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Chronobiology of Skin and Skin Disorders*

Many skin functions are circadian rhythmic. The proliferation of skin cells varies by up to 30-fold in the 24 hours, being greatest at midnight and least at noon (1). In women, blood flow, amino acid content and water loss are roughly 25 percent higher at night than morning or afternoon. These rhythms persist in oral contraceptive pill users, although the rate of water loss and blow flow is greater by 10 percent while the content of amino acid is reduced by 35 percent (2). Oil production by skin glands is twice as great at noon than between 02:00 and 04:00. The skin is more acidic during sleep than around midday and its temperature is higher in the evening than morning (3,4). Skin temperature must be about a degree higher at 16:00 compared to 04:00 before sweating begins, although sweat production is greater in the afternoon than morning (5,6).

Day-Night Differences in Skin Appearance

Circadian rhythms in skin biology give rise to day-night differences in the texture, radiance and overall appearance of facial skin. A group of French women self-rated the natural appearance of their facial skin best around 10:00 and worse at night. The same women found the effect of a restorative rejuvenating cosmetic preparation (Noctosome, Lancome) depended on the time of its application. Bedtime application had a significantly better effect, particularly in women between 25 and 35 years of age and ones of fair complexion. The better effect of the nighttime application was anticipated since the product was specifically designed to work in relation to the known circadian rhythms of facial skin (7).

Circadian Rhythms in Skin Disorders

Psoriasis: Psoriasis is a chronic inflammatory disease that typically produces a bumpy, flaky condition of the skin especially areas of the scalp, elbows, knees, and back. The cell proliferation rate of the affected skin is much higher than normal skin and shows marked circadian variation (8). In the epidermis, the cell proliferation rate in areas of psoriasis is highest between 21:00 and 03:00 and least at 09:00. However, in the dermis the rhythm is reversed; cell proliferation is greatest at 09:00 and least at 03:00 (9). The inflammatory activity of psoriasis also varies greatly. It is highest at night and lowest in the morning (10).

Atopic Dermatitis: Atopic dermatitis is a chronic inflammatory disease which shows marked circadian variation in the intensity of symptoms. Itching is most intense late in the evening and may disrupt nighttime sleep (11). The day-night pattern in the severity of the itching seems to be dependent on the circadian rhythm of the skin’s sensitivity to histamine, which is highest at night (12).

Skin Cancer: The experimental study of circadian rhythms in the susceptibility of skin to tumor induction in humans is not possible. However, it can be easily done in laboratory animals by applying tumor-causing chemicals at various times of the day and night. Results show the risk of developing skin cancer differs dramatically with the time of the day of their application. Generally, tumor development is greater when contact occurs in the animal’s activity span (when the genetic or DNA material of skin cells is replicating) than in the rest period (13,14,15). These findings may imply that human beings are at greater risk when regularly coming in contact with cancer-causing agents in the late afternoon and evening.

Skin Rhythms Affect Diagnostic Allergy Tests

Allergy Testing: Most allergy tests involve the injection of a small quantity of allergens like house dust extract or different kinds of pollens just under the skin of the upper arm or back. Positive responses are shown by the development of large red areas with light-colored swelling in the center. The time of day and time of menstrual cycle allergy tests are done influence their results. The skin is much less reactive to testing early in the day than afternoon and evening. This means the severity of allergies and even exact identification of specific sensitivities may be misjudged when tests are conducted early in the day (16). Menstrual cycle variation in skin reactivity also occurs in young women not using oral contraceptives; it is greater by about 25 percent at menstruation than ovulation (17).

Tuberculosis Testing: The tuberculin skin reaction of persons who had past exposure to the bacteria is nearly 3-fold greater when testing is done at 07:00 rather than at 22:00 (18).

Circadian Rhythms of Skin Medications

The effects of cream and patch medications show circadian periodicity. Twice as much of lidocaine is taken up by the skin when applied as a cream at 16:00 than at 08:00 (19). The rate at which nicotine penetrates the skin is several-fold faster at 04:00 than in the afternoon (20). The pain-deadening effect of lidocaine lasts 2-3 times longer when injected into the skin at 15:00 than at 07:00 or 23:00; the pain-deadening effect of betoxycaine lasts 2 times longer when injected at 15:00 than in the morning or evening (21). The activity of a popular topical anti-inflammatory corticosteroid cream medication is greater when applied in the afternoon than morning (22).

Summary

1. Certain cosmetic products are fabricated for application at specific times of the day. Use them as directed to ensure they work with skin rhythms.

2. Apply skin creams and ointments that retard moisture loss at night to reduce the depth of wrinkles and give the skin a more youthful look.

3. The results of allergy and medical tests that are applied to the skin maybe strongly affected by the time of day or day of the menstrual cycle they are done.

4. There are time or day differences in the efficiency of pain and other patch medications and adjust the dosing time of their application to improve effects.

*Summary of background information for chapter 15 in:
SMOLENSKY M.H. and LAMBERG.L : Body Clock Guide to Better Health ;
H.Holt , NY., 2001

References

(1) Scheving LE. Mitotic activity in the human epidermis. Anatomical Record. 1959;135:7-20.

(2) Reinberg A, Touitou Y, Soudant E, et al. Oral contraceptives alter circadian rhythm parameters of cortisol, melatonin, blood flow, transepidermal water loss and skin amino acids of healthy young women. Chronobiology International. 1996;13:199-211.

(3) Verschoore M, Ponet M, Krebs B, Ortonne J-P. Circadian rhythms in the number of actively secreting sebaceous follicles and androgen circadian rhythms. Chronobiology International. 1993;5:349-359.

(4) Yosipovitch G, Xiong GL, Haus E, et al. Time-dependent variations of the skin barrier function in humans: Transdermal water loss, stratum corneum hydration, skin surface pH, and skin temperature. Journal of Investigative Dermatology. 1998;110:20-23.

(5) Stephenson LA, Wenger CB, OíDonovan BH, Nadel ER. Circadian rhythm in sweating and cutaneous blood flow. American Journal of Physiology. 1984;246:R321-324.

(6) Timbal J, Colin, J, Boutelier C. Circadian variation in the sweating mechanism. Journal of Applied Physiology. 1975;39:226-230.

(7) Reinberg A, Koulbains C, Soudant E., et al. Day-night differences in effects of cosmetic treatments on facial skin. Effects on facial skin appearance. Chronobiology International. 1990;7:69-79.

(8) Gelfant S, Ozawa A, Chalker DK, Smith JG jr. Circadian rhythms and differences in uninvolved and involved psoriatic skin in vitro. Journal of Investigative Dermatology. 1982;78:58-62.

(9) Rubin NH, Scheving LE. Circadian Rhythm (Letter). Journal of Investigative Dermatology. 1983;80:79-80.

(10) Pigatto PD, Radaelli A, Tadini G, et al. Circadian rhythm of the in vivo migration of neutrophils in psoriatic patients. Archives of Dermatological Research. 277:185-189,1985.

(11) Borelli S, Chlebarov S, Flach E. Atopic neurodermatitis, and the problem of its 24-hour rhythm and its dependence on weather and climate. Munchen Medicinishe Wochenschrift. 1966;108:474-480.

(12) Cormia FE. Experimental histamine pruitus. I. Influence of physical and psychological factors on threshold reactivity. Journal of Investigative Dermatology. 1952;19:21-34.

(13) Mottram JC. A diurnal variation in the production of tumors. Journal of Pathology and Bacteriology. 1945;57:265-267.

(14) Frei JV, Ritchie AC. Diurnal variation in the susceptibility of mouse epidermis to carcinogen and its relationship to DNA synthesis. Journal of the National Cancer Institute. 1964;32:1213-1220.

(15) Iversen OH, Iversen UM. A diurnal variation in the tumorigenic effect response of mouse epidermis to a single application of the strong short-acting chemical carcinogen methylnitrosourea. A dose-response study of 1, 2 and 10 mg. In Vivo. 1995;9:117-132.

(16) McGovern JP, Smolensky MH, Reinberg A. Circadian and circamensual rhythmicity in cutaneous reactivity to histamine and allergenic extracts. In: McGovern JP, Smolensky MH, Reinberg A. (eds.) Chronobiology in Allergy and Immunology. Thomas, Springfield, IL. 1977, pp. 79-116.

(17) McGovern JP, Smolensky MH, Reinberg A., Ibid.

(18) Cove-Smith JR, Pownall R, Kabler TA, Knapp MS. Circadian variation in cell-mediated immune response in man and their response to prednisolone. In: Reinberg A, Halberg F (eds.) Chronopharmacology. Pergamon, Oxford. 1979, pp. 369-374.

(19) Bruguerolle B, Giaufre E, Prat M. Temporal variations in transcutaneous passage of drugs: The example of lidocaine in children and in rats. Chronobiology International. 1991;8:277-282.

(20) Reinberg AE, Soudant, E, Koulbanis C, et al. Circadian dosing time dependency in the forearm skin penetration of methyl and hexyl nicotinate. Life Sciences. 1995;57:1507-1513.

(21) Reinberg A, Reinberg M-A. Circadian changes of the duration of action of local anaesthetic agents. Naunyn-Schmiedeberg’s Archives of Pharmacology. 1977;297:149-159.

(22) Pershing LK, Corlett JL, Lambert LD, Ponclet CE. Circadian rhythm of topical 0.05% betamethasone diproprionate in human skin in vivo. Journal of Investigative Dermatology. 1994;102: 734-739.

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