John Wilkinson

Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome.

We describe here eleven different mutations in SPINK5, encoding the serine protease inhibitor LEKTI, in 13 families with Netherton syndrome (NS, MIM256500). Most of these mutations predict premature termination codons. These results disclose a critical role of SPINK5 in epidermal barrier function and immunity, and suggest a new pathway for high serum IgE levels and atopic manifestations.

Monitoring levels of preservative sensitivity in Europe - A 10-year overview (1991-2000)

A 10‐year multicentre analysis of the frequency of sensitivity to common preservatives collected in 16 centres in 11 countries has shown stable but persisting high levels of sensitivity to formaldehyde and 5‐chloro‐2‐methyl‐4‐isothiazolin‐3‐oneu2003+u20032‐methyl‐4‐isothiazolin‐3‐one (MCI/MI). It has also revealed a significant increase in the level of reactivity to methyldibromoglutaronitrile (MDBGN) from 0.7% in 1991 to 3.5% in 2000. The current high level of sensitivity to MDBGN requires an urgent safety re‐evaluation and risk assessment update along with consideration of immediate lowering of use concentrations, especially in leave‐on products.

Fragrance contact dermatitis: a worldwide multicenter investigation (Part II)

The purpose of this study was to determine the frequency of responses to selected fragrance materials in patients who were fragrance sensitive. 178 patients were evaluated in 8 centers worldwide with a fragrance mix (FM) and 20 other fragrance materials. Reaction to the fragrance mixture (FM) occurred in 78.7% of the subjects. Substances reacting at a rate of 2% or higher included jasmine absolute, geranium oil bourbon, l‐citronellol, spearmint oil, 1,3,4,6,7,8‐hexahydro‐4,6,6,7,8,8‐hexamethylcyclopenta‐γ‐2‐benzopyran, omega‐6‐hexadecenlactone, dimethyltetrahydrobenzaldehyde (isomer mixture), and α‐amylcinnamaldehyde. These chemicals should be furthur evaluated to corroborate their allergenicity. We are constantly looking for new fragrance allergens to extend the diagnostic capability of the fragrance mix (FM).

Fragrance contact dermatitis: A worldwide multicenter investigation (Part I)☆

OBJECTIVEnThe aim of this study was to determine the prevalence of responses to selected fragrance materials in patients with suspect fragrance allergy and to evaluate risk factors and associations with such responses. The validity of using specific fragrance ingredients versus a mixture of fragrances was evaluated in terms of predicting allergy to different fragrance ingredients.nnnMETHODSnOne hundred sixty-seven subjects were evaluated in seven centers worldwide with a fragrance mix, the eight ingredients in the fragrance mixture, six other well-known fragrance allergens, balsam of Peru, and 15 lesser studied fragrance materials.nnnRESULTSnThe age of the patients was 44.9 +/- 17.5 years (mean +/- SD). More than 85% were women. A relatively high proportion gave a past history of atopic disease. Facial eruptions (40%) and hand involvement (26.7%) were the most common topographic sites. All but 4 of the 35 fragrance materials produced a positive response in > 1%. A reaction to fragrance mix occurred in 47.3%. Seven of the 34 ingredients tested produced an allergic response in more than 10% of those tested. Men were more likely than women to exhibit a positive response to five fragrance ingredients. White persons were more likely to react to perfume mix (52.8% versus 25.3%) and certain ingredients in the mix than Asian persons. Allergy to benzyl salicylate was more common in Japan than in Europe or the United States.nnnCONCLUSIONnThe age at which patients with perfume allergy present for evaluation is similar to that of other contactants. Atopic individuals may be overrepresented in this group of patients. Face involvement is likely. White persons are more likely to react to fragrance mix, whereas in Asian patients benzyl salicylate was a more frequent allergen. Fragrance mix corrected with 85.6% of positive responses to fragrance ingredients. The addition of ylang ylang oil, narcissus oil, and sandalwood oil to fragrance mix would be expected to pick up 94.2% with positive responses to fragrance materials; adding balsam of Peru increases this to 96%.

Localization of the Netherton Syndrome Gene to Chromosome 5q32, by Linkage Analysis and Homozygosity Mapping

Netherton syndrome (NS [MIM 256500]) is a rare and severe autosomal recessive disorder characterized by congenital ichthyosis, a specific hair-shaft defect (trichorrhexis invaginata), and atopic manifestations. Infants with this syndrome often fail to thrive; life-threatening complications result in high postnatal mortality. We report the assignment of the NS gene to chromosome 5q32, by linkage analysis and homozygosity mapping in 20 families affected with NS. Significant evidence for linkage (maximum multipoint LOD score 10.11) between markers D5S2017 and D5S413 was obtained, with no evidence for locus heterogeneity. Analysis of critical recombinants mapped the NS locus between markers D5S463 and D5S2013, within an <3.5-cM genetic interval. The NS locus is telomeric to the cytokine gene cluster in 5q31. The five known genes encoding casein kinase Ialpha, the alpha subunit of retinal rod cGMP phosphodiesterase, the regulator of mitotic-spindle assembly, adrenergic receptor beta2, and the diastrophic dysplasia sulfate-transporter gene, as well as the 38 expressed-sequence tags mapped within the critical region, are not obvious candidates. Our study is the first step toward the positional cloning of the NS gene. This finding promises a better understanding of the molecular mechanisms that control epidermal differentiation and immunity.

Cosmetic allergy: incidence, diagnosis, and management.

A recent epidemiologic survey in the UK revealed that 23% of women and 13.8% of men experience some sort of adverse reaction to a personal care product over the course of a year. Although most of these reactions may be due to subjective sensory irritation, various studies reveal that up to 10% of dermatologic patients who are patch tested are allergic to cosmetic products or their constituent ingredients. Causative products include deodorants and perfumes, skin care products, hair care products, and nail cosmetics.Allergic contact dermatitis mainly results from fragrance chemicals and preservatives. Recent work has suggested that additional fragrance chemicals may need to be tested in order to identify those patients ‘missed’ by the current fragrance mix; in particular, hydroxy-isohexyl-3-cyclohexene carboxaldehyde (HMPPC Lyral®) has been singled out as an important sensitizing agent. The increased usage of natural fragrances and botanic extracts can also cause problems in their own right or through co-reactivity. The preservative methyldibromo glutaronitrile has also been recognized as an increasingly important sensitizer in Europe, which has led to the recent recommendation that it should be prohibited from ‘leave-on’ products until information on ‘safe’ consumer levels becomes available. Other emerging allergens include UV filters, tosylamide/formaldehyde resin, and nail acrylates.The diagnosis of cosmetic allergy should be confirmed with patch testing, including testing of ‘whole’ products, when necessary, and repeat open application tests can be used to confirm the relevance of reactions in cases of doubt.

Subcorneal pustular dermatosis

rare condition is still controversial and little is really known about its etiology or pathogenesis. This partly reflects the confusion that has arisen in the literature from reports that have included patients outside the original diagnostic criteria or have misinterpreted the histology of the subcorneal pustule. These have most likely represented cases of pustular psoriasis or pemphigus, with which subcorneal pustular dermatosis shares overlapping clinical and histological features. A significant proportion of reports, particularly the early ones, additionally lack sufficient detail to allow a critical review. Modern investigative techniques, however, have allowed the identification of a possible subgroup, subcorneal pustular dermatosis type IgA pemphigus,2 also known as intraepidermal IgA pustulosis. It is on this that the latest reports have focused. Our recent experience has once again raised the long-standing issue as to whether some cases of subcorneal pustular dermatosis represent a variant of psoriasis. This is an unanswered controversy that has faded from the literature in recent times, perhaps indicating that subcorneal pustular dermatosis is now more generally accepted as an entity. In light of these developments the question arises as to whether subcorneal pustular dermatosis might represent an entity with more than one etiology. Pathogenesis

Monitoring the European standard series in 10 centres 1996-2000

A 5‐year retrospective study of the frequency of sensitization to the 25 allergens of the European standard series (ESS) was conducted in 10 centres in 8 European countries. Included were the results of 26u2003210 patients. The range in sensitivities differed moderately between the centres. Combining results of different centres and drawing conclusions on incidences can be done only with great care. The information on the ranking of the allergens and their sensitization incidence in the clinics are useful for decisions on the future composition of the standard series. The ESS is still a valid screening tool, and no substances should be deleted.

Oral prednisone suppresses allergic but not irritant patch test reactions in individuals hypersensitive to nickel

A multicentre, randomized, double‐blind, crossover study was designed to investigate the effects of prednisone on allergic and irritant patch test reactions. 24 subjects with known allergy to nickel were recruited and patch tested with a nickel sulfate dilution series in aqueous solution, 5% nickel sulfate in petrolatum and 2 dilution series of the irritants nonanoic acid and sodium lauryl sulfate. The subjects were tested ×2, both during treatment with prednisone 20u2003mg oral daily and during placebo treatment. The total number of positive nickel patch test reactions decreased significantly in patients during prednisone treatment. The threshold concentration to elicit a patch test reaction increased and the overall degree of reactivity to nickel sulfate shifted towards weaker reactions. The effect of prednisone treatment on the response to irritants was divergent with both increased and decreased numbers of reactions, although there were no statistically significant differences compared with placebo. It is concluded that oral treatment with prednisone suppresses patch test reactivity to nickel, but not to the irritants tested.

A study of new fragrance mixtures.

OBJECTIVEnTo determine the frequency of responses to four mixtures of fragrance materials in routine clinic patients undergoing patch testing for suspect allergic contact dermatitis. The validity of using fragrance mixtures alone, or in combination, was evaluated in terms of predicting allergy to fragrance judged on the basis of finding a response to at least one of the fragrance mixtures.nnnMETHODSnA total of 752 subjects were patch tested in five centers worldwide with (1) fragrance mix 8% (FM), (2) balsam of Peru 25%, (3) a mixture of seven of the eight FM 8% ingredients and other fragrance ingredients including jasmine absolute (jasmine/FM mix), and (4) a mixture of five selected natural fragrance ingredients (NM).nnnRESULTSnOf 752 subjects, 100 (13%) had positive patch tests to at least one of the four fragrance mixtures. The age of the patients was 45.2 +/- 18.3 years (mean +/- SD). Ninety-six percent were Caucasian. Facial eruptions and hand involvement were the most common topographic sites. Of subjects exhibiting a positive response, 67% reacted to FM, 63% to the jasmine/FM mix, 47% to the NM, and 38% to balsam of Peru. Testing with FM and NM identified 84% of the perfume-allergic patients. FM 8% tested simultaneously with the jasmine/FM mix identified 86% of the perfume-allergic patients. Testing simultaneously with three test materials combining either the NM or the jasmine/FM mix with balsam of Peru and FM identified 95% of the perfume-sensitive patients.nnnCONCLUSIONSnThe simultaneous testing of NM or jasmine/FM mix, in addition to the conventional use of FM 8% and balsam of Peru, increases the sensitivity of testing for fragrance allergy from 81% to 95%.