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Summary: Objective. The association of allergic conjunctivitis (AC) with rhinitis and/or asthma is poorly understood. The objective of this study was to apply the Consensus Document for Allergic Conjunctivitis (DECA) criteria for the classification of AC to a population of patients with AC to assess the association between the severity and duration of AC and rhinitis and/or asthma. Methods. Patients with ocular symptoms of AC who participated in the 'Alergológica 2015' study were included. The demographics, classification according to the DECA criteria, etiology, and comorbidities were evaluated by age groups (less or equal than 14 and greater than 14 years). Results. A total of 2,914 patients (age range, 1-90 years) were included in the "Alergológica 2015" study. Of these, 965 patients (33.1%) were diagnosed with AC (77.5% > 14 years). AC was classified as severe, moderate, or mild in 1.8%, 46.4%, and 51.8%, respectively; and as intermittent or persistent in 51.6% and 48.4% of the patients. AC alone occurred in 4% of patients. AC was mainly associated with rhinitis (88.4%), asthma (38.2%), food allergy (8.3%) and atopic dermatitis (3.5%). In allergic respiratory disease rhinitis preceded AC and asthma developed later. The severity and duration of AC was significantly associated with severity and duration of rhinitis (p less than 0.001 for both age groups) and asthma (p less than 0.001 only in adults). Conclusions. The application of the new DECA classification for AC reveals a direct relationship between AC, rhinitis and asthma respect to severity and duration. These relationships suggest that AC should be considered an integral part of the "one airway, one disease" hypothesis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used throughout the world. They are frequently involved in hypersensitivity reactions, which range from local or mild reactions to systemic and severe reactions. Consequently, it is necessary to perform an exhaustive study of patients in order to make an accurate diagnosis, search for safe procedures in the case of severe reactions, and identify alternative treatment options. Various guidelines and protocols address the management of hypersensitivity to NSAIDs, although these vary widely from country to country. The Committees of Asthma, Rhinoconjunctivitis, and Drug Allergy of the Spanish Society of Allergy and Clinical Immunology (SEAIC) propose the present position statement on available options for provocation testing with aspirin/NSAIDs. This document is the fruit of an exhaustive review of current evidence and is based on recent publications addressing the diagnosis of patients with hypersensitivity to NSAIDs and on a consensus-oriented discussion among a group of experts from the SEAIC. The main objective was to draft an easy-toread, practical guideline for health care professionals in specialist areas who assess and manage patients with suspected hypersensitivity to NSAIDs. Furthermore, indications, contraindications, and procedures for oral, bronchial, and nasal provocation tests with aspirin/NSAIDs have been updated.

Objectives: Cryopyrin-associated periodic syndromes (CAPS) usually start during infancy as an urticarial-like rash and a marked acute phase response, with additional manifestations appearing during its evolution. The aim of this study was to expand the clinical diversity of CAPS by the description of novel atypical features., Methods: Clinical data were collected from patients' medical charts. Sanger sequencing analyzed NLRP3. Response to anti-IL-1 blockade was evaluated by clinical assessments and by measurements of laboratory parameters., Results: Seventeen patients from two families (A and B), carrying the p.Ala439Thr and p.Arg260Trp NLRP3 mutations respectively, were enrolled. The disease was unexpectedly atypical in all members of Family A, with a 16-year-old asymptomatic carrier, and onset in adulthood associated with absence of skin lesions in four affected members. Surprisingly, one patient from each family suffered from severe haemorrhagic cystitis due to AA amyloidosis in the urinary bladder. Members of Family B displayed a classical phenotype, with two patients suffering from olfactive disorders., Conclusions: Our evidence suggests that CAPS may occasionally be presented as a late-onset, recurrent inflammatory disease without urticarial-like rash. In some patients, AA amyloidosis in strange locations like urinary bladder may complicate the clinical course. The response to IL-1 blockade in these atypical CAPS was similar to that described in classical forms. Consequently, we suggest that CAPS should be included in the differential diagnosis of adult patients with unexplained, recurrent inflammatory diseases, and once confirmed, the early initiation of anti-IL-1 blockade will probably prevent the development of life-threatening complications.

Background: Despite the socioeconomic importance of allergic rhinitis (AR), very few prospective studies have been performed under conditions of clinical practice and with a sufficiently long observation period outside the clinical trial scenario. We prospectively estimated the direct and indirect costs of AR in patients attending specialized clinics in Spain., Methods: Patients were recruited at random from allergy outpatient clinics in 101 health centers throughout Spain over 12 months. We performed a multicenter, observational, prospective study under conditions of clinical practice. We analyzed direct costs from a funder perspective (healthcare costs) and from a societal perspective (healthcare and non-healthcare costs). Indirect costs (absenteeism and presenteeism [productivity lost in the workplace]) were also calculated. The cost of treating conjunctivitis was evaluated alongside that of AR., Results: The total mean cost of AR per patient-year (n = 498) was €2326.70 (direct, €553.80; indirect, €1772.90). Direct costs were significantly higher in women (€600.34 vs €484.46, P = 0.02). Total costs for intermittent AR were significantly lower than for persistent AR (€1484.98 vs €2655.86, P < 0.001). Total indirect costs reached €1772.90 (presenteeism, €1682.71; absenteeism, €90.19). The direct costs of AR in patients with intermittent asthma (€507.35) were lower than in patients with mild-persistent asthma (€719.07) and moderate-persistent asthma (€798.71) (P = 0.006)., Conclusions: The total cost of AR for society is considerable. Greater frequency of symptoms and more severe AR are associated with higher costs. Indirect costs are almost threefold direct costs, especially in presenteeism. A reduction in presenteeism would generate considerable savings for society., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The variability of symptoms observed in patients with respiratory allergy often hampers classification based on the criteria proposed in guidelines on rhinitis and asthma., Objectives: We assessed specific aspects of allergic respiratory disease (ARD) that are not explicitly addressed in the guidelines in order to issue specific recommendations and thus optimize clinical practice., Methods: Using the Delphi technique, 40 Spanish allergists were surveyed to reach consensus on 71 items related to ARD., Results: Consensus was achieved for 95.7% of the items. These included the following: the clinical manifestations of ARD are heterogeneous and individual airborne allergens can be related to specific clinical profiles; the optimal approach in patients with ARD is based on the global assessment of rhinoconjunctivitis and asthma; aeroallergens are largely responsible for the clinical features and severity of the disease; and clinical expression is associated with the period of environmental exposure to the allergen. Pharmacological treatment of ARD is often based on the intensity of symptoms recorded during previous allergen exposures and cannot always be administered following a step-up approach, as recommended in clinical practice guidelines. Allergen immunotherapy (AIT) is the only option for overall treatment of respiratory symptoms using an etiological approach. AIT can modify the prognosis of ARD and should therefore be considered a valuable first-line treatment., Conclusions: The present study highlights gaps in current asthma and rhinitis guidelines and addresses specific aspects of ARD, such as global assessment of both asthma and rhinitis or the specific role of variable allergen exposure in the clinical expression of the disease.

Food allergy and respiratory allergy are two frequently associated diseases and with an increasing prevalence. Several reports show the presence of respiratory symptoms in patients with food allergy, while certain foods may be related to the development or exacerbation of allergic rhinitis and asthma. The present update focuses on this relationship, revealing a pathogenic and clinical association between food and respiratory allergy. This association is even more intense when the food hypersensitivity is persistent or starts in the early years of life. Food allergy usually precedes respiratory allergy and may be a risk factor for allergic rhinitis and asthma, becoming a relevant clinical marker for severe atopic asthma. Furthermore, the presence of co-existing asthma may enhance life-threatening symptoms occurring during a food allergic reaction. Recommendations for dietary restrictions during pregnancy and breastfeeding to prevent the development of respiratory allergy are controversial and not supported by consistent scientific data. Current recommendations from medical societies propose exclusive breastfeeding during the first four months of life, with the introduction of solid food in the fourth to the seventh month period of life. A delayed introduction of solid food after this period may increase the risk of developing subsequent allergic conditions. Further studies are encouraged to avoid unjustified recommendations involving useless dietary restrictions., (Copyright © 2015 SEICAP. Published by Elsevier Espana. All rights reserved.)

Unlabelled: : Familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome are dominantly inherited autoinflammatory diseases associated to gain-of-function NLRP3 mutations and included in the cryopyrin-associated periodic syndromes (CAPS). A variable degree of somatic NLRP3 mosaicism has been detected in ≈35% of patients with CINCA. However, no data are currently available regarding the relevance of this mechanism in other CAPS phenotypes., Objective: To evaluate somatic NLRP3 mosaicism as the disease-causing mechanism in patients with clinical CAPS phenotypes other than CINCA and NLRP3 mutation-negative., Methods: NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. Apoptosis-associated Speck-like protein containing a CARD (ASC)-dependent nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants., Results: A variable degree (5.5-34.9%) of somatic NLRP3 mosaicism was detected in 12.5% of enrolled patients, all of them with a MWS phenotype. Six different missense variants, three novel (p.D303A, p.K355T and p.L411F), were identified. Bioinformatics and functional analyses confirmed that they were disease-causing, gain-of-function NLRP3 mutations. All patients treated with anti-interleukin1 drugs showed long-lasting positive responses., Conclusions: We herein show somatic NLRP3 mosaicism underlying MWS, probably representing a shared genetic mechanism in CAPS not restricted to CINCA syndrome. The data here described allowed definitive diagnoses of these patients, which had serious implications for gaining access to anti-interleukin 1 treatments under legal indication and for genetic counselling. The detection of somatic mosaicism is difficult when using conventional methods. Potential candidates should benefit from the use of modern genetic tools., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Nasal hyperreactivity is the abnormal reaction of nasal tissue to a stimulus that is innocuous to most people. This response is caused by dysregulation of the autonomic nervous system at various levels of the nasal autonomic reflex arc. Various stimuli (methacholine, histamine, adenosine 5'-monophosphate, cold air, mannitol, rapsaicin, phentolamine, and distilled water) have been used in an attempt to find the test that most reliably differentiates between healthy individuals and patients and also between different types of rhinitis. Despite the small number of publications available, in the present review, we provide an update on current nonspecific nasal provocation techniques. The studies published to date are not comparable: the stimuli applied act through different mechanisms and are used to assess different pathways, and the methodologies differ in terms of selection of participants, concentrations used, and assessment of response (criteria for positivity). Given the limited use of nonspecific nasal provocation tests in routine clinical practice, we believe that more studies are warranted to address the research issues we present at the end of the present review, for example, the need to standardize the methodology for each test or even the clinical benefits of knowing whether or not a patient has nasal hyperreactivity.

Background: Nasal polyposis (NP) is a chronic inflammatory disease that constitutes a major health problem with significant comorbidities and a considerable associated socioeconomic burden., Objective: To describe the clinical features and management of patients with NP attending Spanish allergy centers, the use of health care resources, and the degree of compliance with the diagnostic and therapeutic recommendations of the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS)., Methods: We performed a multicenter, observational, and cross-sectional epidemiologic study of 671 patients consulting for NP in 67 Spanish allergy departments. We used sociodemographic and clinical questionnaires to evaluate clinical characteristics, use of health care resources, diagnostic methods, and treatment administered., Results: NP was closely associated with asthma (66%), allergic rhinitis (45.9%), and hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) (26%). Atopy was present in the 50% of cases, with Dermatophagoides pteronyssinus as the most frequent sensitizing allergen. Eleven percent of NP patients visited the emergency department during the previous year, and more than 58% used primary care, allergy, or otorhinolaryngology services. The most frequently used diagnostic tests were skin prick tests (93.6%) and anterior rhinoscopy (79.4%). Intranasal corticosteroids were the drug class most frequently prescribed by allergists (74.6%). Specific immunotherapy was prescribed in 21% of patients., Conclusions: NP is a chronic inflammatory disease that generates considerable use of health care resources. The close association with atopy, asthma, and NSAID hypersensitivity highlights the usefulness of an allergy workup in all patients with NP. Analysis of the clinical management of NP by allergists in Spain revealed a high degree of compliance with EPOS diagnostic and therapeutic recommendations.

Allergic conjunctivitis (AC) is an inflammatory disease of the conjunctiva caused mainly by an IgE-mediated mechanism. It is the most common type of ocular allergy. Despite being the most benign form of conjunctivitis, AC has a considerable effect on patient quality of life, reduces work productivity, and increases health care costs. No consensus has been reached on its classification, diagnosis, or treatment. Consequently, the literature provides little information on its natural history, epidemiological data are scarce, and it is often difficult to ascertain its true morbidity. The main objective of the Consensus Document on Allergic Conjunctivitis (Documento dE Consenso sobre Conjuntivitis Alérgica [DECA]), which was drafted by an expert panel from the Spanish Society of Allergology and Spanish Society of Ophthalmology, was to reach agreement on basic criteria that could prove useful for both specialists and primary care physicians and facilitate the diagnosis, classification, and treatment of AC. This document is the first of its kind to describe and analyze aspects of AC that could make it possible to control symptoms.

Background: Nasal polyposis (NP) is a chronic inflammatory disease of unknown etiology that impairs quality of life (QoL). The role of atopy in NP is not established. The aim of this study was to describe the clinical characteristics and QoL in a broad sample of patients with NP and to evaluate the influence of allergy on this disease., Methods: A multicenter, observational, cross-sectional study was conducted in 67 allergy units in Spain. NP and nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity were diagnosed following EP(3)OS guidelines. Rhinitis and asthma were classified following Allergic Rhinitis and Its Impact on Asthma and the Global Initiative for Asthma guidelines, respectively. Skin tests with a battery of aeroallergens were performed on all patients. A visual analog scale (VAS) and Short-Form 12 (SF-12) and 31-item Rhinosinusitis Outcome Measure (RSOM 31) questionnaires were completed by all the patients., Results: Of the 671 patients included, 611 were evaluable. Mean age was 46 years and 50% of patients were men. Also, 50% were atopic. Asthma was present in 66% of patients and NSAID hypersensitivity was present in 26%. The most frequent symptoms were nasal congestion and rhinorrhea. Mean value of VAS was 58.6. Global health and bodily pain were the items most frequently identified in the SF-12 questionnaire and nasal and ocular symptoms in the RSOM-31 questionnaire. There was a good correlation between VAS score and QoL (p < 0.0001). Rhinitis was more severe in nonallergic patients. Asthma was more frequent in atopic patients, whereas ASA triad was more frequent in nonatopic patients. Atopic patients showed higher VAS scores and worse QoL., Conclusion: Atopic NP patients showed worse QoL, higher incidence of asthma and a less severe form of rhinitis than non-atopic patients.

Specific nasal provocation testing (NPT) consists of eliciting a response from the nasal mucosa by controlled exposure to allergens. It is indicated in the diagnostic confirmation of allergic rhinitis and when discrepancies arise or difficulties exist in the assessment of a patient's medical history and the results of skin and/or serological tests. The technique is also applied to evaluate sensitivity to the allergen, the efficacy and safety profile of treatment, and in research on the pathophysiological mechanisms of nasal response to allergens. NPT also provides information on the etiology of occupational respiratory diseases of allergic origin. Although there have been many studies and publications on the use and standardization of bronchial provocation tests with allergen, few analyze specific NPT. In this review, the Rhinoconjunctivitis Committee of the Spanish Society of Allergy and Clinical Immunology discuss the methodology, monitoring, and assessment of allergen-specific NPT in order to provide a practical and up-to-date review of the technique.

Background: Allergic rhinitis is the most frequent chronic allergic disease in children, and may be an important risk factor for the subsequent development of asthma., Objective: To describe the characteristics of patients younger than 14 years of age presenting with rhinitis and the possible association with asthma., Methods: We carried out a prospective, observational, descriptive, cross-sectional epidemiologic study (Alergológica 2005) of 917 patients under the age of 14 consulting for the first time in allergy departments in Spain., Results: Rhinitis was diagnosed in 42.5% of the children. The association between asthma and rhinitis was significantly higher in children than in adults (44.9% vs 35.5%; P<.05). Time from onset of rhinitis was significantly associated with the development of asthma (2.97 vs 2.06 years; P<.0001). Allergy was the most frequent cause of rhinitis in children with and without asthma. Allergy to epithelia and fungi was more frequent in children with rhinitis and asthma than in children with rhinitis alone. We found no differences in the frequency of treatment with immunotherapy between children with and without asthma., Conclusion: Rhinitis was frequently associated with asthma in children consulting for the first time at allergy departments. Time since onset of rhinitis and sensitivity to epithelia and fungi were associated with the development of asthma.

Background: Allergic rhinitis (AR) is considered to be the most frequent allergic disorder., Objective: To present the data from the Alergológica-2005 on the characteristics of patients with AR., Methods: An observational, descriptive, cross-sectional epidemiologic study was performed on 4991 patients consulting for the first time in Allergology services in Spain., Results: Fifty-five percent of patients consulting Allergology services for the first time were diagnosed with AR, of whom 65% also had conjunctivitis and 37% asthma. Two out of every three subjects with AR consulted their primary care physician twice in the previous 4 months. One third was treated by another specialist in the preceding year and one of every five required treatment in emergency departments. AR affected the quality of life (SF-12), in some cases causing time off work and school. The most frequently involved allergens were pollens (51%), followed by dust mites (42%). Polysensitization was found in 31% of cases. Antihistamines and nasal topical corticoids were the most widely used drugs. In 38% of patients, treatment with specific immunotherapy was begun., Conclusions: AR was the leading cause of consultations in Alergológica-2005. Rhinitis was frequently associated with other allergic disorders in 65% of patients with conjunctivitis and 37% with asthma. The illness led to a substantial use of healthcare resources and significantly affected the quality of life of the sufferers.

Background: Patients with aspirin-sensitive respiratory and skin diseases experience cross reactions to all nonsteroidal anti-inflammatory drugs (NSAIDs) which inhibit cyclooxigenase (COX) enzymes. The need to identify an alternative drug that is safe and reliable is a common problem in clinical practice., Objective: The aim of this study was to test the tolerability of meloxicam in NSAID-sensitive patients., Methods: Between January 2005 and February 2006 we performed single-blind oral challenge tests with meloxicam in NSAID-intolerant patients, exposing them first to placebo and then, after 30 minutes, to the first dose of meloxicam (7.5 mg). After 30 minutes, if no response appeared, the last dose of meloxicam (15 mg) was given, for a total accumulated dose of 22.5 mg. The test was considered positive if urticaria, erythema. and/or angioedema appeared., Results: We tested 114 patients: 36% men and 64% women whose mean age was 45.81 years. Meloxicam was well tolerated in 109 of the 114 patients (95.62%) and only 5 (4.38%) developed an adverse reaction (urticaria in all cases)., Conclusion: This study shows that meloxicam can be a good option for NSAID-intolerant patients: it was safe for over 95% of the patients and is easier to obtain than celecoxib or etoricoxib. However, we think that a patient should be tested in an allergy unit before it is prescribed.

Several studies have shown the relationship between gastro-oesophageal reflux, bronchial asthma and chronic nocturnal cough and this should not be neglected, particularly in patients who present an unfavourable development in spite of conventional treatment. For diagnosis of gastroesophageal reflux, amongst other investigations, esophageal gammagraphy of swallowing, that detects alterations in the mobility of the oesophagus, secondary to a possible oesophagitis. The objective of this study was to evaluate the clinical progress and gammagraphy of a group of children with chronic predominantly nocturnal cough (with or without bronchial asthma) with initially pathological esophageal gammagraphy, after three months of treatment with gastrokinetic drugs (cisapride against domperidone) and postural dietetic limits, in comparison with a reference group who, although having followed the limits in question had not received the pharmacological treatment. From the clinical viewpoint, cough disappeared in 64.5% of cases without significant statistical differences between the two groups. Gammagraphy became normal in 20/55 cases, improved in 10/55 cases and was unchanged in 25/55. Although there was no significant difference, gammagraphy development was better in children who received domperidone. The agreement between clinical progress and gammagraphy was 60% with a large number of false positives in the gammagraphy. We believe that the simple introduction of the postural-dietetic measures may improve the clinical control in the type of patients who present with a chronic nocturnally predominant cough that does not yield to conventional treatment.

A variety of "hypoallergenic" formulas have appeared on the market over the last few years for feeding lactating infants prone to a high atopic risk of allergy to cow's milk. These formulas consist of soya preparations, hydrolyzed proteins and so-called basic formulas. This paper describes the main characteristics of such formulas, with particular emphasis on their tolerance, indications, related immunological aspects and antigenic capabilities. Notifications of anaphylactoid reactions with hydrolyzed proteins and the possibility of interactions with the IgE antibodies in cow's milk indicate such formulas in cases of non-IgE-mediated intolerance. Although soya preparations may be allergenic, they do not present interactions with the proteins in cow's milk; thus, they are particularly indicated in children with protein allergy to cow's milk with specific IgE antibodies.