What’s new in specialist dermatology? Back

Introduction

Specialist Dermatology Academy, 2015, Dubai, United Arab Emirates

Many millions of people are affected by chronic skin diseases in which patients have to cope with the effects of their disease and also the reaction of others to their condition. There has been a stigma attached to skin diseases for centuries and chronic skin conditions can impact a patient’s quality of life (QOL) beyond the skin. Many millions of people are affected by chronic skin diseases in which patients have to cope with the effects of their disease and also the reaction of others to their condition. There has been a stigma attached to skin diseases for centuries and chronic skin conditions can impact a patient’s quality of life (QOL) beyond the skin.

These are however exciting times for the specialist dermatologist community with new developments in non-communicable skin disease that will ultimately lead to improved clinical outcomes, QOL and enhanced patient care. In January 2015, the US Food and Drug Administration (FDA) approved secukinumab, a fully human anti-interleukin-17A (IL-17A) monoclonal antibody (mAb), for the treatment of moderate-tosevere plaque psoriasis in adult patients. It is the first in class and only biologic currently approved for use first line in psoriasis in the European Union (EU), the United States (US) and Canada.1-5 The approval of secukinumab is based on the efficacy and safety outcomes from 10 Phase II and III studies, which included over 3,990 patients with moderate-to-severe plaque psoriasis. These trials included four pivotal Phase III trials, named ERASURE, FIXTURE, FEATURE and JUNCTURE.2 The pivotal head-to-head FIXTURE trial demonstrated that the proportion of patients achieving a 75% reduction in Psoriasis Area Severity Index (PASI 75) at Week 12 was significantly higher with secukinumab than placebo or the well-established biologic agent, etanercept (Figure 1A).6 Up to 80% of patients receiving secukinumab achieved a PASI 75 at Week 12 and the proportions of patients achieving a PASI 90 and PASI 100 were significantly higher with secukinumab than with etanercept through to Week 52 (Figure 1B and C).6 Similarly, the proportion of patients with a Dermatology Life Quality Index (DLQI) response of 0 or 1 (indicating no QOL effects) at Week 12 or Week 52 was significantly higher with secukinumab than with placebo or etanercept.6 The latest developments in management in the fields of psoriasis, chronic spontaneous urticaria (CSU), hidradenitis suppurativa (HS), atopic dermatitis (AD) and vitiligo were the focus of the Royal College of Physicians-accredited, educational, Specialist Dermatology Academy, 2015, Dubai, United Arab Emirates. This two-day meet ing was supported by Novartis and the key points discussed are presented within this Key Opinions in Medicine (KOM).

Dermatological diseases are extremely important – they have a huge impact on QOL, but also on work performance.
T.
Zuberbier

Important new advances in specialist dermatology

Psoriasis
Diamant Thaçi

Psoriasis is a chronic, systemic inflammatory skin condition.7 Severe, but also mild and moderate psoriasis carries significant disease burden and we are currently experiencing a better understanding of the patient perspective in psoriasis. It is clear that patient perceptions of factors contributing to disease severity are different to those of the dermatologists.8,9

PASI 50 is no longer sufficient.
D. Thaçi

Although European S3 Guidelines on the systemic treatment of psoriasis in 2009 propose 75% or more improvement in the Psoriasis Area Severity Index from baseline (PASI 75) and a DLQI of 0 or 1 as treatment goals,10 physicians acknowledge that a PASI of more than 75 or 90 are closer to meeting the patient’s expectations, and now are realistic treatment goals. Furthermore, patients who achieved a PASI 90 response have a significantly higher QOL improvement than patients who achieved a PASI 75.11 Our understanding of psoriasis pathogenesis has evolved considerably over the last 30 years, leading to the development of targeted therapies (Figure 2).12 Studies have demonstrated a role for T Helper (Th)1 and Th17 cells as important regulators of psoriatic skin inflammation and IL-17, the principal effector cytokine of Th17 cells, stimulates keratinocytes to produce chemokines, cytokines and other proinflammatory mediators to sustain chronic inflammation. This model underlies the rationale for inhibiting IL-17 signalling as a potential therapeutic approach to disrupt the psoriatic inflammatory loop.12

Wave goodbye – targeting Il-17 could be the key.
D. Thaçi

Comparative efficacy among therapies is best evaluated in rigorous head-to-head randomised trials. As discussed in the introduction, secukinumab has shown superior efficacy to the tumour necrosis factor (TNF) inhibitor etanercept in moderate to severe plaque psoriasis (FIXTURE trial).6 CLEAR, the second head-to-head trial of secukinumab, directly compared the efficacy and safety of secukinumab with ustekinumab, a human anti-IL-12/23 mAb that functions upstream of IL-17, in individuals with moderate to severe plaque psoriasis.12 In this 52-week, double- blind study, secukinumab was clinically and statistically superior to ustekinumab as assessed by faster response (PASI 75 at week 4) and higher clearing potential (PASI 90 and PASI 100) responses at week 16 (Figure 3).13

Urticaria
Torsten Zuberbier

Urticaria is a common, mast celldriven disease characterised by the sudden appearance of itchy wheals, angioedema or both.14 The spectrum of clinical manifestations of the different urticarial types and side severe allergic diseases in terms of impact.14,16 The detrimental effects on QOL were recently confirmed in a real world study (ASSURE-CSU).17 ASSURE-CSU is the first study to address disease burden in the large number of patients (up to 50%) who do not respond to H1- antihistamines at licenced dose.18 This observational study involved around 700 patients from seven countries with more than 50% of patients presenting with angioedema at enrollment.18 Preliminary results indicate a high and often underestimated burden of disease with significant effects on QOL, work and activity impairment (Figure 4).18,19

Treatments leading to complete symptom control are called for.
T. Zuberbier

The SOLVE-BOI study was conducted in five EU countries and analysed data on 369 patients with chronic wheals (a proxy for CSU) from the National Health and Wellness Survey (NHWS).20 Preliminary results indicate that CSU patients experience declines in QOL, psychological complications, and rates of work impairment and healthcare comparable to that observed with psoriasis.20 Taken together, these data strengthen the evidence that CSU poses a substantial burden to patients and society.18-20 A better understanding of CSU will result in a more optimised approach to patient management.17

Hidradenitis suppurativa
Sylke Schneider-Burrus

Hidradenitis suppurativa (HS) is a common, debilitating inflammatory skin disease.21 In contrast to other dermatological disorders with well-established definitions, HS has only relatively recently been defined, pathogenesis only recently described and diagnostic criteria only recently established.22,23 The painful, deep-seated and inflamed lesions cause severe discomfort, have a serious psycho-social impact and a high economic cost.21 Recently, the association between HS and depression and anxiety was confirmed and it is important that dermatologists treating HS patients remain acutely aware of this important association.24

Many new insights into this exciting disease offer the promise to improve QOL for HS patients.
S. Schneider-Burrus

As a systemic inflammatory disease, HS affects many different organ systems and recent evidence indicates that HS is associated with cardiovascular disease (CVD), inflammatory bowel disease (IBD) and spondyloarthropathy.25-27 2015 saw the publication of the first European treatment guidelines for HS (Figure 5).28 These guidelines recommend treatment based on individual subjective impact and objective severity. Whilst pharmacotherapy with antibiotics or biologics is more appropriate for inflamed lesions, surgery is required in contracting scars and sinus tract formations.28

Atopic dermatitis
Ana Giménez-Arnau

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterised by areas of severe itching, redness and scaling. It is a complex disorder involving multiple genetic and environmental factors.29 The main symptom is an itchy rash which disturbs sleep and seriously impacts on psychological wellbeing, particularly in patients with severe disease.29 Recent progress in understanding the genomics and pathophysiology has revealed that AD is highly heterogeneous with regard to clinical phenotype and natural history.30 There is now an urgent need for identification and validation of biomarkers in AD and to develop disease-modifying strategies with the goal to stop or even reverse the atopic march.30

AD is a puzzle that needs addressing as a complete entity.
A. Giménez-Arnau

Moving forward, the ability to define the pathological phenotype of the atopic patient will enable physicians to control the earliest signs and symptoms (e.g., dry skin) and prevent the development of more severe forms of the disease, potentially avoiding the development of AD.

Vitiligo
Maja Hofmann

Vitiligo is a common, de-pigmenting skin disease characterised by the total absence of melanocytes.31 Although the causes of vitiligo remain poorly understood, it is now established that regulatory T cells (Tregs) are crucial to the development of self-tolerance and highlight the opportunities for Treg cell-based therapies.31 Despite the fact that vitiligo is a well-characterised autoimmune disorder, the disease is often considered “cosmetic”. Evidence has accumulated and in 2015 vitiligo was designated a medical and not a “cosmetic” disease, which has a profound impact on QOL.32

Significant QOL issues reinforce that vitiligo should not be considered a cosmetic disease. New and potential drugs are urgently needed in this disease.
M. A. Hofmann

The recent consensus treatment guidelines published by the European Dermatology Forum describe the current evidence-based recommendations.33 Although no defined therapy exists for vitiligo, treatment guidelines currently include avoidance of triggers, local therapies (corticosteroids and calcineurin inhibitors), ultraviolet B (UVB) therapy and systemic steroids.33 Despite a recent proliferation in research, there remains an unmet need for effective treatments as highlighted in a recent Cochrane review.34 Clinical studies currently underway include afamelanotide, minocycline, simvastatin and abatacept, and preliminary data from an in vitro study suggests that low-dose cytokines are a potential therapy.35

Managing skin diseases

Psoriasis co-morbidities as a treatment consideration
Emel Bülbül Başkan

It is well established that psoriasis is associated with multiple nondermatological diseases and is now considered a chronic, systemic, inflammatory condition.7,36 In 6–42% of psoriasis patients, the disease progresses to affect the joints, enthesitis and/or spine to cause psoriatic arthritis (PsA), which without appropriate treatment can be progressive, destructive and deforming.37 Psoriasis has also been associated with excess morbidity/ mortality due to co-morbid conditions including CVD.38-40 The burden of co-morbid diseases may increase with increasing psoriasis severity and represent a substantial economic burden.41,42 Although the mechanisms linking psoriasis to CVD remain incompletely defined, it has been suggested that treatment of skin inflammation may diminish the pro-inflammatory and pro-thrombotic pathways leading to development of CVD in psoriasis.43 Indeed, early systemic psoriasis therapies have a positive impact on co-morbidities such as CVD.44 The recognition of psoriasis as a systemic disorder with characteristic skin symptoms and associated diseases has substantially changed the treatment paradigm. A more holistic approach to disease control should be adopted, considering the presence of PsA and co-morbidities important factors in treatment.45

Changing treatment goals in psoriasis
Wolf-Henning Boehncke

Several high-quality, evidence-based guidelines are available describing psoriasis treatments and defining treatment goals. 46-49 A PASI 75 is the current standard for assessment of response in most psoriasis clinical trials and is currently often the treatment goal for moderate-to-severe psoriasis in clinical practice.50 Achieving a PASI 90 response however has a more pronounced impact on the QOL of psoriasis patients, and improvements in DLQI are most evident when a PASI 90 or PASI 100 is achieved (Figure 6).11,51 PASI 90 has for many years been considered an important measure of treatment success by the European Medicines Agency (EMA) and although a PASI 75 response is still used as an endpoint in many clinical trials, PASI 90 and PASI 100 response rates are increasingly important endpoints.52,53 Recent clinical trials with secukinumab have demonstrated PASI 90 responses (reflecting clear or almost clear skin) in a high proportion of patients, suggesting this is now a realistic treatment goal.6

CSU diagnosis, classification and the challenges for optimal management
Shirina Alsowaidi

Significant advances have been made in defining the pathophysiology of urticaria leading to new developments in CSU classification, diagnosis and treatment.14,54,55 The wide diversity and number of different urticarial subtypes that have recently been described reflects an increased understanding of CSU pathobiology and this is the rationale/basis for the most recent revision/update to the European Academy of Allergy and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF) and the World Allergy Organisation (WAO) guidelines.14 This update includes the most recent evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria including CSU and describes a diagnostic algorithm that can differentiate between CSU and chronic inducible urticaria (CindU) (Figure 7).14 According to the guidelines, the first step in diagnosis is a thorough history, the second step is a physical examination and all subsequent diagnostic steps will depend on patient history and urticaria subtype.14 The guidelines contain a series of recommendations relating to diagnosis (Table 2) and although intensive and expensive screening for the cause of urticaria is advised against, Table 3 outlines diagnostic tests for spontaneous urticaria.14 For optimal management, it is also essential to identify aggravating factors and evaluate disease activity, impact and response to treatment.14 The guidelines recommend the 7-day Urticaria Activity Score (UAS7) to assess disease activity and response to treatment.14 A recent study has confirmed the association between CSU and autoimmune diseases and has provided further support for a common pathogenic mechanism.55 CSU is associated with an increased incidence of rheumatoid arthritis, Sjögren’s syndrome, celiac disease, type I diabetes mellitus and systemic lupus erythematous and these observations will have important implications in the diagnosis, management and prognosis of CSU patients.55

Evolution of CSU treatment
Torsten Zuberbier and Anwar Al Hammadi

Whilst urticaria classification is important from a diagnostic point of view, the therapeutic approach is universal and based on the same principles as other mast-cell-dependent diseases; elimination/avoidance of triggers, symptomatic pharmacological treatment and induction of tolerance.14 Treatment is usually focused on symptomatic relief and guidelines recommend a step-wise treatment algorithm (Figure 8) aiming for complete symptom control as safely as possible.14 Guidelines now recommend against the use of first-generation (sedating) antihistamines and second-generation antihistamines should be considered as first-line therapy in CSU with updosing recommended as second-line treatment.14 CSU can be difficult to treat and if a high dose of antihistamines fail to control CSU, other currently available treatment options include corticosteroids, cyclosporine and omalizumab.14,56 Corticosteroids are recommended by EAACI/ GA2LEN/EDF/WAO for treatment of exacerbations, however long-term studies of their effect and optimal dosing are lacking and use is limited by multiple side effects including diabetes, hypertension, osteoporosis and gastrointestinal bleeding.14,56 Although cyclosporine has a better risk-benefit profile than corticosteroids, the incidence of nephrotoxicity remains a cause for concern.14,57 Omalizumab is an anti-immunoglobulin E (IgE) monoclonal antibody (mAb) currently approved as an add-on treatment for CSU in patients with inadequate response to H1-antihistamines in more than 50 countries with a strong evidence base (clinical trials and case-reports) supporting its use.14,58-68 Omalizumab was shown to be highly effective in three pivotal Phase III trials; ASTERIA I, ASTERIA II and GLACIAL.64-66 Results from ASTERIA I were consistent with ASTERIA II and GLACIAL in demonstrating that omalizumab resulted in rapid and sustained improvements in itch severity (Figure 9), and results from several studies including GLACIAL have demonstrated that significantly more patients achieved a well-controlled CSU or complete response vs. placebo at Week 12.64-66 Although no head-to-head studies are available, two parallel, retrospective, observational studies have demonstrated greater improvement in DLQI scores, symptoms and QOL with omalizumab vs. cyclosporin in antihistamine refractory CSU.67 Pooled safety data from omalizumab clinical trials and real world evidence contribute to a well-established safety profile.64-67 No new safety signals have arisen in the Xolair pregnancy registry (EXPECT).68 Taken together, the efficacy and safety data indicate that omalizumab represents a tremendous step forward for the treatment of CSU.

Importance of patient reported outcomes in chronic symptomatic urticarial
Torsten Zuberbier and Ana Giménez-Arnau

Urticaria symptoms can vary considerably, occur unpredictably, have a huge impact on QOL and healthcare providers almost never see a representative picture of the disease during a consultation. Patientreported outcome (PRO) tools are therefore fundamentally important in CSU assessments and are also useful in the standardisation of clinical trials.14 Not only do they improve and standardise medical record keeping and care (including response to treatment), they also free up valuable time for physicianpatient consultation.17 Several PRO tools have been validated for the assessment of disease activity, disease control and healthrelated QOL in CSU (Table 4).17 Current guidelines recommend using UAS7 to assess disease severity and CU-Q2OL and AE-QOL for measuring QOL impairment.14

Managing atopic dermatitis
Ana Giménez-Arnau

As described in Figure 10, it is generally accepted that avoidance of inflammatory triggers (acquired immunity) and maintenance of barrier function (innate immunity) are critical concepts in AD management and modification/prevention of the “atopic march”.25,65 Experts endorse a holistic approach to the management of difficult-totreat AD.29 Patient education and an appreciation of the chronic nature of AD, exacerbating factors and appropriate treatment options are important considerations.29 Consensus guidelines for the treatment of AD updated in 2012 note that management must reflect the individual symptomatic variability of the disease.69 First line therapy involves hydrating topical treatments and avoidance of trigger factors.69 Topical anti-inflammatories including corticosteroids and topical calcineurin inhibitors (TCI) are used for management of flares and microbial colonisation/infection may require antimicrobial treatment.69 Even though most patients respond to topical anti-inflammatory drugs, around 10% will require systemic treatments.70 These treatment options are however limited with only three currently approved (depending on country) for patients with severe disease and inadequate response to topical agents.69 Advances in our understanding of AD immunopathogenesis has led to the development of targeted agents with the potential to inhibit the “atopic march”.70 Dupilumab, a fully human mAb directed against IL-4 and IL-13, is currently in Phase III development and constitutes one of the biggest therapeutic promises in AD.70 It has demonstrated rapid and marked improvements in all evaluated measures of AD disease activity including 50%, 75% and 90% improvements in the eczema area and severity index (EASI) scores in two recent, Phase III, randomised controlled clinical trials (Figure 11).71,72 Although great strides have been made, significant unmet needs remain as diagnosis and treatment of severe AD remain challenging. As a result, experts call for educational initiatives and, development/validation of biomarkers and PROs.

Impact of pruritus across skin diseases
Jacek Szepietowski

Pruritus is a well-recognised medical condition and a common and distressing symptom that arises from a variety of skin conditions and systemic diseases.73 The International Forum for the Study of Itch (IFSI) classification is now widely accepted (Figure 12)73 Pruritus is the most frequent symptom observed in dermatology and has a substantial impact on QOL and emotional well-being.74 Prevalence is high in the general population (around 13%) and extremely high in specific populations including patients with psoriasis where rates of up to 80% have been reported.75 Itch is associated with a significant burden with psoriasis patients citing itch as their most bothersome symptom. Patients require effective, long-term antipruritic therapy to improve their QOL and reduce the potential risk of depression.8,76 European guidelines describe a diagnostic algorithm for chronic pruritus that incorporates clinical examinations and laboratory screening (Figure 13).77 It is important to note that the guideline addresses pruritus as a symptom and not a disease, and due to the diversity of possible underlying diseases, no single therapy is recommended.77

Managing skin diseases in clinical practice

Understanding the impact of PsA
Wolf-Henning Boehncke and Kitti Totemchokchyakarn

Psoriasis is typically present for several years before joint manifestations of PsA emerge, placing dermatologists in an ideal position for the early detection of PsA through routine screening of psoriasis patients and active monitoring for signs of joint involvement, enthesitis and dactylitis.78,79 PsA can follow an aggressive clinical course, and differentiating it from other arthropathies is often difficult (Table 5).37,78,79 The primary treatment goal in psoriasis and PsA is to maximise long-term QOL through control of signs and symptoms and prevention of structural damage.80 PsA impacts the overall management of psoriatic disease and a more comprehensive approach to treatment is required to address all aspects including skin, nail and joint symptoms as well as physical functioning and QOL.81 A multidisciplinary approach has been recommended by the European League Against Rheumatism (EULAR) since 2012, and active and regular collaboration between dermatologists and rheumatologists will enable optimal control of skin and joint symptoms, ultimately improving long-term patient outcomes.78,82 Although current recommendations only specify further investigations in patients in whom there is a strong suspicion of PsA, many clinicians/experts believe that dermatologists should screen all psoriasis patients for evidence of PsA.78 Results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey identified unmet needs and revealed significant gaps in psoriasis and PsA management with 45% of psoriasis patients not seeing a physician for a year and 59% of PsA patients receiving no treatment or topical treatment only.8 Experts agree there is an urgent need to optimise care and improve clinical outcomes with dermatologists and rheumatologists acting collaboratively to manage skin and joint aspects of psoriasis and PsA. An example on how this could be achieved in a specific country is a recently completed exercise in Switzerland, defining recommended screening procedures, treatment goals, and tasks for dermatologists and rheumatologists alike.81 The treatment of PsA has changed dramatically over recent years and the current, evidence-based EULAR guidelines only include treatments available at that time.82 The guidelines recommend using a single drug to control both skin and joint manifestations and although a number of traditional psoriasis treatments (methotrexate and cyclosporine) are also effective for PsA, these agents are often inadequately effective and associated with significant safety concerns.78 TNF inhibitors such as etanercept, infliximab and adalimumab have demonstrated efficacy in PsA, however, a substantial number of patients do not respond well and efficacy may decline over time.78 Emerging treatments such as secukinumab have shown encouraging clinical results in the treatment of psoriasis and/or PsA.78 Two Phase III studies have shown secukinumab to be significantly more effective than placebo in improving the signs and symptoms of PsA (Figure 14).2,4,83,84 These results further validate IL-17 as a therapeutic target and indicate that secukinumab has the potential to fulfil the current unmet need for a highly effective and well-tolerated treatment option that improves skin and joint manifestations, enthesitis and dactylitis.83-85

Regional differences in management of urticaria
Willie Visser

Urticaria is widely held to be one of the most frequent diseases leading to a consultation with general practitioners, paediatricians, dermatologists and allergists worldwide.86 There are no known racial or geographical differences in terms of prevalence and CSU is not more common in Africa.86 Urticaria has however been associated with parasitic infections, Tuberculosis (TB), human immunodeficiency virus (HIV) and the multiple drug regimens associated with these diseases.87-89 Because of this, regional eliciting factors in urticaria must be considered in countries such as South Africa. Although it is important to take a good history to eliminate druginduced urticaria, the EAACI/ GA2LEN/EDF/WAO guidelines for classification, diagnosis and treatment should be followed and there is no requirement for any specific regional modifications.

Urticaria in the “real world”
Torsten Zuberbier

Randomised controlled trials (RCTs) are generally considered the most robust form of clinical evidence and are the established “gold standard” for establishing the efficacy and safety of a drug. In general, RCTs use a rigorous experimental design with the primary goal of understanding the overall benefit and risk in a highly selected group of patients. However, even when an RCT demonstrates clear and substantial benefit for a drug, its optimal role in routine clinical practice can remain unclear. Concerns frequently relate to the efficacy and safety of the drug in different clinical settings and in a broader patient population than that included in the RCT. Real-world studies are essential to assess efficacy and safety in large, unselected populations with patients taking openlabel treatments over long periods, and support the evidence from traditional RCTs.

A “real-world” approach to CSU requires a real-world doctor, real-world interactions with patients and really effective drugs.
T. Zuberbier

Omalizumab has recently emerged as a safe and highly effective real world treatment option in CSU patients non-responsive to antihistamines.14,58-68 Importantly, the efficacy and safety of omalizumab have been confirmed in a real world setting.59 Data from a retrospective clinical analysis demonstrate that omalizumab is a highly effective and rapidly acting treatment in difficult- to-treat CSU and chronic inducible urticarial (CindU) patients; Omalizumab treatment led to complete remission in 83% of CSU and 70% of CindU patients after 4 weeks of treatment (Figure 15).59 CSU is still perceived as a difficult to manage disease in the “real world”.90 Although several guidelines on the management of CSU have been published over the past ten years, these are not always aligned on key points such as the most appropriate diagnostic tests and/or treatment choices for specific clinical situations.14,54,91-93 In a real world clinical situation, it is important that each patient is considered as an individual and it may not always be possible to apply consensus guidelines.

Conclusions

Skin diseases have a substantial impact on QOL. They range from minor, transient conditions to severe, debilitating diseases associated with significant morbidity. Skin diseases affect multiple aspects of daily living and often pose significant challenges in terms of diagnosis and treatment in the real world. Development of up-to-date guidelines, increased recognition of co-morbidities and significant advances in understanding the pathophysiology of autoimmune skin diseases leading to the development of targeted therapies will ultimately improve clinical outcomes and enhance patient QOL. We have seen that the range of skin conditions experienced in the dermatology clinic is often overwhelming and although there is still an enormous amount to learn, it is clear that the significant advances made over the past few years promise to change dermatological practice and enhance the lives of dermatology patients.

Dermatologists have the tools to make their patients very happy.
M. Hoffman

Acknowledgements

Writing support was provided by Lizzie Davison, PhD, medical writer, and funded by Novartis. All drafts were fully reviewed by the presenters.

Figures 1 and 11 reprinted with permission from Massachusetts Medical Society.
Figures 2, 9 and 15 reprinted with permission from Elsevier.
Figures 4, 12 and 13 were reproduced with the permission of the authors.
Figure 14 was reprinted from The Lancet with permission from Elsevier.
Please see relevant citation for full reference.

Disclosures

This article was written by Dr Lizzie Davison who has no conflicts of interest to declare. This article was developed based on the content presented during a Novartis sponsored educational meeting.
Diamant Thaçi receives research support from Abbvie, Almiral, Amgen, Astellas, Biogen-Idec, Boehringer-Ingelheim, Celgene, Dignity, Elli-Lilly, Forward-Pharma, Glaxo-Smith-Kline, Leo, Janssen- Cilag , Maruho, MSD, Mitsubishi Pharma, Novartis, Pfizer, Roche and Sandoz, and is a consultant/ speaker for Abbvie, Biogen- Idec, Celgene, Dignity, Galapagos, Maruho, Mitsubishi, Novartis, Pfizer and Xenoport.
Torsten Zuberbier receives research support from and is a consultant/ speaker for Ansell, Bayer Schering, DST, FAES, Fujisawa, HAL, Henkel, Krolan, Menarini, Merck, MSD, Novartis, Proctor and Gamble, Ranbaxy, Sanofi-Aventis, Schering Plough, Stallergenes, Takeda and UCB.
Sylke Schneider-Burrus receives research support from and is a consultant/speaker for AbbVie and Novartis.
Ana Gimenaz-Arnau receives research support from Intendis, Bayer, Uriach Pharma and Novartis is a consultant/speaker for Uriach Pharma, Genentech and Novartis wirth educational activities sponsored by Uriach Pharma, Novartis, Genentech, Menarini, GSK, MSD and Almirall.
Maja Hofmann receives research support from and is a consultant/ speaker for Allmirall Hermal GmbH, Bayer HealthCare, Candela Deutschland GmbH, Galderma GmbH, Glaxo Smith Kline, IFC Dermatologie Deutschland GmbH, Laserwelt, Leo Pharma, Loréal Deutschland GmbH, Novartis GmbH, Novoxel and Pierre Fabre Dermatokosmetics GmbH.
Emel Bülbül Başkan is a consultant/ speaker for Novartis, Abbvie, Pfizer and Janssen.
Wolf-Henning Boehncke is a consultant/ speaker for AbbVie, Biogen Idec, Celgene, Centocor, Covagen, Janssen, Lilly, MSD, Novartis, Pantec Biosolutions, Pfizer and UCB. Shira Alsowaidi has not declared any conflict of interest.
Al Hammadi has not declared any conflict of interest.
Jacek C Szepietowski receives research support from and is a consultant/speaker for Abbvie, Astella, Actavis, Adamed, Berlin- Chemie, Mennarini. Biogenetics International Laboratories, Celgene, Egis, Fresenius, Janssen, Leo Pharma, Merck-Serono, Mitsubishi Pharma, Novartis, Pierre-Fabre, Polpharma, Sandoz, Toray Corporation and Vichy.
Kitti Totemchokchyakarn receives research support from and is a consultant/speaker for Roche, Pfizer, Novartis, Janssen-Cilag and Rottapharm.
Willie Visser receives research support from and is a consul- tant/speaker for Novartis, Merck, Roche, Eucerin, iNova, Bayer, Astellas and Adcock Ingram.

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