Search PubMed⌕ Search

Biomedical subjects

J P McFadden

Publications and source records attributed to J P McFadden.

At least 19 recordsLinked to original sources

Simultaneous sensitivity to fragrances.

BACKGROUND: Cinnamal/cinnamic alcohol and isoeugenol/eugenol are pairs of related fragrance chemicals found in Fragrance Mix I (FM I), and thus are routinely tested in combination with other fragrances in the European standard patch test series. Their close structural similarity makes the occurrence of simultaneous sensitivity within these chemical pairs likely, although at present there are no robust data to support this hypothesis. OBJECTIVES: To establish the frequency of simultaneous reactions to these fragrance chemicals in patients with suspected fragrance allergy attending a contact dermatitis clinic; to provide evidence in support of proposed metabolic pathways; and to determine whether including all four separately in FM I is necessary to avoid missing a diagnosis of fragrance allergy. METHODS: We analysed retrospectively the records of patients patch tested to the European standard series during the 15-year period 1984-98 for positive reactions to FM I. In a subset of patients tested to the constituents of FM I, positive reactions to cinnamal, cinnamic alcohol, isoeugenol and eugenol were sought. Data were analysed using 2x2 contingency tables (Fisher's exact test). RESULTS: During this period, 23,660 patients were tested to the European standard series, of whom 1811 (7.7%) had positive reactions to FM I. Of the 1112 patients tested to the constituents of FM I, 934 had positive reactions to at least one constituent (total 1324 positive reactions to constituents). Of these 934, 826 also had positive reactions to FM I itself; 108 were negative to FM I but reacted to one or more of its constituents. One hundred and seventy-eight patients did not react to any of the breakdown constituents of FM I; 34 of these had positive reactions to FM I itself. Of 139 patients allergic to cinnamic alcohol, 87 were also allergic to cinnamal (63%), compared with 108 (11.1%) of 973 cinnamic alcohol-negative patients (P<0.00001). Of 231 patients allergic to isoeugenol, 50 were also allergic to eugenol (22%), vs. 109 (12.4%) of 881 isoeugenol-negative patients (P=0.0002). CONCLUSIONS: These data support in vitro experiments indicating that cinnamal and cinnamic alcohol may generate a common hapten and are consistent with the view that simultaneous sensitization to isoeugenol and eugenol occurs to a limited extent, despite their being metabolized via different pathways. In view of the substantial number of isolated reactions to each of these fragrance chemicals, all four should continue to be included separately as constituents of FM I.

Acrolein↗

p-Phenylenediamine allergy: the role of Bandrowski's base.

p-Phenylenediamine (PPD) is a commonly used hair-dye and a potent skin allergen. The mechanism of sensitization is unknown, as PPD is protein unreactive. We studied Bandrowski's base (BB), a PPD trimer, as well as 1,4-benzoquinone (BQ), a PPD hapten. PPD patch-test positive patients were patch-tested to BB and BQ. All tests were negative to 0.01% BQ and 0.01% BB. Five of 14 (35.7%) tested had true positive reactions to 0.1% BQ. One percent BQ was found to be irritant. Seven of 43 tested (16%) were positive to either 0.1% or 1% BB. The positive reactions to BB were weak, even when PPD reactions were strong. Mice lymph node assay gave EC3 values of 0.14% for PPD compared with 0.03% for BB. Therefore, BB is approximately 10 times more potent than PPD, taking into account the molarity. We suggest that while PPD may act as a prohapten, there is probably a spectrum of antigenic determinants in vivo. BB may be bound or metabolized by keratinocytes before it reacts with Langerhans cells.

Animals↗

Role of land-surface changes in arctic summer warming.

A major challenge in predicting Earth's future climate state is to understand feedbacks that alter greenhouse-gas forcing. Here we synthesize field data from arctic Alaska, showing that terrestrial changes in summer albedo contribute substantially to recent high-latitude warming trends. Pronounced terrestrial summer warming in arctic Alaska correlates with a lengthening of the snow-free season that has increased atmospheric heating locally by about 3 watts per square meter per decade (similar in magnitude to the regional heating expected over multiple decades from a doubling of atmospheric CO2). The continuation of current trends in shrub and tree expansion could further amplify this atmospheric heating by two to seven times.

Alaska↗

Analysis of para-phenylenediamine allergic patients in relation to strength of patch test reaction.

BACKGROUND: Despite having a positive patch test reaction to para-phenylenediamine (PPD), some patients continue to dye their hair, while others are forced to give up or abandon this practice. This difference in patient behaviour could be due to the degree of sensitization. OBJECTIVES: To establish whether the ability to continue dyeing hair in PPD allergic patients is related to the strength of patch test reaction. To note differences in other clinical features in relation to the strength of patch test reaction. METHODS: We analysed retrospectively the patch test records of 400 sequential PPD-positive patients for the strength of patch test reaction (+, ++, +++) and different clinical features. Data were analysed using Cochran-Mantel-Haenszel chi2 tests. RESULTS: There was a strong linear relationship between the strength of patch test reaction and continuation with hair dyeing. Patients were more likely to report a history of hair dye reaction with increasing strength of patch test reaction. There was no difference in strength of patch test reaction in relation to age, site of rash, occupation (hairdressing) or history of atopic eczema. Overall concomitant reactivity with related aromatic amine allergens (benzocaine, N-isopropyl-N-phenyl-para-phenylenediamine, para-aminobenzoic acid) was infrequent. CONCLUSIONS: Patients with stronger patch test reactions (++, +++) are more likely to have a clear history of reacting to hair dye and are less likely to still be dyeing their hair.

Adolescent↗

Immediate contact reactions to fragrance mix constituents and Myroxylon pereirae resin.

We have studied patients who have positive-patch test reactions to fragrance-allergic screening substances fragrance mix (FM) or Myroxylon pereirae resin (balsam of Peru) for immediate contact reactions to the standard FM, the constituents of the FM and Myroxylon pereirae resin. In the fragrance-positive subjects (n = 60), there were positive immediate contact reactions to Myroxylon pereirae resin in 56.6% and to FM in 11.6%. In a control group (n = 50) of eczematous, patch test-negative patients there were positive immediate reactions to Myroxylon pereirae resin in 58.0% subjects and to FM in 12.0%. The absence of a significant difference between the fragrance-allergic group and control group is in keeping with a non-immunological basis for the majority of the immediate reactions seen.

Adult↗

Intra-individual variation of irritant threshold and relationship to transepidermal water loss measurement of skin irritation.

Irritant susceptibility studies have used either visual assessment or transepidermal water loss (TEWL) to determine subject response. We have developed a visual assessment method which determines subject irritant threshold. We examined the relationship between sodium lauryl sulfate (SLS) irritant threshold and TEWL measurements from normal skin and SLS patch tests. 19 subjects were recruited. The irritant threshold of each subject was measured and TEWL measurements made from the applied SLS patch tests. Individuals with a lower irritant threshold (easily irritated skin) had elevated TEWL levels compared to those with higher thresholds. The irritant threshold test had a low intraindividual variation. This study showed that the 2 methods grouped patients in a similar manner. The variation seen may reflect the different outcomes measured: irritant threshold visually assesses the skin inflammatory response while TEWL measures skin barrier modification.

Adult↗

Lymphomatoid contact dermatitis to para-tertyl-butyl phenol resin.

Lymphomatoid contact dermatitis refers to the relatively little known phenomenon of allergic contact dermatitis producing histological features suggestive of cutaneous T-cell lymphoma. We report the first case of lymphomatoid contact dermatitis in response to para-tertyl-butyl phenol resin.

Aged↗

The frequency of fragrance allergy in patch-tested patients increases with their age.

BACKGROUND: The most likely age of sensitization to fragrance chemicals is unknown. OBJECTIVES: To investigate the frequency of allergy to the 8% fragrance mix (FM) in each decade of life in patients undergoing patch testing for the investigation of skin symptoms. METHODS: Patients (n = 23 846; 14 104 female and 9742 male) underwent patch testing to a standard series between 1 January 1984 and 31 December 1998. All data were recorded on a computerized database. RESULTS: We found that 8.4% of females and 6.4% of males were allergic to the FM. The frequency of fragrance allergy was low in the first two decades of life (2.5-3.4%). It gradually increased in females after the age of 20 years to peak in the 60s at 14.4% of those tested, with a decline to 11.6% in the 80s. The prevalence in males rose more slowly and peaked at 13.7% in the 70s, declining to 10.8% in the 80s. The youngest patients sensitized were aged 2 years. CONCLUSIONS: These findings support the hypothesis that allergy to fragrance results from a combination of repeated environmental exposure and age-related susceptibility factors.

Adolescent↗

Relationship between 2,4-dinitrochlorobenzene elicitation responses and individual irritant threshold.

Contact dermatitis shows significant interindividual variation. We studied the relationship between an individual's irritant threshold and the elicitation of experimentally induced allergic sensitization. The results suggest that there is an association between reactivity to an irritant and the likelihood of positive elicitation reactions to lower hapten concentrations. This novel finding would be compatible with the proposal that contact allergy is best explained using a danger model with cutaneous irritancy determining sensitization. However, the enhanced allergic reactivity of individuals with a lower irritant threshold was not apparent on visual inspection, suggesting that the determinants of skin reactivity to haptens are multifactorial.

Adult↗

Contaminating resin acids have not caused the high rate of sensitivity to oak moss.

Commercially available oak moss absolute patch test material has recently been shown to contain resin acids of the type found in colophony (colophonium). We wished to assess whether the high frequency of positive patch tests to oak moss absolute at this institute was likely to reflect significant contamination by resin acids. The rate of positive reactions to colophony among our oak moss-allergic patients patch tested during 1984-2000 was retrospectively investigated. 25395 patients were tested to the European standard series during this period and 1963 (7.7%) were allergic to the fragrance mix. 342 of these patients were allergic to oak moss absolute, of whom 73 (21.3%) were allergic to colophony. In comparison, 115 (13.4%) of 861 fragrance mix-positive but oak moss-negative patients were allergic to colophony (p = 0.0002, Fisher's exact test). This strongly statistically significant association between oak moss absolute and colophony shows only a small increase in rates of allergy to colophony in oak moss-positive patients. Thus we conclude that contaminating resin acids have not alone caused the high rate of sensitivity to oak moss.

Acids↗

Dose-time relationships for elicitation of contact allergy to para-phenylenediamine.

Skin-sensitizing chemicals exhibit dose-response relationships for the elicitation of contact dermatitis. Previously, considerable work has been carried out in which the elicitation of allergic skin reaction has been examined as a function of the applied concentration. However, the relationship between exposure time, dose and response has not been explored in any depth. The present work has extended our initial assessment of the relationship between both exposure time and concentration for para-phenylenediamine (PPD) in a group of 19 PPD-allergic volunteers. The results clearly demonstrate that a relationship exists between both exposure time and concentration. Positive responses to PPD were directly proportional to exposure time: at 5 min 16% responded; at 15 min, 38%; at 30 min, 50%; and at 120 min, 69%. A similar direct relationship was found between concentration of PPD and response: after 120 min, 22% of patients had responded to 0.01%, and 69% to 1% PPD. All exposures for 1 and 2 min were negative. Subsequent evaluation using repeated 5 min open application testing demonstrated a cumulative effect, as after 8 days 39% of the panel reacted, more than double the number that reacted to a single occluded 5-min treatment. It was noted that there was marked subject variability in exposure time and dose required to elicit an allergic response. These results are of relevance for the general interpretation of patch test data, especially with regard to risk assessment.

Adolescent↗