Smoking

The adverse health risks associated with smoking are well documented and this is also important for overall skin health. Smoking has been associated with the positive and negative prevalence of numerous diseases and conditions of the skin (see Table 14.2).^{15, 16}

Table 14.2 Skin diseases and the effect of smoking

Epidemiological studies have demonstrated that tobacco smoking is one of many factors that significantly contributes to premature skin ageing in addition to other factors such as age, sex, skin pigmentation, sun exposure history, and alcohol consumption.^17–20 Moreover, smoking is the causal factor of smoker’s wrinkles. Similarly, as with chronic exposure of the skin to ultraviolet radiation, tobacco also promotes manifested alterations in the structure and composition of the epidermis and dermis, similarly to that observed with photo-ageing. ^{21, 22, 23} In a recent study, tobacco smoking, but not ultraviolet exposure, was determined to be a strong predictor of skin ageing.²⁴

Although smoking may have certain beneficial effects on some skin diseases (as described in Table 14.2), it is exceptionally difficult to favour this habit which is highly damaging to overall health. Tobacco smoking is currently the leading preventable cause of disease and death in Western countries, and some of its beneficial effects on the skin are significantly dwarfed when compared to the hazard risks to health encountered with habitual tobacco use for both smokers and those who are exposed to secondary tobacco smoke, therefore it cannot be recommended.

Alcohol

The long-term consumption of alcohol in excessive quantities can damage every organ system in the body. A recent report has documented that chronic excessive alcohol consumption in alcoholics was associated with a wide range of skin disorders that included urticaria, porphyria cutanea tarda, flushing, cutaneous stigmata of cirrhosis, psoriasis, pruritus, seborrheic dermatitis and rosacea.²⁵

Life stressors

Psycho-emotional stressors have long been expected to exacerbate or even trigger allergic diseases such as atopic dermatitis (see Figure 14.1).^{26, 27}

Figure 14.1 Stress axes exacerbating inflammatory skin diseases/conditions

Psychodermatological or psychocutaneous disorders are conditions resulting from the interaction between the mind and the skin. There are 3 major groups of psychodermatological disorders recognised; psychophysiologic disorders, psychiatric disorders with dermatologic symptoms, and dermatologic disorders with psychiatric symptoms.²⁸

A number of human studies have reported associations between personality traits and psychic disturbances such as stress perception, anxiety, or depression and atopic dermatitis severity or even onset.^29–32

Depression in dermatology patients often is multi-factorial in its cause. Genetic factors, psychosocial stressors, age of patients at onset of skin disease, body areas involved, physical discomfort (i.e. pruritus, pain, or burning), and clinical severity all are potential contributors.

The nature of the mechanisms that link stress and exacerbation of skin inflammation remain largely unknown. Recent studies suggest psycho–neuro–immunologic factors and emotional stressors are important in its evolution (Figure 14.1).³³

The established explanation is that immune balance is altered by activation of 2 stress axes; namely, activation of the hypothalamic–pituitary–adrenal (HPA) axis that raises cortisol levels, and activation of the sympathetic nervous systems which raises adrenaline levels (Figure 14.1).³⁴ This mechanism of activity has been further investigated in wound-healing experiments. For more than a decade it has been extant that stress/stressors (which can range in magnitude and duration) can significantly slow wound healing.^{35, 36}

Itch is a major feature of many skin diseases, which adversely affects patient’s quality of life. Recently it was shown that cognitive factors, such as helplessness and worrying, and the behavioural response of scratching were indicated as possible worsening factors. This is consistent with overall findings that implicate a biopsychosocial model for the itch sensation.³⁷

Environmental insults

There is increasing evidence that over-exposure of the skin to damaging environmental influences such as ultraviolet radiation, climatic determinants, chemicals and infections can significantly disrupt skin homeostasis.

Sunlight/ultraviolet (UV) exposure

Sunlight exposure produces a variety of adverse cutaneous effects, such as erythema, photosensitivity, and immunologic alterations, that represent acute events.

Among harmful environmental factors that contribute to extrinsic ageing, are the long-term effects of repeated exposure to UV that leads to carcinogenesis and photo-ageing as long-term consequences.

Contact allergy and the skin

Contact allergy caused by ingredients in cosmetic products is a well-known problem (see Table 14.3). In the US it has been reported that approximately 6% of the general population has a cosmetic-related contact allergy, mainly caused by constituent compounds such as preservatives or fragrances in the cosmetic product.^46–49

Table 14.3 Important allergens for consideration in cosmetics

(Source: data adapted and modified from Ortis, Yiannias⁴⁹ and Orton, Wilkinson)⁵⁰

Cognitive behavioural therapy (CBT)

It has been reported that CBTs deal with dysfunctional thought patterns (cognitive) or actions (behavioural) that can damage the skin or can interfere with dermatologic therapies.⁵² CBT-responsive skin disorders include:

Moreover, it has also been reported that addition of hypnosis to CBT can facilitate aversive therapy and enhance desensitisation and other CBTs.

Hypnosis

Dermatologic conditions that responded to hypnosis are presented in Table 14.4.

Table 14.4 Skin conditions responsive to hypnosis^{54, 55}

The mechanism by which hypnosis produces improvement in symptoms and in skin lesions is not completely understood. Hypnosis may help regulate blood flow and other autonomic functions not usually under conscious control. The relaxation response that accompanies hypnosis may alter neurohormonal systems that in turn regulate many body functions.⁵³

Hypnosis may be used to help control harmful habits, such as scratching. It also can be used to provide immediate and long-term analgesia, reduce symptoms such as pruritus, improve recovery from surgery, and facilitate the mind–body connection to promote healing of the skin.

Biofeedback

Biofeedback can be a training program in which a person is given information about physiological processes (e.g. heart rate or blood pressure) that is not normally available with the goal of gaining conscious control of them.

Instrumentation that can measure galvanic skin resistance, skin temperature, or other manifestations of autonomic nervous system activity in the skin and then display it in a visual, auditory, or kinesthetic mode gives the individual sensory biofeedback. With training, individuals may learn consciously how to alter autonomic nervous system associated responses for skin problems, and with enough repetition may establish new habit patterns.⁵⁶

Early reports show that biofeedback of galvanic skin resistance for hyperhidrosis and biofeedback of skin temperature for dyshidrosis and Raynaud’s syndrome can be effective.^{57, 58} When biofeedback was combined with hypnosis the efficacy was reported to be enhanced.

Psychological/educational interventions

Food sensitivities

Population-based assessments of food allergy are scarce.⁷¹ Despite the difficulties in obtaining firm population-based data on the prevalence of food allergies, there has been evidence for a general increase in food allergies, documented best for peanut, sesame, and kiwi, that could be attributed to environmental and dietary factors including reduced immune stimulation from infection; that is, the hygiene hypothesis. There have been changes in the components of the diet, including antioxidants, fats, and nutrients such as vitamin D, as well as the use of medications.^{72, 73, 74}

Addressing food allergies (food sensitivities), is an important nutritional elimination procedure. These are reactions to foods that are far broader than the classical reactions such as urticaria, itchy eyes, and rhinitis. They include any inflammatory manifestation as well as a variety of neurological and other non-inflammatory conditions.⁷⁵

Food hypersensitivity can be the first stage in the development of allergic diseases, such as atopic eczema.⁷⁶ It has been reported that clinicians have found that elimination of specific foods found by food challenge to elicit symptoms can lead to significant improvement in eczematous symptoms.⁷⁷ There is a vast amount of scientific literature claiming that dietary elimination causes improvement of atopic eczema in some cases. However, a recent systematic review portrays the evidence available as weak and the issue of exclusion diets in atopic eczema remains contentious.⁷⁸

Diets

The eradication from the diet of chemicals is an effective way to eliminate potential skin diseases that are aggravated by chemicals. The Palaeolithic diet has addressed such issues in the scientific/medical literature.⁷⁹ The essential of this diet involves the consumption of those foods that have a low glycemic index (GI) and consists of meat, fish, vegetable, fruit, roots, and nut consumption and excludes grains, legumes, dairy products, salt, refined sugar, and processed oils. Adherence to this diet in turn minimises the consumption of pesticides, petroleum-based fertilisers, preservatives, artificial flavourings, and artificial food colours.

Vitamins

High doses of vitamin A should be avoided (for used cautiously with contraception) in women who may wish to conceive due to potential teratogenicity effects on the fetus.

There have been approximately 2500 new retinoid compounds synthesized.⁹⁰ Vitamin A stimulates various aspects of wound repair. It affects fibroplasia, collagen synthesis, epithelialisation, and angiogenesis and is involved in inflammatory processes with specific effects on macrophages, which play a dominant role in wound healing.⁹¹

Retinoids already approved for the treatment of dermatological conditions include:

The treatment of disorders of abnormal keratinisation, such as Darier’s disease and Kyrle’s disease, has been ascribed to etretinate and acitretin which are established in Europe for the treatment of Darier’s disease and ichthyosis, especially the nonbullous congenital type.⁹² In the US, however, these compounds have only been approved by the FDA for psoriasis. Palmoplantar keratoderma also responds well to these drugs, but treatment is justified only in severe cases.⁹³ Pityriasis rubra pilaris has been treated successfully with isotretinoin in the past,⁹⁴ but now acitretin seems to be the drug of choice in Europe.

It has been reported that retinoids possess certain properties that make them good candidates for cancer prevention and therapy. They are metabolically active compounds that can induce changes in cellular function and appearance, and that can modify the expression of a variety of genes involved in cell growth and differentiation.⁹⁵

Topical tretinoin, at concentrations of 0.05% and 0.1%, have been used in combination with hydroquinone and corticosteroids for the treatment of melasma.⁹⁶ Isotretinoin, etretinate, and acitretin have all been used in recalcitrant cases of lichen planus and cutaneous lupus erythematosus with good results.⁹⁷ Erythropoietic protoporphyria responds to treatment with beta-carotene.

The use of retinoids has been significantly more successful in skin cancer prevention in high-risk patients. Treatment of patients suffering from xeroderma pigmentosum with 2mg/kg/day isotretinoin for 2 years resulted in an average reduction of 63% in the number of skin cancers compared with the 2-year interval before intervention.⁹⁸

Furthermore, patients with nevoid basal cell carcinoma (BCC) syndrome have been reported to benefit from the same dose of isotretinoin treatment, as there was a rapid decrease in the number of new BCCs.⁹⁹ Also transplant recipients are also a high-risk group for the development of skin cancer. It has been reported that etretinate at a dose of 50mg/day and acitretin at 30mg/day reduced the incidence of skin cancer in renal transplant recipients.¹⁰⁰ An additional group that is appropriate for skin cancer chemo-prevention includes patients with premalignant lesions and a history of 1 or a few skin cancers. Vitamin A (25 000IU per day) appears to benefit patients with many actinic keratoses and a history of fewer than 3 skin cancers¹⁰¹ but not those with 4 or more cancers.¹⁰² Albeit retinoids have shown promise as skin cancer chemo-prevention agents, their benefits do not persist after discontinuation of treatments. It should be also noted that long-term use is associated with possible severe side-effects and therefore careful patient monitoring is required.

Researchers have reported favourable responses to isotretinoin and etretinate in patients with multiple keratoacanthomas.^{103, 104} Other studies with patients with SCC were also reported to be successfully treated with oral isotretinoin.¹⁰⁵ However, in most cases responses of advanced skin cancers to retinoids have been largely disappointing.

Vitamin C (Ascorbate)

Ascorbate has a known catalytic role and hence is a co-factor for a number of enzymes. Most cutaneous manifestations of ascorbate deficiency (scurvy) can be attributed to its role as a cofactor for prolyl and lysyl hydroxylase. Ascorbate plays a critical role in wound healing.¹⁰⁶

Moreover, ascorbate has the potential to act as a photo-protectant. Skin damage caused by UV radiation includes acute events like sunburn and photosensitivity reactions as well as long-term exposure events that can lead to photo-ageing and skin cancer. It is important to note that ascorbate levels of the skin can be severely depleted after UV irradiation.¹⁰⁷

Vitamin C has been reported to protect the skin from UVA-mediated and UVB-mediated phototoxic reactions,^{108, 109} and when it is combined with a UVA sunscreen, a greater than additive protection is noted. Reduced sunburn reaction, measured by minimal erythema dose and cutaneous blood flow, has also been reported in human studies after systemic administration of 2g vitamin C and 1000IU of vitamin E for 8 days.¹¹⁰ Orally administered vitamin C has been shown to protect mice from UV induced dermal neoplasms. These studies have reported that increases in dietary vitamin C decreased the incidence and delayed the onset of malignant lesions.^{111, 112}

Numerous reviews have consistently reported on studies that have demonstrated that ascorbate can be photo-protective and aid skin repair.^113–118

Vitamin E

Vitamin E includes tocopherols and tocotrienols and is a putative antioxidant with no known catalytic roles. However, given that it is a fat soluble (lipophilic) vitamin, it may have important intracellular metabolism modifying functions.¹¹⁸

In contrast, a study by Werninghaus and colleagues¹²² has reported that daily supplementation of healthy individuals with 400IU of natural-source vitamin E for up to 6 months did not significantly alter UV-induced skin damage, as assessed by minimal erythema dose and sunburn cell formation.

A recent review¹²³ has cited numerous topical studies (laboratory animal and human studies) that have demonstrated that vitamin E application prior to UV exposure significantly reduced:

Early uncontrolled trials, using topical application of vitamin E have demonstrated relief of pain and aided in the healing of oral herpetic lesions (gingivostomatitis or herpetic cold sores). In 2 studies, the affected area was dried and cotton saturated with vitamin E oil (20 000–28 000IU per ounce) was spread over the lesions for 15 minutes.^{124, 125} Pain relief was noted within 15 minutes to 8 hours, and the lesions regressed more rapidly than normal. In some cases, a single application was beneficial, but large or multiple lesions responded better when treated 3 times daily for 3 days. In a further study of 50 patients with herpetic cold sores, the content of a vitamin E capsule was applied to the lesions every 4 hours. The results of this study¹²⁶ demonstrated prompt and sustained relief of pain and the lesions healed more rapidly than was otherwise expected.

When assessing studies on the use of vitamin E, the natural versus the synthetic form of the vitamin needs to be taken into consideration. There are numerous studies that have reported on negative effects and these studies have utilised the synthetic form of the vitamin.

Vitamin D

The essential biochemistry of vitamin D3 begins with it being one of the major regulators of calcium homeostasis. It is absorbed from the gut but is also synthesized in the skin following exposure to UV light. It is activated by hydroxylation first in the liver to form 25-hydroxyvitamin D3 (25OHD3) and then in the kidneys to form a variety of metabolites, the most potent of which is 1,25(OH)2D3.

B Group Vitamins

The vitamin B complex consists mainly of thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12) and folate (vitamin B9). Also vitamins of the B complex are not widely used for the treatment of dermatological disorders.

Sporadic studies have been reported in the scientific literature which investigated the topical application of specific B group vitamins to the skin. Topical nicotinamide, the physiologically active form of niacin, was reported to have efficacy comparable to that of topical clindamycin in the treatment of acne vulgaris¹³⁸ and has produced good results in patients with necrobiosis lipoidica.¹³⁹ In combination with tetracycline, nicotinamide was successful in 1 patient with dermatitis herpetiformis.¹⁴⁰ The combination of nicotinamide and tetracycline has also been proposed as an alternative to systemic steroids in the treatment of bullous pemphigoid.¹⁴¹ The success of nicotinamide in the treatment of these skin disorders perhaps is attributable to a re-regulation of the inflammatory state of the skin.

Other B-complex vitamins that have been used in the treatment of skin disorders include pyridoxine, for the management of erythropoietic protoporphyria,¹⁴² and vitamin B12, in combination with folic acid, for the treatment of vitiligo.¹⁴³

Zinc

Zinc is an essential component of many metallo-enzymes involved in cell activities such as protein synthesis DNA and RNA replication, and cell division and it is crucial for the normal development of the skin.¹⁴⁴

Selenium

Selenium has a catalytic role, as a component of glutathione peroxidase, in the regulation of oxygen metabolism, particularly in catalysing the breakdown of H₂O₂. Studies with laboratory animals have implicated selenium deficits in skin cancer tumorigenesis.¹⁶² Human studies however have proven controversial.

Alpha-hydroxy acids (AHAs)

AHAs are weak organic acids that can be found in fruits, milk sugars, and plants. Glycolic acid (from sugar cane) and lactic acid (from milk) are 2 types of AHAs found in over the counter acne products, but these AHAs are often chemically synthesized rather than isolated from natural sources. Moreover, fruit acids are a special group of organic acids found in many natural foods and consist of citric, gluconic, gluconolactone, glycolic, malic and tartaric acids.

Salicylic acid

Salicylic acid is a phytohormone, a plant product that acts like a hormone by regulating cell growth and differentiation. It is a beta hydroxy acid that is chemically similar to the active component of aspirin. It functions as a topical desquamating agent, dissolving the intercellular cement holding the cells of the stratum corneum together. It is used as a topical keratolytic agent.

Coenzyme Q₁₀ (CoQ₁₀)

CoQ₁₀ is ubiquitous in human tissues, although its level is variable. The level of CoQ₁₀ is highest in organs with high rates of metabolism such as the heart, kidney and liver.¹⁷⁷ Compounds such as coenzyme Q₁₀ have been reported to play an increasing beneficial role in skin care. The benefits range from skin conditions such as acne and psoriasis to protection against environmental insults.¹⁷⁸

Lipoic acid

Low molecular weight compounds such as lipoic acid have also been reported to be protective low molecular weight antioxidants through a diet rich in fruits and vegetables or by direct topical application for photo-damaged skin.¹⁸² However, studies investigating the efficacy of lipoic acid in treating photo-damaged skin are lacking.

Probiotics

A recent review has documented the numerous experimental studies that have found that probiotics exert specific effects in the intestinal lumen and on epithelial cells and immune cells with anti-allergic potential.¹⁸³ The review also documented that the barrier function and the innate immune system of the skin indicates that the skin’s microbiota have a beneficial role, much like that observed with the gut microflora.¹⁸⁴

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