Psychoneuroimmunoendocrinology describes the unity of mental, neurological, hormonal, and immunological functions, addressing the impact of cognitive images of the mind (whatever its elusive definition) on the central nervous, endocrine, and immune systems. It encompasses biofeedback and voluntary controls, impacts on physiology of thought and belief, past/present stress, placebos, social relationships, and "energy medicine." This column highlights clinical applications of cogent studies from these arenas of holistic medicine in the new millennium.

Skin Disease: Eczema, Psoriasis

Atopic Eczema and Laughter
Atopic eczema patients often complain of sleep disturbance, and blood levels of melatonin in eczema patients are low vs. healthy subjects. Laughter increases NK cell activity in blood and free radical-scavenging capacity in saliva in healthy subjects. In a study of 48 infants age five to six months with atopic eczema (AE) and allergy to latex and house dust mites, 24 of the nursing mothers of these infants had AE, while another 24 mothers were healthy without atopic eczema. In crossover fashion, the mothers viewed both an 87-min humorous DVD featuring Charlie Chaplin and an 87-min non-humorous weather information DVD at 8 PM. Melatonin in breast milk was then checked sequentially in samples from 10 and 12 PM and 2, 4, and 6 AM. Laughter from viewing the humorous DVD increased levels of breast-milk melatonin in mothers with AE (p<.01) and healthy mothers (p<.05) with no changes after viewing non-humorous information. Allergic skin responses to latex and dust mites of infants were reduced by feeding with breast milk after laughter of mothers with AE (p<.01) or of healthy mothers (p<.05).

Kimata H. Laughter elevates the levels of breast-milk melatonin. J Psychosom Res. 2007; 62:699.

COMMENT: Laughter increased levels of breast-milk melatonin in mothers with or without atopic eczema, and feeding infants milk with higher levels of melatonin significantly reduced their allergic skin responses. We probably greatly underestimate both the mind-brain effect on atopic dermatitis and the effect of humor and laughter on a variety of physiological and pathological functions. In this sense, humor is a serious business.

Acne Vulgaris, Biofeedback, and Imagery
In 30 patients with acne vulgaris, those randomly assigned to undergo an intervention involving continued medical treatment plus 12 biofeedback and imagery sessions over six weeks experienced significantly greater gains vs. a medical treatment-only group and vs. a monitoring-only control group (p<.01). Those continuing home practice maintained their gains, whereas those who discontinued regressed.

Hughes H, et al. Treatment of acne vulgaris by biofeedback relaxation and cognitive imagery. J Psychosom Res. 1983; 27(3):185.

COMMENT: Imagery is particularly successful in dermatological conditions, probably because the skin is so visible. Vivid imagery of internal organs is more difficult for those who have not studied anatomy. And the vividness of imagery is correlated with outcomes (Achterberg J, Lawlis GF. Bridges of the Bodymind. Champaign, IL: I.P.A.T;1990). Imagery is usually inserted into relaxation processes, which shift the basic brain rhythm to a lower frequency (i.e., from the beta range of 13-31 Hz to the alpha range of 8-13 Hz). Images presented to the mind-brain in this altered state of consciousness are much more effective. Staying in the alpha frequency has also been demonstrated to reduce catecholamine synthesis, in turn reducing the generation of free radicals. Since many of these dermatological conditions involve inflammation and free-radical excesses, the mechanism of successful action may be partially explained.

Atopic Dermatitis and Hypnosis
Eighteen adults with resistant atopic dermatitis, mean age 33, were treated with three hypnotherapy sessions with significant improvement lasting through more than two years of follow-up. Nineteen out of 20 (19/20) children with severe treatment-resistant atopic dermatitis, aged two to 15, had immediate improvement, with ten maintaining marked improvement in itching and scratching; nine, in sleep disturbance; and seven, improvement in mood at 18 months of follow-up. Elements in the protocol included relaxation; stress management (problem-solving techniques); direct suggestion of non-scratching behavior; direct suggestion of skin comfort and coolness; ego strengthening; post-hypnotic suggestions of relaxation, skin coolness and ease of self-hypnosis; and instruction in self-hypnosis. For children, these elements were placed on a "magic music" tape to be played at home. At two years, patients’ assessments included improvement in itching (p<.05), scratching (p<.05), sleep disturbance (p<.01), and tension (p<.01); at 16 weeks, mean decrease in use of topical steroids was 60%.

Stewart A, et al. Hypnotherapy as a treatment for atopic dermatitis in adults and children. Br J Dermatol. 1995 May; 132(5):778-83.

COMMENT: The use of suggestion in various forms in children usually meets with great success. Those under the age of ten or eleven have not yet been convinced to be skeptical and jaded about their potential and life in general. In using biofeedback and suggestion with children over the years, I never met with anything but resounding successes. Suggestion is a powerful element in the treatment of warts (see below). I do not understand why its use, especially with children, is so limited.

Atopic Dermatitis and Stress
Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease with symptoms including eczematous skin lesions and severe pruritus. Thirty-six AD patients and 37 nonatopic controls were exposed to laboratory stressors including a spontaneous speech and mental arithmetic tasks in front of an audience (the Trier Social Stress Test, TSST). Leukocyte subsets were significantly elevated ten minutes after the TSST (all p<0.001) with no intergroup differences. Eosinophils, however, were significantly elevated only in atopic dermatitis patients (p<0.01). AD patients, but not controls, showed increased IgE levels (p<0.05) 24 hours later. Exposure to the TSST resulted in elevation of IFN-g (p<0.001) and attenuation of IL-4 (p<0.001) with no significant intergroup differences (p>0.05).

Buske-Kirschbaum A, et al. Stress-induced immunomodulation is altered in patients with atopic dermatitis. J Neuroimmunol. 2002; 129(1-2):161.

COMMENT: Stress may be associated with atopy-relevant immune changes in atopic dermatitis, explaining the common observation of stress-induced aggravation of symptoms. It is very common for a variety of inflammatory skin conditions to flare when stress is added to the mix. Relaxation processes and meditation are one answer for the management of the downstream effects of stress.

Warts and Hypnosis
Subjects with warts on their hands and/or feet were randomly assigned to a hypnotic suggestion, topical salicylic acid, placebo, or no-treatment control condition. Subjects in the three treated groups developed equivalent expectations of treatment success. Nevertheless, at the six-week follow-up interval, only the hypnotic subjects had lost significantly more warts than the no-treatment controls.

Spanos NP, et al. Effects of hypnotic, placebo, and salicylic acid treatments on wart regression. Psychosom Med. 1990; 52:109-14.

COMMENT: One theory about warts is that they are caused by viruses. In any event, the immune system appears to play a role in their rejection. From the success of nutritional treatments, including topical garlic (Dehghani F et al., Int J Dermatol. 2005; 44:612) and oral zinc (Al-Gurairi FT et al., Br J Dermatol. 2002; 146:423), we infer that the immune system, when strengthened, does a better job with the viruses involved. Precisely how the immune system is strengthened by imagery and hypnosis remains murky, but the empirical evidence from several different disciplines is highly persuasive.

Tuberculin Skin Testing and Hypnosis
Four PPD-positive subjects were retested after hypnosis sessions in which it was suggested that they "not react." Three had completely negative PPD reactions; the fourth had a trace response nonetheless read as negative.

Black S, et al. Inhibition of Mantoux reaction by direct suggestion under hypnosis. Br Med J. 1963 Jun 22; 1(5346):1649-52.

COMMENT: We think of tuberculosis skin-testing as a certain process on which serious therapy decisions are based. We never check out either the belief systems of the patients involved or the suggestions they may be consciously or unconsciously giving themselves.

Dermal Reactions and Hypnosis/Guided Imagery
In a study of tuberculin skin testing, a suggestion was made under hypnosis in a healthy volunteer to increase the post-hypnotic reaction in one arm and decrease it in the other; significant differences in erythematous area and palpable induration were apparent (p<.01). Laser doppler measurements showed a 19% difference in erythema and a 44% difference in dermal infiltrate thickness.

Zacheriae R, et al. Modulation of type I immediate and type IV delayed immunoreactivity using direct suggestion and guided imagery during hypnosis. Allergy. 1989 Nov; 44(8):537-42.

COMMENT: We consistently and constantly underestimate the power of the mind to influence what we believe to be isolated body effects. Humans are not minds and bodies but integrated holistic beings. Individual hypnosis case histories have demonstrated that pupil size can be reduced in one eye and simultaneously increased in the other eye. We are surely only beginning to understand the enormity of the power of the mind and brain to influence health and healing.

Dermatoses and the Mind
It is only recently that Western physicians are rediscovering the link between thought and health. The spectrum of causative factors in inflammatory dermatoses are often multifactorial. Stress and negative thoughts are major factors in dermatological conditions. This review article begins with some basic information on the ways that thoughts affect health. Practical methods of intervention, including meditation, journal writing, affirmations, prayer, biofeedback, and hypnosis, are presented. In the same journal issue, another review points out that skin does more than present one's "face" to the world; it plays a vital role in the maintenance of physical and mental health.

As our most ancient interface, skin retains the ability to respond to both endogenous and exogenous stimuli, sensing and integrating environmental cues while transmitting intrinsic conditions to the outside world. As such, it has long been a target for the application of both medical and nonmedical therapies of healthy and diseased states. Our understanding of how the skin and topical therapies affect health is in its infancy. Conversely, we know little of how our internal systems affect our skin. By exploring an elaborate web of neuro-immuno-cutaneous-endocrine (NICE) phenomena, we seek to shed light on the generally acknowledged, but inadequately defined, relationship between mental and physical health. We use skin as our window, noting some of the biological mediators linking nervous, immune, cutaneous, and endocrine functions. It is likely that these mediators are important in homeostasis and that they affect several dermatological and psychiatric conditions.

Bilkis MR, Mark KA. Mind-body medicine. Practical applications in dermatology. Arch Dermatol. 1998; 134:1437-41.
O'Sullivan RL, et al. The neuro-immuno-cutaneous-endocrine network: relationship of mind and skin. Arch Dermatol.1998; 134:1431-35.

COMMENT: I could have not stated it any better.

Herpes Labialis and Stress
Forty-nine freshmen nursing students reported recurrences of herpes labialis for a year and completed a battery of four psychological tests. Sixteen out of 49 (16/49) had recurrences in a year. Significant correlations with aspects of the psychological tests resulted (from NS to p<.05 to p<.01). One-third to one-half of all recurrences could be predicted from combinations of sociometric and psychological variables.

Katcher AH, et al. Prediction of the incidence of recurrent herpes labialis and systemic illness from psychological measurements. J Dent Res. 1973; 52:49-58.

COMMENT: This and similar studies repeatedly show that psychological characteristics demonstrating how an individual will handle the physical and psychosocial stresses of life will predict the frequency with which they will succumb to outbreaks of herpetic skin reactions.

Herpes and Stress
In 49 first-year medical students, those falling in the above-median scores on the obsessive-compulsive, depression, anxiety, hostility, and symptom index scales of the Brief Symptom Inventory experienced high stress scores and excessive rises in herpes antibody titers on the day prior to exams (p<.0001) vs. those in the below-median group. High loneliness was positively correlated with higher EA (early antigen) and VCA antibody titers.

Glaser R, et al. Stress, loneliness, and changes in herpesvirus latency. J Behav Med. 1985; 8:249 60.

COMMENT: Yes, we do have to treat the herpetic outbreaks. Better we should help the patient evoke the preventive strategies to prevent the outbreak in the first place.

Hives and Expectation
In this case report, a subject known to be prone to the development of hives was tested by striking the forearm with a small paddle, leading to the immediate development of a reactive hyperemia and development of an urticarial reaction. Some time later, when the reaction had dissipated, a sham blow was delivered to the arm (the paddle was stopped a quarter-inch short of the skin), resulting in the same change in reactive hyperemia and hive formation in spite of the fact that the skin had not actually been struck.

Graham DT. The pathogenesis of hives: Experimental study of life situations, emotions and cutaneous vascular reactions. Proc Ass Res Nerv Ment Dis. 1950; 29:987-89.

COMMENT: This ancient case report from one of the great contributors to the psychosomatic literature from the medical residents of Harold Wolff at Cornell contributes volumes to what we must understand about the power of expectation. The hive formation in this hives-prone patient from a sham or simulated blow was equivalent to that from the real blow. Many of our patients live with powerful untoward reactions to psychological blows they believe will happen to them.

Ichthyosis and Hypnosis
A 16-year-old boy presented with fissured, thickened, papillomatous skin lesions, which had progressed from a mild presentation at birth and now completely covered several areas of his body. Attempted surgical excisions resulted in severe contractures. Hypnosis was undertaken. At the initial session, the suggestion was made that the lesions would clear from one arm. Within five days, a heavy dermal layer of the left arm sloughed off, leaving soft pink skin from the shoulder to the wrist ten days later. Histologic sections of the sloughed skin revealed ichthyosis. There was no positive family history. Main body parts were systematically targeted in following hypnosis sessions resulting in 50-90% clearing of different areas. There was no relapse at the end of one year.

Mason AA. A case of congenital ichthyosiform erythrodermia of Brocq treated by hypnosis. BMJ. 1952 Aug 23; 2(4781):422-31.

COMMENT: Hypnosis is often thought of when all else fails. It deserves to be used much earlier in the treatment of many conditions. It also has great utility in ancillary treatment to augment many conventional approaches.

Psoriasis and Meditation
Thirty-seven patients with psoriasis about to undergo ultraviolet phototherapy (UVB) or photochemotherapy (PUVA) were randomly assigned to either a mindfulness, meditation-based, stress reduction intervention guided by audiotaped instructions during light treatments, or to be controls receiving light treatments alone. Psoriasis status was assessed by direct inspection by unblinded clinic nurses; direct inspection by physicians blinded to the patient's random assignment; and blinded physician evaluation of photographs of psoriasis lesions. Four sequential indicators of skin status were monitored during the study: a First Response Point, a Turning Point, a Halfway Point, and a Clearing Point. Subjects in the meditation tape groups reached the Halfway Point (p=.013) and the Clearing Point (p=.033) significantly more rapidly than those in the no-tape condition, for both UVB and PUVA treatments.

Kabat-Zinn J, et al. Influence of a mindfulness meditation-based stress reduction intervention on rates of skin clearing in patients with moderate to severe psoriasis undergoing phototherapy (UVB) and photochemotherapy (PUVA). Psychosom Med. 1998; 60:625-32.

COMMENT: John Kabat-Zinn has authored numerous papers on the beneficial effect of mindfulness meditation in managing pain and other conditions. Here, a brief mindfulness, meditation-based, stress reduction intervention delivered by audiotape during conventional ultraviolet light therapy increased the rate of resolution of lesions in patients with psoriasis. One cannot imagine a more efficient use of resources than the use of a "canned" audiotape to enhance mindfulness.

Dermatomyositis and Meditation
A dermatomyositis patient used Transcendental Meditation and visual imagery for 294 days, recovering against significant statistical odds. In regression analysis between measures of arm strength, rash, and pain and application of mind-body treatments, significant relationships for both meditation (p = 0.02 to 0.001) and visual imagery (p=0.02 to 0.002) emerged. Stress had a significant negative impact on skin symptoms but not arm strength. Benefits of meditation had half-lives of 48-59 days for skin condition and no detectable decay for arm strength. Benefits of visual imagery were more transient, with half-lives four to 18 days. The effects of stress had half-lives of only one to three days.

Collins MP, Dunn LF. The effects of meditation and visual imagery on an immune system disorder: dermatomyositis. J Altern Complement Med. 2005; 11:275.

COMMENT: Since dermatomyositis is a humorally mediated immune microvasculopathy, the benefits of meditation and imagery comport with a growing body of evidence showing that these techniques influence immune system function. A few decades from now, these integrated holistic approaches will have supplanted many conventional therapies that are often likened to using a sledge hammer to kill a gnat.

Robert Anderson is a retired family physician who has authored several major books, Stress Power!, Wellness Medicine, Clinician's Guide to Holistic Medicine (McGraw Hill, 2001), and The Scientific Basis for Holistic Medicine, (6th edition 2004), available from American Health Press, holos@charter.net. Anderson founded the American Board of Integrative Holistic Medicine, is a past president of the AHMA, and former Assistant Clinical Professor of Family Medicine at the University of Washington. Dr. Anderson teaches The Art of Primary Care at Bastyr University.

Robert Anderson, MD
614 Daniels Drive NE
East Wenatchee, WA 98802-4036 USA