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Frontal fibrosing alopecia (FFA) is a progressive, scarring alopecia of the frontotemporal scalp that poses a substantial burden on quality of life. Large-scale global profiling of FFA is lacking, preventing the development of effective therapeutics.To characterize FFA compared to normal and alopecia areata using broad molecular profiling and to identify biomarkers linked to disease severity.This cross-sectional study assessed 33,118 genes in scalp using RNA sequencing and 350 proteins in serum using OLINK high-throughput proteomics. Disease biomarkers were also correlated with clinical severity and a fibrosis gene set.Genes differentially expressed in lesional FFA included markers related to Th1 (IFNγ/CXCL9/CXCL10), T-cell activation (CD2/CD3/CCL19/ICOS), fibrosis (CXCR3/FGF14/FGF22/VIM/FN1), T-regulatory (FOXP3/TGFB1/TGFB3), and Janus kinase/JAK (JAK3/STAT1/STAT4) (Fold changes [FCH]1.5, FDR.05 for all). Only one protein, ADM, was differentially expressed in FFA serum compared to normal (FCH1.3, FDR.05). Significant correlations were found between scalp biomarkers (IL-36RN/IL-25) and FFA severity, as well as between JAK/STAT and fibrosis gene-sets (r.6; P .05).This study was limited by a small sample size and predominantly female FFA patients.Our data characterize FFA as an inflammatory condition limited to scalp, involving Th1/JAK skewing, with associated fibrosis and elevated T-regulatory markers, suggesting the potential for disease reversibility with JAK/STAT inhibition.

Treatment of congenital ichthyoses primarily focuses on reversing skin scaling and is not pathogenesis based. Recent studies showed Th17 immune skewing, as in psoriasis, across the spectrum of ichthyosis, suggesting that targeting this pathway might broadly reduce disease severity.To determine whether secukinumab, an IL-17A inhibitor, can improve ichthyosis across several congenital ichthyosis subtypes.Exploratory 16-week double-blind, randomized, placebo-controlled trial comparing secukinumab 300 mg every 4wks to placebo (1:1 randomization) in adults with the four major congenital ichthyosis subtypes (NCT03041038), followed by a 16-week open-label phase to evaluate response of the placebo-first group and a 20-week extension for safety. Significant differences in secukinumab- vs. placebo-treated subjects at Wk16 in the Ichthyosis Area Severity Index (IASI) score and lack of increased mucocutaneous bacterial and/or fungal infections were the co-primary efficacy and safety endpoints, respectively.Two tertiary referral centers: Northwestern University Feinberg School of Medicine, Chicago, and Mount Sinai Icahn School of Medicine, New York.Twenty subjects ≥ 18 yo with genotype-confirmed epidermolytic ichthyosis, Netherton syndrome, lamellar ichthyosis, or congenital ichthyosiform erythroderma with at least moderate erythroderma.IL-17A inhibition did not significantly reduce severity or increase mucocutaneous infections among the 18 who completed the 16-week double-blind phase. Five patients with 29-50% clinical improvement at Wk32 requested drug continuation. Th17-related biomarkers were not significantly reduced vs. baseline or placebo-treated levels.Small sample size; heterogeneous ichthyosis subsets.IL-17 inhibition with secukinumab is safe, but not efficacious across the spectrum of adult ichthyoses. CLINICALTRIALS.NCT03041038; first posted on 02/02/2017.

Background In the SARS-CoV-2/COVID-19 pandemic, we need to understand the impact of immunomodulatory medications on COVID-19 symptom severity in patients with inflammatory diseases, including the type 2/Th2 polarized skin disease, atopic dermatitis (AD). Objective Because it is believed that type 1/Th1 immunity controls viral infections and that there is a Th1/Th2 counter-regulation, we hypothesized that Th2 targeting with the IL-4Rα-antagonist, dupilumab, in patients with moderate-to-severe AD would rebalance the Th1/Th2 axis, potentially leading to attenuated COVID-19 symptoms. Methods A total of 1237 patients with moderate-to-severe AD in the Icahn School of Medicine at Mount Sinai Department of Dermatology were enrolled in a registry. Patients were screened for COVID-19-related symptoms and assigned a severity score (asymptomatic [0]-fatal [5]). Scores were compared among 3 treatment groups: dupilumab (n = 632), other systemic treatments (n = 107), and limited/no treatment (n = 498). Demographic and comorbid covariates were adjusted by multivariate generalized logistic regression models. Results The dupilumab-treated group showed reduced incidence and severity of COVID-19 symptoms versus other treatment groups. Dupilumab-treated patients were less likely to experience moderate-to-severe symptoms versus patients on other systemics (P = .01) and on limited/no treatment (P = .04), and less likely to experience any symptoms versus patients on other systemics (P = .01). This effect was seen in our entire cohort and in the subgroup of patients with verified COVID-19 or high-risk exposure. Conclusions Patients on dupilumab experienced less severe COVID-19 manifestations and lesser symptoms compared with patients on other systemics and on limited/no treatment. These results suggest that Th2 modulation with dupilumab may have a protective effect on anti-viral immune response in patients with AD.

Background: Brodalumab is an interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe plaque psoriasis. Our prior publication reported significant disease improvement with brodalumab in psoriasis patients who had previously failed treatment with an anti-IL-17A agent. Objectives: We set out to investigate factors that differed between the patients who had treatment success with brodalumab and those who did not, including disease severity and underlying comorbidities. Other secondary endpoints included the extent of improvement in non-responders, characterization of the patients who discontinued early from the trial, and time to improvement on brodalumab. Methods: We conducted an Institutional Review Board (IRB)-approved open-label study of a total of 39 subjects enrolled at 3 sites with moderate-to-severe psoriasis. All patients previously failed treatment with an IL-17A agent. Subjects received brodalumab 210 mg via subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every 2 weeks, up to week 16. Subjects were evaluated monthly for improvement in PASI and sPGA. Results: Of the baseline comorbidities assessed, the only statistically significant difference between responders and non-responders was the presence of higher weight/BMI in non-responders in the AO dataset; this trend disappeared in the NRI dataset. Of the patients that dropped out of the trial early, 3 of the 5 had PASI improvements of >60%. A rapid onset to disease improvement was seen in the trial. Conclusion: These results indicate that brodalumab may be a good treatment choice for psoriasis patients, including those with severe disease and/or underlying comorbidities.

BACKGROUND Treatments for alopecia areata (AA) patients with extensive scalp hair loss are limited, and recent evidence supports a role for type 2 T-cell (Th2)-immune response in AA. Dupilumab, a monoclonal antibody inhibiting Th2 signaling, approved for type 2 diseases including atopic dermatitis, was evaluated in AA patients. METHODS Alopecia areata patients with and without concomitant atopic dermatitis were randomized 2:1 to receive weekly subcutaneous dupilumab (300 mg) or placebo for 24 weeks, followed by another 24-week dupilumab open-label phase. The primary outcome was change from baseline in the Severity of Alopecia Tool (SALT) score at week 24; secondary outcomes included a range of measures of hair regrowth. RESULTS Forty and 20 patients were assigned to the dupilumab and placebo arms, respectively. At week 24, disease worsening was documented in the placebo arm, with a least-squares mean change in the SALT score of -6.5 (95% confidence-interval [CI], -10.4 to -2.6), versus a change of 2.2 (95% CI, -0.6 to 4.94) in the dupilumab arm (p

The presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment with imiquimod 3.75%. Biopsies were collected prospectively from 21 patients and examined histologically. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Imiquimod decreased number of AKs by study endpoint at week 14 (p p p p

Background Psoriasis of the intertriginous, anogenital, and facial regions remains a therapeutic challenge, with current algorithms lacking a topical agent that exhibits both high efficacy and minimal side effects. Objective To assess the safety and efficacy of crisaborole 2% ointment—a nonsteroidal phosphodiesterase 4 inhibitor—in the treatment of intertriginous, anogenital, and facial psoriasis. Methods A double-blind, randomized, vehicle-controlled trial was conducted in 21 participants. Participants were randomized 2:1 to receive 4 weeks of twice-daily treatment with either crisaborole 2% ointment (n = 14) or vehicle ointment (n = 7), followed by 4 weeks of open-label treatment with crisaborole 2% ointment. Disease severity was measured by using the Target Lesion Severity Scale (TLSS). Results After 4 weeks, participants in the crisaborole group demonstrated 66% improvement compared with 9% in the vehicle group (P = .0011). Participants in the crisaborole group continued to experience improvement through the open-label phase, demonstrating 81% lesional improvement by week 8, with 71% of these participants achieving clinical clearance. There were no adverse events. Limitations The study was limited to a single tertiary care center and small sample size. Conclusion Treatment with crisaborole 2% ointment was well-tolerated and led to clinical improvement in participants with intertriginous, anogenital, or facial psoriasis.

BACKGROUND Alopecia areata (AA) is characterized by immune dysregulation in both scalp and blood, but a large-scale approach establishing biomarkers of AA incorporating both scalp tissue and serum compartments is lacking. We aimed to characterize the transcriptomic signature of AA lesional and nonlesional scalp compared to healthy scalp and determine its relationship with the blood proteome in the same individuals, with comparative correlations to clinical AA disease severity. METHODS We evaluated lesional and nonlesional scalp tissues and serum from patients with moderate-to-severe AA (n = 18) and healthy individuals (n = 8). We assessed 33,118 genes in AA scalp tissue using RNAseq transcriptomic evaluation and 340 inflammatory proteins in serum using OLINK high-throughput proteomics. Univariate and multivariate approaches were used to correlate disease biomarkers with Severity of Alopecia Tool (SALT). RESULTS A total of 608 inflammatory genes were differentially expressed in lesional AA scalp (fold change/FCH>1.5, false discovery rate/FDR

Although there is increased understanding of the alopecia areata (AA) pathogenesis based on studies in scalp tissues, little is known about its systemic profile.To evaluate the blood proteomic signature of AA and determine biomarkers associated with increased disease severity.In a cross-sectional study, we assessed 350 inflammatory and cardiovascular proteins using OLINK high-throughput proteomics in patients with moderate to severe AA (n = 35), as compared with healthy individuals (n = 36), patients with moderate to severe psoriasis (n = 19), and those with atopic dermatitis (n = 49).Seventy-four proteins were significantly differentially expressed between AA and control individuals (false discovery rate,.05) including innate immunity (interleukin [IL] 6/IL-8), T helper (Th) type 1 (interferon [IFN] γ/CXCL9/CXCL10/CXCL11), Th2 (CCL13/CCL17/CCL7), Th17 (CCL20/PI3/S100A12), and cardiovascular-risk proteins (OLR1/OSM/MPO/PRTN3). Eighty-six biomarkers correlated with AA clinical severity (P .05), including Th1/Th2, and cardiovascular/atherosclerosis-related proteins, including SELP/PGLYRP1/MPO/IL-18/OSM (P .05). Patients with AA totalis/universalis showed the highest systemic inflammatory tone, including cardiovascular risk biomarkers, compared to control individuals and even to patients with atopic dermatitis and those with psoriasis. The AA profile showed some Th1/Th2 differences in the setting of concomitant atopy.Our analysis was limited to 350 proteins.This study defined the abnormalities of moderate to severe AA and associated circulatory biomarkers. It shows that AA has systemic immune, cardiovascular, and atherosclerosis biomarker dysregulation, suggesting the need for systemic treatment approaches.

Alopecia areata (AA) is a common autoimmune disease that results in non-scarring hair loss. AA pathogenesis is thought to involve multiple inflammatory cytokines. Apremilast is a phosphodiesterase 4 (PDE4) inhibitor that reduces pro-inflammatory cytokine production. Recent studies demonstrate upregulation of PDE4 in human scalp lesions of AA patients and hair regrowth in a humanized AA mouse model upon apremilast treatment, suggesting a possible potential of apremilast in AA. To assess the efficacy and safety of apremilast in AA, we conducted a double-blind, placebo-controlled single-center pilot study in 30 moderate-to-severe AA patients (≥ 50% scalp involvement) that were randomized 2:1 to receive apremilast (n = 20) or placebo (n = 10) orally for 24 weeks. The primary endpoint was the percentage of patients achieving 50% reduction in severity of alopecia tool (SALT) score (SALT50) at 24 weeks compared to baseline, and the secondary endpoints included the percent change in SALT score at weeks 24 and 48. Eight patients in the apremilast arm withdrew prior to week 24 along with two patients in the placebo group, mostly due to lack of efficacy and adverse events. At 24 weeks, only 1 of 12 apremilast-treated subjects achieved SALT50, and similarly 1 of 8 placebo-treated subjects achieved SALT50. The difference between the mean percent improvement in SALT score at week 24 compared to baseline of the two study arms was not statistically significant (p = 0.38). The lack of treatment response in most of our patients argues against a pathogenic role for PDE4 specifically in moderate-to-severe AA, but targeting this pathway may still be of value in patients with mild AA as there is less of an inflammatory burden in this population. However, future larger studies may be needed to conclude apremilast’s lack of efficacy in moderate-to-severe AA.

Acne vulgaris affects millions of individuals and can lead to psychosocial impairment as well as permanent scarring. Previous studies investigating acne pathogenesis have either examined a targeted set of biological parameters in a modest-sized cohort or carried out high-throughput assays on a small number of samples. To develop a more comprehensive understanding of acne pathophysiology, we conducted an in-depth multi-omic study of 56 acne patients and 20 individuals without acne. We collected whole blood, skin punch biopsies, microbiota from skin follicles, and relevant clinical measurements to understand how multiple factors contribute to acne. We provide an integrative analysis of multi-omics data that results in a molecular network of acne. Comparisons of lesional and non-lesional skin highlighted multiple biological processes, including immune cell and inflammatory responses, response to stress, T cell activation, lipid biosynthesis, fatty acid metabolism, keratinocytes, antimicrobial activity, epithelial cell differentiation, and response to wounding, that are differentially altered in acne lesions compared to non-lesions. Our results suggest baseline differences in the skin that may predispose individuals to develop acne. These datasets and findings offer a framework for new target identification and reference for future studies.

Background: The presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma (SCC) by greater than six-fold. It is difficult to predict which AKs will progress to become SCC, and topical treatments such as imiquimod are used to treat the entire affected field indiscriminately, effectively eliminating AKs in 50% of patients but sometimes resulting in severe inflammation and pain. Defining biomarkers to predict response to treatment would be helpful to guide therapy. Objectives: To evaluate the effect of imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment in patients treated with imiquimod. Methods: Biopsies were collected prospectively from 21 patients with presumptive AK and examined histologically. All patients were treated with imiquimod 3.75% on a short cyclical treatment regimen. 19 patients had available pre-treatment AK biopsies and 14 patients had paired pre- and post-treatment biopsies. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Results: Imiquimod significantly decreased total number of AKs by study endpoint at week 14 (p Conclusions: NanoString analysis of AKs pre- and post-treatment with imiquimod shows downregulation of genes implicated in oncogenesis and immune suppression. Differences in gene expression were found between pre-treatment samples in CR versus IR, suggesting that higher levels of inflammation pre-treatment may play a part in regression of AKs. Further, presence of adverse effects in response to therapy was associated with an improved response to imiquimod. These findings show that the pre-treatment immune micro-environment impacts responsiveness of AKs to imiquimod and that clinical inflammation during treatment is associated with AK resolution. Further characterization of the immune micro-environment in AKs may help develop biomarkers predictive of response to topical immune modulators and may guide therapy in patients with high numbers of AKs at risk for SCC. Citation Format: Megan H. Trager, Emanuelle Rizk, Sharon Rose, Branden Lau, Ben Fullerton, Kuixi Zhu, Jaya Pradhan, Michael Moore, Ayush Chandra, Margaret Bogardus, Giselle Singer, Robyn Gartrell-Corrado, Rui Chang, Larisa Geskin, Yvonne Saenger, Gary Goldenbery. Transcriptomic analysis identifies changes in gene expression in Actinic Keratoses after treatment with imiquimod and differential gene expression [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO063.

Background IL-22 is potentially a pathogenic cytokine in patients with atopic dermatitis (AD), but the molecular effects of IL-22 antagonism have not been defined in human subjects. Objective We sought to evaluate the cellular and molecular effects of IL-22 blockade in tissues from patients with moderate-to-severe AD. Methods We assessed lesional and nonlesional skin from 59 patients with moderate-to-severe AD treated with anti–IL-22 (fezakinumab) versus placebo (2:1) using transcriptomic and immunohistochemistry analyses. Results Greater reversal of the AD genomic profile was seen with fezakinumab versus placebo, namely 25.3% versus 10.5% at 4 weeks (P = 1.7 × 10−5) and 65.5% versus 13.9% at 12 weeks (P = 9.5 × 10−19), respectively. Because IL-22 blockade showed clinical efficacy only in patients with severe AD, we used baseline median IL-22 mRNA expression to stratify for high (n = 30) and low (n = 29) IL-22 expression groups. Much stronger mean transcriptomic improvements were seen with fezakinumab in the IL-22–high drug-treated group (82.8% and 139.4% at 4 and 12 weeks, respectively) than in the respective IL-22–high placebo-treated group (39.6% and 56.3% at 4 and 12 weeks) or the IL-22–low groups. Significant downregulations of multiple immune pathways, including TH1/CXCL9, TH2/CCL18/CCL22, TH17/CCL20/DEFB4A, and TH22/IL22/S100A's, were restricted to the IL-22–high drug group (P Conclusions This is the first report showing a profound effect of IL-22 blockade on multiple inflammatory pathways in AD. These data, supported by robust effects in patients with high IL-22 baseline expression, suggest a central role for IL-22 in AD, indicating the need for a precision medicine approach for improving therapeutic outcomes in patients with AD.

Background Interleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function. Objective Evaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD). Methods We performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point. Results At 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 ± 2.7 in the fezakinumab arm and 8.0 ± 3.1 in the placebo arm (P = .134). In the severe AD patient subset (with a baseline SCORAD of ≥50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 ± 3.8 vs 9.6 ± 4.2, P = .029) and 20 weeks (27.4 ± 3.9 vs 11.5 ± 5.1, P = .010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% ± 2.4 vs 6.2% ± 2.7; P = .009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 ± 0.2 vs 0.3 ± 0.1; P = .034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections. Limitations The limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD. Conclusion Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.

Although ultrasound imaging is employed ubiquitously today, its use to examine and assess the skin is a relatively new technology. We explored the clinical application and use of high-frequency, high-resolution ultrasound in Mohs micrographic surgery.To evaluate the ability of ultrasound to accurately determine lesion length and width of tumor borders in order to reduce the number of surgical stages.This was an institutional review board-approved single-center study of 26 Mohs surgery patients. Ultrasound images were taken to record lesion dimensions, and then the investigator documented clinical estimation of the first stage. Extirpation of the tumor and histological analysis were performed thereafter.The results of 20 patients were included in the analysis. A paired-samples t-test revealed no significant difference between clinical and ultrasound widths (t=-1.324, p=.20). Similarly, there was no significant difference between the lengths found from clinical assessment and ultrasound (t=-1.093, p=.29). For different tumor types, there was no significant difference between clinical and ultrasound widths or lengths for basal cell carcinoma (t=-1.307, p=.23; t=-1.389, p=.20) or squamous cell cancer (t=-0.342, p=.73; t=0.427, p=.68). CONCLUSION There is a diagnostic role for high-resolution ultrasound in Mohs surgery regarding the delineation of surgical margins, but its limitations preclude its practical adoption at this time.

Background Chronic hand and foot eczema (CHFE), a prevalent debilitating disorder affecting approximately 15% of the population, presents a socioeconomic and psychosocial burden for patients and often follows a chronic course, refractory to conventional therapies. Thus, a large need exists for more effective therapeutics; the excimer laser (308 nm) is effective for some inflammatory skin diseases, but its efficacy has not been evaluated for CHFE. Methods The study is a retrospective chart review conducted on 30 patients with recalcitrant CHFE (19 with hand involvement, four with foot involvement, and seven with both) treated twice weekly with excimer laser (308 nm) single wavelength ultraviolet (UV)B radiation between January 2013 and December 2014. Results Improvements in clinical scores included a 69% reduction in average physician's global assessment (PGA) scores (from 2.77 at baseline to 0.87 after treatment, P < 0.0001) with a parallel reduction in average modified total lesion/symptom scores of 70% (from 10.2 to 3.1, P < 0.0001). Only mild sunburn-like reactions were observed. Conclusion This report evaluates excimer laser for patients with refractory CHFE and shows excellent and sustained efficacy for this treatment. Compared to other UV therapies, excimer laser offers lower cumulative doses of UV radiation by targeting specific areas. This effective treatment should be considered alone or in combination with other established or newer therapies.

Ingenol mebutate gel is a topical field treatment of actinic keratosis (AK). One of several proposed mechanisms of action for ingenol mebutate is induction of cell death in proliferating keratinocytes, suggesting a preferential action on AKs rather than healthy skin. Local skin reactions (LSRs) during 2 sequential 4-week cycles of AK treatment with ingenol mebutate gel 0.015% on the face or scalp were evaluated to test the hypothesis that reapplication of the study product would produce lower LSR scores than during the first treatment cycle. In this unblinded study, 20 participants with AKs on the face or scalp were treated with ingenol mebutate gel 0.015% once daily for 3 days in 2 sequential 4-week cycles. Composite LSR scores were evaluated during both cycles. The composite LSR score during the second cycle was found to be significantly lower than the first cycle (P=.0002). The proportion of participants who experienced LSRs in the second treatment cycle was less than the first cycle. Ingenol mebutate gel 0.015% may cumulatively reduce the burden of sun-damaged skin over 2 treatment cycles by targeting and removing transformed keratinocytes.

To evaluate the efficacy of sequential therapy of cryotherapy and sinecatechins 15% ointment BID versus cryotherapy alone in treatment of external genital warts (EGW).Forty-two subjects with at least two EGW lesions underwent cryotherapy to all lesions. One week following cryotherapy, subjects were randomized 1:1 to receive either no additional treatment or treatment with sinecatechins 15% ointment BID up to 16 weeks or until complete clearance. The total number of visible baseline and new EGW were recorded at each visit. Subjects were followed for a total of 65 weeks post-treatment.There was a significant reduction in mean number of lesions from baseline after 16 weeks of treatment in the cryotherapy-sinecatechins ointment group compared to cryotherapy alone (-5.0 lesions vs -2.1 lesions respectively, P=0.07).Cryotherapy plus sinecatechins 15% ointment BID resulted in a significant improvement in the reduction of EGW compared to cryotherapy alone. Clinicaltrials.gov registration identifier: NCT02147353.

Background Pseudoxanthoma elasticum (PXE) is a systemic connective tissue disorder involving elastic fiber calcification and fragmentation with major clinical manifestations occurring in the cutaneous, ocular, and cardiovascular systems. Normalization of the serum calcium-phosphate product through hemodialysis in a previous patient with perforating periumbilical PXE and elevated serum phosphate resulted in regression of skin lesions. Objective We sought to study the effect of pharmacologically limiting the intestinal absorption of phosphate in patients with PXE. Methods Patients received baseline skin examinations, target skin lesion evaluation, and photography; renal function tests and serum calcium and phosphate levels; urine calcium, phosphate, and creatinine levels; skin biopsy; and eye examinations and indocyanine-green angiography. Patients were treated with aluminium hydroxide tablets or liquid and returned every 2 to 4 months for skin photography and lesion evaluation. Repeated skin biopsies were performed on clinically improved target sites. Ophthalmologic evaluation was obtained at yearly intervals. Results Of 6 patients, 3 showed significant clinical improvement of skin lesions and all 3 of these patients showed histopathologic regression of disease in their target lesions. No deterioration of eye disease was seen in any of the 6 patients at 1-year follow-up. Conclusion Our results demonstrate that the calcification seen in PXE may be reversible in some patients. This could hold true for eye and vascular lesions and for skin. Further studies supporting these results could reveal the first real treatment option for PXE.

The safety and efficacy of 0.1% tacrolimus ointment for the treatment of psoriasis on the face, intertriginous areas, or both were evaluated in an open-label, clinical trial of 21 patients with psoriasis. Patients applied 0.1% tacrolimus ointment twice daily for 8 weeks. Efficacy was assessed through the investigator's evaluation of the individual signs and symptoms of psoriasis, and the physician's global evaluation of change in disease status. Assessments of cutaneous atrophy and other adverse events were made throughout the study to evaluate the safety of tacrolimus ointment. A total of 21 patients were enrolled in the study; 21 patients at least 18 years of age received study medication. Statistically significant improvement in the physician's assessment of the individual signs and symptoms was observed during the study. A total of 81% of patients (17 of 21) experienced complete clearance at day 57 (end of treatment). Only 2 patients reported adverse events, which were limited to itching and the feeling of warmth at the application site. None of the patients had atrophy, telangiectasia, or striae develop during the study. In summary, tacrolimus 0.1% ointment may be a safe and effective treatment option for patients with psoriasis on the face, intertriginous areas, or both. (J Am Acad Dermatol 2003;48:564-8.)

Background The treatment options for facial and intertriginous skin are limited because these sites are more susceptible to corticosteroid-induced atrophy. The long-term management of these corticosteroid-sensitive sites requires the use of dosing regimens that are effective, but also safe. Methods The affected areas in 21 patients with atopic dermatitis were treated twice daily for 2 weeks, and then once daily for two consecutive days each week for eight more weeks. Results After 2 weeks, treatment success occurred in 95% of facial and intertriginous lesions and also in 95% of nonfacial, nonintertriginous lesions. During long-term therapy, treatment success was maintained in > 76% of facial and intertriginous lesions, and > 76% of other lesions. Recurrence rates were low, and skin atrophy and telangiectasia did not occur. Conclusions Patients with atopic dermatitis of facial and intertriginous areas were successfully treated with a limited application of fluticasone propionate ointment, 0.005%. The treatment resulted in rapid healing and provided efficacy with a low rate of recurrence and no evidence of skin atrophy or telangiectasia over 8 weeks.

Background: Staphylococcus aureus has been implicated in the pathogenesis of adult hand/foot dermatitis. Objective: The authors hypothesized that retapamulin 1% ointment and clobetasol propionate 0.05% foam would decrease disease severity in subjects with hand/foot dermatitis and provide a higher clearance of Staphylococcus aureus colonization, when compared to vehicle (placebo) ointment and clobetasol propionate 0.05% foam. Methods: Adult subjects with moderate to very severe hand/foot dermatitis had twice-daily topical application of clobetasol propionate 0.05% foam to hands/feet for 14 days and were randomized to apply either retapamulin 1% ointment or vehicle ointment twice daily to hands/feet and nares for five days. Results: Seventy-three percent of subjects in the retapamulin/clobetasol group were clear/almost clear at Day 15 compared to 47 percent of subjects in the vehicle/clobetasol group (p-value of 0.04). The percentage of subjects who had both negative skin and nares cultures and were clear/almost clear was also statistically significant in favor of the retapamulin/clobetasol group at Day 15 (p-value of 0.05). Limitations: Sample size, study population. Conclusion: At Day 15, retapamulin 1% ointment with clobetasol propionate 0.05% foam was more efficacious than vehicle ointment and clobetasol propionate 0.05% foam for disease improvement and Staphylococcus aureus clearance in adult subjects with hand/foot dermatitis.

Acne scarring is a consequence of abnormal resolution of wound healing after damage that occurs in the sebaceous follicle during acne inflammation. No trial to date has evaluated the efficacy of the combination of microdermabrasion and photodynamic therapy for acne scarring. This single-center, double-blinded pilot study enrolled subjects with moderate-to-severe acne scarring who were randomly assigned in a blinded fashion to use aminolevulinic acid and vehicle in a split-face fashion after full-face treatment with microdermabrasion. On average, 80 percent of the patients displayed more improvement in scarring on the aminolevulinic acid split face versus the vehicle split face after five treatments. Using two different noninvasive mechanisms of targeting acne scarring provided for a safe treatment regimen characterized by more efficacious results with respect to higher rates of scarring improvement.

Background Pseudoxanthoma elasticum (PXE) is a rare connective tissue disorder involving fragmentation and mineralization of elastic fibers predominantly in the skin, eyes, and cardiovascular system. Objective The objective of this study was to assess the efficacy of sevelamer hydrochloride on the reversal of elastic fiber calcification and clinical lesions of PXE. Methods This was a randomized, double-blind, placebo-controlled, two-part prospective study. In the first year, 40 patients with PXE were randomized to receive either sevelamer hydrochloride (800 mg by mouth three times daily) or placebo in a 1:1 ratio. In the second year, all patients received sevelamer hydrochloride (800 mg by mouth three times daily). Results In the first year, the placebo and treatment groups' mean calcium scores decreased from 29.52 to 15.97 (41.93% mean improvement) and 27.48 to 16.75 (38.37% mean improvement), respectively. In the second year, the mean calcium scores decreased to 13.36 (53.94%) and 14.03 (51.35%) in these groups. The mean clinical score in the placebo group decreased from 6.25 to 6.05 at year 1 (2% improvement) whereas the mean clinical score in the sevelamer hydrochloride group decreased from 7.10 to 6.55 (7% improvement). In year 2, the scores in the original placebo and sevelamer hydrochloride groups decreased to 5.33 (14% improvement) and 5.72 (19% improvement), respectively. Limitations Magnesium stearate in our placebo and active drugs may have played a confounding role in this study, contributing to the small differences observed in these two groups. Conclusion Sevelamer hydrochloride produced a reduction in both calcification levels and clinical scores; however, this difference was not statistically significant compared with placebo. Future clinical studies should examine the inhibitory role and potential therapeutic effect of magnesium in PXE.

The treatment options for facial and intertriginous skin are limited because these sites are more susceptible to corticosteroid-induced atrophy. The long-term management of these corticosteroid-sensitive sites requires the use of dosing regimens that are effective, but also safe.The affected areas in 21 patients with atopic dermatitis were treated twice daily for 2 weeks, and then once daily for two consecutive days each week for eight more weeks.After 2 weeks, treatment success occurred in 95% of facial and intertriginous lesions and also in 95% of nonfacial, nonintertriginous lesions. During long-term therapy, treatment success was maintained in76% of facial and intertriginous lesions, and76% of other lesions. Recurrence rates were low, and skin atrophy and telangiectasia did not occur.Patients with atopic dermatitis of facial and intertriginous areas were successfully treated with a limited application of fluticasone propionate ointment, 0.005%. The treatment resulted in rapid healing and provided efficacy with a low rate of recurrence and no evidence of skin atrophy or telangiectasia over 8 weeks.

Background: Actinic keratosis (AK) is the earliest clinical manifestation of squamous cell carcinoma. Metastatic SCC causes the majority of the 1300 to 2300 deaths attributed to nonmelanoma skin cancer in the United States each year. Recent studies have shown that intralesional administration of interferon can be used successfully in the treatment of AK. Objective: Imiquimod is an immune response modifier, currently approved for the treatment of genital warts. The topically applied immune response modifier acts by up-regulating interferon and other cytokines involved in the cell-mediated immune response at the site of application. The aim of this was to determine the efficacy and safety of imiquimod 5% cream for the treatment of AK. Methods: Twenty-two patients with AK lesions were treated with imiquimod 5% cream, initially at 3 times per week for 8 weeks, or until total clearance of lesions. Patients applied imiquimod to lesions on one side of the body and vehicle cream to the other side. A total of 17 patients who completed treatment were evaluated for number of lesions and adverse reactions before treatment and at weeks 2, 4, 6, and 8 after initiation of treatment. AK lesions were also assessed 4 and 8 weeks after treatment. Results: A significant reduction in the average number of lesions per patient was observed for patients treated with imiquimod. The most frequent reactions to treatment were erythema, itching, and scabbing; however, all adverse events were mild to moderate. Conclusion: Imiquimod 5% cream may be a promising treatment for AK. (J Am Acad Dermatol 2002;47:553-6.)

Short-contact application of 0.1% tazarotene gel for acne was devised to minimize local adverse effects. Its efficacy and safety are unknown.To assess acne improvement and tolerability during 12 weeks of short-contact treatment with 0.1% tazarotene gel vs a nonmedicated gel control.A randomized, masked, vehicle-controlled trial.Outpatient facilities at an urban medical school and an affiliated suburban office practice.Ninety-nine volunteers with facial acne were enrolled; 81 completed the study.Thirty-three patients were randomly assigned to each of 3 groups: T + T applied 0.1% tazarotene gel twice daily, T + V applied 0.1% tazarotene gel once daily and vehicle gel once daily, and V + V applied vehicle gel twice daily. Patients adjusted the contact period as tolerated, between 30 seconds and 5 minutes per application.Acne efficacy by reduction in acne lesions, treatment success (50%-100% improvement in global response to treatment) and improvement in overall disease severity. Local adverse effects, scored from none to severe.By week 12, T + T and T + V achieved significantly greater improvement in acne than V + V based on mean percentage reduction in noninflammatory lesions (46% and 41% vs 2%; P =.002) and inflammatory lesions (38% and 34% vs 9%; P =.01), percentage of treatment successes (64% and 61% vs 15%; P.001), and reduction in overall disease severity (30% and 29% vs 3%; P.001). Local adverse effects did not differ significantly among the 3 groups after week 4.Short-contact 0.1% tazarotene gel therapy is a safe and effective new method of acne treatment.

Background: Facial and intertriginous skin is more susceptible to corticosteroid-induced atrophy. Dosing regimens are needed for long-term management of corticosteroid-sensitive sites. Objective: The safety and efficacy of 0.005% fluticasone propionate ointment were assessed in the short-and long-term management of moderate to severe psoriasis of facial and intertriginous areas compared with nonfacial, nonintertriginous areas. Methods: Affected areas in 20 patients with psoriasis were treated twice daily for 2 weeks, then once daily for 2 consecutive days every week for 8 more weeks. Results: More than 50% improvement occurred after 2 weeks (day 15) in 100% of facial and intertriginous lesions and was maintained during long-term therapy in more than 85% of facial and intertriginous lesions. More than 50% improvement for nonfacial, nonintertriginous areas reached only 80% by day 15. Recurrence rates for facial and intertriginous areas were lower than in the nonfacial, nonintertriginous areas. Skin atrophy and telangiectasia did not occur. Facial and intertriginous sites responded more quickly to topical fluticasone propionate ointment than nonfacial, nonintertriginous skin. Conclusion: Limited application of fluticasone propionate ointment over a period of 10 weeks is effective and delays lesion recurrence without causing skin atrophy in patients with moderate to severe psoriasis in areas at risk for corticosteroid application, such as facial and intertriginous areas. (J Am Acad Dermatol 2001;44:77-82.)