Psychodermatology

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Original release date 12/06. Approved for CME credit through November 2007.

Educational Objectives

After reading this article, you will be familiar with:

• The recent findings in the basic science and clinical aspects of the skin-brain connection.
• The association between dermatologic disorders and psychiatric symptoms.
• The dermatologic disorders seen in psychiatric patients.

Who will benefit from reading this article?

Psychiatrists, primary care physicians, dermatologists, neurologists, nurse practitioners, psychiatric nurses, and other mental health care professionals. Continuing medical education credit is available for most specialties. To determine whether this article meets the CE requirements for your specialty, please contact your state licensing board.

Dr Gupta is professor in the department of psychiatry at the Schulich School of Medicine and Dentistry, University of Western Ontario in London, Ontario. She reports that she has no conflicts of interest concerning the subject matter of this article.

The skin is the largest organ of the body and functions as a social, psychological, and metabolically active biologic interface between the individual and the environment. Recent studies have demonstrated that as the biologic interface, the skin plays an important role in the multidirectional communication between the endocrine, immune, and central nervous systems; in addition to acting as an effector organ, the skin is also a producer of humoral and neural signals that act both locally and centrally.^1,2

Biologically, the skin is an active barrier that separates the organism's internal homeostatic milieu from the stresses and "insults" of the external environment. The skin is therefore equipped to respond to continuous stresses and insults, eg, from solar radiation, mechanical trauma, changes in humidity, and infectious agents, and it has the capability to "fine-tune" itself so that it can differentiate between "environmental noise" and biologically relevant stimuli and stresses. It is possible that this important and somewhat unique role of the skin is also the basis for its sensitivity to psychological stressors; from an evolutionary perspective, physical stressors such as mechanical trauma and infections often have an important psychological component. This article reviews some of the recent findings in the basic science and clinical aspects of the skin-brain connection. The article also reviews some of the major dermatologic associations of psychiatric disorders and the psychiatric disorders encountered in patients with dermatologic disorders.³

Recent research indicates that the skin and its appendages are both a target of key stress mediators (such as corticotropin releasing hormone [CRH], cortisol, catecholamines, prolactin, substance P, and nerve growth factor) and a source of these classic immunomodulatory mediators of the response to psychologic stress.^1,2

The skin-brain connection may be the basis for the observation that a wide range of inflammatory skin conditions such as atopic dermatitis and psoriasis are exacerbated by psychological stress. Clinically, the importance of psychosomatic factors in dermatologic disorders is well recognized; psychosomatic factors are important in at least one third of all dermatology patients. Furthermore, the placebo response in certain dermatologic disorders is greater than 30%, which further emphasizes the importance of psychosomatic mechanisms in dermatology.

The skin is a powerful organ of communication starting at birth-on the social, psychological, and biologic levels. The skin and its appendages are well innervated with a dense network of afferent sensory nerves and efferent autonomic nerves. The afferent sensory nerves convey sensations of touch, pain, itch, temperature, and other physical stimuli. The efferent autonomic nerves play a role in maintaining cutaneous homeostasis by regulating vasomotor and pilomotor functions and the activity of the apocrine and eccrine sweat glands. The apocrine sweat glands, which produce the protein equivalent of pheromones in humans, become functional at puberty and respond to catecholamines (and not acetylcholine) as do the eccrine sweat glands.

As an organ of communication, the skin plays a vital role in attachment starting in infancy. Freud observed that during early development, the ego is rooted in the body, especially the skin. Bodily sensations and experiences, both internal and from the surface of the body, form the core around which the ego develops. The skin remains a very important organ of communication throughout a person's lifetime. It may react to emotional states such as extreme fear, anxiety and stress, and embarrassment with blanching, increased perspiration, flushing, and blushing reactions.

In addition, the overall appearance of the skin, even when minimally flawed, can have a profound effect on the body image of the person, especially in adolescence, and can result in body image pathology. As an organ of communication, the skin continues to play an important role in later life, when the appearance of the skin projects socially important attributes such as chronologic age and social status. The idea that chronologic age does not necessarily signal the beginning of old age is becoming increasingly widespread, and an attempt to reverse some of the aging-related bodily changes frequently involves medical and surgical procedures on the skin.

Basic science
Histologically, the skin is composed of 2 main structures-the epidermis and the dermis. The skin and the nervous system share some common embryologic origins. The keratinocytes, hair follicle and sebum-forming sebaceous glands, and apocrine and eccrine sweat glands originate from the embryonic ectoderm. The Merkel cells and melanocytes that migrate to the epidermis from the neural crest are also of ectodermal origin. The dermal components, with the exception of nerves and specialized receptors, are of mesodermal origin.

Cutaneous equivalent of HPA axis
One of the main adaptive responses to systemic stress is mediated by the central hypothalamic-pituitary- adrenal (HPA) axis. Activation of the HPA axis centrally starts with the hypothalamic production of corticotropin-releasing hormone (CRH), which activates the CRH type 1 (CRH-1) receptor in the anterior pituitary and induces the release of proopiomelanocortin (POMC)-derived peptides adrenocorticotropin (ACTH), α-melanocyte stimulating hormone (a-MSH), and ß-endorphin. ACTH stimulates the production and secretion of cortisol in humans by the adrenal cortex.

It has been demonstrated that the skin expresses a neuroendocrine system involving CRH, urocortin (a CRH-like neuropeptide that has been identified in the brain and has a high affinity for the CRH-2 receptor in addition to the CRH-1 receptor), and the POMC-derived peptides ACTH, α-MSH, and ß-endorphin. Skin cells also express functional receptors activated by these neuropeptides.

It has been proposed that the central HPA axis acts as a coordinator of the local cutaneous response to stress, and the local cutaneous effectors of the HPA axis (ie, CRH, urocortin, and the POMC-derived peptides like ACTH and a-MSH) regulate the skin pigmentary, immune, epidermal, adnexal, and dermal systems. In addition, local cholinergic, catecholaminergic, and serotoninergic/ melatoninergic systems and some elements of the pituitary-thyroid axis have been demonstrated in the skin.^1,2

Neuroendocrine-immune circuitry and stress-mediated skin disorders
Stress-mediated production of glucocorticoids may induce the suppression of T helper 1 (T_H1)-mediated cellular immunity and create a shift towards T helper 2 (T_H2)-mediated humoral immunity. Neurohormonal responses to stress also involve the activation of the sympathetic nervous system (SNS) with a subsequent increase of catecholamines. The SNS has been shown to directly participate in cutaneous inflammation. Sympathetic nerve fibers travel with sensory nerves and innervate the dermis and epidermis, where they release norepinephrine.

Catecholamines have a suppressive effect on cutaneous Langerhans cells, which anatomically are associated with cutaneous nerves. The bone marrow-derived Langerhans cells participate in the cutaneous immune response and migrate from skin to lymph nodes. They possess surface receptors common to macrophages and function as antigen-presenting cells to T or B lymphocytes.

The skin responds differently to acute versus chronic stress. Skin responses to acute stress include an enhanced skin immune function with increased intracutaneous migration of immunocompetent cells, while chronic stress may suppress cutaneous immunity. Lymphocytes express adrenergic receptors and respond to increased levels of catecholamines with the development of stress-induced lymphocytosis, changes in lymphocyte trafficking, circulation, proliferation, and cytokine production.

Acute stress experienced prior to the exposure to a novel antigen has been shown to increase memory T-cell formation, and acute stress experienced during antigen reexposure may enhance the secondary immune response. Alternatively, chronic stress may reduce the immune response to vaccines, slow wound healing (since the cellular immune response plays a key role in the early phase of wound healing), and reactivate latent viral infections such as herpesviruses.

Stress and the mast cell
Acute stress is associated with increased mast cell activation and degranulation.¹ The mast cell is a key player in the skin-brain connection and an important regulator of neurogenic inflammation during the stress response. A wide range of stress-related mediators such as CRH, ACTH, cytokines, and substance P are triggers for mast cell activation, which, in turn, results in the synthesis and/or release of prestored mediators that may lead to the onset or exacerbation of a wide range of dermatologic disorders that are known to be exacerbated by psychological stress.

The skin mast cell is not only triggered by classic stress mediators such as ACTH and CRH, it is also a generator of stress hormones such as CRH. The skin mast cell is one of the richest sources of CRH outside the brain.¹ Some of the dermatologic disorders in which mast cells play an important role include urticaria and angioedema, alopecia areata, atopic dermatitis, psoriasis, contact dermatitis, acne vulgaris, and various pruritic states that may be associated with mast cell activation and histamine release.

Acute psychological stress and skin barrier function
Some recent studies have demonstrated that acute psychological stress, which is associated with increased glucocorticoid levels, adversely affects skin barrier function recovery induced by tape stripping; in contrast, chronic psychological stress, which may be a feature of chronic posttraumatic stress disorder (PTSD), is often associated with an attenuated HPA axis response and has been associated with an enhancement in skin barrier function recovery. Glucocorticoids most likely act by inhibiting epidermal cell proliferation and lipid synthesis.

Clinical perspectives
Psychodermatologic disorders have generally been classified into 2 major categories³:

• Cutaneous associations of psychiatric disorders.
• Psychiatric associations of cutaneous disorders.

Some of the dermatologic presentations of primary psychiatric symptoms are summarized in Table 1. The self-induced dermatoses represent the fact that stimulation of the skin, which is richly innervated and has bilateral communication with the CNS, serves as a means of regulating affect and coping with intense emotional states. In some instances the self-induced cutaneous lesions also communicate emotional distress.

Table 2 highlights some of the psychiatric associations of primary dermatologic disorders; this group can be further divided into 3 subcategories.

• Disorders that have a primary dermatopathologic basis but may be influenced by psychosomatic factors, eg, psoriasis, atopic dermatitis, urticaria and angioedema, lichen planus, acne, and alopecia areata.
• Disorders that represent an accentuated physiologic response, eg, hyperhidrosis and blushing.
• Disorders that result in an emotional reaction primarily as a result of cosmetic disfigurement, social stigma, and the overall impact of the disorder on the quality of life of the patient.

These 3 subcategories are not mutually exclusive. Most of the disorders in the first category, such as psoriasis, atopic dermatitis, chronic urticaria, lichen planus, and alopecia areata, have an immunologic component. Second, most of these primary dermatologic disorders have been associated with both psychiatric comorbidity,³ (most frequently depressive disease and anxiety disorders) and with psychosocial stress, which typically is reported to exacerbate the skin disorder.

In up to 70% of cases of psoriasis, atopic dermatitis, chronic urticaria, and acne, psychological stress has been identified as an exacerbating factor. Some reports suggest that psoriasis is one of the most stress-reactive dermatoses. The association between stress and exacerbations of alopecia areata and lichen planus is less robust. A wide range of other dermatologic disorders, such as viral infections of the skin, and a range of other skin disorders that may also be immunologically mediated, such as vitiligo, may be exacerbated by psychological stress and have a psychosomatic component. However, an exhaustive review of these disorders is outside the scope of this paper. In some disorders, such as psoriasis, a significant component of the psychosocial stress arises from the impact of the skin disorder on quality of life and the daily hassles associated with having to cope with a chronic disfiguring disorder.⁴

Some of the major psychiatric disorders (DSM-IV-TR) that are encountered in dermatology include mood disorders: major depressive disorder; anxiety disorders: obsessive-compulsive disorder (OCD), social phobia, anxiety disorder caused by a general medical condition, and PTSD; somatoform disorders: body dysmorphic disorder (BDD); psychotic disorders: delusional disorder, somatic type encountered in delusions of parasitosis, and shared psychotic disorder or folie deux; and eating disorders: anorexia nervosa and bulimia nervosa. The personality disorders, especially borderline, narcissistic, histrionic, and obsessive-compulsive, may be encountered in certain groups of dermatology patients. Among these, the most frequently encountered psychiatric disorders are major depressive disorder, anxiety disorders, and somatoform disorders.

Major depressive disorder
Depressive disease is one of the most commonly encountered psychiatric syndromes in dermatology. A direct correlation has been observed between the severity of depression and pruritus or itch severity in psoriasis, atopic dermatitis, and chronic idiopathic urticaria. Pruritus is one of the most bothersome symptoms in dermatology and has been associated with suicide. The sleep difficulties encountered in depressive disease may lower the threshold for pruritus perception; alternatively, intractable pruritus may further contribute toward disruption of sleep.

The severity of the skin disorder and severity of depression and suicidal ideation are generally correlated in some disorders, such as psoriasis. In other conditions, such as acne, the severity of depression and suicidal ideation are often not related to the severity of the dermatosis. Even mild acne has been associated with depression, suicidal ideation, and completed suicide.⁵ The high prevalence of psychiatric morbidity among patients with mild to moderate acne is most likely due to the fact that the peak incidence of acne occurs during mid-adolescence, a life stage that is also associated with depressive disease and body image disorders. The association between acne and depression is further confounded by reports of a possible link between isotretinoin (which is used to treat acne) and suicide.⁶

Obsessive-compulsive disorder
Some of the compulsive scratching and picking of the skin in OCD may exacerbate psoriasis as a result of the Koebner phenomenon, and exacerbate eczema and a wide range of other pruritic conditions, or further contribute to the inflammatory process in acne, and/or lead to scarring that is encountered in acne excorie. OCD may also result in hand dermatitis caused by excessive handwashing. In some instances OCD may manifest as an obsessive preoccupation with some aspect of the skin, and these symptoms may overlap with BDD.

Social phobia
Patients with hyperhidrosis and rosacea often perspire or blush excessively and may develop a social phobia as a result. Social phobia is also encountered in patients with cosmetically disfiguring skin conditions such as acne and psoriasis, and may interfere with normal socialization. Exposure to the feared social situation may trigger a situationally bound panic attack, which in turn can cause flare-ups of the underlying skin condition. Social phobia is typically underdiagnosed because the very nature of the disorder prevents patients from seeking medical help.

Posttraumatic stress disorder
The autonomic dysregulation in PTSD can lead to exacerbations of stress-mediated dermatoses such as psoriasis and atopic dermatitis. Urticarial reactions and angioedema have been associated with an acute stress response⁷; urticarial reactions and angioedema may represent a conditioned response to a stimulus that had been previously associated with a traumatic experience. Patients with PTSD who have dissociative symptoms may present with a wide range of cutaneous sensory complaints and/or self-induced dermatoses such as trichotillomania.

Body dysmorphic disorder
The skin and hair are frequently the focus of excessive body image concerns. BDD often involves excessive concerns about thinning hair, acne, wrinkles, scars, vascular markings, paleness or redness of the complexion, swelling, facial disproportion or asymmetry, or excessive facial hair. BDD may be comorbid with acne and acne excorie. Some associated features include excessive grooming behavior such as excessive hair combing, hair removal, hair picking, or ritualized makeup application.

Summary
Some of the recent advances in psychodermatology expand on the traditional concept of psychosomatic medicine because there is increasing evidence that the impact of psychological stress on the skin is not necessarily mediated primarily by the CNS but is mediated by a local stress response system in the skin that is the equivalent of the central HPA axis, and that further interacts with the central HPA axis response. These findings refute the traditional mind-body dichotomy. The local stress response system that has been recently described in the skin^1,2 may be present in other organ systems and therefore may not be unique to the integumentary system; however, the stress response can be observed most easily in the skin. A psychodermatologic evaluation may therefore give the psychiatrist further insights into the mental state of the patient.

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References:

1. Arck PC, Slominski A, Theoharides TC, et al. Neuroimmunology of stress: skin takes center stage. J Invest Dermatol. 2006;126:1697-1704.
2. Slominski A, Wortsman J. Neuroendocrinology of the skin. Endocr Rev. 2000;21:457-487.
3. Gupta MA, Gupta AK. Psychodermatology: an update. J Am Acad Dermatol. 1996;34:1030-1046.
4. Gupta MA, Gupta AK, Kirkby S, et al. A psychocutaneous profile of psoriasis patients who are stress reactors: a study of 127 patients. Gen Hosp Psychiatry. 1989;11:166-173.
5. Gupta MA, Gupta AK. Depression and suicidal ideation in dermatology patients with acne, alopecia areata, atopic dermatitis and psoriasis. Br J Dermatol. 1998;139:846-850.
6. Hull PR, D'Arcy C. Acne, depression, and suicide. Dermatol Clin. 2005; 23:665-674.
7. Pistiner M, Pitlik S, Rosenfeld J. Psychogenic urticaria. Lancet. 1979;ii:1383.