Comprehensive ophthalmological evaluation in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD), a chronic Type 2 inflammatory skin disease, is frequently associated with ocular surface diseases (OSD) which may appear or worsen under anti-Type 2-targeted treatments. However, the exact prevalence of OSD and the ophthalmology referral criteria remain ill-defined in AD patients before initiating such biotherapies. OBJECTIVE: We aimed to characterize the prevalence, the nature and the factors related to OSD development in AD that may justify an ophthalmological management. METHODS: A total of 98 consecutive AD inpatients without biological treatment were retrospectively included. These were systematically evaluated by an ophthalmologist during their dermatological care. Clinical and laboratory data were analyzed to characterize OSD and their risk factors. RESULTS: OSD were found in 83/98 AD patients (85%); mainly dry eye syndrome (64%, 63/98), allergic conjunctivitis (42%, 41/98), posterior (33%, 32/98), and anterior blepharitis (27%, 26/98). In AD patients without ocular symptoms, OSD were also frequently found (63%, 12/19) and were mostly mild. Risk factors for OSD were history of allergic rhinitis, allergic sensitization, head and neck AD, ocular symptoms (foreign body sensation in the eye, burning, itching, photophobia), and total IgE level >3000kU/L. CONCLUSION: The prevalence of OSD was high, even in asymptomatic patients. The risk factors identified may indicate the need for ophthalmological examination for therapeutic management, especially when biological agents targeting Type 2 inflammation are considered.

EAACI position paper on the clinical use of the bronchial allergen challenge: Unmet needs and research priorities.

Allergic asthma (AA) is a common asthma phenotype, and its diagnosis requires both the demonstration of IgE-sensitization to aeroallergens and the causative role of this sensitization as a major driver of asthma symptoms. Therefore, a bronchial allergen challenge (BAC) would be occasionally required to identify AA patients among atopic asthmatics. Nevertheless, BAC is usually considered a research tool only, with existing protocols being tailored to mild asthmatics and research needs (eg long washout period for inhaled corticosteroids). Consequently, existing BAC protocols are not designed to be performed in moderate-to-severe asthmatics or in clinical practice. The correct diagnosis of AA might help select patients for immunomodulatory therapies. Allergen sublingual immunotherapy is now registered and recommended for controlled or partially controlled patients with house dust mite-driven AA and with FEV1 ≥ 70%. Allergen avoidance is costly and difficult to implement for the management of AA, so the proper selection of patients is also beneficial. In this position paper, the EAACI Task Force proposes a methodology for clinical BAC that would need to be validated in future studies. The clinical implementation of BAC could ultimately translate into a better phenotyping of asthmatics in real life, and into a more accurate selection of patients for long-term and costly management pathways.

Birch allergen challenges in allergic conjunctivitis using standard conjunctival allergen challenge and environmental exposure chamber.

BACKGROUND: Environmental exposure chambers (EECs) have been used extensively to study allergic rhinoconjunctivitis. Few studies have been published using EECs in conjunctivitis only, and none have used conjunctival allergen challenge as a selection criterion. The present study validated ALYATEC EEC in allergic conjunctivitis to birch pollen. METHODS: Sixteen patients with a positive conjunctival allergen challenge (CAC) were exposed to 60 ng/m3 of Bet v 1 in an EEC on two consecutive days for a maximum of 4 h to validate EEC exposure to birch. Reproducibility was tested among seven of the patients. A conjunctival positive scoring during the CAC and the EEC exposure was defined as a Total Ocular Symptom Score (TOSS) ≥ 5. RESULTS: Fifty percent of patients had a conjunctival positive scoring during first exposure and 75% during second exposure. The mean time to a conjunctival response was 81.2 ± 33.9 min and 101.6 ± 57 (P > 0.05) during first and second exposure, respectively. No difference in TOSS occurred between the two exposures. The time necessary to obtain a positive response during the CAC was significantly shorter than with the EEC. The estimated quantity of Bet v 1 inducing a positive response was 0.07 ± 0.03 ng (exposure 1), 0.07 ± 0.07 ng (exposure 2), 980 ± 784 ng (CAC). Conjunctival positive scoring and quantity of Bet v 1 was reproducible in all six EEC exposures. CONCLUSIONS: Early conjunctival responses induced by birch allergen exposures in EEC were different than from those identified with direct instillation during CAC. EEC appears to be closer to natural exposure than CAC.

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA2 LEN consensus.

BACKGROUND: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. METHODS: A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. RESULTS: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). CONCLUSIONS: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.

2019 ARIA Care pathways for allergen immunotherapy.

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients.

Diagnosing and managing allergic conjunctivitis in childhood: The allergist's perspective.

Allergic conjunctivitis in childhood often poses problems of diagnosis and management for the allergist. We present the salient points concerning the diagnosis and treatment of ocular allergy emerging from a large cohort survey conducted jointly in the departments of ophthalmology and paediatric allergy in a French teaching hospital. Seasonal acute conjunctivitis is a common disorder and not overly difficult to diagnose and treat when associated with rhinitis leading to allergic rhinoconjunctivitis. An ophthalmologist should be consulted when conjunctivitis occurs alone and if another form of conjunctivitis is suspected, such as perennial allergic conjunctivitis, vernal keratoconjunctivitis or atopic keratoconjunctivitis. When IgE-mediated hypersensitivity assessment does not establish aetiological diagnosis, a conjunctival allergen provocation test can be performed. The principal non-IgE-mediated allergy is chronic blepharoconjunctivitis. The main problem for differential diagnosis is the presence of signs suggestive of dry eye. Management includes non-pharmacological treatments, such as lacrimal substitutes, avoidance measures and protection of the ocular surface. Second-line treatment consists of eye drops, preferably single dose or without additives and with dual local action, mast cell stabilizer action and antihistaminic action. Third-line treatment is reserved for severe forms. Short-lasting local steroid therapy can control flare-ups of allergic keratoconjunctivitis, which should have specialized follow-up. Cyclosporine is a disease-modifying treatment, which is both effective and well tolerated.

Peanut oral immunotherapy in adolescents: study protocol for a randomized controlled trial.

BACKGROUND: Peanut allergy is an increasingly common health problem. Current treatment guidelines are based on strict avoidance. However, in the last few years, oral immunotherapy protocols have shown promising results yielding increased tolerance to peanut in allergic children. Adolescence is particularly at risk. METHODS/DESIGN: We have designed a randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of peanut oral escalating immunotherapy in a 12- to 18-year-old population with proved allergy to peanut. Patients are selected when the threshold of peanut intake is over 100 mg and 2 cumulated g on the first double-blind, placebo-controlled oral food challenge (DBPCOFC). During the build-up placebo-controlled blinded phase, doses containing peanut or placebo will be administered by gradual up-dosing from 10 mg to 2 g with 2-weekly increments. After this first randomized phase, the desensitized participants will continue to intake native peanut in an unblinded process during 13 or 37 weeks following a second randomization. Adverse events are picked up and managed throughout the entire protocol. The main endpoint is the percentage of patients with negative DBPCOFC at the threshold of 2 g of cumulative peanut at the end of the build-up phase of 24 weeks. Secondary endpoints include: (1) desensitization 6 weeks and 6 months after the end of the maintenance phase; (2) adverse effects during the build-up phase; (3) immunological profile confirming peanut desensitization. Immunologic assays will be carried out at every DBPCOFC and at the middle of the build-up phase to evaluate the peanut immunologic profile modifications. DISCUSSION: This double-blind, placebo-controlled study will be, to our knowledge, the first evaluation of a peanut oral immunotherapy protocol in teenagers in the purpose to reduce severe reactions after unexpected intake and to improve quality of life. TRIAL REGISTRATION: ClinicalTrial.gov: NCT02046083 (23 January 2014).

Impact of a short early therapeutic education program on the quality of life of asthmatic children and their families.

OBJECTIVES: Few studies have been made on the impact of therapeutic education (TE) on the quality of life (QOL) of asthmatic primary-school aged children. We attempted to assess the beneficial effects on the QOL of children and their parents of a short TE program initiated immediately after the first consultation with a pediatric pulmonologist. METHODS: The QOL of 31 families of asthmatic children (aged 5-11) was measured before and 3 months after a short and early programme of TE by the French version of the Pictured Child's Quality of Life Self Questionnaire (AUQUEI, AUtoquestionnaire QUalité de vie Enfant Imagé) for the children, and by the Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) for the parents. The other criteria studied were asthma management, school and workplace absenteeism and functional respiratory parameters. RESULTS: TE did not significantly alter the AUQUEI score (P = 0.67). No change was observed in the different areas studied: autonomy (P = 0.97), leisure activities (P = 0.64), functions (P = 0.88), and social relations (P = 0.51). In contrast, the PACQLQ score considerably improved after TE (P < 0.001), as evidenced by reduced activity limitations (P < 0.001) and improved emotional functioning of parents (P < 0.001). These results were accompanied by a significant improvement in asthma management, with, in particular, a major decrease in the use of medication (P < 0.001) and the number of unscheduled medical consultations (P < 0.001) and visits to the emergency department (P = 0.02); a decrease in school absenteeism (P = 0.009); and an improvement in forced expiratory volume in 1 sec (FEV1 ) (P = 0.05). CONCLUSIONS: Our TE program had rapid and beneficial effects on numerous objective and subjective parameters, thereby contributing to the well-being of the families and probably to a subsequent decrease in the overall cost of asthma management. Pediatr Pulmonol. 2015; 50:213-221. © 2014 Wiley Periodicals, Inc.

Human complement C3 deficiency: Th1 induction requires T cell-derived complement C3a and CD46 activation.

Human T helper type 1 (Th1) responses are essential in defense. Although T cell receptor (TCR) and co-stimulator engagement are indispensable for T cell activation, stimulation of additional receptor pathways are also necessary for effector induction. For example, engagement of the complement regulator CD46 by its ligand C3b generated upon TCR activation is required for IFN-γ production as CD46-deficient patients lack Th1 responses. Utilizing T cells from two C3-deficient patients we demonstrate here that normal Th1 responses also depend on signals mediated by the anaphylatoxin C3a receptor (C3aR). Importantly, and like in CD46-deficient patients, whilst Th1 induction are impaired in C3-deficient patients in vitro, their Th2 responses are unaffected. Furthermore, C3-deficient CD4(+) T cells present with reduced expression of CD25 and CD122, further substantiating the growing notion that complement fragments regulate interleukin-2 receptor (IL-2R) assembly and that disturbance of complement-guided IL-2R assembly contributes to aberrant Th1 effector responses. Lastly, sustained intrinsic production of complement fragments may participate in the Th1 contraction phase as both C3a and CD46 engagement regulate IL-10 co-expression in Th1 cells. These data suggest that C3aR and CD46 activation via intrinsic generation of their respective ligands is an integral part of human Th1 (but not Th2) immunity.

Human C3 deficiency associated with impairments in dendritic cell differentiation, memory B cells, and regulatory T cells.

Primary C3 deficiency, a rare autosomal inherited disease (OMIM 120700), was identified in a 2-year-old male suffering from recurrent pyogenic infections from early infancy with undetectable total complement hemolytic activity (CH50) and C3 values. The nonconsanguineous parents and the two patients' two siblings had 50% normal serum C3 concentration. The molecular abnormality associated a paternal allele coding C3 with the missense mutation p.Ser(550)Pro and an apparently null maternal allele, with production of a defective protein that could no longer be secreted. Vaccination of the child did not induce a long-term Ab response. Accordingly, switched memory IgD(-)CD27(+) B cells were barely detected, amounting to only 2.3% of peripheral blood CD19(+) cells. Cells were significantly defective in stimulating alloreactive responses. The in vitro development of immature dendritic cells and their maturation capacity were greatly impaired, with decreased CD1a expression and IL-12p70 secretion ability. These cells were unable to induce autologous B cell proliferation and Ig secretion in the presence of CD40L and C3. Finally, the regulatory T cell development ability of CD4(+) T cells after CD3 and CD46 activation in the presence of IL-2 was significantly impaired. Thus, the association of important functional defects of dendritic cells, acquisition of B cell memory, and regulatory T cells with human C3 deficiency strongly supports a major role for C3 in bridging innate and adaptive immunity in humans.