Successful Treatment of Persistent Melanoma In Situ with 5% Imiquimod Cream

Background. Five percent imiquimod cream, a topically applied immune response modifier with potent antiviral and antitumor activity, has been reported to be effective in the management of lentigo maligna and cutaneous metastases from melanoma.
Objective. We report a case in which 5% imiquimod cream was effective in the management of a persistent melanoma in situ.
Methods. Five percent imiquimod cream was applied to the affected area twice to three times a week, as tolerated.
Results. After 4 months of treatment, repeated biopsies of the previously affected areas showed complete regression of the melanoma.
Conclusion. Treatment of melanoma in situ of sun-damaged areas with 5% imiquimod cream certainly appears warranted in selected cases where surgical procedures have failed or are not feasible owing to factors such as size and/or localization of the lesion, advanced age, or deteriorated medical status of the patient. Rigorous posttreatment follow-up is mandatory, because long-term recurrence rates after treatment of melanoma in situ with imiquimod are yet unknown.     

Fluorouracil cream 0.5% for the treatment of actinic keratoses on the face and anterior scalp: interim results of an 18-month open-label study

Objective: This study further assessed the long-term safety and efficacy of fluorouracil cream 0.5% in patients with multiple actinic keratosis (AK) on the face/anterior scalp and other body sites. Design/setting: This 18-month, prospective, open-label, multicenter study comprised two treatment cycles separated by 12 months. Cycle 1 included treatment of AK lesions on the face, anterior scalp, posterior scalp, ears, neck, lips, arms, and/or hands. Once-daily fluorouracil cream 0.5% was applied for four weeks as tolerated, followed by four weeks of follow-up in each treatment cycle. Participants: Adults (N=277) with five or more visible and/or palpable AK lesions on the face/anterior scalp and five or more lesions on the posterior scalp, ears, neck, lips, arms, and/or hands were enrolled. Measurements: Main outcome measures included adverse events (AEs) and reduction/clearance of AK lesions on the face/anterior scalp after four weeks of treatment. Results: Results for treatment of AK lesions on the face/anterior scalp for Cycle 1 are reported. All 277 patients were treated during Cycle 1. Besides anticipated application-site reactions (67.9% and 19.1% of patients experiencing mild-to-moderate and severe events, respectively) and eye irritation, overall incidence of treatment-emergent AEs was low. No individual AE appeared in greater than four percent of patients. At the end of Cycle 1, significant reductions were noted in lesion counts on the face/anterior scalp (84.8%; P<0.0001). Clearance rate for lesions on the face and anterior scalp was 39.8 percent at eight weeks. Conclusion: Results indicate that fluorouracil cream 0.5% is safe and effective for patients with multiple AK lesions on the face/anterior scalp.     

An Investigator-initiated Study to Assess the Safety and Efficacy of Imiquimod 3.75% Cream When Used After Cryotherapy in the Treatment of Hypertrophic Actinic Keratoses on Dorsal Hands and Forearms

Objective: To evaluate the efficacy of combination cryotherapy and imiquimod 3.75% cream versus cryotherapy alone in the treatment of hypertrophic actinic keratosis on the dorsal hand and forearm. Methods: Twenty subjects with at least three hypertrophic actinic keratoses on each dorsal hand or forearm underwent cryotherapy treatment to hypertrophic actinic keratoses. Following cryotherapy, subjects were randomized to have either their right or left dorsal hand or forearm treated with imiquimod 3.75% cream to begin on the same day as cryotherapy treatment. Subjects then utilized the two weeks on, two weeks off, two weeks on regimen of imiquimod 3.75% cream application. Local skin reactions were also assessed. Results: For the cryotherapy/imiquimod 3.75% arm, the median total hypertrophic actinic keratosis reduction was −5.12 and for the cryotherapy alone arm, the median total hypertrophic actinic keratosis reduction was −2.24 (P<0.0094). Limitations: Local skin reactions unbind the investigator. Conclusion: Cryotherapy plus imiquimod 3.75% cream resulted in a statistically significant improvement in the reduction of hypertrophic actinic keratoses than cryotherapy alone at 14 weeks.Actinic keratoses (AKs) are common cutaneous lesions associated with chronic ultraviolet radiation exposure.1 Ultraviolet radiation produces local and systemic immunosuppression, mutations in the p53 tumor suppressor gene, and deoxyribonucleic acid pyrimidine covalent dimmers, each of which is believed to contribute to the dysplasia seen in AK.2–4 While most authorities consider AK as a premalignant lesion, gene expression studies and other evidence is accumulating that AKs are part of a spectrum of lesions ranging from sun-damaged skin to squamous cell carcinoma in situ (SCC).2,5–7 The risk for progression to SCC for an individual AK is reportedly low, but highly variable. In one large study, the risk of progression of AK to primary SCC (invasive or in situ) was 0.60 percent at one year and 2.57 percent at four years. Additionally, approximately 65 percent of all primary SCCs and 36 percent of all primary BCCs diagnosed in the study cohort arose in lesions that previously were diagnosed clinically as AKs.7 However, as patients often have multiple AKs, the overall risk for progression over a lifetime can be significant, and thus treatment of AKs is warranted.5,7,8 In addition, the skin around clinically obvious AK lesions has been subject to the same chronic ultraviolet exposure, resulting in genetic damage and mutations, resulting in field cancerization. Subclinical AKs may progress to clinical AKs, or even de novo invasive SCCs.The current therapies for the treatment of AK include excisional surgery, cryotherapy, electrodessication and curettage, topical chemotherapy, and photodynamic therapy. Though there are no standard guidelines for cryotherapy with liquid nitrogen, liquid nitrogen has been effectively used for decades and several studies have assessed efficacy after complete freezing of actinic keratoses.9 Efficacy can be improved by increasing the freeze time, but this is often associated with greater discomfort, more severe skin necrosis, and increased risk of post-treatment hypopigmentation. In addition, as with other lesion-directed therapies, cryotherapy does not treat subclinical lesions in the surrounding skin. In a study comparing cryotherapy, imiquimod 5%, and 5-fluorouracil (5-FU), sustained clearance at 12 months was 28 percent (7/25) for cryotherapy, 54 percent (16/24) for 5-FU, and 73 percent (19/26) for imiquimod 5%. Sustained clearance of the total treatment field was 33 percent (8/24) for 5-FU and 73 percent (19/26) for imiquimod 5%.10 A significant limitation of this study is a small number of patients treated.Imiquimod is a topical immune response modifier that activates the innate immune system via Toll-like receptor 7, as well as enhances the acquired immune system. Initially approved in the 5% form, imiquimod demonstrated 84-percent median lesion reductions of AKs after one 12-week treatment course.11 More recently, a newer 3.75% pump formulation was approved for the treatment of AKs on the face or balding scalp. Subjects in the Swanson et al12 trial applied cream daily to the entire face or balding scalp for two, two-week treatment cycles, separated by a two-week “rest period” (“2 weeks on, 2 weeks off, 2 weeks on”). Subjects achieved a median lesion reduction of 82 percent, and more than one-third demonstrated complete clearance.12 Topical imiquimod treatment may also reduce subclinical lesions in the treatment area, resulting in fewer new AK lesions developing over the same period of time when compared to local treatment, such as cryotherapy. In fact, more than 80 percent of subjects in the Swanson et al12 trial demonstrated subclinical lesions. Tan et al13 reported that while application of imiquimod or vehicle following cryotherapy resulted in comparable target, AK clearance rates at 12 weeks of 79 percent versus 76 percent, respectively, the imiquimod group had fewer total AKs and fewer subclinical AKs. One recent randomized, doubleblind, placebo-controlled, multicenter study evaluating cryotherapy followed by 3.75% imiquimod cream also found that a short, cyclical treatment course of field-directed daily 3.75% imiquimod cream following lesion-directed cryotherapy was well tolerated and provided additional therapeutic benefits to cryotherapy alone.14Treatment of AKs with cryotherapy followed by imiquimod appears to be logical, as cryotherapy has cytodestructive effects with immediate short-term efficacy on treated AKs, while imiquimod has a slower onset. Imiquimod is also able to treat the entire field via an immunological mechanism with good long-term efficacy outcomes and may treat subclinical lesions that might evolve to clinically visible lesions over time. Thus, using imiquimod post cryotherapy should combine the immediate effects of cryotherapy and the long-term benefits of the imiquimod. Use of imiquimod 3.75% daily allows for a shorter imiquimod treatment duration (6 weeks) than the currently approved 16-week (United States) and eight-week (Europe) regimen for imiquimod 5%. Additionally, imiquimod 3.75% has demonstrated safety and efficacy for the treatment of a 200cm² area (full face or balding scalp) as compared to a patch treatment of 25cm² for the currently approved 5% imiquimod.     

Imiquimod: An Effective Alternative for the Treatment of Invasive Cutaneous Squamous Cell Carcinoma

BACKGROUND: Some patients with invasive cutaneous squamous cell carcinoma are either not adequate surgical candidates or present with lesions in cosmetically sensitive areas in which a surgical procedure might result in an apparent and/or a cosmetically unacceptable scar. OBJECTIVE: To evaluate the effectiveness of imiquimod 5% cream in the treatment of an invasive squamous cell carcinoma in the nose of a young man. METHODS: Imiquimod 5% cream was applied to the lesion five times a week for 12 weeks. RESULTS: Complete clinicopathologic tumor clearance and an excellent cosmetic result were achieved after 12 weeks of imiquimod treatment. CONCLUSION: Imiquimod 5% cream may represent a reasonably effective alternative for the management of invasive squamous cell carcinoma in selected patients.     

Topical Imiquimod Treatment for Nodular Basal Cell Carcinomas: An Open-Label Series

BACKGROUND: Imiquimod has been used for basal cell carcinomas (BCCs). This is the first open-label series using imiquimod for nodular BCC with Mohs surgery resection for confirmation of treatment. OBJECTIVE: To evaluate the efficacy of topical imiquimod in patients with biopsy-proven nodular BCC. RESULTS: After 12 weeks for three times a week application, treatment sites at week 15 were surgically excised using Mohs micrographic surgery. All 15 treatment subjects were clear of BCC. At the 18-month follow-up, no patients had recurrent tumor. CONCLUSION: Imiquimod 5% cream may be another treatment modality for nodular BCC.     

Postsurgical Use of Imiquimod 5% Cream in the Prevention of Earlobe Keloid Recurrences: Results of an Open-Label, Pilot Study

Background. Traditional surgical modalities for the management of earlobe keloids are often associated with high recurrence rates. A recent report suggests that imiquimod 5% cream can be effective in the prevention of keloid recurrences after surgical excision.
Method. To establish the safety and efficacy of imiquimod 5% cream in the prevention of recurrences of excised earlobe keloids.
Methods. Patients who attended a dermatologic surgery clinic for the treatment of earlobe keloids were recruited into the study. Earlobe keloids underwent parallel shave excision. Imiquimod 5% cream was applied daily for 8 weeks followed by an observation period of 16 weeks. In patients who presented with bilateral earlobe keloids, paired comparisons of imiquimod versus intralesional steroid injections were performed.
Results. Eight earlobes were treated with imiquimod 5% cream after parallel keloid removal. Twenty-four weeks after surgery, six (75%) remained recurrence free. Four patients underwent bilateral paired comparisons. At the end of the observation period, two patients (50%) remained recurrence free in the imiquimod-treated areas while experiencing recurrences in the intralesional steroid–treated areas. Local irritation secondary to imiquimod application required rest periods in three cases. In all cases, patients were able to resume therapy and completed the study without further complications.
Conclusion. Although small and uncontrolled, the results of this open-label, pilot study suggest that imiquimod 5% cream may prove to be a reasonably effective adjuvant therapeutic alternative for the prevention of recurrences in excised earlobe keloids.
DR. Martín-García HAS BEEN A CONSULTANT AND SPEAKER FOR 3M PHARMACEUTICALS.     

Treatment of Lentigo Maligna with Imiquimod before Staged Excision

BACKGROUND Imiquimod 5% cream has demonstrated effectiveness in the treatment of lentigo maligna (LM) in several small studies. None of the studies to date have included posttreatment surgical removal to confirm negative histologic margins.
OBJECTIVE The aim of this retrospective analysis was to assess the efficacy of topical imiquimod in LM by circumferentially examining vertically oriented sections from a geometrically designed "picture frame" margin as well as bread-loafed sections of the central portion after staged excisions of imiquimod-treated lesions of LM.
METHODS Forty patients with biopsy-confirmed LM were treated five times a week for 3 months with 5% imiquimod cream before staged excision. Tazarotene 0.1% gel was added when no clinical signs of erythema developed with imiquimod alone after 1 month (10 patients). After the course of topical therapy, patients were assessed for clinical and complete histologic clearance after staged excision.
RESULTS A total of 33 of 40 patients had a complete clinical response as determined by the absence of remaining clinical lesion on physical examination. Upon histologic review, 30 of 40 patients had no evidence of LM whereas 10 of 40 harbored residual disease. One patient was found to have histologic evidence of invasion after completing the topical protocol. After a mean follow-up of 18 months (range, 12–34 months) and after complete surgical excision of the treatment site, none of the imiquimod-treated patients had evidence of recurrence.
CONCLUSIONS Imiquimod appears to be an effective adjunctive treatment for LM but does not qualify as a replacement therapy for surgery.     

Therapeutic Response of a Brother and Sister with Xeroderma Pigmentosum to Imiquimod 5% Cream

BACKGROUND: Xeroderma pigmentosum (XP) is an autosomal recessive disease marked by solar sensitivity, photophobia, early onset of freckling, and solar-induced cutaneous neoplastic changes. These patients can often develop hundreds of cutaneous tumors, making surgical therapy difficult. Imiquimod 5% cream has been shown to have activity in treating various cutaneous malignancies. OBJECTIVE: To examine the effectiveness and tolerability of imiquimod 5% cream in treating facial basal cell carcinomas (BCCs) in a brother and sister with XP. These patients were developing skin cancers faster than could be managed surgically and had failed 6 months of chemoprophylaxis with isotretinoin. METHODS: Imiquimod 5% cream was applied to the faces of these two patients as frequently as tolerated, with the goal of gaining control over the many clinically evident BCCs present on the faces of these siblings. We also examined whether we could reduce the rate of new neoplasm development. RESULTS: The brother in our study tolerated imiquimod 5% cream twice a day every day with minimal inflammatory response. He had clinical resolution of many of the BCCs present within the treatment area as well as shrinking of many of the remaining lesions. He has continued to produce new tumors at a substantially reduced rate relative to his pretreatment baseline. The sister in our study exhibited a severe inflammatory response to imiquimod 5% cream, with facial swelling and erosion of the treated area with application as infrequent as three times a week. In spite of the vastly different inflammatory response, her cutaneous tumors responded favorably to therapy as well. CONCLUSION: Imiquimod 5% cream was effective in treating facial BCCs in these siblings with XP. As well, we have noted a significant reduction in the development of new tumors within the imiquimod-treated area. The inflammatory response to this medicine was at opposite extremes among these two siblings. However, this did not appear to alter the therapeutic benefit of this therapy.     

Topical imiquimod in conjunction with Nd:YAG laser for tattoo removal

The purpose of this study is to evaluate the efficacy of tattoo removal using topical imiquimod 5% cream in conjunction with the 1,064-nm Nd:YAG laser. This procedure for tattoo removal will be compared to laser treatment alone, which is the standard for cosmetic removal of tattoos. Previous studies have linked partial tattoo removal to imiquimod application in a guinea pig model. Methods: This was a small-sized, double-blinded, placebo-controlled trial with patients with Fitzpatrick skin types I-IV (light skin) who were 18–65 years of age. The patients were required to have had two tattoos of similar age and dark blue or black in color in areas that can be covered by clothing. There were four visits in total, with laser treatment and photography being performed on the first visit. Laser settings were with 1,064-nm Nd:YAG with a 10-ns pulse, 3-mm spot size, and 4 J of energy, a standard laser used for tattoo removal. During the second visit, tattoos were randomized and chosen to receive either the laser-imiquimod treatment course or laser-vehicle cream treatment. The patients returned 1 month after the completion of cream application (week #10) and 2 months after the completion of treatment with cream (week #14) for final evaluation and photographing. Results: Three patients were enrolled in this study. All of them are Fitzpatrick skin type IV. All of the patients were compliant with the drug application and have good tolerability with only mild pruritus without changing of vascularity or pigmentation. None of the patients had ulceration or scar development during the cream application. Conclusions: imiquimod plus laser therapy demonstrated a more favorable outcome when evaluated by the investigators or subjects. The mean scores for tattoo clearance from baseline to 2 months after completion of treatment with 5% imiquimod cream versus placebo cream were 4.3 versus 2.7 as rated by investigators and 4.7 versus 2.3 as rated by subjects. No textural changes were observed after therapy and were not shown to be different between the two groups. Further large-scale studies are important in developing a role for the use of imiqumod in laser-assisted tattoo removal.     

Imiquimod 5% Cream for Keloid Management

BACKGROUND: Keloid treatment represents a therapeutic challenge. New adjuvant therapy is needed to reduce the high recurrence rate (50%) of excised keloids. OBJECTIVE: To describe the method for using imiquimod 5% cream in the prevention of keloid recurrence after surgery. METHODS: This is a review of the scientific rationale and clinical experience of using imiquimod 5% cream for keloid management. CONCLUSION: Topical application of imiquimod 5% cream after surgery reduces keloid recurrences.     

Safety and Efficacy of Multiple 16-week Courses of Topical Imiquimod for the Treatment of Large Areas of Skin Involved with Actinic Keratoses

Objective: Safety of multiple 16-week courses of imiquimod applied to large areas (>25 cm²) of skin with actinic keratoses. Design: Subjects applied 1 to 6 packets two times per week for 16 weeks; if actinic keratoses were persistent at two months post-treatment, up to two additional courses could be administered within the 18-month study period. Setting: Multicenter, outpatient. Participants: Adults with ≥4 actinic keratoses on the head, torso, and/or extremities. Measurements: Treatment discontinuations, adverse events, lesion counts. Results: Safety analyses included 551 subjects. At baseline, mean overall treatment area was 625±1114cm². Overall, the mean days on study was 467±157, and the mean exposure 215±133 packets with 155, 150, and 250 subjects receiving 1, 2, or 3 treatment courses, respectively. Of the 155 subjects (28.1%) who did not complete the study, 20 (3.6%) and 9 (1.6%) were discontinued for adverse events and local skin reactions, respectively. Adverse events related to study drug were reported by 40.5 percent of subjects. The local skin reactions rated as severe reported by the most subjects were erythema (31.4%), flaking/scaling/drying (23.8%), and scabbing/crusting (22.0%). For 525 subjects with analyzable lesion data, the mean baseline lesion count was 45.5±2.4. Overall reduction in target lesion count was 80.2 percent (p<0.0001, 95% CI 77.2–83.3%), with overall complete clearance rate of 36.4 percent and partial clearance rate (≥75% reduction) of 68.6 percent. Conclusion: Multiple 16-week courses of imiquimod to treat actinic keratoses were well tolerated and significantly decreased lesions in subjects with extensive actinic keratoses.Actinic keratoses (AKs) are common cutaneous lesions induced by chronic ultraviolet (UV) light exposure that are early stage precursors to in-situ and invasive squamous cell carcinoma (SCC).^1–3 Chronic UV radiation exposure causes cutaneous immunosuppression, the formation of deoxyribonucleic acid pyrimidine covalent dimers, and mutations in the p53 tumor suppressor gene in keratinocytes resulting in alterations within these keratinocytes, all of which promote the formation of AKs.^4,5 The progression of AK to invasive SCC has been reported to range from as low as 0.025 to as high as 16 percent per year.⁶ Although some AKs may regress spontaneously, with a reported regression rate as high as 25 percent over a 12-month period,⁷ there are no clinical criteria to predict which AKs will evolve into invasive SCC. Therefore, treatment of AKs and monitoring of therapeutic response and potential disease progression over time are warranted.⁸Treatment options for AK include physical modalities, such as cryotherapy, curettage, electrodessication, dermabrasion, chemical peels, laser vaporization, surgical excision, and photodynamic therapy as well as topical therapies, such as topical 5-flurouracil, diclofenac, and imiquimod.⁹ Imiquimod is a Toll-like receptor agonist that directly activates the innate immune system, resulting in cytokine production; in addition, imiquimod indirectly augments acquired immunity.^10,11 Application of imiquimod to cutaneous lesions, including AKs, is associated with upregulation of genes associated with dendritic cell, cytotoxic T cell, and natural killer cell activation as well as genes associated with apoptosis.^12–14 Imiquimod 5% cream was originally approved in 1997 for the treatment of external genital warts and subsequently for treatment of superficial basal cell carcinoma (BCC). In 2004, the United States Food and Drug Administration (FDA) approved imiquimod 5% cream for the treatment of AK. The approved treatment regimen for AK is application of one packet (250mg of cream) to a 25cm² area on the face or balding scalp two times per week (2x/wk) for a full 16-week regimen.¹⁵ The pivotal studies conducted for approval were limited as to the treatment location (the face), the treatment area (25cm²), and the treatment duration (one 16-week course). This article reports the safety and efficacy results of an open-label, multicenter study of application of up to six packets of imiquimod 5% cream 2x/wk to AKs, applied to a more extensive body surface area on the head, torso, and/or extremities, for one, two, or three 16-week treatment courses.     

复方倍他米松联合5%咪喹莫特治疗瘢痕疙瘩的临床观察

目的：观察复方倍他米松注射液皮损内注射联合5%咪喹莫特外涂治疗瘢痕疙瘩的临床疗效和安全性。方法：将80名瘢痕疙瘩患者分为两组,治疗组给予复方倍他米松注射液皮损内注射,每2周1次,同时外涂5%咪喹莫特隔日1次,总疗程为8周;对照组单纯给予复方倍他米松注射液皮损内注射。结果：1个月随访时,治疗组及对照组改善率分别为67.57%及60.47%,无显著差异;3个月随访时,治疗组改善率为80.56%,显著高于对照组的65.85%。治疗期间无失访患者,不良反应为注射部位轻中度疼痛感、不适感,偶见轻度萎缩、轻度毛细血管扩张及多毛。结论：复方倍他米松注射液皮损内注射联合5%咪喹莫特外涂治疗瘢痕疙瘩安全有效、复发率低,患者依从性好。     

Treatment of Bowen''s Disease with Topical 5% Imiquimod Cream: Retrospective Study

BACKGROUND: Topical 5% imiquimod cream is an FDA-approved treatment for superficial basal cell carcinomas. It has also been utilized in the treatment of Bowen's disease (squamous cell in situ). The current literature on this subject, however, is scant, and this treatment is only validated by case reports and two small open label studies. OBJECTIVE: The objective was to assess the efficacy of topical 5% imiquimod cream in the treatment of squamous cell in situ in a larger open-label case series. METHODS A retrospective study of 49 patients was performed. RESULTS: Forty-two of the 49 (86%) patients in the study had a complete response with topical imiquimod. The remaining 7 (14%) failed therapy and required additional treatments. The mean follow-up duration was 19 months, with a range of 1 to 44 months. CONCLUSION: Topical 5% imiquimod cream appears to be clinically beneficial in the treatment of Bowen's disease and should be considered as a treatment option.     

Imiquimod治疗9例外生殖器尖锐湿疣的临床报告

目的观察用i miqui mod治疗9例外生殖器尖锐湿疣的疗效及相关问题。方法5%i mqui mod霜睡前使用1次,每周3次,致疣体消失为止,疗程不超过16周。结果5例疣体在用药5周后完全消失,2例在6周后消失,2例在用药4周后改用电灼术去除疣体。患者均有局部药物不良反应,可耐受。2例治疗结束后2个月复发。结论I miqui mod可用于治疗外生殖器尖锐湿疣。     

Successful Treatment of Multiple Superficial Basal Cell Carcinomas with Topical Imiquimod: Case Report and Review of the Literature

BACKGROUND: The use of imiquimod 5% cream for the treatment of superficial basal cell carcinoma (BCC) has been described. Its clinical efficacy was first shown in a study in patients with biopsy-proven superficial and nodular BCC. OBJECTIVE: To evaluate the efficacy of topical imiquimod in a patient with multiple superficial BCCs unresponsive to topical 5-fluorouracil and to review the literature on this treatment modality for BCCs. RESULTS: After 12 weeks of topical imiqmod, the patient's lesions had resolved. The patient was evaluated three months after discontinuation of treatment. There was no clinical evidence of any recurrent tumor. CONCLUSION: Imiquimod 5% cream appears to be effective for multiple, superficial BCCs unresponsive to other modalities.     

Successful Treatment of Earlobe Keloids with Imiquimod after Tangential Shave Excision

BACKGROUND: The treatment of earlobe keloids has historically been suboptimal; characterized by discomfort, poor response, and high rates of recurrence. Keloids are characterized by increased fibroblast activity in the setting of an altered cytokine profile. OBJECTIVE: To investigate whether topical imiquimod 5% cream applied postoperatively after tangential excision can prevent recurrence of earlobe keloids. METHODS AND MATERIALS: Four patients with a total of eight large pedunculated earlobe keloids (five of which were recurrent lesions) were treated with debulking by tangential shave excision followed by daily application of imiquimod 5% cream for 6 weeks. RESULTS: At 6 and 12 months post-treatment there was an excellent cosmetic result and no evidence of recurrence in any of the lesions. Patients with keloids that were itchy and painful were completely asymptomatic at the conclusion of the study. CONCLUSION: In this pilot study, imiquimod 5% cream following tangential shave excision was efficacious for the treatment of earlobe keloids. Further study is warranted to confirm the utility of imiquimod 5% cream in the treatment of earlobe keloids, as illustrated herein.     

Photodynamic therapy with methyl aminolevulinate for prevention of new skin lesions in transplant recipients: a randomized study

BACKGROUND: Organ transplant recipients on long-term immunosuppressive therapy are at increased risk of non-melanoma skin lesions. Repeated field photodynamic therapy using topical methyl aminolevulinate (MAL) may have potential as a preventive treatment. METHODS: This open randomized, intrapatient, comparative, multicenter study included 81 transplant recipients with 889 lesions (90% actinic keratoses (AK)]. In each patient, the study treatment was initially administered to one 50 cm area on the face, scalp, neck, trunk, or extremities (n=476 lesions) twice (1 week apart), with additional single treatments at 3, 9, and 15 months. On each occasion, the area was debrided gently and MAL cream (160 mg/g) applied for 3 hr, before illumination with noncoherent red light (630 nm, 37 J/cm2). The control, 50 cm2 area (n=413 lesions) received lesion-specific treatment (83% cryotherapy) at baseline and 3, 9, and 15 months. Additionally, all visible lesions were given lesion-specific treatment 21 and 27 months in both treatment and control areas. RESULTS: At 3 months, MAL photodynamic therapy significantly reduced the occurrence of new lesions (65 vs. 103 lesions in the control area; P=0.01), mainly AK (46% reduction; 43 vs. 80; P=0.006). This effect was not significant at 27 months (253 vs. 312; P=0.06). Hypopigmentation, as assessed by the investigator, was less evident in the treatment than control areas (16% vs. 51% of patients; P<0.001) at 27 months. CONCLUSION: Our results suggest that repeated field photodynamic therapy using topical MAL may prevent new AK in transplant recipients although further studies are needed.     

Imiquimod to Treat Different Cancers of the Epidermis

BACKGROUND: Topical immunomodulatory therapy with imiquimod has been recently used for the treatment of actinic keratoses, intraepithelial carcinoma, and small basal cell carcinoma (BCC) besides the licensed indication of extragenital warts (condyloma). METHODS: We treated several patients with particular epidermal neoplasias such as squamous cell cancer (SCC) and basal cell cancer of sclerodermiform type three times per week for 4 to 12 weeks. RESULTS: We report several novel aspects of the treatment of epidermal cancers with self-applied, nonpainful, immunomodulatory therapy. First, we treated-for the first time-two immunosuppressed renal transplant patients for invasive SCC with imiquimod. Interestingly, systemic immunosuppression did not adversely affect the response to therapy. Second, one patient with the high-risk and aggressive growth pattern of basal cell cancer (sclerodermiform histology) was cured from his disease at a particular location in the face, suggesting sufficient penetration despite scarring. No recurrence was detected in another patient who suffered from 29 BCCs until almost 2-years follow-up. Third, the treatment of actinic keratoses in the face is substantially shorter (in the order of 4 to 6 weeks) as opposed to other skin cancers. Immunomodulatory treatment with imiquimod led to the demarcation of in situ actinic keratosis lesions that could not be identified using the dermatologist's experience, probably because of the existence of exclusive alterations on the molecular level. CONCLUSION: Several novel aspects of immunomodulatory treatment with imiquimod and new indications such as selected cases of sclerodermiform BCC and SCC have been described. The texture of the skin at various different body locations may explain the varying sensitivities to imiquimod when facial skin is compared with skin on the extremities.     

曲安奈德局部注射联合外用5%咪喹莫特治疗瘢痕疙瘩疗效观察

目的：观察曲安奈德局部注射联合外用5%咪喹莫特乳膏治疗瘢痕疙瘩的临床疗效。方法：将患者随机分为两组,治疗组给予曲安奈德局部注射治疗,每10～15天注射1次,2～3次为1个疗程,最多不超过3个疗程。同时外用5%咪喹莫特每周3次,连续外用3个月;对照组单纯给予曲安奈德注射液局部注射治疗。治疗结束后随访1年,判断疗效并观察复发情况。结果：治疗组有效率96.4%,明显优于对照组（P〈0.05）,差异有显著性意义。治疗组复发率低于对照组。结论：曲安奈德局部注射联合外用5%咪喹莫特乳膏治疗瘢痕疙瘩治愈率高,疗效确切。     

Imiquimod Treatment of Superficial and Nodular Basal Cell Carcinoma: 12-Week Open-Label Trial

BACKGROUND: Imiquimod is an immune response modifier shown to be effective in basal cell carcinoma (BCC). OBJECTIVE: To evaluate the efficacy, tolerability, and response durability of imiquimod 5% cream in selected patients with superficial and/or nodular BCCs. METHODS: Seventy-five superficial and 19 nodular BCCs in 49 patients were treated with imiquimod once daily three times a week for up to 12 weeks. RESULTS: Of the 49 enrolled patients, 1 discontinued the study and 1 was lost to follow-up. After 12 weeks of treatment, a complete response occurred in 70 of 75 (93.3%) superficial BCCs and a partial response in 4 of 75 (5.3%) superficial BCCs. Ten of 19 (52.6%) nodular BCCs cleared after 12 weeks, whereas 7 (36.8%) showed partial remission. Adverse side effects were limited to local skin reactions. Recurrence was observed in 2 of 70 (2.9%) successfully treated superficial BCCs 6 and 8 months after treatment discontinuation. No recurrence was detected in 68 of 70 (97.1%) superficial BCCs and in 10 successfully treated nodular BCCs after 12 to 34 months of follow-up (mean 23 months). CONCLUSIONS: In our patient population, treatment of superficial BCCs with topical imiquimod for 12 weeks produced an excellent clinical response overall, with complete remission maintained after a mean of 23 months.