Psoriasis: Symptoms, Causes and Prevalence

• Psoriasis is a phenotypically heterogeneous, immune-mediated chronic inflammatory skin ailment.
• The condition appears with redness and scaling due to abnormal differentiation and hyper-proliferation in the epidermis and follows a relapsing and remitting course.
• Globally, psoriasis affects 2% of the general population, about 100 million.
• 4-6 million people in the U.S. have psoriasis.
• Approximately 150,000 new cases are diagnosed each year in the U.S.
• In Sweden, 3% of the population has psoriasis.
• In Italy and Russia, the prevalence rate is 4%.
• Peak onset typically occurs between 20 and 30 years and then again between 50 and 60 years.
• Psoriasis affects both genders equally, but is more common in white patients and rare in North and South American Indians.
• Annual outpatient costs range from $1.6 to $3.2 billion in the U.S.
• Around 400 people die each year from psoriasis-related causes.
• Over 1.5 million people see their doctor for psoriasis annually.
• The National Psoriasis Foundation and the National Institutes of Health are resources for information.

Psoriasis Co-Morbidities

• Psoriasis can coincide with conditions like arthritis, cardiovascular disease, obesity, hypertension, depression, diabetes, and hyperlipidemia.

Psoriasis Hallmarks

• Sustained inflammation results in uncontrolled keratinocyte proliferation and dysfunctional differentiation.
• Histology reveals acanthosis (epidermal hyperplasia) overlying inflammatory infiltrates of dermal dendritic cells, macrophages, T cells, and neutrophils.
• Neovascularization is often a feature.
• Inflammatory pathways active in plaque psoriasis and other clinical variants overlap, yet have variances influencing phenotype and treatment outcomes.

Immune Cell Types

• Disturbances in innate and adaptive cutaneous immune responses are responsible for psoriatic inflammation.
• Genetic studies highlight antigen presentation as a fundamental element in the disease; dendritic cells activate T cells and are a source of pro-inflammatory cytokines and chemokines.
• Keratinocytes play a critical role in the early stages of disease pathogenesis and later in the amplification of chronic inflammatory circuits.
• Neutrophils are involved in the early stages of psoriasis, recruiting and activating T cells, and promoting the proliferation and differentiation of keratinocytes.
• While the role of macrophages remains not fully understood, threefold increases in cell numbers are noted in affected areas.
• Activated macrophages produce high levels of TNFα and are likely regulators of angiogenesis.
• Psoriasis is known as an autoimmune process driven by abnormally activated helper T cells.
• The presence of multiple T cell subsets, including CD4+ Th1, Th17, and Th22 producing IFNγ/TNFα, IL-17/IL-22, and IL-22, are relevant in the disease progression.
• Psoriasis involves a complex interplay between immune cell types and cytokine networks within self-perpetuating feedback loops, driving cutaneous inflammation.

Etiology: Multifactorial Factors

• In genetic factors, the risk is 14% if one parent has psoriasis, and if both parents have psoriasis, the risk increases to 41%.
• HLAs associated with psoriasis includes HLA-B13, HLA-B17, HLA-B27, HLA-Cw6 (strongest connection), HLA-DR7.
  • HLA-Cw6 is related with earlier disease onset and can be harder to treat.
• PSORSI is the main gene related to psoriasis.
• Genome-wide methylation levels are significantly increased in psoriasis patients' lesions compared to healthy controls, correlating positively with psoriatic lesion area and severity index (PASI) scores.

Environmental Factors

• Physical trauma can lead to isomorphic or Koebner phenomenon.
• Infections such as streptococcal pharyngitis and Staph aureus.
• Hypocalcemia and stress.
• Rapid weight changes, ETOH Consumption, and tobacco use which initiates the formation of free radicals.
• Abnormal glucose metabolism and excessive proliferation of keratinocytes are like those in tumor cells.
• Psoriasis exhibits increased glucose uptake and elevated glycolytic levels, which produce increased ATP that promotes keratinocyte proliferation.
• New studies establish that the amino acids and autoantigens caused by metabolism of arginine is abnormal.
• Autoimmune skin diseases as psoriasis are characterized by local and systemic inflammation that is mediated by the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway.
• Increased production of ROS and reactive nitrogen species (RNS), along with decreased antioxidant concentrations are causes of psoriasis.
• Epidemiological studies claim psoriasis is more likely to occur with circadian rhythm disturbances, and with cytokines like IL-17, IL-6, and IL-1ß releases.
• Medications like lithium, beta blockers, antimalarials, interferon, and rapid tapers of systemic corticosteroids can have an adverse effect.

Psoriasis Subtypes

• Chronic plaque is the most common at 90%.
• Guttate is the second most common at 2%.
• Inverse.
• Erythrodermic.
• Pustular which can be life-threatening.

Chronic Plaque Psoriasis

• Chronic plaque-type psoriasis corresponds to around 90% of psoriasis cases.
• Symptoms are defined as sharply demarcated, erythematous, pruritic plaques covered in silvery scales.
• Plaques can coalesce and cover large areas of skin, commonly on the trunk, extensor surfaces of the limbs, and scalp.

Guttate Psoriasis

• The variant is the acute onset of small erythematous plaques.
• Affecting children or adolescents.
• It's triggered by group-A streptococcal infections of tonsils.
• About one-third of patients develop plaque psoriasis throughout their adult life.

Inverse Psoriasis

• It is also called flexural psoriasis.
• This variant affects intertriginous locations.
• Symptoms are slightly erosive erythematous plaques and patches.

Erythrodermic Psoriasis

• With this variant, over 90% of the total body surface is erythematous and inflamed.
• Erythroderma can develop on any kind of psoriasis type and it requires emergency treatment.

Pustular Psoriasis

• The variant is characterized by multiple, coalescing sterile pustules and can be localized or generalized.
• Psoriasis pustulosa palmoplantaris (PPP) and acrodermatitis continua (ACS) of Hallopeau are two distinct localized phenotypes that affect the hands and feet.
• PPP is restricted to the palms and soles.
• ACS is more distally located at the tips of fingers and toes which affects the nail apparatus.
• Generalized pustular psoriasis presents with acute, progressive, diffuse redness, and subcorneal pustules accompanied by systemic symptoms.

Nail Abnormalities

• Nail abnormalities, including pits, oil slicks, subungual hyperkeratosis, and onycholysis, are common.
• The abnormalities that can occur account for up to 55% of cases.

Conventional Treatments

• Consists of skin care.
• Phototherapy.
• Methotrexate.
• Cyclosporine.
• Acitretin.
• Biologic immune response modifiers like TNF antagonists, IL-12/IL-23 inhibitors, and IL-17 inhibitors for targeted treatments.
• Oral and topical Phosphodiesterase inhibitors, Janus kinase inhibitors, A3 adenosine receptor agonists, IL-1 antagonists are other conventional treatments.
• Topical pharmaceuticals.
• Botulinum toxin.

Skin Care

• Skin care should include bathing in cool to tepid water with gentle cleansers like Cetaphil.
• Applying emollients and colloidal oatmeal in bath form such as Aveeno is also a key step.
• Oatmeal baths can be made from oats ground in a blender into a fine powder; add water to oat flour for a slurry or a paste as a poultice.
• Natural oils like avocado, almond, and olive are effective skin soothers.

Phototherapy Treatments

• Psoriasis improves in the summer due to exposure to UV light.
• UVB Includes radiation with wavelengths between 290 and 320 nm, narrow-band being the most effective (between 308 and 313 nm).
  • UVB Decreases DNA synthesis.
  • Has immunosuppressive effects.
  • Decreases inflammation.
• Possible side effects of ultraviolet B is short-term erythema, xerosis, pruritus, increased frequency of herpes simplex outbreaks, long-term photoaging and at times increased risk of skin cancers.
• UVA: Ultraviolet A and Psoralen Therapy (PUVA) includes psoralens that are furocoumarins in limes, parsley, figs, and celery.
  • Psoralens can be used orally or topically.
  • They incorporate DNA strands and absorb photons in the range of 320 to 400 nm which causes DNA cross-linkage causing cell cycle arrest
  • It also interacts with ROS to cause cell membrane damage.
• Possible side effects from UVA includes erythema at the site.
• Psoralens last for 24 hours in the patient and require eyewear, avoided sun and strict photo protection.
  • Should not be administered to patients with renal or liver disease.
  • Possible results is oral psoralens, nausea and vomiting, sunburn, and persistent pruritus.
• Increased risk of developing squamous cell carcinoma of the skin may occur in treatment with UV.
• Later treating with immunosuppressive therapy increases the risk of squamous cell carcinoma.
• There is also an increased risk of developing basal cell carcinomas or melanoma of the trunk or extremities.
• Increased risk of developing lymphoma if patients used PUVA and methotrexate

Other Phototherapy Facts

• Success has been achieved for phototherapy used successfully with agents as combination therapy to treat recalcitrant psoriasis.
• Recent studies have specified immunologic effects of phototherapy linked to treatment effectiveness.
• Advances include targeted phototherapy modalities for areas such as scalp psoriasis.
• Though old, phototherapy is still a mainstay with promising advancement.

Methotrexate Facts

• It is a folic acid antagonist, which blocks the formation of the building blocks needed for DNA synthesis, leading to cell cycle death that is immunosuppressive and anti-inflammatory.
• The treatment involves raising tissue levels of adenosine and adding 1 mg of folic acid daily for patients to take qd.
• Possible side effects include GI Symptoms, pancytopenia, hepatotoxicity, pulmonary fibrosis, cancer, and teratogenicity. Methotrexate with PUVA increases cancer.
• CBC, renal, and liver function needs to be monitored.
• A liver Bx needs to be done after a cumulative dose of 1.5 to 2 grams.

Cyclosporine Facts

• It was initially isolated from soil fungus Tolypocladium inflatum.
• It inhibits IL-2 gene transcription, leading to decreased T-cell proliferation and activation, which inhibits various pro-inflammatory cytokines transcriptions.
• Possible side effects include renal dysfunction, HTN, hypertrichosis, gingival hyperplasia, GI upset, headache, tremor, paresthesias, electrolyte imbalances, sleep disturbances, acneiform eruptions, hypertriglyceridemia, decreased seizure threshold, BM suppression.
• There is a need to monitor BP, renal function, CBC, liver function tests, and Magnesium, potassium, uric acid. Cyclosporine is Cleared through the P-450 CYP3A4 enzyme system, resulting in interaction with medications and herbal therapies.

Acitretin Facts

• It is an oral retinoid that has anti-proliferative action through retinoid receptor binding.
• Anti-inflammatory effects reduces lymphocyte proliferation and decreases archidonic acid metabolism.
• Acitretin has a dose of 10, 25, 50 mg a day and is used for rapid control of pustular psoriasis.
• Since it is a retinoid, it is teratogenic and can cause drying of skin and mucous membranes.
  • A side effect is decreased night vision.
• This can result in pseudotumor cerebri especially if given with tetracycline, and Arthralgias/Myalgias that can lead to elevation of cholesterol and triglycerides as well as Elevation of liver enzymes rarely toxic hepatitis. Bony changes (hyperostosis) may develop that leads to poor wound healing and Gl symptoms.
• Dry skin may be improved with 800 IU of vitamin E daily which is a blood thinner.
• Monitoring considerations need to include pregnancy tests, lipid panel, liver function tests, CBC with platelets, renal function tests, and Creatine phosphokinase.

Biologic Immune Response Modifiers

• The complex engineered molecules including monoclonal antibodies and receptor fusion proteins are directed specifically at neutralizing cytokines to decrease the inflammatory response.
• Act predominantly in the chronicity and development of IL-23/Th17 axis and TNF-alpha the signalling of psoriatic plaque targeted through biologics, the message that block costimulatory cells are important for the transduction of signaling and activation of T cells by secreting costimulatory messages of accessory products.
• Alefacept: fusion protein that Blocks the costimulatory signal between leukocyte function associated antigen 3 (LEA-3) and CD2 needed for antigen mediated T-cell activation and given s.c.
• Etanercept: A humanized chimeric monoclonal antibody to TNF-alpha.
• Given s.c.
• Efalizumab: monoclonal antibody directed against CD1la (a component of LEA-1) Blocks the costimulatory interaction between LEA-1 and intercellular adhesion molecule-1 (ICAM-1) which prevents T-cell activation.
• Infliximab: monoclonal antibody, Neutralizes TNF-alpha by binding to both soluble and transmembrane TNF-alpha that reduces apoptosis of TNF-alpha-expressing cells, inhibits other pro inflammatory Cytokines which decreases keratinocyte proliferation.
  • Given IV.
• Ustekinumab: human monoclonal antibody that Blocks both IL-12 and IL-23 caused by differentiation of CD4' T cells to types 1 and 17 helper cells as a mediators.
• Adalimumab: Human monoclonal antibody that against TNF-alpha given via s.c injection
• Certolizumab: Fab portion of humanized monoclonal antibody that against TNF-alpha and Given s.c.
• Thorough evaluation including P/E and blood work are prerequisites and baseline medications require vaccination completion before commencement of therapy.

Topical Pharmaceuticals

• Keratolytics decrease the thickness of the psoriatic plaques, increasing comfort as thinner plaques enhances topicals therapy.
• Example: Salicylic acid (2% to 10%), urea (up to 40%), alpha-hydroxy acid, glycolic acid, and lactic acid.
• Topical Salicylic acid should not be applied extensively on the body of children due to risk of Systemic absorption which can cause salicylism, Tinnitus, nausea and vomiting.
• Coal tar created from gasses produced during cooling by distillation of coal extraction that are condensed, resulting in dark liquid and ammonia that contains 10,000 chemical compounds such as Phenols, polycyclic aromatic hydrocarbons, and Nitrogen bases.
• Coal tar has anti-proliferative & anti-inflammatory impacts.
• Use includes 5% to 20% preparations with UV radiation that increases potential risk of developing Phototoxicity, skin cancer Contact allergy, Irritant dermatitis and Acneiform eruptions.
• Anthralin is synthetic derivative of chrysarobin extracted from Goa powder from araroba tree for cells differentiation.
  • 0.5% to 1% preparation applied needs to be washed off after 10-30 minutes with qd or BID process.
  • Irritation to normal skin can be decreased by using petrolatum protection or zinc oxide around psoriatic plaques causing stains due to messy brownish color.
• Hair discoloration decreases when coated due to henna powder.

Other Topical Treatments

• Calcipotriene the bioactive form (1,25-dihydroxycholecalciferol) inhibits keratinocyte proliferation that affects calcium.
• Supplement adequate oral dosages, dosage is 0.005% cream ointment, lotion or cream applied BID.
• Self-limited irritant dermatitis often occurs and Photosensitivity after calcipotriene administration after UVB is an option.
• Monitor for Hypercalcemia as a risk when is kept above less than 100 grams a week.
• Tazarotene gel is a topical retinoid and vitamin A derivative that increases keratinocytes differentiation used daily with 0.05% to 0.1% gel in topical steroid resulting to pruritus and skin irritation.
  • It is also teratogenic.
• Steroids which lead to alterations gene transcription are the most common treatment strategy associated with tachyphylaxis and is less potent over time, combining topical steroids with other pharmaceuticals will minimize the issue of dosage affect.
• A combination of vitamin D analogue and a corticosteroid improves with calcipotriene and betamethasone with disrupts of the IL-36 and IL-23/IL-17 positive feedback loop for psoriasis.
• JAK Inhibitors are an option through use of Tofacitinib and Ruxolitinib treatments.

Additional Traditional Treatments

• Botulinum Toxin Study shown improvement on a study for with no significancy of side effects that uses novel the treatments of plague psoriasis, which had improvements with Psoriasis symptoms and Animal studies.
• To assist personalized medicine therapies patients often need to undergo changes with diet.
• Avoid pro-inflammatory foods with meat such as fish, foul, and lamb, and those that contain acid and white wines.
  • Suggest removing pizza and white products.
• Encourage patients remove foods that contain nicotine.

Nutrition changes

• Tell to avoid foods that involve nightshade family with tomatoes and derivations especially and patient use, the rate is approximate close to 25%.
• Other food to exclude are egg plants and peppers those that are in the same category.
• Encourage patients to avoid taking soft drinks as a result of risk factors is accumulating over consumption of mass index.
• Suggest to drink to increase amount of water in take and eliminate alchol.
• Avoid when possible foods the patient is allergic to as a part of the weight loss diet.
• It is important body mass and weight needs be to controlled even taking medication in PASI ( Psoriasis severity index).
• Antioxidants has been known to assist beneficially over time also, if those that consider supplementation take 1 fish oils and for those with additional supplementation, it's not yet available for high effectiveness.

Nutritional Facts and Supplements

• EPA/DHA supports use in inflammatory since it inhibits the 1l-6 level which can decrease levels of Leukotrienes.
• A double blind test was done over high dose of fishoil verse olive oil (capsule) was discovered the main group itching, scaling, erythema when administered for over for 6 weeks.
• Other treatment was random over acute based lipid or omega 3 fatty acids in a IV administration process in a hospital to get involved with is over 10% of body which was very important for results.
• Also know can cause omega -3 which can lower the hypertriglyceridemia levels and with kidney nephrotoxicicity risks factors.
• Should not use over 3,000 mg of EPA/DHA with anticoagulants which then will result can cause blood thinners.

Supplement Side Effects

• Side effects during supplementation zinc causes toxicity like nausea, vomitting, and metallic taste with higher doses that cause watery with diarrhea and gut erosion from kidney necrosis as well.
• Inositol needs to be used during the cases a lithium based medication is used, around (6 grams a day) that will improve the psoriasis effect during medication.
• It’s important to replace vitamins and check levels D for the patient to have better results with reduction with the overall clinical severity during psoriasis cases, in skin cases for better effects to take orally.
• Practitioners have stated lecithin helps.
• Should use a tbsp for TID for 5 days to help, however, to prevent those that are in soy or allergins and it's important to to provide antioxidants which is caused by inflammation.

Topical botanical facts

• Local skin and irritation can affect total (27 in total) assessment addressing effective use of mahonia plants to relieve the symptoms irritation or skin problems. Capsaicin substance is the ability to affect skin that helps for expression over activation of the substance and eliciting of the potential for skin irritation. • Is an extraction that acts over QID (quadrant into 4th) to check for improvement and has a double blind that shows the test.
• The topical cream administration for redness from skin requires a .025% usage with TID to QID base cream but watch for burning sensations during the application and after the process patients shall avoid washing the area with the medication applied due to effects to NF-kB which causes itch/redness.
• This can further be improved through Aloe vera for it help reduce scale accumulation, redness, and reducing inflammation of the plagues with the addition for extracts it shows help inhibiting to reduce keratinocytes.
• Licorice aids in treatment and contains good substances, however there's minimal testing to prove affect during psoriasis symptoms.
• M with Aquifolum patients has shown to help well tolerated those that had a MILD condition.

Systemic botanicals to support treatment.

• Curcumin helps to create a active ingredients that help that for the patients to take small dosage of complex that contains 95% over 9x for 12x over time that is also needed to show high performance during oral trials to alleviate psoriasis like conditions, this is only a suggestion as the evidence is not high.
• Milk thistle protects against the liver or DNA injury, and protein based synthesis, the test can vary with patients needs for usage or insulin.
• Resveratrol, helps that by preventing and reducing the production of cytokines
• Quercetin uses plant based material that provides support with psoriasis, this has the support to improve that status over IMQ testing to improve that that for (animal testing).
• Kaempferol supports polyphenols and is a natural option prevent the diseases and inflammation effects, this has shown high affects with animal related products of keratinocytes.
• Naringin or the citrus is high effects can be found beans and cherries which will produce and reduce some of the cytokines due to immunological effects for high performance
• EGCG or plant compound product extracted reduces some of the inflammatory

Additional recommendations

• Meditation can aid with those who were diagnosed which does have benefit as they go through the process.
• 2 weeks to have benefits for the the current tape those using both UVb or puva tape to alleviate stress
• Hypnosis may be a strategy for a high improvement factor.

TCM or Traditional Chinese Medicine

• The main cause for skin eruptions comes from nutrients for skin, which shows that a good way for skin quality
• external heat and wind
• Acculumlated blood heat caused by lifestyle
• Q1 which caused stasis of bad blood and organs affected.
• Preparations do need to be tested to stay free of chemicals, the 10 most tested herbs have been tested over time for psoriasis.
  • Most important to prevent herbal regulation which will affect the damage of the products.

Acupuncture Recommendations

• Depends on the factor for points regarding the psoriasis conditions helps with those that have severe cases over the sessions, and has is is a good approach overall .

• The way is to to make patients move to dryer areas to allow for for skin quality by preventing stress as the results do come from stressful events and mental support, with saliva test its always a a solid approach to determine a good option.

• Use mouthwash for infections, listerine product it can go to use full scale on the body with a quart.

Final Topical and Application Notes.

The following mixtures will decrease and help symptoms.

• Baking Soda water paste: 2oz of Aple cider, 4 oz -7 oz to apply to head scalp (test head first).
• This includes shampoos which must be used 1-2 times per week as a result of oils.

After 1 hour of the application process to reduce pain shampoo after.

• Apply the mix on head
• Dry with the cloth that you own with a cool set
• Also suggest, use coconut oil, petroleum jelly to support the body for additional
• There is also a zinc pyrithione that helps to alleviate the skin by using the process that can affect vitiligo, cadmium can affect the process too, do blood tests to take measure!

Conclusion & Summarization of Ailments

• Traditional and alternative medicines have great effective value as there's need now for the reduction side and improving Gl level, to improve the process that uses LDN effect to promote great support.
• Baker's is great topical for skin which includes the hair line that will improve hair quality!
• Psoriasis usually a common skin form has a specific treatment, which are on feet for skin issues that usually come along with nail psoriasis.
• In the skin over the week, zinc , the oils (peanut, olive), or castor can be applied and make a significant.
• There needs to to be a way to improve the epidermis condition from zinc, omega and others.
• It is important to also keep nails very short before the process takes place.