Conjunctivitis in atopic dermatitis patients with and without dupilumab therapy - international eczema council survey and opinion.

BACKGROUND: Conjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab. OBJECTIVE: To survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC). METHODS: Electronic survey and in-person discussion of management strategies. RESULTS: Forty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist. LIMITATIONS: The study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey. CONCLUSION: The IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

Determining Effects of Superfine Sheep wool in INfantile Eczema (DESSINE): a randomized paediatric crossover study.

BACKGROUND: Despite limited evidence, woollen clothing has traditionally been considered to be an irritant that should be avoided by individuals with atopic dermatitis (AD). Wool fibres come in a range of diameters, and have beneficial thermodynamic and moisture transport properties. OBJECTIVES: This study examines the effects of superfine merino wool on symptoms in participants with mild-to-moderate AD. METHODS: The trial was a 12-week, randomized, assessor-blinded, crossover, prospective, cohort study of 39 patients with mild-to-moderate AD, aged between 4 weeks and 3 years, comparing superfine merino wool ensembles with standard cotton clothing chosen by parents. Participants were assigned to wool or cotton clothing and assessed every 3 weeks for 6 weeks, before crossing over to wear the other clothing material for a further 6-week period, with similar 3-weekly reviews. The primary end point was the SCORing Atopic Dermatitis (SCORAD) index after each 6-week period, with Atopic Dermatitis Severity Index (ADSI), Infants' Dermatitis Quality Of Life Index (IDQOL) and topical steroid use as secondary end points to measure AD severity and quality of life. RESULTS: Overall, compared with baseline, superfine wool ensembles were associated with a reduction in mean SCORAD of 2·5 [95% confidence interval (CI) -4·7 to -0·4] at 3 weeks and 7·6 (95% CI -10·4 to -4·8) at 6 weeks when compared with the cotton ensembles. A similar change was observed in ADSI and IDQOL scores for the same period. Body steroid use was also reduced. Conversely, changing ensembles from wool to cotton resulted in an increase in scores. CONCLUSIONS: Superfine merino wool may assist in the management of childhood AD.

A comparison study of clinician-rated atopic dermatitis outcome measures for intermediate- to dark-skinned patients.

BACKGROUND: Atopic dermatitis (AD) assessment is more difficult in patients with skin of colour (SOC). OBJECTIVES: To compare the reliability of commonly used outcome measures for assessing AD in patients with SOC and to evaluate a novel greyscale in this population. METHODS: Twenty-five patients with AD each attended a 1-day scoring exercise based in either Sydney or Melbourne, Australia. Each patient was scored by the same five physicians using the Eczema Area and Severity Index (EASI), objective Scoring Atopic Dermatitis (oSCORAD), Investigator's Global Assessment (IGA) and a novel greyscale. Patients also completed the Patient-Oriented Eczema Measure and quality-of-life measures. A Mexameter was used to measure baseline melanin indices. Ten random patients were rescored to test intrarater reliability. RESULTS: We included 11 light-skinned patients (melanin index ≤ 200) and 14 patients with SOC (melanin index > 200) in the cohort. The inter-rater intraclass correlation coefficients (ICCs) were EASI 0·83 [95% confidence interval (CI) 0·66-0·94] for light skin and 0·77 (95% CI 0·60-0·91) for SOC; oSCORAD 0·68 (95% CI 0·44-0·88) for light skin and 0·74 (95% CI 0·54-0·89) for SOC; and IGA 0·80 (95% CI 0·62-0·93) for light skin and 0·70 (95% CI 0·49-0·87) for SOC. The greyscale had an ICC of 0·78 (95% CI 0·60-0·91) when replacing the EASI's erythema scale for patients with SOC. All scores showed excellent intrarater reliability for all skin types. Erythema component analysis showed that erythema did not contribute to variability. CONCLUSIONS: EASI showed excellent reliability for patients of all skin colours, and is recommended as the optimal core measure for patients with all skin colours.

The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI): grading disease severity and assessing responsiveness to clinical change in epidermolysis bullosa.

BACKGROUND: The lack of validated outcome measures for epidermolysis bullosa (EB) presents major barriers to evaluating disease severity and comparing the efficacy of therapies. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) was recently introduced as a valid and reliable instrument for EB; however, its interpretation for use in clinical practice and clinical trials is yet to be defined. OBJECTIVE: To assess the interpretability of the EBDASI in classifying patients according to disease severity and clinical response. METHODS: A total of 53 outpatients with EB at two interstate institutions were prospectively evaluated. At each visit, the principal dermatologist completed the EBDASI and global assessments of disease severity and change. Classifications for mild, moderate and severe disease using the EBDASI were determined using receiver operating characteristic curves. Minimal clinically important differences for the EBDASI activity subscale were calculated and compared with the standard error of measurement. RESULTS: Total EBDASI score ranges of 0-42, 43-106 and 107-506 corresponded to mild, moderate and severe disease respectively. Reduction in EBDASI activity scores of greater than 9 indicated clinically significant improvement. An increase of 3 in the activity score indicated deterioration. CONCLUSION: The EBDASI is a responsive tool and may be useful in characterizing disease severity and response. The cut-offs proposed in this study provide the first practical guide for interpreting the EBDASI, further supporting its use for longitudinal patient assessment and in clinical trials.

Frequency of undiagnosed psoriatic arthritis among psoriasis patients in Australian dermatology practice.

BACKGROUND: Psoriatic arthritis commonly develops in psoriasis patients and, if undiagnosed, can lead to potentially avoidable joint damage and an increased risk of comorbidity and mortality. Increased awareness of PsA symptoms among dermatologists provides an opportunity for earlier diagnosis, more timely therapy and prevention of disability. OBJECTIVE: To provide Australian epidemiological data on the frequency of undiagnosed PsA among psoriasis patients in dermatology practice, and to investigate the impact of psoriasis on quality of life and work productivity. METHODS: Nine tertiary centre dermatology practices enrolled patients presenting with plaque psoriasis and no prior rheumatologist-confirmed PsA diagnosis. Patients were screened using the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire and were referred to a rheumatologist for assessment of PsA status using CASPAR criteria if they had a PASE score ≥44. RESULTS: Based on the composite and sequential application of PASE and CASPAR criteria, undiagnosed PsA among psoriasis patients in this study is 9% [95% CI: 6, 12]. The PPV of PASE in this setting is 26% [95% CI: 19, 34]. Nail involvement and chronic large plaque psoriasis were identified as independent positive predictors of PsA, whereas scalp psoriasis was an independent negative predictor of PsA. Patients with moderate-to-severe psoriasis (PASI ≥15) had lower quality of life scores than patients with less severe psoriasis. CONCLUSION: In this study, the frequency of undiagnosed PsA in Australian dermatology practice was 9% among plaque psoriasis patients with no prior PsA diagnosis. Compared with psoriasis alone, the impact of undiagnosed PsA on health-related quality of life of psoriasis patients is substantial.

Furano-1,2-naphthoquinone inhibits EGFR signaling associated with G2/M cell cycle arrest and apoptosis in A549 cells.

Furano-1,2-naphthoquinone (FNQ), prepared from 2-hydroxy-1,4-naphthoquinone and chloroacetaldehyde in an efficient one-pot reaction, exhibits an anti-carcinogenic effect. FNQ exerted anti-proliferative activity with the G(2)/M cell cycle arrest and apoptosis in A549 cells. FNQ-induced G(2)/M arrest was correlated with a marked decrease in the expression levels of cyclin A and cyclin B, and their activating partner cyclin-dependent kinases (Cdk) 1 and 2 with concomitant induction of p53, p21, and p27. FNQ-induced apoptosis was accompanied with Bax up-regulation and the down-regulation of Bcl-2, X-linked inhibitor of apoptosis (XIAP), and survivin, resulting in cytochrome c release and sequential activation of caspase-9 and caspase-3. Western blot analysis revealed that FNQ suppressed EGFR phosphorylation and JAK2, STAT3, and STAT5 activation, but increased in activation of p38 MAPK and c-Jun NH2-terminal kinase (JNK) stress signal. The combined treatment of FNQ with AG1478 (a specific EGFR inhibitor) significantly enhanced the G(2)/M arrest and apoptosis, and also led to up-regulation in Bax, p53, p21, p27, release of mitochondrial cytochrome c, and down-regulation of Bcl-2, XIAP, survivin, cyclin A, cyclin B, Cdk1, and Cdk2 in A549 cells. These findings suggest that FNQ-mediated cytotoxicity of A549 cell related with the G(2)/M cell cycle arrest and apoptosis via inactivation of EGFR-mediated signaling pathway.

Dressings used in epidermolysis bullosa blister wounds: a review.

There is little rigorous evidence on the management of epidermolysis bullosa, so management is based on the patient's and clinician's preferences. However, there is a consensus that advanced dressings help promote healing and reduce pain.

Anorexia nervosa: the cost of long-term disability.

This study was performed to estimate the cost of long-term disability in people who have anorexia nervosa (AN) that live in the province of British Columbia (BC), Canada. Canada provides universal socialized health and welfare services, and each of the 10 provinces is responsible for its own funding. As the provincial government of BC does not categorize its disability payments by the cause of the disability, a survey was used to determine the rate of disability from AN. A sensitivity analysis was performed to assess the influence of variations on the yearly cost of disability in BC: the number of patients with AN was varied between 1.0 and 2.0% of the female and 0.05 and 0.1% of the male population; the percentage of patients with AN receiving disability payments was determined by the survey to be 35%; the cost of these payments was varied between the lowest and highest benefits a single person can receive from the BC provincial government; and finally, to allow for possible sampling bias and a possible lower prevalence of AN, the lower limit of the sensitivity analysis was derived by dividing the lowest estimate above by seven. The sensitivity analysis revealed that the total estimated cost of long-term disability in BC could be as low as $2.5 million (Canadian) or as high as $101.7 million per year, which is a cost of up to 30 times the total yearly cost of all tertiary care services for the treatment of eating disorders in BC. In view of this finding, an increase in funding is warranted for primary, secondary and tertiary prevention programs for AN in BC.

Differential diagnoses to consider at an eating disorders clinic.

OBJECTIVE: To determine the reasons for referral of patients without eating disorders who were within a cohort of patients referred to an adult tertiary care eating disorders program. METHODS: Cases were obtained by retrospectively reviewing all the charts of patients who had been referred to a single eating disorders program over a 20-year period from 1981 to 2000. All referred cases had been screened by a nurse using a telephone or written questionnaire. RESULTS: Thirty-three out of 987 patients (3.3%) were identified as having no eating disorders. Four subjects were males (12.1%) and 29 were females (87.9%). After investigation, 16 were found to have a psychiatric diagnosis, 8 had a medical diagnosis, and 8 had no identifiable diagnosis. CONCLUSIONS: This study shows that the screening process for referral to a tertiary care eating disorders program is highly reliable and suspicion for a patient without an eating disorder should be low; in comparison with the eating disorder population, these patients are more likely to be male and psychiatric illnesses are twice more likely than medical disorders to be diagnosed.

Zinc supplementation in the treatment of anorexia nervosa.

The clinical manifestations of zinc deficiency and anorexia nervosa are remarkably similar, and a number of studies have demonstrated that there may be a positive correlation between zinc therapy and the rate of recovery of anorexia nervosa patients. However, because of the different interpretations of the results of these studies, the use of zinc supplementation varies. This article examines the evidence supporting zinc supplementation in the treatment of anorexia nervosa. Randomised, double-blind, controlled clinical trials indicate that zinc therapy enhances the rate of recovery in anorexia nervosa patients by increasing weight gain and improving their levels of anxiety and depression. On the basis of these findings and the low toxicity of zinc, zinc supplementation should be included in the treatment protocol for anorexia nervosa.

Osmotic stress-induced changes of sucrose metabolism in cultured sweet potato cells.

The intra- and extracellular sugar contents, the activities of sucrose-metabolizing enzymes, and the metabolism of [U-(14)C] glucose in a pulse-chase experiment were compared between the normal and osmotically stressed (by 0.6 M sorbitol) sweet potato (Ipomoea batatas) suspension cells. The stress enhanced the levels of sucrose and sucrose phosphate synthase (SPS) activity. Northern blot analysis also showed that prolonged osmotic stress enhanced the SPS gene expression at the transcriptional level. Stressed cells also had higher activities of sucrose cleaving enzymes, such as alkaline invertase and sucrose synthase. The (14)C-sucrose isolated from normal and stressed cells had (14)C-fructose and (14)C-glucose ratios of 0.68 and 1, respectively. These data suggest the continual cycling of degradation and synthesis of sucrose in both types of cells. Among the enzymes used in constructing such futile cycling, besides invertase and SPS, sucrose synthase (SS) should be involved in normal cells, but not in stressed ones. It is apparent that the osmotic stress caused a significant change in the pattern of sucrose metabolism.

Differentially and developmentally regulated expression of three rice sucrose synthase genes.

The spatial and temporal distribution of sucrose synthase (RSuS) in rice (Oryza sativa L.) was studied by Western and immunohistochemical analyses using the monospecific antibodies for three RSuS isoforms. In leaf tissues, RSuS1 was localized in the mesophyll while RSuS2 was in the phloem in addition to the mesophyll. In the roots, only RSuS1 was found in the phloem. No RSuS3 could be detected in any parts of etiolated seedlings. The expression of each RSus gene is closely linked to the seed development. RSuS1 was present in the aleurone layers of developing seeds, and at a low level in endosperm cells. RSuS2 was evenly distributed in seed tissues other than the endosperm. RSuS3 was localized predominantly in the endosperm cells. The tissue specific localizations of the three gene products suggest that RSuS1 plays a role in sugar transport into endosperm cells where the reaction catalyzed by RSuS3 provides the precursor of starch synthesis. RSus2, which is ubiquitously expressed, may play a housekeeping role.

Epidermolysis bullosa acquisita in childhood.

This case report of an 11-year-old girl describes a juvenile form of epidermolysis bullosa acquisita, an autoimmune disease of IgG antibodies to basement membrane type 7 collagen. Our case illustrates an unusually severe, acute inflammatory presentation of this condition with prominent mucosal and constitutional features requiring admission to a paediatric burns unit. The treatment consisted of supportive topical and systemic agents, prednisolone and dapsone. She responded to dapsone alone and the course of the illness was uneventful.

Allergic contact dermatitis from azo dyes.

Contact allergy to textile dyes usually occurs with disperse dyes of the azo or anthraquinone groups. A case is reported of a woman with clinical features of contact allergy to coloured nylon stockings who had multiple sensitivities to dyes of different azo groups.

Fatal granulomatous amoebic encephalitis caused by Balamuthia mandrillaris.

Granulomatous amoebic encephalitis caused by Balamuthia mandrillaris is rare (63 human) cases reported worldwide) and fatal. We report a case in a five-year-old boy who had previously been well. For 18 months, he had had a slowly progressive, granulomatous mid facial lesion, but despite extensive investigation definitive diagnosis was made only with the acute onset of neurological signs in the last two weeks of life, when a brain biopsy specimen revealed amoebic trophozoites and cysts. Infection with B. mandrillaris should be considered in the differential diagnosis of chronic skin lesions with non-specific granulomatous histopathology and negative microbiological test results.

Trigeminal trophic syndrome.

A case report of a 51-year-old woman who developed trigeminal trophic syndrome following craniectomy is presented. This syndrome represents trophic ulceration by self-induced trauma to skin in the trigeminal area. Treatment of the present case was complicated by the patient's underlying psychological problems.

Atopic eczema: its impact on the family and financial cost.

OBJECTIVE: To evaluate the impact of childhood atopic eczema on families and assess the personal financial cost of its management. DESIGN: Cross sectional survey. SETTING: Paediatric dermatology and paediatric diabetology outpatient clinics. PATIENTS: Parents of 48 randomly selected children with atopic eczema and 46 with insulin dependent diabetes mellitus. MAIN OUTCOME MEASURES: The impact on family score, the reported cost of relevant medical treatments, medical consultations, relevant hospitalisation, and income loss. RESULTS: Families of children with moderate or severe atopic eczema had a significantly higher impact on family score than families of diabetic children. A conservative estimate of the annual personal financial cost of managing mild, moderate, and severe eczema was Aus$330, 818, and 1255, respectively. The financial cost to the community for the management of atopic eczema in the study groups was greater. The personal financial cost of managing eczema was greater than for asthma. CONCLUSION: Childhood atopic eczema has a profound impact on the social, personal, emotional, and financial perspectives of families.

Complete structures of three rice sucrose synthase isogenes and differential regulation of their expressions.

By cloning and sequencing cDNA and genomic DNA and transcription initiation site mapping, the total structures including at least 1 kb of putative regulatory sequences upstream of the transcription initiation sites of three genes encoding rice sucrose synthase isoprotomers were either newly established or amended. The third type of SS gene, RSus3, has not been found in other plants. The structures of the three genes and the gene products were compared and their evolutionary sequence was proposed. Specific probes for the three SS mRNA's were developed and used for analyzing their steady state levels at different organs and under some physiological stress conditions. It appears that RSus2 is a house-keeping gene, RSus3 is highly specific to the grain, and the expression of RSus1 shows a tendency to complement that of RSus3. A possible cause of the presence of the third rice SS gene was discussed. We also reported a novel method to synthesize single-stranded DNA for S1 mapping of a transcription initiation site associated with extended secondary structures.

Two types of Russell's viper revealed by variation in phospholipases A2 from venom of the subspecies.

This study compared the phospholipases A2 (PLA2S) present in four commercially available venoms of Russell's viper subspecies by HPLC fractionation and partial sequence analysis. A potent heterodimeric PLA2 neurotoxin (designated a Russtoxin) was found in the venoms of all Russell's vipers except Daboia russelli (Sri Lanka and South India). The venom PLA2S of D. r. russelli (southern India) used in a previous study appear to be the same as those of D. r. pulchella (Sri Lanka), while the venom PLA2S of D. r. russelli (Pakistan) and D. r. siamensis (Burma and Thailand) resemble those of D. r. formosensis (Taiwan). This study provides evidence for the presence of two types of Russell's viper. Daboia russelli formosensis (Taiwan). D. r. siamensis (Thailand and Burma) and D. r. russelli (Pakistan) represent one type whose venom contains PLA2S having an Asn residue at the N-terminus, while D. r. pulchella (South India and Sri Lanka) represents the other type, whose venom contains PLA2S with a N-terminal residue Ser.