M. Minelli

Post‐marketing survey on the safety of sublingual immunotherapy in children below the age of 5 years

Background The age below 5 years is considered a prudential limit for immunotherapy in view of the possible severity of side‐effects. Sublingual immunotherapy (SLIT) seems to be safe, but no study in very young children is available. We performed a safety post‐marketing surveillance study in children below 5 years.

Oral hyposensitization to nickel induces clinical improvement and a decrease in TH1 and TH2 cytokines in patients with systemic nickel allergy syndrome.

Some patients with nickel (Ni) allergic contact dermatitis suffer from systemic (intestinal or cutaneous) symptoms after ingestion of Ni-rich foods and experience symptoms reduction with low-Ni diet, a condition termed “systemic Ni allergy syndrome” (SNAS). We aimed at evaluating whether oral administration of low nickel doses improved clinical conditions and modulated immunological aspects of SNAS, without significant side effects. Thirty-six SNAS patients were enrolled. Treatment started after 1-month of low-Ni diet and consisted in an incremental oral NiOH dose phase (0.3ng to 1.5 μg/week) followed by a 12-months maintenance phase (1.5 μg/week). Randomly, twenty-four patients added Ni therapy to low-Ni diet and 12 remained with diet alone. All patients were allowed rescue medications (antihistamines and topical steroids). After 4 months, Ni-rich foods were gradually reintroduced. In vitro allergen-driven IL13, IL5 and IFNγ release by peripheral blood mononuclear cells was evaluated before and after treatment. Twenty-three patients receiving NiOH and the 12 control patients completed the study. Evaluation of SNAS clinical severity (by VAS and drug consumption) showed a significant difference in favor of NiOH-treated patients compared to controls. Twenty of 23 patients in the NiOH group and none in the control group tolerated Ni-rich food reintroduction. Release of all studied cytokines in culture supernatants was significantly lower after NiOH treatment. In conclusion NiOH is effective in reducing symptoms and drug consumption in SNAS and is able to modulate inflammatory parameters.

Nickel oral hyposensitization in patients with systemic nickel allergy syndrome

Abstract Background: This is the first randomized, double-blind, placebo-controlled trial (EUDRACT No. 2009-013923-43) evaluating nickel oral hyposensitizing treatment (NiOHT) in patients with “systemic nickel allergy syndrome” (SNAS), characterized by Ni-allergic contact dermatitis and systemic reactions after eating Ni-rich food. Methods: Adults with positive Ni-patch test, who reported symptoms suggesting SNAS, which improved after Ni-poor diet, and were positive to Ni-oral challenge were eligible. Patients were randomly assigned to three treatments (1.5 μg, 0.3 μg, or 30 ng Ni/week) or placebo for a year, with progressive reintroduction of Ni-rich foods form the 5th month. Out of 141 patients randomized, 113 completed the trial. Endpoints were efficacy and tolerability of treatment. Results: During Ni-rich food re-introduction, the 1.5 μg Ni/week group had a mean VAS score significantly higher than placebo (p = 0.044), with significant improvement of gastrointestinal symptoms (p = 0.016;) and significantly fewer rescue medications. Cutaneous manifestations also improved but without reaching statistical significance. After the treatment, oral challenge with higher Ni doses than at baseline were needed to cause symptoms to flare-up in significantly more patients given 1.5 μg Ni/week than placebo (p = 0.05). Patients reported no side-effects. Conclusions: NiOHT is effective in SNAS, in particular on gastrointestinal manifestations, with trend toward improvement of cutaneous symptoms.

Lactose intolerance in systemic nickel allergy syndrome.

Some patients affected by nickel-contact allergy present digestive symptoms in addition to systemic cutaneous manifestations, falling under the condition known as Systemic Nickel Allergy Syndrome (SNAS). A nickel-related pro-inflammatory status has been documented at intestinal mucosal level. The aim of the present study is to evaluate the prevalence of lactose intolerance in patients affected by SNAS compared to a healthy population. Consecutive patients affected by SNAS referring to our departments were enrolled. The control population consisted of healthy subjects without gastrointestinal symptoms. All subjects enrolled underwent lactose breath test under standard conditions. One hundred and seventy-eight SNAS patients and 60 healthy controls were enrolled. Positivity of lactose breath test occurred in 74.7% of the SNAS group compared to 6.6% of the control group. Lactose intolerance is highly prevalent in our series of patients affected by SNAS. Based on our preliminary results, we can hypothesize that in SNAS patients, the Nickel-induced pro-inflammatory status could temporarily impair the brush border enzymatic functions, resulting in hypolactasia. Further trials evaluating the effect of a nickel-low diet regimen on lactase activity, histological features and immunological pattern are needed.

Intermittent and Persistent Allergic Rhinitis and Association with Asthma in Children

The natural history of allergic rhinitis (AR) is commonly characterized by worsening of symptom severity, frequent comorbidity with asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts in early childhood. AR classification has been recently revised, and some studies investigated the new types: intermittent (IAR) and persistent (PER) AR. However, no study has been carried out on children regarding this issue. This preliminary study was performed on a large cohort of children with allergic rhinitis to evaluate the type and severity of rhinitis and its possible association with asthma, including severity grade. One hundred and thirty-nine children (86 males, 53 females, mean age 11.8 years, range 3.5–17.7 years) with allergic rhinitis were prospectively and consecutively evaluated. Seventy-one children had rhinitis alone and 68 had rhinitis associated with asthma. Forty children had IAR, 30 of whom with moderate-severe grade. Ninety-nine children had PER, 65 of whom had moderate-severe grade. The severity of AR was not associated with asthma presence (Fisher χ2 = 0.5765; Prob.=0.9018). Regarding asthma severity, 30 children had the intermittent form, whereas 38 had the persistent form: 15 mild, 22 moderate, and 1 severe. This study provides the first evidence concerning the ARIA classification in children, partially confirming findings obtained in adulthood.