| 1. |
- Ekelund, Maria, 1970-
(författare)
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Psoriasis and Temporomandibular Joint Involvement in Juvenile Idiopathic Arthritis (JIA) : A Longitudinal Study of the Nordic JIA Cohort
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Juvenile idiopathic arthritis, JIA, is used as an umbrella term covering a heterogeneous group of chronic arthritis forms in children, many of which have important differences compared to adult arthritis, while others possibly represent similar diseases among children and adults. Classification aims to give a better understanding of the pathogenesis, patterns, disease trajectories and treatment responses. For the juvenile psoriatic arthritis, JPsA, the classification criteria are currently being debated. The distribution of affected joints in JIA differs greatly and it is unknown why some joints appear to be more affected than others. The temporomandibular joint (TMJ) can be affected early in the course of the disease and often the symptoms are mild and without obvious swelling.This thesis has its origin in the Nordic Study Group of Paediatric Rheumatology and the population-based prospective study of 510 children with newly diagnosed JIA included between 1997 and 1999. Totally 440 children were included in the eight-year follow-up, and in the TMJ study 265 patients were examined and underwent cone-beam computed tomography, CBCT, 17 years after onset.After eight years a considerable proportion of the children with definite psoriasis were classified as undifferentiated JIA based on the exclusion criteria in the ILAR classification. Our data also presents the heterogenicity of JPsA and the development over time of clinical variables supporting a psoriatic diathesis, as well as the overlap between JPsA and enthesitis-related arthritis in a group of patients. We found that extensive symptoms and dysfunctions of the TMJ are seen in JIA 17 years after disease onset, even in patients registered with inactive disease or remission. Individuals with substantial condylar damage on CBCT were found in all JIA categories. The deeper understanding of a chronic disease over time is crucial for research initiatives to improve care as well as for clinical decisions and planning of the health care.Our findings suggest a need for a more appropriate classification of JPsA and also that aspects of TMJ involvement should be included in the general health assessment in JIA.
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| 2. |
- Lysell, Josefin, et al.
(författare)
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Antiviral therapy in children with hydroa vacciniforme
- 2009
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Ingår i: Acta Dermato-Venereologica. - : Society for Publication of Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 89:4, s. 393-397
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Tidskriftsartikel (refereegranskat)abstract
- Hydroa vacciniforme is a rare, usually quite severe, photo-dermatosis. Association with Epstein-Barr virus infection and a possibly increased risk of lymphoproliferative malignancy have been demonstrated. We describe here four patients with Epstein-Barr virus-associated hydroa vacciniforme treated with acyclovir/valacyclovir therapy with a good clinical response. The children were reported to have less fatigue, fewer eruptions, less scarring, and increased ability to spend time outdoors without provoking new eruptions. This was also in agreement with clinical observations. However, one patient progressed into an anaplastic lymphoma kinase-1-negative anaplastic large-cell lymphoma in the upper jaw. This was preceded by an increase in EBV viral load. Acyclovir/valacyclovir therapy is a safe treatment. Further studies are required to confirm these results.
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| 3. |
- Lysell, Josefin
(författare)
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Clinical and genetic stratification of childhood psoriasis
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psoriasis is a clinically heterogeneous and common disease affecting about 2-3% of the population in Sweden. Twin and family studies have shown a strong and complex genetic background in psoriasis. The strongest known linkage association is for HLA-C*06 on chromosome 6p21.3. During the last decade several genome-wide association studies (GWAS) have independently replicated strong association with HLA-C*06 and found numerous other loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing psoriasis. Environmental factors such as infections, stressful life events and medication also contribute to disease development. Although psoriasis is such a highly heterogeneous disease most psoriasis susceptibility genes have been identified in cohorts of mixed clinical phenotypes and exploration of genes in clinical subtypes is scarce. Age of onset is one factor that can be used for stratification. Onset of psoriasis can occur at any age in life but is most common in young adults and onset in childhood and adolescence is not uncommon. Studies stratifying for age of onset of psoriasis have in principle been limited to comparing onset before or after 40 years of age as defined by Henseler and Christophers in 1985. However, 75% of patients develop disease before 40 years of age, thus stratification for early onset of psoriasis using this definition comprises the majority of patients. The overall aim of this thesis was to characterize the clinical phenotype and genetic background in psoriasis patients with disease onset in childhood and adolescence. Our hypothesis was that different genetic background could influence age of onset, clinical presentation and prognosis. Within this PhD project patients with onset of psoriasis in childhood and adolescence have been included for careful clinical and genetic characterization. For stratification for age of onset patients were divided into four groups (0-9, 10-20, 21-40, > 40 years). This approach revealed different genetic variations even within the group of patients with onset before 20 years of age (0-9 vs. 10-20 years at onset) (paper I, II and IV). In paper II genetic association with IL22 in early onset psoriasis was linked to functional alterations in IL-22 responses in Tcells. In paper III we describe clinical phenotypes at onset (< 12 months after onset) in children < 16 years. Pre-pubertal children more often had genital lesions, especially boys, whereas guttate phenotype and facial lesions associated with HLA-C*06 which was more common in children with onset at puberty. Diagnosing psoriasis in potential children for inclusion was not always easy and eczema was the most common differential diagnosis. In conclusion the data presented in this thesis stresses the importance of careful phenotypic characterization and stratification for age of onset in genetic studies in psoriasis. Differences in genetic background could have an impact on the development of comorbidities, treatment response and prognosis. Thus, exploration of the genetic background in stratified materials may help in determining prognostic genotype and tailored biologic treatment for patients in the future.
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| 4. |
- Nikamo, Pernilla, et al.
(författare)
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Genetic variants of the IL22 promoter associate to onset of psoriasis before puberty and increased IL-22 production in T cells.
- 2014
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 134:6, s. 1535-1541
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Tidskriftsartikel (refereegranskat)abstract
- Most psoriasis susceptibility genes were identified in cohorts of mixed clinical phenotypes and the exploration of genes in clinical subtypes is scarce. IL-22 has an established role in host defense and in psoriasis skin pathology, reflecting the delicate balance between control of infection and immunopathology. In a case-control study, we compared the genetic association to IL22 in psoriasis onset in patients between 0-9 (n=207), 10-20 (n=394), and 21-40 (n=468) years with healthy controls (n=1,529). Logistic regression analysis revealed association to regulatory elements in the IL22 promoter confined to onset of psoriasis before puberty (odds ratio=1.45, P<0.0007). The associated variants contain putative binding sites for AhR, a potent inducer of IL-22 expression. In a luciferase assay, transcriptional activity of a high-risk gene variant resulted in 80% higher promoter activity (P=0.012) compared with a low-risk variant. Ex vivo stimulated T cells from peripheral blood were analyzed with flow cytometry. Children with psoriasis carrying a high-risk variant produced 1.7 times more IL-22 compared with low-risk variants (P=0.042). Our combined genetic and functional data support the notion that a genetic IL22 variant that promotes epithelial barrier defense is preferentially enriched in and may precipitate the onset of psoriasis at an early age.
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| 5. |
- Padhi, Avinash, et al.
(författare)
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IL-22 Downregulates Peptidylarginine Deiminase-1 in Human Keratinocytes : Adding Another Piece to the IL-22 Puzzle in Epidermal Barrier Formation
- 2022
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Ingår i: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 142:2, s. 333-342.e6
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Tidskriftsartikel (refereegranskat)abstract
- Increased presence of IL-22(+) cells in the skin is a characteristic finding in skin barrier defects, such as psoriasis and atopic dermatitis. However, mechanistic insight into effects of IL-22 on epidermal functioning is yet to be elucidated. One crucial step during epidermal differentiation is deimination or citrullination. Here, we show reduced levels of peptidylarginine deiminase 1, an enzyme that converts peptidylarginine into citrulline in lesional psoriatic skin. IL-22 signaling through the IL-22 receptor complex was found to suppress expression of peptidylarginine deiminase 1 in epidermal keratinocytes. Subsequently, total peptidylarginine deiminase activity and extent of protein deimination in keratinocytes treated with IL-22 were reduced together with a significant decrease in deimination of keratin 1 and FLG, both important for epidermal differentiation. Vitamin D and acitretin partly restored the peptidylarginine deiminase 1 defect caused by IL-22. Collectively, we show that IL-22 downregulates deimination, thus identifying a potential target for treatment of skin barrier defects.
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