Neri Pucci

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.

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.

Risk factors for severe pediatric food anaphylaxis in Italy.

To cite this article: Calvani M, Cardinale F, Martelli A, Muraro A, Pucci N, Savino F, Zappalà D, Panetta V, the Italian Society of Pediatric Allergy and Immunology (SIAIP) anaphylaxis’ study group. Risk factors for severe pediatric food anaphylaxis in Italy. Pediatr Allergy Immunol 2011: 22: 813–819.

Scoring atopic dermatitis in infants and young children: distinctive features of the SCORAD index

Background:  Atopic dermatitis (AD) affects infants, children, and adults with a wide degree of severity; several scoring systems have been used in trials and clinical practice. Infants and young children have a typical distribution of the lesions, but a correlation among skin surface involvement, intensity and subjective symptoms has not been reported in age groups.

Anaphylaxis: a 7-year follow-up survey of 46 children

BACKGROUND Little is known about the frequency of and the features associated with recurrent anaphylaxis in pediatric populations. During 1994 to 1996, we enrolled 76 children affected by anaphylaxis in a prospective study to analyze their clinical and allergic features. OBJECTIVE To undertake a follow-up study of these children to ascertain how many experienced a recurrence of anaphylaxis. METHODS After a mean interval of 7 years, a pediatric allergist conducted a telephone interview of patients who had been enrolled in our 1994-1996 study. RESULTS A telephone interview was successfully completed in 46 (61%) of the 76 patients who had been enrolled in our 1994-1996 study. Of these 46 patients, 14 (30%) had experienced a recurrence of anaphylaxis. Children with atopic dermatitis either during 1994 to 1996 (64% vs 34%; P = .04) or at the time of the current study (43% vs 16%; P = .03) and those with urticaria-angioedema at the time of the current study (93% vs 31%; P = .0002) were found to be at a significantly higher risk for recurrent anaphylaxis. Furthermore, those children who were sensitive to at least 1 food allergen during 1994 to 1996 were more likely to have experienced a recurrence of anaphylaxis (93% vs 56%; P < .04). CONCLUSIONS This study suggests that patients may have a greater risk of recurrence of anaphylaxis if they have atopic dermatitis, urticaria-angioedema, or at least 1 positive result of skin prick tests to food allergens.

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.

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<.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.

Cytokine Expression in CD3+ Cells in an Infant with Food Protein-Induced Enterocolitis Syndrome (FPIES): Case Report

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by severe vomiting, diarrhea, and often failure to thrive in infants. Symptoms typically resolve after the triggering food-derived protein is removed from the diet and recur within few hours after the re-exposure to the causal protein. The diagnosis is based on clinical symptoms and a positive food challenge. In this study, we report a case of FPIES to rice in an 8-month-old boy. We performed a double-blind placebo-controlled food challenge (DBPCFC) to rice and we measured the intracellular T cell expression of interleukin-4 (IL-4); IL-10, and interferon γ (IFN-γ) pre-and post-challenge during an acute FPIES reaction and when tolerance to rice had been achieved. For the first time we describe an increase in T cell IL-4 and decrease in IFN-γ expression after a positive challenge with rice (i.e. rice triggered a FPIES attack) and an increase in T cell IL-10 expression after rice challenge 6 months later after a negative challenge (i.e., the child had acquired tolerance to rice) in an 8 month old with documented FPIES to rice. A Th2 activation associated with high IL-4 levels may contribute to the pathophysiology of the disease. On the other hand, T cell-derived IL-10 may play a role in the acquisition of immunotolerance by regulating the Th1 and Th2 responses.