A. Cianferoni

Efficacy and safety of cyclosporine eyedrops in vernal keratoconjunctivitis

BACKGROUNDnCorticosteroids 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.nnnOBJECTIVEnThis study sought to evaluate the efficacy and safety of ocular administration of cyclosporine in VKC.nnnMETHODSnTwenty-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.nnnRESULTSnCompared 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.nnnCONCLUSIONSnCyclosporine 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)

BACKGROUNDnAlthough 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.nnnOBJECTIVEnTo describe in a nonselected population the clinical characteristics and the treatments of acute anaphylaxis triggered by different agents.nnnMETHODSnThis 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.nnnRESULTSnMost 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.nnnCONCLUSIONSnAnaphylaxis 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.

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 (Pu2003=u20030.0026). 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

PURPOSEnWe determined the prevalence of and risk factors for latex sensitization in patients with spina bifida.nnnMATERIALS AND METHODSnA 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.nnnRESULTSnLatex 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.nnnCONCLUSIONSnA 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.

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

BACKGROUNDnLittle 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.nnnOBJECTIVEnTo undertake a follow-up study of these children to ascertain how many experienced a recurrence of anaphylaxis.nnnMETHODSnAfter a mean interval of 7 years, a pediatric allergist conducted a telephone interview of patients who had been enrolled in our 1994-1996 study.nnnRESULTSnA 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).nnnCONCLUSIONSnThis 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.

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.

Cross-reactivity between IgE-binding proteins from Anisakis simplex and Dermatophagoides pteronyssinus.

An association was found between Anisakis simplex (As) and Dermatophagoides pteronyssinus (Dp) sensitization. One recent study shows a cross-reactivity between As and Dp and tropomyosin (tr) is suspected as being one of the proteins responsible of this cross-reaction. The aim of our study was: 1) to confirm the cross-reactivity between Dp and As; 2) to determine the importance of tr in this cross reaction. SDS-PAGE analysis of Dp and As (metabolic and somatic) extracts was carried out. Then an IgE immunoblotting test using serum from a patient who had specific IgE only to Dp and As and immunoblotting inhibition experiments using Dp extract and tr as inhibitors were performed. We found that patients serum reacted: 1) against larval As antigens with a molecular weight (mw) of 25 kilodalton (kD) and a mw > 100 kD, 2) against various metabolic As antigens with a mw > 100 kD, a mw ranging approximately from 35 to 50 kD, and a mw around 20 kD, and 3) against Dp proteins with mw between 35 and 55 kD. Preincubation of patients serum with Dp extract caused the disappearance of reactivity against antigens with a mw > 100 kD in both larval and metabolic As extracts and against proteins with mw ranging approximately from 35 to 50 kD in the metabolic As extract. Preincubation of patients serum with As extract caused the disappearance of reactivity against antigens with mw between 35 and 55 kD in the Dp extract. Pre-incubation of patients serum with tr did not induce any change in the immunoblotting profile. The results show that 1) cross-reactive components between Dp and As are some proteins with a mw ranging approximately from 35 to 50 kD and with a mw > 100 kD, and 2) tr is not involved in cross-reactivity between As and Dp.

High intracytoplasmatic levels of Il-4 and Il-5 in a patient with Gleichs syndrome: case report.

Gleichs syndrome is characterized by recurrent localized angioedema, hypereosinophilia, elevated levels of IgM, rapid weight gain, itchy urticaria and fever. Little is known about the pathogenesis of this disease. Increased serum levels for IL5, IL6 and C5a have been reported before and during clinical exacerbations. In order to better understand the role of the T cells in Gleichs syndrome we analyzed the intracellular cytokine expression in CD3+ cells of a patient affected by the disease. As hypereosinophilia was documented, we asked whether IL-4 and IL-5 levels were increased, and the intracytoplasmatic expression of these Th2-cytokines was determined. The percentage of T lymphocytes (CD3-gated cells) of both CD8− and CD8+ phenotype expressing different cytokines showed an unusually high percentage of Th2-related cytokine (IL-4, IL-5 and IL-13) expressing T lymphocytes. The two new variants (myeloproliferative and lymphoproliferative) seem to account for hypereosinophilia in patients with hypereosinophilic syndrome (HES). In the lymphroliferative variant, the presence of a clonal CD3-CD4+ Th2 like lymphocyte secreting IL-4 and IL-5 in peripheral blood, may explain the hypereosinophilia and the hyper-IgE. In our study we show that the patient had a lymphoproliferative variant and her T cell had a Th2 type phenotype. Moreover, we suggest that Th2 lymphocytes may play a role in the pathogenesis of Gleichs syndrome. Further studies are needed to evaluate the possibility that a polyclonal aspecific activation of Th2 type cells can lead to hypereosinophilia, IgE production and the other manifestations typical of Gleichs syndrome.