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Vicilin Buried Peptides (VBPs) from edible plants are derived from the N-terminal leader sequences (LS) of seed storage proteins. VBPs are defined by a common α-hairpin fold mediated by conserved CxxxCx((10–14))CxxxC motifs. Here, peanut and walnut VBPs were characterized as potential mediators of both peanut/walnut allergenicity and cross-reactivity despite their low (~17%) sequence identity. The structures of one peanut (AH1.1) and 3 walnut (JR2.1, JR2.2, JR2.3) VBPs were solved using solution-NMR, revealing similar α-hairpin structures stabilized by disulfide bonds with high levels of surface similarity. Peptide microarrays identified several peptide sequences primarily on AH1.1 and JR2.1 which were recognized by peanut, walnut, and dual-allergic patient IgE, establishing these peanut and walnut VBPs as potential mediators of allergenicity and cross-reactivity. JR2.2 and JR2.3 displayed extreme resilience against endosomal digestion, potentially hindering epitope generation and contributing to their reduced allergic potential.

Background Neurocysticercosis is a growing public health problem in the United States. Albendazole is a mainstay of medical therapy for neurocysticercosis, and here we present a case of hypersensitivity to albendazole leading to life-threatening disease progression. Objective To report the first successful albendazole desensitization protocol. Methods An oral albendazole 12-step desensitization protocol was developed, starting with 0.001 mg and progressing at 15 minutes intervals. Dosage for each subsequent step was as follows: 0.003 mg, 0.01 mg, 0.03 mg, 0.1 mg, 0.3 mg, 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300mg. Results The patient rapidly improved from a symptomatic standpoint, and repeat MRI showed a dramatic improvement in lesions. Conclusions This successful desensitization protocol to albendazole can be of value to other patients with history suggestive of IgE-mediated allergy needing treatment for parasitic infections.

Hyperoeosinophilic syndrome (HES) is rare, and clinicians may not recognize its potential association with malignancy. Red flag signs of HES include steroid resistance, older age, and significant lymphadenopathy that can be indicative of malignancy. In this case, an elderly male presenting with right chest wall erythema and axillary lymphadenopathy was initially diagnosed with and treated for cellulitis. Labs were significant for hypereosinophilia. Evidence of end organ damage raised concern for HES. Over the course of three hospitalizations, he was found to have a rising eosinophil count despite high-dose corticosteroid treatment. Further investigation eventually revealed a diagnosis of Hodgkin’s Lymphoma. This case highlights steroid-resistant HES as a presenting sign of malignancy and allows for discussion of potential investigative approaches for HES therapy. Though corticosteroids are first-line treatment for hypereosinophilia and HES, they are well known to have many adverse effects. Biologics, such as mepolizumab and benralizumab, have more acceptable side effect profiles and are effective in treating non-myeloid HES. The use of biologics as first-line treatment for HES has yet to be investigated.

Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency but does not always result in clinical disease. This may in part be due to the definition based on serum IgA, while most IgA is secreted at mucosal surfaces, not amenable to measurement. Clinical complications include increased risk of sinopulmonary infections with bacteria and viruses, gastrointestinal infections with a predilection for Giardia lamblia, a myriad of autoimmune diseases including systemic lupus erythematosus, hyper- and hypo-thyroidism, Type 1 diabetes, celiac disease, and rarely, malignancy. SIgAD must be differentiated from IgA deficiency that may be seen with IgG2 or IgG4 deficiency, specific antibody deficiency, or as an early manifestation prior to a diagnosis of common variable immunodeficiency. Secondary IgA deficiency is increasingly recognized and may be due to medications such as anti-epileptics, or antibiotics with disruption of the microbiome which can influence IgA levels, infections or malignancies. Patients with SIgAD should be monitored at regular intervals and educated to be aware of particular complications. There is a rare chance of development of anti-IgA IgE antibodies in patients with complete deficiency, which can result in anaphylaxis if blood products with IgA are administered. Prophylactic antibiotics may be indicated in some cases, and very rarely, supplemental IgG infusions., Highlights • Selective IgA deficiency is the most common primary immunodeficiency. • It is associated with an increased risk of infections, allergic and autoimmune diseases, and rarely, malignancy. • There is a risk of transfusion reactions due to the rare development of IgE against IgA in blood products. • Treatment is supportive and directed at complications, with extremely rare use of immune globulin therapy. • Selective IgA deficiency should be considered when evaluating patients with autoimmune disorders.

Six patients came to our attention in the Sacramento, CA area who developed cough or asthma after the ingestion of one brand (Brand 1) of refrigerated Mexican-style salsa, labelled "fresh". These patients had consumed other brands previously, not necessarily sulfited, but noted cough or asthma only in relation to consumption of this brand. Patients 1 and 2 developed reproducible severe cough and throat tightness after ingestion. Patients 3 and 4 developed status asthmaticus within minutes of ingesting salsa, requiring intubation and mechanical ventilation. Patients 5 and 6 experienced mild flares of their asthma after eating the salsa. The mean sulfite concentration of 6 containers of Brand 1 salsa was 1,803 ppm (range 1,630 to 1,920 ppm). Two other brands of salsa averaged 766 and 373 ppm sulfite, respectively. The manufacturer of Brand 1 salsa eliminated sulfites from their product after learning of the adverse reactions. These cases suggest that the amount of sulfite used was unnecessarily and dangerously high, and for one known sulfite-sensitive asthmatic, the use of the term "fresh" was misleading, resulting in near-fatal bronchospasm. Manufacturers should be careful to use only the minimum amount of sulfiting agent necessary.

Background Little is known about the longitudinal change in the quality of acute asthma care for hospitalized children and adults in the United States. We investigated whether the concordance of inpatient asthma care with the national guidelines improved over time, identified hospital characteristics predictive of guideline concordance, and determined whether guideline-concordant care is associated with a shorter hospital length of stay (LOS). Methods This study was an analysis of data from two multicenter chart review studies of hospitalized patients aged 2 to 54 years with acute asthma during two time periods: 1999-2000 and 2012-2013. Outcomes were guideline concordance at the patient and hospital levels, and association of patient composite concordance with hospital LOS. Results The analytic cohort for the comparison of guideline concordance comprised 1,634 patients: 834 patients from 1999-2000 vs 800 patients from 2012-2013. Over these 15 years, inpatient asthma care became more concordant at the hospital-level, with the mean composite score increasing from 74 to 82 ( P P = .009). Conclusions Between 1999 and 2013, the guideline concordance of acute asthma care for hospitalized patients improved. However, interhospital variability remains substantial. Greater concordance with evidence-based guidelines was associated with a shorter hospital LOS.

Histamine fish poisoning, also known as scombroid poisoning, is the most common cause of ichythyotoxicosis worldwide and results from the ingestion of histamine-contaminated fish in the Scombroidae and Scomberesocidae families, including mackerel, bonito, albacore, and skipjack. This disease was first described in 1799 in Britain and re-emerged in the medical literature in the 1950s when outbreaks were reported in Japan. The symptoms associated with histamine fish poisoning are similar to that of an allergic reaction. In fact, such histamine-induced reactions are often misdiagnosed as IgE-mediated fish allergy. Indeed, histamine fish poisoning is still an underrecognized disease. In this review, we discuss the epidemiology, pathophysiology, evaluation, and treatment of scombroid disease. Because more than 80 % of fish consumed in the USA is now imported from other countries, the disease is intimately linked with the global fish trade (National Marine Fisheries Service, 2012). Preventing future scombroid outbreaks will require that fishermen, public health officials, restaurant workers, and medical professionals work together to devise international safety standards and increase awareness of the disease. The implications of scombroid poisoning go far beyond that of fish and have broader implications for the important issues of food safety.

The aim of this study was to investigate changes in walnut allergenicity after processing treatments by in vitro techniques and physiologically relevant assays. The allergenicity of walnuts subjected to high hydrostatic pressure and thermal/pressure treatments was evaluated by IgE-immunoblot and antibodies against walnut major allergen Jug r 4. The ability of processed walnut to cross-link IgE on effector cells was evaluated using a rat basophil leukaemia cell line and by skin prick testing. Susceptibility to gastric and duodenal digestion was also evaluated. The results showed that walnuts subjected to pressure treatment at 256 kPa, 138 C, were able to diminish the IgE cross-linking capacity on effector cells more efficiently than high pressure treated walnuts. IgE immunoblot confirmed these results. Moreover, higher susceptibility to digestion of pressure treated walnut proteins was observed. The use of processed walnuts with decreased IgE binding capacity could be a potential strategy for walnut tolerance induction. © 2014 Elsevier Ltd. All rights reserved.

Tattoos are defined as the introduction of exogenous pigments into the dermis in order to produce a permanent design. This process may occur unintentional or may be deliberately administered for cosmetic or medical reasons. Tattoos have been around for over 5000 years and over time have evolved to represent a common cosmetic practice worldwide. Currently, adverse reactions are relatively rare and generally unpredictable and predominantly include immune-mediated reactions and skin infections. Along with better healthcare standards and more stringent public health mandates such as the provision of disposable needles, major infectious complications related to hepatitis and human retroviral infections have decreased significantly. When they do occur, skin infections are most frequently associated with Staphylococcus aureus or Streptococcus pyogenes. The aim of this study is to review the types and rates of medical complications of permanent tattoos. PubMed search and search dates were open ended. Acute local inflammation is the most common complication, but infections, allergic contact dermatitis, and other inflammatory or immune responses that are not well-characterized may occur. As many patients with immune reactions to tattoos do not react on skin or patch testing, it is postulated that the antigens contained in dyes or pigments are such small molecules that they need to be haptenized in order to become immunogenic. Red ink is associated more frequently with long-term reactions, including granulomatous and pseudolymphomatous phenomena or morphea-like lesions and vasculitis. Exacerbation of preexisting psoriasis, atopic dermatitis, and pyoderma gangrenosum may occur after tattooing. There is no well-defined association between cancer and tattoos. The treatment of tattoo-related complications may include local destructive measures (cryotherapy, electro-surgery, dermabrasion, chemical destruction, ablative laser destruction), surgical excision, and thermolysis of the pigment using Q-switched laser therapy.

To cite this article: Maleki SJ, Teuber SS, Cheng H, Chen D, Comstock SS, Ruan S, Schein CH. Computationally predicted IgE epitopes of walnut allergens contribute to cross-reactivity with peanuts. Allergy 2011; 66: 1522–1529. Abstract Background: Cross-reactivity between peanuts and tree nuts implies that similar immunoglobulin E (IgE) epitopes are present in their proteins. Objective: To determine whether walnut sequences similar to known peanut IgE-binding sequences, according to the property distance (PD) scale implemented in the Structural Database of Allergenic Proteins, react with IgE from sera of patients with allergy to walnut and/or peanut. Methods: Patient sera were characterized by western blotting for IgE binding to nut protein extracts and to peptides from walnut and peanut allergens, similar to known peanut epitopes as defined by low PD values, synthesized on membranes. Competitive enzyme-linked immunosorbent assay (ELISA) was used to show that peanut and predicted walnut epitope sequences compete with purified Ara h 2 for binding to IgE in serum from a cross-reactive patient. Results: Sequences from the vicilin walnut allergen Jug r 2, which had low PD values to epitopes of the peanut allergen Ara h 2, a 2S albumin, bound to IgE in sera from five patients who reacted to either walnut or peanut or both. A walnut epitope recognized by sera from six patients mapped to a surface-exposed region on a model of the N-terminal pro-region of Jug r 2. This predicted walnut epitope competed for IgE binding to Ara h 2 in serum as well as the known IgE epitope from Ara h 2. Conclusions: Sequences with low PD value (

Asthma is probably the most common serious medical disorder that may complicate pregnancy. A third of pregnant women with asthma will experience worsening of their symptoms, a third will see improvement of their symptoms and a third will see no change. The primary goal is to maintain optimal control of asthma for maternal health and well-being as well as fetal maturation. Vital patient education should cover the use of controller medication, avoidance of asthma triggers and early treatment of asthma exacerbations. Proper asthma management should ideally be started in the preconception period. Since smoking is probably the most modifiable risk factor of asthma, pregnant woman should avoid active and passive smoking. Acute asthma exacerbation during the first trimester is associated with an increased risk of congenital malformations. Poorly controlled asthma is associated with low birth weight, preeclampsia, and preterm birth. Medications used for asthma control in the non-pregnant population are generally the same in pregnancy with a few exceptions. Inhaled corticosteroids (ICS) are the preferred controller therapy. Budesonide is the preferred ICS. Long-acting B-agonists (LABA) are the preferred add-on therapy to medium to high dose ICS. Major triggers for asthma exacerbations during pregnancy are viral infections and ICS nonadherence.

Allergy to penicillin is the most commonly reported antibiotic allergy. However, most patients who report a positive history of a prior reaction to penicillin are not found to be allergic to penicillin upon skin testing. Often, this history is vague or based on a parent's recollection of an event that occurred in the distant past. Avoidance of penicillin based on self-reported allergic history alone often leads to the use of an alternate antibiotic with greater cost or side effect profile. Patients with a negative skin test to both major and minor determinants may generally be given penicillin, with a statistical risk of developing an allergic reaction similar to that observed in the general population. A more cautious approach in these cases where the degree of suspicion is low, an allergic etiology is unproven, or there is a negative skin test, is to do a graded challenge. If the skin test is positive, an alternate antibiotic should be used. If, however, an alternate antibiotic is not available, then desensitization may be performed, but there are limitations to desensitization as well, and tolerance is not permanent. Avoidance of cephalosporins may be recommended in cases of penicillin allergy, but newer generation cephalosporins have demonstrate less cross-reactivity to penicillin than earlier generation ones. Desensitization protocols for cephalosporins are available but not standardized. The mechanisms of antibiotic sensitization are not clearly understood.

Background: IgE-reactive proteins have been identified in almond; however, few have been cloned and tested for specific patient IgE reactivity. Here, we clone and express prunin 1 and prunin 2, isoforms of the major almond protein prunin, an 11S globulin, and assay each for IgE reactivity. Methods: Prunin isoforms were PCR-amplified from an almond cDNA library, sequenced, cloned and expressed in Escherichia coli. Reactivity to the recombinant (r) allergens, Pru du 6.01 and Pru du 6.02, was screened by dot blot and immunoblot assays using sera from almond-allergic patients and murine monoclonal antibodies (mAbs). Sequential IgE-binding epitopes were identified by solid-phase overlapping peptide analysis. Epitope stability was assessed by assaying denatured recombinant proteins by immunoblot. Results: IgE reactivity to rPru du 6.01 and rPru du 6.02 was found in 9 of 18 (50%) and 5 of 18 patients (28%), respectively. Four patients (22%) demonstrated reactivity to both isoforms. Murine anti-almond IgG mAbs also showed greater reactivity to rPru du 6.01 than to rPru du 6.02. Both stable and labile epitopes were detected. Six IgE-binding sequential epitope-bearing peptide segments on Pru du 6.01 and 8 on Pru du 6.02 were detected using pooled almond-allergic sera. Conclusions: rPru du 6.01 is more widely recognized than rPru du 6.02 in our patient population. The identification of multiple sequential epitopes and the observation that treatment with denaturing agents had little effect on IgE-binding intensity in some patients suggests an important role for sequential epitopes on prunins.

English walnuts are implicated in severe, IgE-mediated food allergy in humans. We sought to determine if polyphenolic compounds extracted from the edible nut could promote IgE production to a coadministered allergen. BALB/c mice were sensitized to ovalbumin (OVA) with or without alum (AL) or polyphenolic-enriched extract via intraperitoneal injection. Serum was analyzed for total IgE and OVA-specific IgE, IgG(1,) and IgG(2a/2b). Coadministration of walnut polyphenolic-enriched extract with antigen and AL increased serum concentrations of antigen-specific IgE and IgG(1). When AL was excluded from the injections, polyphenolic extract tended to enhance OVA-specific IgE and IgG(1) over levels induced by OVA alone, but the increase did not reach significance. Serum IgG(2a/2b) levels were similar between mice receiving OVA/AL and OVA/AL with polyphenolics. Thus, walnut polyphenolic extract enhanced the Th2-skewing effect of an aluminum hydroxide adjuvant. This indicates that walnut polyphenolic compounds may play a role in allergic sensitization of genetically predisposed individuals.

Tree nuts, including walnuts, are important elicitors of food allergy. We examined the ability of walnut kernel polyphenolics and purified ellagic acid (EA) to modulate cytokine production and cellular proliferation from stimulated human peripheral blood mononuclear cells (PBMC). IL-13 and TNF-alpha production decreased while no change was observed in IL-4 production. Paradoxically, EA and the walnut polyphenolics all significantly and dose-dependently inhibited stimulated [phytohemagglutin (PHA), alpha-CD3, and phorbol myristate acetate (PMA)/ionomycin] PBMC proliferation while simultaneously increasing IL-2 production. When added at time 0 min and 2 h, EA dose-dependently inhibited PHA-induced proliferation. However, at 30 min and 1 h, low doses of EA (10 and 1 muM) significantly increased proliferation above that of PHA alone, although higher doses led to inhibition. Our data do not support the hypothesis that walnut polyphenolics skew a cytokine response toward Th2 in an in vitro environment. However, immunomodulatory effects are present, including an inhibition of cellular proliferation despite no decrease in IL-4 or IL-2.

Macrophage activation syndrome (MAS) is a phenomenon characterized by cytopenia, organ dysfunction, and coagulopathy associated with an inappropriate activation of macrophages. Current diagnostic criteria are imprecise, but the syndrome is now recognized as a form of hemophagocytic lymphohistiocytosis that is characteristically associated with autoimmune diatheses. The diagnosis of incipient MAS in patients with autoimmune disease requires a high index of suspicion, as several characteristics of the disorder may be present in the underlying condition or infectious complications associated with the treatment thereof. Proposed treatment regimens include aggressive approaches that require validation in future controlled studies. This review discusses the major aspects of the pathophysiology, diagnosis, and management of MAS with a focus on the association with autoimmune disease.

The solubility of almond, Brazil nut, cashew nut, hazelnut, macadamia, pecan, pine nut, pistachio, walnut, and peanut proteins in several aqueous solvents was qualitatively and quantitatively assessed. In addition, the effects of extraction time and ionic strength on protein solubility were also investigated. Electrophoresis and protein determination (Lowry, Bradford, and micro-Kjeldahl) methods were used for qualitative and quantitative assessment of proteins, respectively. Depending on the seed, buffer type and ionic strength significantly affected protein solubility. The results suggest that buffered sodium borate (BSB; 0.1 M H(3)BO(3), 0.025 M Na(2)B(4)O(7), 0.075 M NaCl, pH 8.45) optimally solubilizes nut seed proteins. Qualitative differences in seed protein electrophoretic profiles were revealed. For a specific seed type, these differences were dependent on the solvent(s) used to solubilize the seed proteins. SDS-PAGE results suggest the polypeptide molecular mass range for the tree nut seed proteins to be 3-100 kDa. The results of native IEF suggested that the proteins were mainly acidic, with a pI range from >4.5 to

Allergic reactions to walnuts and hazelnuts can be serious. The 11S globulins (legumins) have been identified as important allergens in these and other nuts and seeds. Here we identify the linear IgE-binding epitopes of walnut and hazelnut 11S globulins, and generate 3D 11S globulin models to map the locations of the epitopes for comparison to other allergenic homologues. Linear IgE-epitope mapping was performed by solid-phase overlapping 15-amino acid peptides probed with IgE from pooled allergic human sera. Several walnut (Jug r 4) and hazelnut (Cor a 9) 11S globulin peptides with reactivity to patient IgE were identified. Comparative alignment with cashew (Ana o 2), peanut (Ara h 3), and soybean G1 (Gly m 6.0101) and G2 (Gly m 6.0201) allergenic homologues revealed several shared allergenic 'hot spots'. Homology modeling was performed based on the atomic structure of the soybean glycinin. Surface map comparisons between the tree nut and peanut homologues revealed structural motifs that could be important for IgE elicitation and binding and show that, contrary to predictions, the reactive epitopes are widely distributed throughout the monomeric subunits, both internally and externally, including regions occluded by quaternary subunit association. These findings reveal structural features that may be important to allergenicity and cross-reactivity of this protein class.

The complement system is composed of more than 30 serum and membrane-bound proteins, all of which are needed for normal function of complement in innate and adaptive immunity. Historically, deficiencies within the complement system have been suspected when young children have had recurrent and difficult-to-control infections. As our understanding of the complement system has increased, many other diseases have been attributed to deficiencies within the complement system. Generally, complement deficiencies within the classical pathway lead to increased susceptibility to encapsulated bacterial infections as well as a syndrome resembling systemic lupus erythematosus. Complement deficiencies within the mannose-binding lectin pathway generally lead to increased bacterial infections, and deficiencies within the alternative pathway usually lead to an increased frequency of Neisseria infections. However, factor H deficiency can lead to membranoproliferative glomerulonephritis and hemolytic uremic syndrome. Finally, deficiencies within the terminal complement pathway lead to an increased incidence of Neisseria infections. Two other notable complement-associated deficiencies are complement receptor 3 and 4 deficiency, which result from a deficiency of CD18, a disease known as leukocyte adhesion deficiency type 1, and CD59 deficiency, which causes paroxysmal nocturnal hemoglobinuria. Most inherited deficiencies of the complement system are autosomal recessive, but properidin deficiency is X-linked recessive, deficiency of C1 inhibitor is autosomal dominant, and mannose-binding lectin and factor I deficiencies are autosomal co-dominant. The diversity of clinical manifestations of complement deficiencies reflects the complexity of the complement system.

Previous studies have shown that those with severe food allergies have significant gaps in knowledge about their disease and how to prevent recurrences. The purpose of this study was to address these deficiencies by creating and testing an educational packet, “Coping with Food Allergies.” Participants included 46 of 58 adults with documented severe food allergies (response rate = 79%); and indeed, over half (57%) of the participants had experienced a food allergic reaction in the past year. The educational packet was tested in waves, with comments from participants used to revise the next version of the packet. Language targeted a lay audience and hand-drawn illustrations were added to make the material more appealing. Most participants recommended expanding sections dealing with symptom management and approaches to take when eating at restaurants. These sections became prominent features of the final edition. The participants were equally divided regarding preferred learning type: text-based compared with visual. No significant associations could be drawn between learning style and perceived clarity of information, with 93% finding the packet very clear and easy to read. Participants commented that the simple illustrations were ideal for a child with allergies or someone reading at a 6th to 8th grade level. Even among this group with longstanding food allergy, over 60% reported that they learned something new from the packet. “Coping with Food Allergies” will be made available to the public via the Food Safety Educators web site of the USDA and the allergy support group, Food Allergy and Anaphylaxis Network (FAAN).

Background Minimal data exist on the prevalence and characteristics of in-flight reactions to foods. Objectives To characterize reactions to foods experienced by passengers aboard commercial airplanes and to examine information about flying with a food allergy available from airlines. Methods Telephone questionnaires were administered to individuals in a peanut, tree nut, and seed allergy database who self-reported reactions aboard aircraft. Airlines were contacted to obtain information on food allergy policies. Results Forty-one of 471 individuals reported allergic reactions to food while on airplanes, including 4 reporting more than 1 reaction. Peanuts accounted for most of the reactions. Twenty-one individuals (51%) treated their reactions during flight. Only 12 individuals (29%) reported the reaction to a flight attendant. Six individuals went to an emergency department after landing, including 1 after a flight diversion. Airline personnel were notified of only 3 of these severe reactions. Comparison of information given to 3 different investigators by airline customer service representatives showed that inconsistencies regarding important information occurred, such as whether the airline regularly serves peanuts. Conclusions In this group of mainly adults with severe nut/seed allergy, approximately 9% reported experiencing an allergic reaction to food while on board an airplane. Some reactions were serious and potentially life-threatening. Individuals commonly did not inform airline personnel about their experiences. In addition, the quality of information about flying with food allergies available from customer service departments is highly variable and, in some cases, incomplete or inaccurate.

Summary Background Patients allergic to cashew nuts often report allergy to pistachio, which could be a result of cross-reactivity between the two as both are members of the Anacardiaceae family. Objective Because cashew 7S globulin (vicilin, Ana o 1) is a recognized major allergen, we cloned the pistachio homologue and assayed it for IgE reactivity and cross-reactivity with Ana o 1. Methods Degenerate primers for 7S globulin were used in PCR to amplify DNA from a pistachio cDNA library. An isolate was sequenced, cloned and expressed in Escherichia coli. Reactivity to the allergen was screened by dot blot using 19 pistachio and/or cashew-allergic patients’ sera. Cross-reactivity was investigated by inhibition dot- and Western immunoblot assays using pistachio/cashew-allergic patients’ sera, and monoclonal antibodies (MAbs) raised against recombinant Ana o 1 (rAna o 1). Results An isolate was found that coded for a 7S vicilin-like protein, designated Pis v 3. IgE reactivity to Pis v 3 was found in the serum of seven of the 19 (37%) patients with histories of allergy to both pistachio and cashew or who were allergic to cashew but had never eaten pistachio. The seven patients with IgE that recognized rPis v 3 also recognized rAna o 1. Six of nine anti-rAna o 1 MAbs also showed reactivity to rPis v 3 on dot blots. Conclusion Of the 37% of pistachio/cashew-allergic patients’ sera that recognized the pistachio allergen, rPis v 3, all showed complete cross-reactivity with rAna o 1. The data does not identify the primary sensitizing agent but suggests that IgE reactivity to rPis v 3 and rAna o 1 is focused on the most conserved regions of the proteins. Clinical histories suggest that in some cases, cashew was the sensitizing agent. rPis v 3 is a likely contributor to the observed co-sensitivity to pistachio and cashew in some patients.

Cashew apple juice has the potential to be a natural source of vitamin C and sugar in processed foods. The juice of the cashew apple is obtained by pressing the fleshy peduncle or receptacle, which forms a rounded apple that sits above the true fruit, the cashew nut. Cashew nut allergy is the second most commonly reported tree nut allergy in the United States. To determine if cashew apple juice contains cashew nut allergens, immunoblotting was performed using a cashew apple juice 6X concentrate that was extracted and further concentrated through dialysis, lyophilization, and resuspension. Serum IgE of individuals allergic to cashew nut bound proteins in the cashew apple juice concentrate extract. For some serum samples, IgE reactivity could be inhibited by preincubation of the serum with cashew nut extract, suggesting the presence of cashew nut-related allergens. Using monoclonal antibodies specific for cashew nut allergens, the concentrate was found to contain Ana o 1 (vicilin) and Ana o 2 (legumin). Neither IgE from cashew nut allergic sera nor the monoclonal antibodies bound any peptides in 5 kDa filtered cashew apple juice concentrate. The cashew apple juice concentrate used in these studies contains proteins with IgE-reactive epitopes, including cashew nut legumin and vicilin. No IgE-binding peptides remained after 5 kDa filtration of the concentrate.

With the implementation of vaccination programs and the use of antibiotics, developed countries have seen a decline in infection-related pediatric bronchiectasis. However, significant morbidity from bronchiectasis is still seen and both infectious and noninfectious causes of bronchiectasis in the pediatric population remain. A review of the literature will be presented including causes of pediatric bronchiectasis, clinical symptoms and signs, laboratory evaluation and imaging, as well as treatment options. This review stresses the importance of early evaluation and treatment in children with recurrent cough, sinusitis, potential foreign-body aspiration, or gastroesophageal reflux to prevent the complications of ongoing respiratory disease and bronchiectasis.

Polyarteritis nodosa, as a diagnosis, has been progressively narrowed from a collection of ill-defined vasculitides to its current definition as a systemic transmural necrotizing vasculitis that usually affects medium-sized muscular arteries and sometimes small muscular arteries, commonly within the kidneys, gastrointestinal tract, skin, nerves, joints, and muscles. In this review, we will highlight the clinical features and classification of this disease and emphasize that more accurate diagnosis of subtypes leads to more effective treatment.

Peanuts, tree nuts, cow’s milk, soy, wheat, hen’s egg, fish, and crustaceans are considered the “Big Eight” foods in discussions of immunoglobulin E (IgE)-mediated or -associated food allergy both internationally and in the United States. These foods account for approximately 90% of food allergies in the best-studied group in the United States: children with atopic dermatitis. Although the Big Eight foods account for about 90% of clinical reactions in children with atopic dermatitis in referral centers, the pattern of foods causing reactions prompting emergency department visits is somewhat different in the United States. However, the Big Eight foods remain highly useful for labeling rules because the vast majority of individuals with food allergy will be helped, and specific fruits or vegetables are easier to avoid once the allergy is identified and the patient receives appropriate education on avoidance. The chapter reviews the eight dominant foods associated with food allergic reactions along with sesame. Cow's milk allergy is the most common food allergy in infants reported from developed Western nations. Most infants with IgE-mediated or IgE-associated allergy to cow’s milk protein will do well on isolated soy protein-based formula and that there is no need to spend money on more expensive, less-palatable formulas.

Background Despite the significant burden of childhood asthma, little is known about prevention-oriented management before and after hospitalizations for asthma exacerbation. Objective To investigate the proportion and characteristics of children admitted to the intensive care unit (ICU) for asthma exacerbation and the frequency of guideline-recommended outpatient management before and after the hospitalization. Methods A 14-center medical record review study of children aged 2 to 17 years hospitalized for asthma exacerbation during 2012-2013. Primary outcome was admission to the ICU; secondary outcomes were 2 preventive factors: inhaled corticosteroid (ICS) use and evaluation by asthma specialists in the pre- and posthospitalization periods. Results Among 385 children hospitalized for asthma, 130 (34%) were admitted to the ICU. Risk factors for ICU admission were female sex, having public insurance, a marker of chronic asthma severity (ICS use), and no prior evaluation by an asthma specialist. Among children with ICU admission, guideline-recommended outpatient management was suboptimal (eg, 65% were taking ICSs at the time of index hospitalization, and 19% had evidence of a prior evaluation by specialist). At hospital discharge, among children with ICU admission who had not previously used controller medications, 85% were prescribed ICSs. Furthermore, 62% of all children with ICU admission were referred to an asthma specialist during the 3-month posthospitalization period. Conclusion In this multicenter study of US children hospitalized with asthma exacerbation, one-third of children were admitted to the ICU. In this high-risk group, we observed suboptimal pre- and posthospitalization asthma care. These findings underscore the importance of continued efforts to improve prevention-oriented asthma care at all clinical encounters.

© 2015 American Academy of Allergy, Asthma & Immunology. Background: Earlier studies reported that many patients were frequently hospitalized for asthma exacerbation. However, there have been no recent multicenter studies to characterize this patient population with high morbidity and health care utilization. Objective: To examine the proportion and characteristics of children and adults with frequent hospitalizations for asthma exacerbation. Methods: A multicenter chart review study of patients aged 2 to 54 years who were hospitalized for asthma exacerbation at 1 of 25 hospitals across 18 US states during the period 2012 to 2013 was carried out. The primary outcome was frequency of hospitalizations for asthma exacerbation in the past year (including the index hospitalization). Results: The cohort included 369 children (aged 2-17 years) and 555 adults (aged 18-54 years) hospitalized for asthma exacerbation. Over the 12-month period, 36% of the children and 42% of the adults had 2 or more (frequent) hospitalizations for asthma exacerbation. Among patients with frequent hospitalizations, guideline-recommended outpatient management was suboptimal. For example, among adults, 32% were not on inhaled corticosteroids at the time of index hospitalization and 75% had no evidence of a previous evaluation by an asthma specialist. At hospital discharge, among adults with frequent hospitalizations who had used no controller medications previously, 37% were not prescribed inhaled corticosteroids. Likewise, during a 3-month postdischarge period, 64% of the adults with frequent hospitalizations were not referred to an asthma specialist. Although the proportion of patients who did not receive these guideline-recommended outpatient care appeared higher in adults, these preventive measures were still underutilized in children; for example, 38% of the children with frequent hospitalizations were not referred to asthma specialist after the index hospitalization. Conclusions: This multicenter study of US patients hospitalized with asthma exacerbation demonstrated a disturbingly high proportion of patients with frequent hospitalizations and ongoing evidence of suboptimal longitudinal asthma care.

Background The identity of allergenic almond proteins is incomplete. Objective Our objective was to characterize patient IgE reactivity to a recombinant and corresponding native almond allergen. Methods An almond cDNA library was screened with sera from patients with allergy for IgE binding proteins. Two reactive clones were sequenced, and 1 was expressed. The expressed recombinant allergen and its native counterpart (purified from unprocessed almond flour) were assayed by 1-dimensional and 2-dimensional gel electrophoresis, dot blot, and ELISA, and screened for cross-reactivity with grass profilin. Results The 2 selected clones encoded profilin (designated Pru du 4) sequences that differed by 2 silent mutations. By dot-blot analyses, 6 of 18 patient sera (33%) reacted with the recombinant Pru du 4 protein, and 8 of 18 (44%) reacted with the native form. ELISA results were similar. Almond and ryegrass profilins were mutually inhibitable. Two-dimensional immunoblotting revealed the presence of more than 1 native almond profilin isoform. The strength of reactivity of some patients' serum IgE differed markedly between assays and between native and recombinant profilins. Conclusion Almond nut profilin is an IgE-binding food protein that is cross-reactive with grass pollen profilin and is susceptible to denaturation, resulting in variable reactivity between assay types and between patients. Clinical implications Serum IgE of nearly half of the tested patients with almond allergy reacts with almond nut profilin. Because most patients also had pollinosis, the well-known cross-reactivity between pollen and food profilins could account for this pattern of reactivity.

Allergy to walnut is the most frequently reported tree nut allergy in the United States. Walnut 2S albumin, a vicilin-like protein, and a lipid transfer protein allergen have previously been described. Our objective was to clone and express a cDNA encoding a legumin group protein, assess IgE-binding with sera from walnut allergic patients, and investigate cross-reactivity with selected nuts. Primers were used to obtain the cDNA by 5' and 3' rapid amplification of cDNA ends from walnut mRNA. The cDNA was subcloned into the pMAL-c2X vector and the recombinant fusion protein, named rJug r 4, was expressed in Escherichia coli. The obtained cDNA encoded a precursor protein with a predicted molecular weight of 58.1 kD, which showed significant sequence homology to hazelnut and cashew legumin allergens. Serum IgE from 21 of 37 (57%) patients bound the rJug r 4 fusion protein. In vitro cross-reactivity was demonstrated with hazelnut, cashew, and peanut protein extracts.

TABLE OF CONTENTS I. Preface S1 II. Glossary S2 III. Executive Summary S3 IV. Summary Statements S6 V. Classification of Major Food Allergens and Clinical Implications S11 VI. Mucosal Immune Responses Induced by Foods S12 VII. The Clinical Spectrum of Food Allergy S15 VIII. Algorithm and Annotations S18 IX. Prevalence and Epidemiology S21 X. Natural History of Food Allergy S22 XI. Risk Factors and Prevention of Food Allergy S23 XII. Cross-reactivity of Food Allergens S24 XIII. Adverse Reactions to Food Additives S30 XIV. Genetically Modified Foods S32 XV. Diagnosis of Food Allergy S33 XVI. Food-Dependent Exercise-Induced Anaphylaxis S39 XVII. Differential Diagnosis of Adverse Reactions to Foods S40 XVIII. General Management of Food Allergy S44 XIX. Management in Special Settings and Circumstances S45 XX. Future Directions S47 XXI. Appendix: Suggested Oral Challenge Methods S48 XXII. Acknowledgments S49 XXIII. References S50

With regard to the allergenicity of edible seeds and nuts, certain proteins may not be immediately accessible to digestion in the stomach and the upper small intestine because of the nature of the organization of such proteins into protein body organelles. Protein body hydration status, interactions between proteins, phytochemicals, protease inhibitors, and other matrix effects may contribute to the ability of a protein or package of proteins to reach the sites of active immune sampling in the gastrointestinal mucosa and thus be an influence on the potential allergenicity of a protein.

Background: Intravenous immunoglobulin (IVIG) is the mainstay therapy in human immune deficiency states characterized by qualitative and quantitative reductions in B cells. In addition, however, there is widespread use of IVIG in a number of other areas, including neuroimmunologic, infectious, dermatologic, hematologic, autoimmune, inflammatory and idiopathic disorders. In many of these cases, there are little objective data to support the use. Methods: We performed a review of more than 400 publications in PubMed using the key words ‘intravenous immunoglobulin’ and excluded publications that focused on immune deficiency, for which the indication for IVIG is already clear. Results: For a number of off-label indications, there is significant evidence of efficacy and IVIG has become the standard of care for many clinical syndromes other than immune deficiency. In some conditions, however, the data have not been well controlled or randomized and are often limited to case reports that are difficult to interpret. Although the critical shortage of IVIG of the last decade is no longer an issue, IVIG is expensive and not without risk. The use of IVIG should be based not only on clinical data, but also, and especially, on the biological rationale for its use. Conclusions: The appropriate use of IVIG is an important issue that is difficult to resolve, and will continue to challenge clinicians based on expense and potentially limited supply, including the intrinsic limitations of donor plasma. The establishment of national and international voluntary registries to report use of IVIG in disorders for which evidence is lacking would be a first step toward facilitating randomized, controlled clinical trials.

The immunological basis of eosinophilic gastroenteritis (EGE) is an interesting contrast between the enigma of urticaria and the increasing usage of molecular technology in clinical allergy. Little is known about the natural history of EGE. It has been known to spontaneously remit, but the typical course, especially in adults, is one of chronic and intermittent disease. Given the often chronic nature of this disease, it is important to use relatively benign treatments initially and limit the use of systemic corticosteroids. Also, given the fact that eosinophilic infiltration of the gastrointestinal tract may also be a manifestation of other potentially dangerous disease processes, such as malignancy or hypereosinophilic syndrome, which may be initially diagnosed as EGE, routine surveillance of the cardiopulmonary and gastrointestinal systems is important. We present a patient who demonstrates the variability of presentation and treatment response in this multifaceted disease. The fact that he has apparently entered remission also makes his an uncommon presentation of EGE.

The ubiquitous presence of allergens in the human food supply coupled with increased awareness of food allergies warrants undertaking appropriate preventive measures to protect sensitive consumers from unwanted exposure to offending food allergens. Attempts to reduce or eliminate food allergenicity through food processing have met with mixed results. The rationale for using food processing to reduce/eliminate allergenicity and limitations to using this approach are discussed.

Anaphylaxis is a source of anxiety for patients and healthcare providers. It is a medical emergency that presents with a broad array of symptoms and signs, many of which can be deceptively similar to other diseases such as myocardial infarction, asthma, or panic attacks. In addition to these diagnostic challenges, anaphylaxis presents management difficulties due to rapid onset and progression, lack of appropriate self-treatment education and implementation by patients, severity of the allergic response, exacerbating medications or concurrent disease, and unpredictability. The most common causes of anaphylaxis are food allergies, stinging insects and immunotherapy (allergy shots) but idiopathic anaphylaxis, latex allergy and drug hypersensitive all contribute to the epidemiology. Reactions to IVP and other dyes are coined anaphylactoid reactions but have identical pathophysiology and treatment, once the mast cell has been degranulated. As many antigens can be the trigger for fatal anaphylaxis, it is useful to examine the features of each etiology individually, highlighting factors common to all fatal anaphylaxis and some specific to certain etiologies. Generally what distinguishes a fatal from non fatal reaction is often just the rapidity to apply correct therapy. Prevention is clearly the key and should identify high-risk patients in an attempt to minimize the likely of a severe reaction. Although fatal anaphylaxis is rare, it is likely underreported.

Summary Background Tree nuts, including English walnuts (Juglans regia), are sources of food allergens often associated with life-threatening allergic reactions. It is unknown if seed storage proteins from other Juglans species have IgE epitopes similar to those of the important English walnut allergens, Jug r 1 (2S albumin) and Jug r 2 (vicilin-like). Objective To screen for potential germplasm sources of hypoallergenic seed storage proteins of relevance in walnut food allergy. We sought to identify English walnut cultivars (cvs) or other Juglans species that showed decreased IgE binding to major seed storage proteins or an inability to cross-react with Jug r 1 or Jug r 2. Methods We determined if IgE in sera of patients who have had life-threatening systemic reactions to English walnut bound protein extracts from all tested walnut cvs (57 cvs total) or species (six) by Western immunoblot. Further, we used immunoblot inhibition to determine the in vitro cross-reactivity of Jug r 1 and Jug r 2, native and recombinant, with several walnut species. Results All walnut cvs and species contain allergenic proteins. Furthermore, as shown by in vitro immunoblot inhibition, the major walnut allergens in the species tested cross-reacted with those in J. regia cv. Chandler and J. nigra cv. Thomas extracts. Conclusions Based on our findings, it is unlikely that a composite hypoallergenic walnut could be bred from available germplasm. In addition, patients with severe allergy to English walnut are likely to be clinically allergic to all commercial English walnut cvs and other closely related Juglans species.

Whole unprocessed almonds, cashew nuts and walnuts were each subjected to γ-irradiation (1, 5, 10 and 25kGy) followed by heat processing including autoclaving (121 ◦ C, 15psi for 15 and 30min), dry roasting (138 and 160 ◦ C for 30min each, 168 and 177 ◦ C for 12min each), blanching (100 ◦ C for 5 and 10min), oil roasting (191 ◦ C, 1min) and microwave heating (500W for 1 and 3min). Rabbit polyclonal antibodies were raised against each major protein isolated from defatted, but not subjected to γ-irradiation and/or any thermal processing, almond, cashew nut and walnut flours. Immunoreactivity of almond, cashew nut and walnut proteins soluble in borate saline buffer, normalised to 1mg protein ml −1 for all samples, was determined by inhibition enzyme-linked immunosorbent assay (ELISA) and Western blotting. ELISAs and Western blotting experiments indicated that almond, cashew nut and walnut proteins exposed to γ-irradiation alone or followed by various thermal treatments remained antigenically stable.  2004 Society of Chemical Industry