Topical Imiquimod Research Articles

Plasma Cell Vulvitis: A Systematic Review.

This systematic review aimed to present the available literature on plasma cell vulvitis (PCV), a relatively uncommon form of inflammatory vulvovaginal dermatitis. A literature search was performed in PubMed, Science Direct, and Google Scholar using the following key words: "plasma cell vulvitis," "Zoon vulvitis," and "vulvitis circumscripta plasmacellularis." Specific variables were assessed in each article, including patient age, menopausal status, comorbidities, presenting symptoms, symptom duration, histological description, treatment, and treatment response. Thirty-nine articles met inclusion criteria, including 38 case reports and 1 observational study, with a total of 96 cases of PCV reported. The mean age of diagnosis was 52.9 years, with an age range of 8-76 years. Most common presenting symptoms included pruritis and vaginal discomfort, with average duration of symptoms 28.2 months (range = 2 months to 10 years). All reports demonstrated subepithelial plasma cell infiltrate on histology. Five percent of PCV cases reported concomitant autoimmune conditions and 6% sexually transmitted infections. Most common treatment modalities included topical corticosteroids (n = 41), tacrolimus (n = 6), and imiquimod (n = 6). In 53 reported outcomes, 88.7% of patients had resolution of symptoms with treatment. Clinical research is needed to better determine the diagnostic criteria and to assess the efficacy of treatment options for PCV.

Abstract 2814: Dynamic imaging of tumor-immune microenvironment (TiME) and microvasculature identifies ‘hot' and ‘cold' tumor phenotypes in vivo in patients

Abstract Investigating the dynamic crosstalk between the tumor-immune microenvironment (TiME) and microvasculature in vivo in patients can lead to important insights into the underlying biology, help identify tumor phenotypes and reveal attractive druggable targets. Dynamic non-invasive label-free imaging of TiME and microvasculature in real-time directly in patients using reflectance confocal microscopy (RCM) was investigated on 60 skin cancer patients (basal cell carcinoma, BCC; squamous cell carcinoma, SCC), followed by automated and machine-learning based quantification of TiME and microvasculature features such as vascular density, leukocyte trafficking and immune cell density. Manual (two readers) and histopathological evaluation (dermatopathologist) of these features was also performed. Molecular correlation of imaging features and phenotypes was performed using anti-CD3/anti-CD20 IHC staining for tertiary lymphoid structures (TLS) and total lymphocyte density (n=33), flow cytometry for immune cells (n=3), and differential RNA expression (n=14). Correlation of RCM features and phenotypes at baseline (before treatment) with treatment response was also evaluated on 9 cancer lesions undergoing topical immunotherapy imiquimod. High agreement for feature presence on RCM and Histology, and manual and automated RCM features was observed. Unsupervised clustering on total TiME and microvasculature features on RCM using principal component analysis (PCA) indicates four distinct tumor phenotypes (PCA 1). The phenotype with high inflammation, high trafficking and higher density of vessels or the denoted ‘hot' phenotype correlated with higher activated CD8+ Granzyme B+ cells (67% of total CD8+cells). The clustering pattern on RCM was compared to TLS and lymphocyte density (PCA 2) and gene expression following CIBERSORT analysis (PCA 3). The clustering in RCM correlated better with gene expression (PCA 1 and 3, 100% agreement) than TLS and lymphocyte density (PCA 1 and 2, 86% agreement). The ‘hot' phenotype in RCM correlated with higher immune gene signatures and higher TLS/lymphocyte density. Increased plasma, CD8, activated CD4 memory and activated NK cells, M1 macrophages and monocytes, along with up-regulation of JAK-STAT, chemokine and cell adhesion signaling cascade were found in the ‘hot' RCM phenotype. Statistical modeling for correlating phenotypes with treatment outcomes was performed using principal component-linear discriminant analysis (PC-LDA). Two responders with tumor regression were predicted as ‘hot' phenotype while the non-responding patients (remaining 7) were classified as cold phenotype; suggesting that RCM 'hot' phenotype correlates with better treatment response. Thus, we demonstrate the potential utility of noninvasive RCM imaging in identifying ‘hot' and ‘cold' tumor phenotypes directly in patients. Citation Format: Aditi Sahu, Melissa Gill, Miguel Cordova, Anthony Santella, Kivanc Kose, Teguru Tembo, Anabel Alfonso, Pratik Chandrani, Christi Fox, Salvador Gonzalez, Nicholas Kurtansky, Melissa Pulitzer, William Phillips, Madison Li, Kimeil King, Stephen Dusza, Shuaitong Liu, Ning Yang, Haaris Jilani, Paras Mehta, Ashfaq Marghoob, Allan Halpern, Anthony Rossi, Liang Deng, Chih-Shan Jason Chen, Milind Rajadhyaksha. Dynamic imaging of tumor-immune microenvironment (TiME) and microvasculature identifies ‘hot' and ‘cold' tumor phenotypes in vivo in patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2814.

Multidisciplinary Approach for the Management of Penoscrotal Extramammary Paget's disease –An eUROGEN study

IntroductionWe reviewed the medical and surgical management and long-term outcomes for patients diagnosed with penoscrotal extramammary Pagets disease (EMPD) within an eUROGEN centre. Patients and MethodsRetrospective review of cases from an institutional database with biopsy proven penoscrotal EMPD. ResultsA total of 10 patients were identified with penoscrotal EMPD over a 10-year period. Two patients had a previous history of gastrointestinal and urogenital cancers (20%) and no synchronous or metachronous cancers were identified. Eight patients with non-invasive EMPD (80%) underwent wide local excision of the affected skin, with at least a 5mm macroscopic resection margin and in selected cases simultaneous multiple mapping biopsies around the lesion were performed. Residual disease was present at the margins in seven patients (87.5%), of which three required further surgical excision or adjuvant topical immunotherapy (42.8%). Recurrence after complete excision was 12.5% and was successfully treated with topical imiquimod immunotherapy and CO2 laser therapy. Two patients (20%) had invasive carcinoma and metastatic disease at diagnosis. ConclusionReported recurrence rates of non-invasive penoscrotal EMPD are high and residual disease is present in most cases requiring either close clinical surveillance or adjuvant treatment. We propose an algorithm in the management of this rare disease.

Vulvar pseudotumoral acyclovir-resistant herpes in an HIV-negative, non-immunosuppressed patient: A therapeutic challenge.

BackgroundVulvar pseudotumoral herpes infections have been reported in HIV-positive patients. A 32-year-old HIV-negative woman presented with a 6-month history of a vulvar pseudotumor that had been unresponsive to oral acyclovir and valacyclovir, as well as topical imiquimod.ObjectiveThis study aimed to evaluate the therapeutic efficacy of a multidrug regimen for vulvar pseudotumor herpes infection in an HIV-negative patient.MethodsHistology revealed multinucleated giant cells, consistent with a herpes infection. The patient's herpes simplex virus type 2 was resistant to acyclovir. Immunomodulatory agents (thalidomide and topical imiquimod) were started.ResultsThe lesion enlarged after 6 weeks of treatment. Topical cidofovir 1% gel was added. There was gradual decrease in the pseudotumor size. After 7 months, the Pseudotumor had resolved.ConclusionThis is the first reported case of vulvar pseudotumoral herpes in an immunocompetent, HIV-negative patient. Oral thalidomide, in association with topical imiquimod and topical cidofovir, was effective in treating acyclovir-resistant pseudotumoral herpes of the vulva.

Neoplasia-related spiny keratoderma: Dermoscopic findings of two cases and a literature review.

Neoplasia-related spiny keratoderma: Dermoscopic findings of two cases and a literature review.

Plasma Cell Vulvitis: A Systematic Review of Interventions.

Plasma cell vulvitis (PCV) is a rare chronic inflammatory disorder, where the symptoms can be severe and may affect patient's quality of life. However, there are currently no evidence-based treatment guidelines. The aims of this systematic review were to evaluate efficacy of individual treatments and to inform future research. A systematic search was conducted of publication between 1952 and August 2020 via MEDLINE, Embase, and Emcare. All publications that evaluated the efficacy of treatments for patients with PCV were included. Forty-seven publications comprising 45 case reports and case series and 2 cohort studies were included. To date, there are no randomized controlled trials evaluating the efficacy of different treatment options. There are also no studies that assess the impact of treatment on quality of life. Topical corticosteroids are the most frequently used first-line therapy, with limited evidence to support their efficacy, followed by topical imiquimod and surgical excision. The least supported intervention is cryotherapy. Although descriptive studies support the use of topical corticosteroids and, to a lesser degree, topical calcineurin inhibitors and imiquimod, this review highlights the need for standardized outcome measures and randomized clinical trials for more definitive therapeutic recommendations for women with PCV.

Guidelines of care for the management of actinic keratosis: Executive summary

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. 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. 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. Analysis of the evidence resulted in 18 recommendations, suggesting there are several effective treatments available for AK. 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. 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.

Effects of Dietary Protein Intake on Cutaneous and Systemic Inflammation in Mice with Acute Experimental Psoriasis.

Background: Psoriasis is a systemic inflammatory disorder, primarily characterized by skin plaques. It is linked to co-morbidities including cardiovascular disease and metabolic syndrome. Several studies demonstrate that dietary habits can influence psoriasis development and severity. However, the effect of different dietary protein levels on psoriasis development and severity is poorly understood. In this study, we examine the influence of dietary protein on psoriasis-like skin disease in mice. Methods: We fed male C57BL/6J mice with regular, low protein and high protein chow for 4 weeks. Afterwards, we induced psoriasis-like skin disease by topical imiquimod (IMQ)-treatment on ear and back skin. The local cutaneous and systemic inflammatory response was investigated using flow cytometry analysis, histology and quantitative rt-PCR. Results: After 5 days of IMQ-treatment, both diets reduced bodyweight in mice, whereas only the high protein diet slightly aggravated IMQ-induced skin inflammation. IMQ-treatment induced infiltration of myeloid cells, neutrophils, and monocytes/macrophages into skin and spleen independently of diet. After IMQ-treatment, circulating neutrophils and reactive oxygen species were increased in mice on low and high protein diets. Conclusion: Different dietary protein levels had no striking effect on IMQ-induced psoriasis but aggravated the systemic pro-inflammatory phenotype.

P318 Intra-dermal with topical imiquimod pre-treatment versus intra-muscular hepatitis B vaccination in inflammatory bowel disease patients: a double-blind randomized controlled trial

Abstract Background Patients with inflammatory bowel disease (IBD) are often immunocompromised and at risk of various opportunistic infections including viral hepatitis. Vaccination is recommended to prevent hepatitis B infection, but efficacy with conventional intra-muscular hepatitis B vaccination in IBD patients is suboptimal. Intra-dermal vaccination has been shown to be an effective way in augmenting immune response in poor vaccine responders. In addition, topical imiquimod, a synthetic agonist of toll-like receptor 7, has been shown to further boost the immunogenicity when applied to the injection site before intra-dermal vaccination. Our study compared the efficacy of intra-dermal hepatitis B vaccination with topical imiquimod with conventional intra-muscular hepatitis B vaccination in IBD patients. Methods This is a double-blind, randomized-controlled trial. IBD patients with no evidence of active or past infection nor history of vaccination i.e. negative serology to all HBsAg/Anti-HBc/Anti-HBs were recruited. They were randomized in 1:1 ratio to receive either intra-dermal recombinant hepatitis B vaccine with topical imiquimod pre-treatment to site of injection (ID) or intra-muscular recombinant hepatitis B vaccine with topical aqueous cream (IM). Same dose (20mcg) of vaccine (Engerix B, Glaxo Smith Klein) was administered to both groups at 0, 1, 6 month. The primary outcome was the sero-protection rate at 12-month, defined as percentage of recruited subjects with anti-HBs titre ≥ 10 mIU/mL. Results 104 patients (mean age 46; 68% male; 50% Crohn’s and 50% UC) were enrolled, with 53 received ID and 51 received IM vaccine. The percentage of patients using steroids, immunomulators and biologics at the time of randomization was 15, 55 and 22 %, respectively. Baseline demographic, disease characteristic, and laboratory parameter were comparable between the ID and IM groups. Sero-protection rate at 12-month was significantly higher in the ID arm compared to the IM arm (91% vs. 69%, P=0.005; Figure). Percentage of good responders at 12 month (anti-HBs titre > 100 mIU/mL) was also higher in the ID arm than in the IM (77% vs 59%, P=0.042). Multivariate analysis showed that use of ID vaccine (OR 4.45, 95% CI 1.40-14.47) and a higher albumin level (OR 1.30, 95% CI 1.06-1.58) are associated with better sero-protection rate. There was no significant difference in adverse effects reported in (64% in ID vs 55% in IM; Table). Conclusion ID hepatitis B vaccination with topical imiquimod is safe and offers superior seroprotection against hepatitis B among IBD patients.

RAS-association domain family 1A regulates the abnormal cell proliferation in psoriasis via inhibition of Yes-associated protein.

Psoriasis is a chronic, inflammatory skin disease with a high incidence and recurrence; however, its exact pathogenesis and aetiology remain unclear. This study aimed to analyse the effect of the upstream negative regulator RAS‐association domain family 1A (RASSF1A) on Yes‐associated protein (YAP) in psoriasis. Skin lesions of 22 patients with psoriasis and 19 healthy controls were used. Human epidermal keratinocytes stimulated by M5 (IL‐1α, IL‐17, IL‐22, TNF‐α and oncostatin M) were used to establish a psoriatic cell model. BALB/c mice treated with topical imiquimod were used to establish a psoriatic mouse model. As the methylation level of RASSF1A increased, its expression in psoriatic patients and mice model decreased. Addition of the methylation inhibitor 5‐Aza‐CdR or RASSF1A‐overexpressing lentivirus vector increased RASSF1A and reduced YAP expression; meanwhile improved skin lesions, reduced cell proliferation, induced cell cycle arrest in the G0/G1 phase, increased apoptosis, reduced inflammatory cytokines and activities of ERK, STAT3 and NF‐κB signalling pathways. The results indicated that RASSF1A could play a role in the treatment of psoriasis by inhibiting YAP expression. Based on these findings, targeted drugs that can inhibit the methylation or increase the expression of RASSF1A may be useful for treating psoriasis.

Interventions for basal cell carcinoma: abridged Cochrane systematic review and GRADE assessments.

Basal cell carcinoma (BCC) is the most common cancer affecting white-skinned individuals, and the worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. To assess the effects of interventions for primary BCC in immunocompetent adults. We updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and LILACS. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation method. We used standard methodological procedures expected by Cochrane. We included 52 randomized controlled trials with 6990 participants (median age 65years; range 20-95). Mean study duration was 13months (range 6weeks-10years). Ninety-two per cent (n=48/52) of studies exclusively included histologically low-risk BCC (nodular and superficial subtypes). The certainty of evidence was predominantly low or moderate for the outcomes of interest. Overall, surgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with Mohs micrographic surgery over surgical excision for primary, facial BCC (high-risk histological subtype or located in the 'H-zone' or both) (low-certainty evidence). Nonsurgical treatments, when used for low-risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior. Surgical interventions have lower recurrence rates and remain the gold standard for high-risk BCC. Of the nonsurgical treatments, topical imiquimod has the best evidence to support its efficacy for low-risk BCC. Priorities for future research include agreement on core outcome measures and studies with longer follow-up.

Patient assessment of 5-fluorouracil and imiquimod for the treatment of actinic keratoses: a retrospective study of real-world effectiveness

Background Despite the superior efficacy of topical therapies for the treatment of actinic keratoses in clinical trials, cryosurgery remains a frequent treatment modality in clinical practice. Little is known about patients’ experience of real-world use of topical therapy. Objective To determine the real-world effectiveness and tolerability of 5-fluorouracil and imiquimod in the treatment of actinic keratoses. Methods A phone survey and chart review was conducted among 51 patients prescribed 5-fluorouracil (N = 27) or imiquimod (N = 24) for actinic keratoses. Results Six patients (22%) in the 5-fluorouracil group and five patients (21%) in the imiquimod group reported severe local skin reactions, and three patients in both groups (11% and 13%, respectively) were unwilling to use the respective topical therapies again. Patients in the 5-fluorouracil group had, on average, 3.3 fewer cryosurgery spot treatments following topical treatment. Patients in the imiquimod group averaged 2.0 fewer spot treatments. Limitations While this study provides information on real-world experiences, patients’ responses were limited by the ability to recall treatment and potential adverse effects. Conclusion High rates of skin reactions, prolonged discomfort, and the continued need for procedural treatments may make patients less willing to use topical 5-fluorouracil or imiquimod for actinic keratoses.

STAT3 gain-of-function variants and T cell-mediated inflammation

Abstract STAT3 is a transcription factor that plays a role in the proliferation, survival, and function of many different cell types. In T cells, STAT3 is required for the polarization and function of Th17 cells and can inhibit development of peripheral Tregs. STAT3 polymorphisms have been linked to several common autoimmune disorders where the balance between Th17 and Tregs has been disrupted. Patients with germline gain-of-function variants in STAT3 present with a syndrome of early-onset poly-autoimmunity. We generated two mouse models of STAT3 GOF by CRISPR/Cas9. In these models, mice have a single point mutation, p.G421R or p.T716M, which are two of the exact amino acid substitutions identified in patients. Heterozygous STAT3 GOF mice do not show spontaneous disease or constitutive activation of STAT3 and instead display delayed STAT3 de-phosphorylation following IL-6 stimulation. We hypothesized that STAT3 GOF would enhance Th17 responses and found increased Th17 polarization from naïve STAT3 GOF T cells in vitro. To test whether this increased disease susceptibility in vivo, we treated WT and STAT3 GOF mice with topical imiquimod. Compared to WT, STAT3 GOF mice have more severe disease as demonstrated by ear swelling and epidermal thickness, as well as increased numbers of Th17 cells in peripheral organs at day 7 and in the skin at day 14. No difference was observed in IL-17+ γδ T cell populations in these organs at either time point. STAT3 GOF mice crossed to Rag 1 −/− or IL-22−/− show decreased disease severity, indicating that this response may be mediated by adaptive lymphocytes and IL-22 signaling. These data indicate that STAT3 GOF can exacerbate disease by enhancing Th17 responses that may drive autoimmunity.

Follicular extension of atypical keratinocytes predicts the resistance of actinic keratosis to topical imiquimod treatment: A single-center retrospective analysis.

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 4weeks, 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.

A Perspective on Imiquimod Microneedles for Treating Warts.

Warts are a common skin problem and are caused by infection with a virus. Warts are currently mainly treated by therapies involving ablating tissue or interrupting cellular division. However, all these existing treatments are either invasive or cause skin pain and tissue destruction. Imiquimod is a synthetic compound that belongs to the imidazoquinolinone family. It has been successfully used as a topical drug to treat external anogenital warts. However, topical imiquimod cream for warts is restricted by low skin permeability, and several side effects such as itching, pain, and erosions occur most frequently following topical treatment. Microneedle technology, a minimally invasive drug delivery system, has the potential to overcome the barrier of the stratum corneum. This technique would also offer a painless treatment choice and provide personalized therapies. In the study, we loaded imiquimod within dissolving microneedles using the molding method. Gelatin was used as a structural material for microneedle formation without adding a crosslinker. To our knowledge, this is the first study of using dissolving microneedles and exploring their utilization with imiquimod for the treatment of warts. First, we added fluorescent dye and trypan blue into the microneedles to evaluate the status of drugs in the microneedles and the degradation property of microneedles made of gelatin, respectively. Here we also prove the strength of the imiquimod microneedles and study their capability to penetrate the skin. The results show no apparent differences in mechanical failure after an additional imiquimod-loaded. Besides, we provide evidence that imiquimod microneedles induce secreted embryonic alkaline phosphatase (SEAP) in the RAW 264.7 macrophages. Gelatin does not affect the imiquimod in microneedles; a similar immune response was affected by the imiquimod alone or imiquimod complexed with gelatin. Our research demonstrates a proof of concept of using imiquimod microneedles for future warts treatment.

Topical Imiquimod Does Not Provide an Adjuvant Effect When Administered With Inactivated Influenza A/H5N1 Vaccine in Healthy Young Adults.

Safe, effective, and easy to deploy adjuvants are needed for influenza prepandemic preparedness. Based on recent reports, we hypothesized that preapplication of topical imiquimod followed by intradermal (ID) vaccination with monovalent inactivated influenza A/H5N1 vaccine (MIV A/H5N1) results in improved serologic responses. We randomized 50 healthy adults in a 1:1 ratio to receive topical imiquimod (group 1) or control cream (group 2) followed by ID injection of 9 µg of the hemagglutinin MIV A/H5N1 in 2 doses, 21 days apart. Subjects were followed for safety and serologic responses as measured by the hemagglutination inhibition (HAI) and microneutralization (MN) assays. Solicited and unsolicited adverse events were comparable between groups 1 and 2, and were mostly mild to moderate in severity. At 21 days after dose 2, the geometric mean titers (GMTs) of HAI antibodies against the vaccine strain were 16.2 and 24.3 in groups 1 and 2, respectively. The MN antibody GMTs were 9.3 and 10.7 in groups 1 and 2, respectively. There were no significant differences in antibody levels between groups at study time points. Topical imiquimod administration combined with ID MIV A/H5N1 was safe but did not result in improved serologic responses to the vaccine.Clinical Trials Registration. NCT03472976.

Topical imiquimod as a neo-adjuvant chemotherapy for cartilage salvage in the treatment of nodular basal cell carcinomas of the head and neck

Topical imiquimod as a neo-adjuvant chemotherapy for cartilage salvage in the treatment of nodular basal cell carcinomas of the head and neck

Guidelines of care for the management of actinic keratosis

Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. 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. 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. Analysis of the evidence resulted in 18 recommendations. 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. 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.

Grzybowski's Generalized Eruptive Keratoacanthomas in a Patient with Terminal Kidney Disease-An Unmet Medical Need Equally Ameliorated by Topical Imiquimod Cream and Lapacho Tea Wraps: A Case Report.

IntroductionDevelopment of singular keratoacanthoma (KA) is generally considered a benign condition as it has a tendency to regress spontaneously in spite of histological similarity to squamous cell carcinoma. Most KAs undergo excision to rule out differential diagnoses. Several alternative treatment modalities (keratinolytic, ablative, immunomodulating, antiproliferative, or targeted therapy) have been described in the past with varying success, underlining the therapeutic challenges associated with large or multiple lesions. Isomorphic response (Koebner phenomenon) may limit the efficacy of ablative options, and comorbidity may limit the use of systemic treatments. Less aggressive topical immunomodulatory treatment options represent an alternative with varying therapeutic success.Case ReportHere, we describe the clinical course of a 51-year-old male patient with terminal kidney disease who suffered from the rare benign pruritic condition of Grzybowski’s generalized eruptive keratoacanthomas (GEKA) and experienced a significant reduction of lesions and symptoms upon topical therapy with imiquimod 5% cream and lapacho tea dressings alike.ConclusionsVery little is known about the potential antiinflammatory or antiproliferative effects on the epidermis of the popular phytotherapeutic agent lapacho tea. More studies are warranted considering both the etiology and treatment of GEKA and topical use of phytotherapeutics in dermatology in general. Management of large or multiple KAs remains challenging.

Topical 5% Imiquimod as Monotherapy for Primary Cutaneous and Cutaneous Metastatic Melanoma: Systematic Review of the Literature

Background: Surgery is the gold standard treatment for primary cutaneous melanoma but may not be suitable given some comorbiditiies, lesion size or location, or anticipated functional impairment. Imiquimod (IMQ) is a topical immunotherapy infrequently used for melanoma, often in combination with other treatments. Objective: The present work aims to review the available literature on the safety and efficacy of imiquimod in the treatment of cutaneous primary and metastatic melanoma. Methods: We systematically reviewed the literature on topical imiquimod as monotherapy for melanoma, excluding in situ disease. MEDLINE, EMBASE, and CINAHL searches were conducted using terms related to imiquimod and melanoma, results summarized according to the PRISMA Guidelines and quality of evidence assessed using the GRADE tool. Results: Of 559 citations identified, 14 case reports and series with 38 patients with 95 lesions met inclusion criteria. There was heterogeneity in treatment regimens, including the number of applications and treatment length. Complete clearance was observed in 39% of cases, while the stable or progressive disease was seen in 42% of cases; treatment efficacy was limited in cases with prior metastatic disease. Conclusion: The current literature for the use of imiquimod in cutaneous primary and metastatic melanoma remains scarce, with most evidence derived from case reports and series likely to be influenced by selection bias for positive treatment results. Nevertheless, imiquimod remains a relatively well-tolerated treatment for cutaneous primary and metastatic melanoma that may be used in selected cases.