February 05, 2019

The primary outcomes were extent of repigmentation, color match, and pattern of repigmentation at 24 weeks.

In patients with vitiligo and a short duration of clinical stability (DS) of 3 to 6 months, use of a novel combination of noncultured epidermal cell suspension (NCES) and noncultured dermal cell suspension (NDCS) is associated with an excellent response compared with the use of NCES alone, according to results of a single-center, randomized clinical trial (ClinicalTrials.gov identifier: NCT03013049). This study was conducted in the Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Findings from the study were published in JAMA Dermatology.

In this pilot study, the investigators sought to evaluate the efficacy of transplantation of NCES plus NDCS vs NCES alone in patients with vitiligo and DS for 3 months to 6 months or DS for >12 months. Overall, 40 patients with focal, segmental, or generalized vitiligo of 3 to 6 months’ duration or >12 months’ duration were enrolled in the study. According to DS, 2 groups containing 20 patients each were recruited for the study (DS in group 1: 3-6 months; DS in group 2: >12 months). Each of these groups was then further randomly assigned to 2 subgroups, A and B.

Patients in subgroups 1A and 2A received NCES alone, whereas patients in subgroups 1B and 2B received NCES plus NDCS. The main study outcomes included the extent of repigmentation, color match, and pattern of repigmentation at 24 weeks. The mean participant age was 24.9±4.0 years; 60% of the patients were women.

In group 1 (DS for 3-6 months), >75% repigmentation at 24 weeks was reported among all 10 patients in subgroup 1B (NCES+NDCS) compared with 3 of 10 patients in subgroup 1A (NCES alone; 100% vs 30%, respectively; P =.003), which was statistically significant. In contrast, in group 2 (DS for >12 months), >75% repigmentation at 24 weeks was observed in 6 of 10 patients in subgroup 2A and in 7 of 10 patients in subgroup 2B (NCES; 60% vs 70%; P >.99), which was not statistically significant.

The investigators concluded that the use of combined NCES and NDCS is a novel technique that can be used successfully in patients with vitiligo who have a short duration of disease stability (ie, 3-6 months). Future studies with larger sample sizes and longer follow-up periods are warranted to monitor the long-term stability of achieved repigmentation and to further examine the implication of dermal mesenchymal stem cells in individuals with active vitiligo.

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Reference

Thakur V, Kumar S, Kumaran MS, Kaushik H, Srivastava N, Parsad D. Efficacy of Transplantation of combination of noncultured dermal and epidermal cell suspension vs epidermal cell suspension alone in vitiligo: a randomized clinical trial [published online January 2, 2019]. JAMA Dermatol. doi: 10.1001/jamadermatol.2018.4919

February 04, 2019

Further research is needed to analyze the mechanisms that are needed for an effective intervention program.

Improving health literacy for patients with psoriasis may lead to improved self-management skills, self-efficacy, and quality of life, according to a study published in the British Journal of Dermatology.

Researchers of this cross-sectional study evaluated the relationship between health literacy, psoriasis severity, medical comorbidities, psoriasis knowledge, quality of life in relation to dermatology, and self-efficacy in patients with moderate to severe psoriasis who participated in the Norwegian Climate Helio therapy program. Questionnaire packets were mailed to 1275 adults who participated in the therapy program between 2011 and 2017.

Of the 825 patients (mean age, 53.3 years) who completed the questionnaires, 47.4% were women, 14.3% were using biological medicines, 35.5% had a history of depression, 66.8% reported joint pain. In regards to the first 5 scales in the health literacy questionnaire, “actively managing my health” (mean score=2.78, SD=0.51) had the highest score and “appraisal of health information” (mean score=2.54, SD=0.54) had the lowest score. In regards to the last 4 scales in the health literacy questionnaire, “understanding health information well enough to know what to do” (mean score=3.56, SD=0.62) had the highest score and “navigating the healthcare system” (mean score=3.10, SD=0.71) had the lowest score.

After bivariate associations were calculated for demographic data, men had a lower score on “actively managing my health” (β=0.1; P =.01), while education level predicted “ability to find good health information” (β=-0.13; P =.01) and “ability to understand health information well enough to know what to do” (β=0.12; P =.01). After bivariate associations were calculated for clinical variables, fewer comorbidities were related to higher scores in “having social support for health” (-β=0.12; P =.01) and “ability to navigate the healthcare system” (-β=0.10; P =.001). Self-efficacy was significantly associated with all health literacy scales, the Dermatology Life Quality Index significantly predicted higher health literacy scores in all scales other than “actively managing health” and “critical appraisal”, and psoriasis knowledge significantly predicated higher health literacy scores in all scales other than “actively managing health” and “social support for health.”

Limitations of this study include the questionnaires only being paper-based and in Norwegian, which could limit response rates, and that all answers are self-reported without clinical verification. Further research is needed to analyze the mechanisms that are needed for an effective intervention program.

The researchers concluded that “improving [health literacy] may be a useful strategy for reducing disparities in self-management skills, self-efficacy and [quality of life]” in patients with moderate to severe psoriasis.

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Reference

Larsen MH, Strumse YAS, Borge CR, Osborne R, Andersen MH, Wahl AK. Health literacy – a new piece of the puzzle in psoriasis care? [published online December 31, 2018]. Br J Dermatol. doi: 10.1111/bjd.17595

February 04, 2019

The primary outcome of the study included identifying somatic mutations linked with cherry angiomas.

A study recently published in JAMA Dermatology has identified 5 genetic factors contributing to cherry angiomas, supporting the role of genetics in its pathogenesis. Hot spot variants of R183 and Q209 suggest a common genetic family between cherry angiomas and other vascular anomalies.

This single-center case series utilized cherry angioma tissue samples from 10 participants whose ages ranged from 26 to 79 years; 60% were women. Samples were paraffin-embedded, formalin-fixed, and sequenced across a collection of 323 cancer-related genes. A large portion of mutations (215 out of 234) were excluded due to poor mapping quality, germline, or evidence of intronic mutations. The primary outcome of the study included identifying somatic mutations linked with cherry angiomas. A functional impact score was assigned to each mutation, with the majority of scores ranging from -2 to 4 and higher scores correlating with higher likelihood of either a driver or functional mutation.

There were 5 samples in which 19 somatic missense mutations with high functional impact scores (≥3.5) were identified, occurring in GNA11 (Q209H) and GNAQ (Q209R, R183G, and Q209H). Vascular entities associated with these genetic hot spots include uveal melanoma, blue nevi, hepatic small-vessel neoplasms, Sturge-Weber syndrome, port-wine stains, and anastomosing and congenital hemangiomas. GNAQ/GNA11-wild-type and -mutant samples did not differ in terms of the number of structural variants, though structural variants were higher in female participants (P =.002).

Limitations to this study included a lack of separation of specific angioma cell variants from others as well as a small sample size. Future studies should include additional samples as well as the prospective biopsy of several lesions on one participant.

The study researchers concluded that there is “a possible role for GNAQ– and GNA11-mediated signaling in [cherry angioma] pathogenesis, a finding consistent with the genetic underpinnings of vascular anomalies. We observed both R183 and Q209 hot spot variants among [cherry angiomas], suggesting that [cherry angiomas] are possibly on a shared genetic spectrum with vascular entities, such as congenital and anastomosing hemangiomas, capillary malformations, port-wine birthmarks, and Sturge-Weber syndrome, and melanocytic growths, such as blue nevi, melanoma associated with blue nevus, and uveal melanoma.”

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Reference

Klebanov N, Lin WM, Artomov M, et al. Use of targeted next-generation sequencing to identify activating hot spot mutations in cherry angiomas [published online January 2, 2019]. JAMA Dermatol. doi: 10.1001/jamadermatol.2018.4231

February 01, 2019

Of the 3 interventions, only patients who received the polyherbal combination tablets showed a significant decrease in facial redness of 40% compared with baseline.

A 4-week regimen of 4000 mg turmeric polyherbal combination tablets was found to be superior to turmeric alone and placebo in improving facial redness, according to a study recently published in the Journal of Integrative Medicine.

In this prospective, single-center, grader-blinded, double-blind randomized pilot study, generally healthy patients aged 25 to 60 years (N=28) completed the trial at the Department of Dermatology, University of California, Davis from August 2016 and July 2017. Participants were each given a bottle of 240 tablets and instructed to take 4 tablets orally twice daily. The tablets contained one of 3 possible interventions: placebo (n=9), turmeric (n=10), and turmeric polyherbal supplements (n=9). Facial redness was assessed by clinical grading and image-based analysis at baseline and at 4 weeks.

Of the 3 interventions, only patients who received the polyherbal combination tablets showed a significant decrease in facial redness of 40% compared with baseline (P =.03). There were no statistically significant changes in facial redness in either the placebo or turmeric tablet groups. A positive correlation was found between facial redness intensity and distribution that trended toward decrease only in the polyherbal combination group, although this trend was not significant (P =.1).

Limitations of this study included short study duration, although facial redness can be detected at an earlier stage than clinical changes. Participants were advised to avoid all turmeric-containing foods in their diets during the study course, but intake of other herbs would have been difficult to monitor.

These findings suggest that the antioxidant and anti-inflammatory properties of the turmeric-containing polyherbal tablet play a role in the factors related to facial erythema. Further studies are warranted to quantify the effects of turmeric polyherbal formulations.

Disclosure: One author declared affiliations with the pharmaceutical industry. Please refer to reference for a complete list of authors’ disclosures.

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Reference

Vaughn AR, Pourang A, Clark AK, Burney W, Sivamani RK. Dietary supplementation with turmeric polyherbal formulation decreases facial redness: a randomized double-blind controlled pilot study [published online November 22, 2018]. J Integr Med. doi: 10.1016/j.joim.2018.11.004

February 01, 2019

Cosentyx is a human interleukin-17A antagonist

According to pooled data from four Phase 3 studies, treatment with secukinumab (Cosentyx; Novartis) was associated with improvement in mobility, self-care, and usual activities (e.g., work, study, housework, family or leisure activities) when compared with placebo in patients with moderate-to-severe plaque psoriasis.

In the ERASURE, FIXTURE, FEATURE, and JUNCTURE trials, psoriasis patients who reported problems in these quality of life measures (through the EQ-5D-3L questionnaire) were randomized to receive secukinumab 300mg or placebo and were assessed at weeks 4, 8, and 12. Results showed that at week 4, the percentage of patients reporting no problems in mobility (60.7%), self-care (71.4%), or change in usual activities (63.8%) was higher in the secukinumab group than in the placebo arm (38.5%, 40.9%, and 31.1%, respectively); similar trends were observed at week 8 and 12.

“Moderate-to-severe plaque psoriasis can impact every aspect of a person’s life,” stated Steven R. Feldman, MD, PhD, Wake Forest School of Medicine. “These findings suggest that helping patients feel better through improved quality of life and ability to function should be a goal as important as skin clearance in psoriasis management.”

Cosentyx, a human interleukin-17A antagonist, is FDA-approved for the treatment of: moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy; adults with active psoriatic arthritis; and adults with active ankylosing spondylitis.

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For more information visit Novartis.com.

February 01, 2019

Biologic-naive patients who were HLA-C*06:02 positive and PsA negative exhibited a significantly poorer response to adalimumab at 12 months.

HLA-C*06:02 status is a predictive biomarker that influences response to adalimumab and ustekinumab in patients with psoriasis, according to a study published in The Journal of Allergy and Clinical Immunology.

The investigators sought to explore whether HLA-C*06:02, which is the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologic agents — the antitumor necrosis factor alpha adalimumab and the anti-interleukin-12/23 ustekinumab.

The prospective, observational study used information from participants in a national psoriasis registry. All participants were >16 years of age and were enrolled in the Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) study and the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR). BSTOP was conducted across 60 UK dermatology centers that include biologic sample collection.

 BADBIR is a pharmacovigilance register that has recruited >16,000 patients with psoriasis from the United Kingdom and Ireland who are receiving systemic conventional or biologic therapy. Longitudinal treatment and response observations, along with detailed clinical data, are included in BADBIR.

HLA alleles were imputed from genome-wide genotype data for a total of 1326 patients for whom 90% reduction in Psoriasis Area and Severity Index 90 response status was observed following 3, 6, or 12 months of treatment. Regression models of Psoriasis Area and Severity Index 90 response were developed that examined the interaction between HLA-C*06:02 and the type of drug (adalimumab or ustekinumab) administered, taking into consideration any potential confounding variables.

Results of the study demonstrated that those who were negative for HLA-C*06:02 were significantly more likely to respond to adalimumab therapy than to ustekinumab therapy at all time points, with the strongest response at 6 months (odds ratio [OR] 2.95; P =5.85×10^-7). In fact, this difference was greater in patients who were negative for HLA-C*06:02 and had psoriatic arthritis (OR 5.98; P =6.89×10^-5).

Those who had never taken biologic drugs and were positive for HLA-C*06:02 and negative for psoriatic arthritis exhibited a significantly poorer response to adalimumab at 12 months (OR 0.31; P =3.42×10^-4). Results from the HLA-wide analysis were consistent with HLA-C*06:02 itself being the primary effect allele contributing to patients’ biologic responses. This role still warrants exploration in larger samples, however, to fully investigate the possible role played by other alleles.

The researchers concluded that HLA-C*06:02 status might help inform optimal selection of first-line biologic therapy for patients with severe psoriasis.

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Reference

Dand N, Duckworth M, Baudry D, et al; BADBIR study group, the BSTOP study group and the PSORT consortium. HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis [published online December 19, 2018]. J Allergy Clin Immunol. doi: 10.1016/j.jaci.2018.11.038

February 01, 2019

Obesity is an independent risk factor for development of psoriasis and is associated with a worse prognosis.

Psoriasis and obesity have a complex interrelationship. Obesity is a common comorbidity in patients with psoriasis and observational studies initially pointed to a greater likelihood of obesity in these patients, suggesting it might be a risk factor for the development of psoriasis.

Carrying excess weight both exacerbates the manifestations of psoriasis and interferes with treatment;¹ weight loss is associated with an improvement in symptoms.¹ These factors point to an important link between the two diseases, although they do not necessarily share a common mechanism. As Stephen M. Schleicher, MD, director of the DermDOX Center for Dermatology in Hazleton, Pennsylvania, explained to Dermatology Advisor, psoriasis is an inflammatory process linked to immune dysfunction, while obesity has multiple origins.

Obesity, as measured by body mass index (BMI) [results in an] increased [risk] for developing psoriasis,” Dr Schleicher said, adding that “independent of BMI, there is a higher risk for developing psoriasis with weight gain for both males and females.” Results from the HUNT study, which prospectively examined data from 33,734 people in the general population in Norway, found that long-term increases in body weight of even 1 standard deviation substantially increased the risk for psoriasis and that obesity and large waist circumference doubled the risk.²

Possible Linked Mechanisms

Psoriasis is believed to be caused by a perfect storm of genetics, immune dysfunction, and environmental triggers. While it has been linked to multiple features of metabolic syndrome — including dyslipidemia, insulin resistance, diabetes, and obesity — obesity in particular may influence the development and expression of psoriasis as a direct result of inflammation. Current theory points to an important inflammatory role of visceral fat produced by adipose tissues, in which cytokines ([tumor necrosis factor] TNF-α, [interleukin] IL-6, IL-17) and adipokines (adiponectin, omentin, chemerin) contribute in multiple ways to the development of psoriasis, as well as metabolic syndrome.

Obesity is an independent risk factor for the development of psoriasis and is associated with a worse prognosis.⁴ In a commentary linked to the HUNT study, Gisondi and Girolomoni³ suggested that a disequilibrium of pro- and anti-inflammatory cytokines in obese individuals creates a state of chronic low-grade inflammation, which could create an opportunity for psoriasis to develop de novo or worsen in people who have already been diagnosed with psoriasis. While a number of studies have linked the presence of psoriasis to a greater risk for metabolic syndrome,^4,5 whether or not psoriasis increases the risk for obesity is not as clear. In a 2016 review, Chirocozzi, et al⁴ first mentioned the possibility of a bidirectional mechanism when they suggested that “psoriasis-signature proinflammatory cytokines may alter lipid metabolism, enhancing the risk of adiposity…” Further investigation is needed to confirm this.

The Impact of Obesity on Psoriasis Management

In addition to the effects of increased BMI and waist circumference on the risk for developing psoriasis, actual excess weight also complicates treatment. “Certain therapies for psoriasis (such as cyclosporine and ustekinumab) are dosed based on weight,” Dr Schleicher explained, which may contribute to poor response in some patients. Takeshita, et al⁶ reported in 2017 that responses to fixed-dose biologic therapies such as adalimumab, etanercept, and ustekinumab were reduced in obese patients, while responses to weight-based doses of infliximab were not affected. The investigators suggested that current regimens of fixed-dose biologic agents may be insufficient to adequately treat psoriasis in patients who are overweight or obese, while weight reduction may improve response to the current dose.

Also complicating treatment is a 2-fold higher risk for developing non-alcoholic fatty liver disease (NAFLD) associated with obesity in patients with plaque psoriasis.¹ “Obese individuals are at greater risk for developing cirrhosis when treated with methotrexate,” Dr Schleicher said, noting that the risk was significant enough to warrant avoiding methotrexate therapy in patients who are obese. “Weight loss is also listed as an AE [adverse event] for apremilast,” he pointed out, “although many obese patients with psoriasis view this in a positive light.”

Another important factor in the relationship between psoriasis and obesity is that increased BMI compounds the cardiovascular risks posed by either psoriasis or obesity alone.¹ “Obesity is linked to metabolic syndrome characterized by hypertension, elevated lipids, and insulin resistance. All of these factors contribute to increased morbidity,” Dr Schleicher said, suggesting that clinicians should encourage weight loss in patients who are overweight at clinic visits.

Treatment Strategies

Weight reduction is believed to reduce psoriasis severity and may have indirect benefits through improvement of diseases contributing to metabolic syndrome.⁴ “Excess weight contributes to other comorbidities associated with psoriasis,” Dr Schleicher observed. “Obese patients with psoriasis are urged to achieve and maintain a more ideal body weight,” he said, which is best accomplished by reducing caloric intake and alcohol consumption.

Chirocozzi, el al⁴ also suggested that designing treatment strategies aimed at balancing pro- and anti-inflammatory adipokine levels in patients with psoriasis who are obese could benefit both conditions and reduce further complications of metabolic syndrome.

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References

1. Jensen P, Skov L. Psoriasis and obesity. Dermatology. 2016;232:633-639.

2. Snekvik I, Smith CH, Nilsen TIL, et al. Obesity, waist circumference, weight change, and risk of incident psoriasis: perspective data from the HUNT study. J Invest Dermatol. 2017;137:2484-2490.

3. Gisondi P, Girolomoni G. The multifaceted association between psoriasis and obesity. Br J Dermatol. 2019;180:24.

5. Owczarczyk-Saczonek A, Placek W. Compounds of psoriasis with obesity and overweight. Postepy Hig Med Dosw (Online). 2017;71:761-772.

4. Chiricozzi A, Raimondo A, Lembo S, et al. Crosstalk between skin inflammation and adipose tissue-derived products: pathogenic evidence linking psoriasis to increased adiposity. Expert Rev Clin Immunol. 2016;12:1299-1308.

6. Takeshita J, Grewal S, Langan SM Et al. Psoriasis and comorbid diseases: Implications for management. J Am Acad Dermatol 2017;76:393-403.

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January 31, 2019

The median total charges submitted to Medicare increased, but there was not a significant increase in the actual amount paid from Medicare.

Trends in Medicare payments to dermatologists may be affecting practice patterns and reducing patient access, according to a retrospective study published in JAMA Dermatology.

Researchers analyzed records from the Medicare Provider Utilization and Payment Data: Physician and Other Supplier data set to assess changes in Medicare utilization by dermatologists from 2012 to 2015. Medicare providers, location of providers, number of services performed, unique treatment beneficiaries, submitted Medicare charges, and actual Medicare payments were characterized by either drug services or medical services.

Results indicated that the number of dermatologists utilizing Medicare increased by 6.2% over the 3-year time frame while the median number of services per clinician (P =.98) and the median number of unique beneficiaries (P =.80) remained the same. The median total charges submitted to Medicare increased (P <.001), but there was not a significant increase in the actual amount paid from Medicare (P =.47).

In regards to drug services, there was a significant increase in the median number of drug services provided, median number of unique beneficiaries, amount of charges submitted to Medicare, and the amount paid from Medicare (P <.001, for all). In regards to medical services, there was only a significant increase in the median number of beneficiaries (P =.01) and amount of submitted charges to Medicare (P <.001). According to the Gini coefficient, there was a moderate and stable level of inequality for the total amount paid by Medicare with urban and metropolitan areas receiving more payments.

The limitations of this study include the limited time frame, the potential of insurance compensation, and possible billing by physician extenders.

In conclusion, these trends may affect patients’ access to dermatologists if providers opt out of Medicare due to lack of payments. “[I]t is important to consider how Medicare payments can be optimized to maintain dermatologist access across the entire Medicare population,” the study authors suggested. 

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Reference

Ya J, Ezaldein HH, Scott JF. Trends in Medicare utilization by dermatologists, 2012-2015 [published online December 19, 2018]. JAMA Dermatol. doi: 10.1001/jamadermatol.2018.4212

January 31, 2019

Desoximetasone with and without phone reminders was associated with clinical improvement in both psoriasis and atopic dermatitis.

Desoximetasone spray has demonstrated efficacy for treatment-resistant atopic dermatitis and psoriasis, according to a study recently published in the Journal of Cutaneous Medicine and Surgery.

This open-label, single-center study included 24 participants, 12 of whom had treatment-resistant atopic dermatitis and 12 of whom had treatment-resistant psoriasis. In each group, 6 participants were randomly assigned to desoximetasone 0.25% spray with phone reminders twice per day, and 6 were assigned to the spray without phone reminders. Baseline assessments included current medications and medical history. To assess severity of disease, the Pruritus Visual Analog Scale, Investigator’s Global Assessment, Psoriasis Area and Severity Index, Eczema Area and Severity Index, and Total Lesion Severity Score were used. Results from visit to visit were compared using paired t-tests, whereas variances between the 2 treatment groups were assessed using a Wilcoxon 2-sample test.

Desoximetasone with and without phone reminders was associated with clinical improvement in both psoriasis and atopic dermatitis. Statistically significant improvement was achieved among the psoriasis group with phone reminders, the psoriasis group without phone reminders in Total Lesion Severity Score and Pruritus Visual Analog Scale measures, and among those with atopic dermatitis in various assessments.

Limitations to this study included small sample size, a short time period of evaluation, and a lack of patient measures such as self-reported adherence.

The study researchers concluded that “[patients] with ‘treatment-resistant’ [psoriasis] and [atopic dermatitis] generally responded well to the use of desoximetasone spray in the trial setting. This may be due to better adherence in the study environment or patients’ preference for the spray vehicle. Patient reminders contributed to improved clinical outcomes in [psoriasis] and [atopic dermatitis] patients with ‘treatment-resistant’ disease.”

Disclosure: This project was funded by Taro Pharmaceuticals. Author SR Feldman reports financial associations with other pharmaceutical companies. For a full list of author disclosures, visit the reference.

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Reference

Hogue L, CardwellLA, Roach C, et al. Psoriasis and atopic dermatitis “resistant” to topical treatment responds rapidly to topical desoximetasone spray [published online December 17, 2018]. J Cutan Med Surg. doi:10.1177/1203475418818082