A set of clinical and laboratory markers differentiates hyper-IgE syndrome from severe atopic dermatitis.

Hyper-IgE syndrome (HIES) patients may share many features observed in severe atopic dermatitis (SAD), making a diagnostic dilemma for physicians. Determining clinical and laboratory markers that distinguish both disorders could provide early diagnosis and treatment. We analyzed patients (DOCK8 deficiency:14, STAT3-HIES:10, SAD:10) with early-onset SAD. Recurrent upper respiratory tract infection and pneumonia were significantly frequent in HIES than SAD patients. Characteristic facial appearance, retained primary teeth, skin abscess, newborn rash, and pneumatocele were more predictable for STAT3-HIES, while mucocutaneous candidiasis and Herpes infection were common in DOCK8 deficiency, which were unusual in SAD group. DOCK8-deficient patients had lower CD3+ and CD4+T cells with a senescent phenotype that unique for this form of HIES. Both DOCK8 deficiency and STAT3-HIES patients exhibited reduced switched memory B cells compared to the SAD patients. These clinical and laboratory markers are helpful to differentiate HIES from SAD patients.

Tissue Doppler and speckle tracking echocardiography assessment of left ventricular function in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis may lead to left ventricular (LV) dysfunction. This dysfunction can be documented by methods such as tissue Doppler echocardiographic (TDI) imaging and two-dimensional speckle tracking echocardiography (STE) in early stage. STUDY DESIGN: This was prospective cohort study. METHODS: A total of 34 patients diagnosed with cystic fibrosis (mean age and SD 9.9 ± 4.9 years) and 37 healthy control subjects with a comparable gender and age distribution (mean age 9.8 ± 4.3) were studied. The results for the two groups were compared along with the results of published reports. RESULTS: No significant relationship was found between the groups in terms of systolic and diastolic measurements of the interventricular septum and posterior left ventricular wall, and ejection fraction (P > .05). Myocardial performance indexes of left ventricular free wall and interventricular septum increased in the patient group compared with the controls (P < .05). As measured by STE, seven segments in the LV myocardial longitudinal strain and three segments in the LV myocardial circumferential strain showed significant reductions in patients with cystic fibrosis compared with controls (P < .05). The longitudinal global, circumferential global, and total global strain values had no significant difference between the groups (P > .05). Longitudinal strain rates and circumferential strain rates were both lower in five segments in the patient group (P < .05). CONCLUSIONS: Tissue Doppler echocardiographic imaging and STE may help identifying subclinical LV dysfunction in cystic fibrosis patients with unremarkable conventional echocardiography. They may be considered for the routine follow-up of cystic fibrosis patients.

The effect of peripheral blood eosinophilia on inflammatory markers in asthmatic patients with lower respiratory tract infections.

BACKGROUND: To investigate the behaviour of the inflammatory marker neutrophil-to-lymphocyte ratio (NLR) in the presence of peripheral blood eosinophilia (PBE) in paediatric asthma patients with lower respiratory tract (LRT) infections. METHODS: This retrospective study enrolled consecutive patients aged ≥5 years who were diagnosed with asthma and whose haemogram values were available. The patients were further subdivided based on the presence or absence of LRT infections and allergies. NLR and C-reactive protein (CRP) were evaluated in relation to the presence or absence of PBE (≥4% eosinophils). RESULTS: A total of 991 patients were enrolled in the study. Patients with LRT infections had significantly higher leucocyte and neutrophil counts, a greater NLR and a higher level of CRP compared with patients without LRT infections. Overall, patients with PBE had significantly lower NLRs and CRP regardless of the presence or absence of an LRT infection. The PBE percentage showed moderate inverse correlations with NLR ( r = -0.34) and CRP ( r = -0.20). CONCLUSION: The presence of PBE was significantly associated with lower NLR and CRP regardless of the presence or absence of an infectious condition.

Pulmonary hydatid cyst disease mimicking necrotizing pneumonia in a child with leukocytoclastic vasculitis.

The diagnosis and management of pulmonary hydatid cyst disease represents an important clinical problem in countries of the world that are endemic to echinococcal infection. Atypical clinical and radiologic findings including multiple cavitary lesions in the lung and pleural effusion may lead to misdiagnosis or delay in diagnosis in these patients. We report a patient who was followed up in our hospital with rashes and, clinical and radiologic findings of necrotizing pneumonia in whom there was no response to broad spectrum antibiotherapy. Lung computed tomography showed multiple thick-walled cystic lesions and pleural effusion and the diagnosis of pulmonary hydatid cyst disease was confirmed by surgical and serologic examinations. Antibiotic treatment was changed to albendazole 10 mg/kg/day. There was no liver involvement in terms of cyst hydatid disease with ultrasonographic examination. Skin biopsy showed leukocytoclastic vasculitis. Complete clinical and radiologic improvement was achieved in three months and albendazole treatment lasted six months.

Knowledge levels related to allergen specific immunotherapy and perspectives of parents whose children were diagnosed with asthma and/or allergic rhinitis in Turkey.

Isik S, Çaglayan-Sözmen S, Asilsoy S, Kiliçarslan SK, Anal Ö, Karaman Ö, Uzuner N. Knowledge levels related to allergen specific immunotherapy and perspectives of parents whose children were diagnosed with asthma and/or allergic rhinitis in Turkey. Turk J Pediatr 2018; 60: 50-55. In the present study, we aimed to evaluate the knowledge levels and perspectives about allergen specific immunotherapy (ASI) of parents whose children were diagnosed with asthma and/or allergic rhinitis with positive skin prick test. The study was conducted between September 2014 and January 2015. Surveys that were filled by 198 parents were analyzed. One hundred-ninety-eight parents were included in the study; 42.9% of the parents had knowledge about ASI. Parents obtained information about the ASI from respectively pediatric allergy specialists (25.5%), relatives and friends (17.8%), media (12.9%), and pediatrician (8.2%). There is a strong association between educational level of the mother, atopy background of the family, the monthly per capita income, and having knowledge about the ASI. Multivariate regression analysis revealed that individuals with a monthly income higher than 2,000 TL were more likely to be aware of the ASI application (OR: 4.35, 95% CI: 1.13-16.71; p < 0.05). Eighty-nine percent of the parents stated that they would prefer the sublingual ASI instead of subcutaneous ASI because it is easy to use and its severe side effects risk is low. The awareness of the ASI is at high rates in our patient population.

Effects of Intraperitoneal Injection of Allogeneic Bone Marrow-derived Mesenchymal Stem Cells on Bronchiolitis Obliterans in Mice Model.

Bone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate a variety of lung diseases such as asthma, lung fibrosis, and acute lung injury by its anti-inflammatory and immunmodulatory effects. In this study, we developed a mouse model of bronchiolitis obliterans (BO) and evaluated the effects of the intraperitoneal administration of BMSCs on lung histopathology and cytokine levels. 25 BALB/c mice were divided into four groups; control group (Group I), BO developed and 1x106 BMSCs-injected group (Group II), non-BO, 1x106 BMSCs-injected group (Group III), and BO developed and saline-injected group (Group IV). Histological and immunohistochemical findings of the lung tissue and the migration of BMSCs to the lung were evaluated using light and confocal microscopy techniques. Confocal microscopy evaluations showed that there was no noteworthy amount of BMSCs in the lung tissue of group III while significant amount of BMSCs was detected in group II. Wall thicknesses of terminal bronchiole and periterminal bronchiolar collagen deposition were significantly lower in group II compared to the group IV (p<0.05). Furthermore, according to the immunohistochemical staining results, CD3, CD4, CD8, CD20, CD68 and neutrophil elastase positive immune cells of group II were stained more positive than group IV cells (p<0.05). IFN-γ IL-2 and TNF-α levels in bronchoalveolar lavage fluid (BALF) were significantly lower in group II compared to group IV (p<0.05). The findings of this study indicate that intraperitoneally administered BMSCs have potent effects on histopatological changes of the lung tissue and cytokine levels in the murine model of BO.

Intraperitoneal mesenchymal stem cell administration ameliorates allergic rhinitis in the murine model.

Previous studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) could ameliorate a variety of immune-mediated and inflammatory diseases due to their immunomodulatory and anti-inflammatory effects. In this study, we developed a mouse model of ovalbumin (OVA) induced allergic inflammation in the upper airways and evaluated the effects of the intraperitoneal administration of BMSCs on allergic inflammation. Twenty-five BALB/c mice were divided into five groups; group I (control group), group II (sensitized and challenged with OVA and treated with saline-placebo group), group III (sensitized and challenged with OVA and treated with 1 × 106 BMSCs), group IV (sensitized and challenged with OVA and treated with 2 × 106 BMSCs), and group V (sensitized and challenged with phosphate buffered saline (PBS) and treated with 1 × 106 BMSCs). Histopathological features (number of goblet cells, eosinophils and mast cells, basement membrane, epithelium thickness, and subepithelial smooth muscle thickness) of the upper and lower airways and BMSCs migration to nasal and lung tissue were evaluated using light and confocal microscopes. Levels of cytokines in the nasal lavage fluid and lung tissue supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Confocal microscopic analysis showed that there was no significant amount of BMSCs in the nasal and lung tissues of group V. However, significant amount of BMSCs were observed in group III and IV. In OVA-induced AR groups (group II, III, and IV), histopathological findings of chronic asthma, such as elevated subepithelial smooth muscle thickness, epithelium thickness, and number of goblet and mast cells, were determined. Furthermore, the number of nasal goblet and eosinophil cells, histopathological findings of chronic asthma, and IL-4, IL-5, IL-13, and NO levels was significantly lower in both BMSCs-treated groups compared to the placebo group. Our findings indicated that histopathological findings of chronic asthma were also observed in mice upon AR induction. BMSCs migrated to the nasal and lung tissues following intraperitoneal delivery and ameliorated to the airway remodeling and airway inflammation both in the upper and lower airways via the inhibition of T helper (Th) 2 immune response in the murine model of AR.

Severe Neck and Face Edema in an Adolescent-Delayed Hypersensitivity Reaction to Hair Dye.

Allergic contact reactions to hair dyes arise mostly due to sensitization to para-phenylenediamine (PPD). Para-phenylenediamine, a derivative of p-nitroanaline, is widely used as an oxydizable hair dye and is also found in black henna tattoo. Subsequent exposure to PPD may lead to delayed type IV hypersensitivity reaction manifesting as acute contact dermatitis. Here, a 15-year-old girl is presented, who developed a hypersensitivity reaction after first exposure to hair dye. She was found to have been sensitized to PPD before, through application of black henna tatto.

Celiac disease in children and adolescents with Hashimoto Thyroiditis.

AIM: The aim of this study was to evaluate clinical and laboratory findings and determine the prevalence of celiac disease (CD) in children with Hashimoto thyroiditis (HT). MATERIAL AND METHODS: The data of a total of 80 patients with positive anti-thyroid antibodies who were aged between 6 and 17.9 years were retrospectively studied. Age, gender, complaints at the time of presentation, family history of thyroid disorders, clinical and laboratory findings were recorded. The levels of thyrotropin, free thyroxin, thyroid autoantibodies (thyroid peroxidase and thyroglobulin antibodies), immunoglobulin A (IgA), anti-tissue transglutaminase antibodies (IgA-tTG), and thyroid ultrasonography findings were enrolled. RESULTS: Eighty patients (65 females (81.2%) and 15 males (18,8%)) were included in the study. Family history of thyroid disease was present in 38 (47.5%) patients. The most common complaints at the time of presentation were goiter (%30) and weight gain (%25). Forty three (53.8%), 23 (28.7%), and 14 (17.5%) patients presented with euthyroidism, subclinical hypothyroidism and obvious hypothyroidism. Thirty seven (46.2%) patients had goiter. IgA-tTG was found to be positive after a diagnosis of HT was made in only one patient (1.25%) and the diagnosis of CD was confirmed when intestinal biopsy of this patient revealed villus atrophy, crypt hyperplasia and increase in the intraepithelial lymphocyte count. CONCLUSIONS: In our study, it was found that the most common complaints at presentation in patients with a diagnosis of hashimoto thyroiditis included goiter, weakness and weight gain and the prevalence of celiac diseases was found to be 1.25% (1/80). This study shows that the prevalence of CD in patients with a diagnosis of HT is higher compared to the prevalence in the healthy pediatric population.

Resveratrol ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis-like lesions through effects on the epithelium.

Background. Resveratrol is a natural polyphenol that exhibits anti-inflammatory effects. The aim of this study was to investigate the effects of resveratrol treatment on epithelium-derived cytokines and epithelial apoptosis in a murine model of atopic dermatitis-like lesions. Material and Methods. Atopic dermatitis-like lesions were induced in BALB/c mice by repeated application of 2,4-dinitrofluorobenzene to shaved dorsal skin. Twenty-one BALB/c mice were divided into three groups: group I (control), group II (vehicle control), and group III (resveratrol). Systemic resveratrol (30 mg/kg/day) was administered repeatedly during the 6th week of the experiment. After the mice had been sacrificed, skin tissues were examined histologically for epithelial thickness. Epithelial apoptosis (caspase-3) and epithelium-derived cytokines [interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP)] were evaluated immunohistochemically. Results. Epithelial thickness and the numbers of IL-25, IL-33, TSLP and caspase-3-positive cells were significantly higher in group II compared to group I mice. There was significant improvement in epithelial thickness in group III compared with group II mice (p < 0.05). The numbers of IL-25, IL-33, and TSLP-positive cells in the epithelium were lower in group III than in group II mice (p < 0.05). The number of caspase-3-positive cells, as an indicator of apoptosis, in the epithelium was significantly lower in group III than in group II mice (p < 0.05). Conclusion. Treatment with resveratrol was effective at ameliorating histological changes and inflammation by acting on epithelium-derived cytokines and epithelial apoptosis.

Effects of Quercetin Treatment on Epithelium-derived Cytokines and Epithelial Cell Apoptosis in Allergic Airway Inflammation Mice Model.

Quercetin is a dietary flavonoid which has anti-inflammatory effects. This study aimed to evaluate the influence of quercetin on histopathological aspects and airway epithelium in  allergic airway  inflammation mice model. Twenty-eight BALB/c mice were randomly divided into four groups: Group I (control), Group II (untreated mice with allergic airway inflammation), Group III (allergic airway inflammation quercetin-treated [16mg/kg/day]), Group IV (allergic airway inflammation dexamethasone-treated [1mg/kg/day]). Ovalbumin was administered intraperitoneally and via inhalation to achieve allergic airway inflammation mice model and treatments were also given intraperitoneally. Epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness were examined on samples isolated from lung. Immunohistochemical evaluationof lung tissues was performed using  IL-25, IL-33, thymic stromal lymphopoietin (TSLP), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases(caspase)-3 antibodies. IL-4, IL-25, IL-33, TSLP were quantified in bronchoalveolar lavage (BAL) and OVAspecific IgE levels was measured in serum by standard ELISA protocols. IL-25, IL-33, thymic stromal lymphopoietin (TSLP) and cysteine-dependent aspartate-specific proteases (caspase)-3. Quercetin treatment led to lower epithelial thickness, subepithelial smooth muscle thickness, goblet and mast cell numbers compared to untreated  mice with allergic airway inflammation (p<0.05). However, quercetin treatment was not effective on improving basal membane thickness. Immunohistochemical scores of IL-25, IL-33, TSLP, caspase-3 and TUNEL were lower in quercetin-treated mice  t compared to untreated mice with allergic airway inflammation (p<0.05). IL-4, IL-25, IL-33, TSLP levels in BAL and OVA-specific IgE in serum were lower in quercetin treated mice compared to untreated mice (p<0.05). These findings suggest that quercetin improves chronic histopathological changes except basal membrane thickness in lung tissue and its beneficial effects on inflammation might be related to modulating epithelium derived cytokines and epithelial apoptosis.

Efficacy of asthma education program on asthma control in children with uncontrolled asthma.

We aimed to evaluate the efficacy of a group education program on asthma control for children with uncontrolled asthma. Patients were randomized to receive 1-hour group education program with their parents or usual care. Our primary outcome was the change in asthma control test (ACT) between baseline and month 3 and secondary outcomes were health care utilizations and self report of exacerbations of asthma symptoms and missed school days. Change of ACT between baseline and 1st month and 3rd month was not significant in education and usual care groups. Health care utilizations and self reported exacerbations in the study groups were similar while missed school days were significantly higher in usual care group. The results of the study suggest that group education may play a useful role in the management of children with uncontrolled asthma but it is not significantly effective when compared with usual care.

Cyclosporin treatment improves skin findings in omenn syndrome.

Omenn syndrome is a combined immunodeficiency characterized by a generalized erythematous skin rash, enlarged lymph nodes, hepatosplenomegaly, severe susceptibility to infections, eosinophilia, and hyperimmunoglobulinemia E. A 3-month-old girl was admitted to our hospital with a history of recurrent sepsis. Physical examination revealed severe erythroderma, hepatosplenomegaly, lymphadenopathy, and failure to thrive. Laboratory findings revealed leukocytosis, lymphocytosis with high CD3 T-cells, a high CD4:CD8 ratio, absence of CD19 B-cells, high eosinophil count, and low immunoglobulin levels. A heterozygote RAG1 gene mutation was found. She had itchy, scaling, ichthyosiform erythroderma and protracted diarrhea. Cyclosporin treatment up to 10 mg/kg effectively resolved erythroderma and lowered total eosinophil counts, and she gained weight during treatment. Since extensive erythroderma with generalized itching causes patient discomfort in Omenn syndrome, cyclosporin treatment can be considered while waiting for treatment with hematopoietic stem cell transplantation.

Cross-reactivity syndromes: presentation of two cases and review of the literature.

Cross-reactivity has important consequences in some immune disorders, including allergic and autoimmune diseases, which can affect both diagnostic and therapeutic approaches. One of the most common cross-reactivity syndromes is pollen-food syndrome (PFS). The patient is sensitized with pollen by the airways and exhibits an allergic reaction to food antigen with a structural similarity to the pollen. PFS usually presents with pruritus and swelling of the mouth and throat during or just after ingestion of fresh, uncooked fruits and vegetables. Latex fruit syndrome is another cross-reactivity syndrome. It is the association of latex allergy and allergy to plant foods, which affects up to 50% of latex-allergic patients. Here, we present two cases with crossreactivity syndrome.

Survival of an infant with homozygous surfactant protein C (SFTPC) mutation.

Lung diseases caused by surfactant protein C (SFTPC) mutations are inherited as autosomal traits with variable penetrance and severity or as sporadic disease caused by a de novo mutation on one allele. Here, we report the case of a child surviving with a homozygous surfactant protein C mutation after aggressive clinical management unlike his six siblings who died in infancy. This presentation raises the suspicion of an autosomal recessive inheritance that is discussed in this report.

Cold, cholinergic and aquagenic urticaria in children: presentation of three cases and review of the literature.

Urticaria can be induced with a wide variety of environmental stimuli, such as cold, pressure, vibration, sunlight, exercise, temperature changes, heat, and water. Urticaria caused by physical factors has been reported as the cause of 6-17% of the chronic urticaria in children. We present three cases here - cholinergic, cold and aquagenic urticaria - in which the diagnosis was proven with exercise, ice-cube and water provocation tests, respectively.