Helicobacter pylori and recurrent pain abdomen
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《美国医学杂志》
Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
Abstract
OBJECTIVE: Pain abdomen is a common problem in childhood. Many factors i.e., organic changes in the gut, psychological and environment contribute to recurrent pain abdomen (RAP) in children. Helicobacter pylori infects children very early in childhood and stays indefinitely in the gut without its eradication. It may be responsible for pain abdomen and peptic ulcers in children. This study was done to assess the HP status in children with RAP diagnosed and evaluate the effects of eradication of HP infection in them. METHODS: 76 children were included in the study. RESULT: Out of 76 children studied 14.8% had evidence of a secondary cause for pain abdomen and responded to appropriate therapy. 65.45% of children who had undergone UGIE, had evidence of HP infection in the upper gastrointestinal tract. Most of these children responded to HP eradication therapy by becoming free of abdominal pain after the eradication therapy with OCA or OMA regimen. We could not do repeated endoscopies in all of them to prove the eradication due to parents' refusal and this is the main drawback of this study. CONCLUSION: However, in view of clinical response to HP eradication therapy in almost all the cases, we strongly advocate this therapy for those children with RAP, in whom HP infection of the upper gastrointestinal tract can be established beyond doubt.
Keywords: H. pylori; Recurrent pain abdomen; Peptic ulcer
Recurrent abdominal pain (RAP) is a common problem in children. The incidence varies from 8 to 10 cases per 1000 children in a hospital set up.[1] Conventionally most of these patients are thought to have pain of functional origin or pain due to helminthiasis. In a large number of cases no definite cause for pain is found. The search is, there fore on to find out the etiology of pain for this group and evolve a consensus on investigation and management of this benign but persistent problem.
Helicobacter pylori (HP) are probably the most common bacterial infection in humans. In some countries 50% of infants are infected which increases to 90% by 5 years.[2] It had been incriminated in many systemic disorders in adults and its principal site of colonization is the gastrointestinal tract. It spreads by feco-oral, oro-oral or gastro-oral route.[2] Abdominal pain and occasional vomiting had been described with HP infection.[3],[4] It may also be asymptomatic.[5]
Overcrowding, poor housing, and contaminated water supply, increase the risk of infection in children. Its prevalence in USA and Europe is about 5-10% in children below 10 years of age and about 50% at 50 years of age, where as in India 25% of healthy population is infected by 10 years of age and 83% by the age of 19 years.[2],[6]
H pylori had been associated with chronic gastritis, peptic ulcer, B-Cell lymphoma of stomach, Maltoma and chronic gastritis in adults and it is considered as a class 1 carcinogen.[7],[8] Since HP is a chronic infection beginning in early childhood, it might play a role in RAP in children. Its eradication, therefore may lead to a cure.
Materials and methods
This is a hospital based prospective study from January, 1997 to December, 2000. A total of 76 children with RAP were included. A detailed history of similar pain in the family members, treatment received outside, school absenteeism and nocturnal pain was recorded in a proforma. Other causes of pain abdomen were ruled out by doing Haemoglobin, Total leukocyte count, Differential count, Peripheral smear, Mantoux test, Hepatitis B surface antigen, Ultrasonography of abdomen, Stool microscopy examination, Urine routine examination and microscopy, and nocturnal smear for microfilaria. Indirect Hemoagglutination test (IHA) for filarial antigen was done in cases with persistent eosinophilia. Those children having no definite cause for pain abdomen after the above investigations were subjected to Upper Gastrointestinal Endoscopy (UGIE). UGIE was performed with pentax FG-24V endoscope under general anaesthesia using Ketamine, diazepam and atropine.
In addition to looking for evidence of erosive lesions in the esophagus, stomach, and duodenum, antral biopsies were taken for histopathological study, giemsa stain for H.P. and Urease test. Urease test was done by a freshly prepared solution of Urease test reagent and the test was recorded as positive if the colour of the solution turned pink within 24 hours. Children having 2 out of the following 3 tests positive were considered to have HP infection.
1. Positive Urease test.
2. Giemsa stain positive for HP.
3. Histopathological evidence of chronic gastritis.
Initially all the children having HP infection were given Omeprazole, Metronidazole and Amoxicillin (OMA) regimen for 14 days and UGIE was repeated after 8 weeks. Those children who had persistent HP infection after this OMA regimen were given Omeprazole, Clarithromycin and Amoxicillin (OCA) for 7 days. In the later patients due to poor clinical eradication with OMA regimen, the initial therapy was changed to OCA for 7 days. They were seen after 7 days and 14 days to asses drug compliance. Drug compliance was ensured during the full duration of eradication therapy by marking in a notebook against the date.
Results
76 children were recruited for this study. 50(68%) of them were girls and 26(32%) were boys. None of the family members of these children had abdominal pain. Only 2(2.6%) children had a history of school absenteeism due to severe abdominal pain. After the routine investigations a secondary cause for pain abdomen was found in 11 patients (14.8%) only. Of them four had evidence of filariasis with persistent eosinophilia in the range of 25-30% and a positive IHA test for filarial antibody. None of them had microfilaria in their peripheral smear after a diethyl carbamazine (DEC) provocation test. Four children had cysts of Entamoeba histolytica (EH) in stool, one had pulmonary tuberculosis, one had giardiasis and one had choledochal cyst. These patients responded to appropriate therapy and were pain free for 6 months to 2 years on follow up.
Parents of 13 children refused endoscopy in spite of repeated explanation regarding the safety of this procedure. 52 children (.35 boys and 17 girls) with an age range of 2-13 years underwent UGIE (total endoscopies=62: Figure1. UGIE detected abnormality in the stomach in four cases only; though 34(65.4%) children had HP infection and 18(34.6%) were negative. Two children had ulcers in the gastric antrum and proximal duodenum and one had scarring of proximal duodenum. All the three had HP infection. One child having erosive gastritis was negative for HP and responded to ranitidine therapy. Esophagitis was not detected in any of these children.
Out of 34 children with HP infection 28 were followed up (OCA=7 AND OMA=21). Ten children from the OMA group had no pain for 2-6 months, but 11 were having pain table1.
The second endoscopy could be done in 10 cases only. Eight of them had received O M A and 2 had taken OCA. Others refused a second endoscopy. One child (HP-Negative) continued to have pain and later on developed features of rheumatoid arthritis .She responded to aspirin therapy. The other child in this group who had gastric ulcer on first UGIE had no pain but had only erosions and was found to be HP negative. Six children in this group remained pain free for 2-6 months after eradication therapy table1.
Second UGIE was done in 8 cases from the OMA group. Seven of them were having pain and six were positive for HP. They were given OCA and all of them responded by being free of pain for 2 to 6 months. One child having pain had no evidence of HP. One child cured of pain from OMA group was negative for HP.
Seventeen children who had no evidence of HP on 1st endoscopy, only twelve had further follow up. Seven of these children were pain free at 6 months and five of them were still having pain.
Five (42.8%)out of 12 children from HP negative group were having pain and 7 (57.2%) of them were free of pain at the end of 6 months. Thirteen children who refused for endoscopy, only two came for follow up in the child psychiatry clinic for counselling as cases of functional pain abdomen and were still having pain at 6 months Figure1
Except one case of gastritis there was no other side effect noted during the eradication therapy. This child with gastritis could complete his course of antibiotics after modification of diet only.
Discussion
Eleven (14%) Children were found to have a secondary cause for pain abdomen. Those with amebiasis, filariasis, giardiasis, responded to appropriate therapy within 7 days and repeat tests for these causes subsequently were negative. Organic causes like gastritis, amebiasis and giardiasis had been reported to be present in only 5-10% of RAP cases in one series but in a significant number of children in another study.[6], [9]
A child with primary pulmonary TB without any definite evidence of abdominal tuberculosis responded to anti tuberculous drug therapy within 1 month of initiating therapy. It could have been due to the referred pain from thorax. The child with the choledochal cyst was cured of pain after the surgery.
During the initial period of the present study the children with HP were given OMA for 14 days. All the children in this group could complete the course. As the HP eradication with this regimen was poor, resistance to metronidazole was suspected and the resistance to macrolide was reported in more than 50% cases with eradication failures, there fore, the subsequent drug regimen used for eradication was OCA.[7],[10],[11] Drug compliance with this regimen was also 100%.
Four of the present study cases had abnormality on UGIE. Two of them had ulcers in stomach and duodenum and one had scarring of proximal duodenum and all the three had HP infection. HP infection had been described to be associated with chronic gastritis and peptic ulcer disease in children but its association with RAP had been inconsistent.[8], [12], [13] These three children responded to the HP eradication therapy by healing of ulcers and staying free of pain for a period of 2 mo to 2 years.
Eradication therapy had been strongly recommended in children with peptic ulcer disease associated with HP infection as it had been associated with 90 to 100% of cases with peptic ulcer disease in children.[10],[14],[15],[16] The third child having erosive gastritis had no evidence of HP and responded to ranitidine therapy.
Out of the thirty four children having HP infection, twenty eight were followed up. They had received HP eradication therapy. All of them responded to OCA regimen and remained pain free for a period of 6 months except one case. Third endoscopy could not be done in many of them to clinch the evidence of eradication. There is consistent evidence emerging that H pylori infection is associated with antral gastritis in children though with nonspecific symptoms and is a cause for RAP in children.[13] Very high success rate (83-100%) has been achieved with symptomatic relief of chronic pain in cases with RAP, after the eradication of HP in children even in absence of ulcers in stomach and duodenum.[14] However a metaanalysis of 45 series of HP related studies found no consistent association of HP with RAP.[12]
In the present study 68% of cases (34 out of 52 cases) were having H pylori infection with RAP though, H.pylori infection had been reported to be an uncommon cause of RAP in children by some studies.[13], [17], [18] Also because of a high incidence of natural infection with HP in developing countries it becomes extremely difficult to establish a cause and effect relationship with RAP.[19] HP infection had been associated with growth failure in adolescent girls and its eradication had been recommended in specific situations with antral gastritis, mostly for the prevention of carcinoma in future.[15],[20]
The recurrence of pain in children after the initial response of pain relief could be due to re infection as the reinfection rate is very high in our environment. It is reported to be as high as 11-40 % in developing countries but 0.62 to 1.2% in developed countries annually.[19] Reinfection after the eradication of HP occurs in majority of patients within few months.[21] The failure of eradication of H.pylori by OMA regimen in the present study could be due to the drug resistance of this organism to various antimicrobials. The data regarding the primary resistance of H.pylori to drugs is scarce. In a French series of 150 strains 43% strains were resistant to metronidazole, 21% to clarithromycin, and 9% to both metronidazole and clarithromycin. H.pylori is susceptible to a wide variety of antimicrobials including ampicillin, amoxicillin, tetracycline, metronidazole, clindamycin, clarithromycin and bismuth salts.[5],[22] Also the children can be infected with multiple strains bearing different genotypes or with a single strain able to modify the expression of its antibiotic resistance genes under selective conditions. It is possible that different strains co exist in the stomach where the resistant ones could be selected by an antibiotic treatment prescribed for another infection.[5]
Resistance of H.pylori to metronidazole is increasing and is around 80 % in developing countries where as 90% in urban U.K. and 68% in Australia.[11] The acquired resistance of H pylori after eradication failure in a large cohort of 569 children was 46%.[5] Clarithromycin is a less used macrolide antibiotic and except rare reports of its failure in eradicating the HP in OCA regimen OCA is a good combination for eradicating the reinfected and refractory HP.[19], [21] Hence the H.pylori eradication regimen in our country in the present scenario should not contain metronidazole. Though relatively costly, better compliance to a 7 days regimen and good eradication rate of OCA regimen is probably a suitable option for H.pylori eradication.
It is still not clear whether to treat the HP infection in children with RAP. In this study a majority of children had significant relief of pain abdomen after the eradication therapy of HP. In symptomatic children who had a 2nd UGIE done also predominantly showed evidence of HP and became pain free after the OCA therapy, though we could not establish the eradication of HP by a 3rd UGIE in all of them due to unwillingness of the parents for the procedure especially after they became free of abdominal pain. This was the main limitation of the present study. Less invasive tests like Entero test, Anti HP-antibody detection and non invasive test like breath hydrogen test may prove to be better alternative methods of demonstrating the presence of HP infection in children in future.[23] However, clinical setting, local expertise and availability of resources must be considered by the clinician to obtain the best diagnostic yield.[20]
Conclusion
HP infection is a chronic infection and is very unlikely to be eradicated on its own and the therapy for its eradication resulted in pain free life in the study children for a considerable duration. So, it is believed that it is unjustified to deny the benefit of eradication of HP to these children with RAP, in whom an infection by H pylori is established beyond doubt. Extra abdominal cause like tuberculosis and filariasis should be looked for in each case of RAP in our country.
Abbreviations:
OCA=Omeprazole, Clarithromycin, Amoxicillin.
OMA=Omeprazole, Metronidazole, Amoxycillin.
HP=Helicobacter-pylori.
RAP=Recurrent pain abdomen.
References
1. Apley J, Nash N. Recurrent pain abdomen. A full survey of 1000 school children. Arch Dis Child 1958; 33: 165-170.
2. Holcombe C, Omotara BA, Eldridge J, Jones DM. H Pylori, the most common bacterial infection in Africa: a random serologic study. Am J Gastroenterol 1992; 87: 28-30.
3. De Giacomo C, Lisato L, Negrini RJ, Maggiore G. Serum immuno response to HP infection: Epidemiological and clinical applications. J Pediatr 1991; 119: 205-210.
4. Raymond J, Bergeret M, Benhamou RH, Menash K, Duponi CA. 2 year study of HP in children. J Clin Microbiology 1994; 82: 461-463.
5. Reifen R, Rasooly I, Drumm B, Murphy K, Sherman P. H. pylori infection in children; Is there specific symptomatology. Dig Dis Sci 1994; 39: 1488-1492.
6. Balamani B, Patwari AK, Bajaj P, Diwan N, Anand V K. RAP: A reappraisal. Ind Ped 2000; 37: 876-881.
7. Patric B, Jeanne-Marie D, Luigi C et al. Twelve year observation of primary and secondary antibiotic resistant H pylori strains in children. Pediatric Infect Dis J 2001; 20: 1033-1038.
8. Richard M, Peek Jr, Baser MJ. Pathophysiology of Helicobacter pylori induced gastritis and peptic ulcer disease. Am J Med 1997; 102: 200-207.
9. Libman WM. RAP in children, a retrospective study in 119 patients. Clin Pediatr 1978; 17: 149-153.
10. Bourke B, Nicholae J, Serman P. H. pylori infection and peptic ulcer disease in children. Ped Inf Dis J 1996; 15: 1-13.
11. Graham DY. Antibiotic resistance in H pylori: Implications for therapy. Gastroenterology 1998; 115: 1272-1277.
12. Sonny KF, Chong, Lou Q, Asnicar MA et al. HP infection in recurrent pain abdomen in childhood: comparison of diagnostic tests and therapy. Pediatrics 1995; 96: 211-215.
13. MacArthur C, Saunders N, Freidman W. H. pylori, gastroduodenal disease and RAP in children. JAMA 1995; 273: 729-734.
14. Thappa BR. H pylori in children with RAP. Ind J Gastroenterology 1989; 8: (Suppl) A32.
15. Kumar M, Yachha SK, Khanderi A et al. Endoscopic,histologic,microbiologic evaluation of upper abdominal pain with special reference to HP infection in children. Ind Ped 1996; 33: 905-909.
16. Kali bridge PM, Dahams BB, Czinn SJ. Campylobacter Pylori associated gastritis and peptic ulcer disease in children. Am J Dis Child 1988; 142: 1149-1152.
17. Mc McCarthy C, Patchett S, Collins RM, Beattie S, Keone C, Omorain C. Long-term perspective study of H pylori in non-ulcer dyspepsia. Dig Dis Sci 1995; 40: 114-119.
18. Cameron Imrie, Rowland M, Bourke B, Drum B. Is H pylori infection in childhood a risk factor for gastric cancer Pediatrics 2001; 107: 373-380.
19. Merja Ashorn, Ari M,Tarja R,Pekka L,Markku M. Seroepidemiological study of HP infection in infancy. Arch Dis Child 1996; 74; F141-142.
20. Vieira U, Galta L, Ricci c.d AnnaL, Iglioli MM. H. Pylori disease. Tests and treatment. Dig Liver Dis 2001; 33(9): 788-794.
21. Bhatia SJ, Abraham P. H pylori in the Indian environment. Ind J Gastroenterology 1995; 14: 139-144
22. Wash D, Goggin N, Rowland M, Durnin M, Moriarty S, Drumn B. One-week treatment for H pylori infection. Arch Dis Child 1997; 76: 352-355.
23. Perez TE, Montes M, Alcorta M, Zubillaga P, Telleria E. Non endoscopic method to obtain H. pylori for culture. Lancet 1995; 345: 622-634. of HP eradication therapy.(Biswal Niranjan, Ananatha)
Abstract
OBJECTIVE: Pain abdomen is a common problem in childhood. Many factors i.e., organic changes in the gut, psychological and environment contribute to recurrent pain abdomen (RAP) in children. Helicobacter pylori infects children very early in childhood and stays indefinitely in the gut without its eradication. It may be responsible for pain abdomen and peptic ulcers in children. This study was done to assess the HP status in children with RAP diagnosed and evaluate the effects of eradication of HP infection in them. METHODS: 76 children were included in the study. RESULT: Out of 76 children studied 14.8% had evidence of a secondary cause for pain abdomen and responded to appropriate therapy. 65.45% of children who had undergone UGIE, had evidence of HP infection in the upper gastrointestinal tract. Most of these children responded to HP eradication therapy by becoming free of abdominal pain after the eradication therapy with OCA or OMA regimen. We could not do repeated endoscopies in all of them to prove the eradication due to parents' refusal and this is the main drawback of this study. CONCLUSION: However, in view of clinical response to HP eradication therapy in almost all the cases, we strongly advocate this therapy for those children with RAP, in whom HP infection of the upper gastrointestinal tract can be established beyond doubt.
Keywords: H. pylori; Recurrent pain abdomen; Peptic ulcer
Recurrent abdominal pain (RAP) is a common problem in children. The incidence varies from 8 to 10 cases per 1000 children in a hospital set up.[1] Conventionally most of these patients are thought to have pain of functional origin or pain due to helminthiasis. In a large number of cases no definite cause for pain is found. The search is, there fore on to find out the etiology of pain for this group and evolve a consensus on investigation and management of this benign but persistent problem.
Helicobacter pylori (HP) are probably the most common bacterial infection in humans. In some countries 50% of infants are infected which increases to 90% by 5 years.[2] It had been incriminated in many systemic disorders in adults and its principal site of colonization is the gastrointestinal tract. It spreads by feco-oral, oro-oral or gastro-oral route.[2] Abdominal pain and occasional vomiting had been described with HP infection.[3],[4] It may also be asymptomatic.[5]
Overcrowding, poor housing, and contaminated water supply, increase the risk of infection in children. Its prevalence in USA and Europe is about 5-10% in children below 10 years of age and about 50% at 50 years of age, where as in India 25% of healthy population is infected by 10 years of age and 83% by the age of 19 years.[2],[6]
H pylori had been associated with chronic gastritis, peptic ulcer, B-Cell lymphoma of stomach, Maltoma and chronic gastritis in adults and it is considered as a class 1 carcinogen.[7],[8] Since HP is a chronic infection beginning in early childhood, it might play a role in RAP in children. Its eradication, therefore may lead to a cure.
Materials and methods
This is a hospital based prospective study from January, 1997 to December, 2000. A total of 76 children with RAP were included. A detailed history of similar pain in the family members, treatment received outside, school absenteeism and nocturnal pain was recorded in a proforma. Other causes of pain abdomen were ruled out by doing Haemoglobin, Total leukocyte count, Differential count, Peripheral smear, Mantoux test, Hepatitis B surface antigen, Ultrasonography of abdomen, Stool microscopy examination, Urine routine examination and microscopy, and nocturnal smear for microfilaria. Indirect Hemoagglutination test (IHA) for filarial antigen was done in cases with persistent eosinophilia. Those children having no definite cause for pain abdomen after the above investigations were subjected to Upper Gastrointestinal Endoscopy (UGIE). UGIE was performed with pentax FG-24V endoscope under general anaesthesia using Ketamine, diazepam and atropine.
In addition to looking for evidence of erosive lesions in the esophagus, stomach, and duodenum, antral biopsies were taken for histopathological study, giemsa stain for H.P. and Urease test. Urease test was done by a freshly prepared solution of Urease test reagent and the test was recorded as positive if the colour of the solution turned pink within 24 hours. Children having 2 out of the following 3 tests positive were considered to have HP infection.
1. Positive Urease test.
2. Giemsa stain positive for HP.
3. Histopathological evidence of chronic gastritis.
Initially all the children having HP infection were given Omeprazole, Metronidazole and Amoxicillin (OMA) regimen for 14 days and UGIE was repeated after 8 weeks. Those children who had persistent HP infection after this OMA regimen were given Omeprazole, Clarithromycin and Amoxicillin (OCA) for 7 days. In the later patients due to poor clinical eradication with OMA regimen, the initial therapy was changed to OCA for 7 days. They were seen after 7 days and 14 days to asses drug compliance. Drug compliance was ensured during the full duration of eradication therapy by marking in a notebook against the date.
Results
76 children were recruited for this study. 50(68%) of them were girls and 26(32%) were boys. None of the family members of these children had abdominal pain. Only 2(2.6%) children had a history of school absenteeism due to severe abdominal pain. After the routine investigations a secondary cause for pain abdomen was found in 11 patients (14.8%) only. Of them four had evidence of filariasis with persistent eosinophilia in the range of 25-30% and a positive IHA test for filarial antibody. None of them had microfilaria in their peripheral smear after a diethyl carbamazine (DEC) provocation test. Four children had cysts of Entamoeba histolytica (EH) in stool, one had pulmonary tuberculosis, one had giardiasis and one had choledochal cyst. These patients responded to appropriate therapy and were pain free for 6 months to 2 years on follow up.
Parents of 13 children refused endoscopy in spite of repeated explanation regarding the safety of this procedure. 52 children (.35 boys and 17 girls) with an age range of 2-13 years underwent UGIE (total endoscopies=62: Figure1. UGIE detected abnormality in the stomach in four cases only; though 34(65.4%) children had HP infection and 18(34.6%) were negative. Two children had ulcers in the gastric antrum and proximal duodenum and one had scarring of proximal duodenum. All the three had HP infection. One child having erosive gastritis was negative for HP and responded to ranitidine therapy. Esophagitis was not detected in any of these children.
Out of 34 children with HP infection 28 were followed up (OCA=7 AND OMA=21). Ten children from the OMA group had no pain for 2-6 months, but 11 were having pain table1.
The second endoscopy could be done in 10 cases only. Eight of them had received O M A and 2 had taken OCA. Others refused a second endoscopy. One child (HP-Negative) continued to have pain and later on developed features of rheumatoid arthritis .She responded to aspirin therapy. The other child in this group who had gastric ulcer on first UGIE had no pain but had only erosions and was found to be HP negative. Six children in this group remained pain free for 2-6 months after eradication therapy table1.
Second UGIE was done in 8 cases from the OMA group. Seven of them were having pain and six were positive for HP. They were given OCA and all of them responded by being free of pain for 2 to 6 months. One child having pain had no evidence of HP. One child cured of pain from OMA group was negative for HP.
Seventeen children who had no evidence of HP on 1st endoscopy, only twelve had further follow up. Seven of these children were pain free at 6 months and five of them were still having pain.
Five (42.8%)out of 12 children from HP negative group were having pain and 7 (57.2%) of them were free of pain at the end of 6 months. Thirteen children who refused for endoscopy, only two came for follow up in the child psychiatry clinic for counselling as cases of functional pain abdomen and were still having pain at 6 months Figure1
Except one case of gastritis there was no other side effect noted during the eradication therapy. This child with gastritis could complete his course of antibiotics after modification of diet only.
Discussion
Eleven (14%) Children were found to have a secondary cause for pain abdomen. Those with amebiasis, filariasis, giardiasis, responded to appropriate therapy within 7 days and repeat tests for these causes subsequently were negative. Organic causes like gastritis, amebiasis and giardiasis had been reported to be present in only 5-10% of RAP cases in one series but in a significant number of children in another study.[6], [9]
A child with primary pulmonary TB without any definite evidence of abdominal tuberculosis responded to anti tuberculous drug therapy within 1 month of initiating therapy. It could have been due to the referred pain from thorax. The child with the choledochal cyst was cured of pain after the surgery.
During the initial period of the present study the children with HP were given OMA for 14 days. All the children in this group could complete the course. As the HP eradication with this regimen was poor, resistance to metronidazole was suspected and the resistance to macrolide was reported in more than 50% cases with eradication failures, there fore, the subsequent drug regimen used for eradication was OCA.[7],[10],[11] Drug compliance with this regimen was also 100%.
Four of the present study cases had abnormality on UGIE. Two of them had ulcers in stomach and duodenum and one had scarring of proximal duodenum and all the three had HP infection. HP infection had been described to be associated with chronic gastritis and peptic ulcer disease in children but its association with RAP had been inconsistent.[8], [12], [13] These three children responded to the HP eradication therapy by healing of ulcers and staying free of pain for a period of 2 mo to 2 years.
Eradication therapy had been strongly recommended in children with peptic ulcer disease associated with HP infection as it had been associated with 90 to 100% of cases with peptic ulcer disease in children.[10],[14],[15],[16] The third child having erosive gastritis had no evidence of HP and responded to ranitidine therapy.
Out of the thirty four children having HP infection, twenty eight were followed up. They had received HP eradication therapy. All of them responded to OCA regimen and remained pain free for a period of 6 months except one case. Third endoscopy could not be done in many of them to clinch the evidence of eradication. There is consistent evidence emerging that H pylori infection is associated with antral gastritis in children though with nonspecific symptoms and is a cause for RAP in children.[13] Very high success rate (83-100%) has been achieved with symptomatic relief of chronic pain in cases with RAP, after the eradication of HP in children even in absence of ulcers in stomach and duodenum.[14] However a metaanalysis of 45 series of HP related studies found no consistent association of HP with RAP.[12]
In the present study 68% of cases (34 out of 52 cases) were having H pylori infection with RAP though, H.pylori infection had been reported to be an uncommon cause of RAP in children by some studies.[13], [17], [18] Also because of a high incidence of natural infection with HP in developing countries it becomes extremely difficult to establish a cause and effect relationship with RAP.[19] HP infection had been associated with growth failure in adolescent girls and its eradication had been recommended in specific situations with antral gastritis, mostly for the prevention of carcinoma in future.[15],[20]
The recurrence of pain in children after the initial response of pain relief could be due to re infection as the reinfection rate is very high in our environment. It is reported to be as high as 11-40 % in developing countries but 0.62 to 1.2% in developed countries annually.[19] Reinfection after the eradication of HP occurs in majority of patients within few months.[21] The failure of eradication of H.pylori by OMA regimen in the present study could be due to the drug resistance of this organism to various antimicrobials. The data regarding the primary resistance of H.pylori to drugs is scarce. In a French series of 150 strains 43% strains were resistant to metronidazole, 21% to clarithromycin, and 9% to both metronidazole and clarithromycin. H.pylori is susceptible to a wide variety of antimicrobials including ampicillin, amoxicillin, tetracycline, metronidazole, clindamycin, clarithromycin and bismuth salts.[5],[22] Also the children can be infected with multiple strains bearing different genotypes or with a single strain able to modify the expression of its antibiotic resistance genes under selective conditions. It is possible that different strains co exist in the stomach where the resistant ones could be selected by an antibiotic treatment prescribed for another infection.[5]
Resistance of H.pylori to metronidazole is increasing and is around 80 % in developing countries where as 90% in urban U.K. and 68% in Australia.[11] The acquired resistance of H pylori after eradication failure in a large cohort of 569 children was 46%.[5] Clarithromycin is a less used macrolide antibiotic and except rare reports of its failure in eradicating the HP in OCA regimen OCA is a good combination for eradicating the reinfected and refractory HP.[19], [21] Hence the H.pylori eradication regimen in our country in the present scenario should not contain metronidazole. Though relatively costly, better compliance to a 7 days regimen and good eradication rate of OCA regimen is probably a suitable option for H.pylori eradication.
It is still not clear whether to treat the HP infection in children with RAP. In this study a majority of children had significant relief of pain abdomen after the eradication therapy of HP. In symptomatic children who had a 2nd UGIE done also predominantly showed evidence of HP and became pain free after the OCA therapy, though we could not establish the eradication of HP by a 3rd UGIE in all of them due to unwillingness of the parents for the procedure especially after they became free of abdominal pain. This was the main limitation of the present study. Less invasive tests like Entero test, Anti HP-antibody detection and non invasive test like breath hydrogen test may prove to be better alternative methods of demonstrating the presence of HP infection in children in future.[23] However, clinical setting, local expertise and availability of resources must be considered by the clinician to obtain the best diagnostic yield.[20]
Conclusion
HP infection is a chronic infection and is very unlikely to be eradicated on its own and the therapy for its eradication resulted in pain free life in the study children for a considerable duration. So, it is believed that it is unjustified to deny the benefit of eradication of HP to these children with RAP, in whom an infection by H pylori is established beyond doubt. Extra abdominal cause like tuberculosis and filariasis should be looked for in each case of RAP in our country.
Abbreviations:
OCA=Omeprazole, Clarithromycin, Amoxicillin.
OMA=Omeprazole, Metronidazole, Amoxycillin.
HP=Helicobacter-pylori.
RAP=Recurrent pain abdomen.
References
1. Apley J, Nash N. Recurrent pain abdomen. A full survey of 1000 school children. Arch Dis Child 1958; 33: 165-170.
2. Holcombe C, Omotara BA, Eldridge J, Jones DM. H Pylori, the most common bacterial infection in Africa: a random serologic study. Am J Gastroenterol 1992; 87: 28-30.
3. De Giacomo C, Lisato L, Negrini RJ, Maggiore G. Serum immuno response to HP infection: Epidemiological and clinical applications. J Pediatr 1991; 119: 205-210.
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