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.

Automated colour identification in melanocytic lesions.

Colour information plays an important role in classifying skin lesion. However, colour identification by dermatologists can be very subjective, leading to cases of misdiagnosis. Therefore, a computer-assisted system for quantitative colour identification is highly desirable for dermatologists to use. Although numerous colour detection systems have been developed, few studies have focused on imitating the human visual perception of colours in melanoma application. In this paper we propose a new methodology based on QuadTree decomposition technique for automatic colour identification in dermoscopy images. Our approach mimics the human perception of lesion colours. The proposed method is trained on a set of 47 images from NIH dataset and applied to a test set of 190 skin lesions obtained from PH2 dataset. The results of our proposed method are compared with a recently reported colour identification method using the same dataset. The effectiveness of our method in detecting colours in dermoscopy images is vindicated by obtaining approximately 93% accuracy when the CIELab1 colour space is used.

Association of paediatric mastocytosis with a polymorphism resulting in an amino acid substitution (M541L) in the transmembrane domain of c-KIT.

BACKGROUND: The receptor tyrosine kinase c-KIT plays a key role in normal mast cell development. Point mutations in c-KIT have been associated with sporadic or familial mastocytosis. OBJECTIVES: Two unrelated pairs of apparently identical twins affected by cutaneous mastocytosis attending the Mastocytosis Clinic at the Royal Children's Hospital, Melbourne, provided an opportunity to assess the possible contribution of c-KIT germline mutations or polymorphisms in this disease. METHODS: Tissue biopsy, blood and/or buccal swab specimens were collected from 10 children with mastocytosis. To detect germline mutations/polymorphisms in c-KIT, we studied all coding exons by denaturing high pressure liquid chromatography. Exons showing mismatches were examined by direct sequencing. The influence of the substitution identified was further examined by expressing the variant form of c-KIT in factor-dependent FDC-P1 cells. RESULTS: In both pairs of twins, a heterozygous ATG to CTG transition in codon 541 was observed, resulting in the substitution of a methionine residue in the transmembrane domain by leucine (M541L). In each case, one parent was also heterozygous for this allele. Expression of M541L KIT in FDC-P1 cells enabled them to grow in human KIT ligand (stem cell factor, SCF) but did not confer factor independence. Compared with cells expressing wild-type KIT at a similar level, M541L KIT-expressing cells displayed enhanced growth at low levels of SCF, and heightened sensitivity to the KIT inhibitor, imatinib mesylate. CONCLUSIONS: The data suggest that the single nucleotide polymorphism resulting in the substitution M541L may predispose to paediatric mastocytosis.

Clinical heterogeneity in recessive epidermolysis bullosa due to mutations in the keratin 14 gene, KRT14.

BACKGROUND: Epidermolysis bullosa simplex (EBS), the most common subtype of EB, is usually inherited as an autosomal dominant trait caused by mutations in either the keratin 5 (KRT5) or keratin 14 (KRT14) genes. Recessive EBS (R-EBS) is extremely rare. METHODS: We present the first Australian patient diagnosed with R-EBS, to our knowledge, and a comprehensive review of genotypes and phenotypes of R-EBS reported cases. RESULTS: The female proband, of Turkish descent with consanguineous parentage, was referred to us at the age of 8 years. Clinically, she had a severe phenotype including generalized blisters, mucosal involvement and EB naevi. Immunofluorescence mapping and electron microscopy were consistent with a diagnosis of EBS. Staining for Keratin 14 (K14) was negative. The basal layer, however, reacted with monoclonal antibodies to keratins 6 (K6) and 16 (K16). Mutation screening from genomic DNA showed that the proband was homozygous for the truncation mutation Y204X in exon 3 of KRT14, and both unaffected parents were heterozygous for a single KRT14 Y204X mutation. The phenotype of our patient is reported in more detail and with longer follow-up than those of others published in the literature. DISCUSSION: The proband's phenotype was severe as an infant but improved with age, suggesting that an alternative keratin is pairing with K5 in her skin to compensate for the loss of K14--a novel biological compensatory mechanism. It is interesting that K6 and K16 were expressed, as these are normally positive in hyperproliferative skin disorders.

Nurse-led clinics reduce severity of childhood atopic eczema: a review of the literature.

BACKGROUND: The increasing prevalence and impact of atopic eczema in children in Western countries such as Australia substantiate the need to evaluate the current management of this illness. It has been well documented that the most important aspects in the management of atopic eczema are to allow adequate time for education and demonstration of treatments. However, current models of healthcare funding restrict the opportunity for patient education during medical consultation times. The contribution of nursing to patient care through nurse-led clinics has significant potential in the management of many common chronic illnesses, although atopic eczema has received minimal attention by researchers to date. OBJECTIVES: To discuss the current clinical management of atopic eczema, and to identify the evidence surrounding the benefits of nurse-led clinics in managing patients with chronic illnesses. METHODS: Systematic searches were undertaken using the Cochrane Library, MedLine, PUBMed and CINAHL from 1995 to 2005. Manual searches of references of retrieved articles identified two additional key studies from 1990 and 1993 which were also included in the review. RESULTS: In total, 22 relevant publications were identified. These included both primary research and descriptive studies that covered the medical management of eczema, patient education and improved patient outcomes. The evidence emerging from the literature indicates that the current management of eczema through doctor-led clinics could be improved, with doctors often lacking the time to offer sufficient patient education to manage chronic illnesses effectively. The literature supports the efficacy of nurse-led clinics in the management of chronic illnesses. The benefits of nurse-led clinics include increased patient satisfaction, longer consultations resulting in improved patient education and similar health outcomes when compared with care from a doctor. No studies were identified comparing nurse-led and doctor-led clinics in the management of eczema. CONCLUSIONS: The most effective way to manage atopic eczema is to provide adequate time for education and demonstration of treatments, which the literature suggests can be achieved through nurse-led clinics. The literature review supports an investigation researching the outcomes of a nurse-led clinic on reducing the severity of eczema in children.

Ciclopiroxolamine cream for treating seborrheic dermatitis: a double-blind parallel group comparison.

BACKGROUND: The aim of this study was to compare the efficacy and tolerability of topically applied ciclopiroxolamine cream with that of the corresponding vehicle in patients with seborrheic dermatitis of the face. PATIENTS AND METHODS: The study was conducted as a multicenter prospective, randomized, double-blind parallel group comparison at 14 centers in Australia and New Zealand. 189 patients with clinically diagnosed seborrheic dermatitis participated in the study. Each patient applied ciclopiroxolamine 1% cream or the corresponding vehicle twice daily as a thin film to the affected skin areas and to clinically unaffected skin areas surrounding the lesions for 29 days. RESULTS: The rate of treatment success was significantly higher with ciclopiroxolamine than with vehicle (73.9 vs 53.6%; p = 0.003). Treatment with ciclopiroxolamine reduced the sum score of the clinical signs of seborrheic dermatitis to a greater extent than the vehicle (p

The -590C/T and -34C/T interleukin-4 promoter polymorphisms are not associated with atopic eczema in childhood.

Susceptibility to the development of asthma and other atopic diseases is known to have a genetic component. To date, several studies have linked chromosome 5q31 to asthma and atopy in human beings. This region harbors a cluster of cytokine and growth factor genes, IL-4 presenting as a prime atopy candidate gene, inasmuch as it plays a pivotal role in the atopy pathway. Our approach was to identify polymorphisms within the promoter regions of IL-4 and test their association with atopic eczema. Polymorphisms were typed in a cohort of 76 small nuclear families and 25 triads with childhood atopic eczema. The genotypes were used to test for linkage in the presence of association with atopic eczema. A new polymorphism, -34C/T, was identified and studied with a known polymorphism, -590C/T. On its own, each polymorphism showed no association with atopic eczema. The 2 polymorphisms were used to generate haplotypes, and a significant result was found for the -590C/-34C haplotype. However, after Bonferroni correction for multiple testing, the association became nonsignificant. Neither polymorphism predisposes to early-onset atopic eczema by itself, but suggestive linkage was found for the -590C/-34C haplotype in this study.

Effect of localized cytokine dysregulation: accelerated rejection of IL-2-expressing skin grafts.

Transgenic mice were created in which a sheep keratin promoter directed the expression of IL-2 into the dermis. These KIL-2 transgenic mice were used to investigate the effects of localized IL-2 dysregulation on immune responses. Peripheral tolerance to skin antigens was not broken by in situ IL-2 expression because syngeneic KIL-2 skin grafts were not rejected. However, MHC Class I-disparate skin grafts from KIL-2 donors were rejected faster (median survival time (MST) 12 days) than grafts of non-transgenic littermate skin (MST 18 days). In contrast, the kinetics of KIL-2 H-Y-disparate skin graft rejection (MST 14 days) did not differ significantly from controls (MST 16 days), suggesting that upregulation of IL-2 at the effector site could affect CD4+ T cell- independent, but not CD4+ T cell-dependent, responses. No effect on rejection kinetics was observed when wild type allogeneic skin was grafted onto transgenic mice that expressed bcl2 constitutively in their lymphocytes (MST of 14 days, both sets), indicating that this was not simply due to increased longevity of T cells within the IL-2 expressing graft. We therefore suggest that aberrant expression of IL-2 can accelerate helper-independent CD8+ T cell responses by increasing proliferation and/or differentiation of cytolytic T cells at the effector site.

Porphyria cutanea tarda.

Porphyria cutanea tarda (PCT) is a metabolic disorder of haem biosynthesis caused by decreased activity of uroporphyrinogen decarboxylase. Porphyria cutanea tarda is manifest by fragility, erosions, bullae, milia and scars on sun-exposed skin. Excess porphyrins in the skin interact with light of approximately 400 nm-wavelength radiant energy, forming reactive oxygen species. Porphyria cutanea tarda is categorized as familial, acquired or toxic. Factors that may induce clinical expression of PCT in susceptible individuals include alcohol, oestrogen, iron, polyhalogenated compounds and viral infections. Porphyria cutanea tarda is associated with an increased incidence of the haemochromatosis gene. Treatments for PCT include withdrawal of aggravating factors, phlebotomy and oral antimalarial medications.

Night blindness precipitated by isotretinoin in the setting of hypovitaminosis A.

A 16-year-old male developed night blindness 2 weeks after starting isotretinoin at a dose of 20 mg per day for cystic acne. He also had cystic fibrosis, complicated by hepatic cirrhosis. Despite long-term oral vitamin A supplementation, serum vitamin A levels were found to be 0.3 mumol/L (normal range 0.9-2.5 mumol/L). Oral vitamin A replacement was instituted with resolution of his visual symptoms in 6 months. Isotretinoin therapy was successfully continued with no deterioration in liver function. Isotretinoin has been reported to cause deterioration in night vision. In vitro evidence suggests isotretinoin may interfere with the processing of endogenous vitamin A in the retina. This case highlights the need for careful monitoring of serum vitamin A status in patients with malabsorptive states on isotretinoin therapy.

A case of spontaneous mutation in the keratin 9 gene associated with epidermolytic palmoplantar keratoderma.

Epidermolytic palmoplantar keratoderma appears to be due to defects in keratin 9, the palmoplantar specific type 1 keratin. We report a case of spontaneous mutation, a C to T transition at codon 162, resulting in an arginine to tryptophan substitution in the 1 A region of the alpha helical rod domain of keratin 9. This provides further evidence that this codon is an important spot for mutation in keratin 9.

Grades of severity and the validation of an atopic dermatitis assessment measure (ADAM).

There has generally been a dearth of good clinical descriptions of grades of disease severity. The aim of this study was to produce reliable and valid descriptions of grades of severity of Atopic Dermatitis (AD). The ADAM (AD Assessment Measure) measure was used to assess AD severity in 171 male and female paediatric patients (mean age = 54 months) at the Royal Children's Hospital in Melbourne, Australia. The assessments were subject to Partial Credit analyses to produce clinically relevant "word pictures" of grades of severity of AD. Patterns of AD were shown to vary according to age, sex and severity. These descriptions will be useful for clinical training and research. Moreover, the approach to validation adopted here has important implications for the future of measurement in medicine.

The development of a practical and reliable assessment measure for atopic dermatitis (ADAM).

Previous measures of Atopic Dermatitis (AD) have not been adequate for research purposes. This paper describes a study conducted in dermatology clinics of the Royal Children's Hospital, Melbourne, Australia, to develop a reliable, valid and practical measure. A pool of items to describe both site and morphology of AD was generated from a literature survey and expert opinion. Selected items were incorporated into a measure with each item rated on a four point scale. The measure was piloted and revised to a simpler format and called the Atopic Dermatitis Assessment Measure (ADAM). Unidimensionality was established. Reliability was determined by comparing two doctors blind ratings on 51 patients (mean age = 70 months). Agreement varied depending upon site and morphology with more agreement on "mild" AD than on "severe" AD. These results imply that operational definitions of the scales need to be defined more clearly. The measure satisfies the assumptions for a partial credit analysis.

Auricular ossification.

A patient with extensive bilateral auricular ossification presented with chondrodermatitis nodularis helicis on one side. The condition was otherwise asymptomatic. Ossification was detected on radiological and histological examination. Underlying medical conditions were not found. We believe this developed as a consequence of cold injury. Auricular ossification is an unusual cause of the so-called petrified external ear, in which the subcutaneous tissue is stony hard. It is more commonly caused by dystrophic calcification. Calcification and ossification are clinically identical and histological examination is required to definitively differentiate them.

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.