Assessment of Skin Photoallergy Risk in Cosmetics Containing Herbal Extract Ingredients.

BACKGROUND/OBJECTIVE: In recent years, herbal extracts are becoming increasingly popular ingredients added in cosmetics; however, the assessment of their potential adverse effects on the skin remains unclear. As Coptis, Phellodendron amurense, curcumin, and shikonin are herbs currently used in cosmetic ingredients, the aim of this study was to assess their skin photoallergy (PA) potential and the concentrations at which they could safely be used. METHODS: In the patch test, Coptis, P. amurense, curcumin, and shikonin with 5, 10, 25, and 50% concentration were applied on 33 healthy Chinese subjects using the T.R.U.E. TEST® patch test system for 48 h. Photopatch testing was performed on 206 Chinese subjects with predisposed photosensitivity history using the Scandinavian photopatch series, and subjects were irradiated by 50% UVA minimum erythema dose. Photopatch testing of herbal extracts was then performed on subjects diagnosed with PA. RESULTS: Thirty-three subjects (14 with type III skin and 19 with type IV skin) completed contact patch testing of herbal extracts. Coptis induced a contact allergy (CA) reaction on 2 subjects at 25% concentration and on 2 subjects at 10% concentration. P. amurense induced a CA reaction on 1 subject at 10% concentration and on 1 subject at 5% concentration. Shikonin induced a stimulating reaction on 1 subject at 10% concentration. Curcumin induced a stimulating reaction on 1 subject at 10% concentration. Of the 206 Chinese subjects predisposed for photosensitivity, 10.19% had PA, 16.5% showed CA, and 1.45% had both PA + CA. PA-induced substances were promethazine hydrochloride (15%, n = 31), chlorpromazine hydrochloride (10.84%, n = 19), perfume mix (5.82%, n = 12), atranorin (3.39%, n = 7), 6-methyl coumarine (3.39%, n = 7), balsam Peru (1.94%, n = 4), fentichlor (1.94%, n = 4), 3,3',4',5-tetrachloro salicylanilide (0.97%, n = 2), hexachlorophene (0.97%, n = 2), chlorhexidine digluconate (0.97%, n = 2), and 4-aminobenzoic acid 2-hydroxy-4-methoxybenzophenone (0.97%, n = 2). Coptis at 25, 10, and 5% concentration and P. amurense, shikonin, and curcumin each at 10 and 5% concentration induced negative photopatch test results in all 10 photosensitive subjects. CONCLUSION: We have shown that Coptis, shikonin, or curcumin at 5% concentration in cosmetics could be applied safely without inducing contact allergic and photosensitive reactions on the skin. These findings advance the understanding of herbal extract use in cosmetic ingredients as related to the fields of dermatopharmacology and dermatotoxicology.

Benzodiazepine-induced photosensitivity reactions: A compilation of cases from literature review with Naranjo causality assessment.

OBJECTIVE: Benzodiazepines have been reported to cause photosensitivity reactions. We characterized the clinical presentation and diagnosis of benzodiazepine-associated photosensitivity and adjudicated these cases for a causal association with benzodiazepines. METHODS: A literature search on PubMed's "MeSH" search feature and CINAHL (1964 to 2019) was performed using search terms: benzodiazepine, photosensitivity, and photosensitivity disorders/chemically induced. We applied the Naranjo scale, a standardized causality assessment algorithm, to identified cases. RESULTS: We identified eight published cases, with 50% of patients being female with a mean age of 46.3 years. Alprazolam, tetrazepam, clobazam, and clorazepate induced phototoxic reactions. Chlordiazepoxide induced one photoallergic reaction. Photosensitivity occurred between 1-3 days (37.5%), 7-14 days (25%), and >14 days (25%). Photosensitivity resolved after drug discontinuation within 2 weeks (62.5%). Benzodiazepine rechallenge confirmed photosensitivity in 75% of cases. Photopatch testing was negative in two patients; however, these patients had positive oral provocation testing. However, an oral photoprovocation test, an ideal diagnostic test, was not administered to several patients. Despite these challenges, the Naranjo scale identified 5 cases as definite benzodiazepine-induced photosensitivity. CONCLUSION: Five benzodiazepines induced photosensitivity reactions. Five patients showed a definite association with the Naranjo scale. Reporting to pharmacovigilance databases may help identify other benzodiazepines causing photosensitivity reactions.

In vitro assessment of the photo(geno)toxicity associated with Lapatinib, a Tyrosine Kinase inhibitor.

The epidermal growth factor receptors EGFR and HER2 are the main targets for tyrosine kinase inhibitors (TKIs). The quinazoline derivative lapatinib (LAP) is used since 2007 as dual TKI in the treatment of metastatic breast cancer and currently, it is used as an oral anticancer drug for the treatment of solid tumors such as breast and lung cancer. Although hepatotoxicity is its main side effect, it makes sense to investigate the ability of LAP to induce photosensitivity reactions bearing in mind that BRAF (serine/threonine-protein kinase B-Raf) inhibitors display a considerable phototoxic potential and that afloqualone, a quinazoline-marketed drug, causes photodermatosis. Metabolic bioactivation of LAP by CYP3A4 and CYP3A5 leads to chemically reactive N-dealkylated (N-LAP) and O-dealkylated (O-LAP) derivatives. In this context, the aim of the present work is to explore whether LAP and its N- and O-dealkylated metabolites can induce photosensitivity disorders by evaluating their photo(geno)toxicity through in vitro studies, including cell viability as well as photosensitized protein and DNA damage. As a matter of fact, our work has demonstrated that not only LAP, but also its metabolite N-LAP have a clear photosensitizing potential. They are both phototoxic and photogenotoxic to cells, as revealed by the 3T3 NRU assay and the comet assay, respectively. By contrast, the O-LAP does not display relevant photobiological properties. Remarkably, the parent drug LAP shows the highest activity in membrane phototoxicity and protein oxidation, whereas N-LAP is associated with the highest photogenotoxicity, through oxidation of purine bases, as revealed by detection of 8-Oxo-dG.

Light-emitting-diode and Grass PS 33 xenon lamp photic stimulators are equivalent in the assessment of photosensitivity: Clinical and research implications.

The assessment of the effect of photic stimulation is an integral component of an EEG exam and is especially important in patients referred for ascertained or suspected photosensitivity with or without a diagnosis of epilepsy. A positive test result relies on eliciting a specific abnormality defined as the "photoparoxysmal response". Reliability of this assessment is strongly influenced by technical and procedural variables, a critical one represented by the physical properties of the stimulators used. Established clinical norms are based on data acquired with the "gold-standard" Grass PS stimulators. These are no longer commercially available and have been replaced by stimulators using light emitting diode (LED) technology. To our knowledge no comparative study on their efficacy has been conducted. To address this gap, we recruited 39 patients aged 5-54 years, referred to two specialized centers with confirmed of suspected diagnosis of photosensitive epilepsy or generalized epilepsy with photosensitivity in a prospective randomized single-blind cross-over study to compare two commercially available LED-bases stimulation systems (FSA 10® and Lifeline® stimulators) against the Grass PS 33 xenon lamp device. Our findings indicate that the LED systems tested are equivalent to the Grass stimulator both in identifying the PPR in affected individuals.

Assessment of Predictors of Sun Sensitivity as Defined by Fitzpatrick Skin Phototype in an Ecuadorian Population and Its Correlation with Skin Damage.

BACKGROUND: The Fitzpatrick skin phototype scale (FSPTS) is a widely used instrument to assess skin type. METHODS: A cross-sectional survey collected responses from 254 subjects from Quito regarding self-reported FSPTS, gender, age, education, and tobacco and alcohol consumption. Univariate and multivariate logistic regression analyses were performed to determine if ethnicity, hair color, and eye color significantly predict FSPTS. In addition, we studied the correlation between FSPTS and the SCINEXA scale with Pearson's correlation coefficient. RESULTS: Ethnicity, eye color, and hair color are significant independent predictors of FSPTS (p < 0.0001). CONCLUSIONS: Patient self-reported race and pigmentary phenotypes are inaccurate predictors of sun sensitivity as defined by Fitzpatrick skin phototype. Our study does not fully represent the population of the country. There are limitations to using patient-reported race and appearance in predicting individual sunburn risk.

Assessment of the risk and characterization of non-melanoma skin cancer in Kindler syndrome: study of a series of 91 patients.

BACKGROUND: Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of squamous cell carcinoma (SCC) in these patients. SCC developed in 13 of the 91 patients. RESULTS: The youngest case arose in a 29-year-old patient; however, the cumulative risk of SCC increased to 66.7% in patients over 60 years of age. The highly aggressive nature of SCCs in KS was confirmed showing that 53.8% of the patients bearing SCCs develop metastatic disease. Our data also showed there are no specific mutations that correlate directly with the development of SCC; however, the mutational distribution along the gene appears to be different in patients bearing SCC from SCC-free patients. The body distribution of the tumor appearance was also unique and different from other bullous diseases, being concentrated in the hands and around the oral cavity, which are areas of high inflammation in this disease. CONCLUSIONS: This study characterizes SCCs in the largest series of KS patients reported so far, showing the high frequency and aggressiveness of these tumors. It also describes their particular body distribution and their relationship with mutations in the FERMT-1 gene. These data reinforce the need for close monitoring of premalignant or malignant lesions in KS patients.

In vitro assessment of skin sensitization, photosensitization and phototoxicity potential of commercial glyphosate-containing formulations.

This study evaluated the applicability of a modified Direct Peptide Reactivity Assay (DPRA) (OECD N° 442C, 2015) through the 10-fold reduction of reaction volume (micro-DPRA, mDPRA) for skin sensitization evaluation of six commercial glyphosate-containing formulations. In addition, another modification of DPRA was proposed by adding a UVA (5J/cm2) irradiation step, namely photo-mDPRA, to better characterize (photo)sensitizer materials. The phototoxicity profile of pesticides was also evaluated using the 3T3 Neutral Red Uptake Phototoxicity Test (3T3-NRU-PT) (OECD N° 432, 2004). The mDPRA could represent an environmentally acceptable test approach, since it reduces costs and organic waste. Peptide depletion was greater in photo-mDPRA and changed the reactivity class of each test material, in comparison to mDPRA. Thus, the association of mDPRA with photo-mDPRA was better for correctly characterizing human (photo)sensitizer substances and pesticides. In general, cysteine depletion was greater than that of lysine for all materials tested in both mDPRA and photo-mDPRA. Furthermore, while 3T3-NRU-PT is unable to predict (photo)sensitizers, it was capable of correctly identifying the phototoxic potential of the tested agrochemical formulations. In conclusion, mDPRA plus photo-mDPRA and 3T3-NRU-PT seem to be preliminary non-animal test batteries for skin (photo)sensitization/phototoxicity assessment of chemicals, agrochemical formulations and their ingredients.

Burden of lupus on work: Issues in the employment of individuals with lupus.

BACKGROUND: Systemic lupus erythematosus (SLE) or Lupus is one of the leading causes of work disability in the United States, accounting for about 20% of the more than estimated 1.5 million Americans with a work disability. The symptoms of lupus can have a profound impact on the person's employment. Impacts of lupus are more pronounced among young and middle-adulthood. Studies have shown that loss in work hours cost the nation nearly $13 billion annually. The loss also impacts the individual's work, quality of life, self-management, and self-efficacy. OBJECTIVE: In this article, the author describes the financial burden of lupus. The article also describes the substantial impact of lupus on employment outcomes for individuals living with the condition. The author also reviews major signs and symptoms of disease and their impact on employment. RESULTS: Findings from this research can be used to identify various accommodations and strategies for individuals to prevent flare-ups. CONCLUSIONS: The paper presents innovative strategies that include early interventions and how employers andco-workers can provide helpful support that includes job accommodations to individuals with lupus.

Impact assessment of energy-efficient lighting in patients with lupus erythematosus: a pilot study.

BACKGROUND: Patients with lupus erythematosus (LE) are often abnormally photosensitive. Ultraviolet (UV) exposure can not only induce cutaneous lesions but may also contribute to systemic flares and disease progression. Various forms of energy-efficient lighting have been shown to emit UV radiation. OBJECTIVES: To determine the effects of these emissions on individuals with LE. METHODS: This assessment investigated cutaneous responses to repeated exposures from three types of lighting: compact fluorescent lamp (CFL), light-emitting diode (LED) and energy-efficient halogen (EEH). The subjects were 15 patients with LE and a control group of five healthy volunteers. RESULTS: No cutaneous LE lesions were induced by any of the light sources. Delayed skin erythema was induced at the site of CFL irradiation in six of the 15 patients with LE and two of the five healthy subjects. Erythema was increased in severity and more persistent in patients with LE. One patient with LE produced a positive delayed erythema to the EEH. A single patient with LE produced immediate abnormal erythemal responses to the CFL, LED and EEH. Further investigation revealed that this patient also had solar urticaria. All other subjects had negative responses to LED exposure. CONCLUSIONS: Compact fluorescent lamps emit UV that can induce skin erythema in both individuals with LE and healthy individuals when situated in close proximity. However, this occurs to a greater extent and is more persistent in patients with LE. EEHs emit UVA that can induce erythema in patients with LE. LEDs provide a safer alternative light source without risk of UV exposure.

A quantitative assessment of the effects of formal sun protection education on photosensitive patients.

PURPOSE: To quantitatively assess the effect of formal sun protection education on sun exposure habits and quality of life in photosensitive patients. METHODS: Patients with chronic actinic dermatitis (CAD) or polymorphous light eruption (PLE) were randomized to either the intervention or the control group. General advice about sun protection and broad-spectrum sunscreen were provided to all participants. The intervention group was given two additional intensive sun protection instruction classes at the beginning of spring and then in summer. At baseline and 12 months, each participant completed interviews that included a questionnaire about sun protection behaviors and a modified Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: In the intervention group, after the first intensive sun protection instruction, all aspects of sun exposure habits were significantly improved from baseline (P < 0.01). At study's end, there had been no significant change in sun exposure habits in the control group compared with baseline, whereas sun exposure habits in the intervention group significantly improved (P < 0.01). After two intensive sun protection training sessions, the modified DLQI significantly decreased in the intervention group compared with baseline (P < 0.001), while no change was observed in the control group. CONCLUSION: Formal sun protection education improved sun exposure and protection behaviors as well as quality of life in photosensitive patients.

Assessment of the photosensitization properties of cationic porphyrins in interaction with DNA nucleotide pairs.

We present a theoretical assessment of the photosensitization properties of meso-mono(N-methylpyridyl) triphenylporphyrin (1, MmPyP(+)), which interacts with DNA nucleotide pairs [adenine (A)-thymine (T); guanine (G)-cytosine (C)] via an external binding mode. The photosensitization properties of the arrangements 1A, 1T, 1G and 1C were investigated. A set of density functionals (B3LYP, PBE0, CAM-B3LYP, M06-2X, B97D) with the 6-31G(d) basis set was used to calculate the electronic absorption spectra in solution (water) following TD-DFT methodology. In all the arrangements, with the exception of 1C, the functional PBE0 produced the lowest deviation of the Soret band (0.1-0.2 eV). Using this functional, we show that the porphyrin-nucleotide interaction is stabilized, as reflected by a larger HOMO-LUMO gap than free porphyrin. A more important effect of the interaction corresponds to the red-shift of the Soret band of MmPyP(+), which is in agreement with experimental results. This behavior could be explained by the higher symmetry found in arrangements with a lower dipole moment, and by the more symmetrical distribution of electronic density along the molecular orbitals, which provokes electronic transitions of lower energy. The structural model allowed us to show that MmPyP(+) improves the characteristics as a photosensitizer when it interacts with nucleotide pairs due to the longer wavelength required for the Soret band. Results obtained for porphyrins with larger monocationic substituents (2, MmAP+; 3, MONPP+) do not lead to the same behavior. Although the structural model is insufficient to describe porphyrin photosensitization, it suggests that improvements in this property are produced by the inclusion of a cationic charge in the pyridyl ring and a smaller size of the substituent leading to a better communication in the porphyrin-nucleotide pair.

Voriconazole-induced photosensitivity: photobiological assessment of a case series of 12 patients.

BACKGROUND: Voriconazole, a broad-spectrum triazole antifungal agent increasingly used to treat aspergillosis, has been linked with acute photosensitivity and skin carcinogenesis. The action spectrum of the photosensitivity is unknown, while an indirect retinol effect secondary to the antifungal's impact on CYP450 enzymes has been proposed to contribute to the underlying mechanism. OBJECTIVES: To perform a detailed photobiological assessment of the photosensitivity presenting in a series of 12 patients treated with voriconazole. METHODS: Minimal erythemal dose thresholds (MED) to narrow wavebands of ultraviolet (UV) A, UVB and visible light were determined. Provocation testing was performed to broadband UVA (310-400 nm) and to solar-simulated radiation (SSR) (290-400 nm). Patients underwent routine photopatch testing and laboratory investigations including serum vitamin A (retinol). RESULTS: Patients (eight men, four women; median age 54years, range 40-63) experienced moderate-severe cutaneous erythema (n = 12), burning pain (n=5), itching (n=3), scaling (n=5), vesiculation (n=5) and oedema (n=1) following sunlight exposure; increased lentigines (n=4) and actinic cheilitis (n = 4) were also observed. While the majority (n=8) of patients showed normal MED thresholds to monochromator phototesting to UVB, UVA and visible light, a low MED to UVA was observed in four patients. Repeated provocation testing with broadband UVA and SSR provoked an abnormal erythema in eight and 10 patients, respectively. Serum retinol levels were mildly elevated in two patients but normal in the majority. CONCLUSION: UVA sensitivity is the predominant finding in acute voriconazole-induced photosensitivity. We found little evidence of elevated circulating retinol as the causal factor. Patients with voriconazole-induced photosensitivity require education in appropriate UVA protective measures in addition to consideration of skin surveillance for malignant sequelae.

Assessment of a new questionnaire for self-reported sun sensitivity in an occupational skin cancer screening program.

BACKGROUND: Sun sensitivity of the skin is a risk factor for the development of cutaneous melanoma and other skin cancers. Epidemiological studies on causal factors for the development of melanoma must control for sun sensitivity as a confounder. A standardized instrument for measuring sun sensitivity has not been established yet. It is assumed that many studies show a high potential of residual confounding for sun sensitivity. In the present study, a new questionnaire for the assessment of self-reported sun sensitivity is administered and examined. METHODS: Prior to an occupational skin cancer screening program, the 745 participating employees were asked to fill in a questionnaire for self-assessment of sun sensitivity. The questionnaire was developed by experts of the working group "Round Table Sunbeds" (RTS) to limit the health hazards of sunbed use in Germany. A sun sensitivity score (RTS-score) was calculated using 10 indicators. The internal consistency of the questionnaire and the agreement with other methods (convergent validity) were examined. RESULTS: The RTS-score was calculated for 655 study participants who were 18 to 65 years of age. The correlation of the items among each other was between 0.12 and 0.62. The items and the RTS-score correlated between 0.46 and 0.77. The internal consistency showed a reliability coefficient with 0.82 (Cronbach's alpha). The comparison with the Fitzpatrick classification, the prevailing standard, was possible in 617 cases with a rank correlation of rs = 0.65. The categorization of the RTS-score in four risk groups showed correct classification to the four skin types of Fitzpatrick in 75% of the cases. Other methods for the assessment of sun sensitivity displayed varying agreements with the RTS-score. CONCLUSION: The RTS questionnaire showed a sufficient internal consistency. There is a good convergent validity between the RTS-score and the Fritzpatrick classification avoiding shortcomings of the prevailing standard. The questionnaire represents a simple, reliable and valid instrument for the assessment of sun sensitivity. The questionnaire can be useful for epidemiological studies as well as for skin cancer prevention. Further development and standardization of sun sensitivity assessments is necessary to strengthen the evidence of epidemiological studies on causal factors of melanoma and other skin cancers.

Reactive oxygen species assay-based risk assessment of drug-induced phototoxicity: classification criteria and application to drug candidates.

We have previously demonstrated that the phototoxic potential of chemicals could be partly predicted by the determination of reactive oxygen species (ROS) from photo-irradiated compounds. In this study, ROS assay strategy was applied to 39 marketed drugs and 210 drug candidates in order to establish provisional classification criteria for risk assessment of drug-induced phototoxicity. The photosensitizing properties of 39 model compounds consisting of phototoxic and non-phototoxic chemicals, as well as ca. 210 drug candidates including 11 chemical series were evaluated using ROS assay and the 3T3 neutral red uptake phototoxicity test (NRU PT). With respect to marketed drugs, most phototoxic drugs tended to cause type I and/or II photochemical reactions, resulting in generation of singlet oxygen and superoxide. There seemed to be a clear difference between phototoxic drugs and non-phototoxic compounds in their abilities to induce photochemical reactions. A plot analysis of ROS data on the marked drugs provided classification criteria to discriminate the photosensitizers from non-phototoxic substances. Of all drug candidates tested, 35.2% compounds were identified as phototoxic or likely phototoxic on the basis of the 3T3 NRU PT, and all ROS data for these phototoxic compounds were found to be over the threshold value. Furthermore, 46.3% of non-phototoxic drug candidates were found to be in the subthreshold region. These results verify the usefulness of the ROS assay for understanding the phototoxicity risk of pharmaceutical substances, and the ROS assay can be used for screening purposes in the drug discovery stage.

The polymorphous light eruption-severity assessment score does not reliably predict the results of phototesting.

BACKGROUND: Polymorphous light eruption (PLE) is a very common photodermatosis in which patient history is highly specific. Phototesting is used to confirm the diagnosis and to determine the action spectrum and the severity of this disease. In daily practice and in research studies, it would be convenient to assess disease severity by patient history only. OBJECTIVES: This study aims to assess PLE disease severity via patient history and compares this with severity assessment via phototesting. PATIENTS AND METHODS: Sixty-one patients with PLE were asked 10 standard questions and all were phototested. The answers to the standard questions were coded with linear scores ranging from 0 to 10. The score of each question was plotted as independent variable in a multiple linear regression model against the score of the phototest (minimal number of irradiations necessary to elicit a positive skin lesion, with a maximum of 6 irradiations) as dependent variable using an enter approach. Furthermore, the scores of the separate questions were added to form a total score, the PLE-severity assessment score (PLE-SAS). The medians of these PLE-SASs were compared with the result scores obtained by phototesting. Phototesting was done with ultraviolet A and ultraviolet B irradiation. RESULTS: Fifty-seven of the 61 patients had a positive test result (93%). Using the multiple linear regression model, the severity assessment by patient history (PLE-SAS) compared with the result of phototesting showed two significant contributing questions (adjusted PLE-SAS) (P < 0.05) but with a regression coefficient of 0.2. A significant difference in median scores with the severity assessment (PLE-SAS and adjusted PLE-SAS) between patients testing positive after 1-3 irradiations compared with those testing positive after 4-6 irradiations was present (P < 0.05). However, the overlap quartile range between both groups was such that the PLE-SAS and the adjusted PLE-SAS have little predictive value in individual patients. CONCLUSIONS: We showed that in PLE, disease severity as determined using the PLE-SAS or adjusted PLE-SAS did not reliably predict severity as assessed by phototesting. Two significant contributing questions were not discriminating enough to be used as predicting questions to assess severity. Accurate patient history proved to be a reliable method to diagnose PLE. Phototesting is useful to determine the responsible ultraviolet action spectrum and to exclude differential diagnoses like photosensitive eczema, lupus erythematosus or chronic actinic dermatitis. PLE-SAS cannot replace phototesting for determining the severity of PLE.

[Therapeutic modalities and economic assessment in the treatment of superficial basal cell carcinomas and multiple actinic keratoses by French dermatologists]. / Evaluation médico-économique de la prise en charge des carcinomes basocellulaires superficiels et des kératoses actiniques multiples par les dermatologues français.

INTRODUCTION: To date, no prospective studies have been conducted in France describing the management of actinic keratoses (AK) and superficial basal cell carcinomas (sBCC). The aim of the present study was to describe the therapeutic modalities for AK and sBCC adopted by French dermatologists and to determine the direct annual medical costs. PATIENTS AND METHODS: This was a prospective, observational study conducted in France between January and June 2004 in a random selection of representative dermatologists (n=202). The first 5 adult patients seen for one or more sBCCs and the first patient with at least 4 AKs over a period of four non-consecutive weeks were included in the study. The following data were recorded using a standardized questionnaire at inclusion: date of birth, gender, habitat, professional activity, social insurance regimen, site, number and maximum size of lesions. The therapeutic modalities, the physicians involved and the laboratory examinations during the 3 months following diagnosis were recorded prospectively. Medical management costs were calculated taking into account the usual parameters (e.g. French nomenclature of medical acts). RESULTS: 512 patients with sBCC (mean age: 69 years; sex-ratio M/F: 0.92) were included in the study. sBCC was isolated in 80% of cases, measured less than 2 cm in 90%, and was located on the head/neck in 51% and on the trunk in 37%. Histological confirmation of diagnosis of BCC was obtained in 85% of cases. Treatment comprised surgical excision in 70% of cases, cryotherapy in 13%, topical therapy in 7% and curettage/electrodessication in 4%. Clinical follow-up was performed in 79% of cases. The mean cost per patient over 3 months was 139 euros (CI95%: 125-153). In addition, 226 patients with AK (mean age: 76 years; sex-ratio M/F: 2.1) were included in the study. AKs were located on the head/neck in 74% of cases and on the trunk in 6%. Treatment consisted of cryotherapy in 92% of cases. The mean cost per patient over 3 months was calculated at 85 euros (CI95%: 71-99). An on-site audit of 5% of the investigators gave a concordance rate of 98.8%. DISCUSSION: This is the first study conducted in France to evaluate both the medical approach and treatment costs of sBCC and AK. Finally, the mostly surgical treatment of sBCC observed is in accordance with the recent French ANAES guidelines. When extrapolating the results of the present study, the annual cost of treatment of sBCC by French dermatologists may be estimated at between 10.2 and 10.6m euros.