David J. Gawkrodger

The prevalence of childhood atopic eczema in a general population

BACKGROUND Atopic eczema has become more common during recent decades, but few studies have looked at its prevalence in the general community. OBJECTIVE Our purpose was to ascertain the prevalence of atopic eczema, its age of onset, and its relationship to breast-feeding and ear piercing in a general practice population. METHODS Children (N = 1104), aged 3 to 11 years, were identified from a computerized register in a socially and ethnically mixed English general practice population of 13,314. Of these, 1077 children (97.6% recruitment) were interviewed with parents or guardians, and the resultant data were recorded on a survey form. RESULTS The lifetime occurrence of atopic eczema was 20% in boys (12% in the past year) and 19% in girls (11% in the past year). Prevalence in the past year was 10% to 14% in boys aged 3 to 11 years but fell in girls from 15% at 3 to 5 years to 8% at 9 to 11 years. Atopic eczema developed in the first 12 months of life in 60% of the children who had the condition, and it developed in the first 6 months of life in three quarters of these children. Ear piercing had been performed in 35% of girls and 3% of boys and was most prevalent in social classes 3, 4, and 5. More than half the girls aged 9 to 11 years had pierced ears. Breast-feeding did not affect the prevalence of atopic eczema. CONCLUSION The lifetime prevalence of atopic eczema was 20% in children aged 3 to 11 years. There was no evidence that ear piercing perpetuated eczema in this age group. Breast-feeding did not protect against the development of atopic eczema.

Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo

BACKGROUND Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases. METHODS To identify generalized vitiligo susceptibility loci, we conducted a genomewide association study. We genotyped 579,146 single-nucleotide polymorphisms (SNPs) in 1514 patients with generalized vitiligo who were of European-derived white (CEU) ancestry and compared the genotypes with publicly available control genotypes from 2813 CEU persons. We then tested 50 SNPs in two replication sets, one comprising 677 independent CEU patients and 1106 CEU controls and the other comprising 183 CEU simplex trios with generalized vitiligo and 332 CEU multiplex families. RESULTS We detected significant associations between generalized vitiligo and SNPs at several loci previously associated with other autoimmune diseases. These included genes encoding major-histocompatibility-complex class I molecules (P=9.05x10(-23)) and class II molecules (P=4.50x10(-34)), PTPN22 (P=1.31x10(-7)), LPP (P=1.01x10(-11)), IL2RA (P=2.78x10(-9)), UBASH3A (P=1.26x10(-9)), and C1QTNF6 (P=2.21x10(-16)). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07x10(-15)) and GZMB (P=3.44x10(-8)), and in a locus containing TYR (P=1.60x10(-18)), encoding tyrosinase. CONCLUSIONS We observed associations between generalized vitiligo and markers implicating multiple genes, some associated with other autoimmune diseases and one (TYR) that may mediate target-cell specificity and indicate a mutually exclusive relationship between susceptibility to vitiligo and susceptibility to melanoma.

The relationship between stress and the onset and exacerbation of psoriasis and other skin conditions

Summary The role of stressful life events in the progress of various skin conditions was studied retrospectively in patients who presented with either psoriasis (where there is some agreement about the importance of stress), urticaria, acne, alopecia and non‐atopic eczema (where there is some uncertainty regarding the role of stress), or malignant melanoma, fungal infection, basal cell carcinoma and melanocytic naevi (where stress is considered less relevant). When patients in the three groups were matched for age, those with psoriasis were more likely to report that the experience of stress pre‐dated the onset and exacerbations of their condition than patients with other skin diseases. For the psoriasis patients the most common types of life events were family upsets (such as bereavements), and work or school demands, but chronic difficulties were also common. There was no relationship between the severity of stress and time to onset or exacerbations. The results support the notion that stress is more likely to be associated with the onset of psoriasis than other conditions, but also that there may be considerable individual variation in the ability to cope, suggesting that psychological interventions may be helpful for particular patients.

Guideline for the diagnosis and management of vitiligo

This detailed and user‐friendly guideline for the diagnosis and management of vitiligo in children and adults aims to give high quality clinical advice, based on the best available evidence and expert consensus, taking into account patient choice and clinical expertise.

Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo

We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis (3,187 cases and 6,723 controls) identifying 13 additional vitiligo-associated loci. These include OCA2-HERC2 (combined P = 3.80 × 10−8), MC1R (P = 1.82 × 10−13), a region near TYR (P = 1.57 × 10−13), IFIH1 (P = 4.91 × 10−15), CD80 (P = 3.78 × 10−10), CLNK (P = 1.56 × 10−8), BACH2 (P = 2.53 × 10−8), SLA (P = 1.58 × 10−8), CASP7 (P = 3.56 × 10−8), CD44 (P = 1.78 × 10−9), IKZF4 (P = 2.75 × 10−14), SH2B3 (P = 3.54 × 10−18) and TOB2 (P = 6.81 × 10−10). Most vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components that likely mediate immune targeting and the relationships among vitiligo, melanoma, and eye, skin and hair coloration.

Guidelines for the management of vitiligo: the European Dermatology Forum consensus.

The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence‐based and expert‐based recommendations (S1 level).

The European baseline series in 10 European Countries, 2005/2006 : results of the European Surveillance System on Contact Allergies (ESSCA)

Background: Continual surveillance based on patch test results has proved useful for the identification of contact allergy.

Rosacea: A study of clinical patterns, blood flow, and the role of Demodex folliculorum

BACKGROUND Rosacea is a common facial eruption that has various clinical presentations. OBJECTIVE We studied blood flow in lesional skin and explored the role of Demodex folliculorum in patients with rosacea. METHODS A survey of clinical presentations was made in 108 patients with rosacea. Facial blood flow was studied by laser-Doppler flowmetry. The presence of Demodex was determined by microscopy of skin samples. RESULTS The sex incidence was equal. The incidence peaked in the fourth and seventh decades of life. Lymphedema was common and was seen in 26 patients. Rhinophyma was present in 15 patients, mostly men. Eleven patients were black, an unexpectedly high number. Laser-Doppler flowmetry showed that lesional blood flow was three to four times that of control subjects. Demodex folliculorum was found in 20 of 25 rosacea patients examined but in only 2 of 20 control subjects. CONCLUSION The findings indicate that the papillary dermal vasculature is dilated in rosacea. Demodex may be present. These findings give no definitive clue as to the origin of the disease.

A single-nucleotide polymorphism in the gene encoding lymphoid protein tyrosine phosphatase ( PTPN22 ) confers susceptibility to generalised vitiligo

Vitiligo is an acquired hypomelanotic skin disorder resulting from the loss of functional melanocytes from the cutaneous epidermis and autoimmunity has been suggested to play a part in its pathogenesis. Recently, the missense R620W polymorphism in the PTPN22 gene, which encodes lymphoid protein tyrosine phosphatase (LYP), has been associated with susceptibility to autoimmune disorders. The objective of this study was to ascertain if the disease-associated 1858T allele was also associated with generalised (nonsegmental) vitiligo and so the frequencies of the PTPN22 1858C/T alleles were investigated in 165 English patients with generalised vitiligo and 304 ethnically matched control subjects. The results indicated that the 1858T allele was significantly over-represented in the vitiligo patient group compared with the control cohort. Of 330 vitiligo alleles, 48 (14.5%) encoded the Trp620 variant compared to 52 of 608 (8.6%) control alleles (P=0.006; odds ratio=1.82, 95% confidence interval=1.17–2.82). The results indicate that the LYP missense R620W polymorphism may have an influence on the development of generalised vitiligo and provide further evidence for autoimmunity as an aetiological factor with respect to this disease.

The melanin-concentrating hormone receptor 1, a novel target of autoantibody responses in vitiligo

Vitiligo is a common depigmenting disorder resulting from the loss of melanocytes in the skin. The pathogenesis of the disease remains obscure, although autoimmune mechanisms are thought to be involved. Indeed, autoantibodies and autoreactive T lymphocytes that target melanocytes have been reported in some vitiligo patients. The objective of this study was to identify pigment cell antigens that are recognized by autoantibodies in vitiligo. Using IgG from vitiligo patients to screen a melanocyte cDNA phage-display library, we identified the melanin-concentrating hormone receptor 1 (MCHR1) as a novel autoantigen related to this disorder. Immunoreactivity against the receptor was demonstrated in vitiligo patient sera by using radiobinding assays. Among sera from healthy controls and from patients with autoimmune disease, none exhibited immunoreactivity to MCHR1, indicating a high disease specificity for Abs against the receptor. Inhibition of MCH binding to its receptor by IgG from vitiligo patients was also shown.