Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial
Facial seborrheic dermatitis (SD) is an inflammatory skin disease characterized by erythematous and scaly lesions on the skin with high sebaceous gland activity. The yeast <i>Malassezia</i> is regarded as a key pathogenic driver in this disease, but increased <i>Staphylococcus</...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/14315 |
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| author | Jannik Rousel Mahdi Saghari Lisa Pagan Andreea Nădăban Tom Gambrah Bart Theelen Marieke L. de Kam Jorine Haakman Hein E. C. van der Wall Gary L. Feiss Tessa Niemeyer-van der Kolk Jacobus Burggraaf Joke A. Bouwstra Robert Rissmann Martijn B. A. van Doorn |
| author_facet | Jannik Rousel Mahdi Saghari Lisa Pagan Andreea Nădăban Tom Gambrah Bart Theelen Marieke L. de Kam Jorine Haakman Hein E. C. van der Wall Gary L. Feiss Tessa Niemeyer-van der Kolk Jacobus Burggraaf Joke A. Bouwstra Robert Rissmann Martijn B. A. van Doorn |
| author_sort | Jannik Rousel |
| collection | DOAJ |
| description | Facial seborrheic dermatitis (SD) is an inflammatory skin disease characterized by erythematous and scaly lesions on the skin with high sebaceous gland activity. The yeast <i>Malassezia</i> is regarded as a key pathogenic driver in this disease, but increased <i>Staphylococcus</i> abundances and barrier dysfunction are implicated as well. Here, we evaluated the antimicrobial peptide omiganan as a treatment for SD since it has shown both antifungal and antibacterial activity. A randomized, patient- and evaluator-blinded trial was performed comparing the four-week, twice daily topical administration of omiganan 1.75%, the comparator ketoconazole 2.00%, and placebo in patients with mild-to-moderate facial SD. Safety was monitored, and efficacy was determined by clinical scoring complemented with imaging. Microbial profiling was performed, and barrier integrity was assessed by trans-epidermal water loss and ceramide lipidomics. Omiganan was safe and well tolerated but did not result in a significant clinical improvement of SD, nor did it affect other biomarkers, compared to the placebo. Ketoconazole significantly reduced the disease severity compared to the placebo, with reduced <i>Malassezia</i> abundances, increased microbial diversity, restored skin barrier function, and decreased short-chain ceramide Cer[NSc34]. No significant decreases in <i>Staphylococcus</i> abundances were observed compared to the placebo. Omiganan is well tolerated but not efficacious in the treatment of facial SD. Previously established antimicrobial and antifungal properties of omiganan could not be demonstrated. Our multimodal characterization of the response to ketoconazole has reaffirmed previous insights into its mechanism of action. |
| first_indexed | 2024-03-10T22:39:52Z |
| format | Article |
| id | doaj.art-fefc9342294646a0bbf5de7336f22e9b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:39:52Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fefc9342294646a0bbf5de7336f22e9b2023-11-19T11:11:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181431510.3390/ijms241814315Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept TrialJannik Rousel0Mahdi Saghari1Lisa Pagan2Andreea Nădăban3Tom Gambrah4Bart Theelen5Marieke L. de Kam6Jorine Haakman7Hein E. C. van der Wall8Gary L. Feiss9Tessa Niemeyer-van der Kolk10Jacobus Burggraaf11Joke A. Bouwstra12Robert Rissmann13Martijn B. A. van Doorn14Centre for Human Drug Research, 2333 CL Leiden, The NetherlandsCentre for Human Drug Research, 2333 CL Leiden, The NetherlandsCentre for Human Drug Research, 2333 CL Leiden, The NetherlandsLeiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The NetherlandsCentre for Human Drug Research, 2333 CL Leiden, The NetherlandsWesterdijk Fungal Biodiversity Institute, 3508 AD Utrecht, The NetherlandsCentre for Human Drug Research, 2333 CL Leiden, The NetherlandsCentre for Human Drug Research, 2333 CL Leiden, The NetherlandsCentre for Human Drug Research, 2333 CL Leiden, The NetherlandsCutanea Life Sciences, Wayne, PA 19087, USACentre for Human Drug Research, 2333 CL Leiden, The NetherlandsCentre for Human Drug Research, 2333 CL Leiden, The NetherlandsLeiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The NetherlandsCentre for Human Drug Research, 2333 CL Leiden, The NetherlandsCentre for Human Drug Research, 2333 CL Leiden, The NetherlandsFacial seborrheic dermatitis (SD) is an inflammatory skin disease characterized by erythematous and scaly lesions on the skin with high sebaceous gland activity. The yeast <i>Malassezia</i> is regarded as a key pathogenic driver in this disease, but increased <i>Staphylococcus</i> abundances and barrier dysfunction are implicated as well. Here, we evaluated the antimicrobial peptide omiganan as a treatment for SD since it has shown both antifungal and antibacterial activity. A randomized, patient- and evaluator-blinded trial was performed comparing the four-week, twice daily topical administration of omiganan 1.75%, the comparator ketoconazole 2.00%, and placebo in patients with mild-to-moderate facial SD. Safety was monitored, and efficacy was determined by clinical scoring complemented with imaging. Microbial profiling was performed, and barrier integrity was assessed by trans-epidermal water loss and ceramide lipidomics. Omiganan was safe and well tolerated but did not result in a significant clinical improvement of SD, nor did it affect other biomarkers, compared to the placebo. Ketoconazole significantly reduced the disease severity compared to the placebo, with reduced <i>Malassezia</i> abundances, increased microbial diversity, restored skin barrier function, and decreased short-chain ceramide Cer[NSc34]. No significant decreases in <i>Staphylococcus</i> abundances were observed compared to the placebo. Omiganan is well tolerated but not efficacious in the treatment of facial SD. Previously established antimicrobial and antifungal properties of omiganan could not be demonstrated. Our multimodal characterization of the response to ketoconazole has reaffirmed previous insights into its mechanism of action.https://www.mdpi.com/1422-0067/24/18/14315seborrheic dermatitisomigananketoconazole<i>Malassezia</i><i>Staphylococcus</i>skin barrier |
| spellingShingle | Jannik Rousel Mahdi Saghari Lisa Pagan Andreea Nădăban Tom Gambrah Bart Theelen Marieke L. de Kam Jorine Haakman Hein E. C. van der Wall Gary L. Feiss Tessa Niemeyer-van der Kolk Jacobus Burggraaf Joke A. Bouwstra Robert Rissmann Martijn B. A. van Doorn Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial International Journal of Molecular Sciences seborrheic dermatitis omiganan ketoconazole <i>Malassezia</i> <i>Staphylococcus</i> skin barrier |
| title | Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial |
| title_full | Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial |
| title_fullStr | Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial |
| title_full_unstemmed | Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial |
| title_short | Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial |
| title_sort | treatment with the topical antimicrobial peptide omiganan in mild to moderate facial seborrheic dermatitis versus ketoconazole and placebo results of a randomized controlled proof of concept trial |
| topic | seborrheic dermatitis omiganan ketoconazole <i>Malassezia</i> <i>Staphylococcus</i> skin barrier |
| url | https://www.mdpi.com/1422-0067/24/18/14315 |
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