An HIV-positive man with painless ulcer and pustules: mpox, syphilis, or both?

Abstract

Mpox (formerly monkeypox) is a viral illness endemic in certain parts of the world such as Africa. Travel to these endemic areas has increased outbreaks in regions typically unaffected by this poxvirus. Mpox infection is characterized by prodromal symptoms including fever, chills, and lymphadenopathy, followed by a vesiculopustular exanthem. Genital lesions are common especially in vulnerable populations, such as those who engage in high-risk sexual behaviors. We report a 50-year-old man living with HIV who presented for evaluation of multiple painless genital lesions and later tested positive for both mpox and syphilis. With recent outbreaks, clinicians should evaluate genital lesions with a broad sexually transmitted infection differential. Rapid diagnosis and treatment are imperative to prevent more severe disease progression in immunocompromised patients.

CASE SUMMARY

A 50-year-old man with a history of well-controlled HIV (CD4 count 594 cells/μL and viral RNA copies <200 copies/mL) and previous syphilis infection presented in August 2022 with an enlarging, painless, necrotic ulcer on the dorsal shaft of the penis for 1 week, along with painless pustules on the penile shaft, buttocks, and forehead. He denied any subjective fever, malaise, myalgia, and inguinal lymphadenopathy. Two weeks before the clinic visit, the patient had unprotected sexual contact with a male of unknown sexually transmitted infection (STI) status. Physical examination included a thorough skin exam and visualization of mucosal sites including the oropharyngeal airway, genital tract, and anus. This patient had an unremarkable physical exam except for the presence of a 1.4 cm black-based ulcer with black eschar on the left dorsal penile shaft with an adjacent 0.4 cm pustule as well as pustules on the buttocks and forehead (Figure 1). A new RPR titer was elevated at 1:16 from a nonreactive baseline <1:1 3 months earlier, indicating a new syphilis infection. Atypical pustules on the penile shaft, gluteal cleft, and forehead prompted ordering of orthopoxviral polymerase chain reaction (PCR) from the penile pustule, which was positive. With a diagnosis of primary syphilis and mpox coinfection, the patient received penicillin G benzathine 2.4 MU but did not receive tecovirimat since the patient’s HIV was well controlled and the lesions remained localized to the genital region. All lesions healed within 42 days of initial onset without evolution.

Figure 1.

(a) A 1.4 cm painless ulcer with black eschar and 4 mm pseudopustule on an erythematous base on the dorsal shaft of the penis. (b) Painless pseudopustules with erythematous halos on left and right buttock. (c) Forehead with 3 mm pustule with erythematous halo.

Key points

• The average number of days between exposure and onset of clinical symptoms in mpox is 5 to 13 days.

• Workup for genital lesions should include testing for common, known infectious causes, and testing for uncommon pathogens in the setting of a global outbreak such as mpox.

• Physical examination should include visualization of the patient’s external lesions but also a thorough evaluation of the mucosa, especially in patients who engage in receptive oral sex.

• The diagnosis of mpox is performed via polymerase chain reaction testing for orthopoxviral DNA on suspicious lesions.

• Medical management depends on the severity of infection and comorbidities, with most cases being self-limited. In patients who require antiviral treatment, tecovirimat (TPOXX) is the current treatment of choice. For prevention, Jynneos vaccine is recommended for high-risk groups to mitigate transmission.

CLINICAL QUESTIONS

1. Match the descriptions of cutaneous manifestations to associated STIs: acute HIV infection, mpox, primary syphilis, secondary syphilis.

   1. Small lesions that progress through several stages beginning as macules and then developing into papules and/or pseudopustules before crusting

   2. A single papule that soon ulcerates and becomes indurated with well-defined margins and is typically described as painless

   3. Diffuse maculopapular eruption several weeks after exposure, typically seen on the trunk with possible extension to the palms and soles

   4. Eruption of well-circumscribed, monomorphic pink macules usually 48 to 72 hours after onset of viral mononucleosis or a flulike prodrome

2. In a confirmed mpox case, which public health authority should you report to first?

   1. State, tribal, local, or territorial health department

   2. Hospital medical safety officer

   3. Centers for Disease Control and Prevention

Correct answers are given at the end of the article.

DISCUSSION

Background

Mpox, an orthopoxvirus, was first isolated in 1958 from monkeys in an animal facility in Denmark. The first known human case was recorded in 1970 in the Congo. Prior to 2022, most human cases were exclusively outside of the United States, with most cases in Nigeria. Mpox has two distinct clades, West Africa and Congo Basin, with the latter being more severe and transmissible.

The current 2022 mpox outbreak is thought to have originated from the West Africa clade. Transmission occurs from sexual contacts among people with anogenital lesions, especially in men who have sex with men (MSM); other routes include saliva and upper respiratory secretions. Mpox infection is characterized by prodromal symptoms including fever, chills, and lymphadenopathy lasting 1 to 5 days, followed by cutaneous manifestations that appear 1 to 2 days before or 3 to 4 days after systemic illness.¹

Presentation and diagnosis

Coinfection of multiple STIs (syphilis, gonorrhea, chlamydia) has been occasionally seen in predisposed patient populations such as MSM. Choudhry et al reported a case series of 102 patients with concurrent STIs and found that syphilis was the most common STI (48%).² Risk factors include sexual orientation, occupational history, and travel history. A recent study from the Centers for Disease Control and Prevention reviewed 1969 patients diagnosed with mpox between May 17 and July 2022 across the US and found that 61% of patients were either HIV positive or had been diagnosed with a different STI within the previous 12 months, with 18% of patients having both. STIs included syphilis, gonorrhea, and chlamydia.³ A literature review highlighted that coinfection of mpox, HIV, and syphilis is seen in patients who are involved in high-risk sexual behavior and likely have coexisting STIs (Table 1).^4–7

Table 1.

Reported cases of mpox and syphilis coinfections

Case/ref	Demographic	HIV status: CD4 count, Rx	Coinfections	Mpox onset	Lesions
1/current case	50-year-old man, HIV+, MSM	CD4 count 571 cells/μL, dolutegravir-lamivudine	Mpox, HIV, primary syphilis	11 days, no prodrome	Painless 1.4 cm ulcer and 0.4 cm pustule on penile shaft Painless pustules on buttocks and forehead
24	34-year-old man, HIV+, MSM	CD4, ART unknown	Mpox, HIV, primary syphilis	9 days after exposure, 4 days after syphilis treatment	Painless vesicles ×5 on forehead Pustules with erythematous halo on left trunk Perianal umbilicated papules
35	30-year-old man, HIV+, MSM	CD4 unknown, tenofovir-lamivudine- dolutegravir	Mpox, HIV, primary syphilis, hepatitis A	2 weeks	10 pustules in anogenital area Progressive dissemination to the face, ear, trunk, limbs, and oral mucosa
46	27-year-old man, HIV+, MSMW	CD4, ART unknown	Mpox, HIV, primary syphilis	Unknown	Scattered 1–2 mm umbilicated pustules on the neck, face, arms, legs, and trunk
57	34-year-old male-to-female transgender, HIV+	CD4 count 200 cells/μL, noncompliant with ART	Mpox, HIV, neurosyphilis	6 days, prodromal headache and fever	4 painful perianal papules with erythematous base that umbilicated

ART indicates antiretroviral therapy; HIV, human immunodeficiency virus; MSM, men who have sex with men; MSMW, men who have sex with men and women; Rx, prescriptions.

Mpox can have cutaneous manifestations similar to other STIs but is differentiated based on the timeline of exposure and clinical manifestations. Mpox has an incubation period of 5 to 13 days prior to symptom onset, with or without flulike prodromes. Once cutaneous lesions are present, transmission of mpox can occur through direct contact of infectious lesions and bodily fluid. Lesions progress through several stages beginning with the presence of small macules (2–5 mm), which develop into shiny umbilicated papules or pseudopustules before crusting over 7 to 14 days after onset, indicating the lesions are no longer infectious.⁸ Physical examination should include visualization of the patient’s external lesions but also a thorough evaluation of the mucosa. With an adequate light source, clinicians should ask the patient to elevate the palate and uvula, depress and elevate the tongue, evaluate the upper and lower gingiva, and ensure a patent airway. Abnormalities should be noted on physical exam, as mpox is a reported cause of pharyngitis/ tonsillitis that can result in airway obstruction and respiratory distress.^9,10

Classically, a primary syphilis lesion, known as a chancre, usually begins as a 1 to 2 cm painless papule at the inoculation site. The incubation period is around 3 weeks from exposure and progresses to a punched-out ulcer with an indurated margin. The lesion heals within 3 to 6 weeks without treatment.¹¹ Within the next weeks to months, patients may develop systemic infection and present with constitutional symptoms and diffuse rash. Lesions are characterized as diffuse patches and plaques involving the trunk, palms, and soles.

Mpox is diagnosed via vigorous swabbing of the suspected lesions for PCR testing for orthopoxvirus DNA. It is recommended to take two different swabs from each specimen. In patients with cutaneous manifestations, a throat swab may be performed to measure viral DNA but is not necessary in confirming the diagnosis. Per guidelines of the Centers for Disease Control and Prevention, if an orthopoxvirus PCR is positive, that meets sufficient criteria for a “probable” diagnosis of mpox. Negative, positive, and equivocal results should be reported first to state, tribal, local, or territorial health departments, such as the Dallas County Health and Human Services Department in this case.⁸ Pathology reveals ballooning degeneration, acanthosis, spongiosis, keratinocyte necrosis, multinucleated syncytial keratinocytes, and epidermal intracytoplasmic inclusions consistent with Guarneri bodies, along with superficial and deep perivascular and lichenoid infiltrate.¹

Management

Medical management of mpox patients depends on severity of infection and comorbidities. In most cases, the disease is self-limited and will resolve on its own without medical intervention. Patients who develop infection in sites that are at high risk for pain such as the rectum, eyes, or oropharynx should be counseled with a multimodal pain management approach. Pain-reducing measures include over-the-counter remedies such as acetaminophen, nonsteroidal antiinflammatory drugs, and sitz baths. There are several indications for tecovirimat (TPOXX), the current off-label antiviral treatment of choice; some criteria for using antiviral therapy include severe manifestation, immunocompromised status such as HIV with CD4+ count <200 cells/μL, site of lesions that associate with stricture, and lesions such as in the pharynx and anal canal. Dosing and duration of therapy is individualized, but commonly is given as 600 mg orally or 200 mg intravenously every 12 hours for 14 days.¹² Coinfection management should follow the current established therapeutic regime.

High-risk patients, including individuals with occupational risks or engaging in receptive intercourse involving mucosal sites, may receive the Jynneos vaccine as prevention to mitigate transmission.¹² When determining patient risk and developing the proper treatment course, referral to an infectious disease physician or a public health official is of utmost importance.

This patient’s case not only shows coinfection of mpox, HIV, and syphilis, but also highlights that mpox can present as painless lesions similar to primary syphilis, prompting a thorough physical exam including total mucosal and skin surfaces. If a patient tests positive for mpox, a full STI panel should be performed to investigate for coinfections. Patients in high-risk categories should receive preventive measures and education regarding transmission of STIs and practices to minimize infection.

Disclosure statement/Funding

No funding or potential conflict of interest was reported by the authors.

ANSWERS FOR CLINICAL QUESTIONS

1a, monkeypox; 1b, primary syphilis; 1c, secondary syphilis; 1d, acute HIV infection; 2, a.