Atopy


Article Author:
Angel Justiz Vaillant


Article Editor:
Arif Jan


Editors In Chief:
Myron Bodman
Donald Kushner


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
9/26/2019 3:44:56 PM

Introduction

Atopy is a predisposition to respond immunologically to diverse antigens/allergens, leading to  CD4+ Th2 differentiation and overproduction of immunoglobulin E (IgE). The clinical consequence of this is the propensity to develop hypersensitivity reactions to allergens. Allergic bronchial asthma and allergic rhinitis are the most common manifestations of atopy followed by atopic dermatitis and food allergy. Two or more clinical diseases can coexist in an individual at the same time or at different times.

Other diseases described as atopic are allergic conjunctivitis, IgE-mediated drug allergy, insect bites, urticaria and angioedema, and anaphylactic shock.[1][2][3][4]

Etiology

The etiology of atopy is unknown. Twin and epidemiological studies, as well as family and animal experiments, provide striking evidence that the genetic factors play a crucial role in the propensity for atopy, regulating the total IgE synthesis, and in the production of IgE antibodies to specific epitopes. The inheritance of several genes influences the tendency to overproduce IgE, and this runs in families as shown clearly in the autosomal transmission of allergy, but the full inheritance pattern is believed to be multigenic.[5]

 A theory that explains the genesis of atopy suggests that it may arise through abnormal regulation by T helper cells and suppressor T lymphocytes that should help in the production of IgE by plasma cells.[6][7]

 Examples of chromosomal locations and genes associated with atopy are 5q associated with cytokine gene cluster (IL-3, IL-4, IL-5, IL-13, CD14, beta-2-adrenergic receptor, and GM-CSF). IL-4 and IL-13 promote IgE switching, and IL-5 stimulates eosinophil growth and activation. Beta-2-adrenergic receptors regulate contraction of bronchial smooth muscles. The chromosome 6p houses MHC class II, and some of the alleles regulate T cell responses to environmental antigens or allergens. The chromosome 11q gene (high-affinity IgE receptor beta-subunit) that mediates mast cell activation. Chromosome 12q houses genes for stem cell factor (intervene in mast cell growth and differentiation), IFN-gamma (inhibits IL-4 synthesis) and STAT6 (mediates IL-4 signal transduction). Other genes associated with atopy are IL-4 receptor alpha chain, DPP10 (a protein that regulates chemokine and cytokine activity), ADAM33 metalloproteinase, which is involved in airway remodeling, and CD80/CD86 located in 3q and RANTES in 17q are genes thought to be involved in atopy. Finally, PHF11 in 13q encodes for a transcriptional regulator involved in the clonal expansion of B cells and immunoglobulin expression.[8][9][10][11]

Nonspecific triggers of asthma include infections (viral respiratory infections), climatic factors (ozone, cold air, and SO2), physiologic factors (exercise, hyperventilation, psychological factors) and ingestants (aspirin and nonsteroidal anti-inflammatory drugs).

There is a list of occupational allergens causing IgE-mediated allergic asthma that includes animal products (cows, pigs, mice, dogs, cats, and horses), insect dusts (mealworms, storage mites, cockroaches, bees, and flies), plant products (dust, flours, grain and cotton dusts), fruits, seeds, leaves and pollens (castor beans, tobacco and weeping fig), vegetable, dusts, gums and extracts (western red, California redwood, and exotic woods), microbial agents (fungal allergens, alginates, protozoa, bacteria, and fungi), enzymes (papain, hog trypsin, pancreatic extracts, subtilisin, and pineapple bromelain), therapeutic agents (penicillins, tetracycline, cephalosporins, sulfonamides, and spiramycin), sterilizing agents (chloramides), inorganic chemicals (metal fumes and salts, aluminum, cobalt, fluoride, nickel, platinum, vanadium, and zinc) and organic chemicals (amines, anhydrides, and azodicarbonamide).[10]

Epidemiology

Atopy affects a significant portion of the general population, usually estimated at 10 to 30% in developed countries. About 80% of atopic individuals have a family history of allergy compared with only 20% of the average population. In monozygotic twins, there is only 50% concordance. The susceptibility for atopic diseases is genetic, but rather than one or two causative dominant genes evidence suggests that there are many genes with moderate effects involved.[12]

Allergic rhinitis occurs in 10% to 12% of the US population. The prevalence and morbidity rate is due to the geographic distribution of common allergens including dust mite and allergenic plants. Both sexes are equally affected.  The prevalence of bronchial asthma varies worldwide. It is a common disease that affects 5% of the population of Western countries. It causes in the US above 3000 deaths per year. Increasing mortality and morbidity rates occur despite substantial advances in immunotherapy.[13][14] There were 8.4 million children with asthma in the U.S. in 2014, and 11.1% lived in poor-urban areas.[15]

Pathophysiology

The pathophysiology of atopy characteristically demonstrates by mast cell activation. Antigen binding to IgE cross-links Fc epsilon RI proteins on mast cells. It activates protein tyrosine kinases (Lyn and Syk) that in turn cause activation of a MAP kinase cascade and a phosphatidylinositol-specific phospholipase C, which catalyzes the release of the following molecules: IP3 and DAG from membrane PIP2. Inositol trisphosphate (IP3) causes the release of intracellular calcium from the endoplasmic reticulum. DAG and calcium activate PKC that phosphorylates substrates such as myosin light chain molecule and thus leads to degradation and release of preformed mediators. MAP kinases and calcium react to activate the enzyme cytosolic phospholipase A2, which stimulates the synthesis of lipid mediators including PGD2, LTC4, LTD4, and LTE4. Ras/MAP kinases in the presence of calcium and PKC cause cytokine gene expression, which releases TNF and other cytokines (IL-4, IL-5, IL-6, IL-13 among others). Lipid mediators, cytokines and histamine cause an inflammatory response.[16][17][18]  

Basophils and mast cell mediators include biogenic amines and enzymes stored preformed in granules, cytokines and lipid mediators, which are mainly newly synthesized on cell activation. Histamine and other biogenic amines, as well as lipid mediators, induce vascular leakage, and intestinal hypermotility, which are all components of immediate allergic responses. Cytokines and lipids mediators add to inflammation that is part of a late-phase reaction. Enzymes presumably contribute to tissue damage. Activated eosinophils release enzymes as well as cationic proteins that are toxic to parasites and host cells. The thinking is that some eosinophil granule enzymes participate in tissue damage in chronic allergic disorders.[19][20][21]

Defective lymphocyte regulation is a possible explanation in allergic dermatitis. Delayed hypersensitivity skin test responses to allergens, in vitro lymphocyte responses to mitogens or allergens, and autologous mixed lymphocyte reactions have all been reported to be defective. It has been reported in atopic dermatitis an increased susceptibility to vaccinia virus, molluscum contagiosum, warts, herpes simplex virus, and dermatophyte skin infections are in harmony with a defect in the T lymphocyte effector mechanism. There are suggestions that an anomalous or defective CD4+ helper T cell population could explain the failure of CD8+ T cells to function as immunosuppressors of the production of IgE.[22][23]

Histopathology

Atopy presents with a histopathologically characteristic wheal and flare reaction in the skin, which is in response to an allergen-stimulated release of mediators from mast cells, local blood vessels that dilate and become leaky to proteins and fluids, which produces local swelling and redness.[24]

Histologic characteristics of bronchial asthma show a diseased bronchus with excessive mucus production, many submucosal inflammatory cells, including lymphocytes and eosinophils, thickened basement membrane, and smooth muscle hypertrophy.

History and Physical

In the following atopic diseases, there is a history of atopy (hypersensitivity to many allergens, and elevated IgE serum levels). Patients are symptom-free in the absence of exposure. 

Atopic rhinitis

  • Characterized by nasal congestion 
  • Rhinorrhea 
  • Sneezing  
  • Itching of the nose  
  • Post-nasal drainage  
  • Dry cough  
  • Ocular symptoms  
  • Rhinoscopy shows a pale, swollen nasal mucosa with watery secretions   
  • The conjunctivae are hyperemic and edematous   

Allergic asthma symptoms

  • Asthma may begin at any age  
  • Frequent attacks of wheezing and dyspnea  associated with chest tightness and coughing(often nocturnal in children) at times productive of thick and tenacious sputum
  • Fatigue  
  • Malaise    
  • Use of accessory muscles of respiration
  • The lung fields are hyper-resonant  
  • Diminished breath sounds, rhonchi, and wheezes on auscultation  
  • The expiratory phase is prolonged  
  • In severe attacks breath, sounds and wheezing may both be absent

Atopic dermatitis

  • The disease almost always begins in infancy
  • Itching that worsens at night and exacerbates by irritants such as wool
  • There is a strong family history of atopy
  • Scratching and rubbing cause the typical eczematous skin eruption to flare
  • Ingestion of allergenic food may cause exacerbations
  • The skin is typically dry and scaly
  • Presence of active skin lesions with prurigo and erythema 
  • Chronic lesions are thickened and lichenified
  • Distribution of the lesions is dependent on age - in childhood mostly affects the forehead and cheeks

Food allergy can manifest as 

  • Rhinoconjunctivitis
  • Asthma
  • Respiratory symptoms alone are rare
  • Usually part of systemic anaphylaxis 
  • Hypotension
  • Arrhythmias
  • Nausea and vomiting
  • Abdominal cramping or diarrhea

Evaluation

The evaluation of immediate hypersensitivity includes obtaining a complete blood cell count, assessment of immunoglobulin IgE and skin prick test.[25] 

Quantitative Serum Immunoglobulins

  • IgM, IgG, and IgA 

Total Leukocyte Count and Differential

  • Hb (decreased in autoimmune hemolytic anemia)
  • Eosinophilia 
  • Lymphocyte studies (CD4/CD8 count and suppressor T cells count that may be lower than the standard value)

Allergic test

  • Skin prick tests utilizing various allergens from animal, plants, food, pathogens and environmental pollutants
  • The radioallergosorbent test (RAST): Use to determine specific IgE antibodies 

Other tests

  • Serum protein electrophoresis (to rule out IgE myeloma)
  • Stool examination (for intestinal parasitism)
  • Appropriate exclusion diet and blinded provocation (for food allergy diagnostic clarification)
  • Chest X-ray (in bronchial asthma)

Treatment / Management

Allergic rhinitis

The treatment of allergic rhinitis consists of environmental measure to prevent allergen exposure, drugs, and desensitization. As an allergic disease, the prophylactic treatment by avoidance of allergens is the most potent means of treatment. However, avoidance is not always possible because of that drugs are needed to control symptoms or the use of desensitization.

Environmental measures include the avoidance of an allergen by a clinical history of allergy and not because of a positive skin test or RAST alone. The environmental control covers the removal of household pets, cleaning of house dust by frequent cleaning, avoidance of toys and other objects. The use of air-cleaning devices may be helpful. Prevention of pollen and outdoor mold growth is necessary.

Antihistamines are the most regularly used drugs in allergy rhinitis and should be administered with care for the avoidance of side effects although new nonsedating antihistamines are available that restrain most common side effects. Orally administered nasal decongestants may be helpful in combination with antihistamines. For treating allergic conjunctivitis antihistaminic eyes, drops are critical. The treatment with cromolyn by nasal spray four times daily is beneficial and free of immediate or long-term toxicity. Systemic corticosteroids are remarkably effective in reducing symptoms of allergic rhinitis, but since it is a chronic and benign condition should be used with much care. Desensitization (allergen injection therapy) should be given to patients whose symptoms are uncontrolled despite appropriate previous therapeutic measures.[26]

Allergic asthma

It is a manifestation of atopy localized in the bronchus. There is a release of critical mediators including histamine, leukotrienes, and cytokines including IL-4, IL-5, IL-13, TNF and eosinophil chemotactic factor. The aim of symptomatic asthma is controlling the hyperirritable bronchial mucosa using environmental measures, drugs, and other therapies.

The drug treatment of bronchial asthma includes environmental control as referred to in atopic rhinitis. The drug treatment includes the use of sympathomimetic beta-adrenergic bronchodilators drugs, which are useful and use in acute attack or for long term management. Epinephrine can be successfully given in a dose of 0.2-0.5 mL subcutaneously. Albuterol, metaproterenol, pirbuterol, and isoetharine are selective beta-adrenergic bronchodilators dosed via inhalation in the aerosol. Theophylline is a potent bronchodilator when used in combination with sympathomimetic medication. Intravenous theophylline can be used in a dosage of 250 to 500 mg and administered swiftly in an acute asthmatic attack. Glucocorticoids are remarkably successful in the treatment of allergic asthma. Although their effectiveness should be used in asthma only when other therapeutic options have failed. A dose of 30 to 60 mg of prednisone daily is usually enough.[15]

Cromolyn sodium (20 mg) can be given in a metered-dose inhaler and for long-term prophylactic therapy. It never reverses an acute attack. Antibiotics are an option in allergic asthma if secondary bacterial bronchitis or bronchopneumonia occurs. Hydration and expectorants are effective for thick sputum. The effectiveness of desensitization in allergic asthma works well as in allergic rhinitis. An example of it is injection treatment in pollen hay fever. Antileukotrienes such as montelukast and zafirlukast can be administered in allergic asthma and atopic rhinitis.

Atopic dermatitis

Atopic dermatitis presents as a chronic skin disease requiring proper skin care, environmental control, drugs and avoidance of the allergen. The most preventive measure is the use of nonirritating topical lubricants for skin itching. Topical steroids are effective when skin involvement is less severe, but in systemic eczema, systemic corticosteroids are necessary, often initiating with a high dosage and then tapering until achieving a therapeutic effect. Oral antihistamines help to control the itching. Patients should not engage in frequent bathing, or use irritating fabrics, and harsh detergents. If infection occurs, an appropriate antibiotic is necessary.[27]

Food allergy

The treatment of a food allergy consists of a strict elimination of offending allergen. Having an emergency care plan and a written anaphylaxis action plan is of utmost importance. A form of self-injectable epinephrine and a medical alert bracelet is critical to signal healthcare professionals of what is going on. The most common food allergens in children are cow's milk, soy wheat, egg, and peanut that account for 91% of reactions. In adults, the most common allergens are fish, shellfish, peanuts, tree nuts, eggs, fruits, and vegetable.[28]

Differential Diagnosis

Atopy should be differentiated from diseases associated with elevated total serum IgE, which include:

  • Allergic bronchopulmonary aspergillosis
  • Parasitic diseases
  • Immunodeficiency with ataxia-telangiectasia
  • Hyper-IgE syndrome
  • Wiskott-Aldrich syndrome 
  • IgE myeloma
  • Thymic alymphoplasia
  • Graft-versus-host reaction

Differential diagnosis of atopic rhinitis

  • Chronic nonallergic (vasomotor) rhinitis
  • Rhinitis medicamentosa
  • Infectious rhinitis 
  • Vernal keratoconjunctivitis

Differential diagnosis of allergic bronchial asthma

  • Pulmonary emphysema
  • Acute bronchiolitis
  • Cystic fibrosis
  • Aspiration of a foreign body
  • Airway obstruction caused by a congenital vascular anomaly
  • Cardiac asthma caused by left ventricular failure
  • Carcinoid tumors

Differential diagnosis of atopic dermatitis

  • Localized neurodermatitis (lichen simplex chronicus)
  • Allergic or irritant contact dermatitis
  • Seborrhea and dermatophytoses
  • Pompholyx (dyshidrosis)

Pertinent Studies and Ongoing Trials

  • A recent meta-analysis showed the use of multi-strain probiotics to be most useful for eczema prevention in children.[29] 
  • A study indicates that the administration subcutaneously of a single-dose of tralokinumab (150 to 600 mg), a  human monoclonal antibody in clinical development for atopic dermatitis and asthma, was well tolerated in healthy Japanese volunteers. This study was a phase I, single-blind, randomized, placebo-controlled, and single ascending-dose study, and supports the 300 mg dose selection for Japanese patients with asthma.[30] 
  • Epicutaneous immunotherapy (EPIT) can be used to treat food allergy. EPIT activates the skin natural desensitization pathway and offers a progressive, possibly sustained response. This immunotherapy provides potential alternatives for atopic immunotherapy, which is less invasive and also carries a lower risk for systemic reactions than oral immunotherapy.[31] 
  • Oral immunotherapy consists of administering rising doses of a food antigen to food-allergic subjects, to provoke a state of desensitization. Tolerability, efficacy, and safety remain an ongoing concern.[32] 
  • Randomized placebo-controlled studies showed that ciclesonide, an inhaled corticosteroid, can initiate and maintain disease control in individuals with persistent asthma of all disease severities.[33]
  • Randomized controlled trials (RCTs) exploring the capacity of vitamin D to stop acute respiratory infections have yielded positive results. Vitamin D supplementation was safe, and it also protected against acute respiratory infections overall in very deficient individuals and those subjects not receiving bolus doses as well as experienced the benefit.[34]

Prognosis

Atopic individuals have a lifelong tendency for the development of allergic reactions as it is incurable. Nevertheless, the manifestations of atopy often change over some time. Atopic dermatitis has a better prognosis and is treatable with some success with immunotherapy. Allergic asthma has a prognosis that varies according to the persistence of the causative environmental allergen, the IgE levels in blood or tissues, and the genetic makeup.

Systemic anaphylaxis is the occurrence of an immunoglobulin E mediated reaction simultaneously in multiple tissues. The causative allergen is an insect venom, food or drug. The reaction is potentially fatal and can be evoked by a tiny quantity of allergen. The prognosis of anaphylaxis is very poorly and requires immediate medical care.

Complications

Complications of allergic rhinitis - untreated cases can lead to: 

  • Sinusitis
  • Otitis media
  • Nasal polyps
  • Apnea

Complications of allergic bronchial asthma:

  • Pneumothorax
  • Subcutaneous emphysema

Complications of atopic dermatitis:

  • Secondary infections caused by Staphylococcus
  • Eczema herpeticum
  • Secondary contact dermatitis (due to antibiotics)
  • Hand dermatitis (by excessive contact with water)
  • Ophthalmic complications  include atopic keratoconjunctivitis, keratoconus, and atopic cataracts

Anaphylaxis[35][36][37]:

  • It can lead to acute, life-threatening respiratory failure
  • It is a medical emergency and IgE mediated with massive and rapid release of histamines and leukotrienes from mast cells
  • In severe cases acute laryngeal edema, bronchospasm, hypotension, cyanosis, and shock are present.
  • There is a list of drugs and additives that cause anaphylactoid reactions including nonsteroidal anti-inflammatory drugs including aspirin, aminopyrine, fenoprofen, flufenamic acid, ibuprofen, indomethacin, and naproxen; opiate narcotics including morphine, codeine, and meperidine; mannitol, radiographic iodinated contrast media, dextran, curare, and d-tubocurarine
  • Anaphylactoid reactions should be treated similarly as anaphylaxis

Consultations

  • Allergy specialist
  • Dermatologist
  • Pulmonary physician
  • Immunologist

Deterrence and Patient Education

Patient education is crucial and in children involves educating parents especially to identify and avoid triggers in the first place.

Patients should also receive counsel on how to manage the reactions initially and when to seek specialist help.

Enhancing Healthcare Team Outcomes

Atopy should be recognized earlier, often requires early identification by the pediatrician and early referral to an allergy specialist for disease confirmation and management. Later on, pulmonologists and dermatologist input may be necessary as well. The primary care provider, specialty-trained nurses, and pharmacists should educate the patient on keeping a diary of allergens and carrying an epinephrine injector with them. All these professionals need to collaborate as an interdisciplinary team to guide cases to the best possible outcome. [Level V] Additionally, these individuals should be told to wear an ID bracelet if they have previously suffered from an anaphylactic reaction.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Atopy - Questions

Take a quiz of the questions on this article.

Take Quiz
Which one of the following chromosomal locations are related to atopy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 5-year-old female is brought to the clinic for nasal congestion, rhinorrhea, sneezing, and a dry cough. Laboratory investigations show marked eosinophilia and increased serum IgE. Her family history is significant for asthma in the mother and eczema in an elder brother. The immunopathogenesis of the likely diagnosis involves which of the following interleukins?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 5-year-old boy is brought to the emergency department with difficulty breathing for the past 12 hours. He has had repeated episodes of bronchitis since birth. Family history is strongly positive for atopy, including asthma, eczema in food allergies in siblings and mother. On examination, he is dyspneic and has a heart rate of 130/min. Chest auscultation reveals bilateral expiratory wheezes and prolonged expirations. Which of the following is the most likely diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 78-year-old female is admitted to the medical floor for massive angioedema of the face associated with laryngeal stridor. She was treated with IV hydrocortisone. She has a history of hypertension and diabetes for which she takes aspirin, enalapril, metformin, and glipizide. Long-acting insulin was added to her regimen two months ago. She had a similar attack a month ago when she had to be intubated and ventilated in the ICU. Which of the following is the most likely cause of the patient's symptoms?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A woman presents to the hospital after being stung by a wasp. She had previously been stung on various occasions, the latest being three weeks ago. Within four minutes, she complains of light-headedness, collapses and starts making gasping sounds. Which of the following is the best next step in the management of this patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Atopy - References

References

West CE, Probiotics for allergy prevention. Beneficial microbes. 2016;     [PubMed]
Baverel P,She D,Piper E,Ueda S,Yoshioka T,Faggioni R,Gevorkyan H, A randomized, placebo-controlled, single ascending-dose study to assess the safety, tolerability, pharmacokinetics, and immunogenicity of subcutaneous tralokinumab in Japanese healthy volunteers. Drug metabolism and pharmacokinetics. 2018 Jun;     [PubMed]
Bird JA,Sánchez-Borges M,Ansotegui IJ,Ebisawa M,Ortega Martell JA, Skin as an immune organ and clinical applications of skin-based immunotherapy. The World Allergy Organization journal. 2018;     [PubMed]
Yee CS,Rachid R, The Heterogeneity of Oral Immunotherapy Clinical Trials: Implications and Future Directions. Current allergy and asthma reports. 2016 Apr;     [PubMed]
Passalacqua G,Compalati E,Canonica GW, Investigational drugs for allergic rhinitis. Expert opinion on investigational drugs. 2010 Jan;     [PubMed]
Chiesa Fuxench ZC, Atopic Dermatitis: Disease Background and Risk Factors. Advances in experimental medicine and biology. 2017;     [PubMed]
Eckl-Dorna J,Villazala-Merino S,Linhart B,Karaulov AV,Zhernov Y,Khaitov M,Niederberger-Leppin V,Valenta R, Allergen-Specific Antibodies Regulate Secondary Allergen-Specific Immune Responses. Frontiers in immunology. 2018;     [PubMed]
Zugic V,Mujovic N,Hromis S,Jankovic J,Drvenica M,Perovic A,Kopitovic I,Ilic A,Nikolic D, Pattern of Response to Bronchial Challenge with Histamine in Patients with Non-Atopic Cough-Variant and Classic Asthma. Journal of clinical medicine. 2018 Jul 12;     [PubMed]
Byrne AL,Marais BJ,Mitnick CD,Garden FL,Lecca L,Contreras C,Yauri Y,Garcia F,Marks GB, Asthma and atopy prevalence are not reduced among former tuberculosis patients compared with controls in Lima, Peru. BMC pulmonary medicine. 2019 Feb 13;     [PubMed]
Resende SD,Magalhães FC,Rodrigues-Oliveira JL,Castro VN,Souza CSA,Oliveira EJ,Carneiro M,Geiger SM,Negrão-Corrêa DA, Modulation of Allergic Reactivity in Humans Is Dependent on {i}Schistosoma mansoni{/i} Parasite Burden, Low Levels of IL-33 or TNF-α and High Levels of IL-10 in Serum. Frontiers in immunology. 2018;     [PubMed]
Brand PL,Luz García-García M,Morison A,Vermeulen JH,Weber HC, Ciclesonide in wheezy preschool children with a positive asthma predictive index or atopy. Respiratory medicine. 2011 Nov;     [PubMed]
Martineau AR,Jolliffe DA,Greenberg L,Aloia JF,Bergman P,Dubnov-Raz G,Esposito S,Ganmaa D,Ginde AA,Goodall EC,Grant CC,Janssens W,Jensen ME,Kerley CP,Laaksi I,Manaseki-Holland S,Mauger D,Murdoch DR,Neale R,Rees JR,Simpson S,Stelmach I,Trilok Kumar G,Urashima M,Camargo CA,Griffiths CJ,Hooper RL, Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health technology assessment (Winchester, England). 2019 Jan;     [PubMed]
Lloyd CM,Snelgrove RJ, Type 2 immunity: Expanding our view. Science immunology. 2018 Jul 6;     [PubMed]
Hon KL,Tsang KY,Kung JS,Leung TF,Lam CW,Wong CK, Clinical Signs, Staphylococcus and Atopic Eczema-Related Seromarkers. Molecules (Basel, Switzerland). 2017 Feb 14;     [PubMed]
Qi S,Liu G,Dong X,Huang N,Li W,Chen H, Microarray data analysis to identify differentially expressed genes and biological pathways associated with asthma. Experimental and therapeutic medicine. 2018 Sep;     [PubMed]
Pinto LA,Stein RT,Kabesch M, Impact of genetics in childhood asthma. Jornal de pediatria. 2008 Aug;     [PubMed]
Weidinger S,Klopp N,Wagenpfeil S,Rümmler L,Schedel M,Kabesch M,Schäfer T,Darsow U,Jakob T,Behrendt H,Wichmann HE,Ring J,Illig T, Association of a STAT 6 haplotype with elevated serum IgE levels in a population based cohort of white adults. Journal of medical genetics. 2004 Sep;     [PubMed]
Barnes KC,Freidhoff LR,Nickel R,Chiu YF,Juo SH,Hizawa N,Naidu RP,Ehrlich E,Duffy DL,Schou C,Levett PN,Marsh DG,Beaty TH, Dense mapping of chromosome 12q13.12-q23.3 and linkage to asthma and atopy. The Journal of allergy and clinical immunology. 1999 Aug;     [PubMed]
Blumenthal MN, The role of genetics in the development of asthma and atopy. Current opinion in allergy and clinical immunology. 2005 Apr;     [PubMed]
Atanaskovic-Markovic M,Gomes E,Cernadas J,du Toit G,Kidon M,Kuyucu S,Mori F,Ponvert C,Terreehorst I,Caubet JC, Diagnosis and management of drug-induced anaphylaxis in children: an EAACI position paper. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2019 Feb 7;     [PubMed]
Dillman JR,Trout AT,Davenport MS, Allergic-like contrast media reaction management in children. Pediatric radiology. 2018 Nov;     [PubMed]
Bardash Y,Tham T,Olson C,Khaymovich J,Costantino P, Anaphylactoid hypersensitivity reaction from intra-arterial cetuximab: Clinical considerations and management. SAGE open medical case reports. 2019;     [PubMed]
Celakovská J,Bukac J,Ettler K,Vaneckova J,Krcmova I,Ettlerova K,Krejsek J, Evaluation of Peripheral Blood Eosinophilia in Adolescent and Adult Patients Suffering from Atopic Dermatitis and the Relation to the Occurrence of Allergy to Aeroallergens. Indian journal of dermatology. 2019 Jan-Feb;     [PubMed]
Heffler E,Blasi F,Latorre M,Menzella F,Paggiaro P,Pelaia G,Senna G,Canonica GW, The Severe Asthma Network in Italy: Findings and Perspectives. The journal of allergy and clinical immunology. In practice. 2018 Oct 25;     [PubMed]
Campo P,Eguiluz-Gracia I,Bogas G,Salas M,Plaza Serón C,Pérez N,Mayorga C,Torres MJ,Shamji MH,Rondon C, Local allergic rhinitis: Implications for management. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2019 Jan;     [PubMed]
Katainen E,Kostamo K,Virkkula P,Sorsa T,Tervahartiala T,Haapaniemi A,Toskala E, Local and systemic proteolytic responses in chronic rhinosinusitis with nasal polyposis and asthma. International forum of allergy     [PubMed]
Kim JH,Lee SY,Kang MJ,Yoon J,Jung S,Cho HJ,Kim HB,Hong SJ, Association of Genetic Polymorphisms with Atopic Dermatitis, Clinical Severity and Total IgE: A Replication and Extended Study. Allergy, asthma     [PubMed]
Hemler JA,Phillips EJ,Mallal SA,Kendall PL, The evolving story of human leukocyte antigen and the immunogenetics of peanut allergy. Annals of allergy, asthma     [PubMed]
Sinclair R,Russell C,Kray G,Vesper S, Asthma Risk Associated with Indoor Mold Contamination in Hispanic Communities in Eastern Coachella Valley, California. Journal of environmental and public health. 2018;     [PubMed]
Jung S,Suh DI,Lee SY,Yoon J,Cho HJ,Kim YH,Yang SI,Kwon JW,Jang GC,Sun YH,Woo SI,Youn YS,Park KS,Cho HJ,Kook MH,Yi HR,Chung HL,Kim JH,Kim HY,Jung JA,Woo HO,Hong SJ, Prevalence, Risk Factors and Cutoff Values for Bronchial Hyperresponsiveness to Provocholine in 7-Year-Old Children. Allergy, asthma     [PubMed]
Huang JL, Asthma severity and genetics in Taiwan. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi. 2005 Jun;     [PubMed]
Maciel-Guerra H,Penha MÁ,Jorge MFS,Libório RDS,Carrijo ACNDA,Parise-Fortes MR,Miot HA, Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil. Anais brasileiros de dermatologia. 2018 Mar;     [PubMed]
Justiz Vaillant AA,Zito PM, Hypersensitivity Reactions, Immediate 2018 Jan;     [PubMed]
Chen X,Guan WJ,Sun SX,Zheng PY,Sun LH,Chen DH,Wang DD,Chen C,Sun BQ,Douglas Zhang XH, Effects of Intranasal Cellulose Powder on Asthma Control in Children With Mild-to-Moderate Perennial Allergic Rhinitis: A Randomized, Placebo-Controlled Trial. American journal of rhinology     [PubMed]
Sullivan PW,Vahram G,Abhishek K,Prakash N,Friedman HS,Benjamin O, Trends in Asthma Control, Treatment, Healthcare Utilization and Expenditures among Children in the United States by Place of Residence: 2003-2014. The journal of allergy and clinical immunology. In practice. 2019 Feb 14;     [PubMed]
van der Schaft J,Thijs JL,Garritsen FM,Balak D,de Bruin-Weller MS, Towards personalized treatment in atopic dermatitis. Expert opinion on biological therapy. 2019 Feb 15;     [PubMed]
Braun C,Eigenmann P, [Management of childhood food allergies]. Revue medicale suisse. 2019 Feb 13;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Surgery-Podiatry APMLE Part 2. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Surgery-Podiatry APMLE Part 2, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Surgery-Podiatry APMLE Part 2, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Surgery-Podiatry APMLE Part 2. When it is time for the Surgery-Podiatry APMLE Part 2 board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Surgery-Podiatry APMLE Part 2.