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Kristian Thestrup-Pedersen

Publications and source records attributed to Kristian Thestrup-Pedersen.

At least 19 recordsLinked to original sources
PubMed2007

Spectral karyotyping demonstrates genetically unstable skin-homing T lymphocytes in cutaneous T-cell lymphoma.

We initially established cell lines from skin biopsies from four patients (MF8, MF18, MF19 and MF31) in early stages of cutaneous T-cell lymphoma (CTCL) in 1999. After 3 weeks of culture, skin-homing T lymphocytes were stimulated with phytohaemagglutinin. Metaphase spreads were analysed using spectral karyotyping (SKY), a molecular cytogenetic technique. MF18 and MF19 had predominantly normal karyotypes. MF8 had recurrent numerical aberrations resulting in two T lymphocyte clones: one with trisomy 21 (12/20 cells) and the other with monosomy chromosome 22 (3/20 cells). MF8 also exhibited a clonal deletion, del(5)(p15.1), as well as multiple non-clonal structural aberrations. MF31 had a clonal deletion, del(17)(p12) and other non-clonal deletions involving chromosomes 2, 5, 10, 11. MF18 had a single abnormal cell that contained two reciprocal translocations t(1;2)(q32;p21) and t(4;10)(p15.2;q24). In 2001, three of the original patients had new skin biopsies taken and cell lines were established. SKY analysis revealed the continued presence of a T-cell clone in MF8 with trisomy 21 (4/20 cells). Additionally, a new clone was seen with a del(18)(p11.2) (17/20 cells). MF31 had only one aberrant cell with a del(17)(p12). MF18 had a clonal deletion, [del(1)(p36.1) in 3/20 cells] and non-clonal aberrations involving chromosomes 3, 4, 5, 6, 12, 13, 17 and 18. Thus, three of four patients continued to show numerous numerical and structural aberrations, both clonal and non-clonal, with only MF8 having a recurring T lymphocyte clone (+21). Our findings demonstrate high genetic instability among skin-homing T lymphocytes even in early stages of CTCL. We did not see genetic instability or evidence of clones in cell lines from a patient with atopic dermatitis and one with psoriasis.

Adult↗
PubMed2006

Phenotypic variation and allelic heterogeneity in young patients with Papillon-Lefèvre syndrome.

Papillon-Lefèvre syndrome is an autosomal recessive disorder characterized by palmoplantar hyperkeratosis and aggressive periodontitis. The aim of the study was to identify underlying cathepsin C mutations in 39 subjects with Papillon-Lefèvre syndrome and to explore any phenotypic associations. Genotyping and mutation analyses were performed using standard molecular techniques, and dermatological and oral characteristics were assessed with a semiquantitative clinical score. Three genotypes were present at microsatellite marker D11S1780 and two underlying mutations were identified. The most common genotype (183/183) was associated with an 815G --> C mutation in exon 6 resulting in an arginine to proline change at amino acid 272 (R272P). Patients with the 173/173 genotype revealed an exon 7 G300D mutation resulting in a glycine to aspartic acid change at amino acid 300. The mutation in a family with 189/189 genotype remained unknown. A significant difference in hyperkeratosis of the feet was found between the patients with mutations G300D and R272P ( p < 0.05), but not regarding hands or periodontal condition. Young girls displayed significantly less palmoplantar hyperkeratosis ( p < 0.05) than young boys. In conclusion, considerable phenotypic heterogeneity was observed within the two cardinal mutations and in the 189/189 genotype.

Adolescent↗
PubMed2006

Glucocorticoid-induced tumour necrosis factor receptor (GITR) and its ligand (GITRL) in atopic dermatitis.

The glucocorticoid-induced tumour necrosis factor receptor-related gene (GITR) is expressed on regulatory T-cells (Treg), which are CD4+CD25+ lymphocytes. Binding of the GITR-ligand (GITRL) leads to downregulation of the regulatory function of Tregs. Patients suffering from a defect in their Tregs exhibit a condition in their skin resembling atopic dermatitis. GITR also exists in a soluble form, and increased levels of this lead to decreased levels of GITRL and thereby increased Treg activity. We have measured the levels of GITR and GITRL in plasma from atopic dermatitis patients and found it not to be increased. Furthermore, plasma levels of GITR and GITRL did not correlate with SCORAD. Both GITR and GITRL correlated with the levels of thymus- and activation-regulated chemokine/CCL17 and cutaneous T-cell-attracting chemokine/CCL27, two chemokines believed to play a major role in the pathogenesis of atopic dermatitis and the migration of Tregs and skin-homing T-cells. Immunohistochemistry showed GITR and GITRL were present in few dermal cells of both patients with atopic dermatitis, and normal healthy volunteers, and often localized in close proximity to each other. Since regulatory T-cells are localized in the vicinity of GITRL-expressing cells in atopic dermatitis skin, the GITR/GITRL interaction may serve to perpetuate the inflammation locally.

Adolescent↗
PubMed2005

Stable incidence of atopic dermatitis among children in Denmark during the 1990s.

An increase in the prevalence of atopic dermatitis (AD) has been reported since the 1960s. The increase could be due to many factors including a genuine increase of incidence or duration of AD. We decided to study if the increasing trend persisted during the 1990s by comparing the cumulative incidence of AD in 1993 and 1998. Further, we studied the severity and management of AD among children. Two samples of children born in Denmark were drawn from the Danish Medical Birth Register. In the 1993 and 1998 studies a mailed questionnaire with identical questions concerning AD was sent out. In the 1998 follow-up study the questionnaire included a severity score and questions concerning management of AD. In the 1993 study the cumulative incidence of AD at age 7 was 18.9% and in 1998 it was 19.6%. There was no difference in the age-adjusted AD incidence in the 5-year observation period. In the 1998 study, 81% had mild to moderate AD, 90% had been seen by a doctor at least once, 36% had mainly been treated by a dermatologist, and 2% had been hospitalized. It should be kept in mind that we base most of our common knowledge of the disease on AD patients selected for management in dermatology clinics and departments.

Child↗
PubMed2005

Thymus is enlarged in children with current atopic dermatitis. A cross-sectional study.

Atopic dermatitis is a common skin disorder of unknown aetiology with peak incidence in early childhood. The disease is associated with peripheral T-cell accumulation in the skin. The thymus is a key organ of the cellular immune response early in life. We hypothesized that atopic dermatitis is associated with an unbalanced establishment of the peripheral T-lymphocyte system. This cross-sectional study was performed to compare thymus sizes in patients with atopic dermatitis and healthy controls. Thirty-seven children with current atopic dermatitis were enrolled and compared with 29 healthy controls. An interview and medical examination were performed by one doctor, an ultrasound scan was performed within 3 days of the examination, and the thymus index, a marker of thymus size, was measured. The thymus index was on average 32% higher (95% CI 3%-67%) in children with active atopic dermatitis compared with healthy controls. It declined with age in both children with atopic dermatitis and healthy controls, but the reduction in size was only significant for healthy controls. We demonstrate increased size of thymus among children with active atopic dermatitis compared with healthy controls. The larger size of thymus is compatible with increased thymic activity and emission of T lymphocytes.

Case-Control Studies↗
PubMed2005

Self-inflicted skin diseases. A retrospective analysis of 57 patients with dermatitis artefacta seen in a dermatology department.

We analysed clinical symptoms, gender, age and social relations among 57 patients for whom a final diagnosis of dermatitis artefacta was established. The study is retrospective and the patients were seen in our department from 1982 to 2002. We observed that the diagnosis was 2.8 times more common in females than males. Symptoms were most common in the age group 18-60 years, median age 39 years. The skin lesions were 'multiple' among 88% of the patients. When self-infliction was suggested as the cause, two-thirds of patients initially denied it and only one patient agreed to meet with a psychiatrist. Only one-quarter had a job, the rest were unemployed or on sick leave. Many patients (61%) received medical treatment with anxiolytica. Ten patients (18%) had a psychiatric diagnosis. Among our 57 patients, 11 were deceased at the time of our study, but none because of suicide. Four had died before the age of 70, of whom two suffered from alcoholism and two had diabetes mellitus. Therapy should include an optimal nursing relationship with the patient so that social problems can be discussed. Psychological or psychiatric intervention appeared unhelpful because of patient denial.

Adolescent↗
PubMed2005

The risk of cancer among patients previously hospitalized for atopic dermatitis.

In treatment of severe atopic dermatitis, drugs with carcinogenic potentials are used to manage the disease. We therefore analyzed whether patients having severe atopic eczema had an increased cancer risk. The study population included all individuals hospitalized in Denmark with a primary diagnosis of atopic dermatitis during 1977-1996. Follow-up was conducted in 1996 in the Danish Cancer Register. A total of 6275 persons were included. Among 2030 adult patients, an increased risk of cancer was observed, standard morbidity ratio (SMR)=1.5 (95% CI: 1.2-1.9). Half the excess cases of cancer was keratinocyte carcinomas of the skin diagnosed within the first 9 y of follow-up, SMR=2.4 (95% CI: 1.4-3.9). For men, SMR=2.7 (95%CI: 1.2-5.4). In conclusion, earlier hospitalized adult atopic dermatitis patients had an increased risk of cancer. Half the excess cases of cancer were keratinocyte carcinomas. This may be a result of a detection bias or due to the carcinogenic potentials of some of the therapies of severe atopic dermatitis.

Adolescent↗
PubMed2005

In vitro culture of skin-homing T lymphocytes from inflammatory skin diseases.

We, in this study, describe how T lymphocytes in a skin biopsy can proliferate in vitro for up to 3 months by using T-cell growth factors - interleukin-2 (IL-2) and IL-4 yielding approximately 100-160 million T lymphocytes within 1 month. We established cell lines from three tuberculin skin tests, four positive patch tests, 15 of 16 biopsies from atopic dermatitis (AD), 15 of 19 biopsies from mycosis fungoides (MF), 12 of 24 biopsies from psoriasis vulgaris, which was significantly less than AD (P < 0.05), and with a reduced cumulative number of lymphocytes (P < 0.05). Omitting IL-2 and IL-4 led to immediate halt of proliferation. Blood mononuclear cells from patients and biopsies from healthy persons never gave cell lines. All cells were T lymphocytes expressing CD45RO+, HLA-DR+ and CD150. The CD7 expression was significantly increased in cell lines from AD (P < 0.05). T-cell receptor beta-chain studies by using reverse transcription-polymerase chain reaction showed that all T lymphocytes had access to the skin compartment. Single-stranded conformational analysis showed clonally expanded T cells numbering between 40 and 60 clones. After approximately 2 months of growth, the mean CD4+ : CD8+ ratio was for AD 1.20, MF 0.65 and psoriasis 0.85. Patients with AD treated with cyclosporin-A had almost no growth of CD8+ cells in vitro. Our findings indicate a changed homeostasis among skin-homing lymphocytes for in vitro culture. Our culture system of skin-homing T lymphocytes leads to a prominent cellular expansion allowing for a range of studies of in vivo activated skin T lymphocytes.

Adolescent↗
PubMed2004

Oral alitretinoin (9-cis-retinoic acid) therapy for chronic hand dermatitis in patients refractory to standard therapy: results of a randomized, double-blind, placebo-controlled, multicenter trial.

OBJECTIVE: To assess the efficacy and safety of oral alitretinoin (9-cis-retinoic acid), 10 mg/d, 20 mg/d, and 40 mg/d, compared with placebo control, in the treatment of chronic hand dermatitis. DESIGN: Multicenter, randomized, double-blind, placebo-control, prospective trial. SETTING: A total of 43 outpatient clinics in 10 European countries. PATIENTS: Of 348 patients screened, 319 with moderate or severe refractory chronic hand dermatitis were randomized, in the ratio of 1:1:1:1, to 4 treatment groups and received allocated intervention. Of 75 patients who withdrew, 24 withdrew owing to adverse events. INTERVENTIONS: Placebo or 10 mg, 20 mg, or 40 mg of oral alitretinoin (9-cis-retinoic acid) taken once daily for 12 weeks. Safety was assessed for all patients during a follow-up period of 4 weeks, and responders were observed for a follow-up period of 3 months. MAIN OUTCOME MEASURE: Physician's global assessment of overall chronic hand dermatitis severity. RESULTS: Alitretinoin led to a significant and dose-dependent improvement in disease status, with responses in up to 53% of patients, and up to a 70% mean reduction in disease signs and symptoms. Treatment was generally well tolerated, with dose-dependent effects comprising headache, flushing, mucocutaneous events, hyperlipidemia, and decreased hemoglobin and decreased free thyroxin levels. Three months after discontinuation of treatment, the rate of relapse was 26%, independent of dose. CONCLUSION: Alitretinoin given at well-tolerated doses induced substantial clearing of chronic hand dermatitis in patients refractory to conventional therapy.

Administration, Oral↗