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Plaque psoriasis is a common inflammatory condition of the skin characterized by red, flaking lesions. Current therapies for plaque psoriasis target many facets of the autoimmune response, but there is an incomplete understanding of how oxidative damage produced by enzymes such as myeloperoxidase contributes to skin pathology. In this study, we used the Aldara (Imiquimod) cream model of plaque psoriasis in mice to assess myeloperoxidase inhibition for treating psoriatic skin lesions. To assess skin inflammation severity, an innovative mouse psoriasis scoring system was developed. We found that myeloperoxidase inhibition ameliorated psoriasis severity when administered either systemically or topically. The findings of this study support the role of oxidative damage in plaque psoriasis pathology and present potential new therapeutic avenues for further exploration.

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide, with ever increasing incidence and mortality. While most patients can be treated successfully with surgical excision, cryotherapy, or radiation therapy, there exist a subset of patients with aggressive cSCC who lack adequate therapies. Among these patients are solid organ transplant recipients who due to their immunosuppression, develop cSCC at a dramatically increased rate compared to the normal population. The enhanced ability of the tumor to effectively undergo immune escape in these patients leads to more aggressive tumors with a propensity to recur and metastasize. Herein, we present a case of aggressive, multi-focal cSCC in a double organ transplant recipient to frame our discussion and current understanding of the immunobiology of cSCC. We consider factors that contribute to the significantly increased incidence of cSCC in the context of immunosuppression in this patient population. Finally, we briefly review current literature describing experience with localized therapies for cSCC and present a strong argument and rationale for consideration of an IL-2 based intra-lesional treatment strategy for cSCC, particularly in this immunosuppressed patient population.

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c-Jun N-terminal protein kinase 1 (JNK1) is involved in multiple biological processes but its implication in inflammatory skin diseases is still poorly defined. Herein, we studied the role of JNK1 in the context of Aldara®-induced skin inflammation. We observed that constitutive ablation of JNK1 reduced Aldara®-induced acanthosis and expression of inflammatory markers. Conditional deletion of JNK1 in myeloid cells led to reduced skin inflammation, a finding that was associated with impaired Aldara®-induced inflammasome activation in vitro. Next, we evaluated the specific role of JNK1 in epidermal cells. We observed reduced Aldara®-induced acanthosis despite similar levels of inflammatory markers. Transcriptomic and epigenomic analysis of keratinocytes revealed the potential involvement of JNK1 in the EGFR signaling pathway. Finally, we show that inhibition of the EGFR pathway reduced Aldara®-induced acanthosis. Taken together, these data indicate that JNK1 plays a dual role in the context of psoriasis by regulating the production of inflammatory cytokines by myeloid cells and the sensitivity of keratinocytes to EGFR ligands. These results suggest that JNK1 could represent a valuable therapeutic target in the context of psoriasis.

The expanding number of research studies utilizing the imiquimod-induced psoriasiform dermatitis model attests to the usefulness of this procedure. Advantages of this model include rapid development of the skin response and cost-effectiveness. A major limitation is that application of imiquimod cream over large areas of skin, as well as licking and ingestion of the cream, may lead to severe systemic inflammation, which can cause a general decline in health, splenomegaly, and death. In this protocol, Finn chambers are used to localize the imiquimod cream to a small area of the skin. This results in production of severe and reproducible psoriatic skin reactions with significantly less imiquimod, greatly reducing the possibility of untoward systemic effects. Moreover, having psoriasiform and control skin areas on the same mice decreases inter-animal differences. The protocol can be readily adapted for other skin disease models involving topical application of test agents. This article also details functional measurements performed during assays, including skin thickness, blood perfusion, semiquantitative histopathological evaluation, determination of scaling score to monitor psoriatic symptoms, and collection of spleen and body weight data to identify systemic effects. © 2020 The Authors. Basic Protocol: Use of Finn chambers to induce psoriasiform skin reactions with imiquimod Support Protocol 1: Measurement of double-fold dorsal skin thickness Support Protocol 2: Measurement of blood perfusion Support Protocol 3: Determination of scaling score Support Protocol 4: Semiquantitative histopathological scoring Support Protocol 5: Assessment of systemic side effects in response to imiquimod application.

BACKGROUND: Surgical excision is considered standard treatment for nodular basal cell carcinoma (nBCC). However, patients who reject or are unsuited for surgery may benefit from imiquimod (IMQ) 5% cream as an alternative treatment.
OBJECTIVE: The objective of this study was to conduct a systematic review on the efficacy and safety of IMQ for the treatment of nBCC.
METHODS: The terms basal cell carcinoma AND imiquimod OR Aldara were searched on Ovid-MEDLINE, EMBASE, and Cochrane Library databases. Articles were included if they reported the efficacy or side effects of IMQ for nBCC. Primary outcomes included clearance (clinical and histological), recurrence rates, and adverse events. Number of lesions/subjects, treatment regimens, length of treatment, and time to recurrence were secondary outcomes.
RESULTS: Thirty-nine publications, totaling 738 lesions, revealed a 77.4% (335/433 lesions) clinical and 72.9% (390/535 lesions) histological clearance rate. Regimens ranged from once daily 2 days a week to twice daily 7 days a week. Average treatment duration was 8.81 (±3.49) weeks. There was a 1.80% recurrence rate after an average follow-up period of 13.03 (±15.09) months. Common adverse effects included erythema (77.2%), crusting (50.5%), pruritus (34.1%), tenderness/irritation (27.3%), ulceration (25.4%), burning (22.1%), and erosion (21.7%). Unforeseen side effects included conjunctivitis, keratitis, depigmentation, comedone formation, and ruptured epidermoid cysts.
CONCLUSIONS: Imiquimod showed clinical and histological clearance rates of over 70% for nBCC, with a recurrence rate of 1.80%. Although clearance rates are lower than surgery, IMQ can be considered as a treatment option for nBCC in those who decline or are unfit for surgical intervention.

Treatment for cervical intraepithelial neoplasia (CIN) often consists of an excisional procedure. However, less invasive treatment methods have been explored, such as topical treatment with imiquimod cream. Imiquimod has been proven to be effective in the regression of vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VAIN). Previous studies have investigated the effect of imiquimod in CIN and showed well tolerated adverse effects. During a current study in the Netherlands, a number of adverse events have occurred. This case series presents a selection of these. Gynaecologists should be aware of the possible adverse effects of topical treatment with imiquimod cream.

Genome-wide association studies have found that polymorphisms in genes for IL-23 and its receptor are important in psoriasis, and blocking IL-23 is an effective therapy in the disease. The use of Aldara™ , a cream that contains the TLR7 and TLR8 agonist imiquimod (IMQ), was found to exacerbate psoriasis in some patients with pre-existing disease. Intradermal injections of IL-23 and topical application of Aldara/IMQ induce skin inflammation in mice with features similar to psoriasis-including epidermal hyperplasia and accumulation of inflammatory cells in epidermis and dermis-which is mediated by IL-17A, IL-22, and other factors implicated in the human disease. Consequently, these models can be used in preclinical studies to investigate the molecular and cellular pathogenesis of psoriasis, as well as in the evaluation of potential therapies. This article provides detailed methodologies for creating and evaluating the IL-23- and Aldara/IMQ-induced mouse models of psoriasis. The article also provides a protocol for analyzing skin leukocytes by flow cytometry. © 2019 by John Wiley & Sons, Inc.