Robert A. Wood

A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy.

BACKGROUND Orally administered, food-specific immunotherapy appears effective in desensitizing and potentially permanently tolerizing allergic individuals. OBJECTIVE We sought to determine whether milk oral immunotherapy (OIT) is safe and efficacious in desensitizing children with cows milk allergy. METHODS Twenty children were randomized to milk or placebo OIT (2:1 ratio). Dosing included 3 phases: the build-up day (initial dose, 0.4 mg of milk protein; final dose, 50 mg), daily doses with 8 weekly in-office dose increases to a maximum of 500 mg, and continued daily maintenance doses for 3 to 4 months. Double-blind, placebo-controlled food challenges; end-point titration skin prick tests; and milk protein serologic studies were performed before and after OIT. RESULTS Nineteen patients, 6 to 17 years of age, completed treatment: 12 in the active group and 7 in the placebo group. One dropped out because of persistent eczema during dose escalation. Baseline median milk IgE levels in the active (n = 13) versus placebo (n = 7) groups were 34.8 kUa/L (range, 4.86-314 kUa/L) versus 14.6 kUa/L (range, 0.93-133.4 kUa/L). The median milk threshold dose in both groups was 40 mg at the baseline challenge. After OIT, the median cumulative dose inducing a reaction in the active treatment group was 5140 mg (range 2540-8140 mg), whereas all patients in the placebo group reacted at 40 mg (P = .0003). Among 2437 active OIT doses versus 1193 placebo doses, there were 1107 (45.4%) versus 134 (11.2%) total reactions, with local symptoms being most common. Milk-specific IgE levels did not change significantly in either group. Milk IgG levels increased significantly in the active treatment group, with a predominant milk IgG4 level increase. CONCLUSIONS Milk OIT appears to be efficacious in the treatment of cows milk allergy. The side-effect profile appears acceptable but requires further study.

Oral Immunotherapy for Treatment of Egg Allergy in Children

BACKGROUND For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy. METHODS In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months. RESULTS After 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months. CONCLUSIONS These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.).

ICON: Food allergy

Food allergies can result in life-threatening reactions and diminish quality of life. In the last several decades, the prevalence of food allergies has increased in several regions throughout the world. Although more than 170 foods have been identified as being potentially allergenic, a minority of these foods cause the majority of reactions, and common food allergens vary between geographic regions. Treatment of food allergy involves strict avoidance of the trigger food. Medications manage symptoms of disease, but currently, there is no cure for food allergy. In light of the increasing burden of allergic diseases, the American Academy of Allergy, Asthma & Immunology; European Academy of Allergy and Clinical Immunology; World Allergy Organization; and American College of Allergy, Asthma & Immunology have come together to increase the communication of information about allergies and asthma at a global level. Within the framework of this collaboration, termed the International Collaboration in Asthma, Allergy and Immunology, a series of consensus documents called International Consensus ON (ICON) are being developed to serve as an important resource and support physicians in managing different allergic diseases. An author group was formed to describe the natural history, prevalence, diagnosis, and treatment of food allergies in the context of the global community.

The Natural History of Food Allergy

On a population level, it is well recognized that some IgE-mediated childhood food allergies, such as milk and egg allergies, are more likely to resolve than others, such as peanut and tree nuts allergies. Unfortunately, some studies suggest that resolution rates may have slowed compared with impressions from past decades. The clinician can apply the knowledge of the epidemiology of these allergies to describe likely patient outcomes, and direct management in a general manner. However, the ability to evaluate and predict the natural course of specific food allergies for individual patients is essential to inform personalized patient care. Data are accumulating to assist in identifying whether a childs allergy has likely resolved, informing the timing of oral food challenges or subsequent testing. Exciting recent studies are increasingly identifying early prognostic markers as well. Emerging food allergy therapies carry risks and costs. Identifying which egg-allergic patient has likely persistent allergy, and which patient with peanut allergy may experience natural resolution, is becoming an important goal to identify the best candidates for these therapies. Although more work needs to be done to identify reliable predictive markers and validate them, there is already much known about the natural course of food allergies that can be applied by the clinician to improve patient care.

The effect of cat removal on allergen content in household-dust samples

To evaluate the effect of cat removal on cat-allergen content in the home, serial house dust samples were collected from 15 homes during a 9- to 43-week period after cat removal. Samples were obtained with a hand-held vacuum cleaner, and allergen content was quantitated by a radioimmunoassay specific for the major cat allergen, Fe1 d I. Baseline Fe1 d I content ranged from 7.8 Food and Drug Administration units per gram of dust to 436.7 U/gm (median 61.2 U/gm), consistent with levels found in homes with a pet cat. Fe1 d I levels declined gradually in most homes, and by 20 to 24 weeks after cat removal, eight of 15 reached levels consistent with levels found in control homes without cats. In two of those homes, allergen levels fell much more rapidly after aggressive environmental control measures were undertaken. In the other seven homes, however, the decline occurred at a much slower rate, with three homes demonstrating persistent elevations in Fe1 d I content for 20 or more weeks. These data demonstrate that the task of allergen elimination from an indoor environment is extremely difficult, even when the source of a specific allergen can be identified and removed.

Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature.

The true incidence of sarcoidosis in common variable immunodeficiency (CVID) is unknown. We report here 8 cases of sarcoidosis among 80 patients with CVID followed in our clinics, along with 22 well-documented cases reported in the literature. Sarcoidosis, therefore, represents an important entity to consider among patients with CVID who exhibit clinical, radiographic, laboratory, and biopsy findings compatible with sarcoidosis. Conversely, the diagnosis of CVID should be considered in patients with sarcoidosis who do not exhibit the characteristic hypergammaglobulinemia and who have a history of recurrent infections. Although many features of sarcoidosis are similar in patients with CVID to those in patients with sarcoidosis alone, there are many important differences. Patients with CVID in whom sarcoidosis develops present with hypogammaglobulinemia rather than hypergammaglobulinemia and have a higher prevalence of recurrent infections, thrombocytopenia, and splenic involvement. Steroids, in most cases, appeared helpful in reducing adenopathy and splenomegaly, improving uveitis, lowering serum alkaline phosphatase, and reversing hematologic abnormalities. The underlying pathophysiology responsible for the association of these 2 disorders in the same patient remains obscure. However, as more patients are identified, it may be possible to gain a better understanding of the immunologic defect responsible for the dual presentation of these 2 relatively uncommon diseases.

Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial

BACKGROUND There are presently no available therapeutic options for patients with peanut allergy. OBJECTIVE We sought to investigate the safety, efficacy, and immunologic effects of peanut sublingual immunotherapy (SLIT). METHODS After a baseline oral food challenge (OFC) of up to 2 g of peanut powder (approximately 50% protein; median successfully consumed dose [SCD], 46 mg), 40 subjects, aged 12 to 37 years (median, 15 years), were randomized 1:1 across 5 sites to daily peanut or placebo SLIT. A 5-g OFC was performed after 44 weeks, followed by unblinding; placebo-treated subjects then crossed over to higher dose peanut SLIT, followed by a subsequent crossover Week 44 5-g OFC. Week 44 OFCs from both groups were compared with baseline OFCs; subjects successfully consuming 5 g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders. RESULTS After 44 weeks of SLIT, 14 (70%) of 20 subjects receiving peanut SLIT were responders compared with 3 (15%) of 20 subjects receiving placebo (P < .001). In peanut SLIT responders, median SCD increased from 3.5 to 496 mg. After 68 weeks of SLIT, median SCD significantly increased to 996 mg (compared with Week 44, P = .05). The median SCD at the Week 44 Crossover OFC was significantly higher than baseline (603 vs 71 mg, P = .02). Seven (44%) of 16 crossover subjects were responders; median SCD increased from 21 to 496 mg among responders. Of 10,855 peanut doses through the Week 44 OFCs, 63.1% were symptom free; excluding oral-pharyngeal symptoms, 95.2% were symptom free. CONCLUSIONS Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared with placebo. Longer duration of therapy showed statistically significant increases in the SCD.

A comparison of skin prick tests, intradermal skin tests, and RASTs in the diagnosis of cat allergy.

BACKGROUND Skin testing and RASTs are the most commonly used methods for the diagnosis of allergy. Questions remain, however, as to the accuracy of these tests, particularly with regard to the role of intradermal skin tests (IDSTs) in the evaluation of respiratory allergy. OBJECTIVE The purpose of this study was to determine the predictive value of skin prick tests (SPTs), IDSTs, and RASTs in the diagnosis of cat allergy. METHODS Patients were challenged with a well-characterized cat exposure model after evaluation by history, SPTs, IDSTs (if SPT results were negative), and RASTs. All patients were evaluated with respect to their upper respiratory responses, although only those patients with asthma were included in the analysis of lower airway responses. Challenge results were considered positive if the mean upper respiratory symptom score was 0.5 or more, the mean lower respiratory symptom score was 0.4 or more, or the maximum fall in FEV1 value was 15% or more. RESULTS One hundred twenty patients were evaluated. SPT values were positive in 81 patients; of the remaining 39 patients, IDST values were positive in 26 patients. RASTs were performed in 89 patients; the values were positive in 45 of 51 patients with a positive SPT value and were negative in all patients with a negative SPT value. When any positive challenge outcome was considered, positive challenge results were seen in 38 of 41 patients with a positive SPT score, in 10 of 39 patients with a negative SPT score, in 6 of 26 patients with a positive IDST score, in 4 of 13 patients with a negative IDST score, in 27 of 27 patients with a positive RAST score, and in 12 of 44 patients with a negative RAST score. CONCLUSION Although both SPT and RAST values exhibited excellent efficiency in the diagnosis of cat allergy, IDST scores added little to the diagnostic evaluation.

Cat antigen in homes with and without cats may induce allergic symptoms

Although Fel d 1, the major cat allergen, has been found in settled dust samples from homes both with and without cats, the clinical relevance of this allergen has never been studied. In this study we measured airborne concentrations of Fel d 1 in homes both with and without cats and then attempted to relate these levels to those obtained in our experimental cat challenge model to assess their clinical significance. In baseline samples we found measurable levels of airborne Fel d 1 in all 37 homes with cats (range, 1.8 to 578 ng/m3; median, 45.9 ng/m3) and in 10 of the 40 homes without cats (for detectable samples: range, 2.8 to 88.5 ng/m3; median, 17 ng/m3). Fel d 1 was present in the settled dust of 38 of 40 homes without cats (range, 39 to 3750 ng/gm; median, 258 ng/gm), although these levels were only weakly predictive of airborne levels. Repeat samples obtained weekly from 12 homes without cats yielded measurable airborne levels. Fel d 1 in at least one of the four samples from all homes. When compared with challenges performed in our cat room facility at low levels of airborne Fel d 1 (<500 ng/m3), these home levels are within the range capable of causing upper and lower respiratory symptoms in subjects allergic to cats. We therefore conclude that the low level cat exposure that occurs in many homes without cats is capable of inducing symptoms in some patients who are sensitive to cats. The assessment of cat exposure should not be based solely on the presence or absence of a cat in the home.

Laboratory animal allergy

Approximately one third of laboratory animal workers have occupational allergy to animal danders, and a third of these have symptomatic asthma. Sensitization generally occurs with the first 3 years of employment, and risk factors include atopic background, as well as job description as it relates to the intensity of exposure. A symptomatic worker can reduce allergen exposure with personal protective devices. A laboratory can further reduce exposure with generally available equipment, such as laminar flow caging, and procedures, such as frequent wet washing of vivaria and careful maintenance of ventilation systems. It is advisable to institute periodic medical screening of all laboratory animal workers with questionnaires and allergy skin testing in addition to providing them with training programs to reduce personal exposure.