Background: Tree nut allergy affects approximately 1% of the U.S. population and the prevalence is increasing. Walnut allergy is the most commonly reported tree nut allergy in the United States. This study aimed to investigate the IgE cross-reactivity between walnut allergen Jug r 4 and peanut allergen Ara h 3 in individuals with dual walnut and peanut allergies. Methods: Jug r 4 was purified from whole walnut extract and analyzed via western blot using anti-Ara h 3 antibodies alongside serum IgE from walnut allergic patients. Sera from individuals allergic to both peanuts and walnuts were utilized to examine peptide microarrays comprising synthetic overlapping 15 mer peptides, offset by five amino acids, of Ara h 3 and Jug r 4. These results were compared against computationally predicted IgE epitopes using the Structural Database for Allergic Proteins (SDAP). Additionally, SWISS-MODEL protein modeling software was employed to map IgE epitopes onto Ara h 3 and Jug r 4. Results: Our findings revealed previously unreported IgE epitopes for dual-allergic sera within both allergens, highlighting the locations of empirically determined and SDAP-predicted IgE epitopes. Conclusions: While six epitopes were predicted as cross-reactive, only three were frequently recognized by IgE in dual-allergic individuals, underscoring their potential significance in clinically relevant cross-reactivity.

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.

Indiscriminate food allergy (FA) screening can result in unnecessary food avoidance and anxiety. A retrospective chart review of 236 pediatric patients with FA testing at our institution revealed that the majority (76%) of testing was done for non-IgE mediated symptoms, such as chronic abdominal pain and behavioral issues. A quality improvement project using an electronic medical record (EMR) intervention consisting of a hard-stop alert with FA panel order placement, and recommendation of targeted testing instead, was implemented in February 2021. To evaluate the effectiveness of the intervention, we conducted a retrospective review of pediatric and adult patients in UC Davis-affiliated outpatient clinics for whom FA panels were ordered 12 months prior to and following the intervention. A total of 318 charts were reviewed. In the year post-intervention, 98 FA panels were ordered, a 55.5% reduction from the previous year. Pre-intervention, 18.3+/-7.2 food panels per month were ordered, compared to 8.1+/- 1.8 post-intervention (p<0.0001). 25 patients total (7.9%) had symptoms consistent with IgE-mediated FA. The most common presenting symptoms were chronic abdominal pain (37.4%) and recurrent rash (22.3%). For those with positive tests, 42.2% were instructed to eliminate the food from their diet, while 49% of patients were given no clear dietary instructions. Inappropriate food IgE testing remains overutilized for patients with chronic, nonspecific symptoms resulting in unnecessary and potentially harmful food elimination. An EMR alert is an effective strategy to reduce FA panel ordering.

The published rate of subcutaneous allergen immunotherapy (SCIT)-associated systemic reactions (SR) with conventional build-up protocols is 0.1-0.2% or 1-2 per 1,000 injection visits, but we have observed a higher rate locally. To evaluate overall safety and identify patterns and potential risk factors, we reviewed SR at two of our clinical sites.

We recently read with great interest the report authored by Nguyen et al1Nguyen A.P. Kong J.S. Teuber S.S. Severe topical corticosteroid withdrawal syndrome from over-the-counter steroids.J Allergy Clin Immunol Pract. 2021; 9: 4147-4148Google Scholar regarding a possible severe topical corticosteroid (TCS) withdrawal syndrome (TCWS) case presenting in an adult with chronic atopic dermatitis using low-dose topical corticosteroids. TCWS is a rare entity, with the current literature remaining sparse and exhibiting low quality of evidence. As discussed in the National Eczema Association systematic review of topical corticosteroid withdrawal, this distinct clinical adverse event is likely correlated to the improper use of TCSs.2Hajar T. Leshem Y.A. Hanifin J.M. Nedorost S.T. Lio P.A. Paller A.S. et al.(the National Eczema Association Task Force). A systematic review of topical corticosteroid withdrawal (“steroid addiction”) in patients with atopic dermatitis and other dermatoses.J Am Acad Dermatol. 2015; 72: 541-549Google Scholar As with the use of any medication, common and rare adverse events are important points of discussion. TCSs consistently demonstrate efficacy in improving skin lesion severity and quality of life in patients with inflammatory skin conditions.3Eichenfield L.F. Tom W.L. Berger T.G. Krol A. Paller A.S. Schwarzenberger K. et al.Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies.J Am Acad Dermatol. 2014; 71: 116-132Google Scholar They are considered the first-line therapy for patients with atopic dermatitis and with appropriate step-up and step-down approaches have an excellent safety profile—this is especially true for low-potency TCSs such as class VII hydrocortisone used in the highlighted case. In spite of TCWS being a poorly characterized disorder, there is a growing presence in social media. Importantly, there is a need to mitigate the spread of misinformation, which can lead to unnecessary avoidance of an important treatment mainstay of several dermatologic conditions and delay in diagnoses and increase unnecessary anxiety. Importantly as stated above, TCWS is a rare disorder lacking clear diagnostic criteria and should be considered a diagnosis of exclusion. Indeed, it is a diagnosis that requires careful consideration because overdiagnosis may lead to health care professionals avoiding prescribing safe and inexpensive TCSs and negatively impact patient adherence and acceptance of an important therapeutic option. Clinically, TCWS tends to present predominantly with burning/stinging as the primary symptom, rather than the intense pruritis with oozing and crusting, fever, and malaise as described in the patient in this article. In making the diagnosis of TCWS, it is important to note other clinical entities in the differential diagnosis including flaring atopic dermatitis, allergic contact dermatitis, drug hypersensitivity reactions, infectious causes, and cutaneous T-cell lymphoma, all of which are possibilities in the referenced patient. Patch testing may be warranted given the possibility of an allergy to the steroid molecule itself or a cream excipient versus other potential triggers. Histopathology may also be helpful and is essential for excluding some entities in the clinical differential diagnosis. Although it is possible that the case presented by Nguyen et al is an atypical presentation of a rare disorder, we have concerns that in this particular case the correct diagnosis was not established given the lack of diagnostic evaluation such as biopsy or patch testing. Clinical guidelines support that TCSs, when used appropriately, remain key to the management of inflammatory skin conditions. Given the rarity of this condition and lack of high-quality evidence, the diagnosis of TCWS should remain a diagnosis of exclusion handled with caution to avoid unnecessary deviation from the standard of care. Reply to “Severe topical corticosteroid withdrawal syndrome or enigmatic drug eruption?”The Journal of Allergy and Clinical Immunology: In PracticeVol. 10Issue 4PreviewWe thank Tracy et al1 for their comments regarding our report on topical corticosteroid withdrawal syndrome (TCWS) as it provides an opportunity to further elaborate on TCWS as a diagnosis. As allergists and immunologists, we are no strangers to the use of corticosteroids via all routes of administration. We certainly continue to use corticosteroids on a day-to-day basis for our patients for a myriad of conditions. This relative comfort with our mainstay of therapy, however, should not leave us complacent. Full-Text PDF

Background: Vicilin seed storage proteins are translated with N-terminal leader sequences (LSs) that are cleaved to yield the mature protein. These LSs were thought to be unstructured and rapidly degraded. However, Ara h 1 and Jug r 2 LS (A1LS, J2LS) have been identified in seeds, and immunodominant IgE epitopes detected. Here, common sequences containing structured CxxxC-repeat motifs were identified as potential mediators of IgE cross-reactivity despite very low (17%) sequence identity. Method: Linear IgE epitopes were identified by peptide microarrays, in which overlapping 15-mer peptides on glass slides, were incubated with sera from peanut, walnut or dual allergic individuals. Similar epitopes were computationally predicted. Peanut A1LS and walnut J2LS fragments (J2.1, J2.2, J2.3) each with a CxxxC vicilin LS motif were identified, cloned, expressed, purified and their structures solved using solution-NMR to locate and assess epitopes on the structure. Results: A1LS and J2LSs reveal similar helix-turn-helix motifs connected by disulfide bonds between adjacent CxxxC repeats forming α-hairpin structures. Peanut-allergic IgE bound more frequently to the J2LSs, regardless of walnut allergic status or A1LS binding. IgE binding pattern to peptides from both J2LS and A1LS, along with structure and computational predictions, suggest that the structure and conserved amino acid properties of peptides determine cross-reactivity. The properties of LS IgE epitopes were closely related to epitopes in 2S albumins. Conclusion: The shared α-hairpin structure is a stable scaffold that contributes to cross-reactivity despite low sequence identity. Biophysical properties are a better predictor of distant cross-reactivity than traditional measures of evolutionary conservation.

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 COM prehensive P rotein A llergen RE source (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

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.

The prevalence of food allergy (FA), including peanut allergy (PA), has been on the rise around the globe. Although the prevalence of FA is greater in childhood, FA can develop at any age, and this is true for PA. Regardless of the age of onset, PA can lead to significant morbidity, impaired quality of life, and higher health care costs. The increase in PA over time is likely due to a combination of rising prevalence in children with spontaneous resolution in only 20%,1Skolnick H.S. Conover-Walker M.K. Koerner C.B. Sampson H.A. Burks W. Wood R.A. The natural history of peanut allergy.J Allergy Clin Immunol. 2001; 107: 367-374Abstract Full Text Full Text PDF PubMed Scopus (443) Google Scholar along with the possibility of adult-onset PA. Although epidemiological data cannot explain causal relationships, it can assist in diagnosis, prognosis, and the general management of FA, which changes with the age and life conditions of the food-allergic individual. For example, in the early 2000s, the LEAP study team found that the risk of developing PA was 10 times higher among Jewish children in the United Kingdom as compared with Israeli children with similar ancestry and presumably similar genetic background.2Du Toit G. Katz Y. Sasieni P. Mesher D. Maleki S.J. Fisher H.R. et al.Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy.J Allergy Clin Immunol. 2008; 122: 984-991Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar This was attributed to early consumption of peanut in infancy by Israeli children and became the foundation of the landmark Learning Early About Peanut Allergy or LEAP study, which has shaped our understanding of not only PA, but FA in general, and our current guidelines for primary prevention. Accurately determining the prevalence of FA is difficult and depends on numerous factors, including the definition of allergy, the characteristics of the study population, the foods included, geographic location, dietary and environmental exposure, economic status, and more. Estimation of FA prevalence in adults is even more difficult to determine due to factors such as development of natural tolerance, cross-reactivity, including pollen-food syndrome, and adults frequently self-diagnosing and pursuing dietary elimination in the absence of a formal diagnosis by an allergist. This is further complicated by the overuse of IgE food panels in primary care and by direct-to-consumer food allergy and "sensitivity" testing, leading to overdiagnosis of FA in both medical and home settings. To date, there have been few studies evaluating the prevalence of FA in adults, with there being heterogeneity in design and varied results, some of which are presented in Table I.Table IAdult FA studiesStudy country and when surveyedAdult PA prevalenceAdult FA prevalenceOverall FA prevalenceData collection and commentsReferencesCanada 2008-20090.78%8.34%8.07%Cross-sectional telephone survey of the general population; SCAAALR study of 9667 individuals from 10 Canadian provinces, including 7469 adults. Different prevalence estimates were made: adult FA prevalence dropped to 6.58% and total to 6.67% if milk, egg, wheat, and/or soy allergy in adults were excludedSoller L, Ben-Shoshan M, Harrington DW, Fragapane J, Joseph L, St Pierre Y, et al. Overall prevalence of self-reported food allergy in Canada. J Allergy Clin Immunol 2012;130:986-8.Canada 2010-20110.4%-1.1%NA6.4%-8.9%The SPAACE study, using 2006 Canadian Census data, was a random telephone survey of 5734 households (15,022 participants), which targeted vulnerable Canadians (ie, those of low income, New Canadians, and of self-reported Aboriginal identity)Soller L, Ben-Shoshan M, Harrington DW, Knoll M, Fragapane J, Joseph L, et al. Prevalence and predictors of food allergy in Canada: a focus on vulnerable populations. J Allergy Clin Immunol Pract 2015;3:42-9.EU 2005-2009•Athens•Reykjavik•Utrecht•Lodz•Madrid•Zurich0%-0.45%0.3%1.4%2.1%2.8%3.3%5.6%2%-37% for 24 foods1%-19% for any foodA multicenter cross-sectional study (2005-2009) of the general population, with a combination of self-reported FA and matching IgE-sensitization and of confirmed FA (diagnosed by double-blind placebo-controlled food challenge) in adults across Europe, using the EuroPrevall 2009 data (adults aged 20-54 y), 81.6% of which had PFSLyons SA, Burney PGJ, Ballmer-Weber BK, Fernandez-Rivas M, Barreales L, Clausen M, et al. Food allergy in adults: substantial variation in prevalence and causative foods across Europe. J Allergy Clin Immunol Pract 2019;7:1920-8.Israel 20160.14%0.67%NAA study of 12,592 Israeli adults (aged 17-18 y) that included OFCs confirmed a prevalence of 0.67%, with tree nuts 0.28% > milk 0.16% > peanut > fish > sesame > egg 0.015% as most common adult food allergens. All recruits were from 1 urban area recruitment center of the Israel Defense Forces over a period of 6 moNachshon L, Schwartz N, Elizur A, Schon Y, Cheryomukhin M, Katz Y, et al. The prevalence of food allergy in young Israeli adults. J Allergy Clin Immunol Pract 2019;7:2782-9.India 2009-20150.01.2%NARandom screening of 11,791 adults aged 20-54 y in South India. Case-control study of 236 cases and 352 controls. Part of EuroPrevall-INCO. FA defined as +sIgE and self-reported adverse symptoms. Cow's milk (0.5%) and apple (0.5%) accounted for mostMahesh PA, Wong GWK, Ogorodova L, Potts J, Leung TF, Fedorova O, et al. Prevalence of food sensitization and probable food allergy among adults in India: the EuroPrevall INCO study. Allergy 2016;71:1010-9.Kuwait 20171.6%5.4%NAA total of 974 paper questionnaires were distributed to Kuwait University students (mean age, 20.7 y), 865 returned. Probable FA in 47 who reported being diagnosed by a physician who used 1 or more confirmatory tests. 14% were onset age 16-19 y, but all PA was earlier onsetAli F. A survey of self-reported food allergy and food-related anaphylaxis among young adult students at Kuwait University. Med Princ Pract 2017;26:229-34.Saudi Arabia 20203%19.7%NAA nationwide (13 regions) cross-sectional survey conducted via phone interviews in June 2020; 4709 (75.48%) participants completed the interview. Most common self-reported FAs were egg 3.7% > shellfish > peanut 3%. No questions were asked to ascertain for IgE-mediated symptoms or physician diagnosis of food allergyAlthumiri NA, Basyouni MH, Al Mousa N, Al Juwaysim MF, BinDhim NF, Alqahtani SA. Prevalence of self-reported food allergies and their association with other health conditions among adults in Saudi Arabia. Int J Environ Res Public Health 2021;18:347.Saudi Arabia 2008-2018NR9.6% (19.2% adult-onset)NAAn online survey-based cross-sectional study of 5497 students surveyed regarding presence and age of onset of FA. Of the 526 students who had a positive screening history, 174 students had clinically diagnosed FA, of which 19.2% had adult onset of FA and 38% did not have epinephrine at the time of their most recent reactionHassan A, Alsaihati A, Al Shammari M, Alaithan H, Al-Johani W, Al Shamlan N, et al. AACI Food allergy among university students: uncharted territory. Allergy Asthma Clin Immunol 2020;16:1-6.US 20020.6%1.3% any nutNAA nationwide, cross-sectional, random telephone survey using a standardized questionnaire that included 4855 households, a census of 13,493 individuals. A male dominance in children with peanut/tree nut allergy and a female dominance in adults with a 1.4% peanut-tree nut or both overallSicherer SH, Munoz-Furlong A, Sampson HA. Prevalence of peanut and tree nut allergy in the US determined by means of a random digit dial telephone survey. J Allergy Clin Immunol 2003;112:1203-7.US 2005-20061.3%0.9%-1.2%2.5% for 4 foods 0.6% in >60-y-oldsA total of 8203 participants in the National Health and Nutrition Examination Survey 2005-2006 had food-specific serum IgE measured to peanut, cow's milk, egg white, and shrimp. Estimated clinical FA in order was 2.5% (peanut + milk + shrimp + egg). In order: peanut 1.3% > shrimp > milk > egg 0.23%Liu AH, Jaramillo R, Sicherer SH, Wood RA, Bock SA, Burkset AW, et al. National prevalence and risk factors for food allergy and relationship to asthma: results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol 2010;126:798-806.US 2007-20100.9%9.7%9%Self-reported FA from a US population-based door-to-door survey conducted between 2007 and 2010. Self-reported FA was compared with the subjects who reported consumption of milk, shellfish, fish and peanutMcGowan EC, Keet CA. Prevalence of self-reported food allergy in the Health and Nutrition Examination Survey (NHANES) 2007-2010. J Allergy Clin Immunol 2013;132:1216-9.US 2015NA (9% adult-onset)NA (15% adult-onset)NANot a population study, but a retrospective chart review of 1111 adults with FA physician diagnosis in Chicago; 171 cases were adult-onset. They excluded PFS. Patient eligibility required a positive SPT result. FAs in order: shellfish 54%, tree nuts > finfish > soy > peanut 9%Kamdar Peterson S, Lau CH, Saltoun CA, Gupta RS, Bryce PJ. Prevalence and characteristics of adult-onset food allergy. J Allergy Clin Immunol Pract 2015;3:114-5.US 2015-20161.8%10.8% (48% adult-onset)NAA nationally representative, cross-sectional FA survey via telephone and web in 2015 and 2016, resulting in complex-survey weighted data for 40,443 adults. Reported higher-than-anticipated numbers of adults with convincing adult-onset FA to "childhood" allergens. FA order: shellfish 2.9% > milk > peanut > tree nut > fin fish 0.9%. Reported 39% with 1 ED visit/life and 9% 1 ED visit/that year. Nearly 19% of adults believed they had FA, but only 10.8% were "convincing"Gupta RS, Warren CM, Smith BM, Jiang J, Blumenstock JA, Davis MM, et al. Prevalence and severity of food allergies among US adults. JAMA 2019;2:e185630.US 2015-20161.8% (17.5% adult-onset)10.8%NASame database as above; 2.9% reported PA, but only 1.8% were convincingWarren et al3Warren C. Lei D. Sicherer S. Schleimer R. Gupta R. Prevalence and characteristics of peanut allergy in US adults.J Allergy Clin Immunol. 2021; 147: 2263-2270.e5Abstract Full Text Full Text PDF PubMed Scopus (4) Google ScholarED, Emergency department; EuroPrevall-INCO, EuroPrevall International Cooperation; NA, not applicable; OFC, oral food challenge; PFS, pollen-food syndrome; SCAAALAR, Surveying Canadians to Assess the prevalence of food Allergies and Attitudes towards food Labelling and Risk; sIgE, specific IgE; SPAACE, Surveying Prevalence of Food Allergy in All Canadian Environments; SPT, skin prick test.Adult onset: where data are available, adult onset for FA is indicated in the table. Open table in a new tab ED, Emergency department; EuroPrevall-INCO, EuroPrevall International Cooperation; NA, not applicable; OFC, oral food challenge; PFS, pollen-food syndrome; SCAAALAR, Surveying Canadians to Assess the prevalence of food Allergies and Attitudes towards food Labelling and Risk; sIgE, specific IgE; SPAACE, Surveying Prevalence of Food Allergy in All Canadian Environments; SPT, skin prick test. Adult onset: where data are available, adult onset for FA is indicated in the table. Given the many unanswered questions regarding adult PA, Warren et al3Warren C. Lei D. Sicherer S. Schleimer R. Gupta R. Prevalence and characteristics of peanut allergy in US adults.J Allergy Clin Immunol. 2021; 147: 2263-2270.e5Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar published a large study in the journal determining the prevalence and characteristics of PA in US adults (included in Table I). They demonstrate the prevalence of adult PA to be significantly higher than previously reported, with differences in PA based on adult versus childhood age of onset, and that 17.5% of adults with convincing PA developed PA in adulthood.3Warren C. Lei D. Sicherer S. Schleimer R. Gupta R. Prevalence and characteristics of peanut allergy in US adults.J Allergy Clin Immunol. 2021; 147: 2263-2270.e5Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Key findings include that despite similar demographic characteristics and symptoms among childhood and adult onset of PA, those with adult-onset PA are less likely to carry an epinephrine autoinjector and are more likely to treat reactions with antihistamines. There are also higher levels of adult females with childhood-onset PA, indicating that females may be less likely to outgrow childhood PA. Adults with PA were more likely to be female, nonwhite, and have more self-reported comorbid atopic conditions than adults without PA. In the case of children, factors such as timing and exposure through the skin or inhalation before known ingestion have been shown to contribute to development of PA, whereas early oral ingestion has been shown to be preventative. Exposures via skin,4Minami T. Fukutomi Y. Sekiya K. Akasawa A. Taniguchi M. Hand eczema as a risk factor for food allergy among occupational kitchen workers.Allergol Int. 2018; 67: 217-224Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar respiratory mucosa (pollen-food syndrome), and gut, in addition to sex,3Warren C. Lei D. Sicherer S. Schleimer R. Gupta R. Prevalence and characteristics of peanut allergy in US adults.J Allergy Clin Immunol. 2021; 147: 2263-2270.e5Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar vitamin D deficiency,5Kim S.H. Ban G.Y. Park H.S. Kim S.C. Ye Y.M. Regional differences in vitamin D levels and incidence of food-induced anaphylaxis in South Korea.Ann Allergy Asthma Immunol. 2016; 116: 237-243.e1Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar comorbid conditions,6Lyons SA, Knulst AC, Burney PGJ, Fernandez-Rivas M, Ballmer-Weber BK, Barreales L, et al. Predicting food allergy: the value of patient history reinforced [published online ahead of print September 7, 2020]. Allergy. https://doi.org/10.1111/all.14583.Google Scholar and occupational and environmental7Fukutomi Y. Occupational food allergy.Curr Opin Allergy Clin Immunol. 2019; 19: 243-248Crossref PubMed Scopus (5) Google Scholar exposures, have been implicated in the development of FA in adults. Although the report by Warren et al3Warren C. Lei D. Sicherer S. Schleimer R. Gupta R. Prevalence and characteristics of peanut allergy in US adults.J Allergy Clin Immunol. 2021; 147: 2263-2270.e5Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar offers valuable insight into adult PA, the authors acknowledge the limitations of a survey-based design and self-reported FA diagnosis in the absence of diagnostic testing. Although it is impractical to complete appropriate skin prick testing, specific IgE levels, and/or a physician-supervised oral food challenge in such a large cohort, the absence of this essential diagnostic information necessitates that the results be interpreted with caution, because it may lead to overestimating the true prevalence of PA in US adults. Woods et al8Woods R.K. Stoney R.M. Raven J. Walters E.H. Abramson M. Thien F.C. Reported adverse food reactions overestimate true food allergy in the community.Eur J Clin Nutr. 2002; 56: 31-36Crossref PubMed Scopus (120) Google Scholar demonstrated minimal agreement between self-reported FA and the presence of sensitization based on skin prick test, with only 1.5% of adults likely to have a "true FA" based on these criteria.8Woods R.K. Stoney R.M. Raven J. Walters E.H. Abramson M. Thien F.C. Reported adverse food reactions overestimate true food allergy in the community.Eur J Clin Nutr. 2002; 56: 31-36Crossref PubMed Scopus (120) Google Scholar Similarly, Fleischer et al9Fleischer D.M. Bock S.A. Spears G.C. Wilson C.G. Miyazawa N.K. Gleason M.C. et al.Oral food challenges in children with a diagnosis of food allergy.J Pediatr. 2011; 158: 578-583.e1Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar showed that in individuals aged 1 to 19 years, 84% were able to tolerate a food despite there being a reported history of food reaction, including 76% of those with reactions involving the skin, 18% with respiratory reactions, and even 5% of patients with anaphylaxis. In 2020, Solymosi et al10Solymosi D. Sardy M. Ponyai G. Interdisciplinary significance of food-related adverse reactions in adulthood.Nutrients. 2020; 12: 3725Crossref Scopus (2) Google Scholar conducted a prospective evaluation of FA in adults and found only 1% to have a physician-diagnosed FA, despite many individuals reporting symptoms of acute urticaria on exposure to a culprit food. We commend the authors for using stringent symptoms (see Fig E1 in this article's Online Repository at www.jacionline.org), which led to a convincing history of FA, but note that many of these symptoms are subjective (difficulty swallowing, throat tightening, chest tightening, trouble breathing, rapid heartbeat, etc), and routinely encountered in clinical practice even in the absence of IgE-mediated allergic reactions. In addition, the results in Table V in Warren et al suggest that a significant percentage of adults who report adult-onset PA also report adult onset of allergy to other foods, such as cow's milk (17.3%), egg (10.1%), wheat (13.7%), and soy (17.7%). These results mirror previous studies citing self-reported allergies but are contrary to the typically accepted natural history of FA, where these specific food allergies are almost exclusively diagnosed in early childhood, with most resolving by adolescence. However, we can hypothesize that these adults, because they report significantly higher environmental allergies, might have had IgE-facilitated antigen presentation to plant-derived food proteins that initially were recognized because of pollen-food cross-reactivity, but now have IgE directed to other epitopes and a progression beyond oral allergy syndrome. The high prevalence of tree nut, wheat, and soy allergy could be supported by this hypothesis, but the high level of milk and egg allergy is not. The prevalence of adult FA, including PA, can have important impacts on both the individual and community, and as clinicians, we must therefore take all measures to make an accurate diagnosis of PA regardless of age. Although survey-based studies have limitations, they have advantages as well. Large survey-based results are more likely to assess characteristics, such as socioeconomic determinants and prevalence of FA in underrepresented populations, as apparent in the study by Warren et al in which Asians, blacks, and Hispanics were significantly overrepresented in the group with PA compared with adults without current PA.3Warren C. Lei D. Sicherer S. Schleimer R. Gupta R. Prevalence and characteristics of peanut allergy in US adults.J Allergy Clin Immunol. 2021; 147: 2263-2270.e5Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Such surveys do not have to contend with recruitment-associated challenges such as cost, time, convenience, and location-dependent demographics involved with a physician-based diagnosis, particularly in adults. Indeed, this may be an acceptable or desirable method to specifically target studies to the less-reachable populations, as described in the self-reported food allergy survey of vulnerable populations in Canada (Table I). Despite limitations, the study by Warren et al is an important epidemiological study with novel insights into PA in US adults, an area of unmet need. The study stresses the need for future research into numerous aspects of adult FA, including prevalence, demographic characteristics, impact on quality of life, and appropriate treatment options, along with the differences between adult and childhood-onset FA. Prevalence and characteristics of peanut allergy in US adultsJournal of Allergy and Clinical ImmunologyVol. 147Issue 6PreviewPeanut allergy (PA) is the leading pediatric food allergy and a common cause of anaphylaxis. Little is known, however, on the prevalence and characteristics of PA in the adult population and whether phenotypic differences exist between adult-onset and childhood-onset PA. Full-Text PDF

Oral immunotherapy (OIT) studies have demonstrated decreased sensitization to a target allergic tree nut as well as cross-desensitization with other similar tree nuts. Walnut OIT results in high rates of desensitization to pecan, yet lower rates of desensitization to other tree nuts such as hazelnut and cashew. We hypothesize that OIT driven cross-desensitization occurs more frequently between similar tree nuts due to immunoglobulin E (IgE) binding to sequentially different, yet homologous epitopes. We collected serum from patients allergic to walnut, pecan, hazelnut, and/or cashew. We measured IgE binding to tree nut allergens using linear peptide microarrays. We identified the major epitopes recognized by tree nut-allergic individuals and measured their similarity to known and newly identified walnut epitopes using the Structural Database of Allergenic Proteins (SDAP). Common homologous and cross-reactive epitopes were identified, aligned, and compared among walnut, pecan, hazelnut, and cashew. Many walnut epitopes were recognized by pecan, hazelnut and/or cashew-allergic individuals. We identified several epitopes recognized only by hazelnut and/or cashew-allergic individuals. Walnut epitopes recognized by pecan, hazelnut, and/or cashew-allergic individuals may underlie cross-reactions and cross-desensitization during walnut OIT. Epitopes uniquely shared among certain tree nuts, for example, those recognized by cashew or hazelnut, but not walnut or pecan-allergic individuals may be valuable for targeted multi-tree nut therapeutics. These results may also help identify those hazelnut or cashew-allergic individuals who would benefit from walnut OIT due to their recognition of walnut homologous epitopes.

A 34-year-old man suddenly developed an erythematous and exfoliative facial rash. Within days, his skin became intensely pruritic and painful, and the rash spread to his entire body. He also acquired malaise with fever of 39.7°C, necessitating hospitalization. Examination revealed thickened and oozing plaques covering his face; in addition, multiple erythematous papules erupted on his torso and bilateral extremities, but no mucosal erosions (Figure 1). His history was notable for lifelong atopic dermatitis self-treated with hydrocortisone ointment/cream 1% (up to 2.5%) multiple times daily, with use of class III potency topical corticosteroids (TCS) intermittently for flares.

IgE testing for foods in individuals who do not have a history consistent with food allergy (FA) has a high false positive rate. This results in anxiety, inappropriate diets, and is a waste of healthcare resources. Retrospective chart review of patients ages 0 to 18 years for whom food IgE levels were ordered in a single institution over a fifteen-month period. Fisher's exact test was used for calculating significance. 263 charts were reviewed. 113 "food allergy" panels were ordered through pediatrics (69%) or family medicine (31%). Only 3 patients had symptoms highly supportive of IgE-mediated FA. 76% had symptoms unlikely to be due to FA, such as behavioral issues or abdominal pain. Twenty-nine (26%) were advised to eliminate foods based on testing, and 27 patients were eventually seen by allergy – of those, 5 (18.5%) were advised to continue avoiding a food. 150 patients had targeted sIgE testing. 58% had histories highly suggestive of FA and 17% of patients (compared to 76% above, p < .001) had symptoms unlikely to be related to FA. 72% were eventually seen by allergy, and of these, 73% were advised to continue to avoid the food (compared to 18.5% above, p < .01). Indiscriminate use of food specific IgE testing is still prevalent, especially through the use of "food allergy" panels for nonspecific symptoms that resulted in unnecessary food elimination.

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.

While mast cells have been implicated in human disease since the early 1900s, mast cell activation syndrome (MCAS) was only recently discovered and recognized as a disorder caused by aberrant release of mast cell mediator enzymes. These mediators trigger a wide variety of symptoms ranging from headache, pruritis and gastrointestinal discomfort to life-threatening anaphylaxis. MCAS is frequently unrecognized and misdiagnosed because symptoms associated with MCAS are often present in other medical conditions and are highly variable among patients. We describe a case of a 62-year-old male who presented to the emergency department (ED) with three days of recurrent flushing, diarrhea, mild edema of his hands bilaterally, and severe emotional lability with recurrent crying. In the ED, he was misdiagnosed with severe anxiety and directly sent to a mental health clinic for assistance. However, he was previously seen in allergy clinic for suspected MCAS. Fortuitously standing labs including plasma histamine, tryptase, and urine studies that were ordered in allergy clinic were drawn concurrently with the initial ED workup. He was found to have elevated histamine level during his ED episode and treatment for MCAS was initiated. In subsequent visits, his symptoms, except for episodes of “brain fog” and emotional lability, improved significantly on a combination of antihistamines, oral cromolyn sodium, and montelukast. Additionally every other day prednisone has substantially cleared the neurocognitive symptoms. This case highlights the difficulty of MCAS diagnosis and the importance of assessing for MCAS, especially in patients who have multisystem complaints.

The needle length of epinephrine autoinjectors (EIA) is not adequate for IM injection in some patients, but pressure on an ultrasound transducer in previous reports, to mimic activation pressure, decreased the skin-to-muscle distance. We have extended these observations by using a standardized method of compression to confirm that compression can change the skin-to-muscle distance. Convenience sample of adult patients who consecutively agreed to participate in the study. The protocol was approved by the IRB. Demographic data were obtained, including height and weight. The skin-to-muscle distance at a consistent location on the right anterolateral thigh was calculated with and without addition of a 7 lb weight to an endovaginal ultrasound transducer which was a similar size to an EIA. Eighty-three consented to participate: 58 female, 25 male, mean age 49.7 years (5 African-American, 4 Asian, 57 Caucasian, 3 Filipino, 11 Hispanic, 3 Other). Thirty-three of 83 (40%) had a calculated BMI >30. At baseline without compression, 39 of 83 (47%) had a skin-to-muscle distance >1.59 cm, but this decreased to only 7 of 83 (8.4%) with compression. All 7 were female, with a mean calculated BMI of 33.9, range 25-51.5. With the addition of a 7 pound weight to the transducer to mimic the force needed to activate an EIA, 32 of the 39 patients (82%) with a baseline skin-to-muscle distance >1.59 cm now were in the range for intramuscular penetration of the most commonly prescribed EIA containing a 0.3 mg dose in the United States.

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.

Peanut allergy continues to be a problem in most developed countries of the world. We sought a processing method that would alter allergenic peanut proteins, such that allergen recognition by IgE from allergic individuals would be significantly reduced or eliminated. Such a method would render accidental exposures to trace amounts of peanuts safer. A combination of boiling and frying decreased recovery of Ara h 1 and Ara h 2 at their expected MWs. In contrast, treatment with high pressures under varying temperatures had no effect on protein extraction profiles. Antibodies specific for Ara h 1, Ara h 2, and Ara h 6 bound proteins extracted from raw samples but not in boiled/fried samples. However, pre-incubation of serum with boiled/fried extract removed most raw peanut-reactive IgE from solution, including IgE directed to Ara h 1 and 2. Thus, this method of processing is unlikely to generate a peanut product tolerated by peanut allergic patients. Importantly, variability in individual patients' IgE repertoires may mean that some patients' IgE would bind fewer polypeptides in the sequentially processed seed.

Many peanut allergic individuals also have allergies to tree nuts. Our previous work has shown that there are epitopes with different amino acid sequences, but similar physical and chemical properties that are recognized by the same IgE molecule. Anti-Ara h 2 monoclonal antibodies were produced. They were epitope mapped and the binding sites shown by molecular modeling. Western blots were used to test the binding of these monoclonals to almond, cashew, peanut, pistachio, soy, green pea and walnut extracts and to purified Jug r 2 leader sequence, Jug r 1 and Ara h 2 and Ara h 6. Proteins in the reactive bands were identified by mass spectrometry. These monoclonal antibodies were tested for their ability to compete with IgE for binding to Ara h 2 by ELISA and histamine release assays. Searching the Structural Database for Allergic Proteins (SDAP) and empirical determination of the cross-reactive allergens in different nuts, revealed many potential IgE epitopes with similar physicochemical properties in nut allergens. Specific, anti-Ara h 2 monoclonal antibodies, made against surface exposed areas of native Ara h 2 recognized vicillins, conglutinins, and glycinins in multiple nuts. Four of the monoclonals were highly reactive with Jug r 2 leader sequence, and all recognized Jug r 1. Most of the monoclonals competed for IgE binding to Ara h 2 and prevented histamine release by Ara h 2 to different extents. The presence of highly cross reactive, repeat peptide motifs is confirmed here and we produced monoclonal antibodies that inhibit IgE binding to these sequences.

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.