Utama edisi 4-2007.indd - Acta Medica Indonesiana

3 downloads 0 Views 2MB Size Report
to 50% seroprevalence in general population all over ..... Rani AA. Penatalaksanaan mutakhir infeksi Helicobacter pylori di Indonesia dan dampaknya bagi ...
ORIGINAL ARTICLE

Helicobacter pylori Infection: Prevalence in Chronic Urticaria Patients and Incidence of Autoimmune Urticaria (Study in dr. Cipto Mangunkusumo Hospital, Jakarta) Grace Nami Sianturi*, Retno W. Soebaryo*, Farida Zubier*, Ari Fahrial Syam**

ABSTRACT Aim: to determine the prevalence of Hp infection in patients with chronic urticaria (CU) and to evaluate the result of autologous serum skin test (ASST) in CU patients with Hp infections. Methods: in this cross-sectional study, 16 patients with chronic urticaria and 16 non-urticaria volunteers were investigated (matched for age and sex). All subjects were examined for Hp infection with the 13C-urea breath test. Autologous serum skin test was performed in patients with proven Hp infection. Results: Helicobacter pylori was detected in 12.5% of patients and 0% of the control group. There was no signicant difference between the two groups (p = 0.484 using Fisher exact test). Autologous serum skin test was positive in 1 of 2 CU patients with Hp infection. Conclusion: in this study, there was no significant difference in the seroprevalence of Hp infection between CU patients and controls. Autologous serum skin test was positive in 1 of 2 CU patients with Hp infection. Key words: chronic urticaria, H. pylori infection, autoimmune urticaria. INTRODUCTION

Chronic urticaria (CU) is a common problem for patients and physicians, due to the unknown etiology in 80-90% of cases.1-4 This group is considered as idiopathic chronic urticaria (ICU). Further studies found pathogenic autoantibody in 30-50% of ICU cases and included in autoimmune urticaria (AU) group, while the other part of the cases is still considered idiopathic.4-6 Pathogenic autoantibody could be detected using several tests, such as autologous serum skin test (ASST) also known as Greaves Test.7-10 This examination is * Department of Dermatovenereal Disease, ** Department of Internal Medicine, Faculty of Medicine University of Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta

considered the best in vivo test to detect histamine release activity in AU.8,9 Helicobacter pylori (Hp) infection is the most common chronic bacterial infection in human, with up to 50% seroprevalence in general population all over the world.11-16 The role of Hp infection as the etiology of gastrointestinal disease has been clearly recognized. Further study found evidences that Hp infection also plays a role in extragastrointestinal diseases, including ICU.17-19 A number of studies in several countries showed the high prevalence of Hp infection in ICU patients, followed by clinical remission of ICU after Hp eradication therapy. The prevalence in initial study was up to 80% and clinical remission after Hp eradication therapy was found in 95-100% patients.11,18,20 A metaanalysis study on Hp infection in ICU concluded that the chance of urtica resolution was fourfold in patients receiving Hp eradication therapy compared to patients not receiving therapy.1 However, total remission was only found in one-third of patients. There are several hypotheses explaining the role of Hp infection in ICU. One of them links Hp infection with AU based on the evidence that Hp infection triggers pathogenic autoantibody formation in some ICU cases.6,15,22 The production of pathogenic autoantibody is thought to be due to molecular similarity. Lipopoly saccharides of several Hp strains are structurally similar to Lewis X and Lewis Y blood type antigen, which are expressed by the gastric mucosa. The antigen resemblance causes immune tolerance to Hp antigen or induction of autoantibody which recognizes the gastric mucosa epithelial cell.6,15,22 Hp infection could be detected using invasive and non-invasive tests.23-36 Urea breath test (UBT) is the gold standard of non-invasive tests to diagnose Hp infection, due to the Indonesian Helicobacter pylori Study Group (IHPSG) or Kelompok Studi Helicobacter 157

Grace N. Sianturi, et al

pylori Indonesia (KSHPI) recommendation and the Asia Pacic Hp Management Consensus 1997.12,27,28 The advantage of UBT compared to other tests is that it is non-invasive, more comfortable for the patient, simple, easy, able to detect Hp active infection, could be used to assess the success of eradication therapy, and shows high sensitivity and specicity (90-98% and 92-100%).23-32 Currently there is no studies on the prevalence of Hp infection in CU nor the Indonesian population in general. The aim of this study is to obtain the information of the prevalence of Hp infection in CU compared with the non-urticaria control group, and also the distribution of positive autologous serum skin test (ASST) in CU patients infected with Hp as the additional result in this study.

Acta Med Indones-Indones J Intern Med

urticaria was more common in females, about 81.25% of all cases. The educational level in most SP was at middle level, similar in both groups.

METHODS

The design of this study is cross sectional, comparing between groups. The study subjects (SS) were 16 CU patients and 16 non-CU control patients visiting the Allergy-Immunology outpatient clinic, Department of Dermato-venereology and patients visiting endoscopy room at Gastroenterology Division, Department of Internal Medicine Dr. Cipto Mangunkusumo Hospital (CMH) Jakarta. Sample size was calculated based on the hypothesis formula for two proportions. The two groups were matched for age and sex. The study was initiated in November 2005 and ended in June 2006. An urea breath test (UBT) was performed on all SP using 13C atom (UBiTRIR-300, Otsuka, Japan). ASST was performed in CU patients infected with Hp. ASST was considered positive when the diameter of serum urtica was³ 1.5 mm compared to the negative control. The inclusion criteria for all SP were over 15 years of age and willing to sign the informed consent. Exclusion criteria for all SP were the use of systemic antibiotic agent less than 1 week before UBT test and proton pump inhibitor (PPI) agent less than 2 weeks before UBT test. Exclusion criteria for the CU group were patients with urtica lesions persisting for > 48 hours and use of agents that could interfere with ASST test result based on the agent’s half life. RESULTS Characteristics and Clinical Distribution of Study Subjects

Age, sex, and educational level between both groups were comparable. The youngest age was 17 years and the oldest was 67 years old. The mean SP age in experimental group was 36.25 ± 14.31 years old, and 37.13 ± 12.33 years in the control group. Chronic 158

There was no reference clearly mentioning the frequency of gastrointestinal symptoms in ICU patients, however in general there was no signicant difference in dyspepsia symptoms between ICU patients and general population. In this study there was no signicant difference in dyspepsia symptoms between CU and control group (p=1.000). Based on the clinical characteristics of CU patients, the duration of last CU episode was relatively long, between 7 weeks and 7 years (median 28.00 weeks). Most (93.75%) patients complained that the urtica occurred more than two times in a week. All patients had received medications before coming to CMH and most of them (81.25%) using combination therapy. The most common combination of therapy was antihistamine, systemic corticosteroid, and topical antipruritus, by 7 (43.75%) patients. Angioedema/history of angioedema was found in 10 (62.5%) cases. Prevalence of Hp Infection

Hp infection was found in 2 (12.5%) patients in experimental group, but none in the control group. Fisher exact test did not nd signicant difference in prevalence between experimental and control group (p=0.484). Two CU patients with Hp infection were consulted to the Gastroenterology Division Department of Internal Medicine for further management. Both received Hp eradication therapy regimen. Follow up at 1 and 2 months after eradication therapy showed clinical improvement in both patients.

Vol 39 • Number 4 • October - December 2007

Distribution of Positive ASST in CU Patients Infected with Hp

Incidence of AU marked by positive ASST result was obtained in 1 CU patient with Hp infection, a 48-yearold female patient. Distribution of positive ASST in CU patients infected with Hp was only an additional result in this study, so no statistical analysis was performed.

DISCUSSION

Studies on the prevalence of Hp infection in several countries among CU patients showed variative results,

Helicobacter pylori Infection: Prevalence in Chronic Urticaria

between 10-87%.11,18,20,22,37,39-45 This was probably due to various Hp infection identication methods being used and also demographic and sosioeconomic difference. Most studies used serologic tests to identify Hp infection, which could not determine active Hp infection. Only one study was done in a developing country using UBT to identify Hp infection in ICU patients, by Ghazzawi et al. (2004) which was in Jordan.42 In the study, Hp infection was found in 87 (87%) patients. However, the control group in that study did not undergo UBT but used serologic test instead. In this study we compared CU patients with the non-urticaria control group, considering the prevalence

159

Grace N. Sianturi, et al

of Hp infection is relatively high in general population. There are currently no data on prevalence of Hp infection in general population in Indonesia, using whether serologic test or UBT. Based on a clinical review by Miwa et al (2002), seroprevalence of Hp infection in general population in Asian countries ranged between 31.4-91.7%, with mean 60.1%.46 When using the Fisher exact test, we did not nd signicant difference in the prevalence of Hp infection between CU patient group and control group (p=0.484). In this study we found that the number of Hp infection prevalence in CU was 12.5% while none had Hp infection in control group. This is similar to the study by Burova (1998) which found 10% prevalence from 20 ICU patients2, and Wustlich (1999) who found 16% prevalence in 188 CU patients.3 Identication method for Hp infection used in the Burova study was UBT and serology, while Wustlich used UBT. Other studies also using UBT or combination between UBT and other test as identication method found varied prevalence, which ranged from 24 to 87%. Studies using other identication methods found 39-82% prevalence. The difference in study results was probably due to demographic, socioeconomic, race/ethnicity, Hp infection identication method being used, and variability of UBT instruments. The low prevalence of Hp infection in this study is also thought to be due to the low prevalence of Hp infection among the general population in Indonesia. However, data on Hp infection prevalence in Indonesian population are not available. The only available data in Indonesia is prevalence of Hp infection in dyspepsia. Role of Hp infection as an etiology in gastrointestinal diseases has been widely accepted, and the prevalence of Hp infection in gastrointestinal disease is higher compared to the prevalence in extragastrointestinal disorders. However, Syam et al (2005) reported that only 13.5% of Hp infection in dyspepsia patients were identied by UBT.47 The number is close to the one obtained in this study. Related to Hp infection, dyspepsia occurred as a complaint in a small number of Hp-infected patients.48 El-Ammawi et al (2004) found gastrointestinal symptoms in 24 (60%) out of 40 ICU patients infected with Hp.44 Similar result was found in this study, where dyspepsia was found in 12 (75%) CU patients. In order to know whether the prevalence of Hp infection in CU patients is higher in patients with dyspepsia, the relationship between dyspepsia and Hp infection was analyzed. Fisher exact test did not nd signicant result between dyspepsia and Hp infection in CU patients (p=1.000). 160

Acta Med Indones-Indones J Intern Med

This study also performed the ASST test to observe the incidence of AU in Hp-infected CU patients. According to Greaves (2004), Hp infection is not a direct cause of CU, but related to autoimmunity instead.2 Relationship between Hp infection and autoimmune disease, including AU, was based on the evidence that Hp infection triggers pathogenic autoantibody formation in some ICU cases due to antigenic immunogenicity of Lewis X and Y blood types found in Hp cell envelope polysaccharides.2,15,22 Autoantibody is found due to molecular resemblance, analogue with the role of Campylobacter jejuni in other autoimmune diseases such as Guillain-Barre syndrome.2,14,15 In this study, Hp infection was found in 2 CU patients. One was a 67-year-old male and the other was a 48-year-old female. Positive ASST test was found in female patients. Hizal et al (2000) found positive ASST result in 40% Hp-infected CU patients and only 15% in CU patients not infected with Hp.44 Atta et al (2004) did not nd signicant difference in anti-IgE antibody level between the two groups.49 This result was further supported by Baskan et al (2004) who did not find significant relationship between Hp infection and ASST.22 CONCLUSION

Prevalence of Hp infection in CU patients was not signicantly different with non-urticaria controls (p=0.484). Therefore, the study hypothesis is not proven. Incidence of AU marked by positive ASST result was found in 1 of 2 Hp-infected CU patients. Based on this study, we suggest to commence a larger study with larger sample size, an identication test for Hp infection (such as UBT) could be considered in the management procedure of CU patients, further study on the effectivity of Hp eradication therapy to clinical remission of urticaria in Hp-infected CU patients, and evaluation on the result of positive ASST distribution in Hp-infected CU patients.

Vol 39 • Number 4 • October - December 2007

ACKNOWLEDGEMENT

The authors would like to thank Dr. Joedo Prihartono,MPH, as statistical consultant, Prof. Malcolm W. Greaves, Emeritus Professor of Dermatology St. Johns Institute of Dermatology, St. Thomas HospitalLondon and National Skin Centre-Singapore. REFERENCES 1.

2.

3.

4. 5.

6. 7. 8. 9.

10.

11. 12.

13. 14. 15. 16.

Charlesworth EN. Chronic urticaria and angioedema: background, evaluation, and treatment. In: Adelman DC, Casale TB, Corren J, eds. Manual of allergy and immunology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2002. p.187-98. Greaves MW, Kaplan AP. Chronic urticaria: autoimmune chronic urticaria and idiopathic chronic urticaria. In: Greaves MW, Kaplan AP, eds. Urticaria and angioedema. New York: Marcel Dekker Inc; 2004. p. 321-41. Saltoun CA, Metzger WJ. Urticaria, angioedema, and hereditary angioedema. In: Greenberger PA, Grammer LC, eds. Patterson’s allergic disease. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 239-56. Sheikh J. Urticaria. e-Medicine journal. From: www.emedicine. com.med/topic 3014.htm Cited on March 9th; 2004. Grattan CE. Clinical aspects: urticaria. In: Bruijnzeel-Koomen CAFM, Knol EF, eds. Immunology and drug therapy of allergic skin diseases. Switzerland: Birkhauser Verlag Basel; 2000. p. 17-56. Greaves MW. Urticaria and angioedema. In: Leung DYM, Greaves MW, eds. Allergic skin disease. New York: Marcel Dekker Inc; 2000. p. 171-93. Ring J, Brockow K, Ollert M, Engst R. Antihistamines in urticaria. Clin Exp Allergy. 1999; 29 Supp1:31-7. Godse KV. Autologous serum skin test in chronic idiopathic urticaria. Indian J Dermatol Venereol Leprol. 2004;70:283-4. Sabroe RA, Grattan CEH, Francis DM, Barr RM, Black AK, Greaves MW. The autologous serum skin test for autoantibodies in chronic idiopathic urticaria. British J Dermatol. 1999;140:446-52. Fiebiger E, Hammerschmid F, Stingl G, Maurer D. AntiFceRIa autoantibodies in autoimmune-mediated disorders: identication of a structure-function relationship. J Clin Invest. 1998; 101(1): 243-51. Dauden E, Jimenez-Alonso, Garcia-Diez. Helicobacter pylori and idiopathic chronic urticaria. Int J Dermatol.2000;39:446-52. Rani AA. Penatalaksanaan mutakhir infeksi Helicobacter pylori di Indonesia dan dampaknya bagi kesehatan masyarakat. Presented in the speech on the declaration as FMUI Emeritus Professor in Internal Medicine, Jakarta, 2003. Moss SF, Sood S. Helicobacter pylori. Curr Opinion in Infect Dis. 2003;16:445-51. Covacci A, John LT, Giudice GD, Parsonnet J, Rappuoli R. Helicobacter pylori virulence and genetic geography. Science 1999; 284:1328-33. Vandenplas Y. Helicobacter pylori infection. World J Gastroenterol. 2000;6(1):20-31. Hegar B. Helicobacter pylori in children. Presented at Mini Symposium Helicobacter pylori: kuman di lambung yang harus selalu diwaspadai, Jakarta, 29th May 2006.

Helicobacter pylori Infection: Prevalence in Chronic Urticaria

17. Tsang KW, Lam SK. Extragastroduodenal conditions associated with Helicobacter pylori infection. HKMJ. 1999;5(2):169-74. 18. Gonzales D. Chronic urticaria and Helicobacter pylori: review article. Allergol Immunol Clin. 2000;15:366-73. 19. Tsang KW, Lam SK. Helicobacter pylori and extradigestive disease. J Gastroenterol Hepatol. 1999;14:844-50. 20. Tebbe B, Geilen CC, Schulzke JD, Bojarski C, Radenhausen M, Orfanos CE. Helicobacter pylori infection and chronic urticaria. J Am Acad Dermatol. 1996;34:685-6. 21. Soter NA, Kaplan AP. Urticaria and angioedema. In: Freedberg IM, Eisen AZ, Wolff K, Ausien KF, Goldsmith LA, Katz SI, et al,eds. Fitzpatrick’s dermatology in general medicine. 6th ed. New York: McGraw Hill; 2003. p.1129-39. 22. Baskan EB, Turker T, Gulten M, Tunali S. Lack of correlation between Helicobacter pylori infection and autologous serum skin test in chronic idiopathic urticaria. Int J Dermatol. 2004;0(0):1-3. 23. Megraud F. Helicobacter pylori testing. Eur pharmacotherapy. 2003:36-8. 24. Stone MA. Non-invasive testing for Helicobacter pylori. Postgrad Med J. 1999;75:74-7. 25. Syam AF, Rani A. Helicobacter pylori. In: Djauzi S, Sundaru H, eds. Imunisasi dewasa. Jakarta: Balai Penerbit FKUI, 2003. p.136-42. 26. Syam AF. Diagnosis dan penatalaksanaan infeksi Helicobacter pylori. Presented at Mini Symposium Helicobacter pylori: kuman di lambung yang harus selalu diwaspadai. Jakarta, 29th of May 2006. 27. Konsensus Nasional Penatalaksanaan Infeksi Helicobacter pylori 2003. Jakarta: Pusat Informasi dan Penerbitan bagian Ilmu Penyakit Dalam FKUI; 2003. p. 6-10. 28. Asia Pacic Consensus Conference on the management of H. Pylori infection, 1997. 29. Abdullah M, Rositawati W. Pemeriksaan 13C-Urea Breath Test untuk diagnosis infeksi Helicobacter pylori aktif. Informasi Laboratorium Prodia. 2003;1:3-5. 30. Berger A. Helicobacter pylori breath test: how does it work? BMJ. 2002;324:1263. 31. Otsuka Pharmaceutical Co. Petunjuk untuk melakukan uji pernapasan UBiTâ-IR300;2001. 32. Ng FH, Lai KC, Wong BCY, Wong WM, Wong SY, Chow KC, et al. 13C-urea breath test without prior fasting and without test meal is accurate for the detection of Helicobacter pylori in Chinese. J Gastroenterol Hepatol. 2002;17:834-8. 33. Okuda M, Nakazawa T, Booka M, Miyashiro E, Yosikawa N. Evaluation of a urine antibody test for Helicobacter pylori in Japanese children. J Pediatr. 2004;144(2):196-9. 34. Vinette KM, Gibney KM, Proujansky R, Fawcett PT. Comparison of PCR and clinical laboratory test for diagnosing H.pylori infection in pediatric patients. BMC Microbiol. 2004; 4(1):5. 35. Syam AF, Rani AA, Abdullah M, Manan C, Simadibrata M, Djojodiningrat D, et al. Accuracy of Helicobacter pylori stool antigen for the detection of Helicobacter pylori infection in dyspeptic patients. World J Gastroenterol. 2005;11(3):386-8. 36. Simadibrata P, Simadibrata R, Simadibrata M. Detection of Helicobacter pylori infection with stool antigen: comparison with other techniques. Indonesian J Gastroenterol Hepatol Digest Endos. 2002;3(2):46-9. 37. Liutu M, Kalimo K, Uksila J, Kalimo H. Etiologic aspects of chronic urticaria. Int J Dermatol. 1998;37(7):515-9. 38. Doyle ME. Helicobacter pylori. Food and research institute 1997. From:www.wisc.edu/fri/Hpy/Hpylori.htm Disitasi 16 Sept 2003 161

Grace N. Sianturi, et al

39. Ozkaya-Bayazit E, Demir K, Ozguroglu E, Kaymakoglu S, Ozarmagan G. Helicobacter pylori eradication in patients with chronic urticaria. Arch Dermatol. 1998;134:1165-6. 40. Greaves MW. Chronic Idiopathic Urticaria (CIU) and Helicobacter pylori – not directly causative, but could there be a link? ACI International. 2001;13(1):23-6. 41. Schnyder B, Helbling A, Pichler WJ. Chronic idiopathic urticaria: natural course and association with Helicobacter pylori infection. Int Arch Allergy Immunol. 1999;119:60-3. 42. Ghazzawi IM, Obidat NA. The role of Helicobacter pylori infection in the pathogenesis of chronic urticaria. Pak J Med Sci. 2004;20(2):101-4. 43. El-Ammawi TS, El-Fatah ME, Ramadan MY. Prevalence of Helicobacter pylori in patients with idiopathic chronic urticaria. Pak J Med Sci. 2004;15(2):75-80. 44. Hizal M, Tuzun B, Wolf R, Tuzun Y. The relationship between Helicobacter pylori IgG antibody and autologous serum test in chronic urticaria. Int J Dermatol. 2000;39:443-5.

162

Acta Med Indones-Indones J Intern Med

45. Bakos N, Hillander M. Comparison of chronic autoimmune urticaria with chronic idiopathic urticaria. Int J Dermatol. 2003; 42:613-5. 46. Miwa H, Sato N. H. pylori and gastric cancer: the Asian enigma. Am J Gastroenterol. 2002;97(5):1106-12. 47. Syam AF, Rani AA, Abdullah M, Manan C, Makmun D, Simadibrata M, et al. Accuracy of 14C-urea breath test (UBT) for the detection of Helicobacter pylori infection in dyspeptic patients. J Gastroenterol Hepatol. 2005;20(Suppl):A162. 48. Bener A, Uduman SA, Ameen Alwash R, Pasha MA, Usmani MA, et al. Prevalence of Helicobacter pylori infection among low sosio-economic workers (abstr). Entrez PubMed 2004 (cited on April 14th, 2004). From: www.ncbi.nlm.nih.gov/entrez/ 49. Atta AM, Rodriguez MZA, Sousa CP, Medeiros J, Sousa-Atta MLB. Autoantibody production in chronic urticaria is not associated with Helicobacter pylori infection. Braz J Med Biol Res. 2004;37(1):13-7.