Katlein França - Stress and Skin Disorders: Basic and Clinical Aspects

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Ruqiya Shama Tareen Associate Professor

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Stress or more precisely psychological stress is defined in many ways but a simple definition captures the essesnce of it a state of psychological strain or pressure due to a adverse or demanding situation. A stressor or a stress full event is the one, which either disrupts or threaten to disrupt an organisms homeostasis. The stress full event can be a good event like a job promotion, marriage, having a child or a bad one like divorce, financial stress or death of a loved one, or it can be just a internal or external change in normal homeostasis like move, interpersonal relationship difficulties, suffering from pain or having a medical illness. It does not matter what kind of stress one faces, what matter most is how our mind and body respond to it and how we cope with it over all. All organisms are equipped to deal with stress no matter where they are on the ladder of evolution as specie. We as human have extensive and intricate systems and subsystems that work in tandem to help us cope with any stressor both emotionally and physically. However, our ability to respond to psychological stress depends on various variables. Age when the stressor occurred, early age of psychological stress can have much significant impact on psychological and physical well being. Nature of the stressor and its importance to the person in stress is also important as not every stressor has same impact for every one. While one might take job promotion in stride and deals with initial challenges of it with some difficulty another person may struggle to overcome the same kind of challenges, becoming psychologically overwhelmed and it may impact their physical well being. Chronicity of the stressor can overwhelm a persons adaptive level of responding to stress adequately. A child growing up in a dysfunctional family is under stress earlier on and exposed to some kind of stress on regular basis, constantly challenging his or her neuro-endocrine-immune response system to cope with stress, resulting in constant activation and ultimately failure of the stress response system.

The role of chronic stress in the pathogenesis of skin disease has been proposed by patients and physicans alike since the early days of modern medicine. It is only in last few decades we have achieved good scientific grounds to establish this connection [).

Psychoneuroimmunology, a relatively new field which relates to the study of complex and synchronous activation and interactions of behavioral, neural, endocrine, and immune systems leading to a successful defense response to an internal or external challenge including psychosocial stress. This intriguing phenomenon explains that immune system is rather one part of a multisystem response of a body challenged by an internal or external threat or psychological stress. This multisystem interplay that initiates and orchestrate a defense response helps us understand the complexities and intricacies of stress and adaptation of a body to it and how imbalance caused by severe or continual stress in can be detrimental to physical and mental wellbeing (Fig. ).

The intricate multidimensional workflow of central and peripheral nervous systems, endocrine and immune system when gets overwhelmed or gets disturbed by high level of stress it results in expression of a disease process, including skin diseases. These three systems while respond to stress on their own they also interact with each other to orchestrate a stress response. The interaction of these three systems prepare body and mind to adapt to the stess induced changes by utilizing a series of neuropetides, neurotransmitters, and neurohormones. While stress affects a person at different levels, stress can impact each and every cell and organ in a body. Skin being the most outer, biggest and most innervated organ can show the burden of stress in most obvious way. Stress plays amajor role in the pathogenesis and expression of many skin diseases and dermatological diseases can appear de novo or relapse in response to psychological stress. Skin and brain both share an embryological origin from the single layer of germinal cells; the ectoderm. A specialized population of multi-potent cells known as neural crest cells emerge from the junction of neural and surface ectoderm; these cells can develop in different types of cells like epidermis, sympathetic nervous system, peripheral sensory neurons, and melanocytes [].

The complex relationship between stress and skin disease can not be fully explained unless we understands the mecahnisms by which the body responds to stress at macro and micro levels.

Central nervous system (CNS) modulates the immune response to stress via three distinct mecahnisms; activation of hypothalamic-pituitary-adrenal axis (HPA axis) and autonomic nervous system (ANS) and modulation of microglia on local level. This two prong activation of ANS as well as HPA axis ensures a prompt yet sustained respose to a particular stress stimuli as long as it is needed. Both of these systems work in-synch to each other in a bidirectional way to maintain the equilibirium in the stess response and to rheostat the intensity and duration of immune response [].

ANS activation starts the releases of norepinephrine from the adrenal cortex. Most of the organs are innervated with noradrenergic postganglioning nerver fibers and lymphoid argans are no exception. Primary and secondary lymphoid organs like spleen, thymus, bone marrow, mucosal lymph glands and lymph nodes are activated through release of norepinephrine via peptidergic nerve fibers. The sympathetic innervations generally follow a similar pattern in different tissues. The nerve fibers are more dense in T-cell zones as compared to the B-cell zone. These nerve fibers makes neuroeffector junctions with lymphoid cells like macrophages to exert effect on immune systems. It has been known that any inturruption of this pathway can lead to impairment in immune response [].

The release of norephnephrine within lyphoid cells can activate different receptors like - adrenergic receprtors to influence the direction of stress response in certain way thus fine tunning the immune response to a particular offender. Norepinephrine has shown to modulate immune resonse by modulating thymocyte mitogenesis, lymphocyte proliferation in some lymph nodes, cell expression of antigens, antibody response, deters complement activation, and inhibits macrophages mediated lysis of certain cancerous or infectious cells. Lymphoid tissues have catecholamine and various neuropeptide-specific receptors. Catecholamines and other neurotransmitters released from nerve fibers can activate theses receptors and can modulate the immune response via intracellular signals influencing a particular cell line proliferation, antibody and cytotoxin production etc. This can lead to vasodilation and adhesions of leukocytes which can further modulate local inflammatory response in response to stress Watson and Nance [].