OBJECTIVE:To test the hypothesis that allergic proctocolitis, a cause of self-limiting rectal bleeding in infants, can predispose to the development of functional gastrointestinal disorders (FGIDs) later in childhood. STUDY DESIGN:We studied a cohort of 80 consecutive patients diagnosed with allergic proctocolitis. Their sibling or matched children presenting to the same hospital for minor trauma served as controls. Parents of the patients with allergic proctocolitis and controls participated in a telephone interview every 12 months until the child was at least 4 years old. At that time, they were asked to complete the parental Questionnaire on Pediatric Gastrointestinal Symptoms, Rome III version. RESULTS:Sixteen of the 160 subjects (10.0%) included in the study met the Rome III criteria for FGIDs. Among the 80 patients with allergic proctocolitis, 12 (15.0%) reported FGIDs, compared with 4 of 80 (5.0%) controls (P = .035). After adjustment for age and sex, the OR for FGIDs in allergic proctocolitis group was 4.39 (95% CI, 1.03-18.68). FGIDs were significantly associated with iron deficiency anemia, duration of hematochezia, and younger age at presentation. In a multivariate analysis, only the duration of hematochezia was significantly associated with the development of FGIDs (OR, 3.14; 95% CI,1.72-5.74). CONCLUSIONS:We have identified allergic proctocolitis as a new risk factor for the development of FGIDs in children. Our data suggest that not only infection, but also a transient early-life allergic inflammatory trigger may induce persistent digestive symptoms, supporting the existence of "postinflammatory" FGIDs.

Objectives: Oral viscous budesonide is a recent therapeutic option for eosinophilic oesophagitis (EoE) compared with dietary restriction and inhaled steroids. This single-centre, open-label, not blinded study aims to evaluate the efficacy and safety of a new, preprepared oral viscous budesonide suspension (PVB) in children and adolescents with EoE.Methods: We treated 36 children with PVB (29 boys; median age 12 years) with EoE diagnosed according to European Society for Paediatric Gastroenterology Hepatology and Nutrition guidelines. Patients <150 and >150 cm height received 2 and 4 mg PVB daily, respectively, for 12 weeks. Upper gastrointestinal endoscopy was performed at baseline, after 12 weeks of therapy and 24 weeks after the end of therapy. Baseline and post-treatment scores were calculated for symptoms, endoscopy, and histology. Serum cortisol was performed at baseline, 12, and 36 weeks.Results: At the end of PVB trial, endoscopy showed Macroscopic remission in 32 patients (88.9%), whereas at histology median pre- and post-treatment peak eosinophil count/high power field (HPF) markedly decreased from 42.2 (range: 15-100) to 2.9 (range: 0-30); moreover, mean symptom and histology scores impressively improved compared with baseline (P < 0.01). At 24 weeks after the end of PVB therapy, endoscopy showed oesophageal relapse in 21 patients (58.3%), whereas 15 (41.7%) were still in remission. Seven children (19.4%) with positive multichannel intraluminal impedance pH were treated also with proton pump inhibitors. No significant difference between pre-/post-treatment morning cortisol levels occurred.Conclusions: The new PVB suspension presented in the present study is effective and safe for treating children with proven EoE. Larger placebo controlled clinical trials would provide more information about dosing, efficacy, and long-term safety of this formulation, specifically designed for the oesophagus.

ABSTRACTObjectives:The long‐term effects of amino acid–based formula (AAF) in the treatment of cow's milk allergy (CMA) are largely unexplored. The present study comparatively evaluates body growth and protein metabolism in CMA children treated with AAF or with extensively hydrolyzed whey formula (eHWF), and healthy controls.Methods:A 12‐month multicenter randomized control trial was conducted in outpatients with CMA (age 5–12 m) randomized in 2 groups, treated with AAF (group 1) and eHWF (group 2), and compared with healthy controls (group 3) fed with follow‐on (if age <12 months) or growing‐up formula (if age >12 months). At enrolment (T0), after 3 (T3), 6 (T6), and 12 months (T12) a clinical evaluation was performed. At T0 and T3, in subjects with CMA serum levels of albumin, urea, total protein, retinol‐binding protein, and insulin‐like growth factor 1 were measured.Results:Twenty‐one subjects in group 1 (61.9% boys, age 6.5 ± 1.5 months), 19 in group 2 (57.9% boys, age 7 ± 1.7 months) and 25 subjects in group 3 (48% boys, age 5.5 ± 0.5 months) completed the study. At T0, the weight z score was similar in group 1 (−0.74) and 2 (−0.76), with differences compared to group 3 (−0.17, P < 0.05). At T12, the weight z score value was similar between the 3 groups without significant differences. There were no significant changes in protein metabolism in children in groups 1 and 2.Conclusion:Long‐term treatment with AAF is safe and allows adequate body growth in children with CMA.

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.

BACKGROUND:Lymphoid nodular hyperplasia (LNH) of the lower gastrointestinal tract is a common finding during paediatric colonoscopies, and its clinical significance has not yet been clearly established.OBJECTIVE:The purpose of this prospective, parallel multi-arm, randomized clinical trial was to study relationship between food allergy and LNH.METHODS:We recruited 268 children who had undergone a diagnostic colonoscopy between 1 January 2009 and 30 September 2011. The inclusion criteria were the following: (i) demonstration of LNH; (ii) no concomitant inflammatory or immune disease; (iii) no treatment since the clinical onset. The patients were assigned 1:1:1 to elimination diet (Group A), mesalamine (Group B) or symptomatic treatment with antispasmodics or antidiarrhoeal drugs (Group C) for an 8-wk period. Patients were followed for 24 months.RESULTS:We enrolled 72 of 97 children with intestinal LNH who were referred for haematochezia (76%), recurrent abdominal pain (68%) and/or chronic diarrhoea (32%). Clinical improvement was observed in 75%, 83% and 79% of the patients in Groups A, B and C, respectively. The difference in the response to treatment among the groups and the association to the clinical, endoscopic and allergic features of the patients were not statistically significant.CONCLUSIONS:Intestinal LNH should be considered a benign finding in children without red flags, because the symptoms are largely self-limiting. The use of mesalamine or elimination diet does not modify the clinical outcome compared to symptomatic therapy. The presence of food allergy was not predicted by allergy skin testing and was found in a minority of patients.

Background: Eosinophilic oesophagitis is an inflammatory condition characterized by a dense eosinophilic infiltrate. The migration of eosinophils into the oesophagus is influenced by cytokines such as IL-5, IL-13 and eotaxin-3. The aim of this study was to evaluate changes in the cytokine expression profiles (IL-5, IL-13 and eotaxin-3/CCL26) in children after topical steroid treatment.Methods: a prospective case-control study was performed in 23 paediatric patients (age 5-16 years) with a histological diagnosis of eosinophilic oesophagitis. Histological evaluation and cytokine levels assay (IL-5, IL-13 and eotaxin-3/CCL26) in the proximal and distal oesophagus were performed before, and after 8 weeks of topical budesonide. Data were compared with a matched healthy control group.Results: quantitative expression levels of IL-5, IL-13 and eotaxin-3 were significantly higher in the eosinophilic oesophagitis group both compared to healthy subjects (p < 0.0001). A significant reduction of the eosinophil infiltrate as well as of IL-5, IL-13 and eotaxin-3 mucosal profiles was observed after steroid treatment both at the proximal and distal oesophagus (p < 0.0001).Conclusions: IL-5, IL-13 and eotaxin-3/CCL26 are significantly over-expressed in the oesophageal epithelium of children with eosinophilic oesophagitis. Topical steroid treatment (inhaled and swallowed budesonide) can induce clinical response with partial mucosal remission. (C) 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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 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.

Objectives To prospectively evaluate the effect of different dietary management strategies on the rate of acquisition of tolerance in children with cow milk allergy (CMA). Study designOtherwise healthy children (aged 1-12months) diagnosedwith CMAwere prospectively evaluated. The study population was divided into 5 groups based upon the formula used for management: (1) extensively hydrolyzed casein formula ([EHCF], n = 55); (2) EHCF + Lactobacillus rhamnosus GG [LGG], n = 71); (3) hydrolyzed rice formula (RHF, n = 46); (4) soy formula (n = 55); and (5) amino acid based formula (n = 33). A food challenge was performed after 12 months to assess acquisition of tolerance. Results Two hundred sixty children were evaluated (167 male, 64.2%; age 5.92 months, 95% CI 5.48-6.37; body weight 6.66 kg, 95% CI 6.41-6.91; IgE-mediated CMA 111, 42.7%). The rate of children acquiring oral tolerance after 12 months was significantly higher (P < .05) in the groups receiving EHCF (43.6%) or EHCF + LGG (78.9%) compared with the other groups: RHF (32.6%), soy formula (23.6%), and amino acid based formula (18.2%). Binary logistic regression analysis (B) revealed that the rate of patients acquiring tolerance at the end of the study was influenced by 2 factors: (1) IgE-mediated mechanism (B 2.05, OR 0.12, 95% CI 0.06-0.26; P < .001); and (2) formula choice, such that those receiving either EHCF (B 1.48, OR 4.41, 95% CI 1.44-13.48; P = .009) or EHCF + LGG (B 3.35, OR 28.62, 95% CI 8.72-93.93; P < .001). Conclusions EHCF accelerates tolerance acquisition in children with CMA if compared with other dietetic choices. This effect is augmented by LGG. (J Pediatr 2013;-:---).

OBJECTIVES:To prospectively evaluate the effect of different dietary management strategies on the rate of acquisition of tolerance in children with cow's milk allergy (CMA). STUDY DESIGN:Otherwise healthy children (aged 1-12 months) diagnosed with CMA were prospectively evaluated. The study population was divided into 5 groups based upon the formula used for management: (1) extensively hydrolyzed casein formula ([EHCF], n = 55); (2) EHCF + Lactobacillus rhamnosus GG [LGG], n = 71); (3) hydrolyzed rice formula (RHF, n = 46); (4) soy formula (n = 55); and (5) amino acid based formula (n = 33). A food challenge was performed after 12 months to assess acquisition of tolerance. RESULTS:Two hundred sixty children were evaluated (167 male, 64.2%; age 5.92 months, 95% CI 5.48-6.37; body weight 6.66 kg, 95% CI 6.41-6.91; IgE-mediated CMA 111, 42.7%). The rate of children acquiring oral tolerance after 12 months was significantly higher (P < .05) in the groups receiving EHCF (43.6%) or EHCF + LGG (78.9%) compared with the other groups: RHF (32.6%), soy formula (23.6%), and amino acid based formula (18.2%). Binary regression analysis coefficient (B) revealed that the rate of patients acquiring tolerance at the end of the study was influenced by 2 factors: (1) IgE-mediated mechanism (B -2.05, OR 0.12, 95% CI 0.06-0.26; P < .001); and (2) formula choice, such that those receiving either EHCF (B 1.48, OR 4.41, 95% CI 1.44-13.48; P = .009) or EHCF + LGG (B 3.35, OR 28.62, 95% CI 8.72-93.93; P < .001). CONCLUSIONS:EHCF accelerates tolerance acquisition in children with CMA if compared with other dietetic choices. This effect is augmented by LGG.

Background: The so-called component-resolved immunotherapy of allergies proposes an immunization tailored to the molecular sensitization profiles of individual patients.Objectives: We sought (1) to investigate the profiles of IgE sensitization to Phleum pratense in children with grass pollen allergy and (2) to define the compatibility of these profiles with a mixture of recombinant allergenic molecules of P pratense previously proposed for specific immunotherapy.Methods: We examined 200 children (age, 4-18 years; 126 boys) with allergic rhinitis, asthma, or both ascertained through validated questionnaires. Each child underwent skin prick testing (ALK-Abello) and serum IgE assays (ImmunoCAP, Phadia) with 9 pollen extracts. Sera reacting against P pratense were tested for the individual molecules (rPhl p 1, rPhl p 2, rPhl p 4, nPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, and Phl p 12). Through a combinatorial approach, the IgE individual sensitization profiles were matched against an experimental allergen-specific immunotherapy (SIT) preparation containing Phl p 1, Phl p 2, Phl p 5, and Phl p 6.Results: Among the 176 of 200 children with IgE sensitization to P pratense extract, 39 profiles of sensitization to the 8 allergenic molecules tested (cutoff, 0.35 kU/L) were identified. This high heterogeneity was reduced by considering only 6 or 4 P pratense molecules but not by increasing the cutoff levels of IgE positivity. The molecular profile of the experimental SIT preparation matched that of 7 (4%) of 176 patients only; the remaining 169 patients were classified in 4 mismatch categories: underpowered (29%), overpowered (32%), underpowered/overpowered (32%), and unrelated (3%).Conclusions: IgE sensitization profiles to P pratense are highly heterogeneous. Molecularly designed SIT preparations tailored to patients' needs should consider this high heterogeneity and be driven by locally performed population studies. (J Allergy Clin Immunol 2012;129:834-9.)

Background: Allergic 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 formulaMethods: We 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.Results: Prick 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%, cow's milk (50%), soy (28%), egg (21%), rice (14%), wheat (7%). Follow-up rectosigmoidoscopy confirmed the remission of APC in all infants.Conclusions: These 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.

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 cow's 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 microm 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.

A child aged 3 years 4 months, breast-fed for the first 3 months of life, with a clinical history of persistent constipation unaffected by treatment with laxatives presented recurrent episodes of complete rectal prolapse after the introduction of cow's milk into his diet.The rectal prolapse disappeared after this substance was eliminated from the diet.There was no family history of atopy.Before admission for observation, the child had presented eight episodes of rectal prolapse in the space of 3 years (the last two a fortnight before being admitted).While the results of prick tests carried out to ascertain whether the constipation was a symptom of food allergy proved negative, a patch test with cow's milk was positive.Total IgE were within the normal values and there were no specific IgE.The sweat test was negative.Parasitic infestation and coeliac disease were excluded.Colonoscopy revealed disorders of the mucosa compatible with the diagnosis of lymphoid hyperplasia, as confirmed by histologic examination of the biopsy specimens.This finding, which proves frequent in allergic enteropathies, suggested that an elimination diet for cow's milk protein might prove effective.

The skin prick test (SPT) is regarded as an important diagnostic measure in the diagnostic work-up of cow's milk protein allergy. It is not known whether commercial extracts have any advantage over fresh milk. The aims of the study were to (i) compare the diagnostic capacity of SPTs for the three main cow's milk proteins (alpha-lactalbumin, casein and beta-lactoglobulin) with fresh milk and (ii) determine a cut-off that discriminates between allergic and tolerant children in a controlled food challenge. A study was carried out on 104 children consecutively attending two paediatric allergy clinics for suspected cow's milk allergy. A clinical history, SPTs with fresh cow's milk and commercial extracts of its three main proteins and a challenge test were performed on all the children. A study of the validity of the prick test was also performed by taking different cut-off points for fresh milk and its proteins. Twenty-eight of 104 challenge tests (26.9%) were positive. At a cut-off point of 3 mm, fresh milk showed the greatest negative predictive value (98%), whereas casein showed the greatest positive predictive value (PPV, 85%). Calculation of 95% predicted probabilities using logistic regression revealed predictive decision points of 12 mm for lactalbumin, 9 mm for casein, 10 mm for beta-lactoglobulin and 15 mm for fresh cow's milk. We found that the greater the number of positive SPTs for milk proteins, the more likely the positive response to challenge. Having a positive SPT for all three milk proteins had PPV of 92.3% and would seem more clinically useful than any cut-off. Both fresh milk and cow's milk extract of the three main proteins could be useful in the diagnostic work-up of cow's milk allergy. Finding positivity to all three cow's milk proteins seems to be a simpler and more useful way of avoiding oral food challenges.

INTRODUCTION Increased risk of osteoporosis and fractures has been reported in patients with inflammatory bowel disease (IBD) primarily because of the inflammatory process itself and corticosteroid therapy (1,2). Vertebral fractures (VF) have rarely been reported in children with IBD, and only in the case of Crohn disease (CD) (3). We describe a case of vertebral compression fractures complicating the course of ulcerative colitis (UC) in a 7-year-old girl with increased sensitivity to corticosteroids. CASE REPORT A 7-year-old girl with a 13-month-long history of relapsing UC was referred to our unit for severe back pain associated with weakness and functional limitation of the lower limbs beginning 1 month before admission. The patient had undergone three 2-month cycles of oral corticosteroid therapy (dosage, 2 mg/kg/day) alternated with 5-aminosalicylates and salazopirin from the onset of the illness up to the time of our initial examination, but without achieving any lasting remission of the symptoms. One month before our first examination, during admission to a different hospital center, a radiographic result of the lumbar spine proved normal, and electromyography revealed features attributed to a nonspecific polyradiculopathy. There were marked Cushing-like features and severe back pain in the lumbar region. The lower limbs were hypotonic and extremely weak, and stretch tendon reflexes were absent. The girl was confined to bed and could not move her legs. The Babinski sign was present bilaterally. The girl also complained of bloody stools, tenesmus and abdominal pain. Colonoscopy revealed active diffuse UC. The medication used on admission was 40 mg/d of methylprednisolone. Azathioprine (dosage, 50 mg/d) and sulfasalazine (dosage, 2.5 g/d) were introduced and the use of corticosteroids tapered. Although there was slow improvement regarding the abdominal complaints, the back pain was unchanged. Antibiotics were administered on day 18 because of fever and pulmonary opacity revealed by a radiograph of the chest. As the back pain persisted, another radiograph of the lumbar spine was performed, which revealed multiple vertebral compression fractures (Fig. 1). Osteoporosis was suspected because of the IBD and corticosteroid therapy. A dual-energy x-ray absorptiometry scan of the lumbar spine was performed, revealing a severe reduction in bone mineral density (BMD; z score, −3.5 SD). The corticosteroid dosage of 2 mg/kg/day, which is typical for pediatric patients with IBD, was not to account for the severity of the clinical conditions, even in view of the duration of the treatment. This suggested the possibility of increased sensitivity to corticosteroids. A study of glucocorticoid cytotoxicity was thus carried out on lymphocytes from the patient with the use of dexamethasone and methylprednisolone. The concentration of the drug with a lethal effect on 50% of the cells proved much lower in both cases than with the controls (dexamethasone, 0.251 mmol/L, vs controls, 0.8 ± 0.15 mmol/L; methylprednisolone, 0.691 mmol/L, vs controls, 1.1 ± 0.2 mmol/L). The girl refused an orthopedic corset because of pain, and physical, manual or exercise therapies were precluded because of low compliance. A slow intravenous infusion of pamidronate (dose, 1 mg/kg) was therefore administered 2 weeks after admission for 3 consecutive days. There were no adverse effects during the first day, and then a slight temperature and headache, which disappeared with acetaminophen, on the second and third days. Intravenous pamidronate was preferred to oral alendronate; oral alendronate is not recommended for recumbent patients because of severe esophageal adverse effects. Treatment was also commenced with calcium (dosage, 1 g/d) and 25-OH-D3 (dosage, 30 μg/d) per os.FIG. 1: Lateral radiograph of the lumbar spine before treatment with pamidronate showing severe diffuse rarefaction and decrease in height of the lumbar vertebral bodies.The back pain began to improve 10 days after starting infusion. Four days later, the patient started to move her legs and accepted the corset. Five days later, she was able to remain in an almost seated position; 1 week later, she could use a wheelchair with no pain. She was then referred to the rehabilitation unit, where she stayed for 1 month. The girl was then readmitted to our unit. She could walk and had no back pain at all. Slight tenderness was noted on compression of the lumbar vertebrae. Ulcerative colitis was in remission. She was discharged with a prescription of sulfasalazine, azathioprine, oral calcium and vitamin D. Three months after treatment with pamidronate, she exhibited no difficulties in locomotion and no trace of the back pain and intestinal symptoms. A second dual-energy x-ray absorptiometry scan revealed a 30.5% increase in BMD (z score, −2.3), and a spine x-ray showed improved mineralization with sclerosis of vertebral bodies (Fig. 2). A course of oral alendronate (dosage, 5 mg/d) was planned for 3 months. She was discharged after 5 days.FIG. 2: Lateral radiograph of the lumbar spine after treatment showing increased cortical thickness of the vertebral bodies and sclerosis of the end plate.DISCUSSION Low BMD is a widely recognized complication of IBD in both adults and children (1). The estimated prevalence of low BMD in IBD varies greatly among the studies, ranging from 5% to 70%, in relation to the definition used, the methods of assessing BMD and the nature of the study population (5-7). Frank osteoporosis is observed in approximately 15% of patients (8). The prevalence of low BMD in children with IBD is reported to be as high as 70% (5). Reduced BMD in patients with IBD is multifactorial and thought to result from vitamin D deficiency, malabsorption, restriction diets and the inflammatory process itself (1,2), whereas conflicting data have been reported on the effects of corticosteroid therapy (9,10). Other variables, such as genetic predisposition, reduced physical activity, growth failure and alteration of sex hormones, have been implicated in the occurrence of BMD reduction in patients with IBD (4). The patient, on admission to our unit, exhibited severe back pain with functional limitation and negative emotional impact, and was found to have severe osteoporosis and VF. Severe osteoporosis and VF are the most commonly reported pathological fractures from osteoporosis in patients with IBD and have been mainly described in adult patients with CD, with a prevalence of 22% (11). Their association with UC is not as well documented (7,12). Vertebral fractures have rarely been described in pediatric patients with IBD, and only in children with CD (8,11). Attention has been given to the increased duration of systemic corticosteroid use and higher daily doses among the various risk factors for the occurrence of fractures in patients with IBD and osteoporosis (10). The patient was subjected to three 2-month-long cycles of oral corticosteroid therapy during the 13 months between the onset of the illness and the time of our examination. The dose administered was not, however, sufficient to account for the onset of severe osteoporosis with multiple fractures. The hypothesis of increased individual sensitivity to corticosteroids was borne out by laboratory tests. The patient's VF healed after the administration of intravenous pamidronate, and full locomotion was recovered in a few weeks. No significant adverse effects were observed after the use of the drug. Antiresorptive agents, such as bisphosphonates (including alendronate and pamidronate), are frequently used in adults with osteoporosis of different etiology. These drugs irreversibly inhibit bone resorption by becoming incorporated into the mineralized bone matrix, especially at the sites of osteoclastic activity. Their use in pediatrics is, however, still rare and debated because there is no evidence for their efficacy and long-term effect in children. They are mostly used for osteogenesis imperfecta, in which they serve to reduce fracture frequency and improve bone mass and locomotion (13-15). To the best of our knowledge, there have been no reports on the use of bisphosphonate in children with osteoporosis and IBD. Our case shows that bisphosphonates can be suggested as treatment for the critical reduction in BMD in children with IBD, particularly if osteoporosis is complicated by fractures. Controlled trials with these drugs in this population are therefore warranted. It also provides further proof that BMD evaluation is warranted in every patient with IBD and that spinal radiography should be performed in the presence of low BMD and clinical symptoms such as back pain. At the same time, it bears out the view that although corticosteroids do not seem to alter the course of IBD (16), their use may be associated with troublesome and dangerous complications, especially when there is increased sensitivity to these drugs. Acknowledgment: The authors are grateful to I. Drigo, MD, Biomedical Sciences Department, University of Trieste, Italy, for laboratory support with the glucocorticoid cytotoxic test.

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 (FEV(1)) 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.