Risk factors of zinc deficiency in children with atopic dermatitis.

Summary: Background and objectives. Zinc deficiency increases risk of infections, allergies and autoimmunity. We wished to determine risk factors in severe atopic dermatitis (AD) and identify of hypozincemia rate. Materials and methods. Retrospective study done on AD children (≤ 14 years) with serum zinc test. Data included demographic and laboratory tests (serum zinc level, IgE, food-specific IgE), and skin tests. Results. 168 AD children, aged 38.9 months with concomitant allergies in 47 (28%), family history of allergies in 131 (80%), and parental consanguinity in 134 (79.9%). AD was mild in 12 (7.2%, SCORAD 15.8) children, moderate in 41 (24.5%, SCORAD 30.4), and severe in 115 (68.3%, SCORAD 69.4). Hypozincemia was observed in 42 (25%, zinc 8.6 ± 1.1 µmoI/L) children and associated only with severe AD (p = 0.0418) and elevated IgE (p = 0.001). Conclusions. Hypozincemia is rather prevalent in AD, and severe AD and high IgE increase its risk. An adjunct oral zinc may help reducing severe poorly responsive AD.

Non-truncating LIFR mutation: causal for prominent congenital pain insensitivity phenotype with progressive vertebral destruction?

We present a Qatari family with two children who displayed a characteristic phenotype of congenital marked pain insensitivity with hypohidrosis and progressive aseptic destruction of joints and vertebrae resembling that of hereditary sensory and autonomic neuropathies (HSANs). The patients, aged 10 and 14, remained of uncertain genetic diagnosis until whole genome sequencing was pursued. Genome sequencing identified a novel homozygous C65S mutation in the LIFR gene that is predicted to markedly destabilize and alter the structure of a particular domain and consequently to affect the functionality of the whole multi-domain LIFR protein. The C65S mutant LIFR showed altered glycosylation and an elevated expression level that might be attributed to a slow turnover of the mutant form. LIFR mutations have been reported in Stüve-Wiedemann syndrome (SWS), a severe autosomal recessive skeletal dysplasia often resulting in early death. Our patients share some clinical features of rare cases of SWS long-term survivors; however, they also phenocopy HSAN due to the marked pain insensitivity phenotype and progressive bone destruction. Screening for LIFR mutations might be warranted in genetically unresolved HSAN phenotypes.

Novel aspects of Kindlin-3 function in humans based on a new case of leukocyte adhesion deficiency III.

BACKGROUND: Kindlin-3 is a novel integrin activator in hematopoietic cells, and its deficiency leads to immune problems and severe bleeding, known as leukocyte adhesion deficiency III (LAD-III). Our current understanding of Kindlin-3 function primarily relies on analysis of animal models or cell lines. OBJECTIVES: To understand the functions of Kindlin-3 in human primary blood cells. PATIENTS/METHODS: We analyzed primary and immortalized hematopoietic cells obtained from a new LAD-III patient with immune problems, bleeding, a history of anemia, and abnormally shaped red blood cells. RESULTS: The patient's white blood cells (WBCs) and platelets showed defects in agonist-induced integrin activation and botrocetin-induced platelet agglutination. Primary leukocytes from this patient exhibited abnormal activation of ß(1) integrin. Integrin activation defects were responsible for the observed deficiency in the botrocetin-induced platelet response. Analysis of patient genomic DNA revealed a novel mutation in the Kindlin3 gene. The mutation abolished Kindlin-3 expression in primary WBCs and platelets, owing to abnormal splicing. Kindlin-3 is expressed in red blood cells (RBCs), and its deficiency is proposed to lead to abnormally shaped RBCs. Immortalized patient WBCs expressed a truncated form of Kindlin-3 that was not sufficient to support integrin activation. Expression of Kindlin-3 cDNA in immortalized patient WBCs rescued integrin activation defects, whereas overexpression of the truncated form did not. CONCLUSIONS: Kindlin-3 deficiency impairs integrin function, including activation of ß(1) integrin. Abnormalities in glycoprotein Ib-IX function in Kindlin-3-deficient platelets are secondary to integrin defects. The region of Kindlin-3 encoded by exon 11 is crucial for its ability to activate integrins in humans.

Is high prevalence of vitamin D deficiency evidence for asthma and allergy risks?

BACKGROUND: Studies suggest a link between vitamin D deficiency and development of asthma and allergic diseases. AIM: To determine a) the association between vitamin D and asthma among children, b) difference in level of vitamin D in asthmatic children and control, and c) effect of vitamin D on atopy markers. SETTING: Case-control study done, between October 2009 to July 2010, on asthmatics and controls (< 15 years) at Pediatric Allergy-Immunology Clinics and Primary Health care Clinics (PHC), Qatar. METHODS & SUBJECTS: A total of 483 cases and 483 controls matched by age, gender and ethnicity. Sociodemographic & clinical data was collected through physician diagnosis and questionnaire. Their health status was assessed by past or present clinical manifestations, family history, physical examination, BMI, and serum 25(OH) vitamin D, calcium, and phosphorus. RESULTS: 44.8% of asthmatic and 50.0% of controls were males, and 55.2% of asthmatic and 50% of controls were females. The mean age (+/- SD, in years)for asthmatic versus controls was 7.0 +/- 3.8 vs. 8.4 +/- 3.6. Vitamin D deficiency was more prevalent in asthmatics than controls. The mean value of Vitamin D in asthmatics was much lower than the normal value, and there was a significant difference found in the mean values of vitamin D between asthmatics (17.5 +/- 11.0) and the controls (20.8 +/- 10.0). Furthermore, there were statistically significant differences between asthmatic subjects and controls with respect to serum level of vitamin D (p < 0.001). Lower Vitamin D levels were associated with more allergic disease and elevated serum IgE. CONCLUSION: Serum vitamin D levels were lower in asthmatic than control. Vitamin D deficiency was higher among children with asthma, allergic rhinitis, atopic dermatitis, acute urticaria, and food allergy. In addition, vitamin D deficiency was associated with IgE atopy markers in asthmatic children more than controls.

The impact of air pollution on hospital admission for respiratory and cardiovascular diseases in an oil and gas-rich country.

OBJECTIVES: Aim of this study was to evaluate the impact of air pollution on hospital admissions for respiratory and cardiovascular diseases in an oil rich developing country, State of Qatar. METHODS: A prospective cohort population based study was conducted at different stations of Qatar during the period (2002-2005) for recording the concentration of air pollutants daily for sulphur dioxide (SO2), nitric oxide (NO), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3) and particulate matter (PM10). Hospital admission data were collected from the inpatient discharge database of the Medical Records Department, Hamad General Hospital. RESULTS: An average of 5.36 admissions from ischemic heart diseases was counted daily in all the population which was even higher than the respiratory diseases (3.4/day). Minimum temperature was inversely correlated with all pollutants except for O3 and SO2. CONCLUSION: There was an association between increasing air pollutant levels and patients admitted for respiratory and cardiovascular diseases.

Montelukast treatment in children with moderately severe atopic dermatitis.

BACKGROUND: Moderately severe atopic dermatitis makes up nearly one-fifth of children with atopic dermatitis. OBJECTIVE: To determine the clinical and laboratory effects of montelukast in moderately severe atopic dermatitis. METHODS: Randomized, double-blind, placebo-controlled, crossover trial with washout period, conducted from May 2002 to February 2006. The study involved 25 patients, 2-16 years old with dermatitis. Patients received oral montelukast (9 patients, Group B) or placebo (16 patients, Group A) in phase 1, and were crossed over to placebo or montelukast, respectively, for phase 2. Patients included if > 10% of skin was involved and failed response to 2 week conventional treatment. Itching, sleep disturbance, frequency of use of oral antihistamines & topical steroids, severity scores were serially assessed. In addition, eosinophil and serum IgE were serially collected. RESULTS: Most of patients were 6-10 years of age. Both groups had comparable gender distribution. The patients in Group B were more likely to have a history of bronchial asthma (55.6%) or allergic rhinitis (33.3%) than patients in Group A, but were less likely to have a positive history of atopy. While on montelukast, there was a reduction of mean score for itching in phase 2, for sleep disturbance in phase 2, for antihistamines in phase 1, for extent-of-disease in phase 1 and 2, and for severity score in phase 2 and blood eosinophil & IgE in phase 2. CONCLUSION: Montelukast reduces itching, sleep disturbance, disease extent and severity, blood eosinophil count and serum IgE.

Role of breast feeding in primary prevention of asthma and allergic diseases in a traditional society.

BACKGROUND: The fact that breastfeeding may protect against allergic diseases remains controversial, with hardly any reports from developing countries. Prolonged breastfeeding was shown to reduce the risk of allergic and respiratory diseases. AIM: The aim of this study was to assess the relationship between breastfeeding and the development of childhood asthma and allergic diseases in Qatari children at age 0-5 years. Additionally, this study investigated the effect of prolonged breastfeeding on the allergic diseases in a developing country. DESIGN: This is a cross sectional survey. SETTING: Well baby clinics and Pediatric clinics in the 11 Primary Health Care Centers and Hamad General Hospital, Hamad Medical Corporation, State of Qatar. SUBJECTS: A multistage sampling design was used and a representative sample of 1500 Qatari infants and pre-school children with age range of 0-5 years and mothers aged between 18 to 47 years were surveyed during the period from October 2006 to September 2007 in Qatar. Out of the 1500 mothers of children, 1278 mothers agreed to participate in this study with the response rate of 85.2%. METHODS: A confidential, anonymous questionnaire was completed by the selected subjects assessing breastfeeding and allergic diseases. Questionnaires were administered to women who were attending Primary Health Centers for child immunization. Questionnaire included allergic rhinitis, wheezing, eczema, and additional questions included mode and duration of breastfeeding, tobacco smoke exposure, number of siblings, family income, level of maternal education, parental history of allergies. Univariate and multivariate statistical methods were performed for statistical analysis. RESULTS: More than half of the infants (59.3%) were exclusively breastfed, followed by infants with partial breastfeeding (28.3%) and artificial fed (12.4%). There was a significant difference found across these three categories of infants in terms of their age groups, smoking status of father, socio-economic status and parental consanguinity. Asthma (15.6%), wheezing (12.7%), allergic rhinitis (22.6%), and eczema (19.4%) were less frequent in exclusive breast fed children, compared to infants with partial breast feeding and formula milk. Ear infection (P = 0.0001) and eczema (P = 0.007) were found significant in infants with the history of maternal atopy, while asthma (P = 0.0001) and allergic rhinitis (P = 0.015) were found significant in infants with the history of paternal atopy. The main factors associated with mode of feeding were mothers having first baby, asthmatic mother and parental history of allergic rhinitis. The risk of allergic diseases, eczema, wheeze and ear infection in particular, were lower in children with prolonged breast feeding (>6 months) than in those with short-term breast feeding duration (<6 months). CONCLUSION: The current study indicates that exclusive breast-feeding prevents development of allergic diseases in children. The main factors associated with breastfeeding for allergic diseases were being the first baby, maternal history of asthma, and parental history of allergic rhinitis. The study findings opens a big avenue for interventional role of breastfeeding. Therefore, we recommend breastfeeding is as one possible way to reduce the risk of onset asthma and allergic diseases in developing countries.

Topical sodium cromoglycate in the treatment of moderate-to-severe atopic dermatitis.

BACKGROUND: Unsatisfactory treatment results for severe atopic dermatitis have led to many experimental therapies, including cromolyn sodium in various vehicles at concentrations ranging from 1% to 10%. Results suggest that the vehicle used to deliver the cromolyn is relevant to its effectiveness. OBJECTIVE: To test the efficacy of low concentrations of cromolyn in a water-soluble vehicle in the treatment of moderate-to-severe atopic dermatitis in a double-blind, placebo-controlled study. METHODS: Twenty-six pediatric patients who had failed to respond to conventional therapy were randomized into 2 treatment groups: patients in group A used the study drug for 1 month (phase I), then received the placebo for 1 month (phase II); and patients in group B used the placebo for 1 month, then received the study drug for 1 month. The study drug was cromolyn sodium inhalation solution mixed into a water-based emollient cream to a final concentration of 0.21%. Upon enrollment and at each follow-up visit, every patient was given a severity score based on extent and severity of skin involvement. RESULTS: At enrollment, there were no significant differences between groups A and B in severity scores, age, sex, race, skin test and/or RAST positivity, eosinophil levels, IgE concentrations, or the presence of concomitant rhinitis or asthma. After the first phase of the study treatment, severity scores had decreased significantly for both groups with a significant difference between group A (cromolyn) and group B (placebo). After crossover, both groups had significantly lower severity scores than at entry into the study. CONCLUSION: Treatment with topical cromolyn in a hydrophilic emollient vehicle has a significant anti-inflammatory effect on moderate-to-severe atopic dermatitis. We have now incorporated this treatment into our clinical practice.

Increased circulating levels of soluble HLA class I heterodimers in patients with sickle cell disease.

This study examined the presence of a persistent state of low-grade inflammation in sickle cell anemia patients by measuring circulating sHLA-I heterodimers and C-reactive protein during the steady state and after recent crises. Thirty-nine pediatric sickle hemoglobinopathy patients were studied during the steady state and 11 patients were evaluated within 1 month of a painful crisis. A disease severity score was generated for each patient, and soluble HLA-I (sHLA-I) and C-reactive protein levels were determined. Soluble HLA-I was significantly elevated in 55% of the steady-state group and in 36% of the recent-crisis group. The percentage of patients with elevated sHLA-I differed in the various disease subgroups in the steady state: 46% of Hb SS patients, 70% of Hb SC patients, 75% of Hb S beta-thal patients, and 20% of Hb SSF patients. Steady-state and recent-crisis sHLA-I levels were not significantly different. C-reactive protein levels were elevated in 11% of steady-state patients and in 9% of recent-crisis patients. Soluble HLA-I levels did not correlate with C-reactive protein levels or disease severity score, age, hemoglobin, reticulocyte count, platelet count, or white cell count. These results show that the majority of sickle hemoglobinopathy patients have elevated sHLA-I levels during the steady state and after recent crisis, suggesting the presence of chronic inflammation during the steady state.

Elevated levels of soluble HLA class I (sHLA-I) in children with severe atopic dermatitis.

BACKGROUND: Atopic dermatitis is characterized by increased production of IgE and interleukin-4, immediate skin test reactivity to allergens, increased expression of CD23 on mononuclear cells, and decreased production of interferon-gamma. Soluble HLA-I molecule levels are elevated in conditions where T cells are activated such as viral infections, autoimmune diseases, and organ transplantation. OBJECTIVE: We wished to determine if sHLA-I heterodimers were also elevated in patients with atopic dermatitis and if sHLA-I elevations correlated with disease activity. METHODS: Fourteen children with atopic dermatitis resistant to conventional treatment were followed over an 8-week period during an ongoing trial of treatment with topical sodium cromoglycate. Extent of skin involvement, disease severity, absolute eosinophil counts, IgE and HLA-I levels were determined at the time of enrollment into the study. Additional sHLA-I levels were measured after 4 and 8 weeks of therapy. RESULTS: Mean sHLA-I levels were significantly elevated in atopic dermatitis patients, 2.07 +/- 1.14 versus 1.00 +/- 0.22 microg/mL in controls (P < .0001). Nine of 14 patients (64%) had elevated sHLA-I antigens. Soluble HLA-I levels did not correlate with the extent of disease, disease severity score, eosinophil count, or IgE levels. There was a remarkable consistency in sHLA-I levels at baseline and after 4 and 8 weeks of therapy, even with significant clinical improvement. CONCLUSION: We conclude that sHLA-I heterodimers are elevated in 64% of our patients with atopic dermatitis and that elevations persist after clinically effective therapy. This conclusion supports recommendations for prolonged preventative and treatment measures in this atopic disease.

Radiological and orthopedic abnormalities in Satoyoshi syndrome.

Satoyoshi syndrome is a rare disorder of unknown etiology characterized by progressive, painful intermittent muscle spasms, severe skeletal abnormalities mimicking a skeletal dysplasia, malabsorption, alopecia, and amenorrhea. We further report on a 20 1/2-year-old Caucasian woman with characteristic manifestations of the syndrome. Since the establishment of the diagnosis 1 year ago, she has been treated with prednisone with good response. However, treatment of the multiple deformities and fractures has been difficult and challenging. The early recognition and treatment of this disorder is of utmost importance, as the skeletal deformities and fractures seem to be secondary to the muscular spasms, as suggested by Satoyoshi.

Care of asthma: allergy clinic versus emergency room.

BACKGROUND: Demographic and socioeconomic factors have an impact upon the morbidity and mortality rates of asthma in inner-city pediatric populations. Many pediatric patients with asthma use the emergency room as their primary care physician, while a smaller number of children with asthma use the allergy-immunology clinic. OBJECTIVE: We examined the demographic and socioeconomic characteristics of asthmatic patients using the emergency room as their primary care physician and of those attending the allergy-immunology clinic in the same inner-city hospital. We compared the morbidity and cost of care of asthmatic patients who received their medical care in the emergency room to that of those who received their care in the allergy-immunology clinic. METHODS: Fifty consecutive emergency room patients and 25 clinic patients were studied using an identical questionnaire. RESULTS: There was no difference between the two groups in the total number of individuals per household, children per family, monthly income, type or size of dwelling, financial problems purchasing medications, health insurance type, distance to the medical center, or education of the caretaker. Severity of asthma was not different in the two groups before the start of the study. The only significant demographic difference was in age: 10.6 years for the clinic group and 7.8 years for the emergency room group (P < .002). Clinically, in the year preceding the interview, the clinic group had significantly less nocturnal cough (P < .025), sleep interruption (P < .001), weekly asthma (P < .05), and emergency room visits (P < .09). The allergy clinic group had an approximate average savings of $137 per patient per year. Hospital admissions and emergency room costs were increased by a small group of three allergy clinic patients, decreasing the difference in the cost of care between the two groups. CONCLUSION: The data showed that patients who attended the emergency room and those who attended the allergy-immunology clinic were not demographically or socioeconomically different. The decreased morbidity of asthma and cost of care for the allergy clinic patients, as opposed to the emergency room patients, are likely due to the care given in the allergy-immunology clinic.

New concepts in the immunology of sickle cell disease.

OBJECTIVE: Our objective is to review the role of adhesion molecules, cytokines, and inflammation in the abnormal adherence of sickle red blood cells to vascular endothelia in the pathogenesis of vascular complication in patients with sickle cell anemia. DATA SOURCES: The MEDLINE database was used to review the hematologic, immunologic, and allergy literature in English with respect to the adhesion molecules involved in sickle hematopoiesis and vascular complications. STUDY SELECTION: Studies selected for review were those that identified the adhesion molecules involved in reticulocyte-endothelial adhesion and the influence that cytokines, infections, and atopy have upon the expression of these molecules. RESULTS: In sickle cell disease, a constant low level of inflammation caused by abnormal adhesion of sickle erythrocytes to endothelial cells in the microvasculature produces low-level tissue ischemia. Allergic and infectious inflammations are likely to lead to increased sickle erythrocyte trapping in the microvascular endothelia which progresses to vessel obstruction, end organ ischemic damage, and dysfunction. CONCLUSION: The identification of underlying immune defects that predispose patients to infections and inflammation needs to be emphasized. Anti-inflammatory medications, anti-adhesion molecule monoclonal antibodies, and adhesion molecule binding-site analogs may have a future in the treatment of the acute vascular complications of sickle cell disease.

Acute asthma: treatment and outcome of 2000 consecutive pediatric emergency room visits in Doha, Qatar.

The case files of 2000 asthma episodes seen in our pediatric emergency room (PER) over a 2-month period were reviewed. Patients included 1429 males and 571 females with 66.2% < 48 months old. More than 60% of patients had been symptomatic for <24 hr and 88.5% had tried inhaled beta2-agonist before coming to the PER. In the PER, 57% responded to a single salbutamol aerosol and 35.5% responded to a combination of 2-3 salbutamol, IV hydrocortisone, and aminophylline drip < or = 6 hr. Only 7.5% were admitted to the hospital. Of the admitted patients, 82% had been symptomatic for > 24 hr and 60.6% were <4 years old.

Satoyoshi syndrome: an unusual postnatal multisystemic disorder.

Satoyoshi syndrome is a rare disorder of unknown cause characterized by progressive, painful intermittent muscle spasms, malabsorption, alopecia, amenorrhea, and skeletal abnormalities mimicking a skeletal dysplasia. We describe a 19-year-old Caucasian woman with characteristic manifestations starting at age 9. The report of this patient confirms that this condition is not limited to the Asian population.

Home nebulizer therapy in asthmatics in Qatar.

We reviewed charts of 50 asthmatic children who were on home nebulizer therapy for treatment of their asthma over a 1-year period. Patients served as their own controls for comparison of the asthma-related variables between periods of 6 months before and 6 months after the initiation of home nebulizer treatment. There was a 74% and 70% reduction in the emergency room visits and hospitalizations, respectively, during the period when the patients were on home nebulizer therapy. We suggest that this form of therapy, if properly used in appropriately selected asthmatic children, will reduce the need for hospital care.

Recurrent wheezing in children with respiratory syncytial virus (RSV) bronchiolitis in Qatar.

Records of 70 infants admitted to Hamad General Hospital with RSV bronchiolitis and a similar number of controls were retrospectively reviewed. Two years after admission, 44% of the infants with RSV bronchiolitis developed recurrent wheezing compared with only 12.9% of controls (P = 0.001). A family history of atopy appeared not to be a significant predisposing factor for the occurrence of recurrent wheezing in post RSV bronchiolitis patients. These results are similar to those from similar studies in industrialized countries.

Childhood chronic renal failure in Qatar.

Thirty children below the age of 12 with chronic renal failure (CRF) were studied. In 21 patients (70%) the renal failure was secondary to congenital or familial aetiology. Obstructive uropathy (53.3%), mostly due to posterior urethral valves (40%), comprised the majority of cases. Four cases (13.3%) were secondary to reflux nephropathy. It is concluded that the majority of cases of CRF in the state of Qatar are secondary to potentially treatable or preventable conditions. Use of antenatal ultrasonography combined with aggressive management of obstruction and urine infection may help reduce morbidity and mortality.