Introduction

There is a colloquial folk belief that there is an influence of ‘mind over matter’ and that this can influence the onset, progression and resolution of disease. That is, that the state of mind can, to some extent, have a significant bearing not only upon how an illness is perceived but also on its severity and content. The concept of ‘wellbeing’ is common to all cultures and associated with declarations of ‘life forces’, ‘vital life energies’, chi in Chinese, ki in Japanese and prana in Sanskrit. In the presence of physical symptoms and disease, how is it that we may gain a further understanding of the curative value of ‘talking therapies’ and the physical effect that they have on recovery? Why do patients with depression suffer more physical illness? Is it related to immune suppression (Irwin, 2002) and how is this effect mediated?

This chapter will describe briefly the historical relationship between diseases of the skin and neuropsychiatry. In addition it will survey the anatomy of the structures in the brain, nerves and skin, which are all embryologically derived from the ectoderm. They show their origins from the neural plate where both the central nervous system (CNS) and peripheral nerves develop from the neural crest, as do the cutaneous structures, melanocytes and Merckel cells (Bernstern, 1983).

Skin disease is very common among children and young people. For example, up to 20% of young children develop eczema and the majority of young people develop some symptoms of acne temporarily during adolescence (McHenry et al., 1995; Smithard et al., 2001). However, there is surprisingly little research on the psychological impact of skin disease in childhood and the focus of most research in paediatric psychology has been on life-threatening conditions, such as cancer. Despite the lack of research, there is widespread acknowledgement of the impact of skin disease on the psychological well-being and quality of life of children, and increasing awareness of the importance of understanding the psychological impact of skin disorders on children and their families (Howlett, 1999).

This chapter will start by outlining some key issues in understanding the relationship between skin disorders and psychological factors for children. This includes the importance of considering both a developmental and systemic framework for childhood problems, and potential difficulties that may arise in communicating with a child about sensitive topics, such as how they feel about their appearance. The chapter will then describe current theoretical models of the psychological impact of physical disease on children and their families, and how these inform our understanding of the impact of skin disease. The next section will review research on the impact of skin conditions on the relationship between a mother and her baby or child, and the impact of skin conditions on the child's self-esteem.

Introduction

The concept of trying to measure the impact that skin disease has on patients' lives has only gained wide acceptance over the past 10 years. Dermatologists have always, presumably, been aware of the devastating effect that skin disease can have upon the lives of their patients, but historically most publications have focused on the pathology of the skin rather than on the subsequent effect on the patient. This chapter will introduce the reasons why measurement methods are needed, review the major techniques that have been described and detail how they are validated. Some recent research findings will be reviewed and current challenges for further research in this area identified.

What is quality of life?

The concept of what constitutes quality of life (QoL) is controversial (Koller & Lorenz, 2002) and whether it can be meaningfully measured even more so. The following attempt at defining QoL emphasises the difficulties in defining what most people feel they instinctively understand: & ‘Quality of life can be defined as the individual's perception of their position in life, in relation to their goals and to the value-system which they have accepted and incorporated in to their decision making’ (Sartorius, 1993). There is a more limited concept of health-related QoL that is limited to the effects that health or its absence has on life. The World Health Organisation (WHO) has given definitions of and explained how disease can lead to impairment, which leads to disability and which in turn may lead to handicap (WHO, 1980).

Introduction

There has been a considerable increase, in the last two decades, in cosmetic surgery and dieting as well as the profile of the fashion and cosmetic industry. The ‘appearance industry’ is a multi-million pound business aimed at selling beauty products to the widest possible market and this has served to increase the pressure that many people feel to conform to unreachable standards in physical aesthetics. Particularly in the Western world, we see adverts that project the agenda that ‘attractive people are popular, happy, successful, interesting and are often loved and worshipped’ (Papadopoulos & Walker, 2003). This is particularly acute when looking at adverts for facial washes and scrubs for acne that intentionally contrast the relative social successes of individuals with and without a given skin disease. Of course, cosmetic and physical perfection are rarely associated with those experiencing cutaneous conditions and so people with dermatological illnesses are often left feeling minimised as people. Modern adverstising can promote just the kind of messages that psychological health professionals try to minimise; that is, to put your life on hold until the skin disease clears and to feel less worth than those around you with clear skin. Skin disease patients can, understandably, be highly sensitive to the social significance of their actions and appearance, and the development of beliefs about their disease are influenced by the information they receive from their culture (Papadopoulos & Bor, 1999).

Introduction

The enormous growth in the last two decades in cosmetic surgery, dieting and the fashion industry are all the indicators of the huge investment that society puts into the ‘appearance industry’. In the western world, people are subjected to the same message constantly: ‘Attractive people are popular, happy, successful, interesting and are often loved and worshipped’ (Papadopoulos & Walker, 2003). Of course, cosmetic and physical perfection are rarely associated with those experiencing cutaneous conditions. Consequently, people with dermatological illnesses are left feeling minimised as individuals, tend to be highly sensitive to the social significance of their actions and appearance, to anticipate rejection by others, and to experience embarrassment and/or shame (Kellett & Gilbert, 2001).

Therefore, it is not surprising that due to their visibility and appearance-altering quality, skin disorders have important psychological implications for the sufferer, making the long-established link between psychological factors and dermatology even stronger. Yet, little attention has been paid to them or to the ways in which to address them. Indeed, as the prevalence and aetiology of the majority of skin diseases are neither well known nor understood by the general public, dermatological ailments are often surrounded by misconceptions and stigma.

The link between dermatological and psychological problems has long been prominent in the published literature. Dermatology has a distinct relation with psychosomatics as the skin has strong psychological implications.

Introduction

It is increasingly acknowledged that whilst it is likely that a large number of people living with skin conditions adjust well to their condition, there is a risk for some of them experiencing social, psychological, and physical distress (Gupta, Chapter 3, this volume). In common with other chronic illnesses and appearance-altering conditions there appears to be no simple relationship between single biomedical and demographical factors, such as severity and age, and psychological adjustment (Papadopoulos et al., 1999a; Thompson & Kent, 2001; Rumsey & Harcourt, 2004).

This chapter reviews the literature pertaining to adjusting to a life with a chronic dermatological condition. It aims to briefly outline the potential psychosocial impacts and then detail the likely factors that have been implicated in playing key mediating roles in explaining individual variation in coping and adjustment.

Defining ‘skin conditions’

Consideration of dermatological diagnoses is outside of the remit of this chapter and those interested are referred to an appropriate medical text (e.g. Gawkrodger, 2002). However, it is important to acknowledge that there are multiple types of skin conditions, which can differ widely in terms of both specific symptoms and treatments, as such factors may have an impact upon the adjustment process (Porter et al., 1986). The term ‘skin condition’ as opposed to skin disease, will be used here when discussing this population in general, so as to be inclusive of the full range of dermatological conditions. This will include those acquired congenitally, such as port wine stains, as well as those resulting from diseases, such as psoriasis.

‘I remember a few months back, when I used to see his knuckles, how they were dry, cracked and bloody, and then I noticed his arm, and when I gently inquired … he would retreat and change the subject. This was also before we became close. He has slowly grown more comfortable and one night, after cuddling and holding each other for a while, he asked me if I'd like to see and I said please. He took off his shirt and I saw the extent of his condition. His entire back, arms and parts of his legs were red, with patches of dry skin and blood. It struck my heart, and I suddenly felt very close to him. I wasn't shocked or afraid, and I think he sensed that because he seemed to relax a little. I reached up and touched his shoulders and lightly stroked his back. He later told me he was grateful for how accepting I was, and how he hadn't been touched in a long time. His condition does not bother me, in fact, I admire him. He has a tremendous amount of strength. We have since been intimate, and while I do my best to make him feel comfortable, I can't seem to avoid situations that cause him pain; like when he rests his head on my chest when we lay together, and then he gets up, seeing the trail he has left on my black sweater … and I see the pain flash across his face.

It can be argued that all research on stigma and stigmatisation is a footnote to the sociologist Erving Goffman. In a few short, elegantly written books (e.g. Goffman, 1968), he provided a wealth of ideas and insights, giving much inspiration to work on this topic. Goffman defined a ‘stigma’ as a mark or sign that not only sets a person apart from others but also leads to their devaluation. He distinguished between three types of stigma: ‘tribal identity’ (such as race, gender or religion); ‘character blemishes’ (such as mental illness or addiction); and what he called ‘abominations of the body’. Although today we would not wish to use such terms as ‘defects’, ‘abnormalities’ or ‘flaws’ to describe the bodies of people with physical differences, Goffman quite sensitively discussed the issues faced by people whose appearance or function has been compromised in some way.

One of Goffman's central ideas was that the mark or sign comes to take on ‘master’ status, becoming the most important characteristic of the affected individual. This is illustrated by the following description, given by a person with psoriasis. He is recalling a time when his psoriasis took on more importance in the eyes of others than his more relevant sporting skills and efforts:

When considering the impact of skin disease, many people fail to realise just how important the psychological aspects can be. Skin disease is often considered to be ‘only cosmetic’ by many medical professionals and lay-people alike, but unlike most internal illnesses, skin disease is often immediately visible to others. It is for this reason that traditional views do not account for the often profound psychological impact that it can exert on those affected. Skin disease can affect the quality of life, self-esteem and body image, as well as the way patients live their day-to-day lives. Furthermore, the way that skin disease affects a person often has no relation to traditional conceptualisations of medical severity. To truly understand the effect, we need to understand the person behind the condition. Through the course of our work we have encountered individuals whose skin disease covers the majority of the surface of their skin but whose social and psychological functioning were unaffected by the condition. Conversely, individuals with the smallest of lesions in non-visible areas have been so affected by their condition that occupational, social and sexual interactions have fallen prey to their functional inability to cope with their condition. The unique nature of skin disease has the potential to make it both the easiest or most difficult disease to suffer and how a person copes and adapts to the challenges presented is due to a great number of factors.

Introduction

The psychiatric comorbidity in dermatological disorders is often one of the most important indices of the overall disability associated with the dermatological condition (Panconesi, 1984; Gupta & Gupta, 1996; Woodruff et al., 1997; Picardi et al., 2000; Gupta & Gupta, 2003; Picardi et al., 2004; Sampogna et al., 2004). It is well established that significant psychiatric and psychosocial comorbidity is present in at least 30% of dermatological patients, and untreated comorbid psychiatric disorders may adversely affect the response of the dermatological disorder to standard dermatological therapies (Picardi et al., 2003). Psychiatric pathology is important in both (i) the cutaneous associations of primary psychiatric disorders such as delusional states and some of the self-inflicted dermatoses such as dermatitis artefacta, and (ii) a wide range of primary dermatological disorders that have psychiatric comorbidity. Any dermatological disorder that is cosmetically disfiguring can be associated with significant psychiatric morbidity. Stress-related neuroimmunomodulation may affect the course of viral infections such as warts, and possibly the course of certain malignancies such as melanoma. There is a group of disorders such as psoriasis, atopic dermatitis, chronic idiopathic urticaria, alopecia areata and acne that have a stronger psychiatric and psychosocial component as they are often exacerbated by psychosocial stress and are frequently comorbid with major psychiatric syndromes such as depressive illness.

The skin has long been recognised as the ‘organ of expression’ (Sack, 1928) and serves as the boundary between ourselves and the outside world, a ‘first point of contact’ when strangers meet us. It is also the largest organ of the body. The ways in which the skin can react to many different stimuli, both physiological (i.e. a rash caused by an external noxious substance) and psychological (an individual may blush when feeling embarrassed) highlight the complexity of the relationship between the skin, and external and internal factors. Dermatological disorders have an immediate impact on tactile communication, sexual contact and bodily interaction in particular and fear, anxiety and shame as well as sexual pleasure and excitement can be indicated visibly by growing pale, blushing and hair rising (Van Moffaert, 1992).

Unlike most internal illnesses, skin disease is often immediately visible to others and therefore people suffering from dermatological conditions may suffer social and emotional consequences.

Introduction

Xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD) are rare neurocutaneous disorders caused by mutations in genes involved with nucleotide excision repair (NER) and also DNA transcription. Initially these recessive disorders were categorized clinically (Table 29.1) and by complementation studies, but more recently specific genes have been identified for most of the different subtypes (Table 29.2). Genotypic and phenotypic characteristics are being studied to determine the basis for the clinical heterogeneity within each disorder and across (overlap) entities, including XP neurological (DeSanctis-Cacchione) syndrome and xeroderma pigmentosum/Cockayne syndrome (XP–CS). Thus, specific mutation sites may determine abnormal protein–protein interactions as subunits in a protein complex involved in NER and/or DNA transcription. Study of these interactions has helped to clarify the clinical features of specific disorders, including sensitivity to ultraviolet (UV) light, propensity to cutaneous neoplasms (XP disorders), overlap syndromes, and a greater appreciation of the importance of normal DNA repair mechanisms and how DNA repair, replication, transcription and translation mechanisms interact at a molecular level. Currently treatment of these disorders is limited to avoidance of sunlight or other sources of UV light, monitoring and removal of skin neoplasms, and symptomatic treatment of other features. Improved understanding of genetic and molecular mechanisms may result in innovative approaches to diagnosis, prevention, and management of these rare neurocutaneous disorders and could lead to better understanding and management of disorders of aging, neoplasia, and neural degeneration.

Introduction

Homocystinuria due to cystathionine β-synthase (CBS) deficiency (MIM # 236200) is the most common inborn error of sulfur amino acid metabolism. It is inherited as an autosomal recessive trait. The frequency of the disease has been estimated between 1 in 200 000 and 1 in 335 000 (Mudd et al., 1989), though several lines of evidence indicate that this frequency might be higher (Mudd et al., 1995).

Sulfur-containing amino acids, homocysteine, methionine and cysteine are linked by the remethylation cycle and the trans-sulfuration pathway (Fig. 26.1). CBS (shape l-serine hydrolyase; EC 4.2.1.22) catalyzes the condensation of homocysteine with serine to form the thioether cystathionine, a reaction requiring pyridoxal-phosphate as cofactor (Fig. 26.1, enzyme 2). Cystathionine is cleaved to cysteine and α-ketobutyrate by another pyridoxal-phosphate-dependent enzyme, γ-cystathionase (enzyme 3). The trans-sulfuration pathway ends converting sulfite to sulfate and is catalyzed by sulfite oxidase (enzyme 4), requiring a molybdenum cofactor. Conversion of methionine into homocysteine proceeds via methionine adenosyltransferase (enzyme 1) yielding S-adenosylmethionine, a methyl-group donor used in several transmethylation reactions, and S-adenosylhomocystein e, which is cleaved to adenosine and homocysteine. About 50% of homocysteine, not entering the trans-sulfuration pathway, is recycled into methionine. This step involves methyl transfer either from 5-methyl-tetrahydrofolate (THF), catalyzed by cobalamin-requiring 5-methyl THF-homocystei ne methyltransferase (methionine synthase, MS, enzyme 5), or from betaine, catalyzed by betaine-homocysteine methyltransferase (enzyme 6).

Introduction

The nevoid basal cell carcinoma syndrome (NBCCS) is characterized by numerous basal cell cancers and epidermal cysts of the skin, odontogenic keratocysts of the jaws, palmar and plantar pits, calcified dural folds, various neoplasms or hamartomas (ovarian fibromas, medulloblastoma, lymphomesenteric cysts, fetal rhabdomyomas, etc.) and various stigmata of maldevelopment (rib and vertebral abnormalities, cleft lip and/or palate, cortical defects of bones, etc.).

The condition, first described independently over 100 years ago by Jarisch (1894) and White (1894), probably existed during dynastic Egyptian times (Satinoff & Wells, 1969). It has been variously known as basal cell nevus syndrome, Gorlin–Goltz syndrome, Gorlin syndrome and nevoid basal cell carcinoma syndrome. Admittedly, none is satisfactory as selection of only one facet (and in blacks a relatively uncommon one) is highly biasing. The term nevus does not project the truly cancerous nature of the skin lesions, although only a small number of basal cell carcinomas become aggressive. Eponyms imply priority of description (and are often wrong, frequently chauvinistic, and say nothing about the disorder). They serve to plague residents who are required to memorize them.

Early American reports are those of Binkley and Johnson (1951), Howell and Caro (1959), and Gorlin and Goltz (1960). Comprehensive systematic surveys (Gorlin, 1987, 1995; Evans et al., 1993; Shanley et al., 1994; Kimonis et al., 1997; LoMuzio et al., 1999) and historic reviews (Howell, 1980; Gorlin, 1987) of the syndrome are available.

Introduction

Spurred by recent developments in molecular neurobiology, the 1990s have seen a burgeoning of interest in the genetic aspects of cerebrovascular diseases. Many types of cerebrovascular lesions are associated with well-defined, genetically determined conditions: cerebral aneurysms accompany polycystic kidney disease; cerebral arteriovenous malformations (AVM) are a major component of hereditary haemorrhagic telangiectasia (HHT, Rendu–Osler–Weber disease); and cerebral cavernous angiomas are associated with at least two genetic mutations (Lozano & Leblanc, 1992; Putnam et al., 1996; Gunel et al., 1995). In this context the elaboration of a new neurocutaneous syndrome, hereditary neurocutaneous angiomatosis (HNA), a condition characterized by the presence of vascular lesions of the skin and brain, is of interest because its molecular characterization may shed light on the etiology of common sporadic cerebrovascular lesions such as AVMs and developmental venous anomalies (DVA) with which it is associated (Zaremba et al., 1979; Hurst & Baraitser, 1988; Leblanc et al., 1996). Most AVMs and DVA are sporadic lesions without associated cutaneous anomalies.

Clinical manifestations

Cutaneous manifestations

The clinical manifestations of the vascular nevi in HNA depend on their size and location. The lesions, including cavernous angiomas, AVMs, and venous malformations, are multiple and they can range from a few millimetres in apparent diameter to up to 1–2 cm. The color of the lesions depends on their depth, the deeper ones appearing as a flat bluish discoloration, the more superficial and larger ones as elevated, bluish or reddish, raspberry-like, blanching, compressible structures (Fig. 21.1). Palpable phleboliths are sometimes present.

Introduction

Equally powerful for generalists or specialists, with simple principles available for every field of medicine, genetics is fundamental to diagnosis and prevention. Neurocutaneous syndromes illustrate the value of the genetic approach, since they often exhibit Mendelian inheritance. They also illustrate the value of pattern recognition, since the association of congenital brain and skin anomalies often predicts a broad spectrum of disease. This chapter presents basic principles of genetics and dysmorphology, illustrating the use of these principles in approaching the spectrum of neurocutaneous diseases.

Key to the genetic approach are resources that provide information on rare diseases. Paramount among these is the catalogue of genetic diseases originally assembled by Victor McKusick (Online Mendelian Inheritance in Man, 2002). Each disease thought to exhibit Mendelian inheritance and, more recently, each characterized human gene or protein has been assigned a 6-digit number. McKusick numbers will be provided for the genetic and neurocutaneous diseases mentioned in this chapter, allowing easy reference at the on-line website. Management of the more common disorders is discussed by Wilson & Cooley (2000).

The genetic approach in medicine

While individual genetic disorders may be rare, the effect of genetic factors on disease is widespread. Coronary artery disease is an example where a focus on extreme disease (young people with heart attacks) identified a gene involved in cholesterol uptake. Once autosomal dominant hypercholesterolemia was characterized by mutations in the low density lipoprotein receptor, cholesterol testing became an indicator of genetic risk that led to diet or drug therapy.