Clinical reviews in allergy & immunology
-
Clin Rev Allergy Immunol · Apr 2019
ReviewUpdate on the Use of C1-Esterase Inhibitor Replacement Therapy in the Acute and Prophylactic Treatment of Hereditary Angioedema.
In the vast majority of patients with hereditary angioedema (HAE), angioedema attacks are due to the quantitative or functional deficiency of C1-esterase inhibitor (C1-INH), which leads to increased vascular permeability and unregulated release of bradykinin. Exogenous administration of C1-INH is a rational way to restore the concentration and functional activity of this protein, regulate the release of bradykinin, and attenuate or prevent subcutaneous and submucosal edema associated with HAE. Recent international guidelines for the management of HAE include C1-INH as an option for acute treatment of HAE. ⋯ Both formulations when administered twice weekly have been shown to reduce the frequency and severity of HAE attacks. The SC formulation of C1-INH obviates the need for repeated venous access and may facilitate self-administration of HAE prophylaxis at home, as recommended in HAE treatment guidelines. As with most rare diseases, the costs of HAE treatment are high; however, the development of additional acute and prophylactic medications for HAE may result in competitive pricing and help drive down the costs of HAE treatment.
-
Clin Rev Allergy Immunol · Apr 2019
ReviewMast Cell-Mediated Orchestration of the Immune Responses in Human Allergic Asthma: Current Insights.
Improving the lung function after experimental allergen challenge by blocking of mast cell (MC) mediators and the capability of MC mediators (including histamine, prostaglandin (PG) D2, and leukotriene (LT) C4) in induction of mucosal edema, bronchoconstriction, and mucus secretion provide evidence that MCs play a key role in pathophysiology of asthma. In asthma, the number of MCs increases in the airways and infiltration of MCs in a variety of anatomical sites including the epithelium, the submucosal glands, and the smooth muscle bundles occurs. MC localization within the ASM is accompanied with the hypertrophy and hyperplasia of the layer, and smooth muscle dysfunction that is mainly observed in forms of bronchial hyperresponsiveness, and variable airflow obstruction. ⋯ MC-released preformed mediators including chymase, tryptase, and histamine and de novo synthesized mediators such as PGD2, LTC4, and LTE4 in addition of cytokines mainly TGFβ1, TSLP, IL-33, IL-4, and IL-13 participate in pathogenesis of asthma. The release of MC mediators and MC/airway cell interactions during remodeling phase of asthma results in persistent cellular and structural changes in the airway wall mainly epithelial cell shedding, goblet cell hyperplasia, hypertrophy of ASM bundles, fibrosis in subepithelial region, abnormal deposition of extracellular matrix (ECM), increased tissue vascularity, and basement membrane thickening. We will review the current knowledge regarding the participation of MCs in each stage of asthma pathophysiology including the releasing mediators and their mechanism of action, expression of receptors by which they respond to stimuli, and finally the pharmaceutical products designed based on the strategy of blocking MC activation and mediator release.
-
Clin Rev Allergy Immunol · Dec 2018
ReviewThe Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis.
Psoriasis is a chronic, immune-mediated, inflammatory disease that is pathogenically driven by proinflammatory cytokines. This article reviews the immunologic role of interleukin (IL)-17, the major effector cytokine in the pathogenesis of psoriatic disease, along with the rationale for targeting the IL-17 cytokine family (IL-17A, IL-17F, and IL-17 receptor A) in the treatment of psoriasis and psoriatic arthritis. ⋯ The critical importance of the IL-23/IL-17A axis to the pathogenesis of psoriatic disease has resulted in many new biologic treatments targeting these cytokines. These biologics dramatically improve skin and joint symptoms in patients with moderate-to-severe psoriasis and psoriatic arthritis.
-
Clin Rev Allergy Immunol · Oct 2018
ReviewOral and Sublingual Immunotherapy for Treatment of IgE-Mediated Food Allergy.
Development of active therapies for IgE-mediated food allergy is a critical action step toward alleviating the adverse medical, psychosocial, and economic burdens on affected patients and families. Significant progress has been observed specifically in the application of single-allergen oral and sublingual immunotherapy for treatment of IgE-mediated food allergy, with emphasis on milk, egg, and peanut as the primary allergens. Oral immunotherapy (OIT) has demonstrated efficacy in promoting immunomodulatory effects that lead to the clinical outcome of desensitization, defined as reduced reactivity while on active OIT, in the majority of treated individuals; however, achievement of sustained unresponsiveness following cessation of therapy has been observed in a smaller subset of treated subjects. ⋯ Sublingual immunotherapy (SLIT) has been utilized for the treatment of food allergy and pollen-food allergy syndrome, demonstrating moderate efficacy, a favorable safety profile and variable tolerability, with oropharyngeal symptoms most commonly observed. Although studies directly comparing OIT and SLIT are limited, in general, the favorable safety profile associated with SLIT comes at the expense of reduced efficacy, while the more robust clinical effects observed with OIT come at the risk of potentially intolerable, treatment-limiting side effects. Future investigation to address specific knowledge gaps including optimal dose, duration, age of initiation, maintenance schedule, mechanisms, predictors of risk and therapeutic response will be important to maximize efficacy, minimize risk and develop personalized, effective approaches to targeting food allergy.
-
Clin Rev Allergy Immunol · Aug 2018
ReviewDietary Therapy for Eosinophilic Esophagitis: Elimination and Reintroduction.
Eosinophilic esophagitis (EoE) is a food antigen-mediated disorder of the esophagus characterized by eosinophil predominant inflammation and symptoms of esophageal dysfunction. Dietary antigen elimination induces clinical and histological remission in patients with EoE. The most restrictive of elimination diets (the elemental diet) removes all possible food antigens while empiric elimination diets remove all (or a subset) of food antigens most commonly reported to cause esophageal eosinophilia and food allergies (milk, egg, wheat, soy, peanuts, tree nuts, fish, or legumes). ⋯ Foods that are commonly eliminated, especially milk, are also nutrient-dense and therefore their elimination may result in inadequate nutrient intake or deficiencies without careful diet planning to include nutritionally comparable and safe food substitutes. After remission is achieved with elimination diets, foods can be reintroduced sequentially to identify specific food triggers, but this reintroduction is not standardized. Food elimination and food reintroductions should consider the patient's lifestyle, nutrition needs, and skills and ideally be managed by a team with knowledge of eosinophilic gastrointestinal disorders and nutrition.