Annica Inerot

Age at onset and different types of psoriasis

Summary The age at onset of psoriasis has been analysed for 11,366 psoriasis patients. The age at onset for siblings of probands has been analysed for 805 probands having one affected sibling and for 1 79 probands having two affected siblings. The age at onset curve for all probands shows a dominating maximum at about puberty but also indications for two more maxima at about 30 and 50 years of age, respectively. A more relevant picture of the risk of getting psoriasis at different ages is obtained if the onset for old people having psoriasis is investigated. The three maxima come out more clearly in this case, and the puberty maximum is not so dominating. For the families with one proband and two affected siblings there is a statistically significant correlation (Plt;0·001) between the age at onset of the proband and of the siblings, and also between the siblings. The correlation coefficient is between 0·30 and 0·45. For the probands with one affected sibling, the ages at onset of the siblings mainly fall in the same range as those of the probands. These data indicate three groups of patients with respeel to age at onset. However, the overlap between the different groups is considerable. The data presented are compatible with three, possibly genetically different, variants of psoriasis vulgaris. By studying the occurrence of psoriasis among parents of the probands, the gene frequency can be estimated assuming a recessive mode of inheritance. It then turns out that the gene frequency of the group with the earliest age at onset has a gene frequency of about 0·25, the next earliest, 0·18, and the latest, 0·14.

Unexpectedly high incidence of persistent itching nodules and delayed hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer

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.

A population genetic study of psoriasis.

We present epidemiological data for 5197 families with psoriasis. Errors in reporting have been analysed. Analysis of the data provides indications of random mating with respect to whether the partner has the skin disease or not. Data on psoriasis among parents, siblings and children are provided, and particular attention has been paid to the age at onset of psoriasis. Psoriasis was present in the parents of about 36% of the probands. In families in which one or both parents have psoriasis, the occurrence of the disease among the siblings does not provide any information which differentiates between a dominant and recessive mode of inheritance, but is compatible with both. In families in which neither parent had psoriasis, provided there was a proband with psoriasis, the probability of the siblings suffering from psoriasis was close to 0.25, indicating a recessive mode of inheritance. The distribution of psoriasis among the parents of all probands, and among the children of probands, was also compatible with this mode of inheritance. The prevalence of psoriasis in the elderly was estimated to be about 5%, and the gene frequency in the whole population 25%.

Analysis of three suggested psoriasis susceptibility loci in a large Swedish set of families: confirmation of linkage to chromosome 6p (HLA region), and to 17q, but not to 4q.

Psoriasis is known to be a heterogeneous disease with so far three reported major psoriasis susceptibility loci on chromosome 4q, 6p and 17q. In this study we investigated three reported gene locations by nonparametric and parametric linkage analysis in a large family set consisting of 104 families (153 sib pairs) from Sweden. We could confirm linkage to chromosome 6p. A maximum heterogeneous lod score of 2.78 was reached at locus D6S276 (α = 0.60). Allelic association studies within the HLA region indicated linkage disequilibrium at locus TNFβ with a significant p value of 0.0009. Furthermore, we obtained weak evidence of linkage to the locus on chromosome 17q while no evidence of linkage could be found to the chromosome 4q region.

Genetic counselling in psoriasis: empirical data on psoriasis among first‐degree relatives of 3095 psoriatic probands

The risk of getting psoriasis dependent on the occurence of psoriasis in the family has been determined empirically. Altogether 3717 families with one or both parents who had psoriasis have been analysed with regard to the number of children with or without psoriasis. The lifetime risk of getting psoriasis if no parent, one parent or both parents have psoriasis is 0.04, 0.28 and 0.65, respectively. If there is already one affected child in the family, the corresponding risks are 0.24, 0.51 and 0.83, respectively. The risk of getting psoriasis before the age of 32 years is dependent on the age‐of‐onset of psoriasis in one affected parent.

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.

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.

Association of psoriasis to PGLYRP and SPRR genes at PSORS4 locus on 1q shows heterogeneity between Finnish, Swedish and Irish families.

Abstract:  A susceptibility locus for psoriasis, PSORS4, has been mapped to chromosome 1q21 in the region of the epidermal differentiation complex. The region has been refined to a 115 kb interval around the loricrin (LOR) gene. However, no evidence of association between polymorphisms in the LOR gene and psoriasis has been found. Therefore, we have analysed association to three candidate gene clusters of the region, the S100, small proline‐rich protein (SPRR) and PGLYRP (peptidoglycan recognition protein) genes, which all contain functionally interesting psoriasis candidate genes. In previous studies, the SPRR and S100 genes have shown altered expression in psoriasis. Also polymorphisms in the PGLYRP genes have shown to be associated with psoriasis. We genotyped altogether 29 single nucleotide polymorphisms (SNPs) in 255 Finnish psoriasis families and analysed association with psoriasis using transmission disequilibrium test. A five‐SNP haplotype of PGLYRP SNPs associated significantly with psoriasis. There was also suggestive evidence of association to SPRR gene locus in Finnish families. To confirm the putative associations, selected SNPs were genotyped also in a family collection of Swedish and Irish patients. The families supported association to the two gene regions, but there was also evidence of allelic heterogeneity.

Stronger association with HLA-Cw6 than with corneodesmosin (S-gene) polymorphisms in Swedish psoriasis patients

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 × 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.

Collecting a set of psoriasis family material through a patient organisation; clinical characterisation and presence of additional disorders

BackgroundThe aim of the present study was to describe the clinical characteristics of a population of psoriatics sampled from a patient organisation and not from hospitals or out-patient clinics. Furthermore, we wanted to compare siblings with and without psoriasis regarding the occurrence of other diseases.MethodsAt the end of 1991, we initiated a project which aimed to study genetic factors leading to psoriasis. Firstly, we sent questionnaires to all the members of the Swedish Psoriasis Association. We then examined 1,217 individuals (570 with psoriasis) from 310 families, in their homes in the southern part of Sweden. All the available family members were examined clinically and asked about the course of the skin disease and the occurrence of other diseases. The eight hundred members of the proband generation were divided into two groups, with or without psoriasis, and their clinical features were compared.ResultsMost individuals in this study population had a mild form of psoriasis. The siblings with psoriasis had joint complaints significantly more frequently than their siblings without the skin disease and those with joint complaints had more widespread skin disease. Among the other studied concomitant diseases (iritis, heart or hypertension disease, endocrine disease, inflammatory bowel disease and neurological disease), we were not able to find any difference. Seventy-seven of 570 persons were found to be in remission (13.5%). Females had a mean onset 2.5 years earlier than males. We were not able to find any correlation between the extent of the skin disease and age at onset. Twice as many persons with joint complaints were found among those with psoriasis than among those without, 28% versus 13%. Almost half (48%) the psoriatics who also had joint complaints had psoriasis lesions on their nails. Endocrine disorders were found in 9% of those without any allele for Cw6, but only in 1% of those who had Cw6. In fact, none of 183 Cw6 carriers had diabetes, as compared to the population prevalence of 3–5% in Sweden.ConclusionWith the exception of joint complaints, persons with psoriasis, collected from a patient organisation, did not have an increased frequency of (studied) co-existing diseases.

Unexpected loss of contact allergy to aluminium induced by vaccine.

Background. In studies in Gothenburg, Sweden, in the 1990s of an aluminium hydroxide‐adsorbed pertussis toxoid vaccine, 745 of ∼76 000 vaccinated children developed long‐lasting itchy subcutaneous nodules at the vaccination site. Of 495 children with itchy nodules patch tested for aluminium allergy, 376 (76%) were positive.