Atypical presentation of herpes simplex virus 2 primary infection: a case report

Abstract

Background

Cervicitis, an infectious or noninfectious inflammation of the cervix, encompasses a wide range of clinical conditions, from asymptomatic infections to severe lesions, making its diagnosis difficult. Acute cervicitis may develop into pelvic inflammatory disease. In patients with cervicitis, current guidelines recommend testing for herpes simplex virus when external genital lesions are present. Here, we present the case of a patient with an atypical primary herpes simplex virus 2 infection manifesting as cervicitis without genital lesions.

Case presentation

A 29-year-old Caucasian woman was hospitalized for pelvic inflammatory disease. The patient complained of severe suprapubic pain, fever, and heavy vaginal discharge. The external genitalia were unremarkable, so empirical antibiotic treatment was initiated. Despite 48 hours of well-administered antibiotic therapy, her complaints persisted. Polymerase chain reaction for possible microbial causes was negative for Chlamydia trachomatis and Neisseria gonorrhoeae. There was no bacterial vaginosis. Repeat gynecological examinations with endovaginal ultrasound revealed an enlarged cervix, and pelvic magnetic resonance imaging supported a diagnosis of cervicitis. At this point, additional screening for other sexually transmitted infections and infectious disease-related etiologies of cervicitis was performed, and the polymerase chain reaction analysis of newly isolated samples was positive for herpes simplex virus 2. No antiviral treatment was initiated given the delay in diagnosing herpes simplex virus 2 infection and the slow but spontaneous abatement of symptoms.

Conclusion

Herpes simplex virus infection should be considered as a possible cause of cervicitis, even in the absence of typical genital lesions. Early detection of herpes simplex virus allows early treatment, helping to reduce the duration and severity of symptoms and therefore potentially reducing recurrences and improving disease control. These data and data from future cases might spur changes in the guidelines on cervicitis testing and treatment.

Introduction

Cervicitis is a clinical syndrome characterized by inflammation of the cervix, which can present with wide clinical variability, ranging from no symptoms to mucopurulent cervical discharge and systemic signs. The exact prevalence of cervicitis is unknown due to the lack of a standard definition and variation between populations. It may affect 30–40% of patients seen in sexually transmitted infection (STI) clinics [1]. For patients with cervicitis, the current guidelines recommend testing for herpes simplex virus (HSV) when external genital lesions are present [1, 2]. HSV, especially type 2, is one of the most common STIs worldwide, with a seropositivity rate of approximately 12% in the European population in 2023 [3]. Genital HSV infection ranges from asymptomatic to typically painful vulvar ulcers but can manifest as cervicitis, which makes it difficult to diagnose [4]. Here, we report a rare case of cervicitis due to HSV infection with no lesions to highlight the importance of considering HSV in the etiological diagnosis of any cervicitis, even in the absence of typical genital lesions, because early recognition of the infection allows for better management of the disease.

Case presentation

A 29-year-old Caucasian woman with no relevant personal history other than cephalosporin allergy was admitted with suspected pelvic inflammatory disease (PID). She presented to the emergency department with 24 hours of suprapubic pain and 48 hours of pyrexia. She described mild mictalgia and a liquid, transparent, odourless vaginal discharge requiring a change in sanitary napkins every 2 hours; 3 days before admission, the patient had been separately seen by an emergency physician at the same hospital for discharge, which was initially considered urinary incontinence, resulting in the prescription of a single 3-g dose of oral fosfomycin. This antibiotic treatment did not improve her symptoms. Her last sexual intercourse, with an occasional male partner, was 14 days prior and involved the use of a condom. The patient was nulliparous and compliant with combined oral contraceptives. Her previous gynecology consultation session was 2 years before admission, and her last cervicovaginal smear, performed 3 years earlier, was unremarkable.

On initial clinical examination, there was abdominal pain in the suprapubic area and iliac fossae without guarding or rebound tenderness. The vulva was unremarkable. Pelvic examination revealed a diffusely tender vagina with uterine pain upon mobilization. Speculum examination confirmed abundant fluid discharge and revealed a slightly edematous cervix without any other lesions. Endovaginal ultrasound did not reveal adnexal masses, and biological investigation revealed a C-reactive protein level of 76 mg/L (N < 5 mg/L) without hyperleukocytosis. The urinary sediment test was negative. Accordingly, the patient was diagnosed with an early presentation of PID with no adnexal abscess. Classic PID investigation, consisting of vaginal swabs for Chlamydia trachomatis, Neisseria gonorrhoeae, and bacterial vaginosis, was conducted. The patient was hospitalized in our gynecology department and was given empirical antibiotic therapy. Given her allergy to cephalosporins, treatment included 100 mg of oral doxycycline twice daily, 500 mg of intravenous metronidazole three times daily, and 500 mg of intravenous ciprofloxacin twice daily (see Fig. 1 for the case timeline).

Fig. 1

Case timeline

After 48 hours of well-conducted antibiotic therapy, the patient’s clinical condition remained unfavorable, with increased pain and a persistent subfebrile state. Polymerase chain reaction (PCR) run on vaginal swabs for Chlamydia trachomatis and Neisseria gonorrhoeae, as well as bacterial cultures, were negative. A substantially enlarged cervix, measuring 53.9 × 37.1 × 39.6 mm on endovaginal ultrasound, was evident during a repeat gynecological examination (Fig. 2), while other abdominal pathologies were ruled out by abdominal ultrasound. Findings on pelvic magnetic resonance imaging (MRI) supported a diagnosis of cervicitis, as it revealed that the cervix was substantially swollen and edematous in appearance, and diffusion-weighted imaging (DWI) revealed a hyperintense signal caused by the high water content of cervical cells, confirming inflammation. However, no significant decreases in the apparent diffusion coefficient were observed, which made malignancy unlikely (Figs. 3 and 4). Nonspecific left external iliac adenopathy measuring 8 mm was also detected. Given these results, additional screening for other STIs and infectious disease-related etiologies of cervicitis, such as syphilis, hepatitis B, hepatitis C, human immunodeficiency virus (HIV), Mycoplasma genitalium, Trichomonas vaginalis, HSV-1, and HSV-2, was performed. On day 4, PCR and culture results for HSV-2 were positive, and subsequent HSV-2 serological evaluation showed that the samples were positive for HSV-2 immunoglobulin M (IgM) and negative for HSV-2 IgG. The final diagnosis of HSV-2 cervicitis was made, and a mild favorable clinical outcome was achieved. In light of the late diagnosis and after an informal discussion with infectiologists, no antiviral treatment was given, and antibiotic treatment was stopped when she was discharged from hospital on day 6 after admission.

Fig. 2

On day 2 after admission, endovaginal ultrasound revealed an enlarged cervix measuring 53.9 × 37.1 × 39.6 mm

Fig. 3

T2-weighted magnetic resonance (MR) images showing significant cervical swelling and edema on (A) sagittal, (B) transverse, and (C) coronal views (white arrows)

Fig. 4

Diffusion-weighted (DW) image showing a hyperintense signal from the cervix (transverse view)

A follow-up assessment 1 week after hospital discharge revealed persistent and heavy vaginal discharge but resolution of pain, and 3 months after discharge, MRI revealed regression of the swelling and edema of the uterine cervix and a lack of hyperintense DWI signals (Fig. 5).

Fig. 5

T2-weighted MR images showing regression of the swelling and edema of the uterine cervix on (A) sagittal and (B) transverse imaging (white arrows)

Discussion and conclusion

We report a case of cervicitis resulting from a primary genital HSV-2 infection whose diagnosis was delayed due to the absence of external genital lesions. This case report describes a patient with a clinical presentation on admission suggestive of PID who, upon subsequent clinical, imaging and laboratory examination, was diagnosed with an atypical genital HSV-2 infection manifesting as cervicitis without external lesions.

Cervicitis is characterized by mucopurulent endocervical exudates, and sometimes, cervical friability with endocervical bleeding. This condition can have either an infectious or noninfectious origin, the latter of which includes chemical or mechanical irritation [5]. In this case, despite the absence of a friable cervix or metrorrhagia, the patient was diagnosed with cervicitis on the basis of the presence of transparent leukorrhea and cervical edema observed during speculum examination, which was further confirmed by imaging (US and MRI).

To identify the etiology of suspected cervicitis, current guidelines recommend testing for C. trachomatis and N. gonorrhoeae, as these pathogens account for up to 25% of infectious cervicitis cases, and testing should also include M. genitalium and T. vaginalis [2, 6]. Testing for HSV in the context of cervicitis is not recommended unless there is high clinical suspicion (diffuse erosive and hemorrhagic lesions accompanied by frank ulceration) [1, 2, 5], although genital HSV infections are frequently unrecognized due to their subclinical or atypical presentations [6]. Cervicitis is thought to occur in 15% of women with clinically evident primary HSV-2 genital infection [5]. Our patient had no characteristic genital lesions suggesting that HSV was the pathogenic agent. Corey L. et al. reported that up to 8% of women who presented to their clinic with mucopurulent cervicitis without evidence of external genital lesions tested positive for HSV-2, but they noted that no such cases had been published [7]. Only a few cases of primary herpes infections mimicking cervical neoplasia without ulcerated skin lesions in immunocompetent individuals have been documented [8,9,10,11]. Our case differs from those published, given the acute nature of the complaints and the appearance of the cervix on clinical examination, which did not suggest a malignant cause. Our initial diagnosis of PID was called into question given the unfavorable clinical evolution of the patient after well-conducted antibiotic therapy. Upon diagnosing cervicitis, we promptly conducted all necessary infection tests to determine its etiology. Despite no strong clinical suspicion of herpes, we tested for it. The positive result highlights the importance of including HSV in the panel of tests in cervicitis patients even in the absence of clinical external lesions.

After primary infection, HSV-2 spreads in a retrograde manner to the sensory ganglia and establishes a latent infection. The virus may reactivate and induce asymptomatic viral shedding or recurrent infections [7]. Recurrence can be increased by several factors, such as immunodeficiency and the severity and length of the primary episode [12, 13]. Given the chronic nature of the disease, HSV infection can be detrimental to the physical, psychological, and social functions of infected individuals and may significantly impact a patient’s quality of life [14]. According to moderate-quality evidence [4], early oral antiviral therapy seems to decrease the duration and severity of symptoms by days to weeks, with minimal adverse drug effects, as well as reduce the risk of complications of infections (for example, urinary retention). Even persons with first-episode herpes who have mild clinical manifestations initially can experience severe or prolonged symptoms during recurrent infections. Therefore, all patients with first episodes of genital herpes should receive antiviral therapy [6]. Treatment should last 7–10 days. All three available antiviral drugs (valacyclovir 1 g orally twice a day, acyclovir 400 mg orally 3 times per day, and famciclovir 250 mg orally 3 times per day) have equivalent benefits and adverse effects [4, 6]. European guidelines recommend treatment initiation within 5 days of clinical onset or when new lesions are identified [15]. In our patient, no antiviral treatment was initiated, as the diagnosis of HSV-2 infection was confirmed 7 days after the onset of symptoms, and no new lesions were observed at the time of diagnosis. Earlier suspicion of HSV-2 could have allowed earlier treatment and might have reduced the duration and severity of the patient’s symptoms. The proposed management strategies for cervicitis are presented in Table 1.

Table 1 Suggested management of cervicitis

This case highlights the importance of considering HSV infection in the etiological diagnosis of cervicitis, even in the absence of typical genital lesions. Awareness of the possibility of HSV-2 in cervicitis patients may prevent the underdiagnosis of genital herpes. Early detection of the first episode of genital HSV infection is essential because it enables early initiation of antiviral treatment, efficiently reducing the severity and duration of symptoms. In addition to antiviral therapy, patient education, recurrence management, and transmission prevention are crucial for reducing the individual and socioeconomic impacts of this chronic infection. Additional evidence could help influence the current guidelines on testing for the presence of HSV infection in patients with cervicitis.