Mpox (Monkeypox) Presenting as Cervical and Vulvar Disease

Abstract

BACKGROUND: 

Since the beginning of the current mpox (formerly “monkeypox”) outbreak in May 2022, 23,465 confirmed cases of monkeypox virus infection have been reported in Europe; women represent less than 1% of these cases. Mpox lesions are found with greater frequency in the genital area, and, in women, have been described primarily in the vulva.

CASE: 

We present a case of monkeypox virus infection in a 28-year-old woman confirmed by polymerase chain reaction testing, in which the only clinical manifestation was the appearance of concomitant lesions in the cervix and the vulva, with no other clinical features. No other sexual transmitted diseases were found. The lesions disappeared spontaneously in 2 weeks.

CONCLUSION: 

Mpox lesions can affect the cervix; thus, recognition by gynecologists is important. Given the current epidemic outbreak, correct identification is essential to help control disease transmission.

In Brief

Proper identification of mpox (monkeypox) lesions affecting the lower genital tract in women is an important part of achieving proper control of the disease.

Teaching Points

1. Monkeypox virus infection generally manifests with genital, anal, and oral mucocutaneous lesions.
2. Monkeypox virus infection should be seen as a causative agent for cervical vulvar lesions, especially if an infectious etiology is suspected.
3. A rapid diagnosis of monkeypox virus infection by multiarray polymerase chain reaction testing is crucial, because early detection of new cases is the key to reducing disease transmission.

Mpox (formerly “monkeypox”) is a viral zoonotic infection caused by a double chain DNA virus of the genus Orthopoxvirus of the Poxviridae family.^1,2 It is so called because it causes cutaneous lesions similar to those described in laboratory monkeys infected by the smallpox virus. The current worldwide outbreak is considerably less contagious and deadly than conventional smallpox. Since the beginning of May 2022, more than 60,000 cases of monkeypox virus infection in more than 50 countries have been reported, leading the World Health Organization (WHO) to declare mpox a “moderately worrying evolving threat to public health” on June 23, 2022.³ The majority of cases (92–98%) have been reported in men having sex with men.^4–6 Infection of women during this outbreak has been uncommon, with scant mention in the literature.³

In epidemic outbreaks previous to this one, mpox has run its course with mucocutaneous lesions in many parts of the body, including the face, arms, legs, and, less commonly, the palms of the hands, plantar surfaces of the feet, and the genitals.⁷ These manifestations typically are preceded by a prodromal phase marked by fever, myalgia, and swollen lymph glands. However, cases in the current outbreak are atypical, with the appearance of lesions in fewer parts of the body (mainly genital and perianal) and with less serious prodromal symptoms.^4,7 A recent observational study in Spain noted that the most prevalent symptoms were the presence of vesicular-umbilicated and pseudo-pustular skin lesions (93.8%), asthenia (66.6%), and fever (52.1%). In addition, the location of the lesions in the genital and perianal areas was related to the patient's role in sexual intercourse.⁸ Although lesions secondary to monkeypox virus infection are currently found most frequently in the genital area, the reported involvement of the female genital tract is circumscribed to vulvar lesions. We present one of the first reported and documented cases to date of monkeypox virus infection in a woman whose only clinical manifestation was the appearance of concomitant lesions in both the cervix and vulva.

CASE

A 28-year-old woman presented to the emergency department for a vulvar lesion of at least 3 days' duration. She had no significant medical history and was nulliparous, unvaccinated against smallpox, vaccinated against human papillomavirus, and had a history of negative cytologic screening. She reported having unprotected sexual relations with an asymptomatic heterosexual man 3 weeks before the appearance of the lesion. She was afebrile and had no other systemic symptoms or dermatologic lesions.

On exploration, a flat papula-type lesion measuring 1 cm was detected on the lower third of the left hemivulva-perineum, with slightly raised borders and causing no pain on palpation (Fig. 1). The cervix had an area of irregular raised keratosis around the external cervical os. The tissue had a granulomatous appearance, with areas of necrosis in the endocervical canal (Fig. 2). On colposcopy, no changes were seen after application of 5% acetic acid. Schiller test was negative.

Fig. 1.: A. Vulvar image with flat papula-type lesion measuring 1 cm on the lower third of the left hemivulva-perineum, with slightly raised borders. B. Magnified image of the vulvar lesion.

Fig. 2.: A. Image of the cervix, with an area of irregular raised keratosis around the external cervical os. Tissue with a granulomatous appearance, with areas of necrosis in the endocervical canal. B. Magnified image of the cervical lesion. C. Colposcopy: Schiller test.

Vulvar and endocervical samples were obtained for generic culture testing, polymerase chain reaction (PCR) testing for monkeypox virus infection, and multiarray PCR testing for sexually transmitted infections (STIs) (Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, Ureaplasma urealiticum, and Trichomonas vaginalis). A serologic panel was obtained to test for STIs (human immunodeficiency virus [HIV] antibodies, hepatitis B [anti-HBs antigen, anti-HBcore, HBs antigen], hepatitis C antibodies, and Treponema pallidum antibodies). An endocervical canal biopsy was taken for histologic study. Empirical presumed STI treatment was prescribed, including intramuscular ceftriaxone (500 mg) and penicillin G (2.4 million international units) single-dose, together with oral doxycycline (100 mg twice a day for 14 days).

Test results revealed positive cervical and vulvar PCR for monkeypox virus, negative bacterial and fungi culture, and negative STI multiarray PCR. Serologic test results were negative for current infection but showed previous contact with herpes simplex 1–2 (immunoglobulin G [IgG]), Epstein-Barr virus (EBNA-IgG), Mycoplasma pneumonia (IgG), and Chlamydia pneumonia (IgG).

An anatomopathologic study with hematoxylin and eosin staining revealed squamous epithelium with the presence of necrotic keratinocytes, some of them with degenerative balonization, with inflammatory infiltrate and presence of lymphocytes and polymorphonuclear leukocytes. It also revealed nuclear alterations with nuclear enlargement, hyperchromasia, and the presence of balonization. Taken together, these observations suggest infection in the vesicular phase (Fig. 3).

Fig. 3.: A. Squamous epithelium with presence of necrotic keratinocytes, some of them with degenerative balonization, with inflammatory infiltrate and presence of lymphocytes and polymorphonuclear leukocytes (hematoxylin and eosin ×200). B. Nuclear alterations with nuclear enlargement, hyperchromasia, and the presence of balonization (hematoxylin and eosin ×200).

After the diagnosis of genital lesions secondary to monkeypox virus infection, the case was reported to the health authorities. Quarantine and sexual abstention were indicated until complete disappearance of the lesions, but no specific treatment was prescribed for mpox. Based on WHO recommendations, the patient was instructed to use condoms during any sexual activity for 12 weeks after resolution. On follow-up 7 days after the previous medical visit, the patient was asymptomatic. Physical examination showed complete resolution of the cervical lesion and an almost complete resolution of the vulvar lesion (Fig. 4). After an additional 2 weeks, the vulvar lesion was resolved.

Fig. 4.: Seven days after diagnosis. A. Physical examination showed the disappearance of the cervical lesion. B. Vulvar lesion in the process of clearance.

Further medical visits were carried out at 15 and 30 days, both confirming the complete resolution of the lesions. At present, the patient is asymptomatic and without sequelae. Additionally, serology was carried out at 1 month and 3 months from initial appearance, ruling out HIV and viral hepatitis infection, respectively.

DISCUSSION

This is a case of concomitant genital involvement of mpox in both the cervix and vulva. This is an unusual presentation of the disease in that, in the current outbreak, genital monkeypox virus infection in women has been described only in the vulva. This was described on September 13, 2022, by the European Centre for Disease Prevention and Control and the regional office of the WHO. At the time of that report, there were only 339 confirmed cases in women compared with 23,194 cases in men; women represent less than 1% of the total.³ A prospective observational cohort study published on confirmed cases in Spain reported six cases in women, representing 3% of the cases in the study.⁴

In 95% of cases, the main mechanism of transmission is sexual,^9,10 with direct contact with infectious ulcers, eschars, or bodily fluids.⁵ Microabrasions of the mucous membrane are another possible route of entry.¹¹ The normal incubation period has been established at between 5 and 13 days, although it can range from 4 to 21 days.⁷ In our case, the patient reported unprotected sexual relations with an asymptomatic heterosexual man 3 weeks before the appearance of the vulvar lesion.

In the current mpox outbreak, the guiding symptoms are papular, vesicular, and pustular cutaneous lesions, principally in the genital area and the oral mucous membrane.⁸ The lesions progress through various stages in an asynchronous manner,⁶ beginning as macular-like eruptions 2–5 mm diameter, and then evolving to papules, vesicles, and pustules.¹² The lesions are well-defined, deeply ingrained, and often become umbilicated. They present clinically in most cases as itchy and painful when the mucous membrane is involved.^6,13 The lesions typically develop scabs and then disappear at 7–14 days. When there is involvement of the mucous membranes, there may be associated painful adenopathies in the affected area.⁸ In addition, in 50% of cases, mpox also manifests with systemic clinical signs (fever, fatigue, muscle pain, chills, headache).^3,14 Although the patient may not report systemic symptomatology or painful adenopathies, the mucocutaneous lesions are morphologically similar to those described in this type of infection, and they are limited to the genital area, affecting the vulva and cervix.

Although the clinical characteristics may be useful in carrying out a differential diagnosis of the mpox lesions compared with other vesicular or pustulous eruptions (herpes simplex, Zoster virus, smallpox, and STIs such as syphilis, venereal lymphogranuloma, and canker), laboratory confirmation is required for a definitive diagnosis. This may be easily and effectively accomplished with PCR testing for monkeypox virus DNA.^15,16 If there is suspicion for STIs, it is appropriate to begin treatment with empirical antibiotic therapy pending laboratory results, as was done in the present case.^17–22 This is of paramount importance in women because some STIs, especially chlamydia infections, are associated with infertility, which can easily be prevented with a “test and treat” policy.^23–25

Another diagnostic strategy to be considered, especially when the lesions affect the cervix, is anatomopathologic study. In histopathologic terms, mpox lesions are indistinguishable from those of smallpox; they both present with stratum basale necrosis, with adjacent dermal papillae and necrosis of the stratum spinosum.^26,27 In our case, in addition to these characteristic changes, we also observed alterations that suggested that the infection was in its vesicular phase.

There are two drugs currently approved by the U.S. Food and Drug Administration and the European Medicines Agency for treatment of severe cases of mpox: tecovirimat and brincidofovir (prodrug of cidofovir with fewer adverse events).^14,28 Vaccination against smallpox was demonstrated through several observational studies to be about 85% effective in preventing mpox.^29,30 At present, the Centers for Disease Control and Prevention recommends prior vaccination against smallpox for at-risk individuals.^28,29 The role of vaccination after exposure is less clear. Current recommendations in this case are quarantine and sexual abstinence until complete disappearance of the lesions, but no specific treatment is prescribed for mpox. In our patient, the evolution was favorable, with complete resolution of the lesions.

Although there currently are minimal data available concerning the efficacy of intravenous immunoglobulin for the treatment of complications in mpox, its use may be considered in serious cases or for the prophylaxis of recently exposed individuals with limited cellular immunity for whom the mpox vaccine is contraindicated.¹⁵

Mpox cases reported in the current outbreak are infrequent in women; in those with genital infection, vulvar lesions have been described primarily to date. As in this case, cervix involvement is possible and requires a thorough gynecologic examination and testing. Given the current mpox outbreak, correct diagnosis of these mpox lesions is essential to help minimize disease transmission.