DermatologyResearch Review

TM

Email geoff@researchreview.com.au Phone 1300 132 322

CT = computed tomography; IL = interleukin;PDT = photodynamic therapy; QALY = quality-adjusted life-year;QOL = quality of life; UVB = ultraviolet B.

Abbreviations used in this issue:

@ ResearchRevAusVisit https://twitter.com/ResearchRevAus

Follow RESEARCH REVIEW Australia on Twitter now

Claim CPD/CME points Click here for more info.

11

Issue 38 - 2017Making Education Easy

www.researchreview.com.au a RESEARCH REVIEW publication

Welcome to issue 38 of Dermatology Research Review.This issue begins with Australian research showing that wearing superfine merino woollen clothing may help manage children with atopic dermatitis. Researchers from the US have reported that patients with hidradenitis suppurativa have changes in the expression of genes encoding enzymes involved in sphingolipid metabolic pathways. Research from Queensland reports on patients treated with diphenylcyclopropenone (diphencyprone) for in-transit melanoma. We finish up this month with research suggesting an adjunctive role for radiological imaging for assisting with diagnosing calciphylaxis.

I hope these and the other papers included in this issue are of interest and helpful to you. As always, your comments and feedback are welcome.

Kind Regards,

Dr Warren Weightmanwarren.weightman@researchreview.com.au

Determining Effects of Superfine Sheep wool in INfantile Eczema (DESSINE)Authors: Su JC et al.

Summary: Thirty-nine patients aged 4 weeks to 3 years with mild-to-moderate atopic dermatitis wore superfine woollen or cotton clothing for 6 weeks in a randomised crossover manner, with review every 3 weeks. Compared with cotton clothing, woollen clothing was associated with significant reductions in SCORAD (Scoring Atopic Dermatitis) score at 3 weeks and 6 weeks (primary endpoint) of 2.5 and 7.6 points, respectively, with similar changes seen for ADSI (Atopic Dermatitis Severity Index) and IDQOL (Infants’ Dermatitis Quality Of Life) scores, and a reduction in body steroid use. Changing from woollen to cotton clothing led to increased scores.

Comment: Wool is generally considered to be an irritant in patients with atopic dermatitis, but there have been few studies looking at this and none assessing the role of different wool fibre diameters such as in superfine wool. This is the first original clinical study to examine the clinical effects of superfine merino wool on childhood atopic dermatitis. Superfine wool has a diameter of 15–18.5μm. Merino wool is generally less than 24μm, and prickle and itch are usual not sensed with fibres less than 19–21μm. Wool demonstrates superior properties of insulation, water absorbency, fire resistance and liquid repellency compared with other natural and manmade fibres. Its thermoregulatory and moisture transport properties may possibly benefit patients with atopic dermatitis, as skin barrier dysfunction leads to moisture and temperature dysregulation. This clinical study highlights the need for further studies on the effects of clothing, and of the microenvironment between clothing and the skin in atopic dermatitis.

Reference: Br J Dermatol 2017;177(1):125–33Abstract

Ciclosporin compared with prednisolone therapy for patients with pyoderma gangrenosumAuthors: Mason JM et al., and on behalf of the U.K. Dermatology Clinical Trials Network's STOP GAP team

Summary: This analysis of data from the STOP GAP randomised trial sought to compare the cost effectiveness of cyclosporin versus prednisolone for initial treatment of pyoderma gangrenosum. A base case analysis revealed that compared with prednisolone, cyclosporin was associated with lower net costs and an improvement in QOL, but this appeared to be driven by a minority of patients with large lesions ≥20 cm2. The incremental cost effectiveness of cyclosporin for most patients with smaller lesions was £23,374 per QALY, although this estimate is imprecise; the likelihood of cyclosporin being cost effective at a willingness-to-pay of £20,000 per QALY was 43%.

Comment: Treatment of pyoderma gangrenosum can be difficult with prednisolone, the usual first-line treatment, and cyclosporin, a common, and my, second-line treatment. The prescribing of cyclosporin has been difficult in private practice until recently because of the cost, but now it is on a general PBS prescription, so access is not a limiting factor. There was no significant difference between either treatment in speed of healing, 6-month healing rate, recurrence or QOL. There was almost a significant difference in side effects, with prednisolone worse, particularly increased infections. The main contributor to the increased cost of prednisolone was the higher inpatient stay, but the cost-effectiveness benefit was only seen in ulcers ≥20 cm2. The cost effectiveness is difficult to transfer to the Australian population with different drug, inpatient and outpatient costs. Interestingly, only 50% of ulcers had healed by 6 months on either drug, and adverse events were common with both drugs. The choice of which drug is mainly determined by patient comorbidities and doctor preference.

Reference: Br J Dermatol; Published online May 31, 2017Abstract

In this issue: > Wearing superfine wool helps in atopic dermatitis

> Cyclosporin vs. prednisolone for pyoderma gangrenosum

> Nephrogenic systemic fibrosis: 15-year experience

> Long-term follow-up of melanocyte-keratinocyte transplantation for leucodermas

> Sphingolipid metabolism gene expression altered in hidradenitis suppurativa

> Pulsed dye laser for acne vulgaris/erythema

> Overweight plus smoking increases androgenetic alopecia severity

> Daylight PDT with methylene blue for plane warts

> Diphenylcyclopropenone for cutaneous in-transit melanoma metastases

> Calciphylaxis: detecting small-vessel calcification on imaging

UNCOVER WHAT’S NOW POSSIBLE IN PLAQUE PSORIASIS.

PP-IX-AU-0120. ELT0086h/V1/DPR.

22

www.researchreview.com.au a RESEARCH REVIEW publication

Dermatology Research ReviewTM

Nephrogenic systemic fibrosis: a 15-year retrospective study at a single tertiary care centerAuthors: Wilson J et al.

Summary: This small retrospective medical chart review of eight patients with nephrogenic systemic fibrosis from a single centre sought to investigate whether improvement of renal function following successful transplantation or via return of renal function after acute kidney injury correlates with improvement of nephrogenic systemic fibrosis. A significant correlation was seen between improved renal function and improved nephrogenic systemic fibrosis (p=0.0286), with all four patients who experienced renal function improvement also experiencing improvement of their nephrogenic systemic fibrosis (two had end-stage renal disease and a successful kidney transplant, and two had acute kidney injury that resolved). There was no improvement in nephrogenic systemic fibrosis without kidney function resolution.

Comment: The incidence of nephrogenic systemic fibrosis has fallen after it was first recognised in 2000. Since 2006, there has been a link between exposure to gadolinium, and the avoidance of gadolinium contrast in high-risk renal patients is likely to have led to this decrease. Although multiple treatments have been tried, the results have been mixed with no single treatment showing consistent benefit. Although this study only had small numbers, it suggests that the best treatment is improvement of renal function and this should be the main goal, and this may mean renal transplantation. This study didn’t look at whether the duration or extent of the renal impairment influenced resolution, and this could be looked at in future studies.

Reference: J Am Acad Dermatol 2017;77(2):235–40Abstract

Long-term follow-up of patients undergoing autologous noncultured melanocyte-keratinocyte transplantation for vitiligo and other leukodermasAuthors: Silpa-Archa N et al.

Summary: This retrospective review of 63 evaluable patients who underwent melanocyte-keratinocyte transplantation for 157 vitiligo or other leucoderma lesions assessed long-term repigmentation. Improvements in VASI (Vitiligo Area Scoring Index) score were seen for segmental vitiligo, nonsegmental vitiligo and physical leucoderma lesions (–75.6, –59.2 and –32.4 points, respectively). For vitiligo, the respective 24-, 48- and 72-month >75% repigmentation rates were 53%, 64%, and 53%.

Comment: Melanocyte-keratinocyte transplantation is a simple procedure that can be done in one visit. There are good results at 6 months, but there are limited studies on long-term outcomes. The majority of patients maintained greater than 75% repigmentation at 72 months, which is reassuring for the patient. Age, skin phototype and anatomic location had no effect on repigmentation. After melanocyte-keratinocyte transplantation, the patients were allowed to continue their prior treatment, but there was no mention in this article what this treatment was and how long it was continued for. Other studies have shown that follow-up treatment with narrow-band UVB increases the response after melanocyte-keratinocyte transplantation, so it would have been useful to know what was used. This was a retrospective review, and a prospective study looking at whether follow-up treatments such as narrow-band UVB or topical agents show a higher maintenance rate or further increase the amount of repigmentation are worthwhile.

Reference: J Am Acad Dermatol 2017;77(2):318–27Abstract

Gene expression of sphingolipid metabolism pathways is altered in hidradenitis suppurativaAuthors: Dany M & Elston D

Summary: This research sought to establish if there is alteration of gene expression of enzymes involved in sphingolipid metabolic pathways in patients with hidradenitis suppurativa. Expression of sphingolipid-related enzymes was compared between inflammatory skin lesions obtained from 17 patients with hidradenitis suppurativa with skin tissue samples obtained from 13 healthy subjects. Compared with the healthy skin samples, hidradenitis suppurativa lesional skin samples exhibited decreased expression of ceramide- and sphingomyelin-generating enzymes, increased expression of enzymes catabolising ceramide to sphingosine, and increased expression of enzymes converting ceramide to galactosylceramide and gangliosides.

Comment: The pathogenesis of hidradenitis suppurativa is still not clearly understood, but there has been a big increase in knowledge and numerous studies over recent years leading to the recent PBS approval of adalimumab for severe cases. Recent research has also highlighted the role of other cytokines including IL-1 and IL-17, which could lead to the anti-IL-1 and IL-17 inhibitors undergoing trials, although there are current case reports and small series that suggest these treatments are effective. Recent evidence has shown that sphingolipid species, such as ceramide and sphingosine-1-phosphatase, act as biologically active stimulating molecules, and in hidradenitis suppurativa, sphingolipid metabolism may be abnormal leading to increased inflammation. This study shows that sphingolipid metabolism is altered in hidradenitis suppurativa, and this may lead to drugs with an alternate mode of action being developed for hidradenitis suppurativa.

Reference: J Am Acad Dermatol 2017;77(2):268–73Abstract

Please click here to review the full Product Information before prescribing.References: 1. TALTZ® (ixekizumab) Approved Product Information, 4 January 2017. 2. Griffiths C et al. Lancet 2015;386:541–551.Abbreviations: PASI, Psoriasis Area Severity Index. TALTZ® is a registered trademark of Eli Lilly and Company. Eli Lilly Australia Pty Ltd. 112 Wharf Road, West Ryde NSW 2114, Australia. ABN 39 000 233 992. Medical Information: 1800 454 559. Date of preparation: January 2017. PP-IX-AU-0120. ELT0086h/V2/DPR.

TALTZ®: For moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.1

NEW

AT WEEK 12 (UNCOVER-2 PHASE III TRIAL):

90%PASI 751,2

OF PATIENTS ACHIEVED

71%PASI 901,2

OF PATIENTS ACHIEVED

41%PASI 1001,2

OF PATIENTS ACHIEVED

PBS INFORMATION: Authority required. For the treatment of

severe chronic plaque psoriasis. Refer to PBS Schedule for full

authority information.

33

www.researchreview.com.au a RESEARCH REVIEW publication

Dermatology Research ReviewTM

Randomized, controlled trial split-faced study of 595-nm pulsed dye laser in the treatment of acne vulgaris and acne erythema in adolescents and early adulthoodAuthors: Lekwuttikarn R et al.

Summary: Thirty adolescents and young adults with mild-to-moderate acne vulgaris or acne erythema received two sessions of 595nm pulsed dye laser (8 J/cm3 for 10 msec; spot size 7mm) to one randomised side of their face every 2 weeks, with the other side left untreated for comparison. Change in papule count at week 4 was –1.828 on the treated side of the face versus 0.103 on the nontreated side (p=0.0018), but no significant difference was seen for acne severity or erythema grades.

Comment: Pulsed dye laser is often used to reduce erythema after acne has cleared, especially after isotretinoin treatment where there may be persisting and severe erythema. This study showed it had no benefit when given when the acne is active and still being treated. These results suggest that pulsed dye laser may not be of much benefit in post-acne erythema either, with the reduction of erythema occurring because of the passage of time. Laser trials for post-acne erythema have all had small numbers and poor designs and were not well controlled. There was also no significant benefit in reducing the acne severity, so because of its high cost pulse dye laser cannot be recommended in acne treatment.

Reference: Int J Dermatol 2017;56(8):884–8Abstract

The combination of overweight and smoking increases the severity of androgenetic alopeciaAuthors: Fortes C et al.

Summary: Risk factors for androgenetic alopecia severity among 351 Caucasian outpatients were identified in this cross-sectional research. The risk of moderate or severe androgenetic alopecia was significantly increased in current smokers with body mass index ≥25 kg/m2 (adjusted odds ratio 5.96 [95% CI 1.65–21.5]); age and gender were also significantly associated with androgenetic alopecia in the multivariate model.

Comment: This study showed an independent association of obesity and smoking with androgenetic alopecia. This does not prove a causal mechanism, but may be related to the proinflammatory changes occurring in obesity also occurring in the hair follicle. If there is a real causal action, then stopping smoking or losing weight may lead to an improvement in the androgenetic alopecia or at least slow its progression. This is a study that would be interesting to do.

Reference: Int J Dermatol 2017;56(8):862–7Abstract

Daylight photodynamic therapy with methylene blue in plane wartsAuthors: Fathy G et al.

Summary: Patients with multiple plane warts received daylight PDT with topical 10% methylene blue gel as a photosensitiser (n=20) or placebo (haematoxylin; n=20) in this research. In the treatment group, the complete clearance rate was 65%, 10% of participants had a good response and 25% had a poor response. No responses were seen in the placebo group. There were no serious adverse events and the pain was well tolerated. There were no relapses during 12 months of follow-up.

Comment: This is a novel and simple treatment for plane warts with 75% showing complete clearance or a good result. The clearance was assessed both clinically and dermoscopically. The treatment regimen was similar to daylight PDT for actinic damage, but all patients had pretreatment for 1 week with 0.05% isotretinoin cream to aid penetration, and treatment times varied between 90 minutes and 120 minutes depending on whether it was sunny or not. Treatments were given weekly for a maximum of 6 weeks or until complete clearance, and some patients only needed three treatments for complete clearance. The majority of patients (95%) had facial plane warts, which is the most common and often the most difficult area to treat, due to the potential for scarring with many treatments. Methylene blue may be a preferred choice for daylight PDT, as its strongest absorption is with wavelengths greater than 620nm. Pain was the main side effect, but was relatively mild and short lived. This is a safe and simple treatment that is worthwhile considering in patients with multiple facial plane warts.

Reference: Photodermatol Photoimmunol Photomed 2017;33(4):185–92Abstract

Selection of papers and comments are provided by Dr Warren Weightman, who has practiced Dermatology for over 25 years and is currently Head of the Department of Dermatology at the Queen Elizabeth Hospital, Adelaide and a Senior Lecturer with Adelaide University. He has been Chief Censor and President of the Australasian College of Dermatologists. Dr. Weightman has been involved in clinical research and has a particular interest in treatment of actinic keratoses and superficial basal cell cancers with topical therapies including methyl aminolevulinate and photodynamic therapy, imiquimod, and ingenol mebutate. His other interests include the management of non-melanoma skin cancer in transplant patients, the use of biologics in psoriasis and other skin disorders, and the role of oral retinoids.

Dermatology Research ReviewTM

Please click here to review the full Product Information before prescribing.

References: 1. TALTZ® (ixekizumab) Approved Product Information, 4 January 2017. 2. Gordon K et al. N Engl J Med 2016;375:345–356 (supplementary appendix). Abbreviations: PASI, Psoriasis Area Severity Index; sPGA, static Physician’s Global Assessment. TALTZ® is a registered trademark of Eli Lilly and Company. Eli Lilly Australia Pty Ltd. 112 Wharf Road, West Ryde NSW 2114, Australia. ABN 39 000 233 992. Medical Information: 1800 454 559. Date of preparation: January 2017. PP-IX-AU-0120. ELT0086h/HP/DPR.

THROUGH WEEKS 12–60 (UNCOVER-1 AND UNCOVER-2 PHASE III TRIALS; POOLED RESULTS):

TALTZ®: For moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.1NEW

OF WEEK-12 RESPONDERS (sPGA 0/1) MAINTAINED OR ACHIEVED58%COMPLETE CLEARANCE (PASI 100) AT WEEK 602

PBS INFORMATION: Authority required. For the treatment of severe chronic plaque psoriasis. Refer to PBS Schedule for full authority information.

www.researchreview.com.au a RESEARCH REVIEW publication

44© 2017 RESEARCH REVIEW

Research Reviews are prepared with an independent commentary from relevant specialists. To become a reviewer please email geoff@researchreview.com.au.Research Review Australia Pty Ltd is an independent Australian publisher. Research Review receives funding from a variety of sources including Government depts., health product companies, insurers and other organisations with an interest in health. Journal content is created independently of sponsor companies with assistance from leading local specialists. Privacy Policy: Research Review will record your email details on a secure database and will not release them to anyone without your prior approval. Research Review and you have the right to inspect, update or delete your details at any time. Disclaimer: This publication is not intended as a replacement for regular medical education but to assist in the process. The reviews are a summarised interpretation of the published study and reflect the opinion of the writer rather than those of the research group or scientific journal. It is suggested readers review the full trial data before forming a final conclusion on its merits. Research Review publications are intended for Australian health professionals.

Australian Research Review subscribers can claim CPD/CME points for time spent reading our reviews from a wide range of local medical and nursing colleges. Find out more on our CPD page.

Dermatology Research ReviewTM

Diphenylcyclopropenone for the treatment of cutaneous in-transit melanoma metastasesAuthors: Read T et al.

Summary: Clinical outcomes were reported for 54 evaluable participants with cutaneous in-transit melanoma metastases from a prospective, nonrandomised, noncomparative, single-centre study of topical 0.005–1% diphenylcyclopropenone cream applied twice per week for 24–48 hours’ duration. The complete response rate was 22% (occurring in a mean time of 10.5 months and with a mean disease-free interval of 12.3 months), the partial response rate was 39%, the stable disease rate was 24% and the progressive disease rate was 15%. The recurrence rate among complete responders was 41%. A significantly higher response rate was seen in epidermotropic disease.

Comment: This study follows on from Diona Damian’s work and shows similar results, although her results showed a higher benefit with complete and partial response rates of 46% and 39%, respectively. There was an increased response in the epidermotropic group compared with the nodular group. Seventy-five percent of patients who experienced complete remission had a severe treatment reaction, which suggests that a good immune response is associated with eventual tumour regression. Complete responders also had a higher median overall survival time. Immune sensitising topical agents may have a synergistic effect when combined with systemic immunotherapies such as anti-Pd-1 antibodies. Topical diphenylcyclopropenone is a worthwhile option in selected patients, and may offer some prognostic information in those who have a severe response.

Reference: J Eur Acad Dermatol Venereol; Published online July 13, 2017Abstract

Calciphylaxis: comparison of radiologic imaging and histopathologyAuthors: Halasz CL et al.

Summary: These researchers compared diameters of calcified vessels in routine skin biopsy specimens and radiology images from seven patients with calciphylaxis presenting to a single community hospital between 2009 and 2016. Plain films from three patients revealed small-vessel calcification as small as 0.1–0.3mm, mammography in three patients revealed 0.1–0.2mm small-vessel calcification and CT in one patient revealed 0.1–0.2mm small-vessel calcification.

Comment: The diagnosis of calciphylaxis is usually confirmed with a skin biopsy, but there may be sampling errors and involved vessels are not always seen. A relatively large incisional biopsy is therefore needed, and this is more likely to break down and cause a large painful ulcer. In this study, plain x-rays, mammograms and CT scans were all able to detect small-vessel calcification to a resolution close to that of histopathology. A skin biopsy is more specific as it can detect occlusion of the calcified vessels, which is the pathognomonic feature, but radiography is useful as an adjunctive investigation to help support the diagnosis of calciphylaxis or when the biopsy is nondiagnostic or difficult to do.

Reference: J Am Acad Dermatol 2017;77(2):241–6Abstract

This online educational activity is endorsed by the Australian Nursing and Midwifery Federation (ANMF) Federal Office.

Completion attracts 1 CPD hour. For more information click here