Lives of Skin Lesions in Monkeypox: Histomorphological, Immunohistochemical, and Clinical Correlations in a Small Case Series

Abstract

Monkeypox (mpox), a former rare viral zoonosis, has increasingly made it into the public eye since the major outbreak that started in May 2022. Mpox presents with skin lesions that change over time and go through different stages (macular, papular, pustular, and early and late ulceration). In this study, we evaluated skin biopsies of all stages. Therefore, five biopsies from four patients were analyzed histologically, immunohistochemically with anti-Vaccinia virus antibodies, and electron-microscopically. Notably, the early macular stage only showed subtle viropathic changes; it did not express of Orthopoxvirus proteins in immunohistochemistry and therefore can easily be missed histologically. In later stages, immunohistochemistry with anti-Vaccinia virus antibodies might be useful to distinguish mpox from differential diagnoses such as herpes virus infections. In the ulcerative stages, the identified occlusive vasculopathic changes could be an explanation for the severe pain of the lesions reported by some patients. Despite the small number of samples examined, our analysis suggests that the histological findings of mpox are highly dependent on the stage of the biopsied lesion. Therefore, knowledge of all different stages of histology is necessary to reliably diagnose mpox histologically, especially when molecular testing is not available.

Monkeypox Virus Immune Evasion and Eye Manifestation: Beyond Eyelid Implications

“…Obliterating vascular changes typically cause intense ischemic pain, likely correlating with the sometimes severe pain reported by patients. Hence, it is plausible that both direct viral cytopathic effects and the host's immunological response contribute equally to the clinical and histological stage-like presentation of MPXV [137]. Conjunctival phlyctenules, stemming from a type IV hypersensitivity reaction (cell-mediated), are occasionally reported (Figure 3) [138,139].…”

Pan‐microscopic examination of monkeypox virus in trophoblasts cells reveals new insights into virions release through filopodia‐like projections

“…The acquisition of additional membrane of the trans‐Golgi cisternae or plasma membrane causes a change in the state of the virion which becomes wrapped and or wrapped extracellular. Current data on virion morphology are due to transmission electronic microscopy 10–15 …”

“…Fetal death has been reported in several cases to be accompanied by morphological changes in the placenta, consisting of necrotic villi and large amounts of fibrin deposits, with hemorrhages in the placental villi. 18 Although electron microscopy has provided a better understanding of the cellular infection mechanisms of MPXV by investigating biopsies from animal 19 or human, 10,12,13 and in vitro cell lines, 14,15 the exact mechanisms by which orthopoxviruses cross the placenta during pregnancy have yet to be characterized. 20 Interestingly, one hypothesis for the vertical transmission of MPXV to the fetus in pregnant women is that MPXV could originate from the vagina or maternal bloodstream to infect placental syncytiotrophoblasts via transcytosis or fusion with the trophoblast membrane.…”

“…Current data on virion morphology are due to transmission electronic microscopy. [10][11][12][13][14][15] Vertical transmission and pregnancy loss have been described following MPXV infection. 16 Although trophoblasts, the epithelial cells of the placenta, are highly resistant to infection, MPXV is able to cross the placental barrier using endocytic pathways commonly used by viruses for entry, such as clathrin-or caveolae-mediated pathways.…”

Enhancing diagnostic accuracy in common human poxvirus infections during mpox outbreak: A dermoscopy review

“…Atypical cutaneous lesions may also occur. 8 , 22 , 24 Dermoscopy plays a valuable role in recognizing mpox. Dermoscopic findings vary with the clinical stage.…”