Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43.

Dominant transmission of multiple uterine and cutaneous smooth-muscle tumors is seen in the disorder multiple leiomyomatosis (ML). We undertook a genomewide screen of 11 families segregating ML and found evidence for linkage to chromosome 1q42.3-q43 (maximum multipoint LOD score 5.40). Haplotype construction and analysis of recombinations permitted the minimal interval containing the locus, which we have designated "MCUL1," to be refined to an approximately 14-cM region flanked by markers D1S517 and D1S2842. Allelic-loss studies of tumors indicated that MCUL1 may act as a tumor suppressor. Identification of MCUL1 should have wide interest, since this gene may harbor low-penetrance variants predisposing to the common form of uterine fibroids and/or may undergo somatic mutation in sporadic leiomyomata.

Heterozygous germline missense mutation in the p63 gene underlying EEC syndrome.

Mutations in the p63 gene have recently been delineated as the molecular basis for some cases of the ectrodactyly, ectodermal dysplasia and cleft lip/palate (EEC) syndrome, an autosomal dominant disorder (MIM 129900). In this report, we describe a 35-year-old woman with EEC syndrome and document a heterozygous germline missense mutation, R304W, in exon 8 of the p63 gene. As with most other p63 mutations in EEC syndrome, this mutation has arisen de novo and is located within the core DNA-binding domain of p63. Identification of this mutation has implications for genetic counselling and the feasibility of future DNA-based prenatal diagnosis in this individual.

Eosinophilic spongiosis in association with bullous pemphigoid and chronic lymphocytic leukaemia.

We report the onset of an unusual blistering eruption following a diagnosis of B-cell chronic lymphocytic leukaemia (CLL). The histology consistently showed eosinophilic spongiosis, but the diagnosis of bullous pemphigoid was only confirmed after 13 years by repeated immunofluorescence studies. The occurrence of subepidermal blistering diseases in association with B-cell lymphoproliferative disorders is rare; a recent study showed that the majority of these cases are epidermolysis bullosa acquisita, confirmed by immunological studies. Only two cases of immunofluorescence-proven bullous pemphigoid in association with CLL have been previously reported.

Validation of the U.K. diagnostic criteria for atopic dermatitis in a population setting. U.K. Diagnostic Criteria for Atopic Dermatitis Working Party.

One reason why so little is known about the epidemiology of atopic dermatitis (AD) is lack of suitable diagnostic criteria. A simple list of diagnostic criteria for AD for use in epidemiological studies has recently been developed by a U.K. working party. These have performed well in hospital validation studies of subjects with skin diseases. This study sought to validate the newly proposed criteria for AD in a population setting by conducting a cross-sectional survey of 695 schoolchildren aged 3-11 years in three randomly selected primary schools in West Lambeth, London. As a point prevalence measure, the U.K. criteria had a sensitivity of 70%, a specificity of 93%, and a positive predictive value of 47% when compared with a dermatologist's examination findings. Subsequent analysis suggested that most children classified as false positives had suffered from AD in the last year, but were inactive at the time of examination. When adjusted for these cases, the sensitivity and specificity increased to 80 and 97%, respectively, corresponding to positive and negative predictive values of 80 and 97%, respectively. The U.K. diagnostic criteria for AD appear to work well as a 1-year period prevalence measure in London schoolchildren. Further validation in adults and other countries are needed.

Infraorbital crease, ethnic group, and atopic dermatitis.

BACKGROUND AND DESIGN: The usefulness of a prominent infraorbital skin crease as a marker of atopic dermatitis (AD) was examined in 160 consecutive children aged 3 to 11 years in a population setting of a primary school in London, England. Infraorbital crease was recorded by two trained observers according to a strict protocol, and AD was determined by an independent dermatologist who was blinded to the study design. RESULTS: A prominent infraorbital crease was present in only four (27%) of 15 children with AD, compared with 49 (34%) of 145 children who did not have AD (P = .80). A prominent crease was a common finding in black children, even in the absence of AD, affecting 49% (34/69) of normal black children and 25% (11/44) of white children (P = .02). Interobserver agreement for the presence of infraorbital crease was low, with a kappa value of 0.38 (95% confidence interval, 0.23 to 0.53). CONCLUSIONS: While infraorbital crease may be of some use in diagnosing individual cases of AD in a hospital setting, it may be less useful in population-based studies because of its poor validity and repeatability. Studies that still use this sign as an indication of allergy need to take ethnic group differences into account.

London-born black Caribbean children are at increased risk of atopic dermatitis.

BACKGROUND: Previous reports suggest that atopic dermatitis is more common in black Caribbean children born in the United Kingdom than in white children. It is unclear whether these differences are caused by selection bias or variations in the use of the word "eczema" in the groups studied. OBJECTIVE: Our objective was to explore ethnic group differences in the prevalence of atopic dermatitis in London schoolchildren. METHODS: A cross-sectional prevalence survey of 693 junior school children in three schools was performed. Atopic dermatitis was defined in three ways: (1) by a dermatologist, (2) by visible flexural dermatitis as recorded by an independent observer, and (3) by a history of flexural dermatitis according to the child's parents. RESULTS: The prevalence of atopic dermatitis according to examination by a dermatologist was 16.3% in black Caribbean children and 8.7% in white children. This increased risk was present for different methods of defining of a atopic dermatitis and persisted after adjustment for potential confounders. CONCLUSION: London-born black Caribbean children appear to be at an increased risk of having atopic dermatitis.

The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis.

A working party of 13 dermatologists, two family practitioners and a paediatrician was assembled, with the aim of developing a minimum list of reliable discriminators for atopic dermatitis. Each physician was asked to select 10 consecutive new cases of unequivocal mild to moderate atopic dermatitis and 10 controls with other inflammatory dermatoses. Each subject was examined by two independent observers, who were blind to the clinical diagnosis and study aim, with regard to 31 clinically useful diagnostic features for atopic dermatitis. Two hundred and twenty-four patients were studied (120 cases and 102 controls). Using the key physician's clinical diagnosis as a gold standard, the sensitivity and specificity of each of the 31 diagnostic criteria were tested. Using multiple logistic regression techniques, a minimum set of diagnostic criteria for atopic dermatitis was derived. These were: history of flexural involvement, history of a dry skin, onset under the age of 2, personal history of asthma, history of a pruritic skin condition, and visible flexural dermatitis. Adjustment for age, sex, region, social class and ethnic group did not alter the choice of final criteria. The discriminatory value of these criteria was also satisfactory when tested against a further sample of 150 patients drawn from the community, who did not have skin disease.

The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. III. Independent hospital validation.

In order to qualify as a case of atopic dermatitis, we propose that an individual must have an itchy skin condition plus three or more of the following: history of flexural involvement, a history of asthma/hay fever, a history of a generalized dry skin, onset of rash under the age of 2 years, or visible flexural dermatitis. When tested in an independent sample of 200 consecutive dermatology outpatients of all ages, this arrangement of the diagnostic criteria achieved 69% sensitivity and 96% specificity when validated against physician's diagnosis. Based on the findings of this first exercise, minor modifications in the wording of the criteria were undertaken, and these were tested on a sample of 114 consecutive children attending out-patient paediatric dermatology clinics. Overall discrimination improved, with a sensitivity of 85% and specificity of 96%. The simplified criteria are easy to use, take under 2 min per patient to ascertain, and do not require subjects to undress. These two independent validation studies suggest that the newly proposed criteria for atopic dermatitis perform reasonably well in hospital out-patient patients. Further validation in community settings and in developing countries is needed.

Livedo reticularis and massive thoracoabdominal aneurysm.

Cholesterol crystal embolization arising from an atheromatous aortic aneurysm is a potentially treatable condition. We report a 55-year old man with a sudden onset of painful livedo reticularis of the buttocks and lower limbs secondary to a massive thoracoabdominal aortic aneurysm, discovered incidentally when the patient underwent a liver ultrasound test. The diagnosis of cholesterol crystal embolization of the skin requires a high degree of clinical suspicion. Abdominal ultrasound should be considered in the routine assessment of lower limb livedo reticularis.