“Man is made by his beliefs—as he believes so he is”.
—Bhagavad Gita
“There is a part in our body if it is healthy the whole body is healthy, if it is sick the whole body is sick, that is mind”.
—Prophet Muhammad
The age old adage ‘face is the mirror of mind’ is applicable not only to the face but to the whole skin of our body. This dictum has acquired tremendous importance in recent decades. The mind and body are considered as a single unit instead of mind versus body dualism, and this stresses the need for holistic approach of disease management. Formerly, the biomedical concept of disease was very prevalent, which compared the human body to a machine and the doctor was like a technician doing the repair work of human machine, where the mind was completely neglected. But in this recent concept, the mind has very important role in health, disease causation and healing.2
Every dermatologist knows that chronic skin diseases, especially on visible areas, may lead to considerable emotional and psychosocial stress in the affected individuals, more so if the lesion is disfiguring or tends to heal with scars. In the same way, emotional or psychological disorders may trigger skin diseases also.
The relationship between skin and psyche is getting increasing attention and several theories postulate psychophysiological mechanisms underlying various dermatological disorders. Emotional or sociocultural factors of influence have dramatically changed the morbidity, pathogenic understanding of causality, and therapy concepts in dermatology over the past decades. Since both skin and brain originated from the same ectoderm, skin diseases can affect mind and vice versa. Psychosomatic dermatology addresses skin diseases in which psychogenic causes, consequences, or concomitant circumstances have an essential and therapeutically important influence. In the narrower sense, it covers every aspect of intra- and interpersonal problems triggered by skin diseases and the psychosomatic mechanisms of eliciting or coping with dermatoses. The skin is a complex system made up of blood vessels, nerves, glands, and muscle elements, many of which are controlled by the autonomic nervous system and can be influenced by psychological stimuli. They have the capacity to cause autonomic arousal and are capable of affecting the skin and the development of various skin disorders. In dermatology practice, various studies have shown that psychiatric morbidity in outpatients ranges from 30–40%, and in inpatients it is up to 60%. Anxiety, depression, adjustment disorders and social withdrawal are common problems.
STRESS AND PSYCHONEUROIMMUNOLOGY
Skin is a part of NICE (neuro-immuno-cutaneous-endocrine) system and stress can induce or exacerbate many of the pathogenic mechanisms in a variety of dermatological conditions. Various researches in this field for last 30 years have established the close relationship between CNS and the immune system. Stressors activate two major neural pathways, hypothalamo-pituitary-adrenal (HPA) axis and sympathetic nervous system. The hypothalamus secretes corticotropin-releasing hormone (CRH), arginine and vasopressin. CRH release activates the HPA axis, leading to release of adrenocorticotropic hormone (ACTH) from pituitary gland. ACTH3 induces downstream release of glucocorticoids from the adrenal cortex. Activation of the noradrenergic pathways by CRH results in secretion of norepinephrine and epinephrine from the adrenal medulla and norepinephrine by the peripheral sympathetic nervous system. CRH and noradrenergic neurons in the CNS innervate and stimulate each other producing complementary effect. The activation of these two neurochemical pathways and release of hormones and transmitters have profound downstream effects on immune function. As a result the body produces innumerable hormones, cytokines and other neurohumeral chemical mediators, which triggers and maintains the skin disease without much response to therapy.
Neurogenic Inflammation
Neurogenic cutaneous inflammatory response is triggered by the stress induced products of cutaneous sensory nerve endings. The skin is innervated primarily by sensory C-fibers. Their free nerve endings contain neuropeptides, such as substance P (SP), Calcitonin gene-related peptide (CGRP), and pituitary adenylate-cyclase-activating polypeptides (PACAP). These bind to receptors on cutaneous blood vessels, inducing vasodilatation, increased vessel permeability, chemotaxis, exocytosis, and activation of neutrophils. These peptides, in conjunction with keratinocyte-derived CRH and nerve growth factor (NGF) act on mast cells resulting in the degranulation of these cells, secretion of TNFα, histamine, and tryptamine leading to cutaneous inflammation. It is also observed that stress will increase the production and release of proinflammatory cytokines and nitric oxide from macrophages and this leads to selective redistribution of immune cells from one organ to another (for example: reduction in number and percentage of cells in the peripheral blood and concomitant increase of immune cells in the skin).
Stressors also activate intracellular transcription factors that play a central role in mediating the physiological effects of proinflammatory cytokines. Altogether stress has a significant role in the initiation and maintenance of cutaneous inflammatory response.
Stress and Immune Response
Acute or Mild Stress
Studies conducted in laboratory animals have shown that brief and mild stressors enhance acquired immunity. In a series of experiments4 in rats, it has been shown that a brief stressor (two hours of physical restraint or shaking) applied before antigen challenge significantly enhances delayed type hypersensitivity (DTH). Similarly, rodents exposed to acute or mild stressors or both before antigen presentation have been reported to enhance humoral immunity by producing more antibodies than control groups. But if the intensity or duration of stress is increased opposite effect is observed even if the same stressor type is used. It is observed that the enhancing effect of immunity is due to the stress-related release of corticosteroids and epinephrine. But chronic stress or chronic administration of corticosteroids suppresses the immunity. Human studies with parachute jumping and first time public speaking as stressors have shown many enumerative changes in the immune cells. These changes include increase in total white blood cells count, CD8 T cell, natural killer (NK) cells, NK cell activity and CD4/CD8 ratio. But it also decreases the number of total B and T cells. It also favors the production of TH-1cytokine IFN-gamma. In humans, it is also observed that acute stress rapidly evolves into chronic stress in terms of immune system effect.
Chronic or Severe Stress
Chronic or severe stressors in animals and humans are associated with alterations in immune system that leads to development of diseases. Studies conducted in individuals appearing for examinations and those caring a demented spouse have shown that both cellular and humoral immunity are affected adversely. The ability to suppress the activity of latent viruses decreases and it also interferes with antibody production after vaccination.
The enumerative changes include increase in circulating white blood cells, Th2 cytokines IL-4, IL-10, but decrease in CD4 (helper), CD8 (cytotoxic) cells, ratio of CD4/CD8 cells, B cells, T cells, and natural killer cells. Chronic stressors also suppress DTH, NK cell activity, memory T cell response, TH-1 cytokines IFN-gamma and IL-2 production.
In short, chronic or severe stress-leads to activation of the HPA axis that results in the secretion of catecholamines and glucocorticosteroids. They have a profound effect on immunity, inducing a Th2 shift by upregulating the production of Th2-cytokines IL-4, IL-10, and IL-13 and by suppressing Th1-cytokine IL-12 production and macrophages.5
In this manner, chronic stress inhibits cell-mediated immunity, favoring antibody-mediated and allergic responses. This combined effect on the Th1–Th2 balance may explain why the activity of some diseases like autoimmune diseases, including pemphigus or conditions with Th2 predominance, such as atopic eczema appears to deteriorate during periods of stress (Fig. 1).6
STRESS AND BARRIER FUNCTION OF THE SKIN
The barrier function of the skin gets impaired during period of stress. Stress liberates histamine, vasoactive neuropeptides and causes hemodynamic changes such as variation in skin temperature, blood flow and sweat response which in turn contributes to increased transepidermal water loss. Altered skin-barrier function creates increased susceptibility to cutaneous inoculation with environmental agents (e.g. allergens such as dust mites, dander, bacteria, and viruses) that are potential precipitants of atopic flares.
STRESS AND WOUND HEALING
It is observed that wounds healed significantly slower in healthy students during periods of examinations compared with non-stressful times. Delayed healing is seen in couples with poor marital relationships. Thus, the process of wound healing is affected by stressful life conditions and can be improved through psychological intervention and/or changes in lifestyle. The mechanisms which occur in the nervous system, both central and peripheral, that alter innate and cellular immunity in the skin in response to wound healing require further studies.
Psoriasis
Emotional stressors have been reported to precede the onset and flares of psoriasis. It is observed that psoriatic patients who suffered traumatic sensory denervation had resolution of lesions in the areas innervated by the sectioned nerves and the disease reappeared when nerve fibers regenerated. Psoriatic plaques display increased nerve fiber density and altered content of neuropeptides such as substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide, and nerve growth factor (NGF). High expression of NGF mediates T cell and keratinocyte proliferation, mast cell migration, degranulation, and memory T cell chemotaxis, which are hallmarks of psoriasis. It is also noted that stress reduction interventions has successful result in psoriasis management.
Atopic Dermatitis
Patients with atopic dermatitis (AD) have severe impairment in their quality of life, resulting in significant emotional distress that7 leads to exacerbation of the disease. AD patients have up regulation of glucocorticoid receptors on peripheral leukocytes and there is a cytokine shift from Th1 to the Th2 immune response. Stress-induced local and systemic secretion of epinephrine and norepinephrine also accelerate the Th2 differentiation by production of IL-13 and IL-4. There is also a redistribution of lymphocytes and eosinophils in atopic skin. Psychotherapeutic procedures for stress reduction like insight-oriented psychotherapy, cognitive behavior therapy, psychoeducation, hypnosis and biofeedback have been reported to be effective in improving the skin manifestations of AD patients.
Infections
Various studies have demonstrated that stressors have deleterious effects on the evolution of bacterial and viral infections of the skin. It is observed that stress can lead to the activation of herpes simplex virus remaining dormant in the dorsal nerve root ganglion.
CONCLUSION
Stress and mental tension are the inseparable part of modern life producing innumerable health hazards to the humanity. All human organs are linked with mental health, especially the skin. Stressors are acting as a trigger in the onset or chronic progression of many psychophysiological conditions like psoriasis, atopic dermatitis, urticaria, lichen planus, alopecia areata, vitiligo, prurigo nodularis, auto immune diseases like systemic lupus erythematosus, scleroderma, pemphigus and infections like recurrent herpes simplex infection, reactions in Hansen's disease etc. Hence stress management is very essential along with standard dermatological management for an early and better clinical response.
FURTHER READING
- Ader R, Feilten DL, Cohen N. Psychoneuroimmunology. 3rd edition. New York: Academic Press. 2001.
- Dhabhar FS, McEwen BS. Enhancing versus suppressive effects of stress hormones on skin immune function. Proc Natl Acad sci. USA. 1999;96:1059.
- Harth W, Gieler U, Kusnir D, Tausk FA (Eds). Clinical Management in Psychodermatology. Springer Publication, Germany; 2009.
- Jaremka LM. Synergistic relationships among stress, depression, and troubled relationships: Insights from Psychoneuroimmunology. Depression and Anxiety. in press [Retrieved 2013-04-08].doi:10.1002/da.22078.