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Topical imiquimod 5% cream has been investigated as off-label primary or adjuvant treatment for melanoma in situ, lentigo maligna type (LM). Herein, we present the largest known case series of lentigo maligna treated with topical imiquimod, with up to 17 years of follow-up, and include a recurrence-free survival analysis. In this case series, 103 lesions were retrospectively evaluated for treatment response and recurrence following a course of topical imiquimod with or without tazarotene gel 0.1% pretreatment between January 1, 2002 and March 31, 2019, and prospectively followed through November 15, 2019. Over median follow-up of 5.1 years (mean = 6.2 years, S = 5.2 years, range, 0.08ndash;17.1 years), including 29.1% LM withgt;10 years follow-up, we observed a response rate of 97.1% (100/103), with 8 local recurrences (8/100, 8.0%) developing at mean 2.9 years (SD: 2.7 years). Local recurrence was significantly associated with a history of failed excision (P= 0.001),lt;60 applications of imiquimod (P= 0.04) and partial clinical clearance (P= 0.0003). Recurrence-free survival analysis demonstrated significant risk-stratification for low and high-risk groups (P= 0.0001). Long term risk for recurrence showed significant differences among low- and high-risk cases, with low-risk cases demonstrating favorable long-term outcomes, comparable to conventional and staged surgery. Our observed low recurrence in a large case series with long-term follow-up suggests the efficacy of topical 5% imiquimod for LM and emphasizes the need for randomized control trials comparing imiquimod with, or as an adjunct to, surgical treatment. J Drugs Dermatol. 2021;20(3):346-348. doi:10.36849/JDD.5660.

Spontaneous hair repigmentation of physiologically white or gray hair is a rare occurrence that may be associated with melanoma in elderly individuals. We present the first case of this phenomenon in a man. A gray-haired, 80-year-old man presented to dermatology clinic with a 3-cm lock of black hair on his vertex scalp that developed over 1 year. Punch biopsies showed an increase in junctional dendritic melanocytes with rare pagetoid cells and extension along the follicular outer root sheath epithelium and interfollicular epidermis, associated with prominent dendritic melanocytic hyperplasia and pigment-containing melanocytes within the hair bulbs. Although the findings on the biopsies were not diagnostic of melanoma in situ, an irregular interfollicular distribution of melanocytes was concerning for an adjacent atypical process. A complete excision was performed and revealed melanoma in situ, lentigo maligna type. Rare reports describe spontaneous hair repigmentation as a harbinger of lentigo maligna in women. Repigmentation can occur in the setting of proliferation of malignant pigment-producing melanocytes or by paracrine stimulation of benign bulbar melanocytes through receptor tyrosine kinase KIT activation. Presence of prominent dendritic melanocytic hyperplasia and pigment-containing melanocytes within the hair bulbs in our patient's biopsies was suggestive of paracrine or physiologic stimulation of bulbar melanocytes. Given the importance of early melanoma detection and the low visibility of the scalp, this report raises awareness of an extraordinary presentation of lentigo maligna and exemplifies the importance of close clinicopathologic correlation to ensure optimal clinical management and patient outcome.

Smartphone-based fluorescence imaging systems have the potential to provide convenient quantitative image guidance at the point of care. However, common approaches have required the addition of complex optical attachments, which reduce translation potential. In this study, a simple clip-on attachment appropriate for fluorescence imaging of protoporphyrin-IX (PpIX) in skin was designed using the built-in light source and ultrawide camera sensor of a smartphone. Software control for image acquisition and quantitative analysis was developed using the 10-bit video capability of the phone. Optical performance was characterized using PpIX in liquid tissue phantoms and endogenously produced PpIX in mice and human skin. The proposed system achieves a very compact form factor (3) and can be readily fabricated using widely available low-cost materials. The limit of detection of PpIX in optical phantoms was 2 >0.99). Both murine and human skin imaging verified that in vivo PpIX fluorescence was detected within 1 hour of applying aminolevulinic acid (ALA) gel. This ultracompact handheld system for quantification of PpIX in skin is well-suited for dermatology clinical workflows. Due to its simplicity and form factor, the proposed system can be readily adapted for use with other smartphone devices and fluorescence imaging applications. Hardware design and software for the system is made freely available on GitHub (https://github.com/optmed/CompactFluorescenceCam).

Leishmaniasis is a neglected tropical disease with notable worldwide burden and increasing prevalence in the United States due to globalization. We describe 2 cases of cutaneous leishmaniasis in New England, United States, both caused by the New World subgenus Viannia, in adults returning from Central America. Both patients underutilized preventive measures against bites from phlebotomine sand flies while abroad. They were successfully treated with oral miltefosine, which was well tolerated. Avoidance of vector transmission is the most important preventive measure. Prompt identification and treatment of cutaneous leishmaniasis caused by species with potential for mucocutaneous spread are key to limiting morbidity and mortality. This responsibility should be shared among medical specialties, including dermatologists. Partnering with the Centers for Disease Control and Prevention (CDC) is critical for timely diagnosis and thus treatment. Miltefosine should be considered a first-line agent for cutaneous leishmaniasis given its efficacy, tolerability, availability, and ease of administration. Ondansetron can be prescribed concurrently.

Background Daylight-activated PDT has seen increased support in recent years as a treatment method for actinic keratosis and other non-melanoma skin cancers. The inherent variability observed in broad-spectrum light used in this methodology makes it difficult to plan and monitor light dose, or compare to lamp light doses. Methods The present study expands on the commonly used PpIX-weighted effective surface irradiance metric by introducing a Monte Carlo method for estimating effective fluence rates into depths of the skin. The fluence rates are compared between multiple broadband and narrowband sources that have been reported in previous studies, and an effective total fluence for various treatment times is reported. A dynamic estimate of PpIX concentration produced during pro-drug incubation and treatment is used with the fluence estimates to calculate a photodynamic dose. Results Even when there is up to a 5x reduction between the effective surface irradiance of the broadband light sources, the effective fluence below 250 μm depth is predicted to be relatively equivalent. An effective threshold fluence value (0. 70 J e f f / c m 2 ) is introduced based on a meta-analysis of previously published ALA-PpIX induced cell death. This was combined with a threshold PpIX concentration (50 nM) to define a threshold photodynamic dose of 0.035 u M J e f f / c m 2 . Conclusions The threshold was used to generate lookup tables to prescribe minimal treatment times to achieve depth-dependent cytotoxic effect based on incubation times and irradiance values for each light source.

Daylight-mediated photodynamic therapy (d-PDT) as a treatment for actinic keratosis (AK) is an increasingly common technique due to a significant reduction in pain, leading to better patient tolerability. While past studies have looked at different light sources and delivery methods, this study strives to provide equivalent PpIX-weighted light doses with the hypothesis that artificial light sources could be equally as effective as natural sunlight if their PpIX-weighted fluences were equalized. Normal mouse skin was used as the model to compare blue LED light, metal halide white light, and natural sunlight, with minimal incubation time between topical ALA application and the onset of light delivery. A total PpIX-weighted fluence of 20 J(eff)/cm(2) was delivered over 2 hours, and the efficacy of response was quantified using three acute bioassays for PDT damage: PpIX photobleaching, Stat3 crosslinking, and quantitative histopathology. These bioassays indicated blue light was slightly inferior to both sunlight and white light, but that the latter two were not significantly different. The results suggest that metal halide white light could be a reasonable alternative to daylight PDT, which should allow a more controlled treatment that is independent of weather and yet should have similar response rates with limited pain during treatment.

Background Hypoxic lesions often respond poorly to cancer therapies. Particularly, photodynamic therapy (PDT) consumes oxygen in treated tissues, which in turn lowers its efficacy. Tools for online monitoring of intracellular pO2 are desirable. Methods The pO2 changes were tracked during photodynamic therapy (PDT) with δ-aminolevulinic acid (ALA) in mouse skin, xenograft tumors, and human skin. ALA was applied either topically as Ameluz cream or systemically by injection. Mitochondrial pO2 was quantified by time-gated lifetime-based imaging of delayed fluorescence (DF) of protoporphyrin IX (PpIX). Results pO2-weighted images were obtained with capture-times of several seconds, radiant exposures near 10 mJ/cm2, spatial resolution of 0.3 mm, and a broad dynamic range 1−50 mmHg, corresponding to DF lifetimes ≈20−2000 μs. The dose-rate effect on oxygen consumption was investigated in mouse skin. A fluence rate of 1.2 mW/cm2 did not cause any appreciable oxygen depletion, whereas 6 mW/cm2 and 12 mW/cm2 caused severe oxygen depletion after radiant exposures of only 0.4−0.8 J/cm2 and Conclusions Time-gated imaging of PpIX DF seems to be a unique tool for direct online monitoring of pO2 changes during PDT with a promising potential for research purposes as well as for comparatively easy clinical translation to improve efficacy in PDT treatment.

Photodynamic therapy (PDT) for actinic keratosis (AK) and certain non-melanoma skin cancers (NMSC) is performed with either blue light (415nm Lamp), red light (630nm LED Lamps) or with sunlight. The differences in PDT efficacy can be high when using the latter broad-spectrum activation of PpIX. The purpose of this work was to establish a predictive treatment plan approach to daylight PDT which incorporated both local weather forecast information as well as prediction of wavelength-depth dependence upon the efficacy. The concept of PpIX-weighted light fluence is now well established as a way to compare effective light doses from daylight PDT to traditional lamp PDT, but there is limited work to date considering the effects of tissue optical properties or the dynamic distribution of PpIX at depths into the tissue. Using a Monte Carlo model of light fluence in a multi-layer skin geometry we estimate the effective fluence at depth in tissue. The result of these simulations in combination with a model for PpIX production and photobleaching at a range of depths are used to generate lookup tables for the time needed to reach a specific photodynamic dose at a predicted lesion thickness. These tables are then used as the foundation of a web-based application that will better inform the dermatology team of light dosing options. GPS-derived location is used to retrieve forecasted and historical weather patterns automatically, and used as an additional input to further refine prescribed dosing of daylight-PDT. The application is currently being tested in conjunction with fluorescence dosimetry, as a method to verify and alleviate clinical variation in lesion clearing from daylight PDT.

Background: Aminolevulinic acid (ALA)-based photodynamic therapy (PDT) provides selective uptake and conversion of ALA into protoporphyrin IX (PpIX) in actinic keratosis and squamous cell carcinoma, yet large response variations in effect are common between individuals. The aim of this study was to compare pre-treatment strategies that increase the therapeutic effect, including fractionated light delivery during PDT (fPDT) and use of iron chelator desferrioxamine (DFO), separately and combined. Methods: Optical measurements of fluorescence were used to quantify PpIX produced, and the total amount of PpIX photobleached as an implicit measure of the photodynamic dose. In addition, measurements of white light reflectance were used to quantify changes in vascular physiology throughout the PDT treatment. Results: fPDT produced both a replenishment of PpIX and vascular re-oxygenation during a 2 h dark interval between the first and second PDT light fractions. The absolute photodynamic dose was increased 57% by fPDT, DFO and their combination, as compared with PDT group (from 0.7 to 1.1). Despite that light fractionation increased oedema and scab formation during the week after treatment, no significant difference in long-term survival has been observed between treatment groups. However, outcomes stratified on the basis of measured photodynamic dose showed a significant difference in long-term survival. Conclusions: The assessment of implicit photodynamic dose was a more significant predictor of efficacy for ALA-PDT skin cancer treatments than prescription of an enhanced treatment strategy, likely because of high individual variation in response between subjects.

In clinical delivery of PDT, in-situ measurement of PpIX concentration is rarely done, and yet point-probe measurements have shown extreme heterogeneity exists between patients and between lesions. Direct measurements of PpIX can provide guidance in PDT, informing critical decisions about treatment time and retreatment or further skin preparation. In this work, we present a smartphone-based fluorescence imaging system to map PpIX concentration onto a 2D image for the use in PDT treatment optimization. The hand-held system utilizes a custom application on an iPhone 6s in conjunction with a 3D-printed measurement base containing custom miniaturized light source and electronics and filter system. The prototype has been produced and tested in phantoms and in pre-clinical evaluation. Intralipid phantom measurements detected clinicallyrelevant concentrations of PpIX within the 0.05μM - 4μM range. Preclinical tests on mice showed the ability to detect PpIX concentration for topically applied ALA within 20-30 minute incubation. These results showcase the viability of the system to map pixel intensities to PpIX concentrations and perform in-vivo detection within a clinically relevant timeframe. Clinical trials are in preparation with results expected in the next few months.

No abstract available.

Abdominal wall transplants are relatively new procedures that are frequently performed in conjunction with multivisceral transplants. The skin of the abdominal wall transplant is often the first site for graft rejection to manifest itself. Prompt recognition can lead to appropriate treatment before the involvement of the underlying viscera. However, the signs of graft rejection are nonspecific and can overlap with other entities. We present a case of a patient who received a multivisceral and abdominal wall transplant from 2 different donors, who presented with acute and eventually chronic graft rejection of the abdominal wall graft. Serial biopsies performed during the course of her treatment demonstrated progressive sclerotic changes in the dermis. Because these changes were confined to the abdominal wall graft, they could represent either chronic graft rejection or graft-versus-graft disease. To date, graft-versus-graft disease has not been documented in these patients. This case illustrates the possibility that patients with multidonor transplants may be at an increased risk for graft failure secondary to multiple potential etiologies.

Background: Little is known about whether history of allergies and atopy is related to the occurrence of keratinocyte cancers. Thus, we evaluated the association between history of allergies and atopy and the incidence of squamous cell carcinoma (SCC) and early onset basal cell carcinoma (BCC). Methods: As part of a population-based case–control study, interviews were conducted with 1,050 residents of New Hampshire (375 early onset BCC cases and 251 controls, 254 SCC cases and 432 controls). ORs of SCC and early onset BCC and history of allergy and atopic dermatitis were computed using logistic regression, while controlling for potential confounding factors. Results: An overall inverse association was observed between a history of allergy and early onset BCC [OR, 0.61; 95% confidence interval (CI), 0.38–0.97] but not SCC (OR, 1.18; 95% CI, 0.78–1.79). Among women, we found reduced ORs of both early onset BCC and of SCC in relation to allergy history (early onset BCC OR, 0.53; 95% CI, 0.31–0.92 and SCC OR, 0.59; 95% CI, 0.29–1.19). Among men, we observed no clear association with early onset BCC (OR, 0.87; 95% CI, 0.39–1.99) and an increased risk of SCC (OR, 1.58; 95% CI, 0.93–2.69). Conclusion: Our findings suggest that allergies and atopy may influence risk of early onset BCC and SCC, and that effects may be gender specific. Impact: A deeper understanding of the immune mechanisms underlying allergies and atopy may provide new routes of preventing keratinocyte cancers. Cancer Epidemiol Biomarkers Prev; 24(4); 749–54. ©2015 AACR.

We report the case of a 6-year-old girl with no notable medical history who presented to the dermatology clinic for evaluation of left leg pain with an overlying erythematous rash of 4 days' duration. Clinical examination revealed pink patches and plaques in a unilateral L5 distribution with an isolated pinpoint vesicle. Direct fluorescent antibody testing confirmed varicella-zoster virus (VZV) infection, establishing a diagnosis of herpes zoster (HZ). The patient previously had received the VZV vaccine in the left leg and arm and had no history of primary VZV infection. We summarize this case and discuss the epidemiology and clinical characteristics of HZ in vaccinated children.

Background Sunlight can activate photodynamic therapy (PDT), and this is a proven strategy to reduce pain caused byconventional PDT treatment, but assessment of this and other alternative low dose rate light sources, and their efficacy, has not been studied in an objective, controlled pre-clinical setting. This study used three objective assays to assess the efficacy of different PDT treatment regimens, using PpIX fluorescence as a photophysical measure, STAT3 cross-linking as a photochemical measure, and keratinocyte damage as a photobiological measure. Methods Nude mouse skin was used along with in vivo measures of photosensitizer fluorescence, keratinocyte nucleus damage from pathology, and STAT3 cross-linking from Western blot analysis. Light sources compared included a low fluence rate red LED panel, compact fluorescent bulbs, halogen bulbs and direct sunlight, as compared to traditional PDT delivery with conventional and fractionated high fluence rate red LED light delivery. Results Of the three biomarkers, two had strong correlation to the PpIX-weighted light dose, which is calculated as the product of the treatment light dose (J/cm2) and the normalized PpIX absorption spectra. Comparison of STAT3 cross-linking to PpIX-weighted light dose had an R = 0.74, and comparison of keratinocyte nuclear damage R = 0.70. There was little correlation to PpIX fluorescence. These assays indicate most of the low fluence rate treatment modalities were as effective as conventional PDT, while fractionated PDT showed the most damage. Conclusions Daylight or artificial light PDT provides an alternative schedule for delivery of drug-light treatment, and this pre-clinical assay demonstrated that in vivo assays of damage could be used to objectively predict a clinical outcome in this altered delivery process.

Background: Actinic cheilitis is a common precancerous disorder of the lower lip caused by ultraviolet radiation. Photodynamic therapy (PDT) is a potential treatment for actinic cheilitis, however controlled clinical trials regarding this treatment are needed.Objective: To evaluate the safety and efficacy of PDT with blue light and topical δ-aminolevulinic acid (Levulan®) in the treatment of actinic cheilitis.Methods: We conducted a single center, investigator-initiated, nonrandomized, open-label, proof of concept study of PDT with blue light for the treatment of actinic cheilitis. We enrolled 24 subjects, 20 meeting inclusion and exclusion criteria. One subject withdrew from the study prior to treatment. The study consisted of a screening visit, one to three scheduled treatments, and two follow-up visits. The primary outcome was clinical improvement in actinic cheilitis from baseline, estimated as no (0%), mild (25%), moderate (50%), marked (75%), or excellent improvement (100%). Post-treatment assessment of swelling, erythema, flaking/scaling, crusting, vesiculation/pustulation, and erosion/ulceration was also recorded. Subjects completed the Dermatological Life Quality Index questionnaire, subject global assessment of improvement, and pain assessment at each visit.Results: 65% of subjects achieved clinical improvement of 75% or greater and 20% achieved 100% improvement by the end of the study. Treatments were well tolerated with minimal discomfort. Subjects experienced transient mild adverse effects.Conclusion: Overall, our study supports using PDT for the treatment of actinic cheilitis.

Significance: While clinical treatment of actinic keratosis by photodynamic therapy (PDT) is widely practiced, there is a well-known variability in response, primarily caused by heterogeneous accumulation of the photosensitizer protoporphyrin IX (PpIX) between patients and between lesions, but measurement of this is rarely done. Aim: Develop a smartphone-based fluorescence imager for simple quantitative photography of the lesions and their PpIX levels that can be used in a new clinical workflow to guide the reliability of aminolevulinic acid (ALA) application for improved lesion clearance. Approach: The smartphone fluorescence imager uses an iPhone and a custom iOS application for image acquisition, a 3D-printed base for measurement standardization, an emission filter for PpIX fluorescence isolation, and a 405-nm LED ring for optical excitation. System performance was tested to ensure measurement reproducibility and the ability to capture photosensitizer accumulation and photobleaching in pre-clinical and clinical settings. Results: PpIX fluorescence signal from tissue-simulating phantoms showed linear sensitivity in the 0.01 to 2.0 μ M range. Murine studies with Ameluz® aminolevulinic acid (ALA) gel and initial human testing with Levulan® ALA cream verified that in-vivo imaging was feasible, including that PpIX production over 1 h is easily captured and that photobleaching from the light treatment could be quantified. Conclusions: The presented device is the first quantitative wide-field fluorescence imaging system for PDT dosimetry designed for clinical skin use and for maximal ease of translation into clinical workflow. The results lay the foundation for using the system in clinical studies to establish treatment thresholds for the individualization of PDT treatment.

Melanoma in situ (MIS) is a noninvasive form of melanoma for which nonsurgical therapeutic options continue to be explored. The off-label use of topical 5% imiquimod cream in the management of MIS has shown potential but reported recurrence rates vary considerably between 0% and 40%. Furthermore, the long-term efficacy of imiquimod is not well established.To determine the recurrence rate of MIS among patients treated with topical 5% imiquimod cream at Dartmouth-Hitchcock Medical Center with at least 1 year of follow-up.A retrospective chart review identified 12 patients with MIS who have been treated with topical 5% imiquimod cream for 6 to 12 weeks. Patients who underwent surgical treatment for MIS were excluded from analysis.Of 12 patients with histologically confirmed MIS treated with topical 5% imiquimod cream, there were 2 recurrences (17%) during a median follow-up time of 5.5 years.Although surgery is still considered the gold standard for the treatment of MIS, imiquimod may represent a potentially effective noninvasive treatment option for patient who are not surgical candidates.

The immune checkpoint targeted agents, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and anti-programed cell death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) inhibitors are frequently associated with cutaneous side effects that are often dose limiting and can lead to discontinuation of therapy. Ipilimumab, a CTLA-4 inhibitor, is most commonly associated with a morbilliform eruption on the trunk and extremities and pruritus. More severe cutaneous toxicities reported include toxic epidermal necrolysis and severe drug rash with eosinophila and systemic symptoms. Recent case reports of Sweet syndrome and cutaneous sarcoidosis have also recently been described after treatment with ipilimumab. The cutaneous events usually occur early in the course of treatment and are dose dependent. PD-1 inhibitors, nivolumab and pembrolizumab, induce similar but less severe toxicities compared with the CTLA-4 inhibitors. The most common cutaneous adverse events include lichenoid reactions, eczema, vitiligo, and pruritus. Lichenoid oral mucosal lesions located on the tongue, buccal mucosa, lips, or gingivae or located on all of these have also recently been described. The time of onset of the cutaneous events with the PD-1 inhibitors occurs later than that seen with the CTLA-4 inhibitors. Anti-PD-L1 antibodies, such as atezolizumab, have a similar side effect profile compared with the PD-1 inhibitors. Combination of immune checkpoint inhibitors, ipilimumab and nivolumab, has recently been approved for the treatment of advanced melanoma. The combination therapy is associated with a more severe side effect profile compared with the agents used as monotherapy. We discuss the most frequently encountered cutaneous side effects of the immune checkpoint inhibitors and review the recommended management strategies.

Intertriginous and facial involvement are manifestations of psoriasis that require a different approach than is used for typical plaque psoriasis on other skin areas. Topical corticosteroids are the primary treatment for psoriasis; however, the side effects of corticosteroids are magnified on intertriginous and facial skin. Topical tacrolimus offers the potential for anti-inflammatory effect without the atrophy or other local side effects associated with the use of topical corticosteroids.To determine the efficacy and tolerability of 0.1% tacrolimus ointment for the treatment of facial or intertriginous psoriasis.One hundred sixty-seven patients 16 years or older were evaluated in an 8-week, randomized, double-blind, vehicle-controlled, multi-center study. Upon entry into the study, patients were randomized 2:1 to apply the tacrolimus ointment 0.1% or vehicle twice daily to all psoriatic lesions of the face or intertriginous areas for 8 weeks. The physician's global assessment was used to assess improvement from baseline. The inverse psoriasis severity for patients was measured using a 6-point scale from clear to very severe.As early as day 8, more patients ( P = .004) had cleared or achieved excellent improvement in the 0.1% tacrolimus ointment group compared to the vehicle group (24.8% vs 5.8%). At the end of the 8-week treatment period 65.2% of the tacrolimus ointment group and 31.5% of the vehicle were clear or almost clear ( P.0001) based on a Static Severity Score. Adverse events were similar in the 0.1% tacrolimus ointment and vehicle groups. Conclusion Tacrolimus ointment is an effective treatment for psoriasis of the face or intertriginous areas.

not available. Disclosures: Study supported by Celgene. Copyright SKIN 2018

Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response.

In North America, the most common cause of vulvar ulcers is infection with herpes simplex virus. However, Epstein-Barr virus can also cause vulvar ulcers, and may be underrecognized. Unlike herpes simplex virus, Epstein-Barr virus is not necessarily sexually transmitted. Therefore, it is particularly important to include in the differential diagnosis of genital ulcers for patients for whom a diagnosis of a venereal infection has important psychosocial consequences. We report three cases of acute primary Epstein-Barr virus infection in which the presenting symptoms were vulvar ulceration.

Vitamin A is required for the proper functioning of many important metabolic and physiologic activities, including vision, gene transcription, the immune system and skin cell differentiation. Both excessive and deficient levels of vitamin A lead to poor functioning of many human systems. The biologically active form, retinoic acid, binds to nuclear receptors that facilitate transcription that ultimately leads to it's physiological effects. Retinoids are derivatives of vitamin A that are medications used to treat acne vulgaris, psoriasis, ichthyosis (and other disorders of keratinization), skin cancer prevention as well as several bone marrow derived neoplasias. Systemic retinoids are teratogenic and have to be prescribed with caution and close oversight. Other potential adverse events are controversial. These include the relationship of retinoid derivatives in sunscreens, their effects on bone mineral density, depression and suicidal ideation and inflammatory bowel disease. These controversies will be discussed in detail.