8 2 4 Sherman et al. The Journal of Pediatrics May 1993

Helicobacter pylori infection in adolescents with eating disorders and dyspeptic symptoms

Philip Sherman, MD, Karen Leslie, MD, Eudice Golderg, MD, Jamie MacMi l lan, MSc, Richard Hunt, MD, and Peter Ernst, DVM

From the Divisions of Gastroenterology, Adolescent Medicine, and Clinical EpidemIology, the Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, and the Departments of Medicine and Immunology, McMaster University, Hamilton, Ontario, Canada

The potent ia l role of Hellcobacter pylori infect ion of the antrum as a cause of symptoms of dyspepsia in patients with eat ing disorders was e v a l u a t e d with an assay to de tec t H. pylori-specitic IgG in serum. H. pylori-specific opt ica l -den- sity readings were c o m p a r a b l e for adolescents with eat ing disorders (0.133 _ 0.063, m e a n _ SD) and for two compar ison groups, and were lower than readings for chi ldren with d o c u m e n t e d H. pylori infect ion. Symptoms referable to the gastrointest inal tract did not corre la te with H. pyloristatus in the t eenag - ers with ea t ing disorders. (J PEOiAI'R 4993;422:824-6)

Patients with eating disorders frequently have multiple symptoms consistent with nonulcer dyspepsia, t The poten- tial role of ttelicobacter pylori infection as a cause of dys- peptic symptoms in patients with anorexia nervosa and bu- limia nervosa had not been examined previously. Therefore we undertook a prospective, controlled study to determine the frequency of H. pylori infection among female adoles- cents with eating disorders.

M E T H O D S

Patients. Between November 1990 and February 1992, serum samples were collected prospectively from patients with eating disorders followed in the adolescent clinic at the Hospital for Sick Children, Toronto. Patients had previ- ously been identified as having anorexia nervosa, bulimia nervosa, or unclassified eating disorders, according to the established criteria. 2 On the day that serum samples were collected, subjects were also asked to complete a standard- ized questionnaire that sought to determine current and previous symptoms of vomiting, hematemesis, melena, ab- dominal pain, excessive belching and flatulence, use of ant- acids and acid-suppressing agents, heartburn, diarrhea or

Supported by grants from the Medical Research Council of Can- ada and the Canadian Foundation for Ileitis and Colitis. Dr. Sher- man is the recipient of a Career Scientist Award from the Ontario Ministry of Health. Submitted for publication June 10, 1992; accepted Dec. 14, 1992. Reprint requests: Philip Sherman, MD, FRCPC, Division of Gas- troenterology (Room 1448), Hospital for Sick Children, 555 Uni- versity Ave., Toronto, Ontario M5G IX8, Canada. Copyright �9 1993 by Mosby-Year Book, Inc. 0022-3476/93/$1.00 +.10 9/28/44874

constipation, laxative use, and family history of peptic ul- cer disease.

Serum samples obtained from well-nourished patients seen in the hospital's adolescent clinic for the evaluation of acute medical conditions unrelated to the gastrointestinal tract were used for comparison. Serum samples obtained previously from patients with documented chronic inflam- matory bowel diseases were matched, on a group basis, for age and sex with the patient samples collected prospectively.

Stored serum samples obtained previously from adoles- cents with endoscopic and serologic evidence of either the presence of H. pylori infection or the absence of H. pylori colonization of the antrum 3 were used in the immunoassay as positive control samples and negative control samples, respectively. All serum samples were held at - 7 0 ~ C until their use in the immunoassay. The study was reviewed and approved by the hospital's human subjects review commit- tee.

lmmnnoassay. A commercial enzyme-linked immunosor- bent assay (Whittaker Bioproducts, Walkersville, Md.), , based on an assay used previously with success, 3,4 was em-

ployed in this study to detect H. pylori-specific IgG anti- bodies. An arbitrary cutoff optical density of >--0.150 was considered a positive result. Serum samples were assayed in triplicate.

Statistical analysis. Results are expressed as means + SD. The two-tailed Fisher Exact Test 5 was employed to de- termine the significance of differences in groups defined by the presence or absence of findings. Analysis of variance and the Student t test (two-tailed), with the Bonferroni adjust- ment, were used to compare differences in mean values be- tween groups. 5

The Journal of Pediatrics Sherman et al. 8 2 5 Volume 122, Number 5, Part 1

R E S U L T S

Serum samples obtained previously from 18 children and adolescents With H. pylori gastritis (confirmed by culture and silver stain of antral biopsy specimens and by previous positive antibody responses) and an equal number of sub- jects without H. pylori infection and with a negative immune response were used to establish the sensitivity (83.3%) and specificity (88.9%) of the immunoassay. These were comparable lo the sensitivity and specificity of previ- ous immunoassays employed to detect H. pylori.

As shown in the Table, H. pylori-specific lgG antibody was present in I0 (20.8%) of 48 female adolescents with eating disorders. Optical-density values for these teenagers were comparable to those for children not infected with H. p.vlori (p = 0.65) and were less than the antibody response in children with documented H. pylori infection (p <0.00 I). The frequency of a positive H. pylori-specific antibody re- sponse in female adolescents with chronic inflammatory bowel diseases and in female teenagers without gastrointes- tinal symptoms (t5/64, 23.4%) was comparable to that in the eating disorder group (10/48, 20.8%; p >0.05). The op- tical-density readings were also comparable (0.133 -+ 0.063 vs 0.130 +_ 0.053;p >0.05).

A structured questionnaire was completed by 33 teenag- ers with eating disorders. Current and previous symptoms of vomiting, belching, heartburn, abdominal pain, diarrhea, constipation, and upper or lower gastrointestinal tract hemorrhage did not correlate with H. pylori serologic status. A family history of peptic ulcer disease and urban residence also did not correlate with 14. pylori seroposi- tivity.

D I S C U S S I O N

The results of this serologic study indicate that 11. pylori infection is not an identifiable cause of the symptoms of nonulcer dyspepsia that affect the majority of patientswith eating disorders. 1, 2 The potential role of H. pylori infection as a cause of these symptoms was examined because some previous studies had suggested a role of this bacterial infec- tion in the pathogenesis of dyspeptic symptoms.6

The precise role of H. pylori colonization of the antrum as a cause of dyspeptic symptoms in the absence of acute peptic ulceration remains controversial. 6 H. pyloriinfection and antral chronic-active gastritis frequently occur in the absence of clinical symptoms. The prevalence of asymp- t~ H" pylori infection increases with advancing chro- nologic age. 4 Resolution of the symptoms of noaulcer dys- pepsia after therapy to eradicate H. pylori infection suggests an etiologic role for the organism. 7 However, studies of subjects with nonulcer dyspepsia demonstrate a considerable placebo effect. 8 Therefore, to determine the

Table. H. pylori-specific IgG response in female

adolescents with eating disorders, chronic inflammatory bowel diseases, and other, nonintestinal, medical conditions

Positive antibody response*

No. of Optical Slucly group subjects No. % densltyt

Eating disorder 48 10 20.8 0.133 ___ 0.063 Anorexia nervosa 23 4 0.121 4- 0.047 Btilimia nervosa 18 5 0.156 ___ 0.083 Unclassified 7 I 0.117 ___ 0.032

Control subjects 64 15 23.4 0.130 +__ 0.053 Inflammatory 39 4 0.115 ___ 0.028

bowel diseases Crohn disease 25 3 0.120 + 0.026 Ulcerative colitis 14 I 0.105 ___ 0.030

Other medical 25 I I 0.153 __. 0.073 conditions

*Optical density of 0.150 was used as the cutoff value for positive results. "~Resu~ts are expressed a s means -'i-- SD. The frequency of positive antibody responses and optical-density readings was lower in each of the study group~ than in children ~ith previously documented 14. pylori infection (positive antibody response in 15 of 18 subjects: analysis of variance, p <0.001; op- tical density, 0.245 4- 0.082; p <0.001).

potential role of H. pylori infectio n in adolescents with eat- ing disorders, we employed two comparison groups of com- parable ages in this study.

The optical-density readings for the sera of the 18 chil- dren with previously documented H. pylori infection and H. pylori seropositivity (0.245 _+ 0.080) were lower than those for adult-derived control sera provided in the commercial immunoassay kit (0.295 to 0.393). A lower immune re- sponse in children compared with adults has been reported previously. 9 This may relate to the severity of the gastritis and the density of bacterial colonization of the antrum, both of which are less in children than in adults. There is no ev- idence that the host humoral immune response is impaired in adolescents compared with adults.

A potential criticism of this study is that the sample size was too small to detect statistical significance. Hov~ever, we did not observe clinically important differences for compar- isons with p >0.05. For example, the observed difference in optical-density readings between control subjects and pa- tients with ealing disorders was less than 0.33 SD. The power to detect this difference was 65%, too low to be con- sidered clinically important.

Currently many commerciai immunoassays are available for use in the detection of H. pylori -specific IgG in serum. The assays employ either multiple bacterial surface anti- gens, as in the enzyme-linked immunosorbent assay utilized in this study, or purified H. pylori-specific surface antigens

8 2 6 Sherman et al. The Journal of Pediatrics May 1993

such as urease and high molecular weight outer-membrane proteinsJ ~ A recent multicenter collaborative study indi- cates that these immunoassays are of comparable sensitiv- ity and specificity regardless of the test antigen employed, and that the precise cutoff value employed is not a critical factor in a comparative, age-matched, controlled study such as the one described herein. I1

The results of numerous previous studies (including our own previous study 3) using the same reagents as those now available commercially and used in our current analysis, indicate that H. pylori-specific serum IgG is a sensitive and specific marker of H. pylori infection. Therefore the sero- logic data likely provide a true reflection of the prevalence of 11. pylori infection in female adolescents with eating dis- orders, even though diagnostic endoscopy plus mucosal bi- opsies were not employed in our study. The results of this study indicate that the prevalence of H. pylori in sera of patients with eating disorders is not higher than in compa- rably aged female subjects with either chronic inflamma- tory bowel diseases or acute medical conditions unrelated to the gastrointestinal tract. Medical therapy directed at the eradication of H. pylori infection is therefore not justified for teenagers with eating disorders and H. pylori seropos- itivity in the absence of endoscopic evidence of peptic ulcer- ation.

Immunoassay kits were kindly provided to Dr. Ernst by NCS Diagnostics Inc., Mississauga, Ontario.

REFERENCES

!. Waldholtz BD, Andersen AE. Gastrointestinal symptoms in anorexia nervosa: a prospective study. Gastroenterology 1990; 98:1415-9.

2. Herzog DB, Copeland PM. Eating disorders. N Engl J Med 1985;313:295-303.

3. Drumm B, Perez-Perez GI, Blaser M J, Sherman PM. Intra- familial clustering of Helicobacter pylori infection. N Engl J Med 1990;322:359-63.

4. Dooley CP, Cohen H, Fitzgibbons PL, et al. Prevalence of He- licobacter pylori infection and histologic gastritis in asymp- tomatic persons. N Engl J Med 1989;321:1562-6.

5. Fleiss JL. The design and analysis ofclinical experiments. New York: John Wiley & Sons, 1986.

6. Elta GH. Helicobacter pylori in patients with nonulcer dyspepsia. Rev Infect Dis 1991;13(suppl 8):$696-9.

7. Goh KL, Parasakthi N, Pch SC, Wong NW, Lo YL, Puthuc- heary SD. Helicobacter pylori infection and nonulcer dyspep- sia: the effect of treatment with colloidal bismuth subcitrate. Scand J Gastroenterol 1991;26:1123-31.

8. Heatley RV, Rathbone BJ. Dyspepsia: a dilemma for doctors? Lancet 1987;2:779-82.

9. Crabtree JE, Mahoney M J, Taylor JD, Heatley RV, Little- wood JM, Tompkins DS. Immune responses to Helicobacter pylori in children with recurrent abdominal pain. J Clin Pathol 1991;44:768-71.

10. Newell DG, Rathbone BJ. The serodiagnosis of Campylobac- terpylori infection. Serodiagnosis and Immunotherapy in In- fectious Disease 1989;3:1-6.

11. Talley N J, Newell DG, Ormand JE, et al. Serodiagnosls of Helicobacter pylori: comparison of enzyme-linked immu- nosorbent assays. J Clin Microbiol 1991;29:i635-9.

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