Long-term safety and efficacy of topical cyclosporine in 156 children with vernal keratoconjunctivitis.

Vernal keratoconjunctivitis (VKC) is a chronic and potentially sight-threatening disease. Topical corticosteroids (Cs) seem to be the only effective treatment for this condition, although severe side effects may occur owing to their prolonged use. More recently, cyclosporine (Cyc) eye drops have been reported as a valid alternative, but so far such treatment has only been successfully experimented for a short time and in small numbers of patients. The aim of our study is to evaluate the long term safety and efficacy of topical cyclosporine eye drops in children suffering from VKC. Over a period of 7 years we followed a large group of children suffering from severe VKC. They were selected to start cyclosporine eye drop treatment, because of the prompt relapse of their disease as soon as they stopped topical corticosteroids administration. All patients were followed-up in an ambulatory care assessment. A total of 156 children with VKC were treated with topical cyclosporine eye drops over a period ranging from two to seven years [mean time 3.8 +/- 1.09 years] during the seasonal relapse [range 9-66 months; mean time 24.7+/-10.4 months]. Two formulations, at 1% and 2% (82% and 18%, respectively) concentrations, of cyclosporine eye drops were made. The dosage administered was one drop in each eye from two to four times a day, depending on the severity of the disease and the season. The ocular objective scores were determined and compared every year, at the beginning and at the end of each treatment period. Blood samples were collected once a year in order to check both kidney and liver functions, as well as cyclosporine serum levels. We enrolled 156 patients (mean age 8.31+/-2.79 years; 116 males and 40 females) who were followed-up over a period of 7 years [156 (100%) children during the first and the second year; 138 (88.5%) patients until the third year; 90 (57.7%) until the fourth year; 32 (20.5%) until the fifth year; 10 (6.4%) until the sixth year and 2 (1.3%) until the seventh year]. The ocular objective scores significantly improved (p less than 0.001) over the years when comparing them at the beginning and the end of each seasonal treatment period, except for the last year. Over the treatment period, non-significant changes were recorded in terms of kidney and liver enzymatic activities and also in terms of cyclosporine serum levels. Cyclosporine eye drops, either at 1% or 2% concentrations, resulted safe and effective for long-term treatment of VKC in 156 children. The lack of significance of the score results during the seventh year can be explained by the small number of subjects treated for such a long period. A systematic ocular examination and both liver and kidney functional investigations allowed us to exclude the possibility of local or systemic side effects due to cyclosporine. If either transient or long-lasting, the occurrence of burning was referred by some of the patients treated, but none of them required to discontinue the drug. In conclusion, this is the first study showing that topical cyclosporine is easily handled even by children, with safe and effective results even when it is used over a long period of time. Our findings, though encouraging, need to be confirmed by further studies.

Macrophage migration inhibitory factor -173 polymorphism and risk of coronary alterations in children with Kawasaki disease.

OBJECTIVE: To investigate the possible relationship between MIF -173 polymorphism and susceptibility to, and severity of, Kawasaki disease (KD) in a cohort of Italian patients. METHODS: Sixty-nine patients (43 F, 26 M, median age 29 months, range 3-135 months) with KD and 60 sex-matched healthy caucasian children were genotyped for MIF-173. Typing of the MIF gene -173 G/C was performed by PCR and restriction fragment length polymorphism. RESULTS: Eight out of 69 (12%) KD children were non-responders: 7 required an additional IVIG infusion, while 1 received 2 IVIG infusions and then steroid administration. 9/69 (13%) KD children developed coronary artery abnormalities (CAA) during the second to fourth week of disease, and 4 of them required an additional IVIG infusion. MIF genotyping did not show significant differences between patients and controls. KD patients carrying a MIF -173*C allele developed CAA more frequently than those without MIF- (7/9 77.8% vs. 16/60 26.7%, OR 9.6, 95% CI 1.80-21.2, p<0.005). Non-responders to a single IVIG infusion carried the MIF -173*C allele more frequently than responders (6/8 = 75% vs. 17/61 = 28%, OR 5.1, 95% CI 1.42-22.31 p<0.014). In multiple regression analysis, KD patients carrying a MIF -173*C allele were found to have an increased risk of coronary involvement (OR 7.7, 95% CI 1.36-16.1, p=0.021). CONCLUSIONS: We showed that children carrying the MIF polymorphism -173*C had a higher percentage of CAA. A potential relationship between a MIF polymorphism and risk of CAA in KD might be considered.

Allergen specific nasal challenge to latex in children with latex allergy: clinical and immunological evaluation.

There are no data concerning the significance of allergen specific nasal challenge to latex (ASNCL) in the pediatric population and the effect of mometasone furoate nasal spray (MFNS), topic corticosteroid exerting a potent anti-inflammatory activity in children with latex allergic rhinitis. The aims of this study are: to investigate the clinical and immune pathological effects of ASNCL in children with latex allergy; to study the effects of MFNS pre-medication on the clinical and immune pathological effects of ASNCL in children with latex allergy. Thirteen children: 6 male and 7 female, mean (SD) age 9.6 (2.9) years, with latex allergy and seven children: 3 male and 4 female, mean (SD) age 9.9 (3.8) years, without latex allergy underwent ASNCL. Nasal symptoms were recorded, nasal lavage fluid was collected to measure tryptase, eosinophil cationic protein (ECP), interleukin-5, interferon-gamma levels, and spirometric test was performed for each patient without or with premedication with MFNS. ASNCL induced a clinical allergic response and increased tryptase levels only in children with latex allergy. No serious adverse events occurred after ASNCL. MFNS premedication reduced both tryptase and ECP levels only in children with latex allergy. ASNCL is a simple, reliable and useful tool to make or confirm the diagnosis of nasal symptoms due to latex; it allows us to study both clinical symptoms and local immunological changes. MFNS premedication before an ASNCL may prevent some immunological responses induced by ASNCL without clinical allergic modifications.

Cost of varicella-related hospitalisations in an Italian paediatric hospital: comparison with possible vaccination expenses.

OBJECTIVE: The aims of the study were to evaluate the economic burden of hospitalisations due to varicella in an Italian paediatric hospital during a 1-year period and to compare the data with potential expenses projected for a varicella mass vaccination programme. RESEARCH DESIGN AND METHODS: An observational, retrospective, cohort study was designed to measure hospital admission costs in a cohort of paediatric patients with varicella in a 12-month period. A cost comparison with a vaccination programme planned to prevent varicella in a whole birth cohort was performed. All children 0-16 years referred to the Anna Meyer Children's Hospital (AMCH) were considered. Since AMCH is a tertiary-level hospital and accept patients from other Italian regions, in order to avoid overestimation of hospitalisation expenses, all analyses pertaining to both vaccination and hospitalisation costs were uniquely calculated on the basis of the cohort of residents in the district of Florence. RESULTS: A total of 279 children were examined in the emergency department for varicella; 47/279 (16.8%) were sent to the inpatient clinic. The highest rate of hospitalisation (85.1%) was found in children < 4 years of age, and the largest number of complications (87.2%) occurred in previously healthy children. Mean length of hospitalisation (5.7 +/- 0.6 days) was similar to that reported in other western countries. CONCLUSION: Excluding any indirect cost, permanent sequelae and serious outcomes such as death, hospital expenses (corresponding to euro239 654 in a 1-year period), would account for around 80% of total expenses for vaccinating an entire birth cohort (euro310353).

Eyelash length in children with vernal keratoconjunctivitis: effect of treatment with cyclosporine eye drops.

The upper eyelashes in vernal keratoconjunctivitis (VKC) patients have been reported to be longer than in healthy age- and gender-matched subjects. Eyelash length positively correlated to the severity of the disease and negatively to the employment of cyclosporine eye drops, suggesting that specific humoral factors could be involved in both ocular inflammation and elongation of the eyelashes. The aim of the present study is to evaluate a possible relationship between eyelash length and the duration of topical cyclosporine treatment. The length of the upper eyelashes of 34 VKC patients never treated with topical cyclosporine (Cyc-NT) was matched with that of 58 VKC patients treated with cyclosporine (Cyc-T). The latter group was divided into three subgroups, depending on the duration of therapy: 1-6 months (group 1; 21 subjects) , 7-12 months (group 2; 19 subjects), greater than 12 months (group 3; 19 subjects). Cyc-NT patients eyelashes were significantly longer than those of VKC patients treated for 1-6 months (group 1). No significant difference was found between Cyc-NT and Cyc-T patients in group 2 and group 3. The differences between Cyc-T patients and group 1 and 2, group 2 and 3, and group 1 and 3 were not statistically significant. The eyelash shortening observed seems directly related to the rapid improvement of ocular symptoms induced by the treatment. A receptor down-regulation by mediators of ocular inflammation may explain this data, although different cytokines, hormones or other humoral mediators could be expressed on the ocular surface at different stages of the disease, mainly in periods of rapid change of the clinical course.

Diagnostic value of three different latex extracts.

The diagnosis of latex allergy is made on clinical history, but a confirmatory skin prick test (SPT) or a serological assay based on a commercial latex extract is always recommendable. Different raw materials can be used in the preparation of commercial latex extracts. Such extracts can consequently show both different qualitative profiles and a different diagnostic potential. Therefore, the selection of a proper latex extract is essential for in vitro and in vivo diagnosis of latex allergy. In the present study three different latex extracts, prepared from different raw materials (ammoniated -AL-, serum -SL-, or rubber particles -RPE- latex), are compared by in vitro techniques using sera from twenty patients with latex allergy. SDS-PAGE technique was used to compare the antigenic profile of the three latex extracts. Subsequently, their allergenic profiles were evaluated by immunoblotting technique using the individual sera from the twenty latex allergic patients. The diagnostic potential of the three latex extracts was also evaluated using direct Radio-Allergo-Sorbent Test (RAST) as well as skin prick tests (SPTs). In order to establish the more appropriate latex extract in a perspective of in vivo diagnosis of latex sensitization, the same latex extracts were subsequently compared by an in vivo SPT involving ten of the above subjects. The SDS-PAGE profiles of the three latex extracts examined were quite different. SL extract showed numerous bands comprised between 10-100 kDa. RPE extract was characterized by two intense bands at 14 and 20 kDa while AL extract showed the poorer antigenic composition. Analogously, immunoblotting analysis evidenced a different profile in relation to both different patients and extracts. For only two out of the twenty sera, direct RAST results showed a same positive class in relation to the different latex extracts used. SPT with SL extract showed, in respect to the other extracts (AL, RPE), a significantly higher wheal. This study showed that SL extract is able to express the best in vitro and in vivo diagnostic potential. Thus, its use should be preferred for the diagnosis of patients affected by latex allergy.

Vertical hepatitis C virus transmission is not related to mother-child class-1 HLA concordance.

Mother-child human leukocyte antigen (HLA)diversity is protective for vertical transmission of some viruses. The aim of this study is to evaluate the role of mother-child HLA diversity on hepatitis C virus (HCV) vertical transmission. Forty consecutive HCV infected and 46 consecutive control uninfected children born to HCV-RNA positive mothers were evaluated for HLA class-1 type concordance with their mothers. No significant difference in the degree of HLA concordance was found between HCV infected and uninfected children both when A, B, C (p=0.30) and when only A and B alleles were evaluated (p=0.59). Mother-infant HLA concordance does not affect HCV vertical transmission.

Atopy and serum eosinophil cationic protein in 110 white children with vernal keratoconjunctivitis: differences between tarsal and limbal forms.

BACKGROUND: A predominance of Th2 response has been suggested in vernal keratoconjunctivitis (VKC), and a high prevalence of IgE-sensitized (IgE-S) patients has been reported (positive skin prick test or serum-specific-IgE). Palpebral and bulbar VKC are considered to be expressions of the same disease and only occasional racial and histopathological differences are described between the two forms. Tear levels of eosinophil cationic proteins have been correlated with the severity of ocular symptoms; however, there is no published study that demonstrates the presence of serum markers of disease activity. OBJECTIVE: This study was performed to evaluate the prevalence of IgE-sensitization in palpebral, bulbar and mixed VKC and to determine possible useful markers of disease activity in peripheral circulation. METHODS: A total of 110 white VKC patients (mean age 8.3 years, range 3.2-18 years) were evaluated for ocular score in the active phase of the disease. Skin prick tests and serum-specific IgE for common allergens, serum-total IgE, peripheral blood eosinophil counts (PBECs) and serum eosinophil cationic protein (s-ECP) were determined. Fifteen age-matched non-IgE-S control children underwent the same determinations. RESULTS: s-ECP, PBECs and s-total IgE were significantly higher in IgE-S than in non-IgE-S VKC patients and in non-IgE-S VKC patients than in controls. A lower prevalence of IgE-S patients was found in bulbar vs. tarsal (P = 0. 050) or mixed forms (P = 0.002). The score of giant papillae was strongly correlated with s-ECP levels (P < 0.001) and with PBECs (P = 0.001). CONCLUSIONS: Our data suggest that an overall eosinophilic response is present in VKC independently of IgE-sensitization; bulbar forms, unlike tarsal and mixed forms, were associated with a low prevalence of IgE-sensitization. Serum ECP was a useful marker of disease activity in tarsal and mixed forms.