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There has been an increase in the amount of research being undertaken in vitiligo over recent years and dermatologists have an improved understanding of the natural history and different types of the condition. Here you will find a brief summary of research into a number of areas, with references to the original research articles, for those of you who wish to follow these up.

Researchers are looking at :

  • The effectiveness of existing treatments;
  • Possible causes of vitiligo;
  • How the condition develops;
  • Segmental vitiligo;
  • The association of vitiligo with other conditions;
  • The psychological effects of vitiligo.

It is hoped that the improvements in scientific understandings will in future lead to more effective treatments for vitiligo.

Identifying key components for psychological intervention for people with vitiligo

A poster based on the findings of a survey of patients and health professionals to identify psychological interventions for vitiligo has been accepted for display at the 2015  BAD meeting in Manchester.   The work was funded by a grant from the UK Dermatology Clinical Trials Network.

Many of our members will have taken part in this survey which has provided useful information to assist in developing new ways of addressing the psychological impact of vitiligo on people’s lives. The value of psychological interventions in the management of vitiligo has been recognised as a research priority.  Despite this, there is only one published randomised trial on the use of group cognitive behavioural therapy (CBT) compared with group person-centred therapy for vitiligo.  As far as we are aware, no published paper has tried to establish an appropriate psychological therapy for vitiligo from both patient and clinician perspectives.  The unique survey referenced here is therefore of value to the future treatment of vitiligo patients.

On­-line questionnaires were submitted by people with vitiligo and a separate version was also completed by health professionals involved in the care of vitiligo patients.  The patients’ survey recorded personal data and focused on the effect of vitiligo on normal life,. It also sought to establish the most difficult problems faced by patients as well as which approaches they thought would be helpful to them in coping with their vitiligo. The survey also looked at the feasibility of providing these interventions under the NHS.

A hundred vitiligo patients, 82% of whom had vitiligo for 10 years or more, responded to the patient questionnaire . 70% of the respondents were female; 92% were Caucasian (a similar proportion of the population in the national statistics).  Thirty nine health professionals completed the survey of whom 67% were dermatologists and 15% were psychologists.

The most important issues reported by patients were: acceptance of their vitiligo, the duration of the disease and managing embarrassment.  Other concerns were participating in sporting activities and   exposure to sunlight.  Similar results were found in the survey completed by healthcare professionals, although the psychosexual issues indentified by them were not considered as important to the patients.

Patients thought that mechanisms that helped in accepting and understanding vitiligo were important when designing interventions, as was coping with embarrassment caused by the disease in social situations.  Improving self-confidence and self-esteem were also key issues.

Interventions considered useful by professionals to address these issues included: cognitive behavioural therapy (CBT,) acceptance and commitment therapy (ACT) and mindfulness therapy.   These therapies could be delivered in groups or individually, although 58% of patients had a preference for individual therapy.

This survey confirmed that both patients and healthcare professionals support the need for psychological interventions in vitiligo.

The authors of the survey are A Ahmed, E Steed, E Burden-Teh, R Shah, S Tour, S Sanyal, M Whitton,
J Batchelor, A Bewley

Piperine update report

Black pepper, piperine and vitiligo – a personal history from Amala Soumyanath (nee Amala Raman).

Amala Soumyanath led the research that discovered piperine as a potential treatment for vitiligo. Here she tells the story from her personal point of view, and brings us up to date with current developments:

A Personal Passion: My First Introduction to Vitiligo

My connection with vitiligo began on an ordinary working day –  almost 20 years ago!  As a registered pharmacist with a Ph.D, I held a faculty position in the Department of Pharmacy, King’s College London.

I taught courses and led a research group in my favorite subject – pharmacognosy, the scientific study of medicinal agents from nature. One day, out of the blue, I received a telephone call from a “Maxine Whitton of the Vitiligo Society.”  She stated that a member had received a Chinese herbal prescription with several named plants, and asked if I could find out if any of them might be estrogenic.I agreed to help, but the first thing I had to do was to look up what “vitiligo” was! I was surprised to discover that “vitiligo” was the name of a skin disorder that I had observed in multiple individuals. The condition is characterized by patches of depigmented skin, and I already knew of it by another name, “leucoderma.”As a pharmacist and scientist studying medicinal plants I was immediately intrigued by the disease, its causes, and the fact that PUVA therapy for vitiligo, was based on psoralens which are derived from plants. I also learned that there was no really effective treatment for vitiligo. I decided right then I would apply my scientific skills to search for a new treatment, and that this search would begin with plants used in traditional herbal medicine. Little did I know that I would go on to develop vitiligo myself, making my pursuit of a treatment more than just an interesting research project.

The Discovery of Piperine

The first step was to research and compile a list of herbs described in different herbal medicine systems for the treatment of vitiligo. We focused on Ayurvedic and Chinese medicinal plants as these systems were well documented. The first graduate students to work on this project were Dania Kowalska and Zhixiu Lin. We obtained plant samples, made extracts of these herbs, and developed a method to test them for the ability to stimulate melanocyte (pigment cell) growth [1]. This property would be necessary to repigment vitiligo patches. The cells we used were mouse melan-a cells grown in culture dishes. The cells, training, and a lot of very helpful advice were provided by Professor Dorothy Bennett, an expert in melanocyte biology based at St. Georges Hospital, London. Out of almost 30 herbs we tested- one extract stood out! A water extract of black pepper not only made the pigment cells grow faster, it also made them put out finger-like projections, called dendrites, which are important for their function in the skin. One component from black pepper, a compound called piperine, also showed the same effects [2]. In pharmaceutical parlance, piperine represented a “lead” molecule, one that could be developed, in original or modified form, for use in treating a disease.

Validating Piperine as a â€œLead” Molecule

Our early work was supported by pilot grants from the Vitiligo Society UK and the Institute of Chinese Medicine, UK. A donation of £250 from the Gulam K. Noon Foundation allowed us to buy a multichannel micropipettor, a small, but essential, piece of lab equipment. However, once we had our lead compound, I was able to raise substantially larger funding (£200,000) from BTG plc, a UK technology transfer company. My research also brought me into close contact with the Vitiligo Society UK. I was honored to serve the Society as a council member and secretary for a number of years. This valuable experience gave me a greater understanding of the issues and difficulties faced by people with vitiligo.

Over the next few years (1997–2002), we completed additional studies at King’s College London, in which we made chemical variations (analogs) of piperine and tested them for their ability to stimulate melanocyte proliferation in culture dishes [3]. Two analogs of piperine, abbreviated to THP and RCHP, showed particularly good activity, so we then tested piperine, THP and RCHP for effects on skin pigmentation in mice. We were thrilled to find that all three compounds were able to stimulate the growth of pigment cells in a special strain of lightly pigmented mice, causing their skin to visibly darken. This effect was enhanced if we used UV light in addition to the compounds [4]. Essential to this research were collaborations I had established with Professor Robert Hider (a medicinal chemist) and Professor Antony Young (a photobiologist), and the dedication and hard work of Radhakrishnan Venkatasamy (a PhD student) and Dr Laura Faas (a postdoctoral fellow). These studies allowed us to secure international patents for the use of piperine and its analogs to treat vitiligo.                            

Keeping the Vitiligo Fire Burning                                    

At this point, I had an exciting development in my personal life – I got married and relocated to the USA! I left King’s College London in late 2002, and found employment as a research faculty member in the Department of Neurologyat Oregon Health &Science University (OHSU), Portland, Oregon. Although the emphasis of my research shifted to studying herbs used in neurological diseases, I had not forgotten piperine and vitiligo. The Department of Neurology Chair, Dr. Dennis Bourdettewas very supportive of my continuing this work, so I set about making contacts at OHSU who could help move the piperine project forward.

Having shown effectiveness in cells and in mouse skin earlier in London, my next goal was to move toward testing piperine in humans. OHSU incorporates a medical school, research centers, and most importantly, a hospital. The Department of Dermatology has a strong research focus, and I approached Dr. Andrew Blauvelt, who worked in that department, to support my efforts. This led to an introduction to dermatologists Dr. Eric Simpson and Dr. Ben Ehst, with whose help I developed a detailed plan (protocol) for a clinical trial of piperine in patients with vitiligo. However, prior to actually performing a clinical study, it was important to get more data on piperine’s effects on human pigment cells, as opposed to cells from mouse skin. It was also important to investigate the safety of piperine when applied to the skin. Of particular relevance are piperine’s effects on the development of melanoma (a pigment cell cancer). I was fortunate to find, and enlist the support of Dr. Philippe Thuillieran expert in skin cancer studies, and Assistant Professor at OHSU’s Department of Public Health and Preventive Medicine. Our experiments, funded by AdPharma, Inc., showed that piperine does indeed stimulate the replication of human melanocytes in culture, including those from uninvolved skin of a vitiligo patient. We used cell lines that were kindly provided by Dr. Caroline lePoole of Loyola University, Chicago for this study. Piperine also stimulated human melanocytes when grown within a reconstructed skin model [5]. For this project we had excellent support from colleagues in OHSU’s Biomedical Engineering and Dermatology departments (Professor Steven Jacques, Dr Kevin Phillips and Ravikant Samatham) who used innovative optical methods to image pigmentation and melanocytes in the skin models [6].

 Significantly, and in agreement with other laboratories, we found that piperine has an inhibitory effect on cultured melanoma cells and prevents melanoma cell growth in a reconstructed full skin model [5]. To further this aspect of our study, we have introduced the HGF mouse model of melanoma (developed by the National Cancer Institute) to OHSU with the help of funds I raised from OCTRI (the Oregon Clinical and Translational Research Institute). We are presently studying the effects of piperine in this model with pilot funding from the Department of Dermatology’s Jesse Ettelson Fund for the Advancement of Dermatology Research. These ongoing studies are important to establish the safety of piperine.

Heading for the Homestretch: Will Piperine work in humans?

 In July 2013, this project received a tremendous boost with the appointment of a new Chair of Dermatology, Professor Sancy Leachman. Professor Leachman is a dermatologist and research scientist. Fortuitously for this project, she is an expert in pigment cell biology, and has a particular interest in pigment cell disorders such as vitiligo and melanoma! Professor Leachman is extremely enthusiastic about this project and has pledged her commitment and expertise to developing piperine as a new treatment for vitiligo. As a bonus, she has also brought two additional team members on board. The first is Dr. Pamela Cassidy, a medicinal chemist with experience in skin culture techniques, and specifically with the HGF mouse model of melanoma mentioned earlier. The second addition is Eric Smith, a talented scientist with expertise in the immunohistochemical evaluation of skin samples.  A core group consisting of myself, Professor Leachman, Dr Cassidy, Dr Thuillier and Eric Smith are working hard to steer this discovery to the clinic.

My Personal and Professional Commitment to Discovering a Treatment.  

So, a simple phone call from Maxine Whitton (recently awarded an MBE for her services to vitiligo), the spark of an idea, and a good measure of commitment and persistence on my part have brought piperine to the brink of being tested in humans. It has been rewarding to apply my knowledge of the drug development process to such an exciting and potentially groundbreaking project. This has only been possible due to the support of all the excellent collaborators, postdoctoral fellows and students who have joined and supported my vision for piperine and vitiligo, with their unique areas of expertise. As mentioned earlier, my goal to develop piperine as a treatment for vitiligo has an additional personal impetus. In 2006, after a vacation in Central America, I too developed vitiligo. I now have noticeable patches on my face, hands and legs and I would love to have them go away! I feel privileged that my research has led to new hope of a treatment for this difficult condition.

The piperine project has attracted the dedication and commitment of a talented team of researchers at OHSU – a world renowned center with outstanding facilities for clinical and basic science research. We are determined to continue research on piperine and vitiligo – to evaluate its efficacy in humans and to understand more about its effects on melanocytes. At the project helm is Dr. Sancy Leachman, an experienced dermatologist and pigment cell expert, and my continued dedication and scientific vision as initiator and ongoing champion of this project.

Will Piperine Treat Vitiligo? How you can help.

If we are able to define how piperine works and to demonstrate the safety and efficacy of piperine in a small “proof of concept” human study, this would be sufficient to attract a large pharmaceutical company to move forward rapidly with a product for treating vitiligo. Sadly, the missing element is funding for these studies. We continue to approach standard funding sources, but their response time is slow and resources are limited.  With this excellent team ready to get to work on this project, we are now reaching out to the general community for funding.  Funds raised will support our ongoing studies on piperine at both the clinical and basic science levels. With the high incidence of vitiligo worldwide, donations of any size from those affected by this condition would soon add up and make a real difference to our rate of progress.  You can support our research on piperine for vitiligo, by making an online donation to our Vitiligo Research Fund.

I thank you in advance for your support and assure you of my continued dedication to this project.

Amala Soumayanath

References

1.                   Lin ZX, Hoult JR, Raman A. Sulphorhodamine B assay for measuring proliferation of a pigmented melanocyte cell line and its application to the evaluation of crude drugs used in the treatment of vitiligo.J Ethnopharmacol 1999; 66(2): 141-150.

2.                   Lin Zet al. Stimulation of mouse melanocyte proliferation by Piper nigrum fruit extract and its main alkaloid, piperine.Planta Med 1999; 65(7): 600-603.

3.                   Venkatasamy Ret al. Effects of piperine analogues on stimulation of melanocyte proliferation and melanocyte differentiation.Bioorg Med Chem 2004; 12(8): 1905-1920.

4.                   Faas Let al. In vivo evaluation of piperine and synthetic analogs as potential treatments for vitiligo using a sparsely pigmented mouse model. British Journal of Dermatology 2008; 158: 941-950.

5.                   Thuillier P et al Effects of piperine on human melanocytes and melanoma cells in vitro. Manuscript prepared for submission.

6.                   Samatham R et al,  Progress in Biomedical Optics and Imaging – Proceedings of SPIE7883, art. no. 788309, 2011.

Hyperlinks (opens in a new window):

Quality of life and psychological aspects research

Dr Kiprono and colleagues from Tanzania found that in vitiligo patients of African descent there was a moderate impairment of quality of life when studied using the Dermatology Life Quality Index (DLQI: International Journal of Dermatology 2013; 52: 191-4). In Turkey, Dr Bilgic and colleagues looked at depression in children and adolescents with vitiligo (see Clinical and Experimental Dermatology 2011; 36: 360-5).

They found that vitiligo relates to the severity of depression in children, but a similar effect was not observed in adolescents, and suggested that the location of the lesions is a significant factor that leads to quality of life impairment, possibly because of its effects on identity development. In Korean adolescents with vitiligo, researchers found that quality of life is closely related to the patients’ apprehensions about their disease, psychosocial adjustment, and psychiatric morbidity, rather than the clinical severity of the condition itself (Choi et al. Journal of the European Academy of Dermatology and Venereology 2010; 24: 524-9).

The ways in which British Asian women manage and adjust psychosocially to vitiligo, and the potential role of ethnicity and culture in this process have been investigated (Thompson et al. British Journal of Dermatology 2010; 163: 481-6).  Asian women described feeling visibly different and all had experienced stigmatization to some extent. Avoidance and concealment were commonplace. Experiences of stigmatization were often perceived to be associated with cultural values related to appearance, status, and myths linked to the cause of the condition.

Researchers from Belgium found that the quality of life impairment in women affected with vitiligo assessed using the DLQI, was equal to the impairment caused by psoriasis (Ongenae et al. British Journal of Dermatology 2005; 152: 1165-72).  Sukan and Maner researching in Turkey, found that vitiligo had a negative impact on the sex lives of women with vitiligo (Journal of Sex and Marital Therapy 2007; 33: 55-64.).

Thyroid disease and skin cancer

In the course of their clinical work, dermatologists have noted for some years an association between vitiligo and thyroid disease. Vrijman and colleagues from Amsterdam, The Netherlands, undertook a review of this and found that there was indeed an association (see British Journal of Dermatology 2012; 167: 1224-35).

They discovered the frequency of thyroid disease in vitiligo patients was 15.1% , autoimmune thyroid disease 14.3% and the presence of thyroid-specific autoantibodies 20·8%.  This suggests that all patients with vitiligo should have their thyroid function checked.

The risk of skin cancer in patients with vitiligo might be thought of as increased since there is a tendency to burn when in the sun. This matter has been investigated by a team from The Netherlands (see Teulings et al. British Journal of Dermatology 2013; 168: 162-71). They conducted a survey designed to assess lifetime prevalences of malignant melanoma and non-melanoma skin cancer (NMSC) in patients with vitiligo, compared with non-vitiligo controls. Their findings suggest that patients with vitiligo have a threefold lower probability of developing malignant melanoma and NMSC. The reasons for this have yet to be fully understood. Hear about this on BBC iPlayer. Click Here (Opens in a new window)

Segmental vitiligo and the classification of vitiligo

Segmental vitiligo, is characterized by a unilateral and localised distribution of vitiligo patches.  Dr van Geel and collaborators have looked at this type of vitiligo (see British Journal of Dermatology 2013; 168: 56-64).  So far, the underlying mechanism is still an enigma.

In order to obtain an insight into the causes of segmental vitiligo, the researchers compared its distribution pattern with those of skin conditions with a possible mosaic or neurogenic background. (Mosaicism is a condition in which cells within the same person have a different genetic makeup). The results showed that the distribution pattern of segmental vitiligo is not entirely similar to any other skin condition, although some mosaic skin disorders have more overlap with segmental vitiligo than others. Dr van Geel and colleagues concluded that cutaneous mosaicism may be involved in segmental vitiligo.

Experts have looked at how vitiligo is classified (Ezzedine et al. in Pigment Cell and Melanoma Research 2012; 25: E1-13). They concluded that segmental vitiligo be classified separately from all other forms of vitiligo and that the term ‘vitiligo’ be used as an umbrella term for all non-segmental forms of vitiligo; this includes ‘mixed vitiligo’ in which segmental and non-segmental vitiligo are combined and which is considered a subgroup of vitiligo. The experts recommended that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the condition, as the latter is difficult to define.

Koebner phenomenon and Halo Naevi

The Koebner phenomenon (KP) refers to the development of vitiligo within an area of skin that has been damaged by localised, often mild trauma eg an injury.  Dr N van Geel and colleagues of Ghent have looked at this phenomenon (see British Journal of Dermatology 2012;167:1017-24.). They developed a new assessment method for KP, taking into account both the history and clinical examination of people with vitiligo; this seems to be a useful and valuable tool for assessing KP in daily practice.

The results support the hypothesis that KP may be used to assess and predict the course of vitiligo.

Halo naevi are common moles with a white ring around them, showing the sort of pigment loss that is seen in vitiligo. Dr van Geel and researchers have looked at how these moles can present together with vitiligo or separately (British Journal of Dermatology 2011; 164: 743-9). Their results support the theory that halo naevi can represent a distinct condition but in a subset of people, the occurrence of halo naevi may be an initiating factor in the pathogenesis of vitiligo.

Pathogenesis (how the condition develops)

The pathogenesis of vitiligo is believed to involve oxidative stress (an imbalance between the presence of toxic so-called reactive oxygen species (ROS) and the body’s ability to detoxify them). Based on this, according to Dell’Anna and colleagues in Rome, Italy, the generation of reactive oxygen species (ROS) by the mitochondria within melanocytes and blood cells may be relevant in the development of vitiligo (Journal of Cellular Physiology 2010; 223: 187-93).

These authors suggest that the modification of membrane lipid components in vitiligo cells may be a biochemical basis for the mitochondrial impairment and the subsequent production of intracellular ROS following the exposure to a mild stress.

Although the exact cause of vitiligo remains obscure, evidence suggests that autoimmunity plays a role in the pathogenesis of the disease. Previously, tyrosine hydroxylase (important in the production of melanin pigment) was identified as an autoantigen target in vitiligo. Researchers at the University of Sheffield have found that tyrosine hydroxylase is an antibody target in non-segmental vitiligo (antibodies found in 23%) but not in the segmental type.  Also, tyrosine hydroxylase antibodies appear to be more frequent in people with active vitiligo (see Kemp et al. Experimental Dermatology 2011; 20: 35-40).

Genetic and epidermis research

The research group of Professor Richard Spritz in the University of Colorado USA has undertaken many important studies of the genetic basis of vitiligo over the last few years. In the most recent paper (Nature Genetics 2012; 44: 676-80) they summarise that most genes that indicate a susceptibility to vitiligo are involved with proteins or parts of the pigment cell that are important for the functioning of the immune system.

From Dalian China, comes some interesting research on the epidermis (the uppermost layer of the skin, where the pigment cells are situated) in vitiligo. Dr Lui and colleagues (Skin Pharmacology and Physiology 2010; 23: 193-200) noted that studies have demonstrated that alterations in skin biophysical properties in vitiligo have not yet been well defined. In their study, stratum corneum (SC) hydration, the skin surface acidity and epidermal permeability barrier function in vitiligo were evaluated. They found that in addition to SC hydration, both melanin and erythema index were significantly lower in vitiligo skin than in non-lesional sites, while no difference in skin surface acidity between vitiligo-involved and uninvolved areas was observed. In addition, the SC integrity in the involved areas was similar to that in the uninvolved areas. However, barrier recovery in vitiligo-involved sites was significantly delayed in comparison with uninvolved sites.

Systemic treatments

It is difficult to find a systemic treatment for vitiligo at the moment (one that affects the whole body). Dr Szczurko et al have looked at ginkgo biloba (BMC Complementary and Alternative Medicine 2011 Mar 15;11:21).  They report on a trial given to twelve participants aged 12 to 35 years old who were treated with 60 mg of standardized Ginkgo biloba two times per day for 12 weeks.

Effectiveness was assessed using the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF), which are validated outcome measures evaluating the area and intensity of depigmentation of vitiligo lesions. Taking 60 mg of Ginkgo biloba BID was associated with a significant improvement in total VASI vitiligo measures and VETF score spread, and a trend towards improvement on VETF measures of vitiligo lesion area and staging. However, proper clinical trials are needed before this can be generally recommended as a treatment.

Piperine, derived from black pepper, has been suggested as a potential treatment for vitiligo.  So far there have only been studies in animals, which have shown an increase in pigmentation in mice treated with a piperine derivative (Faas et al. British Journal of Dermatology 2008; 158: 941-50).

With regard to cosmetic camouflage treatment, Tanioka and colleagues from Kyoto Japan discovered that this improves quality of life (Journal of Cosmetic Dermatology 2010; 9: 72-5). New European guidelines have been introduced (see Taieb et al. British Journal of Dermatology 2013; 168: 5-19).

Surgical treatments

Surgical treatments are only suitable for people with stable vitiligo.  They involve transplanting pigment cells (melanocytes) from someone’s normally pigmented skin into their vitiligo skin.  Recent research in India suggests that the results of this procedure can be improved by suspending the melanocytes in the patients’ own serum (plasma in blood). 

This could be an important innovation in the surgical management of patients with stable vitiligo. (See the research of Shane and colleagues in the journal Dermatologic Surgery 2011; 37: 176-82).

Recell is quite a new procedure that involves taking a sample of normal skin, separating out the skin cells and then spraying them onto the vitiligo patches.  Recent research has assessed the effectiveness of the ReCell kit (Clinical Cell Culture, Cambridge, U.K.) for treating vitiligo, comparing it with conventional transplantation (known as melanocyte-keratinocyte transplantation or MKT).  Dr Mulekar and colleagues (British Journal of Dermatology 2008; 158: 45-9) found that, of the five lesions treated with ReCell, two lesions showed 100%, one 65% and one 40% repigmentation, and one lesion failed to repigment.  With the five lesions treated by conventional MKT, three showed 100% and one 30% repigmentation and one failed to repigment.  (ReCell is not generally available in the UK).

Topical, light and laser treatments

Treatments in the form of creams or ointments are the usual place to start with treatments for vitiligo, although it does depend on where it is on the body and its extent. They are known as topical immunomodulator s because they can suppress the immune response in vitiligo patches.

Current research suggests that topical tacrolimus is effective for localised vitiligo. (Tacrolimus is also known as protopic).  Further details can be found in the study by Bhuvana et al (Indian Journal of Dermatology 2001; 56: 445-6)

Researchers have also found that pimecrolimus  (also known as elidel)  might be useful for people with vitiligo.  There was a study on this by Eryilmaz and colleagues (Journal of the European Academy of Dermatology and Venereology 2009; 23: 1347-8).

The use of tacrolimus and pimecrolimus is included in already published guidelines for medical practitioners.

The use of targeted narrow-band ultraviolet B (UVB) light treatment is now well known for treating localised vitiligo.  This is usually given in the form of the Excimer laser.  The treatment has been advocated by researchers ( see Le Duff et al (British Journal of Dermatology 2010; 163: 188-92).  However, this therapy is not available to most dermatologists in the UK at the moment.

People with vitiligo often question whether lasers (other than the Excimer) will help their condition. Research suggests that some lasers can help with depigmentation, on the rare occasions when this is indicated. Hossani-Madani et al (of Washington DC, USA) have shown that the Q-switched ruby laser does seem to have the advantage of inducing depigmentation more quickly than the usual topical depigmentation treatment of monobenzyl ether of hydroquinone, but with more discomfort (Giornale Italiano Di Dermatologia e Venereologia 2011; 146: 373-95).