Role of Helicobacter Pylori in the Pathogenesis of Lichen Planus

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1 Med. J. Cairo Univ., Vol. 83, No. 1, March: , Role of Helicobacter Pylori in the Pathogenesis of Lichen Planus NAHLA HUNTAR, M.D.*; MOHAMED EL KOMY, M.D.*; DINA KADRY, M.D.*; RAGIA WESHAHY, M.Sc.*; WAFAA RASHEED, Ph.D.** and LAILA RASHED, M.D.** The Departments of Dermatology* and Biochemistry**, NRC, Faculty of Medicine, Cairo University Abstract Background: Lichen planus (LP) is a common, chronic inflammatory disease that affects the skin, nails, hair follicles and mucous membranes. The exact etiology of LP is unknown but triggering factors such as infections and stress has been suggested. Helicobacter pylori () is a versatile organism exerting its effect through the production of urease, phospholipase, alcohol dehydrogenase, vacuolating cytotoxin, hemolysin, platelet activating factor, and mucolytic factor. Studies showed an asscociatian between and increasing number of dermatologic diseases including rosacea, chronic idiopathic urticaria, psoriasis, Behcet's disease, cutaneous B cell lymphoma, nodular prurigo, alopecia areata and Henoch- Schönlein purpura and LP. Objectives: Is to measure the levels of anti Helicobacter pylori antibodies in the blood of patients of LP to find if it has a role in the pathogenesis of the disease. Methods: The study included 34 blood samples from patients with LP and 34 blood samples from apparently healthy subjects as controls. Anti antibodies (Ig G, Ig M and Ig A) were detected in all patients and control subjects using enzyme-linked immunosorbent assay (ELISA). Results: Our results revealed a significant higher levels of Ig G and Ig M in patients rather than controls. Also serum levels of Ig A were higher in patients than controls but not statistically significant. However results detected no statistical significance regarding colonization of between patients and control subjects. Conclusion: This may implicate to have an immunological role rather than direct etiology. Key Words: Lichen planus Helicobacter pylori. Introduction LICHEN planus is defined as, a chronic papulosquamous inflammatory disease that appears in middle-aged adults and affects the skin, mucous membranes, hair and nail [1]. Lichen planus is a T Correspondence to: Dr. Nahla Huntar, The Department of Dermatology, NRC, Faculty of Medicine, Cairo University cell mediated disease, occurs as a result of a complex interaction between T cells and basal keratinocytes that express altered self antigen on their surface [2,3]. The exact etiology of LP is unknown but triggering factors such as infections and stress have been suggested [4]. Helicobacter pylori is a Gram-negative spiralshaped microaerophillic bacteria. It colonizes the gastric mucosa of humans and non-human primates naturally but is not normally found in other species. Helicobacter pylori is a major cause of human morbidity [5]. Helicobacter pylori is one of the most common bacteria colonizing the human GIT, affecting nearly half of the world population [6]. Although H. pylori is causally related to gastroduodenal diseases, studies have shown that H. pylori seropositivity is associated with various cardiovascular, respiratory, extragastroduodenal digestive, neurologic, dermatologic, autoimmune, and growth disorders [7,8]. An increasing number of dermatologic diseases have been related to H. Pylori infection including LP [9]. The aim of this study is to detect a possible role of in the pathogenesis of LP weather direct or immunological by measuring the levels of anti Helicobacter pylori antibodies in the blood of patients of LP. Patients and Methods Thirty-four patients with cutaneous LP and 34 control subjects were conducted in this study. Patients were collected from those attending the Dermatology Outpatient Clinic in Kasr El-Aini Hospital, Cairo University from December 2011 to May Patients did not receive any systemic or local treatment for LP within the last 4 weeks prior to the study. The diagnosis of LP was made 161

2 162 Role of Helicobacter Pylori in the Pathogenesis of Lichen Planus clinically and confirmed by histopathological examination. Patients with oral or actinic LP were excluded from the study. Control samples were taken from normal subjects who voulnteered. All subjects enrolled in this study gave their written consent. A full medical history was taken from all patients. After complete clinical examination, a venous blood samples were taken from every patient and control subjects for detection of anti H. Pylori antibodies using enzyme-linked immunosorbent assay. Serum samples were collected into a serum separator tube. After clot formation, centrifugation of samples at 2000 x g for 10 minutes were done and sera were separated and stored at 70ºc until analysis. Anti helicobacter antibodies Ig G, A and M were detected quantitatively by the enzymelinked immunosorbent assay (ELISA) method. According to the kit used (Accubind*) helicobacter pylori is colonized when serum levels of Ig G and Ig A >20 and Ig M >40. All patients were diagnosed with infection. Patients with positive Ig G and Ig A were diagnosed as old H. Pylori infection while patients with positive Ig M were diagnosed as recent H. pylori infection. Data were statistically analysed using Microsoft Excel version 15 (Microsoft Corporation, Seattle, WA, U.S.A.) and SPSS statistical program (SPSS, Chicago, IL, U.S.A.). Results Thirty four patients were eligible for participation in this study whose ages ranged from 18 to 80 years with mean age of (41.59 ± 14.51) years. Twenty patients representing 58.8% suffered from gastric manifestations, including constipation and/or heartburn and 1 from both. While 14 patients representing 41.2% did not have gastric manifestations. All patients gave no history of receiving treatment for helicobacter pylori infection. All patients had classic LP except for 4 patients who had hypertrophic LP. Thirty-four control subjects were included in this study; 14 females and 20 males, their age ranged from 18 to 65 years with a mean age of 46.79± Six participants representing 17.6% gave history of heartburn. In the present study anti antibodies were measured in both patients and control subjects. * Accubind ELISA microwells, Monobind Inc. Lake frorest CA 92630, USA. In patients, the serum level of anti-helicobacter pylori Ig G ranged from 0.6 to with a mean level 49.1 ± Serum level of anti-helicobacter Ig A ranged fro 12.2 to with a mean level ± Serum level of Ig M ranged from 15.6 to with a mean level ± All patients were diagnosed with infection. Patients with positive Ig G and Ig A were diagnosed as old infection while patients with positive Ig M were diagnosed as recent H. pylori infection. All patients suffered from old infection while 18 patients suffered from old and recent infection, indicating ongoing infection. As shown in Table (1). In Controls, the serum level of anti-helicobacter pylori Ig G ranged from 0.6 to 51.7 with a mean level 20.7 ± Serum level of antihelicobacter Ig A ranged from 8.2 to U/ ml with a mean level ± Serum level of Ig M ranges from 2.3 to 70.3 with a mean level 31.47± Twenty nine control subjects were diagnosed with infection while 5 were free of infection. Twenty nine patients suffered from old infection while 10 patients suffered from old and recent infection, indicating ongoing infection. Data illustrated in Table (2). In the present study, serum levels of Ig G, A, M were compared between patients and controls. Serum levels of Ig G, A and M were all higher in patients than controls but with statistical significance in Ig G and M only as shown in Table (3). The present study showed that H.Pylori infection was colonized in all patients and in 29 controls, but with no statistical significant difference as shown in Table (4). Old infection was detected in all patients representing 100% and in 29 control subjects representing an 85.3% with no statistical significant difference (p - value=0.053) while recent infection was detected in 18 patients representing 52.1% and in 10 control subjects representing 29.4% with a statistical significant difference (p-value=0.027), as shown in Table (5). Serum level of Ig G in patients with classic LP ranged from 0.6 to with mean 39 ±23.9U/ ml, while serum level of Ig G in patients with hypertrophic LP ranged from 52.7 to with mean 124.8± Regarding serum level of Ig G a highly statistically significant increase was detected among cases with hypertrophic LP

3 Nahla Huntar, et al. 163 compared to those with classic type (p-value= 0.005). Serum level of Ig A in patients with classic LP ranged from 12.2 to with mean 64.1±40.5, while in patients with hypertrophic LP, its level ranged from 44.9 to with mean 68.2 ± No statistical significant difference was found (p-value=0.36). Serum level of Ig M in patients with classic LP ranged from 15.6 to with mean 53.3 ±32.7, while in patients with hypertrophic LP, the serum level of Ig M ranged from 46.7 to 99.7 with mean 67.5±22.5. No statistical significant difference (p-value=019). Data illustrated in Table (6). Table (1): Serum levels of anti H. pylori antibodies in patients. No. Ig G Ig A Ig M H.P A/Pr Type of Pr Old Pr Old Pr Old Pr Old + recent Pr Old + recent Pr Old + recent Pr Old Pr Old Pr Old + recent Pr Old Pr Old Pr Old + recent Pr Old Pr Old + recent Pr Old Pr Old + recent Pr Old + recent Pr Old + recent Pr Old Pr Old + recent Pr Old + recent Pr Old Pr Old Pr Old + recent Pr Old Pr Old + recent Pr Old + recent Pr Old + recent Pr Old Pr Old + recent Pr Old + recent Pr Old Pr Old + recent Pr Old Table (2): Serum levels of anti H. pylori in controls. No. Ig G Ig A Ig M H.P A/Pr Type of A Pr Old Pr Old Pr Old Pr Old A Pr Old Pr Old + recent Pr Old + recent Pr Old + recent Pr Old Pr Old Pr Old + recent Pr Old +recent A Pr Old Pr Old + recent Pr Old Pr Old A Pr Old Pr Old Pr Old A Pr Old + recent Pr Old Pr Old Pr Old+ recent Pr Old + recent Pr Old + recent Pr Old Pr Old Pr Old Pr Old A: Absent. N: Negative. P: Positive. Pr: Present. Table (3): Comparison between patients and controls regarding Ig G, A, and M. Ig G ± Ig A ± Ig M ± Patients Controls p-value ± * ± ± * Table (4): Comparison between patients and controls regarding the colonization of helicobacter pylori. Patients Controls p-value Colonized 34 (100%) 29 (85.3%) Not colonized 0 (0%) 5 (14.7%)

4 164 Role of Helicobacter Pylori in the Pathogenesis of Lichen Planus Table (5): Comparison between patients and controls regarding old and recent infection. Patient N=34 Control N=34 Old 34 29/5 (present/absent) (100%) (85.3/34%) Recent 18/16 10/24 (present/absent) (52.9/ 47.1 %) (29.4/70.6%) Table (6): Comparison between Ig G, A & M and type of LP. Classic Hypertrophic p-value Ig G 39± ± * Ig A 64.1± ± Ig M 53.3± ± Discussion p-value * In the present study, serum levels of antihelicobacter Ig G and Ig M antibodies were significantly higher in patients with LP than control subjects. Also anti-helicobacter Ig A antibodies were higher in patients than control subjects but with no statistical significant difference. While another study examined serum anti H. pylori Ig G in patients with oral LP and reported that they were not different than controls [10]. However, their study was conducted in Iran where the population has different genetic background than our population. In addition, the study examined only patients with oral lichen planus. And because lewis antigens are also expressed on gastric epithelial surface, a potential biological role for bacterial lewis antigens is a molecular mimicry [11]. This could allow H. pylori escape host immunological defence mechanisms by preventing the formation of antibodies directed against shared bacteria and host epitopes [12]. Moreover, the authors did not investigate the levels of anti-helicobacter pylori Ig A and Ig M. In the current study, no statistical significant difference between patients and controls regarding colonization with H. pylori. This is in agreement with several studies [9,10,13]. However, in Pourshahidi et al., [10] infection in control was more than in patients, although in a non significant manner. Izol et al., [9] diagnosed infection using upper endoscopy and biopsy rather than antibodies in patients with oral LP, notebly 71% of their patients suffered from cutaneous LP as well. Zenouz et al., [13], used urea breath test in the diagnosis of infection. These results may be due to the high prevalence of in human population, which is estimated to be 50% [14]. However, this is not in agreement with Moravvej et al., [7] and Devrajani et al., [15], who detected the presence of helicobacter pylori in patients more than controls. However, these 2 studies used stool antigen test in detection of H. pylori rather than serological tests. In the current work, no statistical significant difference was detected regarding type of LP (classic or hypertrophic) and anti-helicobacter pylori Ig M and Ig A antibodies. On the other hand, serum level of anti-helicobacter Ig G antibody was found to be statistically higher in hypertrophic LP than classic LP. This is not in agreement with (Pourshahidi et al., [10] who did not detect any relation between serum anti-helicobacter Ig G antibody level and type of OLP, though their study was on OLP and not cutaneous. Conclusion: In the current study, although there was no significant difference in colonization of H. pylori between patients and control subjects, a significant higher serum anti-h. pylori Ig G antibodies in patients than control. This may implicate an immunological role of H. pylori infection in the pathogenesis of LP rather than direct etiology. References 1- LEHMAN J.S., TOLLEFSON M.M. and GIBSON L.E.: Lichen planus. Int. J. Dermatol., 48: , TETSUO S. and YOKO K.: Lichen planus and lichenoid disorders in text book of Dermatology, edited by Bolognia J., Jorizzo J.L., Schaffer J.V et al., Vol. 1, 3 rd edn. Mosby Elsevier, Chapter 11: , MARSHMAN G.: Continuing Medical Education Review Lichen planus Aust. J. Dermatol., 39: 1-13, VAINIO E., HUOVINEN S., LIUTU M., UKSILA J. and LEINO R.: Peptic ulcer and Helicobacter pylori in patients with lichen planus. Acta. Derm. Venereol., 80: 427-9, PETERSON W.L.: Helicobacter pylori and peptic ulcer disease. N. Engl. J. Med., 324: , MORAVVEJ H., HOSEINI H., BARIKBIN B., MOLE- KZDEH R., and RAZAVI G.M.: Association of Helicobacter pylori with lichen planus. Indian J. Dermatol., 52: , TSANG K.W. and LAM S.K.: Extragastroduodenal conditions associated with Helicobacter pylori infection. Hong Kong Med. J., 5: , SHITONI A., OKADA K., YANAOKA K., ITOH H., et al.: Beneficial effect of Helicobacter pylori eradication in dermatological diseases. Helicobacter, 6: 60-5, 2001.

5 Nahla Huntar, et al İZOL B., AYSE ANIL K., IBRAHIM B., MEHMET G. and MERAL E.: Investigation of upper gastrointestinal tract involvement and H. pylori presence in lichen planus: A case-controlled study with endoscopic and histopathological findings Int. J. Dermatol., 49 (Issue 10): , POURSHAHIDI S., FAKHRI F. and EBRAHIMI H.: Lack of association between Helicobacter pylori infection and oral LP. Asian Pacific J. Cancer Prev., 13: , APPELMELK B.J., MONTEIRO M.A., MARTIN S.L., MORAN A.P. and VANDENBROUCKE-GRAULS C.M.: Why Helicobacter pylori has Lewis antigens. Trends Microbiol., 8: , ZHENG P.Y., HUA J., YEOH K.G and HO B.: Association of peptic ulcer with increased expression of Lewis antigens but not caga, icea, and vaca in Helicobacter pylori isolates in an Asian population. Gut., 47: 18-22, ZENOUZ A.T., MEHDIPOUR M. and HEYDARLOU M.J.: Relationship between lichen planus and helicobacter pylori infection. J. Dent Res. Dent Clin. Dent Prospect, 4 (1): 17-20, WEDI B. and KAPP A.: Helicobacter pylori infection in skin diseases: A critical appraisal. Am. J. Clin. Dermatol., 3: , DEVRAJANI B.R., BAJAJ D.R., BALOCH G.H., DEVRAJANI T., SHAH S.Z.A. and BIBI I.: Frequency of helicobacter pylori infection in patients with lichen planus. World J. Med. Sci., 4 (2): 74-78, 2009.