Enrico Lombardi

Efficacy and safety of cyclosporine eyedrops in vernal keratoconjunctivitis

BACKGROUND Corticosteroids have been the only effective topically administered treatment for severe vernal keratoconjunctivitis (VKC), but their prolonged use is often associated with complications. Topical cyclosporine therapy has been used in the past decade, but few controlled trials have been conducted, and conflicting results have been reported. OBJECTIVE This study sought to evaluate the efficacy and safety of ocular administration of cyclosporine in VKC. METHODS Twenty-four children with severe VKC were treated with cyclosporine 2% eyedrops. The treatment began in spring and lasted 4 months. One eye was treated with cyclosporine (Cs-eye); the fellow eye received the vehicle as placebo (Pl-Cs-eye) during the first 2 weeks in a double-blind, placebo-controlled trial and thereafter was treated with cyclosporine (open trial). Patients were instructed to protect their eyes against sunlight. Ocular symptoms and signs were scored at entry and at 2 weeks, 4 weeks, and 4 months after the beginning of treatment. All children underwent biochemical and immunologic evaluations. RESULTS Compared with baseline, scores for ocular signs and symptoms at 2 weeks decreased significantly in the Cs-eyes (P < 0.001), and signs improved in the Pl-Cs-eyes (P = 0.001). A significant difference was noted between Cs-eyes and Pl-Cs-eyes at 2 weeks for both subjective (P < 0.005) and objective (P < 0.001) scores. At 4 weeks, scores for signs (P < 0.001) and symptoms (P = 0.01) were reduced in the Pl-Cs-eyes, with no further improvement in the Cs-eyes. At 4 months, clinical scores had declined further, and serum eosinophil cationic protein levels were significantly lower than at entry (P = 0.009). Most patients reported mild burning sensation and tearing after administration of cyclosporine. Four patients (17%) required an additional brief period of topical corticosteroid therapy. CONCLUSIONS Cyclosporine eyedrops were effective and safe for treating severe VKC, without causing major side effects. Most of the therapeutic effect was achieved after 2 weeks. The initial therapeutic effect was maintained during the next 3 months, with a further slow decrease in the symptoms.

Natural history of “intrinsic” atopic dermatitis

. IT is well known that allergy plays a pathogenic role in the development of atopic dermatitis (AD) (1). However, approximately 20% of AD patients suffer from a skin disease that clinically resembles the skin lesions and the distribution pattern of AD, but is not associated with atopic status. This kind of ‘‘intrinsic’’ AD (iAD) seems to differ from the classical or ‘‘extrinsic’’ form (eAD) both in the T-cell cytokine production and in the immunohistology (2, 3), but no data are available about its natural history. In this study, we investigated the persistence of AD and the development of respiratory allergic diseases in a group of children seen at the ages of 2 and 11 years according to the skin prick test (SPT) reactivity to allergens at those ages. The parents of 111 children with AD evaluated at our allergy unit in 1989–90 were asked for re-evaluation of the children about 9 years later. Seventy percent of the children (77/111) underwent clinical history, and SPTs to food (egg white, wheat, milk, tomato, codfish, and soy [Lofarma, Milan, Italy]) and inhalant allergens (dust mite, cat, dog, Alternaria, grass pollen, Parietaria, mugwort, olive pollen, and Cupressus sempervires [Lofarma]). AD was diagnosed according to Hanifin & Rajka (4). The presence of asthma and SPT reactivity was studied as previously described (5, 6). According to the SPT results, we defined the following groups: 1) ‘‘early atopic’’, i.e., those children who were already SPT positive at age 2 and were still SPT positive at age 11 2) ‘‘late-onset atopic’’, i.e., those who were negative at age 2 but became SPT positive by the age of 11 3) ‘‘nonatopic’’, i.e., those who were SPT negative at the ages of both 2 and 11. We considered patients SPT negative at age 2 as having iAD. The data were analyzed by the statistical program SPSS 6.0 for Windows with the chi-square and chi-square for trend tests. A two-sided type 1 error lower than 0.05 was considered statistically significant. Seventy-seven AD patients, with a mean age (uSE) of 24.1u2.28 months at the first evaluation, and 132u3.24 months at the second evaluation, were identified. At diagnosis, all of them had AD (77/77), 22% (17/77) had asthma, and 64% (49/77) had at least one positive SPT. At 11 years of age, 46% of them had AD (36/77), 43% (33/77) had asthma, and 84% had (65/77) at least one positive SPT. Forty-nine out of the 77 (64%) studied children had early atopy, 16/77 (21%) had late-onset atopy, and 12/77 (15%) were nonatopic. None of the nonatopic children developed asthma by age 11 (0/12), compared with the 25% (4/16) and the 59% (29/49) of the late-onset and early atopic children, respectively (chi square for trend, P,0.0002). AD was still present by age 11 in 67% (8/12) of nonatopic AD as compared with 44% (7/16) and 43% (21/49) of the late-onset and early atopic children (Fig. 1). Altogether, the 28 AD children ALLERGY 2001: 56 :452^463 . COPYRIGHT G MUNKSGAARD 2001 . ISSN 0105-4538 . ALL RIGHTS RESERVED . CONTRIBUTIONS TO THIS SECTION WILL NOT UNDERGO PEER REVIEW, BUT WILL BE REVIEWED BY THE ASSOCIATE EDITORS .

Clinical features of acute anaphylaxis in patients admitted to a university hospital: an 11-year retrospective review (1985–1996)

BACKGROUND Although anaphylaxis is considered a life-threatening event, there is a lack of information on the clinical characteristics at presentation, both in adults and in children. OBJECTIVE To describe in a nonselected population the clinical characteristics and the treatments of acute anaphylaxis triggered by different agents. METHODS This is a retrospective review of the clinical features of 113 episodes of acute anaphylaxis resulting in admission to a university hospital. Initially, the 107 patients visited the emergency room and were then admitted to the hospital. RESULTS Most anaphylactic events (63%) occurred at home. The most frequent symptoms involved the respiratory system (78%) and the skin (90%). Drugs, especially nonsteroidal anti-inflammatory drugs and antibiotics, were the most frequent cause of anaphylaxis in adults (49%). Patients with drug-induced anaphylaxis were older and more often had cardiovascular symptoms (hypotension and tachycardia) (P = 0.0064). Hymenoptera venom was the second most frequent cause of anaphylaxis (29%). Most of the patients with hymenoptera venom anaphylaxis were male (80%) and more frequently they had no history of atopy (P = 0.012). In food-induced anaphylaxis, the cardiovascular system was less likely to be involved (P < 0.05) (39%). Seafood seems to be frequently involved in food-induced anaphylaxis in our area. Specific immunotherapy-induced anaphylaxis occurred more often in younger patients (P = 0.032). Epinephrine seems to be underused in Italy (only 15% of patients received it), especially for respiratory symptoms. CONCLUSIONS Anaphylaxis triggered by different agents may have different clinical presentations and may occur in different types of patients. In Italy, the inadequate use of epinephrine for anaphylaxis treatment needs to be publicized to both physicians and the general population.

Mould/dampness exposure at home is associated with respiratory disorders in Italian children and adolescents: the SIDRIA-2 Study

Aims: To report on the relation between home mould and/or dampness exposure and respiratory disorders in a large sample of children and adolescents in Italy, accounting for age at time of exposure. Methods: 20 016 children (mean age 7 years) and 13 266 adolescents (mean age 13 years) completed questionnaires on indoor exposures and respiratory symptoms/diseases. Statistical analyses were adjusted for sex, age, questionnaire’s compiler, area of residence, season of interview, parental educational status, family history of asthma, rhinitis, eczema, chronic obstructive pulmonary disease, presence of gas water heaters, passive smoking, pets, and active smoking (only for adolescents). Population attributable risk % (PAR) was also computed. Results: Asthma was more strongly related to only early than to only current exposure, both in children (OR 1.80, 95% CI 1.41 to 2.30) and adolescents (OR 1.89, 95% CI 1.38 to 2.59). The same result was found for rhino-conjunctivitis (OR 1.46, 95% CI 1.17 to 1.82), in children, and for wheeze among adolescents (OR 1.56, 95% CI 1.15 to 2.11). In children, wheeze (OR 1.98, 95% CI 1.47 to 2.66) and eczema (OR 1.44, 95% CI 1.09 to 1.91) were more strongly related to mould/dampness when exposed both early and currently; the same occurred in adolescents for rhino-conjunctivitis (1.78, 95% CI 1.30 to 2.45). Although persistent cough/phlegm was significantly related to mould/dampness exposure in children, regardless of exposure timing, no significant association between mould/dampness exposure and eczema or cough/phlegm was found among adolescents. PAR estimates were higher for only early than only current exposures. Avoiding early only exposure would abate wheeze by 6%, asthma or cough/phlegm by 7%, rhino-conjunctivitis in children by 4%, and in adolescents, asthma by 6%, and wheeze by 4%. Conclusions: Respiratory disorders such as wheeze and asthma can often be explained by exposure to home mould/dampness, especially early in life. The association seems more evident in children than in adolescents. These findings may suggest the need for environmental prevention strategies.

Urinary eosinophil protein X and serum eosinophil cationic protein in infants and young children with atopic dermatitis: Correlation with disease activity ☆ ☆☆ ★

BACKGROUND Eosinophil cationic protein (ECP) and eosinophil protein X (EPX) or eosinophil-derived neurotoxin (EDN) are released by eosinophil granulocytes in allergic diseases. Serum ECP (s-ECP) levels have been correlated with disease activity in atopic dermatitis (AD) in adults and young patients, and high urinary EPX (u-EPX) levels in asthmatic patients seem to reflect active disease. A relationship between AD severity and u-EPX concentration in young children has not been previously studied. OBJECTIVE This study was performed to evaluate whether the severity of AD in infants and young children was correlated with s-ECP and u-EPX levels. METHODS Fifty-four infants and children (mean age, 17.7 months; range, 4-48 months) with AD and without other allergic conditions were evaluated. The severity of AD was measured by using the SCORAD index. S-ECP, serum total IgE, serum-specific IgE for common allergens, and peripheral blood eosinophil counts (PBECs) were determined. In forty-two children u-EPX was also measured. Seven age-matched control patients underwent the same determinations. RESULTS S-ECP and u-EPX were significantly higher in children with AD than in control children (mean, 23.9 vs 3.5 microg/dL [P <.001] and 57.7 vs 6.0 microg/mmol creatinine [P <.001]). A significant correlation was found between SCORAD and s-ECP (P =.002), u-EPX (P =.01), and PBECs (P =.01) and between symptom index and uEPX (P =.0004). PBECs were strongly correlated to s-ECP and u-EPX (P <.0001). However, 5 patients with moderate and severe AD (11.9%) showed low levels of s-ECP, u-EPX, and PBECs. CONCLUSION S-ECP and u-EPX were useful markers of AD activity in infants and young children. When taken together, the two determinations could give more information about the clinical course of the illness. Some patients seemed to have clinical exacerbations without an involvement of eosinophils and their products.

Prevalence and risk factors of latex sensitization in an unselected pediatric population.

BACKGROUND The prevalence of latex sensitization has been investigated in population groups considered at high risk, but it has not been systematically surveyed among the general population. OBJECTIVE We sought to determine the prevalence of and the risk factors associated with latex sensitization in a general pediatric population. METHODS We investigated 1175 children (mean age +/- SD, 105 +/- 17.5 months) in 11 elementary schools in Tuscany (Italy). All parents answered a questionnaire, and children underwent skin prick tests (SPTs) with latex, six aeroallergens (Dermatophagoides pteronyssinus, D. farinae, cat, grass pollen, Alternaria tenuis, and Parietaria judaica), three food allergens (milk, egg white, and wheat), and three insect venoms (honeybee, wasp, and Polistes). RESULTS Eight subjects (0.7%; mean age +/- SD, 123 +/- 9.28 months) had positive SPT responses to latex. No children showed allergic reactions to latex. One or more positive SPT responses to aeroallergens were present in 340 children (28.9%); one or more positive SPT responses to food allergens were present in 26 (2.2%); one or more positive SPT responses to aeroallergens, food allergens, or both were present in 353 (30.0%); and one or more positive SPT responses to one or more insect venoms were present in 43 subjects (3.7%). Significant (p < 0.05) risk factors associated with latex sensitization included: positive SPT responses to aeroallergens, food allergens, or both; a positive response to one or more insect venoms; a positive response to mite, milk, egg white, wheat, honeybee venom, wasp venom, Polistes venom, or a combination thereof; and increased age. CONCLUSION This report shows a very low prevalence of latex sensitization with an absence of clinical symptoms to latex. This study demonstrates a significant association between latex sensitization and the presence of one or more positive SPT responses to aeroallergens, food allergens, or both; one or more positive SPT responses to one or more insect venoms; and increased age.

An Official American Thoracic Society Workshop Report: Optimal Lung Function Tests for Monitoring Cystic Fibrosis, Bronchopulmonary Dysplasia, and Recurrent Wheezing in Children Less Than 6 Years of Age

Although pulmonary function testing plays a key role in the diagnosis and management of chronic pulmonary conditions in children under 6 years of age, objective physiologic assessment is limited in the clinical care of infants and children less than 6 years old, due to the challenges of measuring lung function in this age range. Ongoing research in lung function testing in infants, toddlers, and preschoolers has resulted in techniques that show promise as safe, feasible, and potentially clinically useful tests. Official American Thoracic Society workshops were convened in 2009 and 2010 to review six lung function tests based on a comprehensive review of the literature (infant raised-volume rapid thoracic compression and plethysmography, preschool spirometry, specific airway resistance, forced oscillation, the interrupter technique, and multiple-breath washout). In these proceedings, the current state of the art for each of these tests is reviewed as it applies to the clinical management of infants and children under 6 years of age with cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheeze, using a standardized format that allows easy comparison between the measures. Although insufficient evidence exists to recommend incorporation of these tests into the routine diagnostic evaluation and clinical monitoring of infants and young children with cystic fibrosis, bronchopulmonary dysplasia, or recurrent wheeze, they may be valuable tools with which to address specific concerns, such as ongoing symptoms or monitoring response to treatment, and as outcome measures in clinical research studies.

Epidemiology of insect venom sensitivity in children and its correlation to clinical and atopic features

The aim of this study was to obtain more accurate figures of the prevalence of cutaneous sensitivity to Hymenoptera venoms (HV) and its correlation with other parameters of atopy in a population of primary schoolchildren. Parents filled out a structured questionnaire and children were tested with a panel of inhalant and food allergens as well as standardized freeze‐dried extracts of HV. Among the 1175 children who completed the study there was a personal history of rhinoconjunctivitis in 242 (20.8%) and a current wheezing in 114 (9.78%). Two‐hundred twenty‐eight (19.40%) children had a history of Hymenoptera sting (HS) reactions (224 or 19.06% of local reactions and 4 or 0.34% of local and systemic reactions). Positive skin‐prick tests (SPT) to any given HV extract were present in 43 children (3.66%). Most subjects had positive SPT to honey bee venom (35/1175; 2.98%); 17/1175 (1.45%) had positive SPT to wasp and only 12 subjects (1.02%) had positive SPT to polistes venom. There was a correlation between a positive SPT to HV and the history of clinical reactions to HS (P = 0.0026). Positive SPT to at least one of the inhalant and food allergens tested were found in 353 subjects (30.04%). Factors such as age, sex, reactions to HV, positive SPT to mite, cat dander, grass, Alternaria, Parietaria, cows milk, egg white and wheat were significantly associated with a positive SPT to HV using a univariate regression analysis. Only age, reactions to HV, a positive SPT to grass, Parietaria, cows milk, and egg white were significantly associated with a positive SPT to HV using a multiple regression analysis. In this study, the frequency of immunological sensitization to HV in a population of unselected children is not so high as in adults. There is an association between the presence of positive SPT to HV and an atopy linked humoral IgE response. The presence of a significant and independent association between positive SPT to food of animal origin and positive SPT to HV is surprising and needs further study.

PREVALENCE OF AND RISK FACTORS FOR LATEX SENSITIZATION IN PATIENTS WITH SPINA BIFIDA

PURPOSE We determined the prevalence of and risk factors for latex sensitization in patients with spina bifida. MATERIALS AND METHODS A total of 59 consecutive subjects 2 to 40 years old with spina bifida answered a questionnaire, and underwent a latex skin prick test and determination of serum IgE specific for latex by RAST CAP radioimmunoassay. We also noted the relationships of total serum IgE skin prick tests to common air and food allergens. In addition, skin prick plus prick tests were also done with fresh foods, including kiwi, pear, orange, almond, pineapple, apple, tomato and banana. RESULTS Latex sensitization was present in 15 patients (25%) according to the presence of IgE specific to latex, as detected by a skin prick test in 9 and/or RAST CAP in 13. Five latex sensitized patients (33.3%) had clinical manifestations, such as urticaria, conjuctivitis, angioedema, rhinitis and bronchial asthma, while using a latex glove and inflating a latex balloon. Atopy was present in 21 patients (35.6%). In 14 patients (23%) 1 or more skin tests were positive for fresh foods using a prick plus prick technique. Tomato, kiwi, and pear were the most common skin test positive foods. Univariate analysis revealed that a history of 5 or more operations, atopy and positive prick plus prick tests results for pear and kiwi were significantly associated with latex sensitization. Multivariate analysis demonstrated that only atopy and a history of 5 or more operations were significantly and independently associated with latex sensitization. CONCLUSIONS A fourth of the patients with spina bifida were sensitized to latex. Atopy and an elevated number of operations were significant and independent predictors of latex sensitization in these cases.

Reference ranges for interrupter resistance technique: the Asthma UK Initiative

Measuring interrupter resistance (Rint) is an increasingly popular lung function technique and especially suitable for preschool children because it is simple, quick and requires only passive cooperation. A European Respiratory Society (ERS)/American Thoracic Society (ATS) Task Force recently published empirical recommendations related to procedures, limitations and interpretation of the technique. However, for valid interpretation, high-quality reference equations are required and these have been lacking. The aim of the present study was to collate Rint data from healthy children in order to produce more robust reference equations. A further aim was to examine the influence of methodological differences on predicted Rint values. Rint data from healthy children were collected from published and unpublished sources. Reference equations for expiratory and inspiratory Rint were developed using the LMS (lambda, mu, sigma) method. Data from 1,090 children (51% males) aged 3–13 yrs were collated to construct sex-specific reference equations for expiratory Rint and data from 629 children (51% males) were collated for inspiratory Rint. Height was the best independent predictor of both expiratory and inspiratory Rint. Differences between centres were clinically irrelevant, and differences between ethnic groups could not be examined. The availability of a large and generalisable sample and the use of modern statistical techniques enabled the development of more appropriate reference equations for Rint in young children.