Is oxidative stress involved in vernal keratoconjunctivitis? Results from a pilot study in children.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a rare chronic conjunctivitis characterized by a predominantly eosinophil-mediated inflammatory disorder that could develop critical complications such as blindness. Oxidative stress plays a pivotal role in the pathogenesis of several allergic diseases. The role of oxidative stress has been hypothesized in VKC, but no study explored this issue. Furthermore, cyclosporine A (CsA) exerts an anti-inflammatory and antioxidant action on the conjunctiva. This study aimed to assess the oxidative stress in VKC patients and controls and to study the effect of CsA on oxidative stress in these subjects. METHODS: Thirty-six consecutive children, including 12 VKC (nine males, 75%; mean age 10.17; SD ± 2.48) patients without treatment, 12 VKC patients treated with CsA (nine males, 75%; mean age 9.08; SD ± 2.75), and 12 controls (CT) (seven males, 58%; mean age 8.58; SD ± 1.78), were recruited. A cross-sectional study was performed to compare H2 O2 in the serum with that in the tears of these children. RESULTS: Compared with CT and VKC children treated with CsA, VKC untreated children had significantly higher values of hydrogen peroxide (H2 O2 ) in the serum and the tears. No significant differences were observed between CT and VKC treated with CsA. A significant correlation was found at the linear regression analysis between serum and tear H2 O2 levels. CONCLUSION: This study provides the first report attesting that patients with VKC have high oxidative stress; furthermore, it suggests that CsA could have an anti-inflammatory and antioxidant action that could be useful to prevent the poor VKC outcome.

High-mobility group box-1 (HMGB-1) and serum soluble receptor for advanced glycation end products (sRAGE) in children affected by vernal keratoconjunctivitis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a chronic disease affecting conjunctiva even though the immunopathogenetic mechanisms underlying this inflammation are unclear. The aim of our study is to investigate serum levels of HMGB1 and circulating sRAGE in children affected by VKC before and after treatment with cyclosporine A (CsA) eye drops and in a group of healthy children. METHODS: Twenty-four children affected by VKC aged between 5 and 12 yrs of life were enrolled at the Department of Pediatrics, Division of Allergy and Immunology, 'Sapienza' University of Rome. Twenty-four healthy children without atopy, ocular, and systemic disease, cross-matched for sex and age to patients affected by VKC, represented the controls. All children affected by VKC were treated with CsA 1% eye drops for 4 wks, and blood samples were collected before and 2 wks after the end of treatment while the controls underwent to a single blood sample at the time of enrollment. RESULTS: Serum basal levels of HMGB1 and sRAGE were higher in children with VKC when compared with controls while, in patients affected by VKC, no difference was detected between atopic and non-atopic, and between ANA-positive and ANA-negative children. A significant reduction in serum HMGB1 and sRAGE levels was detected after the therapy while CsA serum levels were negative. CONCLUSIONS: Our study gives a support to the definition of VKC as a systemic inflammation in which HMGB1 and its soluble receptors could play a role.

Vitamin D levels in children affected by vernal keratoconjunctivitis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a chronic and often severe bilateral conjunctivitis. VKC etiology still remains unclear although endocrine, genetic, neurogenic and environmental factors have been implicated. Vitamin D is a fat-soluble prohormone whose main function is the regulation of calcium and phosphate metabolism. The aim of this study was to evaluate serum vitamin D in children affected by VKC compared to the healthy children and investigate the relationship between its levels and disease severity. METHODS: A total of 110 children, 47 affected by VKC, aged between 5 and 12 years were enrolled at the Department of Pediatrics, Division of Allergy and Immunology, "Sapienza" University of Rome. Used as controls were 63 healthy children with negative skin prick test (SPT), without allergic, ocular and systemic disease. Serum samples were obtained in April from all the children included in the study. Vitamin D dosage was repeated in October in 20 patients after therapy and in 20 controls. A conjunctival scraping was performed in all children affected by VKC. RESULTS: Children affected by VKC had lower vitamin D levels compared to healthy controls and we found an increase in vitamin D levels after therapy with cyclosporine eye drops 1% although this increase was lower than that of healthy controls. Moreover we found significant correlations between vitamin D level and the severity of the disease. CONCLUSIONS: The study shows that children affected by VKC have lower vitamin D levels when compared to healthy controls and highlights a significant correlation between its levels and disease severity.

Mean Platelet Volume, Vitamin D and C Reactive Protein Levels in Normal Weight Children with Primary Snoring and Obstructive Sleep Apnea Syndrome.

INTRODUCTION: Studies on Mean Platelet Volume (MPV) in children with Sleep Disordered Breathing (SDB) report conflicting results and the hypothesis of an intermittent hypoxemia leading to a systemic inflammation is reaching consensus. Vitamin D exerts anti-inflammatory properties and its deficiency has been supposed to play a role in sleep disorders. Emerging interest is rising about Primary Snoring (PS) since it is reasonable that also undetectable alteration of hypoxia might predispose to an increased production of inflammatory mediators. In this perspective, in a group of children affected by SDB, our aim was to investigate MPV, vitamin D and C Reactive Protein (CRP) levels, which had been previously evaluated separately in different studies focused only on Obstructive Sleep Apnea Syndrome (OSAS). MATERIALS AND METHODS: We enrolled 137 children: 70 healthy controls (HC), 67 affected by SDB undergoing a polysomnographic evaluation, 22 with a diagnosis of PS and 45 with a diagnosis of OSAS. All patients underwent routine biochemical evaluations including blood cell counts, CRP and vitamin D. RESULTS: Children affected by SDB had a mean age of 8.49±2.19 and were prevalently males (23 females, 34%; 44 males, 66%). MPV levels were higher in OSAS and PS when compared to HC; platelet count (PLT) and CRP levels were higher while Vitamin D levels were lower in children with SDB when compared to HC. MPV levels were correlated with PLT (r = -0.54; p<0.001), vitamin D (r = -0.39; p<0.001) and CRP (r = 0.21; p<0.01). A multiple regression was run to predict MPV levels from vitamin D, CRP and PLT and these variables significantly predicted MPV (F = 17.42, p<0.0001; adjusted R2 = 0.37). Only platelet count and vitamin D added statistically significantly to the prediction (p<0.05). CONCLUSION: The present study provides evidence of higher MPV and lower vitamin D levels in children with PS as well as in children with OSAS, and supports the underlying inflammation, hence, highlighting the importance of an early diagnosis of this previously considered benign form of SDB.

Assessment of corneal alterations by confocal microscopy in vernal keratoconjunctivitis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a bilateral chronic, seasonally exacerbated inflammation of the ocular surface that especially affects male children and young boys. AIM: To evaluate the corneal microscopic features of patients affected by VKC and to assess whether some corneal changes were associated with specific ocular symptoms and/or signs. METHODS: 20 children aged between 4 and 14 years were enrolled. All patients underwent corneal confocal microscopy by Confoscan CS3 (Nidek). 350 images of the central cornea of each eye were obtained with a ×40 noncontact lens 3,5 micron gap in automode. RESULTS: Some alterations of the sub-basal and stromal corneal nerves were detected. These alterations were more evident in patients with higher severity of photophobia. On the other hand, there were scarce other signs of the anterior segment of the eye. CONCLUSIONS: Our preliminary findings show that there is another group of patients affected by VKC, characterized by an intense photophobia caused by corneal damage and without other significant ocular alterations. Therefore confocal microscopy may be useful for an early identification of corneal alterations before the onset of severe ocular symptoms and to set an appropriate therapeutic management.

Pathogenesis of Vernal Keratoconjunctivitis and Associated Factors.

AIM: To investigate the role of some variables, including allergy and autoimmunity, in the pathogenesis of vernal keratoconjunctivitis (VKC). The VKC is a chronic and often severe form of bilateral keratoconjunctivitis. Usually, it begins during the first decade and disappears during the end of the second decade of life. MATERIALS AND METHODS: 26 patients with VKC were selected. The diagnosis was performed by the ophthalmologist through a score based on ocular signs and subjective symptoms before and after administration of 1% cyclosporine A (Cy) eyedrops. Each variable was graded: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. Patients with a total score ≥7 were included in the study. Blood samples were collected at the initial time for the determination of autoimmunity by total IgE and antinuclear antibodies (ANA). A Skin Prick Test (SPT) was performed on each patient to common inhalants and food allergens. RESULTS: 53.8% of the children resulted atopic. The most important allergens were house dust mites and grasses. 46.1% of the patients showed total IgE >100 UI/ml and 30.8% had ANA positivity at the first determination. The photophobia occurred in 42.3% of children, most frequently with respect to other symptoms like secretion or tearing (30.8%), foreign body sensation (15.4%), itching and conjunctival hyperemia (11.5%). CONCLUSIONS: Fortunately all children improved their symptoms after Cy eyedrop therapy. Moreover, there was an elevated percentage (30.8%) of children with ANA positivity compared with the values in the general pediatric population. Despite the fact that it is a non-specific autoantibody, its high presence in a population of children with VKC may have an important role in clarifying etiopathogenesis and chronic inflammation.

Assessing the relationship between serum resistin and nasal obstruction in children with allergic rhinitis.

BACKGROUND: Nasal obstruction has been reported as a "key symptom" of allergic rhinitis (AR) because it is deeply associated with impaired quality of life and it reflects more directly the allergic inflammation in the nasal mucosa. Resistin is known to be involved in inflammatory processes exerting an important role in the regulation of cytokine production even though its effective proinflammatory activity at nasal level has never been fully established. This study investigates the relationship between resistin levels and nasal obstruction assessed by an objective method such as active anterior rhinomanometry. METHODS: Fifty-three children between 4 and 10 years of age affected by persistent allergic rhinitis (PAR) were enrolled and subdivided in two groups. Serum resistin levels were detected in all children. The same day patients underwent rhinomanometry, which was considered negative (no nasal obstruction) when the fraction of predicted values (p.v.'s) was between 71 and 100% and it was considered positive when the fraction of p.v. was ≤70%. RESULTS: The serum resistin levels were significantly higher in children with moderate-severe PAR than in patients with mild PAR (p < 0.03). Furthermore, serum resistin levels were significantly higher in children with positive rhinomanometry compared with negative rhinomanometry (p < 0.03). The fraction of p.v.'s of nasal flows in patients with nasal obstruction had a significant negative correlation with serum resistin levels (p < 0.001). CONCLUSION: This study provides evidence that resistin levels are increased in children with severe nasal obstruction measured by an objective and quantitative approach.