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(Investigative Ophthalmology and Visual Science. 2006;47:501-508.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-0323
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Prevalence and Treatment of Helicobacter pylori in Patients with Blepharitis

Sergio Claudio Saccà,1 Antonio Pascotto,1 Gian Maria Venturino,1 Guido Prigione,1 Antonio Mastromarino,1 Franco Baldi,1 Claudio Bilardi,2 Vincenzo Savarino,2 Carlo Brusati,3 and Alfredo Rebora3

1From the Department of Neurosciences, Ophthalmology and Genetics, Clinica Oculistica, the 2Department of Internal Medicine, Operative Unit of Gastroenterology, and the 3Department of Endocrinology and Metabolic Diseases, Section of Dermatology, University of Genoa, Genoa, Italy.


   Abstract
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 Abstract
Materials and Methods
 Results
 Discussion
 References
 
PURPOSE. Helicobacter pylori is a major pathogen etiologically associated with gastritis, peptic ulcer disease, gastric cancer, and primary gastric lymphoma. This study was conducted to investigate a possible association between Helicobacter pylori infection and blepharitis. Two hundred fifty consecutive patients with symptomatic blepharitis and 250 control subjects without blepharitis symptoms were evaluated. After exclusions, the blepharitis group consisted of 186 patients with blepharitis and a control group of 215 patients.

METHODS. Blepharitis was diagnosed on the basis of findings in ophthalmic and dermatologic examinations. All patients underwent a 13C-urea breath test (UBT) to detect H. pylori infection, and impression cytology was performed before and after eradication therapy. The follow-up period was 4 months ± 28 days.

RESULTS. The blepharitis group showed an H. pylori infection prevalence of approximately 76.3% (UBT-positive group with blepharitis: n = 142 patients), compared with 42.3% of the control group (UBT-positive group with blepharitis [although asymptomatic]: n = 66 patients; UBT-positive group without blepharitis: n = 25 patients). Furthermore, we observed blepharitis in 30.6% (n = 66 patients) of UBT-positive control subjects and 13.4% (n = 29 patients) of UBT-negative control subjects. Impression cytology revealed that blepharitis was more severe in UBT-positive patients than in negative ones, and a clinical improvement in blepharitis was noted in approximately 50% of patients after H. pylori eradication.

CONCLUSIONS. Even though possible sources of error in defining the association of two highly prevalent conditions must be considered, the data seem to validate an association between H. pylori infection and blepharitis, but may not be indicative of a causal association. Eradication of H. pylori improved ocular cytology results. It is possible that chronic blepharitis is an extradigestive manifestation of H. pylori infection.

The pathogen Helicobacter pylori, a microaerophilic Gram-negative bacterium, is considered to be the main cause of peptic ulcers and a risk factor for gastric cancer and MALT (mucosa-associated lymphoid tissue) lymphoma.1 2 Although its role is debatable, this bacterium has also been associated with nondigestive manifestations3 such as Raynaud’s phenomenon,4 5 cardiovascular diseases,6 7 Sjögren’s syndrome,8 9 urticaria,10 and rosacea.11 12

Eye involvement is common in rosacea, including chronic conjunctivitis (3% of all chronic conjunctivitis), blepharitis, chalazia, and keratitis. Therefore, it is reasonable to postulate a role of H. pylori infection in ophthalmic diseases such as chronic ocular inflammation13 and glaucoma.14 15 Moreover, the prevalence of HP infection has been found to be significantly higher in central serous chorioretinopathy-affected subjects.16 17

We studied the prevalence of H. pylori infection in patients with chronic blepharitis and its relationship to conjunctival cytology results.


   Materials and Methods
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 Abstract
 Materials and Methods
Results
 Discussion
 References
 
The Ethics Board of the Department of Neurosciences, Ophthalmology and Genetics, Clinica Oculistica, Genoa University, approved the study. The protocol prescribed the prospective recruitment of 500 patients. The blepharitis group, selected in our ophthalmic section, comprised 250 consecutive patients with chronic symptomatic blepharitis. The control group consisted of another 250 consecutive patients selected in the Gastroenterology Department, to verify the prevalence of H. pylori infection in patients without ophthalmic symptoms. Patients with blepharitis with chronic systemic diseases and patients on long-term therapy with topical eye drops and with diseases such as atopic dermatitis were excluded. The research followed the tenets of the Declaration of Helsinki.

All diagnoses of blepharitis were performed by means of an ophthalmic examination, including slit lamp examination with lissamine green and fluorescein staining, tear break-up time, and Schirmer’s test. Patients were classified according to McCulley’s criteria (Table 1) .18 19 Impression cytology was performed in all patients by pressing a 6 x 8-mm cellulose acetate paper sheet (Hwap 304 FO; Millipore, Bedford, MA) on different locations of the bulbar conjunctiva and then staining the adherent cell layer with Gill’s modified Papanicolaou stain, according to the technique described by Tseng.20 To interpret the results, we used the morphologic characteristics summarized in Table 2 . A conjunctival swab was also obtained from subjects in the blepharitis group, to evaluate the microbiologic flora. One horse blood agar plate and one chocolate agar plate were inoculated with each conjunctival swab. The plates were placed in an incubator set to 35°C with 5% CO2. All plates were observed daily for 7 days for the formation of microbial colonies. The bacteria were identified with kits (Analytab Products, Inc., Plainview, NY), in conjunction with appropriate supplementary tests, by using standard microbiologic techniques.21


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  		TABLE 1. Classification of Chronic Blepharitis18 19

 

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  		TABLE 2. Morphologic and Morphometric Criteria Used in Impression Cytology

 
A dermatologist evaluated all patients. All underwent laboratory blood examinations (red cell binding, PRIST [paper radioimmunosorbent test], RAST [radioallergosorbent test], and prick test) to exclude any allergic disorder. Patients with clinical signs of atopic dermatitis were excluded from the study. Those in the blepharitis group with chronic systemic diseases were also excluded. Dermatologists reported the concomitant presence of dermatological signs (Table 3) , confirming the clinical diagnosis.


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  		TABLE 3. Dermatologic Inclusion Criteria22

 
All enrolled patients confirmed their voluntary participation in the study by signing an informed consent form, after explanation of the nature and possible consequences of the study.

All patients underwent the 13C-urea breath test (UBT)23 24 specifically for H. pylori infection. UBT remains the first-line noninvasive test for the assessment of the efficacy of anti-H. pylori treatment and has been validated by some studies for sensitivity and specificity superior to 90%.25

UBT-positive (UBT+) patients underwent 1 week of triple therapy: a combination of 400 mg ranitidine bismuth citrate twice daily, 250 mg clarithromycin twice daily, and 500 mg metronidazole twice daily.26 Tear substitutes were added.

All patients underwent impression cytology 40 ± 12 days (SD) after eradication of the H. pylori infection. Patients who were still UBT+ after eradication treatment underwent another cycle of therapy, with the following therapeutic regimen for 10 days: 20 mg omeprazole twice daily, 500 mg tetracycline twice daily, and 500 mg tinidazole twice daily. Impression cytology was repeated 1 month later (80 ± 9 days from the beginning of follow-up).

Follow-up was approximately 4 months ± 28 days. If patients became UBT negative (UBT–) after impression cytology, they were withdrawn from the study. At the end of follow-up, the UBT– patients were also withdrawn, after undergoing a further impression cytology test. Patients who continued to have the infection were followed up for 4 months ± 28 days.

Consecutive patients recruited at the Gastroenterology Department were investigated with questions that were intended to exclude the possibility of the presence of any ophthalmic symptom. The question put to each of the patients in the control group was: "Do you suffer from eye irritation? For example: burning, soreness, redness, lacrimation, foreign body sensation, or itching in one or both of your eyes?" Patients who replied in the affirmative, even if only for one symptom, were excluded from the study. We established 5 years as the minimum period without symptoms for patients to be enrolled in the study.

All patients recruited as control subjects were apparently healthy and had no specific symptoms. They had been referred to the Gastroenterology Section to undergo 13C-urea breath testing, because they were exposed to the risk of H. pylori infection (e.g., cohabiting with infected persons). All underwent UBT and were examined by slit lamp to verify the presence of blepharitis.

To evaluate the results, all data were considered as relative percentages and analyses were conducted on computer (StatView software; Abacus Concepts Inc., Berkeley, CA). The {chi}2 test was used to test for differences in age and time groups at P < 0.05. All data are presented in Table 4 , both as the number of cases and as percentages.


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  		TABLE 4. Demographic Data

 

   Results
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 Abstract
 Materials and Methods
 Results
Discussion
 References
 
Ninety-nine patients did not complete the study (56 did not comply with follow-up, 27 took drugs incompatible with our protocol, and 16 had to undergo surgery). Therefore, 401 patients were included in the analysis: 186 with chronic blepharitis in the blepharitis group, and 215 without ophthalmic symptoms in the control group (see the flow diagram in Fig. 1 ).


Figure 1
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  		FIGURE 1. Flow diagram of subjects’ progress through the phases of study. The patients were selected in the Ophthalmology and Gastroenterology departments during the whole period of the study and were placed in two groups: patients with symptomatic blepharitis (n = 186) and control subjects who had no symptoms of blepharitis (n = 215). After undergoing UBT, these groups were subdivided into UBT+ and UBT–. The UBT+ patients were treated with up to a maximum of two cycles of therapy to eradicate Helicobacter infection. At the end of the follow-up, UBT– patients from the control group left the study after undergoing further impression cytology. *Patients who completed therapy and left the study after testing negative on the second UBT.

 
The age and sex of patients are shown in Table 4 . In the blepharitis group, seborrheic blepharitis was observed in 94 (50.4%) patients, rosacea blepharitis in 72 (38.7%), and mixed blepharitis in 20 (10.8%; Table 5 ). On objective examination, blepharitis was also found in 66 UBT+ control subjects (31.7%), even though they were completely free of symptoms. In the blepharitis group, the prevalence of seborrheic blepharitis showed a tendency to decrease with age, whereas the prevalence of rosacea blepharitis tended to increase. However, the {chi}2 test was not significant (Table 5) . In UBT– control subjects, blepharitis was found in 29 (13.4%) patients.


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  		TABLE 5. Numeric and Percentage Distribution by Age and Clinical Diagnosis in the Blepharitis Group

 
The most common bacteria identified in the patients with blepharitis were Staphylococcus epidermidis (93.8%), Propionibacterium acnes (79.2%), Corynebacterium sp. (71.2%), Staphylococcus aureus (16%) and Acinetobacter sp. (12.1%). No difference was found in the distribution of these bacteria between the UBT+ and UBT– subjects (Table 6) . The culture examination was not performed in the control group.


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  		TABLE 6. Percentage of Distribution of Common Bacteria Identified in the Patients with Positive and Negative 13C-UBT Results in the Blepharitis Group

 
The rate of H. pylori infection was proportionally higher with increasing age in the three groups of patients—less than 40 years, 40 to 60 years, and more than 60 years—with a remarkable difference between the blepharitis and control groups ({chi}2 = 49, 136 df = 5, P < 0.0001; Table 7 ).


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  		TABLE 7. Rates of Total Positive UBT Results Indicating H. pylori Infection by Age

 
H. pylori infection, detected by means of UBT, was found in 233 (58%) patients and was significantly more common in patients with blepharitis (76%) than in control subjects (42%; {chi}2 = 47.231, P < 0.01) and in people older than 60 years (42%) than in younger people (26%; {chi}2 = 49.1, P = 0.002; Table 7 ).

A comparison of ophthalmic patients with control subjects showed a significant difference between patients with and without blepharitis ({chi}2 = 116.0, P < 0.001), but no difference was found between patients with blepharitis coming from the two different departments (Gastroenterology and Ophthalmology; {chi}2 = 0.29, P = 0.58). Hence, blepharitis symptoms were independent of the H. pylori infection.

In the patients with blepharitis, the distribution of morphologic type of blepharitis did not show a statistically significant difference between UBT+ and UBT– subjects (Table 8) .


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  		TABLE 8. Distribution of the Type of Blepharitis in the Two Groups with 13C-UBT Positive or Negative Results

 
Impression cytology did not show different patterns based on the clinical type of blepharitis, because the differences probably depended on the age of the patient. Indeed, there was a morphologic and functional decline with age, which was easily verifiable by means of impression cytology, both in normal patients and in patients with blepharitis (Fig. 2) . Furthermore, there was a substantial difference in cytology between UBT+ and UBT– patients with blepharitis (Fig. 3) .


Figure 2
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  		FIGURE 2. Impression cytology in normal subjects and patients with blepharitis. Impression cytology changed with age, both in normal subjects (A–C) and in those with blepharitis (AI–CI). The number of muciparous cells decreased, and the epithelial cells became less cohesive. The nucleus-to-cytoplasm (N-C) ratio increased. (A) Patient 2, a 27-year-old man with normal impression cytology. The goblet cells (black) showed well-delineated borders and a 15- to 25-µm diameter. (B) Patient 13, a 53-year-old man. Muciparous cells were less numerous, epithelial cells were less cohesive, and their nuclei were smaller, with a relative increase of the cytoplasm (N-C: 1:3). (C) Patient 19: a 73-year-old woman. Muciparous cells decreased in number and their borders were irregular. Mucus was leaking from an unknown source. Epithelial cells have folded borders and a very small nucleus (N-C 1:7). (AI) Patient 9: a 33-year-old woman. Muciparous cells were morphologically normal, but were less numerous. Epithelial cells were normal with less cohesion. (BI) Patient 55: a 53-year-old woman. Muciparous cells were scanty, with irregular borders. Intercellular cohesion was very poor. (CI) Patient 122: a 72-year-old man. Muciparous cells varied in size, were scanty, and had irregular borders. Epithelial cells were irregularly grouped. Magnification, x2.5.

 

Figure 3
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  		FIGURE 3. Impression cytology in UBT+ patients with blepharitis, before and after eradication treatment. UBT+ specimens showed a lower cell number and more worse morphology than those from noninfected patients. In these patients, too, cytology findings worsened with age. Improvement in cytology was observed in approximately 50% of cases after eradication. (AI) Patient 11: a 34-year-old man with seborrheic blepharitis. Muciparous cells were scanty with irregular borders, whereas epithelial cells were normal. (AII) After therapy, impression cytology became completely normal. (BI) Patient 39: a 50-year-old woman. Muciparous cells were absent, and epithelial cells folded with irregular borders and small nuclei. (BII) After therapy, muciparous cells reappeared, though scanty with irregular diameters and borders. Epithelial cells were morphologically normal but showed scanty intercellular cohesion. (CI) Patient 129: a 75-year-old man. Before therapy, squamous metaplasia was obvious. (CII) After therapy, a few muciparous cells with irregular borders reappeared and the epithelial cells returned to a normal appearance, although the N-C ratio was 1:5. Magnification, x2.5.

 
After the first cycle of therapy, 188 (80.6%) patients became free of H. pylori infection. After the second, infection was eradicated in another 28 (12.1%) patients, and at the end of follow-up 17 (7.3%) patients remained UBT+. Of this last group, eight (3.4%) had rosacea, seven (3%) seborrhea, and two (0.85%) mixed blepharitis (P = 0.538; see flow diagram in Fig. 1 ).

In the 208 UBT+ patients with blepharitis (n = 142 + 66, see Fig. 1 ), after eradication therapy, cytologic patterns remained similar in 50% of cases (n = 105). Nevertheless, we observed a remarkable improvement in 35% of the cases (n = 73)—that is, an increase in the number of cells and a better cytologic morphology. According to our classification (Table 2) , we observed a class transition across at least two sub-classes—for example, from 2a to 3b. In 15% of cases (31 patients), the improvement was slight, consisting only of an increase in the number of cells—that is, from 1b to 2a.

In particular, from a clinical standpoint, a remarkable improvement was observed in 37 (18%) patients with rosacea, in 27 (13%) with chronic seborrheic blepharitis, and in 9 (4.5%) with mixed blepharitis. However, there was no statistically significant difference between the patients with rosacea and those with seborrheic blepharitis (P = 0.872).

In UBT– patients with blepharitis (n = 29 patients), in whom the only therapy administered was 2% hyaluronic acid sodium salt at the end of the follow-up, we noted a marked improvement in 3.4% of cases and a slight improvement in 10.3%. The remaining 86.3% did not show any clinical changes.

Among the patients in whom the infection was eradicated, no recurrence was noted, although we cannot rule out the possibility that there may have been some recurrence among the patients who exited the study during follow-up.


   Discussion
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 Abstract
 Materials and Methods
 Results
 Discussion
References
 
Blepharitis is a very common disease in elderly patients. Seborrheic dermatitis is the most common cause of anterior lamellar or marginal blepharitis, whereas blepharitis of the posterior lamella is due to meibomian gland dysfunction. Eyelid margins have focal or diffuse inflammation, with telangiectasia around the meibomian gland orifices.18

Several other factors play an etiologic role, including exogenous irritants and allergens, staphylococcal infection, and rosacea.19 Patients with rosacea often report digestive disturbances,12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 which have been considered to be directly related to blepharitis.28 Digestive troubles are related more to rosacea than to seborrhea,27 although there is much that binds these two pathologic conditions.29 There seems to be a connection between H. pylori infection and rosacea,11 whereas the association between seborrhea and H. pylori, which has been reported in another study,30 seems to be more uncertain. Moreover, seborrheic dermatitis may be seen in conjunction with other skin diseases, such as rosacea, blepharitis, or ocular rosacea, and acne vulgaris.31 It can therefore be claimed, albeit with some uncertainty, that digestive troubles correlate with the presence of blepharitis, or, in any case, that their association is likely.

Our study confirms that the relation between blepharitis and H. pylori infection is not influenced by its clinical appearance or degree,32 and it seems that the only common factor is chronic inflammation of the eyelid and gastrointestinal tract.

From a cytological point of view, blepharitis demonstrates a diversity in whether the UBT result is positive or negative. However, there is no correlation with its subjective symptoms, as happens in chronic gastritis caused by H. pylori.

H. pylori infection may explain this intriguing relationship. The infection may also induce lid inflammatory changes by several mechanisms. First, H. pylori produces nitric oxide and gastrin,33 both potent vasodilators that may play a role in producing flushing reactions on the face and neck. Eyelids and conjunctiva are certainly involved in vasodilation, and this effect may be the starting point of a chronic inflammation. Second, the chronic release of large amounts of inflammatory mediators caused by H. pylori infection or, more likely, cross-mimicry mechanisms between bacterial and extradigestive antigens, could affect extradigestive organs.34 35 Indeed, rosacea could be considered one of the major extragastric disease-complex associations of H. pylori infection, probably mediated by H. pylori-related cytotoxins and cytokines.13 36

Third, H. pylori has been found in the mouth,37 but it is not known whether the oral cavity acts as a permanent reservoir for this bacterium.38 However, from the oral cavity, it may reach the anterior surface of the eye, causing blepharitis or worsening it, at least on the basis of cytological criteria (Fig. 2) .

Blepharitis in approximately 50% of our patients improved after eradication treatment of H. pylori. This was especially so in the case of younger patients, in whom blepharitis has often been reported to be associated with rosacea.39 It is important to stress that oral metronidazole has been successfully used in blepharitis with rosacea,40 41 though the beneficial effects of metronidazole in acne vulgaris are attributable to its anti-inflammatory activities rather than to its antibacterial ones.42

Furthermore, the antibiotic therapy used acts not only against H. pylori infection but also against lid bacteria, particularly Staphylococcus (>90% in our sample; see Table 6 ), which can influence the clinical appearance of blepharitis. Therefore, the improvement we observed might be the result of the combined therapeutic action on H. pylori infection and lid bacteria. It is known that the associations between chronic blepharitis and eyelid meibomian gland lipids and microflora involve important relationships between these lipids and chronic blepharitis disease states. Moreover, antibiotics like tetracycline can inhibit lipase activity and therefore decrease the release of noxious free fatty acids,43 thereby resulting in decreased bacteriologic lipase activity.44 45 Indeed, therapeutic results of systemic antibiotics in the treatment of blepharitis have recently been reported.46 However, in our study, the clinical improvements were obtained after the eradication of H. pylori infection (Fig. 2) .

Except in the case of Staphylococcus pathogenesis,47 blepharitis is not completely resolved. Usually, the antibiotic therapy is intended to reduce the microbial proliferation that has a direct or indirect role in chronic blepharitis.48 Systemic antibiotic therapy may be helpful in patients with meibomian gland dysfunction39 or in cases of rosacea.40 Moreover, metronidazole has been used successfully in patients with blepharitis with resistant rosacea.41 48

Symptoms of dry eye are complex and variable. An important and causal relationship can exist between H. pylori and blepharitis without a strong treatment effect, and elements of the treatment are standard for blepharitis already. Other elements of the treatment are not.

The complex interactions between H. pylori infection and the eye is another field of ongoing research, though the association remains unclear. The precise pathophysiology of central serous chorioretinopathy is also uncertain. Choroidal microcirculation abnormalities, vascular wall antigens and antibody reactivity could be involved.49 50 H. pylori infection may influence the pathophysiology of glaucoma by releasing various proinflammatory and vasoactive substances, as well as by influencing the apoptotic process, parameters that may also exert their own effects in the induction and/or progression of glaucomatous neuropathy.51 It is possible that the "link" is the oxidative damage that recurs in circulation disorders,52 in inflammation,53 54 55 and in glaucoma.56 Indeed, H. pylori infection could affect the pathophysiology of glaucoma, by producing oxidative stress and circulating lipid peroxides,55 and may contribute to central serous chorioretinopathy by increasing endothelin 1, nitric oxide,57 and inducible nitric oxide synthase and releasing proinflammatory and vasoactive substances. The latter substances may be involved in the pathophysiology of blepharitis.

In conclusion, our data seem to confirm a relationship between chronic blepharitis and H. pylori infection, even though they may not indicate a causal association. However, we recommend that caution be exercised in interpreting the results, as possible sources of error must be considered in defining the association of two highly prevalent conditions. Although the exact role of H. pylori infection in chronic inflammation of the eyelids is unknown, eradication of H. pylori by means of the antibiotic therapy described herein improves conjunctival cytology, and can, especially in the young, alleviate blepharitis. In any case, chronic blepharitis is a disorder of great interdisciplinary interest, in that it may be a clinical sign of an internal infection.

Further studies to elucidate the role of H. pylori infection in the pathogenesis of blepharitis are therefore indicated.


   Acknowledgements
 
The authors thank Silvana Schenone (University of Genoa) for performing the impression cytology.


   Footnotes
 
Supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC) and from the University of Genoa.

Submitted for publication March 14, 2005; revised June 1, 2005; accepted December 14, 2005.

Disclosure: S.C. Saccà, None; A. Pascotto, None; G.M. Venturino, None; G. Prigione, None; A. Mastromarino, None; F. Baldi, None; C. Bilardi, None; V. Savarino, None; C. Brusati, None; A. Rebora, None

The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Corresponding author: Sergio Claudio Saccà, Department of Neurosciences, Ophthalmology and Genetics, Clinica Oculistica, University of Genoa, Ospedale San Martino, Pad. 9 Viale Benedetto XV 16132, Genoa, Italy; sergio.sacca{at}hsanmartino.it.


   References
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 Abstract
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 Results
 Discussion
 References
 

  1. Hiyama T, Haruma K, Kitadai Y, et al. Clinicopathological features of gastric mucosa-associated lymphoid tissue lymphoma: a comparison with diffuse large B-cell lymphoma without a mucosa-associated lymphoid tissue lymphoma component. J Gastroenterol Hepatol. 2001;16:734–739.[CrossRef][ISI][Medline][Order article via Infotrieve]
  2. Umehara S, Higashi H, Ohnishi N, et al. Effects of Helicobacter pylori CagA protein on the growth and survival of B lymphocytes, the origin of MALT lymphoma. Oncogene. 2003;22:8337–8342.[CrossRef][ISI][Medline][Order article via Infotrieve]
  3. Gasbarrini A, Carloni E, Gasbarrini G, Menard A. Helicobacter pylori and extragastric diseases: other helicobacters. Helicobacter. 2003;8(suppl 1)68–76.[Medline][Order article via Infotrieve]
  4. Gasbarrini A, Serricchio M, Tondi P, et al. Raynaud’s phenomenon and Helicobacter pylori infection. Int J Angiol. 1998;7:307–309.[CrossRef][Medline][Order article via Infotrieve]
  5. Savarino V, Sulli A, Zentilin P, et al. No evidence of an association between Helicobacter pylori infection and Raynaud phenomenon. Scand J Gastroenterol. 2000;35:1251–1254.[CrossRef][ISI][Medline][Order article via Infotrieve]
  6. Migneco A, Ojetti V, Specchia L, et al. Eradication of Helicobacter pylori infection improves blood pressure values in patients affected by hypertension. Helicobacter. 2003;8:585–589.[CrossRef][ISI][Medline][Order article via Infotrieve]
  7. Haider AW, Wilson PW, Larson MG, et al. The association of seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease: a prospective study. J Am Coll Cardiol. 2002;40:1408–1413.[Abstract/Free Full Text]
  8. Collin P, Karvonen AL, Korpela M, et al. Gastritis classified in accordance with the Sydney system in patients with primary Sjogren’s syndrome. Scand J Gastroenterol. 1997;32:108–111.[ISI][Medline][Order article via Infotrieve]
  9. Theander E, Nilsson I, Manthorpe R, et al. Seroprevalence of Helicobacter pylori in primary Sjogren’s syndrome. Clin Exp Rheumatol. 2001;19:633–638.[ISI][Medline][Order article via Infotrieve]
  10. Gala Ortiz G, Cuevas Agustin M, Erias Martinez P, et al. Chronic urticaria and Helicobacter pylori. Ann Allergy Asthma Immunol. 2001;86:696–698.[ISI][Medline][Order article via Infotrieve]
  11. Diaz C, O’Callaghan CJ, Khan A, Ilchyshyn A. Rosacea: a cutaneous marker of Helicobacter pylori infection?—results of a pilot study. Acta Derm Venereol. 2003;83:282–286.[CrossRef][ISI][Medline][Order article via Infotrieve]
  12. Rebora A. The management of rosacea. Am J Clin Dermatol. 2002;3:489–496.[CrossRef][Medline][Order article via Infotrieve]
  13. Franceschi F, Gasbarrini A, Fontana L. Role of Helicobacter pylori infection in ophthalmology. Ophthalmology. 1998;105:1351–1352.[Medline][Order article via Infotrieve]
  14. Kountouras J, Mylopoulos N, Boura P, et al. Relationship between Helicobacter pylori infection and glaucoma. Ophthalmology. 2001;108:599–604.[CrossRef][ISI][Medline][Order article via Infotrieve]
  15. Galloway PH, Warner SJ, Morshed MG, Mikelberg FS. Helicobacter pylori infection and the risk for open-angle glaucoma. Ophthalmology. 2003;110:922–925.[CrossRef][ISI][Medline][Order article via Infotrieve]
  16. Giusti C. Association of Helicobacter pylori with central serous chorioretinopathy: hypotheses regarding pathogenesis. Med Hypotheses. 2004;63:524–527.[CrossRef][ISI][Medline][Order article via Infotrieve]
  17. Ahnoux-Zabsonre A, Quaranta M, Mauget-Faysse M. Prevalence of Helicobacter pylori in central serous chorioretinopathy and diffuse retinal epitheliopathy: a complementary study. J Fr Ophtalmol. 2004;27:1129–1133.[ISI][Medline][Order article via Infotrieve]
  18. Mc Culley JP, Doughertly J, Deneau DG. Classification of chronic blepharitis. Ophthalmology. 1982;89:1173–1180.[ISI][Medline][Order article via Infotrieve]
  19. McCulley JP, Shine WE. Eyelid disorders: the meibomian gland, blepharitis, and contact lenses. Eye Contact Lens. 2003;29:S93–S95.[CrossRef][Medline][Order article via Infotrieve]
  20. Tseng SCG. Staging of conjunctival squamous metaplasia by impression cytology. Ophthalmology. 1985;92:728–733.[ISI][Medline][Order article via Infotrieve]
  21. Lennette EH Balows A Hausler WJ, Jr Shadomy HJ eds. Manual of Clinical Microbiology. 1985; 4th ed. 52–65. American Society for Microbiology Washington, DC. 143–349, 413–472, 526–541
  22. Fitzpatrick JE. Common inflammatory skin diseases of the elderly. Geriatrics. 1989;44:40–46.[Medline][Order article via Infotrieve]
  23. Savarino V, Vigneri S, Celle G. The 13C urea breath test in the diagnosis of Helicobacter pylori infection. Gut. 1999;1:I18–22.
  24. Chen TS, Chang FY, Chen PC, et al. Simplified 13C-UBT with a new infrared spectrometer for diagnosis of Helicobacter pylori infection. J Gastroenterol Hepatol. 2003;18:1237–1243.[CrossRef][ISI][Medline][Order article via Infotrieve]
  25. Bilardi C, Biagini R, Dulbecco P, et al. Stool antigen assay (HpSA) is less reliable than UBT for post-treatment diagnosis of Helicobacter pylori infection. Aliment Pharmacol Ther. 2002;16:1733–1738.[CrossRef][ISI][Medline][Order article via Infotrieve]
  26. Savarino V, Zentilin P, Bisso G, et al. Optimal duration of therapy combining ranitidine bismuth citrate with clarithromycin and metronidazole in the eradication of Helicobacter pylori infection. Aliment Pharmacol Ther. 1999;13:43–47.[CrossRef][ISI][Medline][Order article via Infotrieve]
  27. Kendall SN. Remission of rosacea induced by reduction of gut transit time. Clin Exp Dermatol. 2004;29:297–299.[CrossRef][ISI][Medline][Order article via Infotrieve]
  28. Ghanem VC, Mehra N, Wong S, Mannis MJ. The prevalence of ocular signs in acne rosacea: comparing patients from ophthalmology and dermatology clinics. Cornea. 2003;22:230–233.[CrossRef][ISI][Medline][Order article via Infotrieve]
  29. Boni R. Rosacea, acne and other diseases of the seborrheic spectrum. Schweiz Rundsch Med Prax. 2000;89:566–570.[Medline][Order article via Infotrieve]
  30. Charlett A, Dobbs RJ, Dobbs SM, et al. Parkinsonism: siblings share Helicobacter pylori seropositivity and facets of syndrome. Acta Neurol Scand. 1999;99:26–35.[Medline][Order article via Infotrieve]
  31. Gupta AK, Bluhm R, Cooper EA, et al. Seborrheic dermatitis. Dermatol Clin. 2003;21:401–412.[CrossRef][ISI][Medline][Order article via Infotrieve]
  32. Michel JL, Cabibel F. Frequency, severity and treatment of ocular rosacea during cutaneous rosacea. Ann Dermatol Venereol. 2003;130:20–24.[ISI][Medline][Order article via Infotrieve]
  33. Gasbarrini A, Gabrielli M, Fiore G, et al. Association between Helicobacter pylori cytotoxic type I CagA-positive strains and migraine with aura. Cephalalgia. 2000;20:561–565.[CrossRef][ISI][Medline][Order article via Infotrieve]
  34. Gasbarrini A, Franceschi F. Autoimmune diseases and Helicobacter pylori infection. Biomed Pharmacother. 1999;53:223–226.[CrossRef][Medline][Order article via Infotrieve]
  35. Amedei A, Bergman MP, Appelmelk BJ, et al. Molecular mimicry between Helicobacter pylori antigens and H+, K+-adenosine triphosphatase in human gastric autoimmunity. J Exp Med. 2003;198:1147–1156.[Abstract/Free Full Text]
  36. Szlachcic A. The link between Helicobacter pylori infection and rosacea. J Eur Acad Dermatol Venereol. 2002;16:328–333.[CrossRef][ISI][Medline][Order article via Infotrieve]
  37. Song Q, Lange T, Spahr A, et al. Characteristic distribution pattern of Helicobacter pylori in dental plaque and saliva detected with nested PCR. J Med Microbiol. 2000;49:349–353.[Abstract/Free Full Text]
  38. Umeda M, Kobayashi H, Takeuchi Y, et al. High prevalence of Helicobacter pylori detected by PCR in the oral cavities of periodontitis patients. J Periodontol. 2003;74:129–134.[CrossRef][ISI][Medline][Order article via Infotrieve]
  39. Frucht-Pery J, Sagi E, Hemo I, Ever-Hadani P. Efficacy of doxycycline and tetracycline in ocular rosacea. Am J Ophthalmol. 1993;116:88–92.[ISI][Medline][Order article via Infotrieve]
  40. Bannatyne RM. Metronidazole, its bioactive metabolites and acne. Curr Med Res Opin. 1999;15:298–299.[ISI][Medline][Order article via Infotrieve]
  41. Lowe NJ. Use of topical metronidazole in moderate to severe rosacea. Adv Ther. 2003;20:177–190.[ISI][Medline][Order article via Infotrieve]
  42. Baum JL. Antibiotic use in ophthalmology. Tasman W Jaeger EA eds. Duane’s Clinical Ophthalmology. 1994External Diseases. 1994;4:1–25. JB Lippincott Philadelphia.
  43. Gutgesell VJ, Stern GA, Hood CI. Histopathology of meibomian gland dysfunction. Am J Ophthalmol. 1982;94:383–387.[ISI][Medline][Order article via Infotrieve]
  44. Dougherty JM, McCulley JP, Silvany RE, Meyer DR. The role of tetracycline in chronic blepharitis: inhibition of lipase production in Staphylococci. Invest Ophthalmol Vis Sci. 1991;32:2970–2975.[Abstract/Free Full Text]
  45. Gulbenkian A, Myers J, Fries D. Hamster flank organ hydrolase and lipase activity. J Invest Dermatol. 1980;75:289–292.[CrossRef][ISI][Medline][Order article via Infotrieve]
  46. Ta CN, Shine WE, McCulley JP, et al. Effects of minocycline on the ocular flora of patients with acne rosacea or seborrheic blepharitis. Cornea. 2003;22:545–548.[CrossRef][ISI][Medline][Order article via Infotrieve]
  47. Dougherty JM, McCulley JP. Comparative bacteriology of chronic blepharitis. Br J Ophthalmol. 1984;68:524–528.[Abstract/Free Full Text]
  48. Junk AK, Lukacs A, Kampik A. Topical administration of metronidazole gel as an effective therapy alternative in chronic Demodex blepharitis: a case report. Klin Monatsbl Augenheilkd. 1998;213:48–50.[Medline][Order article via Infotrieve]
  49. Kitaya N, Nagaoka T, Hikichi T, et al. Features of abnormal choroidal circulation in central serous chorioretinopathy. Br J Ophthalmol. 2003;87:709–712.[Abstract/Free Full Text]
  50. Franceschi F, Sepulveda AR, Gasbarrini A, et al. Cross-reactivity of anti-CagA antibodies with vascular wall antigens: possible pathogenic link between Helicobacter pylori infection and atherosclerosis. Circulation. 2002;106:430–434.[Abstract/Free Full Text]
  51. Kountouras J, Zavos C, Chatzopoulos D. Induction of apoptosis as a proposed pathophysiological link between glaucoma and Helicobacter pylori infection. Med Hypotheses. 2004;62:378–381.[CrossRef][ISI][Medline][Order article via Infotrieve]
  52. DeLano FA, Balete R, Schmid-Schonbein GW. Control of oxidative stress in microcirculation of spontaneously hypertensive rats. Am J Physiol. 2005;288:H805–H812.
  53. Halliday GM. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis. Mutat Res. 2005;571:107–120.[ISI][Medline][Order article via Infotrieve]
  54. Sun YQ, Girgensone I, Leanderson P, Petersson F, Borch K. Effects of antioxidant vitamin supplements on Helicobacter pylori-induced gastritis in Mongolian gerbils. Helicobacter. 2005;10:33–42.[CrossRef][ISI][Medline][Order article via Infotrieve]
  55. Kountouras J, Deretzi G, Zavos C, et al. Association between Helicobacter pylori infection and acute inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol. 2005;12:139–143.[CrossRef][ISI][Medline][Order article via Infotrieve]
  56. Saccà SC, Pascotto A, Camicione P, Capris P, Izzotti A. Oxidative DNA damage in the human trabecular meshwork: clinical correlation in patients with primary open-angle glaucoma. Arch Ophthalmol. 2005;123:458–463.[Abstract/Free Full Text]
  57. Kountouras J, Zavos C, Chatzopoulos D. Primary open-angle glaucoma: pathophysiology and treatment. Lancet. 2004;364:1311–1312.[CrossRef][ISI][Medline][Order article via Infotrieve]




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