Discussion
This systematic review is the first to explore the GI manifestations of Mpox patients. Previous studies, especially those that arose from the 2022 outbreak, mainly described general symptoms, lacking GI manifestations which are less prominent in Mpox cases. Overall, five GI presentations in Mpox patients commonly reported across studies were abdominal pain, anorexia, diarrhea, nausea and/or vomiting, and proctitis. All but one manifestation (diarrhea) was found to be heterogeneous, with an I2 value above 75%. The exception is diarrhea, which was consistently low across studies (I2=27%). We reported that the most frequently occurring GI symptom was anorexia (47%), despite only being reported by three studies. This was followed by nausea and/or vomiting (12%), proctitis (11%), abdominal pain (9%), and diarrhea (5%).
Interestingly, our subgroup analysis showed that non-African studies and studies including only adults generally had lower GI symptoms. This suggests that more GI symptoms were potentially driven by pediatric patients and those infected by the African strain of MPV. A possible explanation for this difference is the genetic clade of the virus that contributed to the more recent outbreak (in 2022). A phylogenetic analysis of the MPV which caused the 2022 outbreak shared a common ancestry with the West Africa clade [35]. Due to genomic mutations and the absence of an immune-modulating factor, the West African clade is less virulent than the other major clade of MPV, such as the Central Africa/Congo Basin clade [36]. Previous outbreaks could have involved the Congo Basin clade of the MPV, thus explaining the higher prevalence of GI symptoms, especially abdominal pain, manifesting as higher virulence. Furthermore, the higher prevalence of GI symptoms in children could be explained by the general tendency of higher virulence of Mpox in children, which was observed in previous outbreaks. The possible biological explanation for this finding rests in the difference in the innate and adaptive immune responses of children compared to adults[37].
The common GI manifestations were generally reported by studies published during different outbreaks throughout the decades since the discovery of Mpox, except for proctitis. Only studies published in 2022 and those reported patients during the 2022 Mpox outbreak reported proctitis as one of the GI symptoms. The emergence of proctitis as a novel presentation of Mpox in this outbreak had been noted by previous case reports such as those by Yakubovsky et al. and Gedelaet al. [32, 38]. A possible explanation suggested that proctitis is caused by the direct inoculation of the MPV to the anorectal mucosa during receptive anal sex [32]. Direct inoculation is an established pathophysiology in proctitis in cases of sexually transmitted infections, including HSV-2, chlamydia, syphilis, and gonorrhea [39]. The sudden increase in the prevalence of proctitis among Mpox cases during the 2022 outbreak suggested that this presentation could be used as a sign precluding the diagnosis of Mpox [40, 41]. The use of proctitis as an entry point to considering Mpox diagnosis became increasingly important since the reporting of cases such as those confirmed Mpox patients who presented without any typical cutaneous lesion but were found to have proctitis as a primary disease manifestation [32].
Despite only being reported by three studies, anorexia, or lack of appetite, was the most frequently reported GI manifestation in Mpox (47%). Pittman et al. reported that all Mpox patients with anorexia presented with the symptom during the first three days after admission, with most patients (98.1%) recovering from it [24]. Abdominal pain, and nausea and/or vomiting, although encountered less frequently, could potentially alter the appetite of Mpox patients. Moreover, oropharyngeal lesions such as ulcers and pharyngitis, commonly encountered in Mpox patients, can lead to dysphagia and reduced oral intake [42]. Anorexia, in conjunction with other gastrointestinal symptoms, could lead to more severe complications, such as dehydration. However, there is a lack of understanding in available literature as to whether anorexia or other GI manifestations of Mpox signify a more severe disease or poorer patient outcomes.
To our knowledge, this meta-analysis is the first to consolidate available data from studies that report GI and/or liver manifestations of Mpox patients. However, this meta-analysis has several limitations. First, some of the studies included in the analysis were found to be of low quality, primarily due to the nature of the study design, such as cross-sectional or retrospective studies. Second, due to the paucity of data available, liver manifestations of Mpox infection were underreported and could not analyze further. This could be due to the lack of Mpox patients who presents with liver manifestations, suggesting that further studies capture any hepatic manifestations encountered by Mpox patients. Lastly, significant heterogeneity was observed in most GI manifestations, possibly due to the different characteristics of subjects at baseline.