Review article
Atopic dermatitis: recent insight on pathogenesis and novel therapeutic target
Enza D’Auria, Giuseppe Banderali, Salvatore Barberi, Lorenzo Gualandri, Benedetta Pietra, Enrica Riva, Amilcare Cerri

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease . It affects infancy, but it is also highly prevalent in adults and it is cause of burden to patients and their families. Nowaday, AD is recognized as an heterogenous disease, including different subtypes with variable clinical manifestations, in which the impairments of the skin barrier are crucial. The severity of AD dictates the level of treatment. Current AD treatment focuses on restoration of barrier function, mainly through moisturizers and on the control of inflammation by the use of corticosteroids, topical calcineurin inhibitors and immunosuppresive drugs in the most severe cases. However, targeted disease-modifying therapy are under investigations. The most recent findings on the skin microbial dysbiosis is a promising future direction for the development of new treatments. We need to improve the understanding of the complex microbiome-host interactions, the role of autoimmunity, the comparative effectiveness of therapies and the ways to implement the educational strategies.
DOI 10.12932/AP0732.34.2.2016


Original articles
Association of the chromosome 11p13.5 variant and atopic dermatitis with a family history of atopy in the Chinese Han population
Fang Cheng, Jin-Hua Zhao, Xian-Fa Tang, Hui Cheng, Yu-Jun Sheng, Xiao-Yun Jiang, Ling Fang, Xiao-Guang Zhang, Xian-Bo Zuo, Xiao-Dong Zheng, Fu-Sheng Zhou, Hua-Yang Tang, Sen Yang, Feng-Li Xiao, Xue-Jun Zhang

Background: Recent genome-wide association studies (GWAS) and a meta-analysis of GWAS for atopic dermatitis (AD) have identified some AD genetic loci in European and Japanese populations.
Objective: To investigate whether some novel susceptibility loci are associated with AD in the Chinese Han population.
Methods: We first selected eight novel susceptibility loci to replicate in 2,205 AD patients and 2,116 healthy controls using the Sequenom platform. Data were analyzed with PLINK 1.07 software.


Association between interleukin-17a gene polymorphisms and asthma risk: a meta-analysis
Min Zhu, Ting Wang, Renzhi Chen, Chengdi Wang, Shouzhi Liu, Yulin Ji
Background: Interleukin-17A (IL-17A), a proinflammatory cytokine, plays an important role in the pathogenesis of asthma. Considerable research has assessed the association between IL-17A polymorphisms and asthma risk, but the results are inconsistent.
Objective: This meta-analysis was carried out to make a more precise estimation of the relationship between IL-17A polymorphisms and asthma risk.
Methods: The PUBMED, MEDLINE, EMBASE, Chinese National Knowledge Infrastructure and Wan Fang databases were searched systemically on December 12, 2014 and data were extracted from eligible studies by two independent reviewers. Meta-analysis, sub-group analysis, sensitivity analysis and publication bias assessments were all done using Stata 12.1 software.
Results: The IL-17A -737C/T polymorphism and IL-17A -197G/A polymorphism were included in the analysis with seven case-control studies. Asthma patients (n = 2882) and healthy controls (n = 2093) were included. The IL17A -737C/T polymorphism was found to have a significantly protective effect on asthma in the allele model (OR = 0.86, 95% CI 0.78-0.96, P = 0.007), dominant model (OR = 0.76, 95% CI 0.65-0.88, P <0.001) and heterozygous model (OR = 0.75, 95% CI 0.64-0.88, P < 0.001) in the overall analysis. Stratified by ethnicity and age, the effects were also significant in the Asian population and in children. However, for IL-17A -197G/A, no significant association was revealed either in the overall analysis in the ethnicity-special subgroup analysis.
Conclusions: The IL-17A -737C/T polymorphism is likely to contribute to protection against asthma, while the IL-17A -197G/A polymorphism may not be associated with asthma susceptibility.
DOI 10.12932/AP0680.34.2.2016

Association between JAK1 gene polymorphisms and susceptibility to allergic rhinitis
Yang Shen, Yun Liu, Xia Ke, Hou-Yong Kang, Guo-Hua Hu, Su-Ling Hong

Objectives: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Janus kinase 1(JAK1), a member of JAK family, has recently been found to participate in the immune response and the development of allergic airway disease. This study was performed to evaluate the potential association of JAK1 polymorphisms with AR in a Chinese Han population.
Design and Methods: A case-control study was performed in 450 Chinese AR patients and 615 healthy controls. Three SNPs in the JAK1 gene, including rs3790532, rs310241 and rs2780815, were detected using a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP).
Results: An association between SNPs rs310241 inthe JAK1 gene and AR in a Chinese Han population. However, no significant association was observed between rs3790532, rs2780815 polymorphisms and AR. For rs310241, the CC genotype and the C allele significantly increased the risk of AR. Furthermore, we found that the ACG haplotype in JAK1 gene was positively correlated with AR, while the GTG haplotype was associated with a significantly decreased risk of AR.
Conclusion: This study indicates that JAK1 rs310241 C-related genotype and allele are likely involved in AR susceptibility, making them potentially useful genetic biomarkers for AR susceptibility in the Chinese Han population.
DOI 10.12932/AP0630.34.2.2016

Evaluation of drug provocation tests in Korean children: a single center experience
Jinwha Choi, Ji Young Lee, Kwang Hoon Kim, Jaehee Choi, Kangmo Ahn, Jihyun Kim
Background: Drug provocation tests (DPTs) are difficult to perform in clinical practice, even though they are the gold standard for the diagnosis of adverse drug reactions (ADRs).
Objective: The aims of this study were to evaluate the common causative drugs of type B ADRs and to analyze the relationships between host factors and the results of DPTs in Korean children.
Methods: We retrospectively reviewed the medical records of all children younger than 19 years of age who underwent a DPT between November 1994 and November 2014. Open provocation tests were performed with non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, aminopenicillins, cephalosporins, non-β-lactam antibiotics, antiepileptic drugs, or other drugs.
Results: Overall, 84 DPTs were performed in 56 patients whose median age was 7.5 years (range, 6 months to 18 years). DPTs were positive in 25 (29.8%) of 84 cases, which translated to 18 (32.1%) positive findings in 56 patients. Drugs that provided positive results included NSAIDs (7 cases, 28.0%), aminopenicillins (5 cases, 20.0%), acetaminophen (4 cases, 16.0%), cephalosporins (3 cases, 12.0%), and non-β-lactams (2 cases, 8.0%). Anaphylaxis was noted in 5 (20.0%) of 25 cases. There were no serious
complications of DPTs in any of the subjects. The median age was 10.5 years for children who had a positive result following the DPT and 5.0 years for those with negative results (P value = 0.019).
Conclusions: DPTs can be performed safely in children with suspected ADRs in order to achieve a correct diagnosis.
DOI 10.12932/AP0692.34.2.2016


Minimal clinical important difference (MCID) of the Thai Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL)
Kanokvalai Kulthanan, Leena Chularojanamontri, Papapit Tuchinda, Chuda Rujitharanawong, Ilaria Baiardini, Fulvio Braido
Background: Chronic urticaria (CU) has negative impacts on patients’ daily lives. The Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) evaluates quality of life impairment attitudes among chronic urticarial patients. Although the CU-Q2oL has been validated in several languages, the minimal clinical important difference (MCID) of the CU-Q2oL has never been determined. Objective: This study aimed to investigate the validity, reliability, responsiveness to change, and MCID of the Thai CU-Q2oL.
Methods: The Thai CU-Q2oL was translated with permission from the authors of the original Italian version. The Thai CU-Q2oL, the validated Thai Dermatology Life Quality Index (DLQI), and the Urticaria Activity Score were assessed for 166 patients to evaluate validity and internal consistency. The three questionnaires were then administered to 124 patients to determine the test-retest reliability, responsiveness, and MCID of the Thai CU-Q2oL.
Results: The Thai CU-Q2oL contained only three domains, whereas the Italian version revealed six domains. Nevertheless, the total variance of the Thai CU-Q2oL (60.5%) was very close to that of the Italian version (60.0%). The validity of the Thai CU-Q2oL was shown by strong correlations between CU-Q2oL and DLQI scores. The Thai CU-Q2oL also had high internal consistency and test-retest reliability. Distribution-based, receiver operating characteristic analysis, and anchor-based approaches yielded MCID values of 3.9–8.0, 15, and 21.1, respectively.
Conclusions: The Thai CU-Q2oL is a valid and reliable instrument. We propose that a difference in the Thai CU-Q2oL score of 15 (MCID) is the smallest change patients perceive as a meaningful improvement.
DOI 10.12932/AP0674.34.2.2016

Analysis of solar urticaria in Thai patientsNarumol Silpa-archa, Chanisada Wongpraparut, Vichit Leenutaphong
Background: Solar urticaria (SU) is an uncommon photodermatosis characterized by erythema and whealing within minutes to a few hours after exposure to sunlight or an artificial light source.
Purpose: To determine the clinical features, photobiological characteristics and treatment outcomes in Thai SU patients visiting a tertiary referral hospital.
Method: A retrospective analysis of 13 patients with SU was conducted. Demographic data, disease characters, phototesting results, laboratory investigations, treatment and outcome were evaluated.
Results: Of the 13 patients diagnosed with SU from 2000 to 2012, most patients were female (10, 77%). The mean age of onset was 29 years (15-51). The mean duration of SU was 46 months (6-120) at presentation. The most common affected location was the upper extremities (92%), followed by head and neck (77%). The responsible action spectra were visible light in 8 patients (61.5%), ultraviolet A (UVA) in 1 patient (8%), and both visible light and UVA in 4 patients (31%). The median course from disease onset to disease resolution was 63 months (95% confidence interval 30-95). After 13 months and 55 months from the onset of symptoms, 23% and 49% of patients, respectively, were predicted to recover from their symptoms.
Conclusion: Solar urticaria is a rare condition in Thailand. The common eliciting spectra of SU were visible light and UVA. Management of SU remains challenging.
DOI 10.12932/AP0632.34.2.2016

Identification of wheat sensitization using an in-house wheat extract in Coca-10% alcohol solution in children with wheat anaphylaxis
Punchama Pacharn, Sasaros Kumjim, Puntanat Tattiyapong, Orathai Jirapongsananuruk, Surapon Piboonpocanun

Background: Identification of wheat sensitization by a skin prick test (SPT) is essential for children with wheat-induced anaphylaxis, since oral food challenge can cause serious adverse effects. Wheat allergens are both water/salt and alcohol soluble. The preparation of wheat extract for SPT containing both water/salt and alcohol soluble allergen is needed.
Objective: To determine if a wheat extract using Coca’s solution containing 10% alcohol (Coca-10% EtOH), prepared in-house, contians both water/salt and alcohol soluble allergens.
Methods: Serum of children with a history of anaphylaxis after wheat ingestion was used. Wheat flour was extracted in Coca-10% alcohol solution. An SPT with both commercial and in-house wheat extracts was performed as well as specific IgE (sIgE) for wheat and omega-5 gliadin. Direct and IgE inhibition immunoblots were performed to determine serum sIgE levels against water/salt as well as alcohol soluble (gliadins and glutenins) allergens in the extracts.
Results: Six children with history of wheat anaphylaxis had positive SPT to both commercial and in-house extracts. They also had different levels of sIgE against wheat and omega-5 gliadin allergens. The results of direct immunoblotting showed all tested sera had sIgE bound to ~35 kDa wheat protein. Further IgE inhibition immunoblotting identified the ~35 kDa wheat protein as gliadin but not gluten allergen.
Conclusion: The in-house prepared Coca-10% EtOH solution could extract both water/salt and alcohol soluble allergens. The ~35 kDa gliadin appears to be a major wheat allergen among tested individuals.
DOI 10.12932/AP0696.34.2.2016

Validation Study of the Pediatric Allergic Rhinitis Quality of Life Questionnaire.A Mavroudi, E Chrysochoou, RJ Boyle, A Papastergiopulos, N Karantaglis, A Karagiannidou, I Xinias, E Farmaki, E Hatziagorou, F Kirvassilis, G Kourentas, J Tsanakas, JO Warner

Background: The Paediatric Allergic Rhinitis Quality of Life Questionnaire (Ped-AR-QoL) is the first tool developed for the assessment of health-related quality of life (QoL) in Greek children with allergic rhinitis (AR).
Objective: The aim of the current study was to validate the child and parent forms of the Ped-AR-QoL in children aged 6-14 years-old who suffered from AR and were followed in a pediatric allergy clinic.
Methods: The Ped-AR-QoL, which was completed by 112 children and their parents, was correlated to the generic QoL questionnaire (Disabkids), which is already valid in Greece for children with chronic disorders, as well as with expert opinions on the severity of disease.
Results: The Ped-AR-QoL child and parent forms had very good internal consistency (α values of 0.797 and 0.872, respectively), while there was a moderate positive correlation of the disease-specific questionnaire with most of the subscales of the generic questionnaire. There has been a statistically significant association between the Ped-AR-QoL and the expert perception of disease severity.
Conclusions: The Ped-AR-QoL had very good reliability and convergent validity when compared with the generic Disabkids QoL. The significance of association between the disease-specific questionnaire and the expert opinion is an important finding validating the questionnaire. The Ped-AR-QoL may become a helpful tool which can be used in everyday clinical practice by clinicians and it may also be used for assessing therapeutic interventions in clinical trials.
DOI 10.12932/AP0651.34.2.2016

Would mean platelet volume/platelet count ratio be used as a novel formula to predict 22q11.2 deletion syndrome?
Bahar Gokturk, Sukru Nail Guner, Reyhan Kara, Mine Kirac, Sevgi Keles, Hasibe Artac, Ismail Reisli

Background: Diagnosis of 22q11.2 deletion syndrome depends on a time-consuming and expensive method, fluorescence in situ hybridisation (FISH).
Objectives: We aimed to determine new parameters which can aid for diagnosis of 22q11.2 deletion syndrome.
Methods: Twenty two patients with 22q11.2 or 10p13 deletion were evaluated retrospectively. Results: Facial-dysmorphism and mental-motor retardation were detected in 100% of patients. Mean platelet (PLT) counts were lower (224.980 versus 354.000, p=0.001), mean PLT volume (MPV) (9.95 versus 7.07, p=0.002), and MPV/PLTx105 ratios (5.36 versus 2.08, p<0.001) were higher in patients with 22q11.2 deletion when compared with control group. Area under the receiver-operator characteristic (ROC) curve was detected as 0.864, sensitivity as 84.6%, specificity as 90.9%, positive predictive value (PPV) as 91.7%, and negative predictive value (NPV) as 83.3% when MPV was 8.6. Area under ROC curve was detected as 0.864, sensitivity as 76.9%, specificity as 90.1%, PPV as 90.1%, and NPV as 76.3% when PLT was 265.500. Area under ROC curve was detected as 0.906, sensitivity as 84.6%, specificity as 100%%, PPV as 100%, NPV as 84.6% when MPV/PLTx105 was 3.3. Expression of PLT surface markers which were not in GPIb-V-IX receptor complex (CD61, CD41a) increased as the surface area increases, but markers which were in complex (CD42a, CD42b) did not change.
Conclusions: High MPV/PLT value can be a good predictor for diagnosis of 22q11.2 deletion syndrome. We suggest that the patient who has facial dysmorphism and retardation in neurodevelopmental milestones and if MPV≥8.6fl, MPV/PLTx105 ratio≥3.3 and PLT count≤265500/mm3, the patient should be tested by FISH analysis to confirm 22q11.2 deletion. If there is not macrothrombocytes, 10p13 deletion should be tested in suspected cases.
DOI 10.12932/AP0604.34.2.2016

A 10-year retrospective study of neonatal lupus erythematous in China
Yingfang Yu, Lizhong Du, Jiarong Pan, Jiyan Zheng, An Chen, Lihua Chen

Background: Neonatal lupus erythematosus (NLE) is not a common disease. The death rate of complete congenital heart block (CCHB), which is the most severe clinical manifestation, is as high as 20% to 30%, so early recognition of infants at risk is important. Objectives: To investigate the clinical features and long-term prognosis of NLE. Methods: Twenty-five cases with NLE were reviewed. The clinical manifestations of patients and their mothers were summarized and analyzed. Autoantibodies were detected, and long-term follow-up was carried out. Results: There were 25 patients (male:female ratio of 11:14). CCHB was detected in only 3 of the 25 patients (12%). Cutaneous neonatal lupus erythematosus (CNLE) was seen in 22 of the 25 patients (88%). Eight babies were treated with intravenous immunoglobulin (IVIG), five of whom had a prolonged PR interval that reverted to normal sinus rhythm. During the follow-up of the patients, we found only two patients with CCHB without a pacemaker, who both exhibited growth delay. One patient with CCHB without a pacemaker died.Conclusions: Children with NLE have an excellent outcome when only skin lesions are present. Even the hepatic, hematological and neurological abnormalities are transient, with generally good outcomes. IVIG might have some effectiveness due to enhanced anti-inflammatory activity to treat early diseases that may bereversible (e.g. prolonged PR interval). The long-term prognosis for patients with NLE is still under investigation, and some infants with NLE may progress to other autoimmune diseases later in childhood.
DOI 10.12932/AP0671.34.2.2016


ISSN: 2228-8694