serval:BIB_83DD35FFCF79
Interleukin 23-Helper T Cell 17 Axis as a Treatment Target for Pityriasis Rubra Pilaris.
10.1001/jamadermatol.2016.5384
000399427100014
28122069
Feldmeyer
L.
author
Mylonas
A.
author
Demaria
O.
author
Mennella
A.
author
Yawalkar
N.
author
Laffitte
E.
author
Hohl
D.
author
Gilliet
M.
author
Conrad
C.
author
article
casereport
2017-04-01
JAMA dermatology
2168-6084
2168-6068
journal
153
4
304-308
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.
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
eng
60_published
true
peer-reviewed
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
University of Lausanne
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