CEBD Evidence Update

June 2018



Take a look:







Welcome to this month’s CEBD Evidence Update, bringing you the latest evidence-based publications in dermatology, with an emphasis on clinical guidelines and systematic reviews.


CEBD Evidence Updates are compiled by the Centre of Evidence Based Dermatology at the University of Nottingham, with funding from Nottingham University Hospitals NHS Trust, as a service to the dermatology community. An archive of these updates is available on the list home page: CEBD-EVIDENCE-UPDATES.


The title of each item provides a link to the abstract in PubMed. If the paper is open-access (indicated in brown text towards the bottom of the PubMed record) or you have an institutional subscription to the journal concerned, you can access it by clicking on the full text link at the top right of the PubMed record. It is important to appraise the quality of systematic reviews before applying to your practice—we recommend the AMSTAR 2 tool, which is very quick and easy to use. See also this open-access article: Research Techniques Made Simple: Assessing Risk of Bias in Systematic Reviews.








Systematic reviews & evidence summaries

Eczema & dermatitis

Psoriasis & psoriatic arthritis

Acne & rosacea

Skin cancers & sun protection

Infections of the skin

Drug & treatment reactions/safety

Vitiligo & pigmentary disorders

Hair & nail disorders

Oral disorders

Chronic wounds & ulcers

Other disorders affecting the skin

Skin conditions & dermatology in general

Skin surgery & lasers

Service delivery & management

Prescribing and safety alerts

CEBD publications & news

Other key publications that have caught our eye










NICE Technology appraisal guidance [TA521] - Guselkumab for treating moderate to severe plaque psoriasis


“Guselkumab is recommended as an option for treating plaque psoriasis in adults, only if:

•the disease is severe, as defined by a total Psoriasis Area and Severity Index (PASI) of 10 or more and a Dermatology Life Quality Index (DLQI) of more than 10 and

•the disease has not responded to other systemic therapies, including ciclosporin, methotrexate and PUVA (psoralen and long-wave ultraviolet A radiation), or these options are contraindicated or not tolerated and

•the company provides the drug according to the commercial arrangement.”

See NICE website for further detailed recommendations.



Scottish Medicines Consortium - guselkumab (Tremfya)


“Following a full submission: guselkumab (Tremfya®) is accepted for restricted use within NHSScotland.

Indication under review: Treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.

SMC restriction: for patients who have failed to respond to conventional systemic therapies (including ciclosporin, methotrexate and phototherapy), are intolerant to, or have a contraindication to these treatments.”



NHS Improvement - Pressure ulcers: revised definition and measurement framework


“The recommendations in this document are designed to support a more consistent approach to the definition and measurement of pressure ulcers at both local and national levels across all trusts.”



NICE Final Appraisal Determination - Dupilumab for treating moderate to severe atopic dermatitis


“1.1 Dupilumab, in combination with topical corticosteroids, is recommended as an option for treating moderate to severe atopic dermatitis in adults, only if:

·         the disease has not responded to at least 1 other systemic therapy, such as ciclosporin, methotrexate, azathioprine and mycophenolate mofetil, or these are contraindicated or not tolerated

·         the company provides dupilumab according to the commercial arrangement (see section 2).

1.2 Stop dupilumab at 16 weeks if the atopic dermatitis has not responded adequately. An adequate response is:

·         at least a 50% reduction in the Eczema Area and Severity Index score (EASI 50) from when treatment started and

·         at least a 4-point reduction in the Dermatology Life Quality Index (DLQI) from when treatment started.

Note: This is the Final Appraisal Determination (FAD), not the final guideline. The FAD will form the basis of the guidance that NICE issues to the NHS in England and Wales.





An update on the Society for Immunotherapy of Cancer consensus statement on tumor immunotherapy for the treatment of cutaneous melanoma: version 2.0.

Sullivan RJ, Atkins MB, Kirkwood JM, Agarwala SS, Clark JI, Ernstoff MS, Fecher L, Gajewski TF, Gastman B, Lawson DH, Lutzky J, McDermott DF, Margolin KA, Mehnert JM, Pavlick AC, Richards JM, Rubin KM, Sharfman W, Silverstein S, Slingluff CL Jr, Sondak VK, Tarhini AA, Thompson JA, Urba WJ, White RL, Whitman ED, Hodi FS, Kaufman HL.

J Immunother Cancer. 2018 May 30;6(1):44. doi: 10.1186/s40425-018-0362-6.


This guideline is produced by the US Society for Immunotherapy of Cancer (SITC) Melanoma Task Force.

“RESULTS: The Task Force considered patients with stage II-IV melanoma and here provide consensus recommendations for how they would incorporate the many immunotherapy options into clinical pathways for patients with cutaneous melanoma.

CONCLUSION: These clinical guidelines provide physicians and healthcare providers with consensus recommendations for managing melanoma patients electing treatment with tumor immunotherapy.”



Merkel Cell Carcinoma, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

Bichakjian CK, Olencki T, Aasi SZ, Alam M, Andersen JS, Blitzblau R, Bowen GM, Contreras CM, Daniels GA, Decker R, Farma JM, Fisher K, Gastman B, Ghosh K, Grekin RC, Grossman K, Ho AL, Lewis KD, Loss M, Lydiatt DD, Messina J, Nehal KS, Nghiem P, Puzanov I, Schmults CD, Shaha AR, Thomas V, Xu YG, Zic JA, Hoffmann KG, Engh AM.

J Natl Compr Canc Netw. 2018 Jun;16(6):742-774. doi: 10.6004/jnccn.2018.0055.


“This selection from the NCCN [US National Comprehensive Cancer Network] Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation and systemic therapy. Included in these sections are discussion of the new recommendations for use of Merkel cell polyomavirus as a biomarker and new recommendations for use of checkpoint immunotherapies to treat metastatic or unresectable disease.”



Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.

Wollenberg A, Barbarot S, Bieber T, Christen-Zaech S, Deleuran M, Fink-Wagner A, Gieler U, Girolomoni G, Lau S, Muraro A, Czarnecka-Operacz M, Schäfer T, Schmid-Grendelmeier P, Simon D, Szalai Z, Szepietowski JC, Taïeb A, Torrelo A, Werfel T, Ring J; European Dermatology Forum (EDF), the European Academy of Dermatology and Venereology (EADV), the European Academy of Allergy and Clinical Immunology (EAACI), the European Task Force on Atopic Dermatitis (ETFAD), European Federation of Allergy and Airways Diseases Patients’ Associations (EFA), the European Society for Dermatology and Psychiatry (ESDaP), the European Society of Pediatric Dermatology (ESPD), Global Allergy and Asthma European Network (GA2LEN) and the European Union of Medical Specialists (UEMS).


“This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy.”

Note: Part 1 appeared in April’s CEBD Evidence Update



Management of congenital ichthyoses: European guidelines of care: Part Two.

Mazereeuw-Hautier J, Hernandez-Martin A, O'Toole EA, Bygum A, Amaro C, Aldwin M, Audouze A, Bodemer C, Bourrat E, Diociaiuti A, Dolenc-Voljc M, Dreyfus I, El Hachem M, Fischer J, Ganemo A, Gouveia C, Gruber R, Hadj-Rabia S, Hohl D, Jonca N, Ezzedine K, Maier D, Malhotra R, Rodriguez M, Ott H, Paige DG, Pietrzak A, Poot F, Schmuth M, Sitek JC, Steijlen P, Wehr G, Moreen M, Vahlquist A, Traupe H, Oji V.

Br J Dermatol. 2018 Jun 13. doi: 10.1111/bjd.16882. [Epub ahead of print]


“These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert-based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.”

Note: Part One not yet on PubMed at time of writing.



Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

Willemze R, Hodak E, Zinzani PL, Specht L, Ladetto M; ESMO Guidelines Committee.

Ann Oncol. 2018 Jun 6. doi: 10.1093/annonc/mdy133. [Epub ahead of print] No abstract available.


These guidelines on primary cutaneous lymphomas are produced by the European Society for Medical Oncology (ESMO) and “were developed in accordance with the ESMO standard operating procedures for Clinical Practice Guidelines development".



S3 Guideline for the treatment of psoriasis vulgaris, update - Short version part 2 - Special patient populations and treatment situations.

Nast A, Amelunxen L, Augustin M, Boehncke WH, Dressler C, Gaskins M, Härle P, Hoffstadt B, Klaus J, Koza J, Mrowietz U, Ockenfels HM, Philipp S, Reich K, Rosenbach T, Rzany B, Schlaeger M, Schmid-Ott G, Sebastian M, von Kiedrowski R, Weberschock T.

J Dtsch Dermatol Ges. 2018 Jun;16(6):806-813. doi: 10.1111/ddg.13538.


This is the updated German guideline for the treatment of psoriasis vulgaris.

“The second part of this short version of the guideline covers the following special patient populations and treatment situations: tuberculosis screening before and during psoriasis treatment, choice of psoriasis treatment for individuals wishing to have children, as well as during pregnancy and breast-feeding, and patients with joint involvement and vaccinations. In addition, recommendations on the choice of treatment are presented for patients with the following comorbidities: hepatitis and other hepatic impairment, HIV, malignancies, neurological and psychiatric disorders, ischemic heart disease and congestive heart failure, diabetes mellitus, renal impairment and inflammatory bowel disease.”



Cutaneous squamous cell carcinoma. Italian guidelines by SIDeMaST adapted to and updating EADO/EDF/EORTC guidelines.

Peris K, Alaibac M, Argenziano G, Di Stefani A, Fargnoli MC, Frascione P, Gualdi G, Longo C, Moscarella E, Naldi L, Pellacani G, Pimpinelli N, Quaglino P, Salgarello M, Sollena P, Valentini V, Zalaudek I, Calzavara Pinton PG; Italian Group of Dermato-oncology (GIDO) of SIDeMaST.

G Ital Dermatol Venereol. 2018 Jun 11. doi: 10.23736/S0392-0488.18.06093-5. [Epub ahead of print] No abstract available.


“These [Italian] guidelines outline all aspects of cSCC [cutaneous squamous cell carcinoma] management, from the clinical and histological diagnosis of primary tumor to the systemic treatment of the advanced or metastatic disease.”



Italian guidelines in pemphigus. Adapted from the European Dermatology Forum (EDF) and European Academy of Dermatology And Venerology (EADV).

Feliciani C, Cozzani E, Marzano AV, Caproni M, Di Zenzo G, Calzavara-Pinton P; "Cutaneous Immunology" group of SIDeMaST.

G Ital Dermatol Venereol. 2018 May 31. doi: 10.23736/S0392-0488.18.06073-X. [Epub ahead of print]


“This guideline for the diagnosis and treatment of pemphigus has been developed by an Italian group of experts taking in account the Italian legislation and local pharmacological governance. Guidelines are adapted from the original article under the guidance of the European Dermatology Forum (EDF) in collaboration with the European Academy of Dermatology and Venereology (EADV).”



[S1 guideline on intermittent pneumatic compression (IPC)].

Schwahn-Schreiber C, Breu FX, Rabe E, Buschmann I, Döller W, Lulay GR, Miller A, Valesky E, Reich-Schupke S.

Hautarzt. 2018 Jun 27. doi: 10.1007/s00105-018-4219-1. [Epub ahead of print]. German.


“Under the direction of the German Society of Phlebology (Deutsche Gesellschaft für Phlebologie) and in cooperation with other specialist associations, the S1 guideline on intermittent pneumatic compression (IPC) was adopted in January 2018. It replaces the previous guideline from March 2005. The aim of the guideline is to optimize the indication and therapeutic use of IPC in vascular diseases and edema.”



Guidelines for the diagnosis and treatment of male-pattern and female-pattern hair loss, 2017 version.

Manabe M, Tsuboi R, Itami S, Osada SI, Amoh Y, Ito T, Inui S, Ueki R, Ohyama M, Kurata S, Kono T, Saito N, Sato A, Shimomura Y, Nakamura M, Narusawa H, Yamazaki M; Drafting Committee for the Guidelines for the Diagnosis and Treatment of Male- and Female-Pattern Hair Loss.

J Dermatol. 2018 Jun 4. doi: 10.1111/1346-8138.14470. [Epub ahead of print]


“This is the secondary English‐language version of the original Japanese manuscript ‘Guidelines for the management of male and female pattern hair loss, 2017’ published in the Japanese Journal of Dermatology 127: 2763–2777, 2017.”


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Systematic reviews & evidence summaries



Eczema & dermatitis


Evaluation of hypothalamic-pituitary-adrenal axis suppression following cutaneous use of topical corticosteroids in children: A meta-analysis.

Wood Heickman LK, Davallow Ghajar L, Conaway M, Rogol AD.

Horm Res Paediatr. 2018 Jun 13:1-8. doi: 10.1159/000489125. [Epub ahead of print]


“RESULTS: Of 128 eligible trials, 12 were selected for meta-analysis with a total of 522 participants. There were 20 observed cases of HPA [hypothalamic-pituitary-adrenal] axis suppression (3.8%, 95% CI 2.4-5.8). The percentage of HPA axis suppression with low- (classes 6-7), medium- (classes 3-5) and high-potency (classes 1-2) TCS [topical corticosteroid] use was 2% (3 of 148 patients, 95% CI 0.7-5.8), 3.1% (7 of 223 patients, 95% CI 1.5-6.3), and 6.6% (10 of 151 patients, 95% CI 3.6-11.8), respectively.

CONCLUSION: There is a low rate of reversible HPA axis suppression with the use of mid- to low-potency TCS compared to more potent formulations. In pediatric clinical practice, the limited use of mid- to low-potency TCS is rarely associated with clinically significant adrenal insufficiency or adrenal crisis. In the absence of signs and symptoms of adrenal insufficiency, there is little need to test the HPA axis of these patients.”



Long-term topical corticosteroid use and risk of skin cancer: a systematic review.

Ratib S, Burden-Teh E, Leonardi-Bee J, Harwood C, Bath-Hextall F.

JBI Database System Rev Implement Rep. 2018 Jun;16(6):1387-1397. doi: 10.11124/JBISRIR-2017-003393.


See below under Skin cancers & sun protection



A systematic scoping literature review of publications supporting treatment guidelines for pediatric atopic dermatitis in contrast to clinical practice patterns.

Siegfried EC, Jaworski JC, Mina-Osorio P.

Dermatol Ther (Heidelb). 2018 Jun 1. doi: 10.1007/s13555-018-0243-4. [Epub ahead of print]


“RESULTS: Published literature partially supports clinical guidelines, with emollients and topical medications being the most investigated. There were disproportionately more publications for topical calcineurin inhibitors (TCI) compared with topical corticosteroids (TCS); however, the search interval may have biased the results toward treatments approved near the beginning of the time frame. In contrast, publications documenting clinical practice patterns reflect greater use of emollients and TCS (over TCI), as well as systemic corticosteroids. Data is relatively limited for long-term and combination treatment, treatment of severe AD, and patients younger than 2 years of age, and completely lacking for systemic corticosteroids.

CONCLUSION: This scoping review demonstrates that available medical literature largely supports published guidelines for topical therapy; however, clinical practice patterns are less aligned. There is a lack of data for older, more frequently used generic treatments, including oral antihistamines, oral antibiotics, and systemic corticosteroids. Overall, literature is lacking for long-term treatment, treatment for patients younger than 2 years of age, and for systemic treatment for severe disease.”



A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis.

Lee HH, Patel KR, Singam V, Rastogi S, Silverberg JI.

J Am Acad Dermatol. 2018 Jun 1. pii: S0190-9622(18)32046-2. doi: 10.1016/j.jaad.2018.05.1241. [Epub ahead of print]


“RESULTS: Overall, 25 studies met inclusion criteria. Seventeen studies reported age of AD[atopic dermatitis]-onset past 16 years and had sufficient data for meta-analysis. The pooled proportion (95% CI) of adult-onset AD was 26.1% (16.5-37.2%). Similar results were found in sensitivity analyses by diagnostic method for AD, study region, and gender. Phenotypical differences were observed across studies for adult vs. child onset AD, including higher rates of foot dermatitis and personal history of atopy, but lower rates of flexural lesions and other signs and symptoms.

LIMITATIONS: Characteristics of adult- vs. child-onset AD were not commonly reported.

CONCLUSIONS: AD is not only a disease of childhood. One in 4 adults with AD report adult-onset disease. Adult-onset AD was associated with distinct clinical characteristics.”



Association between eczema and risk of depression: A systematic review and meta-analysis of 188,495 participants.

Bao Q, Chen L, Lu Z, Ma Y, Guo L, Zhang S, Huang X, Xu S, Ruan L.

J Affect Disord. 2018 May 15;238:458-464. doi: 10.1016/j.jad.2018.05.007. [Epub ahead of print]


“RESULTS: Ten studies with a total of 188,495 patients were included. Overall, the random effects model summarizing all comparisons suggested a positive association between eczema and risk of depression, the pooled RR was 2.02 (95% confidence interval 1.76 to 2.31, I² = 33.7%). Similar results were observed in subgroup analysis by region.

LIMITATIONS: Methodological limitations such as selection biases, sample sizes, severity of other diseases, treatment strategy, age and other factors might have influenced the results.

CONCLUSIONS: Our study showed that patients with eczema were associated with an increased risk of depression. These findings implicated that clinical doctors should continue to be more aware of the association between eczema and the risk of depression.”



[Meta-analysis of traditional Chinese medicine Jianpi therapy in treatment of atopic dermatitis].

Liu Y, Zhao YD, Yan XN.

Zhongguo Zhong Yao Za Zhi. 2018 May;43(9):1922-1933. doi: 10.19540/j.cnki.cjcmm.20180210.001. Chinese.


“Studies have shown that traditional Chinese medicine Jianpi therapy had significantly higher clinical efficacy than western medicine in the treatment of atopic dermatitis. However, due to the publication bias and low quality bias of included RCTs in this study, more multicenter, high quality, large-sample, randomized double-blind controlled trials are needed to further demonstrate the conclusion.”



Effectiveness of interventions for preventing occupational irritant hand dermatitis: a quantitative systematic review.

Papadatou Z, Williams H, Cooper K.

JBI Database System Rev Implement Rep. 2018 Jun;16(6):1398-1417. doi: 10.11124/JBISRIR-2017-003405.


“RESULTS: There were no studies located that met the inclusion requirements of this review.

CONCLUSION: There is currently no evidence available to determine the effectiveness of interventions to prevent OIHD [occupational irritant hand dermatitis] amongst wet workers that met this review's inclusion criteria.”



Contact allergy: A review of current problems from a clinical perspective.

Uter W, Werfel T, White IR, Johansen JD.

Int J Environ Res Public Health. 2018 May 29;15(6). pii: E1108. doi: 10.3390/ijerph15061108.


“In conclusion, diverse sources of exposures to chemicals of widely-differing types and structures, continue to induce sensitisation in man and may result in allergic contact dermatitis. Many of the chemicals are "evergreen" but others are "newcomers". Vigilance and proper investigation (patch testing) are required to detect and inform of the presence of these haptens to which our populations remain exposed.”


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Psoriasis & psoriatic arthritis


Dietary recommendations for adults with psoriasis or psoriatic arthritis from the Medical Board of the National Psoriasis Foundation: A systematic review.

Ford AR, Siegel M, Bagel J, Cordoro KM, Garg A, Gottlieb A, Green LJ, Gudjonsson JE, Koo J, Lebwohl M, Liao W, Mandelin AM 2nd, Markenson JA, Mehta N, Merola JF, Prussick R, Ryan C, Schwartzman S, Siegel EL, Van Voorhees AS, Wu JJ, Armstrong AW.

JAMA Dermatol. 2018 Jun 20. doi: 10.1001/jamadermatol.2018.1412. [Epub ahead of print]


“Findings: We identified 55 studies meeting the inclusion criteria for this review. These studies represent 77 557 unique participants of which 4534 have psoriasis. Based on the literature, we strongly recommend dietary weight reduction with a hypocaloric diet in overweight and obese patients with psoriasis. We weakly recommend a gluten-free diet only in patients who test positive for serologic markers of gluten sensitivity. Based on low-quality data, select foods, nutrients, and dietary patterns may affect psoriasis. For patients with psoriatic arthritis, we weakly recommend vitamin D supplementation and dietary weight reduction with a hypocaloric diet in overweight and obese patients. Dietary interventions should always be used in conjunction with standard medical therapies for psoriasis and psoriatic arthritis.”



Prevalence and possible role of Candida species in patients with psoriasis: a systematic review and meta-analysis.

Pietrzak A, Grywalska E, Socha M, Roliński J, Franciszkiewicz-Pietrzak K, Rudnicka L, Rudzki M, Krasowska D.

Mediators Inflamm. 2018 May 6;2018:9602362. doi: 10.1155/2018/9602362. eCollection 2018.


“We identified nine cross-sectional studies including a total of 1038 subjects with psoriasis (psoriatics) and 669 controls. We found Candida species detection rates for psoriatics were significantly higher than those in the controls, especially in the oral mucosa milieux. These results suggest psoriasis may be one of the systemic diseases that predispose to oral Candida spp. carriage and infection.”



Generalized pustular psoriasis - A model disease for specific targeted immunotherapy, systematic review.

Boehner A, Navarini AA, Eyerich K.

Exp Dermatol. 2018 May 31. doi: 10.1111/exd.13699. [Epub ahead of print]


Our objective was to systematically review the literature for evidence of efficacy of targeted immunotherapy and their mode of action in the context of clinical phenotype, classification and pathogenesis of adult GPP. Classifying GPP is challenging since clinical criteria for description and diagnosis are not consistent between expert centers. We therefore defined diagnostic feasibility of the reviewed cases by assessing four criteria: compatible clinical history, typical dermatological features and/or diagnostic histopathology, consistent clinical pictures and the DITRA status. Pathogenesis of GPP is mediated by pathways that partly overlap plaque type psoriasis, with a more pronounced activity of the innate immune system. Both IL-1 and IL-36 but also IL-17 play a major role in disease formation. We ascertained a total of 101 published cases according to our predefined criteria and identified TNF-α, IL-12/23, IL-17 and IL-1β as targets for immunotherapy for the treatment of GPP. Of those cases, 61% showed complete response and 27% partial response to targeted immunotherapy. Only 12% experienced weak or no response. These data indicate that specific immunotherapy can be used to effectively treat GPP, with most evidence existing for anti-IL-17 agents.



Efficacy and safety of Tripterygium wilfordii Hook F on psoriasis vulgaris: a systematic review and meta-analysis of randomized controlled trials.

Lv M, Deng J, Tang N, Zeng Y, Lu C.

Evid Based Complement Alternat Med. 2018 Apr 22;2018:2623085. doi: 10.1155/2018/2623085. eCollection 2018.


“Results: Twenty eligible RCTs with 1872 participants were included for systematic review and meta-analysis. Studies were assessed using the Cochrane risk of bias tool. The meta-analysis of add-on effect of TwHF [Tripterygium wilfordii Hook F, a Chinese medicine] conferred benefit for psoriasis: combination treatment with compound glycyrrhizin (four studies, OR = 0.34, 95% CI 0.22-0.52, P < 0.00001, I2 = 0%), combination treatment with acitretin (three studies, OR = 0.25, 95% CI 0.10-0.63, P = 0.003, I2 = 50%), and combination treatment with compound amino-polypeptide tablet (three studies, OR = 0.37, 95% CI 0.22-0.63, P = 0.0002, I2 = 0%).

Conclusions: Despite several mild side effects of TwHF, there is evidence that TwHF is an effective therapy for psoriasis. However, the conclusions are limited by the small number of included trials. More well-designed RCTs with extensive follow-up periods are warranted to clarify the effects and safety of TwHF in treating psoriasis.”



Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational and clinical studies.

Alinaghi F, Calov M, Kristensen LE, Gladman DD, Coates LC, Jullien D, Gottlieb AB, Gisondi P, Wu JJ, Thyssen JP, Egeberg A.

J Am Acad Dermatol. 2018 Jun 18. pii: S0190-9622(18)32149-2. doi: 10.1016/j.jaad.2018.06.027. [Epub ahead of print]


“RESULTS: A total of 266 studies were included, examining 976,408 patients with psoriasis. Overall, the pooled proportion (95% confidence interval) of PsA [psoriatic arthritis] among patients with psoriasis was 19.7% (18.5%-20.9%). In children and adolescents (<18 years), the pooled prevalence was 3.3% (2.1%-4.9%). The PsA prevalence was 22.7% (20.6%-25.0%) in European, 21.5% (15.4%-28.2%) South American, 19.5% (17.1%-22.1%) North American, 15.5% (0.009%-51.5%) African, and 14.0% (11.7%-16.3%) in Asian psoriasis patients. The prevalence of PsA was 23.8% (20.1%-27.6%) in studies where the ClASsification criteria for Psoriatic ARthritis (CASPAR) was applied. The incidence of PsA among psoriasis patients ranged from 0.27 to 2.7 per 100 person-years.

LIMITATIONS: Between-study heterogeneity may have affected the estimates.

CONCLUSIONS: We found that one in five patients with psoriasis have PsA. With the growing recognition of CASPAR, more homogenous and comparable prevalence estimates are expected to be reported.”



Epidemiology of psoriasis and psoriatic arthritis in Italy-A systematic review.

Prignano F, Rogai V, Cavallucci E, Bitossi A, Hammen V, Cantini F.

Curr Rheumatol Rep. 2018 May 30;20(7):43. doi: 10.1007/s11926-018-0753-1.


“RECENT FINDINGS: Prevalence of psoriasis in specific regions showed more variability (0.8-4.5%) than that in the total population (1.8-3.1%). Prevalence of psoriatic arthritis in the general population was reported for only two regions, Chiavari (0.09%) and Marche (0.42%). All other studies reported prevalence of psoriatic arthritis in patients with psoriasis in single centres and Italy-wide (4.7-47.1%). Prevalence of psoriatic arthritis was highest in patients with nail and/or scalp psoriasis and/or intergluteal/perianal region involvement. Based on current available data, these conditions appear to affect a substantial number of people and will likely have an important impact on the Italian healthcare system.”



Malignancy development risk in psoriatic arthritis patients undergoing treatment: A systematic review and meta-analysis.

Luo X, Deng C, Fei Y, Zhang W, Li Y, Zhang X, Zhao Y, Zeng X, Zhang F.

Semin Arthritis Rheum. 2018 May 23. pii: S0049-0172(18)30067-2. doi: 10.1016/j.semarthrit.2018.05.009. [Epub ahead of print]


“RESULTS: Nine cohort studies were included, corresponding to a total of 43,115 PsA [psoriatic arthritis] patients undergoing therapy. A significant positive association between therapy and increased risk for overall malignancy was found relative to the general population as the reference group (pooled RR, 1.29; 95% CI: 1.04-1.60). High heterogeneity was found (I2 = 71.37%). Subgroup analysis reported that PsA patients treated with conventional synthetic disease modifying antirheumatic drugs (csDMARDs) presented increased cancer risk (pooled RR, 1.75; 95% CI: 1.40-2.18) but patients treated with biological disease modifying antirheumatic drugs (bDMARDs) did not (pooled RR, 0.957; 95% CI: 0.80-1.14). Compared to controls, patients with PsA undergoing treatment specifically are at increased risk for non-melanoma skin cancers (pooled RR, 2.46; 95% CI: 1.84-3.28).

CONCLUSIONS: This study allowed the estimation of cancer risk in PsA patients during therapy. Large-scale longitudinal studies will be essential to draw firm conclusions regarding PsA-associated risk for treatment-induced malignancy.”


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Acne & rosacea


Association of the TNF-α gene promoter polymorphisms at nucleotide -238 and -308 with acne susceptibility: a meta-analysis.

Wang B, He YL.

Clin Exp Dermatol. 2018 Jun 13. doi: 10.1111/ced.13648. [Epub ahead of print]


“CONCLUSION: Our findings suggest that the TNF-α -238 A allele is associated with increased susceptibility to acne in Asian but not in European populations, while the TNF-α -308 A allele is associated with increased susceptibility to acne in Asian and Turkish populations but not in European or Arab populations.”


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Skin cancers & sun protection


Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in melanoma patients: A meta-analysis.

Zhan H, Ma JY, Jian QC.

Clin Chim Acta. 2018 May 29;484:136-140. doi: 10.1016/j.cca.2018.05.055. [Epub ahead of print]


“RESULTS: Twelve studies with 4593 individuals were included. Patients with elevated NLR [neutrophil-to-lymphocyte ratio] had a significantly shorter overall survival (OS) (HR [hazard ratio]: 1.56, 95% CI: 1.28-1.90, p < .001) and disease-free survival (DFS)/progression-free survival (PFS) (HR = 1.86; 95% CI = 1.24-2.80; P = .003). Subgroup analyses showed that the negative prognostic effect of elevated NLR on OS remained substantial in North American and European populations and patients with non-metastatic and metastatic stage. Additionally, elevated NLR was related to worse OS in patients with melanoma, regardless of the sample size and the cut-off value.

CONCLUSION: Our findings suggest that elevated pretreatment NLR was associated with poor prognosis in melanoma patients, suggesting NLR might be a prognostic factor in patients with melanoma.”



A systematic review of surgical management of melanoma of the external ear.

Sawyer JD, Wilson ML, Neumeister MW.

Plast Reconstr Surg Glob Open. 2018 Apr 13;6(4):e1755. doi: 10.1097/GOX.0000000000001755. eCollection 2018 Apr.


“Results: In our subanalysis, patients who had recurrence were significantly more likely to have had wedge resection versus wide-local excision, and those with no recurrence were more likely to have undergone wide local excision. Nodular tumors had significantly greater thickness. Overall, conservative excisions provided excellent outcomes.

Conclusions: Conservative treatment for external ear melanoma produces satisfactory outcomes. There is no evidence to support the use of radical amputation and little evidence to support the removal of cartilage or perichondrium. Sentinel lymph node biopsy is warranted only with positive nodes. There is no role for elective neck dissection. The roles for chemo/radiation therapy are unclear and guidelines for other cutaneous melanomas should be followed.”



Immediate versus delayed reconstruction of head and neck cutaneous melanoma.

Quimby AE, Khalil D, Johnson-Obaseki S.

Laryngoscope. 2018 Jun 22. doi: 10.1002/lary.27250. [Epub ahead of print]


“RESULTS: Nine studies met inclusion criteria for final analysis. Two of the nine studies directly compared immediate versus delayed reconstruction and demonstrated lower rates of positive margins in the immediate reconstruction group (odds ratio 3.7, [95% CI 0. 79-17. 34]).

CONCLUSION: There are a paucity of studies directly comparing oncologic outcomes associated with immediate versus delayed reconstruction following excision of head and neck cutaneous melanoma. Based on a limited amount of heterogeneous data, single-stage excision with immediate reconstruction may be an oncologically sound alternative to delayed reconstruction for head and neck cutaneous melanoma.”



Long-term topical corticosteroid use and risk of skin cancer: a systematic review.

Ratib S, Burden-Teh E, Leonardi-Bee J, Harwood C, Bath-Hextall F.

JBI Database System Rev Implement Rep. 2018 Jun;16(6):1387-1397. doi: 10.11124/JBISRIR-2017-003393.


“RESULTS: A total of 1703 potentially relevant studies were identified following a comprehensive electronic search. After abstract and title screening, 51 full texts were assessed for eligibility criteria. Of these, no study met the inclusion criteria. No additional records were identified from searching unpublished literature.

CONCLUSIONS: We did not find any studies that could help us establish if long-term TCS [topical corticosteroids] use is associated with skin cancer. Future research using primary care databases might give a better understanding regarding long-term use of TCS and skin cancer.”



Conventional and combination topical photodynamic therapy for basal cell carcinoma: systematic review and meta-analysis.

Collier NJ, Haylett AK, Wong TH, Morton CA, Ibbotson SH, McKenna KE, Mallipeddi R, Moseley H, Seukeran D, Ward KA, Mohd Mustapa MF, Exton LS, Green AC, Rhodes LE.

Br J Dermatol. 2018 Jun 11. doi: 10.1111/bjd.16838. [Epub ahead of print]


“RESULTS: From 2,331 search results, 15 RCTs (2,327 patients; 3,509 BCCs) were included. PDT [photodynamic therapy] efficacy (5-year sustained clearance) was high although inferior to excisional surgery (nBCC [nodular basal cell carcinoma] pooled RR 0.76; 95% CI 0.63-0.91), and without re-treatment of partially-responding lesions, was modestly inferior to imiquimod (sBCC [superficial basal cell carcinoma]: RR 0.81; 95% CI 0.70-0.95) and similar to fluorouracil (sBCC: RR 0.88; 95% CI 0.75-1.04). Five-year sustained clearance was inferior with conventional versus fractionated PDT (sBCC: RR 0.76; 95% CI 0.68-0.84). PDT cosmesis was superior to surgery (sBCC: RR 1.68; 95% CI 1.32-2.14; nBCC: RR 1.82; 95% CI 1.19-2.80) and cryosurgery (BCC: RR 3.73; 95% CI 1.96-7.07), and without re-treatment of partially-responding lesions was similar to imiquimod (sBCC: RR 1.01; 95%CI 0.85-1.19) and fluorouracil (sBCC: RR 1.04; 95% CI 0.88-1.24). Peak pain was higher but of shorter duration with PDT than topical treatments. Serious adverse reactions were rarer with PDT than imiquimod (sBCC: RR 0.05; 95% CI 0.00-0.84) and fluorouracil (sBCC: RR 0.11; 95% CI 0.01-2.04). Combination PDT regimens demonstrated reduced recurrence and improved cosmesis; however, results from these small studies were often non-significant.

CONCLUSIONS: PDT is an effective treatment for low-risk BCC, with excellent cosmesis and safety. Imiquimod has higher efficacy than single-cycle PDT though more adverse effects. Highest efficacy is with excisional surgery. Fractionated and combination PDT options warrant further study.2



Heterogeneous relationships of squamous and basal cell carcinomas of the skin with smoking: the UK Million Women Study and meta-analysis of prospective studies.

Pirie K, Beral V, Heath AK, Green J, Reeves GK, Peto R, McBride P, Olsen CM, Green AC.

Br J Cancer. 2018 Jun 14. doi: 10.1038/s41416-018-0105-y. [Epub ahead of print]


“RESULTS: After 14 (SD4) years follow-up per woman, 6699 had a first registered cutaneous SCC and 48,666 a first BCC. In current versus never-smokers, SCC incidence was increased (RR = 1.22, 95% CI 1.15-1.31) but BCC incidence was decreased (RR = 0.80, 0.78-0.82). RRs varied substantially by anatomical site; for the limbs, current smoking was associated with an increased incidence of SCC (1.55, 1.41-1.71) and a decreased incidence of BCC (0.72, 0.66-0.79), but for facial lesions there was little association of current smoking with either SCC (0.93, 0.82-1.06) or BCC (0.92, 0.88-0.96). Findings in meta-analyses of results from this and seven other prospective studies were largely dominated by the findings in this study.

CONCLUSIONS: Smoking-associated risks for cutaneous SCC and BCC are in the opposite direction to each other and appear to vary by anatomical site.”



Systematic review of sentinel lymph node biopsy in Merkel cell carcinoma of the head and neck.

Karunaratne YG, Gunaratne DA, Veness MJ.

Head Neck. 2018 Jun 22. doi: 10.1002/hed.25345. [Epub ahead of print]


“RESULTS: Twenty-nine publications encompassing 136 patients were included. The SLNB [sentinel lymph node biopsy] finding was positive in 42 patients (30.9%). Primary MCC [Merkel cell carcinoma] was located on the malar/zygomatic (34.4%), forehead/frontal (13.5%), and nasal (13.5%) regions. Recurrence in an SLNB negative nodal basin result occurred in 10 patients (false negative rate of 19.2%). Site of primary MCC was not associated with a false-negative SLNB result; however, there was a non-statistically significant trend for increased frequency among midline lesions.

CONCLUSIONS: Sentinel lymph node biopsy (SLNB) is recommended for eligible patients with classification I and II head and neck MCC.”



Eccrine porocarcinoma: New insights and a systematic review of the literature.

Nazemi A, Higgins S, Swift R, In G, Miller K, Wysong A.

Dermatol Surg. 2018 Jun 8. doi: 10.1097/DSS.0000000000001566. [Epub ahead of print]


“RESULTS: Eccrine porocarcinoma most often presents in elderly patients on the head and neck or lower limbs. Metastatic disease at presentation is not uncommon (22%). Primary tumor location is significantly correlated with presence of metastasis (p = .038). The most common treatment is excision followed by Mohs micrographic surgery (MMS), although the outcomes after MMS were superior to those after surgical excision.

CONCLUSION: This systematic review of individual patient data reveals that all patients should have a histological diagnosis with imaging considered for high-risk cases. Primary tumor location should also be considered in diagnostic and therapeutic decision-making. Although wide local excision (WLE) is currently the first-line treatment, MMS is becoming increasingly used, with evidence indicating improved outcomes as compared to those seen with WLE.”



Malignant transformation of actinic cheilitis: A systematic review of observational studies.

Dancyger A, Heard V, Huang B, Suley C, Tang D, Ariyawardana A.

J Investig Clin Dent. 2018 Jun 4:e12343. doi: 10.1111/jicd.12343. [Epub ahead of print]


See below under Oral disorders


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Infections of the skin


Interventions for necrotizing soft tissue infections in adults.

Hua C, Bosc R, Sbidian E, De Prost N, Hughes C, Jabre P, Chosidow O, Le Cleach L.

Cochrane Database Syst Rev. 2018 May 31;5:CD011680. doi: 10.1002/14651858.CD011680.pub2. [Epub ahead of print]


“AUTHORS' CONCLUSIONS: We found very little evidence on the effects of medical and surgical treatments for NSTI [necrotizing soft tissue infections]. We cannot draw conclusions regarding the relative effects of any of the interventions on 30-day mortality or serious adverse events due to the very low quality of the evidence. The quality of the evidence is limited by the very small number of trials, the small sample sizes, and the risks of bias in the included trials. It is important for future trials to clearly define their inclusion criteria, which will help with the applicability of future trial results to a real-life population. Management of NSTI participants (critically-ill participants) is complex, involving multiple interventions; thus, observational studies and prospective registries might be a better foundation for future research, which should assess empiric antimicrobial therapy, as well as surgical debridement, along with the placebo-controlled comparison of adjuvant therapy. Key outcomes to assess include mortality (in the acute phase of the condition) and long-term functional outcomes, e.g. quality of life (in the chronic phase).”



Innovative nanocompounds for cutaneous administration of classical antifungal drugs: a systematic review.

Santos RS, Loureiro K, Rezende P, Nalone L, Barbosa RM, Santini A, Santos AC, da Silva CF, Souto EB, de Souza DP, Amaral RG, Severino P.

J Dermatolog Treat. 2018 Jun 1:1-37. doi: 10.1080/09546634.2018.1479726. [Epub ahead of print]


“This review provides a comprehensive analysis of the use of nano compounds for the current treatment of topical fungal infections. A special emphasis is given to the employment of lipid nanoparticles, due to their recognized efficacy, versatility and biocompatibility, attracting the major attention as novel topical nanocompounds used for the administration of antifungal drugs.”


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Drug & treatment reactions/safety


Vaccine-induced toxic epidermal necrolysis: A case and systematic review.

Chahal D, Aleshin M, Turegano M, Chiu M, Worswick S.

Dermatol Online J. 2018 Jan 15;24(1). pii: 13030/qt7qn5268s


“RESULTS: A total of 29 articles reporting EM [erythema multiforme], SJS [Stevens-Johnson syndrome], or TEN [toxic epidermal necrolysis] following vaccination were included from >5 countries. Of the 29, 22 articles reported EM, 6/29 reported SJS, and 4/29 reported TEN (3 articles reported cases of both EM and SJS/TEN).

CONCLUSIONS: We suggest consideration of vaccines as an etiology for cases of SJS or TEN that begin with an EM-like presentation, and provide further evidence for the use of etanercept as a viable treatment for TEN.”


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Vitiligo & pigmentary disorders


The global prevalence and correlates of skin bleaching: a meta-analysis and meta-regression analysis.

Sagoe D, Pallesen S, Dlova NC, Lartey M, Ezzedine K, Dadzie O.

Int J Dermatol. 2018 Jun 11. doi: 10.1111/ijd.14052. [Epub ahead of print]


“RESULTS: The pooled (imputed) lifetime prevalence of skin bleaching was 27.7% (95% CI: 19.6-37.5, I2  = 99.6, P < 0.01). The highest significant prevalences were associated with: males (28.0%), topical corticosteroid use (51.8%), Africa (27.1%), persons aged ≤30 years (55.9%), individuals with only primary school education (31.6%), urban or semiurban residents (74.9%), patients (21.3%), data from 2010-2017 (26.8%), dermatological evaluation and testing-based assessment (24.9%), random sampling methods (29.2%), and moderate quality studies (32.3%). The proportion of females in study samples was significantly related to skin bleaching prevalence.

CONCLUSION: Despite some limitations, our results indicate that the practice of skin bleaching is a serious global public health issue that should be addressed through appropriate public health interventions.”


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Hair & nail disorders


[Injection of PRP (Platelet-rich plasma) as a treatment for androgenetic alopecia : a systematic review of the literature].

Oth O, Stene JJ, Glineur R, Vujovic A.

Rev Med Brux. 2018 May 30. doi: 10.30637/2018.17-056. [Epub ahead of print]. French.


“CONCLUSION: This systematic review of the literature resulted in a qualitative analysis of 7 scientific studies on the effect of PRP [platelet-rich plasma] injection as a treatment for androgenetic alopecia. Although all the studies concluded in a favorable effect of this new treatment, a larger, rigorous study with objective analysis of the therapeutic effect is necessary.”



Cases of white piedra of the hair on the American continent: a case report and a systematic literature review.

Ramírez-Soto MC, Andagua-Castro J, Quispe MA, Aguilar-Ancori EG.

J Eur Acad Dermatol Venereol. 2018 Jun 11. doi: 10.1111/jdv.15112. [Epub ahead of print]


“In this report, we describe a case of white piedra of the hair in a Peruvian woman. We also conducted a systematic literature review of all case reports of white piedra on the American continent, with a view to determining the geographical distribution of the condition and identifying Trichosporon spp. commonly associated with this infection.”


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Oral disorders


Surgical versus non-surgical treatment of actinic cheilitis: a systematic review and meta-analysis.

de Vasconcelos Carvalho M, de Moraes SLD, Lemos CAA, Santiago Júnior JF, do Egito Vasconcelos BC, Pellizzer EP.

Oral Dis. 2018 Jun 16. doi: 10.1111/odi.12916. [Epub ahead of print]


“RESULTS: A total of 283 ACs [actinic cheilitis cases] in 10 studies were included. About 2.5% surgically treated cases underwent malignant transformation. The Weighted Remission Rate was higher for surgical (92.8%) compared to non-surgical treatment (65.9%). The Recurrence Rate was lower for surgical (8.4%) compared to non-surgical treatment (19.2%).

CONCLUSION: In this systematic review, the surgical treatment was more favorable than non-surgical for AC. Meanwhile, further studies are needed that should maximize methodological standardization and have greater rigor of the data collection process.”



Malignant transformation of actinic cheilitis: A systematic review of observational studies.

Dancyger A, Heard V, Huang B, Suley C, Tang D, Ariyawardana A.

J Investig Clin Dent. 2018 Jun 4:e12343. doi: 10.1111/jicd.12343. [Epub ahead of print]


“Only one article met the inclusion criteria. Based on the included article, it was determined that the malignant transformation rate of AC [actinic cheilitis] to squamous cell carcinoma (SCC) was 3.07%. Excluded articles focused on the clinicopathological characteristics and treatment efficacies of AC, and no malignant transformation rate was assessed. There is a need for more clinical studies on the malignant transformation of AC, as lip cancer is a public health concern. High-risk populations, including those living in tropical regions, have excessive exposure to UV radiation, and have older aged males, fair-skinned people, and smokers should be identified to prevent AC and its malignant change. Health practitioners should facilitate early intervention to prevent the progression of AC to SCC of the lip.”



Impact of systemic sclerosis oral manifestations on patients' health-related quality of life: a systematic review.

Smirani R, Truchetet ME, Poursac N, Naveau A, Schaeverbeke T, Devillard R.

J Oral Pathol Med. 2018 Jun 1. doi: 10.1111/jop.12739. [Epub ahead of print]


“RESULTS: From 375 screened studies, 6 cross-sectional studies were included in the systematic review. The total number of patients included per study ranged from 84 to 178. These studies reported a statistically significant association between oropharyngeal manifestations of systemic sclerosis (mainly assessed by maximal mouth opening and the mouth handicap in systemic sclerosis scale) and an impaired quality of life (measured by different scales). Studies were unequal concerning risk of bias mostly because of low level of evidence, different recruiting sources of samples, and different scales to assess the quality of life.

CONCLUSION: This systematic review demonstrates a correlation between oropharyngeal manifestations of systemic sclerosis and impaired quality of life, despite the low level of evidence of included studies. Large-scaled studies are needed to provide stronger evidence of this association.”



Oral lesions in Sjögren's syndrome: A systematic review.

Serrano J, López-Pintor RM, González-Serrano J, Fernández-Castro M, Casañas E, Hernández G.

Med Oral Patol Oral Cir Bucal. 2018 Jun 20. pii: 22286. doi: 10.4317/medoral.22286. [Epub ahead of print]


“RESULTS: Seventeen cross-sectional studies and one cohort study were finally included. The results showed that SS [Sjögren's syndrome] patients presented more OL [oral lesions] compared to non-SS patients. The most frequent types of OL registered in primary and secondary SS were angular cheilitis, atrophic glossitis, recurrent oral ulcerations and grooves or fissurations of the tongue, also when compared to a CG [control group].

CONCLUSIONS: OL are common and more frequent in SS patients when compared to a CG. This may be a consequence of low levels of saliva. More studies where these OL and all the possible cofounding factors are taken into account are needed.”



Geographic tongue: Predisposing factors, diagnosis and treatment. A systematic review.

González-Álvarez L, García-Pola MJ, Garcia-Martin JM.

Rev Clin Esp. 2018 Jun 11. pii: S0014-2565(18)30164-4. doi: 10.1016/j.rce.2018.05.006. [Epub ahead of print] English, Spanish.


“RESULTS: A total of 33 articles met these criteria. We analysed 4998 patients with GT [geographic tongue], with an age range of 0 to 85 years, and the burning sensation symptom was present in 9.2-47% of these patients. The GT diagnosis was clinical in 98.81% of the cases, and GT displayed an association with psoriasis, allergies and anxiety. Candida infection was present in 7.6% (24/315) of the cases, and the presence of caries was statistically significant. The only analysed clinical trial proposed treatment through the topical application of 0.1% triamcinolone acetonide combined or not with 0.05% retinoic acid.

CONCLUSIONS: The diagnosis of GT is mainly clinical. GT is an asymptomatic disorder that usually requires no treatment. Understanding GT is necessary due to the comorbid intraoral and extraoral diseases that accompany the condition.”


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Chronic wounds & ulcers


Dressings and topical agents for treating venous leg ulcers.

Norman G, Westby MJ, Rithalia AD, Stubbs N, Soares MO, Dumville JC.

Cochrane Database Syst Rev. 2018 Jun 15;6:CD012583. doi: 10.1002/14651858.CD012583.pub2. [Epub ahead of print]


“AUTHORS' CONCLUSIONS: More research is needed to determine whether particular dressings or topical agents improve the probability of healing of venous leg ulcers. However, the NMA [network meta-analysis] is uninformative regarding which interventions might best be included in a large trial, largely because of the low certainty of the whole network and of individual comparisons. The results of this NMA focus exclusively on complete healing; whilst this is of key importance to people living with venous leg ulcers, clinicians may wish to take into account other patient-important outcomes and factors such as patient preference and cost.”



Extracorporeal shock wave therapy for the healing and management of venous leg ulcers.

Cooper B, Bachoo P.

Cochrane Database Syst Rev. 2018 Jun 11;6:CD011842. doi: 10.1002/14651858.CD011842.pub2. [Epub ahead of print]


“AUTHORS' CONCLUSIONS: We found no RCTs assessing the effectiveness of extracorporeal shock wave therapy in the healing and management of venous leg ulceration. The lack of high-quality evidence in this area highlights a gap in research and may serve to justify the need for further research and evidence to provide guidance concerning the use of this treatment option for this condition. Future trials should be of clear design and include concomitant use of the current best practice treatment, multilayer compression therapy. Recruitment should aspire to best represent patients seen in clinical practice and patient-related outcome measures should be included in study design.”



A meta-analysis to compare four-layer to short-stretch compression bandaging for venous leg ulcer healing.

De Carvalho MR, Peixoto BU, Silveira IA, Oliveria BGRB.

Ostomy Wound Manage. 2018 May;64(5):30-37.


“The search yielded 557 papers; 21 met the study criteria for full-text analysis, and 7 met the meta-analysis inclusion criteria. The studies included 1437 patients, average age 70 (range 23-97) years with 1446 venous leg ulcers. Most (5) studies were classified as being at low risk of bias. At 12 and 16 weeks, 259 ulcers (51.08%) healed completely in the 4-layer and 234 (46.34%) in the short-stretch bandage groups, respectively (P = .41). At 24 weeks, 268 ulcers (69.07%) in the 4-layer and 257 (62.23%) in the short-stretch bandage groups, respectively, had healed (P = .16). The 2 bandage systems evaluated were similar in achieving complete healing at their respective study endpoints. The average time for healing was 73.6 ± 14.64 days in the 4-layer and 83.8 ± 24.89 days in the short-stretch bandage groups; no meta-analysis was done for this outcome due the inability to retrieve all the individual patient data for each study. The choice of compression system remains at the discretion of the clinicians based on evidence of effectiveness, patient tolerability, and preference. Additional randomized controlled trials to compare various wound and patient outcomes between different compression systems are warranted.”



Education of healthcare professionals for preventing pressure ulcers.

Porter-Armstrong AP, Moore ZE, Bradbury I, McDonough S.

Cochrane Database Syst Rev. 2018 May 25;5:CD011620. doi: 10.1002/14651858.CD011620.pub2.


“AUTHORS' CONCLUSIONS: We are uncertain whether educating healthcare professionals about pressure ulcer prevention makes any difference to pressure ulcer incidence, or to nurses' knowledge of pressure ulcer prevention. This is because the included studies provided very low-certainty evidence. Therefore, further information is required to clarify the impact of education of healthcare professionals on the prevention of pressure ulcers.”



Haemorrhage from varicose veins and varicose ulceration: A systematic review.

Serra R, Ielapi N, Bevacqua E, Rizzuto A, De Caridi G, Massara M, Casella F, Di Mizio G, de Franciscis S.

Int Wound J. 2018 May 28. doi: 10.1111/iwj.12934. [Epub ahead of print]


“From literature searching, we identify the following main issues to be discussed in the review: epidemiology and predisposing factors, pathophysiology and forensic aspects, first aid. It has been estimated that deaths for bleeding due to peripheral venous problems account up to 0.01% of autopsy cases. From a pathological point of view, venous bleeding may arise from either acute or chronic perforation of an enlarged vein segment through the weakened skin. From a forensic point of view, in cases of fatal haemorrhage the death scene can even simulate non-natural events, due to crime or suicide. In most cases, incorrect first aid led to fatal complications. Further investigation on epidemiology and prevention measures are needed.”



Self-management interventions for skin care in people with a spinal cord injury: part 1-a systematic review of intervention content and effectiveness.

Baron JS, Sullivan KJ, Swaine JM, Aspinall A, Jaglal S, Presseau J, White B, Wolfe D, Grimshaw JM.

Spinal Cord. 2018 May 25. doi: 10.1038/s41393-018-0138-3. [Epub ahead of print]


“RESULTS: In all, 15 studies testing 17 interventions were included in the review of intervention content. Interventions in these studies included 28 BCTs [Behavior Change Techniques]. The most common were "instructions on how to perform behavior" (16 interventions), "credible source" (12 interventions), and "social support (unspecified)" (9 interventions). Ten RCTs were included in the review of intervention effectiveness and they measured knowledge, self-efficacy, and skills relating to skin care/pressure ulcer (PU) prevention, skin care behaviors, skin status (PU prevalence, severity, and time to PU), and health-care utilization for skin problems. Evidence to support intervention effects on these outcomes was limited, particularly for clinical outcomes. Risk of bias assessments was often inconclusive due to poor reporting.

CONCLUSIONS: There is potential to design SCI [spinal cord injury] skin care interventions that include currently untested BCTs. Further research and better consistency in outcome measurements and reporting are required to synthesize evidence on effectiveness.”



A systematic review and meta-analysis of patient education in preventing and reducing the incidence or recurrence of adult diabetes foot ulcers (DFU).

Adiewere P, Gillis RB, Imran Jiwani S, Meal A, Shaw I, Adams GG.

Heliyon. 2018 May 2;4(5):e00614. doi: 10.1016/j.heliyon.2018.e00614. eCollection 2018 May.


“Findings: Six RCTs met the inclusion criteria. Only five RCTs reported on the incidence of DFU [diabetic foot ulcers] whilst only two reported on amputation rates. There was no advantage of combining different educational approaches in preventing/reducing DFU, relative risk (RR) of 0.50 (95%CI 0.21, 1.17) (P = 0.11). Two RCTs based on foot care education alone were compared with usual care; the result showed a non-significant effect (P = 0.57) with high heterogeneity of 77%. Analysis based on intensive versus brief educational approach showed a statistically reduced risk of incidence of DFU in the intervention group when compared to the control group; (RR, 0.37, 95%CI 0.14, 1.01) (P = 0.05) with high heterogeneity of 91%.

Interpretation: The intensive educational intervention was associated with reduced incidence of DFU.”



Characteristics, prevalence, and outcomes of diabetic foot ulcers in Africa. A systemic review and meta-analysis.

Rigato M, Pizzol D, Tiago A, Putoto G, Avogaro A, Paolo Fadini G.

Diabetes Res Clin Pract. 2018 May 25. pii: S0168-8227(18)30412-1. doi: 10.1016/j.diabres.2018.05.016. [Epub ahead of print]


“According to the data collected, the overall prevalence of foot ulcers was 13% and increased over time, especially since 2001. Approximately 15% of patients with foot lesions underwent major amputation and 14.2% died during hospitalization. In patients with diabetic ulcers, insulin therapy was uncommon and neuropathy was the most common predisposing factor, but the prevalence of peripheral arterial disease correlated with amputation rates. Amputation and mortality decreased over time, probably as result of the implementation of screening programs in the last ten years. Mortality was directly related to previous amputation.”


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Other disorders affecting the skin


Mortality in bullous pemphigoid: A systematic review and meta-analysis of standardized mortality ratios.

Kridin K, Schwartz N, Cohen AD, Zelber-Sagi S.

J Dermatol. 2018 Jun 15. doi: 10.1111/1346-8138.14503. [Epub ahead of print]


“Ten studies were included covering the period 1960-2015 (1736 patients, 746 deaths). Pooled all-cause SMR [standardized mortality ratio] was 3.6 (95% CI, 2.6-5.0). There was no trend in all-cause SMR across the last three decades (regression coefficient 0.02 [change in logSMR/year]; 95% CI, 0.04-0.08; P = 0.545). In conclusion, there is a 3.6-fold increased mortality among patients with BP [bullous pemphigoid] as compared with the age-matched general population. The excess mortality in BP has not changed significantly over the past 30 years.”



Increased risk of mortality in systemic sclerosis-associated digital ulcers: a systematic review and meta-analysis.

Meunier P, Dequidt L, Barnetche T, Lazaro E, Duffau P, Richez C, Couzi L, Truchetet ME, Seneschal J.

J Eur Acad Dermatol Venereol. 2018 Jun 10. doi: 10.1111/jdv.15114. [Epub ahead of print]


“RESULTS: The literature search identified 1473 citations. Fifty-nine studies were examined for full text. Ten articles were included for the meta-analysis. SSc [systemic sclerosis] patients with DUs [digital ulcers] had an increased pooled mortality risk: RR = 1.53 (IC 95%: [1.23-1.90]).

CONCLUSIONS: This meta-analysis revealed a higher mortality in SSc patients with associated DUs. Having DUs may be a predictive factor of developing organ involvement such as pulmonary or cardiovascular events that could be associated with poor survival. It suggests that early screening of DUs in SSc patients is important to identify patients most at risk of poor survival.”



Treatment of acquired reactive perforating dermatosis - a systematic review.

Lukács J, Schliemann S, Elsner P.

J Dtsch Dermatol Ges. 2018 Jun 21. doi: 10.1111/ddg.13561. [Epub ahead of print]


“Most medical literature on the treatment of ARPD [acquired reactive perforating dermatosis] is limited to individual case reports and small series of patients. Various therapies that have been tried include antihistamines, topical keratolytics, corticosteroids, tretinoin, oral drugs such as allopurinol or antibiotics, and phototherapy or photochemotherapy. While there are no specific criteria for the evidence-based selection of treatment options for ARPD, the first priority in management of these conditions should be treatment of an underlying disease if present. None of the described modalities has been approved for first-line therapy. It is recommended to choose a combination of drugs that reduce itching and assist in the resolution of the skin lesions at the same time.”



Impact of systemic sclerosis oral manifestations on patients' health-related quality of life: a systematic review.

Smirani R, Truchetet ME, Poursac N, Naveau A, Schaeverbeke T, Devillard R.

J Oral Pathol Med. 2018 Jun 1. doi: 10.1111/jop.12739. [Epub ahead of print]


See above under Oral disorders


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Skin conditions & dermatology in general


A systematic literature review of the human skin microbiome as biomarker for dermatological drug development.

van der Kolk T, van der Wall HEC, Balmforth C, Van Doorn MBA, Rissmann R.

Br J Clin Pharmacol. 2018 Jun 7. doi: 10.1111/bcp.13662. [Epub ahead of print]


“AIMS: To explore the potential of the skin microbiome as biomarker in six dermatological conditions i.e. atopic dermatitis (AD), acne vulgaris (AV), psoriasis vulgaris (PV), hidradenitis suppurativa (HS), seborrheic dermatitis/pityriasis capitis (SD/PC) and ulcus cruris (UC)…”

“CONCLUSION: For two indications, i.e. AD and AV, there is preliminary evidence to support implementation of the skin microbiome as biomarkers in early phase clinical trials. For PV, UC, SD and HS there is insufficient evidence from the literature. More microbiome-directed prospective studies studying the effect of current treatments on the microbiome with special attention for patient meta-data, sampling methods and analysis methods are needed to draw more substantial conclusions.”



Radiation effects of mobile phones and tablets on the skin: A systematic review.

Keykhosravi A, Neamatshahi M, Mahmoodi R, Navipour E.

Adv Med. 2018 Apr 12;2018:9242718. doi: 10.1155/2018/9242718. eCollection 2018.


“Results: Most of the studies focused on signs and less on skin cancer. In total, 6 studies were included with 392119 participants with age over 25 years. In a nationwide cohort study in Denmark for BCC, the IRR (incidence rate ratios) estimates remained near unity among men and women. In the other studies, they reported an increase in temperature, hypersensitivity of warmth, facial dermatitis, angiosarcoma of the scalp, and burning sensations in the facial skin after mobile phone use on the exposed side and more within the auricle and behind/around the ear.

Conclusions: Overall evaluations showed that the level of evidence associated with the effects of radiation from the mobile phone and tablet on the skin is poor. This review shows a necessity for more studies in this area.”


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Skin surgery and lasers


Effects and safety of triamcinolone acetonide-controlled common therapy in keloid treatment: a Bayesian network meta-analysis.

Zhang Z, Cheng L, Wang R, Cen Y, Li Z.

Ther Clin Risk Manag. 2018 May 29;14:973-980. doi: 10.2147/TCRM.S162315. eCollection 2018.


“Results: Ten randomized controlled trials were included in this meta-analysis. The relative risk of keloids associated with seven adjuvants was analyzed, including placebo, pulsed dye laser (PDL), 5-fluorouracil (5-FU), silicone, verapamil, TAC+5-FU and TAC+5-FU+PDL. Patients treated with the following adjuvants appeared to not have significantly reduced risk of keloid in relation to those treated with TAC [triamcinolone acetonide]: placebo (OR=1.86, 95% CI 1.12-2.61), PDL (OR=1.32, 95% CI 0.53-3.30), 5-FU (OR=1.13, 95% CI 0.48-2.68), silicone (OR=1.28, 95% CI 0.59-2.78), verapamil (OR=1.86, 95% CI 0.67-5.14), TAC+5-FU (OR=0.77, 95% CI 0.38-1.58) and TAC+5-FU+PDL (OR=0.80, 95% CI 0.16-4.03). The surface under the cumulative ranking curve values for each adjuvant were as follows: TAC, 59.9%; placebo, 17.4%; PDL, 46.3%; 5-FU, 48.9%; silicone, 56.2%; verapamil, 84.7%; TAC+5-FU, 68.5% and TAC+5-FU+PDL, 18.1%.

Conclusion: There were no differences between the efficacy of TAC and other common therapies in keloid treatment. TAC also acts as an effective alternative modality in the prevention and treatment of keloids. Incorporating adjuvants particularly verapamil appeared to be significantly associated with a decreased risk of keloids.”



Review: Surgical smoke: Risks assessment and mitigation strategies.

Georgesen C, Lipner SR.

J Am Acad Dermatol. 2018 Jun 11. pii: S0190-9622(18)32061-9. doi: 10.1016/j.jaad.2018.06.003. [Epub ahead of print]


“RESULTS: There are risks associated with surgical smoke, and although some dermatologists are aware of these risks, many are not using hazard reduction strategies such as smoke evacuators and surgical masks.

LIMITATIONS: Most of the data regarding surgical smoke hazards and methods for smoke safety is derived from in vitro and non-human in vivo studies, in addition to resources outside of the dermatology literature.

CONCLUSION: Standardized guidelines for surgical smoke safety should be implemented in the dermatology community and residency curriculum.”



Systematic review of the therapeutic roles of adipose tissue in dermatology.

Walocko FM, Eber AE, Kirsner RS, Badiavas E, Nouri K.

J Am Acad Dermatol. 2018 Jun 11. pii: S0190-9622(18)32071-1. doi: 10.1016/j.jaad.2018.06.010. [Epub ahead of print]


“RESULTS: Thirteen studies matched our inclusion criteria. Six of seven studies on scar treatment, all three studies on wound healing, and all three studies on hair growth demonstrated improved outcomes with adipose tissue treatments.

LIMITATIONS: The literature supporting the use of adipose tissue is limited to case series, cohort studies, and small randomized controlled trials, which have an overall low level of evidence.

CONCLUSION: The existing evidence for adipose tissue as a treatment option in scarring, wound healing, and hair growth is not strong enough to justify changes to current clinical practice. The literature does provide evidence for future large randomized clinical trials.”



Filling procedures for lip and perioral rejuvenation: A systematic review.

Pascali M, Quarato D, Carinci F.

Rejuvenation Res. 2018 Jun 18. doi: 10.1089/rej.2017.1941. [Epub ahead of print]


“This systematic review will focus on the various dermal fillers, of different materials approved by the US Food and Drug Administration (FDA) namely poly-L-lactic acid, calcium hydroxylapatite and hyaluronic acid and also different grafts, for perioral rejuveination, with the goal of determining the optimal approach.”



Efficacy of low-level laser therapy in management of recurrent herpes labialis: a systematic review.

Al-Maweri SA, Kalakonda B, AlAizari NA, Al-Soneidar WA, Ashraf S, Abdulrab S, Al-Mawri ES.

Lasers Med Sci. 2018 May 25. doi: 10.1007/s10103-018-2542-5. [Epub ahead of print]


“Of the retrieved 227 articles, six clinical trials met the eligibility criteria. The wavelengths, the power output, and energy density ranged between 632.5-870 nm, 5-80 W, and 2.04-48 J/cm2, respectively. All included studies found laser to be effective in the management and prevention of RHL [recurrent herpes labialis], without any side effects. The findings of this review suggest that laser is potentially a safe and effective treatment alternative for the management of RHL. However, due to high variability in study designs and inconsistency in laser parameters among the included studies, more well-designed randomized clinical trials with standardized laser parameters are highly warranted.”


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Service delivery & management


None found this month.


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Prescribing and safety alerts



We acknowledge the NICE Medicines Awareness Service and MHRA Drug Safety Update as sources in compiling this section.



European CHMP recommends approval of adalimumab biosimilars (Halimatoz, Hefiya and Hyrimoz)


The European Committee for Medicinal Products for Human Use (CHMP) has recommended approval of three adalimumab biosimilars—Halimatoz, Hefiya and Hyrimoz. According to UK Medicines Information: “Data show that Halimatoz, Hefiya and Hyrimoz have comparable quality, safety and efficacy to Humira (adalimumab). They will be available as a 40-mg solution for injection and are intended for certain inflammatory and autoimmune disorders (each biosimilar has a different license).”



Revised SmPC (Summary of Product Characteristics): Remicade (infliximab) 100mg powder for concentrate for solution for infusion


The SmPC now warns that adults be brought up to date with all vaccinations prior to initiating treatment and to clarify patients on infliximab may receive concurrent vaccinations, except for live vaccines. Linear IgA Bullous Dermatosis has been added as a rare adverse reaction.



Revised SmPC (Summary of Product Characteristics): Propecia (finasteride) 1mg tablets


Anxiety has been added as an adverse drug reaction of unknown frequency.



Revised SmPC (Summary of Product Characteristics): Roferon-A (interferon alfa-2a) solution for injection in pre-filled syringe (all strengths)


Section 4.8 has been updated to include skin depigmentation as an adverse effect with unknown frequency.



Revised SmPC (Summary of Product Characteristics): Siklos (hydroxycarbamide) Film-Coated Tablets – all strengths


Section 4.8 has been revised to include systemic and cutaneous lupus erythmatosus as very rare adverse reactions.



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CEBD publications & news



What's new in atopic eczema? An analysis of systematic reviews published in 2015. Part 2: prevention and treatment.

Lloyd-Lavery A, Rogers NK, Davies E, Grindlay DJC, Thomas KS.

Clin Exp Dermatol. 2018 May 27. doi: 10.1111/ced.13554. [Epub ahead of print]


“Topical corticosteroid withdrawal syndrome, 'steroid addiction', has been evaluated in a high-quality systematic review, which helps better define this entity and the risk factors for it. A Cochrane Review has not demonstrated any association between topical corticosteroid use in pregnancy and adverse outcomes, although very large quantities of potent/very potent topical corticosteroids may be associated with reduced birth weight. House dust mite avoidance strategies do not appear to prevent AE [atopic eczema]. Exposure to probiotics prenatally and in early infancy may help prevent AE, but there is no evidence that maternal diet or supplementation has a preventative effect.”



What's new in psoriasis treatment? An analysis of systematic reviews published in 2015.

Foulkes AC, Ferguson F, Grindlay DJC, Williams HC, Griffiths CEM, Warren RB.

Clin Exp Dermatol. 2018 May 27. doi: 10.1111/ced.13601. [Epub ahead of print]


“The evidence supports weight-loss interventions by dieting and exercise for improvement in disease severity in overweight and obese patients with psoriasis. No significant increased risk of serious infections was reported for the biologic therapies adalimumab, etanercept and ustekinumab compared with appropriate comparators. Evidence could not provide reliable estimates of rare adverse events, emphasizing the need for large prospective registries. Polymorphisms in the tumour necrosis factor (TNF)-α gene may confer improved responses to TNF inhibitor (TNFI) therapy, but the studies to date lack power to detect a true association. From the limited available evidence, multidisciplinary management is both more effective and more satisfactory for patients with psoriasis and psoriatic arthritis than conventional consultations.”



Putting the 'systematic' into searching - tips and resources for search strategies in systematic reviews.

Grindlay DJ, Karantana A.

J Hand Surg Eur Vol. 2018 Jul;43(6):674-678. doi: 10.1177/1753193418778978.


“In this article we aim to provide helpful tips for systematic review authors to avoid common errors and optimize their search strategies. The article should also help readers to critically appraise and interpret existing reviews. It is not intended as a comprehensive guide to systematic searching.”



Interventions for necrotizing soft tissue infections in adults.

Hua C, Bosc R, Sbidian E, De Prost N, Hughes C, Jabre P, Chosidow O, Le Cleach L.

Cochrane Database Syst Rev. 2018 May 31;5:CD011680. doi: 10.1002/14651858.CD011680.pub2. [Epub ahead of print]


See above under Infections of the skin



Long-term topical corticosteroid use and risk of skin cancer: a systematic review.

Ratib S, Burden-Teh E, Leonardi-Bee J, Harwood C, Bath-Hextall F.

JBI Database System Rev Implement Rep. 2018 Jun;16(6):1387-1397. doi: 10.11124/JBISRIR-2017-003393.


See above under Skin cancers & sun protection



James Lind Alliance Psoriasis Priority Setting Partnership - Shortlisting survey now live


The second, shortlisting survey for the James Lind Alliance Psoriasis Priority Setting Partnership (PSP) is now live. Participants are invited to choose up to ten questions to prioritise for research from a list of 55.

“Please take part if you are:

•­ a person who has psoriasis

•­ a carer/relative/friend of someone who has psoriasis

•­ a healthcare professional working with people with psoriasis

•­ from an organisation representing the interests of people with psoriasis.”



UK Dermatology Clinical Trials Network video


UK Dermatology Clinical Trials Network (UK DCTN), based at the CEBD, has launched a short video explaining about the Network and its work. Do take a look!



UK Dermatology Clinical Trials Network Annual Themed Research Call - Research development fund £10,000


Each year the UK Dermatology Clinical Trials Network (UK DCTN) run an open competition on a specified topic to assist research teams in developing their research idea. This award is principally designed to fund feasibility or pilot work that will eventually lead to a randomised controlled clinical trial, or inform the design of such a study.

The 2018 award is encouraging research ideas that have been prioritised by a recently completed Priority Setting Partnership. This mainly includes cellulitis and lichen sclerosus.


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Other key publications that have caught our eye



Emollient prescribing formularies in England and Wales: a cross-sectional study.

Chan JP, Boyd G, Quinn PA, Ridd MJ.

BMJ Open. 2018 Jun 12;8(6):e022009. doi: 10.1136/bmjopen-2018-022009.


“RESULTS: 102 formularies were identified, which named 109 emollients and 24 bath additives. Most were structured in an 'order of preference' (63%) and/or formulation (51%) format. Creams and ointments were the most commonly recommended types of emollients, and three ointments were the most commonly recommended specific emollients (71%-79% of formularies). However, there was poor consensus over which emollient should be used first line and 4 out of 10 of the most recommended lotions and creams contained antimicrobials or urea. Patient preference (60%) and/or cost (58%) were the most common reasons given for the recommendations. Of the 82% of formularies that recommend the use of bath additives, 75% did not give any reasons for their recommendation.

CONCLUSIONS: Emollient formularies in England and Wales vary widely in their structure, recommendations and rationale. The reasons for such inconsistencies are unclear, risk confusion and make for inequitable regional variation. There is poor justification for multiple different, conflicting formularies.”



Adolescents' perspectives on atopic dermatitis treatment: Experiences, preferences, and beliefs.

Kosse RC, Bouvy ML, Daanen M, de Vries TW, Koster ES.

JAMA Dermatol. 2018 May 30. doi: 10.1001/jamadermatol.2018.1096. [Epub ahead of print]


“Results: Three focus groups including 15 adolescents (8 male) with a mean age of 15.3 (range, 12-18) years were conducted. Adolescents were in general satisfied with the efficacy of the treatment; however, they prefer a faster and more persistent effect. Most adolescents had little contact with their physicians and did not completely adhere to the prescribed medication regimen; they developed their own routine of using topical corticosteroids in combination with emollients and moisturizers. They also seemed to have incorrect beliefs about the mechanism of action.

Conclusions and Relevance: Adolescents developed their own way of using topical treatment for atopic dermatitis. Some practical suggestions were mentioned to improve medication use. Health care providers should devote special attention to adolescents with atopic dermatitis to make them more aware of the principles of topical treatment and ensure proper use.”


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Dr Douglas Grindlay
Information Specialist

Centre of Evidence Based Dermatology
University of Nottingham

King’s Meadow Campus
Nottingham, NG7 2NR

+44 (0) 115 8468624



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