Scand J Rheumatol 2002;31:94 –6

SHORT REPORT

The prevalence of H. pylori is still substantial in rheumatic patients

H.T.J.I. de Leest1,2,3, K.S.S. Steen1, S. van Wijngaarden4, W.F. Lems1,2,3, M.A.F.J. van der Laar5 andB.A.C. Dijkmans1,2,3

Departments of Rheumatology, 1VU university medical centre; 2Slotervaart Hospital; 3Jan van Breemen Institute, Amsterdam, 4University MedicalCenter, Utrecht, 5Medisch Spectrum Twente, Enschede, the Netherlands

The separate contribution of NSAIDs and H. pylori in the pathogenesis of peptic ulcer disease has not been fully elucidated. The aim ofthis study was to investigate the seroprevalence of H. pylori in patients with rheumatic diseases and chronic NSAID treatment. Patientswith a rheumatic disease, age 40–80 years, and regular use of NSAIDs (at least 3 times a week) were included (n = 1214) . IgG-antibodiesto H. pylori were found in 39% and increased gradually with age: from 25% in patients in the 40–50 years age group to 48% in patientsaged 70–80 years (p < 0.0001) . No diVerence was observed between men and women, or between the three centres. In our population ofrheumatic patients treated with NSAIDs the seroprevalence of H. pylori is substantial (39%), but seems to be lower than in previousreports, which may be due to a cohort eVect.

Key words: Helicobacter pylori, prevalence, NSAID, rheumatic diseases

Patients with rheumatic diseases who are treated with seroprevalence of H. pylori in the western world (7),we investigated the prevalence of antibodies tonon-steroidal anti-in� ammatory drugs (NSAIDs) are

at increased risk of developing upper gastrointestinal H. pylori in patients with rheumatic diseases, treatedwith NSAIDs, in the Netherlands.(GI ) mucosal damage (1). This GI-damage varies

from gastritis and erosions to gastric and duodenalulcers and their life-threatening complications (e.g. Patients and methodsbleeding and perforation) .

PatientsMuch evidence has accumulated for a pathogeneticrole of Helicobacter pylori in the development of Between September 1999 and April 2000, patientsupper GI damage: there is evidence that it causes were tested for the presence of serumantibodies tochronic gastritis, it is considered as a carcinogen, and H. pylori. After informed consent, patients wereit has been accepted as one of the most important recruited from the outpatient rheumatology clinics ofrisk factors for the development of peptic ulceration Amsterdam (Jan van Breemen Institute and the(2). departments of rheumatology of the VU university

It is generally accepted that eradication of H. pylori medical centre and Slotervaart Hospital ), Utrechtaccelerates healing of ulcers and decreases ulcer recur- (University Medical Centre), and Enschede (Medischrence rates in patients with peptic ulcers and H. pylori Spectrum Twente) for a large, collaborative study toinfection, who are not on NSAIDs (3). However, prevent NSAID-gastropathy . Included were patientsthere is no consensus about the bene� t of eradication aged 40–80 years, with a rheumatic disease (e.g.of H. pylori in the absence of an ulcer. rheumatoid arthritis, psoriatic arthritis, ankylosing

The situation is even more complex in H. pylori- spondylitis and osteoarthritis) . All patients were onpositive patients taking NSAIDs. Data on the inter- chronic NSAID treatment (at least 3 times a week).action between NSAIDs and H. pylori in causing Patients with severe (co-) morbidity were excluded.GI-damage are con� icting: in some studies eradica-tion of H. pylori was bene� cial in NSAID-users (4),

Methodswhile others found impaired ulcer healing aftereradication (5, 6). Serum samples were collected and stored at ± 20°C.

Since some studies suggested a decreasing Serologic assays for H. pylori IgG-antibodies wereperformed with a commercial enzyme-linked immu-

H. T. J. I. de Leest, Dept. of Rheumatology, 4A42, VU university nosorbent assay Pyloriset® new EIA-G (Orionmedical centre, P.O. Box 7057, 1007 MB, Amsterdam, The Diagnostica, Espoo, Finland) according to the manu-Netherlands. facturer’s instructions. A serum sample was consid-E-mail: M.deLeest@VUmc.nl

ered seropositive for IgG antibodies to H. pylori ifthe test result was ³ 300 International Units. InReceived 7 December 2001

Accepted 22 March 2002 earlier studies, this cut-oV showed a sensitivity and

94 © 2002 Taylor & Francis on license from Scandinavian Rheumatology Research Foundation

Scan

d J

Rhe

umat

ol D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y SU

NY

Sta

te U

nive

rsity

of

New

Yor

k at

Sto

ny B

rook

on

11/0

1/14

For

pers

onal

use

onl

y.

Prevalence of H. pylori is substantial (Introduction)

speci� city of 98% and 85%, respectively, in detecting worldwide decline in H. pylori seropositivity wasreported in earlier reports from developed countriesH. pylori infection (8). The ethics committees of all

the participating institutes approved the study. (7). Our recent data suggest that the H. pylori infec-tion rate is lower than in a study of the Dutchpopulation in 1990 in which a seroprevalence of 49%

Statisticswas reported (12). These data con� rm the decline ofseroprevalence of H. pylori.The x2-test for trend was used to examine relation-

ships between the presence of antibodies to H. pylori The relatively low overall prevalence and theincreasing prevalence with age (as described in mostand age, gender and centre. A p value less than 0.05

was considered to be signi� cant. previous studies (10, 11)may be caused by a cohorteVect or an age eVect. Elderly patients could have ahigher prevalence of infection because they were born

Resultsat a time when the risk of infection in childhood washigher than in those born later (cohort-eVect) orA total number of 1214 serum samples were assayed

for presence of H. pylori IgG-antibodies. A positive because they have lived longer (age-eVect). The latterpossibility is less likely as the acquisition of H. pyloritest result for IgG-antibodies was obtained in 39%.

The prevalence rates for the age-categories 40–49, is known to occur mostly in childhood. H. pyloriprevalence rates found in studies that investigated50–59, 60–69 and 70–80 years are shown in Table I.

The seroprevalence of H. pylori was 25% in patients subsequent birth-cohorts suggest that H. pylori pre-valence will decrease in the next decades in thein the 40–50 yr. age group. This prevalence increased

signi� cantly with age up to 48% in patients aged Western population (7).The risk of having antibodies to H. pylori might,70–80 years (p <0.0001). No diVerence in seropreval-

ence of H. pylori was observed neither between men at least theoretically, also be in� uenced by socio-economic status (9), ethnic origin and the use ofand women (35% and 40%, respectively, p =0.08),

nor between the three centres Amsterdam, Utrecht, drugs (NSAIDs, antibiotics, protonpumpinhibitor s(PPI ), and intramuscular gold). In our study, theand Enschede (39%, 39%, and 43%, respectively,

p = 0.60). socio-economic status and ethnic origin of the popula-tion were not investigated. In the literature, there areno convincing data on the eVect of NSAIDs (4), PPI

Discussion(13) or intramuscular gold therapy (14) on theseroprevalence of H. pylori.The main conclusion of the present study is that we

observed a prevalence rate of antibodies to H. pylori As a consequence of the widespread use of NSAIDsand the prevalence of H. pylori infection (especiallyof 39% in patients with rheumatic diseases and

chronic NSAID treatment. A second conclusion is in the elderly), these risk factors often coexist. Theinteraction of NSAIDs with H. pylori is controversialthat seroprevalence increased with age.

Although a seroprevalence of 39% is substantial , it and some data suggest that mutual antagonism exists,leading to one of the pathogenic factors actuallyis lower than was reported in population-based stud-

ies performed in Europe and the United States where deriving some protection from the damaging potentialof the other (6, 15, 16).prevalence rates between 52–68% were observed in

the nineties (9, 10). However, some authors found It is diYcult to speculate on trends in GI-damage,because of the decreasing seroprevalence of H. pylori.a lower prevalence of 32–40% in corresponding

age-groups (11). H. pylori might have declining in� uence on the occur-rence of GI-damage. This may probably lead toUnfortunately, it is diYcult to compare study

results without making allowance for the composition relative more NSAID-induced GI-damage. On theother hand, the rapid development of selective COX-2of the population, selection bias and diagnostic

methods for detection of H. pylori infection. A inhibitors (COXIBs) as safer alternatives to NSAIDs

Table I. Prevalence of sera with antibodies (>300I.U.) to H. pylori in patients with rheumatic diseases treated with NSAIDs.

Age group

40± 49 years 50± 59 years 60± 69 years 70± 80 years Total

Positive 56 (25%) 133 (39%) 152 (42%) 133 (48%) 474 (39%)Negative 168 (75%) 211 (61%) 212 (58%) 146 (52%) 737 (61%)Number per group 224 344 364 279 1211

95

Scan

d J

Rhe

umat

ol D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y SU

NY

Sta

te U

nive

rsity

of

New

Yor

k at

Sto

ny B

rook

on

11/0

1/14

For

pers

onal

use

onl

y.

H. T. J. I. de Leest et al.

of infection rates in childhood. Am J Gastroenterolmight as well have implications for the incidence of1997;92:1480 –2.GI-damage (17). In fact, H. pylori might become the

8. Meijer BC, Thijs JC, Kleibeuker JH, van Zwet AA,major cause of peptic ulceration in COXIB-users. Berrelkamp RJ. Evaluation of eight enzyme immunoassays forThus, since the eVect of both NSAIDs and H. pylori detection of immunoglobulin G against Helicobacter pylori.

J Clin Microbiol 1997;35:292 –4.on GI-damage is decreasing, it is diYcult to predict9. Woodward M, Morrison C, McColl K. An investigation intochanges in incidence of GI-damage over the coming

factors associated with Helicobacter pylori infection. J Clinyears.Epidemiol 2000;53:175 –81.

In summary, we found a substantial prevalence of 10. Epidemiology of, and risk factors for, Helicobacter pyloriantibodies to H. pylori of 39% in patients with infection among 3194 asymptomatic subjects in 17 populations.

The EUROGAST Study Group. Gut 1993;34:1672 –6.rheumatic diseases treated with NSAIDs. The preval-11. Dooley CP, Cohen H, Fitzgibbons PL, Bauer M,ence of H. pylori seems to be lower than in previous

Appleman MD, Perez-Perez GI et al. Prevalence ofreports, which may be due to a cohort eVect.Helicobacter pylori infection and histologic gastritis in asymp-tomatic persons. N Engl J Med 1989;321:1562 –6.

12. LoVeld RJ, Stobberingh E, van Spreeuwel JP, Flendrig JA,ReferencesArends JW. The prevalence of anti-Helicobacter(Campylobacter) pylori antibodies in patients and healthy1. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal tox-

icity of nonsteroidal antiin� ammatory drugs. N Engl J Med blood donors. J Med Microbiol 1990;32:105 –9.13. Kuipers EJ, Klinkenberg-Knol EC, Festen HP, Lamers CB,1999;340:1888 –99.

2. Kuipers EJ. Helicobacter pylori and the risk and management Jansen JB, Snel P et al. Long-term omeprazole therapy doesnot aVect Helicobacter pylori status in most patients. Scand Jof associated diseases: gastritis, ulcer disease, atrophic gastritis

and gastric cancer. Aliment Pharmacol Ther 1997;11 Suppl Gastroenterol 1993;28:978 –80.14. ten Wolde S, Janssen M, van Duijn W, Lamers CB,1:71–88.

3. Current European concepts in the management of Helicobacter Hermans J, Dijkmans BA. No eVect of intramuscular goldtherapy on serological parameters of Helicobacter pylori infec-pylori infection. The Maastricht Consensus Report. European

Helicobacter Pylori Study Group. Gut 1997;41:8–13. tion in patients with rheumatoid arthritis: a 12 month prospect-ive study. Ann Rheum Dis 1994;53:400 –2.4. Malfertheiner P, Labenz J. Does Helicobacter pylori status

aVect nonsteroidal anti-in� ammatory drug-associated gastro- 15. Li EK, Sung JJ, Suen R, Ling TK, Leung VK, Hui E et al.Helicobacter pylori infection increases the risk of peptic ulcersduodenal pathology? Am J Med 1998;104:35S –40S.

5. Hawkey CJ, Tulassay Z, Szczepanski L, van Rensburg CJ, in chronic users of non-steroidal anti-in� ammatory drugs.Scand J Rheumatol 1996;25:42 –6.Filipowicz-Sosnowska A, Lanas A et al. Randomised con-

trolled trial of Helicobacter pylori eradication in patients on 16. Janssen M, Dijkmans BA, Vandenbroucke JP, Biemond I, vanDuyn W, Zwinderman AH et al. Serum values of pepsinogensnon-steroidal anti-in� ammatory drugs: HELP NSAIDs study.

Helicobacter Eradication for Lesion Prevention. Lancet and antibodies to Helicobacter pylori in relation to a historyof peptic ulcer disease and NSAID use. Scand J Rheumatol1998;352:1016 –21.

6. Lazzaroni M, Bianchi PG. Nonsteroidal anti-in� ammatory 1995;24:204 –8.17. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-drug gastropathy and helicobacter pylori: the search for an

improbable consensus. Am J Med 2001;110:S50 –4. Vargas R, Davis B et al. Comparison of upper gastrointestinaltoxicity of rofecoxib and naproxen in patients with rheuma-7. Roosendaal R, Kuipers EJ, Buitenwerf J, van UVelen C,

Meuwissen SG, van Kamp GJ et al. Helicobacter pylori and toid arthritis. VIGOR Study Group. N Engl J Med2000;343:1520 –8, 2.the birth cohort eVect: evidence of a continuous decrease

96

Scan

d J

Rhe

umat

ol D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y SU

NY

Sta

te U

nive

rsity

of

New

Yor

k at

Sto

ny B

rook

on

11/0

1/14

For

pers

onal

use

onl

y.