Understanding Psoriasis Symmetry: The Role of Neuropeptides and Stress

18.06.202313.06.2023 by alexxlab

How does stress impact psoriasis development. What is the connection between symmetry and psoriasis lesions. Can neuropeptides play a role in psoriasis pathogenesis. Why do psoriatic plaques often appear symmetrically on the body. What evidence supports the involvement of substance P in psoriasis.

Содержание

The Intriguing Link Between Stress and Psoriasis

Psoriasis, a chronic autoimmune skin condition, has long puzzled researchers and clinicians alike. One of the most intriguing aspects of this disease is its apparent connection to stress and its tendency to manifest in symmetrical patterns on the body. A groundbreaking study by Farber et al. published in the Journal of the American Academy of Dermatology in 1986 shed light on these phenomena, proposing a novel hypothesis involving neuropeptides.

Why does stress seem to trigger psoriasis flare-ups? The researchers observed that stress often precedes psoriasis exacerbations, suggesting a potential causal relationship. This observation led them to investigate the possible mechanisms linking psychological stress to skin inflammation.

Decoding the Symmetry of Psoriatic Lesions

One of the most striking features of psoriasis is the symmetrical distribution of lesions on the body. But what causes this symmetry? The study authors noted that this pattern might indicate the involvement of the nervous system in the disease process. After all, the nervous system is organized symmetrically in the body, potentially explaining the mirrored appearance of psoriatic plaques.

The Nervous System-Skin Connection

How does the nervous system influence skin inflammation? The researchers proposed that neuropeptides, small protein-like molecules used by neurons to communicate with each other and with other cells, might play a crucial role. These molecules could potentially act as mediators between stress signals in the brain and inflammatory responses in the skin.

Substance P: A Key Player in Psoriasis Pathogenesis?

Among the various neuropeptides, substance P emerged as a particularly interesting candidate in the context of psoriasis. Why did substance P catch the researchers’ attention? Previous studies had already implicated this neuropeptide in inflammatory processes, making it a plausible link between stress and skin inflammation.

The Multifaceted Role of Substance P

What functions does substance P perform in the body? Substance P is known to:

Transmit pain signals
Regulate blood flow
Modulate immune responses
Stimulate the release of other inflammatory mediators

These diverse functions make substance P a potential key player in the complex pathogenesis of psoriasis.

A Hypothesis Uniting Stress, Symmetry, and Skin Inflammation

Based on their observations and existing evidence, Farber et al. proposed a hypothesis that could explain several key features of psoriasis. How does this hypothesis account for the temporal onset with stress, clinical symmetry of lesions, and histopathological features of psoriasis?

The proposed mechanism involves the following steps:

Stress triggers the release of substance P from nerve endings in the skin
Substance P stimulates the release of inflammatory mediators
These mediators promote the characteristic skin changes seen in psoriasis
The symmetrical distribution of nerve fibers results in symmetrical lesions

This hypothesis elegantly ties together the various observations made in psoriasis patients, offering a potential explanation for the stress-induced exacerbations and symmetrical presentation of the disease.

Implications for Psoriasis Treatment and Management

How might this hypothesis impact psoriasis treatment strategies? Understanding the role of neuropeptides in psoriasis pathogenesis opens up new avenues for therapeutic interventions. Potential approaches could include:

Developing drugs that target substance P or its receptors
Exploring stress-reduction techniques as complementary therapies
Investigating the use of neuropeptide modulators in psoriasis management

These novel approaches could potentially offer more targeted and effective treatments for psoriasis patients.

The Broader Impact on Psychodermatology

Beyond psoriasis, how does this research contribute to the field of psychodermatology? The study by Farber et al. highlights the intricate connections between the mind, nervous system, and skin. This work has paved the way for further research into the role of neuropeptides in other stress-related skin conditions, broadening our understanding of the complex interplay between psychological factors and dermatological diseases.

Expanding the Neuroimmune Paradigm

What other skin conditions might benefit from this neuroimmune perspective? The concepts explored in this psoriasis research could potentially apply to:

Atopic dermatitis
Urticaria
Acne
Rosacea

Each of these conditions has been associated with stress and may involve neuroimmune mechanisms similar to those proposed for psoriasis.

Future Directions in Psoriasis Research

While the 1986 study provided valuable insights, it also opened up numerous questions for future investigation. What areas of research have emerged from this seminal work?

Mapping Neuropeptide Networks in Psoriatic Skin

How do neuropeptide levels and distributions differ in psoriatic versus healthy skin? Advanced imaging and molecular techniques now allow researchers to map the intricate network of neuropeptides and their receptors in skin tissues. These studies can provide a more detailed understanding of the neuroimmune interactions in psoriasis.

Genetic Factors in Neuroimmune Signaling

Do genetic variations influence neuropeptide signaling in psoriasis patients? With the advent of genome-wide association studies and high-throughput sequencing technologies, researchers can now explore the genetic underpinnings of neuroimmune interactions in psoriasis. This research may help explain why some individuals are more susceptible to stress-induced flares than others.

Developing Targeted Neuroimmune Therapies

Can we design drugs that specifically target the neuroimmune pathways involved in psoriasis? The pharmaceutical industry has shown increasing interest in developing neuropeptide-based therapies for various conditions. Applying this approach to psoriasis could lead to more effective and personalized treatment options.

The Evolving Understanding of Psoriasis Pathogenesis

How has our understanding of psoriasis changed since the 1986 study? While the neuropeptide hypothesis remains relevant, subsequent research has revealed additional layers of complexity in psoriasis pathogenesis. Current models incorporate:

The role of specific T cell subsets (Th17, Th22)
The importance of innate immune responses
The contribution of genetic factors
The influence of the skin microbiome

These advances have led to the development of highly effective biologic therapies targeting specific immune pathways.

Despite these new insights, the stress-neuropeptide connection in psoriasis remains an active area of research. How do these newer findings integrate with the neuropeptide hypothesis? Recent studies suggest that neuropeptides may modulate the activity of key immune cells involved in psoriasis, providing a potential link between stress signals and the adaptive immune response.

The Gut-Brain-Skin Axis in Psoriasis

Could the effects of stress on psoriasis involve more than just skin-localized neuropeptides? Emerging research points to a complex interplay between the gut microbiome, nervous system, and skin in psoriasis. This “gut-brain-skin axis” may explain how systemic factors, including stress, can influence localized skin inflammation.

How might gut bacteria influence psoriasis? Some hypotheses include:

Modulation of systemic inflammation
Production of metabolites that affect skin homeostasis
Interaction with the enteric nervous system, indirectly influencing skin nerves

This holistic view of psoriasis pathogenesis opens up new possibilities for therapeutic interventions, including probiotics and dietary modifications.

Psychoneuroimmunology: A Framework for Understanding Psoriasis

How does the field of psychoneuroimmunology contribute to our understanding of psoriasis? This interdisciplinary approach integrates psychology, neuroscience, and immunology to explain how psychological factors can influence physical health. Psoriasis serves as a prime example of a condition where these interactions are clinically relevant.

Stress Reduction Techniques in Psoriasis Management

Can stress management improve psoriasis outcomes? Several studies have explored the potential benefits of stress reduction techniques in psoriasis patients. These approaches include:

Mindfulness meditation
Cognitive-behavioral therapy
Biofeedback
Yoga and other mind-body practices

While not a replacement for conventional treatments, these techniques may offer complementary benefits by addressing the stress component of psoriasis.

How effective are these stress reduction techniques? While individual responses vary, some studies have reported improvements in psoriasis severity, quality of life, and reduced frequency of flares in patients practicing stress management techniques. These findings support the importance of addressing psychological factors in comprehensive psoriasis care.

Challenges in Studying the Stress-Psoriasis Connection

What obstacles do researchers face when investigating the relationship between stress and psoriasis? Several factors make this area of study particularly challenging:

Difficulty in objectively measuring stress levels
Individual variations in stress responses
The complex, multifactorial nature of psoriasis
Potential bidirectional relationship between stress and psoriasis symptoms

These challenges necessitate innovative research designs and interdisciplinary collaborations to fully elucidate the stress-psoriasis connection.

Biomarkers of Stress in Psoriasis

Can we develop reliable biomarkers for stress in psoriasis patients? Researchers are exploring various potential biomarkers, including:

Salivary cortisol levels
Heart rate variability measurements
Specific neuropeptide profiles in skin biopsies
Gene expression patterns in peripheral blood cells

These objective measures could help quantify the impact of stress on psoriasis and evaluate the effectiveness of stress-reduction interventions.

As our understanding of psoriasis continues to evolve, the insights from Farber et al.’s 1986 study remain relevant. The complex interplay between stress, neuropeptides, and immune function in psoriasis highlights the need for holistic approaches to both research and treatment. By integrating insights from diverse fields such as neuroscience, immunology, and psychology, we can hope to develop more effective, personalized strategies for managing this challenging condition.

Stress, symmetry, and psoriasis: possible role of neuropeptides

. 1986 Feb;14(2 Pt 1):305-11.

doi: 10.1016/s0190-9622(86)70034-0.

E M Farber, B J Nickoloff, B Recht, J E Fraki

PMID:
2419375
DOI:
10.1016/s0190-9622(86)70034-0

E M Farber et al.

J Am Acad Dermatol.

1986 Feb.

. 1986 Feb;14(2 Pt 1):305-11.

doi: 10.1016/s0190-9622(86)70034-0.

Authors

E M Farber, B J Nickoloff, B Recht, J E Fraki

PMID:
2419375
DOI:
10. 1016/s0190-9622(86)70034-0

Abstract

The role of stress as a triggering factor in the exacerbation of psoriasis and the clinically symmetric distribution of psoriatic plaques suggested a possible role for neuropeptides in the etiopathogenesis of psoriasis. Several observations by other investigators involving substance P suggested to us a possible role for substance P as a modulator of the inflammatory response in psoriasis. A hypothesis for the role of substance P that would account for the temporal onset with stress, the clinical symmetry of lesions, and the histopathologic features of psoriasis is presented.

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MeSH terms

Substances

Plaque Psoriasis: Causes, Triggers, and Treatment: National Psoriasis Foundation

About 80 to 90 percent of people living with psoriasis experience plaque psoriasis.

(Wilson et al. , 2009)

Symptoms

Psoriasis plaques appear as raised, inflamed, and scaly patches of skin that may also be itchy and painful. On Caucasian skin, plaques typically appear as raised, red patches covered with a silvery white buildup of dead skin cells or scale. On skin of color, the plaques may appear darker and thicker and more of a purple or grayish color or darker brown.

Plaques can appear anywhere on the body, although they most often appear on the scalp, knees, elbows, and torso. Plaques generally appear symmetrically on the body, affecting the same areas of the body on the right and left sides.

Plaque psoriasis often accompanies nail psoriasis which may look like discoloration, pitting, or separation of the nail from the nail bed.

Courtesy of Amit Garg, M.D.

Treatment & Care

Learn about different treatment options for psoriasis and psoriatic arthritis and talk to your doctor about what might be right for you.

Treatment & Care for Plaque Psoriasis

Treating Skin of Color

For some psoriasis patients, getting the right diagnosis isn’t always so black and white. And once minorities receive the proper diagnosis, they often face unique risks, challenges and stigmas.

Plaque Psoriasis in Skin of Color

Psoriasis or Eczema?

Similar symptoms may have you confused, so we talked with an expert about differentiating factors.

Read Article

Triggers

Common triggers for plaque psoriasis include:

Certain medications
Starting or stopping medicines
Infections
Injury to the skin
Stress
Tobacco or alcohol use

Treatments

Treatment options for plaque psoriasis include topicals, phototherapy, oral treatments, and biologics. You and your health care provider will discuss the best treatment plan for you based on the severity of your symptoms and your medical history.

Feeling Confused?

Let us walk you through your psoriasis treatment options.

Scalp Psoriasis or Dandruff?

Plenty of people have confused one for the other, so we broke down some key differences.

Seasonal Flares Guide

Learn how the seasons can impact your symptoms and what to do to minimize flares.

Track Your Triggers

Learn about common triggers for psoriatic disease flares – and track your symptoms over time – to help pinpoint things that may cause you to flare. Request your free Psoriasis & Psoriatic Arthritis Flare Guide.

Get your tracker guide today

Last updated on 10/25/2022 by the National Psoriasis Foundation.

Wilson, F. C., Icen, M., Crowson, C. S., McEvoy, M. T., Gabriel, S. E., & Kremers, H. M. (2009). Incidence and clinical predictors of psoriatic arthritis in patients with psoriasis: a population-based study. Arthritis Rheum, 61(2), 233-239. doi:10.1002/art.24172

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Psoriasis

Psoriasis is a chronic skin pathology of an autoimmune nature. Not contagious, it appears as dry, red, raised patches – papules that form plaques. Uric acid 002 1 day

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According to their clinical picture, the affected areas are considered inflammation caused by excessive division of skin cells with the formation of small capillaries.

Risk factors (causes of development)

Psoriasis occurs in approximately 3% of the world’s population, regardless of gender. It starts at any age, but most often between 15 and 30 years of age. There are cases of detection of the disease in infants. The highest prevalence among representatives of the Caucasoid race, less often among the Negroid and Mongoloid.

The disease characterizes a wave course with periods of exacerbation and remission. It has an acute onset in most cases. A monomorphic rash of papules merges into larger plaques, which are then covered with white scales.

The etiology and pathogenesis of skin pathology are not fully understood, both a hereditary predisposition and a neurogenic nature are assumed. Many patients note that the disease manifests itself, and subsequently intensifies during periods of greatest stress. Some researchers believe that an infection may be the cause of the disease, but the virus has not been identified. This theory is contradicted by the fact that the patient’s immediate environment does not get sick, and the presence of psoriasis in a family history increases the likelihood of its diagnosis in descendants.

Manifestations of psoriasis

At the first stage, the disease manifests itself in the form of a single pink papule. It changes, increases in size, grows above the skin, becomes covered with white scales. More often, psoriasis plaques appear in places of friction and increased pressure on the skin: the buttocks, elbows and knees. With the progression of the disease, they can be found absolutely anywhere in the skin, including its hairy parts.

Main clinically diagnosed external signs:

Stearin stains, i.e. easy separation of scales by scraping.
The terminal film remaining after the flake has been removed. Appears as a smooth, shiny, flat pink surface.
Pinpoint bleeding, which can be caused by removing the scale.

Psoriasis develops quite slowly, an increase in the number of plaques and their growth can be observed over several months or years. In a small percentage of patients, the disease may manifest itself more intensely. As a rule, this is preceded by severe mental stress or a serious illness requiring massive medical treatment. In this case, the papules are not pale pink, but bright red, with obvious signs of inflammation, edematous, causing itching.

The second stage of psoriasis is characterized by more extensive lesions. In place of scratching, new papules appear, forming new plaques. As a result of peripheral growth, neoplasms merge with existing ones. Plaques affect symmetrical limbs, form similar patterns and lines.

In the third stage, growth slows down, changes mainly concern the structure of the rash. The boundaries of healthy and affected skin become clearer. The plaques acquire a bluish tint, begin to peel off actively. In the absence of therapy, they thicken, sometimes form papillomatous nevi (brown) and warty growths (flesh-colored).

There is another stage – the regression of the disease, at which time the symptoms fade away. Peeling passes, the definition of the border disappears, the skin normalizes, returns to its original state.

Classification of psoriasis

The disease has many types, but they are all divided into two main types:

Non-pustular psoriasis (simple, plaque, erythrodermic).
Pustular psoriasis (generalized, palmoplantar, annular psoriasis, persistent acrodermatitis, impetigo).

A number of researchers of the disease distinguish such types of psoriasis as:

drug-induced,
reverse type,
seborrheic;
Napkin’s psoriasis (occurs in infants in the diaper area).

According to ICD-10, plaque psoriasis, reverse, guttate, pustular, nail psoriasis (onychodystrophy), psoriatic arthritis and erythrodermic psoriasis are distinguished.

Consider the most common forms of psoriasis in more detail.

1. Pustular form of psoriasis. Characterized by the presence of plaques with scales of the cortical type, impregnated with exudate. When damaged, for example, as a result of scratching or self-injury in the folds of the body, the rashes become wet. They cause itching and burning, cause physical discomfort. This type of disease is more often diagnosed in people with overweight, hypothyroidism and diabetes.

2. Seborrheic type. Affects the scalp. Occurs in people with dandruff and oily seborrhea. This makes it difficult to diagnose at the initial stage of development. Over time, psoriasis lesions grow. They can move to the skin of the forehead, to the auricles, to the back of the neck.

3. Psoriasis of hands, feet and nails. The main rash occurs on the extremities, there are only single papules on the body. The affected nail plates are deformed, acquire a yellow color, and thicken. They can walk away painlessly. A psoriatic border may form around the affected area. There are subungual hemorrhages that look like dark red spots, which then turn black.

4. Pustular (generalized) form. Has a classic pattern of development, starting with a single vesicle that develops to plaques. The lesions are symmetrical and can affect any part of the body. The severe course of this form of psoriasis is characterized by the appearance of intraepidermal pustules. They can unite, forming “purulent lakes”.‎ Pustules do not open on their own, because they are outwardly protected by a dense brown crust.

5. Arthropathic form. The most severe form of psoriasis, in which changes first affect small joints, and then large ones, including the spine. This is expressed by pain symptoms and their deformation. Probably joint fusion, loss of mobility. Against the background of this form of psoriasis, other pathologies arise: ankylosis, osteoporosis, which leads to disability.

Diagnostic methods

Psoriasis is diagnosed and treated by dermatologists. Initially, an external examination of the affected areas is carried out, an anamnesis is collected. Sometimes the disease is similar to other diseases, especially in the first stage. With the defeat of the hands and nails, it is important to exclude the presence of fungal infections. The seborrheic type also requires differential diagnosis. Seborrheic eczema, pink lichen and papular syphilis should also be excluded.

With the active course of the disease and large lesions, a visual analysis of the scraping is used. In the process of scraping, peeling intensifies. In place of the removed flake, an even, thin film is visible. Under mechanical action, it departs, a moistened surface with droplets of blood is exposed.

In most cases, it is not difficult to diagnose psoriasis, it does not even require tests, it is enough to examine the skin. However, the doctor must exclude an error in the diagnosis, determine the presence of concomitant diseases and other pathologies occurring against the background of psoriasis.

The following diagnostic measures can be assigned:

A blood test to detect an elevated level of titers of rheumatoid factor, ESR, proteins, leukocytosis, disorders, characteristic endocrine and biochemical pathologies.
A skin biopsy is performed to confirm psoriasis, clarify its classification and exclude other skin diseases. The nature of the thickening of the cells of the epidermis of the skin, the presence of accumulations of Rete, immunocompetent and other cells is checked.

Laboratory tests are also important when prescribing therapy, to monitor the effectiveness of treatment, to identify the causes and exacerbation of psoriasis.

Test types

The main tests performed for psoriasis include:

Skin biopsy, a piece of skin is examined to differentiate between a bacterial, fungal infection, and oncological diseases.
Complete blood count to detect leukocytosis and anemia.
Erythrocyte sedimentation rate to determine the type of psoriasis. With pustulosis and erythroderma, the indicator remains normal.
Uric acid test to rule out gout.
An HIV antibody test is done because the sudden onset of psoriasis can be caused by HIV infection.
pH-metry of the skin helps to evaluate the effectiveness of the therapy.

If psoriasis affects the joints (arthropathic form), a study of rheumatoid factor is performed. It allows you to differentiate rheumatoid arthritis, in which the protein level is elevated. Contrast arthrography and pneumoarthrography also help to assess the degree of joint damage.

Treatment of psoriasis

The basis of psoriasis therapy is anti-T-cell and anti-cytokine therapy aimed at reducing inflammation and blocking the proliferation (uncontrolled division) of skin keratinocytes. With exacerbations in the winter, a course of cholecalciferol (liquid-soluble vitamin D3) is prescribed. The following medications may be prescribed. To relieve itching, burning, eliminate skin lesions, the use of anti-inflammatory ointments, gels, shampoos is recommended. With a mild form of psoriasis, ointments with corticosteroids are prescribed for a course of treatment under the supervision of a doctor, salicylic ointment, with naftalan, mercury. Recommend baths with a decoction of chamomile and / or sage. Patients undergo a course of ultraviolet therapy, treatment with sea water.

Stages of therapy

In the treatment of mild forms of psoriasis, dermatologists try to avoid medications, allowing the body to cope with pathological processes on its own. Usually, local remedies are used first: creams and ointments. If the desired effect is not observed, and the situation continues to worsen, instrumental medicine is connected. Conduct courses of UV-therapy, wave therapy, photochemotherapy. Only after the lack of results of this treatment, drugs are prescribed.

Patients with psoriasis are prohibited from drinking alcoholic beverages. A diet with limited intake of salt, fats, carbohydrates is recommended. The intake of herbal medicines should be under the strict supervision of the attending physician.

All patients are advised to visit a psychologist. Often the disease worsens during a period of stress, which means that the cause must be removed. Secondly, unaesthetic plaques on different parts of the body, by the very fact of their existence, create stress and depression. According to studies, more than half of patients reduce social communication, experience a sense of embarrassment and shame. Alternative methods of treating psoriasis include the appointment of antidepressants and other psychotropic drugs, diet therapy, hydrotherapy, including the use of plaque-eating fish.

Today, the prognosis of psoriasis treatment is considered conditionally unfavorable. The course of the disease is chronic, sluggish, progressive. The methods developed by modern medicine can only alleviate the condition, but not cure the disease. At the same time, the refusal of medical care can eventually lead to disability.

Prevention of psoriasis

Based on the fact that psoriasis is considered a multifactorial disease with a share of immunopathological, genetic, endocrine, metabolic and possibly infectious components, there are no uniform rules for prevention.

Particular attention to your health should be given to people at risk:

those who have relatives suffering from psoriasis;
those who often and constantly injure the skin;
has chronic infections;
diseases of the nervous system;
endocrine disorders.

Increases the likelihood of pathology increased nervousness, stress, alcohol abuse, frequent hypothermia and sunburn. Unfortunately, it is impossible to completely protect yourself from destructive manifestations.

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Experience in the complex pharmacotherapy of psoriasis in combination with plasmapheresis

Psoriasis is a common chronic inflammatory dermatosis of a multifactorial nature associated with such systemic diseases and conditions as obesity, arterial hypertension, diabetes mellitus, dyslipidemia and metabolic syndrome, as well as with increased risk of cardiovascular diseases, myocardial infarction and stroke [1]. Despite the close attention of scientists to the development of new methods of treatment and prevention of the disease, psoriasis remains an urgent problem in dermatology today. The prevalence of this dermatosis continues to grow both in Russia and abroad. Severe common forms of the disease deserve special attention, namely exudative, erythrodermic, psoriatic arthritis. The most common type of the disease is chronic plaque psoriasis, characterized by well-defined papules and plaques covered with silvery-white scales. The rash is usually symmetrical, but unilateral, zosteriform plaques are also possible. Rashes can last for months and years, localized in one or more “favorite” areas: on the skin of the scalp, elbows, knees, palms and soles, lumbosacral region, intergluteal fold. With the long-term existence of plaques, especially those located on the lower back and buttocks, their infiltration may occur. A pronounced inflammatory reaction is observed more often in overweight individuals, while exudative phenomena develop, sometimes with warty and papillomatous growths. Increased exudation affects the nature of peeling: the silvery hue of the scales disappears, they become yellowish, stick together with the formation of crusts that adhere tightly to the skin surface.

Psoriatic erythroderma can develop due to the gradual progression of the psoriatic process, the fusion of plaque elements. This form of the disease develops more often due to the influence of adverse factors, namely excessive insolation, an overdose of ultraviolet rays and their appointment in the progressive stage of the disease. Irrational external therapy can lead to erythroderma, including the use of irritants before the process enters the stationary stage, the appointment of antimalarial drugs, penicillin and other drugs, and the abrupt withdrawal of glucocorticosteroids. Rarely, psoriatic erythroderma can develop at the very beginning of the disease when rashes of rapidly progressing psoriasis, including pustular psoriasis, merge. Psoriatic erythroderma is characterized by damage to almost the entire skin. The skin acquires a bright red color, becomes edematous, infiltrated to varying degrees, there is abundant small- and large-lamellar peeling. Often the condition is accompanied by severe itching. Psoriatic erythroderma is accompanied by a change in the general condition: weakness, malaise, high fever, loss of appetite. The condition is accompanied by profound metabolic disorders. Persistent hyperemia of the skin leads to an increase in heat transfer through evaporation and convection, and latent water losses increase. Heart failure with high cardiac output may develop. Peeling is accompanied by the loss of a large amount of horny substance, as a result of which the level of serum albumin decreases and swelling of the legs occurs. There are violations of the function of the liver and kidneys. Sweating can be significantly reduced, dehydration develops, an increase in peripheral lymph nodes, hair loss. Joints are often involved in the pathological process [2, 3].

Psoriatic arthritis develops in 5.94-23.9% or more of patients with psoriasis [4]. Psoriatic arthritis may precede skin rashes, debut at the same time, or come after skin manifestations. In 75% of cases, skin lesions precede arthritis, in 10% they occur simultaneously, in 15% of cases psoriatic arthritis may precede skin rashes – in such a situation, when making a diagnosis, it is necessary to focus on a family history [5]. The causes of joint damage remain unclear. It is believed that, as in ordinary psoriasis, heredity and immune disorders, autoimmune reactions play a significant role. The influence of bacterial and other types of infections, including chlamydia, as well as the role of irrational therapy, especially glucocorticosteroid drugs, should be taken into account. In addition, there is evidence of the effect of overweight and obesity on the development of psoriatic joint damage [6].

Radiographically, various changes in the osteoarticular apparatus can be detected without clinical signs of joint damage. Most often, these are periarticular osteoporosis, narrowing of the joint spaces, osteophytes, cystic enlightenment of the bone tissue, less often – bone erosion, ankylosis of small joints.

Clinically characterized by swelling, redness, soreness over the affected joints, with enthesopathy – in the places of attachment of the tendons to the bones. There is a limitation of mobility, with multiple lesions leading to morning stiffness. Fingers become like sausages. There may be joint deformities, mutilating changes, ankylosis, in some patients myositis, atrophic changes in the muscles adjacent to the joints. Psoriatic arthritis, which has developed against the background of erythroderma or pustular psoriasis, often proceeds severely, with a violation of the general condition and function of internal organs. Skin lesions may be absent, but more often (80%) there is a simultaneous exacerbation of the process on the part of the skin and joints. In comparison with rashes in ordinary psoriasis, in psoriatic arthritis there are some features, namely, a tendency to exudation, pustulation, resistance to therapy, the location of the elements of the rash on the flexor surfaces of the limbs, on the distal phalanges with a pronounced lesion of the periungual ridges and nail plates.

Recently, there has been a trend towards an increase in cases of severe forms of psoriasis. This can be due to many reasons, ranging from lifestyle (nutrition, habits, lack of movement, environment) to the irrational use of drugs, including during “self-treatment” (ultraviolet baths, local irritants in the progressive phase of the disease , trigger drugs), as well as with a simultaneous increase in the proportion of somatic pathology. The high prevalence of torpid, non-treatable forms of psoriasis dictates the need to find new approaches to the treatment of this disease.

More and more scientific works of recent decades are devoted to the so-called “ comorbid conditions ” in psoriasis, that is, a pathology that accompanies and exists simultaneously with the psoriatic process. The term “comorbidity” was first introduced by an American doctor, Professor A. Feinstein in 1970 (lat. with – together, morbus – disease) [7]. Experimental and clinical data indicate that psoriasis is associated with arthritis, inflammatory bowel disease, cardiovascular disease, metabolic syndrome (obesity, hypertriglyceridemia, hyperglycemia, arterial hypertension, insulin resistance), depression, non-alcoholic fatty liver disease, malignant neoplasms and diseases. Not so long ago, other disorders were proposed as a pathology associated with the state of chronic inflammation in psoriasis [5].

Abroad, in the complex therapy of psoriasis, as well as a number of other dermatoses, extracorporeal methods have found wide application, in particular, membrane plasmapheresis , which has proven itself as a highly effective treatment for many diseases.

Plasmapheresis is one of the methods of efferent therapy aimed at removing various pathological products from the body (lat. efferens – removal). The term plasmapheresis was proposed in 1914 J. Abel et al. [8], who, using a citrate anticoagulant, conducted a series of experiments on animals with the return of erythrocytes to the donor. Over time, plasmapheresis has been introduced into various fields of medicine: it has been used to obtain donor plasma, to remove pathological cells and toxins from the blood, to reduce the pathological pool of blood cells, to treat patients with Waldenström’s macroglobulinemia and rheumatoid arthritis, etc. Currently, plasmapheresis is used more than 100 different diseases and syndromes. The technique is used in obstetrics and gynecology, hematology, surgery, pulmonology, cardiology, nephrology, neurology, narcology, psychiatry, dermatology, resuscitation, pediatrics, oncology and some other areas of medicine. Abroad, plasmapheresis is included in the complex therapy of scleroderma, dermatomyositis, bullous dermatoses, lupus, chronic urticaria, toxic epidermal necrolysis, pyoderma gangrenosum, severe psoriasis that cannot be treated and other conditions [9]. In our country, positive experience has also been accumulated in the use of plasmapheresis in the treatment of skin diseases, however, for various reasons, the technique is used much less frequently.

Hollow fiber and flat filters are used for membrane plasmapheresis. The size of the holes is 0.2-0.77 mk, which prevents the passage of blood cells through them, while the plasma passes freely. Immune complexes, normal metabolites, exogenous toxins are subject to elimination. In psoriasis, plasmapheresis is indicated for patients with erythroderma, as well as for patients with the exudative form of the disease [10, 11]. There are reports of the effectiveness of this method as an additional treatment for psoriatic arthritis [12]. In case of psoriasis, the course of treatment consists of 7-10 procedures with an interval of 1-2 days with the removal of 800-1000 ml of plasma per procedure. After the first plasmapheresis procedure, the level of circulating immune complexes in the blood increases (the rebound phenomenon), which indicates their movement from the tissues into the bloodstream, and therefore an aggravation of the pathological process is possible. Subsequent procedures are accompanied by an accelerated resolution of skin rashes. It is possible to divide the therapy of psoriasis using plasmapheresis into two stages: at stage I, a course of plasmapheresis is carried out, and subsequently, with the stabilization of the pathological process and the absence of fresh rashes, they proceed to stage II – to the appointment of ultraviolet irradiation, photochemotherapy, cytostatics or synthetic retinoids. The criteria for the effectiveness of treatment are a decrease in infiltration and subsequent regression of papules and plaques, an increase in the number of T-lymphocytes, stimulation of the phagocytic activity of neutrophils, and elimination of circulating immune complexes from the blood [8, 10]. In addition, it is possible to use a treatment technique that includes a hemosorption session, four plasmapheresis sessions in combination with blood irradiation with ultraviolet or laser beams, followed by enterosorption. Conducting 2-3 courses of such therapy led to clinical improvement in 91% of patients [13, 14].

The aim of the study was to study the effect of plasmapheresis on the effectiveness of complex therapy for severe forms of psoriasis.

Material and methods

In the branches of the Moscow Scientific and Practical Center for Dermatovenerology and Cosmetology of the Moscow Health Department “Clinic named after. V.G. Korolenko” and “Veshnyakovsky” in the period 2011-2015. plasmapheresis was included in the complex therapy of severe forms of psoriasis. Under our observation there were 102 patients with torpid, poorly treatable psoriatic process on the skin, with diagnoses: common psoriasis vulgaris, progressive stage, widespread psoriasis, exudative form, progressive stage and psoriatic erythroderma. In some patients, skin rashes were accompanied by psoriatic arthritis. All patients had previously received “reserve” methods and drugs: PUVA therapy, methotrexate, systemic retinoids. The age limit ranged from 18 to 77 years. The disease duration ranged from 9months to 25 years. The hospitalization period ranged from 21 to 28 days. Patients received combination therapy, including detoxification agents (hemodez, 0.9% sodium chloride solution), hepatoprotectors, sedatives and antihistamines (in the presence of severe itching), external agents (ointments containing 2-5% salicylic acid, tar, naftalan, topical steroids, calcipotriol). Membrane plasmapheresis was included in the complex pharmacotherapy of 53 patients. The procedure was carried out on a portable multifunctional device GEMOS-PF for plasmapheresis, hemosorption and other detoxification methods. The device works according to the sparing and safest single-needle scheme for connecting a single peripheral vein. A two-wire connection is also possible. Adaptively adjusts to the patient’s venous blood flow. The Gemos-PF device has an optimal combination of clinical efficiency, increased safety, high reliability, compactness and mobility. The course of treatment consisted of 1-8 procedures, which were performed at intervals of 1 to 3 days. During the course of membrane plasmapheresis, 1-1.5 volumes of circulating plasma were removed. A significant part of the patients combined a course of plasmapheresis with the use of various methods of physiotherapy (intravenous laser blood irradiation, PUVA therapy, magnetotherapy, ultraviolet irradiation). Another group of patients, consisting of 49people, due to various reasons (age, severe concomitant pathology), the use of plasmapheresis procedures was not indicated. These patients acted as a control group. Before treatment, during and at the end of therapy, in addition to visual control over the regression of rashes, the following indicators were evaluated: the PASI index (Psoriasis Area and Severity Index – an index of the prevalence and severity of psoriasis, range 1-72 points) before treatment averaged 29.4 points; DLQI index (Dermatology Life Quality Index – Dermatological quality of life index, range 1-30 points) – before treatment averaged 22.3 points, data from clinical, biochemical blood tests.

Results

According to our observations, the combination therapy method with the inclusion of plasmapheresis procedures turned out to be the most effective, which was reflected in the assessment of the PASI and DLQI indices, as well as the dynamics of the biochemical blood test. At the time of discharge, patients of the 1st group were significantly ahead of the control group in these indicators. Thus, the average PASI index in patients of this group on the day of discharge was 7.2 points, while in the control group it was 18.3 points (Fig. 1). The DLQI index after treatment had a value of 9.8 points against 14.1 points, respectively (Fig. 2). With regard to the dynamics of biochemical blood test parameters, the following was noted: in patients of the 1st group, a more pronounced normalization of hepatic transaminases was observed. In a clinical blood test, no pronounced changes were found that were directly related to any particular method of therapy. If deviations in one direction or another were noted before treatment, then at the time of discharge, most of the indicators approached or reached the limits of normal values both in the study group and in the control group. It should be noted that in patients of the 1st group, clinical recovery occurred faster, and the period of remission, according to the observation data for 2 years, was extended in this group of patients.

Rice. 1. Dynamics of the average PASI index during treatment.

Rice. 2. Dynamics of the DLQI index during treatment.

Clinical case

Patient N ., 36 years old, was admitted to the branch “Clinic named after. V.G. Korolenko” with a diagnosis of common psoriasis vulgaris, progressive stage. The patient complained of rashes on the skin of the scalp, trunk, limbs, accompanied by moderate itching. According to the anamnesis, he considers himself ill for 12 years, when for the first time after suffering stress he noted the appearance of rashes on the skin of the scalp. For several years he was not treated, he noted the gradual spread of rashes to the skin of the extremities. The progress of the disease is associated with the occasional use of strong alcoholic beverages. About 8 years ago, due to the aggravation of the pathological process on the skin, he turned to a dermatologist at the place of residence, psoriasis was diagnosed. He was treated on an outpatient basis (sedatives, hepatoprotectors, external corticosteroid ointments and creams, ointments containing 2-3% salicylic acid), with a temporary positive effect. Exacerbation of the disease was noted up to 2 times a year, mainly in spring and autumn. In the anamnesis, a single hospitalization in the branch “Clinic named after V.G. Korolenko, where methotrexate was prescribed in complex therapy, after which an allergic reaction occurred in the form of acute urticaria. In recent years, rashes have spread to the skin of the face, torso, and limbs. The course of the disease is continuously relapsing, and therefore, for 10 months, he independently uses injections of the drug diprospan on a weekly basis, after an attempt to cancel which, he notes a sharp aggravation of the psoriatic process on the skin (Fig. 3).

Rice. 3. Patient N., 36 years old, at the time of admission to the inpatient department.

During this hospitalization, the following examination was prescribed: clinical and biochemical blood test, general urinalysis, blood test for HBsAg, aHCV, enzyme immunoassay total to Treponema pallidum cavities and kidneys. According to the results of the examination, leukocytosis was detected (10.3 10 ⁹ /l), an increase in the level of hepatic transaminases by 2.5 times from the normal range, according to ultrasound – diffuse changes in the liver.

Given the history and examination results, the appointment of methotrexate and PUVA therapy was not indicated. The patient received complex pharmacotherapy (detoxification agents, sedatives, hepatoprotectors, antihistamines due to moderate itching, externally 2% salicylic ointment with a small amount of glucocorticosteroid) in combination with plasmapheresis procedures. Three procedures of membrane plasmapheresis were performed with an interval of 4 days, and after the second procedure, a pronounced clinical improvement was noted (Fig. 4). The hospital stay was 21 days. According to the results of laboratory screening on the eve of discharge, the level of leukocytes in peripheral blood, as well as the level of transaminases, approached the normal limits. There was a decrease in the PASI index by 75% from the original. Thus, despite the long-term independent use of an injectable prolonged corticosteroid, severe widespread manifestations of psoriasis at the time of admission, the lack of the possibility of prescribing reserve drugs, in a relatively short period of hospitalization, both regression of skin rashes and improvement in laboratory parameters were noted, which indicates the effectiveness of the applied methods.

Rice. 4. Patient N., 36 years old. Clinical picture after the second plasmapheresis procedure.

Terminals

The data obtained during the study suggest that the method of complex pharmacotherapy of psoriasis in combination with plasmapheresis will reduce the time of stay in the hospital, prolong the remission of the disease, and in the future, it is possible to reduce the dosage or even abandon the use of reserve drugs with toxic properties and many side effects.