D. Vita

Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study.

BACKGROUND Cows milk allergy (CMA) in children is a important problem in medical practice. Oral desensitization has been proposed as a therapeutic approach, but current protocols are time-consuming and impractical. OBJECTIVES To establish a patient-friendly desensitization regimen with weekly up-dosing and to evaluate it in a randomized controlled trial. METHODS Thirty children with IgE-mediated CMA confirmed by double-blind placebo-controlled food challenge were equally randomized to desensitization with CM or soy milk as control. The weekly up-dosing lasted 18 weeks. The occurrence and severity of reactions after each dose was evaluated, and the desensitization was stopped if severe reactions occurred. Specific IgE and IgG4 levels to CM were measured at baseline, after 8 weeks, and at the end of the study. The double-blind food challenge was repeated once the desensitization was completed or after premature discontinuation. RESULTS Two active and 1 control patient dropped out. Full tolerance to CM (200 mL) was achieved in 10 active patients and partial tolerance in 1. Two active patients discontinued the desensitization after experiencing severe reactions, whereas no reactions occurred in controls, whose sensitivity to CM remained unchanged. A significant increase in specific IgG4 levels was found only in the active group. CONCLUSIONS This weekly up-dosing desensitization protocol for CMA performed under medical supervision was effective and reasonably safe and induced consistent immunologic changes.

Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in children allergic to Parietaria pollen treated with inhaled fluticasone propionate.

Background Immunotherapy is a recognized treatment for allergic respiratory diseases.

Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria-induced respiratory allergy: a randomized controlled trial†

Background:  The use of immunotherapy in asthmatic children is still controversial. Sublingual immunotherapy (SLIT) may represent an advance, due to the good safety profile, but little is known about its effects on lung function and nonspecific bronchial responsiveness.

A new protocol for specific oral tolerance induction in children with IgE-mediated cow's milk allergy.

IgE-mediated cows milk allergy (CMA) is a heavy burden for patients, particularly for children and their families. Allergen avoidance represents the only therapeutic option, but oral desensitization protocols have been suggested. Because of the long duration and complexity of these protocols we examined the feasibility of an oral tolerance induction protocol using a weekly up-dosing schedule. Children with IgE-mediated food allergy to milk, confirmed by a double-blind placebo-controlled food challenge, were recruited. Six of them were randomized to double-blind desensitization with milk or soy formula as placebo. Seven patients underwent the protocol in open fashion. The desensitization schedule started with one drop of whole CM diluted 1:25 every week. The dose was doubled weekly until the 18th week to achieve an intake of 200 mL in approximately 4 months. Of the 13 children enrolled, 10 children received CM and 3 control children received soy formula. Full tolerance (200 mL of milk) was achieved in 7 children; in 2 children this therapeutic approach failed, because severe reactions occurred during the procedure. One patient achieved a partial tolerance (64 mL of milk). The three control children receiving placebo still showed a positive food challenge at the end of the study. A weekly up-dosing oral tolerance induction could be a viable alternative to traditional protocols for children with IgE-mediated CMA.

Sublingual immunotherapy: adherence based on timing and monitoring control visits.

Allergen Specific Immunotherapy is the only causal treatment that is recognized as effective and as offering long-lasting results (1). In childhood, immunotherapy has been shown to prevent the appearance of new sensitizations in patients monosensitized to house dust mites (2). Subcutaneous immunotherapy (SCIT) has been long considered the only way of giving this treatment, but more recently, the sublingual immunotherapy (SLIT) represents other viable treatment options (3). However, immunotherapy in any form requires commitment by the patient, which makes adherence (or compliance) issues particularly relevant. Currently, the studies on adherence for SLIT show quite high compliance rate(s) from 60% to 90% of patients even if long-term surveillance was carried out (4–6). On the other hand, in real life, a commonsense approach and unpublished data on sales of allergy companies suggest that the SLIT adherence is quite low. This study aimed to investigate prospectively the adherence to treatment for three different methods of timing and monitoring SLIT by collection data on the drop-out rate among 300 children aged 6–16 years who had allergic rhinitis, allergic asthma or both for at least 1 year and were prescribed immunotherapy for only one allergen or homogeneous group of allergens (i.e. Grasses or Mites). All the randomly selected patients were divided into three groups according the timing of clinical visits used. They were in charge by three research doctors during the 2-year follow-up of the survey. Group A consisted of 100 patients who underwent a timing control visit of four times per year; group B consisted of 100 patients who underwent a timing control visit of two time per year; group C consisted of 100 patients who underwent only one clinical visit per year. The entire programme of allergen immunotherapy in its different timing forms was conducted from 2004 to 2008 under controlled conditions in our hospital setting. All children were from Sicily; they received a total reimbursement by the local government health service to buy the vaccines. The extracts used for SLIT were from Stallergenes (Antony – France: Staloral), from Lofarma (Milan – Italy: Lais) from AlkAbello (Horsholm – Denmark: SLITOne) and Allergopharma (Hamburg – Germany: Sublingual Allergopharma). Immunotherapy was performed according the schedules suggested by the manufacturers. A control visit was scheduled at 3-months interval for the group A, at 6-months interval for the group B, and one time per year for the Group C. At each visit, the doctor attending each patient collected the specifically designed charts filled in during the preceding months and registered the time of every interruption. The children who stopped immunotherapy before the planned period of 2 years were considered noncompliant. The percentage of noncompliant individuals was significantly higher in group C (70.4%) compared with group B (32.3% v = 19.82, P < 0.005) and group A (18.5% v = 23.94, P < 0.0005). The percentage of non complaints individuals in group A was also significantly lower in comparison with that in group B (v = 21.1, P<0.05). Timing of treatment withdrawal in three groups during the overall 2-year period is illustrated in Fig. 1. The patients had been treated in real life with the prescriptions of drops or tablets and are required to take with them vials or tablets and showing them to doctors in charge for the study at each control. Adequate adherence with SLIT was reached only in patients called for visits four times per year (group A); the children of other two groups showed a lower adherence: 32.3% (group B) and 70.4% (group C) abandoned allergenspecific immunotherapy. Due to the fact that sublingual immunotherapy (SLIT) is a long lasting treatment, the adherence for SLIT is a pivotal issue in order to achieve an adequate improvement of patients with IgE mediated disorders.

Ass's milk in children with atopic dermatitis and cow's milk allergy: Crossover comparison with goat's milk

Cow milk allergy is a common disease of infancy, often associated with atopic dermatitis (AD). Avoidance of cow milk (CM) implies the use of alternative dietary supports such as mammalian milks. In this study, we assessed the tolerability and clinical effect of asss milk (AM), when compared with the largely used goats milk (GM) in a single‐blind, controlled, randomized crossover. Twenty‐eight children with AD and ascertained allergy to CM were enrolled. The children were randomized to AM or GM for 6 months, then switched to the other milk for further 3 months. The SCORAD index (SI) and a visual analog scale (VAS) were evaluated blindly. After termination of the study, food challenges with GM and AM were performed. An SDS‐PAGE analysis of different milks was performed. Two children from the GM group dropped out after randomization and 26 completed the study. Ass milk invariantly led to a significant improvement of SI and VAS of symptoms (p < 0.03 vs. baseline and inter‐group), whereas GM had no measurable clinical effect. At the end of the study 23 of 26 children had a positive food challenge with GM and one of 26 with AM. Asss milk had a protein profile closer to human milk than GM. Ass milk is better tolerated and more effective than GM in reducing symptoms of AD. It may represent a better substitute of CM than the currently used GM.

Safety of Sublingual Immunotherapy in Children with Asthma

AbstractIntroduction: Two previously published studies on sublingual immunotherapy (SLIT) did not report any serious adverse event associated with the local therapy; however, adverse events were observed in greatly variable percentages. The aim of the study was to evaluate the tolerability profile of sublingual swallow and spit immunotherapy in a large number of children treated for allergic asthma. Methods: Adverse effects related to sublingual administration of allergen vaccines were evaluated in 354 children with allergic asthma. Each patient was followed for at least 37 months and received a monthly dose of major allergens (extract) in the range of 1.5–14.8μg, equivalent to 3–20 times the amount contained in the usual monthly maintenance injections via the subcutaneous routes. Results: No adverse event was observed in 90.4% of the children. We observed 0.155 mild to moderate reactions per 1000 administrations. Dosage adjustment was required in 15 patients. In five children, immunotherapy was stopped as a precaution – one patient developed rhino-conjunctivitis, two patients developed urticaria, and two children developed wheezing. None of the reactions were due to dosage errors. No anaphylactic reaction or multiple-organ life-threatening events occurred. Conclusions: The results of our study showed an incidence of mild to moderate unwanted effects of 9.6%, lower than that previously reported, and no life-threatening adverse effects. Nevertheless, asthma, urticaria, and rhinoconjunctivitis can occur. SLIT is quite a safe therapy for the treatment of allergic children with asthma; however, careful evaluation of the single patient is necessary since SLIT is self-administered and a cumulative monthly dose higher than that normally administered as an injection is usually attainable.

Chronic urticaria and associated coeliac disease in children: A case–control study

Celiac disease (CD) and chronic urticaria (CU) are both sustained by immune mechanisms, but there are so far few data on their clinical association. We performed a case–control study to determine the occurrence of CD in urticaria and matched control children, and to assess the clinical relevance of this association. Children and adolescents were diagnosed to have severe chronic idiopathic urticaria in the presence of hives for more than 6 wk poorly or not responsive to oral antihistamines. Other known causes of urticaria had to be excluded. A matched control group without urticaria was enrolled. In both groups, the presence of CD was searched by assaying antitransglutaminase and antiedomysial antibodies, and confirmed with endoscopic intestinal biopsy. Results. CD was diagnosed and confirmed in 4/79 (5.0%) of children with CU and in 17/2545 (0.67%) of the controls (p = 0.0003). In the four children with urticaria and CD the gluten free diet (GFD) lead to complete remission of urticaria within 5–10 wk, whereas the disappearance of serological markers occurred in longer times (5–9 months). Conclusions. The presence of CD in children with CU was significantly more frequent than in controls. GFD resulted in urticaria remission. CD may be regarded in such subjects as a cause of CU.

Direct comparison between continuous and coseasonal regimen for sublingual immunotherapy in children with grass allergy: a randomized controlled study.

To cite this article: Pajno GB, Caminiti L, Crisafulli G, Vita D, Valenzise M, De Luca R, Passalacqua G. Direct comparison between continuous and coseasonal regimen for sublingual immunotherapy in children with grass allergy: A randomized controlled study. Pediatr Allergy Immunol 2011: 22: 803–807.

Food-exercise-induced anaphylaxis in a boy successfully desensitized to cow milk.

References 1. Bailie GR, Clark JA, Lane CE, Lane PL. Hypersensitivity reactions and deaths associated with intravenous iron preparations. Nephrol Dial Transplant 2005;20:1443–1449. Epub 2005, April 26. 2. Coors EA, Seybold H, Merk HF, Mahler V. Polysorbate 80 in medical products and nonimmunologic anaphylactoid reactions. Ann Allergy Asthma Immunol 2005;95: 593–599. 3. Hegde VL, Venkatesh YP. Anaphylaxis to excipient mannitol: evidence for an immunoglobulin E-mediated mechanism. Clin Exp Allergy 2004;34:1602–1609. 4. Betts CJ, Dearman RJ, Kimber I, Maibach HI. Potency and risk assessment of a skinsensitizing disperse dye using the local lymph node assay. Contact Dermatitis 2005;52:268–272. 5. Goon AT, Gilmour NJ, Basketter DA, White IR, Rycroft RJ, McFadden JP. High frequency of simultaneous sensitivity to Disperse Orange 3 in patients with positive patch test to para-phenylenediamine. Contact Dermatitis 2003;48:248–250. 6. Picardo M, Cannostraci C, Cristaudo A, De Luca C, Santucci B. Study on cross reactivity to the para group. Dermatologica 1990;181:104–108. 7. Chung KT, Stevens SE, Cerniglia CE. The reduction of azo dyes by the intestinal microflora. Crit Rev Microbiol 1992;18:175–190. Food-exercise-induced anaphylaxis in a boy successfully desensitized to cow milk