Atopic Manifestations Are Underestimated Clinical Features in Various Primary Immunodeficiency Disease Phenotypes

Background: Atopic manifestations are described as a clinical feature of various primary immunodeficiency disease (PID) phenotypes and are frequently reported in combined immunodeficiencies. The prevalence of atopic manifestations in other PIDs remains largely unknown. Objective: To evaluate the prevalence of atopic manifestations in PIDs other than combined immunodeficiencies and to identify in which PIDs atopic manifestations are most common with the aim of improving patient care. Methods: A partner-controlled, questionnaire-based study was performed in pediatric and adult PID patients. Data from diagnostic tests to assess atopic manifestations (ie, diagnostic criteria for atopic dermatitis, spirometry, specific IgE against food and inhalant allergens) were collected from adult patients to confirm patient-reported atopic manifestations. Results: Forty-seven children and 206 adults with PIDs and 56 partner-controls completed the questionnaire. Thirty-five pediatric patients (74.5%) and 164 adult patients (79.6%) reported having experienced 1 or more atopic manifestations compared with 28 partner-controls (50.0%). In the comparison of adult patients with partner-controls, prevalence values were as follows: atopic dermatitis, 49.5% vs 27.3% (P=.003); food allergy, 10.7% vs 1.9% (P=.031); asthma, 55.7% vs 14.8% (P<.001); and allergic rhinitis, 49.8% vs 21.8% (P<.001). The frequency of current atopic manifestations reported by patients was higher than the prevalence based on diagnostic tests (atopic dermatitis, 11.2%; food allergy, 1.9%; asthma 16.4%; and allergic rhinitis, 11.5%). Conclusion: Atopic manifestations are prevalent clinical features across a broad spectrum of PIDs and, in our cohort, frequently present in patients with combined immunodeficiencies and predominant antibody deficiencies. Atopic manifestations should be evaluated in patients with PIDs (AU)

Antecedentes: En varios de los fenotipos asociados a las inmunodeficiencias primarias (PID), se describen, frecuentemente, diversas manifestaciones atópicas, en particular, en la inmunodeficiencia combinada. Sin embargo, la prevalencia de las manifestaciones atópicas en otras PID sigue siendo desconocida. Objetivo: Calcular la prevalencia de las manifestaciones atópicas en otras PID e identificar en cuáles de éstas son las más frecuentes con el fin de mejorar la atención a los pacientes. Métodos: Se realizó un estudio basado en un cuestionario validado, tanto en pacientes pediátricos como en adultos diagnosticados de PID. Posteriormente, se recopilaron los resultados de diferentes pruebas diagnósticas para enfermedades atópicas con el fin de corroborar los síntomas notificados por los pacientes adultos; es decir, criterios de diagnóstico para la dermatitis atópica, espirometría e IgE específica contra alérgenos alimentarios e inhalados. Resultados: El cuestionario se completó por 47 niños y 206 adultos con PID, y por 56 controles. Treinta y cinco pacientes pediátricos (74,5%) y 164 adultos (79,6%) informaron haber experimentado alguna vez una o más manifestaciones atópicas en comparación con 28 controles (50,0%). En los pacientes adultos, al comparar la prevalencia con sus controles, se observaron los siguientes resultados, respectivamente: dermatitis atópica 49,5% vs. 27,3% (p = 0,003); alergia alimentaria 10,7% vs. 1,9% (p = 0,031); asma 55,7% vs. 14,8% (p <0,001); y rinitis alérgica 49,8% frente a 21,8% (p <0,001). La frecuencia de manifestaciones atópicas objetivadas en los pacientes fue superior a la prevalencia basada en las pruebas diagnósticas (dermatitis atópica 11,2%, alergia alimentaria 1,9%, asma 16,4% y rinitis alérgica 11,5%) (AU)

Nasal and skin microbiomes are associated with disease severity in paediatric atopic dermatitis.

BACKGROUND: Alterations of the skin microbiome have been associated with atopic dermatitis (AD) and its severity. The nasal microbiome in relation to AD severity is less well studied. OBJECTIVES: We aimed to characterize the nasal and skin microbiomes in children with AD in relation to disease severity. In addition, we explored the differences and correlations between the nasal and skin communities. METHODS: We characterized the microbial composition of 90 nasal and 108 lesional skin samples cross-sectionally from patients with AD, using 16S-rRNA sequencing. In addition, a quantitative polymerase chain reaction was performed for Staphylococcus aureus and Staphylococcus epidermidis on the skin samples, and AD severity was estimated using the self-administered Eczema Area and Severity Index. RESULTS: We found an association between the microbial composition and AD severity in both the nose and skin samples (R2  = 2·6%; P = 0·017 and R2  = 7·0%; P = 0·004), strongly driven by staphylococci. However, other species also contributed, such as Moraxella in the nose. Skin lesions were positive for S. aureus in 50% of the children, and the presence and the load of S. aureus were not associated with AD severity. Although the nose and skin harbour distinct microbial communities (n = 48 paired samples; P < 0·001), we found that correlations exist between species in the nose and (other) species on the skin. CONCLUSIONS: Our results indicate that both the nasal and the skin microbiomes are associated with AD severity in children and that, next to staphylococci, other species contribute to this association.

IgG response against Staphylococcus aureus is associated with severe atopic dermatitis in children.

BACKGROUND: An altered immune response against Staphylococcus aureus might contribute to inflammation and barrier damage in atopic dermatitis (AD). OBJECTIVES: To profile IgG antibodies against 55 S. aureus antigens in sera of children with mild-to-severe AD and to evaluate the association between IgG levels and disease severity. METHODS: In this cross-sectional study, we included children with AD from two interventional study cohorts, the Shared Medical Appointment (SMA) cohort (n = 131) and the older DAVOS cohort (n = 76). AD severity was assessed using the Self-Administered Eczema Area and Severity Index (SA-EASI) and levels of thymus and activation-regulated chemokine (TARC) in serum. IgG antibody levels against 55 S. aureus antigens were quantified simultaneously using a Luminex assay. Pair-wise correlations were calculated between the 55 IgG levels using the Spearman rank correlation test. Linear regression analysis was performed to test for associations between 55 IgG levels and SA-EASI and TARC, adjusting for age, sex and S. aureus colonization. RESULTS: In the SMA cohort, 16 antigens were associated with SA-EASI and 12 with TARC (10 overlapping antigens; P-values 0·001-0·044). The associated IgG antibodies targeted mainly secreted proteins with immunomodulatory functions. In the DAVOS study, IgG levels against only four and one S. aureus antigen(s) were associated with SA-EASI and TARC, respectively (no overlap). CONCLUSIONS: In young children, severity of AD is associated with an IgG response directed against S. aureus antigens with mainly immunomodulatory functions. These findings encourage further evaluation of the role of S. aureus in the pathogenesis of AD.

The prevalence of antibody responses against Staphylococcus aureus antigens in patients with atopic dermatitis: a systematic review and meta-analysis.

BACKGROUND: Staphylococcus aureus plays a role in the pathogenesis of atopic dermatitis (AD), possibly via the expression of various virulence antigens. An altered antibody response towards these antigens might contribute to inflammation. OBJECTIVES: To provide an overview of the varying prevalences and odds of antibody responses against S. aureus antigens in patients with AD. METHODS: Data were systematically obtained from Embase, MEDLINE, Web of Science, Scopus, Cochrane, PubMed and Google Scholar up to 12 February 2016. We selected all original observational and experimental studies assessing antistaphylococcal antibodies in serum of patients with AD. Prevalences and odds ratios (ORs) of IgE, IgG, IgM and IgA against S. aureus in patients with AD vs. healthy controls were pooled using the random-effects model. We calculated I2 statistics to assess heterogeneity and rated study quality using the Newcastle-Ottawa Scale. RESULTS: Twenty-six articles (2369 patients) were included, of which 10 were controlled studies. Study quality was fair to poor. Patients with AD had higher prevalences of IgE against staphylococcal enterotoxin (SE)A (OR 8·37, 95% confidence interval 2·93-23·92) and SEB (OR 9·34, 95% confidence interval 3·54-24·93) compared with controls. Prevalences of antistaphylococcal IgE were 33% for SEA, 35% for SEB and 16% for toxic shock syndrome toxin-1. However, study heterogeneity and imprecision should be taken into consideration when interpreting the results. Data on IgG, IgM and IgA, as well as other antigens, are limited. CONCLUSIONS: Patients with AD more often show an IgE antibody response directed against S. aureus superantigens than healthy controls, supporting a role for S. aureus in AD pathogenesis.

A systematic review and meta-analysis on Staphylococcus aureus carriage in psoriasis, acne and rosacea.

Staphylococcus aureus might amplify symptoms in chronic inflammatory skin diseases. This study evaluates skin and mucosal colonization with S. aureus in patients with psoriasis, acne and rosacea. A systematic literature search was conducted. Both odds ratios (OR) for colonization in patients versus controls and the prevalence of colonization in patients are reported. Fifteen articles about psoriasis and 13 about acne (12 having a control group) were included. No study in rosacea met our inclusion criteria. For psoriasis, one study out of three controlled studies showed increased skin colonization (OR 18.86; 95 % confidence interval [CI] 2.20-161.99). Three out of the five studies that reported on nasal colonization showed significant ORs varying from 1.73 (95 % CI 1.16-2.58) to 14.64 (95 % CI 2.82-75.95). For acne one of the three studies that evaluated skin colonization reported a significant OR of 4.16 (95 % CI 1.74-9.94). A relation between nasal colonization and acne was not found. Limitations in study design and low sample sizes should be taken into consideration when interpreting the results. Colonisation with S. aureus seems to be increased in patients with psoriasis. This bacterial species, known for its potential to induce long-lasting inflammation, might be involved in psoriasis pathogenesis. Information on acne is limited. Prospective controlled studies should further investigate the role of S. aureus in chronic inflammatory skin diseases.

Prevalence and odds of Staphylococcus aureus carriage in atopic dermatitis: a systematic review and meta-analysis.

BACKGROUND: Staphylococcus aureus is increasingly implicated as a possible causal factor in the pathogenesis of atopic dermatitis (AD). However, the reported prevalence rates of skin and nasal colonization in the literature vary widely. OBJECTIVES: This study evaluates the prevalence and odds of skin and nasal colonization with S. aureus in patients with AD. METHODS: A systematic literature search was conducted. Odds ratios (ORs) for colonization in patients vs. controls and the prevalence of colonization in patients were pooled using the random-effects model. RESULTS: Overall, 95 observational studies were included, of which 30 had a control group. The Newcastle-Ottawa Scale was used to assess study quality, with the majority of studies being of fair to poor quality. Patients with AD were more likely to be colonized with S. aureus than healthy controls [OR 19·74, 95% confidence interval (CI) 10·88-35·81]. Differences were smaller in nonlesional skin (OR 7·77, 95% CI 3·82-15·82) and in the nose (OR 4·50, 95% CI 3·00-6·75). The pooled prevalence of S. aureus colonization among patients was 70% for lesional skin, 39% for nonlesional skin and 62% for the nose. In lesional skin, meta-regression showed that the prevalence of colonization increased with disease severity. Study heterogeneity should be taken into consideration when interpreting the results. CONCLUSIONS: These results demonstrate the importance of colonization with S. aureus in AD. Further evaluation of the mechanisms by which S. aureus influences inflammation is required in addition to the development of targeted strategies to decrease skin and nasal S. aureus load.