Translation and Validation of the Self-Assessment Psoriasis Area Severity Index.

BACKGROUND: The self-assessment psoriasis area severity index (SAPASI) is a patient-administered psoriasis assessment tool for which we present a validated translation from English to Swedish. METHODS: Validity was evaluated in this single-centre study using the psoriasis area severity index (PASI) as the standard. Test-retest reliability was assessed using repeated SAPASI measurements. RESULTS: Significant correlations (p < 0.0001) using Spearman's correlation coefficient (r) were found between PASI and SAPASI scores (r = 0.60) for 51 participants (median baseline PASI 4.4, interquartile range [IQR]: 1.8-5.6) and repeated SAPASI measurements (r = 0.70) among 38 participants (median baseline SAPASI 4.0, IQR: 2.5-6.1). Bland-Altman plots showed generally higher SAPASI scores than PASI scores. CONCLUSION: The translated version of SAPASI is valid and reliable, although patients generally tend to overrate their disease severity compared to PASI. Keeping this limitation in mind, SAPASI has the potential of being implemented as a time- and cost-efficient assessment tool in a Scandinavian context.

Impact of Bariatric Surgery on Moderate to Severe Psoriasis: A Retrospective Nationwide Registry Study.

Studies of the effects of bariatric surgery on psoriasis are few, with conflicting results. By linking the Swedish National Register for Systemic Treatment of Psoriasis (PsoReg) with the Scandinavian Obesity Surgery Registry (SOReg), individuals with psoriasis who had undergone bariatric surgery in Sweden during 2008 to 2018 were identified, and matched with data for patients with psoriasis in PsoReg. Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were compared between the groups. Altogether, 50 operated individuals (median body mass index (BMI) 38.7 kg/m2]) and 91 non-operated individuals (median BMI 33.0 kg/m2) were included. Control of disease at baseline was good in both groups. Linear mixed models showed no significant difference in psoriasis disease burden, measured as changes in mean PASI (ΔPASI) (-1.2, p = 0.43) and DLQI (ΔDLQI) (-2.2, p = 0.34). In summary, this study demonstrated no significant effect of bariatric surgery on psoriasis disease burden in patients with relatively well-controlled moderate to severe psoriasis.

Multiple Primary Melanomas: A Common Occurrence in Western Sweden.

Patients diagnosed with a single primary cutaneous melanoma are at increased risk of developing multiple primary melanomas. The aim of this study is to describe the epidemiology of multiple primary melanomas (invasive and in situ) in Western Sweden. Data from the Swedish Melanoma Registry from 1990 to 2013 revealed that 898 patients (7.4%) developed 2,037 multiple primary lesions and 11,254 patients developed single lesions. The proportion of subsequent lesions that were melanoma in situ was 47%, compared with 26% of first melanomas (p < 0.0001).The median and mean time to diagnosis of a subsequent melanoma was 38 and 58 months (95% confidence interval (CI), 53-62 months). In total, 49% of subsequent melanomas were detected within 3 years. Patients and physicians should be aware of the high proportion of multiple primary melanomas in Western Sweden, especially during the first years of follow-up.

Modelling the Future: System Dynamics in the Cutaneous Malignant Melanoma Care Pathway.

Incidence rates for cutaneous malignant melanoma are increasing worldwide. Estimates of the future number of melanoma cases are important for strategic planning of the care pathway. The aim of this study was to use system dynamics modelling to evaluate the long-term effects of changes in incidence, population growth and preventive interventions. Historical data on invasive melanoma cases in Western Sweden from 1990 to 2006 were obtained. Using computer simulation software, a model estimating the accumulated number of melanoma cases for 2014 to 2023 was developed. Five future scenarios were designed: stable incidence, business-as-usual, 25% reduced patient's delay, 50% reduced doctor's delay, and a combination of the last two, called improved overall secondary prevention. After 10 years, improved overall secondary prevention would have resulted in a 42% decrease in melanomas > 4 mm and a 10% increase in melanomas ≤ 1 mm, compared with business-as-usual. System dynamics is a valuable tool, which can help policymakers choose the preventive interventions with the greatest impact.

The risk of skin cancer in psoriasis patients treated with UVB therapy.

Phototherapy is an effective and widely used treatment for generalised plaque psoriasis. Despite the mutagenic effects of UVB this type of therapy is still assumed to be a safe treatment option. We have performed a cross sectional study to assess the risk of skin cancer in the cohort of psoriasis patients treated with UVB. A total of 162 white patients (116 men and 46 women, mean ± standard deviation age 56.0 ± 13.5 years) were included in the study. All patients have previously been treated with UVB at least 100 times in the last 5 years. Eight patients (4.9%, 0.95 CI: 2.2-9.5%) out of the 162 included in the study had histopathologically verified skin cancer. We found that the risk of skin cancer in psoriasis patients treated with UVB correlated with the number of treatments (controlling for age) but not with the type of UVB lamp. How-ever, the overall risk of malignancy in the UVB-treated patients was not greater than in the general population.

Patients' experiences of pain and pain relief during photodynamic therapy on actinic keratoses: an interview study.

Photodynamic therapy (PDT) is a well-known, effective method for treating extensive areas of multiple actinic keratoses in the face and scalp. The main side-effect of PDT is the pain experienced during treatment. The objective of this study was to explore and describe patients' experiences of PDT. The study used individual interviews, and analysis was carried out using phenomenography. The patients had all been treated with PDT for actinic keratoses on the face and scalp, and experienced PDT with and without nerve blocks. The results are presented in 3 themes and 10 categories. Most patients reported that the nerve blocks given prior to PDT altered their experience of pain. Alternative options are needed to reduce pain during PDT based on patients' needs and body site. This study adds a patient perspective highlight-ing patients' own voices as a qualitative complement to statistical analysis using the visual analogue scale.

Predictors of pain associated with photodynamic therapy: a retrospective study of 658 treatments.

Pain is the most common side-effect of photodynamic therapy (PDT). Our main objective was to identify pain predictors in PDT. In total, we performed 658 treatments on 377 patients at our department during 2004. Larger sized treatment areas were the strongest pain predictor, and actinic keratoses were more painful to treat than basal cell carcinomas and Bowen's disease. The most sensitive areas to treat were the face and scalp. Gender and age did not influence pain. Although treatment outcome was not our primary objective, 62% of 95 superficial basal cell carcinomas that were followed for 3 years showed complete clearance. Also, perforation of nodular basal cell carcinomas did not lead to better clinical results. In conclusion, the size of the treatment area, the diagnosis and the lesion location influence pain during PDT. Nevertheless, there is a large variance in visual analogue scale assessment within each group, thereby limiting the ability to predict pain.

5-year recurrence rates of Mohs micrographic surgery for aggressive and recurrent facial basal cell carcinoma.

Mohs micrographic surgery allows for complete microscopic examination of the surgical margin when treating aggressive and recurrent facial basal cell carcinomas. This leads to the highest cure rates and maximal preservation of healthy tissue. The 5-year recurrence rates of 587 aggressive and/or recurrent facial basal cell carcinomas treated during 1993 to 2003 at our centre were studied retrospectively. The resulting 5-year recurrence rates using Kaplan-Meier survival analysis were 2.1% for primary (previously untreated) tumours, 5.2% for recurrent basal cell carcinomas and 3.3% overall. In total, 87.9% of the tumours required at least two stages of Mohs micrographic surgery. The surgical defect's size after complete excision was, on average, approximately twice the size of the defect after excision of the clinically visible tumour with a 2-3 mm margin. Mohs micro-graphic surgery is underused in Scandinavia despite being the treatment of choice for aggressive and recurrent facial basal cell carcinomas.

Fluorescence diagnostics of basal cell carcinomas comparing methyl-aminolaevulinate and aminolaevulinic acid and correlation with visual clinical tumour size.

Fluorescence diagnostics based on aminolaevulinic acid (ALA) fluorescence has been suggested as an in vivo pre-surgical tool for tumour demarcation. We performed fluorescence diagnostics of 35 basal cell carcinomas (BCCs) undergoing photodynamic therapy (PDT) using methyl-aminolaevulinate (MAL). In addition, a semi-automated thresholding algorithm was implemented to detect the potential tumour region. The mean tumour fluorescence contrast was found to be 1.65 ± 0.06 during the first MAL-PDT session, and increased to 1.84 ± 0.07 at the second treatment (p < 0.01). This could imply that disruption of the skin barrier and inflammatory responses after the first session of PDT led to higher accumulation of proto-porphyrin IX during the second session of PDT. The tumour areas detected based on fluorescence in small BCCs (< 1 cm(2)) were in general (n = 18/23) larger than the visual clinical tumour size. In addition, the fluorescence contrast using MAL (1.65 ± 0.06) was found to be significantly higher (p<10(-4)) than the contrast (data from previous study) after application of ALA (1.20 ± 0.06). Thus, MAL generally provides higher tumour contrast than ALA in BCCs, and should be preferred for use in fluorescence diagnostics. Correlation between fluorescence, lack of treatment response and/or pain was not observed.

Cardiorespiratory fitness in late adolescence and long-term risk of psoriasis and psoriatic arthritis among Swedish men.

BACKGROUND: Psoriasis is a chronic immune-mediated disease and psoriatic arthritis is a common coexisting condition. Cardiorespiratory fitness is the overall capacity to perform exertion exercise. Low levels of cardiorespiratory fitness are associated with negative health outcomes. Individuals with psoriasis have lower cardiorespiratory fitness compared with individuals without psoriasis. There are no previous studies exploring the association between cardiorespiratory fitness and new-onset psoriasis and psoriatic arthritis. METHODS: With the objective to investigate whether low cardiorespiratory fitness in late adolescence increases the risk for onset of psoriasis and psoriatic arthritis, a cohort of Swedish men in compulsory military service between 1968 and 2005 was created using data from the Swedish Military Service Conscription Register. Cardiorespiratory fitness, estimated by maximum capacity cycle ergometer testing at conscription, was divided into three groups: high, medium, and low. Diagnoses were obtained using the Swedish National Patient Register and cohort members were followed from conscription until an event, new-onset psoriasis or psoriatic arthritis, occurred, or at the latest until 31 December 2016. Cox regression models adjusted for confounders at conscription were used to obtain hazard ratios with 95% confidence intervals for incident psoriasis and psoriatic arthritis. RESULTS: During the follow-up period (median follow-up time 31 years, range 0-48 years), 20,679 cases of incident psoriasis and 6,133 cases of incident psoriatic arthritis were found among 1,228,562 men (mean age at baseline 18.3 years). There was a significant association between low cardiorespiratory fitness and incident psoriasis and psoriatic arthritis (hazard ratio 1.35 (95% confidence interval 1.26-1.44) and 1.44 (95% confidence interval 1.28-1.63), respectively). CONCLUSIONS: These novel findings suggest that low cardiorespiratory fitness at an early age is associated with increased risk of incident psoriasis and psoriatic arthritis among men, and highlight the importance of assessing cardiorespiratory fitness early in life.

Report on fluorescence lifetime imaging using multiphoton laser scanning microscopy targeting sentinel lymph node diagnostics.

SIGNIFICANCE: Sentinel lymph node (SLN) biopsy is an important method for metastasis staging in, e.g., patients with malignant melanoma. Tools enabling prompt histopathological analysis are expected to facilitate diagnostics; optical technologies are explored for this purpose. AIM: The objective of this exploratory study was to investigate the potential of adopting multiphoton laser scanning microscopy (MPM) together with fluorescence lifetime analysis (FLIM) for the examination of lymph node (LN) tissue ex vivo. APPROACH: Five LN tissue samples (three metastasis positive and two negative) were acquired from a biobank comprising tissues from melanoma patients. Tissues were deparaffinized and subjected to MPM-FLIM using an experimental MPM set-up equipped with a time correlated single photon counting module enabling FLIM. RESULTS: The data confirm that morphological features similar to conventional histology were observed. In addition, FLIM analysis revealed elevated morphological contrast, particularly for discriminating between metastatic cells, lymphocytes, and erythrocytes. CONCLUSIONS: Taken together, the results from this investigation show promise for adopting MPM-FLIM in the context of SLN diagnostics and encourage further translational studies on fresh tissue samples.

Single low-dose red light is as efficacious as methyl-aminolevulinate--photodynamic therapy for treatment of acne: clinical assessment and fluorescence monitoring.

This controlled study investigated single low-dose red light photodynamic therapy and methyl-aminolevulinate (MAL) for treatment of moderate to severe facial acne in 19 patients. The right cheek was treated with MAL (160 mg/g) for 3 h prior to illumination. The left cheek received red light only. Both cheeks were illuminated with narrow-band red light (635 nm) at a light dose of 15 J/cm2. The global severity of acne was assessed at baseline and at follow-up, 10 and 20 weeks after treatment. Fluorescence images, clinical photographs and skin surface biopsies were obtained. Both MAL-photodynamic therapy and control areas showed a significant decrease in acne score at follow-up; no significant difference was found compared with control. MAL-photodynamic therapy was associated with adverse effects such as erythema and stinging. Fluorescence images revealed poor selectivity of MAL-induced fluorescence to the acne lesions, suggesting a general photoablating mechanism rather than selective destruction of sebaceous glands. No significant reduction in Propionibacterium acnes or sebum excretion was found.

Vitamin D production in psoriasis patients increases less with narrowband than with broadband ultraviolet B phototherapy.

BACKGROUND: Phototherapy of psoriasis is an effective treatment. In addition to standard broadband ultraviolet radiation B (UVB), (280-320 nm), narrowband phototherapy (NBUVB) (monochromatic UV between 311 and 312 nm) has become an important treatment for psoriasis. The same wavelength range of UVB (290-315 nm) induces synthesis of vitamin D. The aim was to compare the effect of broadband with NBUVB therapy on vitamin D synthesis in patients with psoriasis. METHODS: Sixty-eight Caucasian patients (17 women and 51 men) mean age 54.1 +/- 16.0 years, with active plaque psoriasis, were treated with broadband UVB (n=26) or NBUVB (n=42) two to three times/week for 8-12 weeks. The serum concentrations of 25-hydroxyvitamin D (25(OH)D3), 1,25-dihydroxyvitamin D (1,25(OH)(2)D3), intact parathyroid hormone (PTH), calcium and creatinine were measured before the first exposure and after the last dose of radiation. RESULTS: In broadband UVB treated patients, 25(OH)D3 increased from 37.9 +/- 16.9 to 69.4 +/- 19.7 ng/ml (P<0.0001) and in patients treated with NBUVB from 34.8 +/- 11.9 to 55.3 +/- 17.6 ng/ml (P<0.0001) and P=0.008 between the treatment groups. PTH decreased on broadband UVB (P<0.05). The serum concentrations of 1,25(OH)(2)D3, calcium or creatinine remained unaltered. CONCLUSION: Serum 25(OH)D3 in psoriasis patients increased less with NBUVB than with broadband UVB phototherapy. Psoriasis improved on both regimens.

Air oxidation increases skin irritation from fragrance terpenes.

BACKGROUND: Linalool and limonene are common fragrance terpenes that autoxidize on air exposure. The pure compounds are not allergenic but their oxidation products can cause contact allergy. Little has been investigated regarding the irritancy of oxidized terpenes. AIM: The aim of this study was to investigate the irritating effect of pure and oxidized R-limonene and linalool in concentration series and to study the MNIC (Maximum Non Irritant Concentration) of autoxidized linalool and limonene. PATIENTS/METHODS: Patch testing was performed in dermatitis patients and controls with sequentially diluted concentrations of oxidized and non-oxidized linalool, and oxidized and non-oxidized R-limonene. Readings were made with visual assessment and using laser Doppler imaging. RESULTS: The non-oxidized terpenes were non-irritating in all tested concentrations. Both linalool and especially R-limonene were more irritating after oxidation compared with the pure compounds. No difference in response was seen between dermatitis patients and controls. CONCLUSION: Autoxidation of the fragrance terpenes linalool and R-limonene increases irritation. Oxidized linalool is less irritating than oxidized R-limonene. In this study, we found no advantages in using laser Doppler technique compared with visual assessment.

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

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

Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005.

Topical photodynamic therapy (PDT) is used to treat nonmelanoma skin cancers, such as actinic keratoses, Bowen's disease, and basal cell carcinoma (superficial and nodular). This article presents up-to-date, practical, evidence-based recommendations on the use of topical PDT using 5-aminolevulinic acid or methyl aminolevulinate for the treatment (and prevention) of nonmelanoma skin cancers. A systematic literature review was conducted (using MEDLINE), and recommendations were made on the basis of the quality of evidence for efficacy, safety/tolerability, cosmetic outcome, and patient satisfaction/preference. Topical PDT is highly effective in the treatment of actinic keratoses, Bowen's disease, superficial and thin nodular basal cell carcinomas, with cosmesis typically superior to that achieved with existing standard therapies. PDT may also be a means of preventing certain nonmelanoma skin cancers in immunosuppressed patients.

Photostability of commercial sunscreens upon sun exposure and irradiation by ultraviolet lamps.

BACKGROUND: Sunscreens are being widely used to reduce exposure to harmful ultraviolet (UV) radiation. The fact that some sunscreens are photounstable has been known for many years. Since the UV-absorbing ingredients of sunscreens may be photounstable, especially in the long wavelength region, it is of great interest to determine their degradation during exposure to UV radiation. Our aim was to investigate the photostability of seven commercial sunscreen products after natural UV exposure (UVnat) and artificial UV exposure (UVart). METHODS: Seven commercial sunscreens were studied with absorption spectroscopy. Sunscreen product, 0.5 mg/cm2, was placed between plates of silica. The area under the curve (AUC) in the spectrum was calculated for UVA (320-400 nm), UVA1 (340-400 nm), UVA2 (320-340 nm) and UVB (290-320 nm) before (AUCbefore) and after (AUCafter) UVart (980 kJ/m2 UVA and 12 kJ/m2 of UVB) and before and after UVnat. If theAUC Index (AUCI), defined as AUCI = AUCafter/AUCbefore, was > 0.80, the sunscreen was considered photostable. RESULTS: Three sunscreens were unstable after 90 min of UVnat; in the UVA range the AUCI was between 0.41 and 0.76. In the UVB range one of these sunscreens was unstable with an AUCI of 0.75 after 90 min. Three sunscreens were photostable after 120 min of UVnat; in the UVA range the AUCI was between 0.85 and 0.99 and in the UVB range between 0.92 and 1.0. One sunscreen showed in the UVA range an AUCI of 0.87 after UVnat but an AUCI of 0.72 after UVart. Five of the sunscreens were stable in the UVB region. CONCLUSION: The present study shows that several sunscreens are photounstable in the UVA range after UVnat and UVart. There is a need for a standardized method to measure photostability, and the photostability should be marked on the sunscreen product.

Expression of genes involved in the regulation of p16 in psoriatic involved skin.

It has been suggested that the up-regulation of the tumour suppressor p16 gene and induction of senescence protect the phenotype of psoriatic involved skin from malignant transformation. On the other hand, Id1, which is inversely correlated with p16 has been shown to be up-regulated in psoriatic involved skin. To test the hypothesis that there may be an altered regulation of p16 in psoriatic involved skin, we have measured genes involved in the Igf-1 receptor signalling through the Ras/MAPK cascade. Igf-1R, IGFBP3, hRas, Ets2, JunB, Egr-1, Id1, MIDA1 and p16 gene expressions were measured using quantitative real-time PCR in total RNA isolated from punch biopsies from psoriatic involved (n = 9) and uninvolved skin (n = 9) and from cutaneous squamous cell cancer (SCC) involved (n = 8) and uninvolved skin (n = 8). The IGFBP3, hRas, JunB, Egr-1, Id1 and MIDA1 genes were up-regulated in psoriatic involved skin compared with uninvolved skin. The p16, JunB and MIDA1 genes were up-regulated in SCC involved skin compared with uninvolved skin. Our results indicate that there may be a balance between the proliferation and induction of senescence in psoriasis. This balance may vary and the psoriatic involved skin represented in this study appears to be in a proliferative state rather than senescence. Furthermore, we suggest that the noted up-regulation of JunB, which has been shown to up-regulate p16, in combination with the previously reported elevation of p16 expression in psoriatic involved skin, may indicate activation of a pathway by which JunB may protect the psoriatic plaque by inducing p16 in an event of malignant stress.

Bispectral fluorescence imaging combined with texture analysis and linear discrimination for correlation with histopathologic extent of basal cell carcinoma.

Fluorescence imaging has been shown to be a potential complement to visual inspection for demarcation of basal cell carcinoma (BCC), which is the most common type of skin cancer. Earlier studies have shown promising results when combining autofluorescence with protoporphyrin IX (Pp IX) fluorescence, induced by application of delta-5-aminolaevulinic acid (ALA). In this work, we have tried to further improve the ability of this technique to discriminate between areas of tumor and normal skin by implementing texture analysis and Fisher linear discrimination (FLD) on bispectral fluorescence data of BCCs located on the face. Classification maps of the lesions have been obtained from histopathologic mapping of the excised tumors. The contrast feature obtained from co-occurrence matrices was found to provide useful information, particularly for the ALA-induced Pp IX fluorescence data. Moreover, the neighborhood average features of both autofluorescence and Pp IX fluorescence were preferentially included in the analysis. The algorithm was trained by using a training set of images with good agreement with histopathology, which improved the discriminability of the validation set. In addition, cross validation of the training set showed good discriminability. Our results imply that FLD and texture analysis are preferential for correlation between bispectral fluorescence images and the histopathologic extension of the tumors.