Skip to main content

Main menu

  • HOME
  • ONLINE FIRST
  • CURRENT ISSUE
  • ALL ISSUES
  • AUTHORS & REVIEWERS
  • SUBSCRIBE
  • RESOURCES
    • About BJGP
    • Conference
    • Advertising
    • BJGP Blog
    • eLetters
    • Feedback
    • Librarian information
    • Alerts
    • Resilience
  • RCGP
    • BJGP for RCGP members
    • BJGP Open
    • RCGP eLearning
    • InnovAIT Journal
    • Jobs and careers
    • RCGP e-Portfolio

User menu

  • Subscriptions
  • Alerts
  • Log in

Search

  • Advanced search
British Journal of General Practice
  • RCGP
    • BJGP for RCGP members
    • BJGP Open
    • RCGP eLearning
    • InnovAIT Journal
    • Jobs and careers
    • RCGP e-Portfolio
  • Subscriptions
  • Alerts
  • Log in
  • Follow bjgp on Twitter
  • Visit bjgp on Facebook
  • Blog
British Journal of General Practice

Advanced Search

  • HOME
  • ONLINE FIRST
  • CURRENT ISSUE
  • ALL ISSUES
  • AUTHORS & REVIEWERS
  • SUBSCRIBE
  • RESOURCES
    • About BJGP
    • Conference
    • Advertising
    • BJGP Blog
    • eLetters
    • Feedback
    • Librarian information
    • Alerts
    • Resilience
Research

Assessing the effectiveness of topical betamethasone to treat chronic chilblains: a randomised clinical trial in primary care

Ibo H Souwer, Jacobus HJ Bor, Paul Smits and Antoine LM Lagro-Janssen
Br J Gen Pract 2017; 67 (656): e187-e193. DOI: https://doi.org/10.3399/bjgp17X689413
Ibo H Souwer
Department of Primary and Community Care, Gender and Women’s Health;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacobus HJ Bor
Department of Primary and Community Care;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul Smits
Department of Pharmacology and Toxicology;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Antoine LM Lagro-Janssen
Department of Primary and Community Care, Gender and Women’s Health; Radboud University Medical Centre, Nijmegen, the Netherlands.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info
  • eLetters
  • PDF
Loading

Abstract

Background GPs prescribe topical corticosteroids to patients with chronic chilblains despite poor evidence for their effectiveness. The authors of the current study therefore decided to assess the effectiveness of topical steroids in a primary care setting.

Aim To assess the effectiveness of topical application of betamethasone valerate 0.1% cream in patients with chronic chilblains.

Design and setting A placebo-controlled, double-blind, crossover, randomised clinical trial in a Dutch primary care setting.

Method The study population consisted of 34 participants suffering from chronic chilblains. Intervention was topical application of betamethasone valerate 0.1% cream twice a day for 6 weeks compared with placebo. Primary outcome was the visual analogue scale on complaints (VOC). Secondary outcome was the visual analogue scale on disability (VOD). Both were assessed with a diary of daily scores on a 100 mm visual analogue scale. The authors took ambient temperatures into account, checked for a carry-over effect, performed additional analysis, and monitored adverse effects.

Results On the primary outcome mean VOC, there was a difference of 0.56 mm (95% confidence interval [CI] = −2.88 to 3.99 mm) in favour of placebo (P = 0.744). On the secondary outcome mean VOD, there was a difference of 0.88 mm (95% CI = −2.22 to 3.98 mm) in favour of placebo (P = 0.567). This study found no carry-over effect and no adverse effects.

Conclusion In this study, topical betamethasone was not superior to placebo in the treatment of chronic chilblains. Topical betamethasone should not be used for chronic chilblains without new evidence.

  • betamethasone
  • chilblains
  • general practice
  • randomised clinical trial
  • therapy

INTRODUCTION

Chronic chilblains are cold-induced painful or itching lesions on the fingers, feet, ears, or thighs. The condition occurs throughout the world during the winter months when daily mean temperatures drop below 12–15°C.1 Prevalence reported by the Netherlands Institute for Health Services Research (NIVEL) varies between 0.9 per 1000 and 1.7 per 1000 depending on year-to-year variation and coding issues; the condition is more common among females than males (prevalence 0.9–2.1 per 1000 and 0.6–1.2 per 1000, respectively) (NIVEL, personal communication, 2016). Patients report serious restrictions in daily life and urgently feel the need for an effective treatment.2 A literature study updated to 15 March 2016 reveals that vitamin D3, corticosteroid-containing cream, nifedipine, and pentoxifylline, together with a wide range of other therapies, are used to treat the symptoms of patients with chronic chilblains.3,4 Two of the current authors found that vitamin D3 was not superior to placebo.5 GPs advise topical corticosteroids for patients suffering from chilblains.6–10 Only one previous study evaluating the effectiveness of topical steroids in patients with chilblains has been published.11 This case-series with topical fluocinolone provides some evidence for the effectiveness of topical steroids for chronic chilblains but the current discussion on the reliability and reproducibility of original studies calls into question the soundness of recommendations based on it.12 As patients suffering from chilblains usually contact their GP for help, the authors decided to assess the effectiveness of topical corticosteroids in a primary care setting. Topical betamethasone was chosen because fluocinolone cream is not available in the Netherlands.

The aim of this study was to assess the proposed superiority of the topical application of betamethasone valerate 0.1% cream twice a day for 6 weeks compared with placebo cream in patients with chronic chilblains in a primary care setting.

METHOD

Trial design

The authors conducted a placebo-controlled, double-blind, crossover, randomised clinical trial in a primary care setting (Netherlands National Trial Register: number NTR 2171). A washout period was not included in the design because, for obvious reasons, the study was dependent on the winter months. A washout period would have caused too long a research period per participant and problems with high ambient temperatures in spring. Instead this study checked for a possible carry-over effect.

Participants

The study population consisted of consecutively recruited participants who suffered from chronic chilblains during the winters of 2010 to 2012. Participants volunteered after being informed about the trial by their GP during a consultation.

How this fits in

Chronic chilblains are cold-induced painful or itching lesions on the fingers, feet, ears, or thighs. The prescription of topical steroids for patients with chilblains finds support in one study. The current randomised, placebo-controlled trial does not confirm the conclusions of this study. Topical betamethasone should not be used in the treatment of chronic chilblains without new evidence.

The authors included participants aged ≥18 years with complaints of chronic chilblains lasting ≥3 weeks. The diagnosis (International Classification of Primary Care [ICPC] A88.01) was confirmed by one author, based on commonly used diagnostic criteria: complaints emerging in the winter months with itching and/or painful purple-blue discoloured lesions on fingers and/or toes and/or other localisations on the feet and/or on the lateral side of the thigh, without a history of complaints persisting in the summer months.1,7 The validity of the confirmation of the diagnosis had previously been demonstrated.5 The authors excluded people with a known rheumatic disorder (for example, rheumatoid arthritis or systemic lupus erythematosus), those who were using nifedipine or other calcium antagonist, those who had been using a corticosteroid-containing cream in the previous 4 weeks, and females who were pregnant or lactating.

Intervention

The intervention to be compared with placebo consisted of topical application of betamethasone 0.1% cream twice a day. The research medication (betamethasone valerate 0.1% cream and placebo) was produced and certified by an independent pharmacy: Pharmacy Waterland Oost, Volendam, the Netherlands.

Outcomes

Primary outcome was the difference between the visual analogue score (VAS) on complaints (VOC) scale in the betamethasone cream and placebo cream groups, respectively, after 6 weeks of treatment. VOC was assessed by a diary and defined as the 100 mm VAS score on pain or the VAS score on itch, depending on which item had the highest value at the moment of sampling. VOC was calculated using the mean value of the last 7 consecutive days of the 6-week treatment period.

Secondary outcome was the difference between the VAS on disability (VOD) score in the betamethasone cream and placebo cream groups, respectively, after 6 weeks of treatment. VOD was assessed by a diary and defined as the VAS score on inability to function normally in daily life. VOD was calculated using the mean value of the last 7 consecutive days of the treatment period.

Additionally, the chilblain lesions were assessed during face-to-face consultations. Redness, purpleness, oedema, and ulceration of the lesions were scored by one author on a VAS for each item. The authors monitored for any adverse effects from the two therapies (skin irritation and signs of skin atrophy).

Sample size

Sample size calculation was based on the following premises. In an earlier study on the effectiveness of vitamin D3 with 33 participants recruited in a similar way, two of the current authors observed a baseline VOC of 27.97 mm (standard deviation [SD] 18.82).5 An estimate was used of the correlation between two VAS scores from the same individual on two occasions of 0.5. Treatment effect was considered to be clinically relevant in the case of a 10 mm decrease in the VOC.

Based on use of a t-test for the difference between two dependent means, one-tail testing, α 0.05, and β 0.10 (power 90%) the authors calculated a minimum sample size of 32 participants.

Randomisation, blinding, and treatment allocation

Block randomisation with a block size of 10 was used to assign one of the two arms (placebo cream first or betamethasone cream first) to research medication sets with consecutive therapy numbers. This procedure was performed by the pharmacy that produced and issued the research medication sets blind to both research personnel and participants. Treatment allocation was ensured by the similarity of the pharmaceutical products and packaging between the betamethasone cream and placebo cream, which were indistinguishable. Consecutively recruited participants received research medication sets with consecutive therapy numbers. The randomisation key was only released after the last subject had left the study.

Study procedures

The participants were randomised over two arms:

  • Arm 1: No creams for 1 week to collect baseline data (phase 0), followed by topical application of betamethasone 0.1% cream twice a day for 6 weeks (phase 1), followed by topical application of placebo cream twice a day for 6 weeks (phase 2).

  • Arm 2: No creams for 1 week to collect baseline data (phase 0), followed by topical application of placebo cream twice a day for 6 weeks (phase 1), followed by topical application of betamethasone 0.1% cream twice a day for 6 weeks (phase 2).

The measuring instrument was a diary to be completed by the subject during the full 13-week research period. Each day the complaints (pain and itch) and disability in normal functions of daily life were documented using a 100 mm VAS for each item. Each day the mean outside air temperature, provided by the Royal Netherlands Meteorological Institute, was documented.

The authors performed six face-to-face assessments: intake (T1), end of week 1 (T2), end of week 4 (T3), end of week 7 (T4), end of week 10 (T5), and end of week 13 (T6). During face-to-face assessments the diary was checked for completeness, therapy compliance was checked by weighing remaining cream, and remaining lesions were documented.

Statistical analysis

The analysis was intention to treat. The authors performed analysis of the primary and secondary outcomes using the two-stage model originally proposed by Grizzle and correcting for temperature changes in the research period for each participant with a mixed effects model (Grizzle’s model using the mixed procedure with random effect, SAS PROC MIXED, SAS version 9.2).13,14 Additional analyses were undertaken and adverse effects monitored using a two sample paired t-test.

RESULTS

Characteristics of the populations

The flowchart (Figure 1) shows the procedure for including participants.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Flowchart for patient inclusion.

Data for 34 participants were available for analysis. The participants had a mean age of 53 years (SD 14.1), 19 were female, and 15 male. Mean duration of complaints at intake was 7 weeks (SD 4.2). At baseline mean VAS score on complaint was 26.80 mm (95% CI = 24.04 to 29.57) and mean VAS score on disability was 17.55 mm (95% CI = 14.90 to 20.20). Eleven participants suffered from a comorbidity that might have been relevant. Five participants smoked. Four participants used possibly relevant drugs (Table 1). Diaries were conscientiously completed. No face-to-face assessments were missed.

View this table:
  • View inline
  • View popup
Table 1.

Baseline data

Outcomes

Figure 2 shows plotted scores of ‘complaint’ and ‘disability’ (mean VAS score per week) not corrected for temperature in each arm and phase.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Plotted scores on complaints (VOC) and disability (VOD) (not corrected for temperature) for each arm and phase. Arm 1 = betamethasone + placebo. Arm 2 = placebo + betamethasone. VAS = visual analogue scale. VOC = visual analogue scale on complaints. VOD = visual analogue scale on disability.

Primary outcome

Mean VOC at 6 weeks of treatment was 9.10 mm (95% CI = 5.31 to 12.88 mm) in the betamethasone cream group and 8.54 mm (95% CI = 4.75 to 12.33 mm) in the placebo cream group (Table 2). This resulted in a difference of 0.56 mm (95% CI = −2.88 to 3.99 mm) in favour of placebo (P = 0.744).

View this table:
  • View inline
  • View popup
Table 2.

Results corrected for temperature differences on primary (VOC) and secondary (VOD) outcome

Secondary outcome

Mean VOD at 6 weeks of treatment was 5.07 mm (95% CI = 2.37 to 7.77 mm) in the betamethasone cream group and 4.19 mm (95% CI = 1.49 to 6.89 mm) in the placebo cream group (Table 2). This resulted in a difference of 0.88 mm (95% CI = −2.22 to 3.98 mm) in favour of placebo (P = 0.567).

Carry-over effect

Carry-over effect on the primary outcome

Mean VOC at 6 weeks of treatment was 10.31 mm (95% CI = 5.82 to 14.79 mm) in Arm 1 (betamethasone cream first) and 7.33 mm (95% CI = 2.28 to 12.38 mm) in Arm 2 (placebo cream first). This resulted in a difference of 2.98 mm (95% CI = −3.78 to 9.74 mm) in favour of Arm 2 (P = 0.376) (Table 2).

Carry-over effect on the secondary outcome

Mean VOD at 6 weeks of treatment was 5.57 mm (95% CI = 2.63 to 8.51 mm) in Arm 1 (betamethasone cream first) and 3.69 (95% CI = 0.38 to 7.00) in Arm 2 (placebo cream first). This resulted in a difference of 1.88 mm (95% CI = −2.56 to 6.31 mm) in favour of Arm 2 (P = 0.396) (Table 2).

Additional analyses

The authors found no statistically significant differences between topical betamethasone cream and placebo cream for assessed redness, purpleness, oedema, and ulceration after 6 weeks of treatment (Table 3).

View this table:
  • View inline
  • View popup
Table 3.

Outcomes on additional analyses (6 weeks of treatment)

Adverse effects

No adverse effects (skin irritation or signs of skin atrophy) were found during betamethasone cream application or during placebo cream use.

DISCUSSION

Summary

There was no clinically or statistically significant difference between treatment with topical betamethasone valerate cream and placebo cream treatment. The authors also found no significant carry-over effect on either the primary or the secondary outcome. Adverse effects were absent.

Strengths and limitations

The main strength of this study was the effort to confirm the findings of the original study that generated weak evidence for the effectiveness of topical steroids in the treatment of chronic chilblains.11 No randomised trial on this topic had previously been performed. Nevertheless, topical steroids are widely prescribed by GPs. The authors used a randomised, placebo-controlled, crossover design and checked for a carry-over effect. The ambient temperature was taken into account as a major confounder.1,3,15,16

The calculated sample size was met. Participant compliance was good. Owing to the recruitment method used for participants in this study, it is possible to generalise the current findings for patients with idiopathic chronic chilblains as seen in primary care.

Chronic chilblains meet the criteria for the definition of a common disease.17 The condition does not endanger health but is annoying to the patient and causes restrictions in everyday life.2 The relatively rare effect studies on patients suffering from chronic chilblains show no consensus concerning outcome measurement. Due to the disease characteristics the authors chose to address the complaints reported by the participants. Primary and secondary outcome were assessed with VAS scores on pain, itch, and disability using a diary. VAS scores are generally used and validated for these purposes.18–20

The decision to test differences on VOC and VOD one-sided is based on a power issue. The aim of the study allows one-sided testing. The prevalence of chronic chilblains is low and inclusion is for obvious reasons limited to the winter months, necessitating the use of a design that requires a limited number of participants.

The authors did not ask participants to change their habits during the study, leaving the possibility of a Hawthorne effect.21 It is not possible to exclude such an effect caused by efforts of participants to diminish their symptoms by changing habits during the study. Nevertheless such an effect is considered to be unlikely because patients with chronic chilblains already try almost everything to relieve their symptoms.2

A remarkable reduction in complaints was found during placebo treatment. First, placebo effect may be responsible.22 Second, almost all studies on chilblains report that 60% to 70% of the patients show improvement on the different treatments.3 Third, the authors compared betamethasone cream with placebo cream and not to no treatment at all. It is possible that treatment with a cream not containing an active pharmaceutical agent is responsible for the reduction of complaints. In the authors’ opinion, however, the reduction of complaints during placebo use reflects a placebo effect as well as the natural course of the disease.

Almost one in four of the participants reported Raynaud’s phenomenon as a comorbidity. This figure may suggest some sort of relationship between chronic chilblains and Raynaud’s phenomenon. Participants suffering from Raynaud’s phenomenon were not excluded. This is because the condition is easy to distinguish from chronic chilblains: Raynaud’s phenomenon is characterised by sudden onset and short episodes with (in typical cases) biphasic discoloration of fingers and toes after exposure to low ambient temperatures, whereas in chronic chilblains prolonged inflammatory symptoms are characteristic.23–25

Comparison with existing literature

The current findings oppose the findings of the original study.11

Implications for practice

The effectiveness of betamethasone valerate 0.1% cream in the treatment of chronic chilblains in primary care is to be called into question. Topical steroids should not be used in the treatment of chronic chilblains without new evidence.

Acknowledgments

The authors thank Mrs CM (Rina) Siemons, research assistant.

Notes

Funding

This work is supported by the Netherlands Organisation for Health Research and Development Programme Common Diseases (grant number 42011006).

Ethical approval

The Dutch Competent Authority (NL 3069509109) and the Medical Research Ethics Committee CMO Arnhem-Nijmegen granted permission for this study (CMO dossier number: 2009/338).

Provenance

Freely submitted; externally peer reviewed.

Competing interests

The authors have declared no competing interests.

Discuss this article

Contribute and read comments about this article: bjgp.org/letters

  • Received June 9, 2016.
  • Revision requested September 5, 2016.
  • Accepted September 14, 2016.
  • © British Journal of General Practice 2017

REFERENCES

  1. 1.↵
    1. Souwer IH,
    2. Lagro-Janssen ALM
    (2011) Chronic chilblains. BMJ 342:d2708.
  2. 2.↵
    1. Souwer IH,
    2. Robins LJH,
    3. Lagro-Janssen ALM
    (2007) Chilblains from the patient’s perspective. Eur J Gen Pract 13(3):159–160.
  3. 3.↵
    1. Souwer IH,
    2. Lagro-Janssen ALM
    (2004) The treatment of chilblains. A literature study. Huisarts Wet 47(12):561–562.
  4. 4.↵
    1. Al-Sudany NK
    (2016) Treatment of primary perniosis with oral pentoxifylline (a double-blind placebo-controlled randomized therapeutic trial). Dermatol Ther 29(4):263–268.
  5. 5.↵
    1. Souwer IH,
    2. Lagro-Janssen ALM
    (2009) Vitamin D3 is not effective in the treatment of chronic chilblains. Int J Clin Pract 63(2):282–286.
  6. 6.↵
    1. Souwer IH,
    2. Lagro-Janssen ALM
    (2004) Perniones. Huisarts Wet 47(12):594–596.
  7. 7.↵
    1. Goette D
    (1990) Chilblains (perniosis). J Am Acad Dermatol 23(2 Pt 1):1–7.
  8. 8.
    1. Vano-Galvan S,
    2. Martorell A
    (2012) Chilblains. CMAJ 184(1):67.
  9. 9.
    1. National Organization for Rare Disorders
    Perniosis, https://rarediseases.org/rare-diseases/perniosis/ (accessed 20 Jan 2017).
  10. 10.↵
    1. Mayo Foundation for Medical Education and Research
    Mayo Clinic Chilblains Treatment, http://www.mayoclinic.org/diseases-conditions/chilblains/diagnosis-treatment/treatment/txc-20165507 (accessed 20 Jan 2017).
  11. 11.↵
    1. Ganor S
    (1973) The treatment of chilblains with fluocinolone cream under occlusive dressing. [In Hebrew]. Harefuah 84(3):163.
  12. 12.↵
    1. Ioannidis JPA
    (2005) Why most published research findings are false. PLoS Med 2(8):e124.
  13. 13.↵
    1. Grizzle J
    (1965) The two-period change-over design and its use in clinical trials. Biometrics 21:467–480.
  14. 14.↵
    1. Wang SJ,
    2. Hung HM
    (1997) Use of two-stage test statistic in the two-period crossover trials. Biometrics 53(3):1081–1091.
  15. 15.↵
    1. Jacob JR,
    2. Weisman MH,
    3. Rosenblatt SI,
    4. Bookstein JJ
    (1986) Chronic pernio. A historical perspective of cold-induced vascular disease. Arch Intern Med 146(8):1589–1592.
  16. 16.↵
    1. Raza N,
    2. Sajid MUD,
    3. Suhail M,
    4. Haroon-ur-Rashid
    (2008) Onset of chilblains in relation with weather conditions. J Ayub Med Coll Abbottabad 20(2):17–20.
  17. 17.↵
    1. Mulder DJ
    (1983) Minor ailments in the first line. [In Dutch]. Ned Tijdsch Geneeskd 127(33):1495–1496.
  18. 18.↵
    1. Feirreira Valente M,
    2. Pais Ribeiro J,
    3. Jensen M
    (2011) Validity of four pain intensity rating scales. Pain 152(10):2399–2404.
  19. 19.
    1. Reich A,
    2. Heisig M,
    3. Phan N,
    4. et al.
    (2012) Visual analogue scale: evaluation of the instrument for the assessment of pruritus. Acta Derm Venereol 92(5):497–501.
  20. 20.↵
    1. Wigley F
    (2002) Raynaud’s phenomenon. N Engl J Med 347(13):1001–1008.
  21. 21.↵
    1. Sedgwick P,
    2. Greenwood N
    (2015) Understanding the Hawthorne effect. BMJ 351:h4672.
  22. 22.↵
    1. Brody H
    (1982) The lie that heals: the ethics of giving placebos. Ann Intern Med 97(1):112–118.
  23. 23.↵
    1. Boonstra A,
    2. Schiphorst Preuper H,
    3. Reneman M,
    4. et al.
    (2008) Reliability and validity of the visual analogue scale for disability in patients with chronic musculoskeletal pain. Int J Rehabil Res 31(2):165–169.
  24. 24.
    1. Maverakis E,
    2. Patel F,
    3. Kronenberg DG,
    4. et al.
    (2014) J Autoimmun, International consensus criteria for the diagnosis of Raynaud’s phenomenon, 48–49, pp 60–65.
  25. 25.↵
    1. Block J,
    2. Sequeira W
    (2001) Raynaud’s phenomenon. Lancet 357:2042–2048.
View Abstract
Back to top
Previous ArticleNext Article

In this issue

British Journal of General Practice: 67 (656)
Br J Gen Pract
Vol. 67, Issue 656
March 2017
  • Table of Contents
  • Index by author
Download PDF
Download PowerPoint
Article Alerts
Or,
sign in or create an account with your email address
Email Article

Thank you for recommending British Journal of General Practice.

NOTE: We only request your email address so that the person to whom you are recommending the page knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Assessing the effectiveness of topical betamethasone to treat chronic chilblains: a randomised clinical trial in primary care
(Your Name) has forwarded a page to you from British Journal of General Practice
(Your Name) thought you would like to see this page from British Journal of General Practice.
Citation Tools
Assessing the effectiveness of topical betamethasone to treat chronic chilblains: a randomised clinical trial in primary care
Ibo H Souwer, Jacobus HJ Bor, Paul Smits, Antoine LM Lagro-Janssen
Br J Gen Pract 2017; 67 (656): e187-e193. DOI: 10.3399/bjgp17X689413

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Assessing the effectiveness of topical betamethasone to treat chronic chilblains: a randomised clinical trial in primary care
Ibo H Souwer, Jacobus HJ Bor, Paul Smits, Antoine LM Lagro-Janssen
Br J Gen Pract 2017; 67 (656): e187-e193. DOI: 10.3399/bjgp17X689413
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
  • Mendeley logo Mendeley

Jump to section

  • Top
  • Article
    • Abstract
    • INTRODUCTION
    • METHOD
    • RESULTS
    • DISCUSSION
    • Acknowledgments
    • Notes
    • REFERENCES
  • Figures & Data
  • Info
  • eLetters
  • PDF

Keywords

  • betamethasone
  • chilblains
  • general practice
  • randomised clinical trial
  • therapy

More in this TOC Section

  • Weight loss as a predictor of cancer in primary care: a systematic review and meta-analysis
  • Abdominal symptoms and cancer in the abdomen: prospective cohort study in European primary care
  • Development of a prediction tool for patients presenting with acute cough in primary care: a prognostic study spanning six European countries
Show more Research

Related Articles

Cited By...

 

BJGP Open

 

@BJGPjournal's Likes on Twitter

 
 

British Journal of General Practice

NAVIGATE

  • Home
  • Current Issue
  • All Issues
  • Online First
  • Authors & reviewers

RCGP

  • BJGP for RCGP members
  • BJGP Open
  • RCGP eLearning
  • InnovAiT Journal
  • Jobs and careers
  • RCGP e-Portfolio

MY ACCOUNT

  • RCGP members' login
  • Subscriber login
  • Activate subscription
  • Terms and conditions

NEWS AND UPDATES

  • About BJGP
  • Alerts
  • RSS feeds
  • Facebook
  • Twitter

AUTHORS & REVIEWERS

  • Submit an article
  • Writing for BJGP: research
  • Writing for BJGP: other sections
  • BJGP editorial process & policies
  • BJGP ethical guidelines
  • Peer review for BJGP

CUSTOMER SERVICES

  • Advertising
  • Contact subscription agent
  • Copyright
  • Librarian information

CONTRIBUTE

  • BJGP Blog
  • eLetters
  • Feedback

CONTACT US

BJGP Journal Office
RCGP
30 Euston Square
London NW1 2FB
Tel: +44(0) 20 3188 7400
Email: journal@rcgp.org.uk

British Journal of General Practice is an editorially-independent publication of the Royal College of General Practitioners
© 2018 British Journal of General Practice

Print ISSN: 0960-1643
Online ISSN: 1478-5242