Publications by authors named "Jacob P Thyssen"

343 Publications

The risk of COVID-19 infection in patients with atopic dermatitis - a retrospective cohort study.

J Am Acad Dermatol 2021 Oct 6. Epub 2021 Oct 6.

Department of Dermatology, Bispebjerg University Hospital, University of Copenhagen, Copenhagen NV, Denmark.

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http://dx.doi.org/10.1016/j.jaad.2021.09.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492899PMC
October 2021

Does aluminium in sunscreens cause dermatitis in children with aluminium contact allergy: A repeated open application test study.

Contact Dermatitis 2021 Sep 18. Epub 2021 Sep 18.

National Allergy Research Centre, Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

Background: Parents report that children with aluminium contact allergy and vaccination granulomas may react to aluminium-containing sunscreen following application.

Objectives: To evaluate whether contact dermatitis develops following repeated application of aluminium-containing sunscreens in children with aluminium sensitization and vaccination granulomas.

Methods: Sixteen children aged 2-9 years (mean age 5 years) with vaccination granulomas and a positive patch test reaction to aluminium chloride hexahydrate 2%/10% petrolatum completed a blinded repeated open application test (ROAT) with two daily applications of two sunscreens for 14 days. One cream contained aluminium and the other did not. The children served as their own controls.

Results: Sixteen children completed the study. Only one child (6%) had a positive skin reaction during ROAT on day 2 to the sunscreen with aluminium. None reacted to the sunscreen without aluminium.

Conclusions: Use of aluminium-containing sunscreens may on a case basis lead to allergic contact dermatitis in aluminium allergic children.
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http://dx.doi.org/10.1111/cod.13973DOI Listing
September 2021

Societal Costs of Moderate-to-severe Atopic Dermatitis Occurring in Adulthood: A Danish Register-based Study.

Acta Derm Venereol 2021 Sep 3;101(9):adv00538. Epub 2021 Sep 3.

Department of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.

To estimate the cost of illness in adult patients with moderate-to-severe atopic dermatitis (AD) a cohort study was conducted identifying Danish citizens (≥ 18 years) diagnosed with AD between 1997 and 2018 in the Danish National Patient Register. Moderate-to-severe AD was defined as ≥3 hospital contacts regarding AD the first year after  diagnosis. Each patient with AD was matched to 3 reference individuals through the Central Person Registry. Societal costs included the direct costs for primary-sector visits, inpatient hospitalizations, outpatient contacts, prescription medicine and indirect costs of lost productivity 3 years before and 5 years after the index date (the study period). A total of 5,245 patients with moderate-to-severe AD were identified. The mean attributable healthcare costs for patients with moderate-to-severe AD were EUR 10,835 (p < 0.0001) during the study period. Moderate-to-severe AD among adults inferred substantial economic burden compared with a group of matched reference individuals.
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http://dx.doi.org/10.2340/00015555-3908DOI Listing
September 2021

Differences in Psychometric Properties of Clinician- and Patient-Reported Outcome Measures for Atopic Dermatitis by Race and Skin Tone: A Systematic Review.

J Invest Dermatol 2021 Aug 2. Epub 2021 Aug 2.

Department of Dermatology, School of Medicine and Health Sciences, George Washington University, Washington, District of Columbia, USA. Electronic address:

The psychometric validity and reliability of widely used atopic dermatitis (AD) outcome measures across different races and ethnicities are unclear. We describe the rates of reporting race, ethnicity, and skin tone in studies testing the psychometric properties of AD outcome measures and compare the psychometric analyses across race, ethnicity, and skin tone. We systematically reviewed MEDLINE and EMBASE for studies reporting psychometric properties of clinician-reported or patient-reported outcome measures in AD (International Prospective Register of Systematic Reviews: CRD42021239614). Overall, 16,100 nonduplicate articles were screened; 165 met inclusion criteria. Race and/or ethnicity were reported in 55 (33.3%) studies; of those, race was assessed by self-report in 10 studies (6.1%) or was unspecified in 45 (27.3%). A total of 16 studies (9.7%) evaluated psychometric property differences by race, and only five (4.4%) of those did not recognize it as a limitation. Properties assessed across race, ethnicity, or skin tone were differential item functioning, convergent validity feasibility, inter-rater reliability, intrarater reliability, test‒retest reliability, and known-groups validity. Multiple instruments demonstrated performance differences across ethnoracial groups. This review highlights the paucity of race/ethnicity consideration for psychometric property testing in AD outcome measurement instruments. More AD outcomes instruments should be validated in diverse populations.
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http://dx.doi.org/10.1016/j.jid.2021.06.033DOI Listing
August 2021

Disease burden, symptoms, and use of analgesics in patients with psoriasis with or without psoriatic arthritis: A cross-sectional study.

J Am Acad Dermatol 2021 Jul 24. Epub 2021 Jul 24.

Department of Dermatology and Allergy, Copenhagen University Hospital-Herlev and Gentofte Hospital, Copenhagen, Denmark; Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark.

Background: Patients with psoriasis have an impaired quality of life and higher use of analgesics than the general population. Whether such use is due to skin pain or a consequence of joint pain resulting from psoriatic arthritis (PsA) is not clear.

Objectives: To assess symptoms, disease burden, and use of analgesics in patients with psoriasis with and without PsA.

Method: Symptoms, general health (EurQol 5-dimension and 5-levels), and use of analgesics were assessed in patients with psoriasis and the general population from the Danish Skin Cohort.

Results: We included 4016 patients with psoriasis (847 with concomitant PsA) and 3490 reference individuals. For patients with psoriasis having PsA, itch, skin pain, and/or joint pain was associated with worse general health. Use of opioids within 12 months was observed among 9.0% of the general population, 14.2% of patients with psoriasis without PsA, and 22.7% of patients with concomitant PsA. Of the symptoms, only joint pain was associated with use of analgesics (odds ratio, 3.72 (2.69-5.14); P < .0001).

Limitations: Cross-sectional design.

Conclusion: Patients with psoriasis (especially concomitant PsA) have a higher use of analgesics compared with the general population, which appears to be a result of increased joint pain.
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http://dx.doi.org/10.1016/j.jaad.2021.07.028DOI Listing
July 2021

Baricitinib Rapidly Improves Skin Pain Resulting in Improved Quality of Life for Patients with Atopic Dermatitis: Analyses from BREEZE-AD1, 2, and 7.

Dermatol Ther (Heidelb) 2021 Oct 18;11(5):1599-1611. Epub 2021 Jul 18.

Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster, Germany.

Introduction: Skin pain (described as discomfort or soreness) is increasingly recognized as a symptom of atopic dermatitis which impacts patient quality of life. This analysis examined the effect of baricitinib on skin pain in atopic dermatitis in three phase 3 studies (BREEZE-AD1, -AD2, and -AD7).

Methods: Patients were randomly assigned 2:1:1:1 to receive once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg in BREEZE-AD1 (N = 624) and -AD2 (N = 615) and 1:1:1 to receive once-daily placebo, baricitinib 2 mg, or 4 mg, with topical corticosteroids, in BREEZE-AD7 (N = 329) for 16 weeks. Patients recorded their skin pain severity using the Skin Pain Numerical Rating Scale (NRS) via an electronic daily diary. Data were analyzed by study as least squares mean change from baseline in daily scores for the randomly assigned patients using mixed model repeated measures analysis. Analysis of Skin Pain NRS response was done using logistic regression using non-responder imputation.

Results: Baricitinib produced significant percentage change from baseline compared with placebo in patient-reported skin pain severity by day 2 in BREEZE-AD1 (baricitinib 4 mg - 11.9%, p < 0.001; baricitinib 2 mg - 6.4%, p = 0.016; baricitinib 1 mg - 6.2%, p = 0.016), -AD2 (baricitinib 4 mg - 12.6%, p < 0.001; baricitinib 2 mg - 5.6%, p = 0.036; baricitinib 1 mg - 6.9%, p = 0.011), and -AD7 (baricitinib 4 mg - 6.9%, p = 0.04; baricitinib 2 mg - 7.9%, p = 0.018). A greater proportion of patients treated with baricitinib reported at least a 4-point reduction in Skin Pain NRS score at week 16 (Skin Pain NRS responders) in BREEZE-AD1 (baricitinib 4 mg 25.3%, p < 0.001), -AD2 (baricitinib 4 mg 20.0%, p < 0.001; baricitinib 2 mg 19.0%, p < 0.001), and -AD7 (baricitinib 4 mg 48.8%, p < 0.001; baricitinib 2 mg 45.2%, p = 0.004) compared to placebo. A significantly higher proportion of Skin Pain NRS responders also achieved at least a 4-point improvement in Dermatology Life Quality Index at week 16 when compared with Skin Pain NRS non-responders in BREEZE-AD1 (89.2%, p < 0.0001), -AD2 (92.5%, p < 0.0001), and -AD7 (88.3%, p < 0.0001).

Conclusion: Baricitinib improved patient-reported skin pain severity as early as day 2. CLINICALTRIALS.

Gov Identifiers: BREEZE-AD1, NCT03334396; BREEZE-AD2, NCT03334422; BREEZE-AD7, NCT03733301.
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http://dx.doi.org/10.1007/s13555-021-00577-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484387PMC
October 2021

Limitations of Using Questionnaires for Assessing the Prevalence of Psoriasis and Atopic Dermatitis Among Adults.

JAMA Dermatol 2021 Aug;157(8):971-977

Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.

Importance: Questionnaire studies are important for estimating the prevalence of psoriasis and atopic dermatitis; however, validity among the adult population remains an important concern.

Objective: To examine the test-retest accuracy of questionnaires for measuring psoriasis and atopic dermatitis prevalence in an adult population.

Design, Setting, And Participants: This nationwide population-based cohort study administered questionnaires on psoriasis and atopic dermatitis to the same 2333 and 2312 randomly selected adults (≥18 years) in Denmark, respectively, at 2 different time points from May 15, 2018, to November 20, 2020. Data were analyzed from January 10 to January 28, 2021. To reduce the risk of participation bias, potential respondents were given information on the research project only after agreeing to participate.

Exposures: Participants were asked identical questions on psoriasis and atopic dermatitis in 2018 and in 2020. Responses were linked at the individual-level.

Main Outcomes And Measures: The test-retest reliability (expressed by Cohen κ).

Results: The psoriasis questionnaire was completed by 2333 (mean [SD] age, 55.1 [16.2] years; 1338 [57.4%] women) participants in 2018 and in 2020. The atopic dermatitis questionnaire was completed by 2312 (mean [SD] age, 55.0 [16.2] years; 1326 [57.4%] women) participants in 2018 and in 2020. Among participants reporting a history of psoriasis, agreement between individual responses was high (κ = 0.7558); however, among those reporting a history of atopic dermatitis, agreement was low (κ = 0.4395). For psoriasis, prevalence changed from 7.8% to 8.0%; for atopic dermatitis, from 8.2% to 7.6%. Of participants who in 2018 reported dermatologist-diagnosed atopic dermatitis, 36.9% claimed in the 2020 questionnaire that they had never had atopic dermatitis. Analyses revealed substantial agreement for psoriasis responses across all age strata; for atopic dermatitis responses, the κ declined with increasing age, to 0.2613 for participants 65 or older.

Conclusions And Relevance: This cohort study found considerable agreement between responses over time when participants were asked about a history of psoriasis. When asked about a history of atopic dermatitis, responses over time were inconsistent. This inconsistency suggests that questionnaires on a history of atopic dermatitis will confer considerable risk of bias and misclassification.
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http://dx.doi.org/10.1001/jamadermatol.2021.2307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264750PMC
August 2021

Reply to "Combined antibiotic, steroid, and moisturizer for atopic dermatitis: A 2-year case series of patient-reported outcomes".

Pediatr Dermatol 2021 05;38(3):736-737

Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

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http://dx.doi.org/10.1111/pde.14612DOI Listing
May 2021

No immediate effect of regulatory reduction of chromium in leather among adult patients with chromium allergy.

Contact Dermatitis 2021 Nov 17;85(5):514-522. Epub 2021 Jul 17.

Department of Dermatology and Allergy, National Allergy Research Centre, Copenhagen University Hospital, Herlev-Gentofte, Hellerup, Denmark.

Background: In March 2014, the European Commission issued a new regulation restricting the content of hexavalent chromium (Cr) in leather to no more than 3 mg/kg. We previously performed a questionnaire study in January 2014 to characterize our patients with Cr contact allergy prior to regulatory intervention.

Objectives: To assess whether clinical characteristics, self-reported sources of Cr exposure, and burden of disease changed in patients with Cr allergy over time.

Methods: A questionnaire study was performed among 172 adult dermatitis patients with Cr allergy and 587 age- and sex-matched dermatitis patients without Cr allergy. A questionnaire was sent to all dermatitis patients patch tested from 2003 to 2018 in August 2019.

Results: The overall response rate was 61.2% (759/1241). Patients with Cr allergy were still more commonly affected by current foot dermatitis (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.07-7.08) and hand dermatitis (OR 1.98, 95% CI 1.13-3.49) compared with controls diagnosed during 2013 to 2018. The proportion of patients with Cr allergy reporting dermatitis caused by leather exposure did not change during 2003 to 2012 vs 2013 to 2018 (71.0% vs 66.2%, P = .5). Furthermore, estimates on occupational performance and disease severity (eg, current dermatitis), number of anatomical locations with dermatitis, worst-case dermatitis, and effect on work were similar in patients with Cr allergy for 2003 to 2012 vs 2013 to 2018.

Conclusion: No immediate sign of improvement was found in patients with Cr allergy concerning severity of disease and dermatitis from leather exposures 5 years after adoption of the regulation against hexavalent Cr in leather. The regulation may have to be revised for better protection of those already sensitized.
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http://dx.doi.org/10.1111/cod.13925DOI Listing
November 2021

Chromium and cobalt release from metallic earrings from the Danish market.

Contact Dermatitis 2021 Nov 7;85(5):523-530. Epub 2021 Jul 7.

National Allergy Research Centre, Department of Dermatology and Allergy, Copenhagen University Hospital Herlev-Gentofte, Hellerup, Denmark.

Background: Chromium and cobalt are important skin sensitizers. It has, however, been difficult to identify causative exposures. Studies on nickel allergy have demonstrated piercing as critical for both sensitization and elicitation. It may be speculated that the same applies for chromium and cobalt.

Objective: To examine the content and release of chromium and cobalt from earrings randomly purchased in Denmark.

Methods: Three hundred four earrings were examined with x-ray fluorescence (XRF) spectrometry. Earrings with measured content of chromium or cobalt were spot tested with diphenylcarbazide spot test (n = 166) or Nitroso-R spot-test (n = 99), respectively. Chromium and cobalt release were quantified in a selected subsample (n = 100) with the artificial sweat test (EN 1811).

Results: Chromium was present in 54.6% (166/304) of earrings and cobalt was present in 72.0% (219/304),- measured by XRF. All chromium spot tests for chromium VI were negative. The cobalt spot test was positive for one component. Chromium release was found from 59/100 (median concentration = -0.06 μg/cm /week) and cobalt release from 29/100 (median concentration = -0.06 μg/cm /week) of earrings in tested subsample.

Conclusion: Earrings for piercing release chromium and cobalt and may on a case basis be a source of chromium and cobalt allergy.
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http://dx.doi.org/10.1111/cod.13917DOI Listing
November 2021

Chemicals in moisturizers may promote type 2 inflammation and food allergy.

J Allergy Clin Immunol 2021 08 16;148(2):652-653. Epub 2021 Jun 16.

Department of Dermatology and Venerology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2021.05.010DOI Listing
August 2021

Contact dermatitis.

Nat Rev Dis Primers 2021 05 27;7(1):38. Epub 2021 May 27.

Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA.

Contact dermatitis (CD) is among the most common inflammatory dermatological conditions and includes allergic CD, photoallergic CD, irritant CD, photoirritant CD (also called phototoxic CD) and protein CD. Occupational CD can be of any type and is the most prevalent occupational skin disease. Each CD type is characterized by different immunological mechanisms and/or requisite exposures. Clinical manifestations of CD vary widely and multiple subtypes may occur simultaneously. The diagnosis relies on clinical presentation, thorough exposure assessment and evaluation with techniques such as patch testing and skin-prick testing. Management is based on patient education, avoidance strategies of specific substances, and topical treatments; in severe or recalcitrant cases, which can negatively affect the quality of life of patients, systemic medications may be needed.
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http://dx.doi.org/10.1038/s41572-021-00271-4DOI Listing
May 2021

Treatment of atopic dermatitis with biologics and Janus kinase inhibitors.

Lancet 2021 Jun 21;397(10290):2126-2128. Epub 2021 May 21.

Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark.

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http://dx.doi.org/10.1016/S0140-6736(21)00717-0DOI Listing
June 2021

Comparison of Cytokines in Skin Biopsies and Tape Strips from Adults with Atopic Dermatitis.

Dermatology 2021 May 10:1-6. Epub 2021 May 10.

Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.

Skin biomarkers for disease severity and treatment response in atopic dermatitis (AD) are needed. Biopsies cause scarring and tape stripping represents an alternative minimally invasive method for stratum corneum sampling. In this study, we examined the gene expression of cytokines in skin biopsies and cytokines in stratum corneum tape strips collected from adults with AD. We collected punch biopsies and tape strips from healthy controls (n = 6) and subjects with AD (n = 12) at baseline and after 2 weeks of topical treatment with mometasone furoate 0.1% cream. We found that IFN-γ, IL-13, and IL-10 mRNA (biopsies) and IL-1β protein expression levels (tape strips) were significantly increased in lesional AD skin compared to healthy control skin. Treatment with topical corticosteroid led to a significant decrease in mRNA levels for IL-13 and IL-4R but no significant differences in cytokine protein levels measured in tape strips. Finally, we found no significant correlations between cytokine levels in tape strips and mRNA levels in skin biopsies.
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http://dx.doi.org/10.1159/000514308DOI Listing
May 2021

Impact of Oral Abrocitinib Monotherapy on Patient-Reported Symptoms and Quality of Life in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis: A Pooled Analysis of Patient-Reported Outcomes.

Am J Clin Dermatol 2021 Jul 5;22(4):541-554. Epub 2021 May 5.

Pfizer Inc., New York, NY, USA.

Background: Atopic dermatitis imparts a substantial patient burden, including itch, sleep disturbance, and decreased health-related quality of life.

Objective: This analysis evaluated changes in patient-reported outcomes of disease-specific signs/symptoms and health-related quality of life in adult and adolescent patients with moderate-to-severe atopic dermatitis treated with once-daily oral abrocitinib 200-mg or 100-mg monotherapy.

Methods: Pooled data from one phase IIb (NCT02780167) and two phase III (NCT03349060, JADE MONO-1; NCT03575871, JADE MONO-2) monotherapy trials in adult and adolescent patients with moderate-to-severe atopic dermatitis were analyzed. Patient-reported outcome assessments included: global severity, itch, and multi-item measures that assess other signs and symptoms of atopic dermatitis. Additional patient-reported outcome assessments measured depression, anxiety, fatigue, disease-specific and general health-related quality of life, and work and general productivity among employed patients.

Results: Overall, 942 patients were included in this analysis. Improvements were observed from the first post-baseline assessment to week 12 across all patient-reported outcomes, including Patient Global Assessment (PtGA) score of 0/1 (35.5%, 19.8%, and 5.9% for 200 mg, 100 mg, and placebo, respectively), ≥ 4-point improvement in Night Time Itch Scale (NTIS; 57.0%, 42.7%, and 12.7%), change from baseline in Patient-Oriented Eczema Measure (POEM) score (- 11.4, - 8.2, and - 3.4), 1-point improvement in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD; 75.2%, 65.1%, and 33.5%), Hospital Anxiety and Depression Scales (HADS) anxiety (- 2.0, - 1.7, and - 1.0) and depression (- 1.7, - 1.3, and - 0.1).

Conclusions: Abrocitinib monotherapy improved disease-specific signs/symptoms and health-related quality of life across multiple domains as reported by adult and adolescent patients with moderate-to-severe atopic dermatitis, complementing clinician-reported efficacy and safety outcomes.

Clinical Trial Registration: NCT02780167 (registered 23 May, 2016), NCT03349060 (registered 21 November, 2017), NCT03575871 (registered 3 July, 2018).
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http://dx.doi.org/10.1007/s40257-021-00604-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200343PMC
July 2021

Subtype-Specific Off-Label Treatment of Rosacea.

Case Rep Dermatol 2021 Jan-Apr;13(1):121-128. Epub 2021 Feb 16.

Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark.

We present 2 cases of rosacea that were successfully managed with off-label treatment. The first is a case of painful, exuding papulopustular lesions of the nose treated with rifaximin, and the other is a case of severe, debilitating and painful flushing treated with sumatriptan. The cases support previous notions that gastrointestinal comorbidities may be related to papulopustular lesions and that flushing may be related to neurogenic inflammation and migraine. The cases also imply that a new approach to rosacea management, based on endotypes and comorbidities, may be warranted.
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http://dx.doi.org/10.1159/000511984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989675PMC
February 2021

The European baseline series: Criteria for allergen inclusion (with reference to formaldehyde releasers).

Contact Dermatitis 2021 Mar 21. Epub 2021 Mar 21.

Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen/Nürnberg, Erlangen, Germany.

Existing criteria for inclusion in the European baseline series are summarized. Additional criteria are developed to aid decision making where the current criteria do not yield an unequivocal result. These include a consideration of whether an allergen (hapten) is better placed in a special series and the frequency with which an allergen cross-reacts with existing markers in the baseline series.
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http://dx.doi.org/10.1111/cod.13836DOI Listing
March 2021

Translating the Investigator's Static Global Assessment to the Eczema Area and Severity Index in Studies of Crisaborole for Atopic Dermatitis.

Dermatol Ther (Heidelb) 2021 Jun 13;11(3):845-853. Epub 2021 Mar 13.

Westphalian Wilhelms University of Münster, Münster, Germany.

Introduction: Atopic dermatitis (AD) severity was measured in two phase 3 US studies of crisaborole ointment, 2%, in patients aged ≥ 2 years using the Investigator's Static Global Assessment (ISGA), an FDA-recommended scale. Eczema Area and Severity Index (EASI) is a validated scale used globally to assess AD severity in clinical trials. The objective of this study is to aid interpretability of ISGA by translating ISGA scores to EASI scores.

Methods: ISGA was mapped to EASI using published EASI severity strata by Chopra et al. and Leshem et al. and pooled data from phase 3 trials CrisADe CORE 1 and CORE 2, which evaluated crisaborole in patients aged ≥ 2 years with mild-to-moderate AD (crisaborole, n = 1016; vehicle, n = 506). Least squares mean (LSM) percentage change from baseline (%CFB) in EASI and proportion of patients with 50%, 75%, and 90% improvement (EASI-50, EASI-75, and EASI-90, respectively) on day 29 were computed for mapped EASI. The relationship between changes in ISGA and changes in EASI was assessed using data from three abrocitinib trials.

Results: ISGA was mapped to EASI using 70,000 random simulations. LSM (standard error) for %CFB in mapped EASI at day 29 (crisaborole versus vehicle) was -26.3% (17) versus 45.2% (35) (P = 0.0671) using Chopra strata and -43.1% (4.6) versus -5.2% (8.4) (P < 0.0001) using Leshem strata. EASI-50, EASI-75, and EASI-90 rates were 72.1% versus 57.6%, 63.0% versus 47.8%, and 55.0% versus 40.1%, respectively, using Chopra strata (P < 0.0001 for each difference). These rates were 68.8% versus 54.0%, 54.8% versus 40.5%, and 38.9% versus 27.2%, respectively (P < 0.0001 for each difference) using Leshem strata. Mean two-point improvement in ISGA was comparable to EASI-90.

Conclusion: Mapped EASI results were consistent with ISGA results in crisaborole phase 3 trials. Simulation methodologies yielded consistent results and may aid in interpretability of ISGA across clinical studies.

Trial Registration: ClinicalTrials.gov identifier: NCT02118766, NCT02118792.
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http://dx.doi.org/10.1007/s13555-021-00509-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163913PMC
June 2021

Nickel release from metallic earrings: A survey of the Danish market and validation of the nickel spot test.

Contact Dermatitis 2021 Mar 13. Epub 2021 Mar 13.

National Allergy Research Centre, Department of Dermatology and Allergy, Copenhagen University Hospital Herlev-Gentofte, Hellerup, Denmark.

Background: Exposure to nickel-releasing ear-piercing jewellery may explain the persistently high prevalence of nickel allergy in Europe. While nickel release from earrings is regulated, field studies show that the regulation is not always respected. More knowledge is needed regarding the risk of piercing exposure including suitable screening methods.

Objective: To examine the proportion of earrings on the Danish market that release more nickel than allowed, and to validate the use of the dimethylglyoxime (DMG) test as a screening tool.

Methods: A total of 304 earrings were purchased and tested with the DMG test and X-ray fluorescence spectrometry. The level of nickel release was quantified in a selected subsample of 100 earrings by the European reference test EN 1811. The DMG spot test was validated against EN 1811 at different thresholds.

Results: Excessive nickel release according to the European regulation was found in 45 (14.8%) tested earrings. The sensitivity of the DMG test decreased with reduced levels of nickel release (sensitivity of 45.2% at ≥0.2 μg/cm /week vs 61.1% at >0.5 μg/cm /week).

Conclusion: Excessive nickel release is common in earrings on the Danish market. Because of low sensitivity, the DMG test has limited use in screening of earrings for research but may still be used clinically.
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http://dx.doi.org/10.1111/cod.13832DOI Listing
March 2021

Biologics for Treatment of Atopic Dermatitis: Current Status and Future Prospect.

J Allergy Clin Immunol Pract 2021 03;9(3):1053-1065

Department of Allergy and Immunology, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass. Electronic address:

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by intense pruritus and recurrent eczematous lesions that significantly impair quality of life. It is a heterogeneous disease affecting both children and adults. The treatment of moderate-to-severe forms of AD is challenging, as topical corticosteroids are often insufficient to achieve disease control or inappropriate and off-label use of immunosuppressants may have significant undesirable side effects. The development of targeted biologic therapies specifically for AD is thus highly desirable. Dupilumab is the only biologic therapy that is Food and Drug Administration approved for the treatment of moderate-to-severe AD in patients 6 years and older, with consistent long-term efficacy and safety trial data. In this article, we review the mechanisms, safety, and efficacy of dupilumab from recent clinical trials, and we review the current data, mechanism of action, clinical efficacy, and limitations of new biologics currently in phase 2 and 3 clinical trials (lebrikizumab, tralokinumab, nemolizumab, tezepelumab, and ISB 830).
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http://dx.doi.org/10.1016/j.jaip.2020.11.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951162PMC
March 2021

Rhinitis prevalence and association with atopic dermatitis: A systematic review and meta-analysis.

Ann Allergy Asthma Immunol 2021 07 5;127(1):49-56.e1. Epub 2021 Mar 5.

Copenhagen Research Group for Inflammatory Skin (CORGIS), Herlev and Gentofte Hospital, Hellerup, Denmark; Department of Dermatology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark; LEO Foundation Skin Immunology Research Center, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Background: Atopic dermatitis (AD) and rhinitis are common atopic diseases that may co-occur owing to an overlap in pathophysiology. Although most cases of both diseases are mild and managed with topical anti-inflammatory medicaments, the advent of new systemic and biologic treatments targeting type 2 inflammation in both diseases warrants further insight in the exact overlap of AD and rhinitis.

Objective: To determine the association between AD and rhinitis.

Methods: A systematic review and meta-analysis of the databases PubMed, Embase, and CNKI were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled prevalence and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.

Results: The search resulted in 10,422 citations, and 341 and 302 articles were included in the qualitative and quantitative analyses, respectively. The pooled prevalence of rhinitis was 40.5% (95% CI 39.0-42.0) in patients with AD and 18.0% (95% CI 16.7-19.2) in the reference individuals without AD. The pooled prevalence of having both rhinitis and asthma was 14.2% (95% CI 13.0-15.5) in patients with AD. There was an association between AD and rhinitis (OR 3.00, 95% CI 2.83-3.18), allergic rhinitis (OR 3.25, 95% CI 2.26-4.66), and nonallergic rhinitis (OR 1.99, 95% CI 1.39-2.86), respectively.

Conclusion: Rhinitis, both allergic and nonallergic forms, is very common in patients with AD. Future investigations should clarify how medications targeting both diseases should be indicated in these patients.
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http://dx.doi.org/10.1016/j.anai.2021.02.026DOI Listing
July 2021

Infusion of Pituitary Adenylate Cyclase-Activating Polypeptide-38 in Patients with Rosacea Induces Flushing and Facial Edema that Can Be Attenuated by Sumatriptan.

J Invest Dermatol 2021 Jul 16;141(7):1687-1698. Epub 2021 Feb 16.

Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark. Electronic address:

Background: The pathogenesis of rosacea is incompletely understood. Signaling neuropeptides, including PACAP, a regulator of vasodilation and edema, are upregulated in rosacea skin. Here, we evaluated PACAP38-induced rosacea features and examined whether a 5-HT receptor agonist could reduce these features.

Methods: A total of 35 patients with erythematotelangiectatic rosacea received an intravenous infusion of 10 pmol/kg/minute of PACAP38 followed by an intravenous infusion of 4 mg sumatriptan or placebo (saline) on two study days in a double-blind, randomized, placebo-controlled, and cross-over trial.

Results: PACAP38 increased facial skin blood flow by 90%, dilated the superficial temporal artery by 56%, and induced prolonged flushing and facial edema. Compared with placebo, sumatriptan reduced PACAP38-induced facial skin blood flow for 50 minutes (P = 0.023), constricted the superficial temporal artery for 80 minutes (P = 0.010), and reduced duration of flushing (P = 0.001) and facial edema (P < 0.001).

Conclusions: We established a clinical experimental model of rosacea features and showed that sumatriptan was able to attenuate PACAP38-induced rosacea flushing and edema. Findings support a key role of PACAP38 in rosacea flushing pathogenesis. It remains unknown whether PACAP38 inhibition can improve rosacea.

Trial Register: The trial was registered at ClinicalTrials.govNCT03878784 in March 2019.
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http://dx.doi.org/10.1016/j.jid.2021.02.002DOI Listing
July 2021

Memory T helper cells identify patients with nickel, cobalt, and chromium metal allergy.

Contact Dermatitis 2021 Jul 22;85(1):7-16. Epub 2021 Mar 22.

Department of Dermatology and Allergy, National Allergy Research Centre, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark.

Background: Patch testing is the gold standard for identifying culprit allergens in allergic contact dermatitis; however, it is laborious and positive reactions are difficult to quantitate. Development of complementary in vitro tests is, therefore, of great importance.

Objectives: This study aimed to improve the in vitro lymphocyte proliferation test (LPT) to detect allergic responses to nickel (Ni), cobalt (Co), and chromium (Cr).

Methods: Twenty-one metal allergic patients with a positive patch test to Ni (n=16), Co (n=8), and Cr (n=3) and 13 controls were included. All were tested by a flow cytometric LPT.

Results: Metal-reactive cells were identified as T helper (Th) cells with high expression of the memory marker CD45RO. Skin-homing (cutaneous lymphocyte-associated antigen positive [CLA+]) Ni-reactive memory Th (Th ) cells identified individuals with a positive patch test for Ni with 100% sensitivity (95% confidence interval [CI] 81%-100%) and 92% specificity (95% CI 67%-100%). Moreover, Co-specific Th cells expressing CCR6 identified patients with a positive patch test for Co with 63% sensitivity (95% CI 31%-86%) and 100% specificity (95% CI 77%-100%). In Cr allergic individuals, Cr-reactive Th cells tended to increased CLA and CCR6 expression.

Conclusion: Metal-reactive Th cells with high expression of CD45RO and coexpression of CLA and CCR6 improved the LPT, making it an attractive supplement to the patch test.
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http://dx.doi.org/10.1111/cod.13809DOI Listing
July 2021

Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised clinical trial.

Cephalalgia 2021 05 10;41(6):731-748. Epub 2021 Feb 10.

Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark.

Objective: To determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks.

Methods: A total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients received an intravenous infusion of 10 picomole/kg/min of PACAP38 over 20 min followed by an intravenous infusion of 4 mg sumatriptan or placebo over 10 min on two study days in a randomised, double-blind, placebo-controlled, crossover study.

Results: Of 37 patients enrolled, 26 (70.3%) completed the study and were included in analyses. Of the 26 patients, four (15%) developed a PACAP38-induced migraine attack on sumatriptan and 11 patients (42%) on placebo ( = 0.016). There were no differences in area under the curve for headache intensity between sumatriptan (mean AUC 532) and placebo (mean AUC 779) ( = 0.35). Sumatriptan significantly constricted the PACAP38-dilated superficial temporal artery immediately after infusion (T30) compared with infusion of placebo ( < 0.001). Early treatment with intravenously administered sumatriptan prevented PACAP38-induced migraine. Prevention of migraine attacks was associated with vasoconstriction by sumatriptan in the earliest phases of PACAP provocation. These results suggest that sumatriptan prevents PACAP38-induced migraine by modulation of nociceptive transmission within the trigeminovascular system. ClinicalTrials.gov (NCT03881644).
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http://dx.doi.org/10.1177/0333102420975395DOI Listing
May 2021

Prevalence, incidence, and severity of hand eczema in the general population - A systematic review and meta-analysis.

Contact Dermatitis 2021 Jun 23;84(6):361-374. Epub 2021 Feb 23.

National Allergy Research Centre, Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

Accurate assessments of the burden of hand eczema (HE) in the general population are important for public awareness and intervention. The aim of this systematic review and meta-analysis was to provide updated estimates of prevalence and incidence, alongside additional epidemiological endpoints on HE in the general population. PubMed, Embase and Web of Science were searched for studies reporting the prevalence and/or incidence of HE in the general population. Proportion meta-analyses were performed to calculate pooled estimates of prevalence, incidence, severity, and the proportion of individuals with HE and a history of atopic dermatitis. Sixty-six studies were included in the quantitative analysis encompassing 568 100 individuals. The pooled estimates for lifetime, 1-year, and point prevalence were 14.5% (95% confidence interval [CI]: 12.6-16.5), 9.1% (95% CI: 8.4-9.8) and 4.0% (95% CI: 2.6-5.7), respectively. The pooled incidence rate of HE was 7.3 cases/1000 person-years (95% CI: 5.4-9.5). The occurrence of HE was 1.5-2 times higher in females than males. More than one third suffered from moderate/severe disease and around one third had a history of atopic dermatitis. HE was a recurrent, long-lasting disease with an average age at onset of the early- to mid-twenties. In conclusion; HE is a highly prevalent disease in the general population and carries a significant risk of long-term or chronic disease.
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http://dx.doi.org/10.1111/cod.13804DOI Listing
June 2021

Treatment Patterns in Danish Patients with Atopic Dermatitis Before and After Hospital Referral.

Dermatol Ther (Heidelb) 2021 Apr 6;11(2):499-512. Epub 2021 Feb 6.

Eli Lilly and Company, Indianapolis, IN, USA.

Introduction: A number of treatments for atopic dermatitis (AD) are available; however, long-term treatment patterns and healthcare consumption in patients with AD are poorly described.

Methods: We conducted a registry-based longitudinal drug utilization study among Danish patients with AD that were referred to their first-ever visit at hospital-based dermatology clinics. Their first visit was in the period between 1 January 2005 and 31 December 2012, and patients were followed up to 5 years after their first visit.

Results: In total, 8213 people with a first-time hospital dermatologist contact for AD were included in the study (3514 aged 0-9 years, 1501 aged 10-19 years, 3198 aged 20 years or older). At first visit, a baseline history of moderately potent topical corticosteroid (TCS) use was seen among 46.6% of children (0-9 years), whereas potent or very potent TCS use was more frequently among older individuals (e.g., 51.1% and 25.6% of people aged 50 years or older had used potent and very potent TCS, respectively). The median (interquartile range) annual number of visits to general practitioners was 4 (2-7) for children and 5 (2-8) for adults, in the 12 months prior to referral. Three years after referral, these numbers had decreased to 2 (1-4) and 3 (1-6), respectively. In the first year after referral, 6% of patients were prescribed systemic corticosteroids, whereas other systemic therapies were used in 5% or less.

Conclusions: After referral, low proportions of patients received systemic treatment, or potent TCS. These findings highlight considerable differences in treatment patterns between general practitioners and private practice dermatologists, compared with hospital-based dermatologists, and emphasize the need for better adherence to evidence-based treatment guidelines.
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http://dx.doi.org/10.1007/s13555-021-00491-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018988PMC
April 2021

Biomarkers in atopic dermatitis-a review on behalf of the International Eczema Council.

J Allergy Clin Immunol 2021 04 28;147(4):1174-1190.e1. Epub 2021 Jan 28.

Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Atopic dermatitis (AD) is a common yet complex skin disease, posing a therapeutic challenge with increasingly recognized different phenotypes among variable patient populations. Because therapeutic response may vary on the basis of heterogeneous clinical and molecular phenotypes, a shift toward precision medicine approaches may improve AD management. Herein, we will consider biomarkers as potential instruments in the toolbox of precision medicine in AD and will review the process of biomarker development and validation, the opinion of AD experts on the use of biomarkers, types of biomarkers, encompassing biomarkers that may improve AD diagnosis, biomarkers reflecting disease severity, and those potentially predicting AD development, concomitant atopic diseases, or therapeutic response, and current practice of biomarkers in AD. We found that chemokine C-C motif ligand 17/thymus and activation-regulated chemokine, a chemoattractant of T2 cells, has currently the greatest evidence for robust correlation with AD clinical severity, at both baseline and during therapy, by using the recommendations, assessment, development, and evaluation approach. Although the potential of biomarkers in AD is yet to be fully elucidated, due to the complexity of the disease, a comprehensive approach taking into account both clinical and reliable, AD-specific biomarker evaluations would further facilitate AD research and improve patient management.
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http://dx.doi.org/10.1016/j.jaci.2021.01.013DOI Listing
April 2021

Association of Potent and Very Potent Topical Corticosteroids and the Risk of Osteoporosis and Major Osteoporotic Fractures.

JAMA Dermatol 2021 03;157(3):275-282

Department of Dermatology, Bispebjerg University Hospital, University of Copenhagen, Copenhagen, Denmark.

Importance: Systemic and inhaled corticosteroids negatively affect bone remodeling and cause osteoporosis and bone fracture when given continuously or in high doses. However, risk of osteoporosis and major osteoporotic fracture (MOF) after application of topical corticosteroids (TCSs) is largely unexplored.

Objective: To examine the association between cumulative exposure to potent and very potent TCSs and risk of osteoporosis and MOF.

Design, Setting, And Participants: This nationwide retrospective cohort study included 723 251 Danish adults treated with potent or very potent TCSs from January 1, 2003, to December 31, 2017. Data were obtained from Danish nationwide registries. Filled prescription data were converted in equipotent doses to mometasone furoate (1 mg/g). Data were analyzed from June 1 to August 31, 2019.

Exposures: Patients were considered exposed when they had filled prescriptions of cumulative amounts corresponding to the equivalent of at least 500 g of mometasone, using filled prescriptions of 200 to 499 g as the reference group.

Main Outcomes And Measures: The co-primary outcomes were a diagnosis of osteoporosis or MOF. Hazard ratios (HRs) adjusted for age, sex, socioeconomic status, medication use, and comorbidity were calculated with 95% CIs using Cox proportional hazards regression models.

Results: A total of 723 251 adults treated with the equivalent of at least 200 g of mometasone were included in the analysis (52.8% women; mean [SD] age, 52.8 [19.2] years). Dose-response associations were found between increased use of potent or very potent TCSs and the risk of osteoporosis and MOF. For example, HRs of MOF were 1.01 (95% CI, 0.99-1.03) for exposure to 500 to 999 g, 1.05 (95% CI, 1.02-1.08) for exposure to 1000 to 1999 g, 1.10 (95% CI, 1.07-1.13) for exposure to 2000 to 9999 g, and 1.27 (95% CI, 1.19-1.35) for exposure to at least 10 000 g. A 3% relative risk increase of osteoporosis and MOF was observed per doubling of the cumulative TCS dose (HR, 1.03 [95% CI, 1.02-1.04] for both). The overall population-attributable risk was 4.3% (95% CI, 2.7%-5.8%) for osteoporosis and 2.7% (95% CI, 1.7%-3.8%) for MOF. The lowest exposure needed for 1 additional patient to be harmed (454 person-years) was observed for MOF with exposure of at least 10 000 g.

Conclusions And Relevance: These findings demonstrate that use of high cumulative amounts of potent or very potent TCSs was associated with an increased risk of osteoporosis and MOF.
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http://dx.doi.org/10.1001/jamadermatol.2020.4968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970335PMC
March 2021

Abrocitinib for atopic dermatitis - Authors' reply.

Lancet 2021 01;397(10270):196

Pfizer, Groton, CT 06340, USA. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(21)00037-4DOI Listing
January 2021
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