C.T.C. Kennedy

A serological mediator in chronic idiopathic urticaria--a clinical, immunological and histological evaluation.

Seven of twelve autologous sera from patients with chronic idiopathic urticaria re‐injected intradermally produced a weal at the site of injection. There was no response in 19 control subjects. Patients showing a positive response had a shorter duration of disease and shorter duration of spontaneous weals, and their urticaria was less likely to be exacerbated by pressure. There was some serological evidence of circulating immune complexes in both positive and negative responders to autologous serum, but only two showed complement abnormalities. When six of the serum‐positive patients were re‐tested after one year, five still showed a positive response with their original stored serum, but only two, whose disease remained active, were positive when challenged with freshly drawn serum, suggesting that a serum mediator is only present when the urticaria is active. A marked neutrophil infiltrate was seen within and around small dermal blood vessels at the injection site in the majority of urticaria patients but this appearance did not correlate with weal formation. In control subjects the cellular response was mild and mainly mononuclear.

Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis

Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of genetic hair loss. In a large Chinese family carrying MUHH, we identified a pathogenic initiation codon mutation in U2HR, an inhibitory upstream ORF in the 5′ UTR of the gene encoding the human hairless homolog (HR). U2HR is predicted to encode a 34–amino acid peptide that is highly conserved among mammals. In 18 more families from different ancestral groups, we identified a range of defects in U2HR, including loss of initiation, delayed termination codon and nonsense and missense mutations. Functional analysis showed that these classes of mutations all resulted in increased translation of the main HR physiological ORF. Our results establish the link between MUHH and U2HR, show that fine-tuning of HR protein levels is important in control of hair growth, and identify a potential mechanism for preventing hair loss or promoting hair removal.

A prospective study of the prevalence and incidence of atopic dermatitis in children aged 0–42 months

Background  There is strong evidence that the incidence and prevalence of atopic diseases is increasing. However, estimates of the prevalence of atopic dermatitis (AD) have varied greatly in the U.K. and most parts of the developed world.

The development of lichen sclerosus et atrophicus in monozygotic twin girls

The development of vulval lichen sclerosus et atrophicus in monozygotic twins is described. This is the first report of the occurrence of lichen sclerosus et atrophicus in two genetically identical individuals, and is considered to provide further evidence that inherited factors are of relevance in the aetiology of this disorder.

The Gene for Hypotrichosis of Marie Unna Maps between D8S258 and D8S298: Exclusion of the hr Gene by cDNA and Genomic Sequencing

Hypotrichosis of Marie Unna (MU) is an autosomal dominant hair-loss disorder with onset in childhood. A genomewide search for the gene was performed in a large Dutch family using 400 fluorescent microsatellite markers. Linkage was detected with marker D8S258, and analysis of this family and a further British kindred with additional markers in the region gave a combined maximum two-point LOD score of 13.42, with D8S560. Informative recombinants placed the MU gene in a 2.4-cM interval between markers D8S258 and D8S298. Recently, recessive mutations in the hr gene were reported in families with congenital atrichia, and this gene was previously mapped close to the MU interval. By radiation-hybrid mapping, we placed the hr gene close to D8S298 but were unable to exclude it from the MU interval. This, with the existence of the semidominant murine hr allele, prompted us to perform mutation analysis for this gene. Full-length sequencing of hr cDNA obtained from an affected individual showed no mutations. Similarly, screening of all exons of the hr gene amplified from the genomic DNA of an affected individual revealed no mutations. Analysis of expressed sequences and positional cloning of the MU locus is underway.

Association of parental eczema, hayfever, and asthma with atopic dermatitis in infancy: birth cohort study

Objective: To evaluate the association of parental history of atopic disease with childhood atopic dermatitis, and to examine the relative strength of associations with maternal and paternal disease. Design: Mothers were recruited to the Avon longitudinal study of parents and children (ALSPAC) from the eighth week of pregnancy. Before parturition, both parents were asked, separately, to report their lifetime history of eczema, asthma, and hayfever. Parents reported symptoms of atopic dermatitis in their children at ages 6, 18, 30, and 42 months. Results: Of 8530 children with complete information on rash at ages 6, 18, 30, and 42 months, 7969 had complete information on maternal atopic disease and 5658 on maternal and paternal atopic disease. There was a strong association between parental eczema and childhood atopic dermatitis: odds ratio 1.69 (95% confidence interval, 1.47 to 1.95) for maternal eczema only, 1.74 (1.44 to 2.09) for paternal eczema only, and 2.72 (2.09 to 3.53) for eczema in both parents. Associations with parental asthma or hayfever were attenuated after controlling for parental eczema. There was no evidence that associations with maternal atopy were stronger than with paternal. Conclusions: Associations between parents’ atopic disease and the risk of atopic dermatitis in offspring vary according to the type of atopic disease in the parents, but not according to parental sex. These results are at variance with previous studies reporting stronger associations with maternal than paternal atopy, and suggest that there is no “parent-of-origin” effect in atopic dermatitis. Parental eczema may be a better marker than parental asthma/hayfever in predisposing to childhood eczema.

Comparison of a hydrocolloid dressing and paraffin gauze in the treatment of venous ulcers.

In‐patients with venous leg ulcers showed increased healing rates with a hydrocolloid dressing (Granuflex®), as compared with a traditional paraffin gauze dressing (Jelonet®), in a randomized sequential crossover trial, although the difference was not statistically significant.

A fatal case of scleredema of Buschke

Summary Scleredema of Buschke is a rare disorder characterized by the development of areas of skin induration which usually resolve spontaneously. It is occasionally associated with a benign gammopathy, and rarely with myelomatosis. We describe B 60‐year‐old woman with extensive skin changes, who developed IgA myeloma. Unusually, her skin disease did not respond to conventional myeloma therapy. Death occurred as a consequence of the progressive skin disease.

Natural history of atopic dermatitis and its relationship to serum total immunoglobulin E in a population-based birth cohort study

We investigated the natural history of atopic dermatitis (AD) in a population‐based birth cohort and assessed whether children at risk of visible eczema at 5 years of age can be identified from total immunoglobulin E (IgE) levels measured at 8, 12 and 18 months. AD data collected included a whole body examination for visible eczema at 49 months (4 years) and 61 months (5 years) of age and parent completed questionnaire data throughout their early lives. Children were divided into four groups based on their natural history of early AD: persistent (AD at 1, 6, 18, 30 and 42 months, n = 34), intermittent early onset (before 18  months of age, n = 495), intermittent late onset (18–42 months of age, n = 273) and unaffected (n = 429). Visible eczema at 5 years of age was present in 12.2% (117/957) (95% confidence interval [CI] 10.1–14.3%) of the children. Levels of total IgE at 8, 12 and 18 months of age were associated with early onset of AD, but not with AD of later onset. For all four natural history groups, the geometric mean total IgE at 12 months was higher in those who subsequently had visible eczema than those who did not. However, the degree of overlap was such that total IgE at 12 months of age was a poor predictor of eczema at age five. A cutoff point of 78 kU/l had the highest positive predictive value for visible eczema at 5 years of age of 28.6%, with a sensitivity of 12% and specificity of 95%.

Idiopathic hypereosinophilic syndrome associated with cutaneous infarction and deep venous thrombosis.

Summary  We report a case of idiopathic hypereosinophilic syndrome (HES) presenting with cutaneous infarction and subsequent extensive deep vein thrombosis. The eosinophilia improved dramatically with systemic corticosteroid therapy. A variety of skin disorders have been associated with HES, although there are no previous reports of HES associated with cutaneous infarction. HES is a rare disorder characterized by a sustained overproduction of eosinophils and multisystem disease. The aetiology of the eosinophilia remains uncertain but clonal populations of abnormal T‐cells producing interleukin 5 may be implicated.