Sandra Lucarelli

Immunomodulation during sublingual therapy in allergic children.

The clinical efficacy of sublingual immunotherapy (SLIT) has been demonstrated, but its mechanism of action is still controversial. The most recent experimental observations suggest that a critical role in the modulation of immune response is sustained by Th2 cytokines, such as interleukin‐4 (IL‐4), IL‐5 and IL‐13, by co‐stimulatory molecules, such as CD40 on B cells, and by hormones and neuropeptides. To better understand whether SLIT affects immune responses we used a double‐blind placebo‐controlled design. Eighty‐six children with mild asthma due to allergy to Dermatophagoides pteronyssinus (33 of whom also had rhinoconjunctivitis) were randomly assigned SLIT (n = 47) or placebo (n = 39). We assessed symptom scores using diary cards of each patient and determined the expression of CD40 on B cells and the serum concentration of ECP, IL‐13, prolactin (PRL) and ACTH at enrolment and after 6 months of therapy. We observed a significant reduction in asthma and rhinitis scores in the immunotherapy group compared with the placebo group, no variation in CD40 and ACTH, but a significant decrease in ECP, IL‐13 and PRL after 6 months of therapy (p <0.01). Our results confirm the efficacy and safety of SLIT, and lead us to believe that it could modulate the synthesis of Th2 cytokines, as revealed from the decrease of IL‐13. In addition, the reduction of PRL might be a signal of reduced activation of T lymphocytes.

The effect of component-resolved diagnosis on specific immunotherapy prescription in children with hay fever

BACKGROUND Sensitization to profilins and other cross-reacting molecules might hinder proper specific immunotherapy (SIT) prescription in polysensitized patients with pollen-related allergic rhinitis (AR). In these patients, component-resolved diagnosis (CRD) might modify SIT prescription by improving the identification of the disease-eliciting pollen sources. OBJECTIVES We sought to measure the effect of CRD on SIT prescription in children with pollen-related AR. METHODS Children (n = 651) with moderate-to-severe pollen-related AR were recruited between May 2009 and June 2011 in 16 Italian outpatient clinics. Skin prick test (SPT) reactivity to grass, cypress, olive, mugwort, pellitory, and/or Betulaceae pollen was considered clinically relevant if symptoms occurred during the corresponding peak pollen season. IgE sensitization to Phl p 1, Phl p 5, Bet v 1, Cup a 1, Art v 1, Ole e 1, Par j 2, and Phl p 12 (profilin) was measured by using ImmunoCAP. SIT prescription was modeled on SPT responses first and then remodeled considering also CRD according to GA(2)LEN-European Academy of Allergology and Clinical Immunology guidelines and the opinions of 14 pediatric allergists. RESULTS No IgE to the respective major allergens was detected in significant proportions of patients with supposed clinically relevant sensitization to mugwort (45/65 [69%]), Betulaceae (146/252 [60%]), pellitory (78/257 [30%]), olive (111/390 [28%]), cypress (28/184 [15%]), and grass (56/568 [10%]). IgE to profilins, polcalcins, or both could justify 173 (37%) of 464 of these SPT reactions. After CRD, the SPT-based decision on SIT prescription or composition was changed in 277 (42%) of 651 or 315 (48%) of 651 children according to the European or American approach, respectively, and in 305 (47%) of 651 children according to the opinion of the 14 local pediatric allergists. CONCLUSIONS In children with pollen-related AR, applying CRD leads to changes in a large proportion of SIT prescriptions as opposed to relying on clinical history and SPT alone. The hypothesis that CRD-guided prescription improves SIT efficacy deserves to be tested.

Pollen-induced allergic rhinitis in 1360 Italian children: comorbidities and determinants of severity.

Pollen‐induced allergic rhinoconjunctivitis (AR) is highly prevalent and rapidly evolving during childhood. General practitioners may not be fully aware of the nature and severity of symptoms experienced by patients and might underestimate the prevalence of moderate or severe disease. Thus, the relevance of early diagnosis and intervention may be overlooked.

Allergic proctocolitis refractory to maternal hypoallergenic diet in exclusively breast-fed infants: a clinical observation.

BackgroundAllergic proctocolitis (APC) in exclusively breast-fed infants is caused by food proteins, deriving from maternal diet, transferred through lactation. In most cases a maternal cow milk-free diet leads to a prompt resolution of rectal bleeding, while in some patients a multiple food allergy can occur. The aim of this study was to assess whether the atopy patch test (APT) could be helpful to identify this subgroup of patients requiring to discontinue breast-feeding due to polisensitization. Additionally, we assessed the efficacy of an amino acid-based formula (AAF) when multiple food allergy is suspected. amino acid-based formulaMethodsWe have prospectively enrolled 14 exclusively breast-fed infants with APC refractory to maternal allergen avoidance. The diagnosis was confirmed by endoscopy with biopsies. Skin prick tests and serum specific IgE for common foods, together with APTs for common foods plus breast milk, were performed. After a 1 month therapy of an AAF all patients underwent a follow-up rectosigmoidoscopy.ResultsPrick tests and serum specific IgE were negative. APTs were positive in 100% infants, with a multiple positivity in 50%. Sensitization was found for breast milk in 100%, cows milk (50%), soy (28%), egg (21%), rice (14%), wheat (7%). Follow-up rectosigmoidoscopy confirmed the remission of APC in all infants.ConclusionsThese data suggest that APT might become a useful tool to identify subgroups of infants with multiple gastrointestinal food allergy involving a delayed immunogenic mechanism, with the aim to avoid unnecessary maternal dietary restrictions before discontinuing breast-feeding.

Neuroimmune Interaction and Anorectal Motility in Children With Food Allergy-Related Chronic Constipation

OBJECTIVES:Food allergy is thought to trigger functional constipation in children but the underlying mechanisms are still unknown. Mast cells (MCs) and their relationship with nerve fibers (NFs) in the rectal mucosa, as well as anorectal motility, were studied in children with refractory chronic constipation before and after an elimination diet for cows milk, egg, and soy proteins.METHODS:Thirty-three children (range: 1–10.8 years) underwent anorectal manometry and suction rectal biopsy before and after 8 weeks of oligoantigenic diet. MCs and NFs were identified immunohistochemically. Quantification of MCs (%MC/area) and MCs within 10 μm of NFs (%MC-NF/area) was performed by computer-assisted analysis.RESULTS:Eighteen children responded to the diet (R-group) and fifteen did not (the NR-group). At baseline there was a significant difference in anal resting pressure (ARP; mm Hg), percentage of relaxation (%R), and residual pressure (RP; mm Hg) of anal canal during rectal distension between the R-group (66±4.1, 84.3±2.8, 10.4±2.3, respectively) and the NR-group (49±5, 92.2±1.7, 4.8±1.7, respectively; P<0.05). After the diet, significant changes in ARP, RP, and %R were observed only in the R-group (44±3.7, 93.7±1.5, 3.8±1.2, respectively; P<0.05). At baseline, the R-group showed an increase in %MC/area (8.3±0.7) and %MC-NF/area (5.2±2.6) with respect to the NR-group (5.1±0.5 and 2.3±0.4, respectively; P<0.05). After the diet, only the R-group showed a significant reduction of %MC/area and %MC-NF/area (4.4±0.5 and 2.2±0.4, respectively; P<0.001). Both ARP and RP significantly correlated with %MC/area and %MC-NF/area; %R showed a significant inverse correlation with both %MC/area and %MC-NF/area.CONCLUSIONS:In children with food allergy-related chronic constipation, an increase in both rectal MC density and spatial interactions between MCs and NFs correlates with anal motor abnormalities. These variables are significantly affected by the diet.

Helicobacter pylori seropositivity in children with atopic dermatitis as sole manifestation of food allergy

A positive association between Helicobacter pylori antibodies and food allergy presenting with gastrointestinal symptoms has recently been reported. A subset of a H. pylori strain possesses an antigen, CagA, as a virulence factor. Anti‐H. pylori and anti‐CagA IgG titre have been determined in children with atopic dermatitis (AD) as the sole clinical manifestation of food allergy. In this study, thirty patients with AD as the sole clinical manifestation of food allergy were examined (group A). For comparative purposes, 30 patients affected by food allergy with gastrointestinal symptoms (group B) and 30 affected by atopic asthma (group C) were studied. Anti‐H. pylori and anti‐CagA immunoglobulin G (IgG) were determined in all individuals by means of the enzyme‐linked immunosorbent assay. The anti‐H. pylori IgG titre was significantly higher in group A and group B vs. group C (p < 0.05); no significant difference was detected between group A and group B (p > 0.05). No significant difference in anti‐CagA titre was found between the groups. These data demonstrate a positive association between H. pylori antibodies and AD as the sole manifestation of food allergy. Further investigations are needed to evaluate the cause–effect relationship between H. pylori seropositivity and AD.

Cyclic vomiting syndrome and food allergy/intolerance in seven children: a possible association

Abstract Cyclic vomiting syndrome (CVS) is characterized by repeated unpredictable, explosive and unexplained bouts of vomiting. The episodes have a rapid onset, persist over a number of hours or days, and are separated by symptom-free intervals. Despite the recent interest in this disorder, its aetiology, pathogenesis and even its target organ remain unknown. The purpose of this study is to investigate the role played by food allergy in CVS. The report concerns eight children (five male, three female), mean age 8 years (3–13 years), suffering from CVS for 2 years at least. The diagnosis of CVS was based on characteristic history, normal physical examination and negative laboratory, radiographic, neurological and endoscopic studies. Despite the absence of clinical signs typical of food allergy, skin prick tests were positive in six of the eight patients (75%). Specific IgE were present in 4/8 (50%) of the patients. Skin tests and specific IgE were positive for cows milk proteins, egg white and soya. IgE levels were higher than the mean + 2SD in 5/8 (63%) of the patients. A double blind placebo controlled food challenge (DBPCFC) was carried out on seven of the eight patients who displayed clinical improvement after an elimination diet for cows milk (and other foodstuffs indicated by positive skin tests). The DBPCFC was positive in all seven children. Clinical follow-up revealed a state of well-being over the 6 months of observation. Conclusion It appears reasonable to suggest that food allergy plays a role in cyclic vomiting syndrome.

Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification.

Pollen‐food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens.

Psychological stress affects response to sublingual immunotherapy in asthmatic children allergic to house dust mite

While the clinical and immunologic efficacy of sublingual immunotherapy (SLIT) in allergic diseases has been extensively demonstrated, some patients display a poor clinical response. Psychological stress has been shown to play a role in atopy and also to affect response to immunomodulating therapies such as vaccination with microbial antigens. This study addresses the possibility of response to SLIT being affected by psychological stress. Forty children with mild asthma caused by allergy to Dermatophagoides pteronyssinus and farinae were subjected to SLIT and then divided after 6 months into two groups based on the results of the stress integrated measure (SIM) test: group 1 (24 stressed patients, mean SIM value of 60.1) and group 2 (16 non‐stressed patients, mean SIM value of 7.6). There was also a higher prevalence of psychosocial stressing factors (divorced/absent parents, low income households, non‐working parents) among stressed patients. The symptom score, peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV1) and serum eosinophie cationic protein (ECP) concentration were evaluated at both times. The serum concentration of neuroendocrine parameters [prolactin, cortisol, adrenocorticotropic hormone (ACTH)] was also measured after 6 months of therapy. While all the clinical parameters and ECP concentration improved after SLIT, symptom score, PEF and ECP showed a significantly greater improvement in non‐stressed patients. The concentration of neuroendocrine parameters was significantly increased in stressed patients. Our findings show that psychological stress can affect response to SLIT also in allergic subjects and are consistent with data recently reported showing a correlation between stress and poor response to antimicrobial vaccines. Our data also suggest that stress evaluation may become a useful prognostic factor in immunotherapy.

Prevalence and Clinical Relevance of IgE Sensitization to Profilin in Childhood: A Multicenter Study

Background: Little is known about the prevalence and clinical relevance of hypersensitivity to the plant panallergen profilin in children. Objectives: The present study aimed to investigate prevalence, risk factors and clinical relevance of profilin sensitization in a large cohort of Italian children of different ages living in different geographic areas. Methods: Children with pollen allergy enrolled by 16 pediatric outpatient clinics sited in three main geographic areas of Italy were studied. SPT were carried out with commercial pollen extracts and a commercial purified date palm pollen profilin. IgE specific for allergenic pollen molecules, Phl p 12 (grass profilin) and Pru p 3 (peach lipid transfer protein) were tested by ImmunoCAP FEIA. Results: IgE to Phl p 12 (≥0.35 kU/l) was observed in 296 of the 1,271 participants (23%), including 17 of the 108 (16%) preschool children. Profilin SPT was positive (≥3 mm) in 320/1,271 (25%) participants. The two diagnostic methods were concordant in 1,151 (91%, p < 0.0001) cases. Phl p 12 IgE prevalence declined from northern to southern Italy and was directly associated with IgE to Phl p 1 and/or Phl p 5 and Ole e 1. Among children with IgE to Phl p 12, OAS was provoked by kiwi, melon, watermelon, banana, apricot and cucumber. Conclusions: Profilin sensitization is very frequent among pollen-allergic children, occurs at a very young age and contributes to the development of childhood OAS with a typical pattern of offending foods. Pediatricians should always consider IgE sensitization to profilin while examining pollen-allergic children, even if they are at preschool age.