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Background Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. Objective This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed. Methods A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. Results Analysis of the evidence resulted in 18 recommendations. Limitations This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data. Conclusions Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

Background Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. Treatment options for AK include topical medications, photodynamic therapy, cryosurgery, and laser ablation. Objective This executive summary provides a synopsis of the 18 evidence-based recommendations for the treatment of AK detailed in the Guidelines of Care for the Management of Actinic Keratosis. Methods A multidisciplinary workgroup conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations Assessment, Development and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. Results Analysis of the evidence resulted in 18 recommendations, suggesting there are several effective treatments available for AK. Limitations The analysis informing the recommendations was based on the best available evidence at the time it was conducted. The results of future studies may necessitate a revision of current recommendations. Conclusions Strong recommendations are presented for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are presented for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

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Topical imiquimod therapy has been widely used for actinic keratosis (AK). However, some cases are refractory to treatment. Therefore, an indicator that can predict its efficacy is desired. Herein, we retrospectively analyzed 52 AK lesions treated with imiquimod to investigate the characteristics of refractory lesions. Imiquimod was applied in a cycle of three times weekly for 4 weeks, followed by a 4-week break. This treatment cycle was repeated up to three times and treatment responses were evaluated. As a result, a complete response (CR) was observed in 78.8% (41/52) of lesions. Next, treatment response of lesions was correlated with clinicopathological characteristics including clinical morphology and thickness, pathological morphology and thickness, and presence of follicular extension (FE). Of these, lesions with FE were significantly less responsive to imiquimod treatment; while 92.6% of AK lesions without FE achieved a CR, only 64.0% of AK lesions with FE achieved a CR (p = 0.029). Logistic regression analysis revealed that FE was the sole significant predictor of its efficacy (p = 0.019). These results suggest that preliminary histological evaluation of FE may be useful to predict the efficacy of imiquimod for AK.

Background Treatment strategies for cutaneous squamous cell carcinoma in situ (cSCCIS) are many but reported cure rates are variable and few studies report 5-year follow-up data. Objective To evaluate the treatment of cSCCIS by curettage followed by topical imiquimod 5% cream (C&I). Methods We evaluated all immunocompetent patients with biopsy proven cSCCIS treated by C&I between January 2008 and December 2012. Results A total of 861 patients with 1,198 cSCCIS were treated, with median follow-up of 71 months. The mean tumor diameter was 10.2 mm. The average duration of treatment with imiquimod 5% cream was 21 days. Kaplan-Meier estimated recurrence-free survival at 5-year follow-up was 99.71% with 95% CI (99.38%, 100.00%). A follow-up questionnaire returned by 45% of patients revealed that 94% were satisfied with their treatment. Six hundred eleven patients developed a new nonmelanoma skin cancer (NMSC) during the follow-up period, and 91% (556/611) of patients chose this combination treatment for at least one new NMSC. Conclusion The combination treatment for cSCCIS of C&I had less than 1% cumulative probability of treatment failure at 5 years. Patients tolerated the treatment well, with the majority choosing this method of treatment for at least one new NMSC.

Background: The innate immune system is recognized as an essential aspect of COVID-19 pathogenesis. Toll-like receptors (TLRs) are important in inducing antiviral response, triggering downstream production of interferons (IFNs). Certain loss-of-function variants in TLR7 are associated with increased COVID-19 disease severity, and imiquimod (ImiQ) is known to have immunomodulating effects as an agonist of TLR7. Given that topical imiquimod (topImiQ) is indicated for various dermatologic conditions, it is necessary for dermatologists to understand the interplay between innate immunity mechanisms and the potential role of ImiQ in COVID-19, with a particular focus on TLR7. Summary: Our objective was to survey recent peer-reviewed scientific literature in the PubMed database, examine relevant evidence, and elucidate the relationships between IFNs, TLR7, the innate immune system, and topImiQ in the context of COVID-19. Despite limited studies on this topic, current evidence supports the critical role of TLRs in mounting a strong immune response against COVID-19. Of particular interest to dermatologists, topImiQ can result in systemic upregulation of the immune system via activation of TLR7. Key Message: Given the role of TLR7 in the systemic activation of the immune system, ImiQ, as a ligand of the TLR7 receptor, may have potential therapeutic benefit as a topical immunomodulatory treatment for COVID-19.

The disease, for which the most important treatment method is the surgical excision, differs from normal condyloma acuminatum cases with its high degree of malignancy. The purpose of this paper is to present the case that reached huge dimensions in the perianal region which was treated with wide resection, came to our outpatient department with recurrence and was successfully treated with topical Imiquimod 5 % cream. Keywords: BuschkeLowenstein tumour, Human papillomavirus, Imiquimod.

Background In the photodynamic therapy (PDT) of non‐aggressive basal cell carcinomas (BCCs), 5‐aminolevulinic acid nanoemulsion (BF‐200ALA) has shown non‐inferior efficacy when compared with methyl aminolevulinate (MAL), a widely used photosensitizer. Hexyl aminolevulinate (HAL) is an interesting alternative photosensitizer. To our knowledge, this is the first study using HAL‐PDT in the treatment of BCCs. Objectives To compare the histological clearance, tolerability (pain and post‐treatment reaction), and cosmetic outcome of MAL, BF‐200 ALA, and low‐concentration HAL in the PDT of non‐aggressive BCCs. Methods Ninety‐eight histologically verified non‐aggressive BCCs met the inclusion criteria, and 54 patients with 95 lesions completed the study. The lesions were randomized to receive LED‐PDT in two repeated treatments with MAL, BF‐200 ALA, or HAL. Efficacy was assessed both clinically and confirmed histologically at three months by blinded observers. Furthermore, cosmetic outcome, pain, post‐treatment reactions fluorescence, and photobleaching were evaluated. Results According to intention‐to‐treat analyses, the histologically confirmed lesion clearance was 93.8% (95% confidence interval [CI] = 79.9–98.3) for MAL, 90.9% (95% CI = 76.4–96.9) for BF‐200 ALA, and 87.9% (95% CI = 72.7–95.2) for HAL, with no differences between the arms (p=0.84). There were no differences between the arms as regards pain, post‐treatment reactions, or cosmetic outcome. Conclusions PDT with low‐concentration HAL and BF‐200 ALA have a similar efficacy, tolerability, and cosmetic outcome compared to MAL. HAL is an interesting new option in dermatological PDT, since good efficacy is achieved with a low concentration. peerReviewed

Little guidance on management of basal cell nevus syndrome in children exists. We report a case series of four patients diagnosed with BCNS in early childhood, in whom several highly suspicious lesions were biopsied, but several smaller and questionably concerning lesions were treated with therapies that are more tolerable for children, including topical imiquimod, 5-fluorouracil, cryotherapy, or touch electrodessication following topical anesthetic cream. These therapies were well tolerated, and all residual or persistent lesions were subsequently biopsied and found to be benign. This approach is often preferable for pediatric BCNS patients, in whom concerning lesions can be identified clinically and managed compassionately. However, any lesion that exhibits growth, bleeding, or symptoms should be biopsied for definitive diagnosis.

Cervical high-grade squamous intraepithelial lesions (cHSILs) develop as a result of a persistent high-risk human papilloma virus (hrHPV) infection. The natural course of cHSIL is hard to predict, depending on a multitude of viral, clinical, and immunological factors. Local immunity is pivotal in the pathogenesis, spontaneous regression, and progression of cervical dysplasia; however, the underlying mechanisms are unknown. The aim of this review is to outline the changes in the immune microenvironment in spontaneous regression, persistence, and responses to (immuno)therapy. In lesion persistence and progression, the immune microenvironment of cHSIL is characterized by a lack of intraepithelial CD3+, CD4+, and CD8+ T cell infiltrates and Langerhans cells compared to the normal epithelium and by an increased number of CD25+FoxP3+ regulatory T cells (Tregs) and CD163+ M2 macrophages. Spontaneous regression is characterized by low numbers of Tregs, more intraepithelial CD8+ T cells, and a high CD4+/CD25+ T cell ratio. A ‘hot’ immune microenvironment appears to be essential for spontaneous regression of cHSIL. Moreover, immunotherapy, such as imiquimod and therapeutic HPV vaccination, may enhance a preexisting pro-inflammatory immune environment contributing to lesion regression. The preexisting immune composition may reflect the potential for lesion regression, leading to a possible immune biomarker for immunotherapy in cHSILs.

The extreme diversity of the human immune system, forged and maintained throughout evolutionary history, provides a potent defense against opportunistic pathogens. At the same time, this immune variation is the substrate upon which a plethora of immune-associated diseases develop. Genetic analysis suggests that thousands of individually weak loci together drive up to half of the observed immune variation. Intense selection maintains this genetic diversity, even selecting for the introgressed Neanderthal or Denisovan alleles that have reintroduced variation lost during the out-of-Africa migration. Variations in age, sex, diet, environmental exposure, and microbiome each potentially explain the residual variation, with proof-of-concept studies demonstrating both plausible mechanisms and correlative associations. The confounding interaction of many of these variables currently makes it difficult to assign definitive contributions. Here, we review the current state of play in the field, identify the key unknowns in the causality of immune variation, and identify the multidisciplinary pathways toward an improved understanding. ispartof: NATURE IMMUNOLOGY vol:22 issue:12 pages:1479-1489 ispartof: location:United States status: published

Made available in DSpace on 2022-04-29T08:45:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01 Chromoblastomycosis (CBM) is an infectious disease caused by fungi that is prevalent in tropical and subtropical countries. Besides few therapeutic options, the classical treatment of CBM needs to be administrated for a long period of time, and unfortunately some patients do not show improvement of the lesions. Thus, it becomes urgent to develop new strategies for the treatment of CBM. This work reports a successful treatment, performed with the combination of oral acitretin (50 mg/kg, once a day) plus topical imiquimod (50 mg/g, five times per week) for 5 months in a patient with CBM. A significant improvement of the lesions was observed in the 1st month, and in the 5th a complete regression of lesions was recorded. Changes in the biochemical parameters were not observed. These data suggest that the combination of acitretin and imiquimod may be effective at treating CBM. Dermatology Department Medical School Clinics Hospital University of São Paulo Laboratory of Pathology of Infectious Diseases Medical School University of São Paulo Dermatology Division Medical School Clinics Hospital University of São Paulo São Paulo State University (UNESP) Institute of Biosciences São Paulo State University (UNESP) Institute for Advanced Studies of Ocean São Paulo State University (UNESP) Institute of Biosciences São Paulo State University (UNESP) Institute for Advanced Studies of Ocean

Penile intraepithelial neoplasia (PeIN) is frequently associated with human papilloma virus (HPV). Three cases of PeIN associated with HPV-type 16 were successfully treated with topical imiquimod and concurrent HPV vaccination. Human papilloma vaccine protects against oncogenic human papilloma viruses. In New Zealand, a decline in incidence of PeIN is anticipated with the recent funding of human papilloma vaccine for boys and young men aged 9-26 years. Therefore, HPV vaccination may have a role for treatment of PeIN and prophylaxis.

The management and prognosis of squamous cell carcinoma largely depend on its invasiveness and grade of differentiation. Pigmented nail fold squamous cell carcinoma represents a therapeutic challenge, needing careful treatment to preserve nail function. Here, we report the use of dermoscopy and Reflectance Confocal Microscopy to monitor nail fold squamous cell carcinoma in situ and its response to treatment with topical imiquimod.

Posttransplant lymphoproliferative disorder (PTLD) describes a varied group of lymphoid proliferative processes that affect immunosuppressed solid organ and bone marrow transplant recipients. Approximately 70% of PTLD cases are related to Epstein-Barr virus (EBV) infection, and the average onset is 8.2 years after transplant.1 Plasmacytoma-like PTLD is a particularly rare monomorphic form of PTLD with plasmacytic differentiation. There are very few cases in the literature describing cutaneous manifestations of plasmacytoma-like PTLD.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 We report a unique case of cutaneous EBV-negative plasmacytoma-like PTLD presenting 25 years after renal transplant, responsive to reduced immunosuppression and topical imiquimod 5% cream.

Flat warts are mainly caused by HPV type 3 and 10. The condition is usually seen in young people in visible skin areas such as the back of hands, face, and forehead. Medical treatment may be prolonged in some situations for months and rarely for years making patients unsatisfactory Surgical approaches such as electrocoagulation, cryosurgery, and laser are used when medical treatment fails to control the disease, but surgical removal carries the risk of scar formation and is usually costly. The current study was planned and carried out to evaluate the response of plane warts to 5% imiquimod cream in a sample of Iraqi patients with plane warts. The present cohort study included 20 patients with plane warts. Those patients were selected from the pool of patients visiting the dermatology consultation unit at Al-Diwaniyah teaching hospital, Al-Diwaniyah Province, Iraq during the period from September 2018 through June 2019. Age, gender, and duration of disease were the main variables included in the study; the outcome was a response to treatment classified as complete, partial, and incomplete. All patients were treated by topically applied 5% imiquimod cream once daily and were followed up for a period of time, ranging from 2 weeks to 12 weeks. The results of the current study revealed that treatment duration and response to treatment is shown in table 2. Mean duration of treatment was 7.95 ±3.33 weeks, and it ranged from 2 to 12 weeks. Complete response was seen in 60 %, partial response was identified in 30 %, and no response was the outcome in 10 % of patients. Treatment response was not correlated to the age or gender of patients, but longer duration of disease predicted poor response to treatment. In view of available data in the current study and in previous reports, 5% topical imiquimod cream appears to be an efficient and safe mode of treatment for flat warts.

Background: Actinic keratoses (AK) represent common cutaneous lesions, appearing in 'Field cancerization areas' and potentially evolving toward invasive neoplasm. Immunosuppressed patients frequently develop numerous and aggressive AKs.Aim: In this observational study, we report our experience with topical Imiquimod 3.75% as 'Field-directed therapy' in a cohort of immunosuppressed patients.Methods: A group of 13 immunosuppressed patients presenting multiple AKs of the balding scalp was treated with topical Imiquimod 3.75%. Each patient underwent clinical examination at fixed timepoints during the treatment (T0, T14, T28, T42) and eight weeks after the end.Results: In our cohort, the treatment was well tolerated, with minimal local adverse events. We observed a good clinical response, in terms of Lmax lesions (maximum lesion count during the course of therapy) and of AK clearance. In our group, 46% of patients showed no detectable lesions at the end of the observation period, and this result was maintained up to 1 year after the end of treatment.Conclusion: Topical Imiquimod 3.75% represents an effective and safe treatment for multiple AK of the scalp also in immunosuppressed patients. To the best of our knowledge, this is the first report on the use of this drug in this category of subjects.

Acquired epidermodysplasia verruciformis (AEV) is a form of epidermodysplasia verruciformis (EV) that is most commonly found in immunocompromised or immunosuppressed patients. EV is commonly associated with human papillomavirus (HPV), which is often found in EV and AEV lesions. Clinical presentation of AEV in patients with organ transplantation, HIV+, congenital HIV+, hematological diseases, and other iatrogenic immunosuppression are reviewed. Treatment options include topical cidofovir, topical retinoids, topical imiquimod, topical glycolic acid, HPV 9-valent vaccine, acitretin, improving cellular immunity, and changing transplant medication to mycophenolate mofetil.

Background: Squamous cell carcinoma (SCC) is one of the most common neoplasms affecting the oral cavity and the face. Its more differentiated forms may be associated with human papilloma virus (HPV) infection. Case report: In this paper, we report the case of an 86-year-old patient with a well-differentiated SCC of the lower lip associated with HPV treated with surgery with a non-complete histological resolution. Imiquimod 5% cream was applied on the surgical scar once a day for two weeks and then once a week. Two years after SCC removal, no relapse has occurred. Conclusions: Topical imiquimod may be a safe and effective treatment after surgery in SCC of the oral area to reduce the risk of relapses.

Chromoblastomycosis is a chronic cutaneous fungal infection caused by dematiaceous fungi. It is a therapeutic challenge because of the lack of specific treatments. We describe a refractory case of chromoblastomycosis in which the lesion did not respond to initial treatment, but then use of topical imiquimod cured the lesion successfully.

Background Intratumoral BCG therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumor. However, an increase in the number of BCG-induced tumor-specific T cells in the tumor microenvironment could lead to enhanced therapeutic effects. Methods Here, we have developed a novel cancer vaccine platform based on BCG that can broaden BCG-induced immune responses to include tumor antigens. By physically attaching tumor-specific peptides onto the mycobacterial outer membrane, we were able to induce strong systemic and intratumoral T cell-specific immune responses toward the attached tumor antigens. These therapeutic peptides can be efficiently attached to the mycobacterial outer membrane using a poly-lysine sequence N-terminally fused to the tumor-specific peptides. Results Using two mouse models of melanoma and a mouse model of colorectal cancer, we observed that the antitumor immune responses of BCG could be improved by coating the BCG with tumor-specific peptides. In addition, by combining this novel cancer vaccine platform with anti-programmed death 1 (anti-PD-1) immune checkpoint inhibitor (ICI) therapy, the number of responders to anti-PD-1 immunotherapy was markedly increased. Conclusions This study shows that intratumoral BCG immunotherapy can be improved by coating the bacteria with modified tumor-specific peptides. In addition, this improved BCG immunotherapy can be combined with ICI therapy to obtain enhanced tumor growth control. These results warrant clinical testing of this novel cancer vaccine platform.

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Extramammary Paget’s disease (EMPD) represents an intraepithelial carcinoma whose diagnosis is often delayed as it can be easily misdiagnosed as a benign inflammatory dermatosis. Surgery is considered to be the standard treatment, but all surgical modalities are associated with high local recurrence rates. We give concern of this disease through the description of a case of primary EMPD in an 83-year-old lady treated with an alternative modality of treatment: the sequential use of topical imiquimod and photodynamic therapy. Topical treatments can be an alternative, and when used in combination, it allows increasing tolerance and, therefore, treatment compliance and satisfactory outcomes.