News forum – latest research

GPs with an interest in dermatology review the latest papers of significance from research teams across the world

Diphencyprone for cutaneous metastatic melanoma
Cardiac complications in deep chemical peels
Hyaluronate fragments in the reversal of skin atrophy
The effects of dermal exposure to antineoplastic drugs
Minocycline’s effectiveness as a first-line oral antibiotic in acne
Itch Severity Scale: a self-report
The use of methotrexate in the treatment of eczema
Artificial fingernails and the risk of contact dermatitis
The safety of topical therapies for patients with dermatitis

Diphencyprone for cutaneous metastatic melanoma
Damian DL, Thompson JF. J Am Acad Dermatol 2007 doi:10.1016/j.jaad.2006.12.018

I am familiar with diphencyprone as a method of treating alopecia; the potent contact sensitiser is applied directly to the skin, restimulating hair growth in areas of previous loss. This is provided locally in secondary care and works well in some cases.

I have also heard of it being used to treat cutaneous warts, but this new case report described a completely new use for it. Coming from sunny Australia, where melanoma skin cancer is more prevalent than in the UK, the report describes the use of diphencyprone for one patient suffering from metastatic malignant melanoma of the scalp.

The primary nodular melanoma was excised, but the patient then went on to develop extensive confluent metastases near the original site, which were unsuitable for further treatment with surgery or radiotherapy.

The team decided to try diphencyprone, which was applied topically as single agent and resulted in a complete regression of all the metastases and a healthy patient 18 months later, with no recurrence. The treatment was cheap, easy and well tolerated by the patient. Obviously, this is only a single case study, but this is an excellent result, and it is to be hoped that it can be reproduced in the future.

- Dr Nigel Stollery is a GP in Kibworth, Leicestershire, and clinical assistant in dermatology at Leicester Royal Infirmary

Cardiac complications in deep chemical peels
Landau M. Dermatol Surg 2007; 33(2): 190-3; discussion 193

Deep chemical peels have been used for more than a century to treat photo-aging, wrinkles, acne scarring and precancerous skin lesions. Although they are well tolerated in the majority of cases, the most important complication is that of cardiotoxicity. This study aimed to determine the incidence of such complications and tried to seek ways of reducing them in the future. During a 12-month period from December 2004 to November 2005, details were recorded of patients undergoing full-face deep chemical peels. Cardiac monitoring was then recorded while the procedure was carried out and any arrhythmias and necessary medical intervention noted.

Throughout the period of the study, data were collected on 181 patients, all of whom were female. The mean age was 56, with a range from 30 to 77 years.

During the procedure, cardiac monitoring revealed arrhythmias in 6.6 per cent, or 12 patients. This was more common in those with other conditions, such as diabetes, hypertension and depression.

In four of those affected, the arrhythmia was self-limiting and required no intervention. In the other eight, 100mg of lidocaine was given IV, which controlled the arrhythmia.

These figures suggest that the incidence of arrhythmias is actually less than previously appreciated and that people with diabetes, hypertension and depression should be warned of their increased risk. NS

Hyaluronate fragments in the reversal of skin atrophy
Kaya G, Tran C, Sorg O et al. PLoS Med 2006; 3(12): e493 doi:10.1371/journal.pmed.0030493

Skin atrophy increases with age and with the average age of the population rising all the time, the reversal of these changes is a challenge to modern medicine, especially with regard to skin healing and ulceration.

The skin of an 80-year-old is, on average, half the thickness it would have been 60 years before, as a result of decreased keratinocyte proliferation. Associated loss of collagen and elastin also means the skin is less likely to stretch and more likely to tear under stress.

One other observation of importance to this study is that aging skin also contains less hyaluronate and CD44, a surface protein with which it interacts, stimulating cell proliferation.

Given these findings, this study proposed to see whether fragments of hyaluronate could be used to reverse skin atrophy. In the study, keratinocytes were isolated from normal mice and CD44-deficient mice, and treated with different-sized fragments of hyaluronate.

The researchers found that the intermediate-sized fragments increased proliferation, but only in the normal mice, not in the CD44-deficient ones.

The next stage of the study involved making a cream that contained the intermediate-sized fragments, which was applied directly to the skin of the normal mice. The result was that epidermal thickening occurred.

This was then tried on six humans for one month and was shown to increase skin thickness, collagen, elastin and vessel content in those with atrophy, although it had no effect on normal skin (differing from the mice studies).

Further research is required to expand on these findings, but the results of this initial study may herald a new and unique treatment for skin atrophy which could prove of therapeutic benefit in the future. NS

The effects of dermal exposure to antineoplastic drugs
Fransman W, Roeleveld N, Peelen S et al. Epidemiology 2007; 18(1): 112-19

Hospital workers can be exposed to antineoplastic drugs on a daily basis. Previous studies have found that exposure to these drugs may adversely affect reproduction. However, these studies have been inconclusive or inconsistent in their findings.

This research looked at more than 4,000 oncology nurses, exposed and non-exposed to the drugs, over a seven-year period. The nurses were given questionnaires relating to pregnancy outcome, work-related exposure and lifestyle.

Exposure to antineoplastic drugs was estimated using task-based dermal exposure methods and self-reported task frequencies. A high response rate (79 per cent) was noted.

The results showed that nurses highy exposed to the drugs took longer to conceive and were more likely to have a premature delivery. However, no correlation was found with spontaneous abortion, stillbirth, congenital anomalies, or sex of offspring. ­

- Dr Waseem Chaudhry is a GPSI in dermatology in Caerphilly

Minocycline’s effectiveness as a first-line oral antibiotic in acne
McManus P, Iheanacho I. BMJ 2007; 334: 154

Adolescents are most likely to develop acne, with an estimated 11 per cent suffering moderate to severe disease. Minocycline has long been established as the antibiotic of choice for acne because of its perceived superior effectiveness.

The authors of this review searched Medline and the Cochrane library to assess the safety and efficacy of minocycline. They found the evidence for its increased efficacy ‘at best, weak’ and limited to a few poor quality trials.

There was no evidence that minocycline is less likely to produce Propionibacteria acnes resistance compared with other tetracyclines and that switching to minocycline from another tetracycline does not improve response. However, they commented that minocycline was more likely than other tetracylines to lead to lupus-like syndrome.

Minocycline is also unique among tetracyclines for potentially causing an irreversible slate-grey hyperpigmentation of the skin. It is also more costly than other tetracyclines.

In conclusion, the researchers recommended that minocycline should not be used as a first-line oral tetracycline for patients with acne because it is no more effective than other tetracylines, is more expensive and has more potential side-effects. Acne patients requiring an oral tetracycline should be prescribed doxycycline, lymecycline or oxytetracycline. WC

Itch Severity Scale: a self-report
Majeski CJ, Johnson JA, Davison SN, Lauzon GJ Br J Dermatol 2007 doi:10.1111/j.1365-2133.2006.07736.x

The assessment of pruritus severity is difficult. A questionnaire quantifying this would provide a more accurate representation of symptoms. In this study, the authors developed a self-reported questionnaire to assess pruritus severity by modifying a more general one.

They produced a seven-item Itch Severity Scale (ISS), which they found correlated moderately with physical and mental health composite scores of the RAND-36 and strongly with the Dermatology Life Quality Index score. Based on these comparisons, the authors believe the ISS may be useful in comparing the severity of pruritus between different diseases and in assessing the effectiveness of treatment. WC

The use of methotrexate in the treatment of eczema
Weatherhead SC, Wahie S, Reynolds NJ, Meggitt SJ Br J Dermatol 2007; 156(2): 346-51

Methotrexate is widely used in the treatment of psoriasis, although it requires close supervision and monitoring. The aim of this study was to assess whether methotrexate could also be successfully used to treat eczema.

Several small retrospective studies have been carried out in the past, suggesting methotrexate is well tolerated and effective in patients with severe eczema. However, this study aimed to look prospectively at the use of methotrexate in eczema.

This was a small study, involving just 12 patients with moderate to severe eczema. All had previously been given second-line therapies and their eczema had only partially responded to potent topical steroids and emollients.

The study was carried out over a 24-week period using an increasing dose regimen until a response was achieved or treatment limited by toxicity. Every four weeks, disease activity was assessed using a six-area sign atopic dermatitis score; this was continued for 12 weeks after the treatment was stopped.

The results were promising and demonstrated an average improvement of 52 per cent in disease activity. Quality of life, body surface area affected and loss of sleep and itch scores were also significantly improved.

Eight of the patients continued to demonstrate improvement in the 12 weeks after the therapy ended. The study also revealed that in those patients who failed to show an improvement after 12 weeks of treatment, continuing to increase the dose made little difference to disease activity, suggesting that there is probably little point in continuing to increase the dose if there is no improvement by 12 weeks. Only one patient dropped out of the study, owing to minor adverse effects.

In their conclusion, the authors state their support for the use of methotrexate in moderate to severe eczema, but point out that a randomised controlled trial is now warranted to expand on these findings. Perhaps we may see an increase in the use of methotrexate in future, but as we are constantly reminded, it does require close monitoring, which may put people off its use.

- Dr Jane Barnard is a GP with an interest in dermatology in Yateley, Hampshire

Artificial fingernails and the risk of contact dermatitis
Lazarov A. J European Acad Dermatol Venerol 2007; 21(2): 169-74

Nail care products are an important cause of contact allergy, leading to adverse reactions and potential cross sensitivities.

The aim of this study was to evaluate the role of allergic contact dermatitis as a cause of adverse reactions related to the use of artificial nails.

This was a retrospective study over four years, looking at patients who had suspected allergic contact dermatitis owing to the use of artificial nails. The patients were tested with the methacrylate artificial nail series and then evaluated clinically.

Half of the patients were beauticians specialising in nail sculpture, who developed occupational allergic dermatitis. All patients had involvement of the hands and fingers. Hand eczema was observed in one-third of patients. Paronychia, nail dystrophy and onycholysis were also observed, but less frequently.

Some patients had atypical features, such as lichenoid and psoriasiform allergic contact dermatitis. In two of the patients, oedema and mucosal erythema developed following dental work, owing to the use of acrylate-based cement. The authors conclude that the components used in nail sculpture are important contact and occupational sensitisers, which can trigger further allergic reactions in different situations, such as dental work.

It is therefore important to consider cross-sensitisation in those patients with a known previous episode of allergic contact dermatitis and beware the painted false fingernails. JB

The safety of topical therapies for patients with dermatitis
Callen J, Chamlin S, Eichenfield LF et al. Br J Dermatol 2007, 156 (2): 203-21

Mechanisms of action of topical therapies for atopic dermatitis range from those with little effect on immunosuppression, such as emollients, to those with more significant effect, such as topical corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus). Hypothetically, these therapies could result in systemic immunosuppression.

The aim of this study was to search current evidence and evaluate the safety profiles of all topical therapies. The method was quite complicated, involving not only database searches, such as Medline and Cochrane, but also US Food and Drug Administration studies and meetings on topical agents. In addition, a qualitative review of the data was carried out at a meeting of the specialists involved.

The results of the study demonstrated that topical reactions, such as erythema and itching, were most common with topical corticosteroids, while infection was seen more commonly with the topical calcineurin inhibitors, although both were relatively infrequent and mild.

Skin tumours were seen with an occurrence rate expected of the normal population, but the research was limited and the topical calcineurin inhibitors had only been available for about five years, so long-term effects were unclear.

Systemic exposure was concluded to be variable, depending on a number of factors, such as disease state, dosage form and individual patient physiology. The only well-documented systemic side-effect was the effect of topical corticosteroids on the HPA axis.

The conclusion was that using available data, the safety of therapies for atopic dermatitis appears to be good and evidence supports their continued use, with no support of one therapy over another. However, throughout the article, it is noted that the current research is lacking, so more robust longer-term clinical trials are required to obtain a clearer idea of risk.

For now, the advice is that choice of therapy should be based on tolerability and efficacy for each individual. JB

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