Psoriasis: etiology, pathogenesis and principles of treatment

Ekaterina Bardova , Ph.D., Department of Dermatovenerology, NMAPE named after. P. L. Shupika (Ukraine)

FROM ANTIQUE TO THE PRESENT

The history of diagnosis and treatment of psoriasis dates back to ancient times, but for most of its “biography” psoriasis was called leprosy, with which it was often confused. Thus, the biblical reference to such leprosy, which, most likely, was precisely psoriasis, is found in the Fourth Book of Kings as “the leprosy of Naaman,” and the phrase “... and he came out of him white from leprosy, like snow” makes many researchers believe this is one of the first mentions of the characteristic peeling of the skin in psoriasis. Hippocrates described a series of progressive exanthems, using the terms “leprosy” (“scaly”) and “psora” (“itchy”), which were probably just psoriasis and leprosy.

Most scientists agree that the first clinical description of psoriasis was given by Aurelius Celsus in his work De re medica. The description of one of the diseases, which he called “impetigo,” contains the phrase “...forms various figures and scales falling from the surface of the skin.” The term “psoriasis,” which comes from the Greek word for “itch,” was first used by Galen. But the historical irony is that the disease he described as psoriasis, an itchy rash on the eyelids and scrotum, is now called seborrheic dermatitis.

The identification and classification of a separate skin disease characterized by the appearance of scaly plaques, which is called “psoriasis,” has remained a task for modern scientists. The first among European dermatologists to describe and study psoriasis as a separate disease was Robert Willan, who in 1808 published the first color tables of skin lesions in a disease that is characterized (in his words) as “scaly psora in various manifestations,” hence the term “psoriasis.” " Nevertheless, Wallan continued to call the disease “leprosy,” although the descriptions of this “leprosy” are so vivid and detailed that there is no doubt that it is psoriasis and not leprosy: “... they have a round or oval shape and covered with dry scales, surrounded by a red border. The accumulating scales form a thick crust.”

Continuing the debate over nomenclature, Ferdinand Hebra (1816–1880), a famous Austrian dermatologist, proposed eliminating the term “leprosy” in favor of the disease name “psoriasis.” His opponents, such as Milton, strongly disagreed: “The sooner the word psoriasis is eliminated, the better. I would like to suggest everyone to avoid the name "psoriasis".

Throughout the 19th century, the symptoms of psoriasis were described by scientists whose names are now forever associated with this disease:

• Heinrich Auspitz (1835–1886), a student of Hebra, identified pinpoint bleeding that occurs when the film is removed from psoriatic plaques, which is now known as the “Auspitz sign.”
• In 1872, Heinrich Koebner described the phenomenon of psoriasis rashes appearing on recently injured areas of the skin. In an address to the Silesian Society of National Culture on psoriasis, he gave examples of the appearance of a fresh psoriatic rash on skin injured by a horse bite and a tattoo. This phenomenon is now called the “Koebner phenomenon.”
• The histology of psoriasis was also studied. Australian pathologist W. J. Munro (1838–1908) noted accumulations of neutrophils in the stratum corneum of psoriatic plaques. Today, these “Munro microabscesses” are considered one of the defining histological characteristics of psoriasis.

Psoriasis still remains an urgent problem in clinical dermatology due to its high prevalence, frequent resistance to therapy, an increase in the frequency of severe disabling forms of the disease and socio-psychological maladjustment of patients.

In the modern world, psoriasis is considered as a severe chronic multifactorial disease, characterized by hyperproliferation of the epidermis, erythematous-squamous rashes, a staged course and often pathological changes in various organs and systems.

According to the International Federation of Psoriasis Associations, the prevalence of psoriasis in the world ranges from 1.2–5%, and the average prevalence is about 3% of the general population. In Ukraine, this figure is about 3%, which in absolute numbers will be about 1,200,000 of the population. Annual losses associated with the incidence of psoriasis amount to millions of dollars. In addition, there is a steady increase in morbidity and disability in severe forms of psoriasis, so the epidemiological, clinical and social significance of psoriasis in modern conditions is difficult to overestimate.

The disease can occur in both childhood and adulthood. Without treatment or with improper treatment, psoriasis causes damage to the joints and visceral systems of the body, and is often accompanied by secondary microbial skin lesions and superinfection.

Psoriasis significantly reduces the patient’s quality of life, so the problem is relevant not only for dermatologists, but also for doctors of various clinical specialties.

Along with this, there is a constant increase in morbidity, especially in children and young people, and the proportion of severe and resistant cases of the disease is increasing.

The prevalence of psoriasis in Ukraine has been steadily increasing over the past decades. The variability of the clinical course, a significant number of forms, complex pathogenesis, ambiguity of therapeutic interventions and their diversity create objective difficulties for the diagnosis and treatment of psoriasis facing specialists.

ETIOLOGY AND PATHOGENESIS

Psoriasis has a multifactorial etiology. Genetic factors and environmental influences are closely interrelated in the pathogenesis of the disease.

The main trigger factors with different levels of evidence of a cause-and-effect relationship include:

• physical damage to the integrity of the skin, trauma: scratches, surgical incisions and infections (isomorphic Koebner reaction);
• infectious, parasitic diseases, including purulent-inflammatory ones, and microbial carriage: tonsillitis, pharyngitis, osteomyelitis, HIV (AIDS), viral hepatitis;
• psychosomatic/somatopsychic factors, stress;
• metabolic disorders: metabolic syndrome, hypocalcemia, disorders of hormonal homeostasis during the perimenopausal period;
• biochemical changes: cyclic nucleotide changes (increased levels of cGMP, decreased levels of cATMP), increased levels of arachnoidic acid and the level of its metabolites, activation of lipid peroxidation, increased levels of polyamines, increased levels of proteinase and its inhibitors, increased levels of calmodulin;
• immunological changes: T-helpers play a leading role; keratinocytes secrete interleukins IL-1, IL-8, which are chemotactic; Langerhans cells produce cytokines that stimulate mitosis;
• medications (beta-adrenergic receptor antagonists, lithium salts, chloroquine, interferons, ACE antagonists, non-steroidal anti-inflammatory drugs, corticosteroids) can worsen the course of psoriasis or cause complications;
• intoxication (alcohol, nicotine, household detergents) and poor nutrition;
• special local factors (swelling of the legs, venous stasis).

COURSE OF THE DISEASE

In the clinical picture of psoriasis, attention should be paid to the monomorphic nature of the papular psoriatic rash, which is located symmetrically in most patients, mainly on the extensor surfaces of the extremities. However, psoriasis can affect any part of the skin: nails, scalp and skin of the musculoskeletal system. Dermatosis has a chronic relapsing course.

The primary element is the epidermodermal papule . The psoriatic papule has a pink color (Pilnov's symptom) of varying intensity: fresh elements are brighter in color (up to red), older elements are faded. The shape of the papules is flat, the surface is rough, covered with silver-white pityriasis-like or fine-plate scales, which are easily removed when scraped. On fresh papules, the scales are located in the center, with a narrow bright rim remaining along their periphery. Then the peeling intensifies, occupying the entire surface of the element. Initially, psoriasis papules have regular rounded outlines and a diameter of 1–2 mm. As the process progresses, psoriatic papules spread around the periphery, enlarge, and form plaques, often reaching large sizes and having bizarre outlines. Often, the same patient simultaneously exhibits papular elements of various sizes and psoriatic plaques.

Difficulties in diagnosis

For the diagnosis of psoriasis, a number of symptoms are valuable, which include the psoriatic triad and the isomorphic reaction, or Koebner phenomenon.

The psoriatic triad includes three sequential phenomena that occur when a psoriatic papule is scraped:

• abundant peeling with silvery-white scales, reminiscent of stearin (the “stearin spot” phenomenon);
• the appearance after removal of the scales of a wet shiny surface (the phenomenon of terminal, or psoriatic film);
• drip bleeding that occurs with further scraping is the phenomenon of pinpoint bleeding (Auspitz), or “blood dew” (A. G. Polotebnov).

The pathohistological essence of psoriasis (parakeratosis, acanthosis, papillomatosis) underlies these phenomena.

An isomorphic reaction in psoriasis (Koebner phenomenon) consists of the development of psoriatic rashes on areas of the skin exposed to irritation by mechanical and chemical agents (scratches, injections, scratching, cuts, friction, irradiation, burns, etc.). After a skin injury, an average of 7–9 days pass before the development of an isomorphic reaction, although cases of the reaction occurring in both shorter (3 days) and longer (21 days) periods have been observed.

Psoriasis may be accompanied by itching (usually in a progressive stage) of varying intensity and a feeling of tightness of the skin.

Depending on the size and nature of the eruptive elements, the following clinical forms of psoriasis are distinguished:

• pinpoint psoriasis (psoriasis punctata) – characterized by papules the size of a pinhead or the size of a millet grain;
• guttate psoriasis (psoriasis guttata or lenticularis) – elements reach the size of a lentil grain;
• coin-shaped psoriasis (psoriasis nummularis) – rashes 3–5 cm in size;
• lichenoid psoriasis (psoriasis lichenoides spinulosa) – manifested by lichenoid papules;
• papillomatous psoriasis (psoriasis papillomatosa, seu verrucosa) – papillomatous growing lesions;
• ring-shaped psoriasis (psoriasis annularis, seu orbicularis) – elements form rings;
• psoriasis gyrata – rashes are arranged in the form of arcs and garlands;
• figured, or geographic psoriasis (psoriasis jigurata, seu geographica) – the outlines of the lesions resemble a geographical map;
• seborrheic psoriasis (psoriasis seborrheica) – observed when the rash is localized in places characteristic of seborrhea, it is small pinkish flaky spots;
• psoriasis inveterata, eczematisata - “old”, eczematized psoriasis, etc.

Diffuse peeling or sharply limited layers of scales may occur on the scalp , often involving the surrounding, smooth skin. However, hair never falls out in the affected area. Very often, the onset of psoriasis begins with the scalp (in about 70% of cases), and is combined with rashes on other areas of the skin in more than 60% of cases. Often the damage to the scalp is focal in nature, located on the back of the head, temples, and crown in the form of clearly raised plaques.

Psoriasis of the genital area accounts for 1/4 of cases (more often among girls), and in the area of large folds it usually occurs as an intertriginous process, but with sharp boundaries and infiltration in the lesions.

The main localization occurs on the limbs (up to 85% of cases) and torso (more than 70%). When the palms and soles are affected (psoriasis palmarum et plantarum), extensive round, scaly, grooved plaques develop in 8–10–12% of cases.

Psoriatic erythroderma is a generalized variant of the disease affecting all or almost all of the skin. Against the background of the presence of typical signs of psoriasis, erythema becomes an important characteristic: the skin is bright red, infiltrated, swollen, and hot to the touch. Peeling differs from peeling in the stationary form of psoriasis in that instead of tightly fitting silver-white scales, superficial peeling is observed. Also characteristic is damage to the nail plates, even in the form of onycholysis. Patients complain of itching, burning and a feeling of tightness of the skin. Sometimes psoriatic erythroderma is accompanied by dyspeptic disorders, enlarged lymph nodes, and symptoms of intoxication - fever, general weakness, headache, and lack of appetite.

PRINCIPLES OF TREATMENT

Treatment of psoriasis should include the following sections:

• basic therapy (medical skin care);
• topical therapy (medicinal forms for external use);
• phototherapy;
• systemic therapy.

It is advisable to distinguish three degrees of severity of psoriasis. It is obvious that treatment of a disease with a mild course can be limited exclusively to basic therapy and topical agents, while psoriasis with a severe course, especially with damage to the joints, will require systemic treatment. However, modern approaches to the treatment of psoriasis do not exclude the use of topical therapy (in particular, glucocorticosteroids) even for severe psoriasis, and phototherapy, especially in the local version, can be used in patients with non-common mild psoriasis.

Basic therapy

Basic skin care products that are recommended for patients with psoriasis include moisturizing creams, emulsions, lotions, and balms. There are a large number of cosmetics that have a moisturizing and softening effect; they may differ in lipid content and their composition. The selection of the optimal product for a particular patient is carried out by a doctor, taking into account the current needs and condition of the patient’s skin.

Emollients can be supplemented with agents of specific action. In particular, it is advisable to prescribe keratolytic agents to eliminate hyperkeratosis. This allows not only to restore the elasticity of the skin, but also to increase the effectiveness of further treatment with topical agents and especially phototherapy, since hyperkeratosis will act as a protective screen from ultraviolet radiation.

For keratolytic purposes, products containing salicylic acid 2–5%, urea preparations 10–30%, as well as other preparations mainly represented by organic acids (lactic, mandelic, etc.) are most often used.

Topical therapy

For topical treatment of psoriasis, topical glucocorticosteroids (GCS) are used, topical calcineurin inhibitors, as well as topical analogues of vitamin D ₃ .

Topical corticosteroids have been and remain the most effective and widespread drugs for the topical treatment of psoriasis.

Basic principles of topical therapy with GCS:

• short-term use of strong TGCS (strength class III) is preferable before long-term use of weak TGCS (I–II CSAS);
• it is preferable to use non-fluorinated THCS, especially on thin skin of the face, genitals, folds;
• it is optimal to prescribe long-acting drugs that can be used once a day, this will increase compliance and, as a result, the effectiveness of therapy;
• at the beginning of treatment, TGCS drugs are prescribed daily, with a gradual decrease in the intensity of therapy (switching to use every other day, then 2 times a week), which will minimize the possible withdrawal effect;
• when choosing a form of TGCS, one should be guided by how acute the disease is in the patient: for example, in the case of infiltrated elements of the rash in the chronic course of psoriasis, it is recommended to give preference to ointment forms, in case of an acute inflammatory process - creams or emulsions;
• for application to sensitive skin of the face, genitals and folds, drugs of class II–III should be used in a short course: the duration of application is less than on the torso or limbs;
• for the scalp, THCS can be used in the form of an emulsion or solution;
• The dosage of the ointment/cream should be selected based on the “fingertip dose” rule;
• Do not use more than 30 grams of the dosage form per week;
• Treatment monitoring should be carried out by a doctor regularly and without fail, which will increase the effectiveness of treatment and avoid possible side effects.

Topical calcineurin inhibitors (TCIs) are a relatively new group of drugs, which includes two drugs - Pimecrolimus (cream 1%) and Tacrolimus (ointment 0.1% for adults and 0.03% for children from 2 to 14 years ).

TIC is applied to the affected areas 1-2 times a day. The duration of the course of therapy is 2–4 weeks and, if necessary, more, as prescribed by the doctor. Since TICs do not have atrophogenic effects, they can be used for a long time.

The most effective drugs in this group are in the case of psoriasis of the folds, on the skin of the face, and genitals. They combine well with emollients and TGCS, with which they can be used sequentially or simultaneously.

_Vitamin D3 analogues (calcitriol and calcipotriol) are drugs for local treatment of psoriasis, which have an anti-cytokine effect associated with the inhibition of pro-inflammatory cytokines, in particular IL-8, and stimulation of the synthesis of anti-inflammatory cytokines, in particular IL-4, IL-10. In addition, this group of drugs has an antiproliferative effect and promotes cell differentiation in psoriasis.

Calcipotriol is available for clinical use as a cream, ointment, or solution, and calcitriol is available as an ointment. There is also a fixed combination of calcipotriol with betamethasone, which is recommended for initial treatment of plaque psoriasis. Only Calcitriol ointment is registered in Ukraine.

The simultaneous use of vitamin _D3 derivatives with salicylic acid is not recommended, as this leads to a decrease in the clinical effect. In case of simultaneous use of calcium supplements and vitamin D derivatives _3, serum calcium levels should be checked regularly.

Phototherapy

Provides for the use of artificial sources of ultraviolet radiation for therapeutic purposes. Natural phototherapy (heliotherapy) has been empirically used thousands of years ago in ancient Egypt and India by rubbing or ingesting plant extracts (such as Ammi Majus, Psoralea Corylifolia) that contain natural photosensitizers into the skin, followed by exposure to the sun. But even today there is the practice of natural phototherapy, mainly in the resorts of the Dead Sea, in India, and South America.

In Ukraine, heliotherapy is used on the shores of the Azov Sea and the salt lakes of Transcarpathia.

In 1989, it was proposed to use narrow-band UVB phototherapy with a spectral characteristic of 311 +/– 2 nm for phototherapy of a number of diseases.

In 1997, an excimer laser with a spectral characteristic of 308 nm was first introduced for phototherapy of limited forms of psoriasis and other diseases.

Systemic therapy

For systemic therapy, drugs with immunosuppressive and cytostatic effects, as well as drugs from the retinoid group, are used.

COSMETOLOGICAL PROCEDURES AND PSORIASIS

Carrying out any cosmetic intervention is appropriate only during the inter-relapse period and using lines of professional cosmetics intended for sensitive skin.

It is also necessary to remember that the sensitive skin of patients with psoriasis is characterized by increased permeability, which is important to consider when carrying out chemical peels . In this case, it is recommended to use glycolic and lactic acids only in gel form with a minimum exposure time and with intervals between treatments of up to 10 days.

You should also limit or completely eliminate procedures associated with damage to the stratum corneum of the epidermis, such as microdermabrasion, medium peeling, etc.

In case of frequent relapses, it is better to abandon injection techniques in favor of therapeutic and physiotherapeutic procedures: laser therapy, light therapy, ultraviolet irradiation, magnetic therapy, microcurrents, non-injection mesotherapy, electroporation, ultrasound therapy, oxygenation, etc.

First published in Les Nouvelles Esthetiques 2015/№1