Psoriasis: Immunopathology, Presentation, Complications and Treatments

Abstract

Psoriasis has been defined as a chronic immune-mediated inflammatory skin disease characterized by uncontrolled proliferation of keratinocytes, activated dendritic cells, release of proinflammatory cytokines, and recruitment of T cells to the skin. This paper discusses the immunopathophysiology, clinical presentation, associated complications, clinical assessment, and interventions related to this condition.

Introduction

Psoriasis has been defined as a chronic immune-mediated inflammatory skin disease characterized by uncontrolled proliferation of keratinocytes, activated dendritic cells, release of proinflammatory cytokines, and recruitment of T cells to the skin. In other words, the life cycle of skin cells is hastened which causes cells to build up rapidly on the surface of the skin. The extra skin cells form scales and red patches that can be itchy and/or painful.

I chose psoriasis as the topic of focus for this paper because my boyfriend, George, was diagnosed with this condition when he was 15 years old. He has the mild-moderate severity of plaque psoriasis. He describes his first experience of noticing this skin condition as itchy red spots that appeared on the back of his knees, chest, and arms after he adopted a cat. He also reports that his path toward diagnosis and treatment took several years because initially he kept getting misdiagnosed with just having dead skin. But after seeking a third opinion, he was correctly diagnosed with plaque psoriasis and found out that he was allergic to cats. He was advised to get rid of the cat and was prescribed coal tar but discontinued using it shortly afterwards because it dried out his skin too much and would leave behind a strong chemical smell. He was then advised to bathe with Selsun blue shampoo due to its acidic properties. This has been his treatment regimen since he was 19 years old and reports that it is effective in managing his outbreaks.

 The incidence and prevalence of psoriasis is difficult to pinpoint due to very little studies on this and also because there is no mandated reporting of diagnosed individuals. Despite this, some national foundations provide some statistics. For example, according to the National Psoriasis Foundation, more than 8 million Americans have psoriasis (2019). Many sources state that prevalence is highest in Caucasians and is second highest for African Americans. A cross-sectional study conducted by Rachakonda et al. (2014) using National Health and Nutrition Examination Survey 2009 through 2010 data determined psoriasis prevalence rates. Their results concluded that 3.2% of US adults ages 20 years and older have psoriasis, an estimated 7.4 million US adults were affected in 2013. The prevalence was highest in Caucasians at 3.6%, followed by African Americans 1.9%, and Hispanics 1.6%.

Pathophysiology

The immunopathophysiology of psoriasis is a topic that has been extensively researched. Recent studies have reported that genetic (ex: family history, HLA antigens) and lifestyle factors (trauma, antigens) are both involved in the development of psoriasis. It is understood that several types of cells and biological components are involved in causing this condition, such as: T cells, antigen-presenting cells (APCs), macrophages, neutrophils, and tumor necrosis factor alpha (TNF-α).

Psoriasis is the result of a chronic immune system activation caused by a trigger(s) that leads to abnormal levels of keratinocytes production and psoriatic plaque. When the dermis layer is inflamed, nearby blood vessels dilate which helps neutrophils penetrate to the epidermis. The neutrophils migrate to the stratum corneum layer which leads it to become thickened.  The inflammation also causes the keratinocytes to proliferate abnormally and rapidly at a rate that outpaces the rate of the dead skin cells sloughing off which leads to skin cell pile ups. Due to the rapid maturity of keratinocytes, many contain defects in shapes and retain their nuclei. The defect in shape causes an issues in these cells adhering to each other which is why psoriatic plaques often look scaly and uneven in shape.

The development cycle begins when the APC (dendritic cells) becomes activated after it comes in contact with an antigen in the skin. The APC then travels to the lymph node where it stimulates the naïve T cells to become an activated memory T cell. After activation, adhesion molecules such as ICAM-1 help the memory T cells migrate through the blood so that reach the site of inflammation in the skin. After extravasation in the dermis layers, memory T cells release cytokines such as TNF-α and interferon gamma and lead to an increased production of keratinocytes which caused psoriatic plaques. IL-12 AND IL-23 are cytokines that are released by dendritic cells which activate other T-cells thus leading to the continuation of the inflammation process.   

There are seven types of psoriasis: plaque, guttate, pustular, inverse, and erythrodermic. In addition to these identifications, the type of psoriasis can be further classified by the following categories: mild, medium, and severe based on how much body surface area the plaques cover. Plaque psoriasis is the most common type and presents with the following symptoms: skin that is raised, inflamed, red, and covered by silvery, white scales that may itch and burn. These patches can appear anywhere on the body but especially in these areas: elbows, knees, scalp, and lower back. Guttate psoriasis is one of the rare forms of this disease and presents with small, pink-red spots on the skin that often appear on the trunk, upper arms, thighs, and scalp. Pustular psoriasi is uncommon but can be dangerous if it spreads all over the body and it presents with pustules surrounded by red skin. Inverse psoriasis presents with patches of skin that are red, smooth, and shiny found commonly in these areas of the body: armpits, groin, and skin folds near the genitals and buttocks. Lastly, erythrodermic psoriasis is another rare condition and presents with very dark red skin that appears as it is burned and can cover a large area of the body. This condition can be dangerous as it may lead to cardiac abnormalities.

Individuals that have psoriasis are at increased risk of suffering complications. Some studies have proven that individuals that are categorized as moderate-severe have a higher risk of developing certain complications such as obesity, hypertension, type 2 diabetes, and kidney disease. The development of hypertension and type 2 diabetes are discussed in further detail. 

One complication that has been linked to psoriasis is hypertension. A prospective cohort study conducted by Salihbegovic et al. (2015) demonstrated a correlation between patients with psoriasis and hypertension. Overall, research has not yet found the exact pathophysiological mechanism for this correlation but Salihbegovic et al. (2015) proposed the following theory that affected individuals may have an increased level of angiotensin-converting enzyme (ACE), endothelin-1 (ET-1), and rennin. Another theory was that medications, such as cyclosporine, are inducing hypertension. It is also important to keep in mind that affected individuals may feel stressed due to their poor health conditions which in turn can lead to the development of high blood pressure.

Another complication is the development of type 2 diabetes mellitus. A study conducted by Lønnberg et al. (2016) examined the association between psoriasis, type 2 diabetes mellitus, and body mass index (BMI) in order to better understand the genetic association. The study population was composed of Danish twins. Their results concluded that a significant association was found between psoriasis and type 2 diabetes mellitus as well as between psoriasis and increasing BMI. The authors discuss that the following components, tumor necrosis factor, tumor necrosis factor receptors, and interleukin 6, are involved the development of psoriasis and are also linked with obesity. The association between type 2 diabetes mellitus and psoriasis could exist because an increased tumor necrosis factor production from psoriatic inflammation and low-grade obesity inflammation contributes to insulin resistance.

Assessment and Intervention:

 Diagnosing psoriasis typically includes conducting a physical exam and taking a patient’s medical history. In rare cases, a biopsy can be performed in order to rule out other skin conditions. Healthcare providers can also order laboratory studies in order to diagnose patients if it suspected they have pustular or erythrodermic psoriasis. With respect to pustular psoriasis, the erythrocyte sedimentation rate (ESR) and uric acid level will be abnormal. The ESR will be abnormal as well for erythrodermic psoriasis. Depending on the type of psoriasis and severity, baseline laboratory studies (CBC, BUN, LFTs, etc) should be conducted if the patient’s treatment plan consists of systemic therapies such as immunological inhibitors.

With respect to interventions, treatments are selected based on the type and severity of psoriasis as well as location on the patient’s body. Treatments are categorized as topical, systemic, or phototherapeutic. For mild psoriasis, topical medications are prescribed. For mild-severe psoriasis, a combination treatment plan of topical and systemic is recommended. Some forms of topical, systemic, and phototherapeutic treatments are discussed in further detail.

 With respect to topical treatments, many options exist. Choices include corticosteroids and medicated shampoos that contain salicylic acid. Topical corticosteroids reduce inflammation and relieve itching. The type of dosage prescribed depends on what areas need to be treated. For example, low dose corticosteroid ointments are used in sensitive areas and high dose corticosteroid ointments can be used for smaller, less sensitive areas. Although this medication is quite effective, it is best to be used as short term because of its side effects. Salicylic acid removes dead skin cells with its acidic properties and is available in shampoos such as Selsun Blue. It can be used to treat scalp psoriasis as well as mild psoriatic plaques located within any body area.

 With respect to systemic treatment, numerous options are also available. One such medication is methotrexate which is an inhibitor of folate biosynthesis that reduces psoriatic inflammation. This is a medication that is best used short term due to its side effects such as severe liver damage (Mayo Clinic, 2019). Cyclosporine another medication that is recommended for temporary use because it is an immunosuppressant. It increases the risk of infection and the development of other conditions, such as cancer and hypertension.

 The last treatment category is phototherapy and it is prescribed to patients that have moderate-severe psoriasis that has been unsuccessfully treated with topical medications. This treatment uses natural or artificial ultraviolet light. One such method of phototherapy used is exposure to sunlight. The xxposure to ultraviolet rays in sunlight or artificial light slows down skin cell replication thus reducing scaling and inflammation. This can be a tricky method because it involves momentary, daily exposures to small amounts of sunlight and if the sun exposure is lengthened then it can worsen symptoms and cause skin damage. Another method is ultraviolet B (UVB) phototherapy which involves measured doses of UVB light from an artificial light source.

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