Search

However, long-term use and high doses may lead to nephrotoxicity. It is unclear whether serum trough levels may be useful for monitoring this risk, similar to patients on cyclosporine for [...]

Background: Various treatments are currently available for melasma. However, results are often disappointing.Objective: We sought to assess the efficacy and safety of nonablative 1550-nm fractional laser therapy and compare results with those obtained with triple topical therapy (the gold standard).Methods: Twenty female patients with moderate to severe melasma and Fitzpatrick skin types II to V were treated either with nonablative fractional laser therapy or triple topical therapy (hydroquinone 5%, tretinoin 0.05%, and triamcinolone acetonide 0.1% cream) once daily for 8 weeks in a randomized controlled observer-blinded study. Laser treatment was performed every 2 weeks for a total of 4 times. Physician Global Assessment was assessed at 3 weeks, 3 months, and 6 months after the last treatment.Results: Physician Global Assessment improved (P < .001) in both groups at 3 weeks. There was no difference in Physician Global Assessment between the two groups. Mean treatment satisfaction and recommendation were significantly higher in the laser group at 3 weeks (P < .05). However, melasma recurred in 5 patients in both groups after 6 months. Side effects in the laser group were erythema, burning sensation, facial edema, and pain; in the triple group side effects were erythema, burning, and scaling.Limitations: Limitations were: small number of patients; only one set of laser parameters; and a possible difference in motivation between groups.Conclusions: Nonablative fractional laser therapy is safe and comparable in efficacy and recurrence rate with triple topical therapy. It may be a useful alternative treatment option for melasma when topical bleaching is ineffective or not tolerated. Different laser settings and long-term maintenance treatment should be tested in future studies. [ABSTRACT FROM AUTHOR]

Objective. Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares.Methods. Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion.Results. Baseline Characteristics of the Patients. The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline.Patient Follow-up and Exposure to Study Medication. The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously.Efficacy. Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (log- rank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had 'severe' or 'very severe' disease at baseline according to the Investigators' Global Assessment, although patients in all baseline disease severity subgroups benefited from treatment. Age had no significant effect.Fewer patients in the pimecrolimus group required topical corticosteroid therapy compared with control (35.0% vs 62.9% at 6 months; 42.6% vs 68.4% at 12 months), and patients in the pimecrolimus group spent fewer days on topical corticosteroid therapy (57.4% vs 31.6% [pimecrolimus vs control, respectively] spent 0 days on topical corticosteroid therapy, 17.1% vs 27.5% 1-14 days, and 25.5% vs 41.0% >14 days over the 12 months of the study). This steroid-sparing effect of pimecrolimus was evident despite pimecrolimus-treated patients being on study longer than patients in the control group. The average proportion of study days spent on second-line corticosteroids was 4.08% in the pimecrolimus group and 9.10% in the control group. Analysis of Eczema Area and Severity Index over time showed significantly lower median scores, thus indicating better disease control in the pimecrolimus group compared with the control group. Similar results were obtained from analysis of the Investigators' Global Assessment (not shown). The treatment groups were well balanced with respect to the number of patients using antihistamines during the study (57.2% vs 62.9%, pimecrolimus vs control, respectively).Safety. There were no appreciable differences between treatment groups in the overall incidence of adverse events. The most frequent adverse events were common childhood infections and ailments, including nasopharyngitis, headache, and cough. The incidence of suspected drug-related adverse events was not significantly different in the pimecrolimus group (24.7% vs 18.7%--pimecrolimus vs control), and the incidence of serious adverse events was low (8.3% vs 5.2%-pimecrolimus vs control). Life-table analysis of incidence of adverse events revealed no significant differences between the treatment groups, except for cough.Local tolerability was good in both treatment groups. The most common application site reaction reported was sensation of burning (10.5% vs 9.3%-pimecrolimus vs control). There were no major differences between treatment groups in the duration or severity of application site reactions, most of which were mild-to-moderate and transient, occurring within the first week of treatment.Skin infections were reported in both groups. There were no between-group differences in the life-table analysis of time to first occurrence of bacterial skin infections nor in the adjusted incidence of bacterial skin infections. Although there were no significant differences between treatment groups in the incidence of individual viral skin infections, the incidence of grouped viral skin infections (12.4% vs 6.3%-pimecrolimus vs control) showed a slightly higher incidence in the pimecrolimus group.Laboratory values and vital signs showed no significant between-group differences.There were no significant differences between treatment groups in response to recall antigens in those patients who remained on study for 12 months.Conclusions. Treatment of early AD signs/symptoms with pimecrolimus was effective in preventing progression to flares in more than half the patients, reducing or eliminating the need for topical corticosteroids. The benefits were consistently seen at 6 months across important disease severity subgroups and with respect to the various predefined efficacy endpoints. Furthermore, these benefits were sustained for 12 months, providing evidence that long-term treatment with pimecrolimus leads to better control of AD. Treatment with pimecrolimus was well tolerated and was not associated with clinically relevant adverse events compared with the conventional treatment group. The results reported here offer the prospect of effective long-term management of AD with reduced need for topical corticosteroids. [Abstract for this article also available on page 158 of printed version. Full article available at http://www.pediatrics.org/cgi/content/full/110/1/e2] [ABSTRACT FROM AUTHOR]

Background: Biomarkers to objectively measure disease severity and predict therapeutic responses are needed in atopic dermatitis (AD)., Objective: Primary aim: To identify biomarkers reflecting therapeutic response in patients with AD treated systemically. Secondary aims: (i) To identify a biomarker pattern predicting responsiveness to systemic treatment. (ii) To identify differences in expression of biomarker in filaggrin gene (FLG) mutation carriers vs. non-FLG mutations carriers., Methods: Thirty-eight severe AD patients treated with methotrexate or azathioprine participated. Serum levels of a proliferation-inducing ligand, B-cell activating factor of the TNF family, thymus and activation-regulated chemokine (chemokine (C-C motif) ligand 17) (TARC (CCl-17)), interleukin-1 receptor antagonist (IL-1RA), interleukin-1 bèta, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-18, IL-31, interferon gamma, tumour necrosis factor alpha, vascular endothelial growth factor (VEGF), monokine induced by interferon gamma (chemokine (C-X-C motif) ligand 9), interferon gamma-induced protein 10 (C-X-C motif chemokine Ligand 10), monocyte chemoattractant protein-1 (chemokine (C-C Motif) ligand 2), macrophage inflammatory protein-1 beta (chemokine (C-C motif) ligand 4), regulated on activation, normal T cell expressed and secreted (chemokine (C-C motif) ligand 5), Cutaneous T-cell-attracting chemokine (chemokine (C-C motif) ligand 27) (CTACK (CCL-27)), thymic stromal lymphopoietin, IL-5, interleukin-1 alpha and granulocyte-colony stimulating factor were analysed by ELISA and Luminex. The primary outcomes were differences in mean absolute change of SCORing Atopic Dermatitis (SCORAD) between groups after 12 weeks compared with baseline. Responders to treatment were defined by a SCORAD reduction in ≥50%. Buccal mucosa swabs were collected to determine FLG genotype status., Results: Thymus and activation-regulated chemokine, CTACK, IL-13 and VEGF showed a significant decrease after treatment with methotrexate or azathioprine. However, no decrease in individual cytokine levels was significantly correlated with a change in any of the outcome parameters. In addition, baseline biomarker levels were not significantly different between responders and non-responders, and FLG and non-FLG mutants showed similar biomarker profiles., Conclusion: Thymus and activation-regulated chemokine and CTACK were confirmed as potential biomarkers. VEGF and IL-13 have a potential value as well. Biomarkers could not be used to discriminate at baseline between responders and non-responders, or FLG genotype status., (© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: The in vivo levels of inflammatory mediators in chronic atopic dermatitis (AD) skin are not well-defined due to the lack of a non-invasive or minimally invasive sampling technique., Objectives: To investigate the cytokine milieu in interstitial fluid (ISF) collected from chronic lesional AD skin as compared to ISF from non-lesional AD skin and/or healthy donor skin., Methods: ISF was obtained using a minimally invasive technique of creating micropores in the skin by a laser, and harvesting ISF through aspiration. We determined the levels of 33 cytokines by Luminex and ELISA in ISF and plasma from sixteen AD patients and twelve healthy individuals. In seven AD patients, we analysed the IL-13, IL-31, IL-17, IL-22 and IFN-γ production by T cells isolated from lesional skin. AD patients were genotyped for the filaggrin gene (FLG)-null mutations 2282del4, R501X, R2447X and S3247X., Results: Twenty-five of 33 examined mediators were detected in the ISF. The levels of IL-1α, IL-1β, IL-18, IL-1RA, IL-5, IL-13, IL-6, IL-8, TNF-α, RANTES(CCL-5), MIG(CXCL-9), IP-10(CXCL-10), TARC(CCL-17), VEGF and G-CSF showed significant differences between either lesional, non-lesional and/or healthy skin. IP-10 levels in ISF from lesional and non-lesional AD skin showed significant correlation with IP-10 blood levels. IP-10 also showed a significant correlation with clinical severity (SCORAD), as did IL-13. Levels of both IP-10 and IL-13 were more pronounced in patients with FLG-null mutations. Furthermore, FLG-null mutation carriers had more severe AD., Conclusion: The presented minimally invasive technique is a valuable tool to determine the in vivo cytokine profile of AD skin., (© 2015 European Academy of Dermatology and Venereology.)

Background/objectives: Environmental exposure and personal susceptibility both contribute to the development of hand eczema. In this study, we investigated the effect of loss-of-function mutations in the filaggrin gene (FLG), atopic dermatitis and wet work exposure on the development of hand eczema in apprentice nurses., Methods: Dutch apprentice nurses were genotyped for the four most common FLG mutations; atopic dermatitis and hand eczema history were assessed by questionnaire. Exposure and hand eczema during traineeships were assessed with diary cards., Results: The prevalence of hand eczema during traineeships was higher among subjects with a history of hand eczema reported at inclusion. Hand washing during traineeships and at home increased the risk of hand eczema. After adjustment for the effects of exposure and FLG mutations, an odds ratio of 2.5 (90% confidence interval 1.7-3.7) was found for a history of atopic dermatitis. In this study, an increased risk of hand eczema conferred by FLG mutations could not be shown, but subjects with concomitant FLG mutations and atopic dermatitis showed the highest risk of hand eczema during traineeships., Conclusion: A history of atopic dermatitis, a history of hand eczema and wet work exposure were the most important factors increasing the risk of hand eczema during traineeships., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background /objectives: Environmental exposure and personal susceptibility both contribute to the development of hand eczema. Here, we report an investigation on wet work exposure and its influence on the risk of developing hand eczema in apprentice nurses., Methods: A prospective cohort study was performed among 721 Dutch apprentice nurses. Participants recorded wet work exposure and symptoms of hand eczema using specially designed diary cards., Results: For 533 apprentice nurses, a follow-up time of 1-3 years was completed. Diary cards were supplied by 383 students. The 1-year period prevalence of hand eczema was 23% in the first year, 25% in the second year and 31% in the third year of follow-up. Eighty-one new cases of hand eczema developed, most of which occurred during the first year of follow-up. In approximately one-third of the participants, wet work exposure exceeded the national guidelines. Frequent hand washing during traineeships [odds ratio (OR) 1.5; 90% confidence interval (CI) 1.0-2.3], frequent hand washing at home (OR 2.3; 90% CI 1.5-3.7) and having a side job involving wet work (OR 1.6; 90% CI 1.0-2.4) were independent risk factors for hand eczema., Conclusion: As a considerable number of apprentice nurses had already developed hand eczema during traineeships, more attention should be paid to skin protection in vocational education., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Objective parameters to assess disease activity in non-segmental vitiligo are lacking. Melanocyte antigen-specific antibodies are frequently found in the sera of patients with vitiligo and the presence of these antibodies may correlate with disease activity., Objective: To investigate the relationship between melanocyte antigen-specific antibodies and recent disease activity in patients with vitiligo and to evaluate the potential usefulness of this objective parameter in daily clinical practice., Methods: The prevalence of tyrosinase, melanoma antigen recognized by T-cells-1 (MART1), melanin-concentrating hormone receptor-1 (MCHR1), gp100 and tyrosine hydroxylase (TH) antibodies was evaluated in 21 patients with non-segmental vitiligo and in 20 healthy controls., Results: In 21 patients, nine (42.8%) showed antibody responses against tyrosinase, MART1, MCHR1, gp100 or TH. No antibody responses were found in the 20 controls. No correlation was found between the presence of antibodies and recent disease activity or other clinical characteristics such as age, gender, extension and duration of vitiligo., Conclusions: In this study, 42.8% of the vitiligo patients showed an antibody response to melanocyte antigen-specific antigens. However, the presence of antibodies against melanocytes did not correlate with recent disease activity or other relevant disease parameters, and for the moment screening for these antibodies in individual patients does not appear to be clinically relevant., (© 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.)

Background: In vitiligo, many provoking factors have been described, but epidemiological data, especially on the role of contact with chemicals, are scarce., Objective: To obtain an insight into the patient-reported factors provoking vitiligo, including contact with chemicals., Methods: A retrospective cohort study was conducted on all 1264 patients with vitiligo who visited the Netherlands Institute for Pigment disorders from January 2003 to December 2007. Patients for whom an exogenous provoking factor was recorded were sent a questionnaire. Subsequently, patients who mentioned a chemical provoking factor were contacted to elucidate the alleged causal relationship between exposure to the chemical and the onset of vitiligo., Results: A total of 300 out of the 1264 patients indicated that provoking factors had played a role in their disease. Two hundred and forty-six patients were sent a questionnaire, which was returned by 177 (response rate of 72%). Emotional stress was indicated as a provoking factor in 98 patients (55.4%), 51 patients (28.8%) recorded sunburn, 34 patients (19.2%) recorded mechanical factors and 20 patients (11.3%) other factors. Of 29 patients (16.4%) who indicated a chemical factor, a presumed causal relationship could be corroborated in four. The chemicals involved were para-tertiary butylphenol (n = 2), captan (n = 1) and diphencyprone (n = 1)., Conclusion: The majority of the patients with vitiligo from this study did not mention provoking factors, but the ones who did point to emotional stress in more than half of the cases. Of the 29 patients who assigned chemical provoking factors, solvents were mainly indicated. However, a presumed relationship with the chemical could be corroborated in only four patients., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

The mechanisms preventing detrimental T-cell responses against commensal skin bacteria remain elusive. Using monocyte-derived and skin-derived dendritic cells (DCs), we demonstrate that epidermal Langerhans cells (LCs), the DCs in the most superficial layer of the skin, have a poor capacity to internalize bacteria because of low expression of FcγRIIa. Furthermore, LCs show deficiency in processing and major histocompatibility complex II (MHC-II)-restricted presentation of bacterial antigens, as a result of a decreased expression of molecules involved in these functionalities. The reduced capacity to take up, process, and present bacterial antigens cannot be restored by LC activation by ectopically expressed Toll-like receptors or by cytokines. Consequently, bacteria-primed LCs poorly restimulate antibacterial memory CD4(+) T cells and inefficiently induce bacteria-specific effector CD4(+) T cells from naive T cells; however, they initiate the development of regulatory Foxp3(+)CD4(+) T cells, which are able to suppress the proliferation of autologous bystander T cells specific for the same bacteria. In contrast, dermal DCs that reside in the deeper dermal layer of the skin efficiently present bacterial antigens and provoke robust antibacterial naive and memory CD4(+) T-cell responses. In conclusion, LCs form a unique DC subset that is adapted at multiple levels for the maintenance of tolerance to bacterial skin flora.

Background/aims: Vitiligo is considered to be an autoimmune disease and is known to be associated with other autoimmune diseases, particularly affecting the thyroid. In children and adolescents this association has been reported in only a few studies, with varying results. The aim of this study was to examine thyroid function and prevalence of thyroid autoimmunity in children and adolescents with vitiligo and to investigate the utility of screening., Methods: Two hundred and sixty patients with vitiligo were enrolled. Plasma TSH, FT4 and anti-thyroid peroxidase (TPO) antibody concentrations were measured. The prevalence of thyroid dysfunction and autoimmunity were compared to the general healthy paediatric population., Results: Autoimmune thyroiditis (AIT) with thyroid hormone disturbances was diagnosed in 16 patients (6.2%). This is significantly higher than the prevalence reported in the general healthy paediatric population. Increased levels of anti-TPO antibodies (= 30 kU/l), without thyroid hormone disturbances, were found in 27 patients (10.5%)., Conclusion: The prevalence of AIT in children and adolescents with vitiligo is significantly higher than in the general population. It may be advantageous to screen thyroid function and antibody levels in all paediatric patients with non-segmental vitiligo. To strengthen recommendations on screening, research on the burden for patients and cost-effectiveness is needed., (Copyright © 2013 S. Karger AG, Basel.)

Background: Vitiligo is a common skin disease characterized by autoimmune melanocyte destruction. Recent genetic studies suggest a lower susceptibility to melanoma in patients with vitiligo; however, lifetime melanoma prevalence in patients with vitiligo has not previously been studied. Nonmelanoma skin cancer (NMSC) prevalence has been studied, but only in small studies and with contradictory results., Objectives: This retrospective, comparative cohort survey was designed to assess lifetime prevalences of melanoma and NMSC in patients with vitiligo compared with nonvitiligo controls., Methods: Patients with nonsegmental vitiligo, who visited our clinic between January 1995 and September 2010, and were aged 50 years or older at the time of the study, were invited to participate in a postal survey. The questions regarded demographics, vitiligo characteristics, phototherapy history, skin cancer risk factors and the number of skin cancers experienced during the patient's lifetime. Patients were asked to have their partner fill in a control questionnaire. All skin cancers were validated by a pathology report. In total 2635 invitations were sent and 1307 eligible questionnaires were returned (50%). Multivariate logistic regression models were used to quantify adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between vitiligo and lifetime prevalences of melanoma and NMSC., Results:  Adjusted for confounders, patients with vitiligo had a threefold lower probability of developing melanoma (adjusted OR 0·32; 95% CI 0·12-0·88) and NMSC (adjusted OR 0·28; 95% CI 0·16-0·50). Subgroup analyses of patients treated with narrowband ultraviolet (UV) B, and psoralen and UVA did not show dose-related trends of increased age-adjusted lifetime prevalence of melanoma or NMSC., Conclusions: Our findings suggest that patients with vitiligo have a decreased risk of both melanoma and NMSC., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background: Erythema dyschromicum perstans and postinflammatory hyperpigmentation (PIH) are characterized by papillary dermal pigmentation or pigment incontinence. To date, no standard treatment is available. Fractional laser therapy (FLT) was recently reported to improve different pigment disorders., Objectives: To assess the efficacy and safety of non-ablative FLT in the treatment of erythema dyschromicum perstans and PIH., Methods: Eight patients with erythema dyschromicum perstans and six patients with PIH were included. In each patient, two similar test regions were randomized to receive either five fractional laser treatments in combination with intermittent daily topical bleaching or the same intermittent regimen of topical bleaching alone. Three months after the last treatment, improvement of hyperpigmentation was assessed by melanin index, reflectance spectroscopy, physician's assessment, patient's assessment and patient's satisfaction. In addition, a biopsy of both laser treated and control site was evaluated by an independent blinded pathologist., Results: No clinical improvement of hyperpigmentation was observed. Reflectance spectroscopy, melanin index, number of melanocytes and amount of dermal melanin did not significantly differ. Patients considered FLT unsatisfactory. Moreover, three patients developed laser-induced PIH., Conclusions: With these specific laser settings, non-ablative FLT was not effective for the treatment of erythema dyschromicum perstans and PIH.

Introduction: Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. Alefacept (a lymphocyte function-associated antigen (LFA)-3 Ig fusion protein that binds to CD2 and functions as an antagonist to T-cell activation) has been shown to result in improvement in psoriasis but has limited effectiveness in PsA. Interleukin-20 (IL-20) is a key proinflammatory cytokine involved in the pathogenesis of psoriasis. The effects of alefacept treatment on IL-20 expression in the synovium of patients with psoriasis and PsA are currently unknown., Methods: Eleven patients with active PsA and chronic plaque psoriasis were treated with alefacept (7.5 mg per week for 12 weeks) in an open-label study. Skin biopsies were taken before and after 1 and 6 weeks, whereas synovial biopsies were obtained before and 4 and 12 weeks after treatment. Synovial biopsies from patients with rheumatoid arthritis (RA) (n = 10) were used as disease controls. Immunohistochemical analysis was performed to detect IL-20 expression, and stained synovial tissue sections were evaluated with digital image analysis. Double staining was performed with IL-20 and CD68 (macrophages), and conversely with CD55 (fibroblast-like synoviocytes, FLSs) to determine the phenotype of IL-20-positive cells in PsA synovium. IL-20 expression in skin sections (n = 6) was analyzed semiquantitatively., Results: IL-20 was abundantly expressed in both PsA and RA synovial tissues. In inflamed PsA synovium, CD68+ macrophages and CD55+ FLSs coexpressed IL-20, and its expression correlated with the numbers of FLSs. IL-20 expression in lesional skin of PsA patients decreased significantly (P = 0.04) 6 weeks after treatment and correlated positively with the Psoriasis Area and Severity Index (PASI). IL-20 expression in PsA synovium was not affected by alefacept., Conclusions: Conceivably, the relatively limited effectiveness of alefacept in PsA patients (compared with anti-tumor necrosis factor (TNF) therapy) might be explained in part by persistent FLS-derived IL-20 expression.

Interleukin (IL)-31 has been associated with pruritus, a characteristic feature of atopic dermatitis (AD). Local T cell responses may be responsible for the increased level of IL-31 mRNA observed in AD. We investigated the frequency of IL-31-producing T cells in AD lesions, as well as their cytokine profile. T cells were isolated from chronic AD lesions, autologous blood and healthy donor skin. Intracellular expression of IL-31, IFN-γ, IL-13, IL-17 and IL-22 was measured using flow cytometry. T cells from AD lesions contained significantly higher percentages of IL-31-producing T cells compared to autologous blood and donor skin. Many IL-31-producing T cells co-produced IL-13 and to lesser extent IL-22, but rarely IFN-γ or IL-17. A substantial part of the IL-31-producing T cells did not co-produce any of the other cytokines and could therefore not be linked to any of the known functionally different T cell subsets. The T cell infiltrates were also relatively enriched for Th2/Tc2 and Th22/Tc22 cells, while frequencies of Th1/Tc1 and Th17 cells were decreased. This is the first report describing the detection of IL-31 at protein level in skin-infiltrating T cells. We show here that T cells in chronic AD skin produce IL-31 and that AD lesions contain increased levels of these IL-31-producing T cells. This suggests that a substantial part of previously reported increased IL-31 mRNA levels in AD skin is T cell derived and that these cells may be involved in the pathogenesis of AD., (© 2012 John Wiley & Sons A/S.)

Background  Ultraviolet radiation following punch grafting may stimulate the migration of melanocytes from the grafts into the vitiliginous skin, thereby increasing the rate of repigmentation. We compared the effects of the 308-nm xenon chloride excimer laser (EL) vs. narrow-band ultraviolet B (NB-UVB) after punch grafting in patients with vitiligo. Objectives  The aims of this study were to evaluate (i) repigmentation (%); (ii) treatment satisfaction; and (iii) patient preferences for EL vs. NB-UVB therapy after punch grafting in vitiligo. Methods  Fourteen patients were treated with the punch-grafting technique on two symmetrical vitiligo patches. Starting 1 week after the punch grafting, the vitiligo patches were treated twice a week during 3 months, with EL on one side and with NB-UVB on the other side. Repigmentation (%) was measured by a digital image analysis system. Patients' satisfaction and preference for treatment were also assessed. Results  Whereas both treatment modalities induced repigmentation, no statistically significant difference was found in grade of repigmentation after 3 months. With EL, 71.4% lower cumulative dose was reached. Patients were significantly more satisfied with NB-UVB and preferred it over EL. Conclusions  The choice between EL and NB-UVB cannot solely be based on repigmentation, but rather on other factors, such as patients' preferences. However, given the lower UV dose of EL, we recommend its use in vulnerable populations, such as in small children and patients with sun-damaged skin with a history of long-term UVB treatment., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

Background: Pulsed dye laser (PDL) is the first choice for treatment of port wine stains (PWS). However, outcome is highly variable and only a few patients achieve complete clearance. The objective of the study was to compare efficacy and safety of single pass PDL with double pass PDL at a 6 minute interval., Methods: We conducted a randomized within-patient controlled study on PWS resistant to multiple single pass PDL treatments. In each patient two similar PWS areas were randomly allocated to PDL treatment (595 nm, 7 mm spot size, 1.5 mseconds pulse duration) using, as a control treatment, a single pass (12 J/cm(2)) or, as a new treatment, a double pass PDL (11 J/cm(2), second pass 6 minutes after the first pass). Both test areas were treated two times, 8 weeks apart. PWS clearance was assessed by two blinded dermatologists, and by color measurement (L*a*b) using reflectance spectroscopy, at 3 months follow-up., Results: Sixteen out of 17 included patients completed follow-up. The mean number of treatments before inclusion was 15. Overall color assessed by spectrophotometer showed no improvement for either single or double pass PDL. Blinded Physician Global Assessment and Patient Global Assessment showed a high variability in outcome, with mostly only moderate improvement of the PWS for either single pass or double pass PDL. Furthermore, there was no significant difference in any of the outcomes between single pass and double pass PDL., Conclusion: At the chosen settings and after two treatment sessions, double pass PDL at a 6 minute interval does not result in improved clearance of PWS as compared to single pass treatment., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Fractional laser therapy (FLT) has become a widely accepted modality for skin rejuvenation and has also been used in various other skin diseases., Objective: To observe long-term histologic effects of nonablative and ablative FLT in the treatment of pigment disorders., Methods: A randomized controlled observer-blinded study was performed in 18 patients with pigment disorders. Two similar test regions were randomized to receive FLT with intermittent topical bleaching or topical bleaching alone. Patients with ashy dermatosis (AD) and postinflammatory hyperpigmentation (PIH) were treated using nonablative 1,550-nm FLT (15 mJ/microbeam, 14-20% coverage), whereas patients with Becker's nevus (BN) were treated with ablative 10,600-nm FLT (10 mJ/microbeam, 35-45% coverage) for three to five sessions. Biopsies were obtained 3 months after the last treatment., Results: At follow-up, dermal fibrosis was observed in four of eight patients treated using ablative FLT and no patients treated using nonablative FLT (p < .05)., Conclusions: Assuming that the dermal response is comparable in AD, PIH, and BN, at the given settings, ablative FLT may induce fibrosis, whereas treatment with nonablative FLT does not. Whether formation of fibrosis has to be regarded as dermal remodeling or a subtle subclinical form of scarring should be investigated in future research., (© 2011 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.)

Background: Nonsegmental vitiligo is considered to be an autoimmune disease and is known to be associated with other autoimmune diseases, particularly affecting the thyroid. Screening patients with nonsegmental vitiligo for thyroid function and for the presence of thyroid autoantibodies has been recommended., Objective: To investigate the prevalence of thyroid dysfunction and thyroid peroxidase-specific (TPO) antibodies in a large cohort of patients with nonsegmental vitiligo in order to help decide whether routine screening is justified., Methods: A total of 434 adults with nonsegmental vitiligo who were referred to our institute were enrolled. Thyroid function and anti-TPO antibody titres were assessed in those patients who had no history of thyroid disease or recent thyroid screening., Results: Forty-three patients had already been diagnosed with thyroid dysfunction, and in 27 patients the general practitioner had performed a thyroid function test with negative results <3months previously. In these patients, thyroid function assessment was not repeated. The remaining 364 patients were screened for thyroid dysfunction. Overt hypothyroidism was newly diagnosed in three (0·8%) patients; subclinical disease was found in 10 (2·7%) patients and increased levels of TPO antibodies, without thyroid disease, were found in 49 (13·5%) patients. An elevated risk for thyroid disease was found among older women and in women with a positive family history of thyroid disease., Conclusion: The overall prevalence of thyroid dysfunction in adult patients with nonsegmental vitiligo was higher than reported in the general population. However, the number of newly diagnosed cases with overt and subclinical thyroid dysfunction in our population was low. Most patients had already been diagnosed by their general practitioner and had symptoms indicative for thyroid disease. Thyroid disease was found predominantly among older women and in subjects with a positive family history of thyroid disease. Thyroid screening including anti-TPO antibodies is advisable in these high-risk subpopulations., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Background: There is a need for biomarkers to screen the effectiveness of (novel) therapeutic agents for psoriasis at an early stage., Objective: We aimed to determine which of the changes in psoriatic skin correlates best with clinical improvement 4 weeks after effective adalimumab therapy., Methods: Twenty-two psoriatic arthritis patients were randomized to receive adalimumab or placebo. T cell numbers and markers of innate immunity were estimated in lesional and nonlesional skin biopsies at baseline and after 4 weeks of treatment., Results: CD161+ and elastase+ dermal cells in lesional skin were significantly reduced upon 4 weeks of successful adalimumab treatment compared with placebo., Conclusion: Early improvement of psoriasis lesions during adalimumab therapy is associated with a marked reduction of infiltrated dermal CD161+ T cells and elastase+ neutrophils, suggesting that these parameters could be used as biomarkers to monitor early changes after active treatment in small proof-of-concept studies of short duration., (Copyright © 2012 S. Karger AG, Basel.)

Background:   Demonstration of adequate reliability and validity is sufficient for concluding that an instrument is applicable for descriptive and predictive purposes, but before we can confidently use an outcome measure in clinical trials, the responsiveness (synonymous with sensitivity to change) and minimal clinically important difference (MCID) should be known. With this study, we aimed to assess responsiveness and MCID of four outcome measures used in atopic eczema: the Severity Scoring of Atopic Dermatitis (SCORAD), the objective SCORAD, Eczema Area and Severity Index (EASI), and the Patient-Oriented Eczema Measure (POEM)., Methods:   Data of three randomized controlled trials were used. To demonstrate responsiveness, we plotted receiver operating characteristic (ROC) curves. MCID was estimated using mean change scores of patients that showed a relevant improvement. Bland and Altman methods were used to quantify the limits of agreement., Results:   Area under the ROC curve for the SCORAD was 0.70 [95% confidence interval (CI): 0.61-0.78], for the objective SCORAD, 0.73 (95% CI: 0.70-0.77), for the EASI, 0.67 (95% CI: 0.60-0.76), and for the POEM, 0.67 (95% CI: 0.59-0.75). Scores above 0.70 represent a fair responsiveness. The MCID was 8.7 points for the SCORAD, 8.2 for the objective SCORAD, 6.6 for the EASI, and 3.4 for the POEM., Conclusion:   The objective SCORAD and SCORAD showed a fair responsiveness. The MCIDs are an important prerequisite for the interpretation of published eczema trials and for the planning/sample size estimation of future trials., (© 2011 John Wiley & Sons A/S.)

Background: Teledermatology, the application of telemedicine in the field of dermatology, has similar accuracy and reliability as physical dermatology. Teledermatology has been widely used in daily practice in the Netherlands since 2005 and is fully reimbursed., Objectives: This study prospectively investigated the effect of teledermatology on efficiency, quality and costs of care when integrated in daily practice and applied following patient selection by the general practitioner (GP)., Methods: Teledermatology consultations between GP and regional dermatologist were performed in daily GP practice in the Netherlands. Efficiency of care was measured by the decrease in the number of physical referrals to the dermatologist. Quality of care was measured by the percentage of teleconsultations for second opinion, physical referrals resulting from these teleconsultations, the response time of the dermatologists and educational effect experienced by the GP. Costs of conventional healthcare without teledermatology were compared with costs with teledermatology., Results: One thousand, eight hundred and twenty GPs and 166 dermatologists performed teledermatology, and 37,207 teleconsultations performed from March 2007 to September 2010 were included. In the group of patients where the GP used teleconsultation to prevent a referral (n =26,596), 74% of physical referrals were prevented. In the group of patients where the GP used teleconsultation for a second opinion (n =10,611), 16% were physically referred after teleconsultation. The prevented referral rate in the total population was 68%. The mean response time of dermatologists was 4·6 h (median 2·0). GPs indicated that there was a beneficial educational effect in 85% of the teleconsultations. The estimated cost reduction was 18%., Conclusions: Teledermatology can lead to efficient care probably at lower cost. We are therefore of the opinion that teledermatology following GP selection should be considered as a possible pathway of referral to secondary care., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Hypertrophic scars are difficult to improve and remain a therapeutic challenge. Several lasers and light sources have been evaluated in the past decades and have been shown to improve hypertrophic scars. However, a systematic review is not available. To assess current evidence of efficacy of all laser and intense pulsed light therapies used in the treatment of hypertrophic scars, we performed a systematic review searching electronic databases MEDLINE, EMBASE and CENTRAL. The quality of the controlled clinical trials was evaluated according to the Cochrane Collaboration's tool for assessing risk of bias. Thirteen articles involving seven different lasers met the inclusion criteria. Most evidence was found for the pulsed dye laser (PDL) 585 nm (eight studies), followed by the PDL 595 nm (two studies), whereas limited evidence (one trial per laser) was available for the fractional nonablative laser 1540 nm, CO₂ laser 10,600 nm, low-level laser therapy, Nd:YAG laser 532 nm and Erbium:YAG laser 2940 nm. Treatment recommendations should be formulated with caution as current evidence is insufficient for comparing the efficacy of different laser therapies. The PDL 585 nm showed a low efficacy for the treatment of hypertrophic scars. With moderate efficacy, the PDL 595 nm is promising, although more research is necessary. Little evidence was found for the efficacy of other lasers. Future research, with a low risk of bias, well-defined scar characteristics, validated outcome measures, standardized measurement methods, follow-up periods of at least 6 months and well-defined laser settings, is needed., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)