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This month, JACI presents the second portion of the comprehensive international consensus (ICON) statement on allergen immunotherapy. The ICON statement is an effort of the International Collaboration in Asthma, Allergy and Immunology (iCALL) that includes the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI) and the World Allergy Organization (WAO). Jutel et al. review the evidence on how allergen immunotherapy (AIT) works and summarize what lies on the horizon ( J Allergy Clin Immunol 2016; 137(2): 358-368 ). A number of mechanisms underlie an allergic response to a substance such as grass pollen, house dust mites, or bee venom. Allergen immunotherapy involves slowly increasing exposure to an allergen over time, ideally resulting in a patient’s increased tolerance and clinical improvement. The literature indicates that administration of AIT leads t...

In early 2014, the Food and Drug Administration approved three sublingual allergen immunotherapy (SLIT) products for use in the United States: a 5-grass tablet, a timothy grass tablet, and a ragweed tablet. The approval was based on multicenter clinical trials with large patient populations and supported by decades of real-life use in Europe. Li et al. have provided a consensus report of the experts of the American Academy of Allergy, Asthma and Immunology (AAAAI) and European Academy of Allergy and Clinical Immunology (EAACI) for the prescribing clinician ( J Allergy Clin Immunol 2016; 137(2): 369-376 ). The decision to use SLIT depends on practical considerations, cost, convenience, and patient preference. Within the current therapeutic options for allergic rhinitis, SLIT offers a therapy that can be self-administered at home and has the potential to permanently alter the course of allergic disease. In addition to those patients who prefer a disease-modifying approach, SLIT may work ...

The diagnosis of occupational asthma (OA) poses challenges to the clinician and requires a stepwise approach. The American College of Chest Physicians has recently published a consensus on this approach, also providing guidelines that indicate “the absence of airway hyper-responsiveness on challenge testing has a fairly high negative predictive value (NPV) for current symptomatic asthma, and can generally be used to rule out active disease.” Pralong et al. have verified this statement, evaluating the sensitivity, specificity, and positive and negative predictive values of the methacholine challenge in the diagnosis of occupational asthma ( J Allergy Clin Immunol 2016; 137(2): 412-416 ). The authors used a Canadian database to review 1012 cases of workers who, between the years of 1983 and 2011, were referred for suspicion of having occupational asthma and who underwent a specific inhalation challenge (SIC). SIC is considered the gold standard for diagnosing OA. It entails a first day o...

Mastocytosis is a condition characterized by expansion of clonal mast cells in various organ systems, often in association with activating KIT mutations. The organs most frequently affected are the skin and bone marrow. Traditionally, the disease is divided in cutaneous mastocytosis (CM) and systemic mastocytosis (SM). CM is further divided into maculopapular cutaneous mastocytosis (MPCM), also known as urticaria pigmentosa, diffuse cutaneous mastocytosis (DCM), and mastocytoma of skin. Children with mastocytosis usually have CM, whereas the majority of adults are diagnosed with SM. Both children and adults usually present with typical cutaneous (red or brown) lesions. These cutaneous lesions are highly heterogeneous, encompassing local and disseminated forms. Overall there is a need for a better definition and a clinically meaningful classification of cutaneous lesions detectable in CM and SM. To address this need, an international task force of experts from the European Competence N...

Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily manifests in synovial joints, such as those in the hands and feet. It can appear at any age in life and affects up to 1% of the population. While it is classified based on the presence of articular inflammation, a growing body of evidence indicates that RA autoimmunity begins outside of the joint. Circulating rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), anti-peptidylarginine deiminases (anti-PAD4), and anti-carbamylated proteins (anti-CarP) have been detected in many people years prior to the development of joint symptoms and an RA diagnosis. Several lines of investigation have implicated mucosal tissues of the lung and oral cavity as possible sites of initial autoantibody generation and inflammation. Mikuls et al. review the recent reports of this line of investigation ( J Allergy Clin Immunol 2016; 137(1): 28-34 ). In addition to harboring host inflammatory cells, mucosal tissues support ...

Autoimmunity and immunodeficiency represent two sides of the same coin. Whether the human body’s defenses attack its own healthy cells or its ability to fight off disease is compromised, both result in a dysfunctional immune system. In their review article, Grimbacher et al. discuss the contribution of various immune system genes to common polygenic autoimmune disorders, as well as the pathophysiological pathways and clinical features of monogenic defects that result in autoimmune disease ( J Allergy Clin Immunol 2016; 137(1): 3-17 ). Multiple single gene defects have been shown to result in rare diseases that show features of both autoimmunity and immunodeficiency. Nearly 300 monogenic traits have been associated with various forms of primary immunodeficiency diseases and auto-inflammatory syndromes. It is likely that more common autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) result from a polygenic inheritance. Genes implicated in single...

Oral immunotherapy (OIT) has shown overall benefit in desensitizing many patients with persistent IgE-mediated food allergy. Still, the treatment is not without adverse reactions. In a large OIT milk treatment program conducted in Israel, approximately 15% of patients were unable to follow it to completion because of IgE-mediated reactions. Some patients with allergy to unheated milk or egg tolerate such foods when they are heated, as heating likely induces conformational changes to a number of the epitopes responsible for IgE binding. Goldberg et al present a study of 14 children who failed unheated- or unbaked-milk OIT who received OIT with baked milk testing the hypothesis that this might result in desensitization to to unheated milk as well ( J Allergy Clin Immunol 2015; 136(6): 1601-1606 ). Only three of the children tolerated the primary outcome dose of 1.3 g of baked milk protein, and eight out of the other 11 experienced IgE-mediated reactions, including two patients with anaph...