Skin diseases in Europe

ARTICLE

Auteur(s) : Peter Fritsch, Walter Burgdorf, Gillian Murphy, Johannes Ring

Definition of aims

• 1) Explain the raison d’être for dermatology, showing its roles in clinical practice, medical education and scientific research.
• 2) Show the wide spectrum of diseases which are treated by dermatologists in Europe.
• 3) Emphasize the impact of cutaneous diseases both at an individual and a societal level, considering selected disorders in more detail.
• 4) Present a catalogue of the accomplishments of dermatology, point out the shortcomings and indicate areas of future development and continuing concern.
• 5) Document the state of dermatology in the European Community, Switzerland and the candidate states of Eastern Europe, as well as introducing the pan-European dermatologic organizations.

The many faces of dermatology

The skin and its diseases: an overview

Dermatology is the science of the skin and its diseases. It includes the study of both the normal skin, i.e. its anatomy, physiology and function, and the skin in disease, i.e. of the causes, morphological appearance and pathophysiology of skin disorders, the methods of diagnosing them, and the strategies of their treatment and management.

The skin is the outer coating of the human body serving many vital protective and sensory roles. It forms a nearly absolute physical barrier between the organism and the environment, thus preventing drying out of the body and penetration of foreign substances. Other essential functions include thermoregulation, protection against mechanical, chemical and ultraviolet insult, host defence mechanisms against microbial invasion, initiation and execution of immune reactions (the skin harbours the most peripheral outpost of the immune system) and perception of touch, heat and cold, pain, itch and other sensations. All these functions may be altered or abolished in skin diseases.

Anatomically, the skin consists of three layers: the epidermis (a keratinizing epithelium), the dermis (the connective tissue) and the subcutis (subcutaneous adipose tissue). The thin epidermis is a self-renewing tissue which, by differentiation, forms the horny layer (the outermost barrier layer) and hosts commensal cells such as melanocytes (pigment-producing cells) and Langerhans cells (skin specific dendritic cells specialized in antigen presentation). The much thicker dermis is responsible for strength and mechanical properties to the skin due to its high content of collagen fibres; the dermis of animal skins is used to make leather, a most stable material. The dermis is also rich in blood and lymphatic vessels as well as nerve fibres. The adnexal organs – hair, nails, sebaceous and sweat glands – are special structures derived from epithelium which perform a variety of special tasks.

The diseases of the skin are particularly common, varied, and plentiful owing to the large size of the skin, its complex structure and its permanent exposure to environmental influences. The number of skin diseases has been estimated at as high as 3000, not counting questionable or ill-defined subtypes – a number higher than in any other organ of the body. Every individual is affected by skin problems during their lifetime. The prevalence of skin diseases tends to increase with age, and there is hardly any individual over 50 years who would not benefit from dermatologic care.

Causes and categories of skin disease. Skin diseases result from an interplay of causative factors which fall into three general categories: dispositional (genetic or acquired), environmental and systemic (influences from the organism as a whole). All three kinds of factors contribute to the pathophysiology of every skin disease, but the relative relevance of each of them may differ widely. The following main groups of skin diseases may be distinguished (with representative examples):

• – Damage from exogenous physical and chemical trauma: e.g. heat and cold trauma, chemical burns.
• – Intolerance reactions against exogenous agents. In these, the character of the skin disease is not so much shaped by the causative trigger factor but by the reaction of the body against it. There is a limited number of reaction patterns which can be elicited by an enormous number of triggers. For example, both hives and eczema have many causes, but conversely, many drugs may cause both.
• – Infections. The skin provides a favourable environment and is normally colonized by non-pathogenic bacteria. Some pathogenic bacteria may cause severe infections requiring prompt treatment, especially if the skin barrier is disturbed. Infections were historically the most important diseases of the skin, and they still are in Third World countries. Classification is usually based on the causative organisms: bacterial (e.g. erysipelas), viral (e.g. herpes virus infections), mycotic (e.g. dermatophytoses) and parasitic (e.g. scabies) infections. In skin infections, the clinical appearance is moulded by the interaction of infectious agents with host defence mechanisms. Incidence and severity of skin infections is much higher in the immunocompromised individual (e.g. in the context of organ transplantation or HIV infection). Furthermore, infectious agents play important roles in eliciting or maintaining classical skin diseases (psoriasis, atopic dermatitis, intolerance reactions).
• – Tumours. Because of its direct exposure to environmental carcinogens and its complex anatomy, the skin has a higher incidence and diversity of tumours than any other organ. Melanoma, the malignant tumour of the pigment cells, is the most serious tumour of the skin and one of the most aggressive human tumours. Its incidence is 10-30/10⁵/year in Caucasians, depending on climatic factors. Squamous and basal cell carcinomas, often collectively referred to as non-melanoma skin cancer, are extremely common in the ageing white population of Europe.

UV light is the most important carcinogen. Increased UV exposure due to changed life style patterns is thought to be the cause of the unprecedented exponential upsurge of melanoma and non-melanoma skin cancer which has been registered in the white population world wide in the past decades (doubling of the incidence every 10-15 years).

Skin tumours tend to be more prevalent and aggressive in immunocompromised individuals (organ transplantation, haematological disease, HIV infection). There are several hereditary syndromes which are associated with high incidences of skin tumours, e.g. the familial atypical mole syndrome, nevoid basal cell carcinoma syndrome, xeroderma pigmentosum and others.

• – Skin diseases caused by “systemic” factors: Historically, skin diseases have been principally perceived as caused by internal disease (“skin as a mirror of the body”). While it is clear that this extrapolation was generally untenable, it still holds true for some skin disorders. Metabolic diseases (e.g. diabetes, hyperlipidemias, porphyrias, amyloidosis) are often accompanied by highly specific skin symptoms which may alert the physician to the correct diagnosis; the same is true for a spectrum of cardiovascular, pulmonary and digestive tract diseases (e.g. dermatitis herpetiformis accompanying gluten sensitive enteropathy) and cancer of internal organs which may be associated with pathognomonic paraneoplasias of the skin. Systemic autoimmune disorders – collagen vascular diseases, systemic vasculitides – are regularly associated with skin symptoms. The skin is also the target of organ specific autoimmune diseases (e.g. alopecia areata, vitiligo) and of autoimmune bullous disorders (pemphigus and pemphigoid groups). The psychogenic causation of skin diseases is an old but still widely held concept whose importance is probably overestimated.
• – Genetic skin disorders. This category is characterized by genetic structural or functional defects of the skin. Major groups include the disorders of keratinization – e.g. ichthyoses; hereditary bullous disorders – epidermolysis bullosa; systemic malformation syndromes – Recklinghausen disease; and diseases associated with increased tumour formation – xeroderma pigmentosum, Werner disease. The genetic basis of many pertinent disorders has been elucidated in the past decade.
• – Inflammatory disorders of unknown aetiology. This group of diseases has traditionally occupied a major part of dermatology but is being slimmed down dramatically, as research offers more and more insights into cutaneous inflammation. Still included in this category are common important diseases such as psoriasis and lichen planus.
• – Diseases of the skin appendages: Acne, an inflammatory disorder involving sebaceous glands and hair follicles, is probably the most common skin disease, affecting almost every teenager. Hair loss (alopecia) is a distressing problem with a variety of causes.

Venereal diseases (sexually transmitted infections, STI). Dermatology has been historically linked to venereology because of the plethora of skin symptoms found in STI, particularly in syphilis. In most European countries, dermatology and venereology are practiced and taught as a single discipline whereas they have been separated in the English-speaking countries. The most common venereal diseases are genital warts caused by human papilloma virus (HPV), and genital herpes infections, both prevalent among adolescents. The classical venereal diseases, syphilis and gonorrhoea, are still relevant: syphilis especially in Eastern European countries and gonorrhoea as imported from the Far-East and because of emerging drug-resistance. Venereal chlamydia infection is continuously increasing, especially among adolescents and young adults, despite modern diagnostics and simple therapy. The AIDS pandemic has greatly increased concern over sexually transmitted infections; dermatological institutions are prominently involved in the management of the HIV infection, particularly in the German-speaking countries.

Spectrum of dermatological care in Europe. Despite its common historical basis and interwoven development, dermatology as a specialty is differently defined in the European countries. Core dermatology consists of medical dermatology, venereology (except Great Britain) and dermatosurgery as well as dermatopathology. Some fields are covered by other specialties along with dermatology: allergology and/or clinical immunology is shared with paediatricians, otolaryngologists and rheumatologists; phlebology with vascular surgeons, and proctology with general surgeons. Dermatology in German-speaking countries is particularly encompassing and also includes andrology along with all the other subspecialties mentioned above. As Europe-wide standards are instituted for medical education and practice, dermatology faces a special challenge in preserving its many facets.

Relevance of skin diseases. Skin diseases are a major source of morbidity. For the population as a whole, morbidity results less from life threatening acute skin disease or malignant skin tumours but rather from chronic dermatologic illness. Occupational dermatoses (eczema) range among the most frequent causes of occupational disability, need for job retraining, and even invalid status with accompanying social costs.

Relatively few skin diseases are directly and acutely life threatening. Included in this small group are acute severe intolerance reactions such as anaphylaxis and angiooedema, bee and wasp venom allergy, and drug rashes like the carbamazepine hypersensitivity syndrome or toxic epidermal necrolysis. Some of the most aggressive tumours of man arise in the skin: melanoma, some types of skin lymphomas, Merkel cell tumours and others. Chronic severe skin disease is much more prevalent and accounts for the most part of the patient’s suffering and incapacitation: psoriasis, atopic dermatitis, recalcitrant bullous diseases, chronic wounds such as venous and decubitus ulcers, smouldering skin lymphomas (usually mycosis fungoides), scleroderma, and genodermatoses including severe ichthyoses and hereditary bullous diseases.

Some skin diseases may not seem to qualify as severe diseases at first glance, but their psychological impact, particularly on the developing personality, may be detrimental. Acne vulgaris, disfiguring birth marks or cutaneous anomalies have a high impact on wellness and the social abilities of adolescents, as does balding (androgenetic alopecia) for both sexes in adulthood. The psychological consequences of atopic dermatitis which vexes its bearers not only by incessant itch but also by its appearance are proverbial (“atopic psyche”).

Moreover, dermatology has to satisfy the patients with those abundant common and relatively mild ailments which fill the waiting rooms and may not be so easy to diagnose and treat despite their often seemingly trivial background: viral warts, eczemas of various kinds, simple bacterial, viral and fungal skin infections, insect bites, dandruff (seborrheic eczema of the scalp), dry skin, the many stigmata of ageing skin, venous insufficiency of the lower limbs and others. Among all these, the skin specialist has always to keep in mind that skin symptoms may be a warning signal of life-threatening internal disease.

Dermatology is both an inpatient and outpatient specialty. Historically, dermatology was one of the “large” medical specialties with similarly large wards as internal medicine, surgery, and gynaecology and obstetrics. With the advent of efficient antimicrobial and anti-inflammatory therapy, many skin infections and intolerance reactions became treatable on an outpatient basis. Due to economic constraints, dermatology wards were reduced – sometimes dramatically – in most European countries, while skin hospital outpatient departments were not accordingly enlarged. The increased number of dermatologists in practice was in many instances not sufficient to account for the lost hospital capacity. National dermatological societies and other professional groups all over Europe have taken a strong stance against further reduction of hospital beds: inpatient care of severe and difficult dermatoses, particularly of skin tumours, is necessary to maintain full competence in diagnosis and treatment for the dermatologist and to maximize effective teaching of medical students and residents. It is foreseen that in the future the patients treated in dermatological wards are more severely ill, suffer from multiple diseases, need more internal drugs and more nursing care than patients from the previous decades.

Who is taking care of skin diseases? A wide range of studies in different countries have demonstrated that dermatologists can diagnose and treat skin diseases more efficiently than a non-dermatologist. Nonetheless, the high incidence and prevalence of the cutaneous disease makes it unfeasible and unreasonable that all such disorders be managed by dermatologists. A large segment of dermatological cases are treated by general practitioners, paediatricians and other specialists, and dermatologists are called in only when their help is needed. This situation is more common in rural areas than in larger cities, where dermatologists are more easily accessible. Dermatological training programs have a long tradition of educating non-dermatologists in the management of common skin diseases.

It has proven an unachievable task to define the borderline between skin diseases which are “common” to all specialties and those which are reserved for the skin specialist, a line which is also dependent on historical, cultural and personal variables. In any event, skin diseases are among the most frequent diseases seen by the general practitioner, and the costs of dermatological treatment (particularly topical agents) is a significant part of most health care budgets. The situation varies in the European countries. In the German-speaking countries, the number of dermatologists is high, and they see a rich spectrum of skin and related diseases. In the United Kingdom, the number of dermatologists and dermatological institutions is low, most skin diseases are managed by general practitioners, and a major role of the skin specialist is to act as a consultant for rare and difficult skin patients.

Skin as a tool for basic medical research. The skin has long been a favoured site for research into a variety of basic biologic processes, because it is accessible and can be easily observed, manipulated and otherwise studied. Many important biological principles were first discovered in the skin. To cite but one example, the study of Langerhans cells by dermatologists opened the way for many exciting advances in dendritic cell biology, providing not only a better understanding of how the body interacts with foreign antigens but even introducing potential therapeutic tools such as cancer vaccines. Dermatology has always been a scientifically oriented specialty, addressing critical problems with the latest scientific methods. In the past fifty years, research tools have advanced from histopathology, immunofluorescence, immuno- and enzyme histochemistry, and electron microcopy to include all of the modern methods of molecular biology and genetics. Experimental dermatology has experienced a “Golden Age” in the past few decades, placing dermatology in the leading group of research-oriented specialties. The main dermatologic research journal, the “Journal of Investigative Dermatology” is a highly regarded journal with a high impact factor.

In addition, many skin diseases are employed as models to investigate modern therapeutic principles, since the disease course can be so easily monitored on the skin. For example, psoriasis and atopic dermatitis are prototypes for the evaluation of modern methods of immune intervention with “biologicals” (agents such as tumor necrosis factor antagonists, antibodies against specific cell types, or cytokines). The progress in the treatment of skin diseases in the past years is impressive; the old saying that “skin diseases can be treated but not cured” was never correct, but today it is becoming even less true, thanks to disease-oriented dermatological research.

Skin disease versus cosmetics. In the last decade, there has been a dramatic trend in dermatology towards what were previously viewed as cosmetic problems. This emphasis has already changed patterns of practice in the USA and threatens to do so in Europe. The skin is responsible for many of the aesthetic attributes of an individual, and one goal of dermatologists has always been to improve the appearance of the skin much to the satisfaction of patients. Traditionally dermatologists have worked with pharmaceutical firms to develop and use skin care products, such as moisturizers or cleansing agents.

In recent years dermatologists have turned towards what their professional forefathers considered “strictly cosmetic problems”. The reasons for this recent shift in emphasis are multiple. Better treatment methods are available for many common skin diseases, freeing up the dermatologist somewhat. In addition, adequate reimbursement for routine non-invasive care, such as for acne, eczema or warts is no longer available in many insurance schemes. Thus dermatologists have started to look for other methods of practice expansion. This trend has fit together perfectly with the increased standard-of-living in western lands, coupled with an emphasis on life style and wellness. Cosmetic surgical procedures such as the removal of harmless skin lesions, epilation, laser treatment of small vascular or pigmented lesions, liposuction, tissue enhancement, skin resurfacing with chemical or laser peeling, and many more are all part of the daily life of many dermatologic practices. For academic dermatology, this swing is viewed as a mixed blessing. First, the residents must now devote a considerable portion of the training time to cosmetic dermatology in order to function in the new market place. Thus, they and consequently their departments have less time and energy to devote to basic and clinical research. In the same tone, it is disappointing that European dermatology with a few spectacular exceptions has devoted relatively little of its intellectual and physical resources to the HIV/AIDS pandemic. A final consideration is that if dermatology becomes too strongly identified as a “luxury specialty” concerned with cosmetic problems, it may draw a short straw in the inevitable battles over distribution of resources for patient care and research.

Impact of skin diseases on the health care system. Skin diseases account for a considerable degree of morbidity in Europe. Their significance is based to some extent on their frequency and their considerable impairment in the “quality of life”, as best documented for psoriasis and atopic dermatitis. As a result, about 20% of the budget for medications in some western European lands is devoted to dermatologic preparations.

The popular image of dermatology, both among colleagues and the general public, points in a different direction. Dermatology is often considered a discipline with an amazingly complex, difficult-to-understand language, dealing with rather mundane problems which can be easily managed by any half-way qualified physician or even in recent years, physicians’ assistant or nurse. In addition, even in countries where dermatology is well-established as a respected scientific discipline, it rarely accounts for more than 1-2% of an overall clinic or health budget, and thus has a limited lobby.

Thus, dermatology is an easy, if not always fair, target for financial management. Dermatologic preparations are easier to eliminate from a formulary than heart medicines, especially if they are products designed for long-term maintenance care to help avoid flares and subsequent hospitalizations. Dermatologic beds are easier to eliminate than those devoted to internal medicine, surgery, pediatrics or obstetrics. In addition, the trend toward reimbursement for a given disease episode (DRG or diagnosis-related group), emphasizes direct intervention with short hospital stays and penalizes a discipline where many problems have traditionally been handled with longer in-patient stays, such as atopic dermatitis, psoriasis or leg ulcers. It does not take a wise man to see that in many European countries, dermatology faces immense financial challenges.

Epidemiology of skin diseases in Europe

Introduction

What is epidemiology?

Clinical epidemiology and health services research is also concerned with evaluating the efficacy and cost-effectiveness of treatments for skin disease, whether these be new drugs, ultraviolet light devices, herbal remedies or different ways of organising dermatological services. Whereas most clinical research is involved in describing individual cases, epidemiology is concerned with studying individuals with a particular skin disease in relation to entire populations, so that effective health care strategies that benefit all can be developed.

This short report summarises some important epidemiological aspects of skin diseases in Europe, and ends by highlighting important future health service and population research issues.

EDEN and the opportunities for studying skin disease in Europe

Recent progress

EDEN was founded in 1995 in order to stimulate co-operation and high standards of research in epidemiology as applied to dermatology. EDEN is organised through a pan-European steering committee. In addition to its own collaborative research projects, EDEN has been successful in running teaching courses and sharing expertise at all major European dermatological meetings, as well as organising its own Congress in collaboration with the International Dermato-Epidemiology Association (IDEA) every three years. EDEN has helped to facilitate networking of like-minded researchers, and has initiated its own collaborative research projects such as the EDEN psoriasis project – a methodological review of all clinical trials of psoriasis over the last 20 years [15]. The aim of such a detailed review is to provide guidance on appropriate future study designs and to encourage better standards of clinical trial reporting in journals. A similar review of trials of interventions for treatment of hand eczema – a common occupational disease of major economic importance, has also been completed [20]. A further EDEN project critically reviewed prevalence surveys of common skin diseases such as psoriasis throughout Europe [16]

The opportunities for studying skin disease in a changing Europe Europe provides a unique “natural experiment” of different ethnic groups, different geophysical conditions such as climate, sunlight and terrain, different socio-economic conditions and varying environmental factors such as industrial pollution and airborne allergens in which to explore the possible causes of skin diseases. The varying methods of dermatological health care delivery within the many countries of Europe also provide a unique opportunity to evaluate the appropriateness and effectiveness of such systems in the light of population-based epidemiological data and high quality evidence of efficacy.

How common is skin disease in Europe?

Inflammatory skin diseases

Various European population based studies have suggested that psoriasis - a disease that can have a profound effect on quality of life of individuals – affects around 2% of the population, with two peaks of onset in early adulthood and in later life. Acne is so common as to be almost universal during teenage years, yet surveys have suggested that few affected individuals receive good medical advice regarding the most appropriate treatment that can prevent lifelong facial scarring.
Table 1 Estimates of the frequencies of common skin diseases (excluding skin cancer)

Infectious skin diseases

Chronic venous insufficiency and leg ulcers

Skin cancers

Melanoma is the most serious form of skin cancer, and its incidence has been rising steeply in the white population over the last 30 years (doubling of cases every 10-15 years), probably due in part to increased leisure exposure to the sun. Melanoma is preventable at least to some degree, yet approaches to educate the public on the dangers of sunbathing have been variable, ranging from non-existent in some European countries to highly proactive educational campaigns aimed at primary prevention (preventing the development of skin cancer in the first place) and secondary prevention (catching established disease early) in others. Melanoma also has the advantage of being curable when recognised at an early stage, yet facilities for detecting such early cases vary widely within relatively short distances in Europe.
Table 2 Age-standardized rates of non-melanoma skin cancer (NMSC) in whites per 100,000 population from Australia, United States and Europe (selected studies after 1990, according to Diepgen & Mahler 2002)

Rarer skin diseases

How does skin disease affect people?

Disability due to loss of function

Mortality

Profound psychological effects

High economic costs

Other costs such as unemployment and losing an economically viable sector of a country’s workforce are also important when considered at a population level. Indirect costs e.g. the adverse effects on quality of life and the opportunity costs due to loss of time spent for daily topical therapy and skin care in many skin diseases also need to be considered in such economic evaluations.

What are the causes of skin diseases in Europe?

Ultraviolet light

Genetic-environmental interaction

Psoriasis is also partly genetically determined, although the exact mode of inheritance is still unclear. Various European studies have suggested that both smoking and excessive alcohol consumption as well as dietary factors may be important risk factors for contributing to disease expression. In addition, several environmental triggering factors, e.g. infections and some drugs, have been identified.

Occupational exposure

Other chemicals can lead to specific forms of skin disease such as a severe form of acne (chloracne) from dioxin and an inflammatory skin disease known as lichen planus, from colour film developing chemicals.

Infectious agents

How can skin diseases be prevented in Europe?

How are skin diseases treated in Europe?

Variation in health services for people with skin diseases in Europe

Some countries, such as Romania and Germany, make heavy use of inpatient services whereas other countries conduct most care in an outpatient or day treatment setting. The density of dermatologists also varies dramatically across Europe ranging from 1 per 150,000 of the population in the UK to 1 per 20,000 in Italy and France [22]. The duration and type of training in order to become a dermatologist also varies substantially, even between different EU countries. These differences are due to the considerable heterogeneity in the definition of dermatology as a specialty and the range of tasks carried out by dermatologists across Europe – an activity that is currently being surveyed by EDEN. In countries such as Germany, The Netherlands and France, dermatologists may be responsible and competent for multisystem dermatological diseases, cancer chemotherapy, dermatosurgery, dermatopathology, allergology, venereal diseases, chronic venous insufficiency and decubitus ulcers, male infertility, as well as traditional dermatology, whereas in the UK, a dermatologist might have a narrower range of responsibilities.

The point of illustrating such variation is twofold. First, such heterogeneity probably reflects historical working patterns that have developed according to health care policies from previous governments. Each country swears by its own system, and to be fair, perhaps those systems currently in operation are the most appropriate for that particular country. Until good health services research examines the relative efficacy, cost-effectiveness, acceptability and appropriateness of the various dermatological systems operating within Europe, the debate on optimal dermatological care for each particular country will continue. Second, the variation of healthcare systems provides a wonderful opportunity to compare the outcomes in these different systems, although such comparative observational data will need to be handled carefully in view of the differences in patient selection and information provided by services in different countries.

How good is the evidence that skin treatments work?

Systematic reviews i.e. summaries of the evidence for the prevention and treatment of skin diseases that have been conducted in an explicit and systematic way, are conducted by volunteers contributing to the Cochrane Skin Group (www.nottingham.ac.uk~muzd), which is based in Europe. The evidence from systematic reviews on skin disease produced to date point to a lack of useful and high quality data. In many cases, the main trials have reflected the priorities of the pharmaceutical industry as opposed to the sorts of questions generated by consumers of services and their carers. EDEN has made a significant contribution to the Cochrane Skin Group, and three members of the steering committee serve as editors.

The future of research and service development

Stepping back from the traditional hospital perspective

Four major research priorities

The first is the complete absence of any comparative prevalence surveys of skin disease in general involving more than one country. Even though skin diseases have the advantage of being easily visible, such population-based surveys are difficult and costly to conduct. They nevertheless provide an essential foundation of data on which to plan appropriate health services.

The second is to explore the evidence of effectiveness for the various health care systems that currently operate within Europe. Such an evaluation should begin with the users’ perspective in mind, rather than possible protectionist motives by dermatologists. Such studies could initially be observational studies based on data already collected within current systems, which could then progress to more elaborate controlled intervention studies.

The third priority is to invest in epidemiological research that seeks to find out the causes of skin diseases which could, in turn, lead to disease prevention.

The fourth is to develop more links between epidemiology and laboratory research so that laboratory research priorities are more guided by important clinical questions thrown up by epidemiological and clinical research. As an example, epidemiological research suggesting that there were at least two different types of psoriasis can then be taken into account when undertaking genetic and cellular studies.

Only when these types of questions are answered will it be possible to have any sensible debate about which is best method for dealing with the increasing consultation and costs of treating skin diseases in Europe.

References

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Websites

27 Cochrane Skin Group: http://www.nottingham.ac.uk/~muzd.

28 Evidence-Based Dermatology: www.evidbasedderm.com and www.ebderm.org.