Florence Libon

Skin Color Is Relevant to Vitamin D Synthesis

Background: Whether dark skin produces less vitamin D after UVB radiation than fair skin remains controversial. Objective: To compare 25-hydroxyvitamin D [25-(OH)-D] levels after a single UVB exposure in fair (phototype II-III) and black-skinned (phototype VI) volunteers. Methods: Fair-skinned volunteers (n = 20, 4 males/16 females, mean age: 23.2 years) and black-skinned (n = 11, 6 males/5 females, mean age: 23.8 years) received a single total body UVB exposure (0.022 J/cm2). The 25-(OH)-D levels were measured on days 0, 2 and 6. Results: On day 0, all volunteers were severely vitamin D deficient. On day 2, 25-(OH)-D levels of fair-skinned volunteers increased significantly (median: 11.9-13.3 ng/ml, p < 0.0001), but not in black-skinned people (median: 8.60-8.55 ng/ml, p = 0.843). Again, on day 6, 25-(OH)-D levels of fair-skinned volunteers increased significantly (median: 11.9-14.3 ng/ml, p < 0.0001), but not in black-skinned people (median: 8.60-9.57 ng/ml, p = 0.375). Conclusion: This study suggests that skin pigmentation negatively influences vitamin D synthesis.

Effect of N-acetylcysteine combined with infliximab on toxic epidermal necrolysis. A proof-of-concept study

INTRODUCTION The pathophysiology of toxic epidermal necrolysis (TEN) is thought to be related to a drug-induced oxidative stress combined with TNFα overexpression by keratinocytes. None of the current treatments for TEN including systemic corticosteroids, cyclosporine and intravenous administration of immunoglobulins has proven superior over supportive care only. METHODS A total of 10 TEN patients were enrolled to be treated at admission in burn units with the antioxidant N-acetylcysteine [NAC, 150mg/kg in a 20-h intravenous (IV) administration], or the combination of the same IV NAC perfusion with the anti-TNFα antibody infliximab (Remicade(®)), administered at a 5mg/kg dosage as a single 2-h IV administration. TEN was confirmed by a skin biopsy taken from a bullous lesion. At entry in the trial and 48h later, the illness auxiliary score (IAS) of clinical severity was determined and the extent in altered skin area (erythema and blisters) was assessed as a relative body area. Skin biopsies of both clinically uninvolved and erythematous areas were collected and immunohistochemistry was performed for assessing the density of inflammatory cells (CD8+ T cells, CD68+ macrophages) and keratinocytes enriched in intracellular calcium (Ca(++)) identified by the Mac387 anti-calprotectin antibody. RESULTS No unexpected drug-induced adverse event was noticed. After 48h of both treatment modalities, improvements were not observed in the extent of skin involvement and in IAS. Immunohistopathology showed the absence of reduction in the amount of intraepidermal inflammatory cells. An increased intracellular Ca(++) load in clinically uninvolved keratinocytes and in erythematous epidermis was noticed. This latter finding suggested the progression in the way of the apoptotic process. On burn unit discharge, the survival in each modality of treatment was not improved compared to the expected outcomes determined from the IAS at admission. CONCLUSIONS In this proof-to-concept attempt, NAC treatment or its combination with infliximab did not appear to reverse the evolving TEN process.

Ipilimumab induces simultaneous regression of melanocytic naevi and melanoma metastases

Ipilimumab blocks cytotoxic T‐lymphocyte‐associated antigen (CTLA)‐4, potentiating the antimelanoma T‐cell host response. Ipilimumab has been shown to improve overall survival in patients with previously treated metastatic melanoma. CTLA‐4 antibodies generate immune responses to the melanoma‐associated antigens Melan‐A, NY‐ESO‐1 and glycoprotein (gp)100 in metastatic melanoma. Digital epiluminescence microscopy (DELM) is a noninvasive method permitting the monitoring of the morphology of melanocytic lesions over time. A 50‐year‐old man with metastatic melanoma received four ipilimumab injections after failure of dacarbazine chemotherapy. Positron emission tomography revealed regression of pulmonary metastases, and simultaneously, DELM showed regression of several melanocytic naevi. On histological examination of the regressing naevi, prominent CD8+, CD4+ and CD45R0 lichenoid lymphohistiocytic infiltrates were seen, whereas nonregressing naevi were almost free of inflammatory infiltrate. Expression of melanoma‐associated antigens in benign melanocytic naevi may explain the induction of naevus regression by ipilimumab. DELM could represent a valuable noninvasive method to monitor ipilimumab efficacy.

Non-dermatophyte Dermatoses Mimicking Dermatophytoses in Humans.

Human dermatophytic cutaneous infections usually present as single or multiple slowly progressing annular erythemato-squamous lesions with a tendency to central healing on the hairless skin. In the intertriginous regions (feet, inguinal, axillar, submammary), dermatophytic colonisations and infections manifest as whitish, slightly hyperkeratotic, pruritic and sometimes fissurated lesions. On the scalp, dermatophytic infections commonly lead to single or multiple more or less inflammatory and alopecic lesions. On the plantar and palmar aspects of the feet and hand, dermatophytosis presents as an eczema-like chronic dermatosis. Abscess-like lesions may occur due to zoophilic dermatomycosis. Dermatophytic infections of the nails reveal ill-defined whitish-yellowish colorations of the distal end or the lateral aspects of the nails, sometimes combined with partial nail embrittlement or even complete destruction. Despite the ubiquity of dermatophytic skin infections and their usually highly typical clinical features, a differential diagnosis has to be considered, in particular when treatment is not efficient or when treatment resistance occurs. This review presents the differential diagnosis in terms of frequency as well as the diagnostic methods permitting the distinction of annular, intertriginous, alopecic, palmoplantar, abscess-like and onychodystrophic lesions.

Effect of Body Site and Surface on Vitamin D and 25-Hydroxyvitamin D Production after a Single Narrowband UVB Exposure

TO THE EDITOR Skin color, body surface area (BSA) exposed to UVB, ability to tan, latitude, altitude, season, solar zenith angle, clothing, age, moment of the day, and use of sunscreen influence the cutaneous synthesis of vitamin D (Chen et al., 2007; Holick, 2003; Libon et al., 2013; Rizzoli et al., 2013; Touvier et al., 2015). There are still many controversies concerning the impact of the UV-exposed anatomical region and BSA on cutaneous vitamin D production. This study was performed in accordance with the Declaration of Helsinki (World Medical Association, 2013) and approved by the university hospital ethics committee. All study procedures were explained to the volunteers. All participants signed an informed consent form. To determine whether various anatomical regions exhibit different vitamin D production capacities, assessed as production per percentage of BSA, this study initially measured cholecalciferol (vitamin D3, representing cutaneous synthesis) and 25(OH)D3 (the circulating form of vitamin D) levels before and on days 1, 2, and 5 in 72 young healthy volunteers, recruited from among medical students (male 1⁄4 25, female 1⁄4 47, mean age 1⁄4 23.0 2.3 years, age range 1⁄4 19e29 years, body mass index 1⁄4 21.6 1.9 kg/m, body mass index range1⁄4 18e25 kg/m, Fitzpatrick’s phototype III) after a single narrowband (310e315nm) UVB exposure of 0.8 minimal erythematous dose (mean 1⁄4 0.22 0.08 J/cm) to different BSAs. BSAs were determined according to real-life clothing habits: group I (n 1⁄4 15): head, neck, and hands (BSA 1⁄4 9%); group II (n 1⁄4 15): head, neck, arms, and hands (BSA 1⁄4 23%); group III (n 1⁄4 15): head, neck, arms, hands, legs, and feet (BSA 1⁄4 50%); group IV (n 1⁄4 15): the total body (BSA 1⁄4 96%), as well as a noneUVBexposed control group (group 0, n 1⁄4 12). The BSA percentages were calculated according to Wallace’s rule (Hettiaratchy and Papini, 2014). 25(OH)D3 analysis was performed using liquid chromatography/tandem mass spectrometry kits for 25(OH) D3 measurement (MassChrom 25OH-Vitamin D3/D2 [LC-MS/MS], Chromsystems, Gräfelfing, Germany) (Cavalier et al., 2014). Cholecalciferol was determined with an in-house developed liquid chromatography/tandem mass spectrometry method. Statistics were expressed as mean and standard deviation for continuous variables and as frequency tables for categorical variables. On graphs, mean values were plotted with their standard error. The general linear mixed model was used to analyze the evolutions of vitamin D and 25(OH)D3 over time and test for group differences. A linear regression was used to compare the area under the curve of vitamin D and 25(OH)D3 with respect to BSA. Results were considered significant at the 5% critical level (P < 0.05). Calculations were done with SAS, version 9.4 (SAS Institute, Cary, NC). Vitamin D level increased with peak levels on day 1 for groups I and II and on day 2 for groups III and IV, and it decreased subsequently in all groups except in the control group (Figure 1). In contrast, 25(OH)D3 increased steadily at all time points in all groups but not in the control group (Figure 1). The larger the exposed area was (group IV > III > II > I), the higher the increase (Figure 1). Expressed as area under the curve, no difference in 25(OH)D3 level was observed between the groups (P 1⁄4 0.29) at day 0. After UVB irradiation, a steady increase in vitamin D and 25(OH)D3 levels was observed in groups I through IV, with a constant increase according to the body surface exposed (Table 1). This study gave evidence that the vitamin D production capacities of various skin regions are not similar at all. In fact, the relative mean vitamin D production expressed as area under the curve for the entire body (group IV) was 314 nmol/L, corresponding to 96% of BSA. Hence, the production per percentage of BSA was 3.3 nmol/L. Consequently, the production in group I was 25.4 nmol/L; in group II, 10.3 nmol/L; and in group III, 5.36 nmol/L.

Sunscreens block cutaneous vitamin D production with only a minimal effect on circulating 25-hydroxyvitamin D

SummaryA 50+ SPF sunscreen decreased significantly cutaneous vitamin D production following a single narrow-band (nb)UVB exposure, independently from the body surface area exposed. In contrast, the circulating 25(OH)D3 levels were only minimally affected. It is probable that another endogenous source of precursors is selected when skin-originated precursors are lacking.PurposeSunscreen use, highly advocated for preventing cutaneous carcinogenesis, is potentially leading to an aggravation of vitamin D deficiency with its consequences on bone health. The effect of sunscreens on circulating vitamin D levels remains debated. This study investigated the effect of sunscreen on cutaneous vitamin D production and circulating 25(OH)D3 levels, according to different body surface areas (BSA).MethodsVitamin D and 25(OH)D3 levels were measured in four groups exposed to a single nbUVB exposure on 9% (group I: head and hands), 23% (group II: head, hands and arms), 50% (group III: head, hands, arms and legs) and 96% (group IV: total body) of the body surface without and with a 50+ sun protection factor sunscreen.ResultsSunscreen use decreased by 83, 88.3, 75.7 and 92.5% the cutaneous vitamin D production in groups I to IV, respectively, but only by 13.2, 10.5, 7.7 and 10.4% the values of circulating 25(OH)D3, correspondingly.ConclusionsAlthough a 50+ sunscreen decreases significantly cutaneous vitamin D production following a single nbUVB exposure, and independently from the BSA, the circulating 25(OH)D3 levels were only minimally affected. This could be explained by a switch to another endogenous source of precursors. Short-term sunscreen use probably does not affect circulating vitamin D levels and hence does not increase the risk for osteoporosis. The effect of long-term sunscreen use remains however to be determined.

Koebner Phenomenon and Mycosis Fungoides

Mycosis fungoides (MF) is the most frequent type of primary cutaneous T-cell/NK-cell lymphoma. The Koebner phenomenon is defined as the appearance of cutaneous lesions on previously noninvolved skin following trauma and is observed in a series of cutaneous diseases including psoriasis, lichen planus, viral warts, molluscum contagiosum, etc. In this case report, 3 patients with longstanding MF are presented, the 1st with the appearance of a circumscribed early-stage type MF lesion rapidly following a surgical excision of an infundibular cyst, the 2nd with the appearance of a unique unilateral palmar tumoral MF lesion at the pressure site of a crutch, and the 3rd presented localized MF early stage lesions at the friction site of a belt. This report suggests that some MF patients may experience Koebner phenomenon-induced MF lesions and that MF should be added to the long list of skin diseases potentially exhibiting the Koebner phenomenon.

Prospective Pilot Evaluation of the Efficacy and Safety of Topical Ingenol Mebutate Gel for Localized Patch/Plaque Stage Mycosis Fungoides

CLINICAL TRIAL STUDY Prospective Pilot Evaluation of the Efficacy and Safety of Topical Ingenol Mebutate Gel for Localized Patch/Plaque Stage Mycosis Fungoides Eve Lebas, Charlotte Castronovo, Jorge E. Arrese, Florence Libon, Nazli Tassoudji, Laurence Seidel and Arjen F. Nikkels Dermatology (Dermato-oncology unit), University Hospital Centre, CHU du Sart Tilman, Liège, Belgium Dermatopathology, University Hospital Centre, CHU du Sart Tilman, Liège, Belgium Biostatistics University Hospital Centre, CHU du Sart Tilman, Liège, Belgium

Melanoma masquerading as nonmelanocytic lesions.

Increased awareness among dermatologists as well as the development of dermoscopy and sequential dermoscopy have contributed significantly toward an increase in the diagnostic accuracy of pigmented melanoma and even of amelanotic melanoma. However, the dermatologist’s nightmare is the small group of melanomas that present as common skin diseases, often associated with a significant delay in diagnosis and hence a poor prognosis. The study was carried out to prospectively assess the number of melanomas lacking any clinical suspicion of melanoma and to describe their clinical and histological features over a 6-year observation period in an University Tertiary Skin Cancer Center. Out of 502 cases of newly diagnosed cases of melanoma, seven (1.4%) nonpigmented and nonamelanotic cases of melanoma were identified. The mean age of the patients was 69 years (two females/five males). All cases were discovered by chance on a punch biopsy. The clinical diagnostic suspicions were basal cell carcinoma, fungal intertrigo, keratoacanthoma, lichenoid keratoma, diabetic foot ulcer, eczema, and necrotic pressure ulcer. Dermoscopy, performed after the punch biopsies, was only partially contributive. The mean histological thickness was 2.7 mm, the mean number of mitoses was 7/mm2, local micrometastases were present in 5/7 (71%), the mean Ki67 count was 18.9%, and a positive sentinel lymph node was observed in 4/6 (66%) cases. Nonpigmented and nonamelanotic melanomas are rare, are at high risk, and have a poor prognosis because of a delayed diagnosis. Dermoscopy is only of partial diagnostic aid. Treatment resistance or atypical behavior of the above-mentioned lesions should lead to biopsy.

Vitamin D Supplementation Does Not Improve the Severity or the Resolution of Ultraviolet B-Induced Acute Erythema

Background: Whether vitamin D supplementation alleviates the severity of ultraviolet B (UVB)-induced erythema and/or facilitates its resolution remains undetermined. Objective: To study the effect of oral vitamin D on UVB-induced erythema and its resolution in fair-skinned subjects. Methods: UVB-induced erythema was quantified using a Chroma Meter® in 50 volunteers 48 h before and 10 days after the random administration of 200,000 IU vitamin D (n = 40) or placebo (n = 10). Resolution of erythema in both groups was assessed by chromametry 24, 48, and 72 h after vitamin D administration. Results: No statistical difference between erythema values before and after administration in the vitamin D-supplemented group (p = 0.44) or the placebo group (p = 0.34) was noted. No statistical difference was evident between both groups with respect to resolution of erythema (p = 0.30). Conclusion: Oral vitamin D supplementation neither improves protection against UVB-induced erythema nor facilitates its resolution.