Mpox challenges in a clinical setting: patterns of skin lesions, diagnostic clues, and long-term consequences

The World Health Organization declared the ongoing Mpox outbreak a public health emergency of international concern on August 14, 2024, in the context of an increased number of cases identified in Africa and a significant international spread. Available data points to a higher fatality rate compared to the 2022 outbreak, specific epidemiologic characteristics of the viral clades, limited resources, and control strategies.¹ As the situation continues to evolve, physicians and community workers across the globe must prepare to prevent and manage the infection,² from the recognition of Mpox signs and symptoms to the fast diagnosis, proper treatment, and long-term care.

The experience of the previous outbreak led to the identification of mucocutaneous lesional patterns, summarized in Dogra et al.'s review.³ The typical rash consists of widespread evolutive lesions, passing through stages of macules and papules, umbilicated pustules and vesicles, crusts, and desquamation over the course of 14–21 days (Figure 1a). However, the reliance on this presentation predisposes to underdiagnosis and continued community spread, as the review authors suggest. This is because endemic cases, usually infected through animal-to-human transmission, have localized lesions confined to the contact area (Figure 1b). The severity of the skin findings can also significantly vary, from no mucocutaneous involvement to severe, profound ulcers (Figure 1c), especially in immunocompromised patients such as people living with HIV—a risk group for the infection.² Mpox facial lesions can be extensive (Figure 1d) and may resolve with unaesthetic scars.

Anogenital lesions (Figure 1e,f), present in the majority of Mpox patients, can be the initial or only skin finding. This localization is of particular interest, considering the great importance of sexual transmission in the 2024 international spread¹ and the multiple possible differentials, such as molluscum contagiosum and herpes. Furthermore, Mpox presentations with a solitary, painless genital ulcer can make the differential with syphilis difficult. In the current issue of the Journal, Gao et al.⁴ report the usefulness of dermoscopy for the correct, timely diagnosis in such presentations, starting from misdiagnosed cases of Mpox presenting solely with genital umbilicated papules, confused with molluscum contagiosum or herpes and treated accordingly. The dermoscopy finding of a dark center, surrounded by a homogenous white, structureless, circular area, artistically compared to a Chinese doughnut,⁴ proved specific for Mpox papules and excluded the initial misdiagnoses.

The infection is usually self-limited, requiring only supportive treatment. However, the skin lesions can progress to various types of scars, some of them disfiguring, which can cause a significant burden and stigmatization of the infection even after its clearance. In the current issue of the Journal, Grau-Echevarría et al.⁵ have analyzed the long-term (12–15 months) consequences of the cutaneous lesions in their cohort of 40 Mpox patients, discovering an alarming prevalence of residual scars (47.5% participants), with a significant impact on the quality of life, especially in facial or genital localizations.⁵ Furthermore, the authors explored a series of determinants for the appearance of post-lesional scars, reporting statistically significant younger patients and earlier development of skin manifestations throughout the infection in the group that developed scars.

As new real-world and practice data emerge, the skin manifestations of the Mpox infection prove to be increasingly challenging. They have varied clinical presentations, are sometimes tricky to diagnose, and can have potential mutilating consequences. Dermoscopy assessment and long-term follow-up appear to be useful strategies for dermatologists worldwide.