Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops.

Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non-IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.

Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops

Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non–IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations.To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. (AU)

El término alergia ocular engloba un conjunto de enfermedades inflamatorias de la superficie ocular de origen inmunoalérgico, con distintos niveles de afectación y gravedad. Están causadas por una variedad de mecanismos inmunes, mediados o no por IgE y pueden involucrar a todos los componentes de la superficie ocular, incluyendo conjuntiva, córnea, párpados, película lagrimal y flora comensal. De estos trastornos, el más común es la enfermedad alérgica conjuntival. En su clasificación se incluyen distintas formas clínicas según el nivel de afectación y la presencia o no de cambios proliferativos en la conjuntiva palpebral, asociación con dermatitis atópica, y estímulos mecánicos por cuerpo extraño, incluyendo lentes de contacto. Las guías terapéuticas para el tratamiento de la conjuntivitis alérgica proponen un tratamiento escalonado, tanto en administración oftálmica como oral, en función de la gravedad de los síntomas, las comorbilidades alérgicas del paciente y el logro de un control adecuado. En general, cuando los síntomas oculares predominan o se presentan de forma aislada, se prefieren las formulaciones oftálmicas de antihistamínicos de administración tópica y, dentro de estas, los colirios. Para mantener el equilibrio de la superficie ocular, las formulaciones tópicas oftálmicas deben mostrar una buena tolerancia. El objetivo principal de este artículo es revisar las características y otras propiedades de los excipientes (conservantes, tampones, agentes para ajustar el pH, viscosizantes, agentes humectantes o cosolventes, antioxidantes, isotonizantes y osmoprotectores) y sustancias activas (antihistamínicos oculares) que deben ser considerados cuando se formulan los preparados de administración tópica oftálmica de agentes antihistamínicos. (AU)

Daily Clinical Practice in the Management of Chronic Urticaria in Spain: Results of the UCREX Study. / [Artículo traducido] Práctica clínica diaria en el manejo de la urticaria crónica en España: resultados del estudio UCREX.

BACKGROUND: Chronic Urticaria (CU) is a debilitating disease whose treatment is mainly symptomatic. UCREX study aimed to identify CU patients' profile, disease management and quality-of-life (QoL) in daily clinical practice in Spain. METHODS: Observational, 12-months prospective, multicenter study, included de novo or established CU patients attending to dermatology/allergy consultations in 39 Spanish hospitals. MAIN VARIABLES: Urticaria Activity Score (UAS), UAS over 7 days (UAS7). Secondary variables: CU-QoL Questionnaire (CU-Q2oL), EuroQol-5 dimensions (EQ-5D), Medical Outcomes Study Sleep (MOS-Sleep) scale, Hospital Anxiety and Depression Scale (HADS). RESULTS: 361 patients included. Of them, 176 (48.8%) considered for the main objective analysis. Mean age (SD) of 46.6 (14.2) years and 71.8% women. The year prior to inclusion, most patients (57.1%) were treated with non-sedating H1-antihistamines (NS-H1AH). At baseline, mean (SD) 3.6 (6.8) visits were registered to primary care. Mean (SD) UAS7 at baseline was 14.3 (11.0) and CU-Q2oL 24.1 (17.0) which tended to improve by 8.6 (9.7) and 13.9 (15.0), respectively, at 12-months. MOS-Sleep and EQ-5D remained steady during the study, except pain/discomfort and anxiety/depression which went from 58.7% and 49.6% to 29.6% and 26.9%, respectively. At baseline, HADS showed a mean (SD) anxiety of 8.7 (4.5) and depression 5.1 (4.4), decreasing to 7.0 (4.3) and 4.7 (4.3), respectively, at 12-months. CONCLUSIONS: Although most CU patients are treated with NS-H1AH, disease activity is still important, negatively affecting patients' QoL, work activity and healthcare resources use. An appropriate disease management could be the basis for symptoms control, QoL improvement and resources optimization.

Daily Clinical Practice in the Management of Chronic Urticaria in Spain: Results of the UCREX Study.

BACKGROUND: Chronic Urticaria (CU) is a debilitating disease whose treatment is mainly symptomatic. UCREX study aimed to identify CU patients' profile, disease management and quality-of-life (QoL) in daily clinical practice in Spain. METHODS: Observational, 12-months prospective, multicenter study, included de novo or established CU patients attending to dermatology/allergy consultations in 39 Spanish hospitals. MAIN VARIABLES: Urticaria Activity Score (UAS), UAS over 7 days (UAS7). Secondary variables: CU-QoL Questionnaire (CU-Q2oL), EuroQol-5 dimensions (EQ-5D), Medical Outcomes Study Sleep (MOS-Sleep) scale, Hospital Anxiety and Depression Scale (HADS). RESULTS: 361 patients included. Of them, 176 (48.8%) considered for the main objective analysis. Mean age (SD) of 46.6 (14.2) years and 71.8% women. The year prior to inclusion, most patients (57.1%) were treated with non-sedating H1-antihistamines (NS-H1AH). At baseline, mean (SD) 3.6 (6.8) visits were registered to primary care. Mean (SD) UAS7 at baseline was 14.3 (11.0) and CU-Q2oL 24.1 (17.0) which tended to improve by 8.6 (9.7) and 13.9 (15.0), respectively, at 12-months. MOS-Sleep and EQ-5D remained steady during the study, except pain/discomfort and anxiety/depression which went from 58.7% and 49.6% to 29.6% and 26.9%, respectively. At baseline, HADS showed a mean (SD) anxiety of 8.7 (4.5) and depression 5.1 (4.4), decreasing to 7.0 (4.3) and 4.7 (4.3), respectively, at 12-months. CONCLUSIONS: Although most CU patients are treated with NS-H1AH, disease activity is still important, negatively affecting patients' QoL, work activity and healthcare resources use. An appropriate disease management could be the basis for symptoms control, QoL improvement and resources optimization.

Therapeutic Strategy According to Differences in Response to Omalizumab in Patients With Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is a heterogeneous condition that can severely impact quality of life. Consequently, rapid disease control is essential. First-line treatment of the symptoms of CSU is the licensed dose of second-generation H1 antihistamines. For second-line treatment, this dose may be increased by up to 4 times. In patients who fail to respond to higher doses of H1 antihistamines, omalizumab for up to 24 weeks is recommended to achieve disease control. After this 24-week period, the patient's response to omalizumab should be assessed in order to identify refractory patients. Optimal management of refractory patients has not been established. Therefore, the aim of the present consensus document, which was drafted by allergists and dermatologists with specific expertise in treating urticaria, was to define specific patient profiles based on differences in their response to omalizumab. We also developed a treatment algorithm based on the specific response profile. After a comprehensive literature review, a group meeting was held to discuss issues related to the therapeutic management of patients with CSU that had not been addressed in previous studies. The experts considered both the available evidence and their own clinical experience with omalizumab. We believe that implementation of the proposed algorithm will optimize management of CSU patients who are refractory to antihistamines, reduce disease-related costs, and improve quality of life.

Therapeutic strategy according to differences in response to omalizumab in patients with chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is a heterogeneous condition that can severely impact quality of life. Consequently, rapid disease control is essential. First-line treatment of the symptoms of CSU is the licensed dose of second-generation H1 antihistamines. For second-line treatment, this dose may be increased by up to 4 times. In patients who fail to respond to higher doses of H1 antihistamines, omalizumab for up to 24 weeks is recommended to achieve disease control. After this 24-week period, the patient's response to omalizumab should be assessed in order to identify refractory patients. Optimal management of refractory patients has not been established. Therefore, the aim of the present consensus document, which was drafted by allergists and dermatologists with specific expertise in treating urticaria, was to define specific patient profiles based on differences in their response to omalizumab. We also developed a treatment algorithm based on the specific response profile. After a comprehensive literature review, a group meeting was held to discuss issues related to the therapeutic management of patients with CSU that had not been addressed in previous studies. The experts considered both the available evidence and their own clinical experience with omalizumab. We believe that implementation of the proposed algorithm will optimize management of CSU patients who are refractory to antihistamines, reduce disease-related costs, and improve quality of life

La urticaria crónica espontánea (UCE) es una afección heterogénea que puede afectar gravemente la calidad de vida, por lo que el control rápido de la enfermedad es esencial. El tratamiento sintomático de primera línea de CSU es la dosis autorizada de antihistamínicos H1 de segunda generación. Para el tratamiento de segunda línea, esta dosis se puede aumentar hasta cuatro veces. En pacientes que no responden a estas dosis más altas de antihistamínicos H1, se recomienda el tratamiento con omalizumab (hasta 24 semanas) para lograr el control de la enfermedad. Después de este período de 24 semanas, se debe definir el perfil de respuesta del paciente a omalizumab para identificar a los pacientes refractarios. El enfoque de manejo óptimo para pacientes refractarios no ha sido establecido. En este contexto, el objetivo del presente estudio de consenso de expertos que involucró a un grupo de especialistas (alergólogos y dermatólogos) con experiencia específica en el tratamiento de la urticaria fue definir perfiles de pacientes específicos en función de sus diferentes respuestas a omalizumab. Otro objetivo fue desarrollar un algoritmo de tratamiento basado en el perfil de respuesta específico. Primero, se realizó una revisión exhaustiva de la literatura. Luego, se llevó a cabo una reunión grupal para discutir todos los temas relacionados con el manejo terapéutico de estos pacientes que no se habían abordado en ningún estudio previo. En todos los casos, los expertos consideraron tanto la evidencia disponible como su propia experiencia clínica con omalizumab. Creemos que la implementación de este algoritmo propuesto ayudará a optimizar la gestión de los pacientes con CSU que son refractarios al tratamiento con antihistamínicos, reduciendo los costos relacionados con la enfermedad y mejorando la calidad de vida de los pacientes

Updosing nonsedating antihistamines in patients with chronic spontaneous urticaria: a systematic review and meta-analysis.

There is a lack of large, randomized, double-blind studies that address antihistamine updosing for chronic spontaneous urticaria (CSU). The objective of this systematic review is to explore and analyse available data to provide clinical evidence for the efficacy of antihistamine updosing. We searched the literature in Medline, Scopus, Google Scholar, Embase, Web of Science and Cochrane databases using the keywords 'chronic, urticaria, antihistamines' to identify studies published between January 1990 and November 2014. We assessed quality using the Jadad score that evaluates quality of randomization, double-blinding and losses to follow-up. We identified 1042 articles and 15 articles were included in the final evaluation. We performed two meta-analyses, one that included studies that analysed treatment response among groups receiving different antihistamine dosages vs. placebo, and another that analysed antihistamine updosing in those patients who did not respond to standard dosages. Only five articles obtained a high quality level score. We did not find significant differences in response rates or number of weals in those patients who received a standard dosage vs. a high dosage. We found a significant improvement only in the pruritus variable of the Urticaria Activity Score scale. The estimated relative risk for improvement by increasing the antihistamine dosage was 2·27 [95% confidence interval (CI) 1·68-3·06]; however, there was significant heterogeneity. The proportion of nonrespondent patients with CSU who responded to antihistamine updosing was 63·2% (95% CI 57-69·6). We found that updosing antihistamines significantly improved control of pruritus but not weal number. However, the relative weakness of the studies and the significant heterogeneity among them made it difficult to reach a final conclusion.

Acute Abdomen in a Patient With Homozygous Type I Hereditary Angioedema: Rapid Improvement in Computed Tomography Scans After C1 Inhibitor Replacement

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Asma y factores psicosociales / Asthma and psychosocial factors

Los factores psicosociales juegan un indudable papel en el asma bronquial, como elemento precipitante de ataques y en el empeoramiento del curso de la enfermedad, sobre todo en el asma refractario y de riesgo vital. Factores como la comorbilidad psiquiátrica -incluyendo trastorno depresivos y de ansiedad-, alcoholismo y toxicomanías, negación, bajo nivel socioeconórnico y otros factores de estrés psicosocial (di funciones familiares graves, entornos amenazantes, etc) contribuyen a la morbimortalidad del asma en todo el mundo. Una correcta coordinación entre paciente, familiares y servicios sanitario debe contribuir al menos, a un enfoque individualizado de e tos pacientes de riesgo, que permita estrategias de prevención eficaces, individuales y colectivas (AU)

Psychosocial factors play an undoubtful role in bronchial asthrna, as triggering factors and as a worsening condition contributing to morbidity and mortality. Psichiatric co-morbidity (including depression and anxiety disorders), alcohol and drug abuse, denial, low socioeconomic status and other factors of psychosocial stress (such as parental or familiar disfunctions, learning impairment or living in a threatening environment) are sorne of these factors. These patients on risk must be detected through an adequate, coordinated relationship between patient, family and health services, leading to effective prevention strategies (AU)

Valor diagnóstico de las pruebas cutáneas en tres casos de reacción tardía por clindamicina / Diagnostic value of skin test in three cases of delayed reaction to clindamycin

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