Karen Thursday S. Tuano

Utility of Component-Resolved Diagnostics in Food Allergy

Allergen component-resolved diagnostic testing (CRD) is a new methodology in clinical food allergy diagnosis, improving the ability to identify specific clinical phenotypes. Instead of relying on the crude allergen extracts used in standard allergy diagnostics, CRD utilizes purified or recombinant allergens for identification of specific molecules causing sensitization or allergy. This method is able to determine risk of the severity of allergic reactions in specific cases, like soy, peanut, and hazelnut allergy. The severity of allergic reaction can be predicted in peanut allergy with Ara h 2, and clinically relevant disease in pollen-allergic patients can be identified. However, age and geographic differences affect CRD results and it should always be utilized in the context of a clinical history. In the future, clinical phenotypes may be differentiated with larger prospective studies utilizing food challenges.

Food allergy in patients with primary immunodeficiency diseases: Prevalence within the US Immunodeficiency Network (USIDNET)

To the Editor: Primary immunodeficiency diseases (PIDDs) are congenital disorders caused by inherent defects in the immune system that typically present with recurrent or severe infections but can also involve autoimmune disease, lymphoproliferation, or allergy.1 Allergic diseases are an important expression of misdirected immunity, and certain PIDDs are frequently associated with atopy. Selective IgA deficiency (SIgAD) has been associated with asthma, allergic rhinitis, atopic dermatitis (AD), and food allergy (FA).2-4 AD/eczema with an increased IgE level is often associated with hyper-IgE syndrome (HIES), Omenn syndrome, immune dysregulation–polyendrocrinopathy–enteropathy–X-linked syndrome, and Comel-Netherton syndrome, whereas 80% to 100% of patients with Wiskott-Aldrich syndrome (WAS) present with AD-like skin problems4,5 and many have evidence of food reactivity. However, there are no definitive data in the United States on the overall prevalence of food allergies as a specific expression of clinically relevant atopy in patients with PIDDs. We present the first broad consideration of the prevalence of FA in patients with PIDDs using the US Immunodeficiency Network (USIDNET). The USIDNET is a research consortium established to advance scientific research in PIDDs.6 A query of 2923 patients with PIDDs registered in the USIDNET was performed to determine the responses to fields in the core registry form relevant to “allergic reactions to food” and “AD/eczema,” which were then cross-referenced to diagnosis. AD/eczema was included in the query as another manifestation of atopy. Of 2923 patients registered, 2263 provided responses to the relevant fields (allergic reactions to food and AD/eczema). There were 14 diagnoses associated with FA, AD, or both (Table I). Surprisingly, in aggregate, the prevalence of both FA and AD in patients with PIDDs (FA, 1.8%; AD, 6%) was lower than that in the general population (FA, 2.5%; AD, 10.7%; Fig 1).7,8 This stands in contrast to experience in other countries, such as Kuwait, where 19% of patients with PIDDs have FA.4 Currently, there are no other prevalence data available for FA and AD in the United States, and the USIDNET experience potentially distinguishes American patients from those in other countries or reflects the experience of those centers and clinics in the United States contributing data to the USIDNET. FIG. 1 Prevalence of FA and AD among patients with PIDDs compared with the general population. TABLE I Prevalence of FA and AD among patients with PIDDs Despite there not being an overall increased prevalence, FA was more commonly reported in patients with specific PIDDs when compared with what would be expected in the general population. This included patients with CD40 ligand deficiency (7.7%), primary hypogammaglobulinemia (7.1%), and HIES (6.3%). There was also an increased prevalence in patients with combined immunodeficiency (CID; 33.3%) and SIgAD (25%), but there were very few of these patients in the registry. Reported reactions include anaphylaxis, angioedema, asthma, bronchospasm, dermatitis, unspecified gastrointestinal reactions, and urticaria, with the most frequent being anaphylaxis (20%). Seventeen of the 40 patients with FA did not have a specified type of allergic reaction. Meanwhile, AD was most commonly reported in patients with nuclear factor κB essential modulator deficiency (62.5%), WAS (41.5%), CID (33.3%), selective IgM deficiency (33.3%), and HIES (25%). PIDDs that were associated with both FA and AD included common variable immunodeficiency (CVID), CID, and HIES. Despite the low numbers of patients, FA was found in 25% of those with SIgAD, which is similar to the findings (30%) of Aghamohammadi et al9 in a prospective cohort of Iranian patients with SIgAD and self-reported FA. In another prospective study children with SIgAD had an increased risk of parentally reported food hypersensitivity at 4 years of age.2 Because the majority of patients with SIgAD have substitution of secretory IgA with secretory IgM, it is not known whether they have adequate mucosal protection. This might allow food antigens to pass more efficiently through the gastrointestinal mucosa and predispose patients with SIgAD to FA. On the other hand, AD was not present in patients with SIgAD at the time of our query. It is possible that patients with SIgAD have a higher incidence of pure IgE-mediated rather than mixed or non–IgE-mediated manifestations of disease. The reports on AD in patients around the world with SIgAD are conflicting. In the Iranian cohort AD was present in 52% of patients with SIgAD,9 whereas it was found in only 2.3% of Brazilian patients with SIgAD.2 This discrepancy might be due to differing physician algorithms for AD diagnosis. In another study from Sweden by Janzi et al,2 parentally reported eczema was not associated with SIgAD. Other diagnoses associated with FA-related disease were more prevalent than in the general presentation, such as CD40 ligand deficiency, hypogammaglobulinemia, HIES, WAS, and CVID. HIES and WAS are associated with increased IgE levels and increased sensitization to specific food antigens. However, a limitation in this query is that genetic diagnosis of HIES was not further characterized, thus allowing for inclusion of patients with increased IgE levels for reasons other than signal transducer and activator of transcription 3, dedicator of cytokinesis 8, or tyrosine kinase 2, some of which might be purely atopic in nature. These molecularly defined PIDDs, except for primary hypogammaglobulinemia, are definitively associated with the substantially altered or defective T-cell immunity necessary for oral tolerance. This deficient immune regulation can lead to a skewed response, resulting in atopic disease. The high prevalence of FA in patients with primary hypogammaglobulinemia might suggest a concomitant T-cell dysfunction in these cases. Importantly, the number of patients with FA, AD, or both registered in the USIDNET at the time of the query was small, and this might underrepresent PIDDs associated with atopy. The overall lower prevalence of FA in patients with PIDDs might also be underestimated because 55% of patients had severe combined immunodeficiency, X-linked agammaglobulinemia, or CVID. A follow-up study should be undertaken in the future. Another limitation of the study is that it is based on a physician report questionnaire form; hence FA and AD rates could be overestimated. Moreover, there was a limitation in the core registry form for further description of reactions to food and AD/eczema. Manifestations of atopy, such as FA and AD, occurring early in life might be a presenting feature before diagnosis of a PIDD4,5 and, if associated with recurrent infections, should warrant clinicians to pursue an immunologic evaluation. Early diagnosis of PIDDs might have a potential benefit of better outcome. Although the prevalence of both FA and AD in patients with PIDDs is lower than in the general population, there should be a lower threshold for suspecting FA in patients with certain PIDDs.

Development of sesame tolerance and cosensitization of sesame allergy with peanut and tree nut allergy in children

linked to a broad differential diagnosis, including primary immunodeficiencies.6 Although generalized erythroderma is an uncommon presentation of zinc deficiency, the deficiency should be considered in patients who have treatment-resistant diarrhea, depression, and erosive dermatitis. Although the triad of zinc deficiency (dermatitis, diarrhea, and alopecia) is only seen in 20% of patients, it is crucial to keep zinc deficiency as part of the differential diagnosis when evaluating patients.7 As seen in this case, zinc deficiency should be regarded when evaluating patients with erythroderma, chronic diarrhea, and laboratory evidence of an acquired immunodeficiency, especially in intensive careeassociated dermatoses. This case highlights the importance of prompt diagnosis because zinc deficiency and its associatedmanifestations may respondmarkedly with adequate supplementation.

Annatto seed hypersensitivity in a pediatric patient

cause because it is often given with cyclophosphamide. Although the positive and negative predictive values of skin testing for cyclophosphamide and mesna are not well defined, it may still be worth pursuing, particularly when the culprit medication is uncertain. A 12-step desensitization protocol can be successfully implemented if there are limited options for treatment, including the pediatric population with underlying autoimmune and renal disease.

Improved diagnostic clarity in shrimp allergic non‐dust-mite sensitized patients

BACKGROUND Allergen specific immunoglobulin E (sIgE) levels predictive of shrimp allergy have not been identified, but these may be helpful in identifying patients at risk for shrimp-induced allergic reactions. OBJECTIVE This study sought to identify component resolved diagnostic tests useful for diagnosis of shrimp allergy in patients with or without house-dust mite (HDM) sensitization to the major allergen cysteine protease (Der p 1). METHODS Patients with positive skin-prick test (SPT) results and/or sIgE values were recruited. Shrimp allergy was classified by oral food challenge (OFC) or by a clear history of anaphylaxis after shrimp ingestion. Patients with shrimp allergy and patients who were tolerant were further classified based on HDM sensitivity (Der p 1 > 0.35 kUA/L). Testing for sIgE to total shrimp, and shrimp and HDM components was performed. The Fisher exact test, Wilcoxon sum rank test, and receiver operating characteristics analyses were used to compare sIgE levels in patients with allergy and patients who were tolerant. RESULTS Of 79 patients recruited, 12 patients with shrimp allergy (7 with positive OFC results and 5 with a history of anaphylaxis) and 18 patients who were shrimp tolerant were enrolled. Of the patients not HDM sensitized, sIgE levels to shrimp (10.5 kUA/L, p = 0.012) and Der p 10 (4.09 kUA/L, p = 0.035) were higher in patients with shrimp allergy. Shrimp sIgE of ≥3.55 kUA/L had 100% diagnostic sensitivity and 85.7% specificity (receiver operating characteristic 0.94 [0.81, 1.0] 95% CI) and Der p 10 sIgE levels of ≥3.98 kUA/L had a diagnostic sensitivity of 80% and specificity of 100% (receiver operating characteristic 0.86 [0.57, 1.0] 95% CI) for prediction of clinical reactivity. CONCLUSION HDM sensitization influences shrimp and HDM component sIgE levels and, consequently, their diagnostic accuracy in shrimp allergy. In our series, in the patients who were non-HDM sensitized, a shrimp sIgE level of >3.55 kUA/L showed 100% sensitivity and, Der p 10 sIgE of >3.98 kUA/L showed 100% specificity for the diagnosis of shrimp allergy. These levels may not be applicable to every patient and, therefore, may not obviate the need for OFC.

Utility of Shrimp and Der p 10 specific IgE for Shrimp Allergy Diagnosis in Non-House Dust Mite Sensitized Patients

Background There are no set specific IgE (sIgE) to predict shrimp allergy as cross-reactivity with other arthropods play a role in shrimp sensitization. Objective This study identifies the allergens associated with shrimp allergy in house dust mite (HDM) and non-HDM sensitized patients. Methods Patients with shrimp sensitization (positive skin prick test [SPT] and/or sIgE) with/without history of clinical reaction were recruited. Allergy was confirmed by oral food challenge (OFC) except for patients with history of anaphylaxis. Shrimp allergic (SA) and shrimp tolerant (ST) patients were further classified based on HDM sensitivity. The sIgE to shrimp, shrimp and HDM components were performed. Fisher’s exact test, Wilcoxon sum rank test and receiver operating characteristics analyses were done. Results Of 79 patients recruited, 12 SA (7 positive OFC and 5 with history of anaphylaxis), 18 ST and 10 non-shrimp sensitized controls (NC) were enrolled. In non-HDM sensitized patients, sIgE to shrimp (10.5 kUA/L, p=0.012) and Der p 10 (4.09 kUA/L, p=0.035) were higher in SA patients. Shrimp sIgE ≥3.55 kUA/L had 100% sensitivity and 85.71% specificity (ROC=0.94[0.81, 1.0]). Der p 10 sIgE ≥3.98 kUA/L had sensitivity of 80% and specificity of 100% (ROC=0.86[0.57, 1.0]). rPen a 1 ≥1.1 kUA/L had sensitivity of 80% and specificity of 85.7% (ROC=0.80[0.47,1.0]). Conclusions In non-HDM sensitized patients, shrimp sIgE ≥3.55 kUA/L and Der p 10 sIgE≥3.98 kUA/L give 100% sensitivity and specificity, respectively, to diagnose shrimp allergy. HDM sensitivity can influence sIgE levels to shrimp and shrimp/HDM components due to cross-reactivity.