Imiquimod Cream Research Articles

Basal cell carcinoma arising in a tattoo

Cutaneous malignancies may uncommonly arise in the setting of injury to the skin from a variety of etiologies. While melanoma, squamous cell carcinoma, and basal cell carcinoma (BCC) have all been reported at tattoo sites, BCC is the least common, with the present case being only the 12th such case reported in the literature. We present a case of a large BCC of 15 years duration arising within a blue/black tattoo on the patient's left upper arm. The patient was treated with 6 weeks of imiquimod cream with promising results and started a second 6-week regimen to clear residual tumor. Of the 12 reported cases of BCC arising within tattoo sites, the majority of patients have been male (7/12 patients) and the majority of the BCCs developed within the blue or black pigment of the tattoo (8/12 patients) on sun-exposed skin (9/12 patients). The average age at the diagnosis is 53.5 years, and the average duration between tattoo placement and BCC onset is 18.3 years. It has been hypothesized that tattoo ink may be related to the development of malignancies as either a primary carcinogen or cocarcinogen with ultraviolet exposure. Nevertheless, the link between tattoo ink and malignancy may also be coincidental considering the number of tattooed individuals worldwide and the extreme rarity of BCCs that have developed in tattoos. Our purpose is to raise the awareness of the development of cutaneous malignancies within tattoo sites and encourage the physicians to include cutaneous malignancy in the differential diagnosis of “rash” arising in a tattoo.

Ghrelin attenuates imiquimod‐induced psoriasiform skin inflammation in mice

AbstractObjectivesThe endogenous peptide ghrelin, which is produced in the stomach, plays a pivotal role in secretion of growth hormone, regulation of energy metabolism, and cardiovascular protection; however, its anti‐inflammatory action has recently gained immense attention, as this peptide is presumed to be effective in patients with heart failure and chronic lung diseases. In dermatology, psoriasis acts as a typical chronic intractable disease, which may be severe, and although biologic agents have been recommended and used for its treatment in recent years, their application is not clear. We administered ghrelin to IMQ‐induced psoriasis‐like mouse model and examined the anti‐inflammatory effect of ghrelin.MethodsIn the present study, we induced psoriasiform skin inflammation via the continuous application of imiquimod cream on the backs of BALB/c mice and examined the gross and histopathological effect of the subcutaneous administration of ghrelin on psoriasiform skin inflammation.ResultsIt was confirmed that the administration of ghrelin improved various scores, including erythema, scales, and epidermal thickening scores, in mice with psoriasiform skin inflammation.ConclusionsThe results suggest that ghrelin may be effective in treating psoriasis, including cases involving intractable skin lesions that are resistant to conventional therapies.

Establishment of Mouse Models of Psoriasis with Blood Stasis Syndrome Complicated with Glucose and Lipid Metabolism Disorders.

Background Psoriasis has been reported as a high-risk factor for quality of life and survival rate in patients with metabolic disorder. However, there is no animal model for studying this disease. This study aimed to establish and evaluate mouse models of psoriasis with blood stasis syndrome (which is a key to psoriasis pathogenesis, according to Chinese Medicine) complicated with metabolic disorders. Method Forty-five C57BL/6 mice were randomly divided into the blank control (Control), psoriasis (Imiquimod (IMQ)), psoriasis with metabolic disorders (IMQ + streptozotocin (STZ)), psoriasis with blood stasis syndrome (BSS) (IMQ + BSS), and psoriasis with blood stasis syndrome complicated with metabolic disorders (IMQ + STZ + BSS) groups (n = 9 mice/group). Psoriasis lesions were induced using IMQ cream (on both the ears and back, except in the Control group). Mice of the IMQ + BSS group were fed a half-fat, high-sugar diet and stimulated with ice-water swimming every day. Mice of the IMQ + STZ group were fed a half-fat, high-sugar diet and injected with STZ. Mice of the IMQ + STZ + BSS group were subjected to the same treatments as the IMQ + STZ and IMQ + BSS groups. After induction, the mice in each group were observed for vital signs, ear thickness, body weight, and psoriasis area and severity index (PASI) score. The mice were fasted for 12 h before determination of related laboratory serum indexes. Dorsal skin lesions, aortic arch pathology sections, and signal transducer and activator of transcription 3 (STAT3) were examined by H&E staining and immunohistochemistry. Results Laboratory indexes in the four model groups were significantly different from those in the Control group (p < 0.01); indicators of the IMQ + STZ, IMQ + BSS, and IMQ + STZ + BSS groups showed varying degrees of difference from those of the IMQ group. Conclusions The established mouse models of psoriasis blood stasis syndrome complicated with glucose and lipid metabolism disorders met the clinical and Chinese Medicine characteristics, and thus they could be used as animal models in future studies of psoriasis complicated with glucose and lipid metabolism disorders.

Imiquimod-oleic acid prodrug-loaded cream reduced drug crystallinity and induced indistinguishable cytotoxicity and apoptosis in mice melanoma tumour

In the present investigation, imiquimod (IMQ) was coupled to oleic acid (OLA; IMQ-OLA) to synthesise prodrug to reduce crystallinity that later amalgamated with oil-in-water (o/w) emulsion cream (IMQ-OLA cream) for the treatment of melanoma tumour. The synthesis of IMQ-OLA prodrug was verified by FT-IR, 1HNMR and mass spectroscopy. The crystalline lattice of IMQ was transformed to somewhat amorphous structure in IMQ-OLA prodrug. IMQ-OLA cream retained 35.6% of IMQ within skin, significantly (p < 0.05) higher than 22.3% and 10.6% retained by marketed IMQ cream and IMQ solution, respectively. IMQ-OLA cream suppressed the melanoma tumour to 70.3 mm3 in C57BL6J mice as compared to 72.6 mm3 tumour, reduced by marketed IMQ cream with no significant difference (p > 0.05) at day 32 over 17-day period of treatment. IMQ-OLA cream followed the multiple mechanisms of cell death. IMQ-OLA cream warrants further in depth investigations for translating in to a clinically viable topical dermal product.

The Influence of Ketogenic Diets on Psoriasiform-Like Skin Inflammation

The Influence of Ketogenic Diets on Psoriasiform-Like Skin Inflammation

咪喹莫特长期刺激诱发小鼠银屑病样皮损及骨丢失

Objective To establish a mouse model of psoriasis complicated by bone loss by long-term topical application of imiquimod. Methods Twelve 10-week-old Kunming mice were randomly and equally divided into 2 groups: experimental group topically treated with 50 mg/d imiquimod cream every day on the shaved back, and control group topically treated with equivalent vaseline ointment every day on the shaved back. Skin manifestations were observed on the mouse back every day. The mice were sacrificed 10 weeks later. Before the sacrifice, the degree of erythema, scaling and skin thickening was evaluated, psoriasis area severity index (PASI) was calculated, mouse weight was measured, and eyeball blood was obtained. After the sacrifice, skin lesions on the back were resected and subjected to hematoxylin-eosin staining, so as to evaluate histological changes. Then, the left tibia was obtained from the mice, immunohistochemical staining was performed to observe the expression and distribution of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-β ligand (RANKL) in bone tissues, and micro-computerized tomography was conducted to determine the bone mass of spongy bone, and the bone volume-to-total volume ratio, number, thickness, spacing and connectivity density of the trabecular bone in the proximal tibia. The left femur was also obtained from the mice, and subjected to three-point bending test for evaluating its biomechanical properties. Enzyme-linked immunosorbent assay (ELISA) was performed to detect serum levels of tumor necrosis factor (TNF) -α and interleukin (IL) -17. RNA was extracted from the right tibia, and real-time PCR was conducted to determine the mRNA expression of OPG and RANKL. Two-independent-sample t test was used to compare the above indices between two groups. Results Ten-week topical stimulation with imiquimod could lead to psoriasiform dermatitis on the mouse back, presenting as erythema, scales and skin thickening. The PASI score was significantly higher in the experimental group (9.167 ± 1.722) than in the control group (0, t = 13.31, P 0.05) . Moreover, no significant differences in the serum levels of TNF-α and IL-17 were observed between the two groups (both P > 0.05) . Real-time PCR revealed that the mRNA expression of OPG and RNAKL was significantly higher in the experimental group than in the control group (P < 0.05, < 0.01 respectively) . Conclusions Long-term topical application of imiquimod can not only induce psoriasiform dermatitis in mice, but also lead to bone loss of spongy bone and micro-architectural deterioration in the proximal tibia. Thus, mouse models of psoriasis complicated by bone loss can be established by long-term imiquimod stimulation. Key words: Psoriasis; Disease models, animal; Osteoporosis; Imiquimod; Bone mass

A Distinct Pretreatment Immune Gene Signature in Lentigo Maligna Is Associated with Imiquimod Response

Lentigo maligna (LM) is a common subtype of in situ melanoma on chronically sun-exposed skin, particularly the head and neck of older patients. Although surgery is the standard treatment, there is associated morbidity, and options such as imiquimod cream or radiotherapy may be used if surgery is refused or inappropriate. Complete response rates following imiquimod treatment are variable in the literature. The aim of this study was to evaluate the host immune response both before and following treatment with imiquimod to better identify likely responders. Paired pre- and post-imiquimod treatment specimens were available for 27 patients. Patients were treated with imiquimod 5 days per week for 12 weeks; at 16 weeks, lesions were excised for histological assessment. Of the 27 patients, 16 were responders and 11 failed to clear the disease. PDL1 protein expression was increased, accompanied by a unique gene signature in lesions from patients that subsequently histologically cleared LM by 16 weeks. This comprised 57 upregulated immune genes in signaling networks for antigen presentation, type I interferon signaling, and T-cell activation. This may represent an early responder group to imiquimod, and this unique gene signature potentially can be used as a biomarker of LM response to imiquimod.

Imiquimod regulating Th1 and Th2 cell-related chemokines to inhibit scar hyperplasia.

Immunological factors play important roles in the occurrence of hypertrophic scars. Imiquimod can be used as an immunosuppressive agent to regulate the function of T-helper (Th) cell subsets Th1 and Th2. In this article, we explored the impact of imiquimod on scar hyperplasia through Th cells. A rabbit ear hypertrophic scar model was built. Four round wounds were cut in each rabbit's ears ventrally with a diameter of 1 cm and bilateral symmetry. All the right ear wounds were treated with 5% imiquimod cream. The blank control group contained all the left ear wounds, which were treated with Vaseline ointment at the same time. Haematoxylin and eosin and Masson staining showed that imiquimod collagen deposition was significantly reduced compared with the control group, scar index (SEI) showed that the proliferative degree reached its peak on the 28th day after operation in blank group, and the degree of hyperplasia was significantly higher than that of the imiquimod group (P < .05). Real-time Polymerase chain reaction results showed that the imiquimod induced the expression of Th2 cell-related chemokines CCL2, CCL3, CCL5, CCL7, and CCL13 at each time point, which were significantly lower than that of the blank control group, and the expressions of Th1 cell-associated chemokines CXCL10 and CXCL12 at each time point was significantly higher than the blank control group (P < .05). Imiquimod can be used to regulate the expression of Th1 and Th2 cell-associated chemokines to control scar hyperplasia.

Effects of metformin on inflammatory status and phosphorylated Stat3 expression in lesions of a psoriasis-like mouse model

Objective To evaluate the effect of metformin on an imiquimod-induced psoriasis-like mouse model, and to explore its related mechanism. Methods A total of 50 male Balb/c mice were randomly divided into several groups: control group, imiquimod group (IM group) and imiquimod combined with metformin group (IM-Met group) . The IM-Met group were classified into 3 subgroups (100, 150 and 200 g/L IM-Met groups) according to the concentration of metformin. Mice in the control group were treated with topical vaseline cream on the back and intraperitoneal injection of 0.9% sodium chloride physiological solution of 0.3 millilitres every day. Mice in the IM group were treated with topical imiquimod cream on the back and intraperitoneal injection of 0.9% sodium chloride physiological solution of 0.3 millilitres every day. Mice in the 100, 150 or 200 g/L IM-Met groups were treated with topical imiquimod cream on the back and intraperitoneal injection of 100, 150 or 200 g/L metformin of 0.3 millilitres respectively every day. The changes of the erythema area, scales and psoriasis area and severity index (PASI) over time in each group were observed by naked eyes. These mice were sacrificed after 7 days of treatment. Western blot analysis was performed to determine the protein expression of interleukin (IL) -17 and phosphorylated signal transducer and activator of transcription 3 (p-Stat3) in the dorsal skin tissues of these mice, and enzyme-linked immunosorbent assay (ELISA) to detect serum levels of IL-17, IL-6 and tumor necrosis factor-α (TNF-α) in these mice. Comparison among these groups was carried out by using one-way analysis of variance, and means of two groups were compared by using least significant difference (LSD) -t test. Results Compared with the IM group, the 100, 150 and 200 g/L IM-Met groups showed alleviated erythema and scaling severity, and significantly decreased PASI score, protein expression of IL-17 and p-Stat3, and serum levels of inflammation factors such as IL-17, IL-6 and TNF-α (all P 0.05, =0.69, =0.76 respectively) . The serum levels of IL-17, IL-6 and TNF-α in the 150 g/L IM-Met group were 33.388 ± 1.556 ng/L, 210.741 ± 4.440 ng/L and 249.434 ± 8.594 ng/L respectively, which were significantly higher than those in the 200 g/L IM-Met group (26.720 ± 2.156 ng/L, 174.997 ± 9.501 ng/L, 193.034 ± 6.661 ng/L respectively; t=7.93, 10.79 and 16.403 respectively, all P<0.05) , but significantly lower than those in the 100 g/L IM-Met group (44.008 ± 1.722 ng/L, 260.926 ± 7.724 ng/L, 271.409 ± 3.037 ng/L respectively; t=-14.47, -17.81 and -7.62 respectively, all P<0.05) . Conclusion Metformin can alleviate psoriasis-like skin lesions and inflammation status in the imiquimod-induced psoriasis-like mouse model to a certain extent, which may be related to the decrease of p-Stat3 protein expression. Key words: Psoriasis; Metformin; Disease models, animal; Interleukins; Tumor necrosis factor-alpha; Signal transducer and activator of transcription 3

Expression of Ki67 in Precancerous Squamous Cell Skin Lesion of Mice Induced by DMBA

Background: Squamous cell carcinoma (SCC) is an invasive skin cancer that is found in the human skin. SCC growth from the precancerous lesion is known as a wart or papilloma. Ki67 is a protein expressed by cells during proliferation. Cells with higher Ki67 expression showed abnormal regulation of apoptosis. 5-FU is an antimetabolite compound that works as a DNA/RNA pyrimidine antagonist molecule that can induce cell apoptosis. The main objective of this research is to evaluate the inhibition proliferation of precancerous squamous cell in skin lesion induced by DMBA/croton oil treated by using 5-FU cream topically compared to 5% imiquimod cream. Methods: This research assesses three different concentrations of 5-FU cream namely 1%, 2%, and 5% topically on 24 wild type mice divided into 6 groups of 4 each including positive control (with carcinogenesis but without treatment), negative control (without treatment ; normal), carcinogenesis with treatment 5-FU cream (1%, 2%, and 5%) or 5% imiquimod cream. The expression of Ki67 was analyzed using immunohistochemistry. Statistical analysis was performed by one-way ANOVA using SPSS version 23. Results: Based on this research, 5-FU cream treatment during 4 weeks (week 10-week 14) showed the decrease of cumulative number of papilloma (p&lt;0.05) and immunohistochemistry analysis resulted in the lowest Ki67 expression in 5-FU 2% and 5% groups compared to 5% imiquimod cream (p&lt;0.05). Conclusions: 5-FU cream treatment during 4 weeks showed a decrease of papilloma and Ki67 expression in 5-FU cream 2% and

Intra-anal use of imiquimod: what is the clinical evidence?

Imiquimod has been demonstrated to be rather effective in patients with anal as well as perianal high-grade squamous intraepithelial lesions (HSILs). Nevertheless, until now the intra-anal use of imiquimod has been considered off-label. The aim of this study is to review the clinical evidence related to the intra-anal use of imiquimod in the treatment of human papillomavirus-related anal lesions. A systematic search in PubMed and Scopus was performed. In total, 422 patients were included. The most common referred comorbidity was HIV infection (281 patients, 66.6%). The principal clinical entities, which were treated with intra-anal imiquimod, were HSILs. The most frequent formulation was self-applied imiquimod cream. In the HSIL group, there was complete healing in 74 patients (35%) and partial in 44 patients (20.9%), while in the wart group, there was complete healing in 128 patients (67%). Recurrence of HSIL was present in 19 patients (15%), while in cases with warts recurrence was present in 38 patients (19.8%). The most common adverse events were pain, itching, and burning sensation. In conclusion, the adverse effects associated with the intra-anal use of imiquimod seem to be minor. The present clinical evidence suggests that imiquimod may be proposed as effective, safe, and relatively well tolerated treatment.

Efficacy and safety of 5% imiquimod cream compared to 10% KOH solution for elimination of molluscum contagiosum lesions in adults

Background: Molluscum contagiosum (MC) is a benign infection caused by the Molluscipox virus that most often affects children and sexually active adolescents. Various topical therapeutic options are available, however, no single intervention is convincingly effective. Potassium hydroxide (KOH) solution is widely used but its usefulness is hampered with adverse effects. Newer preparation, 5% imiquimod cream seems to be as, if not more, effective. However, it is not legally available yet in Indonesia. Aim: To assess the efficacy and safety of 5% imiquimod cream in treating adult molluscum contagiosum. Methods: Literature search was done through Pubmed , EBSCO, dan Cochrane databases. Inclusion criteria included articles in English, available in free full text and matched with the clinical question as well as providing the clinical outcome of papules clearance within 12 weeks. Results: There were three articles found to be related to the clinical question and they were critically appraised for their validity, importance, and applicability. Conclusion: Only two studies were valid and further assessed for their importance and applicability. In regard s to importance, imiquimod has fewer side effects than KOH, yet it was not constantly shown to be superior to KOH in curing MC lesions. We conclude that KOH solution is the preferred treatment of MC in adults . Keywords: imiquimod, KOH, molluscum contagiosum , safety , efficacy

Interventions for the treatment of Paget's disease of the vulva.

This is an updated version of the original Cochrane Review published in Issue 10, 2013.Extramammary Paget's disease is a rare form of superficial skin cancer. The most common site of involvement is the vulva. It is seen mainly in postmenopausal white women. Paget's disease of the vulva often spreads in an occult fashion, with margins extending beyond the apparent edges of the lesion. There is a range of interventions from surgical to non-invasive techniques or treatments. The challenges of interventions are to remove or treat disease that may not be visible, without overtreatment and with minimisation of morbidity from radical surgery. There is little consensus regarding treatment. Surgery, by default, is the most common treatment, but it is challenging to excise the disease adequately, and recurrence is common, leading to repeated operations, and destruction of anatomy. Alternative treatments of photodynamic therapy, laser therapy, radiotherapy, topical treatments or even chemotherapy have been mooted, and it is important to evaluate the available evidence. It is essential to assess whether newer cell-specific treatments, such as photodynamic therapy and imiquimod, can reduce the need for radical surgery. To evaluate the benefits and harms of different treatment modalities for the management of Paget's disease of the vulva. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid) and Embase (via Ovid) up to 8 May 2018. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles. We searched for randomised controlled trials (RCTs) and well-designed non-randomised studies that compared different interventions in women with Paget's disease of the vulva, DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and, therefore, analysed no data. The search for the original version of the review identified 635 unique references. We found 31 references (which reported on 30 studies) in full text after inspection of titles and abstracts, but we excluded them all as they did not meet the inclusion criteria. However, we have included a comprehensive narrative account of studies where we identified an analysis of more than 10 women, as this forms the only evidence base in this rare disease. Surgery continues to be the mainstay of treatment in the current literature, with other treatments limited to case reports or treatment of inoperable or recurrent disease.This update between September 2013 and May 2018 identified 35 new studies. None of these met the inclusion criteria. There was only one prospective study of 5% imiquimod in recurrent Paget's disease of the vulva, which although of good quality only included eight women. Since the last version of the review was published there are many more cases in the literature reporting a clinical response to 5% imiquimod cream. There is one prospective study of eight women treated with 5% imiquimod for recurrent Paget's disease of the vulva, and one prospective trial of 20 women was due to be reported. This increasing evidence for the safety and efficacy of 5% imiquimod will be helpful for women and clinicians alike. Ideally, a multicentre RCT of reasonable size is needed, but ongoing publications of high-quality non-randomised prospective studies will enhance the current available literature.

Prevalence and management of condylomas in consulting population in Chile: "DIACON study"

Condylomas or genital warts (GW) are the most frequently diagnosed sexually transmitted infection (STI) in STI centers in Chile, but there are no population statistics available. To describe the prevalence of GW in patients from 18-60 years of age who attend outpatient dermatology, gynecology and urology practice; the demographic characteristics of the patients and the diagnostic and treatment tools. A sample of Chilean specialists stratified by region, population and gender of patients was provided with a logbook and answered a questionnaire. The GW prevalence was 2.44% for the whole group; 3.76% for the 18-34 age group and 1.29% for the 35-60 years group (p = 0.0000). The average age of patients with GW was 29.4 years in women and 32.7 years in men (p = 0.019). The distribution by age was different according to gender and health system. Visual inspection was the most frequent diagnostic method used and imiquimod cream the most common treatment, however, there were differences in the use of diagnostic and therapeutic tools according to the patient's gender, specialty of the doctor and health system. The high prevalence of GW confirmed the need and importance of public health interventions to address this problem.

The value of 5% topical imiquimod cream for the treatment of flat warts in a sample of Iraqi patients

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.

Observation on the efficacy and mechanism of Hirudoid in preventing psoriasis-like dermatitis in mice

Objective To observe the preventive effect of Hirudoid (MPS) ointment on psoriasis-like dermatitis in mice and explore its mechanism. Methods 21 Balb/C mice were randomly divided into three groups: blank control group, positive control group (imiquimod group) and treatment group (imiquimod+ Hirudoid group). The blank control group was treated with imiquimod matrix. The positive control group was treated with 5% imiquimod cream to induce psoriatic dermatitis in mice′s back. The treatment group was treated with 5% imiquimod cream in the morning and Hirudoid cream in the afternoon. The changes of skin erythema, scales , infiltration severity and skin histopathology in the experimental area of mice back and serum levels of interleukin (IL)-17A and protein expression of tumor necrosis factor-α (TNF-α) in the three groups of mice were observed. Results The clinical and pathological findings of skin lesions in the positive control group showed that 5% imiquimod cream successfully induced psoriasis-like dermatitis in mice. The appearance and pathological feature of skin lesions in the blank control group were almost close to normal skin. The degree of erythema, infiltration and scales in the back of the treatment group was significantly less than that in the positive control group, and the degree of microscopic inflammation in the treatment group was also lighter than that in the positive control group; The serum levels of IL-17A and TNF-α in the treatment group and the blank control group were significantly lower than that of the positive control group, with statistically significant difference (P<0.05). Conclusions Hirudoid can significantly reduce imiquimod-induced psoriasis-like dermatitis by inhibiting the expression of IL-17A and TNF-α. Key words: Psoriasis; Glycosaminoglycans; Mice

656 Psoriasis and obesity: Stearoyl-CoA desaturase 1 deficient mice are resistant to imiquimod-induced psoriasiform dermatitis

Psoriasis is a chronic inflammatory skin condition whose severity has been linked with obesity. In patients with psoriasis, the likelihood of developing new-onset obesity is higher than those without psoriasis. Stearoyl-CoA desaturase (SCD), is an endoplasmic reticulum resident desaturase, that acts as a catalyst in the synthesis of monounsaturated fatty acids. Mice lacking SCD1 are insulin sensitive, resistant to development of obesity and exhibit suppressed fatty acid synthesis. We have earlier shown that skin specific deletion of SCD1 in mice (SKO) results in epidermal proliferation, sebaceous gland hypoplasia and elevated interleukin 6 levels. We hypothesized that SCD1 deficiency will render mice susceptible to imiquimod (IMQ)-induced psoriasiform dermatitis. A topical dose of 62.5 mg IMQ cream was applied daily to the shaved back region of SKO and SCD1 proficient FLOX counterparts for 14 days after which the mice were euthanized. Cumulative average skin thickness in SKO animals following IMQ application, measured prior to excision was significantly (36%) less than that in FLOX animals. Quantitation of epidermal thickness in H&E stained skin sections validated this observation. Further, histological analysis revealed that in spite of skin inflammation and hair follicle dysplasia associated with their genetic background, the degree of IMQ associated inflammatory changes in the SKO mice were remarkably less than that in FLOX counterparts. Keratin 14, the prototypic marker of dividing basal keratinocytes was elevated in IMQ-treated FLOX skin. Moreover, fatty acid binding protein 5, upregulated in psoriasis tissue was reduced in SKO skin. Our data suggests a complex relationship between fatty acid metabolism and cytoskeletal proteins driving aberrant cell proliferation in psoriatic skin. We propose that SCD1 inhibition could be a novel approach for the management of psoriasis, especially in obese individuals.

The effectiveness of imiquimod 5% cream as an anti-wrinkle treatment: A pilot study.

Imiquimod 5% cream is currently approved to treat several dermatologic conditions including actinic keratoses (AK), superficial basal cell carcinoma (sBCC), and genital warts. However, there are numerous studies published on the alternative off-label uses of imiquimod cream. Photoaging of facial skin is an important use for topical skin treatments, yet few studies have evaluated the effect of imiquimod cream for this dermatological condition. This was a prospective, noncomparative pilot study. We included 15 healthy subjects; out of them, 11 subjects completed the study. The subjects were instructed to apply imiquimod 5% cream to the periorbital area on three nonconsecutive days per week for eight consecutive weeks. Photographs were obtained at baseline and after 8weeks of treatment. Improvement in overall periorbital skin appearance was assessed by an independent investigator who compared the baseline and post-treatment clinical photographs. In addition, post-treatment self-assessment was completed by the subjects using a 5-point Likert scale. Eleven of the 15 subjects completed the 8-week regimen. Eight participants (72.7%) noticed at least a fair improvement in periorbital skin changes based on the self-assessed 5-point Likert scale. Quartile score was also assessed by the investigator which indicated that seven subjects (63.6%) had at least 26% improvement. Based on Fitzpatrick wrinkle-scoring system, there was a significant reduction in the subjects' wrinkle severity following treatment (6.8 [mean]±1.7 [SD] vs 4.6±2.5 [P<0.005]). Imiquimod 5% cream may be a safe alternative anti-aging treatment. Larger scale studies are needed to confirm these results.

Notoginseng root enhances healing in imiquimod-induced psoriasis mice model via anti-inflammatory and antiproliferative properties

Purpose: To evaluate the beneficial effect of Panax notoginseng (PN) gel against imiquimod-induced psoriasis in a mice model.Methods: Psoriasis was induced by topical application of imiquimod cream (5 %) on the shaved skin of mice for 7 days. PN group received PN gel (1 %) twice a day with imiquimod cream (5 %) once a day for one week. The effect of PN gel was estimated by scoring skin thickness, scaling and erythema. Reverse transcription polymerase chain reaction (RT-PCR) was used for the determination of the expressions of inflammatory mediators in skin tissues of mice. Moreover, the severity of inflammation was determined by histopathological and immunohistochemical assessment of skin tissues.Results: The severity of inflammation and the expressions of inflammatory mediators were significantly reduced in PN gel-treated group, relative to the negative control group. Treatment with PN gel attenuated the histopathology of skin tissue in the imiquimod-induced psoriatic mice, and significantly decreased the level of intercellular adhesion molecule (ICAM-1), when compared to the negative control group.Conclusion: These results show that PN gel attenuates psoriasis in imiquimod-induced psoriasis mice model by decreasing skin inflammation. Thus, PN gel may be suitable for the management of psoriasis.Keywords: Psoriasis, Panax notoginseng, Inflammatory mediators, Imiquimod, Intercellular Adhesion Molecule-1

Randomized Trial of Four Treatment Approaches for Actinic Keratosis

BackgroundActinic keratosis is the most frequent premalignant skin disease in the white population. In current guidelines, no clear recommendations are made about which treatment is preferred.MethodsWe investigated the effectiveness of four frequently used field-directed treatments (for multiple lesions in a continuous area). Patients with a clinical diagnosis of five or more actinic keratosis lesions on the head, involving one continuous area of 25 to 100 cm2, were enrolled at four Dutch hospitals. Patients were randomly assigned to treatment with 5% fluorouracil cream, 5% imiquimod cream, methyl aminolevulinate photodynamic therapy (MAL-PDT), or 0.015% ingenol mebutate gel. The primary outcome was the proportion of patients with a reduction of 75% or more in the number of actinic keratosis lesions from baseline to 12 months after the end of treatment. Both a modified intention-to-treat analysis and a per-protocol analysis were performed.ResultsA total of 624 patients were included from November 2014 through March 2017. At 12 months after the end of treatment, the cumulative probability of remaining free from treatment failure was significantly higher among patients who received fluorouracil (74.7%; 95% confidence interval [CI], 66.8 to 81.0) than among those who received imiquimod (53.9%; 95% CI, 45.4 to 61.6), MAL-PDT (37.7%; 95% CI, 30.0 to 45.3), or ingenol mebutate (28.9%; 95% CI, 21.8 to 36.3). As compared with fluorouracil, the hazard ratio for treatment failure was 2.03 (95% CI, 1.36 to 3.04) with imiquimod, 2.73 (95% CI, 1.87 to 3.99) with MAL-PDT, and 3.33 (95% CI, 2.29 to 4.85) with ingenol mebutate (P≤0.001 for all comparisons). No unexpected toxic effects were documented.ConclusionsAt 12 months after the end of treatment in patients with multiple actinic keratosis lesions on the head, 5% fluorouracil cream was the most effective of four field-directed treatments. (Funded by the Netherlands Organization for Health Research and Development; ClinicalTrials.gov number, NCT02281682.)