The impact of allergy and immunology on our expanding industrial environment

In summary, allergists and clinical immunologists have assumed a primary role related to the diagnosis and pathophysiology of a wide range of environmental and occupational diseases associated with our increasingly industrialized environment. Prevention, rather than therapy, is the primary goal in managing many of these conditions. With all such diseases, it is most important to take into account the patient's environment and to record a thorough occupational and environmental history. The concept of environmental agents as causative factors of disease in man dates to antiquity but has assumed considerably greater significance in recent years. In this context, it should be remembered that Hippocrates and Socrates both emphasized that a good physician should strongly consider the patient's environment as an aid in diagnosis. Of equal importance was the recommendation by Bernardo Ramazzini in 1713, that, "in addition to the questions and recommendations of Hippocrates," a careful inquiry into the patient's occupation should be made.     

HLA Dr-Dq haplotypes and the TNFA-308 polymorphism: associations with asthma and allergy

BACKGROUND: The HLA (human leukocyte antigen) class II genes DQB1 and DRB1 and the Tumor Necrosis Factor alpha gene (TNFA) within the HLA complex (chromosome 6p21) have been associated with asthma and allergy. Due to the strong linkage disequilibrium characterizing this complex and the multiple asthma/allergy expressions, we aimed to determine which of these genes were primarily involved in specific asthma/allergy traits. METHODS: The DRB1-DQB1 alleles and TNFA-308 polymorphism were genotyped in 959 children from the Environment and Childhood Asthma study and analyzed for possible associations with allergic and non-allergic asthma (with/without at least one positive skin prick test for allergens) and specific allergic sensitization, as well as bronchial hyperresponsiveness and total IgE, using both allele and extended haplotype analyses. RESULTS: Different genes within the HLA complex were associated with separate asthma and allergy traits. Nonallergic asthma was associated with both the TNFA-308A allele [Odds ratio (OR) 1.7 (1.3-2.3)] and DRB1 03 allele [OR 1.6(1-2.6)], but extended DRB1 03-TNFA-308 haplotype analysis suggested that the DRB1-DQB1 association was secondary to linkage disequilibrium with the TNFA-308 polymorphism. Allergies were associated with HLA class II alleles only; birch sensitization with DQB1 0603-DRB1 13 [OR 2.3 (1.4-4.0)] and mugwort sensitization with DQB1 0609-DRB1 13 [OR 7.1 (1.9-27.0)] and DQB1 0501-DRB1 01 [OR 2.0 (1.0-4.0)]. CONCLUSIONS: Our data suggests that asthma is not associated with DRB1 or DQB1 but rather TNFA or a gene(s) in linkage disequilibrium, while sensitization to specific allergens is associated with particular alleles at the DQ and/or DR loci. A novel association between DQB1 0603-DRB1 13 and birch allergy is identified.     

Epidemiology of food allergy/food intolerance in adults: associations with other manifestations of atopy

BACKGROUND: Food allergy and food intolerance (FA/FI) are believed to be frequent medical problems; however, information from epidemiologic studies in adults is scarce. The objective was to determine the frequency of FA/FI and allergic sensitization to food in a large adult sample. Furthermore, the associations between FA/FI and other outcomes of atopy were studied. METHODS: Within a population-based, nested, case-control study, a standardized interview was performed to obtain detailed information on FA/FI and the history of atopic diseases. In addition, a skin prick test with 10 common food and nine aeroallergens was performed. RESULTS: Overall, 20.8% of the 1537 studied subjects (50.4% female, age median 50 years) reported FA/FI (women 27.5%, men 14.0%; OR 2.35, CI 1.80-3.08). Nuts, fruits, and milk most frequently led to adverse effects, and the sites of manifestation were oral (42.9%), skin (28.7%), gastrointestinal (13.0%), systemic (3.2%), and multiple (12.2%). One-quarter of the subjects (25.1%) were sensitized to at least one food allergen in the prick test, with hazelnut (17.8%), celery (14.6%), and peanut (11.1%) accounting for most of the positive reactions. The corresponding frequency estimates for the representative study base (n=4178) were 15.5% for reported adverse reactions and 16.8% for allergic sensitization. Relevant concomitant sensitization to food and aeroallergens was observed. Food-allergic subjects (positive history and sensitization to corresponding allergen) suffered significantly more often from urticaria, asthma, atopic eczema, and especially hay fever (73.1%) than controls (3.0%). Furthermore, hay fever was treated significantly more often in subjects who suffered from concomitant food allergy. CONCLUSIONS: FA/FI in adults is frequently reported and associated with other manifestations of atopy. Hay fever in conjunction with FA/FI tends to be clinically more severe since therapeutic needs are enhanced.     

Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development

PurposeThe aim of this study was to determine the diagnostic yield of whole-exome sequencing (WES) in fetuses with ultrasound anomalies that resulted in fetal demise or pregnancy termination. The results were also utilized to aid in the identification of candidate genes for fetal development and to expand the clinical phenotype of known genetic conditions.MethodsWES was performed on specimens from 84 deceased fetuses. Data were analyzed and final results were classified into one of four categories: positive, possible, negative, and candidate gene only. WES analysis was predominantly performed in fetus–parent trios or quads (61%, n=52).ResultsOverall, 20% (n = 17) of cases were positive, 45% (n=38) were possible, 9% (n=7) had only candidate gene variants and 26% (n = 22) tested negative. The diagnostic yield for definitive findings for trio analysis was 24% (n = 11) compared to 14% (n = 4) for singletons. The most frequently reported ultrasound anomalies were central nervous system (37%, n = 31), hydrops/edema (36%, n = 30), and cardiovascular anomalies (31%, n = 26).ConclusionOur experience supports the use of WES to identify the molecular etiology of fetal ultrasound anomalies, to identify candidate genes involved in fetal development, and to expand our knowledge of the clinical phenotype of known genetic conditions.     

Marshall-Smith syndrome: the expanding phenotype.

We report a child of 3 years 9 months with the Marshall-Smith syndrome (MSS), characterised by the typical facial features, developmental delay, and advanced bone age. After the diagnosis was made at 5 months of age, careful observation for respiratory complications and failure to thrive was initiated. By 3 1/2 years of age, although our patient had no life threatening respiratory complications, investigation showed significant upper airway obstruction, which has been successfully treated. Aggressive treatment for failure to thrive has also allowed her to maintain a weight on the 50th centile. The purpose of this report is to suggest that early diagnosis and aggressive management may improve the ultimate prognosis with respect to the respiratory and feeding difficulties seen in this rare syndrome.     

Currant allergy and the Rosaceae-grass pollen allergy syndrome: a case report.

BACKGROUND: Despite the increasing use of currants in culinary recipes, currant allergy has rarely been reported. OBJECTIVES: To study a case of currant allergy and to explore cross-reactivity between grass pollen and Rosaceae family fruit allergens. METHODS: Skin prick tests to pollen and skin prick-to-prick tests with currants and peach were performed. Specific IgE levels were determined using the CAP method. We prepared a protein extract of 0.1 mg/mL in phosphate-buffered saline using red currant in the presence of protease inhibitors. Immunoblot inhibition studies were performed to explore cross-reactivity between grass pollen and currant allergens. RESULTS: Skin prick test results were positive to Dactylis, arizonic, and olive pollens. Results of skin prick-to-prick tests with fresh red and black currants were negative and positive, respectively, to peach. The specific IgE level was 5.7 KU/L to red currant and 2.92 KU/L to peach (CAP). Western blot analysis with red currant extract revealed specific IgE protein bands of 37 and 26 kDa. Preincubation of sera with extracts from red currant and peach inhibited both IgE bands, and preincubation with Dactylis pollen inhibited the 37-kDa band only. CONCLUSIONS: We report a case of allergy to grass pollen with an oral allergy syndrome involving several fruits from 2 different families of the Rosidae subclass confirmed by in vitro tests. Inhibition studies demonstrated cross-reactivity between different fruits (currant and raspberry) from the Rosidae subclass and were incomplete with grass pollen allergens.     

Soy hypersensitivity in children with food allergy.

To evaluate humoral (IgE antibodies) and clinical (positive challenge test) soy hypersensitivity prevalence, we studied 317 children (271 boys and 100 girls) with a median age of 5 months (range 1-120) who visited the Division of Allergy and Clinical Immunology of the Pediatric Department of the University of Roma "La Sapienza" because of histories and symptoms suggestive of food allergy. Atopic dermatitis (AD) was present in 247/317 children (78%), diarrhea in 19 (6%), urticaria in 22 (7%), and rhinitis and/or asthma in 29 (9%). All children underwent diagnostic procedures including family and personal history, physical examination, PRIST, and RAST to cows milk (CM), egg, wheat, soy, and Dermatophagoides pteronyssinus (Dpt). Open challenge tests to soy were performed in the hospital under observation and with emergency equipment at hand. The prevalence of humoral sensitization to CM was 54%, to egg 46%, to Dpt 35%, to wheat 24%, and to soy 22%. Only five children had IgE only to soy; six to soy and egg; and 58 to soy, CM, and egg. Only ten children (3%) had positive challenge to soy and only five of them had IgE to soy. RAST had a sensitivity of 0.69, a specificity of 0.83, a negative predictive value of 0.77, and a positive predictive value of only 0.06.     

Treatment of peanut allergy with rush immunotherapy.

Peanut and peanut products are a common food in the diet. Peanuts are also one of the most common foods responsible for food-induced anaphylaxis. Patients rarely lose sensitivity to peanuts. Although the ideal treatment is avoidance, this is often not possible because of hidden exposures; therefore, a more effective treatment is needed. Subjects with confirmed peanut allergy were treated in a double-blind, placebo-controlled study with peanut immunotherapy or placebo. Objective measures of efficacy included changes in symptom score during double-blind placebo-controlled peanut challenge (DBPCPC) and titrated end point prick skin tests (PST). Three subjects treated with peanut immunotherapy completed the study. These subjects displayed a 67% to 100% decrease in symptoms induced by DBPCPC. Subjects also had a 2- to 5-log reduction in end point PST reactivity to peanut extract. One placebo-treated subject completed the study. This subject had essentially no change in DBPCPC symptom scores or PST sensitivity to peanut. Two other placebo-treated subjects underwent a second PST session. These subjects had a 1- to 2-log increase in skin test sensitivity to peanut. All peanut-treated subjects were able to reach maintenance dose, and in no case did an anaphylactic reaction occur secondary to the peanut immunotherapy. The current study provides preliminary data demonstrating the efficacy of injection therapy with peanut extract and provides a future line of clinical investigation for the treatment of this potentially lethal disease. It should be noted, however, that the rate of systemic reactions with rush immunotherapy was 13.3%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pediatricians' attitudes towards allergy: past and present attitudes of pediatricians towards allergy.

BACKGROUND: In 1971 we published a survey of pediatricians' knowledge, attitudes, and practices relative to the field of allergy. This current survey was conducted to determine how these attitudes and practices have changed over the past 27 years. METHODS: Our survey, consisting of 17 questions, was sent to 250 board certified pediatricians in the St. Louis area. Seven of the questions were similar to those in the 1971 survey, while the other ten were new questions which we thought were pertinent to the field of allergy currently. RESULTS: In 1971, 75% of the pediatricians felt the specialty of allergy had great or moderate importance for the practice of pediatrics compared with 99% in 1998. In 1998, the number of physicians who felt that there was at least some value to skin testing had increased from 1971, although, only 36% felt it had great value. In 1971, 23% of pediatricians performed their own skin tests compared with 3% in 1998. Nine percent indicated that they had never referred a patient to an allergist in 1971, compared with 2% in 1998. Our new questions looked at to whom respondents were more likely to refer patients with: (1) asthma (68% allergy, 27% pulmonary, 4% both), (2) urticaria (53% allergy, 41% dermatology, 2% both), (3) chronic eczema (45% allergy, 50% dermatology, 2% both), and (4) chronic sinusitis (24% allergy, 74% otolaryngology, 2% both). Older physicians placed greater importance on the field of allergy and skin testing and were more likely to refer to an allergist than physicians under the age of 40 years. CONCLUSION: Our results indicate that although there has been significant change in 27 years, allergists must be more aggressive in developing the knowledge, attitudes, and practices of physicians relative to the field of allergy.