In-vivo and ex-vivo tests for culprit drugs identification in severe cutaneous adverse drugs reactions.

Drug causality assessment in severe cutaneous adverse reactions (SCARs) remains challenging. We investigated the usefulness of in-vivo drug patch tests (PT), ex-vivo interferon (IFN)-γ enzyme-linked immunospot (ELISpot) assay, and lymphocyte transformation test (LTT) in 30 SCARs patients within the past 36 months. Drug PT yielded a 20% positivity rate (n = 6), while IFN-γ ELISpot and LTT showed positive rates of 56.67% (n = 17) and 41.38% (n = 12), respectively. Combining the three tests resulted in an overall positive rate of 66.67% (n = 20) of cases. IFN-γ ELISpot offered additional positivity, especially with oxypurinol. Employing a combined diagnostic approach may enhance the chances of obtaining a positive result.

Accurate surface ultraviolet radiation forecasting for clinical applications with deep neural network.

Exposure to appropriate doses of UV radiation provides enormously health and medical treatment benefits including psoriasis. Typical hospital-based phototherapy cabinets contain a bunch of artificial lamps, either broad-band (main emission spectrum 280-360 nm, maximum 320 nm), or narrow-band UV B irradiation (main emission spectrum 310-315 nm, maximum 311 nm). For patients who cannot access phototherapy centers, sunbathing, or heliotherapy, can be a safe and effective treatment alternative. However, as sunlight contains the full range of UV radiation (290-400 nm), careful sunbathing supervised by photodermatologist based on accurate UV radiation forecast is vital to minimize potential adverse effects. Here, using 10-year UV radiation data collected at Nakhon Pathom, Thailand, we developed a deep learning model for UV radiation prediction which achieves around 10% error for 24-h forecast and 13-16% error for 7-day up to 4-week forecast. Our approach can be extended to UV data from different geographical regions as well as various biological action spectra. This will become one of the key tools for developing national heliotherapy protocol in Thailand. Our model has been made available at https://github.com/cmb-chula/SurfUVNet .

Chronic occupational exposure to lead leads to significant mucocutaneous changes in lead factory workers.

BACKGROUND: Chronic lead toxicity is a worldwide public health problem. Lead possesses deleterious effects on many organ systems. However, little is known regarding its clinical and biophysical effects on the skin. OBJECTIVE: To investigate mucocutaneous signs and biophysical property changes in skin after chronic lead toxicity. METHODS: One hundred and eighty-seven patients who were car battery workers participated in the study. Complete history and physical examination were performed. Blood was collected for laboratory analyses. Thorough skin examination by dermatologists was carried out in 134 subjects. Additionally, 96 patients with blood lead levels (BLL) >70 µg/dL were further evaluated for skin elasticity, sebum content, transepidermal water loss (TEWL), hydration, pH and pigmentation. An equal number of age-, sex- and skin-type-matched subjects were recruited as controls. RESULTS: The mean BLL of all subjects was 74.15 ± 11.58 µg/dL. The most frequently observed signs were gingival brown pigmentation in 112 (83.6%), gingivitis in 111 (82.8%) and lead line in 66 (49.3%) patients. The lead line was found in subjects with significantly higher BLLs (adjusted mean difference 6.45, 95% CI 2.30-10.60 µg/dL, P = 0.003) and in association with gingivitis (adjusted OR 7.32, 95% CI 2.08-25.74, P = 0.002). Mean BLL of the patients who underwent biophysical assessment was 82.77 ± 9.80 µg/dL. Patients exhibited a statistically significant lower skin hydration observed by corneometer as well as elasticity. The adjusted ORs of having dry skin and lower elasticity were 15.32 (95% CI 4.41-53.24), P < 0.001) and 1.96 (95% CI 1.06-3.60), P = 0.031), respectively. These differences were not significant for sebum content, TEWL, pH and pigmentation. CONCLUSION: Importantly, even in normal-appearing skin, level of hydration and elasticity decreased in lead-intoxicated patients. These results suggest that lead might possess harmful effects on the skin at measurable levels.

Skin signs in juvenile- and adult-onset systemic lupus erythematosus: clues to different systemic involvement.

OBJECTIVE: We aim to explore the differences of skin signs between juvenile- and adult-onset systemic lupus erythematosus and to identify their associations to the development of systemic involvement. METHODS: A retrospective chart review of 377 systemic lupus erythematosus patients was performed. RESULTS: In total, 171 patients with juvenile systemic lupus erythematosus and 206 with adult systemic lupus erythematosus were studied. All patients were of Southeast Asian descent. The mean duration of follow up was 8.18 ± 6.19 and 9.36 ± 7.68 years for juvenile systemic lupus erythematosus and adult systemic lupus erythematosus, respectively. At diagnosis, most patients presented with acute cutaneous lupus erythematosus, whereas chronic cutaneous lupus erythematosus was twice as common in adult systemic lupus erythematosus ( p < 0.001). The mean Systemic Lupus Erythematosus Disease Activity Index of juvenile systemic lupus erythematosus was significantly higher than that of adult systemic lupus erythematosus (14.29 ± 7.13 vs 11.27 ± 6.53). Multivariate analysis revealed the following associations in juvenile systemic lupus erythematosus: acute cutaneous lupus erythematosus and non-scarring alopecia with increased risk of arthralgia, mucosal ulcers with leukopenia, cutaneous vasculitis with seizure, and finding of granular casts. On the contrary, the associations for adult systemic lupus erythematosus were oral ulcers with arthralgia and cutaneous vasculitis with myositis. CONCLUSIONS: Cutaneous signs in systemic lupus erythematosus may signal prognostic implication. Interestingly, despite similar cutaneous lesions in systemic lupus erythematosus, different ages of onset are associated with different systemic involvement.

Non-ablative fractional photothermolysis in treatment of idiopathic guttate hypomelanosis.

BACKGROUND: Idiopathic guttate hypomelanosis (IGH) is a common pigmentary disorder affecting a large number of individuals. Many patients seek medical attention due to aesthetic concern. However, no standard treatment is available. OBJECTIVES: To evaluate the efficacy and side-effects of non-ablative fractional photothermolysis (FP) as a treatment of IGH. MATERIALS AND METHODS: A total of 120 lesions from 30 patients with IGH were treated. In each patient, two lesions on the extremities were assigned to treatment group, while lesions from the other side served as control. The treatment was delivered by fractional 1550-nm ytterbium/erbium fibre laser for four times at 4-week intervals. Lesional skin colour was measured by colourimetry. Digital photographs and dermoscopic digital photographs were taken at weeks 0, 4, 8, 12 and 16. In addition, patient satisfaction score and side-effects were recorded. All clinical photographs were evaluated by three experienced dermatologists to determine clinical improvement using a quartile grading scale. RESULTS: Colourimetry of the treatment side showed normalization of skin colour at each visit and was statistically significant when compared with control after two treatments (week 8) and continued to decrease until 4 weeks' follow-up (week 16) (P = 0.047, 0.016 and 0.06 respectively). Physicians' improvement grading score showed that 83.34% of the lesions in treatment group vs. 18.34% in the control group showed some improvement. The difference was statistically significant (P < 0.05). Common side-effects were erythema and oedema in treatment area, which were mild and transient. No post-inflammatory hyperpigmentation was observed. CONCLUSION: Non-ablative FP appears to be an effective way to treat IGH. The improvements are documented by both objective and subjective measurements.

Brain-derived nerve factor and neurotrophins in androgenetic alopecia.

BACKGROUND: Several growth factors and cytokines have been shown to be involved in normal hair cycling as well as in androgenetic alopecia (AGA). However, the molecular cascades in AGA downstream from androgen receptor activation are far from being fully elucidated. OBJECTIVES: We sought to determine the difference in the protein expression of growth factors/cytokines in balding vs. nonbalding scalp specimens from the same individuals affected with AGA. METHODS: Balding and nonbalding scalp specimens were collected from four men with pattern baldness. Dermal papilla (DP) cells were isolated and cultured. Quantifying the protein expression of growth factors and cytokines expressed by these cells was performed using Quantibody® Human Growth Factor Array-1 (RayBiotech, Inc., Norcross, GA, U.S.A.). RESULTS: Brain-derived nerve factor (BDNF) protein expression was upregulated by approximately 12-fold in supernatants obtained from balding as compared with nonbalding DP cells (P < 0·001). Expression of neurotrophin-3 and of ß-nerve growth factor was also upregulated. On the other hand, protein expression of insulin-like growth factor-1 and its binding proteins as well as of the vascular endothelial growth factor family were significantly downregulated in the balding scalp. CONCLUSIONS: Neurotrophic factors, especially BDNF, may be important in mediating the effects of androgens on hair follicles, serving as a negative regulatory control signal. Further studies may lead to novel pharmacological interventions in AGA.

Topical 8-methoxypsoralen enhances the therapeutic results of targeted narrowband ultraviolet B phototherapy for plaque-type psoriasis.

Targeted broadband ultraviolet B (UVB) phototherapy as well as 308-nm excimer laser have been reported to significantly improve or clear localized psoriatic plaques within 5 to 10 treatments when medium fluences [i.e. 4-6 multiples of minimal erythema doses (MED)] were used. Our study was conducted to determine the effects of different concentrations of topical 8-methoxypsoralen (8-MOP) cream when used in combination with targeted UV phototherapy with regard to number of treatments and cumulative UV doses to clear localized psoriasis. Ten evaluable patients with stable plaque-type psoriasis completed the study. Three different concentrations of 8-MOP creams (0.001%, 0.01% and 0.1%) were applied prior to irradiation with 4 MEDs of targeted narrowband UVB (NB-UVB), whereas 0.001% 8-MOP cream was used in conjunction with 5 J/cm(2) UVA. All irradiations took place once weekly for 12 weeks. Psoriasis severity index (PSI) score was used to evaluate the efficacy of the treatment. With area-under-the-curve analysis, 0.1% 8-MOP/NB-UVB was superior to other modalities in reducing the PSI scores. The number of treatments and cumulative NB-UVB doses necessary to achieve PSI-95, a 95% reduction in the scores, was also lower in the 0.1% 8-MOP/NB-UVB group, although the differences were not statistically significant. We conclude that topical 8-MOP cream enhances the therapeutic effects of targeted NB-UVB phototherapy without significantly increasing the short-term adverse effects.

Association of the interleukin-10 distal promoter (-2763A/C) polymorphism with late-onset psoriasis.

Polymorphisms of the IL-10 promoter have been implicated in the genetic susceptibility to many autoimmune diseases, including psoriasis. Four putative functional single-nucleotide polymorphisms (SNPs) within the interleukin-10 promoter region (-3575T/A, -2763A/C, -1082G/A and -592C/A) were analysed in 139 patients with chronic plaque psoriasis and in 155 unrelated healthy controls from Thailand. There were no significant differences in the allele frequencies of any of the four SNPs between patients with psoriasis and controls. However, the frequency of the -2763A allele was increased in patients with late-onset psoriasis compared with controls and patients with early-onset psoriasis [OR=2.94, 95% CI 1.16-7.39, corrected P value (Pc)=0.04 and OR=3.26, 95% CI 1.13-9.51, Pc=0.048, respectively]. The AAGC (-3575/-2763/-1082/-592) haplotype frequency was higher in late-onset compared with early onset psoriasis (OR=4.37, 95% CI 1.24-15.97, Pc=0.027). This study suggests that the -2763A allele and the extended AAGC haplotype can be used as a genetic marker for susceptibility to late-onset psoriasis in a Thai population.

Transdermal penetration of UV filters.

A penetration study of 2-ethylhexyl-4-methoxycinnamate (EHMC), 4-methyl benzylidenecamphor (MBC), butyl methoxydibenzoylmethane (BMBM), 2-ethylhexyl-2,4,5-trimethoxycinnamate (EHTMC) and di(2-ethylhexyl)-2,4,5-trimethoxybenzalmalonate (TMB) through baby mouse skin (Mus musculus Linn.) was carried out using a vertical Franz diffusion cell. At 4.4 mg/cm(2) coverage of UV filter on the skin, 2.98 +/- 0.38, 1.15 +/- 0.14 and 0.80 +/- 0.28% of the applied EHMC, MBC and BMBM were detected in the receptor fluid at 24 h after application. Penetrations of UV filter in an ethanolic solution and lotion forms were comparable. EHTMC and TMB showed insignificant penetration across the baby mouse skins. Baby mouse skins kept at 4, -20 and -80 degrees C gave similar EHMC penetration results. Penetrations of EHMC, BMBM, EHTMC and TMB across human epidermis were carried out upon 5 volunteers using the suction blister technique. The results also confirmed the significant penetrations of EHMC and BMBM and the insignificant penetrations of EHTMC and TMB.

308-nm excimer laser for the treatment of psoriasis: a dose-response study.

OBJECTIVE: To determine the dose-response relationship of excimer laser-generated 308-nm UV-B radiation for treating psoriasis. DESIGN: Pilot study with a before-after design. SETTING: A university dermatology service. PATIENTS: Thirteen consecutive patients with at least 4 large, stable psoriasis plaques. INTERVENTIONS: Excimer laser-generated 308-nm UV-B radiation was given to each of 4 plaques, which received 1, 2, 4, and 20 treatments, respectively. Untreated areas within each plaque served as controls. Within each plaque, 8 doses based on multiples of a predetermined minimal erythema dose (MED) were tested in distinct sites. The multiples were 0.5 and 1 (low dose); 2, 3, 4, and 6 (medium dose); and 8 and 16 (high dose). At every treatment, the dose for each site remained fixed at the same MED multiple. A psoriasis severity index score was determined for each area before, every 2 weeks during, and 2 and 4 months after treatment. RESULTS: The mean+/-SD MED was 203.03+/-57.84 mJ/ cm2. Treatment with high fluences produced significantly better results than that with medium and low fluences at weeks 4, 6, 8, and 10 (P<.05). At 4 months' follow-up, all sites that received low or medium fluences had recurrences, whereas those that underwent a single treatment at 8 and 16 MED multiples remained in remission. CONCLUSIONS: With 308-nm UV-B radiation generated by an excimer laser, it is possible to clear psoriasis with as little as 1 treatment with moderately long remission. In contrast to traditional phototherapy techniques, this handheld excimer laser UV-B therapy is selectively directed toward lesional skin, thus sparing the surrounding normal skin from unnecessary radiation exposure. Treatment of other inflammatory diseases and limited psoriasis seems reasonable to pursue with this modality.

Pendulaser carbon dioxide resurfacing laser versus electrodesiccation with curettage in the treatment of isolated, recalcitrant psoriatic plaques.

BACKGROUND: Treatment of recalcitrant psoriatic plaques located on certain areas of the body remains problematic despite the many therapeutic options available. OBJECTIVE: This study was conducted to determine the efficacy of Pendulaser carbon dioxide (CO(2)) resurfacing laser to that of electrodesiccation with curettage in the treatment of recalcitrant psoriatic plaques. METHODS: A single psoriatic plaque was divided into thirds, one part treated with CO(2) resurfacing laser, another with electrodesiccation and curettage, and the third left untreated. The psoriatic epidermis and papillary dermis were removed by the two treatment modalities. RESULTS: CO(2) resurfacing laser and electrodesiccation with curettage produced similar therapeutic effects in terms of improvement of psoriasis and were significantly better than the control 4 months later, but not at 6 months. CONCLUSION: For limited recalcitrant psoriatic plaques, CO(2) resurfacing laser and electrodesiccation with curettage may provide an alternative short-term treatment; however, caution must be exercised and the moderately high risk of scarring carefully weighed against the potential benefits.

Temperatures reached inside stand-up ultraviolet treatment boxes.

Heat generated within ultraviolet treatment units can exacerbate eczema. To document the actual temperature changes within the treatment units, we measured the air temperatures in standard stand-up psoralen plus ultraviolet A (PUVA), narrowband ultraviolet B (UVB), broadband UVB, and combination UVA/UVB cabinets using a thermocouple thermometer. For the latter unit, we also measured the air temperatures with and without ventilation systems, and actual skin temperatures on individuals undergoing light treatment. The air temperatures rose significantly in all the treatment units, more so with PUVA and narrowband UVB boxes, and were highest with the ventilation systems shut off. Skin temperatures also rose significantly, but less dramatically. Ventilation is essential in maintaining comfortable temperatures within ultraviolet treatment units.