María Pedrosa

Accidental allergic reactions in children allergic to cow's milk proteins

BACKGROUND Cows milk is the main cause of food allergy in children. Patients allergic to food frequently experience accidental exposure. There are few studies analyzing this problem, most of them concerning peanut allergy. OBJECTIVE We sought to calculate the frequency of accidental exposure reactions in children allergic to cows milk during a 12-month period, to analyze the clinical characteristics and circumstances surrounding the reactions, and to identify risk factors for severe reactions. METHODS Eighty-eight children allergic to cows milk (44 boys; median age, 32.5 months) were included in the study. A systematized questionnaire about accidental exposure was used. Reactions were classified as mild, moderate, and severe. Cows milk- and casein-specific IgE antibody titers were determined. RESULTS Thirty-five (40%) children had 53 reactions in the previous year (53% mild, 32% moderate, and 15% severe). Most reactions took place at home (47%) under daily life circumstances (85%). Specific IgE levels to cows milk were higher in children with severe reactions than in those with moderate (median, 37.70 vs 7.71 KUA/L; P = .04) or mild (3.37 KUA/L; P = .04) reactions. The frequency of severe reactions was 10-fold higher in asthmatic children (odds ratio, 10.2; 95% CI, 1.13-91.54). CONCLUSIONS Reactions to accidental exposure are frequent in children with cows milk allergy. The proportion of severe reactions was 15%. The risk factors for such reactions included very high levels of specific IgE to cows milk and casein and asthma.

Shellfish Allergy: a Comprehensive Review

Shellfish allergy is of increasing concern, as its prevalence has risen in recent years. Many advances have been made in allergen characterization. B cell epitopes in the major allergen tropomyosin have been characterized. In addition to tropomyosin, arginine kinase, sarcoplasmic calcium-binding protein, and myosin light chain have recently been reported in shellfish. All are proteins that play a role in muscular contraction. Additional allergens such as hemocyanin have also been described. The effect of processing methods on these allergens has been studied, revealing thermal stability and resistance to peptic digestion in some cases. Modifications after Maillard reactions have also been addressed, although in some cases with conflicting results. In recent years, new hypoallergenic molecules have been developed, which constitute a new therapeutic approach to allergic disorders. A recombinant hypoallergenic tropomyosin has been developed, which opens a new avenue in the treatment of shellfish allergy. Cross-reactivity with species that are not closely related is common in shellfish-allergic patients, as many of shellfish allergens are widely distributed panallergens in invertebrates. Cross-reactivity with house dust mites is well known, but other species can also be involved in this phenomenon.

Peanut seed storage proteins are responsible for clinical reactivity in Spanish peanut-allergic children

Background:  Seed storage proteins (SSP; Ara h 1, Ara h 2, Ara h 3) have been shown to be major peanut allergens, although recently, peanut lipid transfer protein has been reported to be an important allergen in the Mediterranean area. We sought to investigate the sensitization pattern to peanut SSP and vegetable pan‐allergens in a group of peanut‐allergic children compared with a peanut‐tolerant group.

Efficacy and safety of oral desensitization in children with cow's milk allergy according to their serum specific IgE level

BACKGROUND Oral desensitization in children allergic to cows milk proteins is not risk free. The analysis of factors that may influence the outcome is of utmost importance. OBJECTIVE To analyze the efficacy and safety of the oral desensitization according to specific IgE (sIgE) level and adverse events during the maintenance phase. METHODS Thirty-six patients allergic to cows milk (mean age, 7 years) were included in an oral desensitization protocol. Patients were grouped according to sIgE levels (ImmunoCAP) into groups 1 (sIgE <3.5 kU/L), 2 (3.5-17 kU/L), and 3 (>17-50 kU/L). Nineteen children were included as a control group. Serum sIgE levels to cows milk and its proteins were determined at inclusion and 6 and 12 months after finishing the desensitization protocol. RESULTS Thirty-three of 36 patients were successfully desensitized (200 mL): 100% of group 1 and 88% of groups 2 and 3. Desensitization was achieved in a median of 3 months (range, 1-12 months); 90% of the patients in group 1, 50% of the patients in group 2, and 30% of the patients in group 3 achieved tolerance in less than 3 months (P = .04). In the control group only 1 child tolerated milk in oral food challenge after 1 year. During the induction phase, there were 53 adverse events in 27 patients (75%). Patients of groups 2 and 3 had more severe adverse events compared with group 1. During the maintenance phase, 20 of 33 patients (60%) had an adverse event. CONCLUSION Oral desensitization is efficacious. Tolerance is achieved earlier when sIgE is lower. Severe adverse events are frequent, especially in patients with higher sIgE levels.

Peach allergy in spanish children: tolerance to the pulp and molecular sensitization profile

Peach allergy is the main cause of vegetable food allergy in the Mediterranean area. Pru p 3 is the major allergen, and it is mainly found in the peel.

Usefulness of abdominal ultrasonography in the follow-up of patients with hereditary C1-inhibitor deficiency

BACKGROUND Hereditary angioedema (HAE) is caused by the deficiency of functional C1 inhibitor. Symptoms of this disease include cutaneous angioedema, abdominal pain, and even laryngeal edema. OBJECTIVE To evaluate the usefulness of abdominal ultrasonography in patients with hereditary C1-inhibitor deficiency in diagnosing acute abdominal edema attacks and possible adverse effects of long-term prophylaxis with attenuated androgens. METHODS Fifty-nine adult patients with HAE regularly observed in our department were included whether they were symptomatic or not and whether they received long-term androgen prophylaxis or not. We evaluated the ultrasonographic findings in the assessments performed routinely or in the moment of an acute abdominal attack. RESULTS Of the 59 patients, 55 ever had any symptom due to HAE (abdominal location, 78% of the symptomatic patients); 4 patients were asymptomatic. In 11 cases, ultrasonography was performed during acute attacks. Ascites and intestinal wall swelling were found in 7 of these 11 cases and, thus, diagnosis was confirmed. Of the 59 patients, 33 were or had been receiving androgen prophylaxis. Abdominal ultrasonographic assessments were performed routinely in 31 of these patients. Four cases of angiomas, 4 of steatosis, and 1 each of portal hypertension, hepatic cysts, and hepatomegaly were found. Assessments were also performed in 17 patients who did not receive androgen prophylaxis; there were no findings in any of these patients. CONCLUSION Abdominal ultrasonography has been proved useful as an early tool for diagnosing the adverse effects of therapy and for confirming diagnosis in the case of an acute abdominal attack.

The amyloid fold of Gad m 1 epitopes governs IgE binding.

Amyloids are polymeric structural states formed from locally or totally unfolded protein chains that permit surface reorganizations, stability enhancements and interaction properties that are absent in the precursor monomers. β-Parvalbumin, the major allergen in fish allergy, forms amyloids that are recognized by IgE in the patient sera, suggesting a yet unknown pathological role for these assemblies. We used Gad m 1 as the fish β-parvalbumin model and a combination of approaches, including peptide arrays, recombinant wt and mutant chains, biophysical characterizations, protease digestions, mass spectrometry, dot-blot and ELISA assays to gain insights into the role of amyloids in the IgE interaction. We found that Gad m 1 immunoreactive regions behave as sequence-dependent conformational epitopes that provide a 1000-fold increase in affinity and the structural repetitiveness required for optimal IgE binding and cross-linking upon folding into amyloids. These findings support the amyloid state as a key entity in type I food allergy.

Complement Study Versus CINH Gene Testing for the Diagnosis of Type I Hereditary Angioedema in Children

To the Editor, Hereditary angioedema due to C1-inhibitor deficiency (C1INH-HAE) is a rare disease inherited in an autosomal dominant manner, with reduced levels (type I) or impaired function (type II) of C1-inhibitor (C1-INH) [1]. C1-INH regulates the coagulation pathway, fibrinolytic system, complement cascade and kallikrein-kinin system. Uncontrolled activation of these pathways produces increased bradykinin levels which leads to enhanced vascular permeability and edema formation. The most common presentation involves edema of the intestinal wall causing abdominal colicky pain that may mimic an acute abdomen, and edema of the subcutaneous tissue affecting extremities, face or the genital area. Although less frequent, angioedema can also affect the larynx and cause death because of asphyxiation. An early diagnosis is therefore of vital importance. C1-INH-HAE diagnosis is usually performed by determination of antigenic concentration and functional activity of C1-INH (C1-INH, f-C1-INH) in sera/plasma. CINH gene study is also available for diagnosis, although in a few cases the mutation is not found. Most authors advise against testing complement in patients before the age of 1 year [2] because C1-INH levels had been shown to be lower than in adults [3]. However, most complement components increase during the first days, rapidly surpassing adult values [4]. To date, there are no available data comparing C1-INHHAE diagnosis carried out by means of genetic testing versus complement components determination in a pediatric population. Our aim was to assess the accuracy of complement testing in the diagnosis of type I C1-INH-HAEmade by means of genetic testing in a pediatric population. We studied twenty-nine children from twenty-one unrelated families suspected of having C1-INH-HAE due to personal and/or family history. Informed consent was obtained from parents. The Local Ethics Committee approved the study (PI-1377). Suspicion of HAE was based on personal history and/or family history of episodes of angioedema not responding to antihistamines, corticosteroids and epinephrine and/or abdominal episodes of colicky pain that did not subside with conventional therapies, as well as episodes of laryngeal oedema where other causes had been excluded. The last criterion for suspecting HAE was to have a relative who had been diagnosed with Type I C1-INH-HAE. Blood venous samples were collected. Citrated-, EDTAcoated plasma tubes and serum tubes were obtained from patients upon informed consent and approval from the local Ethics committee. C1-INH and C4 levels were quantified on serum samples by nephelometry (Siemens, Marburg, Germany) and C1-INH functionality was assayed in citrated plasma samples with the commercial kit Berichrom (Siemens) following manufacturer ’s instructions. Additionally, DNA samples were obtained from peripheral blood mononuclear cells with the Gentra Puregene BloodCore (Gentra Systems, Minneapolis, MN). Genetic analysis of suspected de novo mutations was carried out by * Maria Pedrosa m.pedrosa.d@gmail.com

Comparison of Methacholine and Adenosine Inhalation Challenge in Patients with Suspected Asthma

Objective. Bronchial hyperresponsiveness is usually measured by bronchial challenge with direct (e.g. methacholine) and indirect (e.g. adenosine) agonists. A prospective, randomized, crossover, single-blind study was performed to compare both methods in the first diagnosis of asthma. Patients and methods. Fifty-seven patients, in which asthma was suspected, were selected (21 male, 36 female). Fifty-four underwent both challenges following the five-breath dosimeter protocol. PC20 was calculated according to ATS guidelines. Data of symptoms developed during the challenge, PC20 methacholine and adenosine, and FEV1 improvement after bronchodilator therapy were recorded. Results. Symptoms at consultation were consistent with asthma in 68.4% patients, asthma and rhinitis in 29.8% and exercise-induced asthma in 1.8%. Atopy was reported in 93%; 49.1% had family history of atopy and 26.3% of asthma. The most frequent symptoms developed during the challenge were cough (40.4% with adenosine and 20.4% with methacholine) and wheezing (26.3% and 7.4% respectively), statistically significant differences. Bronchial challenge with MCh resulted positive in 44.4% of the patients and positive with AMP in 50%. Every patient with negative result to adenosine, was also negative to methacholine. In 94.4% subjects the result of both challenges was concordant (kappa index = 0.889). PC20 in both challenges showed poor linear correlation (Pearson r = 0.43, p < 0.05). Positivity of both challenges was only associated with having a positive skin prick test to danders (p = 0.001). Percentage of improvement after bronchodilator was 34.9% (SD12.2%) with adenosine challenge and 33.9% (SD17.9%) with methacholine (differences non statistically significant). Conclusions. Concordance in the result of both techniques is very high. Cough and wheezing are more frequent with adenosine, though not severe. PC20 with both techniques shows poor linear correlation.

Trimethoprim–sulfamethoxazole (cotrimoxazole) desensitization in an HIV-infected 5-yr-old girl

To the Editor, Opportunistic infections are a major cause of morbidity and mortality in HIV-infected patients. Trimethoprim–sulfamethoxazole (TMP-SMX) (cotrimoxazole) has been shown to dramatically reduce the risk of opportunistic infections, particularly Pneumocystis carinii pneumonia, and has been used extensively in their treatment and prevention (1). Since 2006, WHO has recommended cotrimoxazole preventive therapy for all HIV-exposed infants and children born to mothers living with HIV, and continuing until cessation of risk of HIV transmission (cessation of breastfeeding) and infection can be exclude (2). In HIV-infected patients, cotrimoxazole use causes a higher rate of adverse drug reactions than in the general population (20–100% compared with 5–8% of healthy individuals) (3, 4). Hypersensitivity to cotrimoxazole is the most frequent drug reaction among HIV-infected patients, typically manifesting as a maculopapular rash, with or without fever, and usually occurring 1–2 wk after commencing treatment (5). IgE-mediated hypersensitivity is rare. The pathogenesis of TMP-SMX reactions is complex, multifactorial, and not completely understood. One or more metabolic, toxic, immunologic, or viral factors are likely to contribute, and the typical explanation is based on the variability in metabolic parameters for N-acetylation and N-oxidation (HIV-infected patients are more likely to have a slow acetylator phenotype, which results in greater oxidation and the formation of toxic intermediate SMX-derived metabolites thereby stimulating an immune response) (3, 5, 6). There are three options for the clinical management of hypersensitivity to cotrimoxazole in these patients: treating through the reaction (continuing therapy despite adverse reaction), rechallenge, or desensitization (4). Although a variety of cotrimoxazole desensitization protocols have emerged for HIV-infected patients, there is a lack of desensitization protocols for use in pediatric patients (4). A 5-yr-old Nigerian girl, with no known allergies, who was infected with HIV at birth (MTCT) was referred to the allergy department because a pruritic erythematous maculopapular rash had appeared on her face, chest, and limbs after 2 wk of treatment with cotrimoxazole, 7 ml/day, 3 times/wk (Septrim Pediatric oral suspension : 8 mg trimethoprim/40 mg sulfamethoxazole/1 ml). The reaction had occurred 15 days before she was first seen in the allergy department. She did not present fever or systemic symptoms. Hematological analysis showed a leukocyte count of 6.02 9 10/ll with 44.5% (2.68 9 10/ll) neutrophils and 43.9% (2.64 9 10/ll) lymphocytes. The CD4 T lymphocyte (CD4) count was 6% (158.4 9 10/ll). As CD4 cell count was <200 cells/mm (<200 cells/ll), prophylaxis with cotrimoxazole for at least 6 months was mandatory. After informed consent was obtained, the patient underwent a routine allergy work-up (skin tests) following the protocol of the Drug Allergy Interest Group of European Academy of Allergy and Clinical Immunology (7). Afterward, an oral desensitization protocol was carried out. The procedure was performed at the hospital, with a physician and nurse in attendance and emergency medications readily available. The results of skin prick test (SPT) with trimethoprim (10 mg/ml; Almofarma SL, Barcelona, Spain), and SPT (10 mg/ml), and intradermal test (IDT) with sulfamethoxazole (10 mg/ml; Almofarma SL) were negative. As the reaction related to cotrimoxazole use was very likely a hypersensitivity drug reaction, an oral challenge test was not performed. Instead, an oral desensitization protocol was carried out (Table 1). On the first day, gradually increasing doses of cotrimoxazole (Septrim Pediatric oral suspension ) at 15-min intervals (1 and 5 ml of dilution 1/200 and 1 and 2 ml of dilution 1/20) were tolerated. On the second day, the patient received 3 and 4 ml of 1/20 dilution at 15-min intervals with good tolerance, and on the third day, 2 undiluted doses of 0.5 and 1 ml at 45-min intervals were tolerated. On the fourth day, 30 min after the undiluted dose of 4 ml was administered (cumulative dose 6 ml), she developed a generalized pruritic erythematous maculopapular rash. The reaction immediately subsided after oral administration of dexchlorpheniramine and