Prevalence and Treatment of Helicobacter pylori in Patients with Blepharitis

Sergio Claudio Saccà; Antonio Pascotto; Gian Maria Venturino; Guido Prigione; Antonio Mastromarino; Franco Baldi; Claudio Bilardi; Vincenzo Savarino; Carlo Brusati; Alfredo Rebora

doi:10.1167/iovs.05-0323

Abstract

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 ²Although its role is debatable, this bacterium has also been associated with nondigestive manifestations³such as Raynaud’s phenomenon,⁴ ⁵cardiovascular diseases,⁶ ⁷Sjögren’s syndrome,⁸ ⁹urticaria,¹⁰and 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 inflammation¹³and glaucoma.¹⁴ ¹⁵Moreover, 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

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 ¹⁹Impression cytology was performed in all patients by pressing a 6 × 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.²⁰To 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

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.

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 ²⁴specifically 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.²⁶Tear 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 χ² 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.

Results

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 ).

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 χ² test was not significant (Table 5) . In UBT⁻ control subjects, blepharitis was found in 29 (13.4%) patients.

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.

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 (χ² = 49, 136 df = 5, P < 0.0001; Table 7 ).

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%; χ² = 47.231, P < 0.01) and in people older than 60 years (42%) than in younger people (26%; χ² = 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 (χ² = 116.0, P < 0.001), but no difference was found between patients with blepharitis coming from the two different departments (Gastroenterology and Ophthalmology; χ² = 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) .

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) .

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

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.¹⁹Patients with rosacea often report digestive disturbances,¹² ¹³ ¹⁴ ¹⁵ ¹⁶ ¹⁷ ¹⁸ ¹⁹ ²⁰ ²¹ ²² ²³ ²⁴ ²⁵ ²⁶ ²⁷which have been considered to be directly related to blepharitis.²⁸Digestive troubles are related more to rosacea than to seborrhea,²⁷although there is much that binds these two pathologic conditions.²⁹There seems to be a connection between H. pylori infection and rosacea,¹¹whereas the association between seborrhea and H. pylori, which has been reported in another study,³⁰seems 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.³¹It 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,³²and 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,³³both 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 ³⁵Indeed, 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,³⁷but it is not known whether the oral cavity acts as a permanent reservoir for this bacterium.³⁸However, 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.³⁹It is important to stress that oral metronidazole has been successfully used in blepharitis with rosacea,⁴⁰ ⁴¹though 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,⁴³thereby resulting in decreased bacteriologic lipase activity.⁴⁴ ⁴⁵Indeed, therapeutic results of systemic antibiotics in the treatment of blepharitis have recently been reported.⁴⁶However, in our study, the clinical improvements were obtained after the eradication of H. pylori infection (Fig. 2) .

Except in the case of Staphylococcus pathogenesis,⁴⁷blepharitis 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.⁴⁸Systemic antibiotic therapy may be helpful in patients with meibomian gland dysfunction³⁹or in cases of rosacea.⁴⁰Moreover, 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 ⁵⁰H. 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.⁵¹It is possible that the “link” is the oxidative damage that recurs in circulation disorders,⁵²in inflammation,⁵³ ⁵⁴ ⁵⁵and in glaucoma.⁵⁶Indeed, H. pylori infection could affect the pathophysiology of glaucoma, by producing oxidative stress and circulating lipid peroxides,⁵⁵and may contribute to central serous chorioretinopathy by increasing endothelin 1, nitric oxide,⁵⁷and 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.

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@hsanmartino.it.

Table 1.

View Table

Classification of Chronic Blepharitis¹⁸ ¹⁹

Table 1.

Classification of Chronic Blepharitis¹⁸ ¹⁹

Anterior or Ciliary Blepharitis
Seborrheic	Staphylococcal
Increase in normal fluid meibomian secretion	Bulbar and tarsal conjunctival changes (follicles or papillae) and superficial punctate epitheliopathy
Minimal bulbar, conjunctival injection	Less greasy debris
Minimal or moderate foaming of tear meniscus	Presence of collarettes
Unstable tear film (burning symptoms)	More inflammation
Meibomian secretion
Dermatologic signs
Seborrheic dermatitis involved
Scalp, retroauricular area nasolabial folds and stemum

Posterior Blepharitis
Meibomitis	Mixed	Rosacea
Marked inflammation of the lid or conjunctiva in spotty distribution	One or more lesions belonging to the two former different patterns had to be observed	Periocular erythema
Inflammation of meibomian gland orifices			Lid hyperemia
Solidification of lipid secretion on gland orifices		Interpalpebral conjunctival hyperemia
Punctate epitheliopathy		Chalazia
Bulbar injection		Telangiectasia of the conjunctiva and lid margin
Tarsal papillary hypertrophy		Cornea: punctate keratitis, infiltrates, ulcers
Unstable tear film (increased viscosity)		Marginal keratitis
Dermatologic signs		Dermatological signs
Similar to seborrheic dermatitis		Transient erythema (flushing)
		Papules and pustules
		Telangiectasia
		Dry appearance
		Edema

Classically, these signs are present; however, in this analysis anterior and posterior were grouped. Seborrheic blepharitis always has some manifestation of meibomitis; rosacea blepharitis has staphylococcal contamination. Therefore, the clinical division of anterior and posterior was not observed.

Table 2.

View Table

Morphologic and Morphometric Criteria Used in Impression Cytology

Table 2.

Morphologic and Morphometric Criteria Used in Impression Cytology

Type 1 (Severe Changes)	Type 2 (Moderate Changes)	Type 3 (Normal)
Muciparous cells	Muciparous cells	Muciparous cells
Absent (a)	Morphologically altered	Morphologically regular
Few (b) (1–10/mm²)	Broken cell wall	Normal cell wall
Epithelial cells	<15 μm	25 μm
Morphologically heavily altered	Few (11–20/mm²) (a); (21–30/mm²) (b)	Sufficient in number (30– 60/mm²) (a)
N/C ratio, 1:5 1:6	Epithelial cells	Numerous (>60/mm²) (b)
	Morphologically irregular	Epithelial cells
	Folded borders	Morphologically regular
	N-C ratio, 1:3 1:4	Well delineated borders
		Good intercellular cohesion
		N/C ratio 1/1 1/2

, cell diameter; N/C ratio, nucleus/cytoplasm ratio.

Table 3.

View Table

Dermatologic Inclusion Criteria²²

Table 3.

Dermatologic Inclusion Criteria²²

Rosacea	Seborrheic Dermatitis	Mixed
Flushing	Greasy-looking scales and/or crusts	To diagnose this type of dermatitis or blepharitis, one or more lesions belonging to the two former different patterns had to be observed
Persistent erythema with scattered telangiectasia	Increase of redness and cutaneous color variability
Papules and pustules	Clinical patterns on trunk, scalp, and face (including lids)
Sprays of vessels especially on the nose or cheeks
Phymas

For a diagnosis of blepharitis, one or more lesions must be observed on the eyelid margin with a nongranulomatous inflammatory reaction associated.

Table 4.

View Table

Demographic Data

Table 4.

Demographic Data

Diagnosis Groups	Age Groups (y)
Diagnosis Groups		<40	41–60	>60	Totals
Blepharitis	63	57	66	186
Male/female	28/35	30/27	27/39	85/101
Control	75	65	75	215
Male/female	34/41	31/34	29/46	94/121
Totals	138	122	141	401

Figure 1.

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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.

Table 5.

View Table

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

Table 5.

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

Type of Blepharitis	Age Group (y)
Type of Blepharitis		≤40	41–60	>60
Seborrheic	36 (57.1)	32 (56.1)	26 (39.4)
Mixed	6 (9.6)	7 (12.3)	7 (10.6)
Rosacea	21 (33.3)	18 (31.6)	33 (50.0)

Data are the number of cases (percentage of total group). χ² testing was not significant for sample heterogeneity (χ² = 1.877; df = 2, P = 0.55). n = 186.

Table 6.

View Table

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

Table 6.

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

Bacterium	%
UBT⁺ (n = 142)
Staphylococcus epidermidis	95
Corynebacterium sp.	70.5
Propionibacterium acnes	79.9
Staphylococcus aureus	18
Acinetobacter sp.	12
UBT⁻ (n = 44)
Staphylococcus epidermidis	92.5
Corynebacterium sp.	72
Propionibacterium acnes	78.6
Staphylococcus aureus	14
Acinetobacter sp.	12.2

The distribution of the bacteria in the two groups does not show a significant difference P > 0.5.

Table 7.

View Table

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

Table 7.

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

Group	Age Group (y)
Group		≤40	41–60	>60
Blepharitis (n = 142)	42 (18)	45 (19)	55 (24)
Control (n = 91)	21 (9)	28 (12)	42 (18)

Data are the number of patients (percentage of the total group). The number of positive results on the UBT increased with age, remaining, however, significantly different between the two groups. See also Figure 1 .

Table 8.

View Table

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

Table 8.

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

Group	UBT Positive (n = 208)					UBT negative (n = 73)
Group		Seborrheic	Rosacea	Mixed	Seborrheic	Rosacea	Mixed
Blepharitis	71	55	16	23	17	4
Control	33	26	7	14	12	3
Significance	P = 0.5533	P = 0.529	P = 0.5527	P = 0.508	P = 0.5254	P = 0.5131

In the patients with blepharitis, no statistically significant difference was observed between UBT⁺ and UBT⁻ patients in the distribution of the type of conjunctivitis. Data are the number of patients.

Figure 2.

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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 (A _I–C _I). 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). (A _I) Patient 9: a 33-year-old woman. Muciparous cells were morphologically normal, but were less numerous. Epithelial cells were normal with less cohesion. (B _I) Patient 55: a 53-year-old woman. Muciparous cells were scanty, with irregular borders. Intercellular cohesion was very poor. (C _I) Patient 122: a 72-year-old man. Muciparous cells varied in size, were scanty, and had irregular borders. Epithelial cells were irregularly grouped. Magnification, ×2.5.

Figure 3.

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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. (A _I) Patient 11: a 34-year-old man with seborrheic blepharitis. Muciparous cells were scanty with irregular borders, whereas epithelial cells were normal. (A _II) After therapy, impression cytology became completely normal. (B _I) Patient 39: a 50-year-old woman. Muciparous cells were absent, and epithelial cells folded with irregular borders and small nuclei. (B _II) After therapy, muciparous cells reappeared, though scanty with irregular diameters and borders. Epithelial cells were morphologically normal but showed scanty intercellular cohesion. (C _I) Patient 129: a 75-year-old man. Before therapy, squamous metaplasia was obvious. (C _II) 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, ×2.5.

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

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