Psoriasis

*Author for correspondence

397,Sec-13, Hisar, Haryana, India, GSM: +919416045445, E-mail: sumkhan@hotmail.com

Psoriasis is a common skin disorder characterised by focal
formation of inflamed, raised plaques that constantly shed scales
derived from excessive growth of skin epithelial cells. The disease
is defined by a series of linked cellular changes in the skin: hyperplasia
of epidermal keratinocytes, vascular hyperplasia and ectasia, and
infiltration of T lymphocytes, neutrophils, and other types of leucocyte
in affected skin. Over the last several years, a new generation of
therapies for psoriasis has been in development. These biologic therapies target
the activity of T lymphocytes and cytokines responsible for the inflammatory
nature of this disease .

Key words: T lymphocytes, neutrophils, and autoimmune disease

INTRODUCTION

Psoriasis is a skin disorder characterized by red patches covered by silvery white scales, which can develop almost anywhere on the body, from the scalp down to the soles of the feet. These patches may itch and be quite uncomfortable as well as be a cosmetic embarrassment. The condition is caused by skin cells that divide too rapidly--up to 1,000 times faster than normal skin cells--and accumulate instead of being shed. Psoriasis is not contagious. It is a chronic disorder, which means it can last a long time and can come back frequently. It is most common in people in their 20s30s, and 40s. Psoriasis is rare under age 3. Most people who develop it do so before age 30. In the United States, about two or three out of every 100 people have psoriasis. (1,16,30)

The problem with psoriasis is that there is relief but no permanent cure available
as yet. We don’t know exactly what causes the condition, though it has been
associated with allergies, arthritis, and various dietary and metabolic factors.
Of the topical applications, cortisone works in clearing up psoriasis, but the
effect is temporary, and the condition gets worse when the cortisone is discontinued.
Tar, which can be bought in over-the-counter creams, helps keep down the itching
and inflammation, and mineral oil keeps the skin from drying out. Fish oil,
or MaxEPA, applied topically has been shown to give relief to psoriasis patients.

Psoriasis is an unpredictable condition that can sometimes flare up for no apparent reason. The course of the disease can be different in every individual who has it. People with psoriasis commonly go through periods of embarrassment, frustration, and depression about their condition. Because psoriasis affects exposed skin, it is a highly visible disease.

Psoriasis is not an infection and it is not contagious - you cannot "catch"
it from anyone.

TYPES OF PSORIASIS

There are various types of psoriasis as follows:

Plaque psoriasis, Guttate psoriasis , Seborrheic psoriasis, Palmoplantar psoriasis,
Pustular psoriasis, Erythrodermic psoriasis, Inverse psoriasis

Plaque Psoriasis

This is the most common type of psoriasis. It typically appears as thick, flaky patches of skin on one or more parts of the body. Sometimes the patches of affected skin are large, extending over much of the body. The patches, known as plaques or lesions, can wax and wane but tend to be chronic. (8,14)

Plaque psoriasis can occur anywhere on the body. Commonly affected sites are the elbows, knees, knuckles, scalp, trunk, arms and legs, and external sex organs. The plaques do not always itch, but when scratched they can become inflamed. This is known as the Koebner phenomenon.

Guttate Psoriasis

This type of psoriasis most often affects children and young adults. It appears as small, red bumps-the size of drops of water-on the skin. It usually appears suddenly, often several weeks after an infection such as strep throat. Antibiotics may be used to treat guttate psoriasis that is triggered by an infection. (29) Guttate psoriasis usually responds to treatment and may gradually go away on its own. Many people who have an episode of guttate psoriasis may not have another one for many years.

Seborrheic psoriasis

The scalp may be the first site to be affected by psoriasis. The condition may resemble severe dandruff. Patches of thick, flaky skin may extend to the forehead below the hairline. However, some people may have patches of inflamed skin that resemble seborrheic dermatitis, a type of dandruff eczema that affects the scalp and face

Palmoplantar psoriasis

Psoriasis that affects the palms of the hands and the soles of the feet is called palmoplantar psoriasis. It may appear as chronic flaky patches that crack and bleed. The nails may be affected as well. In severe cases the condition can be disabling.

Pustular psoriasis

In this condition small, deep, pus-filled blisters appear on the palms and soles. They may have a copper-colored hue on a background of red, flaky skin. This condition may also be called palmoplantar pustulosis or acropustulosis.

Erythrodermic psoriasis

People with erythroderma may have fever and chills, and may need to be treated in the hospital.  Factors causes erythroderma are widespread eczema (an inflammatory condition of the skin characterized by redness, itching and oozing lesions), skin reactions to drugs, and a type of skin cancer called cutaneous lymphoma.

Inverse psoriasis

Psoriasis that affects areas of the body where the skin folds, such as the
armpits, groin, and webs of the toes, is called inverse psoriasis or flexural
psoriasis. This type of psoriasis is often white in color, appears softened
as if soaked by water, and may resemble a fungal infection.

PATHOPHYSIOLOGY OF PSORIASIS

ABNORMALITIES OF INTESTINAL MUCOSAL STRUCTURE

Absorption of antigens via the intestinal lymphatic may be a significant source of systemic autointoxication. Because the intestinal lymphatic absorption vessels (lacteals) drain fats and proteins from the bowel, increased permeability through the lacteals should lead to increased serum levels for fats and proteins. Hyperlipoproteinaemia has been documented in psoriasis (17) and is thought to be a primary factor in the comorbidity of psoriasis and heart disease (18). The researchers focused on severe psoriasis (greater than 50% surface area involved). "Both the structural and functional intestinal changes described suggest that there is a decrease in the small bowel surface area in patients with severe psoriasis" (19). Thus, smoothing of the intestinal wall in the jejunal area of the bowel is regarded as a feature of severe psoriasis. In addition to the normal controls, an additional comparison group included sick and wasting individuals. The results indicated that pathological changes in the small bowel mucosal architecture are not specific to psoriasis, but may also be found in patients who are sick and losing weight from other causes. There are at least two types of abnormalities in the duodenal mucosa in psoriasis, one type that is present in most psoriasis patients and characterized by an increase in mast cells and eosinophils, and another that is present in a subgroup of patients with antibodies to gliadin and an increased number of duodenal intraepithelial lymphocytes.

AUTOINTOXICATION

Autointoxication is an ancient theory based on the belief that intestinal toxins can enter the circulation and poison the body. The concept probably originated in Egypt or Greece. The Greek version recognized a broad range of pathological agents including residues of food, bile and phlegm as portrayed in the humoral theory of disease (20). Until the early 20th century, autointoxication was widely accepted and various therapies (such as colonic irrigation) were commonly used for a variety of systemic disorders (21). Unsupported by scientific evidence, the autointoxication concept fell out of favor several decades ago. However, the growing body of information linking intestinal disease, excessive intestinal permeability, and systemic illness has revived the theory (22,23). Similar concepts such as multiple chemical sensitivities (24) and endotoxins (20) are also now gaining in favor.

LYMPHATIC AND IMMUNE SYSTEM DYSFUNCTION

Recently, psoriasis has been grouped with numerous other systemic disorders which are related to immune system dysfunction. One of the seminal events in drawing attention to the autoimmune aspects of psoriasis was the chance clinical observation that psoriasis improved in patients treated with cyclosporine, a drug used to prevent rejection of transplanted organs. Immunotherapeutic drugs have since been used extensively to suppress immune reactions in psoriasis. Autoimmune diseases are caused by over stimulation of the body's own immune defenses, in which the immune cells attack healthy cells. In psoriasis, immune system T cells become activated and stay turned on causing the skin to constantly regenerate itself. The specific trigger for T cell activation is unknown, but may be an antigen, a bacterial or viral infection, or an environmental factor. Various allergens are known to trigger autoimmune responses. Furthermore, autoimmune disorders have inner, self-perpetuating causes, such as medicines and food materials. It is important to keep in mind that food is a primary source of the external environment that interacts with the immune system within the body. In addition to inherently toxic substances that may be ingested, intact peptides and proteins are absorbed into the circulation (27). Thus, diet may play a significant role in autoimmune diseases. If the antigens are passed beyond the liver, they will circulate through the lungs, heart, kidneys, and then to the rest of the body where they may disrupt the functioning of various systems. In a healthy body, appropriate bowel permeability and adequate liver and kidney functioning are able to maintain a level of minimal systemic toxicity which can be easily managed by the immune system.

Beyond the intestinal tract, lymphatic circulation has been implicated in the
pathophysiology of skin disease with regard to lymphocyte migration into the
skin the staining results of inflamed duodenum in DH and CD were identical with
those obtained from inflamed skin. Because more specific markers are not presently
available in the human system, we cannot exclude the possibility that there
is a common lymphocyte-endothelial cell-interaction system for differing sites
of inflammation. Lymphatic/immune system involvement in psoriasis is well established,
although the precise homing mechanism by which lymphocytes migrate to the skin
remains unknown (26). Thus, in viewing psoriasis as a systemic disorder involving
increased autoimmune reactivity in the skin (and to the joints in psoriatic
arthritis), the intestinal tract and lymphatic system take on important roles
with regard to etiology and pathophysiology of the disorder.

TREATMENT

1. Topical therapy
   
2. Phototherapy
   
3. Biological therapy
   
4. Systemic therapy

Topical therapy

Doctors usually use medications applied to the skin first to treat psoriasis. These medications are most useful for treating mild to moderate psoriasis. The medication that is best may depend on the type and location of the psoriasis. For example, ointments may be very effective for thick, flaky plaques on the body but messy and uncomfortable on the scalp.(27)

Tar compounds

Coal tar has been used for more than 100 years to treat psoriasis and it has few side effects. However, it does not work for everyone. Coal tar can be combined with ultraviolet light for treating severe psoriasis.

Topical steroids

Topical steroid medications are one of the most common treatments for mild to moderate psoriasis. They reduce redness (inflammation) and itching and stop the rapid build-up of dead skin cells. A new foam for scalp psoriasis called clobetasol propionate has recently been approved. These medications should not be put on the face or on areas of the body where the skin folds, such as the armpits, groin, and between the toes. (3)

Anthralin

Anthralin is a synthetic medication that has an effect on enzymes in the skin cells of people with psoriasis. Anthralin cream is applied to skin plaques for 30 minutes to two hours, and then thoroughly removed with a detergent-based soap and water. Over a period of weeks, redness and scales decrease and plaques gradually flatten. (5)

Vitamin D

Applying the medication twice a day reduces scales by controlling the build-up of dead skin cells. It is also called calcipotriol or calcipotriene. It is chemically similar as of Vitamin D3 but Vitamin D3 is not the same as the Vitamin D found in over-the-counter vitamin supplements. Vitamin D3 should not be taken by mouth because it may raise blood calcium levels and increase the risk of kidney stones. It should be used with caution in children.

Phototherapy

Sunshine

Brief, regular periods of exposure to natural sunlight can improve or clear psoriasis in some people. Sunburn should be avoided because it can make psoriasis worse. Exposure to sunlight is not recommended for people who are sun-sensitive. Sun exposure can cause aging of the skin. An annual medical checkup is advised because sun exposure can increase the chance of skin cancer.

Ultraviolet therapy

Sunlight contains two kinds of UV light, known as UVB and UVA. Both can be used to treat psoriasis.

1. UVB therapy: Treatment with UVB light is the safest form of phototherapy
for widespread psoriasis or psoriasis that has not responded to medications
applied to the skin. Usually three to five treatments a week is recommended,
with a gradual increase in UV exposure depending on skin type. UVB phototherapy
may be combined with tar, anthralin, topical steroids, or other medications
applied to the skin.

2. UVA therapy: UVA is used for widespread psoriasis or when other
treatments have not been effective. It combines a medication called psoralen
and becomes PUVA. Treatment is given two or three times a week, up to about
25 treatments. The amount of UV exposure may be gradually increased, depending
on skin type. (2)

Biological therapy

For patients with moderate to severe psoriasis, the use of biologic agents to treat psoriasis is a much-welcomed milestone. What makes biologics unique is that these drugs pinpoint precise immune responses involved with psoriasis. Three biologics — alefacept, efalizumab, and etanercept (27,28) — have been approved by the FDA for treating adults with moderate to severe plaque psoriasis.

Alefacept

AMEVIVE  (alefacept) is an immunosuppressive dimeric fusion protein that
consists of the extra cellular CD2-binding portion of the human leukocyte function
antigen-3 (LFA-3) linked to the Fc (hinge, CH2 and CH3 domains) portion of human
IgG1.It is supplied as a sterile, white-to-off-white, preservative-free, lyophilized
powder for parenteral administration. It is available in two formulations a.Intramuscular
injection b. intravenous injection. (28)

Efalizumab

RAPTIVA (efalizumab) (12,13,28) is an immunosuppressive recombinant humanized
IgG1 kappa isotype monoclonal antibody that binds to human CD11a. Efalizumab
has a molecular weight of approximately 150 kilodaltons. RAPTIVA is supplied
as a sterile, white to off-white, lyophilized powder in single-use glass vials
for subcutaneous (SC) injection. The sterile water for injection supplied does
not comply with USP requirement for pH. (6,7)

Etanercept

ENBREL (etanercept) is a dimeric fusion protein consisting of the extra cellular
ligand-binding portion of the human 75 kilodalton tumor necrosis factor receptor
(TNFR) linked to the Fc portion of human IgG1. It is supplied in a single-use
prefilled 1 mL syringe as a sterile, preservative-free solution for subcutaneous
injection. The solution of ENBREL^® is clear and colorless and is
formulated at pH 6.3 ± 0.2. ENBREL multiple-use vial contains sterile,
white, preservative-free, lyophilized powder. (10,11,28)

Systemic therapy

Acitretin

Acitretin is a retinoid (vitamin A derivative) that patients take orally. Studies
show acitretin is effective in treating erythrodermic and pustular types of
psoriasis. It is effective in treating psoriasis on the palms of the hands and
soles of the feet. Combining acitretin with phototherapy has proven effective,
especially in treating severe plaque psoriasis. Oral retinoids, including acitretin,
should not be used by women who are pregnant or plan to become pregnant within
3 years of discontinuing therapy due to the possibility of severe birth defects.
(4)

Cyclosporine is a potent immunosuppressive drug that benefits many with severe
plaque psoriasis and psoriasis of the nails. It is taken in pill or liquid form.
While it proves extremely effective in treating psoriasis, it is generally reserved
for patients with severe cases whose condition has not responded to other therapies.
Patients who respond typically show rapid improvement. Cyclosporine was first
used to prevent rejection in organ-transplant recipients The FDA recommends
that cyclosporine not be used for more than one year. (3)

One of the first chemotherapy drugs, methotrexate has been used for years to
treat moderate to severe psoriasis and continues to be one of the most effective
therapies for patients with erythrodermic and pustular psoriasis. Patients who
respond typically see an improvement within 4 to 6 weeks. After the initial
clearing, the dose may be reduced or other therapies used to keep the psoriasis
under control. Common side effects include nausea, fatigue, and headaches. Methotrexate
is not recommended for patients who have an active infection, liver disease,
or a history of alcohol abuse. (3)

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