Tsakok T.,Guys and St Thomas Hospital |
McKeever T.M.,St Johns Institute of Dermatology |
Yeo L.,University of Nottingham |
Flohr C.,Royal Infirmary
British Journal of Dermatology | Year: 2013
A number of studies have suggested that early life exposure to antibiotics can lead to an increased risk of developing eczema. This systematic review and meta-analysis of observational studies, involving children or young adults aged 0-25 years, assessed the impact of antibiotic exposure either in utero or during the first 12 months of life on subsequent eczema risk. Twenty studies examined the association between prenatal and/or postnatal exposure to antibiotics and development of eczema. The pooled odds ratio (OR) for the 17 studies examining postnatal antibiotic exposure was 1·41 [95% confidence interval (CI) 1·30-1·53]. The pooled OR for the 10 longitudinal studies was 1·40 (95% CI 1·19-1·64), compared with a pooled OR of 1·43 (95% CI 1·36-1·51) for the seven cross-sectional studies. There was a significant dose-response association, suggesting a 7% increase in the risk of eczema for each additional antibiotic course received during the first year of life [pooled OR 1·07 (95% CI 1·02-1·11)]. Finally, the pooled OR for the four studies relating to antenatal exposure was 1·30 (95% CI 0·86-1·95). We conclude that exposure to antibiotics in the first year of life, but not prenatally, is more common in children with eczema. What's already known about this topic? A number of studies have suggested that early life exposure to antibiotics may lead to an increased risk of subsequent eczema. The evidence to date is conflicting and no systematic review has been conducted. What does this study add? Antibiotic exposure in early life may increase the risk of subsequent eczema by up to 40%, with broad-spectrum antibiotics having a more pronounced effect. Each additional antibiotic course may confer a further 7% risk increase. Antibiotics should be prescribed with caution, especially in high-risk children. © 2013 British Association of Dermatologists.
Samrao A.,University of California at San Francisco |
Chew A.-L.,Orpington Hospital |
Chew A.-L.,St Johns Institute of Dermatology |
Price V.,University of California at San Francisco
British Journal of Dermatology | Year: 2010
Summary Background Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia with a distinctive clinical pattern of progressive frontotemporal hairline recession. Currently, there are no evidence-based studies to guide treatment for patients with FFA; thus, treatment options vary among clinicians. Objectives We report clinical findings and treatment outcomes of 36 patients with FFA, the largest cohort to date. Further, we report the first evidence-based study of the efficacy of hydroxychloroquine in FFA using a quantitative clinical score, the Lichen Planopilaris Activity Index (LPPAI). Methods A retrospective case note review was performed of 36 adult patients with FFA. Data were collected on demographics and clinical findings. Treatment responses to hydroxychloroquine, doxycycline and mycophenolate mofetil were assessed using the LPPAI. Adverse events were monitored. Results Most patients in our cohort were female (97%), white (92%) and postmenopausal (83%). Apart from hairline recession, 75% also reported eyebrow loss. Scalp pruritus (67%) and perifollicular erythema (86%) were the most common presenting symptom and sign, respectively. A statistically significant reduction in signs and symptoms in subjects treated with hydroxychloroquine (P < 0·05) was found at both 6- and 12-month follow up. Conclusions In FFA, hairline recession, scalp pruritus, perifollicular erythema and eyebrow loss are common at presentation. Despite the limitations of a retrospective review, our data reveal that hydroxychloroquine is significantly effective in reducing signs and symptoms of FFA after both 6 and 12 months of treatment. However, the lack of a significant reduction in signs and symptoms between 6 and 12 months indicates that the maximal benefits of hydroxychloroquine are evident within the first 6 months of use. BJD © 2010 British Association of Dermatologists.
Pink A.E.,King's College London |
Simpson M.A.,King's College London |
Desai N.,St Johns Institute of Dermatology |
Trembath R.C.,King's College London |
And 2 more authors.
Journal of Investigative Dermatology | Year: 2013
Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin condition of unclear etiology. It may segregate as an autosomal dominant trait, and heterozygous mutations in the γ-secretase genes NCSTN, PSENEN, and PSEN1 have recently been reported in a small number of multiplex kindreds and sporadic cases. These mutations highlight γ-secretase (an enzyme that has been extensively investigated in familial Alzheimer's disease) to have an integral role in cutaneous biology and, more specifically, in HS. In this article, we review the recent genetic data, how they inform disease pathogenesis, and the long-term implications in HS and related diseases. © 2013 The Society for Investigative Dermatology.
Shain A.H.,University of California at San Francisco |
Yeh I.,University of California at San Francisco |
Kovalyshyn I.,Cleveland Clinic |
Sriharan A.,Orlando Health |
And 10 more authors.
New England Journal of Medicine | Year: 2015
BACKGROUND The pathogenic mutations in melanoma have been largely catalogued; however, the order of their occurrence is not known. METHODS We sequenced 293 cancer-relevant genes in 150 areas of 37 primary melanomas and their adjacent precursor lesions. The histopathological spectrum of these areas included unequivocally benign lesions, intermediate lesions, and intraepidermal or invasive melanomas. RESULTS Precursor lesions were initiated by mutations of genes that are known to activate the mitogen-activated protein kinase pathway. Unequivocally benign lesions harbored BRAF V600E mutations exclusively, whereas those categorized as intermediate were enriched for NRAS mutations and additional driver mutations. A total of 77% of areas of intermediate lesions and melanomas in situ harbored TERT promoter mutations, a finding that indicates that these mutations are selected at an unexpectedly early stage of the neoplastic progression. Biallelic inactivation of CDKN2A emerged exclusively in invasive melanomas. PTEN and TP53 mutations were found only in advanced primary melanomas. The point-mutation burden increased from benign through intermediate lesions to melanoma, with a strong signature of the effects of ultraviolet radiation detectable at all evolutionary stages. Copy-number alterations became prevalent only in invasive melanomas. Tumor heterogeneity became apparent in the form of genetically distinct subpopulations as melanomas progressed. CONCLUSIONS Our study defined the succession of genetic alterations during melanoma progression, showing distinct evolutionary trajectories for different melanoma subtypes. It identified an intermediate category of melanocytic neoplasia, characterized by the presence of more than one pathogenic genetic alteration and distinctive histopathological features. Finally, our study implicated ultraviolet radiation as a major factor in both the initiation and progression of melanoma. © 2015 Massachusetts Medical Society. All rights reserved.
Ameen M.,St Johns Institute of Dermatology
Tropical Doctor | Year: 2010
Chromoblastomycosis is a subcutaneous fungal infection caused by the traumatic inoculation of the skin with pigmented saprophytic moulds. Although infection is rarely fatal, it is characteristically chronic and can be complicated by lymphatic damage and malignant transformation. Despite a variety of treatment modalities, which are often combined and include long courses of antifungals, surgical excision and destructive physical therapies, it remains one of the most difficult deep mycotic infections to eradicate.
Green L.,St Johns Institute of Dermatology
Nursing standard (Royal College of Nursing (Great Britain) : 1987) | Year: 2011
Psoriasis is a common, chronic skin condition and nurses can expect to encounter patients with psoriasis in both primary and secondary care settings. This article focuses on the physical and psychosocial effects of the condition and on appropriate management strategies, including the use of biologic therapies to treat moderate to severe psoriasis. Quality of life issues are also addressed.
McGrath J.A.,St Johns Institute of Dermatology |
Mellerio J.E.,St Johns Institute of Dermatology
Dermatologic Clinics | Year: 2010
Pathogenic mutations have now been described in ten different desmosomal proteins: plakophilin 1 (PKP1) and 2 (PKP2); desmoplakin; plakoglobin; desmoglein 1, 2, and 4; desmocollin 2, and 3 corneodesmosin. Nevertheless, the first report of an inherited desmosomal gene disorder, published in 1997, involved loss-of-function mutations on both alleles of PKP1, the PKP1 gene. Loss of PKP1 expression in human skin leads to skin erosions and crusting, notably with perioral fissuring as well as palmoplantar hyperkeratosis with painful cracking of the skin. Other more variable features include abnormalities of ectodermal development with growth delay, hypotrichosis or alopecia, hypohidrosis, and nail dystrophy. In contrast to some other inherited disorders of desmosomes, there is no cardiac pathology in individuals with PKP1 mutations since it is not expressed in the heart. The collection of clinical features in individuals with PKP1 mutations has been termed ectodermal dysplasia-skin fragility (ED-SF) syndrome. This genodermatosis is classified as a suprabasal form of epidermolysis bullosa simplex and thus far there have been 10 published cases. Skin biopsy shows acanthosis, acantholysis, and a reduced number of small, poorly formed desmosomes. Loss of PKP1 expression results in an integral weakness within the desmosomal plaque, leading to desmosomal detachment and cell-cell separation. Thus, the clinicopathologic features attest to the significant role of PKP1 in stabilization of desmosome structure and function, predominantly in the spinous layers of the epidermis. This article reviews the clinical, structural, and molecular pathology of this genetic disorder of desmosomes. © 2010 Elsevier Inc. All rights reserved.
Fassihi H.,St Johns Institute of Dermatology
Photochemical and Photobiological Sciences | Year: 2013
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of DNA repair characterised by photosensitivity, progressive pigmentary change, and an increased incidence of ultraviolet (UV)-induced skin and mucous membrane cancers. Approximately 25% of XP patients also have progressive neurological degeneration. There are eight XP complementation groups (XP-A through to XP-G, and XP variant (XP-V)), corresponding to the affected DNA repair gene. Seven of these genes, XPA to XPG, are involved in nucleotide excision repair, removing UV-induced damage from DNA. The eighth gene, XPV (or POLH), encodes for DNA polymerase η, which is required for the replication of DNA containing unrepaired UV-induced damage. There is wide variability in clinical features both between and within XP complementation groups. The diagnosis is made clinically and confirmed by cellular tests for defective DNA repair. This is followed by identification of the defective gene (complementation analysis) and causative mutation(s). Although there is no cure, sun avoidance and regular follow-up to assess and treat any skin cancers increase life expectancy. The neurological abnormalities are progressive and result in a shortened lifespan. The study of patients with XP has highlighted the importance of nucleotide excision repair in the aetiology of skin cancers and neurological degeneration, and has solidified the link between UV exposure, DNA damage, somatic mutations and skin cancer. This journal is © 2013 The Royal Society of Chemistry and Owner Societies.
Cardoso J.C.,University of Coimbra |
Calonje E.,St Johns Institute of Dermatology
Histopathology | Year: 2015
Cutaneous adnexal tumours can be a diagnostic challenge for the pathologist. This is particularly true in the case of tumours with sweat gland differentiation, due to a large number of rare entities, a multiplicity of names to designate the same neoplasms and consequent lack of consensus regarding their classification and nomenclature. In the traditional view, sweat gland tumours were divided into eccrine and apocrine. However, this has been challenged in recent years, and in fact many of these tumours may have both eccrine and apocrine variants. Some display more complex features and defy classification, due to the presence of other lines of differentiation, namely follicular and/or sebaceous (in the case of apocrine tumours, due to the close embryological relationship between apocrine glands, hair follicles and sebaceous glands). The present paper reviews and updates the basic concepts regarding the following malignant sweat gland tumours: apocrine carcinoma, porocarcinoma, hidradenocarcinoma, spiradenocarcinoma, cylindrocarcinoma, microcystic adnexal carcinoma and related entities, squamoid eccrine ductal carcinoma, digital papillary adenocarcinoma, primary cutaneous mucinous carcinoma, endocrine mucin-producing sweat gland carcinoma and primary cutaneous signet ring cell carcinoma. Particular emphasis is put in recent findings that may have implications in the diagnosis and management of these tumours. © 2015 John Wiley & Sons Ltd.
Marrouche N.,Norwich University |
Grattan C.,Norwich University |
Grattan C.,St Johns Institute of Dermatology
Current Opinion in Allergy and Clinical Immunology | Year: 2012
Purpose of review: The present article reviews childhood urticaria. It provides an update on the current understanding of its pathophysiology and highlights the current practice in the management of this condition. Recent finding: Progress has been made in understanding the pathophysiology of urticaria with the elucidation of an autoimmune basis in a significant proportion of children with chronic spontaneous urticaria. H1-antihistamines remain the mainstay of therapy, but there is increasing awareness on the risks of sedating first-generation antihistamines. Omalizumab is increasingly being used off-license in the most refractory cases. Summary: Urticaria is a common disease that affects children and adults. However, paediatric urticaria has specific features and remains poorly understood. Acute spontaneous urticaria is the most common clinical presentation in childhood. It is caused by viral infection in most cases with an identifiable trigger. By contrast, chronic spontaneous urticaria in children may be autoimmune, but more studies are needed to understand the clinical significance of functional autoantibodies in this subgroup of patients. Investigations should always be guided by history. Treatment remains largely symptomatic. H1-antihistamines are the mainstay of therapy but are insufficient to control symptoms in all patients. There is an urgent need for more efficacious therapies. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.