CEBD Evidence Update

March 2018


CEBD Skin of Colour Resource, bringing together information sources, systematic reviews and review articles on topics of relevance to skin of colour. 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. These updates are the first step in our aim of developing a CEBD Evidence Network, to bring together users of research evidence in dermatology. 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.


Do please forward this e-mail to other colleagues who might be interested and encourage them to sign up.


To join or leave this list, please visit the registration page on the JISCMail web site. Alternatively, you can e-mail [log in to unmask] to ask to be added to the list.


We welcome all feedback and suggestions for improvement—please e-mail Douglas Grindlay, [log in to unmask].








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 [TA511]—Brodalumab for treating moderate to severe plaque psoriasis


“1.1  Brodalumab 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 with the discount agreed in the patient access scheme.


1.2 Stop brodalumab at 12 weeks if the psoriasis has not responded adequately, defined as:

•a 75% reduction in the PASI score (PASI 75) from when treatment started or

•a 50% reduction in the PASI score (PASI 50) and a 5point reduction in DLQI from when treatment started.

1.3 When using the PASI, healthcare professionals should take into account skin colour and how this could affect the PASI score, and make the clinical adjustments they consider appropriate.

1.4 When using the DLQI, healthcare professionals should take into account any physical, psychological, sensory or learning disabilities, or communication difficulties that could affect the responses to the DLQI and make any adjustments they consider appropriate.

1.5 These recommendations are not intended to affect treatment with brodalumab that was started in the NHS before this guidance was published. People having treatment outside these recommendations may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.”



NICE Key therapeutic topic [KTT14] -  Wound care products


This document was updated in February 2018 and summarises the evidence-base on wound care products. It is a key therapeutic topic which has been identified to support medicines optimisation. It is not formal NICE guidance.


“Options for local implementation

• Review and, if appropriate, optimise prescribing of wound dressings to ensure that the least costly dressings that meet the required clinical performance characteristics are routinely chosen.

• Prescribe the minimum quantity of dressings sufficient to meet people's needs.

• Do not routinely choose antimicrobial (for example, silver, iodine or honey) dressings ahead of non-medicated dressings.”






Evaluation and treatment of hirsutism in premenopausal women: An Endocrine Society Clinical Practice Guideline.

Martin KA, Anderson RR, Chang RJ, Ehrmann DA, Lobo RA, Murad MH, Pugeat MM, Rosenfield RL.

J Clin Endocrinol Metab. 2018 Mar 7. doi: 10.1210/jc.2018-00241. [Epub ahead of print]


“Conclusion: We suggest testing for elevated androgen levels in all women with an abnormal hirsutism score. We suggest against testing for elevated androgen levels in eumenorrheic women with unwanted local hair growth (i.e., in the absence of an abnormal hirsutism score). For most women with patient-important hirsutism despite cosmetic measures (shaving, plucking, waxing), we suggest starting with pharmacological therapy and adding direct hair removal methods (electrolysis, photoepilation) for those who desire additional cosmetic benefit. For women with mild hirsutism and no evidence of an endocrine disorder, we suggest either pharmacological therapy or direct hair removal methods. For pharmacological therapy, we suggest oral combined estrogen-progestin contraceptives for the majority of women, adding an antiandrogen after 6 months if the response is suboptimal. We recommend against antiandrogen monotherapy unless adequate contraception is used. We suggest against using insulin-lowering drugs. For most women who choose hair removal therapy, we suggest laser/photoepilation.”


Note: There is also a JAMA Clinical Guidelines Synopsis for this guideline:

Evaluation and treatment of hirsutism in premenopausal women.

Mimoto MS, Oyler JL, Davis AM.

JAMA. 2018 Mar 9. doi: 10.1001/jama.2018.2611. [Epub ahead of print] No abstract available.



Behavioral Counseling to Prevent Skin Cancer: US Preventive Services Task Force Recommendation Statement.

US Preventive Services Task Force, Grossman DC, Curry SJ, Owens DK, Barry MJ, Caughey AB, Davidson KW, Doubeni CA, Epling JW Jr, Kemper AR, Krist AH, Kubik M, Landefeld S, Mangione CM, Silverstein M, Simon MA, Tseng CW.

JAMA. 2018 Mar 20;319(11):1134-1142. doi: 10.1001/jama.2018.1623.


“Findings: The USPSTF [US Preventive Services Task Force] determined that behavioral counseling interventions are of moderate benefit in increasing sun protection behaviors in children, adolescents, and young adults with fair skin types. The USPSTF found adequate evidence that behavioral counseling interventions result in a small increase in sun protection behaviors in adults older than 24 years with fair skin types. The USPSTF found inadequate evidence on the benefits and harms of counseling adults about skin self-examination to prevent skin cancer.

Conclusions and Recommendation: The USPSTF recommends counseling young adults, adolescents, children, and parents of young children about minimizing exposure to UV radiation for persons aged 6 months to 24 years with fair skin types to reduce their risk of skin cancer. (B recommendation) The USPSTF recommends that clinicians selectively offer counseling to adults older than 24 years with fair skin types about minimizing their exposure to UV radiation to reduce risk of skin cancer. Existing evidence indicates that the net benefit of counseling all adults older than 24 years is small. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the presence of risk factors for skin cancer. (C recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of counseling adults about skin self-examination to prevent skin cancer. (I statement).”

See accompanying systematic review under Skin cancers & sun protection



S2k guidelines for the use of topical preparations on the skin.

Wohlrab J, Staubach P, Augustin M, Eisert L, Hünerbein A, Nast A, Reimann H, Strömer K, Mahler V.

J Dtsch Dermatol Ges. 2018 Mar;16(3):376-392. doi: 10.1111/ddg.13473.


“The present guidelines are aimed at dermatology residents and board-certified dermatologists as well as policymakers and insurance companies. Developed by dermatologists in collaboration with pharmacists using a formal consensus process (S2k), they include general aspects with respect to pharmacokinetics and regulatory terminology. Recommendations are provided on the various indications for extemporaneous preparations and their quality assurance. The importance of pharmaceutical vehicles and problems associated with substituting one vehicle for another are discussed. The guidelines include criteria for choosing a suitable pharmaceutical vehicle and for specific aspects in terms of treatment planning. In addition, recommendations are given for managing allergic reactions to vehicles or additives.”



Optimal timing of initial debridement for necrotizing soft tissue infection: A practice management guideline from the Eastern Association for the Surgery of Trauma.

Gelbard RB, Ferrada P, Yeh DD, Williams B, Loor M, Yon J, Mentzer C, Khwaja K, Khan M, Kohli A, Bulger EM, Robinson BRH.

J Trauma Acute Care Surg. 2018 Feb 27. doi: 10.1097/TA.0000000000001857. [Epub ahead of print]


“RESULTS: Two hundred eighty-seven articles were identified. Of these, 42 papers underwent full text review and 6 were selected for guideline construction. A total of 341 patients underwent debridement for NSTI. Of these, 143 patients were managed with early versus 198 with late operative debridement. Across all studies, there was an overall mortality rate of 14% in the early group versus 25.8% in the late group.

CONCLUSIONS: For necrotizing soft tissue infections, we recommend early operative debridement within 12 hours of suspected diagnosis. Institutional and regional systems should be optimized to facilitate prompt surgical evaluation and debridement.”


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Systematic reviews & evidence summaries



Eczema & dermatitis


The association between maternal stress and childhood eczema: A systematic Review.

Chan CWH, Law BMH, Liu YH, Ambrocio ARB, Au N, Jiang M, Chow KM.

Int J Environ Res Public Health. 2018 Feb 25;15(3). pii: E395. doi: 10.3390/ijerph15030395.


“Overall, the included studies showed that a positive correlation exists between the experience of stress among mothers and eczema risk of their child. The findings highlight the importance of the implementation of stress reduction programs for pregnant women and those in their postpartum period within communities in order to enable these individuals to relieve stress effectively.”



Diet during pregnancy and infancy and risk of allergic or autoimmune disease: A systematic review and meta-analysis.

Garcia-Larsen V, Ierodiakonou D, Jarrold K, Cunha S, Chivinge J, Robinson Z, Geoghegan N, Ruparelia A, Devani P, Trivella M, Leonardi-Bee J, Boyle RJ.

PLoS Med. 2018 Feb 28;15(2):e1002507. doi: 10.1371/journal.pmed.1002507. eCollection 2018 Feb.


“Evidence from 19 intervention trials suggests that oral supplementation with nonpathogenic micro-organisms (probiotics) during late pregnancy and lactation may reduce risk of eczema (Risk Ratio [RR] 0.78; 95% CI 0.68-0.90; I2 = 61%; Absolute Risk Reduction 44 cases per 1,000; 95% CI 20-64), and 6 trials suggest that fish oil supplementation during pregnancy and lactation may reduce risk of allergic sensitisation to egg (RR 0.69, 95% CI 0.53-0.90; I2 = 15%; Absolute Risk Reduction 31 cases per 1,000; 95% CI 10-47). GRADE certainty of these findings was moderate. We found weaker support for the hypotheses that breastfeeding promotion reduces risk of eczema during infancy (1 intervention trial), that longer exclusive breastfeeding is associated with reduced type 1 diabetes mellitus (28 observational studies), and that probiotics reduce risk of allergic sensitisation to cow's milk (9 intervention trials), where GRADE certainty of findings was low. We did not find that other dietary exposures-including prebiotic supplements, maternal allergenic food avoidance, and vitamin, mineral, fruit, and vegetable intake-influence risk of allergic or autoimmune disease. For many dietary exposures, data were inconclusive or inconsistent, such that we were unable to exclude the possibility of important beneficial or harmful effects. In this comprehensive systematic review, we were not able to include more recent observational studies or verify data via direct contact with authors, and we did not evaluate measures of food diversity during infancy.”



Association between the age of solid food introduction and eczema; a systematic review and a meta-analysis.

Waidyatillake NT, Dharmage SC, Allen K, Bowatte G, Boyle R, Burgess J, Koplin J, Garcia-Larsen V, Lowe AJ, Lodge C.

Clin Exp Allergy. 2018 Mar 23. doi: 10.1111/cea.13140. [Epub ahead of print]


“RESULTS: A total of 17 papers met the inclusion criteria, reporting results from 16 study populations. Of these, 11 were cohort studies, two case controls, one cross sectional study and, 2 randomised controlled trials. Limited meta-analyses were performed due to heterogeneity between studies. Timing of solid food introduction was not associated with eczema. One randomized controlled trial provided weak evidence of an association between early allergenic (around 4 months) food introduction and reduced risk of eczema.

CONCLUSIONS: The available evidence is currently insufficient to determine whether the timing of introduction of any solid food influences the risk of eczema.”



Serum interleukin-31 level and pruritus in atopic dermatitis: A meta-analysis.

Lu J, Wu K, Zeng Q, Xiang Y, Gao L, Huang J.

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Feb 28;43(2):124-130. doi: 10.11817/j.issn.1672-7347.2018.02.003.


“The Meta-analysis showed that serum IL-31 [interleukin-31] levels were higher in AD [atopic dermatitis] patients than those in the healthy controls. The levels of IL-31 were higher in severe AD patients than those in the mild and moderate AD patients. Moreover, a positive correlation between serum IL-31 levels and severity of pruritus was identified. Conclusion: Increased serum levels of IL-31 generally exist in the AD patients, and it may accelerate the pruritus in the AD patients.”



Topical Antibiotics for Infected Dermatitis: A Review of the Clinical Effectiveness and Guidelines [Internet].

Tran K, Wright MD.

Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Mar 3.

Note: Only just added to PubMed.


“Conclusions and Implications for Decision or Policy Making:

The current evidence suggests that adding topical antibiotics to other topical treatments in people with clinically infected dermatitis provided no additional benefits. The use of intranasal mupirocin application and bleach bath may improve the severity of infected dermatitis. Three guidelines did not recommend the long-term or routine use of topical antibiotics in patients with atopic dermatitis, while another guideline could not make a recommendation because of the lack of clear evidence. Future studies should have a more formal definition of the term, “infected dermatitis”. There is a need for a large good quality study with long-term follow-up to determine when topical antibiotics should and should not be used in individuals with different types of dermatitis and different severity of infection.”


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Psoriasis & psoriatic arthritis


A systematic review and meta-analysis of the efficacy and safety of the interleukin (IL)-12/23 and IL-17 inhibitors ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab for the treatment of moderate to severe plaque psoriasis.

Bilal J, Berlinberg A, Bhattacharjee S, Trost J, Riaz IB, Kurtzman DJB.

J Dermatolog Treat. 2018 Mar 13:1-37. doi: 10.1080/09546634.2017.1422591. [Epub ahead of print]


“METHODS AND RESULTS: 24 randomized placebo-controlled trials were included. Compared to placebo, risk ratios (RR) of achieving PASI-75 and PGA/IGA 0/1 respectively were 20.20 (95% CI 13.82-29.54, p < 0.00001) and 14.55 (10.42-20.31, p < 0.00001) for ustekinumab 90mg, 13.75 (8.49-22.28, p < 0.00001) and 9.81 (5.70-16.89, p < 0.00001) for ustekinumab 45mg, 17.65 (12.38-25.17, p < 0.00001) and 26.13 (16.05-42.53, p < 0.00001) for secukinumab 300mg, 15.36 (10.76-21.94, p < 0.00001) and 20.91 (12.82-34.13, p < 0.00001) for secukinumab 150mg, 18.22 (10.63-31.23, p < 0.000001) and 18.82 (10.36-34.16, p < 0.00001) for ixekizumab 80mg every 4 weeks, 19.83 (11.07-35.52, p < 0.00001) and 20.41 (11.01-37.81, p < 0.00001) for ixekizumab 80mg every 2 weeks, 14.79 (9.86-22.16, p < 0.00001) and 21.93 (15.52-31.01, p < 0.00001) for brodalumab 210mg, 11.55 (7.77-17.18, p < 0.00001) and 16.59 (11.72-23.49, p < 0.00001) for brodalumab 140mg, 12.40 (8.87-17.34, p < 0.00001) and 10.84 (7.91-14.85, p < 0.00001) for guselkumab 100mg, 11.45 (7.45-17.58, p < 0.00001) and 10.97 (6.44-18.69, p < 0.00001) for tildrakizumab 200mg, 11.02 (7.17-16.93, p < 0.00001) and 10.03 (6.45-15.59, p < 0.00001) for tildrakizumab 100mg. Similar outcomes were seen for PASI-90. Safety was satisfactory for each therapy at any dose, but a slightly increased risk of withdrawal due to toxicity was observed in individuals receiving ixekizumab compared to placebo.

CONCLUSION: Ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab were highly efficacious and generally well-tolerated when used as treatments for moderate to severe plaque psoriasis.”



Psoriasis treatment in HIV-positive patients: a systematic review of systemic immunosuppressive therapies.

Nakamura M, Abrouk M, Farahnik B, Zhu TH, Bhutani T.

Cutis. 2018 Jan;101(1):38;42;56.


“A comprehensive systematic review of the literature via a PubMed search of articles indexed for MEDLINE using the terms psoriasis and HIV and psoriatic arthritis and HIV combined with several systemic immunosuppressive agents yielded a total of 25 reported cases of systemic immunosuppressive therapies used to treat psoriatic disease in HIV-positive patients including methotrexate, cyclosporine, etanercept, adalimumab, infliximab, and ustekinumab. The limited data suggest that biologic therapies may be effective for cases of psoriasis recalcitrant to other systemic agents and may have a positive effect on CD4 and viral counts when used in combination with highly active antiretroviral therapy (HAART); however, further studies are needed.”



Use of topical therapies for pediatric psoriasis: A systematic review.

Kravvas G, Gholam K.

Pediatr Dermatol. 2018 Mar 1. doi: 10.1111/pde.13422. [Epub ahead of print]


“A total of 13 relevant articles were identified on the following topical agents: corticosteroids, calcineurin inhibitors, vitamin D analogs, and dithranol. Corticosteroids achieved clearance in 72.7% of patients. Calcitriol lead [sic] to a 57.2%-100% mean improvement in severity, and calcipotriol to 52%-64%. Combination of calcipotriol and corticosteroids achieved an improvement in mean severity ranging between 32.1% and 80%. Treatment with tacrolimus lead to an >50% improvement. Finally, short contact dithranol lead to a variable response in clearance between different studies, ranging between 3.7% and 81%. No serious adverse reactions were documented, the most common local reaction being irritation. Pediatric psoriasis is a common and challenging condition with no easy and definitive solution. Topical agents are safe, easy to use, readily available and cheap. However, they need to be applied repeatedly, may cause skin irritation, and can be messy. Based on the results presented above, we recommend utilizing all the available topical options before escalating to systemic treatments.”



Scaly pink patches: differentiating psoriasis from basal cell carcinoma.

Hanna C, Cook L, Foulke G, Seiverling EV.

Cutis. 2018 Jan;101(1):44-46.


“We performed a systematic review of the literature to assess the role of dermoscopy in evaluating psoriasis, and briefly reviewed the findings with an emphasis on the specificity or sensitivity of the dermoscopic findings of psoriasis. We also describe the case of a 63-year-old man with a history of psoriasis and basal cell carcinoma (BCC) who presented with a new scaly pink patch on the back. This case highlights the importance of dermoscopy in differentiating patches and plaques of psoriasis from BCC.”



The associations between psychological stress and psoriasis: a systematic review.

Stewart TJ, Tong W, Whitfeld MJ.

Int J Dermatol. 2018 Mar 8. doi: 10.1111/ijd.13956. [Epub ahead of print]


“We performed a systematic review of the literature with the aim of determining whether there is a temporal association between psychological stress as the predictor and onset and/or exacerbation of psoriasis as the outcome measure. Our secondary aim was to establish whether there is a relationship between the degree of psychological stress and clinical severity of psoriasis. Our systematic review demonstrates a probable temporal association between different measures of psychological stress and onset, recurrence, and severity of psoriasis. In the light of this, we suggest clinicians include "stress" as a trigger factor in their psoriasis assessment and consider psychological interventions as adjuncts, particularly in those who identify as "stress-responders".”



Association between psoriasis and asthma risk: A meta-analysis.

Wang J, Ke R, Shi W, Yan X, Wang Q, Zhang Q, Chai L, Li M.

Allergy Asthma Proc. 2018 Mar 1;39(2):103-109. doi: 10.2500/aap.2018.39.4109.


“RESULTS: A total of six studies with 66,772 psoriasis cases and 577,415 controls were included. Our meta-analysis showed that psoriasis was significantly associated with the increased risk of asthma (OR 1.32 [95% CI, 1.20-1.46]). The older age patients with psoriasis (≥50 years) (OR 1.64 [95% CI, 1.44-1.88]) had a higher risk of asthma susceptibility compared with the younger patients (20-49 years old) (OR 1.25 [95% CI 1.09-1.44]). Subgroup analysis by ethnicity indicated a significant increase in asthma risk in both Asian populations (OR 1.35 [95% CI, 1.18-1.54]) and white populations (OR 1.27 [95% CI, 1.05-1.54]) with psoriasis compared with those without psoriasis.

CONCLUSION: Results of this meta-analysis indicated that the patients with psoriasis had a higher risk of asthma susceptibility, especially among the older patients with psoriasis.”



The comparative immunogenicity of biologic therapy and its clinical relevance in psoriatic arthritis: a systematic review of the literature.

Balsa A, Lula S, Marshall L, Szczypa P, Aikman L.

Expert Opin Biol Ther. 2018 Mar 13. doi: 10.1080/14712598.2018.1450385. [Epub ahead of print]


“Our evaluation of the published literature shows that the immune responses to the various biologic therapeutic agents currently being used to treat PsA are similar to those observed for these agents in other rheumatic diseases. Moreover, similar to observations in other rheumatic diseases, the incidence of ADA formation to biologic agents in patients with PsA is often decreased when patients are given concomitant treatment with disease-modifying anti-rheumatic drugs. These data strongly suggest that the immune response is a characteristic of the biologic agent. Using therapeutic drug monitoring may be an approach to assess the immune response to the agent and to mitigate the potential impact on efficacy and safety, and consequently optimize treatment.”


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Acne & rosacea


Incidence and prevalence of rosacea: A systematic review and meta-analysis.

Gether L, Overgaard LK, Egeberg A, Thyssen JP.

Br J Dermatol. 2018 Feb 25. doi: 10.1111/bjd.16481. [Epub ahead of print]


“RESULTS: A total of 32 studies were included examining a total of 41 populations with 26,519,836 individuals. 22 populations were from Europe, three from Africa, four from Asia, nine from North America, and three from South America. The pooled proportion of rosacea was 5.46% (95% CI 4.91-6.04) in the general population and 2.39% (95% CI 1.56-3.39) among dermatology outpatients. Self-reported rosacea gave higher prevalence estimates than rosacea diagnosed by clinical examination, suggesting a low specificity of questionnaires based on symptoms. Rosacea affected both women (5.41%, (CI 95% 3.85-7.23)) and men (3.90% (CI 95% 3.04-4.87)), and mostly those aged 45-60 years.

CONCLUSION: We estimated the global prevalence of rosacea based on published data and found that 5.46% of the adult population is affected. However, the prevalence of rosacea depended on the diagnostic method with higher estimates in questionnaire studies and lower estimates in health registries.”


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Skin cancers & sun protection


Surgical re-excision versus observation for histologically dysplastic nevi: A systematic review of associated clinical outcomes.

Vuong KT, Walker J, Powell H, Thomas NE, Jonas DE, Adamson AS.

Br J Dermatol. 2018 Mar 23. doi: 10.1111/bjd.16557. [Epub ahead of print]


“A total of 5,293 records were screened, 18 articles were assessed in full-text, and 12 studies met inclusion criteria. No controlled trials were identified. Most studies (11/12, 92%) were retrospective chart reviews, and one was both a cross sectional and cohort study. Many studies (9/12, 75%) had no head-to-head comparison groups and either only reported HDN [histologically dysplastic nevi] that were re-excised or observed. A total of 2,673 (1535 observed vs 1138 re-excised) HDN of various grades were included. Follow up varied between 2 weeks to 30 years. Nine studies reported that no melanomas developed. Eleven biopsy site melanomas developed across 3 of the studies, 6 among observed lesions (0.39%) and 5 among re-excised lesions (0.44%). Based upon the available evidence the rates of biopsy site primary melanoma was similarly low among observed lesions and re-excised lesions. This suggests that HDNs can be observed with minimal adverse melanoma associated outcomes. However, all included articles were of low quality and further prospective trials could better guide clinical decision making.”



Behavioral counseling for skin cancer prevention: Evidence report and systematic review for the US Preventive Services Task Force.

Henrikson NB, Morrison CC, Blasi PR, Nguyen M, Shibuya KC, Patnode CD.

JAMA. 2018 Mar 20;319(11):1143-1157. doi: 10.1001/jama.2017.21630.


“Results: Twenty-one trials in 27 publications were included (N = 20 561). No studies assessed skin cancer outcomes in pediatric populations; 1 adult trial (n = 1356) promoting skin self-examination found no significant difference in participants diagnosed with melanoma in the intervention group vs the control group at 12-month follow-up (0 vs 1 diagnosis). There was no consistent improvement in prevention of sunburn for children (3 trials [n = 2508]) or adults (6 trials [n = 3959]). There were small to moderate increases in sun protection behavior in pediatric populations (6 trials [n = 4252]) and adults (12 trials [n = 13 099]) and small increases in skin self-examination in adults (11 trials [n = 7771]; odds ratios, 1.16-2.6). One of 3 trials of indoor tanning found an intervention effect; an appearance-focused intervention (n = 430) resulted in a smaller increase in mean indoor tanning sessions at 6 months in the intervention group vs the control group. Harms were rarely reported: 1 trial of skin self-examination (n = 1356) found an increase in skin procedures in the intervention group vs the control group at 6 months (8.0% vs 3.6%, P < .001) but not between 6 and 12 months (3.9% vs 3.3%, P = .50), and 1 trial (n = 217) found no between-group difference in skin cancer worry (28.9% vs 18.4%, P = .16).

Conclusions and Relevance: Behavioral interventions can increase sun protection behavior, but there is no consistent evidence that interventions are associated with a reduction in the frequency of sunburn in children or adults and minimal evidence on skin cancer outcomes. Intervention can increase skin self-examination in adults but may lead to increased skin procedures without detecting additional atypical nevi or skin cancers.”



Are phosphodiesterase type 5 inhibitors associated with increased risk of melanoma?: A systematic review and meta-analysis.

Feng S, Zhou L, Liu Q, He Q, Liao B, Wei X, Li H, Wang K, Zhu Y.

Medicine (Baltimore). 2018 Jan;97(3):e9601. doi: 10.1097/MD.0000000000009601.


“We included 5 studies containing 100,932 participants in our systematic review and meta-analysis. The calculated results suggested positive results of PDE5 inhibitors on melanoma risk (OR: 1.13; 95%CI: 1.04-1.23). For localized and nonlocalized melanoma, the results were different (OR: 1.22; 95%CI: 1.04-1.43 for localized melanoma) (OR: 0.62; 95%CI: 0.39-0.98 for nonlocalized melanoma). It also showed that PDE5 inhibitors were associated with increased BCC risk (OR: 1.18; 95%CI: 1.11-1.27).The association between PDE5 inhibitors and melanoma might not be causal due to potential bias (patient selection, and so on) and limitations.”



Association between phosphodiesterase type 5 inhibitors use and risk of melanoma: a meta-analysis.

Deng T, Duan X, Liu B, Lan Y, Cai C, Zhang T, Zhu W, Mai Z, Wu W, Zeng G.

Neoplasma. 2018;65(2):216-221. doi: 10.4149/neo_2018_170111N23.


“A total of six clinical trials containing more than one million participants were included. ED patients  using PDE5-Is shared a significant high risk of melanoma (RR=1.12, 95% CI=1.03-1.21, p=0.006). Positive associations were observed in all kinds of prescriptions: single prescription (RR=1.20, 95% CI=1.06-1.35, p=0.003), medium number of prescription (RR=1.15, 95% CI=1.01-1.30, p=0.03), and high number of prescription (RR=1.18, 95% CI=1.05-1.34, P=0.006). Additionally, PDE5-Is were also found to be significantly associated with increased risk of basal cell carcinoma (RR=1.14, 95% CI=1.09-1.19, p<0.00001). Our study indicates that PDE5-Is use could significantly increase the risk of melanoma and basal cell carcinoma. However, the risk of melanoma did not rise significantly with the increased number of prescriptions. Consequently, owing to the lack of information about other potential synergistic factors, it is difficult for us to make a solid conclusion that application of PDE5-Is is the direct cause of increased risk of melanoma. Their relationship needs to be validated by further evidences.”



Treatments for Basal Cell and Squamous Cell Carcinoma of the Skin [Internet].

Drucker A, Adam GP, Langberg V, Gazula A, Smith B, Moustafa F, Weinstock MA, Trikalinos TA.

Rockville (MD): Agency for Healthcare Research and Quality (US); 2017 Dec.


“CONCLUSIONS: Based on sparse evidence, surgical and radiation treatments have lower recurrence rates than other modalities for the treatment of low-risk BCC, and PDT [photodynamic therapy] appears to have superior cosmetic outcomes. Large gaps remain in the literature regarding the comparison of individual interventions and SCC in situ, with very little or no information on immunocompromised patients, patients with limited life expectancy, and patients with specific lesion categories, including high-risk BCCs and invasive SCCs.”



Efficacy of hypofractionated radiotherapy in patients with non-melanoma skin cancer: Results of a systematic review.

Gunaratne DA, Veness MJ.

J Med Imaging Radiat Oncol. 2018 Mar 9. doi: 10.1111/1754-9485.12718. [Epub ahead of print]


“Forty relevant publications (1983-2017) encompassing 12,337 irradiated lesions were retrieved. Studies documented a mean age of 71.73 years and male predilection (54.5%). Both external beam radiotherapy and brachytherapy were utilized. Tumour subtype was squamous cell carcinoma (23.5%), basal cell carcinoma (75.2%) or others (1.3%). Irradiated lesions were primary (or denovo) (92.6%), located on the head and neck (95.7%) and received definitive therapy (96.5%). Analysis demonstrated a mean weighted total radiotherapy dose (38.15 Gy), dose per fraction (7.95 Gy) and treatments per week (2.98). Despite significant heterogeneity in the study population, the radiotherapy delivered and follow-up, local recurrence rate (crude or Kaplan-Meier analysis) did not exceed 7.9% in all but three of the 36 publications providing these data. Twenty-nine publications documented local control exceeding 90%. There is a body of evidence documenting the efficacy of hypofractionated radiotherapy as an option that confers no obvious disadvantage in local control when compared to traditional more protracted radiotherapy schedules.”



Incidence of nonmelanoma skin cancer in renal transplant recipients: A systematic review and meta-analysis.

Matinfar M, Shahidi S, Feizi A.

J Res Med Sci. 2018 Feb 20;23:14. doi: 10.4103/jrms.JRMS_817_17. eCollection 2018.


“Results: Twenty-nine studies comprising 36,021 patients meet the criteria for the systematic review. The pooled incidence of NMSC [nonmelanoma skin cancer] in renal transplant recipients was 12.6% (95% CI: 12%-14%) with a majority of squamous cell carcinoma (SCC) 55% (95% CI: 47%-63%). The pooled estimate of the incidence rates of SCC and basal cell carcinoma was 2.7% (95% CI: 2%-3.4%) and 2.2% (95% CI: 1.5%-2.8%), respectively. Subgroup analysis per geographic location showed that pooled incidence of NMSC was 39.1% (95% CI: 26.3%-51.8%), 12.4% (95% CI: 8.8%-16%), and 1.2% (95% CI: 0.4%-2%) in Australia and New Zealand, Europe, and Middle East, respectively.

Conclusion: The results of the current meta-analysis demonstrated that the incidence of NMSC in renal transplant recipients varies widely. Regarding the high incidence of NMSC among renal transplant recipients, awareness of associated risk factors and early diagnosis of the malignancy in the population is a major clinical need.”



The role of radiotherapy in extramammary Paget disease: A systematic review.

Tagliaferri L, Casà C, Macchia G, Pesce A, Garganese G, Gui B, Perotti G, Gentileschi S, Inzani F, Autorino R, Cammelli S, Morganti AG, Valentini V, Gambacorta MA.

Int J Gynecol Cancer. 2018 Mar 17. doi: 10.1097/IGC.0000000000001237. [Epub ahead of print]


“The 18 studies evaluating RT [radiotherapy] as definitive treatment for primary or recurrent disease after surgery reported a complete response rate ranging from 50% to 100%, with a variable rate of local relapse or persistent disease ranging from 0% to 80% of cases. The 9 studies evaluating RT as postoperative adjuvant treatment reported a local relapse or persistent disease rate of 0% to 62.5%. A dose-response relationship was reported suggesting doses greater than or equal to 60 Gy for gross tumor volume treatment. Local control, disease-free survival, and overall survival at 12, 20, and 60 months have been retrieved for available data, respectively. In patients with EMPD [extramammary Paget disease] and concurrent underlying internal malignancy, the prognosis was often worsened by the latter. In this setting, literature analysis showed a potential RT palliative role for symptoms control or local control maintenance.Derma tumor invasion greater than 1 mm and lymph node metastases were reported to be important prognostic factors for distant metastases or death.”


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Infections of the skin


Systemic antibiotics for the treatment of skin and soft tissue abscesses: a systematic review and meta-analysis.

Gottlieb M, DeMott JM, Hallock M, Peksa GD.

Ann Emerg Med. 2018 Mar 9. pii: S0196-0644(18)30142-2. doi: 10.1016/j.annemergmed.2018.02.011. [Epub ahead of print]


“RESULTS: Four studies (n=2,406 participants) were identified. There were 89 treatment failures (7.7%) in the antibiotic group and 150 (16.1%) in the placebo group. The calculated risk difference was 7.4% (95% confidence interval [CI] 2.8% to 12.1%), with an odds ratio for clinical cure of 2.32 (95% CI 1.75 to 3.08) in favor of the antibiotic group. There was also a decreased incidence of new lesions in the antibiotic group (risk difference -10.0%, 95% CI -12.8% to -7.2%; odds ratio 0.32, 95% CI 0.23 to 0.44), with a minimally increased risk of minor adverse events (risk difference 4.4%, 95% CI 1.0% to 7.8%; odds ratio 1.29, 95% CI 1.06 to 1.58).

CONCLUSION: The use of systemic antibiotics for skin and soft tissue abscesses after incision and drainage resulted in an increased rate of clinical cure. Providers should consider the use of antibiotics while balancing the risk of adverse events.”



Topical Antibiotics for Infection Prevention: A Review of the Clinical Effectiveness and Guidelines [Internet].

Banerjee S, Argáez C.

Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Mar 30.

Note: Only just added to PubMed.


“The purpose of this report is to review the existing evidence on the clinical effectiveness of prevention of skin or wound infection with the topical antibiotics: polymyxin B sulfate-bacitracin (Polysporin ointment), polymyxin B sulfate-gramicidin (Polysporin cream), polymyxin B sulfate-bacitracin-gramicidin (Polysporin triple ointment), bacitracin (Bacitin ointment), mupirocin (Bactroban cream/ointment), silver sulfadiazine (Flamazine cream), fusidic acid/fusidate sodium (Fucidin cream/ointment), and fusidic acid 2% with hydrocortisone (Fucidin H). Additionally, this report aims to review evidence-based guidelines for the prevention of skin or wound infection using these topical antibiotics.”



Analgesic effects of local anesthetic cream in cryotherapy for warts: a meta-analysis of randomized trials.

Lee CY, Tung TH, Liu CY, Wang SH, Chi CC.

J Dtsch Dermatol Ges. 2018 Mar;16(3):307-311. doi: 10.1111/ddg.13452.


“RESULTS: We included three RCTs with 228 participants. Two included RCTs had a high risk of reporting bias, with one having a high risk of other bias as well. Use of LAC [local anesthetic cream] decreased the pain associated with cryotherapy for warts on the hardened skin of children (visual analogue scale, mean difference -20.80, 95 % confidence interval -40.71 to -0.89), but not in adults or on the nonhardened skin of either adults or children.

CONCLUSIONS: The available evidence does not support the routine use of LAC applied for ≤ 60 min in cryotherapy for warts.”



Psychosocial burden of localised cutaneous leishmaniasis: a scoping review.

Bennis I, De Brouwere V, Belrhiti Z, Sahibi H, Boelaert M.

BMC Public Health. 2018 Mar 15;18(1):358. doi: 10.1186/s12889-018-5260-9.


“RESULTS: From 2485 initial records, 15 papers met our inclusion criteria. Dermatology life quality index was the most frequent used scale to assess LCL [localized cutaneous leishmaniasis] psychological impact in quantitative studies. Six qualitative studies used individual interviews and/or focus groups discussions to explore the psychological and/or the social burden of this disease. Quantitative assessments using standard scales as well as qualitative research asserts that LCL is a source of psychological suffering, stigmatization, and decreased quality of life (QoL).

CONCLUSION: Most studies showed that LCL has a significant negative effect on the QoL and mental health. However, the fact that the psychosocial burden generated by LCL is time-dependent makes it hard to measure. We recommend to develop a more specific and validated assessment scale to appreciate the full burden of this disease and enhance comparability of findings.”



Eligibility criteria and outcome measures adopted in clinical trials of treatments of cutaneous leishmaniasis: systematic literature review covering the period 1991-2015.

López L, Vélez I, Arbeláez MP, Olliaro P.

Trop Med Int Health. 2018 Mar 9. doi: 10.1111/tmi.13048. [Epub ahead of print]


“RESULTS: We identified 106 eligible trials published between 1991-2015, 74% after the 2001 CONSORT statement; 58% (n=63) were on Old World CL [cutaneous leishmaniasis] and 37% (n=40) in New World CL; overall 11,531 patients enrolled in 243 treatment groups on 30 different treatments. Both requirements and definitions for eligibility and outcome criteria varied. Compliance with CONSORT requirements increased for studies published after the 2010 update. As for entry criteria, 94% of studies had a requirement for sex (74% of those enrolling also women excluded those who were pregnant or lactating), 69% for age (variable age ranges), 99% parasitologic confirmation, 43% prior duration of illness (14% excluded cases with previous episodes), 46% defined the number, 28% the size, and 13% the type of lesions (27% with restrictions as to their anatomical location). Follow-up ranged 1-24 months, with 14% and 91% of studies respectively having defined initial and final cure.

CONCLUSIONS: This review documents changes in reporting before and after the publication of the CONSORT statement. Lack of standardisation, compounded with the small number of trials relative to the magnitude of the disease in its multiple forms, and with the range of treatments tested explains why evidence to inform treatment guidelines is generally weak for CL. Adopting standardised methodologies will improve the quality and consistency of clinical trials, and ultimately yield better treatments for CL.”


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Drug & treatment reactions/safety


Association between HLA-B*1301 and dapsone-induced cutaneous adverse drug reactions: a systematic review and meta-analysis.

Tangamornsuksan W, Lohitnavy M.

JAMA Dermatol. 2018 Mar 14. doi: 10.1001/jamadermatol.2017.6484. [Epub ahead of print]


“Results: From the 3 included studies, there were 111 unique patients with dapsone-induced cADRs [cutaneous adverse drug reactions] (subsequently used in the meta-analysis), 1165 dapsone-tolerant patients, and 3026 healthy controls. The cases included 64 men and 49 women (2 patients were missing from the meta-analysis; 1 each from 2 of the 3 studies); mean age was 39.7 years. An association between HLA-B*1301 and dapsone-induced cADRs was identified (summary OR, 43.0; 95% CI, 24.0-77.2). Subgroup analyses among types of cADRs produced similar findings in DHS (OR, 51.7; 95% CI, 16.9-158.5), dapsone-induced severe cADRs (Stevens-Johnson syndrome and toxic epidermal necrolysis [SJS/TEN] plus drug rash [adverse skin reaction to a drug] along with eosinophilia and systemic symptoms [DRESS]) (OR, 54.0; 95% Cl, 8.0-366.2), dapsone-induced SJS/TEN (OR, 40.5; 95% CI, 2.8-591.0), and dapsone-induced DRESS (OR, 60.8; 95% CI, 7.4-496.2). There was no heterogeneity (I2 = 0%, P = .38).

Conclusions and Relevance: Associations between HLA-B*1301 and dapsone-induced cADRs were found in dapsone-tolerant and healthy control groups. For patient safety, genetic screening for HLA-B*1301 in Asian populations before dapsone therapy is warranted.”



Vascular endothelial growth factor (VEGF) antibody significantly increases the risk of hand-foot skin reaction to multikinase inhibitors (MKIs): a systematic literature review and meta-analysis.

Zhu Y, Zhang X, Lou X, Chen M, Luo P, He Q.

Clin Exp Pharmacol Physiol. 2018 Mar 15. doi: 10.1111/1440-1681.12935. [Epub ahead of print]


“In the meta-analysis, the pooled incidence rates of all-grade and high-grade HFSR [hand-foot skin reaction] among patients who received the combination therapy were 56.9% [95% confidence interval (CI): 45%-71.1%] and 14.3% (95% CI: 9%-24.2%), respectively, with significant differences observed with MKI [multikinase inhibitors] monotherapy (P < 0.05). Further subgroup analysis demonstrated that increasing the dosages of bevacizumab (77.8% vs. 51.1%, P = 0.04) and MKIs (64.3% vs. 52.6%, P = 0.02) significantly increased HFSR incidence. Moreover, combination with chemotherapy exerted a minimal effect on HFSR risk (61% vs. 55.3%, P = 0.5). This updated review and meta-analysis confirm the increased risk of HFSR incidence due to the use of MKIs and anti-vascular endothelial growth factor antibody. Thus, using these therapies requires safety standards.”


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Vitiligo & pigmentary disorders


The role of phototherapy in the surgical treatment of vitiligo: a systematic review.

Lommerts JE, Uitentuis SE, Bekkenk MW, de Rie MA, Wolkerstorfer A.

J Eur Acad Dermatol Venereol. 2018 Mar 24. doi: 10.1111/jdv.14950. [Epub ahead of print]


“After screening and selection of abstracts and full-texts, we found 39 eligible clinical studies with 1624 patients. The eligible studies investigated several phototherapy modalities, such as NBUVB (n=9), PUVA (n=19), UVA (n=1), MEL (n=4) and active sunlight exposure (n=9). Four studies directly compared phototherapy versus no phototherapy and two studies confirmed the benefit of phototherapy for melanocyte transplantation. We found no significant differences in repigmentation in studies directly comparing phototherapy modalities. The overall quality of the studies was moderate to poor and high heterogeneity between studies was found. We found limited evidence that phototherapy improves the outcome of melanocyte transplantation in vitiligo. There is insufficient evidence to recommend a specific type or regimen of phototherapy. More studies should be performed investigating the additional benefit of different phototherapies and the preferred moment of phototherapy.”



Are natural ingredients effective in the management of hyperpigmentation? A systematic review.

Hollinger JC, Angra K, Halder RM.

J Clin Aesthet Dermatol. 2018 Feb;11(2):28-37. Epub 2018 Feb 1.


“RESULTS: Review of the literature revealed few clinical trials that evaluated the treatment of hyperpigmentation with natural ingredients. Despite the limited evidence-based research, several natural ingredients did show efficacy as depigmenting agents, including azelaic acid, soy, lignin peroxidase, ascorbic acid iontophoresis, arbutin, ellagic acid, licorice extracts, niacinamide, and mulberry.

CONCLUSION: The aforementioned ingredients show promise as natural treatments for patients with hyperpigmentation disorders. These agents might also provide clinicians and researchers with a way to further characterize the pathogenesis of dyschromia. However, the paucity of clinical studies is certainly a limitation. Additionally, many of the in-vivo studies are limited by the short length of the trials, and questions remain about the long-term efficacy and safety of the ingredients used in these studies. Lastly, we suggest a standardized objective scoring system be implemented in any further comparative studies.”


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Hair & nail disorders


Treatment options for hirsutism: A systematic review and network meta-analysis.

Barrionuevo P, Nabhan M, Altayar O, Wang Z, Erwin PJ, Asi N, Martin KA, Murad MH.

J Clin Endocrinol Metab. 2018 Mar 7. doi: 10.1210/jc.2017-02052. [Epub ahead of print]


“Results: We included 43 trials. Estrogen-progestin oral contraceptives pills (OCPs), antiandrogens, and insulin sensitizers were superior to placebo, with standardized mean reductions (95% confidence intervals) of -0.94 (-1.49 to -0.38), -1.29 (-1.80 to -0.79), and -0.62 (-1.00 to -0.23), respectively. Antiandrogen monotherapy, the combination of OCP and antiandrogen, the combination of OCPs and insulin sensitizer, and the combination of antiandrogen and insulin sensitizer were superior to insulin sensitizer monotherapy. The combination of OCPs and antiandrogen was superior to OCPs. Antiandrogen monotherapy with flutamide, finasteride, and spironolactone were each superior to placebo but similar to each other in efficacy. OCPs containing levonorgestrel, cyproterone acetate, or drospirenone were similar in effectiveness to other OCPs or had trivial differences. The certainty in comparisons with placebo was moderate and for head-to-head comparisons was low.

Conclusions: Estrogen-progestin OCPs, antiandrogens, and insulin sensitizers are superior to placebo for the treatment of hirsutism.”



Therapeutic management of classic lichen planopilaris: a systematic review.

Errichetti E, Figini M, Croatto M, Stinco G.

Clin Cosmet Investig Dermatol. 2018 Feb 27;11:91-102. doi: 10.2147/CCID.S137870. eCollection 2018.


“Based on previously suggested therapeutic strategies, drug safety profiles/manageability, and the level of evidence/success rates highlighted in this systematic review, it is possible to speculate that topical/intralesional steroids and hydroxychloroquine might be a reasonable first-line therapy in localized and extensive classic LPP [lichen planopilaris] cases, respectively. In the case of topical/intralesional steroids resistance and progressive course, patients with localized forms may be switched to hydroxychloroquine. When experiencing therapy failure with hydroxychloroquine, methotrexate could be used as a second-line therapy, while mycophenolate mofetil and cyclosporine could be considered as third-line therapies, with the first one to be preferred over a long-term period because of the safer adverse effect profile with prolonged use. In our opinion, a short course of systemic steroids should be considered only to halt the progression and to improve symptoms in rapidly progressive and severe cases. When necessary, topical/intralesional steroids may be added to systemic therapies in the case of persistence of limited active areas. Interestingly, according to the results highlighted in this review, pioglitazone could be a promising and effective therapeutic option, although more evidence is needed to confirm its precise role in the LPP management.”



Trichoscopy of alopecia areata: An update.

Waśkiel A, Rakowska A, Sikora M, Olszewska M, Rudnicka L.

J Dermatol. 2018 Mar 22. doi: 10.1111/1346-8138.14283. [Epub ahead of print]


“Of 427 articles retrieved, 30 studies were eligible for quantitative analysis. The reported features of alopecia areata were: yellow dots (6-100% patients), short vellus hairs (34-100%), black dots (0-84%), broken hairs (0-71%) and exclamation mark hairs (12-71%). Tapered hairs (5-81%) were reported in few studies, but a relatively high frequency of this finding in alopecia areata may indicate their important role in the differential diagnosis of hair loss. Rarely reported features, which include upright regrowing hairs (11-96%), pigtail (circle) hairs (4-61%) and Pohl-Pinkus constrictions (2-10%), may also be helpful in the diagnosis of alopecia areata. There is no pathognomonic trichoscopic marker for alopecia areata and the most common trichoscopic features are not the most specific. Therefore, the diagnosis should be based on the coexistence of several trichoscopic findings, not on the presence of a single feature.”



Possible association between androgenic alopecia and risk of prostate cancer and testicular germ cell tumor: a systematic review and meta-analysis.

Liang W, Song L, Peng Z, Zou Y, Dai S.

BMC Cancer. 2018 Mar 12;18(1):279. doi: 10.1186/s12885-018-4194-z.


“RESULTS: The pooled results showed that no specific degree of baldness had an influence on the incidence of cancer or cancer-specific mortality. However, AGA [androgenic alopecia], especially frontal baldness, with the incidence of testicular germ cell tumor (TGCT) (OR = 0.69; 95% CI = 0.58-0.83). A significant increase of risk was observed in relation to high grade prostate cancer (PC) (OR = 1.42; 95% CI 1.02-1.99) and vertex with/without frontal baldness was associated with PC risk.

CONCLUSIONS: The study results supported the hypothesis that AGA is negatively associated with TGCT risk and suggested an overlapping pathophysiological mechanism between them, while the viewpoint that AGA can be used as a phenotypic marker for PC risk was poorly supported.”


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Oral disorders


Impact of oral potentially malignant disorders on quality of life: a systematic review.

Gondivkar SM, Gadbail AR, Gondivkar RS, Sarode SC, Sarode GS, Patil S.

Future Oncol. 2018 Mar 21. doi: 10.2217/fon-2017-0577. [Epub ahead of print]


“A total of 210 titles were retrieved from electronic and manual databases searched from 1960 until September 2017. Out of these, 25 met our strict inclusion criteria as per the preferred reporting items for systematic reviews and meta-analyses guidelines. Most studies have assessed QoL in patients with oral lichen planus, reports of which cannot be generalized to all patients with OPMD. The findings of the studies differ but, overall, do not provide evidence that OPMD patients have a poorer QoL than healthy subjects.”


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Chronic wounds & ulcers


Prevention of pressure ulcers with a static air support surface: A systematic review.

Serraes B, van Leen M, Schols J, Van Hecke A, Verhaeghe S, Beeckman D.

Int Wound J. 2018 Mar 5. doi: 10.1111/iwj.12870. [Epub ahead of print]


“This review focused on the effectiveness of static air mattress overlays to prevent pressure ulcers. There are indications that these mattress overlays are more effective in preventing pressure ulcers compared with the use of a standard mattress or a pressure-reducing foam mattress in nursing homes and intensive care settings. However, interpretation of the evidence should be performed with caution due to the wide variety of methodological and/or reporting quality levels of the included studies.”



Cost of diabetic foot in France, Spain, Italy, Germany and United Kingdom: A systematic review.

Tchero H, Kangambega P, Lin L, Mukisi-Mukaza M, Brunet-Houdard S, Briatte C, Retali GR, Rusch E.

Ann Endocrinol (Paris). 2018 Mar 12. pii: S0003-4266(17)30959-9. doi: 10.1016/j.ando.2017.11.005. [Epub ahead of print]


“RESULTS: Nine studies were included in the analysis. The total cost of amputation ranged from $ 15,046 in 2001 to $ 38,621 in 2005. The direct cost of amputation ranged from $ 13,842 in 2001 to $ 83,728 during 2005-2009. Indirect cost of amputation was more uniform, ranging from between $ 1,043 to $ 1,442. The direct cost of gangrene ranged from $ 3,352 in 2003 to $ 8,818 in Germany. Although, for the same year, 2003, the cost for Spain was almost double that for Germany. The total cost of an uninfected ulcer was $ 6,174 in 2002, but increased to $ 14,441 in 2005; for an infected ulcer the cost increased from $ 2,637 to $ 2,957. The different countries showed variations in the components used to calculate the cost of diabetic foot.

CONCLUSIONS: The E5 incurs a heavy cost from diabetic foot and its complications. There is an unmet need for the identification of cost-cutting strategies, as diabetic foot costs more than major cardiac diseases.”



Local warming therapy for treating chronic wounds: A systematic review.

Yue JH, Zhang SJ, Sun Q, Sun ZR, Wang XX, Golianu B, Lu Y, Zhang Q.

Medicine (Baltimore). 2018 Mar;97(12):e9931. doi: 10.1097/MD.0000000000009931.


“RESULTS: No studies (RCTs) met the inclusion criteria for this review. Thus, it was impossible to undertake a meta-analysis or a narrative description of studies.

CONCLUSIONS: The effects of LWT for treating chronic wounds are unclear because we did not identify any studies that met the inclusion criteria for this review. Quality improvement for LWT trials is urgently needed.”


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Other disorders affecting the skin


Effectiveness of systemic treatments for pyoderma gangrenosum: A systematic review of observational studies & clinical trials.

Partridge ACR, Bai JW, Rosen CF, Walsh SR, Gulliver WP, Fleming P.

Br J Dermatol. 2018 Feb 25. doi: 10.1111/bjd.16485. [Epub ahead of print]


“RESULTS: We found 3,326 citations, of which 375 articles underwent full-text review, and 41 studies met inclusion criteria. There were 704 participants amongst 26 retrospective cohort studies, 3 prospective cohort studies, 7 case series, 1 case-control study, 2 open-label trials, and 2 randomized controlled trials (RCT). Systemic corticosteroids were the most studied (n=32 studies), followed by cyclosporine (n=21), biologics (n=16), and oral dapsone (n=11). One RCT (STOP-GAP, n=121) showed that prednisolone and cyclosporine were similar, with 15-20% complete healing at 6-weeks and 47% at 6-months. Another RCT (n=30) found that infliximab was superior to placebo at 2-weeks (46% vs. 6% response), with 21% complete healing rate at 6-weeks. Two uncontrolled trials showed 60% and 37.5% healing in four months with canakinumab and infliximab, respectively; other data suggest that patients with concurrent IBD may benefit from biologics. The remaining studies were of poor quality and small sample sizes, though supported the use of corticosteroids, cyclosporine, and biologics.

CONCLUSIONS: Systemic corticosteroids, cyclosporine, infliximab, and canakinumab had the most evidence in treating PG. However, current literature is limited to small and lower-quality studies with substantial heterogeneity.”



Influence of cigarette smoking on pemphigus: a systematic review and pooled analysis of the literature.

Lai O, Recke A, Zillikens D, Kasperkiewicz M.

J Eur Acad Dermatol Venereol. 2018 Feb 25. doi: 10.1111/jdv.14886. [Epub ahead of print]


“Electronic searches using PubMed from inception to November 2017 identified 13 reports meeting predetermined inclusion and exclusion criteria. Most were case-control studies partly reporting that pemphigus vulgaris and foliaceus occurred less frequently in current and former smokers. Studies also indicated that duration of smoking and number of cigarettes smoked were lower in patients with pemphigus than controls and that remission may be achieved sooner in those who smoke. However, although a generally low prevalence of smoking was demonstrated in patients with pemphigus, which was lower than in controls by pooled analysis, some investigations found no difference regarding the smoking status compared with non-pemphigus subjects. One study demonstrated more severe mucosal involvement in non-smoking patients with pemphigus, whereas another observed no difference in the rate of cutaneous or mucosal lesions between smokers and non-smokers with pemphigus. This review indicates that smoking may be a possible protective factor in pemphigus, although some compromised study methodologies yet hinder any firm conclusion. Further investigations with a refined quality design are required to resolve the so far partly conflicting results in this area.”



Interventional management of hyperhidrosis in secondary care: A systematic Review.

Wade R, Llewellyn A, Jones-Diette J, Wright K, Rice S, Layton AM, Levell NJ, Craig D, Woolacott N.

Br J Dermatol. 2018 Mar 24. doi: 10.1111/bjd.16558. [Epub ahead of print]


“RESULTS: Fifty studies were included in the review; 32 RCTs, 17 non-randomised trials and one case series. Studies varied in terms of population, intervention and methods of outcome assessment. Most studies were small, at high risk of bias and poorly reported. The interventions assessed were iontophoresis, botulinum toxin injections (BTX), anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland.

CONCLUSIONS: The evidence for the effectiveness and safety of treatments for primary hyperhidrosis is limited overall, and few firm conclusions can be drawn. However, there is moderate quality evidence to support the use of BTX for axillary hyperhidrosis. A trial comparing BTX with iontophoresis for palmar hyperhidrosis is warranted.”



Vitamin D deficiency in patients with chronic and acute urticaria: A systematic review and meta-analysis.

Tsai TY, Huang YC.

J Am Acad Dermatol. 2018 Feb 22. pii: S0190-9622(18)30318-9. doi: 10.1016/j.jaad.2018.02.033. [Epub ahead of print] No abstract available.


“In summary, compared with the control group, the prevalence of 25-hydroxyvitamin D deficiency was significantly higher and the level of 25-hydroxyvitamin D was significantly lower in patients with chronic urticaria but not in those with acute urticaria. The significantly reduced level of 25-hydroxyvitamin D was observed in adult patients but not in pediatric patients. However, the association of vitamin D deficiency with urticaria does not imply causation. Further studies are required to explore the role of vitamin D supplementation in treating urticaria.”



Omalizumab for the treatment of solar urticaria: case series and systematic review of the literature.

Snast I, Kremer N, Lapidoth M, Enk CD, Tal Y, Rosman Y, Confino-Cohen R, Hodak E, Levi A.

J Allergy Clin Immunol Pract. 2018 Mar 20. pii: S2213-2198(18)30132-6. doi: 10.1016/j.jaip.2018.02.032. [Epub ahead of print]


“RESULTS: Our case series included five patients with SU [solar urticarial]. Monthly omalizumab doses of 150 - 600 mg resulted in clinical improvement in all patients and complete remission in four. No adverse effects were reported. The systematic review included 22 studies (48 patients). All patients failed to control disease with antihistamines prior to omalizumab treatment. Patients received omalizumab at monthly doses of 150 - 750 mg over a follow-up period of 4 - 200 weeks. Thirty-eight patients (79%) experienced clinical improvement. Four patients (11%) had mild adverse effects.

CONCLUSION: Omalizumab provided clinical benefits in approximately 80% of SU patients. Patients failing to improve on standard omalizumab doses may benefit from higher monthly dosages.”



Management of pediatric urticaria with review of the literature on chronic spontaneous urticaria in children.

Ben-Shoshan M, Grattan CE.

J Allergy Clin Immunol Pract. 2018 Mar 14. pii: S2213-2198(18)30107-7. doi: 10.1016/j.jaip.2018.02.015. [Epub ahead of print]


“Our findings highlight the efficacy of second-generation antihistamines for the treatment of CSU [chronic spontaneous urticarial] in children and supports the use of omalizumab for more severe cases. However, our study also reveals severe knowledge gaps related to the best management strategy in children with more severe/refractory cases of CSU. Future studies are required to establish the beneficial effect of high doses of second-generation antihistamines as well as the effectiveness and safety of omalizumab and other biologics in young children.”



Topical propranolol for infantile haemangiomas: A systematic review.

Price A, Rai S, Mcleod RWJ, Birchall JC, Elhassan HA.

J Eur Acad Dermatol Venereol. 2018 Mar 23. doi: 10.1111/jdv.14963. [Epub ahead of print]


“Twelve articles with a total of 597 patients and 632 haemangiomas were included. Three topical propranolol preparations were used, creams, ointments and gels, and were all prepared by local pharmaceutical laboratories. The concentration of propranolol ranged from 0.5% to 5%. Treatment duration ranged from two weeks to 16.5 months. Overall, 90% of lesions improved following the initiation of topical propranolol. A good or excellent response, defined as a reduction in size of at least 50%, was seen in 59% of lesions. Earlier initiation of treatment (less than 3 months of age) was associated with improved outcomes. No systemic adverse effects were reported. Minor local reactions were seen in 1.3% of patients. Topical propranolol is safer than oral propranolol, though may be less effective. Topical propranolol may be more suitable for patients with small, superficial haemangiomas at risk of cosmetic sequelae, where the cosmetic or symptomatic impact does not warrant oral propranolol treatment.”



Vascular malformations and health-related quality of life: A systematic review and meta-analysis.

Nguyen HL, Bonadurer GF 3rd, Tollefson MM.

JAMA Dermatol. 2018 Mar 21. doi: 10.1001/jamadermatol.2018.0002. [Epub ahead of print]


“Results: Eleven studies met the inclusion criteria for a total of 692 patients with VAMs [vascular malformations]. Six studies (320 patients) were included in the meta-analysis, whereas 5 studies were included in the qualitative analysis (372 patients). Those with VAMs had lower 36-Item Short-Form Health Survey scores in bodily pain (mean difference, -11.87; 95% CI, -21.45 to -2.29; I2 = 92%; P = .02) and mental health (mean difference, -6.04; 95% CI, -11.55 to -0.52; I2 = 83%; P = .03) compared with the US general population.

Conclusions and Relevance: Patients with VAMs had increased pain and psychosocial distress compared with the US general population. Pain and psychological morbidity are associated with poorer HRQoL [health-related quality of life] and may serve as indicators for quality of life.”



Type I pityriasis rubra pilaris treated with tumor necrosis factor inhibitors, ustekinumab, or secukinumab: a systematic review.

Maloney NJ, Hisaw LD, Worswick S.

J Am Acad Dermatol. 2018 Mar 5. pii: S0190-9622(18)30349-9. doi: 10.1016/j.jaad.2018.02.063. [Epub ahead of print] No abstract available.


“A total of 35 articles describing 54 cases of type I PRP [pityriasis rubra pilaris] satisfied our search/inclusion criteria, and 50 were supported with histological evidence. Overall, we identified 40 instances where PRP response to biologics was marked (37) or partial (3), and no disease relapse was noted. In these 40 patients, the median length of therapy was 21 weeks, and 60% (24/40) of these patients demonstrated complete clearance of disease while on their respective biologic regimen. We identified a median time to primary response of 4 weeks, with >90% (37/40) of cases noting primary improvement at or before week 8 of their biologic regimen (Table I). We identified fourteen cases where either no response to a biologic was observed, or improvement was followed by relapse (median week of relapse = 14). In the majority of cases, reports described patients improving on an alternative regimen. Only one patient completely failed two different classes of biologics.”



A systematic review and meta-analysis of using acupuncture and acupressure for uremic pruritus.

Badiee Aval S, Ravanshad Y, Azarfar A, Mehrad-Majd H, Torabi S, Ravanshad S.

Iran J Kidney Dis. 2018 Mar;12(2):78-83.


“RESULTS: A total of 5 articles, including 6 trials, were enrolled in this systematic review. Only 3 of the six trial studies used a visual analogue scale score for assessing pruritus and acupressure for intervention regime, which were considered for meta-analysis. The combined results showed that acupuncture or acupressure was effective in treatment of uremic pruritus (pooled mean difference, -1.994; 95% confidence interval, -2.544 to -1.445).

CONCLUSIONS: This study confirms that using acupuncture and acupressure is effective in treatment of uremic pruritus. However, further vigorous studies are needed to verify these findings.”


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Skin conditions & dermatology in general


Intramuscular steroids in the treatment of dermatologic disease: A systematic Review.

Thomas LW, Elsensohn A, Bergheim T, Shiu J, Ganesan A.

J Drugs Dermatol. 2018 Mar 1;17(3):323-329.


“FINDINGS: A total of 62 papers were reviewed. Six papers met criteria. They looked at alopecia areata, (2) systemic lupus erythematosus (1), Behcets disease (1), and nail lichen planus (2). Collectively, the studies included 342 patients. Study types included case series (1), retrospective observational (2), randomized prospective (2), and double-blind placebo controlled (1) studies. In this systematic review, intramuscular steroids were found to have comparable efficacy and side effect profile alone or in comparison with other steroid modalities for the select number of dermatoses investigated.

CONCLUSIONS AND RELEVANCE: We conclude that intramuscular steroids can be regarded as having comparable efficacy to other steroid modalities in the treatment of steroid responsive dermatoses; and also appear to be safer in most instances with the exception of dysmenorrhea in females. Additional studies are greatly needed.”



Intralesional and laser-assisted 5-fluorouracil in dermatologic disease: a systematic review.

Prince GT, Cameron MC, Fathi R, Alkousakis T.

J Drugs Dermatol. 2018 Mar 1;17(3):274-280.


“Intralesional and laser-assisted 5-fluorouracil are used in a variety of dermatologic disease processes with a wide range of efficacy and levels of evidence. Based on extent and level of evidence, our disease-specific systematic review found that the evidence is strongest for intralesional 5-FU use in the treatment of keloids, hypertrophic scars, and keratoacanthomas. This review serves as a comprehensive summary of intralesional and laser-assisted 5-fluorouracil use in dermatology.”


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Skin surgery and lasers


Efficacy and adverse effects of topical chloramphenicol ointment use for surgical wounds: a systematic review.

Shen AY, Haddad EJ, Hunter-Smith DJ, Rozen WM.

ANZ J Surg. 2018 Mar 23. doi: 10.1111/ans.14465. [Epub ahead of print]


“RESULTS: After full-text review, five articles were included. Two were randomized controlled trials, one was retrospective case control and two were case studies. There was evidence that chloramphenicol ointment use on surgical wounds produced a non-statistically significant reduction in infection rates. Delayed hypersensitivity and acute oesophagitis were noted as potential side effects of non-ocular topical use. Aplastic anaemia was not reported.

CONCLUSION: There is a paucity of clinical data regarding the use of topical chloramphenicol ointment on surgical wounds. Further randomized controlled trials may be beneficial in order to support or refute its use in this setting.”


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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 Medicines Agency - Updated measures for pregnancy prevention during retinoid use


“The European Medicines Agency (EMA) has completed its review of retinoid medicines, and confirmed that an update of measures for pregnancy prevention is needed. In addition, a warning on the possibility that neuropsychiatric disorders (such as depression, anxiety and mood changes) may occur will be included in the prescribing information for oral retinoids (those taken by mouth).”



European CHMP recommends approval of infliximab biosimilar (Zessly) (PDF)


The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) “has adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Zessly, intended for the treatment of rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and psoriasis”. Zessly is a biosimilar medicinal product, highly similar to the reference product Remicade (infliximab).



MHRA warning about Chinese herbal medicine, Yiganerjing Cream, containing steroids


"The Medicines and Healthcare products Regulatory Agency is warning people who may have purchased a “natural” Chinese herbal medicine, Yiganerjing Cream, as a treatment for skin conditions to stop using it immediately as it has been found to contain an undisclosed steroid and two antifungal ingredients.

MHRA officials have been acting to stop the sale of this cream and have had it withdrawn from many websites and on-line market places but people may have purchased it in the past and still be using it.

Yiganerjing Cream is not a licensed medicine and has been marketed in the UK as a “natural” Chinese herbal medicine for the treatment of a range of skin conditions, most commonly eczema, psoriasis and rosacea…”



MHRA Drug Safety Update: Head lice eradication products: risk of serious burns


The Medicines and Healthcare products Regulatory Agency (MHRA) has issued a warning of a risk of serious burns if hair treated with certain head lice eradication products is exposed to open flames or other sources of ignition, e.g. cigarettes. Eight cases of serious burns associated with Hedrin 4% cutaneous solution have been reported to the MHRA since the product was licensed in 2005, and there have been two further serious burns cases associated with other products.



Revised SmPC (Summary of Product Characteristics): Aknemycin Plus (erythromycin/tretinoin solution for topical administration)


The SmPC now warns: “As with other macrolides, rare serious allergic reactions, including acute generalised exanthematous pustulosis (AGEP) have been reported. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.”



Revised SmPC (Summary of Product Characteristics): Curatoderm Ointment (tacalcitol monohydrate)


The SmPC now indicates that butylhydroxytoluene (E 321), contained in the excipient white soft paraffin, may cause local skin reactions (e.g. contact dermatitis) or irritation to the eyes and mucous membranes.



Revised SmPC (Summary of Product Characteristics): Iomeron (iomeprol) solution for injection


Acute generalised exanthematous pustulosis has now been listed as a potential adverse effect with the use of Iomeron (iomeprol), which is an X-ray contrast medium.



Revised SmPC: Ameluz (5-aminolaevulinic acid) 78 mg/g gel


Directions for use in actinic keratosis and field cancerization with a daylight photodynamic therapy protocol have been added to the SmPC.


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CEBD publications & news



Diet during pregnancy and infancy and risk of allergic or autoimmune disease: A systematic review and meta-analysis.

Garcia-Larsen V, Ierodiakonou D, Jarrold K, Cunha S, Chivinge J, Robinson Z, Geoghegan N, Ruparelia A, Devani P, Trivella M, Leonardi-Bee J, Boyle RJ.

PLoS Med. 2018 Feb 28;15(2):e1002507. doi: 10.1371/journal.pmed.1002507. eCollection 2018 Feb.


See above under Eczema & dermatitis



Investigating the effect of independent, blinded digital image assessment on the STOP GAP trial.

Patsko E, Godolphin PJ, Thomas KS, Hepburn T, Mitchell EJ, Craig FE, Bath PM, Montgomery AA.

Trials. 2017 Feb 2;18(1):53. doi: 10.1186/s13063-017-1779-9.


“METHODS: The STOP GAP trial compared prednisolone to ciclosporin in treating pyoderma gangrenosum. Participants' lesions were measured at baseline and at 6 weeks to calculate the primary outcome, speed of healing. Independent blinded assessors obtained measurements from digital photographs using specialist software. In addition, unblinded treating clinicians estimated lesion area by measuring length and width. The primary outcome was determined using blinded measurements where available, otherwise unblinded measurements were used (method referred to as trial measurements). In this study, agreement between the trial and unblinded measurements was determined using the intraclass correlation coefficient (ICC). The STOP GAP trial's primary analysis was repeated using unblinded measurements only. We introduced differential and nondifferential error in unblinded measurements and investigated the effect on the STOP GAP trial's primary analysis.

RESULTS: Eighty-six (80%) of the 108 patients were assessed using digital images. Agreement between trial and unblinded measurements was excellent (ICC = 0.92 at baseline; 0.83 at 6 weeks). There was no evidence that the results of the trial primary analysis differed according to how the primary outcome was assessed (p value for homogeneity = 1.00).

CONCLUSIONS: Blinded digital image assessment in the STOP GAP trial did not meaningfully alter trial conclusions compared with unblinded assessment. However, as the process brought added accuracy and credibility to the trial it was considered worthwhile. These findings question the usefulness of digital image assessment in a trial with an objective outcome and where bias is not expected to be excessive. Further research should investigate if there are alternative, less complex ways of incorporating blinding in clinical trials.”



Lichen Sclerosus Priority Setting Partnership - Shortlisting Survey now open


The Lichen Sclerosus Priority Setting Partnership (PSP) was set up to identify and prioritise research questions that are important to people who have lichen sclerosus, the people who care for them, and the health professionals who treat them. The PSP now has a list of 38 research areas that have not already been answered, and an online survey is live for participants to help prioritise these by selecting up to ten questions from the list.



Acne & HS: Evidence Based Update Meeting 2018


The reduced early booking rate for this meeting finishes on 8th April, so do book now. This event has been awarded 5 CPD credits.


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Other key publications that have caught our eye



Drug and Therapeutics Bulletin - Dupilumab for atopic dermatitis (subscription required)


Dupilumab is the first biological drug approved in Europe specifically for (moderate-to-severe) atopic dermatitis. This is an independent review of the evidence for the efficacy and safety of dupilumab, which considers its place in therapy. It concludes: “Although dupilumab has produced improvements in the treatment of adults with moderate-to-severe atopic dermatitis, the lack of comparative trials with ciclosporin, limited data on long-term safety and efficacy, and its high price mean that its place in the management of atopic dermatitis is uncertain. It may provide an option for patients who do not respond to ciclosporin or for whom ciclosporin is contraindicated.”



Cellulitis and soft tissue infections.

Bystritsky R, Chambers H.

Ann Intern Med. 2018 Feb 6;168(3):ITC17-ITC32. doi: 10.7326/AITC201802060.


This article reviews the evidence on cellulitis and soft tissue infections, with a series of clinical questions covering prevention, diagnosis, treatment and practice improvement.



Amelanotic melanoma.

Muinonen-Martin AJ, O'Shea SJ, Newton-Bishop J.

BMJ. 2018 Mar 15;360:k826. doi: 10.1136/bmj.k826. No abstract available.


This article summarises the diagnosis and surgical management of amelanotic melanomas.

“What you need to know

- Amelanotic melanomas represent 8% of all melanomas

- They can lack classical features of other melanomas and tend to be red or skin coloured and more symmetrical

- They might be confused with basal cell or squamous cell carcinomas, pyogenic granulomas, or benign acral nail lesions, depending on their appearance.”



UK Medicines Information (UKMi) Medicines Q&As - Do statins cause alopecia? (Word document)


“Most UK licensed statins (hydroxymethylglutaryl coenzyme A reductase inhibitors) have been reported by manufacturers to cause hair loss as a side effect. The Medicines Q&A aims to review incidence of alopecia with UK licensed statins.”



Making real our shared vision for the NHS: optimising the treatment and care of people with long-term skin conditions in England (PDF)


This report is produced by an independent Expert Working Group commissioned by the Association of the British Pharmaceutical Industry (ABPI) Dermatology Initiative. The report seeks to “position the current understanding of care of people with long-term skin conditions within the national policy context” and “recommend achievable and pragmatic next steps for

better-coordinated patient pathways, access and care for this group of patients.” A stated aim is “to address the imbalance in care that has resulted for people with inflammatory skin conditions and particularly long-term skin conditions such as psoriasis, atopic eczema, urticaria, rosacea and acne, as a result of the recent heavy emphasis on skin cancer.”




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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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