Psoriasis: An Overview

Psoriasis Overview

• A phenotypically heterogeneous, immune-mediated, chronic inflammatory skin condition occurs due to autoimmunity.
• Abnormal epidermal differentiation and hyper-proliferation presents redness and scaling, following a relapsing-remitting course.
• Worldwide, 2% of individuals are affected, totaling 100 million people.
• In the United States, 4 to 6 million people have psoriasis.
• Annually, the United States sees 150,000 new cases.
• 3% of the population is affected in Sweden.
• 4% of the population is affected in Italy and Russia.
• Onset typically peaks between 20-30 years or 50-60 years of age.
• It affects males and females equally, more commonly in white individuals while being rare in North and South American Indians
• The annual outpatient costs range from $1.6 to $3.2 billion in the U.S.
• Approximately 400 individuals pass away from psoriasis-related causes each year.
• Over 1.5 million people seek medical consultation for psoriasis on a yearly basis.
• Key resources include the National Psoriasis Foundation and the National Institutes of Health.
• The disease is often associated with other co-morbidities like arthritis, cardiovascular disease, obesity, hypertension, depression, diabetes, and hyperlipidemia.
• Rendon, A., et al. reports on psoriasis pathogenesis and treatment in the Int Jour Mol Science in 2019 (20(6):1475).

Psoriasis Hallmarks and Variants

• Sustained inflammation is the key feature, causing uncontrolled keratinocyte proliferation and dysfunctional differentiation.
• Acanthosis and epidermal hyperplasia is visible in psoriatic plaque histology, overlying inflammatory infiltrates of dermal dendritic cells, macrophages, T cells, and neutrophils; Neovascularization is also prominent.
• Inflammatory pathways in plaque psoriasis and other clinical types share similarities but the differences in phenotype and treatment are due to variances.
• Rendon, A., et al. described psoriasis pathogenesis and treatment in Int Jour Mol Sci 2019;20(6):1475.

Immune Cell Involvement

• Innate and adaptive cutaneous immune response disturbances are responsible for sustained psoriatic inflammation.
• Di Meglio, P., et al. researched Psoriasis, in Cold Spring Harb Perspect Med 2014; 4:6.
• Harden, J., et al. reviewed immunogenetics in psoriasis in Jour Autoimmun 2015; 64:66-73.
• Dendritic cells’ antigen presentation activates T cells, fueling psoriasis with pro-inflammatory cytokines and chemokines.
• Genetic studies indicate that antigen presentation has a key role in the disease.
• Veal, C., et al.’s “Family-based analysis using a dense single-nucleotide polymorphism-based map defines genetic variation at PSORS1, the major psoriasis-susceptibility locus remains in 2002 publication.
• Keratinocytes are essential in early disease stages and chronic inflammation.
• LCE gene deletion after minor skin injury contributes to chronic inflammation development.
• In early stages of psoriasis neutrophils cause recruitment and activation of T cells with proliferation and differentiation of keratinocytes
• The role of macrophages in psoriasis is not completely understood, but numbers triple in affected skin areas and activated macrophages elevate TNFα, likely regulating angiogenesis.
• Fuentes-Duculan, J., et al.'s subpopulation of CD163-positive macrophages is classically activated in psoriasis information from Jour Invest Dermatol 2010;130(10):2412-22.
• Psoriasis is driven by abnormally activated helper T cells with distinct cytokine ranges.
• Kagami, S., et al. reported elevated circulating Th17, Th22, and Th1. cell increase in psoriasis in Jour Invest Dermatol 2010; 130(5):1373-83.
• Psoriasis involves immune cell types and cytokine interactions, self-perpetuating cutaneous inflammation.
• Mahil, S., et al. addressed an update on psoriasis immunopathogenesis and targeted immunotherapy” by the Semin Immunopathol in 2016;38(1):11-27
• Gran, F., et al. wrote on current developments in the immunology of psoriasis” in Yale Jour Biol Med in 2020; 93(1):97–110

Disease Etiology

• Genetic predisposition occurs if one parent has psoriasis, child risk is 14%.
• If both parents have history, child risk rises to 41%.
• Various HLAs are associated with psoriasis
• HLA-Cw6 has the strongest connection, earlier onset, and is harder to treat; HLA-DR7 is also associated with disease
• PSORSI is the major gene. related to psoriasis.
• Genome-wide methylation levels are significantly higher in lesions of patients versus healthy controls and PASI scores
• Klaudia, D., et al. "The role of epigenetic factors in psoriasis," appears in the Int Jour of Mol Sci in 2021; 22:9294.
• Zhang, P., et al., report on aberrant DNA methylation in skin lesions/PBMCs with psoriasis vulgaris, Jour Dermatol Sci 2010.
• Environmental factors include physical trauma where isomorphic or Koebner phenomenon occurs, infections like streptococcal pharyngitis and Staph aureus, hypocalcemia, and stress.
• Rapid weight changes, ETOH consumption, and tobacco
• Tobacco use begins formation of free radicals
• Ibid., Bodemer., Tomi, N., et al., and Armstrong, A., et al. report on toxins, staph, genetics and smoking in a variety of journals listed in the text.
• Altered glucose metabolism mirrors how tumor cells uptake glucose, as glycolysis results in more ATP, promoting keratinocyte proliferation.
• Gray, N., et al. report on Novel functions of SIP in chronic itchy and inflammatory skin diseases, by Jour Eur Acad Dermatol Venereol in 2022
• Unbalanced amino acid metabolism causes abnormal arginine metabolism in keratinocytes.
• Liu, Y., et al. researched Pyruvate kinase M2 in psoriasis by Front Pharmacol in 2021
• Autoimmune skin diseases like psoriasis show local and systemic inflammation largely mediated by Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway
• Howell, M., et al.’s "Targeting the Janus Kinase family in autoimmune skin diseases", appears in Front Immunol 2019 issue
• Elevated reactive oxygen species and decreased antioxidants are important causes of psoriasis.
• Lin, X., et al. wrote of oxidative stress and potential therapeutic use of antioxidants, by Free Radic Res 2016
• Circadian rhythm disruption increases psoriasis likelihood as well as release of cytokines like IL-17, IL-6, and IL-1ß which are associated
• Cibrian, D., et al. write on amino acid transporter efficiently controls skin inflammation in Jour Allergy Clin Immunol 2020
• Medications like lithium, beta blockers, antimalarials, interferon, and rapid systemic corticosteroid tapers can also cause psoriasis

Subtypes of Psoriasis

• Chronic Plaque is the most common at 90%
• Guttate is the second most common occurring in 2% of all patients
• Inverse can also occur
• Erythrodermic psoriasis must be treated immediately
• Pustular psoriasis can be life threatening
• Rendon, A., et al. studied of pathogenesis and treatment in Int Journal of Mol Sci, 2019.

Clinical Presentation & Physical Findings

• Pustular variant has distinct phenotypes such as psoriasis pustulosa palmoplantaris (PPP) and acrodermatitis continua (ACS) of Hallopeau that affect hands/feet
• PPP is restricted to palms and soles where ACS is the tips of fingers/toes and affects the nail apparatus.
• Generalized pustular psoriasis has acute diffuse redness, pustules, and systemic symptoms
• Navarini, A., et al. reported on European consensus phenotypes in pustular psoriasis, Journal Eur Acad Dermatol Venereol, 2017
• About 90% of cases are chronic plaque-type.
• Sharply demarcated, erythematous, pruritic plaques covered in silvery scales are the classic manifestations.
• Plaques can cover large skin areas on the trunk, extensor surfaces of the limbs, and scalp.
• Ortonne, J., et al. reported on scalp psoriasis with treatment algorithm, found in Journal Eur Acad Dermatol Venereol
• Nestle, F reported on cases of psoriasis, found in the NEJM
• Guttate exhibits acute small erythematous plaques and group-A streptococcal tonsil infections in children and adolescents.
• About one-third of patients with guttate psoriasis develop it later on
• Ko, H., et al. wrote of clinical course of guttate psoriasis, which can be found in Journal of Dermatol from 2010
• Martin, B., et al report on the risk of further psoriasis after a single episode of acute guttate psoriasis.

Erythrodermic & Inverse Disease

• Over 90% of body presents erythematous with inflamed skin, requires emergency intervention and can develop on any psoriasis type.
• Inverse is also know as flexural psoriasis.
• Affects intertriginous areas and erosive, erythematous plaques/patches.
• Nail abnormalities occur in 55% of people and includes pits, oil slicks, subungual hyperkeratosis, onycholysis, see Ibid., Bodemer.

Conventional Treatment Options

• Skin care like bathing in cool to tepid water with gentle cleansers like Cetaphil and to apply emollients
• Colloidial oatmeal in bath form with Aveeno
• Oatmeal baths with water to half cup of oat flour.
• A thicker paste can be applied transdermally as a poultice to the affected area, Ibid., Bodemer
• Natural oils like avocado seed oil, almond oil, or olive oil to the affected area, Ibid., Bodemer also helps patients
• UVB decreases DNA synthesis, with radiations between 290-320nm, especially narrowbands between 308-313 nm, Immunosuppressive and anti-inflammatory effects helps patients
• Honigsmann, H., et al., “Ultraviolet light therapy,” in Bolognia, also helps with Dermatology St. Louis in 2003.
• Honigsmann, H reported on Phototherapy for psoriasis, and Clin Exp Dermatol from 2001, helps decrease effects.
• Erythema, pruritus, and even outbreaks can occur
• Long term, photoaging and skin cancers can arise from treatment, Ibid., Bodemer.
• Furocoumarins (used in Psoralens therapy), are found in limes, parsley, figs and celery and can be used topically or orally where they Incorporate DNA strands in the range of 320-400 nm, leading to DNA cross linkage (like chemotherapy that interrupts cycles) from UVB rays.
• Interactions with ROS to cause cell membrane damage include erythematous outbreaks and for 24 hours after requires proper eyewear
• Do not use in hepatic or kidney disfunction from psoralens and oral versions cause vomiting and permanent itching from sunburn which Ibid., Bodemer helps reduce
• Increased risk of squamous cell, tumors, lymphomas from immunosuppressives and leukemia treatment
• Stem, R “Malignant melanoma from methotrexate used to treat. melanoma,” helped with treatment
• Phototherapy has immunologic and combination therapies, successfully treats psoriasis and scalp psoriasis and Nakamura et al, F1000Res 2016 helps with phototherapy.

Methotrexate

• It is a folic acid antagonist blocking DNA synthesis and leads to cell cycle death, It also reduces inflammatory activity, Add 1 mg of folic acid daily for patients
• West, J., et al. shows “Safety and efficacy of methotrexate in Psoriasis,” is available in PLos One in 2016
• Side effects involve GI symptoms, Pancytopenia, cancer, hepatic or pulmonary fibrosis and needs liver enzymes, hepatic functionality, Ibid., Bodemer, from tests

Cyclosporine

• Cyclosporine initially isolated from the soil fungus Tolypocladium inflatum which inhibits expression of IL-2s, leading to immunosuppression
• Lim, K., et al. discusses Cyclosporine in the treatment of Dermatologic Disease:
• Koo, Y., et al. has info on Cyclosporine and related drugs, in Saunders Encyclopedia Side effects include renal, hypertension, excessive hair growth, gum inflammation from the treatment
• Ibid., Bodemer also has adverse effects and needs tests for renal function Magnesiums, cbc, BP and interacts herbal therapies and the paper by Sleymani outlines the guidelines with Cyclosporine
• Acitretin, retinoid with anti proliferative effects, also helps rapid control of inflammatory reactions
• Ibid., Bodemer helps with arthralgia and B tests

Acitretin

• It is an oral retinoid with receptor binding and anti-inflammatory action that can reduce lymphocyte proliferation and arachidonic acid metabolism.
• Rapid pustular psoriasis control, as well as dosages of 10mg up to 50mg
• Due to high Teratogenic potential, additional caution will need to be taken Can Also lead to skin drying, toxic hepatitis, Bony changes ,low healing rate and higher enzymes and cholesterol levels
• Can use dry skin by giving vitamin E with Systemic therapies, Jour Amer Acad Dermatol. (2001) helps
• Also needs lipid and pregnancy levels and has low dosages from what has been said prior