The impact of external factors on psoriasis

Psoriasis is a chronic inflammatory skin disease that affects approximately 1–3% (up to 11.4%) of the general population [1]. The etiology of psoriasis has not been fully elucidated, although in recent years there has been significant progress in therapy for this difficult-to-treat disease. Despite the effectiveness of currently available therapies, it should be remembered that the course of the disease is also influenced by many external factors: diet, exercise, stimulants, and proper skin care. This article discusses the factors influencing the severity of psoriasis that the patient can control: the regular use of emollients, elimination of infectious agents, and reduction of mechanical injuries.

Ailments such as inflammation and dry skin that patients with psoriasis experience are associated with epidermal barrier disorders [2]. This is demonstrated by, among other symptoms, increase in transepidermal water loss (TEWL), decrease in water binding properties, and reduction of lipids on the skin surface [3]. Disruption of the structure of the stratum corneum leads to the promotion of inflammation by increasing the production of proinflammatory cytokines, stimulating keratinocyte activity, increasing skin pH, increasing epidermal protease activity, or stimulating of PAR-2 receptors (protease activated receptor 2) [4]. The promotion of inflammation leads to a secondary aggravation of epidermal barrier dysfunction, resulting in a vicious cycle. Therefore, it is extremely important to counteract these processes by rebuilding the proper skin protection barrier using emollients [4, 5].

Emollients are agents for external use with moisturizing, greasing, and elasticizing properties. Their regular application on the skin increases the protective function of the epidermal barrier, normalizes keratinization, reduces local inflammation and itching, and helps restore the normal microbiome of the skin [6]. As a result, the epidermis is more resistant to environmental factors, risk of irritation and Koebner phenomenon are reduced, and the period of disease remission can be extendeded [7]. Depending on the ingredients contained in the emollients, this effect is achieved with the help of various mechanisms, such as the occlusion effect (significantly reducing TEWL), binding and retaining water within the stratum corneum, and provision of lipid or protein components that are missing in the affected stratum corneum [8] (Fig. 1).

Fig. 1

Emollients are mixtures of hydrophobic and hydrophilic components. Most often they are emulsions: oil in water (O/W) or water in oil (W/O). The most important substances included in the emollients are humectants (including urea), occlusive substances, and lipids [4] (Table 1). Emollients differ in substrates and composition of active substances. Thanks to their variety, it is possible to achieve better therapeutic effects by choosing the right care products, best suited to the patient.

The most important element in emollients is their occlusive properties, because thanks to them a layer is created on the epidermis surface that prevents water from escaping through evaporation. The water remaining in the epidermis penetrates the corneocytes, increases their turgor and volume, sealing the intercellular spaces, thereby increasing the integrity of the epidermal barrier [4]. Among occlusive substances, petrolatum is assigned a key role, which reduces water loss by up to 98%, which is a significant advantage over other oil substances (20–30% reduction) [9].

Humectants are responsible for attracting water molecules from the deeper layers of the epidermis, binding them and keeping them within the stratum corneum. One of the most commonly used humectants in emollients is urea. It is a natural moisturizing factor (NMF). Due to its hygroscopic properties, after topical application, it increases water binding by proteins and lipids, thus moisturizing the stratum corneum, and in higher concentrations, above 10%, also has keratolytic properties [7, 10]. The undoubted advantage is also the fact that as an NMF it does not cause allergies. In the study comparing emollients with 5% and 10% urea concentration, there was no difference in hydration, which indicates that the 5% concentration is sufficient [7]. Urea has also been reported to increase the penetration of glucocorticosteroids (GCS) into the skin [7]. This phenomenon is known as the “steroid-sparing effect” and is observed in patients with psoriasis and atopic dermatitis, among other disorders. In these diseases, moisturizers significantly increase the effectiveness of topical corticosteroids and can prevent exacerbations. The mechanism of action is to increase the penetration of GCS, thanks to emollients containing urea, and the maximum penetration of the drug occurs within inflammatory changes. In this way, emollients reduce the amount of GCS necessary to achieve remission of lesions, and thus they improve the safety of therapy.

Importantly, new research indicates a link between urea and gene regulation. Grether-Beck et al. report that 10% urea concentration regulates the expression of genes involved in keratinocyte differentiation, epidermal lipid synthesis (transglutaminase-1, involucrin, loricrin, and filaggrin), and the production of antimicrobial peptide (antimicrobial peptides and defensin-2) [11]. Since the maintenance of the functional epidermal barrier depends on intact keratinocytes, as well as normal lipid synthesis, these findings provide evidence of the beneficial role of urea in improving barrier function and aiding antimicrobial defense. Fluhr et al. suggested that lipid biosynthesis could be increased by topical application on of highly concentrated urea. In vitro and in vivo data shows reduction of the cells in the DNA synthesis in basal layers (by about 45%), thinning of the epidermis (by about 20%), and reduction of epidermal cells [7]. What is more, it turns out that urea also stimulates the expression of enzymes involved in ceramide synthesis and the expression of aquaglyceroprotein (AQP-3) channels in keratocytes responsible for the transport of water and glycerol, whose level in psoriasis decreases [12].

Other humectants include lactic acid or glycerin, less commonly used in patients with psoriasis. When choosing the right emollient, it should be remembered that moisturizing substances must also be included in the formulation containing occlusive substrates, otherwise water-binding formulations may increase TEWL.

In the case of a damaged epidermal barrier, as in the case of psoriasis, it is necessary to substitute deficiency components, achieved thanks to the physiological epidermal lipids that regulate the correct differentiation of corneocytes. These substances include, among others, unsaturated fatty acids, cholesterol, or ceramides. In psoriasis, ceramide synthesis necessary to maintain normal epidermal structure and skin permeability is often disturbed [13]. As epidermal layer lipids, they inhibit TEWL. In psoriatic lesions altered ceramide distribution is associated with faulty keratinocyte differentiation; skin barrier dysfunction is most likely the result of insufficient amounts of ceramide-1 [14]. Studies confirm that the use of equimolar lipid mixtures can restore the disturbed skin barrier to normal [13]. Similarly, Coderch et al. reported that topical treatment containing lipid precursors may increase the skin's natural ability to synthesize lipids [15].

Other components that may be included in the emollients are antipruritic substances such as local anesthetics (lidocaine), cannabinoid receptor agonists (N-palmitoylethanolamine), and agonists of the TRP group (capsaicin, menthol, camphor) [16]. Interesting are the reports on the effectiveness of local application of substances with immunomodulatory (β-glucan) or bacterial biofilm (xylitol) activity [4, 17]. There are reports on the effectiveness of substances such as niacinamide having anti-inflammatory effects by reducing the level of proinflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) [18] or thermal waters [19].

Emollient skin care has long been recognized as an adjuvant therapy in the treatment of mild plaque psoriasis [20, 21]. What is more, according to current therapeutic standards, it is recommended to use emollients as an adjunctive therapy in psoriasis regardless of the stage of the disease or the treatment [7, 21]. Emollients are very important in the therapeutic process because proper lubrication and hydration of the epidermis, reducing dryness and itching, reduces scratching reflexes, and thus significantly improves the patient's quality of life.

The effectiveness of using emollients in the daily care of the skin of patients with psoriasis is confirmed by numerous clinical studies. Draelos reported “an increase in skin hydration, improvement in very dry to dry or normal skin” after using emollients alone [22]. Already in 1986, Wohlrab showed that the simultaneous use of emollient and GCS significantly increases the penetration of corticosteroids [23]. Whereas Watsky et al. have shown, after examining 96 patients, that the combined use of cream with betamethasone dipropionate and emollient cream or lotion is more effective in the treatment of chronic plaque psoriasis and is associated with the steroid sparing effect [24]. In another study involving 105 patients, Seite et al. proved that after achieving disease remission using local GCS, maintenance therapy with emollients reduces the number of relapses, disease severity assessed according to the Physician Global Assessment (PGA) scale and dry skin [25]. Lacarruba et al. [26] showed that 0.1% cream with hydrocortisone valerate applied twice a day to psoriatic lesions was as effective in reducing disease symptoms as once-daily GCS in combination with emollient (20% urea, 2 % salicylic acid, 2% niacinamide).

Emollients are an important element in the prevention and support of plaque psoriasis treatment. The use of emollients and mild cleansing agents (i.e., with low pH) should be prescribed as part of the treatment in combination with other topical or systemic treatments for psoriasis. Moreover, these measures should be considered as first-line therapy in patients with limited psoriasis and in pregnant or lactating women [20]. Supportive use of basic skin care can significantly increase the effectiveness of conventional therapy, reduce the required amount of drug treatment, and improve compliance with recommendations and prolong disease remission [20].

Microorganisms such as bacteria (Streptococcus pyogenes, Staphylococcus aureus, Porphyromonas gingivalis), Candida albicans and viruses (HIV, HPV5) are important factors triggering the onset or exacerbation of psoriasis [27, 28].

Microorganisms initiate psoriatic inflammation using several mechanisms of the immune response:

patients with psoriasis have an increased production of IgA and IgG antibodies against peptidoglycan-polysaccharide streptococcal cell wall complexes [29, 30];

A characteristic symptom for active inflammation in psoriasis is the Köebner symptom, which occurs in about 25% of patients with psoriasis [79]. This symptom is most common for guttate psoriasis. Typical psoriatic lesions appear at injury sites after 10–20 days. It is believed that the injury causes increased papillary dermis blood flow, which facilitates the access of inflammatory mediators and the development of inflammation [80, 81]. Another factor leading to its development is nerve growth factor (NGF) and vascular endothelial growth factor (VEGF), released by psoriatic keratinocytes under the influence of trauma, and the role of integrin α 2β1, S100A7 (psoriasin) and S100A15 (koebnerisin) [82, 83]. It is also suggested that skin trauma rapidly induces IFNα from keratinocytes and IFN-β from plasmacytoid skin dendritic cells [80]. Recently, the role of resident memory T cells (TRM) has been emphasized, which, even after the psoriatic lesions have disappeared, remain in the epidermis and skin for many months. Under the influence of trigger factors they quickly release IL-17A and IL-22 leading to the development of psoriatic inflammation in specific locations [84].

In recent years, there has been a growing popularity of decorative tattoo or permanent makeup as body art [85, 86]. In patients with active psoriasis, the Koebner reaction is not uncommon, despite general treatment [85, 87]. One study showed that most patients developed generalized psoriasis within a few weeks and a minority developed at a tattoo site [87].

It should be noted that all trauma-related procedures, such as piercing, tattooing and even aesthetic dermatology procedures should not be performed on patients with active psoriasis [62, 88]. There are many literature reports on the long-term persistence of lesions in post-operative scar, smallpox and post-vaccination (BCG) scars, and stretch marks [80, 85]. Even low-intensity stimuli can provoke psoriatic lesions: for example, electrocardiography or wearing jewelry [89, 90].

Koebner's symptom does not have to be only a manifestation of mechanical trauma. Involvement of scalp is particularly common in children and young people in whom the severity of seborrhea is observed physiologically. This promotes the colonization of lipophilic yeast, the appearance of inflammation and itching, which causes the compulsion of scratching and leads to exacerbation of lesions. Analysis of psoriasis in 402 children (<18 y.o.) as part of the Child-CAPTURE registry (Continuous Assessment of Psoriasis Treatment Use Registry) program showed that the percentage of the affected scalp area was significantly higher in children with a positive Koebner phenomenon vs. children with a negative Koebner phenomenon (50% vs. 25% of the affected scalp, p=0,001) [91]. Scalp psoriasis was observed in 87.6% of children, of whom as much as 35.8% reported scalp psoriasis as the initial place of the disease [91].

The second form of psoriasis in which the Koebner symptom is important in the development of lesions is the inverse psoriasis in inguinal folds, under the breasts, axillary folds, and genital area, especially in obese people with insulin resistance. Humidity and heat typical of these places, along with colonization with dermatophytes, Candida albicans, and increased friction, cause psoriatic lesions [92, 93].

The last but no less important form to keep in mind is eczema psoriasis or psoriatic eczema (“eczema in psoriatico”) [94]. In people who are allergic to contact factors, an allergic reaction as a form of Koebner's symptom provokes psoriatic inflammation in a particular region. Inflammation develops, having clinical and histopathological features of psoriasis (papillomatosis and acanthosis), as well as eczema (spongiosis) [9]. Probably the created mechanism of the “vicious circle” is responsible for long-lasting persistence of the changes despite proper treatment and avoidance of allergens. Such a phenomenon is observed in patients with psoriasis, in whom exposure to irritants and allergens at work provokes lesions, which is referred to as occupational contact psoriasis [95]. In addition to allergic factors, mechanical or physical injuries, friction or contact with irritants are important in its development [96] (Fig. 2). Prevention should already apply to young people who choose their profession. They should consider giving up professions involving frequent injuries, increased humidity [96]. In this type of competition, protection (skin care program and barrier creams), the use of appropriate gloves or tools is important. If preventive actions fail, it is advisable to retrain the employee [96] (Table 2).

Fig. 2

The complexity of psoriasis requires a holistic approach to the patient and comprehensive care, not just treatment. Patients, often dissatisfied with the effects of conventional therapy, unaware of aggravating factors, tend to use alternative therapy that can lead to worsening their overall health [97]. Therefore, the task of dermatologists is to educate the patient and to encourage working together to improve the effects of therapy.