Rare Cutaneous Side Effects of Imiquimod: A Review on Its Mechanisms, Diagnosis, and Management

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Abstract

As an immune-response modifier, imiquimod can bind to Toll-like receptors on immune cells and enhance innate and adaptive immune responses, exerting potential antitumor and antiviral effects, which led to its approval by the US Food and Drug Administration for the treatment of actinic keratosis, superficial basal cell carcinomas, and anogenital warts, and to its off-label use in treating many other benign and malignant dermatoses. Although topical administration of imiquimod has been considered well tolerated, an increasing number of cutaneous and noncutaneous side effects are being reported as its clinical applications expand. This review primarily focuses on rare cutaneous side effects. To the best of our knowledge, this is the first article to summarize the mechanism, diagnosis, and management of rare cutaneous side effects of imiquimod, which may help to heighten awareness among physicians, especially dermatologists, about potential imiquimod-induced cutaneous side effects.

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The hair follicle as a dynamic miniorgan.

Marlon R. Schneider, Ruth Schmidt-Ullrich, Ralf Paus (2009)

Hair is a primary characteristic of mammals, and exerts a wide range of functions including thermoregulation, physical protection, sensory activity, and social interactions. The hair shaft consists of terminally differentiated keratinocytes that are produced by the hair follicle. Hair follicle development takes place during fetal skin development and relies on tightly regulated ectodermal-mesodermal interactions. After birth, mature and actively growing hair follicles eventually become anchored in the subcutis, and periodically regenerate by spontaneously undergoing repetitive cycles of growth (anagen), apoptosis-driven regression (catagen), and relative quiescence (telogen). Our molecular understanding of hair follicle biology relies heavily on mouse mutants with abnormalities in hair structure, growth, and/or pigmentation. These mice have allowed novel insights into important general molecular and cellular processes beyond skin and hair biology, ranging from organ induction, morphogenesis and regeneration, to pigment and stem cell biology, cell proliferation, migration and apoptosis. In this review, we present basic concepts of hair follicle biology and summarize important recent advances in the field.

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The Dual Role of Cellular Senescence in Developing Tumors and Their Response to Cancer Therapy

Markus Schosserer, Johannes Grillari, Michael BREITENBACH (2017)

Cellular senescence describes an irreversible growth arrest characterized by distinct morphology, gene expression pattern, and secretory phenotype. The final or intermediate stages of senescence can be reached by different genetic mechanisms and in answer to different external and internal stresses. It has been maintained in the literature but never proven by clearcut experiments that the induction of senescence serves the evolutionary purpose of protecting the individual from development and growth of cancers. This hypothesis was recently scrutinized by new experiments and found to be partly true, but part of the gene activities now known to happen in senescence are also needed for cancer growth, leading to the view that senescence is a double-edged sword in cancer development. In current cancer therapy, cellular senescence is, on the one hand, intended to occur in tumor cells, as thereby the therapeutic outcome is improved, but might, on the other hand, also be induced unintentionally in non-tumor cells, causing inflammation, secondary tumors, and cancer relapse. Importantly, organismic aging leads to accumulation of senescent cells in tissues and organs of aged individuals. Senescent cells can occur transiently, e.g., during embryogenesis or during wound healing, with beneficial effects on tissue homeostasis and regeneration or accumulate chronically in tissues, which detrimentally affects the microenvironment by de- or transdifferentiation of senescent cells and their neighboring stromal cells, loss of tissue specific functionality, and induction of the senescence-associated secretory phenotype, an increased secretory profile consisting of pro-inflammatory and tissue remodeling factors. These factors shape their surroundings toward a pro-carcinogenic microenvironment, which fuels the development of aging-associated cancers together with the accumulation of mutations over time. We are presenting an overview of well-documented stress situations and signals, which induce senescence. Among them, oncogene-induced senescence and stress-induced premature senescence are prominent. New findings about the role of senescence in tumor biology are critically reviewed with respect to new suggestions for cancer therapy leveraging genetic and pharmacological methods to prevent senescence or to selectively kill senescent cells in tumors.

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Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors.

Michael Geiges, Wolfgang Thürlimann, Curdin Conrad … (2004)

It has been proposed that the innate immune system plays a central role in driving the autoimmune T-cell cascade leading to psoriasis; however, there is no direct evidence for this. We observed aggravation and spreading of a psoriatic plaque when treated topically with the toll-like receptor (TLR) 7 agonist imiquimod. The exacerbation of psoriasis was accompanied by a massive induction of lesional type I interferon activity, detected by MxA expression after imiquimod therapy. Since imiquimod induces large amounts of type I interferon production from TLR7-expressing plasmacytoid dendritic cell precursors (PDCs), the natural interferon-producing cells of the peripheral blood, we asked whether PDCs are present in psoriatic skin. We identified high numbers of PDCs in psoriatic skin lesions (up to 16% of the total dermal infiltrate) based on their coexpression of BDCA2 and CD123. By contrast, PDCs were present at very low levels in atopic dermatitis and not detected in normal human skin. This study shows that psoriasis can be driven by the innate immune system through TLR ligation. Furthermore, our finding that large numbers of PDCs infiltrate psoriatic skin suggests a role of lesional PDCs as type I interferon-producing targets for the TLR7 agonist imiquimod.

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Author and article information

Contributors

Lin Wang: lkzwl@126.com

Journal

Journal ID (nlm-ta): Dermatol Ther (Heidelb)

Journal ID (iso-abbrev): Dermatol Ther (Heidelb)

Title: Dermatology and Therapy

Publisher: Springer Healthcare (Cheshire )

ISSN (Print): 2193-8210

ISSN (Electronic): 2190-9172

Publication date (Electronic): 1 August 2023

Publication date PMC-release: 1 August 2023

Publication date Collection: September 2023

Volume: 13

Issue: 9

Pages: 1909-1934

Affiliations

GRID grid.13291.38, ISNI 0000 0001 0807 1581, Department of Dermatovenereology, West China Hospital, , Sichuan University, ; No. 37 Guo Xue Xiang, Chengdu, 610041 Sichuan China

Article

Publisher ID: 978

DOI: 10.1007/s13555-023-00978-0

PMC ID: 10442311

PubMed ID: 37528289

SO-VID: e771f1a4-cf8c-4884-8824-b6c9c53ee74f

License:

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 29 April 2023

Date accepted : 5 July 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100013365, West China Hospital, Sichuan University;

Award ID: ZYJC21051

Award Recipient : Lin Wang

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ScienceOpen disciplines: Dermatology

Keywords: imiquimod,rare,cutaneous side effects,mechanism,diagnosis,management

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ScienceOpen disciplines: Dermatology

Keywords: imiquimod, rare, cutaneous side effects, mechanism, diagnosis, management

Rare Cutaneous Side Effects of Imiquimod: A Review on Its Mechanisms, Diagnosis, and Management

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Abstract

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Karger: Dermatology

Most cited references 144

The hair follicle as a dynamic miniorgan.

The Dual Role of Cellular Senescence in Developing Tumors and Their Response to Cancer Therapy

Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors.

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