Brazilian guidelines for the monitoring and treatment of pediatric allergic conjunctivitis / Diretrizes brasileiras sobre o monitoramento e tratamento da conjuntivite alérgica pediátrica

ABSTRACT Allergic conjunctivitis is an increasingly frequent condition with a higher prevalence in children. It can be debilitating and is responsible for a great economic burden. These guidelines were developed on the basis of the medical literature (PubMed/Medline database) and the experience of an Expert Committee composed of members of the Brazilian Society of Pediatric Ophthalmology, the Brazilian Council of Ophthalmology, the Brazilian Society of Pediatrics, and the Brazilian Association of Allergy and Immunology. Allergic conjunctivitis is considered to be controlled when the ocular symptoms are not uncomfortable or are present, at most, on 2 days a week; the visual analog scale score is below 5; and the degree of conjunctival hyperemia is graded 0 or 1 on the Efron scale. Allergic conjunctivitis should be classified as mild, moderate, severe, and vision-threatening for adequate treatment and monitoring of frequency. The present document is a guideline for diagnosing, treating, and monitoring pediatric allergic conjunctivitis considering the clinical and demographic aspects of allergic conditions in Brazil.

RESUMO A conjuntivite alérgica (CA) é uma condição frequente, debilitante e responsável por grande impacto econômico, proporcionalmente maior quando acomete crianças. Essas diretrizes foram desenvolvidas com base na literatura científica (PubMed/Medline) e na experiência de um Comitê de Especialistas composto por membros da Sociedade Brasileira de Oftalmologia Pediátrica, do Conselho Brasileiro de Oftalmologia, da Sociedade Brasileira de Pediatria e da Associação Brasileira de Alergia e Imunologia. A conjuntivite alérgica é considerada controlada quando os sintomas não são desconfortáveis ou estão presentes por dois dias na semana; o escore visual pela escala analógica é inferior a 5 e o grau de hiperemia conjuntival é de 0-1 pela escala de Efron. A conjuntivite alérgica deve ser classificada em leve, moderada, grave e com risco de perda visual para tratamento e frequência de monitoramento adequados. Esta diretriz orienta o diagnóstico, tratamento e monitoramento da conjuntivite alérgica pediátrica, considerando aspectos clínicos e demográficos das condições alérgicas no Brasil.

Effect of cromolyn sodium combined with diclofenac sodium eye drops on allergic conjunctivitis / 中国医师杂志

Objective:To investigate the application of cromolyn sodium combined with diclofenac sodium eye drops in allergic conjunctivitis (AC) and its effect on tear film function, interleukin-10 (IL-10), interleukin-17 (IL-17) and immunoglobulin E(IgE).Methods:From April 2018 to May 2020, 78 patients with AC collected in Liaoning Armed Police Crops Hospital were divided into control group and observation group according to the random number table method (39 cases in each group). The control group was given cromolyn sodium eye drops, and the observation group was given cromolyn sodium combined with diclofenac sodium eye drops. The efficacy, clinical symptoms, changes of signs, tear film function [tear film rupture time (BUT), Schirmer I test (SIt)], tear inflammation indicators [interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α), IL-10, IL-17], tear allergy mediators [eosinophil cationic protein (ECP), hyaluronic acid (HA), IgE] and safety.Results:The total effective rate of observation group was 100.00%, which was higher than that of control group (84.62%), with statistically significant difference ( P<0.05). After treatment, the scores of eye itching, tearing, photophobia, eye secretion, conjunctival hyperemia, conjunctival edema and blepharoconjunctival papillary follicular hyperplasia in the two groups were significantly lower than those before treatment, and the observation group was lower than the control group, with statistically significant difference (all P<0.05). The BUT in the observation group was higher than that in the control group after treatment, with statistically significant difference ( P<0.05). After treatment, the tear levels of IL-4, TNF-α, IL-10 and IL-17 in the observation group were lower than those in the control group, with statistically significant difference (all P<0.05). After treatment, the tear ECP, HA and IgE level in the observation group were lower than those in the control group, with statistically significant difference (all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Cromolyn sodium combined with diclofenac sodium eye drops is effective in the treatment of AC, which can effectively improve the clinical symptoms and signs, promote stable tear film function, alleviate local metamorphosis and inflammation, and has good safety.

Associação entre alergia ocular leve e ceratocone em crianças / Association between mild ocular allergy and keratoconus in children

RESUMO Objetivo: Avaliar a possibilidade de alterações precoces sugestivas de ectasia detectáveis no Pentacam em casos sutis de alergia ocular em crianças. Métodos: Análise retrospectiva de 49 prontuários, com paciente de ambos os sexos e idades entre 3 e 14 anos. Do total de crianças estudadas, 31 apresentavam alergia ocular grau 1, e 18 não apresentavam qualquer sinal ou sintoma de alergia ocular, servindo como controles. Avaliaram-se diversos índices do Pentacam. Resultados: Houve associação estatisticamente significativa nas variáveis "Df - variação do mapa da elevação anterior da córnea" e "Pentacam combinado", que podem estar relacionadas com a detecção precoce de ectasia corneana nesses pacientes. Conclusão: Houve relação causal entre a prevalência da alergia ocular e alterações tomográficas na córnea, sugestivas de ceratocone em alguns pacientes provavelmente suscetíveis, podendo ser considerado um fator de risco para essa complicação.

ABSTRACT Objective: To assess if early alterations detected by Pentacam in children suffering from mild ocular allergy are suggestive of ectasia. Methods: A retrospective analysis of 49 medical records of patients of both sexes, aged between 3 and 14 years was performed. In this sample, 31 children suffered from grade I ocular allergy, and 18 presented no signs or symptoms of ocular allergy and comprised the control group. Several Pentacam indexes were evaluated. Results: A statistically significant association was found in the variables "Df - variation of the anterior corneal elevation map" and "combined Pentacam", which can be related to the early detection of corneal ectasia in these patients. Conclusion: There was a causal relation between prevalence of ocular allergy and tomographic alterations on the cornea, suggestive of keratoconus in some probably susceptible patients, which may be considered a risk factor for this complication.

Efficacy and safety of dupilumab in two adolescents with severe atopic dermatitis / Eficácia e segurança do uso de dupilumabe em dois adolescentes com dermatite atópica grave

ABSTRACT We report the cases of two adolescent siblings with severe atopic dermatitis, who, despite weighing approximately 40kg, presented a good response to dupilumab with the off-label dose for individuals aged 12 years and weighing 60kg. Both had already used cyclosporine, azathioprine, methotrexate and oral corticosteroids for long periods, plus topical treatments with no adequate disease control. Skin lesions were constant and widespread, with frequent skin infections and very poor quality of life, with numerous physical and psychosocial consequences, such as dropping out of school activities due to severe itching, appearance and bullying. They also showed delayed growth and development. In 2018, dupilumab, an immunobiological agent, was approved for treatment of moderate to severe atopic dermatitis in adults and, in 2019, extended to the 12-17-year age group. Although it had already been approved by the Brazilian Health Surveillance Agency, the 200mg presentation (indicated for the weight of patients) was not available, with no expected arrival date. Therefore, weighing the risks and benefits of the situation of both, we chose to treat them with an adult dose (loading dose of 600mg subcutaneously, and 300mg subcutaneously every 2 weeks) despite the low weight. So far, they have received eight injections, showing significant improvement of disease and quality of life. There were no major adverse effects, only worsening of allergic conjunctivitis in one of them. The patients and their family are very satisfied, and we believe that the therapy has been successful.

RESUMO Relatamos os casos de dois irmãos adolescentes com dermatite atópica grave e que, apesar de pesarem cerca de 40kg, apresentaram boa resposta ao dupilumabe com a dose off-label para indivíduos com 12 anos e peso de 60kg. Ambos já tinham usado ciclosporina, azatioprina, metotrexato e corticoide oral por longos períodos, acrescidos de tratamentos tópicos sem controle adequado da doença. As lesões cutâneas eram constantes e disseminadas, e os irmãos apresentavam infeções de pele frequentes e qualidade de vida muito ruim, com inúmeras consequências físicas e psicossociais, como o abandono da atividade escolar pelo prurido intenso, pela aparência e pelo bullying sofrido. Apresentavam também retardo de crescimento e de desenvolvimento. Em 2018, o dupilumabe, um agente imunobiológico, foi aprovado para o tratamento de dermatite atópica moderada a severa para adultos e, em 2019, ampliado para faixa etária de 12 a 17 anos. Embora já tivesse a aprovação da Agência Nacional de Vigilância Sanitária no Brasil, a apresentação de 200mg (indicada para o peso dos pacientes) não estava disponível, sem previsão de chegada. Assim, pesando os riscos e benefícios da situação de ambos, optamos por tratá-los com dose de adulto (ataque de 600mg por via subcutânea e 300mg por via subcutânea a cada 2 semanas) apesar do baixo peso. Até o momento, eles realizaram oito aplicações, apresentando importante melhora da doença e da qualidade de vida. Não houve efeitos adversos importantes - apenas a piora da conjuntivite alérgica em um deles. Os pacientes e sua família estão muito satisfeitos, e nós avaliamos que a terapia está sendo bem-sucedida.

Pay attention to the drug selection for allergic keratoconjunctivitis / 中华实验眼科杂志

Allergic keratoconjunctivitis is a common allergic disease,but some patients,especially children,cannot be diagnosed and treated timely and correctly.Allergic keratoconjunctivitis is mainly caused by type Ⅰ and Ⅳ allergy,and its treatment is mainly based on topical administration.At present,antiallergic drugs used for the treatment of allergic keratoconjunctivitis include Histamine antagonists,mast cell stabilizers,double effect antiallergic drugs,Nonsteroidal anti-inflammatory drugs,glucocorticoids and immunosuppressants.It is essential to understand the mechanism of various antiallergic drugs and to choose different combinations according to the type of allergy to treat allergic keratoconjunctivitis.Clinicians should pay attention to the principle of choosing different drugs based on the pathogenesis of allergic keratoconjunctivitis,gradually standardize the drug regimen and improve the efficacy of drugs.

Topical tacrolimus for the treatment of severe allergic keratoconjunctivitis in children / Tacrolimus tópico para o tratamento da ceratoconjuntivite alérgica severa em crianças

ABSTRACT Purpose: Administration of eye drops containing antihistamines or sodium cromoglycate and its derivatives for the treatment of allergic keratoconjunctivitis is often insufficient and usually requires the addition of corticosteroids. However, the risk of complications, such as glaucoma and cataract, limits the use of corticosteroids to short courses, resulting in inadequate long-term treatment response. Immunosuppressive drugs have been considered as a valid alternative to steroids for atopic keratoconjunctivitis and vernal keratoconjunctivitis. This study aimed to evaluate the use of topical tacrolimus (TCL) in improving the clinical signs of severe allergic keratoconjuctivitis in children. Methods: Patients with severe allergic keratoconjunctivitis associated with corneal epitheliopathy, gelatinous limbal infiltrates, and/or papillary reaction, along with a history of recurrences and resistance to conventional topical anti-allergy agents, were included in this open clinical trial. Patients were treated with 0.03% TCL ointment for ocular use. A severity score ranging from 0 to 9, with 9 being the highest and 0 being the lowest, was assigned based on signs observed on biomicroscopy prior to and following TCL treatment. Results: Analyses included 66 eyes of 33 patients. After a mean follow-up period of 13 months (range, 12-29 months), TCL treatment significantly decreased the mean symptom score severity for the right (from 5.56 ± 1.18 to 2.76 ± 1.5; p<0.001) and left (from 5.94 ± 1.16 to 2.86 ± 1.64; p<0.001). Conclusion: Topical TCL was effective and significantly improved the clinical signs of allergic keratoconjuctivitis in children. Thus, it is a potential new option for severe and challenging cases of ocular allergy.

RESUMO Objetivos: O tratamento da ceratoconjuntivite alérgica baseado em colírios que contenham anti-histamínicos ou cromoglicato de sódio e seus derivados geralmente são insuficientes. A adição de corticosteróides geralmente é mandatória. No entanto, o risco de complicações como glaucoma e catarata limita o uso dos corticosteróides em curtos períodos de tratamento resultando em respostas inadequadas a longo prazo. Drogas imunossupressoras vem sendo consideradas como uma opção terapêutica alternativa válida para as ceratoconjuntivite atópica (AKC) e ceratoconjuntivite vernal (VKC). Este trabalho tem como objetivo avaliar a melhora nos sinais clínicos durante o uso de tacrolimus (TCL) tópico em crianças com ceratoconjuntivites alérgicas. Métodos: Pacientes com ceratoconjuntivite alérgica severa associada a ceratites, infiltrados limbares gelatinosos e/ou papilas gigantes, com história de recorrências e resistência ao tratamento anti-alérgico tópico convencional foram incluídos neste estudo. Os pacientes foram tratados com TCL 0,03% pomada tópica para uso ocular. Um escore variando de 0 a 9 foi atribuído para os sinais observados na biomicroscopia antes e depois do tratamento. Quanto maiores os escores, mais severos eram os sinais. Resultados: Foram estudados 66 olhos de 33 pacientes. Antes do tratamento a média do escore para o olho direito foi 5,56 ± 1,18 e para o olho esquerdo 5,94 ± 1,16. Após o tratamento com TCL a média do escore para o olho direito foi 2,76 ± 1,5 e para o olho esquerdo 2,86 ± 1,64 (p<0.001 para os dois olhos). O tempo de seguimento médio foi de 13 meses (12-29 meses). Conclusão: O presente estudo sugere que o TCL tópico foi efetivo e demonstrou resultado satisfatório, com melhora nos sinais clínicos na ceratoconjuntivite alérgica em crianças, constituindo uma nova opção para o tratamento de casos severos de alergia ocular.

Supratarsal injection of triamcinolone for severe vernal keratoconjunctivitis in children / Injeção supratarsal de triancinolona na ceratoconjuntivite primaveril grave em crianças

ABSTRACT Purpose: To evaluate the use of supratarsal injection of triamcinolone acetonide in severe vernal keratoconjunctivitis (VKC) in children. Methods: Patients included in this open clinical trial were those with severe VKC-associated with keratitis, gelatinous limbal infiltrates, and/or giant papillae, with a history of recurrence and resistance to conventional topical antiallergic agents. Patients were treated with a supratarsal injection of 20 mg triamcinolone acetonide. Results: Analysis included 27 injections in 23 eyes of 17 patients with severe allergic keratoconjunctivitis. Mean age was 12.3 (range: 7-19) years. Mean follow-up time was 39.3 months (SD=19.21). In the 17 patients, the disease was successfully controlled for an average of 3.6 months (range: 1-16), during which allergy symptoms and signs were significantly improved, with complete resolution of lid edema and conjunctival chemosis, significant decline of pannus and keratitis, and reduction of giant papillae size. Conclusion: Treatment of severe, acute VKC in children with supratarsal injection of 20 mg triamcinolone acetonide showed satisfactory results and was well tolerated by patients; it may therefore constitute a safe option for severe and challenging cases. While full disease remission was not achieved, a significant improvement was found in ocular allergy symptoms and signs, with a reduction in the frequency of acute recurrences.

RESUMO Objetivo: Avaliar o uso da injeção supratarsal de triancinolona na ceratocon junti vite primaveril grave (VKC) em crianças. Métodos: Pacientes com VKC grave associada à ceratite, limbo gelatinoso e/ou papilas gigantes, com história de recidivas e resistência a agentes antialérgicos tópicos convencionais foram incluídos neste ensaio clínico. Os pacientes foram tratados com injeção de 20 mg de acetato de triancinolona supratarsal. Resultados: A análise incluiu 23 olhos de 17 pacientes com ceratoconjuntivite alérgica grave. A idade média foi de 12,3 com intervalo de 7-19 anos. O tempo médio de acompanhamento foi de 39,3 meses (DP 19,21). Dos 17 pacientes, a doença foi controlada com sucesso por uma média de 3,6 meses (intervalo 1-16) em que os sinais e sintomas foram significativamente melhorados com resolução completa do edema palpebral e quemose conjuntival, redução significativa de pannus, ceratite e redução do tamanho das papilas gigantes. Conclusão: O tratamento da VKC grave em crianças com injeção supratarsal de 20 mg de acetato de triancinolona mostrou resultados satisfatórios, sendo bem tolerada pelas crianças às quais foram submetidas, podendo constituir uma opção segura para casos graves e difíceis de VKC. Uma melhora significativa foi encontrada nos sinais e sintomas alérgicos oculares, com diminuição da frequência de recidivas agudas, no entanto sem se mostrar efetiva para a completa remissão da doença.

Inflammatory-promoting roles of thymic stromal lymphopoietin and interleukin-4 in allergic conjunctivitis mice / 中华实验眼科杂志

Background Researches showed that thymic stromal lymphopoietin (TSLP) is an interleukin-17-like inflammatory factor and plays important roles in the pathogenesis and development of allergic diseases.However,the study whether TSLP plays roles in allergic conjunctivitis is rare.Objective This study was to investigate the expression change of TSLP and IL-4 in ocular surface tissue and cervical lymph node in the mice with allergic conjunctivitis induced by artemisia annua,a common plant in China,and to explore the role of TSLP and IL-4 in the pathogenesis and development of allergic conjunctivitis.Methods Twenty female BALB/c mice aged 6-8 weeks were randomized into normal control group and model group.Antigen solution was prepared using 400 μl extracting solution of artemisia annua pollen with 400 μl antigen solvent.The mouse models of allergic conjunctivitis were established by injection of 50 μl antigen solution in footpad followed by ocular topical administration of extracting solution once a day from day 10 to 12 after injection,and no any intervention was given in the normal control group.The mice were sacrificed and eyeballs were obtained 13 days after modeling,and corneal epithelium,conjunctiva and cervical lymph nodes were harvested for the detection of TSLP mRNA and IL-4 mRNA by real-time PCR.Immunochemistry was employed to assay the expression of TSLP and IL-4 proteins in corneal,conjunctival and subconjunctival tissues.Results Ocular inflammatory signs appeared 0.5 hours after ocular topical administration of extracting solution,including eyelid edema,conjunctival congestion,tears,scratching eyelids,etc.The symptoms lasted for 6-24 hours,with the model successful rate 80％.Real-time PCR indicated that the expression of IL-4 was absent in corneal epithelium in both model group and normal control group.The relative expression levels of TSLP mRNA in the corneal epithelium,conjunctiva and cervical lymph nodes in the model group were more (1.63±0.20)times,(2.71±0.48) times and (1.48 ±0.05) times than the normal control group,showing significant differences between the two groups (t =4.44,14.16,5.01,all at P＜0.05).Compared with the normal control group,the relative expression levels of IL-4 mRNA in the model group increased (2.94±0.39) times and (1.74±0.09) times,with significant differences between the two groups (t =9.92,14.54,both at P＜0.05).Immunochemistry assay showed that the expression of TSLP protein in the corneal and conjunctival epithelial cells were enhanced in the model group compared with the normal control group.In addition,an intensive expression of IL-4 protein was seen in subconjunctival tissue in the model group,while the expression of IL-4 was absent in the normal control group.Conclusions TSLP is mainly expressed in the cornea,conjunctiva and cervical lymph nodes of the mice with allergic conjunctivitis,suggesting that TSLP promotes the inflammatory process of cornea and conjunctiva;IL-4 is mainly expressed in conjunctiva,showing IL-4 participates in conjunctival inflammatory process.TSLP and IL-4 play synergistic roles in promoting the inflammatory process of ocular surface in the mice with allergic conjunctivitis,which may be new therapeutic targets.

Pathogenesis of allergic conjunctivitis and trends in its treatment

Allergic conjunctivitis is characterized by specific immunologic responses known as type 1 hypersensitivity, resulting in corneal and conjunctival inflammation. Histamine plays an important role in the pathophysiologic mechanism of allergic conjunctivitis. Five subtypes of allergic conjunctivitis have been defined according to specific signs and symptoms: seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, atopic keratoconjunctivitis and giant papillary conjunctivitis. Above all, avoidance of the offending antigen is the primary behavioral modification used to treat all types of allergic conjunctivitis. However, this may be difficult for practical reasons; therefore, a range of medical treatment options, such as topical antihistamines, mast cell stabilizers, non-steroidal anti-inflammatory drugs, and corticosteroids are prescribed in clinical practice.

Atopic keratoconjunctivitis: long-term results of medical treatment and penetrating keratoplasty / Ceratoconjuntivite atópica: resultados a longo prazo do tratamento clínico e da ceratoplastia penetrante

ABSTRACT Purpose: To evaluate the long-term outcomes of medically or surgically treated patients with atopic keratoconjunctivitis (AKC). Methods: Charts of 16 patients with AKC (32 eyes) observed between 1996 and 2013 were reviewed retrospectively. Outcome measures included demographic features, follow-up duration, and biomicroscopic findings at the first and most recent visits. The corrected distance visual acuity (CDVA; in decimal units) was evaluated at the initial visit and the 1-, 6-, and 12-month follow-up visits. Results: In the medically treated group (25 eyes of 15 patients), the median follow-up duration was 3 (range, 1-9) years, and the median CDVA values were 0.01 (0.001-1.0) at the first visit and 0.01 (0.001-0.8) at the most recent visit (p=0.916). In the penetrating keratoplasty (PK) group (7 eyes of 6 patients), the median follow-up duration was 7 years (range, 1-11), and the median CDVA increased from 0.01 (0.001-0.01) to 0.2 (0.001-0.7) postoperatively (p=0.043). Conclusion: Whereas most AKC patients maintained a useful CDVA with medical treatment, PK may be required in some cases. Despite the frequent occurrence of complications, PK can significantly improve the CDVA.

RESUMO Objetivo: Avaliar os resultados a longo prazo em ceratoconjuntivite atópica (AKC) pacientes que foram tratados clinicamente ou cirurgicamente. Métodos: Os prontuários de 16 pacientes (32 olhos) com AKC, que foram acompanhados entre 1996 e 2013 foram avaliados retrospectivamente. As medidas adotadas foram as características demográficas, tempos de seguimento, e resultados biomicroscópicos da visita inicial e da visita mais recente. A acuidade visual corrigida para distância (CDVA), apresentada em unidades decimais, foi avaliada na visita inicial e nas visitas do 1º mês, 6º mês e 1º ano de seguimento. Resultados: No grupo tratado clinicamente (25 olhos de 15 pacientes), a mediana do tempo de seguimento foi de 3 anos (variação, 1-9) e a CDVA média foi de 0,01 (0,001-1,0) na visita inicial e 0,01 (0,001-0,8) na visita mais recente (p=0,916). No grupo de ceratoplastia penetrante (PK) (7 olhos de 6 pacientes), a mediana de tempo de seguimento foi de 7 anos (variação, 1-11) e a CDVA média aumentou de 0,01 (0,001-0,01) para 0,2 (0,001-0,7) (p=0,043) no pós-operatório. Conclusões: Embora a maioria dos pacientes AKC mantém a CDVA útil com o tratamento clínico, alguns necessitam de PK a fim de obter CDVA útil. Embora as complicações pós-PK ocorrem com freqüência, a CDVA pode melhorar significativamente.

Perspectivas no tratamento da alergia ocular: revisão das principais estratégias terapêuticas / Ocular allergy therapy perspectives: Review on the main therapeutic targets

As alergias oculares englobam uma série de doenças inflamatórias da superfície ocular, causadas por diferentes mecanismos de hipersensibilidade. Acometem aproximadamente 20% da população e podem ser classificadas em formas mediadas por hipersensibilidade tipo I (CAS, CAP), tipo I e IV (CCV, CCA) e tipo IV (BCC, CPG). As formas mais prevalentes são CAS e CAP. As formas crônicas (CCV, CCA) estão mais frequentemente relacionadas a complicações e comprometimento da função visual decorrentes do processo inflamatório e consequente remodelação da superfície ocular. Comorbidades como olho seco e ceratocone podem estar presentes. O tratamento envolve diagnóstico e afastamento dos fatores etiológicos envolvidos, uso de drogas anti-inflamatórias que atuem na ação de linfócitos Th2, eosinófilos, mastócitos e células dendríticas Avanços no conhecimento da ativação e tráfego de células do sistema imune têm sido promissores na perspectiva de novas abordagens terapêuticas.

Ocular allergies encompass a number of inflammatory diseases in the ocular surface which have different hypersensitivity mechanisms and occur in 20% of population. They can be classified as being type I hypersensitivity mediated (PAC, SAC), type I and IV (VKC, AKC) and type IV (BKC, GPC). The most prevalent forms are PAC and SAC. The chronic presentations are mostly related to visual impairment due to remodeling in the ocular surface caused by chronic inflammation. Dry eye disease and keratoconus are comorbidities observed in severe cases. The management is based on accurate diagnosis, avoidance of etiological factors and the rational use of drugs that control the inflammatory events caused by Th2 driven. The advances in knowledge on activation and traffic of immune cells are providing new drugs and many perspectives on different approaches.

Association of prevalence of rhinitis, atopic eczema, rhinoconjunctivitis and wheezing with mortality from infectious diseases and with antibiotic susceptibility at a country level

BACKGROUND: It was previously reported that there is a positive correlation between incidence of type 1 diabetes and prevalence of asthma and atopic eczema. A negative correlation between the prevalence of type 1 diabetes and mortality from infectious diseases as well as a positive correlation with antibiotic susceptibility at a country level have also been reported. OBJECTIVE: The aim of this study was to investigate the association between country prevalence of rhinitis, atopic eczema, rhinoconjunctivitis, and wheezing with mortality from infectious diseases and also with antibiotic susceptibility at a country level. METHODS: Data for prevalence of rhinitis, eczema, rhinoconjunctivitis, and wheezing was obtained from the International Study of Asthma and Allergies in Childhood study (ISAAC). ISAAC Phase one was a multicentre multicountry cross sectional study involving over 700,000 children in 2 age groups of school children, 13-14 years old (adolescents) and 6-7 years old (children) in 156 centres from 56 countries. Mortality from infectious diseases was taken from World Health Organisation data. The Alexander project was used to identify antibiotic susceptibilities to common bacteria. RESULTS: There were significant positive correlations between atopic eczema and mortality from all infectious diseases studied, diarrhoeal illness, tropical infections, and childhood infections. A negative correlation exists between the prevalence of rhinitis and Streptococcus pneumoniae susceptibility to penicillin and to erythromycin, rhinitis and Haemophilus influenzae susceptibility to ampicillin and between rhinoconjunctivitis and H. influenzae susceptibility to ampicillin. CONCLUSION: Th1/Th2 responses might influence the pathogenesis of infectious disease mortality, while antibiotic overprescription could explain the negative association between atopy and antibiotic susceptibility.

Expressions of interleukin-4,5 and 13 in ocular surface with different types of allergic conjunctivitis / 中华实验眼科杂志

Background The pathogenesis of allergic conjunctivitis has not been clearly established.Current researchers indicate that interleukin-4 (IL-4), IL-5 and IL-13 may play an important role in allergic conjunctivitis.But whether the roles of these inflammatory factors are same in different types of allergic conjunctivitis remains unclear.Objective This study was to investigate the expressions of IL-4, IL-5 and IL-13 in ocular surface with different types of allergic conjunctivitis.Methods A prospective cohort study was designed.Eighty individuals were recruited in Shanxi Eye Hospital from April 2013 to September 2014, including 20 patients with vernal keratoconjunctivitis (VKC), 20 patients with seasonal allergic conjunctivitis (SAC), 20 patients with perennial allergic conjunctivitis (PAC) and 20 normal healthy subjects.Surficial tissues were binocularly scraped using disinfected scraper from upper eyelid conjunctiva, and 4 μl of tear fluid was obtained with capillary tube.The expressions of IL-4, IL-5 and IL-13 protein and mRNA in the conjunctival epithelial cells were detected by immunohistochemistry and real-time fluorescence quantitative PCR.The IL-4, IL-5 and IL-13 concentrations in tear fluid were assayed by Luminex method.This study complied with Declaration of Helsinki and the research protocol was approved by the Shanxi Eye Hospital Ethics Committee.Written informed consent was obtained from each subject prior to entering the cohort.Results IL-4, IL-5 and IL-13 were positively expressed in cytoplasm of conjunctival epithelial cells in the VKC group,SAC group and PAC group,but the expressions of IL-4,IL-5 and IL-13 were absent in the normal control group.The relative expression levels of IL-4 mRNA were 4.11±1.24,2.71±0.71 and 2.00±0.80;the relative expression levels of IL-5 mRNA were 4.02±0.43,2.07±0.45 and 1.47±0.50;and the relative expression levels of IL-13 mRNA expression levels were 6.44±0.66,4.35±1.26 and 2.39±0.86 in the VKC group,SAC group and PAC group, showing significant differences among the 4 groups (F =51.32,220.18,162.49, all at P＜0.01).The relative expression levels of IL-4,IL-5 and IL-13 mRNA were significantly higher in the VKC group than those in the SAC group and PAC group;and those in the SAC group were significantly elevated in comparison with the PAC group (all at P＜0.05).No IL-4, IL-5 and IL-13 were detected in the tear fluid in the normal control group;while the concentrations of IL-4,IL-5 and IL-13 in the tear fluid were (14.06±3.50), (10.88±1.82) and (34.28±8.42) pg/ml in the VKC group,and (7.71 ±0.65), (5.10± 1.33), (23.77±6.29) pg/ml in the SAC group as well as (3.30± 1.50) pg/ml, (2.43± 1.28) pg/ml and (17.67 ± 4.28) pg/ml in the PAC group, showing significant differences among the 3 groups (F =200.29,260.49,128.23, all at P＜0.01).IL-4, IL-5 and IL-13 concentrations in the tear fluid were significantly higher in the VKC group than those in the SAC group and PAC group,and those in the SAC group were significantly raised in comparison with the PAC group (all at P＜0.01).Conclusions IL-4,IL-5 and IL-13 participate in the pathogenesis of multiple allergic conjunctivitis,but their expressions in the ocular surficial tissue are discriminatory in different types of allergic conjunctivitis.

Consideration of application of non-steroidal anti-inflammatory drugs in the treatment of allergic conjunctivitis / 中华实验眼科杂志

Allergic conjunctivitis is a very common pathology and its incidence has increased in developing countries with the development of industrialization.At present,the therapy of allergic conjunctivitis is mainly the use of topical eyedrops to eliminate causative factors,relieve symptoms and prevent complications.The drugs used in allergic conjunctivitis have 6 groups,including antihistamine,mastocyte stabilizer,drugs with dual effects (antihistamine and mastocyte stabilizer),non-steroidal anti-inflammatory drugs (NSAIDs),glucocorticoids and immunosuppressors.The goals of topical use of antihistamine,mastocyte stabilizer and drugs of dual effects are to remove the itching and hyperaemia of eye or to treat the patients with acute allergic conjunctivitis; while NSAIDs,glucocorticoids and immunosuppressors are used for the patients with severe or chronic allergic conjunctivitis.The glucocorticoid drugs are more effective because of their arresting effects in several links of the allergic response.Nevertheless,the long-term use of glucocorticoids probably results in ocular hypertension or posterior subcapsular cataract,furthermore,glucocorticoid drugs should be more cautionary in the application of the patients with corneal ulcer.Immunosuppressors inhibit abnormal immune responses,but these drugs should not be used for a long term because of higher cost and adverse effects.NSAIDs have a good anti-inflammatory effect and less irritant,so the topical use of NSAIDs for allergic conjunctivitis appears to be a better choice nowadays.

Change of tear film function in seasonal allergic conjunctivitis between acute exacerbation and non-onset phase / 中国医师进修杂志

Objective To investigate the change of tear film function in patients with seasonal allergic conjunctivitis (SAC) between acute exacerbation and non-onset phase.Methods This was a prospective controlled study.Functional assessment of tear film was performed in 30 eyes of 15 patients with SAC (SAC group) between acute exacerbation and non-onset phase and 15 healthy controls (control group).The tear film function included tear film break-up-time (BUT),Schirmer I test (SIt) and tear film interferometer imager measurement.Results BUT was significantly decreased in SAC group on acuteexacerbation compared with that on non-onset phase and control group [(6.97 ± 1.56) s vs.(11.27 ± 1.39),(12.00 ± 1.11) s],and there was significant difference (U =20.50,P =0.000;U =1.00,P =0.000).Moreover,BUT in SAC group on non-onset phase was similar as control group(U =322.00,P ＞ 0.05).There was no significant difference in SIt among SAC group on acute exacerbation and non-onset phase and control group(P ＞ 0.05).In tear film interferometer imager measurement,80.0％(24/30) was Ⅰ-Ⅱ grade,20.0％(6/30) was Ⅲ grade in control group,20.0％(6/30) was Ⅰ-Ⅱ grade,80.0％(24/30) was Ⅲ-Ⅴ grade in SAC group on acute exacerbation,60.0％(18/30) was I-Ⅱ grade,40.0％(12/30) was Ⅲ-Ⅴ grade in SAC group on non-onset phase,and there was significant difference between SAC group on acute exacerbaiion and SAC group on non-onset phase,control group (x2 =19.27,P =0.000; x2 =8.40,P =0.004),and there was no significant difference between SAC group on non-onset phase and control group (x2 =1.98,P＞0.05).Conclusion SAC can cause the instability of tear film during the acute exacerbation,whereas this instability can be recovered within the non-onset phase of S A C,which is close to the normal control

Tratamento homeopático de crianças com úlcera de córnea em escudo por ceratoconjuntivite primaveril: relato de casos e aspectos bioéticos / Homeopathic treatment of children with shield ulcers of the cornea in vernal keratoconjunctivitis: case reports and bioethical dimensions

Apresentar um tratamento homeo-pático de úlcera de córnea por ceratoconjuntivite primaveril, considerando-o bioeticamente. MÉTODOS: foram usados nove casos, encami-nhados por insucesso terapêutico convencional. Escolheram-se os medicamentos de acordo com características singularizantes dos pacientes que incluíram o psiquismo. Levantaram-se os custos medicamentosos consultando-se três farmácias homeopáticas e três não-homeopáticas de Belo Horizonte. O tratamento convencional foi estimado a partir da medicação usada pelos enfermos antes do início dos cuidados homeopáticos. RESULTADOS: as cicatrizações ocorreram entre quinze e cento e oitenta dias, com custo medicamentoso médio de oito dólares, cerca de treze vezes menor do que a estimativa de custo direto de um mês da abordagem convencional. O manejo terapêutico da similitude pode minimizar preocupações bioéticas relativas à atenção à saúde de crianças com ceratoconjuntivite primaveril. CONCLUSÕES: a homeopatia pode colaborar para o tratamento desta enfermidade, aprimorando-o bioeticamente...

Present a homeopathic treatment of corneal ulcers for vernal keratoconjunctivitis and its bioethical implications. METHODS: nine cases were studied, after having been referred following the failure of conventional treatments. Medications were chosen according to the specific characteristics of the patients, including psychiatric disorders. The medication costs were gathered by consulting three homeopathic and three non-homeopathic pharmacies in Belo Horizonte. The estimate for conventional treatment cost was based on the medication prescribed for the patient prior to the commencement of homeopathic care. RESULTS: scarring occurred between fifteen and one-hundred eighty days, with an average medication cost of eight dollars, roughly one-thirteenth of the estimated direct cost of one month of conventional treatment. The similarity of therapeutic approaches should minimize bioethical concerns regarding the medical care of children with vernal keratoconjunctivitis. CONCLUSIONS: homeopathy can contribute to both the medical and bioethical aspects of treatment of this disease...

Clinical observation of olopatadine in the treatment of allergic conjunctivitis / 中国基层医药

Objective To observe the effect of olopatadine in the treatment of allergic conjunctivitis.Methods 67 cases with allergic conjunctivitis were randomly divided into 2 groups.The observation group was given 0.1％ hydrochloride olopatadine eyedrop twice a day for 7 days,while the control group was given 2％ cromolyn sodium 4 times a day for 7 days.One hour,7 days,20 days after treatment,the changes of symptoms and the incidence of adverse reactions were observed.Results 7 days after treatment,the totsl effective rate of the observation group in treatment of eye itching,conjunctival hyperemia and conjunctiva nipple were 91.18％,91.18％ and 85.19％,better than that of the control group[ 72.7％,75.76％,85.19％ ( all P ＜ 0.05 ) ].Conclusion It's rapid onset long duration of action and high security that olopatadine in the treatment of allergic conjunctivits,and it was worthy to promote to be used in clinic.

Determinación de la prevalencia de conjuntivitis alérgica infantil en ochoescuelas primarias del Cono Sur de Lima, Perú / Determination of the prevalence of childhood allergic conjunctivitis in eight elementary

Introducción: En Lima con casi tres millones de niños, no se han reportado hasta la actualidad estudios de prevalencia de alergia infantil. Objetivos: Determinar las características epidemiológicas actuales de la alergia ocular infantil en los estudiantes de escasos recursos, del nivel primario del sur de Lima. Se tomó muestra significativa a escolares de 8 colegios primarios, de tres distritos del sur de Lima, con 120 000 niños. Material y método: Se hizo un estudio transversal y observacional, se evaluó y examinó, in situ en cada escuela a 2 011 escolares de educación primaria. Para el cálculo de muestras usamos Excel 2003 y para análisis usamos SPSS 15,0. Resultados: Se halló una moderada prevalencia de alergia ocular (16,3%) (p <0,01) en la población escolar entre 6 y 11 años. Con un aumento de la frecuencia de alergia ocular que se incrementa conjuntamente con la edad. La alergia ocular se correlaciona más con la blefaritis y el chalazión. Conclusiones: La prevalencia de alergia ocular de 16,3% es moderada en la población escolar primaria de Lima sur, el comportamiento de la alergia ocular es ascendente según avanza la edad de los escolares (Y=0,0305 X=0,0638); pudiera tener relación con un mayor tiempo de exposición a los alergenos, así como a peculiaridades del estilo de vida del pre adolescente.

Introduction: In Lima with a population of almost three million children it has been not reported until now child allergy prevalence studies. Objectives: To determine the current epidemiological characteristics of childrenÆs eye allergy in the poor elementary students in South of Lima. We took significant sample to students from 8 primary schools in three districts in the South of Lima, with 120,000 children. Material and method: A cross-sectional and observational study was made, assessed and considered, on-site at each school 2,011 elementary students. For the calculation of samples we use Excel 2003 and for analysis we use SPSS 15.0. Results: With an increase in the frequency of eye allergy that increases with age. Eye allergy is more correlated with the blepharitis and the chalazion. Conclusions: The prevalence of eye allergy 16.3% is moderate in the primary school population of Lima South, the eye allergy behavior is rising as advances school age (Y = 0.0305 X=0.0638); It could be related to a longer exposure to allergens, as well as the lifestyle of the teenage pre peculiarities.

Dermatoceratoconjuntivite atópica em pacientes do Ambulatório de Dermatologia Infanto-Juvenil em centro de referência / Atopic keratoconjunctivitis in patients of the pediatric dermatology ambulatory in a reference center

OBJETIVO: Avaliar a frequência de dermatoceratoconjuntivite atópica, seus sintomas e alterações em pacientes do Ambulatório de Dermatologia Infanto-Juvenil da Irmandade da Santa Casa de Misericórdia de São Paulo com diagnóstico prévio de dermatite atópica. MÉTODOS: Foram avaliados 52 portadores de dermatite atópica do Ambulatório de Dermatologia Infanto-Juvenil, menores de 16 anos (média de idade 8,9 ± 4,1 entre 2 e 16 anos) por meio de um protocolo de questões de sintomas e avaliação oftalmológica dos sinais. Os sinais e sintomas foram graduados de 0 (ausente) a 4 (maior intensidade), e em alguns casos apenas como presentes ou não. A análise foi descritiva e estatística, com nível de significância de 5 por cento. RESULTADOS: A frequência da dermatoceratoconjuntivite atópica foi de 76,9 por cento entre os 52 pacientes com dermatite atópica, dos quais 26,7 por cento com conjuntivite atópica e 50,2 por cento com blefarite atópica. No grupo de dermatite atópica encontramos maior número de pacientes do sexo feminino e no grupo conjuntivite atópica maior número de pacientes do sexo masculino. A idade foi praticamente igual nos grupos estudados. Os sintomas mais frequentes foram olho vermelho e prurido, principalmente no grupo de conjuntivite atópica. Este último foi o sintoma com escore mais intenso e presentes em todos os pacientes do grupo conjuntivite atópica. Papilas e blefarite foram os sinais mais encontrados. O tempo de ruptura do filme lacrimal encontrava-se alterado na maioria dos pacientes. CONCLUSÕES: A frequência de dermatoceratoconjuntivite atópica foi de 76,9 por cento nos pacientes com dermatite atópica. O prurido foi o sintoma mais frequente, seguido por olhos vermelhos, mais relacionados ao grupo de conjuntivite atópica. A blefarite e as papilas foram os sinais mais encontrados, também no grupo de conjuntivite atópica. Devido ao crescimento da prevalência da dermatite atópica na população infantil, seria prudente realizar...

PURPOSE: To evaluate the frequency of atopic keratoconjunctivitis, its symptoms and changes in patients of Pediatric Dermatology Service of "Santa Casa de Misericordia de São Paulo" Hospital with a previous diagnosis of atopic dermatitis. METHODS: Fifty-two patients with atopic dermatitis under 16 years old (mean age 8.9 ± 4.1 between 2 and 16 years old) were evaluated through a protocol of questions and assessment of signs and symptoms. The signs and symptoms were graded from 0 (absent) to 4 (highest intensity), and in some cases only as present or not. The analysis was descriptive and statistical, with a 5 percent significance level. RESULTS: The frequency of atopic keratoconjunctivitis was 76.9 percent among the 52 patients with atopic dermatitis, including atopic conjunctivitis (26.7 percent) and atopic blepharitis (50.2 percent). Atopic dermatitis is more frequent in female patients and atopic conjunctivitis in male. Age was practically the same in both groups. The most frequent symptoms were red eye and itching, especially in the atopic conjunctivitis group. Itching was the most intense symptom and was present in all patients of the atopic conjunctivitis group. Blepharitis and papillae were the most common signs. Other signs were less frequent. The tear break-up time was changed in most patients. CONCLUSIONS: The prevalence of atopic keratoconjunctivitis was 76.9 percent in patients with atopic dermatitis. Itching was the most frequent symptom, followed by red eye, in patients with atopic conjunctivitis. Blepharitis and papillae were the most frequent signs in patients with atopic conjunctivitis. Due to the increasing prevalence of atopic dermatitis in children, it would be prudent to perform a routine ophthalmologic evaluation of these patients. From the patients evaluated in this study, none had been previously monitored with ophthalmological exams.

Are cutaneous hypersensitivity tests to inhalant allergens a severity marker for vernal keratoconjunctivitis?

PURPOSE: The purpose of this study was to analyze the cutaneous sensitivity to a variety of allergens in patients with vernal keratoconjunctivitis (VKC) and to demonstrate the relation between skin response and clinical aspects of the disease. METHODS: Twenty patients with vernal keratoconjunctivitis were randomly chosen from the External Disease and Cornea Sector. They were clinically evaluated, and a score ranging from 0 to 20 was applied based on signs and symptoms on ophthalmic examination. All subjects underwent a skin prick test against standardized allergens, such as house dust mites D. pteronyssinus, D. farinae, and Blomia tropicalis, as well as allergens from cat, dog, fungi and feather. RESULTS: Seventy-five per cent of patients were positive for at least one of the allergens tested. House dust mites were responsible for the majority of the cases (75 percent). There was a poor correlation between the clinical score and sensitivity to allergens (r= - 0.119 for fungi; r= - 0.174 for dog; r= - 0.243 for house dust mites; r= - 0.090 for feather). A significant correlation was found only for cat allergen extract (r = - 0.510; p=0.024). CONCLUSIONS: Our study demonstrated poor correlation between cutaneous hypersensitivity tests and clinical findings in patients with vernal keratoconjuntivitis. We concluded that skin response to inhalant allergens is not a useful test to identify clinical severity and chronicity of inflammatory process in this disease.

OBJETIVO: Avaliar o papel da sensibilização cutânea a diferentes aeroalérgenos em pacientes com ceratoconjuntivite vernal e a correlação entre esta e os aspectos clínicos da doença. MÉTODOS: Vinte pacientes do setor de doenças externas e córnea foram aleatoriamente convidados para participar deste estudo. Os pacientes foram avaliados e a eles foi atribuído um escore clínico variando de 0 a 20 de acordo com sinais e sintomas presentes no exame oftalmológico. Todos os pacientes foram submetidos a testes cutâneos de hipersensibilidade imediata contra aeroalérgenos padronizados como os ácaros domiciliares D. pteronyssinus, D. farinae e Blomia tropicalis, assim como também a alérgenos de epitélio de gato, epitélio de cão, mistura de fungos e mistura de penas. RESULTADOS: Setenta e cinco por cento dos pacientes tiveram teste de hipersensibilidade imediata positivo contra pelo menos um dos antígenos testados. Os ácaros domiciliares foram responsáveis pela maioria destes casos (75 por cento). Houve uma pobre correlação entre o escore clínico e a hipersensibilidade cutânea aos alérgenos (r= -0,119 para fungos; r= -0,174 para epitélio de cão; r= -0,243 para ácaros domiciliares; r= -0,090 para mistura de penas). Houve correlação significativa apenas contra epitélio de gatos (r= -0,510; p=0,024). CONCLUSÃO: O estudo demonstrou uma pobre correlação entre os testes cutâneos de hipersensibilidade imediata e os achados clínicos nos pacientes com ceratoconjuntivite vernal. Os testes cutâneos de hipersensibilidade imediata contra aeroalérgenos não foi parâmetro eficaz na identificação dos casos de maior gravidade e cronicidade de ceratoconjuntivite vernal.