Increase of natural killer cells in children with liver transplantation-acquired food allergy

BACKGROUND: Transplantation-acquired food allergies (TAFA) are frequently reported and considered to be caused by immunosuppressive therapy. The aim of this study was to investigate the allergic and immunologic responses in children who had liver or kidney transplantations. METHODS: Twelve children receiving liver transplantations and 10 children receiving kidney transplantations were investigated. All children underwent the allergy work-up and in most of them, lymphocyte screening and serum cytokine measurements were also performed. RESULTS: TAFA were found in 7/12 (58%) children with liver transplantations and in none of the 10 children with kidney transplantations. The mean age at transplantation was significantly lower in children who underwent liver transplantations (p < 0.001). The immunosuppressive therapy administered to children with liver transplantation was tacrolimus in 11 patients and cyclosporine in one patient, while all 10 children with kidney transplantation received tacrolimus plus mycophenolate. The most common antigenic food was egg. The natural killer (NK) cell numbers were significantly higher in liver-transplant children than in kidney-transplant children. No significant differences were found in the serum cytokine levels. CONCLUSIONS: This study confirms that liver-transplant children treated with tacrolimus alone have a higher risk of developing TAFA than kidney-transplant children treated with tacrolimus plus mycophenolate. NK cells might be involved in this difference

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Increase of natural killer cells in children with liver transplantation-acquired food allergy.

BACKGROUND: Transplantation-acquired food allergies (TAFA) are frequently reported and considered to be caused by immunosuppressive therapy. The aim of this study was to investigate the allergic and immunologic responses in children who had liver or kidney transplantations. METHODS: Twelve children receiving liver transplantations and 10 children receiving kidney transplantations were investigated. All children underwent the allergy work-up and in most of them, lymphocyte screening and serum cytokine measurements were also performed. RESULTS: TAFA were found in 7/12 (58%) children with liver transplantations and in none of the 10 children with kidney transplantations. The mean age at transplantation was significantly lower in children who underwent liver transplantations (p<0.001). The immunosuppressive therapy administered to children with liver transplantation was tacrolimus in 11 patients and cyclosporine in one patient, while all 10 children with kidney transplantation received tacrolimus plus mycophenolate. The most common antigenic food was egg. The natural killer (NK) cell numbers were significantly higher in liver-transplant children than in kidney-transplant children. No significant differences were found in the serum cytokine levels. CONCLUSIONS: This study confirms that liver-transplant children treated with tacrolimus alone have a higher risk of developing TAFA than kidney-transplant children treated with tacrolimus plus mycophenolate. NK cells might be involved in this difference.

Anaphylaxis to polyvinylpyrrolidone in eye drops administered to an adolescent

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Azithromycin is more allergenic than clarithromycin in children with suspected hypersensitivity reaction to macrolides.

BACKGROUND: Macrolides are considered safe antibiotics with reduced allergenic activity. However, studies on the safety of macrolides are scarce, particularly in children. OBJECTIVE: The aim of this study was to assess the frequency of hypersensitivity reactions to clarithromycin and azithromycin in a group of children referred to our allergy unit for suspected macrolide allergy. METHODS: We retrospectively reviewed the charts of 90 children aged 1-17 years with symptoms suggestive of hypersensitivity reaction to clarithromycin or azithromycin between December 31, 2008 and December 31, 2013. The allergy workup included skin tests (ie, skin prick tests and/or intradermal tests), determination of serum specific IgE (sIgE) to clarithromycin and azithromycin, and, if necessary to reach a diagnosis, oral provocation tests. RESULTS: Seventy-seven children completed the allergy workup. A reaction to clarithromycin was recorded in 58 children (75.3%): 21 (36.2%) had a history of immediate reactions, and 37 (63.8%) had a history of nonimmediate reactions. A reaction to azithromycin was recorded in 19 children (24.6%): 6 (31.5%) had a history of immediate reaction, and 13 (68.42%) had a history of nonimmediate reaction. Positive results in skin tests and oral provocation tests with the suspect drug confirmed the diagnosis in 15.5% of reactions to clarithromycin (9 of 58) and in 47.3% of reactions to azithromycin (9 of 19) (P = .004). CONCLUSION: A complete allergy workup enabled us to confirm a diagnosis of clarithromycin and azithromycin allergy in 15.5% and 47.3% of cases, respectively. Azithromycin was more allergenic than clarithromycin in children.

Cow's milk allergy and neonatal short bowel syndrome: comorbidity or true association?

BACKGROUND/OBJECTIVES: Neonatal short bowel syndrome (SBS) follows early intestinal resections that may expose the children to increased intestinal contact with undigested food proteins and to the risk of food allergy. We report three consecutive cases of cow's milk allergy (CMA) in SBS infants. SUBJECTS/METHODS: We reviewed three cases of CMA developed in 37 children with neonatal SBS followed up in the last 10 years. The setting of the survey was the Gastroenterology-Hepatology and Nutrition Unit of the Pediatric Hospital 'Bambino Gesù' in Rome. The diagnosis of CMA was based on the oral food challenge and was supported by the results of the skin prick tests (SPT) and/or the specific immunoglobulin (Ig) E. RESULTS: Two patients had persistent liquid stools and periodic episodes of vomiting when they were fed with an intact milk protein-based formula, that disappeared with extensively hydrolyzed formula and amino-acid-based formulae, respectively. The third patient developed maculo-papular rash, flushing and angioedema, when he was introduced a regular formula. The challenge-confirmed CMA in all patients. Positive specific IgE for milk proteins was documented in all the three patients. Two out of the three patients had positive familial history for allergy and positive SPT. CONCLUSIONS: Our findings suggest that the SBS patients require a careful clinical monitoring of the tolerance for the cow's milk proteins, because CMA could be more frequent than expected. A prospective regular assessment for the potential cow milk sensitization by SPT and specific IgE may clarify the nature of the association and support the clinical surveillance. Multicenter studies are required to better evaluate this comorbidity.

Azithromycin is more allergenic than Clarithromycin in children with suspected hypersensitivity reaction to Macrolides

Background: Macrolides are considered safe antibiotics with reduced allergenic activity. However, studies on the safety of macrolides are scarce, particularly in children. Objective: The aim of this study was to assess the frequency of hypersensitivity reactions to clarithromycin and azithromycin in a group of children referred to our allergy unit for suspected macrolide allergy. Methods: We retrospectively reviewed the charts of 90 children aged 1-17 years with symptoms suggestive of hypersensitivity reaction to clarithromycin or azithromycin between December 31, 2008 and December 31, 2013. The allergy workup included skin tests (ie, skin prick tests and/or intradermal tests), determination of serum specific IgE (sIgE) to clarithromycin and azithromycin, and, if necessary to reach a diagnosis, oral provocation tests. Results: Seventy-seven children completed the allergy workup. A reaction to clarithromycin was recorded in 58 children (75.3%): 21 (36.2%) had a history of immediate reactions, and 37 (63.8%) had a history of nonimmediate reactions. A reaction to azithromycin was recorded in 19 children (24.6%): 6 (31.5%) had a history of immediate reaction, and 13 (68.42%) had a history of nonimmediate reaction. Positive results in skin tests and oral provocation tests with the suspect drug confirmed the diagnosis in 15.5% of reactions to clarithromycin (9 of 58) and in 47.3% of reactions to azithromycin (9 of 19) (P=.004). Conclusion: A complete allergy workup enabled us to confirm a diagnosis of clarithromycin and azithromycin allergy in 15.5% and 47.3% of cases, respectively. Azithromycin was more allergenic than clarithromycin in children (AU)

Antecedentes: A los macrólidos se les considera antibióticos seguros, con una reducida capacidad alergénica. Sin embargo, los estudios sobre este tema son insuficientes, especialmente en los niños. Objetivo: El objetivo de este estudio ha sido el evaluar la frecuencia de reacciones hipersensibilidad (HR) a claritromicina (clarithromycin) y a azitromicina (azithromycin) en un grupo de niños, estudiados en nuestra Unidad de Alergia, por sospecha de alergia a los macrólidos. Métodos: Se han estudiado restrospectivamente, 90 niños (de 1-17 años) con síntomas sugestivos de HR a clarithromycin o azithromycin, entre el 31 de diciembre de 2008 y 31 de diciembre de 2013. En el protocolo de estudio se incluyeron la realización de pruebas cutáneas intraepidérmicas (prick, SPT) y/o pruebas intradérmicas (ID)], la determinación de IgE sérica específica (sIgE) a clarithromycin y azithromycin y, si se consideraba necesario para llegar a un diagnóstico, pruebas de provocación oral (OPT). Resultados: Setenta y siete niños completaron el estudio. Cincuenta y ocho (75,3%) referían haber presentado reacciones a clarithromycin: 21 (36,2%) tenían antecedentes de reacciones inmediatas (IR), y 37 (63,8%) tenían antecedentes de reacciones no inmediatas (RIN). Diecinueve de los 77 niños (24,6%) habían presentado una reacción a azithromycin: 6 (31,5%) con una historia de IR y 13 (68,42%) con historia de NIR. Mediante pruebas cutáneas o por positividad en la OPT con el fármaco sospechoso, permitió confirmar el diagnóstico en 15,5% (9 de 58) de los casos de clarithromycin y en 47,3% (9 de 19) de los casos de azithromycin (p= 0,004). Conclusión: Un estudio alergológico completo permitió realizar un correcto diagnóstico de alergia a clarithromycin y azithromycin en 15,5% y 47,3% de los casos, respectivamente. En este trabajo, en niños, la azithromycin fue más alergénica que la clarithromycin (AU)

Azithromycin anaphylaxis in children.

Allergic reactions associated to the use of macrolides are uncommon; in particular only two cases of anaphylaxis with erithromycin and clarithromycin have been reported to date. The aim of this study was to investigate macrolide-induced anaphylaxis. Between December 2007 and December 2011, 136 consecutive children were referred to the Allergy Unit of A. Meyer Children's Hospital because of a past history of reactions to macrolides. Allergy work-ups were carried out according to the European Network for Drug Allergy protocol. Anaphylaxis was diagnosed according to the clinical criteria proposed by Sampson et al. and graded according to Brown SGA et al. Sixty-six out of 136 patients completed the allergologic work-up and among them we investigated three cases of anaphylaxis due to azithromycin which included one child with anaphylaxis to both clarithromycin and azithromycin. In two of the children with anaphylaxis, the diagnosis was only confirmed with the skin prick test, the third was positive to the Intradermal Test. The azithromycin allergy shows a surprisingly high sensitivity to the in-vivo tests. Moreover, this study shows that cross-reactivity may occur between different macrolidic molecules; it has even been suggested that macrolide allergies are unlikely to be class allergies.

Allergy to all mammalian Bovidae proteins but cow's milk in a child

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Usefulness of Atopy Patch Test on a child with milk protein-induced enterocolitis syndrome: a case report.

We describe the case of a child affected by milk-protein induced enterocolitis, in which oral challenge with corn was performed without symptoms after a negative specific Atopy Patch Test. Food protein-induced enterocolitis syndrome (FPIES) is an uncommon nonIgE-mediated gastrointestinal food hypersensitivity of infancy, characterized by severe vomiting and diarrhea arising within 1 to 3 hours after ingestion of the causative food. Little is known about the pathophysiology of FPIES. The absence of food-specific IgE as demonstrated by negative skin prick tests suggests that the disease is not caused by an early onset IgE-mediated reaction. Atopy Patch Test has been described as sensitive and predictive in this syndrome. The hypothesis on the immunological pathogenesis has been discussed on the basis of literature data.

Surgical debridement plus topical cyclosporine A in the treatment of vernal shield ulcers.

Vernal keratoconjunctivitis (VKC) is a severe chronic bilateral inflammation of the ocular surface characterized by seasonal exacerbations. Long-term prognosis is generally good; however, 6% develop sequelae responsible for permanent visual impairment. Corneal involvement is almost always present, consisting of punctate keratitis, shield ulcers (3-11%) and late corneal neovascularization. In recent years, topical cyclosporine A preparations at 2% in oil or at 1% in polyvinyl alcohol, have been successfully proposed for long term VKC treatments. It has been previously proven that medical treatment is not always sufficient, especially when it is employed to treat shield ulcer plaques. In such conditions, surgery may be effective for avoiding long term complications such as amblyopia, strabismus, infections and corneal perforation. In this paper, we show the efficacy of surgical debridement by means of simple scraping associated with topical cyclosporine treatment for the management of vernal shield ulcers complicated with plaques.

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.

CD4+CD25+Foxp3+ T regulatory cells are not involved in oral desensitization.

Oral tolerance has been related to generation of T regulatory cells (Treg) or clonal anergy/deletion, respectively by administering low and high doses of fed antigens. CD4+CD25+ regulatory T cell clones can be induced by the antigen in Peyers patches of animal models. We selected ten subjects (mean age: 89.4 +/- 36.21 months; group A) with severe cows milk allergy. They underwent oral desensitization (OD) according to the current protocols. In six months they reached a tolerance of 50 ml of cows milk. CD4+CD25+Foxp3+ T(reg) blood levels were measured at the beginning of OD (A) and after 6 months (A), but almost the same values were obtained: A = 0.36 +/- 0.11 percent; A prime= 0.59 +/- 0.15 percent. These results were compared with a control group (C) of non-atopic children. Naturally outgrowing cows milk allergy can be related to high blood levels of CD4+CD25+Foxp3+ T(reg), as previously reported in children. On the other hand, a forced oral desensitization through a progressive intake of the antigenic food seems not to be related to an enhancement of CD4+CD25+Foxp3+ T(reg) levels in peripheral blood, making the role of long-lasting systemic immunologic changes unlikely.

Upper airways disease: role of corticosteroids.

Nasal topical steroids (INCSs) are well established effective therapy in allergic rhinitis both in children and adults. There is clear benefit in using INCSs over antihistamines in allergic rhinitis while short courses of oral corticosteroids (CSs) may be indicated in severe cases. The addition of INCSs to oral antibiotics has been proven to be more effective than antibiotics alone for achieving symptomatic improvement in patients with acute rhino sinusitis. INCSs as monotherapy are also effective in the treatment of allergic rhinosinusitis (ARS). Several randomized controlled trials have evaluated the role of INCSs in chronic RS with the majority demonstrating a beneficial effect. In adults, the clinical efficacy of oral corticosteroids in the management of chronic RS with nasal polyposis is well established. There are no randomized controlled trials evaluating the efficacy of systemic CSs in chronic RS without nasal polyposis.

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 gamma (IFN-gamma) 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-gamma 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.