These findings support an association between IgE, IL-18 or IL-12/p40 and AD. The stronger response observed in serum samples from patients with higher SCORAD scores suggest that IgE, IL-18 and IL-12/p40 may be useful in evaluating the progression of AD and in elucidating the mechanisms of disease pathogenesis.

Long-term therapy with the macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time, macrolides have been found to have a large number of anti-inflammatory properties in addition to being antimicrobials. These observations provided the rationale for many studies performed to assess the usefulness of macrolides in other inflammatory diseases including skin and hair disorders, such as rosacea, psoriasis, pityriasis rosea, alopecia areata, bullous pemphigoid, and pityriasis lichenoides. This paper summarizes a collection of clinical studies and case reports dealing with the potential benefits of macrolides antibiotics in the treatment of selected dermatoses which have primarily been classified as noninfectious and demonstrating their potential for being disease-modifying agents.

BackgroundAllergic reactions have been implicated as contributions in a number of atopic disorders, including atopic dermatitis (AD), allergic rhinitis (AR) and bronchial asthma (BA). However, the potential for filaggrin protein, eosinophil major basic protein (MBP) and immunoglobulin E (IgE) to elicit allergic response or to contribute to atopic disorders remains largely unexplored in pediatric patients. This study was undertaken to investigate the status and contribution of filaggrin protein, eosinophil MBP and total IgE in pediatric patients with AD, AR and BA.MethodsSera from 395 pediatric patients of AD, AR or BA with varying levels of disease activity according to the disease activity index and 410 age-matched non-atopic healthy controls were evaluated for serum levels of atopic markers, including filaggrin, eosinophil MBP and IgE.ResultsSerum analysis showed that filaggrin levels were remarkably high in pediatric patients with AD, followed by BA and AR, whereas its levels were low in non-atopic pediatric controls. Eosinophil MBP levels in sera of atopic patients were significantly high as compared with their respective controls, but its levels were highest in AR patients, followed by AD and BA. Total IgE in sera of AD patients was markedly high, followed by AR and BA patients, whereas its levels were low in non-atopic pediatric controls. Interestingly, not only was an increased number of subjects positive for filaggrin protein, eosinophil MBP or total IgE, but also their levels were statistically significantly higher among those atopic patients whose disease activity scores were higher as compared with atopic patients with lower disease activity scores.ConclusionsThese findings strongly support a role of filaggrin protein, eosinophil MBP and IgE in the onset of allergic reactions in pediatric patients with AD, AR and BA. The data suggest that filaggrin, eosinophil MBP or IgE might be useful in evaluating the progression of AD, AR or BA and in elucidating the mechanisms involved in the pathogenesis of these pediatric disorders.

no Variant position Variant Count Amino Acid Change Mutation Types c.8343c>G 37 D2781E missense c.8360g>R 34 R2787[H,R] missense c.6073g>K 32 G2025[G,*] nonsense c.8397g>R 27 NC silent c.1360a>R 25 T454A missense c.5883c>M 25 H1961Q missense c.8084a>R 25 N2695[N,S] missense c.6498t>Y 24 NC silent c.7956a>G 24 0, E2652[D] missense c.8143t>Y 24 S2715[P,S] missense c.8170g>A 24 A2724[T,A] missense c.8208a>R 24 NC silent c.8399a>M 24 Y2800S missense c.8060a>M 23 Y2687S missense c.8265g>C 23 NC silent c.8297g>R 23 R2766H missense c.8260t>Y 22 W2754R missense c.1432c>Y 21 P478S missense c.4126a>R 21 R1376G missense c.8192c>G 21 T2731R missense c.8201a>R 21 H2734R missense c.10307g>S 21 G3436A missense c.5541g>R 20 T1847[H,R] missense c.6580t>Y 20 Y2194H missense c.8312a>R 20 Q2771R missense c.1330g>R 18 G444R missense c.4079g>R 18 R1360H missense c.5051g>R 18 R1684H missense c.9645g>K 18 NC silent c.995g>K 17 G332V missense c.7962t>Y 17 H2654[T,M] missense c.8251t>K 17 S2751[A,S] missense c.8301t>Y 17 NC silent c.8332g>A 17 A2778[T,A] missense c.8382a>W 17 R2794[R,S] missense c.10194t>Y 17 NC silent c.5095c>Y 16 R1699C missense

Bronchial asthma (BA), atopic dermatitis (AD) and allergic rhinitis (AR) are common atopic disorders with complicated etiologies. The atopic march from early AD to BA, AR, or both later in life and the extensive comorbidity among them indicates, that these atopic disorders might share a common mechanism (1). Moreover, heritability of these atopic disorders is high, being 35-95% for BA, 71-84% for AD, 33-91% for AR and 34-68% for allergen-specific serum immunoglobulin E (IgE) levels (1,2). Filaggrin is now considered as a major predisposing gene for many atopic disorders, which result in a major paradigm in dermatology and allergy research (3). Many studies pointed out an association of the filaggrin gene with different atopic disorders. More specifically, loss-of-function mutations in the filaggrin gene have been reported to have an association with various atopic/allergic disorders (3). Batchelor et al., reported that there is a strong and consistent association between filaggrin mutations and development of AD (4), but Summary Bronchial asthma (BA), atopic dermatitis (AD), and allergic rhinitis (AR) are well known atopic disorders with complex etiologies. This study was undertaken to investigate the role of filaggrin, eosinophil major basic protein (MBP) and leukotriene B4 (LTB4) in patients with BA, AD, and AR. Sera from 1,246 patients with different atopic disorders and 410 normal healthy controls were collected and were evaluated for filaggrin, MBP and LTB4 by specific sandwich ELISAs, whereas immunoglobulin E (IgE) was used as a positive control for atopic patients. Serum analysis showed that filaggrin levels were remarkably high in patients with AD and in patients with multiple (mixed) atopic disorders (p < 0.001), whereas its levels in BA and AR patients were low but much higher than in normal human sera (p < 0.01). MBP levels were also high in AR, BA and mixed atopic patients, whereas AD patients showed no increase of MBP (p > 0.05). In contrast, LTB4 level was found to be significantly low in all tested atopic patients groups as compared to the levels of LTB4 present in normal human sera (p < 0.001). In conclusion, these findings support an association between filaggrin, MBP or LTB4 and atopic disorders. Our data strongly suggest that filaggrin, MBP or LTB4 might be useful in elucidating the mechanisms involved in the pathogenesis of these atopic disorders.