celiac disease ( cd ) is a t - cell - mediated disorder , which is induced by gluten ingestion in genetically predisposed individuals . different studies showed that the prevalence of cd is approximately 1% in many populations worldwide . new diagnostic tools increased the consciousness and improved the diagnosis of the disease , thus causing an apparent real increase in the incidence of cd . cd is diagnosed by abnormal histology of duodenal biopsy specimens as well as with diagnostic tools , including serologic tests for antibodies against tissue transglutaminase ( anti - ttg ab ) and deamidated gliadin peptide ( dgp ) . in suspicious cases for example in first degree relatives of patients with cd and in patients with autoimmune disorders , evaluation of hla - dq2 and hla - dq8 haplotypes are useful tools . according to recent guidelines by paediatric gastroenterology hepatology and nutrition ( espghan ) , clinical symptoms of cd and other gluten related disorders can be relieved by adherence to a gluten - free diet and a diagnosis can be made without biopsy taking in certain circumstances , especially in those cases with an increase value of anti - ttg antibodies ( iga ) more than 10 time than upper limit . helicobacter pylori ( h. pylori ) , the causative agent in more than 90% of patients with gastroduodenal disorder , is responsible for many disorders ranging from asymptomatic histological chronic gastritis to some histologically important disorders such as peptic ulcer , upper gastrointestinal bleeding , primary gastric mucosa - associated lymphoid tissue ( malt ) lymphoma , chronic gastritis with atrophy , intestinal metaplasia , and adenocarcinoma . to date although native immune inflammatory response is identified in both h. pylori infection and cd , systemic humoral immune reaction is also involved . increased numbers of intestinal intraepithelial lymphocytes ( iels ) and subsequently villous atrophy , are not specific histological findings in h. pylori infection or cd . they may be found in a large number of other disorders , such as giardia infection , iga deficiency , and crohn s disease . patients with increased iels without serology confirmation do not have cd , but those with positive serological tests and suggestive symptoms are considered as potential cases of cd . various studies reported a high prevalence of h. pylori infection in patients with cd and vice versa . some studies reported that a clinical presentation like atrophic gastritis is common in patients with cd , but others have found poor evidence to support this presentation . different studies reported that number of intraepithelial lymphocytes in the duodenal mucosa are more likely to be increased in patients with h. pylori gastritis , and this can be controlled by the eradication of h. pylori , although epidemiological investigations have failed to show the association between gastritis and cd . other reports have focused on h. pylori - related lymphocytic gastritis and anemia in patients with cd . 
 
 the following keywords were selected and searched alone or in combination in pubmed ( pmc central ) , medline , and google scholar for articles published in english , from january 1985 to october 2015 :  celiac disease  , pathogenesis  ,  helicobacter pylori  ,  lymphocytic gastritis  ,  lymphocytic duodenitis  , ,  clinical presentation  , and  epidemiology .  using the mentioned keywords , only those articles , which reported controversial issues on pathological and clinical aspects of cd and h. pylori infection were assessed . based on the above - reported controversial point of views , in this article we describe an updated review about pathological and clinical correlation between cd and h. pylori infection . lymphocytic gastritis ( lg ) is defined by the presence of 25 - 30 iels per 100 epithelial cells , without accounting the mononuclear inflammatory cell infiltration of the lamina propria . studies showed that lg may be associated with both cd and h. pylori infection even if this evidence is not unanimously recognized . lg was reported in 36 - 45% of children with cd , but h. pylori infection was reported only in 13% of patients . about 38% and 13% of lg cases were associated with cd and h. pylori gastritis respectively . previous studies confirmed that lg was more common in h. pylori positive children than in h. pylori negative ones , both without cd . they reported that duodenal intraepithelial lymphocytosis persisted but lg counts decreased after treatment of h. pylori infection . in a study by broide and colleagues on 40 patients who were candidate for endoscopy , only iels positive for peculiar cd3 and cd8 intraepithelial t - lymphocyte population increased significantly in cd patients with or without h. pylori infection . drut and co - workers concluded that lg was associated with cd in children with iels positive for cd8 , but was not associated with substantial damage to the epithelial cells . nenna and others suggested that exposure to gluten for long time was a possible trigger of lg . lg was reported in 7% of the patients with cd and no control subjects , while h. pylori infection was found in 6 ( 2.7% ) children with cd ( 16.7% had lg ) . in other two studies on children and adults , the prevalence of lg was reported 42% and 84% , respectively . similar to nenna and colleagues , prasad and co - workers reported that the prevalence of h. pylori in patients with cd and lg was 6% . in contrast to previous studies , in 1999 wu and colleagues showed that out of 103 patients with lg , 33% had concomitant cd compared with only 4.1% with h. pylori and therefore declined any association . nielsen and co - workers recently supported these data and demonstrated that lymphocytic gastritis was not associated with active h. pylori infection . these inconsistent outcomes could also be attributable to different variability of h. pylori virulence genes . so , as demonstrated by genta and colleagues , a particular attention must be paid to other causes of gastric inflammation , and cd must be taken into account when h. pylori - negative gastritis is confirmed . 
 
 in the duodenum , the increased number of iels , lymphocytic duodenitis , can be a primary presentation of cd as well as the epiphenomenon of h. pylori infection itself . in accordance with the interpretations of goldstein , memeo and colleagues , determined that the patterns of distribution of duodenal iels in patients with h. pylori gastritis overlap to a significant range with the patterns described for cd . remarkably goldstein reported the non - gluten - sensitive groups with increased iels , included patients with h. pylori gastritis . guz - mark et al . proposed that in children with negative cd , lymphocytic duodenitis is common and is not expressively affected by h. pylori infection . however , this explanation is somehow doubtful as they have evaluated the children with functional recurrent abdominal pain as normal control group . recent study by simondi and others , showed that h. pylori infection is associated with an increase in iels count in both patients with cd and in subjects with duodenal intraepithelial lymphocytosis . losurdo and colleagues demonstrated that , during a 2-year follow - up of 81 patients affected by non - specific duodenal lymphocytosis , 5 ( 6.1% ) were exclusively related to h. pylori infection . in contrast ilus and co - workers reported that co - morbidities such as h. pylori gastritis did not contribute to the persistent intraepithelial lymphocytosis among patients with normal villous structure who adhere to a long - term strict gluten - free diet . several reports have rejected any correlation between severe abnormal histology and severe clinical and typical presentation like diarrhea , abdominal pain , and malabsorption in patients with cd . 
 
 in the study by nielsen and colleagues , the most common presenting symptoms were gerd / reflux ( 35% ) , followed by abdominal pain ( 31% ) , and anemia ( 22% ) . spee and co - workers undertook a meta - analysis of 38 studies to examine the relationship between h. pylori , functional recurrent abdominal pain , and other gastrointestinal symptoms in children . they concluded that h. pylori was not associated with functional recurrent abdominal pain . 
 
 in our previous study , out of 450 dyspeptic patients , 91.3% had histology - based evidence of h. pylori infection , and the most prevalent symptoms were abdominal discomfort ( 78% ) , bloating ( 71.1% ) , and heartburn ( 58% ) . our recent study also confirmed the previous one and showed that among the 250 studied patients , 232 ( 93% ) were h. pylori positive and high prevalent symptoms including abdominal discomfort ( 80% ) , and bloating ( 73% ) were reported in the infected patients . in other study , on 226 children with cd , nenna and colleagues , demonstrated that the most frequent symptoms were abdominal pain , diarrhea , abdominal distension , and poor weight gain . aydogdu and colleagues , showed that bloating was more common at the time of admission of patients with cd and h. pylori gastritis and a gluten - free diet recovers the symptoms in all patients regardless of the presence of h. pylori infection . on the other hand , it has been shown that an increased number of iels can be associated with a variety of other gastrointestinal disorders such as syphilis , hypertrophic gastropathy , mntrier s disease , and crohn s disease . evidence suggests a controversial relationship between h. pylori infection and cd ( table 1 ) . lebwohl and colleagues , have recently proposed the hypothesis of decreased risk of cd in patients with h. pylori infection . in their cross - sectional study , the authors found contrariwise association and showed that h. pylori was significantly prevalent in controls compared with patients with cd ( 8.8% vs 4.4% respectively , p<0.0001 ) . , did not show a significant difference in h. pylori infection between patients with cd ( 36% ) and controls ( 41% ) . na : not available ; iddm : insulin - dependent diabetes mellitus 
 
 eighty - one children with cd and 81 matched children without cd were studied by luzza and co - workers . the result of this study indicated that 18.5% of patients with cd and 17.3% of controls had h. pylori infection and therefore the prevalence and clinical presentation of h. pylori infection is not increased in children with cd . similar prevalence have been reported by diamanti et al.(89% vs. 97% ) and rostami - nejad et al.(82% vs. 86% ) . despite a high prevalence of h. pylori infection found in these two studies , the researchers did not find any relationship between h. pylori infection and cd in their study population . crabtree and other specified that although h. pylori positivity in patients with cd increased with age , the percentage of h. pylori seropositivity was not different from similarly blood donors of the same geographic area . also nenna , jozefczuk and their colleagues , recently confirmed that h. pylori infection was more prevalent in controls than in pediatric patients with cd . lasa and co - workers , showed that out of 312 patients who underwent endoscopy , 12.5% of patients with cd compared with 30% of patients without cd were infected with h. pylori infection . on the other hand konturek and colleagues reported a higher frequency of h. pylori in patients with cd than in controls ( 26% vs. 20% ) , while ciacci and co - workers found that 21% of patients with cd and normal diet , 32% with gluten - free diet , and 55% of controls were infected by h. pylori . data of 96 children with cd and 235 control children who underwent endoscopy showed that 21.8% of patients with cd and 23.8% of controls were infected by h. pylor infection . they concluded that cd might be associated with h. pylori gastritis , and it affected only bloating as associated presentation . lymphocytic gastritis ( lg ) is defined by the presence of 25 - 30 iels per 100 epithelial cells , without accounting the mononuclear inflammatory cell infiltration of the lamina propria . studies showed that lg may be associated with both cd and h. pylori infection even if this evidence is not unanimously recognized . lg was reported in 36 - 45% of children with cd , but h. pylori infection was reported only in 13% of patients . about 38% and 13% of lg cases were associated with cd and h. pylori gastritis respectively . previous studies confirmed that lg was more common in h. pylori positive children than in h. pylori negative ones , both without cd . they reported that duodenal intraepithelial lymphocytosis persisted but lg counts decreased after treatment of h. pylori infection . in a study by broide and colleagues on 40 patients who were candidate for endoscopy , only iels positive for peculiar cd3 and cd8 intraepithelial t - lymphocyte population increased significantly in cd patients with or without h. pylori infection . drut and co - workers concluded that lg was associated with cd in children with iels positive for cd8 , but was not associated with substantial damage to the epithelial cells . nenna and others suggested that exposure to gluten for long time was a possible trigger of lg . lg was reported in 7% of the patients with cd and no control subjects , while h. pylori infection was found in 6 ( 2.7% ) children with cd ( 16.7% had lg ) . in other two studies on children and adults , the prevalence of lg was reported 42% and 84% , respectively . similar to nenna and colleagues , prasad and co - workers reported that the prevalence of h. pylori in patients with cd and lg was 6% . in contrast to previous studies , in 1999 wu and colleagues showed that out of 103 patients with lg , 33% had concomitant cd compared with only 4.1% with h. pylori and therefore declined any association . nielsen and co - workers recently supported these data and demonstrated that lymphocytic gastritis was not associated with active h. pylori infection . these inconsistent outcomes could also be attributable to different variability of h. pylori virulence genes . so , as demonstrated by genta and colleagues , a particular attention must be paid to other causes of gastric inflammation , and cd must be taken into account when h. pylori - negative gastritis is confirmed . in the duodenum , the increased number of iels , lymphocytic duodenitis , can be a primary presentation of cd as well as the epiphenomenon of h. pylori infection itself . in accordance with the interpretations of goldstein , memeo and colleagues , determined that the patterns of distribution of duodenal iels in patients with h. pylori gastritis overlap to a significant range with the patterns described for cd . remarkably goldstein reported the non - gluten - sensitive groups with increased iels , included patients with h. pylori gastritis . guz - mark et al . proposed that in children with negative cd , lymphocytic duodenitis is common and is not expressively affected by h. pylori infection . however , this explanation is somehow doubtful as they have evaluated the children with functional recurrent abdominal pain as normal control group . recent study by simondi and others , showed that h. pylori infection is associated with an increase in iels count in both patients with cd and in subjects with duodenal intraepithelial lymphocytosis . losurdo and colleagues demonstrated that , during a 2-year follow - up of 81 patients affected by non - specific duodenal lymphocytosis , 5 ( 6.1% ) were exclusively related to h. pylori infection . in contrast ilus and co - workers reported that co - morbidities such as h. pylori gastritis did not contribute to the persistent intraepithelial lymphocytosis among patients with normal villous structure who adhere to a long - term strict gluten - free diet . several reports have rejected any correlation between severe abnormal histology and severe clinical and typical presentation like diarrhea , abdominal pain , and malabsorption in patients with cd . 
 
 in the study by nielsen and colleagues , the most common presenting symptoms were gerd / reflux ( 35% ) , followed by abdominal pain ( 31% ) , and anemia ( 22% ) . spee and co - workers undertook a meta - analysis of 38 studies to examine the relationship between h. pylori , functional recurrent abdominal pain , and other gastrointestinal symptoms in children . they concluded that h. pylori was not associated with functional recurrent abdominal pain . 
 
 in our previous study , out of 450 dyspeptic patients , 91.3% had histology - based evidence of h. pylori infection , and the most prevalent symptoms were abdominal discomfort ( 78% ) , bloating ( 71.1% ) , and heartburn ( 58% ) . our recent study also confirmed the previous one and showed that among the 250 studied patients , 232 ( 93% ) were h. pylori positive and high prevalent symptoms including abdominal discomfort ( 80% ) , and bloating ( 73% ) were reported in the infected patients . in other study , on 226 children with cd , nenna and colleagues , demonstrated that the most frequent symptoms were abdominal pain , diarrhea , abdominal distension , and poor weight gain . aydogdu and colleagues , showed that bloating was more common at the time of admission of patients with cd and h. pylori gastritis and a gluten - free diet recovers the symptoms in all patients regardless of the presence of h. pylori infection . on the other hand , it has been shown that an increased number of iels can be associated with a variety of other gastrointestinal disorders such as syphilis , hypertrophic gastropathy , mntrier s disease , and crohn s disease . evidence suggests a controversial relationship between h. pylori infection and cd ( table 1 ) . lebwohl and colleagues , have recently proposed the hypothesis of decreased risk of cd in patients with h. pylori infection . in their cross - sectional study , the authors found contrariwise association and showed that h. pylori was significantly prevalent in controls compared with patients with cd ( 8.8% vs 4.4% respectively , p<0.0001 ) . , did not show a significant difference in h. pylori infection between patients with cd ( 36% ) and controls ( 41% ) . na : not available ; iddm : insulin - dependent diabetes mellitus 
 
 eighty - one children with cd and 81 matched children without cd were studied by luzza and co - workers . the result of this study indicated that 18.5% of patients with cd and 17.3% of controls had h. pylori infection and therefore the prevalence and clinical presentation of h. pylori infection is not increased in children with cd . similar prevalence have been reported by diamanti et al.(89% vs. 97% ) and rostami - nejad et al.(82% vs. 86% ) . despite a high prevalence of h. pylori infection found in these two studies , the researchers did not find any relationship between h. pylori infection and cd in their study population . crabtree and other specified that although h. pylori positivity in patients with cd increased with age , the percentage of h. pylori seropositivity was not different from similarly blood donors of the same geographic area . also nenna , jozefczuk and their colleagues , recently confirmed that h. pylori infection was more prevalent in controls than in pediatric patients with cd . lasa and co - workers , showed that out of 312 patients who underwent endoscopy , 12.5% of patients with cd compared with 30% of patients without cd were infected with h. pylori infection . they established that h. pylori infection was less frequent in patients with cd . 
 
 on the other hand konturek and colleagues reported a higher frequency of h. pylori in patients with cd than in controls ( 26% vs. 20% ) , while ciacci and co - workers found that 21% of patients with cd and normal diet , 32% with gluten - free diet , and 55% of controls were infected by h. pylori . data of 96 children with cd and 235 control children who underwent endoscopy showed that 21.8% of patients with cd and 23.8% of controls were infected by h. pylor infection . they concluded that cd might be associated with h. pylori gastritis , and it affected only bloating as associated presentation . h. pylori is a frequent etiological agent of upper gastrointestinal disorders such as gastritis and peptic ulcer . examinations of the correlation between h. pylori infection and cd have yielded discordant outcomes , undoubtedly because of the diverse frequency of h. pylori prevalence in different studies . intraepithelial lymphocytosis may remain unchanged for a long time despite a strict gluten - free diet and normalization of the small intestinal villous structure . for this reason , a careful clinical and laboratory examination of cases of intraepithelial lymphocytosis must be performed to distinguish between gluten - related disorders ( cd , gluten sensitivity or seronegative cd ) and non - gluten - related conditions . indeed , h. pylori gastritis , drugs such as non - steroidal anti - inflammatory drugs , olmesartan , proton pump inhibitors , and viral gastroenteritis are often associated with increasing intraepithelial lymphocytosis . it was illustrated that h. pylori infection may be the cause of pathogenesis of lg in patients with cd , and its treatment may reduce the number of iels , and inflammation of the intestine , thus leading to an improvement of dyspeptic symptoms . 
 
 in conclusion , different studies demonstrate the prevalence of h. pylori infection in cd population is similar to control subjects . various investigations suggested that histological abnormalities including villous atrophy and endoscopic markers are similar in patients with and without h. pylori infection . although some evidence show a potential preventive role of h. pylori in the pathogenesis of cd , further studies are needed to clarify some controversial points about this topic .