Atypical Invasive Presentation of Chlamydia trachomatis Genotype D Mimicking Lymphogranuloma Venereum

Abstract

Three Chlamydia trachomatis biovars are recognized-trachoma (serovars A-C), urogenital (serovars D-K), and lymphogranuloma venereum (LGV) (serovars L1-L3). Only serovars L1-L3 cause invasive infection with bubo formation. Here, we present an atypical case of C. trachomatis serotype D with clinical presentation of LVG-unilateral inguinal lymph edema plus bubo formation. A 35-year-old male who have sex with men presented to the clinic with unilateral swollen painful right inguinal lymph nodes forming bubo, accompanied by fever up to 39°C and malaise. Complete blood count was tested. Urethral sample for DNA extraction and polymerase chain reaction (PCR) was taken. Ultrasonography and proctoscopy were performed. Fine-needle aspiration from lymph node was tested for malignant cells and PCR diagnostics. A full STI screen was performed. PCR positive for C. trachomatis was detected. The exact classification of C. trachomatis species needed additional genovar-specific C. trachomatis PCR. Surprisingly genotype D instead of LVG L1-L3 was discovered. Co-infection with Mycoplasma genitalium was detected. HIV, Neisseria gonorrhoeae, HSV, and Ureaplasma spp. were negative. Serology excluded syphilis, HBV, HCV, infectious mononucleosis, toxoplasmosis, and cat scratch disease. Malignant cell formation was ruled out. This case highlights the importance for clinicians to consider atypical and invasive presentations of nonLGV C. trachomatis genotypes, as reliance on clinical features alone may lead to misclassification, inappropriate management, and delayed targeted therapy.

Introduction

Chlamydia trachomatis is an obligate intracellular bacterium infecting over 100 million people annually worldwide.[1] It belongs to the genus Chlamydia, family Chlamydiaceae. Three biovars exist: trachoma (genotypes A–C), urogenital (D–K), and lymphogranuloma venereum (LGV, genotypes L1–L3). The trachoma genotypes infect conjunctiva, possibly leading to blindness. Urogenital strains affect the genital tract, causing cervicitis, pelvic inflammatory disease (PID), urethritis, and infertility. LGV genotypes can invade lymphatic tissue, leading to systemic spread.

Unlike genotypes A–K, LGV strains disseminate beyond mucosal surfaces, affecting regional lymph nodes. LGV progresses in three stages: an initial often unnoticed ulcer; secondary lymph node enlargement and bubo formation; and tertiary complications, including fibrosis and irreversible lymphedema.

LGV has been endemic in Africa, Latin America, Southeast Asia, and Caribbean for many years. In recent years, LGV has increasingly affected men who have sex with men (MSM), especially in Europe.[2,3] Since its resurgence in the Netherlands in 2003, LGV is now endemic among MSM across Europe, with reported cases in countries such as France, the UK, Poland, and Bulgaria.[4]

Here, we present the case of a particular importance for diagnostic and therapeutic decision-making, as it demonstrates that urogenital C. trachomatis genotypes can mimic LGV, necessitating genotyping to guide appropriate treatment and follow-up. An MSM patient infected with genotype D C. trachomatis displayed symptoms typically linked to LGV (inguinal lymphadenopathy and bubo), not the expected urogenital manifestation. Genotyping confirmed genotype D, not LGV, per 2019 European LGV management guidelines. The patient was also co-infected with Mycoplasma genitalium.

Case Report

A 35-year-old MSM attended a private dermatology and venereology clinic in Sofia, Bulgaria. He had a 2–3 week history of painful, swollen right inguinal lymph nodes with bubo formation [Figure 1], accompanied by fever (up to 39°C) and malaise for several days. Initial general surgery consultation had ruled out common causes, prompting referral to our clinic.

Figure 1.

Unilateral swollen inguinal lymph nodes with bubo formation

No genital ulcers, skin rash, dysuria, discharge, testicular pain, or rectal symptoms were present. Skin over the lymph nodes appeared normal. Laboratory tests included a complete blood count, C-reactive protein, and ultrasonography of the lymph nodes. Fine-needle aspiration (FNA) ruled out malignancy. Sexually transmitted infection (STI) testing was done after obtaining informed consent.

Ultrasound showed abscess formation. Blood tests revealed elevated leukocyte count (13.5 × 10³/µL) and C-reactive protein (38.2 mg/L). Proctoscopy was normal.

Urethral sample was collected. DNA extraction (DNA-sorb-AM, AmpliSens, Russia) and Multiplex real-time polymerase chain reaction (PCR) (Sacace Biotechnologies, Italy) was performed on urethral and FNA samples, detecting C. trachomatis. In accordance with the 2019 European guideline, genovar-specific PCR was performed using Morré et al.’s protocol.[5] Results were negative for LGV genotypes. Confirmation at the Institute of Medical Microbiology and Hygiene, University Hospital Ulm (Germany) identified genotype D. A complete STI panel found co-infection with M. genitalium. Other organisms tested negative [Table 1.].

Table 1.

The full STI screen used in the diagnostic procedure of the patient

Microorganism tested	Method used	Result
Chlamydia trachomatis	PCR	Positive
Neisseria gonorrhoeae	PCR	Negative
Mycoplasma genitalium	PCR	Positive
Ureaplasma spp.	PCR	Negative
Treponema pallidum	VDRL/TPHA	Negative
Bartonella henselae	PCR	Negative
HSV	PCR	Negative
HBV	HBsAg and total anti-HBc (both IgM and IgG)	Negative
HCV	ELISA	Negative
Epstein-Barr virus	PCR	Negative
Toxoplasma gondii	ELISA	Negative

PCR: Polymerase chain reaction; HSV: Herpes simplex virus; HBV: Hepatitis B virus; HCV: Hepatitis C virus; ELISA: Enzyme-linked immunosorbent assay; VDRL: Venereal disease research laboratory; TPHA: Treponema pallidum hemagglutination Assay; HBsAg: Hepatitis B Surface Antigen; Ig: Immunoglobulin; HBc: Hepatitis B core antibody; STI: Sexually transmitted infections

Treatment followed the 2015 and 2019 European guidelines. Due to medical history and documentation of allergy to doxycycline, azithromycin (1 g weekly for 3 weeks) was prescribed.

Partner tracing was impossible as the suspected contact was a foreign national.

Discussion

C. trachomatis is the most common bacterial STI globally. While treatable, it is often asymptomatic, leading to delayed diagnosis and complications including PID, ectopic pregnancy, infertility, and chronic pelvic pain in women; epididymitis, infertility, and erectile dysfunction in men. Extra-genital manifestations include arthritis, pneumonia, and conjunctivitis.

In 2022, 216,508 chlamydia cases were reported across 27 EU/EEA countries.[6] Between 2018 and 2022, MSM-related cases rose by 72%. LGV cases surged by 58% in 2022, reaching 2,059 cases.[4] LGV remains endemic in most European countries, including Bulgaria, although only two cases have been reported there from retrospective analyses.[7]

We report an unusual clinical case involving right-sided inguinal lymphadenopathy with bubo formation in an MSM patient. These symptoms are typical of LGV’s secondary stage. NAAT confirmed C. trachomatis infection, but further testing identified genotype D, not LGV.

Urogenital genotypes (D–K) typically infect genital epithelial cells, causing urethritis or cervicitis. They rarely lead to lymphatic spread or bubo formation. The pathogenicity behind the invasive presentation of genotype D remains unclear. Potential explanations include unidentified virulence factors or host immune responses. Studies suggest Chlamydia adhesion and invasion are influenced by both bacterial and host elements. In addition, mixed infections (L + D–K genotypes) and recombinant strains have been documented.[8,9] Such possibilities warrant further investigation. Enhanced genotyping and surveillance programs are critical for identifying emerging or atypical strains.[10]

Differential diagnosis for inguinal lymphadenopathy was considered [Table 2].

Table 2.

Differential diagnosis for inguinal lymphadenopathy

Exposure	Diagnosis
General
High-risk sexual behavior	HIV, syphilis, HSV, CMV, HBV, LVG
Cat	Toxoplasmosis, cat-scratch disease
Tick bite	Lyme disease, tularemia
Undercooked meat	Toxoplasmosis
Tuberculosis	Tuberculous adenitis
Recent blood transfusion or transplant	CMV, HIV
Intravenous drug use	HIV, endocarditis, HBV
Travel-related
Arizona, Southern California, New Mexico, Western Texas	Coccidioidomycosis
Southwestern United States	Bubonic plague
Central or South America	American trypanosomiasis (Chagas’ disease)
Southeastern or central United States	Histoplasmosis
Mexico, Peru, Chile, India, Pakistan, Egypt, Indonesia	Typhoid fever
Latin America, Mediterranean, China, East Africa	Kala-azar (leishmaniasis)
Central or west Africa	African trypanosomiasis (sleeping sickness)
India, northern Australia, Southeast Asia	Scrub typhus
Occupational
Trappers, hunters	Tularemia
Fishermen, fishmongers, slaughterhouse workers	Erysipeloid

HIV: Human immunodeficiency virus; HBV: Hepatitis B virus; HSV: Herpes simplex virus; CMV: Cytomegalovirus; LVG: Lymphogranuloma Venereum

All other potential causes were excluded.

From a clinical perspective, this case emphasizes that patients presenting with unilateral inguinal lymphadenopathy and bubo formation should be managed with a broad diagnostic approach, irrespective of presumed LGV status. Clinicians should maintain a high index of suspicion for atypical presentations and ensure comprehensive microbiological testing, including NAAT and genovar-specific PCR. In cases of invasive or unusual lymphadenopathy, routine genotyping may be warranted to differentiate LGV from non-LGV strains, avoid overtreatment or undertreatment, and improve epidemiological surveillance. Incorporating genotyping into the diagnostic algorithm for atypical lymphadenopathy could enhance diagnostic accuracy and inform public health strategies.

The only other positive STI finding was M. genitalium. While doxycycline is first-line therapy for LGV and M. genitalium, azithromycin was used due to a documented allergy (history of skin testing with localized reactions as erythema, swelling, itching, and hives plus controlled drug challenge).

Follow-up visits at weeks 4 and 8 posttreatment showed complete resolution. The patient was asymptomatic, abstinent during this period, and tested negative for C. trachomatis and M. genitalium. Nevertheless, long-term recurrence risk remains unknown.

Of course, this report has several limitations. First, the long-term follow-up data are lacking, preventing the assessment of potential late complications or recurrence. Second, partner notification and testing could not be performed, limiting insights into transmission dynamics and possible strain circulation.

Conclusion

MSM represent a high-risk population for C. trachomatis and LGV. Increased testing and genovar-specific diagnostics are crucial given the atypical presentations and rising incidence of chlamydia infections in Europe.

Inguinal lymphadenopathy demands a multidisciplinary approach involving both clinical and microbiological expertise. The co-infections are common and require comprehensive diagnostic panels. Prompt treatment not only resolves clinical symptoms but also prevents long-term complications and ongoing transmission.

This case underscores the need for vigilance regarding atypical presentations of common pathogens and supports expanded genotyping efforts in STI surveillance programs.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.