Unilesional monkeypox: A report of two cases from Italy.

Dear Editor,

Monkeypox (MPX) is a zoonotic disease caused by a double-stranded DNA virus belonging to the genus Orthopoxvirus in the family Poxviridae [1]. Typical manifestations include fever, lymphadenopathy and a vesico-pustular rash consisting of lesions that progress through different clinical stages [2]. Historically, human-to-human and animal-to-human transmission has been limited to Africa, mainly via close contact and respiratory droplets.

The recent MPX outbreak has challenged this view, crediting sexual transmission as a new route of spread and shaping up as a public health concern across the globe, particularly in Men that have Sex with Men (MSM) [1,2].

Herein, we report two cases of human MPX characterized by a single cutaneous lesion, with no sign of systemic involvement. Demographics, clinical and laboratory features are summarized in Table 1 . Patient 1 was a 35-year-old Italian MSM living with HIV currently under combination antiretroviral therapy with undetectable viral load, while patient 2 was a 29-year-old HIV-negative Italian MSM. Both of them presented at the Sexually Transmitted Infection (STI) Centre of Milan, complaining of a single genital lesion appeared respectively four and two days before; no concurrent systemic symptoms were appreciated. Both had a history of syphilis and patient 2 also reported having been treated for gonorrhea in the past. Physical examination revealed a single, umbilicated vesico-pustular lesion on the foreskin in patient 1 and on the penis shaft in patient 2 (Fig. 1 a and b). In both cases dermoscopy showed whitish structureless areas with a brownish central depression and peripheral erythema (Fig. 1c and d). No other mucosal or cutaneous lesions were observed, and no lymphadenopathy was appreciated on palpation. Patient 1 reported travelling abroad (Greece and Spain) in the preceding weeks, where he had numerous condomless sexual intercourses; patient 2 denied travels, but reported an unprotected intercourse with an unknown partner a few days prior to the onset of the eruption. Moreover, neither had been vaccinated for smallpox. Vesico-pustular swabs tested negative for Herpes simplex virus (HSV), Chlamydia trachomatis (CT) and Treponema pallidum (TP), but positive for MPX on real-time polymerase chain reaction (PCR) in both patients. Interestingly, pharyngeal swabs tested negative for MPX DNA in both cases. Considering the lack of systemic involvement, both patients were sent home for self-isolation for 3 weeks. No new lesions appeared during this period.

Table 1

Epidemiological, clinical and laboratory data of two cases of unilesional MPX.

Patient	Age	Sex/Sexual behaviour	HIV status	Travels abroad	Unprotected sexual intercourses in the previous month	Vaccination for smallpox	Previuos STIs	Number of lesions	Localization	Systemic symptoms	MPX DNA Skin lesions	MPX DNA pharynx
1	35	MSM	+	GreeceSpain	Yes	No	Syphilis	1	Foreskin	No	+	–
2	29	MSM	–	No	Yes	No	Syphilis, Gonorrhea	1	Penis trunk	No	+	–

Fig. 1

Single vesico-pustular lesion with marked umbilication on the foreskin of patient 1 (a) and on the penis shaft of patient 2 (b). Dermoscopy showed whitish structureless areas with a brownish central depression and peripheral erythema in both cases (c,d).

According to a large multicenter study [3], unilesional presentation accounts for about 10% of all MPX cases. Speculatively, either lower viral loads and/or better control of the infection by the host's local immunity may play a role. Indeed, both our cases lacked systemic involvement (e.g., fever, lymphadenopathy, general malaise) and had negative pharyngeal swabs, consistent with a very localized infectious process. Nonetheless, factors contributing to this peculiar clinical picture are still incompletely understood.

A high index of suspicion is required to distinguish this unilesional MPX from other STIs, such as primary syphilis, lymphogranuloma venereum, and notably molluscum contagiosum. As previously reported, dermoscopy can assist the diagnosis, showing a specific pattern [4]. However, possible cases must always be confirmed by means of a Nucleic Acid Amplification Test demonstrating the presence of MPX DNA in the lesions.

In conclusion, unilesional MPX faces us with new challenges, both in terms of diagnostic difficulty and prevention strategies, as its benign course raises the chances of the disease going unnoticed, thus furthering the epidemic.

Funding/support

None.

Authors’ contributions

Eleonora Quattri, Gianluca Avallone and Carlo A. Maronese: Conceptualization, Methodology, Writing-Original Draft, Investigation, Resources. Marco Cusini and Carlo G. Carrera: Data curation, Project administration. Angelo V. Marzano and Stefano Ramoni: Writing-Review and Editing, Supervision.

Declaration of competing interest

All authors declare no conflicts of interest.