Denisa Ferastraoaru

Discordance between aeroallergen specific serum IgE and skin testing in children younger than 4 years.

BACKGROUND Atopic sensitization to aeroallergens in early life has been found to be a strong risk factor for the development of persisting asthma in young children with recurrent wheeze. OBJECTIVE To assess the yield of skin prick test (SPT) compared with allergen specific serum IgE (sIgE) testing at identifying aeroallergen sensitization in atopic children younger than 4 years. METHODS Concordance between SPT and allergen-specific sIgE testing for 7 common aeroallergens was analyzed in 40 atopic inner-city children 18 to 48 months of age (mean [SD], 36 [9] months) with recurrent wheezing and family history of asthma and/or eczema. RESULTS In 80% of children one or more allergen sensitizations would have been missed if only SPT had been performed, and in 38% of children one or more sensitizations would have been missed if only sIgE testing had been performed. Agreement between the SPT and sIgE test was fair for most allergens (κ = -0.04 to 0.50), as was correlation between sIgE levels and SPT grade (ρ = 0.21 to 0.55). Children with high total sIgE (≥300 kU/L) were more likely to have positive sIgE test results, with negative corresponding SPT results (P = .02). CONCLUSION Our study revealed a significant discordance between allergen-specific SPT and sIgE testing results for common aeroallergens, suggesting that both SPT and sIgE testing should be performed when diagnosing allergic sensitization in young children at high risk of asthma. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01028560.

Diagnosing Environmental Allergies: Comparison of Skin-Prick, Intradermal, and Serum Specific Immunoglobulin E Testing:

Background Allergists commonly perform intradermal skin testing (IDST) after negative skin-prick testing (SPT) to comprehensively diagnose environmental allergic sensitization. However, with the availability of modern methods to detect serum-specific immunoglobulin E (ssIgE), it is unclear if ssIgE testing could substitute for IDST. Objective To determine the efficacy of ssIgE testing and IDST when added to SPT in diagnosing environmental allergic sensitizations. Methods SPT, IDST, and ssIgE testing to nine common environmental allergens were analyzed in 75 patients with oculonasal symptoms who presented to our allergy clinics in the Bronx, New York, between January 2014 and May 2015. Results A total of 651 SPT and 499 ssIgE tests were independently performed and revealed 162 (25%) and 127 (25%) sensitizations, respectively. When SPT results were negative, IDST results revealed 108 of 452 additional sensitizations (24%). In contrast, when SPT results were negative, ssIgE test results only revealed 9% additional sensitizations. When both SPT and IDST results were negative, ssIgE testing only detected 3% of additional sensitizations, and ssIgE levels were typically low in these cases (median, 1.25 kU/L; range, 0.357–4.47 kU/L). When both SPT and ssIgE test results were negative, IDST results detected 15% additional sensitizations. Conclusion IDST detected more additional environmental sensitizations compared with ssIgE testing. IDST, therefore, may be useful when the SPT and/or ssIgE testing results were negative, but the exposure history indicated relevant allergic sensitization. Serology added only a little more information if both SPT and IDST results were negative but may be useful in combination with SPT if IDST cannot be performed.

Severe Angioedema Associated With Angiotensin‐Converting Enzyme Inhibitor Therapy in Two Patients With Pollen‐Food Allergy Syndrome

Angiotensin-converting enzyme (ACE) inhibitor therapy can be associated with bradykinin-mediated angioedema, which may occur at any time during the course of therapy. Pollen-food allergy syndrome (PFAS) represents an immunoglobulin E (IgE)–mediated hypersensitivity reaction recognized in patients with birch pollen allergy and is characterized by mouth and throat itching following the ingestion of certain fruits, nuts, and vegetables. PFAS occurs as a result of the structural homology between major allergens from certain fruits and the birch pollen major allergen Bet v 1. In rare cases, PFAS may present with angioedema and/or anaphylaxis. We present the first report of two cases of severe PFAS in patients with concomitant use of ACE inhibitor therapy. Patient 1 was a 65-year-old man with history of hypertension (taking lisinopril 10 mg daily for the previous 10 years) and seasonal allergic rhinoconjunctivitis who experienced two episodes (1 week apart) of tongue and lip angioedema and mouth itching within 10 minutes after apple consumption. During the second episode, he required treatment with epinephrine, corticosteroids, and antihistamine. Laboratory testing demonstrated increased serum-specific IgE levels to apple (3.01 kU/L; class 2) and birch (47.70 kU/L; class 4) and normal serum levels of C1-esterase inhibitor and eosinophils. Given the high suspicion for severe PFAS in the setting of ACE inhibitor therapy, lisinopril was changed to losartan. Three years after this event, no further episodes of angioedema have occurred. Patient 2 was a 45-year-old man with a history of hypertension (taking lisinopril 10 mg daily for the previous year) and seasonal allergic rhinoconjunctivitis who developed three episodes of tongue angioedema and mouth itching within several minutes after the ingestion of jackfruit and cashew nuts. The third episode required treatment with oral prednisone and antihistamine. Laboratory testing demonstrated increased serum levels of birch-specific IgE (8.19 kU/L; class 3), normal serum levels of specific IgE levels to jackfruit (0.13 kU/L; class 0), and C1-esterase inhibitor and eosinophils. Severe PFAS in the setting of concurrent ACE inhibitor therapy was suspected and lisinopril was changed to losartan. No further episodes of angioedema have occurred within 1 year after the ACE inhibitor was changed (Table). ACE inhibitor–related angioedema is bradykininmediated and is distinguished from IgE-mediated angioedema by a slower onset of action, longer duration, lack of urticaria/pruritus, and failure to respond to antihistamines, corticosteroids, or epinephrine. However, our patients most likely did not experience typical bradykinin-induced angioedema, despite being on ACE inhibitor therapy, but rather an IgE-mediated reaction for the following reasons. Both patients were sensitized to birch pollen and developed oral symptoms within minutes after ingestion of foods containing allergens homologous to birch Bet v 1, thereby suggesting a diagnosis of severe PFAS. Moreover, the symptoms responded promptly to the administration of epinephrine, antihistamine, and corticosteroids. Data from in vitro studies demonstrate that a bradykinin analog was a potent inducer of skin mast cell histamine release. Therefore, we believe that the concomitant ACE inhibitor therapy may have been responsible for the severe clinical symptoms. The usual PFAS treatment involves avoiding the raw forms of culprit foods. Developing severe PFAS in the

Nonimmediate Hypersensitivity Reaction After Trastuzumab Infusion: A Suspected Drug-Virus Interaction

Introduction Hypersensitivity reactions to commonly used chemotherapeutic agents range from mild cutaneous eruptions to fatal anaphylaxis. These are mostly immediate reactions that may be amenable to desensitization procedures. Nonimmediate reactions are less frequently reported and are challenging to manage. Trastuzumab (Herceptin; F. Hoffmann-La Roche/Genentech, Nutley, NJ) is a humanized monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2). Treatment with trastuzumab in combination with adjuvant chemotherapy improves disease-free and overall survival in patients with HER2-positive, earlystage breast cancer compared with chemotherapy alone. In addition to the immediate immunoglobulin E (IgE) –mediated drug reactions (time of onset 1 hour), there are nonimmediate and/or delayed drug-induced hypersensitivity reactions (time of onset 1 hour). Rates of severe immediate hypersensitivity reaction to trastuzumab range from 0.6% to 5%. Most of these reactions occur after multiple exposures and can be avoided during subsequent treatments by using desensitization procedures. In contrast, desensitization treatments for delayed hypersensitivity reactions are not consistently successful. Although diagnosis of an immediate allergic reaction to monoclonal antibodies can be confirmed by skin testing, skin tests are rarely informative in the case of a nonimmediate type of reaction because of low sensitivity. Therefore, confirmation of diagnosis of nonimmediate types of reactions to medications, including those to monoclonal antibodies, presents particular challenges. Such considerations are important if the initial allergic reaction occurred during a viral syndrome and a drug-virus interaction cannot be excluded. Herein, we report our management of a nonimmediate hypersensitivity reaction to trastuzumab in a young woman with potentially curable, HER2-positive, early-stage breast cancer.

IgE deficiency and prior malignancy: results of the 2005-2006 National Health and Nutrition Examination Survey (NHANES)

BACKGROUND Data on patients from tertiary-level health care facilities suggest that IgE-deficient (IgE <2.5 kU/L) patients have high rates of prior malignant tumors. OBJECTIVE To investigate the association between IgE levels and diagnosis of malignancy in non-institution-associated patients using the 2005-2006 US National Health and Nutrition Examination Survey (NHANES) cohort. METHODS All individuals with available IgE levels and known prior diagnosis of malignancy were divided into 4 groups: IgE deficient (IgE, <2.5 kU/L), normal IgE levels (2.5-100 kU/L), high IgE levels (100-1,000 kU/L), and very high IgE levels (≥1,000 kU/L). Rates of malignancy were compared among groups. RESULTS Of 4,488 individuals with data on IgE levels and malignancy status, 7.4% had a prior diagnosis of cancer. The rate of prior malignancy was significantly higher in the IgE-deficient group (12.6%) compared with individuals with high (6.7%, P = .04) and very high IgE levels (5.3%, P = 0.04). In the IgE-deficient group, only 3 patients had a diagnosis of malignancy within 3 years of IgE measurement. A mean (SD) of 10.3 (9.6) years elapsed between the time of malignancy diagnosis and IgE collection time; therefore, active neoplasm or recent chemotherapy was less likely to explain the very low IgE levels. Types of malignancies in the IgE-deficiency group included breast cancer (n = 6), nonmelanoma or unknown skin cancer (n = 3), uterine cancer (n = 2), cervical cancer (n = 1), lung cancer (n = 1), prostate cancer (n = 1), and hematologic cancer (n = 1). CONCLUSION In this non-institution-based cohort, IgE deficiency was associated with a higher rate of prior diagnosis of malignancies compared with individuals with high or very high IgE levels. Prospective studies are essential to better evaluate the association between IgE levels and risk of cancer.

Eosinophilia associated with Strongyloides infection, severe asthma, and central bronchiectasis

The primary causative agent of human strongyloidiasis is Strongyloides stercoralis, a soil-transmitted helminth of the Strongyloides genus.1 Although strongyloidiasis characteristically occurs through contact with contaminated soil, rare cases of human transmission have also been documented.1 The nematode can be found globally; however, its prevalence is higher in tropical and subtropical regions.1 Within the United States, the highest rates of strongyloidiasis are seen in immigrants, especially those coming from Latin American countries where intestinal parasites, such as S stercoralis, are endemic.2 Reports indicate that 30 million to 100 million individuals are infected by S stercoralis worldwide and that strongyloidiasis is the primary helminth infection, resulting in the death of immunosuppressed individuals.3 The parasite’s unique ability to autoinfect its hosts and chronically persist with nonspecific symptoms results in diagnostic difficulties.1 This report describes a unique patient with central bronchiectasis and severe asthma who was found to have a coexisting Strongyloides infection. A 65-year-old woman, who emigrated from the Dominican Republic 18 years ago, presented to our allergy/immunology clinic with severe asthma that required high-dose inhaled corticosteroids and multiple previous courses of oral corticosteroids. The patient had a 2-year history of eosinophilia and recent chest imaging that revealed central bronchiectasis and basal infiltrates (Fig 1); she was therefore referred to us for the evaluation of possible allergic bronchopulmonary aspergillosis. On our evaluation, the Asthma Control Test score was 12, and percutaneous skin test results were positive for trees, weeds, and ragweed and negative for Aspergillus fumigatus and many other mold types. Laboratory tests revealed eosinophilia of 28% (absolute eosinophil count, 2100/mL), total serum IgE level of 364.6 IU/mL (reference range, <180 IU/mL), normal quantitative immunoglobulins, negative test results for antineutrophil cytoplasmic antibodies, and negative A fumigatus IgE and IgG test results. Further workup for eosinophilia revealed negative stool study results for parasites but positive results for S stercoralis IgG. She received ivermectin (200 mg/kg per day) for 2 days. The asthma symptoms persisted so the patient was given a prednisone taper for 2 weeks. Two months later, the patient’s asthma symptoms had markedly improved (Asthma Control Test score of 20), and chest radiography revealed resolution of the pulmonary infiltrates. This case presentation demonstrates the difficulty in detecting S stercoralis infection in a patient previously diagnosedwith asthma and concurrent bronchiectasis. The clinical manifestations of strongyloidiasis are heterogeneous; they may be asymptomatic or can present with gastrointestinal, cutaneous, and/or respiratory symptoms.4 The typical respiratory findings include cough,

Strongyloides stercoralis infection in a patient with sickle cell disease

Strongyloides stercoralis is a common intestinal parasitic nematode that infects a large portion of the world’s population, and is endemic to tropical and sub-tropical regions. Infected individuals are often asymptomatic, but may have abdominal pain, diarrhea and other nonspecific findings. Immunocompromised hosts may develop massive invasion of the gastrointestinal and respiratory tracts, which represents a constellation of symptoms known as hyperinfection syndrome. This condition is most commonly seen in immunosuppressed individuals including renal allograft recipients, patients with human T-lymphotropic virus, and patients using corticosteroids. Along these lines, sickle cell anaemia (SCA) is a condition that is marked by functional asplenia and a relative state of immunocompromise, which may increase the incidence of hyperinfection. Along with the predisposition to encapsulated organisms, SCA patients may be unusually susceptible to parasitic infections, which may trigger sickle cell crises (Sodipo et al., 1997). Furthermore, blood samples from SCA patients have demonstrated increased eosinophil numbers and adhesion properties, which may also contribute to the vasoocclusive state (Canalli et al., 2004). Given the observations that strongyloidiasis is characterized by eosinophilia and eosinophils in SCA individuals may be implicated in vasoocclusive crisis (VOC), further data are necessarily to investigate the association between SCA and S. stercoralis infection. We describe a patient with SCA and chronic eosinophilia who presented to our hospital with diarrhea and VOC. She was found to have S. stercoralis infection, and experienced symptomatic improvement following the administration of ivermectin.