Novel severe oculocutaneous manifestations of human monkeypox virus infection and their historical analogues

Abstract

WHO has declared human mpox (formerly known as monkeypox) a global public health emergency since July, 2022. When case numbers were increasing, so did clinicians' exposures to new elements of the disease. Additionally, the burden of mpox is particularly apparent in immunocompromised patients, who can have more variable and severe manifestations of disease across organ systems. In this Grand Round, we report novel and severe oculocutaneous manifestations of mpox in this population, which are both sight and life threatening. Specifically, we highlight two patients with mpox and AIDS who had refractory skin necrosis that progressed to either ocular compromise or panfacial gangrene, or both. Both patients ultimately died due to systemic complications of their infections. Through clinical analogies, we show how past experiences with related orthopoxviruses, such as variola virus (smallpox) and vaccinia virus, can add useful context for understanding and treating these new disease states. We suspect that in patients who are immunocompromised, monkeypox virus can clinically evolve not only via viraemia but also through direct intradermal spread. We propose that intradermal spread occurs by a process clinically and immunologically analogous to progressive vaccinia, a complication previously seen after conventional smallpox vaccination. We share evidence in support of this theory and implications regarding early management and post-exposure prophylaxis for at-risk populations. Content note: this Grand Round contains graphic images of mpox lesions of the eyes and face.

Figure 1

Chronological progression of mpox facial rash (patient one) (A) 1 week after symptom onset: ulcerated vesiculopapular rash involving the malar areas and nasal bridge. Surrounding umbilicated papules. Left-sided periorbital oedema. Image courtesy of patient submission. (B) 3 weeks after symptom onset: confluent necrotic facial rash sparing the forehead with overlying honey-colored exudate. Upper and lower eyelids are oedematous, fibrotic, and immobile. There is substantial angio-oedema of the lips. (C) 7 weeks after symptom onset: prominent eschars of the nasal and malar aspects. Increased purulent exudation overlying necrotic skin. Progressive ulceration of the eyelids and distortion of periorbital contour. (D) 11 weeks after symptom onset: panfacial skin sloughing with obfuscation of baseline features. Patient passed away 1 week later.

Figure 2

Axial CT scans of the orbits (patient one) (A) 3 weeks after symptom onset: extensive facial oedema with intact ocular structures bilaterally. (B) 7 weeks after symptom onset: the right globe is ruptured with disorganised contents. The left cornea shows an anterior defect. (C) 11 weeks after symptom onset: bilateral ruptured globes with disorganised contents.

Figure 3

Chronological progression of mpox facial lesions (patient two) (A) Contiguous and centrifugal progression of facial skin necrosis from initial foci of mpox lesions. There is gradual development of panfacial gangrene. Day 1 marks the first date necrotic facial lesions were observed on clinical examination. (B) Areas of confluent necrosis are bounded by a raised skin edge containing vesicles.

Figure 4

Skin histology (patient two) The skin histology of patient one showed similar findings, but slides were unavailable for publication. (A) There is reticular alteration, ballooning, and necrosis of the epidermis with many keratinocytes exhibiting hyperchromatic or ground-glass nuclei. There is abundant karyorrhectic debris with numerous neutrophils (H&E staining, 200× magnification). (B) Pan T-cell marker CD3⁺ highlights only rare lymphocytes within the underlying dermis (100× magnification).