Clinical healing of erosive oral lichen planus with tildrakizumab implicates the interleukin‐23/interleukin‐17 pathway in the pathogenesis of lichen planus

Ismail, Fathima Ferial; Sinclair, Rodney

doi:10.1111/ajd.13183

Cited by 20 publications

(25 citation statements)

References 11 publications

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“…The IL‐23 units IL12B and IL23A , which are important for the stimulation and pathogenicity of IL‐17A and IL‐22 by lymphocytes, 30 were expressed in PSO and CLP samples (Figure 4B). Of note, recent case studies indicate that IL‐23 neutralization may be effective in OLP 19,21 . Yet, prospective and controlled studies are needed to determine, if IL‐17A or IL‐23 are feasible targets for the treatment of patients with CLP.…”

Section: Discussionmentioning

confidence: 99%

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The inflammation in cutaneous lichen planus is dominated by IFN‐ϒ and IL‐21—A basis for therapeutic JAK1 inhibition

Pietschke

Holstein

Meier

et al. 2020

Experimental Dermatology

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Cutaneous lichen planus (CLP) and psoriasis (PSO) are both common chronic inflammatory skin diseases for which development of new treatments requires the identification of key targets. While PSO is a typical Th17/IL‐17‐disorder, there is some evidence that Th1/IFN‐ɣ dominate the inflammatory process in CLP. Nonetheless, the immunopathogenesis of CLP is not fully explained and key immunological factors still have to be recognized. In this study, we compared the immune signature of CLP lesions with the well‐characterized inflammation present in PSO skin. First, we analysed the histological and immunohistological characteristics of CLP and PSO. Second, we assessed the cytokine expression (IL1A, IL1B, IL4, IL6, IL8, IL10, IL17A, IL19, IL21, IL22, IL23A, IL13, IFNG, TNF, IL12A, IL12B and IL36G) of lesional skin of CLP with PSO by qPCR. Histology revealed a similar epidermal thickness in CLP and PSO. Immunohistochemically, both diseases presented with an inflammatory infiltrate mainly composed by CD3+CD4+ T cells rather than CD3+CD8+. Importantly, mRNA analysis showed a distinct cytokine signature: while levels of IL12B, IL1A, IL6 and IL23 were similar between the two groups, the characteristic PSO‐associated cytokines IL8, IL17A, IL22, IL19 and IL36G were expressed at very low levels in CLP. In contrast, CLP lesional skin was dominated by the expression of IFNG, IL21, IL4, IL12A and TNF. Immunohistochemistry confirmed the dominance of IL‐21, IFN‐ɣ and also pSTAT1 in the dermal infiltrate of CLP, while IL‐17A was more present in PSO. Collectively, this study improves our understanding of the immunological factors dominating CLP. The dominating cytokines and signalling proteins identified suggest that anti‐cytokine therapeutics like JAK inhibitors may be beneficial in CLP.

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Section: Discussionmentioning

confidence: 99%

“…Yet, the exact pathogenic role of Th17 cells in LP still needs to be clarified. First case studies indicate that targeting antibodies neutralizing IL‐17A or IL‐23 may be beneficial for patients with OLP 19‐21 . If CLP would also benefit from IL‐17A or IL‐23 neutralization is uncertain.…”

Section: Introductionmentioning

confidence: 99%

The inflammation in cutaneous lichen planus is dominated by IFN‐ϒ and IL‐21—A basis for therapeutic JAK1 inhibition

Pietschke

Holstein

Meier

et al. 2020

Experimental Dermatology

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“…Studies reported on the presence of increased levels of IL‐17, in blood, sera or the skin [61, 64, 67, 69, 71]. Respectively, there are case reports on the beneficial use of anti‐IL‐17/anti‐IL‐23 treatment, especially in the treatment of erosive MLP [134, 135]. The JAK/STAT pathway, a pathway used by several inflammatory cytokines to downstream their inflammatory signal, gained attention as a potential therapeutic target [136].…”

Section: Management Of Lichen Planusmentioning

confidence: 99%

Lichen planus – a clinical guide

Solimani

Forchhammer

Schloegl

et al. 2021

J Deutsche Derma Gesell

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Summary Lichen planus (LP) is a chronic lichenoid inflammatory disorder of the skin, mucosa and of the appendages. LP is classically characterized by the presence of a rich infiltration of inflammatory T cells, which migrate in the upper part of the dermis, arranged in a band‐like pattern. Different sub types of the disease have been so far described. Albeit LP is clinically well defined, the disease still represents a therapeutic enigma. Especially with regard to mucosal or scalp affecting LP types, which often present a recalcitrant and treatment unresponsive course, efficacious therapeutic options are still lacking. Thus, LP represents a disease with a high psychosocial burden. Yet, development in the deciphering of LP pathogenesis reveals possible new druggable targets, thus paving the way for future therapeutic options. In this clinical guide, we summarize the current clinical knowledge and therapeutic standards and discuss the future perspective for the management of LP.

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“…When a lesion features melanonychia, benign and malignant melanocytic hyperplasia (lentigo, naevus and melanoma) and Bowen's disease should be eliminated as diagnoses. 1,[3][4][5] In the current case, activated melanocytes were observed in the nail bed epithelium, possibly causing melanonychia as observed in our previous case. 1 A definitive diagnosis requires excisional biopsy.…”

Section: Case Lettermentioning

confidence: 69%

Onychopapilloma presenting as longitudinal melanonychia: A case report and literature review

et al. 2021

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Clinical healing of erosive oral lichen planus with tildrakizumab implicates the interleukin‐23/interleukin‐17 pathway in the pathogenesis of lichen planus

Cited by 20 publications

References 11 publications

The inflammation in cutaneous lichen planus is dominated by IFN‐ϒ and IL‐21—A basis for therapeutic JAK1 inhibition

The inflammation in cutaneous lichen planus is dominated by IFN‐ϒ and IL‐21—A basis for therapeutic JAK1 inhibition

Lichen planus – a clinical guide

Onychopapilloma presenting as longitudinal melanonychia: A case report and literature review

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