European Journal of
Original papers
Pediatrics
Eur J Pediatr (1992) 151 : 799-801
9 Springer-Verlag1992
The prevalence of Helicobacter pylori serum antibodies in children with recurrent abdominal pain S. B. van der Meer ~, P. P. Forget 1, R . J . L . F . Loffeld 2, E. Stobberingh 3, R. H. Kuijten 1, and J.W. Arends 4 Departments of 1Paediatrics, 2Internal Medicine, 3Microbiology and 4pathology, Academic Hospital Maastricht, University of Limburg, P.O. Box 5800, NL-6202 AZ Maastricht, The Netherlands Received October 21, 1991 / Accepted after revision March 2, 1992
Abstract. As part of a large, prospective study we investigated the prevalence Helicobacter pylori serum antibodies in children with recurrent abdominal pain (RAP). All patients suffered from recurrent bouts of abdominal pain for at least 6 months and ranged in age from 6 to 12 years. H.pylori antibodies were detected using an enzyme-linked immunosorbent assay. The prevalence of H. pylori antibodies in the R A P group was compared to that of a control group which consisted predominantly of pre-operative children. None of the control group suffered or had suffered from R A P . Antibodies to H. pylori were found in 7 of 82 (8.5%) R A P patients and in 2 of 39 (5.1%) control children. The latter difference is not significant and suggests that R A P is only rarely caused in children by H. pylori infection.
Key words: Recurrent abdominal pain - Children Helicobacter pylori - Serum antibodies
Introduction Ever since the studies performed by Apley and co-workers in 1958 and later years [1, 3] there has been considerable debate in the literature about different aetiological factors possibly playing a role in the enigmatic syndrome of recurrent abdominal pain ( R A P ) in children [4, 12, 21]. Unequivocal somatic causes have scarcely been reported [2, 13] and psychogenic mechanisms were considered to be the main cause of these patients' complaints [10]. The role played by psychogenic factors in R A P has been difficult to establish convincingly [17] and resulted in renewed interest in possible somatic causes. The discovery of Helicobacter pylori and its establishment as an important organism in gastrointestinal disease in adults prompted studies on the role of H. pylori in the paediatric age group. It is now clear that H. pylori plays a role
Correspondence to: S. B. van der Meer Abbreviations: OD = optical density unit; RAP = recurrent abdominal pain
in several gastrointestinal diseases in children, such as antral gastritis and peptic ulcer disease [7, 11]. The role of H. pylori, however, in less well defined and chronic disorders such as the R A P syndrome is as yet, not apparent. In order to assess the prevalence of H. pylori serum antibodies in a group of unselected and well-defined R A P patients we determined H. pylori antibodies by means of an enzyme-linked immunosorbent assay (ELISA) in a group of schoolchildren with R A P and an age-comparable control group.
Patients and methods All RAP patients entering the study met the following inclusion criteria: (1) age between 5.5 and 12 years; (2) at least a 6-month period of RAP of unknown origin; (3) attacks of pain varying in severity, duration and frequency; (4) sometimes accompanied by vegetative symptoms like paleness, nausea or vomiting. The patient group consisted of 28 boys and 54 girls, mean age 10.8 years. They were subjected to a standard protocol consisting of routine laboratory investigations of blood, urine and stools. Additionally, an ultrasound examination of the abdomen, a small bowel permeability test and a lactose breath hydrogen test were performed. Finally, all patients were seen by a psychologist, who performed a variety of psychological tests. Results of these studies have been published separately [24-26]. The control group consisted of 39 children, 25 boys and 14 girls, with a mean age of 6.6 years. They were mainly pre-operative children (ear-nose-throat procedures, fractures, retentio testis) or children attending the outpatient clinics for other than gastrointestinal diseases (epilepsy, asthma, short stature). These children took anti-convulsive or antiasthmatic drugs; none of them used any gastrointestinal drugs. Both study and control groups were of Caucasian origin. All parents of both the RAP and the control groups gave informed conset. Approval for the study was obtained from the ethical committee in our hospital. Atopy, gastrointestinal symptoms and abdominal pain were not present in any of the control children. Blood samples were analysed by ELISA as previously described [15]. For statistical analysis the Fisher test was employed.
Results In the R A P group seven patients (8.5%) gave values above the cut-off point of 1.40 optical density units (OD)
800 6-
>Z uJ 0
_o F-n O 9
v
?o
n
9
~~ o
o
%
~%qb9 ~ p ~ c ,
"~ o
o
oO oql;~o~ ~
o t*t
*
: cut-off value: 1.40 O D
Fig.1. Scattergram representing the OD va!ues of children with RAP and control children
pointing to the presence of H. pylori antibodies. Their mean OD value was 2.95 (SD: 1.14), whereas the rest of the RAP group demonstrated a mean OD of 0.56 (SD: 0.27). In all seven patients no other plausible explanation was found for the abdominal pain, i.e. no other abnormalities were discovered with the additional investigations. In the control group, two individuals (5.1%) with an OD above 1.40 were observed: 1.47 and 1.81 respectively. The other part of the control group showed a mean OD of 0.57 (SD: 0.29). The difference between the prevalence of H. pylori antibodies among the RAP group compared to the control group was not significant. The observed OD values in both study groups are summarized in Fig. 1.
Discussion
As in adults the detection of H. pylori in children relies mainly on the microscopic investigation of endoscopically obtained mucosal biopsy specimens. Because of its invasive character, endoscopy does not always seem to be the appropriate and feasible way of making a diagnosis in children suspected of gastrointestinal disease. Therefore, the availability of a sensitive and specific serological diagnostic test would be much appreciated by paediatricians, parents and children. Several studies have reported on the use of ELISA in detecting the presence of antibodies against H. pylori [9, 18, 27]. The sensitivity and specificity of the latter test appears to be sufficient in clinical practice [19]. In this context we chose to detect H. pylori antibodies by means of an ELISA instead of demonstrating the presence of H. pylori in biopsy specimens. In adults, H. pylori has been reported to be associated with antral gastritis [22], non-ulcer dyspepsia [14] and peptic ulcer disease [5]. Subsequently, there have
been reports on the presence of H.pylori in children with gastrointestinal disorders such as peptic ulcer disease and gastritis [7, 11]. These studies were retrospective investigations of histological biopsy specimens from children with upper gastrointestinal symptoms such as epigastric pain or vomiting. The prevalence of H. pylori in different gastrointestinal disorders in children is reported to range from 6% to 30% [8, 23], depending upon the study design and the study population. In this context it is surprising that no studies have so far been reported explicitly addressing the possible association between RAP and H. pylori. In a retrospective study, Mahony et al. [16] investigated 38 gastric biopsies from children who underwent endoscopy for upper gastrointestinal symptoms. In 9 (38%) of the patients they found histological evidence of H. pylori. The authors concluded that H. pylori represents another identifiable cause of RAP in children. Oderda et al. [20] reported on a series of 51 consecutive children who presented with abdominal complaints. As many as 32 (61%) of the patients showed histological evidence of gastritis and H. pylori was present in the antral biopsy specimens. However, the description of the clinical presentation of the patients is very limited, which makes it uncertain whether "classic" RAP patients are dealt with. In the above-mentioned studies, which mainly concerned patients referred to paediatric gastroenterology units, patient selection could explain the high percentage of gastritis found. The results of our study demonstrate that signs of past or present H.pylori infection are identifiable in some children with RAP. Therefore, H. pylori infection could be regarded as a possible somatic cause of the RAP syndrome. However, if RAP was often accompanied by H. pylori infection, one would have expected a much higher prevalence of LI. pylori antibodies in RAP patients as compared to controls. Since this was not the case, we do not consider H. pylori to be frequently involved in RAP. As the frequency of positive serological findings has been shown [6] to increase with age and as our control children were younger than our RAP patients, we could have expected to find a higher incidence of positive serological findings in the RAP group. On the basis of our study design and the fact that our university hospital is the only referral hospital in this region, we believe we have studied a relatively unselected group of RAP patients. However, a solely serological diagnosis might negatively affect the actual prevalence of H. pylori. As the ELISA we used has been reported to be very sensitive and specific for the detection of H. pylori antibodies [15] our results, so far, probably represent the best estimate of the prevalence of H. pylori serum antibodies among children with RAP. We realize, however, that in view of the limited number of patients, a type 2 or beta statistical error could be responsible for the lack of difference in the frequency of positive serological results in our two groups. Finally, it is still open to discussion whether H. pylori is causally related to RAP in children. From the seven seropositive patients in our RAP group, six demonstrated a higher antibody titre compared with the two seropositive controls. This could imply that
801
H. pylori does play a role in the clinical s y n d r o m e in some patients, A s in adults suffering f r o m n o n - u l c e r dyspepsia, H. pylori can b e r e s p o n s i b l e for the a b d o m i n a l c o m p l a i n t s in some c h i l d r e n suffering f r o m R A P . H o w ever, in t h r e e out of s e v e n seropositive patients the abd o m i n a l p a i n resolved s p o n t a n e o u s l y . I n a d d i t i o n , the n u m b e r of p a t i e n t s is too small to allow conclusions to be drawn. A d o u b l e - b l i n d t h e r a p e u t i c study could help to answer this q u e s t i o n .
Acknowledgements'. The authors wish to thank Anita Boreas, Nadja Sinsel and Huub van den Oever for their efforts in making this study possible. We also thank the Department of Child Health of the City of Maastricht (Head: Dr. F. J. M. Feron) for their collaboration in the RAP study.
References 1. Apley J (i959) The child with abdominal pains. Blackwell, London 2. Apley J, Hale B (1973) Children with recurrent abdominal pain: how do they grow up? BMJ 3:7-9 3. Apley J, Naish N (1958) Recurrent abdominal pains: a field survey of 1000 schoolchildren. Arch Dis Child 33 : 165-170 4. Barr RG, Levine MD, Watkins JB (1979) Recurrent abdominal pain due to lactose intolerance. N Engl J Med 300:14491452 5. Buck GE, Gourley WK, Lee WK, et al (1986) Relation of Campylobacter pyloridis to gastritis and peptic ulcer. J Infect Dis 153 : 664-669 6. Dooley CP, Cohen H, Fitzgibbons PL, Bauer M, Appleman MD, Perez-Perez GI, Blaser MJ (1989) Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons. N Engl J Med 321 : 1562-1566 7. Drumm B, O'Brien A, Cutz E, Shermann P (1987) Campylobacwrpyloridis-associated primary gastritis in children. Pediatrics 80 : 192-195 8. Drumm B, Sherman P, Cutz E, Karmali M (1987) Association of Campylobacterpylori on the gastric mucosa with antral gastritis in children. N Engl J Med 316 : 1557-1561 9. Evans D J, Evans DG, Graham DY, Klein P (1989) A sensitive and specific serologic test for detection of Campylobacter pylori infection. Gastroenterology 96:1004-1008 10. Green M (1967) Diagnosis and treatment: psychogenic, recurrent, abdominal pain. Pediatrics 40 : 84-89 11. Killbridge PM, Dahms BB, Czinn SJ (1988) Campylobacwr pylori-associated gastritis and peptic ulcer disease in children. Am J Dis Child 142:1149-1152
12. Lebenthal E, Rossi TM, Nord KS, Branski D (1981) Recurrent abdominal pain and lactose absorption in children. Pediatrics 67 : 828-832 13. Liebman WM (1978) Recurrent abdominal pain in children: a retrospective study of 119 patients. Clin Pediatr 17:149-153 14. Loffeld RJLF, Potters HVPJ, Arends JW, Stobberingh E, Flendrig JA, Spreeuwel JP van (1988) Campylobacter-associated gastritis in patients with non-ulcer dyspepsia. J Clin Pathol 41 : 85-88 15. Loffeld RJLF, Stobberingh E, Flendrig JA, Spreeuwel JP van, Arends JW (1989) Diagnostic value of an immunoassay to detect anti-Campylobacter pylori antibodies in non-ulcer dyspepsia. Lancet I: 1183-1185 16. Mahony MJ, Wyatt JI, Littlewood JM (1988) Campytobacter pylori gastritis. Arch Dis Child 634 : 654-655 17. McGrath PJ, Goodman JT, Firestone P, Shimpman R, Peters S (1983) Recurrent abdominal pain: a psychogenic disorder? Arch Dis Child 58 : 888-890 18. Mitchell HM, Lee A, Berkowicz J, Borody T (1988) The use of serology to diagnose active Campylobacwr pylori infection. Med J Aust 149 : 604-609 19. Newell DG, Rathbone BJ (1989) Review article: the serodiagnosis of CampyIobacter pylori infection. Serodiagn Immunother 3 : 1-6 20. Oderda G, Vaira D, Holton J, Dowsett JF, Ansaldi N (1989) Serum pepsinogen and IgG antibody to Campylobacterpylori in non-specific abdominal pain in childhood. Gut 30 : 912-916 21. Pifieiro-Carrero VM, Andres JM, Davis RH, Mathias JR (1988) Abnormal gastroduodenal motility in children and adolescents with recurrent functional abdominal pain. J Pediatr 113:820-825 22. Rauws EA, Langenberg W, Houthoff H, et al. (1988) Campylobacter pytoridis-associated chronic acitve antral gastritis. Gastroenterology 94 : 33-40 23. Thomas JE, Eastham EJ, Elliott TJS, Nelson R (1988) Campylobacter pylori in children - a common cause of symptoms. Gut 29 : A707 24. Van der Meer SB, Forget PP, HeidendaI GAK (1990) Small bowel permeability to 51Cr-EDTA in children with recurrent abdominal pain. Acta Paediatr Scand 79 : 422-426 25. Van der Meer SB, Forget PP, Arends JW, Kuijten RH, Engelshoven JMA van (1990) Diagnostic value of ultrasound in children with recurrent abdominal pain. Pediatr Radiol 20 : 501-503 26. Van der Meer SB, Forget PP, Arends JW (1990) Abnormal small bowel permeability and duodenitis in recurrent abdominal pain. Arch Dis Child 65:1311-1314 27. Wyatt JI, Rathbone BJ (1989) The role of serology in the diagnosis of Campylobacter pylori infections. Scand J Gastroenterol 24 [Suppl 160] : 27-34
Original papers
Pediatrics
Eur J Pediatr (1992) 151 : 799-801
9 Springer-Verlag1992
The prevalence of Helicobacter pylori serum antibodies in children with recurrent abdominal pain S. B. van der Meer ~, P. P. Forget 1, R . J . L . F . Loffeld 2, E. Stobberingh 3, R. H. Kuijten 1, and J.W. Arends 4 Departments of 1Paediatrics, 2Internal Medicine, 3Microbiology and 4pathology, Academic Hospital Maastricht, University of Limburg, P.O. Box 5800, NL-6202 AZ Maastricht, The Netherlands Received October 21, 1991 / Accepted after revision March 2, 1992
Abstract. As part of a large, prospective study we investigated the prevalence Helicobacter pylori serum antibodies in children with recurrent abdominal pain (RAP). All patients suffered from recurrent bouts of abdominal pain for at least 6 months and ranged in age from 6 to 12 years. H.pylori antibodies were detected using an enzyme-linked immunosorbent assay. The prevalence of H. pylori antibodies in the R A P group was compared to that of a control group which consisted predominantly of pre-operative children. None of the control group suffered or had suffered from R A P . Antibodies to H. pylori were found in 7 of 82 (8.5%) R A P patients and in 2 of 39 (5.1%) control children. The latter difference is not significant and suggests that R A P is only rarely caused in children by H. pylori infection.
Key words: Recurrent abdominal pain - Children Helicobacter pylori - Serum antibodies
Introduction Ever since the studies performed by Apley and co-workers in 1958 and later years [1, 3] there has been considerable debate in the literature about different aetiological factors possibly playing a role in the enigmatic syndrome of recurrent abdominal pain ( R A P ) in children [4, 12, 21]. Unequivocal somatic causes have scarcely been reported [2, 13] and psychogenic mechanisms were considered to be the main cause of these patients' complaints [10]. The role played by psychogenic factors in R A P has been difficult to establish convincingly [17] and resulted in renewed interest in possible somatic causes. The discovery of Helicobacter pylori and its establishment as an important organism in gastrointestinal disease in adults prompted studies on the role of H. pylori in the paediatric age group. It is now clear that H. pylori plays a role
Correspondence to: S. B. van der Meer Abbreviations: OD = optical density unit; RAP = recurrent abdominal pain
in several gastrointestinal diseases in children, such as antral gastritis and peptic ulcer disease [7, 11]. The role of H. pylori, however, in less well defined and chronic disorders such as the R A P syndrome is as yet, not apparent. In order to assess the prevalence of H. pylori serum antibodies in a group of unselected and well-defined R A P patients we determined H. pylori antibodies by means of an enzyme-linked immunosorbent assay (ELISA) in a group of schoolchildren with R A P and an age-comparable control group.
Patients and methods All RAP patients entering the study met the following inclusion criteria: (1) age between 5.5 and 12 years; (2) at least a 6-month period of RAP of unknown origin; (3) attacks of pain varying in severity, duration and frequency; (4) sometimes accompanied by vegetative symptoms like paleness, nausea or vomiting. The patient group consisted of 28 boys and 54 girls, mean age 10.8 years. They were subjected to a standard protocol consisting of routine laboratory investigations of blood, urine and stools. Additionally, an ultrasound examination of the abdomen, a small bowel permeability test and a lactose breath hydrogen test were performed. Finally, all patients were seen by a psychologist, who performed a variety of psychological tests. Results of these studies have been published separately [24-26]. The control group consisted of 39 children, 25 boys and 14 girls, with a mean age of 6.6 years. They were mainly pre-operative children (ear-nose-throat procedures, fractures, retentio testis) or children attending the outpatient clinics for other than gastrointestinal diseases (epilepsy, asthma, short stature). These children took anti-convulsive or antiasthmatic drugs; none of them used any gastrointestinal drugs. Both study and control groups were of Caucasian origin. All parents of both the RAP and the control groups gave informed conset. Approval for the study was obtained from the ethical committee in our hospital. Atopy, gastrointestinal symptoms and abdominal pain were not present in any of the control children. Blood samples were analysed by ELISA as previously described [15]. For statistical analysis the Fisher test was employed.
Results In the R A P group seven patients (8.5%) gave values above the cut-off point of 1.40 optical density units (OD)
800 6-
>Z uJ 0
_o F-n O 9
v
?o
n
9
~~ o
o
%
~%qb9 ~ p ~ c ,
"~ o
o
oO oql;~o~ ~
o t*t
*
: cut-off value: 1.40 O D
Fig.1. Scattergram representing the OD va!ues of children with RAP and control children
pointing to the presence of H. pylori antibodies. Their mean OD value was 2.95 (SD: 1.14), whereas the rest of the RAP group demonstrated a mean OD of 0.56 (SD: 0.27). In all seven patients no other plausible explanation was found for the abdominal pain, i.e. no other abnormalities were discovered with the additional investigations. In the control group, two individuals (5.1%) with an OD above 1.40 were observed: 1.47 and 1.81 respectively. The other part of the control group showed a mean OD of 0.57 (SD: 0.29). The difference between the prevalence of H. pylori antibodies among the RAP group compared to the control group was not significant. The observed OD values in both study groups are summarized in Fig. 1.
Discussion
As in adults the detection of H. pylori in children relies mainly on the microscopic investigation of endoscopically obtained mucosal biopsy specimens. Because of its invasive character, endoscopy does not always seem to be the appropriate and feasible way of making a diagnosis in children suspected of gastrointestinal disease. Therefore, the availability of a sensitive and specific serological diagnostic test would be much appreciated by paediatricians, parents and children. Several studies have reported on the use of ELISA in detecting the presence of antibodies against H. pylori [9, 18, 27]. The sensitivity and specificity of the latter test appears to be sufficient in clinical practice [19]. In this context we chose to detect H. pylori antibodies by means of an ELISA instead of demonstrating the presence of H. pylori in biopsy specimens. In adults, H. pylori has been reported to be associated with antral gastritis [22], non-ulcer dyspepsia [14] and peptic ulcer disease [5]. Subsequently, there have
been reports on the presence of H.pylori in children with gastrointestinal disorders such as peptic ulcer disease and gastritis [7, 11]. These studies were retrospective investigations of histological biopsy specimens from children with upper gastrointestinal symptoms such as epigastric pain or vomiting. The prevalence of H. pylori in different gastrointestinal disorders in children is reported to range from 6% to 30% [8, 23], depending upon the study design and the study population. In this context it is surprising that no studies have so far been reported explicitly addressing the possible association between RAP and H. pylori. In a retrospective study, Mahony et al. [16] investigated 38 gastric biopsies from children who underwent endoscopy for upper gastrointestinal symptoms. In 9 (38%) of the patients they found histological evidence of H. pylori. The authors concluded that H. pylori represents another identifiable cause of RAP in children. Oderda et al. [20] reported on a series of 51 consecutive children who presented with abdominal complaints. As many as 32 (61%) of the patients showed histological evidence of gastritis and H. pylori was present in the antral biopsy specimens. However, the description of the clinical presentation of the patients is very limited, which makes it uncertain whether "classic" RAP patients are dealt with. In the above-mentioned studies, which mainly concerned patients referred to paediatric gastroenterology units, patient selection could explain the high percentage of gastritis found. The results of our study demonstrate that signs of past or present H.pylori infection are identifiable in some children with RAP. Therefore, H. pylori infection could be regarded as a possible somatic cause of the RAP syndrome. However, if RAP was often accompanied by H. pylori infection, one would have expected a much higher prevalence of LI. pylori antibodies in RAP patients as compared to controls. Since this was not the case, we do not consider H. pylori to be frequently involved in RAP. As the frequency of positive serological findings has been shown [6] to increase with age and as our control children were younger than our RAP patients, we could have expected to find a higher incidence of positive serological findings in the RAP group. On the basis of our study design and the fact that our university hospital is the only referral hospital in this region, we believe we have studied a relatively unselected group of RAP patients. However, a solely serological diagnosis might negatively affect the actual prevalence of H. pylori. As the ELISA we used has been reported to be very sensitive and specific for the detection of H. pylori antibodies [15] our results, so far, probably represent the best estimate of the prevalence of H. pylori serum antibodies among children with RAP. We realize, however, that in view of the limited number of patients, a type 2 or beta statistical error could be responsible for the lack of difference in the frequency of positive serological results in our two groups. Finally, it is still open to discussion whether H. pylori is causally related to RAP in children. From the seven seropositive patients in our RAP group, six demonstrated a higher antibody titre compared with the two seropositive controls. This could imply that
801
H. pylori does play a role in the clinical s y n d r o m e in some patients, A s in adults suffering f r o m n o n - u l c e r dyspepsia, H. pylori can b e r e s p o n s i b l e for the a b d o m i n a l c o m p l a i n t s in some c h i l d r e n suffering f r o m R A P . H o w ever, in t h r e e out of s e v e n seropositive patients the abd o m i n a l p a i n resolved s p o n t a n e o u s l y . I n a d d i t i o n , the n u m b e r of p a t i e n t s is too small to allow conclusions to be drawn. A d o u b l e - b l i n d t h e r a p e u t i c study could help to answer this q u e s t i o n .
Acknowledgements'. The authors wish to thank Anita Boreas, Nadja Sinsel and Huub van den Oever for their efforts in making this study possible. We also thank the Department of Child Health of the City of Maastricht (Head: Dr. F. J. M. Feron) for their collaboration in the RAP study.
References 1. Apley J (i959) The child with abdominal pains. Blackwell, London 2. Apley J, Hale B (1973) Children with recurrent abdominal pain: how do they grow up? BMJ 3:7-9 3. Apley J, Naish N (1958) Recurrent abdominal pains: a field survey of 1000 schoolchildren. Arch Dis Child 33 : 165-170 4. Barr RG, Levine MD, Watkins JB (1979) Recurrent abdominal pain due to lactose intolerance. N Engl J Med 300:14491452 5. Buck GE, Gourley WK, Lee WK, et al (1986) Relation of Campylobacter pyloridis to gastritis and peptic ulcer. J Infect Dis 153 : 664-669 6. Dooley CP, Cohen H, Fitzgibbons PL, Bauer M, Appleman MD, Perez-Perez GI, Blaser MJ (1989) Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons. N Engl J Med 321 : 1562-1566 7. Drumm B, O'Brien A, Cutz E, Shermann P (1987) Campylobacwrpyloridis-associated primary gastritis in children. Pediatrics 80 : 192-195 8. Drumm B, Sherman P, Cutz E, Karmali M (1987) Association of Campylobacterpylori on the gastric mucosa with antral gastritis in children. N Engl J Med 316 : 1557-1561 9. Evans D J, Evans DG, Graham DY, Klein P (1989) A sensitive and specific serologic test for detection of Campylobacter pylori infection. Gastroenterology 96:1004-1008 10. Green M (1967) Diagnosis and treatment: psychogenic, recurrent, abdominal pain. Pediatrics 40 : 84-89 11. Killbridge PM, Dahms BB, Czinn SJ (1988) Campylobacwr pylori-associated gastritis and peptic ulcer disease in children. Am J Dis Child 142:1149-1152
12. Lebenthal E, Rossi TM, Nord KS, Branski D (1981) Recurrent abdominal pain and lactose absorption in children. Pediatrics 67 : 828-832 13. Liebman WM (1978) Recurrent abdominal pain in children: a retrospective study of 119 patients. Clin Pediatr 17:149-153 14. Loffeld RJLF, Potters HVPJ, Arends JW, Stobberingh E, Flendrig JA, Spreeuwel JP van (1988) Campylobacter-associated gastritis in patients with non-ulcer dyspepsia. J Clin Pathol 41 : 85-88 15. Loffeld RJLF, Stobberingh E, Flendrig JA, Spreeuwel JP van, Arends JW (1989) Diagnostic value of an immunoassay to detect anti-Campylobacter pylori antibodies in non-ulcer dyspepsia. Lancet I: 1183-1185 16. Mahony MJ, Wyatt JI, Littlewood JM (1988) Campytobacter pylori gastritis. Arch Dis Child 634 : 654-655 17. McGrath PJ, Goodman JT, Firestone P, Shimpman R, Peters S (1983) Recurrent abdominal pain: a psychogenic disorder? Arch Dis Child 58 : 888-890 18. Mitchell HM, Lee A, Berkowicz J, Borody T (1988) The use of serology to diagnose active Campylobacwr pylori infection. Med J Aust 149 : 604-609 19. Newell DG, Rathbone BJ (1989) Review article: the serodiagnosis of CampyIobacter pylori infection. Serodiagn Immunother 3 : 1-6 20. Oderda G, Vaira D, Holton J, Dowsett JF, Ansaldi N (1989) Serum pepsinogen and IgG antibody to Campylobacterpylori in non-specific abdominal pain in childhood. Gut 30 : 912-916 21. Pifieiro-Carrero VM, Andres JM, Davis RH, Mathias JR (1988) Abnormal gastroduodenal motility in children and adolescents with recurrent functional abdominal pain. J Pediatr 113:820-825 22. Rauws EA, Langenberg W, Houthoff H, et al. (1988) Campylobacter pytoridis-associated chronic acitve antral gastritis. Gastroenterology 94 : 33-40 23. Thomas JE, Eastham EJ, Elliott TJS, Nelson R (1988) Campylobacter pylori in children - a common cause of symptoms. Gut 29 : A707 24. Van der Meer SB, Forget PP, HeidendaI GAK (1990) Small bowel permeability to 51Cr-EDTA in children with recurrent abdominal pain. Acta Paediatr Scand 79 : 422-426 25. Van der Meer SB, Forget PP, Arends JW, Kuijten RH, Engelshoven JMA van (1990) Diagnostic value of ultrasound in children with recurrent abdominal pain. Pediatr Radiol 20 : 501-503 26. Van der Meer SB, Forget PP, Arends JW (1990) Abnormal small bowel permeability and duodenitis in recurrent abdominal pain. Arch Dis Child 65:1311-1314 27. Wyatt JI, Rathbone BJ (1989) The role of serology in the diagnosis of Campylobacter pylori infections. Scand J Gastroenterol 24 [Suppl 160] : 27-34
