Age, sex, and disease status as determinants of skin hydration and transepidermal water loss among children with and without eczema.

PURPOSE: Skin hydration (SH) and transepidermal water loss (TEWL) are important skin biophysical parameters for assessment of childhood eczema. This study investigated whether age, sex, and disease status influence these parameters. METHODS: Skin hydration and TEWL were measured by Delfin MoistureMeterSC and Delfin Vapometer SWL5, respectively, among children aged ≤18 years with and without eczema. Disease status was evaluated using Scoring Atopic Dermatitis (SCORAD) and Nottingham Eczema Severity Score (NESS) clinical tools. RESULTS: Clinical scores and objective measurements were reviewed for 132 patients with eczema and 120 patients without eczema. In both sexes, SH was significantly higher among children aged ≤2 years with and without eczema than among children aged >2 years with and without eczema. Among children aged >2 years, SH was higher among girls with and without eczema than among boys with and without eczema. Regardless of age or sex, SH was lower among children with eczema than among children without eczema. Age-, sex-, and disease-related differences were not observed for TEWL. Skin hydration was negatively correlated with objective SCORAD (r=-0.418, P<0.001), overall SCORAD (r=-0.385, P<0.001), oedema/papulation (r=-0.243, P=0.041), lichenification (r=-0.363, P=0.002), dryness (r=-0.415, P<0.001), and intensity (r=-0.266, P=0.025). Transepidermal water loss was positively correlated with objective SCORAD (r=0.209, P=0.018), overall SCORAD (r=0.215, P=0.015), and lichenification (r=0.240, P=0.043). Skin hydration was negatively correlated with TEWL among children without eczema (r=-0.401, P<0.001), but not among children with eczema. CONCLUSION: Skin hydration can be used to distinguish clinical differences in eczema based on age, sex, and disease status.

Utility of the Pediatric Allergic Disease Quality of Life Questionnaire for childhood eczema.

BACKGROUND: Childhood atopic dermatitis (AD) is a chronic inflammatory disease associated with pruritus and sleep loss. It is important to evaluate quality-of-life (QoL) impairment objectively in atopic diseases in children. OBJECTIVES: To investigate the utility of the Pediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) in children with eczema. METHODS: PADQLQ, Patient-Oriented Eczema Measure (POEM, a short-term subjective symptom score), Nottingham Eczema Severity Score (NESS, a long-term subjective symptom score) and Children's Dermatology Life Quality Index (CDLQI, a short-term subjective symptom score) were compared and correlations evaluated. RESULTS: PADQLQ, POEM, NESS and CDLQI correlated well with each other (n = 132 sets; Spearman correlations: rho = 0·48-0·70, P < 0·001). A Bland-Altman plot showed a reasonably good agreement between CDLQI and PADQLQ. PADQLQ showed that symptoms of asthma, allergic conjunctivitis and allergic rhinitis were present in 20-30%, 45-71% and 58-67% of children with AD, respectively. Nevertheless, there was no association of eczema symptomatology by POEM or NESS with the severity of other allergic diseases. CONCLUSIONS: PADQLQ correlates well with AD-specific severity and QoL scores and reflects all allergic symptoms that holistically influence QoL in children with AD. PADQLQ is hence a composite severity score in terms of clinical symptomatology and QoL impairment for AD.

Are skin equipment for assessing childhood eczema any good?

AIM: Symptomatology and severity of atopic dermatitis (AD) can be objectively measured with equipment. This study aimed to compare skin measurements and investigate their correlations with various clinical severity scores. METHODS: Skin hydration (SH), transepidermal water loss (TEWL), pH, erythema, pigmentation, and ITA (individual typology angle) were measured (using Delfin, Courage + Khazaka, and Mettler Toledo equipment), and correlated with Patient-Oriented Eczema Measure (POEM, a short-term subjective-symptom score), Scoring Atopic Dermatitis (SCORAD, a short-term subjective-symptom and objective-sign score), Nottingham Eczema Severity Score (NESS, a long-term subjective-symptom score), Children Dermatology Life Quality Index (CDLQI, a short-term subjective-symptom score) with Spearman's rho coefficient. RESULTS: 80 sets of clinical scores from eczema patients (mean age: 10.8 ± 4.9 years; 44.6% male) were evaluated. The POEM, objective SCORAD, CDLQI correlated well with each other. Skin pH ranged from 4.3 to 7.0 (mean 5.7 ± 0.61). Skin pH was correlated with Objective SCORAD components, including area (rho = 0.269, p = .036), erythema (rho = 0.302, p = .018), and lichenification (rho = 0.365, p = .026) and with the usage frequency of topical antibiotics. Skin pH was also correlated with other skin measurements, including SH (Delfin equipment: rho = -0.38, p < .001). SH and TEWL as measured by Delfin equipment correlated better with a number of symptoms and signs than Courage + Khazaka equipment. Other clinical measurements including erythema, melanin, and skin color did not demonstrate strong correlations with clinical symptom scores. CONCLUSION: Skin pH (using Mettler Toledo), SH, and TEWL (using Delfin equipment) correlated well with various clinical symptomatology scores. Less acidic pH appears to be associated with worse clinical scores of symptomatology, and increase usage of topical antibiotics, These findings not only support the supplementary usage of equipment in aiding objective documentation of clinical symptomatology in eczema therapeutic research but also the advocacy of maintaining more acidic skin and avoiding alkaline soap and emollient products.

Neonatal epidermolysis bullosa: lessons to learn about genetic counseling.

BACKGROUND: Epidermolysis Bullosa (EB) is a heterogeneous group of congenital blistering diseases that usually presents in the neonatal period. EB is classified into three major categories, each with many subtypes based on the precise location at which separation or blistering occurs, namely epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB). METHODS: We describe genetics of neonatal EB in Hong Kong. RESULTS: Two neonates of consanguineous Pakistani parents had the EB-Pyloric Atresia (EB-PA) variant. One had a 4 kb homozygous deletion of exon 19-25 of the ITGB4 gene, and the other with only a histopathological diagnosis. Both died of sepsis in infancy. Aberrant COL7A1 mutations in the dominant and recessive EB were described. Genetic analysis, together with histopathological classification is important to aid prognosis and counseling. JEB and EB-PA are associated with consanguinity and mortality during infancy. Morbidity and prognosis of the autosomal dominant DEB are optimistic. The autosomal recessive DEB is more severe, with neonatal onset and recurrent blistering. It is also associated with chronicity and malignant changes when the child reaches adulthood. CONCLUSION: Exact genetic diagnosis aids in counseling of the family concerning the prognosis in the affected child and the risk of affected children in future pregnancies.

Galactonic Acid in galactosemia: identification in the urine.

Galactose is converted to galactonic acid in vivo in man. Galactonate was isolated from the urine of galactosemia patients who had been given galactose orally. The identity of the galactonate was established by gas-liquid chromatography and by the preparation of derivatives.

Assessment of adherence to eczema treatment in Hong Kong children.

Introduction: Eczema is the most common childhood skin problem in Hong Kong. Treatment adherence is crucial in symptom management and the effectiveness of eczema management. The Problematic Experiences of Therapy Scale (PETS) is used to assess adherence to treatment among children with eczema. Objective: This study examined the psychometric properties of the translated Chinese version of PETS (C-PETS) among parents and caregivers of children with eczema. Methods: PETS was translated into Chinese and data obtained from a convenience sample of 147 Chinese participants from a regional hospital in Hong Kong. Results: The internal consistency of C-PETS with a Cronbach's α of 0.93 and good test-retest reliability with weighted Kappa ranging from 0.74 to 0.89 were obtained. Significant positive correlations were found among the C-PETS, Children's Dermatology Life Quality Index (r = 0.25, p = .002), and Severity Grading of Atopic Dermatitis scores (r = 0.38, p = .001). A significant negative correlation was found between C-PETS and Chinese adaptation of Generic Self-Efficacy scale (r = -0.40, p = .001). Confirmatory factor analysis showed that the data supported the structural validity of C-PETS. Conclusion: This study indicates that C-PETS is a reliable and valid measure to evaluate treatment adherence for Chinese parents and caregivers of children with eczema.

A case-control study of galactose consumption and metabolism in relation to ovarian cancer.

Consumption or metabolism of dairy sugar and ovarian cancer have been linked based on evidence that galactose may be toxic to ovarian germ cells and that ovarian cancer is induced in animals by depletion of oocytes. We assessed consumption of dairy products and obtained blood for biochemical and molecular genetic assessment of galactose metabolism in 563 women with newly diagnosed epithelial ovarian cancer and 523 control women selected either by random digit dialing or through lists of residents in eastern Massachusetts and New Hampshire. We observed no significant differences between cases and controls in usual consumption of various types of dairy products or total daily lactose (the principal source of galactose in the diet); nor did we find that RBC activity of either galactose-1-phosphate uridyl transferase (GALT) or galactokinase differed. The mean (and SE) activity of uridine diphospho-galactose 4'-epimerase (in micromoles per hour per gram of hemoglobin) was, however, significantly lower (P < 0.005) in cases compared with controls, 20.32 (0.31) versus 21.64 (0.36). Ovarian cancer cases were also more likely to carry the N314D polymorphism of the GALT gene, generally predisposing to lower GALT activity. The difference was most evident for endometrioid and clear cell types of ovarian cancer, in which 3.9% of cases were found to be homozygous for N314D compared with 0.4% of controls, yielding an odds ratio and 95% confidence interval of 14.17 (2.62-76.60). We conclude that, whereas adult consumption of lactose carries no clear risk for the disease, certain genetic or biochemical features of galactose metabolism may influence disease risk for particular types of ovarian cancer.

False-positive amniotic fluid acetylcholinesterase results: the need for a multifacet approach to the prenatal diagnosis of neural tube defects.

Two cases are presented with false-positive amniotic fluid alpha-fetoprotein and acetylcholinesterase results for the prenatal diagnosis of neural tube defects. Stage II ultrasound revealed no lesions of the fetal spine in both cases. The alpha-fetoprotein and acetylcholinesterase results returned to normal on subsequent taps. Both pregnancies resulted in normal outcomes. A protocol is presented for managing pregnancies with abnormal alpha-fetoprotein and acetylcholinesterase results.

Galactose-1-phosphate uridyl transferase activity associated with age at menopause and reproductive history.

Reproductive history was obtained and the activity and electrophoretic pattern of the blood enzyme galactose-1-phosphate uridyl transferase (transferase) was measured in 104 adult Caucasian women, less than 70 years of age, sampled from the general population. Fifteen women were identified as carriers for the Duarte (GtD) or galactosemia (gt) variants of transferase--genes associated with reduced transferase activity compared with normal (Gt+). The mean age at menopause for 8 women with a natural menopause who were GtD/Gt+ or gt/Gt+ was 44.8, significantly younger (P = 0.007) than the mean age of 49.2 reported by 31 naturally postmenopausal subjects with Gt+/Gt+ genotypes and normal transferase activity. Compared with the latter group, women who were Duarte or galactosemia carriers were 13.7 times more likely to have a menopause before age 48 (with 95% confidence limits of 2.0 to 95.5). Six of 13 (46%) married women who were GtD/Gt+ or gt/Gt+ reported more than 2 years' trying to achieve a pregnancy, compared with 11 of 74 (15%) with normal genotypes and activity (P = 0.02). The authors conclude that genetic deficiency of transferase may be associated with infertility and early menopause.

Müllerian aplasia associated with maternal deficiency of galactose-1-phosphate uridyl transferase.

The activity and electrophoretic pattern of galactose-1-phosphate uridyl transferase (transferase), a key enzyme in galactose metabolism, were analyzed in four patients with Müllerian aplasia (Rokitansky-Küster-Hauser syndrome) and their mothers. Mothers of two of the patients had genetic variations of their transferase enzymes with activities below the normal range. Affected daughters from these two mothers also had genetic variations of the transferase enzyme. In one of the patients whose Müllerian aplasia had been diagnosed 15 years previously, premature ovarian failure developed. These case reports suggest a possible association between errors of galactose metabolism, Müllerian aplasia, and premature menopause--an association that is supported by a rodent model in which female offspring of mothers fed a high-galactose diet were born with reduced oocyte numbers and delayed vaginal opening.

Assay of ornithine carbamoyltransferase activity in human liver using carbon-labeled ornithine and thin-layer chromatography.

Ornithine carbamoyltransferase (EC 2.1.3.3) activity in human liver homogenates has been measured using 14C-labeled ornithine and unlabeled carbamoyl phosphate. A thin-layer chromatographic (TLC) procedure is used to separate the radioactive substrate and product, ornithine and citrulline, respectively, and the regions of the chromatogram corresponding to ornithine and citrulline are cut out and counted in a liquid scintillation spectrophotometer. The method has the following advantages: (1) the radioactive substrate ornithine is more stable in solution than carbamoyl phosphate, (2) 14C-labeled ornithine is available in higher specific activity than carbamoyl phosphate, (3) all radioactivity may be accounted for by using the TLC system, (4) the developed thin-layer chromatogram is stable indefinitely, (5) in contrast to colorimetric assays, other compounds in the raction mixture do not interfere with the citrulline determination, and (6) most importantly, the rate of the enzyme reaction at various time intervals can be determined by taking aliquots from the same incubation tube.

Radiochemical assay of minute quantities of galactose-1-phosphate uridyltransferase activity in erythrocytes and leukocytes of galactosemia patients.

A sensitive radioisotopic method has been developed which can detect galactose-1-phosphate uridyltransferase (GALT) activity as low as 0.1% of normal control values in both erythrocytes and leukocytes. This assay utilizes carbon-14 labeled galactose-1-phosphate with high specific activity and requires removal of endogenous galactose-1-phosphate (Gal-1-P) and uridine diphosphate glucose (UDPGlc) through dialysis. Optimal exogenous UDPGlc concentration has been determined with a fixed concentration of Gal-1-P in the incubation. The rate of product, uridine diphosphate galactose (UDPGal), formation is monitored at three different times. Among 423 patients with galactosemia studied by this method, 363 patients exhibited no detectable GALT activity in their erythrocytes and 60 patients were found to have detectable erythrocyte GALT activity ranging from 0.02 to 5.0 units normal values: > 20 units). The former group of patients was designated as classic galactosemia (GG) and the latter group as galactosemia variant (GV). Leucocytes from ten patients belonging to the GG group also showed complete absence of GALT activity while leukocytes from two patients belonging to the GV group showed GALT activity at levels comparable with those found in their erythrocytes. Because there is extensive biochemical heterogeneity among galactosemia patients, we recommend that an assay with increase sensitivity be carried out on blood samples from galactosemia patients so that clinical, biochemical and molecular correlations made by different groups of investigators can be compared.

Prenatal diagnosis of galactosemia.

Prenatal diagnosis of disorders of galactose metabolism was done in one instance in a family with a known galactokinase deficiency and in six cases in five families at risk for galactosemia. The galactokinase activity in cultured amniotic cells was found to be normal, and the diagnosis was confirmed postnatally. In the six pregnancies at risk for galactosemia, four were considered to be unaffected and two to be affected. Of the latter, one was carried to term, and the erythrocyte transferase activity of the baby was shown to be absent. The other pregnancy was terminated, and examination of fetal tissues by biochemical studies confirmed the diagnosis. This experience substantiates the concept that prenatal diagnosis of disorders of galactose metabolism is feasible.

Neurologic complications in galactosemia.

Two siblings, a 27-year-old man and his 24-year-old sister were diagnosed with classic transferase deficiency galactosemia at birth and were treated with strict lactose restriction. Despite well-documented dietary management, both siblings are mentally retarded and manifest a progressive neurologic condition characterized by hypotonia, hyperreflexia, dysarthria, ataxia, and a postural and kinetic tremor. Magnetic resonance imaging revealed moderate cortical atrophy, a complete lack of normal myelination, and multifocal areas of increased signal in the periventricular white matter on T2-weighting. These patients suggest that even with early diagnosis and treatment, individuals with galactosemia may have significant neurologic morbidity with abnormalities of white matter development. This finding raises the possibility of biochemical heterogeneity within the classic transferase deficiency group, as well as the possibility of a lack of available galactose metabolites necessary for glycolipid synthesis causing a disruption of normal myelin development.