Treatment of an extensive superficial basal cell carcinoma of the face with imiquimod 5% cream

The efficacy and safety of imiquimod, an immune-response modifier approved for the treatment of anogenital warts that has antiviral and antitumor activity, in the management of an extensive superficial basal cell carcinoma (sBCC) of the face as an alternative to surgical treatment was evaluated in a 75-year-old male with a 4-year history of a progressively enlarging lesion located on the right temporal region. Imiquimod 5% cream was applied daily until clinical resolution. Histopathological confirmation of clinical diagnosis and of tumor clearance were performed before starting treatment and at the end of treatment, respectively. Moreover, monthly post-treatment follow-up visits were planned. At physical examination, an ovalar, erythematous and slightly infiltrated plaque of 5 x 4 cm in size (approximately 20 cm2), partly eroded and crusted, with a sharp, raised, pearly edge, was evident on the right temporal region of the patient. Histopathological examination of a biopsy specimen showed the typical features of sBCC. Imiquimod 5% cream applied daily for 5 months produced complete clinical and histological clearance. No adverse events but considerable irritation were reported during treatment and no relapses were clinically observed at the 6-month follow-up visit. Our findings confirm current reports from the literature showing imiquimod 5% cream to be an effective treatment for sBCC that is especially valuable in avoiding disfigurement in cases of single large lesions located on the face or in those patients who may not be surgical candidates.     

Imiquimod 5% cream: a new treatment for Bowen's disease

Bowen's disease (BD) is a squamous cell carcinoma in situ. Recent studies suggest that human papilloma virus plays an important role in the development of BD. We investigated whether imiquimod 5%, a topical immune response modifier, is an effective treatment for BD in five immunocompetent patients. The lesions were one genital and four extragenital. The frequency of application varied from three times weekly up to twice daily, and treatment duration ranged from 8-24 weeks. Four patients achieved clinical and histological cure. The patient with the genital lesion gained an important reduction in size and infiltration, which enabled surgical removal of the remaining lesion with good functional and cosmetic result. Our results suggest that topical imiquimod 5% is an effective treatment for BD through its viral and antitumor effects.     

Immune-mediated parasite clearance in mice infected with Plasmodium berghei following treatment with manzamine A

Manzamine A, a sponge-derived alkaloid, was recently shown to possess in vivo antimalarial activity against the blood stages of the rodent malaria parasite Plasmodium berghei. A single intraperitoneal dose of 100 micromol/kg of manzamine A suppressed parasite growth but was followed by parasite recrudescence. Forty percent of mice with recrudescing parasites were able to recover and clear the fulminating parasitaemia. Examination of sera from these mice revealed that infected mice treated with manzamine A had a suppressed IFN-gamma production but an increase in their IL-10 and IgG production. The prolonged survival of infected mice treated with manzamine A and the eventual clearance of recrudescing parasites in some of these mice involve a down-regulation of Thl responses and a switch to antibody dependent-Th2 responses.     

Elidel (pimecrolimus) cream 1%: a nonsteroidal topical agent for the treatment of atopic dermatitis

Elidel is a steroid-free cream containing a 1% strength of the topical immunomodulator pimecrolimus. Elidel was specifically developed as a treatment for atopic dermatitis (AD) and is approved for use in children as young as 2 years of age. The production of inflammatory cytokines by activated T cells in skin is thought to play an important role in the pathogenesis of AD. Elidel potently suppresses cytokine production by dermal T cells without significantly impairing systemic immune responses. Elidel does not cause steroid-associated local effects, such as dermal atrophy, striae, or telangiectasia. In randomized controlled clinical studies, twice-daily application of Elidel was shown to significantly improve the signs and symptoms of AD in infants, children, and adults. The clinical effect of Elidel on pruritus, the most troublesome symptom of AD, can be observed within 1 week of therapy and is maintained for the duration of treatment. Elidel is well tolerated; the risk of application-site reactions, such as itching or burning, is comparable with that of the vehicle. Adverse effects were generally mild in patients receiving Elidel and occurred at rates comparable with those in patients receiving vehicle treatment. In a 1-year study, Elidel significantly reduced the incidence of flares when used at the first signs and symptoms of acute AD. As a result, overall corticosteroid use to treat flares was significantly lower in patients using Elidel for early intervention.     

DNA methylation changes following 5-azacitidine treatment in patients with myelodysplastic syndrome

DNA methyltransferase inhibitor, 5-azacitidine (AC) is effective in myelodysplastic syndromes (MDS) and can induce re-expression in cancer. We analyzed the methylation of 25 tumor suppressor genes in AC-treated MDS. Hypermethylation of CDKN2B, FHIT, ESR1, and IGSF4 gene was detected in 9/44 patients. In concordance with the clinical response, a lack of or decreased methylation in 4 patients with hematologic improvements and persistent methylation in 4 others with no response was observed. The mRNA expression of CDKN2B, IGSF4, and ESR1 was significantly reduced in MDS. Our results suggest that methylation changes contribute to disease pathogenesis and may serve as marker to monitor the efficacy of treatments.     

Genomic instability in human actinic keratosis and squamous cell carcinoma

OBJECTIVE:

To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation.

INTRODUCTION:

Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors.

MATERIAL AND METHODS:

Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers.

RESULTS:

MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III.

DISCUSSION:

The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses.

CONCLUSION:

The overall alterations that were observed in the repetitive DNA of actinic keratoses and squamous cell carcinomas indicate the presence of a spectrum of malignant progression.     

Efficacy of immunotherapy with combination of cryotherapy and topical imiquimod for treatment of Kaposi sarcoma

Multiple treatment modalities for Kaposi sarcoma (KS) have been reported, including chemotherapy, radiation therapy, surgical excision, electrochemotherapy, and cryotherapy. Common topical treatments include timolol, imiquimod, and alitretinoin. We searched our institutional database for patients with ICD-9 or 10 codes for KS seen by a dermatologist with experience in KS management from July 1, 2004 to January 1, 2022. We screened patient charts to include patients who received combination therapy of cryotherapy followed by topical imiquimod three times a week for 2 months (n = 9). Patients were followed in the clinic every 3 months. Time to resolution was assessed by photographic evidence of resolution as determined by a dermatologist and corroborated with clinical documentation in patient charts. Median age (IQR) at KS diagnosis was 58 (27.5) years. All patients were male (n = 9, 100%). Majority were white (n = 7, 78%) and non-Hispanic (n = 8, 89%). Five (56%) had classic KS, one (11%) had HIV-associated KS, and three (33%) were HIV-negative men who have sex with men. Median time to resolution was 30.5 weeks, with a median of two treatments. In our study, 93% (n = 42/45) of lesions and 89% (n = 8/9) of patients experienced complete resolution during a median (range) duration of follow-up of 58 (13–209) weeks. Side effects were limited to pain during cryotherapy, occasional blister formation after cryotherapy, and mild inflammation due to imiquimod. No infections were observed. Combination therapy of cryotherapy and topical imiquimod may be an efficacious and comparatively low-risk treatment for limited, cutaneous KS.     

咪喹莫特乳膏对尖锐湿疣免疫调节作用及复发率的影响

目的 探讨采用咪喹莫特乳膏对尖锐湿疣免疫调节作用以及复发率的情况.方法 将尖锐湿疣患者80例随机分为观察组和对照组,各40例.对照组给予激光治疗;观察组在激光治疗后给予咪喹莫特乳膏治疗.结果 观察组治疗总有效率为92.50％,对照组患者治疗总有效率为80.0％,观察组治疗后复发率为12.50％,而对照组复发率为40.00％,差异具有统计学意义(P＜0.05).治疗后,观察组患者IL-4和IL-10水平低于对照组患者IL-4和IL-10水平,且观察组患者IL-12和IFN-γ水平高于对照组患者IL-12和IFN-γ水平,差异具有统计学意义(P＜0.01).治疗后观察组患者CD +4、CD +4/CD +8、NK水平均高于对照组患者CD +4、CD+ 4/CD+8、NK水平,差异具有统计学意义(P＜0.01).观察组患者CD+8水平低于对照组患者CD +8水平,差异具有统计学意义(P＜0.01).治疗6个月后,观察组尖锐湿疣复发患者的CD+3、CD+4、CD+ 4/CD+8以及NK水平低于未复发患者CD+3、CD+4、CD+ 4/CD+8以及NK水平;且复发患者的CD +8水平高于未复发患者CD +8水平,差异具有统计学意义(P＜0.05).结论 咪喹莫特乳膏治疗尖锐湿疣疗效显著,可有效降低复发率,提高患者细胞免疫调节作用是防止尖锐湿疣复发的重要机制.     

Malignant conversion of florid oral and labial papillomatosis during topical immunotherapy with imiquimod

We report a case of a 61-year-old woman suffering from florid oral papillomatosis with a squamous-cell cancer of the floor of the mouth, which was removed by scalpel surgery combined with a radical neck dissection in 1996. Between 1996 and 2000 several histologically benign papillomatous lesions of mouth and lips were removed with laser and electrosurgery. However, the lesions recurred. In July 2000 hyperkeratotic, wart-like lesions were present at the lower and upper lips and at the right angle of the mouth and the adjacent oral mucosa. Overnight treatment with a topical 5% imiquimod cream on a Monday-Wednesday-Friday schedule was initiated. However, due to severe irritation and pain the application had to be reduced to 4 h per night, three times a week, followed by a therapy-free interval of 2 weeks. Despite this treatment consisting of four cycles of 3 weeks (1 week treatment and 2 weeks pause), the lesions increased markedly in size. A biopsy taken from the tumorous lesion from the right angle of the mouth proved to be a squamous-cell carcinoma. The tumors of the labial and oral mucosal sites as well as the right submandibular lymph nodes were removed by wide scalpel excision. The lips were reconstructed by plastic surgery. 24 months after surgical intervention no recurrence nor metastasis to lymph nodes or distal sites were observed.     

Cytokeratin 17 immunoexpression in actinic keratosis (bowenoid and nonbowenoid) and in Bowen disease

Cytokeratin (CK) 17 immunoexpression has been investigated in nonmelanoma skin cancer as well as in many preinvasive epithelial malignancies. However, there is not any previous study of CK17 immunoexpression in actinic keratosis (AK) or Bowen disease in nonimmunocompromised patients. We evaluated CK17 immunoexpression in 20 cases of AK (10 nonbowenoid and 10 bowenoid) as well as in 10 cases of Bowen disease. We identified expression of CK17 in the superficial layers above the atypical foci. In some cases, there were foci of expression by the full thickness of the epidermis, which was the predominant pattern in very few cases (1 Bowen disease and 1 bowenoid AK). In addition, 1 case of bowenoid AK showed CK17 expression in a “skyline” pattern in the basal layer of the epidermis. Cytokeratin 17 immunostaining did not allow us to distinguish between the 3 entities studied. However, the immunostaining allowed us to distinguish atypical foci in the biopsies, even if atypicality was minimal. In addition, CK17 was useful in identifying surgical borders involved by disease in cases in which the hematoxylin-eosin was difficult to evaluate. Cytokeratin 17 immunoexpression might have a role in evaluating surgical borders in some cases of AK and Bowen disease.     

Successful treatment of aciclovir and foscarnet resistant Herpes simplex virus lesions with topical imiquimod in patients infected with human immunodeficiency virus type 1

Aciclovir (ACV)-resistant Herpes simplex virus type-2 (HSV-2) infections are observed commonly in patients also infected with HIV-1. The use of foscarnet (FOS) in these patients may also lead to resistance. This situation can become a difficult therapeutic challenge. Four cases of patients infected with HIV and with mucocutaneous HSV-2 resistant to ACV and FOS are reported. These patients were treated successfully with topical 5% imiquimod. Imiquimod treatment also appeared to delay the time to recurrence of HSV lesions.     

Innervation and functional changes in mesenteric perivascular calcitonin gene-related peptide- and neuropeptide Y-containing nerves following topical phenol treatment

We have previously shown that age-related reduction of innervation and function in mesenteric perivascular calcitonin gene-related peptide-containing vasodilator nerves takes place in spontaneously hypertensive rats. The present study was performed to investigate innervation and functional changes in perivascular calcitonin gene-related peptide- and adrenergic neuropeptide Y-containing nerves after topical treatment with phenol, which damages nerve fibers, around the rat superior mesenteric artery. Under pentobarbital-Na anesthesia, 8-week-old Wistar rats underwent in vivo topical application of phenol (10% phenol in 90% ethanol) or saline (sham rats) to the superior mesenteric artery proximal to the bifurcation of the abdominal aorta. After the treatment, the animals were subjected to immunohistochemistry of the 3rd branch of small arteries proximal to the intestine and to vascular responsiveness testing on day 3 through day 14. The innervation levels of calcitonin gene-related peptide-like immunoreactivity containing fibers and neuropeptide Y-like immunoreactivity containing fibers were markedly reduced on day 3 to day 14 and on day 5 to day 14 after the treatment, compared with those in sham-operated rats, respectively. In perfused mesenteric vascular beds isolated from phenol-treated rats, adrenergic nerve-mediated vasoconstriction and calcitonin gene-related peptide nerve-mediated vasodilation in response to periarterial nerve stimulation (2-12 Hz) were significantly decreased on day 3 and day 7. Neurogenic release of norepinephrine in phenol-treated rats on day 7 was significantly smaller that that in sham-operated rats. Nerve growth factor content in the mesenteric arteries of phenol-treated rats was significantly lower than that in sham-operated rats. Administration of nerve growth factor using osmotic mini-pumps for 7 days after the phenol treatment resulted in greater density of calcitonin gene-related peptide- and neuropeptide Y-like immunoreactivity fibers than in phenol-treated rats and restored decreased vascular responses to periarterial nerve stimulation. These results suggest that topical phenol-treatment of the mesenteric artery effectively induces functional denervation of perivascular nerves, which can be prevented or reversed by nerve growth factor treatment.     

Characterization of a new type of human papillomavirus (HPV) related to HPV5 from a case of actinic keratosis

Human papillomavirus (HPV) DNA sequences, related to the genomes of HPVs associated with epidermodysplasia verruciformis (EV), were detected in DNA samples extracted from biopsied lesions in 2 of 24 cases of actinic keratosis found in the general population. An HPV DNA was molecularly cloned from one of these samples. Blot hybridization experiments, performed under stringent conditions, revealed a significant cross-hybridization only between this HPV DNA and the DNAs of HPV5 and of the HPV5-related types. The extent of homology between them ranged from 7 to 30%, as evaluated by hybridization in liquid phase at saturation followed by nuclease S1 analysis. This showed that the cloned HPV represented a new type, tentatively named HPV36. HPV36 was not found in the other 22 cases of actinic keratosis, but was detected in scrapings of benign lesions of 7 of 18 (39%) EV patients.     

2% Crisaborole topical ointment for the treatment of mild-to-moderate atopic dermatitis

Introduction: Crisaborole 2% topical ointment is an anti-inflammatory, non-steroidal phosphodiesterase 4 inhibitor which is currently under investigation for its potential role in the treatment of atopic dermatitis and psoriasis.

Areas covered: So far, 7 trials have been completed in atopic dermatitis. The 2% strength appeared to be the superior dosing regimen. Pruritus improved significantly within one week. The improvements in objective efficacy assessments in crisaborole-treated patients were also statistically significant compared to the vehicle.

Expert commentary: Crisaborole has several key features in its mode of action which distinguish it from existing treatments for atopic dermatitis (AD), notably its activity against the phosphodiesterase E4 (PDE4) pathway, regulating cyclic AMP (cAMP) levels. This is less immunosuppressive than other pathways and has no effect on skin thinning. The pathway interrupts the itch sensation (pruritus) which means that the itch-scratch cycle, the bane in the life of patients with AD, is interrupted, usually as early as a few days into treatment. Hence, with the promising safety profile demonstrated, early treatment of mild to moderate AD patients might help to control AD better and improve quality of life for patients.     

Onset of action of pimecrolimus cream 1% in the treatment of atopic eczema in infants

BACKGROUND: Data on the efficacy of pimecrolimus cream 1% within the first days of treatment are scarce, as in previous studies, the first postbaseline assessment was performed only after 1 week. OBJECTIVE: We sought to investigate the onset of action of pimecrolimus cream 1% in infants with mild to very severe atopic eczema. METHODS: We used pimecrolimus cream 1% (n = 129) or vehicle cream (n = 66) administered in a double-blind manner for 4 weeks and then open-label pimecrolimus cream 1% for 12 weeks, with a 4-week follow-up period. RESULTS: Pimecrolimus cream 1% reduced the mean Eczema Area and Severity Index at 4 weeks by 71.5% compared with an increase of 19.4% with vehicle ( P < .001). The reduction in the Eczema Area and Severity Index with pimecrolimus cream 1% was significant at day 4 (38.5% vs 17.6% increase with vehicle). Significant improvements in caregivers' assessments of pruritus and sleep loss were observed with pimecrolimus cream 1% by day 2 ( P < .03) and day 3 ( P = .002), respectively, compared with vehicle. Responses to pimecrolimus cream 1% were sustained during the open-label phase, and pimecrolimus cream 1% was well tolerated. Symptoms of atopic eczema returned gradually after discontinuation. CONCLUSION: Pimecrolimus cream 1% was well tolerated and effective in patients with mild to very severe atopic eczema, with rapid onset of action and no disease rebound after discontinuation.