Atypical Genital Herpes Presenting as Chronic Severe Vulvitis: A Case Report

Introduction

Genital herpes is a relatively common infection caused by herpes simplex virus (HSV) type one or two (HSV‑1, HSV‑2) respectively.¹ Its classic vesicular or ulcerative lesions, however, are absent in a substantial proportion of cases. Atypical presentations include vulvar, penile, or perianal fissures; cystitis; urethritis; vaginal discharge without visible lesions; localized recurrent erythema; radicular or lower back pain; and lesions on the buttocks or thighs.² In fact, over half of culture‑confirmed genital HSV infections manifest with such non‑classic features, frequently leading to misdiagnosis.³ In women, these symptoms often mimic candidal or bacterial vulvovaginitis, contact dermatitis, or plasma cell vulvitis—particularly when chronic vulvitis presents with persistent erythema, exudation, discharge, and pruritus without vesicles. Clinicians routinely prioritize inflammatory dermatoses, allergic reactions, or premalignant conditions, and may overlook HSV in the absence of obvious grouped vesicles.

The clinical spectrum of vulvar viral infections is broad, encompassing not only genital herpes but also condyloma acuminata, molluscum contagiosum, and Lipschütz ulcers, which may be sexually or non‑sexually transmitted and affect patients across all age groups. Lesions can present as papules, verrucous growths, or painful ulcers, often causing significant functional impairment and psychosocial distress. Among these, genital herpes remains the most common viral cause of vulvar ulceration; however, its atypical manifestations—chronic erosions, fissures, vulvar pain, discharge, and recurrent erythema without overt vesicles—pose particular diagnostic difficulties. Early polymerase chain reaction (PCR) or nucleic acid amplification testing is critical for timely antiviral therapy, yet such testing is frequently delayed when classic lesions are absent.

When evaluating vulvar erosions or ulcers, it is essential to distinguish sexually transmitted etiologies from non‑sexually acquired causes. Lipschütz ulcer (acute vulvar ulceration) is a non‑sexually transmitted condition characterized by sudden onset of painful genital ulcers, typically occurring in young, sexually inactive women. It is often underdiagnosed and has been associated with Epstein–Barr virus, cytomegalovirus, Mycoplasma, Ureaplasma, and other infectious agents. Although Lipschütz ulcers are generally self‑limiting and resolve within a few weeks, they must be differentiated from HSV‑related lesions, as both may present with acute painful vulvar ulceration. Unlike HSV, Lipschütz ulcers typically lack vesicular precursors and are non‑recurrent; HSV can be confirmed by PCR or serology, which show positive results in active infection. Recent reviews have highlighted these diagnostic challenges and the need for careful clinical distinction.^4,5

Despite increasing awareness of atypical genital herpes, the specific diagnostic pitfalls in women with chronic, treatment‑refractory vulvitis remain underemphasized.^6,7 In particular, the potential value of simple bedside maneuvers—such as saline cleansing to remove exudate and expose subtle epithelial defects—has not been adequately highlighted as a prompt for virologic testing. We report a 59‑year‑old woman with severe vulvitis misdiagnosed for six months, ultimately confirmed as HSV‑2 after saline cleansing revealed pinpoint erosions. This case illustrates why HSV testing should be considered in refractory vulvitis and demonstrates how a straightforward clinical observation—cleansing exudate to uncover subtle lesions—can guide timely diagnosis, and highlights the importance of maintaining a broad differential that includes both sexually transmitted and non‑sexually acquired vulvar ulcerative diseases.

Case Presentation

A 59-year-old woman presented with a six-month history of vulvar erythema, exudation, increased vulvar discharge, pruritus, and burning pain. Symptoms began in July 2025 with pruritus, followed by erythema and edema of the labia, accompanied by post-void burning pain; urinalysis was unremarkable, excluding urinary tract infection. Initial self-treatment with topical triamcinolone econazole and mupirocin provided no relief. At a local municipal hospital, vaginal discharge analysis showed leukocytes (++), while tests for Chlamydia trachomatis, Mycoplasma, and Neisseria gonorrhoeae were negative. She received intravenous ceftriaxone and topical ethacridine lactate for 10 days, with only transient improvement; recurrent episodes soon followed. In January 2026, the patient experienced aggravated pruritus and was evaluated at our dermatology outpatient clinic. Examination revealed extensive erythema, mild edema, and copious exudate involving the vulva (Figure 1a). A first vulvar biopsy (February 2026) showed mild epidermal hyperplasia, spongiosis, and a dense dermal infiltrate predominantly composed of lymphocytes, eosinophils, and plasma cells (plasma cells comprised <25% of the infiltrate with focal distribution) (Figure 1b); direct immunofluorescence was negative, effectively excluding autoimmune blistering diseases. She was treated with topical ethacridine lactate solution, topical nadifloxacin cream, oral compound glycyrrhizin (Mieneng tablets), and oral doxycycline for one week, but with poor response. The patient was hospitalized at our institution on February 27, 2026. Her relevant background history included menopause at age 43, no history of diabetes mellitus, HIV infection, autoimmune diseases, or other comorbidities; she denied any history of immunosuppressive medication use, prior oral or genital herpes, and had no new sexual exposure in the past year (her partner was reported as healthy). Upon admission, extensive microbiological and serological workup was performed, including tests for syphilis, HIV, candidiasis, bacterial vaginosis, trichomoniasis, and HPV-related disease, all of which were negative. Laboratory findings included: vaginal discharge with leukocytes (++) and cocci (++); eosinophils 14.1% (1.24 × 10⁹/L); and IgE > 1000 IU/mL. Lymphocyte subsets, hepatitis serologies, renal and hepatic function, electrolytes, Dsg1, Dsg3, and BP180 were all within normal limits or negative.

Figure 1 Clinical photograph and histopathology at the time of first biopsy.(a). Clinical photograph of the vulva at first biopsy.(b). Histopathology of the vulvar lesion at first biopsy.(Dense dermal inflammatory infiltrate composed predominantly of lymphocytes, eosinophils, and plasma cells.) (HE×100).

Daily saline cleansing of the vulvar lesions was initiated using a standardized bedside maneuver: a clean cotton swab moistened with normal saline was gently applied to cleanse the local eroded surface. After cleansing, the surface exudate was markedly reduced, exposing several subtle, small, round erosions with red bases that had been partially obscured by secretions (Figure 2a). This observation prompted specific virologic testing. On March 5, 2026, a specimen was collected directly from the base of the vulvar pinpoint erosions for HSV DNA detection using a commercially available kit (Daan Gene Co, Ltd, PCR-fluorescence probe method) with 40 amplification cycles; the positive quantitative Ct value was <27 (linear range of the assay: 5.0×10²–5.0×10⁶ copies). HSV-2 DNA tested positive, while HSV-1 DNA was negative. Serum HSV-1/2 IgM were negative, and IgG were positive. Given the prior episode in July 2025 and the current recurrence in 2026 combined with the IgG-positive/IgM-negative serological pattern, this episode was interpreted as recurrent HSV-2 reactivation rather than a primary infection.

Figure 2 Clinical photograph and histopathology at the time of second biopsy. (a). Clinical photograph of the vulva at second biopsy (Black arrows indicate punctate erosions). (b). Histopathology of the vulvar lesion at second biopsy. (No obvious multinucleated giant cells identified in the epidermis; diffuse lymphocytic and eosinophilic infiltration in the dermis.) (HE×100).

A second vulvar biopsy was performed on March 6, 2026, which showed prominent spongiosis without evident multinucleated giant cells, vacuolated cells, or ballooning degeneration; the dermis contained a diffuse infiltrate of lymphocytes and eosinophils (Figure 2b). Immunohistochemistry for HSV on tissue was negative, and HSV-2 PCR on tissue was not performed, which we acknowledge as a limitation of this case. To assess possible extension to the lower genital tract, colposcopy was performed, which revealed no abnormalities of the vagina or cervix, thus excluding cervical or vaginal HSV co-involvement (Figure 3a and b). Based on the constellation of recurrent vulvar erosions/exudate, positive HSV-2 DNA from the erosion base, and positive serum HSV-2 IgG with negative IgM, the inpatient team established the diagnosis of recurrent genital herpes (atypical presentation) as the cause of the chronic vulvitis.

Figure 3 Colposcopic images of the vagina and cervix (a). Colposcopic image of the vagina. (b). Colposcopic image of the cervix.

On March 5, 2026 (the same day HSV-2 was confirmed), oral valacyclovir 0.5 g twice daily was initiated. This dose was selected as standard suppressive/recurrent-episode therapy per guidelines, given the patient’s prior symptomatic episode in 2025 and the current severe but recurrent presentation. After 5 days of treatment, lesions had not completely healed; considering her history of severe symptoms and short-term recurrence, therapy was extended for an additional 3 days (total 8 days). By day 8, the erosions had healed substantially, with complete resolution of pain, pruritus, discharge, and erythema (Figure 4a–h). No further antiviral therapy was administered thereafter. We acknowledge that no post-discharge photographic documentation was available, which represents a limitation of this case.

Figure 4 Clinical improvement following valacyclovir therapy.(a). Clinical photograph on day 1 post-treatment. (b). Clinical photograph on day 2 post-treatment. (c). Clinical photograph on day 3 post-treatment. (d). Clinical photograph on day 4 post-treatment.(e). Clinical photograph on day 5 post-treatment. (f). Clinical photograph on day 6 post-treatment.(g). Clinical photograph on day 7 post-treatment. (h). Clinical photograph on day 8 post-treatment.

Discussion

Genital herpes is a common sexually transmitted infection with a higher seroprevalence in women than in men in many populations.⁸ First-episode genital herpes may represent primary infection (seronegative for both HSV‑1 and HSV‑2) or non-primary infection (seropositive for one type but newly acquiring the other).⁹ Notably, up to 87–90% of HSV‑2 seropositive individuals aged 14–49 years are unaware of their infection.¹⁰ While these statistics underscore the public health burden of HSV‑2, the present case illustrates a different but equally important challenge: symptomatic infection that remains unrecognized despite repeated medical encounters. Our patient had persistent vulvar symptoms for six months, underwent two biopsies, received multiple antibacterial, antifungal, and anti-inflammatory therapies, yet HSV‑2 was not considered until saline cleansing revealed subtle erosions that prompted targeted testing.

Atypical presentations of genital herpes are common and contribute significantly to diagnostic delay.² The clinical spectrum includes vulvar fissures, recurrent erythema, increased discharge, cystitis, urethritis, cervicitis without external lesions, radiculopathy, and—in immunocompromised hosts—hypertrophic ulcers that may mimic malignancy.^11–16 In immunocompetent patients, however, chronic erosive vulvitis without classic vesicles—as seen in our case—is particularly deceptive. The absence of grouped vesicles led clinicians to pursue alternative diagnoses repeatedly, while the partial symptomatic improvement with antibacterial and anti-inflammatory agents further obscured the underlying viral etiology. This case reinforces that HSV should remain on the differential for any chronic or recurrent vulvitis that fails to respond to conventional therapies, regardless of whether classic vesicular lesions are present.

The serological findings in our patient merit careful interpretation. Serum HSV‑2 IgG was positive while IgM was negative, indicating prior HSV‑2 exposure rather than primary infection. Given the patient’s reported episode of similar symptoms in July 2025 and recurrence in 2026, we interpret this episode as recurrent HSV‑2 reactivation rather than a primary or non-primary first episode. This distinction is clinically relevant: recurrent disease typically requires a lower dose and shorter duration of antiviral therapy than primary episodes. Our patient received valacyclovir 0.5 g twice daily for 8 days, a regimen consistent with standard management of recurrent genital herpes, and achieved complete resolution by day 8.

The differential diagnosis of chronic vulvitis is broad and includes infectious, inflammatory, and neoplastic entities. In this patient, candidal vulvovaginitis was excluded by negative fungal microscopy and culture; gonococcal, chlamydial, and mycoplasmal infections were ruled out by negative nucleic acid amplification tests from vaginal/cervical specimens; bacterial vaginosis and trichomoniasis were excluded by negative wet-mount and culture; and syphilis and HIV were excluded by negative serology. Among non-infectious causes, contact dermatitis was considered but appeared unlikely given the lack of improvement with withdrawal of potential irritants and the persistence of symptoms despite topical corticosteroid therapy. Lichen sclerosus and lichen planus were less consistent with the clinical findings and histology, which showed no characteristic features of these entities. Desquamative inflammatory vaginitis, vulvar intraepithelial neoplasia, extramammary Paget disease, fixed drug eruption, Behçet disease, Crohn-related vulvar disease, and autoimmune blistering diseases were excluded based on the clinical presentation, negative direct immunofluorescence, and absence of systemic or gastrointestinal symptoms. Plasma cell vulvitis (PCV) warrants specific consideration, as the first biopsy showed a dermal infiltrate containing plasma cells. However, plasma cells are normally present in vulvar mucosa, and a proportion of less than 25% of the infiltrate—as observed in our patient—is considered non-specific. The focal distribution and relatively low density of plasma cells in our case did not meet the clinicopathological criteria for PCV, which typically presents as well-demarcated erythematous patches with a dense, band-like plasma cell infiltrate.^17,18 In our immunocompetent patient, however, PCV was not the primary diagnosis.

When evaluating vulvar ulcers or erosions, clinicians must also consider non-sexually acquired causes such as Lipschütz ulcers, which typically present as sudden-onset, painful, symmetrical genital ulcers in young, sexually inactive women, often with prodromal flu-like symptoms and associations with Epstein–Barr virus or Mycoplasma infection. Our patient’s age (59 years), chronic course (six months), recurrent pattern, and positive HSV‑2 testing effectively excluded this entity.

The identification of pinpoint erosions after saline cleansing was the pivotal diagnostic clue in this case. Before cleansing, the vulvar surface was covered with copious exudate that obscured underlying epithelial defects. Using a simple bedside maneuver—a cotton swab moistened with normal saline gently applied to remove exudate—several small, round erosions with red bases became visible. This observation prompted direct sampling from the erosion base for HSV‑2 DNA testing, which returned positive. We emphasize that this observation is based on a single case and does not establish saline cleansing as a validated diagnostic test. Rather, we describe it as a safe, inexpensive, and potentially helpful visualization maneuver that may improve mucosal examination in select patients with exudative vulvar lesions. Larger studies would be needed to assess its generalizability.

The histopathological findings in our case were non-specific and did not show the classic features of HSV infection, such as multinucleated giant cells, ballooning degeneration, or intranuclear inclusions. Two biopsies revealed spongiotic dermatitis with eosinophilic infiltration, a pattern that can be seen in various inflammatory conditions and does not exclude HSV. Immunohistochemistry for HSV on tissue was negative, and HSV‑2 PCR on tissue was not performed, which we acknowledge as a limitation. The absence of viral cytopathic changes on histology should not dissuade clinicians from pursuing virologic testing when the clinical suspicion for HSV is high, particularly in cases with atypical presentations.

We also recognize that the empirical use of topical corticosteroids and antibiotics—while often prescribed for vulvitis—may have contributed to the diagnostic delay by transiently suppressing inflammation or altering local microbial flora, thereby masking the underlying viral process. However, the claim that these agents directly promote HSV replication requires more robust evidence and should not be overstated. A more cautious interpretation is that such therapies may delay correct diagnosis by producing partial or temporary symptom relief without addressing the viral cause, allowing the disease to persist or recur.

Several limitations of this case should be acknowledged. First, as a single-case report, our findings may not be generalizable. Second, HSV‑2 DNA was obtained from the erosion base, but tissue PCR or immunohistochemistry on the biopsy specimens was not performed; thus, we cannot definitively prove that HSV was the sole cause of the entire six-month inflammatory course. Third, the diagnosis of recurrent HSV‑2 reactivation relies on serological interpretation (IgG positive, IgM negative) combined with clinical history, rather than on demonstration of seroconversion or primary infection. Fourth, no post-discharge photographic documentation was available, limiting visual follow-up assessment. Fifth, follow-up duration was limited to two months, and long-term recurrence rates and the potential need for suppressive therapy remain unknown. Finally, the role of saline cleansing in revealing lesions is based on a single observation and requires further validation.

Based on this experience, we offer the following practical recommendations for clinicians evaluating patients with chronic or treatment-refractory vulvitis. First, maintain a low threshold for HSV testing even in the absence of classic vesicles. Second, perform careful physical examination after gentle cleansing of exudate to expose subtle erosions, fissures, or epithelial defects that may represent atypical HSV lesions. Third, when suspicious lesions are identified, obtain HSV nucleic acid amplification testing (PCR) directly from the lesion base rather than relying on vaginal secretions alone, as this improves diagnostic specificity. Fourth, avoid dismissing HSV in patients with non-specific histology; viral cytopathic changes are often absent in atypical presentations. Early recognition and targeted antiviral therapy are essential to prevent prolonged morbidity, unnecessary treatments, and avoidable healthcare costs.

Conclusion

In conclusion, this case demonstrates that genital herpes can present as chronic, treatment‑refractory vulvitis without obvious classic grouped vesicles or large ulcers. For patients with persistent or recurrent vulvar inflammation that fails to respond to antibacterial, antifungal, or anti‑inflammatory therapies, clinicians should consider HSV and obtain nucleic acid amplification testing (PCR) directly from suspicious lesions when feasible. In this patient, gentle saline cleansing helped remove exudate and unmask pinpoint erosions, prompting targeted virologic testing; however, this observation should be regarded as a bedside maneuver rather than a validated diagnostic method. Timely HSV testing and appropriate antiviral therapy can reduce prolonged morbidity and transmission risk, underscoring the importance of careful lesion visualization and lesion directed HSV testing in atypical presentations.