Abstract Chronic abdominal pain has many etiologies, one of them being parasites. The aim of this study was to find an association between chronic abdominal pain in children and Blastocystis hominis (Bh). Clinical files of patients with Bh and functional abdominal pain were reviewed. A comparison was made between patients who showed an improvement of their symptoms and those who did not. Out of the 138 patients who had functional abdominal pain and Bh, 37 patients did not receive any treatment (26.8%), while 101 received it and were treated with different antimicrobial agents (73.2%); regarding the improvement of symptoms, a statistically significant difference (p < 0.001) was observed. Chronic abdominal pain in children has different etiologies; however, we have documented through this work that it is appropriate to provide antimicrobial treatment for patients with Bh and chronic abdominal pain. Blastocystis hominis, chronic abdominal pain, irritable bowel syndrome, children, functional abdominal pain BACKGROUND Functional abdominal pain is one of the most frequent causes for consultation in pediatric routine clinical practice. However, its concept per se is unclear as well as its pathophysiological mechanisms . In 1958, J. Apley defined chronic abdominal pain as at least three episodes of abdominal pain, severe enough to affect their daily activities over a period of 3 months . This concept has been modified through time and, in the Rome III Criteria, it is considered within the functional gastrointestinal disorders (FGID) defined as an episodic or continuous abdominal pain for which there is no evidence of an inflammatory, anatomic, metabolic or neoplastic disease to explain the subject’s symptoms, occurring at least once a week during the last 2 months before its diagnosis . Some parasites such as Giardia lamblia and Entamoeba histolytica are well described as a cause of chronic abdominal pain in children, and Blastocystis hominis (Bh) is a controversial parasite, as it has been found in asymptomatic individuals [4, 5] and its actual role in abdominal pain is still unclear. Blastocystis hominis has been identified as a potential pathogenic agent responsible for FGID, namely, irritable bowel syndrome [6–8]. Although its pathophysiological mechanism is not yet established, an alteration of the intestinal permeation owing to pro-inflammatory cytokines leading to visceral inflammation and hypersensitivity has been proposed . However, the actual role of Bh as a cause of functional abdominal pain in children has not been studied. Therefore, the aim of this study was to find an association between functional abdominal pain and Bh. MATERIAL AND METHODS This was a retrospective, comparative and analytical study. A search was conducted in the electronic capture system of the National Institute of Pediatrics for all stool analyses positive for Bh between January 2003 and October 2015. The reasons for requesting an exam for these samples were screened and only those samples matching a gastroenterological diagnosis were selected. The clinical files of patients matching a referral diagnosis of chronic abdominal pain were reviewed. Functional abdominal pain Clinical files of referred patients with functional abdominal pain were reviewed and classified with functional abdominal pain if they had abdominal pain twice a week in the last 2 months before diagnosis. Stool analyses All stool analyses were conducted at the Parasitology Laboratory, using the FAUST technique. They were considered positive if any of the sent samples were positive for Bh. Response to treatment Treatment response was considered adequate when the patient had no symptoms in the control consultation visit and when three control stool analyses were negative. Files meeting these criteria were used for extracting information about gender, age, treatment, response to established management and control stool analyses results. Those cases where chronic abdominal pain criteria were not met and with incomplete information in the clinical files were excluded. STATISTICAL ANALYSIS The statistical analysis was conducted using the SPSS V21.0 software, through descriptive statistics for demographic endpoints and a chi-squared test for comparing proportions. A p value <0.05 was considered significant. RESULTS A total of 9637 samples in the database were positive for this microorganism, 2425 (28%) of which were sent with diagnoses related to gastrointestinal origin pathologies. A total of 322 samples (13%), corresponding to 166 patients, had a diagnosis of functional abdominal pain; only those of 138 patients were included, as 28 of them did not meet the inclusion criteria. Of the 138 patients with functional abdominal pain, 80 were female (58%) and 58 were male (42%). The mean age of patients was 10.96 (SD + 3.5). Regarding their management, 37 patients did not receive antimicrobial treatment (6.8%), while 101 received different types of antimicrobial agents (73.2%). Of the 101 patients who received treatment, 69 improved, while 32 continued presenting symptoms; of the 37 patients who did not receive treatment, 13 improved, while 24 continued presenting symptoms. When comparing the improvement of symptoms of patients who received treatment vs. that of patients who did not receive antimicrobial therapy, a statistically significant difference (p < 0.001) was found (Fig. 1). Fig. 1. View largeDownload slide Response to treatment comparing patients who receive treatment with those who did not receive. Fig. 1. View largeDownload slide Response to treatment comparing patients who receive treatment with those who did not receive. Table 1 shows a summary of received treatments and response to them. The mostly used treatment was metronidazole (26% patients), followed by the combination of tinidazole and mebendazole (24.6% patients). When comparing the type of treatment and symptoms improvement, secnidazole and the combination of tinidazole/mebendazole showed a similar statistical difference (p < 0.001), while nitazoxanide had less statistical difference, but still significant (p = 0.04). Metronidazole, albendazole, rifaximin and sulfamethoxazole/trimethoprim had no statistically significant differences (Fig. 2). Table 1 Antimicrobial therapy and improvement of symptoms Antibiotic Improvement of symptoms p value No Yes Albendazole 0 1 0.185 Tinidazole/mebendazole 9 25 0.001 Metronidazole 16 20 0.08 Nitazoxanide 1 8 0.004 Sulfamethoxazole/trimethoprim 1 0 0.465 Secnidazole 3 15 0.001 Rifaximin 1 0 0.465 Antibiotic Improvement of symptoms p value No Yes Albendazole 0 1 0.185 Tinidazole/mebendazole 9 25 0.001 Metronidazole 16 20 0.08 Nitazoxanide 1 8 0.004 Sulfamethoxazole/trimethoprim 1 0 0.465 Secnidazole 3 15 0.001 Rifaximin 1 0 0.465 Table 1 Antimicrobial therapy and improvement of symptoms Antibiotic Improvement of symptoms p value No Yes Albendazole 0 1 0.185 Tinidazole/mebendazole 9 25 0.001 Metronidazole 16 20 0.08 Nitazoxanide 1 8 0.004 Sulfamethoxazole/trimethoprim 1 0 0.465 Secnidazole 3 15 0.001 Rifaximin 1 0 0.465 Antibiotic Improvement of symptoms p value No Yes Albendazole 0 1 0.185 Tinidazole/mebendazole 9 25 0.001 Metronidazole 16 20 0.08 Nitazoxanide 1 8 0.004 Sulfamethoxazole/trimethoprim 1 0 0.465 Secnidazole 3 15 0.001 Rifaximin 1 0 0.465 Fig. 2. View largeDownload slide Improvement of symptoms according to the antimicrobial therapy. Note: A = albendazole; M = mebendazole/tinidazole; MET = metronidazole; NIT = nitazoxanide; RIF = rifaximin; S = secnidazole; TMP/SMX = trimethroprim/sulfamethoxazole. Fig. 2. View largeDownload slide Improvement of symptoms according to the antimicrobial therapy. Note: A = albendazole; M = mebendazole/tinidazole; MET = metronidazole; NIT = nitazoxanide; RIF = rifaximin; S = secnidazole; TMP/SMX = trimethroprim/sulfamethoxazole. DISCUSSION Functional abdominal pain is one of the most frequent causes for overall pediatric consultation (2–4%). However, it has only been acknowledged as a global health problem until recently. It is estimated that 13–17% of school-age children suffer from it . The incidence of FGID in children and adolescents is approximately 23%  and it is considered more common among adolescents (7–25%), with a higher frequency in women than in men ; this is consistent with the findings in our study, in which the female population represented 58% of the studied sample, with a mean age of 10.96 years. FGID represent a serious problem considering the parents anguish, multiple hospitalizations, economic expenditure and numerous exams required to rule out organic pathologies. The pathophysiology of FGIDs in children is still unclear. However, it is possible that there are several related factors such as a disrupted intestinal reactivity in response to luminal or psychological stimuli, visceral afferent hypersensitivity and intestinal hypersensitivity to pain . Low-grade persisting inflammation plays an important role in the pathophysiology of this disease and may occur in the deep layers of intestinal tissue, as proven by Torn Blom et al.  who showed the presence of periganglionic lymphocytic infiltration in the myenteric plexus. As previously commented, Bh has been proposed as an etiological agent for FGIDs, mainly for irritable bowel syndrome, as well as for extraintestinal manifestations such as chronic angioedema . This agent is an intestinal unicellular and polymorphic eukaryote parasite, one of the intestinal protozoans mostly found in human and mammal gastrointestinal tracts, with a natural habitat in the colon and cecum . In a study published in 2010, the prevalence of Bh in the mountain chain of Veracruz, Mexico was 80% . As well as other parasites, its presence is associated to a limited access to health services, bad personal hygiene, exposure to domestic animals and consumption of contaminated water and food . Reports are contradictory regarding the pathogenicity of Blastocystis. Its pathogenic mechanisms include different proteases, proteolytic enzymes and pro-inflammatory cytokines, such as Interleukin 6 and tumor necrosis factor-α, with decay of secretory IgA [6, 18, 19]. Some studies, such as the one of Azizian et al. , have shown that the presence of disease and its severity vary according to the parasitic load and subtype of Blastocystis, with a variability in the plasma concentration of cytokines and enzymes, all involved in the development of irritable bowel syndrome . Clinical manifestations in symptomatic individuals are unspecific: abdominal pain, diarrhea, nausea, vomit, decreased appetite, flatulence . However, these are also present in asymptomatic people . Our study documented the presence of Bh in patients diagnosed with chronic abdominal pain followed-up in the outpatient clinic, constituting 13% of samples positive for Bh. This is quite similar with the findings of Gijsbers et al.  who associate chronic abdominal pain with Bh in 18% of their patients. Whether treatment should be given for Bh continues to be a complex subject considering the debate about its true pathogenicity . In the analysis of the 138 patients included in this study, we found a statistical significant difference in favor of providing treatment with an antimicrobial agent, showing an improvement of the symptoms after completion of the regime. There are reports about an adequate response to treatment with metronidazole or sulfamethoxazole/trimethoprim, although some authors consider that clinical improvement may be owing to eradication of secondary pathogens . The mostly prescribed treatment in our group of patients was metronidazole, which achieved symptoms elimination in only 55% of subjects, consistent with the published literature about an increase of resistance of Bh to this antiparasitic drug . Even though the variety of treatments was wide, tinidazole and mebendazole, secnidazole and nitazoxanide showed the best results. Overall, it can be said that in the face of Bh in stool exams of patients with chronic abdominal pain, the use of an antimicrobial treatment improves the symptoms. Dinleyici et al.  carried out a randomized clinical trial in patients with gastrointestinal symptoms and Bh in feces, finding statistically significant differences in favor of establishing a treatment; this difference increased when the authors added Saccharomyces boulardii to the treatment with metronidazole. For being a retrospective study, our study has limitations, including different types of bias, in addition to an initial search conducted only in patients with Bh and not those with functional abdominal pain. However, our study raises the possibility that Bh may play an etiological role in some cases of functional abdominal pain and opens a window for prospective studies and even randomized clinical trials to prove this hypothesis. CONCLUSIONS The etiology of chronic abdominal pain is varied; however, we consider according with our result that it is mandatory to conduct stool exams, and in cases where Bh is present, it is important to provide treatment attempting to eradicate it before initiating expensive diagnostic approaches or classifying a patient as having functional abdominal pain. REFERENCES 1 Korterink JJ , Rutten JM , Venmans L , et al. Pharmacologic treatment in pediatric functional abdominal pain disorders: a systematic review . J Pediatr 2015 ; 166 : 424 – 31 . Google Scholar CrossRef Search ADS PubMed 2 Apley J , Naish N. Recurrent abdominal pains: a field survey of 1000 school children . Arch Dis Child 1958 ; 33 : 165 – 70 . 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Journal of Tropical Pediatrics – Oxford University Press
Published: Aug 1, 2018
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