Search

Morten B Haulrig,1 Claus Zachariae,1,2 Lone Skov1,2 1Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, DK-2900, Denmark; 2Copenhagen Research Group for Inflammatory Skin (CORGIS), Hellerup, DenmarkCorrespondence: Morten B HaulrigDepartment of Dermatology and Allergy, Herlev and Gentofte Hospital, Gentofte Hospitalsvej 15, DK-2900, DenmarkTel +45 38 67 31 32Fax +45 38 67 71 18Email Morten.bahrt.haulrig@regionh.dkAbstract: Psoriasis is a chronic inflammatory skin disease that affects up to 1.2% of children and adolescents. The treatment options for childhood psoriasis are often based on the same principles as in adults. However, most data on safety and efficacy derive from adult studies, and only a few of the frequently used treatments have achieved approval for use in children. The aim of this study was to review the current literature on off-label treatments for psoriasis in children and adolescents. We searched PubMed and identified 50 studies on off-label treatments. Of these, 23 studies were clinical trials (four randomized). There are only a small number of available studies on off-label treatments for children and adolescents with psoriasis, and many of these are retrospective reviews with few participants. Despite the current lack of studies, we still recommend the use of unapproved treatments since we have clinical experience with treatments such as topical corticosteroids, vitamin D analogs, and methotrexate that have shown promising effects. Regular clinical trials are needed to investigate the safety and efficacy of unapproved treatments. Due to The Pediatric Investigation Plans issued by The European Union, new drugs developed by pharmaceutical companies are required to undergo clinical trials in a pediatric population to get their application for marketing authorization processed. This will hopefully lead to much more data on the efficacy and safety of the new treatments, including treatments for children and adolescents with psoriasis.Keywords: psoriasis, unapproved treatment, childhood, adolescents

Charlotte Näslund-Koch,1 Claus Zachariae,1,2 Lone Skov1,2 1Department of Dermatology and Allergy, Herlev and Gentofte Hospital, Copenhagen, Denmark; 2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Claus Zachariae Department of Dermatology and AllergyUniversity of Copenhagen, Herlev and Gentofte Hospital, Gentofte Hospitalsvej 15, Hellerup 2900, DenmarkTel +4538673203Fax +4538677615Email claus.zachariae@regionh.dkAbstract: Psoriasis is a common immune-mediated chronic inflammatory disease, and observations have pointed toward the IL-23/Th17 cell axis as having a key role in the pathogenesis of psoriasis. This new immunological understanding of the pathogenesis has been translated into targeted and highly effective biologic therapies. Tildrakizumab is a humanized IgG1/k monoclonal antibody targeting the p19 unit of IL-23 and has been registered for the treatment of patients with moderate-to-severe chronic plaque psoriasis in adults since 2018. This review provides an overview of the efficacy and safety of tildrakizumab, focusing on the results from clinical trials. In both Phase II and III trials, tildrakizumab 100 and 200 mg was significantly more efficacious than both placebo and etanercept at week 12. The effect of tildrakizumab continued to increase until week 28. Long-term follow-up showed high levels of efficacy for up to 3 years. Despite no difference between 100 and 200 mg in Phase III studies, subgroup analyses showed better efficacy when treated with 200 mg in patients with bodyweight ≥ 90 kg. The overall drug safety was good, and besides discrete higher incidence of nasopharyngitis, the conducted clinical trials show that tildrakizumab was very well tolerated without any safety concerns. Compared to other IL-23p19 inhibitors, tildrakizumab seemed to have slightly lower efficacy. However, to determine its position in the treatment algorithm of psoriasis, head-to-head trials with other IL-17, IL-12/23, and IL-23 inhibitors and long-term real-world data are required.Keywords: tildrakizumab, IL-23p19, biologics, psoriasis, safety, efficacy

Birte Tornøe,1–4 Lars L Andersen,5,6 Jørgen H Skotte,5 Rigmor Jensen,7 Claus Jensen,8 Bjarne K Madsen,7 Gunvor Gard,1 Liselotte Skov,2 Inger Hallström,11Department of Health Sciences, Lund University, Lund, Sweden; 2Department of Pediatrics E, Children’s Headache Clinic, University of Copenhagen, Herlev and Gentofte Hospitals, Copenhagen, Denmark; 3Department of Physiotherapy and Occupational Therapy, University of Copenhagen, Glostrup Hospital, Copenhagen, Denmark; 4Department of Physiotherapy, University of Copenhagen, Herlev and Gentofte Hospitals, Copenhagen, Denmark; 5National Research Centre for the Working Environment, Copenhagen, Denmark; 6Physical Activity and Human Performance group, SMI, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; 7Department of Neurology, Danish Headache Centre, University of Copenhagen, Glostrup Hospital, Copenhagen, Denmark; 8Huge Consulting, ApS, Haslev, Denmark Background: Childhood tension-type headache (TTH) is a prevalent and debilitating condition for the child and family. Low-cost nonpharmacological treatments are usually the first choice of professionals and parents. This study examined the outcomes of specific strength training for girls with TTH. Methods: Forty-nine girls aged 9–18 years with TTH were randomized to patient education programs with 10 weeks of strength training and compared with those who were counseled by a nurse and physical therapist. Primary outcomes were headache frequency, intensity, and duration; secondary outcomes were neck–shoulder muscle strength, aerobic power, and pericranial tenderness, measured at baseline, after 10 weeks intervention, and at 12 weeks follow-up. Health-related quality of life (HRQOL) questionnaires were assessed at baseline and after 24 months. Results: For both groups, headache frequency decreased significantly, P=0.001, as did duration, P=0.022, with no significant between-group differences. The odds of having headache on a random day decreased over the 22 weeks by 0.65 (0.50–0.84) (odds ratio [95% confidence interval]). For both groups, neck extension strength decreased significantly with a decrease in cervicothoracic extension/flexion ratio to 1.7, indicating a positive change in muscle balance. In the training group, shoulder strength increased ≥10% in 5/20 girls and predicted VO2max increased ≥15% for 4/20 girls. In the training group, 50% of girls with a headache reduction of ≥30% had an increase in VO2max >5%. For the counseling group, this was the case for 29%. A 24-month follow-up on HRQOL for the pooled sample revealed statistically significant improvements. Fifty-five percent of the girls reported little to none disability. Conclusion: The results indicate that both physical health and HRQOL can be influenced significantly by physical exercise and nurse counseling. More research is needed to examine the relationship between physical exercise, VO2max, and TTH in girls. Thus, empowering patient education to promote maximum possible outcomes for all children needs more attention. Keywords: empowering patient education, neck and shoulder muscles, muscular fitness, cardiovascular fitness, headache, child, health and physical therapy

Ann Sophie Lønnberg, Claus Zachariae, Lone SkovDepartment of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkAbstract: “Psoriasis” is a chronic immune-mediated inflammatory disorder with epidermal hyperplasia. There is some evidence that the cytokine interleukin-17A (often known as IL-17), which is mainly produced by Th17 cells, has a role in the pathogenesis of psoriasis. “IL-17” is a pro-inflammatory cytokine mainly important in the host's defense against extracellular bacteria and fungi. The three new therapies with biologic drugs – brodalumab, secukinumab, and ixekizumab – all target the IL-17 signaling pathway. Secukinumab and ixekizumab neutralize IL-17A, while brodalumab blocks its receptor. Results from clinical trials have shown marked improvements in disease severity in patients with moderate-to-severe plaque psoriasis, using any of these three drugs. The biologic agents were generally well tolerated, but the duration of the trials was relatively short. In this review, we focus on the role of the IL-17 cytokine family in the pathogenesis of psoriasis; the efficacy, safety, and tolerability of brodalumab, secukinumab, and ixekizumab in clinical trials; and possible differences between targeting of the IL-17A receptor and targeting of the IL-17A ligand.Keywords: anti-IL-17 agents, IL-17, brodalumab, secukinumab, ixekizumab, psoriasis

Birte Tornøe,1,2,5,6 Lars L Andersen,3 Jørgen H Skotte,3 Rigmor Jensen,4 Gunvor Gard,1 Liselotte Skov,2 Inger Hallström1 1Department of Health Sciences, Lund University, Scania, Sweden; 2Children's Headache Clinic, Department of Pediatrics, University of Copenhagen, Herlev Hospital, Herlev, Denmark; 3National Research Centre for the Working Environment, Copenhagen, Denmark; 4Danish Headache Center, Department of Neurology, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark; 5Department of Physiotherapy and Occupational Therapy, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark; 6Department of Physiotherapy, Medical Department, University of Copenhagen, Herlev Hospital, Herlev, Denmark Background: Frequent or chronic tension-type headache in children is a prevalent and debilitating condition for the child, often leading to medication overuse. To explore the relationship between physical factors and tension-type headache in children, the quality of repeated measures was examined. The aim of the present study was to determine the test-retest repeatability of parameters determining isometric neck and shoulder strength and stability, aerobic power, and pericranial tenderness in children. Methods: Twenty-five healthy children, 9 to 18 years of age, participated in test-retest procedures within a 1-week interval. A computerized padded force transducer was used for testing. The tests included the isometric maximal voluntary contraction and force steadiness of neck flexion and extension, and the isometric maximal voluntary contraction and rate of force of the dominant shoulder. Pericranial tenderness was recorded by means of standardized manual palpation, and a submaximal cycle ergometer test predicted maximal oxygen uptake (VO2 max). The measurements were evaluated in steps, using the intraclass correlation coefficient (ICC); changes in the mean between the two test occasions; the levels of agreement, visualized in Bland-Altman Plots; and by quantifying the variability. Results: The results showed an acceptable test-retest repeatability of isometric maximal voluntary contraction (ICC 0.90-0.97). The force steadiness measurements revealed a trend of systematic changes in the direction of neck flexion and need further examination in both healthy and ill children. The rate of force development, Total Tenderness Score, and prediction of VO2 max showed repeatability, with ICC 0.80-0.87. Conclusion: The measurements of strength capacity, aerobic power, and tenderness provide acceptable repeatability, suitable for research in children. Keywords: muscle strength, intratester reliability, cardiovascular fitness

Ann-Britt L Soee,1 Liselotte Skov,1 Svend Kreiner,4 Birte Tornoe,1,2 Lise L Thomsen3 1Department of Paediatrics, Children's Headache Clinic, Copenhagen University Hospital Herlev, Copenhagen, Denmark; 2Department of Physiotherapy, Medical Department O, Copenhagen University Hospital Herlev, Copenhagen, Denmark; 3Department of Neuropediatrics, Juliane Marie Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen Denmark; 4Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark Purpose: To compare tenderness and pain sensitivity in children (aged 7–17 years) with tension-type headache (TTH) and healthy controls using total tenderness score (TTS), pressure pain threshold (PPT), and pain perceived at suprapressure pain threshold (supraPPT). Patients and methods: Twenty-three children with frequent episodic TTH, 36 with chronic TTH, and 57 healthy controls were included. TTS was measured bilaterally at seven pericranial myofascial structures. PPT and supraPPT were assessed in the finger, m. temporalis, and m. trapezius by a Somedic® algometer. SupraPPT was defined as the pain perceived at a stimulus calculated as the individual site-specific PPT + 50%. Statistics: The effect of group, sex, age, headache frequency, intensity, and years on TTS, PPT, and supraPPT was analyzed by general linear models. Confirmatory factor analysis was analyzed for mutual relations between measurements. Results and conclusion: Tenderness increased uniformly in both frequent episodic TTH (median 14; interquartile range [IQR] 10–18; P < 0.001) and chronic TTH (median 13; IQR 9–20; P < 0.001) compared to controls (median 5, IQR 3–11). However, the children with frequent episodic TTH and chronic TTH did not show significantly increased sensitivity when measured by PPT or supraPPT. Factor analysis confirmed that the site-specific measurements depended on general latent variables. Consequently, the PPT and supraPPT tests can be assumed to measure central pain-processing levels. Keywords: sensitization, pain measurement, total tenderness score, pressure pain threshold, pathophysiological mechanisms, suprathreshold stimulation

Ann-Britt L Soee,1 Lise L Thomsen,2 Birte Tornoe,1,3 Liselotte Skov11Department of Pediatrics, Children’s Headache Clinic, Copenhagen University Hospital Herlev, Copenhagen, Denmark; 2Department of Neuropediatrics, Juliane Marie Centre, Copenhagen University Hospital Rigshospitalet, København Ø, Denmark; 3Department of Physiotherapy, Medical Department O, Copenhagen University Hospital Herlev, Herlev, DenmarkPurpose: In order to study pain in children, it is necessary to determine whether pain measurement tools used in adults are reliable measurements in children. The aim of this study was to explore the intrasession reliability of pressure pain thresholds (PPT) in healthy children. Furthermore, the aim was also to study the intersession reliability of the following four tests: (1) Total Tenderness Score; (2) PPT; (3) Visual Analog Scale score at suprapressure pain threshold; and (4) area under the curve (stimulus–response functions for pressure versus pain).Participants and methods: Twenty-five healthy school children, 8–14 years of age, participated. Test 2, PPT, was repeated three times at 2 minute intervals on the same day to estimate PPT intrasession reliability using Cronbach’s alpha. Tests 1–4 were repeated after median 21 (interquartile range 10.5–22) days, and Pearson’s correlation coefficient was used to describe the intersession reliability.Results: The PPT test was precise and reliable (Cronbach’s alpha ≥ 0.92). All tests showed a good to excellent correlation between days (intersessions r = 0.66–0.81). There were no indications of significant systematic differences found in any of the four tests between days.Conclusion: All tests seemed to be reliable measurements in pain evaluation in healthy children aged 8–14 years. Given the small sample size, this conclusion needs to be confirmed in future studies.Keywords: repeatability, intraindividual reliability, pressure pain threshold, pain measurement, algometer

Background: Biological therapies have established efficacy in psoriasis vulgaris. However, palmoplantar pustulosis (PPP) has proven difficult to treat, and data on drug survival in these patients remain scarce. Objective: To investigate drug survival of biological treatments in a nationwide cohort of patients with PPP. Methods: We included all patients treated for PPP with a biologic from a prospective Danish nationwide registry between 2007 and 2019. Descriptive statistics were reported. Drug survival was calculated for all patients and specified for the most frequently used biologics. Drug survival was reported as median time to discontinuation. Kaplan–Meier plots were used to visualize drug survival. Trajectories of Dermatology Life Quality Index (DLQI) scores were plotted by interpolating between the different visits with a dermatologist for each treatment course. Results: We identified 85 individual patients who received biological therapy for PPP across 194 treatment courses during follow‐up. Of the included treatment courses, 151 (77.8%) were discontinued. The most frequent cause of discontinuation was ineffective response to treatment (54.3%), while 18.5% of courses were discontinued due to adverse events. The median drug survival across all therapies for PPP was 9.3 (Inter quartile range (IQR), 3.9–25.6) months. Ustekinumab demonstrated the longest median time to discontinuation of 14.6 (IQR, 9.1–51.8) months. The proportion of bio‐naive patients in treatment at 12 months were according to drug 47.9% for adalimumab, 64.3% for ustekinumab and 40.0% for secukinumab. For bio‐experienced, it was 58.2% adalimumab, 54.5% for ustekinumab and 51.4% for secukinumab. Conclusions: The treatment of PPP poses significant challenges, with limited drug survival observed across all therapies regardless of prior experience with biologics. Ustekinumab demonstrated the longest median drug survival. Notably, patients discontinuing therapy due to inefficacy exhibited higher DLQI scores, highlighting the importance of personalized treatment selection and timely consideration of therapy changes when inefficacy is established. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) endotypes differ with ethnicity. We examined the skin microbiota, cytokine and lipid profiles in Greenlandic Inuit and Danish children with AD. Methods: Twenty‐five Inuit children with AD and 25 Inuit control children were clinically examined and compared to previously collected data from 25 Danish children with AD. Skin tape strips and skin swabs were collected from lesional and non‐lesional skin. Levels of cutaneous immune biomarkers, free sphingoid bases and their (glycosyl)ceramides were analysed. Skin swabs were analysed with 16S rRNA and tuf gene for characterization of bacterial species communities. Results: Bacterial β‐diversity was significantly different between Inuit and Danish AD skin, in both lesional (p < 0.001) and non‐lesional (p < 0.001) AD skin, and there was a higher relative abundance of Staphylococcus aureus in Danish compared to Inuit lesional (53% vs. 8%, p < 0.01) and non‐lesional skin (55% vs. 5%, p < 0.001). Danish AD children had a higher α‐diversity than Inuit children in non‐lesional (p < 0.05) but not in lesional skin. Significantly higher levels of type 2 immunity cytokine interleukin (IL)‐4 (p < 0.05) and IL‐5 (p < 0.01) were identified in Inuit compared to Danish AD children. In contrast, IL‐33 (p < 0.01) was higher in Danish lesional and non‐lesional AD skin. Higher levels of long‐chain glucosylceramide (GlcCER)[S](d26:1) were found in lesional (p < 0.001) and non‐lesional (p < 0.001) Inuit skin compared with Danish AD skin. NMF levels were similar in Inuit and Danish AD skin. Conclusion: Skin microbiota, cytokine and lipid composition differed significantly between Inuit and Danish children with AD and showed a stronger type 2 immune signature in Inuit children. [ABSTRACT FROM AUTHOR]

Mycosis fungoides is the most frequent subtype of primary cutaneous T-cell lymphomas. The diagnosis is based on a thorough clinic-pathologic correlation, which can, especially in early-stage disease, be challenging due to similarities with several benign skin disorders such as psoriasis and atopic dermatitis. Here, we present a case of an 81-year-old man with a 20-year-long medical history of skin problems treated as psoriasis with limited effect. Since December 2021, the patient experienced worsening of his skin symptoms with rapidly growing tumors and widespread patches and plaques. Positron emission tomography/computed tomography evaluation revealed markedly metabolic activity related to the skin tumors and increased FDG uptake in several retroperitoneal lymph nodes. Histological assessment of skin biopsies demonstrated a highly proliferative T-cell lymphoma with a γ/δ+ and CD8+ cytotoxic phenotype. The morphology of the tumor cells appeared blastic with an abnormal immunephenotype CD3+, CD2−, CD5dim, CD4−, CD8+, CD56−, and CD30−. Next-generation sequencing detected a likely pathogenic SOCS1 mutation with an allele frequency of 72% as well as a STAT3 variant of unknown significance. This case highlights the diagnostic complexity of an indolent skin lymphoma evolving into an aggressive cytotoxic lymphoma.