Activation of Janus kinase signaling pathway in acne lesions

Awad, Sara M.; Tawfik, Yasmin M; El‐Mokhtar, Mohamed A.; El-Gazzar, Amira F; Motaleb, Amira A Abdel

doi:10.1111/dth.14563

Cited by 21 publications

(17 citation statements)

References 33 publications

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“…Theoretically, tofacitinib may be effective in severe acne, where JAK 1 and JAK 3 expression are significantly higher in acne lesion than in normal skin 21 . Although not clear, acneiform lesions during AA treatment may be associated with an increase in seborrhea, an increase in the colonization of Cutibacterium acnes, and a change in the hormonal profile during the treatment.…”

Section: Discussionmentioning

confidence: 99%

Experience with oral tofacitinib in severe alopecia areata with different clinical responses

Rota

Emeksiz

Yıldırım

2021

J of Cosmetic Dermatology

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Background Alopecia areata (AA) and generalized form, universalis (AU) are common causes of noncicatricial alopecia, targeting anagen hair follicles. A dominant interferon‐gamma transcriptional signaling and cytotoxic T lymphocytes were accused as the main drivers of disease pathogenesis. Tofacitinib is a Janus kinase inhibitor that has been proven to interfere with the positive feedback loop between the follicular cell and the cytotoxic T lymphocytes in AA. There is an increasing number of studies reporting success with tofacitinib in AA. Aims We aimed to assess oral tofacitinib's safety and efficacy in 13 recalcitrant AA and AU patients. Methods This is a retrospective pilot study performed between 2017 and 2020. The demographic features and the treatment responses were evaluated with Severity of Alopecia Tool score changes. Results Thirteen recalcitrant alopecia areata patients (3 AA, 10 AU), aged between 17 and 49, were included in the study. The treatment duration was 3‐15 months. All three AA patients responded well; however, the therapy was unsuccessful in five of ten AU patients. Relapse was observed in one of the AA and three of the AU responders. Acneiform lesions and elevation of transaminases were the major side effects. Conclusion Tofacitinib seems to be more promising and thriving in the treatment of AA than AU. Starting the therapy earlier can bring more successful results. Unfortunately, even in the cases that fully respond to treatment, relapse can be observed after discontinuation of the treatment. It is essential to inform patients about this situation in reducing the frustrations that may occur later.

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Section: Discussionmentioning

confidence: 99%

Experience with oral tofacitinib in severe alopecia areata with different clinical responses

Rota

Emeksiz

Yıldırım

2021

J of Cosmetic Dermatology

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“…Furthermore, the Janus kinase/signal transducer (JAK/STAT) signaling pathway, which has been implicated in multiple inflammatory skin conditions, may play a role in the pathogenesis of acne vulgaris. mRNA expression of JAK1 and JAK3 in skin biopsies from acne patients were significantly elevated in comparison to controls ( P < .001) 30 …”

Section: Introductionmentioning

confidence: 94%

“…C. acnes activates both innate and adaptive immunity via toll-like receptors (TLRs) and production of inflammatory mediators, including interferon-gamma, interleukins (IL-1, 6, 8, and 12), and tumor necrosis factor-alpha (TNF-α). 30 Tumor necrosis factor alphainduced protein 3 (TNFAIP3) mRNA expression was shown to be elevated in acne lesions compared to clear skin of the same subjects suggesting that TNFAIP3 plays a role in immune homeostasis of the epidermis. 31 Furthermore, the Janus kinase/signal transducer (JAK/STAT) signaling pathway, which has been implicated in multiple inflammatory skin conditions, may play a role in the pathogenesis of acne vulgaris.…”

Section: Acne Vulgarismentioning

confidence: 99%

“…mRNA expression of JAK1 and JAK3 in skin biopsies from acne patients were significantly elevated in comparison to controls (P < .001). 30 Treatment of acne vulgaris is as varied as its complex pathogenesis would suggest. Interventions range from topical therapy, to systemic therapy, to physical interventions.…”

Section: Acne Vulgarismentioning

confidence: 99%

“…Altered immune responses have been linked in the inflammation related to acne vulgaris. C. acnes activates both innate and adaptive immunity via toll‐like receptors (TLRs) and production of inflammatory mediators, including interferon‐gamma, interleukins (IL‐1, 6, 8, and 12), and tumor necrosis factor‐alpha (TNF‐α) 30 . Tumor necrosis factor alpha‐induced protein 3 (TNFAIP3) mRNA expression was shown to be elevated in acne lesions compared to clear skin of the same subjects suggesting that TNFAIP3 plays a role in immune homeostasis of the epidermis 31 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An updated review of the sebaceous gland and its role in health and diseases Part 2: Pathophysiological clinical disorders of sebaceous glands

Shamloul

Khachemoune

2021

Dermatologic Therapy

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Sebaceous glands are sebum-secreting components of pilosebaceous units. In the second of this two-part series, we review the pathologies in which sebaceous glands are primarily and secondarily implicated. They are primarily involved in steatocystoma simplex and multiplex, sebaceous gland hyperplasia, sebaceoma, sebaceous adenoma, sebaceous carcinoma, nevus sebaceus, and folliculosebaceous cystic hamartoma. Sebaceous glands are secondarily involved in acne vulgaris, seborrheic dermatitis, and androgenic alopecia. Steatocystoma multiplex is a benign congenital anomaly presenting as yellow cysts primarily on the upper body. Sebaceous gland hyperplasia is characterized by yellow, telangiectatic papules with a central dell, and it can be treated with topical retinoids or surgical excision. Sebaceoma clinically presents on the head and neck region as a skin-colored nodule and can be distinguished by immunohistochemistry. Stains used in the diagnosis of sebaceous adenoma and carcinoma include epithelial membrane antigen and adipophilin immunoperoxidase. Surgical excision is the preferred treatment for sebaceoma, sebaceous adenoma, and sebaceous carcinoma. Excision is not always indicated for nevus sebaceus. Folliculosebaceous cystic hamartoma is a relatively rare condition exhibiting both epithelial and mesenchymal components. Patients with acne vulgaris commonly present with papules of closed and open comedones displaying hypercornification. Seborrheic dermatitis presents as sharply demarcated yellow or red patches or plaques; antifungal agents, corticosteroids, and combination antifungal/anti-inflammatory therapies are common treatment modalities. As a result of hair follicle miniaturization, females with androgenic alopecia present with diffuse hair thinning, while men tend to present with balding and hairline recession.

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Janus Kinase Inhibitors and Adverse Events of Acne

Martinez,

Manjaly,

Manjaly

et al. 2023

JAMA Dermatol

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ImportanceJanus kinase (JAK) inhibitors are increasingly used across a range of dermatologic conditions. Adverse events of acne have been noted in some studies in clinical practice, but the scope of this outcome across JAK inhibitors has not been established.ObjectiveTo systematically analyze all published phase 2 and 3 placebo-controlled randomized clinical trials (RCTs) of JAK inhibitors for the risk of acne as an adverse effect of these medications.Data SourcesComprehensive search of Ovid MEDLINE and PubMed databases through January 31, 2023.Study SelectionInclusion criteria were phase 2 and 3 placebo-controlled RCTs of JAK inhibitors published in English with reported adverse events of acne.Data Extraction and SynthesisTwo reviewers independently reviewed and extracted information from all included studies.Main Outcomes and MeasuresThe primary outcome of interest was the incidence of acne following JAK inhibitor use. A meta-analysis was conducted using random-effects models.ResultsA total of 25 unique studies (10 839 unique participants; 54% male and 46% female) were included in the final analysis. The pooled odds ratio (OR) was calculated to be 3.83 (95% CI, 2.76-5.32) with increased ORs for abrocitinib (13.47 [95% CI, 3.25-55.91]), baricitinib (4.96 [95% CI, 2.52-9.78]), upadacitinib (4.79 [95% CI, 3.61-6.37]), deucravacitinib (2.64 [95% CI, 1.44-4.86]), and deuruxolitinib (3.30 [95% CI, 1.22-8.93]). Estimated ORs were higher across studies investigating the use of JAK inhibitors for the management of dermatologic compared with nondermatologic conditions (4.67 [95% CI, 3.10-7.05]) as well as for JAK1-specific inhibitors (4.69 [95% CI, 3.56-6.18]), combined JAK1 and JAK2 inhibitors (3.43 [95% CI, 2.14-5.49]), and tyrosine kinase 2 inhibitors (2.64 [95% CI, 1.44-4.86]).Conclusions and RelevanceIn this systematic review and meta-analysis, JAK inhibitor use was associated with an elevated odds of acne. Patients should be properly counseled on this potential adverse effect of these medications before treatment initiation. Future studies are needed to further elucidate the pathophysiology of this association.

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Activation of Janus kinase signaling pathway in acne lesions

Cited by 21 publications

References 33 publications

Experience with oral tofacitinib in severe alopecia areata with different clinical responses

Experience with oral tofacitinib in severe alopecia areata with different clinical responses

An updated review of the sebaceous gland and its role in health and diseases Part 2: Pathophysiological clinical disorders of sebaceous glands

Janus Kinase Inhibitors and Adverse Events of Acne

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