Carla Lombardo

Oral Specific Desensitization in Food-Allergic Children

The possibility of obtaining oral desensitization in patients with food allergy is still a matter of debate. We decided to evaluate the safety and efficacy of standardized protocols for oral desensitization with the most common food allergens. Forty-two children (ages up to 16 years) diagnosed as affected by food allergy (on the basis of clinical history, skin prick tests, measurement of specific IgE, and double-blind, placebo-controlled food challenge) underwent a sublingual-oral desensitizing treatment according to new standardized protocols. The control group consisted of 10 patients who followed an elimination diet. The treatment was successfully completed by 85.7% of the patients. Specific IgE showed a significant decrease, while specific IgG4 showed a significant increase, in all treated patients. The immunological modifications observed in our patients lead us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory and insect sting allergy.

Oral Rush Desensitization in Peanut Allergy: A Case Report

Allergy to peanuts represents one of the most severe food allergies, rarely remitting compared with milk and egg allergy and frequently associated with life-threatening allergic reactions (1, 2). Its prevalence in the United States is 1.1% (3). Clinical manifestations range from vomiting, diarrhea, and local or generalized urticaria–angioedema to dyspnea, hypotension, collapse, and anaphylactic shock (4). Ara h1, Ara h2, and Ara h3 have been identified as the major peanut allergens (5). Currently prolonged strict avoidance represents the only effective means to prevent allergic symptoms, but this is hardly feasible. Peanut-allergic patients are particularly vulnerable to accidental exposure because small traces (doses as low as 100 μg of protein) may provoke severe symptoms (6, 7). Results of peanut allergen monitoring showed a remarkable quantity of products (such as snacks, cereal bars, and potato snacks) with hidden allergen (8). Another study has shown how simple tasks such as shopping and eating in restaurants can be extremely frightening, even perceived as life-threatening (9). We report the case of a woman with peanut allergy who successfully underwent specific rush desensitization by the oral route (10–14).

Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels

BACKGROUND Systemic mastocytosis is a clonal mast cell (MC) disease that can lead to potentially fatal anaphylactic reactions caused by excessive MC mediator release. The prevalence of mastocytosis in patients with Hymenoptera venom allergy is high, and thus the disease should be suspected in patients with severe reactions caused by Hymenoptera stings and increased serum basal tryptase (SBT) levels. OBJECTIVE We sought to evaluate the presence of clonal MC disorders in patients seen at our mastocytosis center with Hymenoptera sting-induced anaphylaxis, documented hypotension, absence of urticaria pigmentosa, and normal SBT levels. METHODS Twenty-two patients with Hymenoptera sting-induced anaphylaxis, without skin lesions, and with tryptase levels of less than 11.4 ng/mL underwent bone marrow evaluation. Bone mineral density was assessed in those patients with ascertained mastocytosis. RESULTS In 16 of 22 patients, a diagnosis of indolent mastocytosis could be established, and 1 patient had a monoclonal MC activation syndrome. Patients with mastocytosis had higher SBT levels (P = .03) but only rarely had angioedema/urticaria associated with hypotension (P = .004). CONCLUSIONS The absence of urticaria or angioedema in severe reactions to Hymenoptera stings with hypotension might represent the most relevant factor in identifying patients with mastocytosis, regardless of their serum tryptase levels.

Tolerability of aztreonam in patients with IgE-mediated hypersensitivity to beta-lactams

Cross-reactivity between aztreonam and penicillins is poor, but clinical tolerance of aztreonam has been assessed, by means of tolerance challenge tests, only in a few groups of penicillin-allergic patients. The aim of this study is to evaluate the tolerability of aztreonam in a large group of betalactam-allergic patients. We studied all patients (> 14 years of age), with a clinical history of immediate reactions to any betalactam and with positive immediate-type skin tests and/or positive specific IgE to any of the studied betalactam; they were studied by means of: skin prick and intradermal tests with penicilloyl polysine, minor determinant mixture, semisynthetic penicillins, cephalosporins, aztreonam and imipenem; detection of specific IgE to penicillin G, penicillin V, ampicillin, amoxicillin, cefaclor and ceftriaxone. Patients with negative immediate-type skin tests with aztreonam then underwent a graded intramuscular challenge. Forty-five patients (mean age 46.1 ± 15.2 years), 27 females and 18 males, had positive skin tests and/or specific IgE to at least one of the studied betalactams. The most involved drugs were amoxicillin (23 cases), ampicillin (9 cases), penicillin G (8 cases) and other betalactams in the remaining cases. The most frequent reactions were anaphylaxis (27 cases) and urticaria (15 cases). All patients had negative intradermal tests with aztreonam and all patients tolerated the intramuscular graded challenge. Our data confirm the lack of cross-reactivity between betalactams and aztreonam. Immediate-type skin tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in betalactam-allergic patients who urgently need this drug.

A Clinical Trial of Oral Hyposensitization in Systemic Allergy to Nickel

Nickel allergy is the most common contact allergy. Some nickel-sensitive patients present systemic (cutaneous and/or digestive) symptoms related to the ingestion of high nickel-content foods, which significantly improve after a specific low nickel-content diet. The etiopathogenetic role of nickel in the genesis of systemic disorders is, furthermore, demonstrated by the relapse of previous contact lesions, appearance of widespread eczema and generalized urticaria-like lesions after oral nickel challenge test. The aim of this study is to investigate the safety and efficacy of a specific oral hyposensitization to nickel in patients with both local contact disorders and systemic symptoms after the ingestion of nickel-containing foods. Inclusion criteria for the recruitment of these patients were (other than a positive patch test) a benefit higher than 80% from a low nickel-content diet and a positive oral challenge with nickel. Based on the previous experiences, our group adopted a therapeutic protocol by using increasing oral doses of nickel sulfate associated to an elimination diet. Results have been excellent: this treatment has been effective in inducing clinical tolerance to nickel-containing foods, with a low incidence of side effects (gastric pyrosis, itching erythema).

Multiple-drug intolerance syndrome: clinical findings and usefulness of challenge tests.

BACKGROUND Multiple-drug intolerance syndrome (MDIS) is characterized by adverse reactions to several classes of chemically unrelated drugs. OBJECTIVE To analyze all patients with a history of adverse reactions to at least 3 drugs at the Allergy Unit of Policlinico Gemelli in a 6-year period to better characterize patients with MDIS and to find safe alternative drugs. METHODS We studied 480 patients (aged >16 years) with a history of adverse reactions to at least 3 unrelated drugs and with negative allergy test results. Patients who had experienced mild adverse reactions that remitted spontaneously underwent challenge tests without any premedication (group A). Patients with a clinical history of moderate reactions received sodium cromolyn, 500 mg, before the challenge (group B). Patients with a clinical history of severe reactions or undergoing parenteral challenges were given an antihistamine 30 minutes before the challenge (group C). RESULTS In group A, 491 tolerance challenge tests were performed: 414 had negative results and 77 had positive results. In group B, 1,077 tolerance challenge tests were performed: 956 had negative results and 121 had positive results. In group C, 240 tolerance challenge tests were performed: 214 had negative results and 26 had positive results. Comparing the tolerance of alternative drugs in groups A and B, groups A and C, and groups B and C, no significant results were observed (P = .24, .14, and .44, respectively). CONCLUSIONS Patients with MDIS can tolerate alternative drugs. Premedication with sodium cromolyn or oral H1-antihistamines may be useful in preventing adverse reactions.

Hypersensitivity to proton pump inhibitors: diagnostic accuracy of skin tests compared to oral provocation test.

For comparison, lung tissue expressed relatively low levels of gap junction and desmosomes and some are fully not detectable (Fig 2,C). Normal human bronchial epithelial cells cultured inALI expressed claudin-17 (P 5 .03) (Fig 2, A). In contrast, primary keratinocyte in ALI cultures expressed uniquely desmocollin-1 (P 5 .02) (Fig 2, D). Keratinocyte ALIs did not express any TJ proteins in addition to the common junctional proteins observed in skin biopsies and monolayer cultures (Fig 2, B). Detailed statistical analysis is shown in Table E1 (in the Online Repository available at www.jacionline.org). Our data demonstrate that monolayer cell cultures express a similar profile of junctionmolecules compared with ALI cultures, however, with relatively low levels. After apicobasal differentiation in ALIs, more junctional molecules are expressed (Fig 2). Interestingly, whole tissues expressed a much broader profile of junctional molecules. The main reason behind having additional junctional mRNAs appearing in the whole tissue of lung and skin can be that other cell types, such as endothelial cells, fibroblasts in both, and smooth muscle cells in the lung, are also expressing junctional molecules. ALIs represent here a more cell-type–specific junctional molecule expression pattern. After performing the detailed expression analyses of interepithelial barrier molecules, we realized that it is essential to study the TJs in a broader way. Although some are dominantly expressed, the determination of one or two junctional molecules, especially TJs, may not represent the whole picture. There are distinct and overlapping patterns of TJs and other cell-cell adhesion molecules expressed in the skin and lung epithelia, which implicate a highly regulated and complex pattern. Each cell type shows its own, unique expression profile reflecting its specialization related to its function within the organism. In addition, we have to take into account that TJs are not uniquely expressed in epithelial cells but are also found and regulated in other cells, especially in endothelium. Furthermore, other mesenchymal tissues also express them as recently observed in smooth muscle cells in asthma. The number of different junctional proteins, which are expressed, interact in multiple ways in every cell type to form appropriate cell-cell contacts and tissue integrity. Our data demonstrated here suggest that the picture of the junctional apparatus in each cell type and tissue is distinct, and the regulation of epithelial integrity might be more complex than being considered so far. Jeannette I. Kast, BSc Kerstin Wanke, MSc Michael B. Soyka, MD Paulina Wawrzyniak, MSc Deniz Akdis, BSc K€ ulli Kingo, MD, PhD Ana Rebane, PhD Cezmi A. Akdis, MD

Tolerability of Aztreonam in Patients with Cell-Mediated Allergy to β-Lactams

Background: Cross-reactivity between aztreonam and β-lactams is poor, but tolerability of aztreonam has been assessed in a few groups of patients suffering from IgE-mediated allergy to β-lactams. The aim of this study was to assess the cross-reactivity of aztreonam with other β-lactams and its tolerability in patients with cell-mediated allergy to these drugs. Methods: We studied 78 patients with cell-mediated allergy to β-lactams who underwent skin prick, immediate and delayed-reading intradermal tests as well as patch tests with penicilloyl-polylysine, minor determinant mixture, semi-synthetic penicillins, cephalosporins, aztreonam and imipenem. Patients with negative allergy testing with aztreonam underwent an intramuscular test dosing and were observed for 3 h. Results: Our patients experienced 94 non-immediate reactions; delayed-onset urticaria (34 cases), maculopapular exanthema (13 cases), urticaria/angioedema (15 cases) and itching erythema (13 cases) were the most reported symptoms. Amoxicillin (35 cases), ampicillin (28 cases) and bacampicillin (18 cases) were the most involved drugs. All patients had a positive patch test and/or a positive delayed-reading intradermal test to at least 1 β-lactam antibiotic and none had a positive patch or delayed-reading intradermal test to aztreonam. Then, 65 patients underwent intramuscular test dosing with aztroenam, and none of them had a clinical reaction. Conclusions: Our data confirm the lack of cross-reactivity between β-lactams and aztreonam in patients with cell-mediated allergy to these drugs. Delayed-reading intradermal tests and patch tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in β-lactam-allergic patients.

Food allergy and food intolerance: diagnosis and treatment

Food allergy is a matter of concern because it affects about 0.5–3.8% of the paediatric population and 0.1–1% of adults, and as well may cause life-threatening reactions. Skin prick testing with food extracts and with fresh foods, the measurement of food-specific IgE, elimination diets and a double-blind, placebo-controlled food challenge are the main diagnostic procedures; many non-validated procedures are available, creating confusion among patients and physicians. The treatment of food allergy is still a matter of debate. Antihistamines, corticosteroids and, if necessary (in case of anaphylaxis), epinephrine, are the drugs of choice for the treatment of symptoms of food allergy. Sodium cromolyn may be used prophylactically even though there are no controlled studies certifying its efficacy. The only etiologic treatment of food allergy is specific desensitization. Sublingual-oral-specific desensitization has been used by our group for the treatment of food-allergic patients with a high percentage of success.

Sublingual desensitization in patients with wasp venom allergy: preliminary results.

The aim of this paper is to assess in an open prospective pilot case-control study the tolerability, safety and efficacy of an ultra-rush sublingual immunotherapy (SLIT) protocol with Vespula venom in wasp allergic patients compared to subcutaneous immunotherapy (SCIT). Forty-one wasp allergic patients were treated with sublingual (SLIT group) or subcutaneous (SCIT group) ultrarush immunotherapy with Vespula venom extract. All patients underwent skin tests and serum specific IgE and IgG4 detection before enrolment and after 6, 12 and 24 months of immunotherapy. The SLIT group consisted of 21 (6 females and 15 males) patients who received increasing doses of Vespula venom (Aquagen, ALK-Abelló) until the final dose of 30 drops of extract in 3 hours, containing 100,000 SQ-U/ml. The maintenance dose was of 10 drops of pure venom extract 3 times a week, for a total dose of 100,000 SQ-U weekly (corresponding to 100 μg of venom extract). The SCIT group consisted of 20 patients (16 males and 4 females) who were treated with subcutaneous ultrarush immunotherapy with Vespula venom extract (Pharmalgen, Alk-Abelló). Patients received 101.1 μg of Vespula venom in 3 hours and were treated with 100 μg of wasp venom monthly. During the ultrarush sublingual treatment 2 patients (9.5%) experienced mild side-effects. Specific IgE and specific IgG to wasp venom did not show any significant modification. Four patients were field-stung by a wasp during the treatment (for a total of 6 stings). Two patients (3 stings), with a previous clinical history of a grade III and IV reaction, did not experience any reaction. One patient, with a previous grade II reaction, showed a large local reaction. The fourth patient, with a previous grade III reaction, was re-stung twice (after 12 and 24 months) with two systemic reactions (SR) (mild throat constriction). During the ultrarush SCIT phase, 3 (15%) patients experienced side-effects: 2 of them showed a large local reaction and 1 had headache and stomach ache. Specific IgE showed a significant (P=0.001) increase after 6 months of treatment and then returned to baseline levels while specific IgG showed a significant (P=0.001) increase after 6, 12 and 24 months in comparison with baseline. Nine patients were field-stung during the treatment: 8 of them experienced large local reactions; one patient (11%) experienced an SR (dizziness). Our results, even if in a small number of patients, suggest that in patients with Hymenoptera sting allergy SLIT could be efficacious with a good tolerability profile when compared to SCIT. Larger studies are needed to assess efficacy, safety and tolerability profile of wasp venom SLIT.