| 1. |
- Bergfors, Elisabet, 1945, et al.
(författare)
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Unexpectedly high incidence of persistent itching nodules and delayed hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer
- 2003
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Ingår i: Vaccine. - 0264-410X .- 0264-410X. ; 22:1, s. 64-9
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Tidskriftsartikel (refereegranskat)abstract
- During trials of aluminium adsorbed diphtheria-tetanus/acellular pertussis vaccines from a single producer, persistent itching nodules at the vaccination site were observed in an unexpectedly high frequency. The afflicted children were followed in a longitudinal observational study, and the presence of aluminium sensitization was investigated in the children with itching nodules and their symptomless siblings by patch tests. Itching nodules were found in 645 children out of about 76,000 vaccinees (0.8%) after both subcutaneous (s.c.) and intramuscular (i.m.) injection. The itching was intense and long-lasting. So far, 75% still have symptoms after a median duration of 4 years. Contact hypersensitivity to aluminium was demonstrated in 77% of the children with itching nodules and in 8% of the symptomless siblings who had received the same vaccines (P<0.001). Children with persistent itching nodules and/or aluminium sensitization should be warned about aluminium containing products (e.g. vaccines and antiperspirants). The reason for the high incidence of itching nodules after SSI vaccines is unknown and should be further investigated.
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| 2. |
- Enerbäck, Charlotta, 1965, et al.
(författare)
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S gene (Corneodesmosin) diversity and its relationship to psoriasis; high content of cSNP in the HLA-linked S gene
- 2000
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Ingår i: J Invest Dermatol. - 0022-202X .- 0022-202X. ; 114:6, s. 1158-63
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a heterogeneous disease in which several reports suggest the presence of a susceptibility gene in or in the proximity of the human leukocyte antigen complex in chromosome 6p. There is an association between HLA-Cw6 and young onset of the disease. The S gene (corneodesmosin), located 160 kb telomeric of HLA-C, is a strong candidate for psoriasis due to its reportedly exclusive expression in differentiating keratinocytes. We have studied this gene in a large Swedish psoriasis population and we report a strikingly high degree of polymorphism in the coding parts of the gene, 1 every 100 base pairs. We used a stratified approach to compare the polymorphic variants in patients and controls. A single nucleotide polymorphism in the coding region leading to an amino acid exchange (Ser-->Phe) that differed significantly between patients and controls was identified (position 619). Owing to a high allele frequency in a larger control group, however, and an insignificant influence of the variant on the age at onset distribution curve based on a large psoriasis population, we could not confirm that this coding single nucleotide polymorphism was involved in disease etiology. We also examined the single nucleotide polymorphism in position 1243, recently proposed to have an influence on the pathogenesis of the disease. This polymorphism showed less association to the disease as compared with the single nucleotide polymorphism at positions 619 and 722. Such a high degree of variation present also in an HLA gene which is not involved in immune response indicates the difficulty involved in assessing the role of a specific allele in the pathogenesis of a complex disease in this region. A strong association effect due to linkage disequilibrium in an extended region in the HLA complex is also a complicating factor.
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| 3. |
- Enerbäck, Charlotta, 1965, et al.
(författare)
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Stronger association with HLA-Cw6 than with corneodesmosin (S-gene) polymorphisms in Swedish psoriasis patients.
- 2000
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Ingår i: Archives of dermatological research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 292:11, s. 525-30
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis vulgaris is strongly associated with certain human leukocyte antigens, especially in early onset. The purpose of this study was to study the HLA-Cw6 allele and its contribution to disease susceptibility in a set of 104 families with at least two affected siblings. A sequencing method was utilized to examine the two exons that build up the antigen binding site of the C locus receptor. DNA from patients homozygous for Cw6 based on haplotype information were sequenced. The results confirmed the identity of the Cw6 allele in affected individuals with the consensus sequence for Cw*0602. We screened the set of families for psoriasis patients homozygous for Cw6 and found 11 individuals with a mean age at onset of 16.1 years. The corresponding figure for the Cw6 heterozygotes was 18.45 years and for the Cw6-negatives 22.36 years. This is indicative of a gene dose effect. We performed a transmission disequilibrium test (TDT) on the Cw6 allele per se, used as a biallelic marker. The analysis resulted in a P-value of 5.3 x 10(-17) (t167/nt45). This greatly exceeds our previous results of a TDT in the region, including microsatellite markers and single nucleotide polymorphisms (SNPs) in the coding part of the S gene (corneodesmosin), which is a suggested candidate gene in the region. The maximum nonparametric linkage (NPL) value was also reached using HLA-C as a marker. We conclude that Cw6 is the allele which shows the highest degree of association with psoriasis in our set of families and we propose that it directly influences the age at onset of the disease rather than increasing the genetic load in accordance with a polygenic theory.
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| 4. |
- Hewett, D., et al.
(författare)
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Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map
- 2002
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 0888-7543. ; 79:3, s. 305-14
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.
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| 5. |
- Inerot, Annica, 1949
(författare)
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Population genetic studies of psoriasis
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psoriasis is a genetically determined, common skin disease affecting about 3 % of the population. The inheritance pattern has earlier been unclear. In collaboration with the Swedish Psoriasis Association, we have collected information on the occurrence of psoriasis in the families of 11,366 members of the Association.Analysis of the answers to a questionnaire showed that 64% of all probands had no parents with psoriasis. The distribution of psoriasis in the parents, the siblings and among the children of probands was compatible with an autosomal recessive inheritance. The cumulative incidence of psoriasis in the elderly can be estimated to 5% and the gene frequency in the population to 25%.Analysis of the ages of onset shows that there is a peak of onset in puberty and that women develop the disease earlier than men. There was a correlation of the onset ages between siblings. Assuming a recessive inheritance, we have calculated the gene frequencies for different onset ages. The earliest onset age, in puberty, is found to have the highest gene frequency, 25%.The risk of acquiring psoriasis depending on the occurrence of psoriasis in the family has been determined empirically. The life-time risk varies from 24%, which is the risk if one sibling already has the disease, to 83%, which is the risk if both parents and one sibling are affected. The risk of getting psoriasis at a certain age is dependent on the age at onset of psoriasis in the affected parent.Family members from 310 families have been examined, altogether 1217 individuals. The body location and extent of psoriasis have been recorded. Remission of the skin disease was found in 13.5% at examination. The accuracy of diagnosis of psoriasis given by the proband was high. We compared concomitant diseases, in the cardiovascular, neurological and endocrine systems, and in joints, as well as iritis and inflammatory bowel disease, in the sibling generation. We found a strong association with joint complaints in persons with psoriasis. For the rest of the disorders studied, we could not find any significant difference. Presence of HLA-Cw6 seemed to protect against diabetes mellitus.
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| 6. |
- Inerot, Annica, 1949, et al.
(författare)
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Symptoms and signs reported during patch testing
- 2000
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Ingår i: Am J Contact Dermat. - 1046-199X. ; 11:1, s. 49-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:In a pilot questionnaire study, there was a high frequency of subjective complaints and distant skin reactions during patch testing as reported at the day of test reading, particularly in female patients. OBJECTIVE: To document in a controlled study possible side-effects of a generalized nature occurring during the test procedure. METHODS: A questionnaire study on symptoms and signs reported at application and at reading of standard patch tests was conducted with 401 patients, with the patients serving as their own controls. RESULTS: An eczematous flare-up during patch testing was observed in 3.7% of the patients. There were plenty of different symptoms of malaise but, with one exception (itch on the back), the number of symptoms tended to be less on the day of reading than on the day of application of the tests. This held true also for itch occurring in the patients' dermatitis. There was no statistical correlation between symptoms and signs on the one hand and positive patch tests on the other. CONCLUSION: Distant skin reactions and impairment of general health occurring during patch testing are often reported at the time of test reading. However, with the exception of itch on the back, symptoms and signs are rather less common after the application of patch tests than before.
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| 7. |
- Lindberg, Magnus, et al.
(författare)
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Are adverse skin reactions to cosmetics underestimated in the clinical assessment of contact dermatitis? A prospective study among 1075 patients attending Swedish patch test clinics.
- 2004
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 0001-5555. ; 84:4, s. 291-295
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Tidskriftsartikel (refereegranskat)abstract
- It is known that cosmetics and skin care products can cause adverse skin reactions. However, the frequency of adverse reactions reported to the Medical Product Agency (MPA) in Sweden is low. The purpose of the present study was to evaluate the occurrence of adverse skin reactions to cosmetics among patients referred for standard patch testing owing to suspected contact dermatitis in general, most frequently hand eczema. Consecutive patients at four patch test clinics in Sweden were invited to participate; 1075 were included. Of these, 47.3% (54.2% women and 30.8% men) reported current or previous adverse skin reactions to cosmetics and skin care products. This group showed significantly more positive patch test reactions, a higher prevalence of atopic dermatitis and the dermatitis was more frequently located in the face and neck region. Our results show that patients referred for standard patch testing have--or have had--a large proportion of self-reported adverse reactions to cosmetics or skin care products. We conclude that among patients with suspected contact dermatitis, adverse reactions to cosmetics can be a more important aetiological and/or complicating factor than is commonly acknowledged and that the reporting of such reactions to the MPA probably can be improved.
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