachomatis NAAT. B Show 2 more As per BASHH 2013 guidelines: Four types of techniques have been described for serological diagnosis of LGV: the complement fixation test, the single L-type immunofluorescence test, the microimmunofluorescence test and the anti-MOMP IgA assay. Serology cannot necessarily distinguish past from current LGV infection, which might prove restrictive given the high number of recurrent LGV infections now seen in MSM. Culture: As per EADV 2019 guidelines, consider isolating Chlamydia trachomatis in cell culture with subsequent specific detection of the LGV genovar for the diagnosis of LGV, recognizing that this method has a suboptimal sensitivity, is labor-intensive, expensive, rarely available and now outdated. As per BASHH 2013 guidelines, culture on cycloheximide-treated McCoy cells is of increasingly restricted availability, because of high cost and limited sensitivity. Rectal smear: recognize that the identification of rectal polymorphonuclear leukocytes in rectal swabs from symptomatic patients is predictive of LGV proctitis, especially in human immunodeficiency virus-positive MSM. Use polymorphonuclear leukocytes number of > 10 5 and > 20 1 per high-power field as significant thresholds, recognizing that the sensitivity and especially specificity of this measurement can be suboptimal. B Testing for other STIs: recognize that the prevalence of human immunodeficiency among MSM with LGV reported to be 67-100% and there is a significant association between human immunodeficiency virus and LGV. A Show 3 more Assessment of sexual partners: Initiate partner notification when the diagnosis of LGV is made. B Offer testing from all exposed sites for Chlamydia trachomatis/LGV in sexual contacts within the last months. B 3. Diagnostic procedures Lymph node biopsy: histology of lymph nodes shows follicular hyperplasia and abscesses in patients with LGV, but such findings are not specific. Nonetheless, histopathologists need to be alert to these changes and include LGV in the differential diagnosis. 4. Medical management https://web.pathway.md/diseases/rec4I7AGkMT1BL6Xj 3/6 6/29/23, 5:56 AM Lymphogranuloma venereum Pathway General principles: As per EADV 2019 guidelines, consider initiating treatment for LGV in MSM with a Chlamydia trachomatis positive anorectal test result having severe proctitis, if no LGV diagnostic test is readily available. C As per BASHH 2013 guidelines, administer antibiotic treatment for at least 3 weeks in patients with LGV to prevent or reduce the chronic complications of the disease. First-line therapy: As per EADV 2019 guidelines, administer doxycycline 100 mg BID PO for 21 days as first-line therapy in patients with symptomatic B or asymptomatic LGV. B Show 3 more As per BASHH 2013 guidelines, administer doxycycline (100 mg PO BID, for 21 days) as first- line therapy in patients with LGV. B Second-line regimens: As per BASHH 2013 guidelines: Consider using erythromycin (500 mg PO QID, for 21 days) second-line therapy for LGV. C Consider using azithromycin (1 g PO once weekly, for 21 days) as second-line therapy for LGV. C Second-line therapy: as per EADV 2019 guidelines, insufficient evidence to support the use of azithromycin in single- or multiple-dose regimens as first-line therapy in patients with symptomatic LGV. Obtain a test of cure if alternative treatment regimen is used. I Alternative regimens: As per EADV 2019 guidelines, consider administering erythromycin (ethylsuccinate) 400 mg QID PO for 21 days as an alternative regimen in patients with LGV. C Show 2 more As per BASHH 2013 guidelines: Consider using minocycline (300 mg loading dose, followed by 200 mg PO BID, for 21 days) as a third-line option for the treatment of LGV. C Consider using tetracycline (500 mg PO QID, for 21 days) as a third-line option for the treatment of LGV. C Management of sexual partners: Initiate empiric treatment with doxycycline in sexual contacts within the last months until Chlamydia trachomatis/LGV has been excluded in the partner. B Insufficient evidence to support the use of alternative shorter course regimens, including azithromycin 1 g single PO dose, in asymptomatic partners. I 5. Therapeutic procedures Aspiration of fluctuant buboes: drain fluctuant buboes via needle aspiration through healthy overlying skin. Consider repeating intervention to ensure reemerging buboes are drained. B https://web.pathway.md/diseases/rec4I7AGkMT1BL6Xj 4/6 6/29/23, 5:56 AM Lymphogranuloma venereum Pathway 6. Surgical interventions Surgical incision: do not perform surgical incision of buboes due to potential complications such as chronic sinus formation. D Reconstructive genital surgery: consider performing surgical repair including reconstructive genital surgery in patients with residual fibrotic lesions or fistulae as they do not benefit from further courses of antibiotics. C 7. Patient education General counseling: As per EADV 2019 guidelines, inform patients that: LGV is a STI that can invade connective tissue and regional lymph nodes, but is curable with antibiotics if left untreated it can have serious and permanent adverse sequelae most of these complications are preventable if treatment is initiated at an early stage in anorectal disease, symptoms should resolve within 1-2 weeks of commencing antibiotic therapy in inguinal disease, symptoms might persist for many weeks and follow-up visits should be implemented. B Show 5 more As per BASHH 2013 guidelines, advise patients that LGV is curable with antibiotics, but can have serious and permanent adverse sequelae if left untreated. Show 2 more 8. Follow-up and surveillance Follow-up: Follow-up all patients with LGV at the end of treatment in order to: ensure treatment compliance, assess side effects, and ensure resolution of symptoms and signs of infection check that adequate partner notification has been completed address any patient concerns arrange suitable follow-up testing for syphilis, gonorrhoea and blood-borne viruses including hepatitis B, C and human immunodeficiency virus. B Show 2 more Clinical findings Patient demographics Symptoms https://web.pathway.md/diseases/rec4I7AGkMT1BL6Xj 5/6 6/29/23, 5:56 AM Lymphogranuloma venereum Pathway Male sex Arthralgia Chills Past medical history Constipation Fatigue Anorectal fistula Fever Human immunodeficiency virus infection Myalgia Rectal discharge Proctitis Rectal tenesmus Sexually transmitted diseases Vaginitis Social history Genitourinary exam MSM Genital papule Lymphatic exam Genital pustule Genital ulcer Draining inguinal lymphadenopathy Lab findings Painful inguinal lymphadenopathy Chlamydia trachomatis deoxyRNA Serological findings Histological findings serum Chlamydia trachomatis antibodies Gamna-favre bodies References 1. H J C de Vries, B de Barbeyrac, N H N de Vrieze et al. 2019 European guideline on the management of lymphogranuloma venereum. J Eur Acad Dermatol Venereol. 2019 Oct;33 10 1821 1828. Open 2. White J, O'Farrell N, Daniels D. 2013 UK National Guideline for the management of lymphogranuloma venereum: Clinical Effectiveness Group of the British Association for Sexual Health and HIV CEG/BASHH Guideline development group. Int J STD AIDS. 2013 Aug;24 8 593 601. Open 3. Bradley P Stoner, Stephanie E Cohen. Lymphogranuloma Venereum 2015 Clinical Presentation, Diagnosis, and Treatment. Clin Infect Dis. 2015 Dec 15;61 Suppl 8 S865 73. Open 4. Romana Ceovic, Sandra Jerkovic Gulin. Lymphogranuloma venereum: diagnostic and treatment challenges. Infect Drug Resist. 2015 Mar 27;8 39 47. Open https://web.pathway.md/diseases/rec4I7AGkMT1BL6Xj 6/6