Primary Prevention of Skin Dysplasia in Renal Transplant Recipients With Photodynamic Therapy: A Randomized Controlled Trial

Organ transplant recipients (OTRs) are at high risk of developing cutaneous squamous cell carcinoma (SCC); prevention includes early treatment of premalignant actinic keratosis (AK). Photodynamic therapy (PDT) is a noninvasive field therapy that reduces new AKs in patients with existing AK and delays SCC development in mice. We investigated the effect of repeated PDT over 5 years for primary prophylaxis of skin dysplasia. These data represent an interim analysis of an on‐going randomized controlled trial. During 2008–2011, 25 renal transplant recipients with clinically normal skin were randomized to split‐side PDT of the face, forearm and hand, the contralateral side serving as untreated control. Patients received PDT on inclusion and at 6‐monthly intervals for 5 years. Blinded evaluation was performed at each visit. We found that prophylactic PDT significantly delayed onset of AK compared with untreated skin, p = 0.020. At 3‐year follow‐up, we observed AK in 63% of patients in untreated skin areas compared with 28% of patients in PDT‐treated skin, with a total number of cumulated AKs in untreated skin (n = 43) compared with PDT‐treated skin (n = 8), p = 0.005. These preliminary data indicate a novel approach to early prevention of skin dysplasia that may reduce morbidity from multiple AKs and SCCs in OTR.     

Detection of Residual Basal Cell Carcinoma by In Vivo Confocal Microscopy

BACKGROUND: Near-infrared reflectance-mode confocal scanning laser microscopy (RCM) represents a novel imaging technique for microscopic analysis of skin lesions and may provide a noninvasive modality for the diagnosis of basal cell carcinoma (BCC). OBJECTIVE: To determine the feasibility of detecting residual or clinically equivocal BCC using RCM. METHODS: In this pilot study, RCM was used in three cases to characterize the histologic features of index lesions in vivo. These were subsequently correlated with corresponding hematoxylin-eosin-stained sections obtained during Mohs micrographic surgery. RESULTS: Evaluation of clinically equivocal lesions by RCM revealed features characteristic of BCC, including tightly packed nests of elongated, monomorphic, polarized nuclei and subjacent ectatic blood vessels with lymphocytes undergoing margination and rolling. Conventional histology confirmed the presence of BCC in all cases. CONCLUSION: We report the use of RCM in the confirmation of residual BCC in two cases and the tentative diagnosis with subsequent pathologic conformation of a third case in which a biopsy was previously inadequate. Our results demonstrate that confocal microscopy may facilitate diagnosis of BCC in vivo and warrant further prospective study to quantify the sensitivity and specificity of this rapidly evolving imaging modality.     

Actinic Keratoses and the Incidence of Occult Squamous Cell Carcinoma: A Clinical–Histopathologic Correlation

BACKGROUND: The ability to clinically diagnose actinic keratoses (AKs) lesions has been taken for granted for some time. The importance of the malignant potential of these lesions is well known. However, a recent Phase IV, multicenter study assessing the long-term benefit of aminolevulinic acid-based photodynamic therapy provided a unique opportunity to prospectively examine the clinical histopathologic correlation of AKs. OBJECTIVE: The objective was to characterize the histopathology of clinically diagnosed AK lesions in the study population. METHODS: Punch biopsies of 220 clinically diagnosed untreated AKs were performed at baseline plus 51 lesions unresponsive to treatment (total, 271). RESULTS: Clinical diagnosis and histopathologic findings agreed in 91% (246/271) of the lesions biopsied. The balance of the biopsied lesions were: (1) benign changes 4% (11/271) and (2) occult cutaneous malignancy in 5% (14/271) of the cases, 12 squamous cell carcinomas and 2 basal cell carcinomas. CONCLUSIONS: In this study, about 1 in 25 clinically diagnosed AK lesions identified by board-certified dermatologist investigator(s) were occult early-stage squamous cell carcinomas on histologic assessment, a fact surmised by the medical community that until now had not been well quantified. These findings should be considered when clinicians decide how to treat and manage AK patients.     

The Kinetics of Skin Cancer: Progression of Actinic Keratosis to Squamous Cell Carcinoma

BACKGROUND: Actinic keratoses (AKs) are intraepidermal skin tumors that have the potential to progress to squamous cell carcinomas (SCCs). SCCs are the second most common cancer with more than 200,000 cases each year in America. Approximately 10% of AKs will progress to SCCs. This progression is thought to be due to chronic sun exposure, specifically ultraviolet B sunlight. OBJECTIVE: Understanding the kinetics of this developmental process can help physicians better evaluate and subsequently treat precancerous AKs. METHODS: To determine the time scale of AK progression, we conducted a retrospective electronic medical record study of all patients diagnosed histopathologically with an SCC between July 1, 2003, and June 30, 2005. RESULTS: Of a total patient population of 6,691, 91 had a histopathologically confirmed diagnosis of an AK at the same site as the subsequent SCC. The length of time for an AK to progress to an SCC was determined to be 24.6 months (95% confidence interval, 21.04-28.16 months). CONCLUSIONS: Although a more controlled in vivo study is indicated, these data provide a good estimate of the time course from an AK to an SCC. In summary, of the estimated 10% of AKs that will develop into an SCC, the progression will take approximately 2 years.     

Photodynamic Photorejuvenation

BACKGROUND: The visible signs of photodamage are characterized by wrinkling, coarse skin texture, pigmentation alterations, telangiectases, and in some case actinic keratosis (AKs). Intense pulsed light (IPL) photorejuvenation has been shown to improve each of the different components of photodamaged skin except AKs. OBJECTIVE: To present photodynamic therapy with topical 5-aminolevulinic acid (ALA-PDT) using IPL as a light source for treatment of AK in patients having IPL photorejuvenation. METHODS: Seventeen patients with varying degrees of photodamage and AKs (total of 38 AKs) were treated with two treatments with a 1-month interval of ALA-PDT using IPL as a light source. RESULTS: Thirty-three of 38 AKs disappeared with two ALA-PDT treatments using IPL. The follow-up period was 3 months. The technique was very well tolerated. Erythema and crusting took 1 week to resolve in the AK area. The cosmetic results were excellent in all patients without pigmentary alterations or scarring. CONCLUSION: This study describes a new application of IPL technology. Patients who are candidates for photorejuvenation procedures presenting with AKs can now have AKs treated as part of the photorejuvenation process rather than necessitating separate topical therapy with 5-fluorouracil (5-FU) or cryotherapy. In addition, many patients with AKs may benefit from the combination treatment with 5-ALA and IPL.     

Reflectance confocal microscopic evaluation of nonmelanocytic lip lesions

Lips display various benign and malignant lesions. Considering their functional and cosmetic importance, noninvasive diagnostic methods are required. In vivo reflectance confocal microscopy (RCM) has already been reported to be useful in the evaluation of various skin lesions. The aim of this study was to define the RCM features of nonmelanocytic lip lesions, compare them with healthy lip, and demonstrate the applicability of RCM as a noninvasive diagnostic method for nonmelanocytic lip lesions. Sixty-seven patients with premalignant/malignant, inflammatory, and infectious lip lesions and twenty-one healthy volunteers were included in the study. Following clinical and RCM examination, histopathological confirmation was obtained in all lesions except herpes labialis, verrucae, and aphthae. RCM features of individual lesions and corresponding groups were evaluated and compared. Pleomorphism was the common feature of premalignant/malignant lesions. Dermal invasion of dyskeratotic keratinocytes was visualized in all squamous cell carcinoma lesions. Spongiosis and inflammatory cells were the common features of inflammatory lesions. Hypergranulosis and necrotic keratinocytes were highly specific for lichen planus. The most specific features for discoid lupus erythematosus were irregular pattern, follicular plugs, and perifollicular inflammatory cells. Virus-infected keratinocytes were visualized in herpes and verrucae. RCM features showed high sensitivity and specificity to detect nonmelanocytic lip lesions. Although the penetration is limited to the papillary dermis in nonmucosal skin, imaging down to the mid-dermis with satisfactory resolution was possible on the lips.     

Using optical coherence tomography to evaluate skin sun damage and precancer

BACKGROUND AND OBJECTIVES: Optical coherence tomography (OCT) is a depth resolved imaging modality that may aid in identifying sun damaged skin and the precancerous condition actinic keratosis (AK). STUDY DESIGN/MATERIALS AND METHODS: OCT images were acquired of 112 patients at 2 sun protected and 2 sun exposed sites, with a subsequent biopsy. Each site received a dermatological evaluation, a histological diagnosis, and a solar elastosis (SE) score. OCT images were examined visually and statistically analyzed. RESULTS: Characteristic OCT image features were identified of sun protected, undiseased, sun damaged, and AK skin. A statistically significant difference (P<0.0001) between the average attenuation values of skin with minimal and severe solar elastosis was observed. Significant differences (P<0.0001) were also found between undiseased skin and AK using a gradient analysis. Using image features, AK could be distinguished from undiseased skin with 86% sensitivity and 83% specificity. CONCLUSION: OCT has the potential to guide biopsies and provide non-invasive measures of skin sun damage and disease state, possibly increasing efficiency of chemopreventive agent trials.     

Discrimination of Actinic Keratoses from Normal Skin with Reflectance Mode Confocal Microscopy

BACKGROUND Recently, a wide range of new noninvasive therapies has been introduced for the treatment of actinic keratoses. As these treatment options do not provide tissue for histopathologic examination, in vivo confocal laser scanning microscopy may become an important method for obtaining a reliable diagnosis.
OBJECTIVE The objective was to validate the diagnostic confocal examination of actinic keratoses.
METHODS Thirty actinic keratoses and skin fields from the contralateral sides of the patients were consecutively sampled and examined using a confocal microscope. Stored images were rated by four independent observers.
RESULTS Distinct diagnostic morphologic features could be visualized. Overall, sensitivity of 93.34% and specificity of 88.34% could be achieved by two clinical dermatooncologists (positive predictive value 88.94%, negative predictive value 93.15%). Assessment of distinct confocal microscopy features showed a moderate interobserver correlation (κ= 0.4–0.6 in five of seven criteria). Classification and regression tree analysis yielded a one-step algorithm based on only one criterion (irregular keratinocyte cell borders), facilitating a correct classification in 86.67% of actinic keratoses and 85% of normal skin.
LIMITATIONS Hyperkeratotic actinic keratoses were excluded from the study set.
CONCLUSIONS This study provides a set of morphologic confocal microscopy criteria showing promise as a noninvasive monitoring tool in the treatment of actinic keratoses.     

Adrenocortical neoplasms: Prognosis and morphology

The clinical data and morphologic findings in 16 cases of adrenocortical carcinoma were compared with those in 11 cases of surgically removed functional adenomas and 12 cases of nonfunctional adenomas found at autopsy. Histopathologic changes of architectural disarray, pleomorphism, increased mitotic activity, vascular invasion, hemorrhage, or necrosis were generally reliable criteria for diagnosis of malignancy. However, weight was the parameter that most consistently correlated with outcome, since all patients with tumors under 50 Gm. survived and all lesions of 95 Gm. or over proved to be malignant.     

Reflectance confocal microscopy as a useful diagnostic tool for monitoring of skin containing vascularized composite allograft rejection: A preliminary study on rats

Vascularized composite allografts can undergo immune‐mediated rejection, and skin biopsies are needed for monitoring of the transplant. However it is an invasive method, and requires processing time and pathological assessment. The purpose of this study is to use a new noninvasive monitoring method of the reflectance confocal microscopy (RCM) to determine severity of the allograft rejection on rats. Five groin flap allotransplantation were performed between 10 male Sprague‐Dawley rats. Immunosuppressive therapy with cyclosporine A was given to the recipients during 10 days after surgery and was ended at the 10th postoperative days to allow acute transplant rejection. Following cessation of CsA, concomitant RCM evaluation and skin biopsy was performed every other day from each animal until total rejection of the allograft. Complete rejection of the allograft took nearly about 10 days and 4 or 5 RCM evaluation and skin biopsy was performed from each rat during this period. A total of 17 specimens were evaluated. A scoring system was developed based on the RCM findings. Skin biopsies were evaluated according to the Banff 2007 working classification criteria. RCM evaluation revealed epidermal irregularity and collagen destruction, however mild perivascular inflammation and degeneration of the basal epidermal layer were observed in early and late rejection period respectively with histopathologic evaluation. High correlation was found between the RCM scores and histopathologic grading. The RCM may be the useful tool to reduce the need for skin biopsy for monitoring of the skin containing vascularized composite allograft. © 2015 Wiley Periodicals, Inc. Microsurgery 36:144–151, 2016.     

Clinical and echographic analysis of photodynamic therapy using methylaminolevulinate as sensitizer in the treatment of photodamaged facial skin

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) using aminolevulinic acid (ALA) has been previously investigated in the treatment of photodamaged skin. The aim was to assess efficacy and tolerability of methylaminolevulinate (MAL) as a substitute for ALA in PDT treatment of actinic keratosis (AK) and photoaging. STUDY DESIGN/MATERIALS AND METHODS: Twenty patients with multiple (n = 137) AKs and severe photodamage of the face were treated. Metvix (Galderma, France) was applied under occlusion for 3 hours before exposure to 37 J/cm(2) of red light (Aklilite CL 128, Photocure, Norway). Two treatments were given at monthly intervals. RESULTS: The clearance rate of AKs was 88.3%, and global score which we use to rate photoaging, mottled hyperpigmentation, fine lines, roughness, and sallowness of the skin showed improvement, but deep wrinkles, teleangiectasia, facial erythema, and sebaceous gland hypertrophy did not change. The treatments were well tolerated. High-resolution echography showed an increase in skin thickness, pixels count and area, as well as a reduction of the subepidermal low-echogenic band (SLEB) thickness. CONCLUSION: MAL-PDT is an effective treatment for multiple AKs. In addition, it improves clinical signs of photodamage of the surrounding skin.     

Mammary hamartoma

For many years, mammary hamartoma was considered to be an under-diagnosed disease. However, with the increasing use of diagnostic procedures in breast tumors (mammography, ultrasound, fine needle aspiration cytology and core needle biopsy), diagnosis of this entity has increased. Mammary hamartomas normally manifest as painless, mobile, palpable lumps without adherence to skin or muscle. Mammography shows well-circumscribed tumors, separated from adjacent normal breast tissue. Macroscopically they are well-defined tumors, consisting of benign mammary glandular tissue, fibrous stroma and fat in variable proportions, sometimes with a pseudoencapulation. Because of the lack of cytological and architectural specificity of hamartomas, correlation between clinical manifestations, imaging techniques and histology is essential. This report describes a case of an 11-cm mammary hamartoma in a 46-year-old woman.     

Split-Face Comparison of Photodynamic Therapy with 5-Aminolevulinic Acid and Intense Pulsed Light Versus Intense Pulsed Light Alone for Photodamage

BACKGROUND: Photodynamic therapy (PDT) with a 5-aminolevulinic acid (ALA) photosensitizing agent and a variety of lasers and light sources has been shown to enhance the treatment of photodamaged skin and its associated actinic keratoses (AKs). The efficacy of short-contact, full-face ALA by PDT in photorejuvenation has also been demonstrated. OBJECTIVE: To evaluate short-contact (30 to 60 min) ALA-PDT with intense pulsed light (IPL) activation by comparing ALA-PDT-IPL with IPL alone. METHODS Sixteen patients were enrolled in a split-face study. One side of each patient's face received ALA-PDT-IPL and the other side received IPL alone. Three treatments were given at 1-month intervals, and follow-up visits occurred at 1 and 3 months after the final treatment. RESULTS: Thirteen patients completed the trial. Three months after the final treatment, improvement was greater in the ALA-PDT-IPL side than in IPL-alone side for all facets of photodamage-crow's feet appearance (55 vs 29.5%), tactile skin roughness (55 vs 29.5%), mottled hyperpigmentation (60.3 vs 37.2%), and telangectasias (84.6 vs 53.8%). The clearance rate of AK lesions was also higher (78 vs 53.6%). CONCLUSION: Short-contact ALA-PDT-IPL brings about greater improvement in photodamaged skin and greater clearance of AK lesions than IPL alone, further confirming the usefulness of ALA-PDT in photorejuvenation.     

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.     

Tolerability of Ingenol Mebutate Gel, 0.05%, for Treating Patients with Actinic Keratosis on the Scalp in a Community Dermatology Practice

Objective: To describe the safety, tolerability, and efficacy of treatment of actinic keratosis on the scalp with two consecutive, once-daily applications of ingenol mebutate gel, 0.05%. Design: Retrospective chart review. Setting: Community dermatology practice. Participants: Male patients (N=78) with a long history of recurrent and relapsed scalp actinic keratosis. Measurements: This chart review extracted non-identifying information on patients’ medical history, pertinent history of actinic keratosis and skin cancer, and prior actinic keratosis treatments. Also collected was information on patients’ treatment of scalp actinic keratosis with ingenol mebutate gel, 0.05%, including the occurrence of local skin reactions and their treatment, adverse events, and efficacy results at short-term and additional follow-up. Results: In these patients, a significant proportion of the scalp had numerous actinic keratoses that were often recurrent and/or hyperkeratotic. Most patients (83%) received cryosurgery to visible scalp actinic keratoses two weeks before ingenol mebutate treatment. Local skin reactions developed on the first day of topical treatment, were predominantly mild or moderate in intensity, and generally were resolved by 10 to 14 days. Local skin reactions were treated with a topical moisturizing product in 44 percent of the patients. Nearly half (45%) of the patients experienced application-site reactions, described as a combination of burning, itching, pain, and/or tenderness; the reactions were mild or moderate in intensity and lasted only a few days. Conclusions: Ingenol mebutate gel, 0.05%, had a good safety and tolerability profile when used to treat scalp actinic keratosis in patients who had a prolonged history of actinic keratosis.Actinic keratosis (AK) is one of the most common conditions encountered by dermatologists. In a survey of dermatologist visits from 1993 to 2010, AK was the leading diagnosis in patients aged 45 years and older.1 The majority of AKs are found on skin sites that have received chronic, long-term sun exposure, such as the head, neck, forearms, and hands.2 The primary concern over AK is that it may progress to squamous cell carcinoma (SCC). Although the progression of a specific AK lesion to SCC cannot be predicted, the majority of clinically diagnosed SCCs do, in fact, originate from concomitant or contiguous AKs.3-5 This association supports the importance of dermatologic evaluation of AKs and the initiation of treatment.6,7Comprehensive management of AK to reduce the risk of progression to SCC often includes both lesion-directed methods, such as cryosurgery,8,9 and topical field therapies, which treat large numbers of visible and subclinical lesions present in contiguous areas of sun-damaged skin.10,11 Ingenol mebutate gel, 0.015%, a topical treatment indicated for the treatment of AK of the face and scalp, is applied once daily for three consecutive days. When used to treat AK on the trunk and extremities, a 0.05% formulation is applied once daily for two consecutive days.12,13Some evidence suggests that AKs on the scalp are not cleared as completely as those on the face with use of the ingenol mebutate, 0.015%, formulation. In a pooled analysis of two Phase 3 studies, rates of complete and partial clearance of AKs, assessed by anatomic location on the face and scalp, were statistically higher with ingenol mebutate gel, 0.015%, than with vehicle gel, but clearance rates on the scalp were noted to be lower than those on the face.14 A retrospective chart review of patients in the author’s practice also showed that the rate of complete clearance of AKs with ingenol mebutate gel, 0.015%, was lower on the scalp than on the face.15 These observations suggested that AKs on the scalp may be more difficult to treat with the 0.015% strength of ingenol mebutate gel and led the author to speculate that scalp AK might respond better to the higher 0.05% formulation of ingenol mebutate. Therefore, over the course of 20 months, the author treated male patients in her community dermatology practice with ingenol mebutate gel, 0.05%, for AK on the scalp. This retrospective chart analysis describes the results with this treatment.     

Topical photodynamic therapy of actinic keratosis in renal transplant recipients

Organ transplant recipients (OTRs) show an increased risk of precancerous (mostly actinic keratosis [AK]) and cancerous (mostly squamous cell carcinomas [SCC] and basal cell carcinomas [BCC]) cutaneous lesions. Their frequency increases with time after transplantation. AKs seem to progress more often and faster to invasive SCC in OTRs compared with the general population. The steady increase of risk of cutaneous premalignancies and malignancies with time after transplantation is an alarming figure because the number of organ allograft recipients who live for many years after transplantion is rapidly growing. This points out the need to devote more resources to skin cancer prevention, detection, and management. Various therapies, including cryotherapy, topical 5-fluorouracil, imiquimod, topical diclofenac, curettage, electrosurgery, carbon dioxide laser, and surgical excision, are available for AKs. However, most of these are limited by frequent relapses and the presence of multiple lesions over a wide area. Topical photodynamic therapy (PDT) represents an innovative therapeutic approach for nonsurgical treatment of cutaneous precancerous lesions and skin cancers. In this study we confirmed the usefulness of PDT in the treatment of AKs in OTRs, even in lesions relapsing or unresponsive to conventional treatment. We showed a complete response rate of 71%, after 2 treatments sessions that were 2 weeks apart. The response rate of scalp/facial lesions (72%) was higher compared with acral lesions (40%). Topical PDT could represent a useful therapeutic alternative for AKs in OTRs because large lesions can be treated with excellent cosmetic outcome.     

Radiation therapy for widespread actinic keratoses

Objective: To profile 16 patients with widespread and resistant actinic keratoses (AKs) treated with radiation therapy. Design: Chart review and phone interviews of 16 patients who were treated with radiation therapy between 2003 and 2010. Setting: A specialized dermatological practice primarily treating patients with skin cancer. Participants: The study population at the time of treatment was aged 70 to 87 with a mean age of 79.6 years and included 14 men and two women. Measurements: Patients were followed at two weeks and six months after treatment to assess clinical outcome. All adverse effects were recorded. Patients were contacted for phone interview to assess patient satisfaction after treatment. Results: Patients all had significant reduction of AKs in the radiation field with a majority (90%) reporting they were "very satisfied" with their treatment outcome. Of 16 patients at two weeks post-treatment, 13 had complete clinical resolution of their AK after radiation therapy. Three of 16 patients had significant reduction (50-99%) in AK in the treatment field. Patients reported improved quality of life, a reduced need for frequent clinic visits, and long-term remission from the development of new AKs within the treatment field. Conclusion: Patients meeting suggested specific criteria developed by the authors may be treated successfully with radiation therapy with good outcomes at six-month follow up and high levels of patient satisfaction.     

Reflectance confocal microscopy for the evaluation of acute epidermal wound healing

The dynamic process of wound healing is routinely evaluated by clinical or histological evaluation. Recently, a number of non‐invasive imaging techniques have been evaluated for their clinical applicability in dermatology. Among them, reflectance confocal microscopy (RCM) represents a non‐invasive imaging technique that allows the in vivo characterization of the skin at near‐histological resolution. The aim of this study was to monitor epidermal wound repair using RCM in a model of tissue damage induced by cryosurgery. For this purpose, contact cryosurgery was performed at ?32 °C for 10 seconds on the volar forearm of five healthy volunteers. Clinical and RCM evaluations were performed at nine consecutive time points. RCM allowed the visualization of edema formation and blood vessel dilatation immediately after cryosurgery, as well as morphologic features of wound repair, including the formation of finger‐like protusions of keratinocytes into the wound bed, the appearance of hairpin‐like vessels, and inflammatory cells. This pilot study illustrates that RCM represents a promising technique for quasi‐real‐time monitoring the kinetics of wound repair non‐invasively and over time, thus offering new insights into in vivo processes of cutaneous wound repair and angiogenesis, as well as potential effects of topically applied drugs on the process of tissue repair.     

Treatment of striae distensae with non-ablative fractional laser: clinical and in vivo microscopic documentation of treatment efficacy

The efficacy of NAFL in the treatment of striae distensae (SD) has been demonstrated. Nevertheless, the base for this improvement has not been clarified yet. The aim of this study is to describe in vivo variations occurring in the skin after the treatment, using reflectance confocal microscopy (RCM). Ten patients asking for the treatment of SD were enrolled. Clinical and RCM images were acquired before the treatment, immediately after 1 and 6 months after the first treatment. One thousand five hundred forty-nanometer laser treatments were performed every 4 weeks for 6 sessions. Efficacy was estimated through the evaluation of pre- and post-treatment clinical pictures by two expert and independent physicians and with GAIS. Improvement of SD was observed in 80% of patients. Temporary erythema and edema were reported. RCM revealed the dissolution of collagen bundles and the appearance of new papillae, as compared to baseline. NAFL represents an effective and safe treatment modality for SD. We report herein in vivo variations occurring in SD after NAFL treatment.