Successful treatment of neurocysticercosis with albendazole desensitization.

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.

Structure, Immunogenicity, and IgE Cross-Reactivity among Walnut and Peanut Vicilin-Buried Peptides.

Vicilin-buried peptides (VBPs) from edible plants are derived from the N-terminal leader sequences (LSs) 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 likely contributing to their reduced allergic potential.

Cloning, expression and patient IgE reactivity of recombinant Pru du 6, an 11S globulin from almond.

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.

The COMPARE Database: A Public Resource for Allergen Identification, Adapted for Continuous Improvement.

Motivation: The availability of databases identifying allergenic proteins via a transparent and consensus-based scientific approach is of prime importance to support the safety review of genetically-modified foods and feeds, and public safety in general. Over recent years, screening for potential new allergens sequences has become more complex due to the exponential increase of genomic sequence information. To address these challenges, an international collaborative scientific group coordinated by the Health and Environmental Sciences Institute (HESI), was tasked to develop a contemporary, adaptable, high-throughput process to build the COMprehensive Protein Allergen REsource (COMPARE) database, a publicly accessible allergen sequence data resource along with bioinformatics analytical tools following guidelines of FAO/WHO and CODEX Alimentarius Commission. Results: The COMPARE process is novel in that it involves the identification of candidate sequences via automated keyword-based sorting algorithm and manual curation of the annotated sequence entries retrieved from public protein sequence databases on a yearly basis; its process is meant for continuous improvement, with updates being transparently documented with each version; as a complementary approach, a yearly key-word based search of literature databases is added to identify new allergen sequences that were not (yet) submitted to protein databases; in addition, comments from the independent peer-review panel are posted on the website to increase transparency of decision making; finally, sequence comparison capabilities associated with the COMPARE database was developed to evaluate the potential allergenicity of proteins, based on internationally recognized guidelines, FAO/WHO and CODEX Alimentarius Commission.

Macrophage activation syndrome in autoimmune disease.

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.

Work Group report: oral food challenge testing.

Oral food challenges are procedures conducted by allergists/immunologists to make an accurate diagnosis of immediate, and occasionally delayed, adverse reactions to foods. The timing of the challenge is carefully chosen based on the individual patient history and the results of skin prick tests and food specific serum IgE values. The type of the challenge is determined by the history, the age of the patient, and the likelihood of encountering subjective reactions. The food challenge requires preparation of the patient for the procedure and preparation of the office for the organized conduct of the challenge, for a careful assessment of the symptoms and signs and the treatment of reactions. The starting dose, the escalation of the dosing, and the intervals between doses are determined based on experience and the patient's history. The interpretation of the results of the challenge and arrangements for follow-up after a challenge are important. A negative oral food challenge result allows introduction of the food into the diet, whereas a positive oral food challenge result provides a sound basis for continued avoidance of the food.

Common variable immunodeficiency: etiological and treatment issues.

One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID). CVID is a syndrome that leads to a reduction in serum immunoglobulins and complications including recurrent infections. Management includes immunoglobulin replacement therapy; however, patients with CVID are at risk for complications of exogenous immunoglobulin administration as well as CVID-associated diseases such as autoimmune processes and malignancies. To assess the current state of knowledge in the field, we performed a literature review of a total of 753 publications covering the period of 1968 until 2008. From this list, 189 publications were selected for discussion. In this review, we demonstrate that while the molecular basis of CVID in many cases remains incompletely understood, significant strides have been made and it is now clear that there is involvement of several pathways of immune activation, with contributions from both T and B cells. Furthermore, despite the current gaps in our knowledge of the molecular pathogenesis of the syndrome, there have been dramatic advances in management that have led to improved survival and significantly reduced morbidity in affected patients.

The clinical implications of selective IgA deficiency.

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.

A review of non-cystic fibrosis pediatric bronchiectasis.

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.

Development of a food allergy education resource for primary care physicians.

BACKGROUND: Food allergy is estimated to affect 3-4% of adults in the US, but there are limited educational resources for primary care physicians. The goal of this study was to develop and pilot a food allergy educational resource based upon a needs survey of non-allergist healthcare providers. METHODS: A survey was undertaken to identify educational needs and preferences for providers, with a focus on physicians caring for adults and teenagers, including emergency medicine providers. The results of the survey were used to develop a teaching program that was subsequently piloted on primary care and emergency medicine physicians. Knowledge base tests and satisfaction surveys were administered to determine the effectiveness of the educational program. RESULTS: Eighty-two physicians (response rate, 65%) completed the needs assessment survey. Areas of deficiency and educational needs identified included: identification of potentially life-threatening food allergies, food allergy diagnosis, and education of patients about treatment (food avoidance and epinephrine use). Small group, on-site training was the most requested mode of education. A slide set and narrative were developed to address the identified needs. Twenty-six separately enrolled participants were administered the teaching set. Pre-post knowledge base scores increased from a mean of 38% correct to 64% correct (p < 0.001). Ability to correctly demonstrate the use of epinephrine self injectors increased significantly. Nearly all participants (>95%) indicated that the teaching module increased their comfort with recognition and management of food allergy. CONCLUSION: Our pilot food allergy program, developed based upon needs assessments, showed strong participant satisfaction and educational value.

Aspirin and nonsteroidal anti-inflammatory drug hypersensitivity.

Acetylsalicylic acid (ASA) or aspirin and nonsteroidal anti-inflammatory drug (NSAID) sensitivities encompass a diverse group of both pharmacological and hypersensitivity reactions. Conventionally, hypersensitivities include aspirin-exacerbated respiratory disease (AERD), ASA-induced urticaria, and anaphylaxis. With an increasing prevalence of coronary artery disease in an aging population, aspirin continues to play a significant role in cardiac prophylaxis in a large patient population. Invariably, the clinician will encounter patients with clear indications for aspirin therapy but a history of aspirin sensitivity. Although protocols have been established for aspirin challenge and desensitization, it is not always an efficacious or safe procedure. This article reviews the different classifications of ASA/NSAIDs hypersensitivities to better guide the clinician in dealing with this patient population. History of crossrelativities between multiple NSAIDs implies a non-IgE-mediated process. Similarly, a history of monosensitivity to one NSAID implies an IgE-mediated process, although specific antibodies are often elusive. Despite the name, AERD can potentially be exacerbated by all cyclooxygenase (COX) inhibitors based on dose-dependent inhibition of COX-1. Aspirin desensitization can be achieved to improve both upper and lower respiratory symptoms for most patient with AERD. Aspirin desensitization can usually be achieved for those in need of the antiplatelet effects of aspirin, with the exception of those with aspirin-induced urticaria and baseline chronic urticaria. However, desensitization should only be attempted in those with stable coronary artery disease because the process of desensitization carries the inherent risk of anaphylaxis/anaphylactoid reaction, which may further increase cardiac demand and bring about ischemic injury. Therefore, desensitization is reserved until coronary artery disease is stabilized.

A critical review of local anesthetic sensitivity.

With their ability to block pain signals to the brain, local anesthetics (LAs) have made possible many surgical procedures and interventions once thought impossible. LAs are generally safe and well tolerated when used correctly by trained professionals. However, adverse reactions do occur, and may generate a referral to an Allergist for evaluation of LA allergy. LA structure, classification, and metabolism will be briefly reviewed. A critical analysis of the studies and case reports involving LA allergy found via PubMed search for "local anesthetic allergy" and "local anesthetic hypersensitivity" will be discussed. In addition, the clinical evaluation of a patient with concern for a LA allergy will be examined.

Polyarteritis nodosa.

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.

Potential adverse events with biologic response modifiers.

In recent years, an explosion of biologic response modifiers has entered the market to combat a variety of immune-mediated diseases. These can be in the form of recombinant cytokines, as in the case of interferon beta in the treatment of multiple sclerosis, or novel engineered antibodies constructed by combining non-human determinants with a human immunoglobulin scaffold, as in the case of omalizumab in the treatment of allergic asthma. More recently, completely human monoclonal antibodies have also been constructed. Adverse reactions related to these agents can be classified as expected or unexpected events. A number of case studies and a handful of randomized trials have demonstrated the potential toxicities with the use of biologic response modifiers. This article aims to review adverse event profiles of select biologic response modifiers for which the most data is available and are common to a rheumatology, allergy/immunology, and dermatology patient population.

Eosinophilic gastroenteritis and citrus-induced urticaria.

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.

Jug r 4, a legumin group food allergen from walnut (Juglans regia Cv. Chandler).

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.