Introduction

Mpox virus, formerly known as Monkeypox, is an emerging zoonotic viral disease caused by the Monkeypox virus, a member of the Poxviridae family, which has been traditionally confined to central African countries, with only sporadic cases outside this region.^1,2 However, Mpox has recently spread worldwide, making it a global health concern.^3,4 Usually, the clinical presentation of Mpox includes fever, headache, lymphadenopathy, and a characteristic rash that progresses through several stages (from macules to papules, vesicles, pustules, and crusts), affecting inoculum areas (eg mucosae and genitalia). Although Mpox primarily presents with systemic and cutaneous symptoms, it can also lead to urological complications, necessitating specialized attention. Furthermore, this symptomatology, which is often initially non-specific, can delay diagnosis and treatment.^5–8 Correct knowledge of the possible clinical manifestations of the virus also by urologists is pivotal, not only for Mpox patient care, but also for its prevention, prompt diagnosis and reduction of contagion.

The aim of this scoping review is to summarize the current evidence regarding the urological manifestations of Mpox, possible complications, and available treatments.

Materials and Methods

Literature Search Strategy

An electronic systematic search of the current literature was conducted through the Medline and NCBI PubMed and Scopus databases on 18^th August 2024. Our study search and inclusion criteria were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.⁹ The search terms and keywords used were: “monkeypox; Mpox” (MeSH Terms), combined with different terms: “urology”, “kidney”, “ureter”, “bladder”, prostate”, “genitals”, “penis”, “testicles”, “urethra”, in all different possible combinations. References from commentaries, editorials, conference publications, review articles, and included studies were hand-searched and cross-referenced to ensure completeness. The research was performed independently by two Authors (GM and GD), and any disagreement was resolved by a third independent researcher (GG). The initial screening was done on the base of titles and abstracts. Any duplicates were screened, identified, and removed by Endnote (Version 9.2; Clarivate Analytics, Philadelphia, PA, USA) automated tools. The research focused on the urological manifestations of Mpox virus. Non-urological manifestations concerning kidney transplant patients were not considered relevant for this review. As regards genital lesions, only those relating to the male genitals were considered in the review.

Inclusion and Exclusion Criteria

Due to the paucity of literature in this field, also case series and case reports about “urological” clinical manifestations of Mpox virus were considered for the review. Other publications such as reviews and editorials were excluded, but screened in order to identify possible articles missed by our search strategy. The most recent publication was considered if the same patient cohort was used in more than one study. Only studies published in English were included.

Data Extraction Design

When available, the following data were extracted from each eligible study: article information (authors, study design, year), objectives, study cohort, sample size, patients’ characteristics, clinical manifestations, involved organs, follow-up, risk factors, and outcomes.

Results

The flow diagram in Figure 1 depicts the number of publications selected or excluded through the different phases of our electronic literature search. After electronic search, we identified 284 studies (118 from PubMed and 166 from Scopus). After duplicates removal we found a total of 193 studies for screening. After careful evaluation we excluded 157 articles for a total of 32 articles included in the systematic review.^10–41

Figure 1 Flow diagram of publications explored.

Type of Articles and Origin

Almost all articles were case reports or small case series, of which only 2 had more than 10 cases described. Most of articles came from US (31.2%) and Italy (18.7%). However, cases were reported from all continents apart from Oceania.

Clinical Data

A total of 116 patients were included, all males. The genitals were the most interested organs, associated with urethritis, while bladder and kidneys seemed to be not impacted by the disease (Table 1). Patients were usually young, with a mean age of 36 years [31.5–40 years]. The most prevalent risk factor was sexual intercourse in the days/weeks before the appearance of symptoms in males who have sex with males (MsM) group. Seventeen studies reported previous sexually transmitted diseases (STDs), while 14 did not report previous comorbidities. Forty patients (34.4%) had HIV co-infection. Fourteen studies reported a genital onset, 17 systemic symptoms before the appearance of genital signs, and two a concomitant onset of both genital and systemic symptoms. In those who reported subsequent genital presentation, this usually occurred after a mean 5 days [4–7 days] after the systemic one. In most cases, the urological presentation was a genital lesion (often penile/foreskin umbilicated pustules or a vesicular/macular lesion) accompanied by swelling. Groin/inguinal mono or bilateral lymphadenopathy could be present. Fever, headache, arthromyalgia, diarrhea and skin lesions were the most commonly associated signs and symptoms. In some patients, urethritis could be concomitant (see Table 1).

Table 1 Overview of Included Studies

Management and Follow-Up

When reported, all patients had a molecular confirmatory diagnosis by a polymerase chain reaction (PCR) test, obtained on swab or biopsies taken from the lesions/pustules. Five articles out of 32 (15.6%) reported the need for surgical debridement of penile and genital lesions due to their clinical worsening. However, in most reports, patients experienced spontaneous resolution of the lesions and symptoms, generally within a month of the onset of signs of the disease. Isolation and contact-tracing were fundamental to decrease disease spreading. Furthermore, in 9 studies (28.1%) patients were managed with tecovirimat, in all cases with a complete resolution. In 13 studies antibiotic prophylaxis or therapy was administered in order to avoid superinfections or to treat concomitant infections such as bacterial urethritis. All patients recovered but one who died due to multiple organ failure.

Discussion

Most urologic Mpox cases were reported as case reports or small case series, with the majority originating from the United States and Europe, while cases were reported from all continents except Oceania. These results suggest that the disease is not limited to specific geographic regions, but is a current global health issue. Although it is more prevalent in sub-Saharan Africa, reporting may be biased towards more developed countries, where healthcare infrastructures allow for better diagnosis and data reporting. Efforts should prioritize surveillance and widespread reporting systems to better characterize the real burden of the urological manifestation of Mpox.

In terms of patient demographics, it is notable that all cases involved were males, mainly with genital involvement. The disease predominantly affects the genital area, while the bladder, kidneys, and organs of the genito-urinary system are spared, possibly underlines the localized nature of the Mpox and its route of infection, at least in its early stages. MsM with a recent sexual activity were found to be at higher risk of urological Mpox. The observed median age of 36 years reflects a relatively young patient population, which may have implications for public health and sexual health education strategies. Systemic symptoms, including fever, headache, and arthromyalgia, were commonly reported prior to genital involvement, with genital symptoms occurring after a median of approximately five days from the onset of systemic signs. This temporal relationship between the onset of systemic and genital signs highlights the need for early recognition of systemic symptoms, which can aid in the diagnosis and management of the disease before genital symptoms fully manifest. However, in several cases the genital manifestation occurred before the systemic symptoms. A serious problem could also lie in the lack of ability of urologists to recognize this pathology, a problem already encountered with other uncommon infectious pathologies uncommon in developed countries, such as genitourinary tuberculosis (GUTB).⁴² The genital lesions observed were predominantly penile or foreskin umbilicated pustules, with vesicular or macular lesions and associated swelling being the most common clinical findings. Lymphadenopathy, particularly in the inguinal area, was also frequently noted, adding to the characteristic presentation of the disease.

The management for these patients focused primarily on confirming the diagnosis by PCR testing of lesion smears or biopsies, with treatment strategies varying depending on the severity of symptoms.

A small proportion of patients (15.6%) required surgical intervention, such as debridement of genital lesions, due to clinical worsening. In the majority of patients, however, the symptoms and lesions resolved spontaneously within a month. This underlines that the disease is self-limiting in most cases, although monitoring and early intervention remain crucial in more severe cases and/or in case of multiple comorbidities. In addition to supportive care, tecovirimat was used in a significant number of cases (28.1%), with all patients experiencing complete symptoms resolution. This highlights the potential role of antiviral therapy in managing more severe or prolonged cases. WHO recommends the use of antiviral treatment with tecovirimat in case of extensive genital lesions. However, the availability of the antiviral is limited to some expanded access program; a second choice is cidofovir i.v.⁴³ The early initiation of the treatment is associated to a better outcome, so the early diagnosis is crucial. Antibiotic treatment may be of help in case of bacterial urethritis, with a comprehensive approach to patient management, addressing not only the primary disease but also the risk of superinfections, co-infections with other sexually transmitted diseases and proactive screening for HIV, HPV and viral hepatitis. The co-occurrence of HIV and MPOX presents unique challenges due to the potential for immunosuppression in people living with HIV (PLWH) and the impact this may have on disease severity. PLWH, especially those with a low CD4 count (<350 cells/µL) or uncontrolled HIV, are at a higher risk of developing severe MPOX.

Despite the generally favorable outcomes, there was one reported death due to multiple organ failure, despite surgical debridement and broad-spectrum antibiotic treatment. The World Health Organization (WHO) expressed global concern about the spread of Mpox and based on the recent experience with the COVID-19 pandemic, in order to alert about the potential impact of Mpox outbreaks on healthcare systems, including medical education and surgical training.⁴⁴

Study Limitations

Most of the data on urologic Mpox cases came from case reports or small case series, leading to potential publication bias. The lack of large, systematic studies limits the ability to generalize findings. Differences in healthcare systems and resources across regions may influence treatment strategies and outcomes, making it difficult to compare clinical treatment methods. In addition, the true burden of the disease in underserved areas may be overlooked. The lack of longitudinal studies limits understanding of the long-term impact of urologic Mpox, including potential sequelae or recurrence. The indirect impact of Mpox outbreaks on healthcare systems, including surgical training, was not consistently addressed in the literature reviewed, leaving a gap in understanding its wider impact.

Conclusions

The current available literature provides few insights into the clinical characteristics, management, and outcomes of patients with urological manifestation of Mpox. Known risk factors such as recent intercourse in the MsM population should drive clinical suspicion. The predominance of genital involvement, the clinical course with systemic symptoms preceding genital lesions, and the need for comprehensive MST screening are key takeaways. Additionally, the role of sexual health education and public health interventions in preventing transmission, particularly in high-risk populations, should be prioritized. Awareness of Mpox and timely diagnosis are crucial for ensuring appropriate treatment and reducing the need for surgical management and the possible risk of long-term sequelae. Finally, collaboration among dermatologists, infectious disease specialists, and urologists is pivotal to effectively managing Mpox patients.