The Photomedicine Society
promotes a greater understanding
of light in health and disease.

Archive of the 21^st Meeting of the Photomedicine Society

Thursday, March 15, 2012, 8:00 a.m. - 5:30 p.m.
Santa Rosa Room, San Diego Marriott
San Diego, California, USA

The presentations were the following, in order of presentation
(Click on each title to see the abstract and its authors.)

1. ULTRAVIOLET B PROTECTIVE PROPERTIES OF CONTACT LENSES WITH INTENDED USE IN PHOTORESPONSIVE EYELID DERMATOSES

   Jennifer DePry¹, Harry Dao², Kevin Cooper², Loretta Szczotka-Flynn², Elma Baron².
   ¹ Providence Hospital Southfield, Michigan
   ² University Hospitals Case Medical Center Cleveland, Ohio

   UV-blocking contact lenses were evaluated to determine if they provide adequate protection for use within a narrowband UVB phototherapy unit, for the treatment of photoresponsive eyelid dermatoses. The theoretical safe exposure durations of the crystalline lens, cornea and conjunctiva were determined.

   Spectral transmittance data for 6 UV-blocking and 2 non UV-blocking contact lenses was generated using a Cary 500 spectrophotometer. The contact lenses were also tested within a narrowband UVB phototherapy unit to measure radiation transmittance using an IL 1700 radiometer and exposed to 1500mJ/cm² of radiation with a 308nm excimer laser to determine if a high dose of UVR would degrade their protective properties. The theoretical safe exposure durations of eye structures were calculated using previous human and animal study data.

   All UV-blocking contact lenses had less than 1% transmittance at 311nm; the peak irradiance produced by narrowband UVB bulbs. Within the narrowband phototherapy unit, all UV-blocking lenses showed less than 1x10^-7 Watts/cm² radiation transmittance. High UV doses from an excimer laser did not significantly degrade UV-blocking capabilities of the contact lenses. The safe exposure durations for the cornea and crystalline lens increased from 24 seconds without the contact lens to 56 minutes with UV-blocking contact lenses, and was 11 seconds for the unprotected conjunctiva.

   Some UV-blocking contact lenses may provide sufficient protection of the cornea and crystalline lens within the narrowband phototherapy unit. While we recommend that patients keep their eyes closed during therapy, the crystalline lens and cornea are sufficiently protected against UV radiation if a person were to open their eyes for a short duration of time.

2. AN IN VIVO AND IN VITRO ASSESSMENT OF PHOTOPROTECTION OFFERED BY FABRICS SUBJECTED TO PROGRESSIVE DURABILITY: AN EVALUATION OF ERYTHEMA AND OTHER PHOTODAMAGE

   RM Sayre¹, D Lott², S Wallace², JC Dowdy¹, SNG Hughes³.
   ¹ Rapid Precision Testing Laboratories, Cordova, TN
   ² Florida Suncare Testing, Inc
   ³ Sun Precautions, Inc., Everett, WA

   Purpose: Fabrics and clothing have continued to make inroads in providing an alternative preferred method for consumers to obtain safe and effective broad-spectrum sun protection. Today label requirements that all topical SPF sunscreens be reapplied every two hours, makes wearing proper sunlight protective clothing a wise choice. As a result, consumers are looking at high SPF and UPF clothing choices and are using them for prolonged periods of time. Our continuing study evaluates the photoprotection offered by fabrics marketed as 30+ SPF and 50+ SPF and comparing them to marketing claims, both after intermediate and long term durability and UV exposure testing.

   Methods: We evaluated photoprotection offered by these fabrics before and after two durability test points (40 standard laundery cycles with 100 UV fading units or 500 launderings with 500 simulated UV days). This phase of the study evaluated the photoprotection using several in vivo methods, one of which is adapted from the standard SPF protocol used by sunscreen industry in the US, and two in vitro methods. Similarly, erythema versus non-specific photodamage was also studied.

   Results: In vitro results revealed that these fabrics were highly photoprotection at or above 50 SPF/UPF. Initial in vivo pass/fall erythema testing indicated these to be above 40 SPF to greater than 50 SPF with neither perceptible erythema nor photoinjury.

   Conclusions: Consumers may rely on stated SPF and UPF photoprotection claims offered by materially durable SPF/UPF rated clothing and assume that the photoprotection deteriorates minimally over time, use and exposure. This is especially relevant given the broad-spectrum UVA an UVB photoprotection goal within the dermatology community.

3. A SURVEY OF THE PRACTICE OF PHOTOTHERAPY WITH NARROWBAND UVB.

   P Anurukpaiboon, TM Rünger.
    Department of Dermatology, Boston University, Boston, MA.

   Background: Phototherapy is a widely-used treatment for various skin diseases. To our knowledge, all published clinical trials on dosing of narrowband UVB (nbUVB) used dosing schedules that were based on the minimal erythema dose (MED) of each patient. However, some dermatologists do not determine a MED prior to starting phototherapy, but instead dose according to the patient’s skin phototype. While there are AAD-guidelines on skin phototype-based dosing, those do not appear to be validated in controlled clinical trials. We hypothesized that the dosing of nbUVB phototherapy varies considerably among dermatologists and that skin phototype-based dosing is commonly used despite the lack of validated guidelines.

   Methods: In order to document the current practice of phototherapy with nbUVB, we contacted 337 US dermatologists known to practice phototherapy with a request to complete a 24-questions online survey about dosing and safety of UVB-phototherapy.

   Results: Responses are still being collected and the preliminary data presented here is based on a response rate of 6%. NbUVB is by far the most frequently used type of UVB-phototherapy, with only 5% of respondents reporting use of broadband UVB. 95% use skin-type based dosing, with 78% using it exclusively (never using MED-based dosing). 88% treat three times a week and 12% twice a week. Initial doses vary, ranging from 80 – 169% of the initial doses recommended by the AAD. The dose increments are mostly higher than the AAD guidelines, with 63% reporting dose increments more than two-fold higher. Dose adjustments after missed treatments or burning vary moderately. Mild burning, pruritus, and xerosis are the most commonly observed adverse events. Burning occurs at any time during the course of nbUVB-phototherapy, but is less common after the initial dose.

   Conclusion: In summary, a majority of dermatologists uses skin phototype-based dosing with higher doses than those recommended by the AAD, but still with a low rate of adverse events. This indicates that controlled clinical trials with skin phototype-based dosing are needed to develop improved guidelines for such dosing regimens.

4. PHOTOTHERAPY GUIDELINES: DO WE FOLLOW PROTOCOLS?

   B Toosi, H Lui, J Shapiro, Y Zhou, S Kalia.
    Psoriasis and Phototherapy Clinic, Vancouver Coastal Health, Vancouver, BC
    Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC

   Purpose: Broadband UVB (BB-UVB) is an effective treatment for several dermatologic conditions. Phototherapy clinics administer BB-UVB in accordance to different guidelines that are based on patients’ skin types. Although several guidelines exist, the adherence to these guidelines has not been thoroughly evaluated.

   Methods: In this study, 1504 patients that received BB-UVB therapy at the Skin Care Centre's Psoriasis & Phototherapy Clinic in Vancouver were reviewed. Patients enrolled into the study were limited to those that received their first treatment session between 2004 and 2011 and completed at least 20 treatment sessions. The starting dose, subsequent increase and maximum dose received by these patients were analyzed, along with demographic variables. In addition, energy fluences were studied in patients receiving photosensitive medications to determine if these influenced dosages given.

   Results/Conclusion: In this study, only 63% received recommended dose increase of 5-10% during the 20 treatment sessions if there was no adverse effect from previous phototherapy treatments. Although the number of patients on photosensitive medications was relatively low, preliminary analysis failed to show a difference in patients’ phototherapy dosages compared to those not receiving photosensitive medications. Overall, the results of this study support that a conservative dose increment is favored; further studies are needed to confirm these findings.

5. NON-INVASIVE METHOD TO ASSESS THE SUN PROTECTION FACTOR (SPF)

   Eduardo Ruvolo¹, Leonardo de Paula¹, Curtis Cole¹ and Nik Kollias^{2
   1} Johnson & Johnson, Skillman, NJ, United States
   ² J&J retiree

   In the past 56 years many different in vitro methodologies have been developed and published to assess the SPF of products but there is no method that has 1:1 correlation with in vivo measurements. Spectroscopic techniques have been used to non-invasively assess the UVA protection factor with good correlation to in-vivo UVA-PF methodologies. This involves the assessment of the remitted intensity of monochromatic UVA radiation (320-400 nm) before and after a sunscreen product was applied on skin. The incident monochromatic UVA radiation is delivered to the skin through a bifurcated optical fiber bundle while a second fiber optic bundle (randomly intermixed with the incident bundle) collects the remitted intensity from the skin. The UVA radiation is attenuated both on its way into the skin and on its way out of the skin by the applied product on the skin's surface. The wavelengths are scanned across the UVA spectrum and thus the absolute UVA absorption spectrum of the tested product can be measured non-invasively. The probe geometry assures that light scattering products as well as colored products may be correctly assessed. This methodology has been extensively tested, validated and reported in the literature.

   To assess the SPF of sunscreen product using the same technique it is necessary to also determine the absorbance spectrum of the test material in the UVB portion of the spectrum (290-320 nm). However, because of the high absorbance characteristics of the stratum corneum and epidermis, the human skin does not remit enough UVB radiation to be used to measure the absorption spectrum of the applied product on skin. In this work we present a new method combining the evaluation of the absolute UVA absorption spectrum, as measured by diffuse reflectance spectroscopy (DRS) with the spectral absorbance “shape” of the UVB absorbance of the test material as determined with current in vitro thin film spectroscopy.

   The in vitro absorption spectrum of the sunscreen was measured using Labsphere^TM UV-2000S UV Transmission Analyzer (Labsphere, North Sutton, NH, USA) with PMMA Helioplates as substrate with one face sand-blasted (mechanical microbeam technique) and with a specific roughness Ra = 2 microns (Helioscience, Marseille, France). The UVB absorbance spectrum (Labsphere) is “attached” to the UVA absorbance spectrum (diffuse reflectance) with the UVB absorbance matched to the UVA absorbance at 330nm to complete the full spectral absorbance from which an estimate the SPF of the product can be calculated. Twenty two test materials with known in vivo SPF values were tested. The correlation of this new method with in vivo clinical SPF values was 0.91 (r²). This new methodology provides a new approach to determine SPF values without the extensive UV irradiation procedures (and biological responses) currently used to establish sunscreen efficacy. Further work will be conducted to establish methods for evaluation of products that are not photostable.

6. HIGH LEVEL OF PHOTOPROTECTION IS NEEDED FOR CAUCASIAN AND HISPANIC SKIN

   Eduardo Ruvolo, Catherine Correa, Paulo Bargo, Georgios Stamatas and Nik Kollias
    Johnson & Johnson, Skillman, NJ, United States

   Dermatologists and the World Health Organization (WHO) recommend simple precautions to prevent sunburn such as wearing protective clothing, avoiding sun exposure in the middle of the day and using a sunscreen. Clinical SPF testing is conducted to establish the SPF of products and all of the established testing protocols (including the FDA, COLIPA and ISO methodology) require that the sunscreens must be applied in an amount of 2 mg/cm² for the SPF label claim. However, in real life according with several studies the amount of sunscreen applied is much lower (0.5 mg/cm² to 1 mg/cm²).

   The objective of this study is to explore the effects of recreational exposure to solar UVR during one day at the beach on the skin of young children and adults. A total of 43 male and female children and their biological mothers (n = 38) were evaluated at baseline and following one day spent at the beach (Ship Bottom, Long Beach Island, New Jersey USA). Children were aged 23 months – 68 months, and their mothers identified their children’s skin types and ethnicities as I-III, Caucasian (n=22) or IV-V, Hispanic (n=19). Mothers were aged 22 – 43 years old, and self identified skin types and ethnicities as I-III, Caucasian (n=21), or IV-V, Hispanic (n=16).

   Subjects were instructed to follow their normal routine during a vacation day at the beach, including time spent outdoors and sun protection routines. Subjects were given a broad-spectrum SPF 50 sunscreen for use on exposed areas. Subjects who typically wore t-shirts at the beach were recruited, and were told to wear their usual t-shirts. Subjects were evaluated in the morning before spending a day at the beach, in the evening of the same day, the next morning (approximately 24 hours after solar UVR exposure), and the following week. Between the beach day and the one week follow-up timepoint, subjects were instructed to avoid significant sun exposure and to apply sunscreen when sun exposure was unavoidable. Non-invasive skin measurements and digital images were acquired of sun exposed and sun protected skin sites at each timepoint and the amount of UVR exposure was also evaluated.

   Skin reactions such as erythema and induced pigmentation were assessed by rapid non-invasive methods (colorimetry, diffuse reflectance spectroscopy, cross polarized image analysis). Baseline differences in skin color and chromophore concentration were observed between Caucasians and Hispanics. Apparent concentrations of melanin and deoxy-hemoglobin (both related to pigmented appearance of skin) were higher in Hispanic children and adults, and the apparent concentration of oxy-hemoglobin (related to perceived erythema) was higher in Caucasian children and adults on sun exposed areas: cheek and forehead.

   These results indicate the need for sun protection in children, even children with darker skin types. The use of a product with a SPF 50 did not prevent subjects with light completion to develop erythema after a day of recreational exposure. Differences in melanocompetency with ethnicity also support the need for sun protection for highly pigmented subjects who consider themselves naturally protected. Further development of pigmentation with exposure is highly dependent on other factors, and is not be accurately predicted by the constitutive level of pigmentation

7. THE ROLE FURIN PLAYS IN THE ACTIVATION OF MMPs IN UV-IRRADIATED HUMAN KERATINOCYTE CELL LINES

   Rethika Ravi¹ and Terrence J. Piva^{2
   1} Biosciences Department, Endeavour College of Natural Health, Vic 3000, Australia
   ² School of Medical Sciences, RMIT University, Bundoora, Vic 3083, Australia

   Ultraviolet radiation (UVR) is known to elevate matrix metalloproteases (MMP) activity in human skin cells. The proprotein convertase furin cleaves many proteases in the cell including MMP-2 and -9. The effect UVR has on the expression and activity of furin, MMP-2 and -9 in human keratinocyte cells are not known. We investigated the effect of 1 MED UVR [UVA (40 KJ/m²), UVB (2 KJ/m²) and UVAB (40+2 KJ/m²)] had on the expression and activity of furin, MMP-2 and MMP-9 24 h post-irradiation in human HaCaT and Colo 16 cell lines. Colo 16 cells were more sensitive to UVB radiation than HaCaT cells, while UVA had no effect on cell viability. Furin levels in HaCaT cells increased 7-fold in response to UVAB while in Colo 16 it was elevated 3-fold following exposure to UVB. In HaCaT cells maximal induction of furin mRNA expression occurred 24 h after UV exposure. The increase in MMP-2 mRNA expression was highest in UVB-irradiated cells compared to UVAB- or UVA-irradiated HaCaT cells, which differed to that seen for furin and MMP-9 in these cells. Similar results were seen for Colo 16 cells except maximal mRNA expression was seen after 4 h for MMP-2, 12 h for MMP-9 and 24 h for furin. In Colo 16 cells (24 and 72 h) but not in HaCaT cells, there was a biphasic induction of MMP-2 and -9 activity following exposure to UVB radiation. The furin inhibitor, Dec RVKR cmk, reduced MMP activity in UV-irradiated HaCaT and Colo 16 cells, which suggests that furin is involved in their maturation. Dec RVKR cmk and metalloprotease inhibitors reduced the migration of UV-irradiated HaCaT and Colo 16 cells in scratch assays. The different responses seen in both cells following exposure to UV radiation may be relate to the tumorigenic nature of these cells.

8. CUTANEOUS EFFECTS OF THE α-MSH-ANALOGUE AFAMELANOTIDE DURING TREATMENT OF ERYTHROPOIETIC PROTOPORPHYRIA

   Uche-Holub E¹, Siegesmund M^1,2, Kuerten V¹, Bodden G¹, Poblete-Gutiérrez P³, Anstey AV⁴, Neumann NJ¹, Hanneken S¹, Frank J^{1,2
   1} Department of Dermatology and German Porphyria Specialist Center, Heinrich Heine University Duesseldorf, Duesseldorf, Germany
   ² GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands
   ³ Department of Dermatology, Annadal Medical Center Maastricht, Maastricht, The Netherlands
   ⁴ Academic Dermatology, Aneurin Bevan Health Board, Newport, UK

   The synthetic analogue of alpha-melanocyte-stimulating hormone [Nle⁴, D-Phe⁷]-α-MSH (afamelanotide) binds to the melanocortin-1 receptor (MC-1R) after sun exposure, thereby stimulating melanocytes to produce melanin. The resulting increase in skin pigmentation, along with putative anti-inflammatory properties of afamelanotide, offers the possibility of therapeutic benefit for some photodermatoses. We report about the cutaneous effects of afamelanotide in a recent clinical trial for the hereditary photosensitivity disorder erythropoietic protoporphyria (EPP). Three dermatology clinical research centres recruited 41 patients with EPP for treatment with afamelanotide (Scenesse^®) in two prospective, double-blinded, placebo-controlled, multicentre phase III trials and during a subsequent compassionate use period (supported by Clinuvel Pharmaceuticals Ltd, Melbourne, Vic., Australia). All subjects received either the active drug or the placebo every two months by means of a slow-releasing subcutaneous implant. The general cutaneous effects observed under this treatment comprised an increased skin pigmentation that was particularly striking in melanocytic naevi and lentigines located in sun-exposed body areas. In single cases, we observed pronounced perioral and localized labial pigmentation, arachnoid-shaped hyperpigmentation at the implantation site and linear postinflammatory hyperpigmentation. Additionally, some patients reported facial flushing shortly after implantation. Afamelanotide appeared to be effective in amelioration of the acute, burning and painful photosensitivity commonly experienced by EPP patients, although formal data analysis has not yet been reported. No major side effects were observed. In conclusion, our preliminary data revealed significant cutaneous responses to this novel drug, which were generally acceptable to patients and would be of sufficient magnitude to explain a therapeutic response in EPP. We strongly believe that a wider benefit for this drug could emerge in other photosensitivity disorders.

9. PROTEOMIC ANALYSIS OF ULTRAVIOLET LIGHT-INDUCED CHANGES IN HUMAN SKIN IN VIVO.

   P OyetakinWhite¹, G Gokulrangan², JE Dazard², E Yohannes², M Matsui³, M Chance², K Cooper¹, E Baron¹.
   ¹ Dept of Dermatology,
   ² Center for Proteomics Case Western Reserve Univ
   ³ R&D, Estee Lauder Inc. Cleveland, OH. Melville, NY

   Statement of Purpose: Ultraviolet radiation causes significant cellular and molecular changes in human skin. The aim of our study was to use a discovery proteomic-based analysis to determine changes in protein expression levels in human skin after in vivo simulated solar radiation (SSR).

   Description of design: Two 2.5cm² areas of full-thickness suction blister epidermis were collected from each of twelve participants (age: 19-53; FST I-IV). Each subject provided unirradiated control and SSR-irradiated (1 MED) skin. The epidermal cell proteome was separated using a 1D gradient SDS PAGE-fractionation approach followed by a label free quantitation of differentially expressed proteins using chromatographic peak volume compilations from the Rosetta Elucidator data analysis platform.

   Summary of results: The samples were collected 24 hours after SSR exposure. A total of 171 proteins were identified from 3420 peptides. A wide variety of proteins demonstrated robust changes in expression levels following UV exposure. Proteins involved in metabolism (Hexokinase 1, Enolase 1, and GAPDH), cell cytoskeleton and adhesion (Keratins 1, 10, 5, 16, Desmocollin 3) and heat shock proteins were significantly upregulated. Many of these proteins are known to play a role in tumor promotion. UV also downregulated proteins involved in structural integrity, tumor suppression, and regulation of differentiation. Protein-protein interaction analysis was performed using the Ingenuity Pathway Analysis (IPA). This linked observed protein changes to well known markers of UV damage such as MAP kinase, and NFкB.

   Statement of conclusions: This gel-based fractionation approach was very useful in mining the epidermal tissue proteome in spite of overwhelming keratin levels. State of the art LC-MS/MS methodology was successfully implemented to perform differential quantitative proteomics in this study. Our findings provide a protocol capable of detecting a wide range of UVR induced simultaneous changes in protein expression in human skin and might therefore be used to assess UVR protection strategies.

10. ERYTHROPOIETIC PROTOPORPHYRIA: NORMALIZATION OF ERYTHROCYTE PROPHYRIN DURING PREGNANCY

    Bafteh PR¹, Hanneken S¹, Uche-Holub E¹, Bodden G¹, Siegesmund M^1,2, Schulte KW¹, Frank J^1,2, Neumann NJ^{1
    1} Department of Dermatology and German Porphyria Specialist Center, Heinrich Heine University Duesseldorf, Duesseldorf, Germany
    ¹ GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands

    Erythropoetic protoporphyria (EPP) is a hereditary disorder of heme biosynthesis due to a catalytic deficiency of ferrochelatase (FC). Pathogenetically, accumulation of protoporphyrin IX leads to acute photosensitivity characterized by painful burning and stinging skin sensations, erythema and edema after sun exposure. There are only few reports of erythrocyte porphyrin (EP) levels in female EPP-patients before, during and after pregnancy. Although amelioration of EP levels in the course of pregnancy has been shown in single EPP patients, complete normalization has not yet been reported. In our porphyria center we had the opportunity to follow up the biochemical changes in a 30-year-old EPP patient during two pregnancies. EP concentrations declined to normal levels six weeks prior to delivery during the first pregnancy and two days after delivery during the second pregnancy. Approximately six months after delivery, however, EP concentrations had returned again to the pathological levels characteristic for EPP, as measured prior to pregnancy. As to the possible pathomechanisms leading to reduction of EP concentrations we hypothesize different possibilities, including amelioration by fetal FC, intermittent modulation of the multidrug transporter protein ABCG2, and supplementation of iron during pregnancy. We feel that the biochemical findings presented here warrant further studies to confirm our data in more EPP patients and elucidate common underlying mechanisms.

11. PSORALEN UNAVAILABILITY: A RETROSPECTIVE STUDY TO ASSESS ITS IMPACT ON PATIENTS WHO HAD BEEN UNDERGOING PUVA THERAPY

    Aaron M Drucker, Akerke Baibergenova, Cheryl F Rosen, Neil H Shear.
     Division of Dermatology, University of Toronto, Toronto, ON

    In March 2010 there was a shortage of 8-methoxypsoralen in Toronto, Canada. Patients discontinued PUVA, and were transitioned to other therapies, including narrow-band UVB (nbUVB). This provided a unique opportunity to study these alternative therapies in patients who had been selected to receive PUVA. Our objective was to determine whether alternatives to PUVA, particularly nbUVB, were effective in these patients.

    A retrospective chart review was conducted of all patients at the Phototherapy Education and Research Centre who discontinued PUVA between March and April 2010. Data extracted included the disease being treated, response to PUVA before it was discontinued and response to the new therapy.

    Sixty-three patients discontinued PUVA due to the unavailability of 8-methoxypsoralen. Thirty-one patients had cutaneous T-cell lymphoma (CTCL), 19 had psoriasis and the remaining 13 had various other conditions. Fifteen of 17 CTCL patients improved after a mean of 57 nbUVB treatments and 10 of 15 psoriasis patients improved after a mean of 34 nbUVB treatments. Patients with higher-stage CTCL were less likely to respond to nbUVB than patients with lower-stage disease.

    PUVA is an important therapeutic modality in dermatology, particularly for CTCL and psoriasis. However, its safety profile is less favourable than nbUVB, and it is often less accessible due to cost and, in our case, drug-availability constraints. The results of our study suggest that nbUVB may be a suitable alternative to PUVA for some of these patients, which could improve access to phototherapy.

12. HEMATOPOIETIC MOSAICISM AFTER TREATMENT OF LARGE B-CELL LYMPHOMA UNDERLIES LATE-ONSET ERYTHROPOIETIC PROTOPORPHYRIA

    Siegesmund M^1,2, Uche-Holub E¹, Stefaniak R³, Kuerten V¹, Poblete-Gutiérrez P⁴, Neumann NJ¹, van Geel M^2,5, Humme D³, Frank J^1,2, Hanneken S^{1
    1} Department of Dermatology and German Porphyria Specialist Center, Heinrich Heine University Duesseldorf, Duesseldorf, Germany
    ² GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands
    ³ Department of Dermatology, Venereology and Allergology, Charité University Hospital, Berlin, Germany
    ⁴ Department of Dermatology, Annadal Medical Center Maastricht, Maastricht, The Netherlands
    ⁵ Department of Dermatology, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands

    Erythropoietic protoporphyria (EPP) is an autosomal semi-dominant disorder caused by a marked deficiency of ferrochelatase (FECH), the last enzyme in the heme biosynthetic pathway. This enzymatic dysfunction results from inheritance of a germline FECH gene mutation on one parental allele in combination with a common hypomorphic intronic FECH variation, IVS3-48C, on the other parental allele. Commonly, EPP manifests in early childhood with burning and stinging sensations, erythema and edema on the sun-exposed areas of the body. Here, we present a 57-year-old Caucasian man who developed severe cutaneous photosensitivity six years after treatment of a large B-cell lymphoma with autologous blood stem cell transplantation and radiation therapy. Biochemical and enzymatic analyses confirmed the diagnosis of EPP. By leukocyte DNA sequencing we found a nonsense mutation, p.R298X, in combination with the hypomorphic IVS3-48C variation in trans. Of note, the chromatographic intensity of the mutated T-allele at position 298 was reproducibly lower than that of the wild type C-allele, suggesting mosaicism. Most of the rare cases of late-onset EPP occurred in association with a myelodysplastic syndrome or myeloproliferative disorder due to a deletion on chromosome 18q, the region in which the FECH gene is located. Hence, we first excluded such a deletion by fluorescence in situ hybridization.Subsequent sequencing of DNA derived from cultured fibroblasts of the patient showed absence of p.R298X, confirming that this mutation arose as a result of mosaicism in the hematopoietic lineage. This is the first report on late-onset EPP due to blood cell mosaicism caused by a spontaneous somatic FECH mutation following autologous blood stem cell transplantation and radiation therapy of a large B-cell lymphoma.

13. INNOVATIVE TREATMENT OPTION FOR MODERATE-TO-SEVERE GENERALIZED PSORIASIS USING 308NM EXCIMER LASER, CLOBETASOL SPRAY, AND CALCITRIOL OINTMENT

    Jillian W. Wong, Tien Nguyen, Faranak Kamangar, Tina Bhutani, John Y. M. Koo
    ¹ University of California San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center, San Francisco, CA

    Study Objective: To ascertain if the combination of the most powerful 308nm UVB Excimer Laser (PhotoMedex XTRAC^® Velocity 700 Laser), clobetasol (Clobex^®) spray, and calcitriol (Vectical^®) ointment can treat moderate-to-severe generalized plaque-type psoriasis fast and very efficaciously without exposing the patient to the risks associated with systemic therapies, such as infection and solid cancer

    Dosing Regimen: This is a 12-week, open-label, pilot trial with 3 distinct treatment periods and protocols:

    • Period 1 (Weeks 1-4): clobetasol spray 2x daily + excimer laser treatments 2x weekly
    • Period 2 (Weeks 5-8): calcitriol ointment 2x daily + excimer laser 2x weekly for weeks 5-6, and then XMR laser as needed for weeks 7-8 (only for patients who achieved less than PASI-75 response)
    • Period 3 (Weeks 9-12): clobetasol spray 2x daily + calcitriol ointment 2x daily + excimer laser treatments as needed (only for patients who achieved less than PASI-75 response)

    Results: This study plans to enroll a total of 30 subjects. From the 1st 14 subjects recruited, 13 completed 6 weeks & 7 completed 12 weeks, to date. 11/13 (85%) patients who completed the 1st 6 weeks achieved PASI 75. 6/7 (86%) patients who completed all 12 weeks achieved PASI 75.

    Conclusion: Preliminary data is promising. This new treatment regimen for the treatment of generalized psoriasis has thus far demonstrated both outstanding efficacy and fast onset of action. External treatment for generalized psoriasis with better efficacy than current internal treatment options and none of the serious systemic risks appears to be within reach. The limitations of this approach are that it may not be usable for those with BSA >20% involvement, who have widely scattered psoriasis (i.e. guttate), who are extremely photosensitive, and who are morbidly obese.

14. RAPID TREATMENT OF HAIRLINE PSORIASIS USING 308 NM EXCIMER LASER AND CLOBETASOL SPRAY: A CASE REPORT

    Jillian W. Wong, Faranak Kamangar, John Y. M. Koo
     University of California, San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center, San Francisco, California

    A 68-year-old Asian female presented with a 16-year history of generalized plaque-type psoriasis. She reported that the most distressing region covered with psoriasis was her hairline because it caused severe pruritus and visible disfigurement. The patient failed past treatment on Soriatane and topical therapies. On examination, there were thick, well-demarcated, plaques of psoriasis with silvery scale over the hairline, including over the forehead, retroauricular, and occipital areas.

    As the patient had a past history of cancer, she was not placed on immunosuppressive therapy. Topical therapy alone was insufficient for treating psoriasis. Therefore, the patient was started on excimer laser therapy (Photomedex XTRAC^® Velocity) in conjuction with clobetasol (Clobex^®) spray.

    The patient was started on a dose of 400 mJ/cm² for the initial laser therapy. Her dose was increased to 500 mJ/cm² after her first treatment. After 2 weeks of therapy, after a total of 4 excimer laser treatments at a dose of 500 mJ/cm² and use of clobetasol spray twice daily to affected areas, she had marked improvement in hairline psoriasis. As the patient responded well to treatment without side effects or irritation, her dose was gradually increased to 666 mJ/cm².

    After a total of 9 laser treatments in conjunction with clobetasol spray used twice daily, her hairline psoriasis had completely cleared. The patient did not report any side effects to laser therapy of the hairline including blistering, burning, hyperpigmentation, or erythema.

    Our case demonstrates the use of excimer laser with topical treatment as a new, effective, and safe method for treating hairline psoriasis, a visible area that may not be appropriately treated by topical therapies alone. Further studies should be performed to investigate the safety and efficacy of treatment of excimer laser for hairline psoriasis. Excimer laser treatment for hairline psoriasis may be recommended in the future.

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