Interleukin 23-Helper T Cell 17 Axis as a Treatment Target for Pityriasis Rubra Pilaris.

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State: Public
Version: Final published version
Serval ID
serval:BIB_83DD35FFCF79
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Interleukin 23-Helper T Cell 17 Axis as a Treatment Target for Pityriasis Rubra Pilaris.
Journal
JAMA dermatology
Author(s)
Feldmeyer L., Mylonas A., Demaria O., Mennella A., Yawalkar N., Laffitte E., Hohl D., Gilliet M., Conrad C.
ISSN
2168-6084 (Electronic)
ISSN-L
2168-6068
Publication state
Published
Issued date
01/04/2017
Peer-reviewed
Oui
Volume
153
Number
4
Pages
304-308
Language
english
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
Abstract
Treatment of pityriasis rubra pilaris (PRP) is solely based on its resemblance to psoriasis rather than any knowledge of its pathomechanism. Insight into pathogenic mediators of inflammation is essential for targeted and valid treatment options that could replace previous serendipitous therapeutic approaches in refractory PRP.
To determine whether blockade of the interleukin 23-helper T cell 17 (IL-23-TH17) pathway with ustekinumab represents an efficacious and, based on its proinflammatory cytokine profile, targeted treatment option in PRP.
In this case report, a patient with PRP received outpatient treatment at a university hospital department of dermatology with ustekinumab according to the dosing regimen approved for psoriasis. Lesional skin biopsy samples were taken from this patient and 2 others with refractory PRP. Messenger RNA (mRNA) expression of proinflammatory innate and T-cell-derived cytokines were measured and compared with skin samples from patients with psoriasis and healthy donors. From 1 patient, lesional skin samples were taken before ustekinumab treatment and 4 and 28 weeks after treatment initiation. Follow-up was completed after 6 months.
Subcutaneous ustekinumab, 45 mg, at weeks 0 and 4 and quarterly thereafter.
The primary outcome was to determine the changes in expression of proinflammatory innate and T-cell-derived cytokines during ustekinumab therapy. The secondary objective was to evaluate the clinical and histopathologic phenotype in relation to the mRNA expression profile of proinflammatory cytokines.
In lesional PRP skin samples from a single patient, upregulated expression levels were found for most proinflammatory innate cytokines, including tumor necrosis factor (TNF), IL-6, IL-12, IL-23, and IL-1β. Among adaptive T-cell cytokines, an increase of TH1 cytokines and, in particular, TH17 cytokines IL-17A, IL-17F, and IL-22 was seen in PRP. The patient with PRP who received ustekinumab showed regression of skin lesions after 2 weeks and almost complete resolution after 1 month. Clinical and histopathologic improvement paralleled the expression levels of TH17 cytokines but not of interferon-γ and TNF, which lagged behind the amelioration.
In this case report, a role of the IL-23-TH17-axis in PRP was identified, suggesting a shared pathogenic inflammatory pathway with psoriasis, despite evident clinical and histopathologic differences. In addition, this report provides a rationale for targeting the IL-23-TH17-pathway as a treatment option for refractory PRP.

Keywords
Adult, Biopsy, Cytokines/genetics, Dermatologic Agents/pharmacology, Dermatologic Agents/therapeutic use, Follow-Up Studies, Humans, Interleukin-23/genetics, Male, Pityriasis Rubra Pilaris/drug therapy, Pityriasis Rubra Pilaris/genetics, Pityriasis Rubra Pilaris/pathology, Psoriasis/pathology, RNA, Messenger/metabolism, Th17 Cells/metabolism, Time Factors, Treatment Outcome, Up-Regulation, Ustekinumab/pharmacology, Ustekinumab/therapeutic use
Pubmed
Web of science
Open Access
Yes
Create date
30/01/2017 19:25
Last modification date
20/08/2019 15:43
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