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.