clair088

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...

The epidemic proportion of atopic diseases in the last 30 years has resulted in major health and economic effects. Atopy is believed to be due to a genetic propensity to produce IgE antibodies in response to an allergen; such propensity is due to an imbalance between various lymphocyte subsets,TH1, TH2 and T regulatory (Treg) cells in particular. In the absence of early intervention, children born with atopic diathesis are likely to develop allergic disease. Zolkipli et al. report the results of a house dust mite allergy prevention study conducted in infants ( J Allergy Clin Immunol 2015; 136(6): 1541-1547 ).  Overcoming maturation deficiencies in the developing immune system and countering T H 2 bias requires a very early strong and adequate immune stimulation. In the first 18 months of life, the gut is the primary site of Treg cells stimulation in response to antigens, suggesting oral exposure is likely the most effective in inducing tolerance. The authors hypothesized that expos...

Chronic rhinosinusitis affects approximately 10% of the adult population in industrialized countries. Its effects range from pain in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) to nasal obstruction and comorbid asthma in those suffering from chronic rhinosinusitis with nasal polyps (CRSwNP). Current therapy approaches, such as pharmacotherapy and endoscopic surgery, focus on these two phenotypes. They have not, however, proved effective regarding long-term control of symptoms or risk of recurrence for many patients with severe polyp disease. Bachert et al. discuss the current shift in treatment focus from phenotype to endotype and the related innovative therapies on the horizon ( J Allergy Clin Immunol 2015; 136(6): 1431-1440 ). A clinical phenotype groups patients with similar clinically observable characteristics. Various pathomechanisms underlie a given phenotype. Understanding and characterizing disease via a shared and unique pathomechanism creates an endoty...

In spite of optimal guidelines-based asthma treatment many children and adolescents with asthma continue to experience exacerbations. Asthma exacerbations have serious consequences, from increased morbidity to disease progression. While exacerbations can occur at any time to any patient, children with advanced disease, greater degrees of atopy, or who have experienced a recent exacerbation appear most susceptible to further exacerbation, and the time of year in which it is most likely to occur is in the autumn. Previous Inner-City Asthma Consortium (ICAC) studies demonstrated higher daily doses of inhaled corticosteroids (ICSs) or the addition of omalizumab to year-round treatment reduced exacerbation frequency. Continuous treatment with either, however, risks side effects and incurs financial cost. Teach et al. have examined a seasonal, preventive approach, finding the addition of omalizumab four to six weeks prior to the start of school to ongoing guidelines-based management signific...