Gluten sensitivities and the allergist: Threshing the grain from the husks.

"Gluten sensitivity" has become commonplace among the public. Wheat allergy (WA) and celiac disease (CD) are well-defined entities, but are becoming a fraction of individuals following a gluten-free diet (GFD). Wheat allergy has a prevalence of <0.5%. Wheat, specifically its omega-5 gliadin fraction, is the most common allergen implicated in food-dependent, exercise-induced anaphylaxis. CD is a non-IgE hypersensitivity to certain cereal proteins: gluten in wheat, secalin in rye, hordein in barley, and to a lesser extent avenin in oat. It is a rare disease, with an estimated prevalence that varied widely geographically, being higher in Northern Europe and the African Saharawi region than in South-East Asia. In addition to suggestive symptoms, serologic testing has high diagnostic reliability and biopsy is a confirmatory procedure. Patients with CD have extra-intestinal autoimmune comorbid conditions more frequently than expected. A third entity is nonceliac gluten sensitivity, which has been created because of the increasing number of subjects who claim a better quality of life or improvement of their variety of symptoms on switching to a GFD. The phenomenon is being fueled by the media and exploited by the industry. The lack of a specific objective test has been raising substantial controversy about this entity. Allergists and gastroenterologists need to pay attention to the multitudes of individuals who elect to follow a GFD. Many such subjects might have WA, CD, or another illness. Providing them with appropriate evaluation and specific management would be of great advantages, medically and economically.

Acute cardiac disease in a patient with hyper-IgE syndrome.

SUMMARY: We describe the case of a 24-year-old male with hyper-IgE syndrome (HIES) which was diagnosed at 4 years of age and died from a very rare cardiac complication. He had typical clinical and laboratory manifestations of HIES, including total serum IgE as high as > 100,000 IU/mL. Stem cell transplantation was not available. During the 20-year follow-up, he suffered numerous various infections of the skin and deep organs, partial lung resection, as well as multiple bone fractures. At age 24, he developed acute decompensated heart failure associated with elevated serum troponin I and brain natriuretic protein. Two-dimensional echocardiogram revealed global hypokinesis of the left ventricle with estimated ejection fraction 20-25%, and catheterization revealed ectasia of multiple coronary arteries. Endomyocardial biopsy showed lymphocytic myocarditis, focal necrosis, mild fibrosis, and myxoid degeneration, but cultures were negative. The patient improved on corticosteroid therapy and was discharged on heart failure therapy and external defibrillator. Six weeks later, he developed supraventricular tachycardia and persistent global hypokinesis and was treated with amiodarone. A trial of intravenous immunoglobulin was initiated and was repeated as outpatient every four weeks for four times. However, his cardiac function did not improve and he developed severe hypotension and pulseless electrical activity arrest. Resuscitation was unsuccessful. To the best of our knowledge, this is the first reported case of HIES complicated with lymphocytic myocarditis. Both immunologists and cardiologists need to be aware of such a complication and practice caution in using immunosuppressants when the patient's immune status is markedly compromised.

Hypersensitivities to sesame and other common edible seeds.

Several seeds have been increasingly incorporated in various food items, with consequent risk of hypersensitivity reactions that are often severe. Identification of the specific seed as the culprit is often not explored or is difficult to verify. In this article, we reviewed the English literature from January 1930 to March 2016 using PubMed and Google Scholar searching for publications relevant to hypersensitivity to common edible seeds, namely sesame, sunflower seed, poppy seed, pumpkin seed, flaxseed, and mustard seed. Considering the worldwide consumption of those seeds, the number of published articles on the subject was relatively small and was mainly as case reports rather than large series. Allergy to sesame was more reported than to other seeds, with an estimated prevalence of 0.1-0.2%. In this review, we summarize the information relevant to each of the six seeds and their oils regarding the manifestations, routes of exposure, identified major allergens, and cross-reactivity with other seeds or other foods. We also addressed the important role of a thorough history taking in suspecting seed allergy, the limited reliability of routine diagnostic procedures, and the importance of verification by appropriate challenge tests. At present, management is basically dietary avoidance and the use of symptomatic medications that may include epinephrine auto-injectors. We did not encounter any well-designed studies on immunotherapy for seed allergy, but it is hoped that such a gap be filled by the development of safe effective protocols in the near future.

Milk-induced wheezing in children with asthma

Background: Food allergy has been gaining increasing attention, mostly as causing gastrointestinal and cutaneous reactions. Its role in asthma seems to be under-recognised. Objectives: This study's aim is to explore the frequency of involvement of a common food, namely cow's milk, in childhood asthma.Methods32 children (5 months to 11 years; median 24 months; mean 34 months) with asthma and a suspected history of cow's milk allergy were studied. They underwent skin prick testing (SPT) and specific IgE (sIgE) testing to whole cow's milk (WCM), casein, α-lactalbumin, and β-lactoglobulin, followed by single-blind oral milk challenge. Results: Reactions to milk challenge occurred in 12 (37.5%) including wheezing in 5 (41.7%, or 15.6% of the whole group). Children who developed wheezing at the time of challenge were younger than those who had negative challenge (23.0 months vs. 34.8 months). Challenge was positive in 33.3% of subjects who had a positive SPT, and SPT was positive in 50% of challenge-positive subjects. Regarding sIgE, challenge was positive in 26.7% of sIgE-positive subjects, and sIgE was positive in 33.3% of challenge positive subjects. Skin or serum testing with individual protein fractions did not seem to add significant advantage over testing with WCM alone. Conclusion: This study shows that cow's milk can cause wheezing in children with asthma. Although SPT seemed to be more reliable than sIgE testing, both had suboptimal reliability. It is worth considering possible milk allergy in children with asthma, particularly when poorly controlled in spite of proper routine management (AU)

Milk-induced wheezing in children with asthma.

BACKGROUND: Food allergy has been gaining increasing attention, mostly as causing gastrointestinal and cutaneous reactions. Its role in asthma seems to be under-recognised. OBJECTIVES: This study's aim is to explore the frequency of involvement of a common food, namely cow's milk, in childhood asthma. METHODS: 32 children (5 months to 11 years; median 24 months; mean 34 months) with asthma and a suspected history of cow's milk allergy were studied. They underwent skin prick testing (SPT) and specific IgE (sIgE) testing to whole cow's milk (WCM), casein, α-lactalbumin, and ß-lactoglobulin, followed by single-blind oral milk challenge. RESULTS: Reactions to milk challenge occurred in 12 (37.5%) including wheezing in 5 (41.7%, or 15.6% of the whole group). Children who developed wheezing at the time of challenge were younger than those who had negative challenge (23.0 months vs. 34.8 months). Challenge was positive in 33.3% of subjects who had a positive SPT, and SPT was positive in 50% of challenge-positive subjects. Regarding sIgE, challenge was positive in 26.7% of sIgE-positive subjects, and sIgE was positive in 33.3% of challenge positive subjects. Skin or serum testing with individual protein fractions did not seem to add significant advantage over testing with WCM alone. CONCLUSION: This study shows that cow's milk can cause wheezing in children with asthma. Although SPT seemed to be more reliable than sIgE testing, both had suboptimal reliability. It is worth considering possible milk allergy in children with asthma, particularly when poorly controlled in spite of proper routine management.

C1 esterase inhibitor concentrate in 1085 Hereditary Angioedema attacks--final results of the I.M.P.A.C.T.2 study.

BACKGROUND: The placebo-controlled study International Multicentre Prospective Angioedema C1-INH Trial 1 (I.M.P.A.C.T.1) demonstrated that 20 U/kg C1 esterase inhibitor (C1-INH) concentrate (Berinert®; CSL Behring, Marburg, Germany) is effective in treating acute abdominal and facial Hereditary Angioedema (HAE) attacks. METHODS: I.M.P.A.C.T.2 was an open-label extension study of I.M.P.A.C.T.1 to evaluate the safety and efficacy of long-term treatment with 20 U/kg C1-INH for successive HAE attacks at any body location. Efficacy outcomes included patient-reported time to onset of symptom relief (primary) and time to complete resolution of all symptoms (secondary), analysed on a per-patient and per-attack basis. Safety assessments included adverse events, vital signs, viral safety and anti-C1-INH antibodies. RESULTS: During a median study duration of 24 months, 1085 attacks were treated in 57 patients (10-53 years of age). In the per-patient analysis, the median time to onset of symptom relief was 0.46 h and was similar for all types of attacks (0.39-0.48 h); the median time to complete resolution of symptoms was 15.5 h (shortest for laryngeal attacks: 5.8 h; 12.8-26.6 h for abdominal, peripheral and facial attacks). Demographic factors, type of HAE, intensity of attacks, time to treatment, use of androgens and presence of anti-C1-INH antibodies had no clinically relevant effect on the efficacy outcomes. There were no treatment-related safety concerns. No inhibitory anti-C1-INH antibodies were detected in any patient. CONCLUSIONS: A single dose of 20 U/kg C1-INH concentrate is safe and provides reliable efficacy in the long-term treatment of successive HAE attacks at any body location.

Serum total IgE level during pregnancy and postpartum.

BACKGROUND: Studies on serum IgE levels during pregnancy are limited. OBJECTIVE: To investigate the course of serum total IgE levels during pregnancy and postpartum. METHODS: 159 pregnant subjects provided 218 serum samples during various stages of pregnancy and the postpartum period. Serum total IgE geometric means were compared at various trimesters and postpartum. In addition, the postpartum IgE data were analysed according to the method of delivery. Analysis was also done according to history of allergy. RESULTS: The geometric mean serum total IgE was 20.5 IU/ml in the first trimester, 20.8 IU/ml in the second and 22.2 IU/ml in the third. Postpartum serum IgE level showed a lower mean, 14.9 IU/ml during the early postpartum period (less than 30 days) compared to 30.3 IU/ml during the late postpartum period (30 days-25 weeks). However this was not statistically significant. Serum IgE in the postpartum period also did not differ according to method of delivery. A history of allergy was positive in 98 samples, negative in 61 and unclear in 59. Using analysis of variance, none of these three groups showed significant change in serum total IgE level during pregnancy or postpartum. CONCLUSION: In this cross-sectional study, serum total IgE levels showed no statistically significant changes during pregnancy or postpartum. This finding would be of greater weight if reproduced in a larger number of subjects with multiple serial samples at fixed regular time intervals during pregnancy and postpartum.

Does heredity determine the allergy manifestation or the sensitisation to a specific allergen?

BACKGROUND: The role of genetics in allergy development is well accepted. However, studies could not delineate the mode of inheritance or what is specifically being inherited. The purpose of this study was to determine the effect of genetics on the development of allergy manifestation, serum IgE level, and sensitization to specific allergens. METHODS: Fifty-eight twin sets (age 7 months to 11 years) were evaluated for allergy by medical history, family history, physical examination, serum total IgE level, and percutaneous testing to selected common allergens. RESULTS: In 25 monozygotic (MZ) sets, concordance of atopy was significantly higher than in 33 dizygotic (DZ) sets (84.6% vs 62.5%). The age at onset tended to be earlier when the mother was allergic than when the father was (23.5 months vs 30.5 months). When both twins were allergic, the intra-pair difference in age at onset was within <6 months in 50% of MZ sets versus 31.8% in DZ sets. Total IgE level in twins showed a very strong correlation in MZ sets (r 0.92), but only a moderate correlation among DZ sets (r 0.57). Skin test positivity to specific allergens did not show a significant concordance between twins in either group. CONCLUSION: Our study indicates that the genetic influence was strongest on the inheritance of IgE phenotype, the development of the atopic tendency, the age of onset, and to some extent on the specific allergy manifestation. The effect seemed less on determining the specific offending allergen(s), suggesting possible roles of epigenetic and environmental factors.

Reliability of a new hand-held device for the measurement of exhaled nitric oxide.

BACKGROUND: Given the importance of airway inflammation in asthma, there has been an effort to incorporate inflammatory markers into its management. Measurement of fractional exhaled nitric oxide (FeNO) is a noninvasive marker of airway inflammation; however, the use of the available FeNO analyzer is limited by several factors including its cost and lack of transportability. The aim of this study was to compare the performance of a new hand-held FeNO measuring device (NIOX MINO) to the current clinical standard - the chemiluminescence FeNO analyzer (NIOX). METHODS: Subjects 6 years and older presenting to an allergy and asthma clinic underwent FeNO evaluation by NIOX and each of three NIOX MINOs. The mean of two acceptable measurements from the NIOX and the first approved measurement from each NIOX MINO were used for analysis. RESULTS: One hundred ten patients aged 6-86 years completed the study. Intrasubject FeNO levels obtained by each of the three NIOX MINOs revealed no significant difference between the measurements (P = 0.59). There was a very strong correlation between FeNO measurements by NIOX and by NIOX MINO (r = 0.98, P < 0.0001). The mean intrasubject FeNO difference between NIOX and NIOX MINO was -0.5 p.p.b. which was not statistically significantly different from zero (P = 0.21). CONCLUSIONS: Fractional exhaled nitric oxide measurements by the NIOX MINO showed a strong correlation and a high degree of agreement with the current standard stationary device. The NIOX MINO may be reliably used in clinical practice.

Adverse food reactions by skin contact.

The skin is very much exposed to food contact, both in the occupational and nonoccupational settings. Through such an exposure, adverse reactions can occur that may be irritant or immunologic. Both such types of reactions are particularly common in children with atopic dermatitis. Immunologic reactions can be immediate (immunoglobulin E-mediated) or delayed (cell-mediated), and can be localized or systemic. The latter can be life-threatening, even following trivial exposure. Clinical and experimental data are accumulating to indicate that epicutaneous exposure to food can induce de novo systemic immunoglobulin E sensitization.

Severe drug rashes in three siblings simultaneously.

BACKGROUND: Adverse reactions to drugs commonly occur sporadically. Certain individuals seem to have an increased susceptibility to develop reactions to multiple drugs. Genetic predisposition has not been elucidated. Our objective was to describe a case of three siblings who developed severe rashes to the same drug simultaneously. METHODS: Review of the patients' medical records for information on the clinical course, and comparing their serum immunoglobulin (Ig) levels initially and during follow-up. RESULTS: The rashes were compatible with erythema multiforme and Stevens-Johnson syndrome and developed in the three siblings within 1-3 weeks after the intake of thiabendazole. Follow-up of serum Ig levels did not show any particular pattern, except for an initial mild to moderate elevation in IgG, IgA and IgM. CONCLUSIONS: The occurrence of such severe cutaneous drug reaction in the three siblings to the same drug suggests a genetic predisposition to adverse drug reactions.

The immunologic workup of the child suspected of immunodeficiency.

OBJECTIVE: This review is intended to provide an outline for the evaluation of patients suspected of having immunodeficiency, a problem that is frequently encountered in clinical practice. DATA SOURCES: Information was obtained through a MEDLINE literature search as well as from standard textbooks in immunology. Also included is information that reflects the authors' clinical experience in the field. RESULTS: In general clinical practice, many physicians feel inadequate to evaluate patients with suspected immune deficiencies. They also think that the process of evaluation is time-consuming, which results in misdiagnosis of a substantial percentage of such disorders. Hence, the prevalence of immunodeficiency disorders is much higher than generally thought. At present, there are >80 unique primary immunodeficiency conditions and >50 syndromes that are associated with various immunologic defects. The prevalence of secondary immunodeficiency has also been increasing because of the tragic epidemic of HIV infection, more usage of immunosuppressive medications and bone marrow stem cell transplantation, and the severe degree of malnutrition in underdeveloped countries. It is necessary for clinicians, particularly the specialists in allergy and immunology, to be able to evaluate the status of the immune system. CONCLUSIONS: Very valuable information can be gathered from the medical history and physical examination that may exclude or increase the suspicion of immunologic defect. Laboratory tests can then be appropriately selected to define the specific defect. Once the diagnosis has been settled, proper medical management can be instituted with subsequent improvement in morbidity and mortality of such disorders.

Unusual presentations of food allergy.

OBJECTIVE: This presentation is designed to critically review information on presentations of food hypersensitivity reactions that may be considered unusual regarding the source or nature of allergen, route of exposure, or clinical manifestation. DATA SOURCES: Information has been gathered primarily through a thorough search of the English literature relevant to human subjects. Some clinical cases were also included from the author's own clinical experience. STUDY SELECTION: Information summarized here was critically selected on the basis of proven or acceptable scientific validity. RESULTS: The findings indicate that food allergy presentation can be unusual in three main aspects. First, the offending allergen may not be the obvious food that was ingested or be a food protein incorporated in a nonfood product. Second, systemic reactions can be provoked by very minute quantities of food allergens that may even get access through noningestant routes, eg, inhalation, odor, skin contact, or mucous membrane contact. Third, the clinical manifestations are not limited to the few gastrointestinal, cutaneous, and respiratory symptoms with which we are generally familiar. CONCLUSIONS: The extent of food allergy presentation is more than has been generally realized. Our awareness of such unusual presentations adds new knowledge and should prompt our interest in carefully evaluating patients with obscure allergic reactions for possible food allergy.

Severe food allergies by skin contact.

BACKGROUND: Ingestion is the principal route for food allergens, yet some highly sensitive patients may develop severe symptoms upon skin contact. CASE REPORT: We describe five cases of severe food allergic reactions through skin contact, including inhalation in one. METHODS: The cases were referred to a university allergy clinic, and evaluation comprised detailed medical history, physical examination, skin testing, serum total and specific IgE, and selected challenges. RESULTS: These cases were found to have a strong family history of allergy, early age of onset, very high total serum IgE level, and strong reactivity to foods by skin prick testing or RAST. Interestingly, reactions occurred while all five children were being breast-fed (exclusively in four and mixed in one). CONCLUSIONS: Severe food allergic reactions can occur from exposure to minute quantities of allergen by skin contact or inhalation. Food allergy by a noningestant route should be considered in patients with the above characteristics.

Osteoporosis for the allergist.

OBJECTIVE: This review is intended to be an authoritative summary of the pathogenesis of osteoporosis, a problem that may be encountered in allergy practice. It also provides an outline for identification of subjects at high risk and directions for their appropriate evaluation, management, and prevention of the disease. DATA SOURCES: References were obtained through a MEDLINE literature search as well as from previous reviews. Relevant articles were critically reviewed and their conclusions were included. RESULTS: Osteoporosis is a relatively common disease that is associated with significant morbidity and mortality. The management and prevention of osteoporosis have been improved by an increased awareness of the magnitude of the problem, a better understanding of the pathogenesis, development of a better technique for assessment of bone mineral density, and the availability of specific medications. With the increase in human life-span and the increasing use of glucocorticosteroids for a wide variety of diseases, the incidence of osteoporosis has been on the rise. CONCLUSION: Glucocorticosteroids are the most common medications that cause or contribute to the pathogenesis of osteoporosis and have been widely used in allergy practice. It is important for physicians to appreciate the current basic understanding of osteoporosis and to be able to identify patients at high risk for this serious disorder, and to initiate appropriate intervention at a sufficiently early time to be effective. Medications for treatment and prevention of osteoporosis include: calcium, vitamin D, estrogen, bisphosphonates, calcitonin, and others are reviewed in this article.

Desensitization to pancreatic enzyme intolerance in a child with cystic fibrosis.

OBJECTIVE: Pancreatic enzyme is essential in the treatment of cystic fibrosis (CF), but intolerance to it occasionally occurs. We encountered a child who was intolerant to multiple commercially available preparations of pancreatic enzymes and, hence, desensitization was attempted, with success. CASE PRESENTATION: A 33-month-old girl was diagnosed with CF at 6 months of age. Initially, she was started on Pancrease MT 16, which was subsequently discontinued because fecal fat studies were normal and she seemed to do well on Nutramigen and vitamin supplements. At 29 months of age, she developed diarrhea with bulky stools and weight loss. A fecal fat 72-hour study revealed a coefficient of absorption of 50%. She was treated with Pancrease MT 16, but had consistent vomiting 1 to 2 hours after administration of enzymes. The vomiting occurred on switching to different pancreatic enzymes preparations, ie, Creon 10, Viokase, and Pancrease MT 16. Vomiting occurred even with small doses of enzymes disguised in food. She had no history suggestive of gastroesophageal reflux, peptic ulcer, or pork allergy, and no vomiting on days when enzymes were not given. This was suggestive of type I hypersensitivity reaction. Pancreatic enzymes were discontinued, and she was given a low-fat, high-carbohydrate diet with satisfactory weight gain. METHODS: Double-blind, placebo-controlled titrated oral challenges with pancreatic enzymes resulted in definite vomiting within 1 to 1.5 hours after challenges with Viokase and Pancrease MT 16, but not with placebo. Rush oral desensitization with Viokase solution was attempted, starting with 5 mg, and the dose was doubled every 20 minutes, aiming to reach a cumulative dose of 700 mg. However, the child vomited when a cumulative dose of 315 mg was reached. Another trial of slower desensitization was done using Pancrease MT 16 (1 capsule: 16 000 U of lipase, 48 000 U of amylase, and 48 000 U of protease), starting with 1/4 capsule per day, with increments of 1/4 capsule every 3 days, until an entire capsule was reached by day 10, then increased by approximately 1/2 capsule every 4 days until reaching the therapeutic dose of 1 capsule with each meal by day 25. RESULTS: The patient tolerated this fairly well and has been on this treatment and regular diet for >1 year, without any adverse reaction. This illustrates a rare case of gastrointestinal adverse reaction to pancreatic enzymes that was treated successfully with desensitization. CONCLUSION: Pancreatic enzyme intolerance, although rare, would be a major problem in the management of patients with CF. Hence, desensitization would be essential and may be accomplished successfully using the protocol described in this report.