Plain Language Summaries


The interpretation of long-term trials of biologic treatments for psoriasis: trial designs and the choices of statistical analyses affect ability to compare outcomes across trials

R.G. Langley, K. Reich

This summary relates to DOI: 10.1111/bjd.12583

British Journal of Dermatology, 169, 1198–1206, December 2013

Summary

Psoriasis is a common skin disease affecting about 2% of the population. In about 90% of cases it requires long-term treatment. For this reason, treatments which have been proved safe and efficient during long-term trials are required. Such treatments for patients with severe psoriasis include biologics (biological drugs – so named because they mimic normal human molecules). There are several different types of biologics and this study demonstrates that while these treatments have individually been shown to be effective and safe, it is difficult to make direct comparisons between the different versions. This is because there is variance in the way the clinical trials (a type of research using real patients) are designed and how the data is analyzed in different studies. The range of variables outlined includes missing data, caused when patients taking part in the trial drop out, stop using the drug or miss assessments, which can bias results. There are four standard strategies for addressing the problem of missing data, and the authors, from Canada and Germany, show how results from a real clinical study changed when the different methods were used. The authors then evaluated the results of existing clinical trials, taking into account the different choices for designing clinical trials and analyzing the data, to determine how these choices may influence how the overall outcomes should be interpreted. They conclude that in the absence of common standards for long-term trials, doctors need to understand the differences in handling data so that they can better compare different therapies, in order to make the best choices for patients.

Narrowband ultraviolet B (NBUVB) phototherapy in children with moderate to severe eczema – a comparative cohort study

S. Darné, S.N. Leech, A.E.M. Taylor

This summary relates to DOI: 10.1111/bjd.12580

British Journal of Dermatology, 170, 150–156, January 2014

Summary

Narrowband UVB (NBUVB) is a type of phototherapy (light treatment) recommended for use in adults with eczema, a common skin disease. However, there are few studies relating to its effectiveness in treating children. This study therefore looked at a group of children, aged 3 to 16 years, with moderate to severe eczema and compared 29 children who received NBUVB (called the ‘treatment cohort’) with 26 who declined it (the ‘unexposed group’). Both groups were assessed at the outset of the study, in relation to their clinical symptoms (using SASSAD, which grades six classic signs of eczema according to how severe they are, and ‘mean surface area involvement’ which measures how much of the skin is affected) and in relation to their quality of life (using five different questionnaires). Those receiving NBUVB then started a 12-week course of phototherapy given twice a week. Both groups were assessed after 12 weeks, and the treatment cohort were assessed again three and six months after treatment. There was a 61% reduction in mean SASSAD score in the treatment cohort, which signifies an improvement in their symptoms, compared with an increase (i.e. worsening) of 6% in the unexposed group. Mean surface area involvement at the end of treatment was 11% for the treatment cohort versus 36% for the unexposed group. These scores remained significantly lower than the unexposed group, both three and six months after treatment. The quality of life scores also showed marked improvements in the treatment group compared to the unexposed group. The study therefore concludes that NBUVB is clinically effective and improves quality of life in children with moderate to severe eczema, and the effect is maintained for six months after treatment. This study was supported by a grant from the British Skin Foundation.

Reliability of quantification measures of actinic keratosis

S.C. Chen, N.D. Hill, E. Veledar, S.M. Swetter, M.A. Weinstock

This summary relates to DOI: 10.1111/bjd.12591

British Journal of Dermatology, 169, 1219–1222, December 2013

Summary

Actinic keratoses (AKs) are areas of sun-damaged skin mainly found on sun-exposed parts of the body, including the face and ears. Although usually harmless in themselves, they are caused by excessive sun exposure over many years, and so indicate that the person may be at increased risk of developing skin cancer. They also can develop into squamous cell carcinoma – the second most common type of non-melanoma skin cancer – although this is not common. AKs can vary greatly in appearance, including in size, colour and texture. At first they can be hard to see, and are more easily felt, being rough, like sandpaper. This broad spectrum of features can mean that quantifying and counting AKs for the purposes of research (for example, to measure the number of AKs before and after treatment) is difficult. A number of studies have been conducted to examine different methods for evaluating the level of AKs on a person. This study, by researchers in the US, reviewed the evidence relating to four such methods: body surface area, which measures the amount of a person's skin affected by AK, counting of ‘big’ lesions that are greater than 0·25 cm, counting of ‘small’ lesions that are smaller than 0·25 cm, and total count irrespective of size. The study looked specifically at methods for use on face and ears. The authors conclude that the total count method is the most reliable and the body surface area is the least reliable means to quantify AKs on the face and ears. The study provides data which can be used to guide future clinical trials.

Efficacy of a general practitioner training campaign for early detection of melanoma in France

F. Grange, A.S. Woronoff, R. Bera, M. Colomb, B. Lavole, E. Fournier, F. Arnold, C. Barbe

This summary relates to DOI: 10.1111/bjd.12585

British Journal of Dermatology, 170, 123–129, January 2014

Summary

Melanoma is the most dangerous form of skin cancer where tumours grow in ‘thickness’ (depth of invasion into the skin) the longer they are left untreated. The ‘Breslow thickness’ of a melanoma lesion, measured in millimetres, is used to assess how advanced it is. Very thick melanomas (VTM) are those that are more than 3 mm, and are harder to treat. In this study, a campaign to educate GPs about melanoma was carried out by dermatologists in one French region. A total of 1241 GPs in this ‘test’ region received educational materials by post and a third attended training sessions provided by dermatologists. The impact of the campaign on melanoma diagnoses was then compared to a second region in France where GPs had not received this training. Following the campaign, the incidence of VTM fell by 34%, the mean thickness of tumours decreased from 1·95 to 1·68 mm, and the proportion of thin (i.e. not advanced) lesions increased by 6·5% in the test region where GPs had received the campaign materials. However, there were no changes in the non-campaign area, where the numbers of VTMs and thin melanomas both remained stable. The authors argue that their results provide a rationale for a larger public health campaign in France, including training of GPs by dermatologists.

Can tissue dielectric constant measurement aid in differentiating lymphoedema from lipoedema in women with swollen legs?

S. Birkballe, M.R. Jensen, S. Noerregaard, F. Gottrup, T. Karlsmark

This summary relates to DOI: 10.1111/bjd.12589

British Journal of Dermatology, 170, 96–102, January 2014

Summary

Lymphoedema and lipoedema are two disorders which both cause swelling to the limbs, but for different reasons. Lymphoedema swelling is caused by excess fluids in the body's tissues, while lipoedema is caused by irregular fatty deposits. They both most commonly affect women and often the lower legs. People with lipoedema often also experience lymphoedema. It is often difficult to distinguish between the two conditions, even for skilled practitioners, and lipoedema is frequently misdiagnosed as lymphoedema. This study tested ‘Tissue Dielectric Constant (TDC) measurement’ on 39 women: 10 healthy controls, 10 with lipoedema, 10 with treated lymphoedema and nine with untreated lymphoedema. TDC measurement uses a handheld device to emit an electromagnetic wave into the affected area and then read how much of the wave is reflected back. Water molecules absorb the energy from the wave rather than reflecting it, so TDC gauges the water content in a particular area of tissue. A higher TDC reading means a higher level of water in the tissue. Fat, which causes lipoedema swelling, has a relatively low water content. The researchers, from Copenhagen, Denmark, found that TDC values of patients with untreated lymphoedema were significantly higher than those who were healthy, had lipoedema or had treated lymphoedema. They conclude that, used on the ankle or lower leg, TDC measurement may effectively show if the patient has lymphoedema, indicated by high water content, or lipoedema, which has a lower water content measurement. The researchers recommend a larger study to confirm their results.

A second look at efficacy criteria for onychomycosis: clinical and mycological cure

M. Ghannoum, N. Isham, V. Catalano

This summary relates to DOI: 10.1111/bjd.12594

British Journal of Dermatology, 170, 182–187, January 2014

Summary

Onychomycosis is more commonly known as ‘fungal nail infection’, in which infected nails turn white or yellowish, and become thickened and crumbly. It is very common, affecting up to 13% of the general population, and up to 25% of elderly people. Antifungal treatments in the form of tablets have been shown to be more effective than treatments applied directly to the nail (topical treatments). Several pharmaceutical companies have tried to make new topical treatments available but have been unsuccessful. This study argues that this failure may not be because such treatments are ineffective, but because the ‘endpoints’ (target outcomes) for their trials are too strict. Moreover, different trials use different endpoints, which include ‘clinical cure’ (80–100% visible clearing of the nail), ‘mycological cure’ (the fungus has been killed), and a combination of both. The researchers, from the US, reviewed mycology samples from 3054 people enrolled in several different studies. Their findings demonstrate flaws in how the results of trials are interpreted. One example is that, while many of the samples examined under a miscroscope were found to contain fungal cells, which would indicate the treatment had not worked, the tests did not differentiate between cells that were active or those that were in fact not ‘viable’ because they were dead or damaged. Furthermore, studies did not always take into account the slow rate of nail growth, meaning that the nail would be unlikely to appear clear immediately after treatment as it would need time for the damage caused by infection to grow out. The researchers propose a number of measures to help allow for more accurate results of topical treatment trials.

The hapten–atopy hypothesis III: the potential role of airborne chemicals

J.P. McFadden, D.A. Basketter, R.J. Dearman, P. Puangpet, I. Kimber

This summary relates to DOI: 10.1111/bjd.12602

British Journal of Dermatology, 170, 45–51, January 2014

Summary

Atopic disorders are a group of conditions which include asthma, eczema and hay-fever and which are caused by the immune system being overly sensitive to some potential ‘allergens’. Atopic disorders are hereditary, but there are factors that can make a person more likely to develop them. These include exposure to certain chemicals that cause allergies, when in the womb or during early childhood, as this affects the child's developing immune system. Previous studies have examined these chemicals when applied to the skin or eaten. This latest review, by researchers in the UK and Thailand, looked at a range of studies and revealed that inhaling airborne chemicals may also play a role. First they examined possible links between the occupation/work of the mother when pregnant, and whether the child then developed eczema. They found that children born to pregnant women from five occupations were at increased risk of eczema, and these occupations were united by their high and persistent exposure to airborne chemicals. They then reviewed studies into chemicals called ‘volatile organic compounds’, found in some household cleaning products and wall paints, and found higher levels of atopic disorders among children exposed to these airborne chemicals during early childhood or during the mother's pregnancy. Similar links were found in the research relating to exposure to airborne chemicals at chlorinated swimming pools during childhood, and living near chemical factories. The researchers conclude that airborne chemicals can result in both skin and inhalation exposure and this, while in the womb or during early childhood, can increase the risk of atopic disease.

The natural course of early-onset atopic dermatitis in Taiwan: a population-based cohort study

T.-C. Hua, C.-Y. Hwang, Y.-J. Chen, S.-Y. Chu, C.-C. Chen, D.-D. Lee, Y.-T. Chang, W.-J. Wang, H.-N. Liu

This summary relates to DOI: 10.1111/bjd.12603

British Journal of Dermatology, 170, 130–135, January 2014

Summary

Atopic dermatitis is a type of eczema that is very common in children. The main symptom is itch, which can be severe enough to stop the child sleeping properly, causing tiredness and irritability. It can be found on any part of the skin, including the face, but the areas that are most commonly affected are the elbows, knees, wrists and neck. The skin is usually red and dry and may bleed from scratching. People with atopic dermatitis are more likely to also suffer from asthma and allergic rhinitis (a runny, itchy nose and sneezing caused by allergens like dust, pollen and animal fur). This study looked at the national medical insurance records for 1404 children in Taiwan who had atopic dermatitis (eczema) for more than 90 days. It focussed on children whose eczema had started while they were under the age of two, and followed them from birth to age 10. Of these, 10·5% also had allergic rhinitis at the time their eczema was first diagnosed, and 8·3% had asthma. The researchers found that in a fifth (19·4%) of the 1404 children, the eczema lasted less than a year, and in almost half (48·7%) it lasted less than four years. 70% of children had not had eczema for at least two years by the time they reached the age of 10. The sex of the child, their age when first diagnosed, and whether they also had asthma or allergic rhinitis, did not affect how long they then had eczema for. The median length of time the eczema lasted was 4·2 years.

Estimating the contribution of occupational solar UV exposure to skin cancer

A. Milon, J.-L. Bulliard, L. Vuilleumier, B. Danuser, D. Vernez

This summary relates to DOI: 10.1111/bjd.12604

British Journal of Dermatology, 170, 157–164, January 2014

Summary

Exposure to ultraviolet light from the sun (‘solar UV’) is the main cause of skin cancer. Squamous cell carcinoma, the second most common type of skin cancer, is linked to longer-term sun exposure accumulating on areas frequently exposed. Outdoor workers (e.g. farmers, construction workers, gardeners) are at particular risk because they spend long working hours outside and may have little shade available, and the disease is becoming increasingly common in people who routinely work outside. This study, by researchers in Switzerland, used 3D computer graphics techniques and ground irradiation data to calculate annual UV doses for the areas of skin most likely to be exposed to the sun, including face, back of the neck, shoulders and forearms. It also assessed the extent to which exposure to the sun during working hours and/or lunch breaks contribute to a person's overall UV exposure, in a variety of occupational scenarios, including year-round or seasonal work. The researchers demonstrated how these variables could then be used to estimate a person's risk of developing SCC, based on inputting the acquired information into a model. The authors conclude that occupational sun exposure is a major contributor to squamous cell carcinoma in outdoor workers and it should therefore be recognized more broadly as an occupational disease.

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