Vitamin D as adjuvant to subcutaneous specific immunotherapy in patients with allergic rhinitis BACKGROUND Allergic diseases are considered the pandemic of the 21 century. Allergic rhinitis (AR) is the most common with an overall prevalence of 4 to 40% in the world. In Latin America, it is a common chronic disease, with an overall prevalence in 8 countries assessed 6.6%. However, the percentage is remarkably lower than that found in ISAAC, which showed a prevalence of 27.9% in patients aged 6 to 7 years and 37.6% in 13 to 14 years. In children under 10 years, the prevalence of 11.6% in Mexico and in children aged 13 to 14 years in Mexico is 15%. Studies in Mexico, with the measuring instrument ISAAC Phase III study, reported an overall prevalence of allergic rhinitis 4.6%. Allergic rhinitis is a chronic inflammatory disease of the nasal mucosa mediated by IgE antibodies specific allergen, with the participation of various cells, cytokines, chemoattractants and mediadores. Allergic rhinitis generates direct and indirect costs including treatment of chronic disease, comorbidities, social and employment impact and escolar absenteeism. The base immunopathological allergic rhinitis is type I hypersensitivity mediated immunoglobulin type E (IgE) specific to a previously sensitized antigen, usually inhalado. Allergic sensitization and response occur in two steps. The first is the antigen uptake by antigen presenting cells (APCs) that can be professional, B lymphocytes or dendritic cell CPA. The CPA, after processing the antigen inside and present on their surface receptors with major histocompatibility complex (HLA) class II, contact a T-collaborator CD4 + (TH2) cell. This activates the TH2 cell interaction, resulting in the release of several cytokines, such as interleukins 4, 5, 9 and 13, which stimulate more TH2 cells, eosinophils and cause the differentiation of specific B cells into plasma cells producing specific immunoglobulin E against allergen. Thus large amounts of specific IgE to the blood are released. These specific IgE adhere to their receptors present high and low affinity on the surface of mast cells (also called mast cells), rendering them "sensitized". The second step is a subsequent exposure to the allergen which binds to membrane IgE producing degranulation of mast cells and release of preformed mediators such as histamine, and de novo synthesis of other mediators, including leukotrienes, prostaglandins, thromboxanes, kinins and proteasas. This response early phase of the allergic reaction occurs 10 to 30 minutes after exposure to allergens. It is useful, practical and recommended follow international guidelines ARIA (Allergic Rhinitis and Its Impact on Asthma) for the diagnosis, classification and treatment of rhinitis alérgica. ARIA proposes to investigate and analyze the clinical findings of the interrogation and physical examination such as watery rhinorrhea, congestion, obstruction and nasal itching, sneezing, allergic shiners, allergic salute, Dennie Morgan lines; and laboratory data as serum eosinophilia, serum total IgE levels increased in the absence of parasitosis and eosinophils present in the nasal cytology, it allows us to confirm the diagnosis of allergic rhinitis and its subtypes, as well as other types of rhinitis. The definitive diagnosis is made by identifying the signs, symptoms and laboratory data previously mentioned the identifiación of IgE specific to the allergen or allergens previously sensibilizado. There are two ways to identify an allergen skin tests and other blood with ImmunoCAP®. Once the definitive diagnosis of allergic rhinitis, management begins with the advice and education for the patient and his family confirmed about the disease and its treatment. Initial measures taken to prevent or mitigate the symptoms of allergic rhinitis is two; First, avoid contact with allergens triggers and second change their environment. The medium-environmental measures often include modifying factors that are known by the patient or are potentially a source of allergic response in areas such as home, school and laboral environment. Drug treatment for allergic rhinitis is with oral antihistamines and topical, oral and topical steroids, leukotriene inhibitors, membrane stabilizing mast cells, limited and controlled application of topical decongestants and anticolinérgicos. The unifying action among these drugs is modulation of the immune response to the allergen. In some cases, the pharmacological agent is specific therapeutic targets (membrane stabilizing mast cells, antihistamines) and in others, the agent has a generalized mode of action in alleviating the immune response (steroids). Skin tests allow to establish which specific allergens are causing the hiperreactividad. This is necessary before starting immunotherapy, which is administered and advised when dealing with a patient with persistent allergic rhinitis and the measures described above are insufficient to control. Documenting specific allergen sensitivity by, preferably with skin testing in vivo IgE, can route the inmunoterapia. Subcutaneous immunotherapy involves injecting staggered amounts of allergen until a "maintenance dose" or the maximum tolerated dose that relieves síntomas13. The only treatment that has succeeded in changing the natural history of disease is specific immunotherapy (SIT) with allergens; today is the treatment of elección14. Subcutaneous immunotherapy has a history of over a hundred years since its first application in England in 1911 by Leonard Noon15. It is applied in two phases: a phase of tolerance induction and maintenance. After the induction phase of tolerance in which the dose is gradually rises to reach the scheduled dose mantenimiento13 phase begins. The maintenance dose is delivered every two to six weeks, depending on the characteristics of extracto14. Immunotherapy is typically continued for three to five years and results in immunological tolerance (defined as the absence of specific immune response against an allergen, whether self or foreign, induced by previous contact) and control symptoms long term, even after suspend, up to 75% of pacientes13,14. The time it takes to start the therapeutic response is prolonged, an average of 6 meses13,14. The main drawback, as a result of this problem, poor adherence to treatment, therefore it is necessary to find strategies to accelerate the response terapéutica16. Today it is clearly known that asthma using vitamin D plus immunotherapy decrease symptoms and medication use associated with increased IgG4, IL10, TGF-b17 and T lymphocytes reg18. Also it inhibits immunological reactions such as increased cytokine profile TH17 and decreased IL-10, mediated by TH1 lymphocytes and TH 1719. In addition reduces inflammation and cytokine-mediated expression TH219 cells. Previously, in an animal model it demonstrated that vitamin D decreases IL-5 and IL-13 in 3 months20. Several estudios21,22,25, show that vitamin D stimulates the production of CD4 + CD25 + FOXP3 Treg +, which would help produce more temprano21 immunological tolerance. In patients with asthma who received immunotherapy more vitamin D compared with another group receiving only immunotherapy improvement of symptoms was documented earlier in the first group, with a statistically significativa21. Clinical trials have proven vitamin D in allergic diseases like allergic rhinitis and asthma and dermatitis atópica22. It is known that vitamin D supplementation more conventional treatment in atopic dermatitis improves the resolution of the severity of symptoms 40% faster than when conventional treatment is used alone, ie avoid the allergen, skin hydration, antihistamines and steroids; also it normalizes patterns of TH1, TH2, TH17 and Treg in 3 months22. The American Society of endocrinology considered normal serum 25 (OH) D when they are above 30 ng / ml, failure between 21 and 29 ng / ml and less than 20 ng / ml23 deficiency. Previous studies recommend that patients benefit from the additional administration of vitamin D are those exhibiting serum 25 (OH) D less than 30 ng / ml24,25. The requirements in children aged 0 to 1 year old are at least 400 IU / day and children over 1 year, at least 600 IU / day.27. To keep blood levels greater than 30 ng / ml are needed at least 1000 IU / day for children older than 1 year. To correct vitamin D deficiency values between 1000 IU and 4000 IU are used in children without graves27 problems arise. If values greater than 5000 IU in children are used estricta27 medical supervision is recommended. The side effects are alterations in serum levels of calcium and parathormona27.