BH, an intestinal parasitic protozoan, exhibits primarily vacuolar, granular, and amoebic features [5]. Clinical presentations of BH infection include abdominal pain and diarrhea. A minority of patients experience symptoms such as anorexia, abdominal distension, constipation, and stomach pain [6]. BH was historically considered to be clinically inconsequential, requiring little attention. However, has emerged as an opportunistic pathogen with relevance to intestinal disease. For instance, a systematic review suggested that intestinal colonization by BH may exacerbate colorectal cancer by altering the host immune response and increasing oxidative damage [7]. Additionally, BH is implicated in the development of irritable bowel syndrome through its influence on serum IgA levels [8]. Moreover, BH infection has been linked with several extraintestinal diseases [9, 10]. In a case involving a boy with Henoch-Schönlein Purpura, who experienced recurrent abdominal pain and rash after steroid treatment, BH was detected in the stool; symptoms improved following BH eradication with a compound triazole [9]. Additionally, BH contributes to the occurrence of Hashimoto's thyroiditis by engaging in immune responses, and BH eradication has shown promise in ameliorating Hashimoto's thyroiditis [10, 11]. Notably, in our case, we detected BH in the patient's stool.

In our case, the boy's platelet count did not improve following first-line treatment. Intriguingly, only after metronidazole was administered to eradicate BH did we observe a recovery in his platelet count. These findings suggest an unidentified relationship between BH infection and the pathogenesis of ITP. Although the mechanism of BH infection in some immune diseases has been elucidated, this is the first instance that BH infection was identified in the stool of patients with ITP. Consequently, the precise manner in which BH contributes to the onset of ITP remains unclear.

The disruption of intestinal microflora is a critical mechanism in understanding ITP. A study involving 16 children with ITP showed an increased abundance of Bacteroides and actinomyces in their stool compared to healthy children. This shift in population potentially contributes to the development of ITP by regulating IgG levels [12]. Remarkably, a study comparing gut flora in BH positive and BH-negative individuals reported alterations in the abundance of Bacteroides and Firmicutes in the former, resembling patterns seen in dysbiotic flora [13]. In addition, another study demonstrated that the presence of BH was associated with increased gut bacterial diversity, with a negative correlation observed with bacteroides levels [14]. This leads us to speculate that BH may play a role in the onset of ITP by influencing the equilibrium of intestinal microflora and the abundance of specific intestinal bacteria. However, since our patient did not undergo a complete stool microbiota examination, further research is necessary to test this relationship.

ITP patients exhibit an imbalance of CD4 + T cell subsets and abnormal secretion of associated cytokines [15]. CD4 + T cells differentiate into TH1 cells (IFN-γ, IL-2, TNF-β) and TH2 cells (IL-4, IL-5, IL-6, IL-10, IL-13), while TNF-α is secreted by macrophages. Collectively they play an important role in the pathogenesis of ITP. Additionally, Th17 cells (IL-17A, IL-17F, IL-21, and IL-22) are known to play an inflammatory role in mediating autoimmune diseases.[15].

One study showed elevated levels of IL-6, IL-17, and IFN-γ in the serum of ITP patients, along with decreased levels of IL-4 and TGF-β [16]. In our patient, we observed an increase in IL-6, IL-17, and IFN-γ, while TNF-α, IL-4, IL-8, IL-10, IL-5 and IL-2 were not significantly altered. It has been shown that BH can modulate immune responses, leading to the activation of immune cells and an increase in various interleukins [17]. The diverse BH subtypes may exert varying effects on intestinal flora and cytokines, resulting in distinct outcomes. One study suggested that the BH3 subtype shows greater therapeutic potential than others, promoting an increase in IFN-γ levels and inducing inflammatory responses [18]. IL-17, a key cytokine involved in regulating autoimmune disease, is secreted by Th17 cells and CD8-positive T cells, both of which are increased in ITP [19]. In cases of steroid-refractory ITP, there is an elevated IL-17 expression [20]. Studies have demonstrated high IL-17 expression in the intestinal mucosa of BH-infected mice [21]. The BH7 subtype has been shown to trigger ERK and JNK pathways in vitro, thereby influencing the expression of pro-inflammatory cytokines in macrophages, including IL-1β, IL-6, and TNF-α [22]. Based on these findings, we speculate that the observed cytokine abnormalities may be a potential mechanism by which BH infection could contribute to the development of ITP. Unfortunately, we did not go further to conduct a genetic classification. In addition, because the father did not agree to draw the patient's blood again, no results were obtained on cytokine levels after ITP remission.

In short, the exact mechanism of thrombocytopenia due to BH infection in this patient is unclear. But this interesting case reminds us of the importance of screening for potential predisposing factors in all ITP patients especially in those who did not respond well to the standard first-line treatment. The optimal treatment strategy for secondary ITP should include the management of the underlying disease.