The five main types of psoriasis are plaque,guttate,inverse,pustular, anderythrodermic.[5] Plaque psoriasis, also known as psoriasis vulgaris, makes up about 90% of cases.[4] It typically presents as red patches with white scales on top.[4] Areas of the body most commonly affected are the back of the forearms, shins,navel area, and scalp.[4] Guttate psoriasis has drop-shaped lesions.[5] Pustular psoriasis presents as small, noninfectious,pus-filledblisters.[10] Inverse psoriasis forms red patches in skin folds.[5] Erythrodermic psoriasis occurs when the rash becomes very widespread and can develop from any of the other types.[4]Fingernails and toenails are affected in most people with psoriasis at some point in time.[4] This may include pits in the nails or changes in nail color.[4]
Psoriasis is generally thought to be agenetic disease that is triggered by environmental factors.[3] If onetwin has psoriasis, the other twin is three times more likely to be affected if the twins areidentical than if they arenonidentical.[4] This suggests that genetic factors predispose to psoriasis.[4] Symptoms often worsen during winter and with certain medications, such asbeta blockers orNSAIDs.[4] Infections andpsychological stress can also play a role.[3][5] The underlying mechanism involves theimmune system reacting toskin cells.[4] Diagnosis is typically based on the signs and symptoms.[4]
Psoriatic plaque, showing a silvery center surrounded by a reddened border
Psoriasis vulgaris (also known as chronic stationary psoriasis or plaque-like psoriasis) is the most common form and affects 85–90% of people with psoriasis.[12] Plaque psoriasis typically appears as raised areas ofinflamed skin covered with silvery-white, scaly skin. These areas are called plaques and are most commonly found on the elbows, knees,scalp, and back.[12][13]
Pustular psoriasis appears as raised bumps filled with noninfectious pus (pustules).[15] The skin under and surrounding the pustules is red and tender.[16] Pustular psoriasis can either be localized or more widespread throughout the body. Two types of localized pustular psoriasis include psoriasis pustulosa palmoplantaris andacrodermatitis continua of Hallopeau; both forms are localized to the hands and feet.[17]
Inverse psoriasis (also known as flexural psoriasis) appears as smooth, inflamed patches of skin. The patches frequently affectskin folds, particularly around thegenitals (between the thigh and groin), thearmpits, in the skin folds of an overweight abdomen (known aspanniculus), between the buttocks in the intergluteal cleft, and under thebreasts in theinframammary fold. Heat, trauma, and infection are thought to play a role in the development of this atypical form of psoriasis.[18]
Napkin psoriasis is a subtype of psoriasis common in infants under the age of two and is characterized by red papules with silver scales in the diaper area that may extend to the torso or limbs.[19][20] Napkin psoriasis is often misdiagnosed asnapkin dermatitis (diaper rash).[21] It typically improves as children age and may later present in more common forms asplaque psoriasis orinverse psoriasis.[22]
Guttate psoriasis is an inflammatory condition characterized by numerous small, scaly, red or pink, droplet-like lesions (papules). These numerous papules appear over large areas of the body, primarily thetrunk, limbs, and scalp, but typically spare the palms and soles. Guttate psoriasis is often triggered by astreptococcal infection (oropharyngeal or perianal) and typically occurs 1–3 weeks post-infection.Guttate psoriasis is most commonly seen in children and young adults, and diagnosis is typically made based on history and clinical exam findings.[23] Skinbiopsy can also be performed which typically shows a psoriasiform reaction pattern characterized by epidermalhyperplasia with elongation of therete ridges.[23]
There is no firm evidence regarding the best management for guttate psoriasis; however, first-linetherapy for mild guttate psoriasis typically includes topical corticosteroids.[23][24]Phototherapy can be used for moderate or severe guttate psoriasis. Biologic treatments have not been well studied in the treatment of guttate psoriasis.[23]
Guttate psoriasis has a betterprognosis than plaque psoriasis and typically resolves within 1–3 weeks; however, up to 40% of patients with guttate psoriasis eventually convert to plaque psoriasis.[23][18]
Psoriatic erythroderma (erythrodermic psoriasis) involves widespread inflammation and exfoliation of the skin over most of the body surface, often involving greater than 90% of the body surface area.[17] It may be accompanied by severe dryness, itching, swelling, and pain. It can develop from any type of psoriasis.[17] It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemicglucocorticoids.[25] This form of psoriasis can be fatal as the extreme inflammation and exfoliation disrupt the body's ability toregulate temperature and perform barrier functions.[26]
Psoriasis in the mouth is very rare, in contrast tolichen planus, another common papulosquamous disorder that commonly involves both the skin and mouth.[27] When psoriasis involves the oralmucosa (the lining of the mouth), it may be asymptomatic,[27] but it may appear as white or grey-yellow plaques.[27]Fissured tongue is the most common finding in those with oral psoriasis and has been reported to occur in 6.5–20% of people with psoriasis affecting the skin. The microscopic appearance of oral mucosa affected bygeographic tongue (migratory stomatitis) is very similar to the appearance of psoriasis.[28] A recent study found an association between the two conditions, and it suggests that geographic tongue might be a predictor for psoriasis.[29]
Psoriatic arthritis is a form of chronic inflammatoryarthritis that has a highly variable clinical presentation and frequently occurs in association with skin and nail psoriasis.[30][31] It typically involves painful inflammation of the joints andsurrounding connective tissue and can occur in any joint, but most commonly affects the joints of the fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes known asdactylitis.[30] Psoriatic arthritis can also affect the hips, knees, spine (spondylitis), andsacroiliac joint (sacroiliitis).[32] About 30% of individuals with psoriasis will develop psoriatic arthritis.[12] Skin manifestations of psoriasis tend to occur before arthritic manifestations in about 75% of cases.[31]
Psoriasis of a fingernail, with visible pittingEffect of psoriasis on the toenails
Psoriasis can affect the nails and produces a variety of changes in the appearance of fingers and toenails. Nail psoriasis occurs in 40–45% of people with psoriasis affecting the skin, and has a lifetime incidence of 80–90% in those with psoriatic arthritis.[33] These changes include pitting of the nails (pinhead-sized depressions in the nail is seen in 70% with nail psoriasis),whitening of the nail,small areas of bleeding from capillaries under the nail, yellow-reddish discoloration of the nails known as the oil drop or salmon spots, dryness, thickening of the skin under the nail (subungual hyperkeratosis), loosening and separation of the nail (onycholysis), and crumbling of the nail.[33]
In addition to the appearance and distribution of the rash, specificmedical signs may be used by medical practitioners to assist with diagnosis. These may includeAuspitz's sign (pinpoint bleeding when the scale is removed),Koebner phenomenon (psoriatic skin lesions induced by trauma to the skin),[19] anditching and pain localized to papules and plaques.[18][19]
The cause of psoriasis is not fully understood. Genetics, seasonal changes, skin damage, climate,immunocompromised state, specific infections, and the use of some medications have been connected with different types of psoriasis.[34][35]
Around one-third of people with psoriasis report afamily history of the disease, and researchers have identified geneticloci associated with the condition.Identical twin studies suggest a 70% chance of a twin developing psoriasis if the other twin has the disorder. The risk is around 20% for fraternal twins. These findings suggest both a genetic susceptibility and an environmental response in developing psoriasis.[36]
Psoriasis has a strong hereditary component, and many genes are associated with it, but how those genes work together is unclear. Most of the identified genes relate to theimmune system, particularly themajor histocompatibility complex (MHC) andT cells. Genetic studies are valuable due to their ability to identify molecular mechanisms and pathways for further study and potential medication targets.[37]
Classic genome-widelinkage analysis has identified nine loci on differentchromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (PSORS1 throughPSORS9). Within those loci are genes on pathways that lead to inflammation. Certain variations (mutations) of those genes are commonly found in psoriasis.[37]Genome-wide association scans have identified other genes that are altered to characteristic variants in psoriasis. Some of these genes express inflammatory signalproteins, which affect cells in the immune system that are also involved in psoriasis. Some of these genes are also involved in other autoimmune diseases.[37]
The major determinant isPSORS1, which probably accounts for 35–50% of psoriasis heritability.[38] It controls genes that affect the immune system or encode skin proteins that are overabundant in psoriasis.PSORS1 is located onchromosome 6 in the MHC, which controls important immune functions. Three genes in thePSORS1 locus have a strong association with psoriasis vulgaris:HLA-C variantHLA-Cw6,[34] which encodes an MHC class I protein;CCHCR1, variant WWC, which encodes acoiled coil protein overexpressed in psoriaticepidermis; andCDSN, variant allele 5, which encodescorneodesmosin, a protein expressed in the granular andcornified layers of the epidermis and upregulated in psoriasis.[37]
Two major immune system genes under investigation are interleukin-12 subunit beta (IL12B) onchromosome 5q, which expresses interleukin-12B; andIL23R on chromosome 1p, which expresses the interleukin-23 receptor and is involved in T cell differentiation. Interleukin-23 receptor andIL12B have both been strongly linked with psoriasis.[34] T cells are involved in the inflammatory process that leads to psoriasis.[37] These genes are on the pathway that upregulates tumor necrosis factor-α andnuclear factor κB, two genes involved in inflammation.[37] The first gene directly linked to psoriasis was identified as theCARD14gene located in thePSORS2 locus. A rare mutation in the gene encoding for theCARD14-regulated protein, plus an environmental trigger, was enough to cause plaque psoriasis (the most common form of psoriasis).[39][40]
Conditions reported as worsening the disease include chronic infections, stress, and changes in season andclimate.[34] Other factors that might worsen the condition include hot water, scratching psoriasis skin lesions,skin dryness,excessive alcohol consumption,cigarette smoking, andobesity.[34][41][42][43] The effects of stopping cigarette smoking or alcohol misuse have yet to be studied as of 2019.[43]
The rate of psoriasis inhuman immunodeficiency virus-positive (HIV) individuals is comparable to that of HIV-negative individuals, but psoriasis tends to be more severe in people infected with HIV.[44] A much higher rate of psoriatic arthritis occurs in HIV-positive individuals with psoriasis than in those without the infection.[44] The immune response in those infected with HIV is typically characterized bycellular signals fromTh2 subset of CD4+ helper T cells,[45] whereas the immune response in psoriasis vulgaris is characterized by a pattern of cellular signals typical ofTh1 subset of CD4+ helper T cells andTh17 helper T cells.[46][47] The diminished CD4+ T cell presence is thought to cause overactivation of CD8+ T cells, which are responsible for the exacerbation of psoriasis in HIV-positive people. Psoriasis in those with HIV/AIDS is often severe and may be untreatable with conventional therapy.[48] In those with long-term, well-controlled psoriasis, new HIV infection can trigger a severe flare-up of psoriasis and/or psoriatic arthritis.[medical citation needed]
Psoriasis is characterized by an abnormally excessive and rapid growth of theepidermal layer of the skin.[51] Abnormal production of skin cells (especially duringwound repair) and an overabundance of skin cells result from the sequence of pathological events in psoriasis.[16] The sequence of pathological events in psoriasis is thought to start with an initiation phase in which an event (skin trauma, infection, or drugs) leads to activation of the immune system and then the maintenance phase consisting of chronic progression of the disease.[37][17] Skin cells are replaced every 3–5 days in psoriasis rather than the usual 28–30 days.[52] These changes are believed to stem from the premature maturation ofkeratinocytes induced by an inflammatory cascade in thedermis involvingdendritic cells,macrophages, and T cells (three subtypes of immune cells).[12][44] These immune cells move from thedermis to the epidermis and secrete inflammatory chemical signals (cytokines) such asinterleukin-36γ,tumor necrosis factor-α,interleukin-1β,interleukin-6, andinterleukin-22.[37][53] These secreted inflammatory signals are believed to stimulate keratinocytes to proliferate.[37] One hypothesis is that psoriasis involves a defect inregulatory T cells, and in the regulatory cytokineinterleukin-10.[37] The inflammatory cytokines found in psoriatic nails and joints (in the case of psoriatic arthritis) are similar to those of psoriatic skin lesions, suggesting a common inflammatory mechanism.[17]
Gene mutations of proteins involved in the skin's ability to function as a barrier have been identified as markers of susceptibility for the development of psoriasis.[54][55]
Deoxyribonucleic acid (DNA) released from dying cells acts as an inflammatory stimulus in psoriasis[56] and stimulates the receptors on certain dendritic cells, which in turn produce the cytokine interferon-α.[56] In response to these chemical messages from dendritic cells and T cells, keratinocytes also secrete cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-α, which signal downstream inflammatory cells to arrive and stimulate additional inflammation.[37]
Dendritic cells bridge theinnate immune system andadaptive immune system. They are increased in psoriatic lesions[51] and induce the proliferation of T cells and type 1 helper T cells (Th1). Targetedimmunotherapy, as well aspsoralen andultraviolet A (PUVA) therapy, can reduce the number of dendritic cells and favors aTH2 cell cytokine secretion pattern over a Th1/Th17 cell cytokine profile.[37][46] Psoriatic T cells move from the dermis into the epidermis and secrete interferon-γ andinterleukin-17.[57] Interleukin-23 is known to induce the production of interleukin-17 and interleukin-22.[51][57] Interleukin-22 works in combination with interleukin-17 to induce keratinocytes to secreteneutrophil-attracting cytokines.[57]
Micrograph of psoriasis vulgaris. Confluentparakeratosis, psoriasiform epidermal hyperplasia [(A), EH], hypogranulosis, and an influx of numerous neutrophils in the corneal layer [(A), arrow]. (B) Transepidermal migration of neutrophils from the dermis to the corneal layer (arrows).[58]
Adiagnosis of psoriasis is usually based on the appearance of the skin. Skin characteristics typical for psoriasis are scaly,erythematous plaques, papules, or patches of skin that may be painful and itch.[18] No specialblood tests or diagnostic procedures are usually required to make the diagnosis.[16]
If the clinical diagnosis is uncertain, a skinbiopsy or scraping may be performed to rule out other disorders and to confirm the diagnosis. Skin from a biopsy shows clubbedepidermal projections that interdigitate with dermis on microscopy.Epidermal thickening is another characteristichistologic finding of psoriasis lesions.[16][59] Thestratum granulosum layer of the epidermis is often missing or significantly decreased in psoriatic lesions; the skin cells from themost superficial layer of skin are also abnormal as they never fully mature. Unlike their mature counterparts,these superficial cells keep theirnuclei.[16] Inflammatory infiltrates can typically be seen on microscopy when examining skin tissue or joint tissue affected by psoriasis. Epidermal skin tissue affected by psoriatic inflammation often has many CD8+ T cells, while a predominance of CD4+ T cells makes up the inflammatory infiltrates of the dermal layer of skin and joints.[16]
Psoriasis is classified as apapulosquamous disorder and is most commonly subdivided into different categories based on histological characteristics.[3][10] Variants include plaque, pustular, guttate, and flexural psoriasis. Each form has a dedicatedICD-10 code.[60] Psoriasis can also be classified into nonpustular andpustular types.[61]
Another classification scheme considers genetic and demographic factors. Type 1 has a positive family history, starts before the age of 40, and is associated with thehuman leukocyte antigen,HLA-Cw6. Conversely, type 2 does not show a family history, presents after age 40, and is not associated withHLA-Cw6.[62] Type 1 accounts for about 75% of persons with psoriasis.[63]
The classification of psoriasis as an autoimmune disease has sparked considerable debate. Researchers have proposed differing descriptions of psoriasis and psoriatic arthritis; some authors have classified them as autoimmune diseases[16][34][64] while others have classified them as distinct from autoimmune diseases and referred to them asimmune-mediated inflammatory diseases.[37][65][66]
No consensus exists about how to classify the severity of psoriasis. Mild psoriasis has been defined as a percentage of body surface area (BSA)≤10, aPsoriasis Area and Severity Index (PASI) score ≤10, and aDermatology Life Quality Index (DLQI) score ≤10.[67] Moderate to severe psoriasis was defined by the same group as BSA >10 or PASI score >10 and a DLQI score >10.[67]
The DLQI is a 10-question tool used to measure the impact of several dermatologic diseases on daily functioning. The DLQI score ranges from 0 (minimal impairment) to 30 (maximal impairment) and is calculated with each answer being assigned 0–3 points, with higher scores indicating greater social or occupational impairment.[68]
The PASI is the most widely used measurement tool for psoriasis. It assesses the severity of lesions and the area affected and combines these two factors into a single score from 0 (no disease) to 72 (maximal disease).[69] Nevertheless, the PASI can be too unwieldy to use outside of research settings, which has led to attempts to simplify the index for clinical use.[70]
Psoriasis is not just a skin disease. The symptoms of psoriasis can sometimes go beyond the skin and can hurt thequality of life of the affected individuals.[71] Additionally, the co-morbidities increase the treatment and financial burden of psoriasis and should be considered when managing this condition.[71]
There is a 2.2 times increased risk of cardiovascular complications in people with psoriasis.[72] Also, people with psoriasis are more susceptible tomyocardial infarction (heart attack) andstroke.[72] It has been speculated that there is systemic inflammation in psoriasis, which drives "psoriatic march" and can cause other inflammatory complications includingcardiovascular complications.[72] A study usedfluorodeoxyglucose F-18 positron emission tomography-computed tomography (FDG PET/CT) to measure aortic vascular inflammation in psoriasis patients, and found increasedcoronary artery disease indices, including total plaque burden, luminal stenosis, and high-risk plaques in people with psoriasis. Similarly, it was found that there is an 11% reduction in aortic vascular inflammation when there is a 75% reduction in the PASI score.[73]
Depression or depressive symptoms are present in 28–55% of people with psoriasis.[74] People with psoriasis are often stigmatized due to visible disfigurement of the skin.Social stigmatization is a risk factor for depression; however, other immune system factors may also be related to the observed increased incidence of depression in people with psoriasis.[74] There is some evidence that increased inflammatory signals in the body could also contribute to depression in people with chronic inflammatory diseases, including psoriasis.[74]
People with psoriasis are at increased risk of developingtype 2 diabetes (~1.5 odds ratio).[75] Agenome-wide genetic study found that psoriasis and type 2 diabetes share four loci, namely, ACTR2, ERLIN1, TRMT112, and BECN1, which are connected via the inflammatory NF-κB pathway.[75]
While no cure is available for psoriasis,[50] many treatment options exist.Topical agents are typically used for mild disease,phototherapy for moderate disease, and systemic agents for severe disease.[76] There is no evidence to support the effectiveness of conventional topical and systemic drugs, biological therapy, or phototherapy for acute guttate psoriasis or an acute guttate flare of chronic psoriasis.[77]
Topicalcorticosteroid preparations are the most effective agents when used continuously for eight weeks;retinoids andcoal tar were found to be of limited benefit and may be no better thanplacebo.[78] Very potent topical corticosteroids may be helpful in some cases; however, it is suggested to only use them for four weeks at a time and only if other less potent topical treatment options are not working.[79]
For psoriasis of the scalp, a 2016 review found dual therapy (vitamin D analogs and topical corticosteroids) or corticosteroid monotherapy to be more effective and safer than topical vitamin D analogs alone.[81] Due to their similar safety profiles and minimal benefit of dual therapy over monotherapy, corticosteroid monotherapy appears to be an acceptable treatment for short-term treatment.[81]
Moisturizers and emollients such asmineral oil,petroleum jelly, anddecubal (an oil-in-water emollient) were found to increase the clearance of psoriatic plaques. Some emollients are even more effective at clearing psoriatic plaques when combined withphototherapy.[82] Certain emollients, though, have no impact on psoriasis plaque clearance or may even decrease the clearance achieved with phototherapy, e.g., the emollientsalicylic acid is structurally similar topara-aminobenzoic acid, commonly found insunscreen, and is known to interfere with phototherapy in psoriasis.Coconut oil, when used as an emollient in psoriasis, has been found to decrease plaque clearance with phototherapy.[82] Medicated creams and ointments applied directly to psoriatic plaques can help reduce inflammation, remove built-up scale, reduce skin turnover, and clear affected skin of plaques. Ointment and creams containing coal tar,dithranol, corticosteroids (i.e.desoximetasone),fluocinonide, vitamin D3 analogues (for example, calcipotriol), andretinoids are routinely used. (The use of thefinger tip unit may help guide how much topical treatment to use.)[41][83]
Vitamin D analogs may be useful withsteroids; steroids alone have a higher rate of side effects.[80] Vitamin D analogs may allow lower doses of steroids to be used.[84]
Another topical therapy used to treat psoriasis is a form ofbalneotherapy, which involves daily baths insaltwater, such as theDead Sea, combined with sun exposure. This is usually done for four weeks, in which exposure time is gradually increased. The primary benefit is attributed to sun exposure and specificallyUVB light. This is cost-effective, and it has been propagated as an effective way to treat psoriasis without medication.[85] Decreases of PASI scores greater than 75% andremission for several months have commonly been observed.[85] Side effects may be mild, such as itchiness,folliculitis,sunburn,poikiloderma, and a theoretical risk of nonmelanoma cancer or melanoma has been suggested.[85] Some studies indicate no increased risk of melanoma in the long term.[86] Data are inconclusive concerning nonmelanoma skin cancer risk, but support the idea that the therapy is associated with an increased risk of benign forms of sun-induced skin damage such as, but not limited to,actinic elastosis orliver spots.[86] Dead Sea balneotherapy is also effective for psoriatic arthritis.[86] Tentative evidence indicates that balneophototherapy, a combination ofsalt bathes and exposure toultraviolet B-light (UVB), in chronic plaque psoriasis is better than UVB alone.[87]Glycerin is also an effective treatment for Psoriasis.[88]
Phototherapy in the form ofsunlight has long been used for psoriasis.[76] UVBwavelengths of 311–313 nanometers are most common.UV-B lamps have been developed for this treatment.[76] The exposure time should be controlled to avoid overexposure and burning of the skin. The UVB lamps should have a timer that turns off the lamp when the time ends. The dose is increased in every treatment to let the skin get used to the light.[76] Increased rates of cancer from treatment appear to be small.[76]Narrowband UVB therapy has been demonstrated to have similar efficacy topsoralen and ultraviolet A phototherapy (PUVA).[89] A 2013 meta-analysis found no difference in efficacy between NB-UVB and PUVA in the treatment of psoriasis, but NB-UVB is usually more convenient.[90]
One of the problems with clinical phototherapy is the difficulty many people have gaining access to a facility.Indoor tanning resources are almost ubiquitous today and could be considered as a means for people to get UV exposure when dermatologist-provided phototherapy is not available. Indoor tanning is already used by many people as a treatment for psoriasis; one indoor facility reported that 50% of its clients were using the center for psoriasis treatment, and another reported 36% were doing the same thing. However, a concern with the use of commercial tanning is that tanning beds that primarily emit UVA might not effectively treat psoriasis. One study found that plaque psoriasis is responsive toerythemogenic doses of either UVA or UVB, as exposure to either can cause dissipation of psoriatic plaques. It does require more energy to reach erythemogenic dosing with UVA.[91]
UV light therapies all have risks; tanning beds are no exception, being listed by theWorld Health Organization ascarcinogens.[92] Exposure to UV light is known to increase the risks of melanoma and squamous cell and basal cell carcinomas; younger people with psoriasis, particularly those under age 35, are at increased risk from melanoma from UV light treatment. A review of studies recommends that people who are susceptible to skin cancers exercise caution when using UV light therapy as a treatment.[91]
A major mechanism of NB-UVB is the induction ofDNA damage in the form ofpyrimidine dimers. This type of phototherapy is useful in the treatment of psoriasis because the formation of these dimers interferes with thecell cycle and stops it. The interruption of the cell cycle induced by NB-UVB opposes the characteristic rapid division of skin cells seen in psoriasis.[89] The activity of many types of immune cells found in the skin is also effectively suppressed by NB-UVB phototherapy treatments.[93] The most common short-term side effect of this form of phototherapy is redness of the skin; less common side effects of NB-UVB phototherapy are itching andblistering of the treated skin, irritation of the eyes in the form ofconjunctival inflammation orinflammation of the cornea, orcold sores due to reactivation of theherpes simplex virus in the skin surrounding the lips. Eye protection is usually given during phototherapy treatments.[89]
PUVA combines the oral or topical administration of psoralen with exposure to ultraviolet A (UVA) light. Themechanism of action of PUVA is unknown but probably involves activation of psoralen by UVA light, which inhibits the abnormally rapid production of cells in psoriatic skin. There are multiple mechanisms of action associated with PUVA, including effects on the skin's immune system. PUVA is associated withnausea,headache,fatigue, burning, and itching. Long-term treatment is associated withsquamous cell carcinoma (but not withmelanoma).[42][94] A combination therapy for moderate to severe psoriasis using PUVA plusacitretin resulted in benefit, but acitretin use has been associated withbirth defects andliver damage.[95]
Biologics are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalized immunosuppressive medical therapies such as methotrexate, biologics target specific aspects of the immune system contributing to psoriasis.[97] These medications are generally well-tolerated, and limited long-term outcome data have demonstrated biologics to be safe for long-term use in moderate to severe plaque psoriasis.[97][99] However, due to their immunosuppressive actions, biologics have been associated with a small increase in the risk for infection.[97]
Guidelines regard biologics as a third-line treatment for plaque psoriasis following inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments.[99] The safety of biologics during pregnancy has not been assessed. European guidelines recommend avoiding biologics if a pregnancy is planned;anti-TNF therapies such as infliximab are not recommended for use in chronic carriers of thehepatitis B virus or individuals infected withHIV.[97]
Several monoclonalantibodies target cytokines, the molecules that cells use to send inflammatory signals to each other.TNF-α is one of the main executor inflammatory cytokines. Fourmonoclonal antibodies (MAbs) (infliximab,adalimumab,golimumab, andcertolizumab pegol) and one recombinant TNF-αdecoy receptor,etanercept, have been developed to inhibit TNF-α signaling. Additional monoclonal antibodies, such asixekizumab,[100] have been developed against pro-inflammatory cytokines[101] and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies.[37] IL-12 and IL-23 share a common domain,p40, which is the target of theFDA-approvedustekinumab.[34] In 2017 theUS FDA approvedguselkumab for plaque psoriasis.[102] There have been few studies of the efficacy of anti-TNF medications for psoriasis in children. One randomized controlled study suggested that 12 weeks of etanercept treatment reduced the extent of psoriasis in children with no lasting adverse effects.[103]
Two medications that target T cells areefalizumab andalefacept. Efalizumab is a monoclonal antibody that specifically targets theCD11a subunit ofLFA-1.[97] It also blocks the adhesion molecules on theendothelial cells that line blood vessels, which attract T cells. Efalizumab was voluntarily withdrawn from the European market in February 2009, and from the U.S. market in June 2009, by the manufacturer due to the medication's association with cases ofprogressive multifocal leukoencephalopathy.[97] Alefacept also blocks the molecules that dendritic cells use to communicate with T cells and even causesnatural killer cells to kill T cells as a way of controlling inflammation.[37]Apremilast may also be used.[12]
Individuals with psoriasis may developneutralizing antibodies against monoclonal antibodies. Neutralization occurs when an antidrug antibody prevents a monoclonal antibody, such as infliximab, from bindingantigen in a laboratory test. Specifically, neutralization occurs when the anti-drug antibody binds to infliximab's antigen-binding site instead of TNF-α. When infliximab no longer bindstumor necrosis factor alpha, it no longer decreases inflammation, and psoriasis may worsen. Neutralizing antibodies have not been reported againstetanercept, a biologic medication that is a fusion protein composed of two TNF-α receptors. The lack of neutralizing antibodies against etanercept is probably secondary to the innate presence of the TNF-α receptor and the development ofimmune tolerance.[104]
There is strong evidence to indicate that infliximab,bimekizumab, ixekizumab, andrisankizumab are the most effective biologics for treating moderate to severe cases of psoriasis.[105] There is also some evidence to support use ofsecukinumab,brodalumab,guselkumab, certolizumab, and ustekinumab.[106][105] In general, anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha biologics were found to be more effective than traditional systemic treatments.[105] Theimmunologic pathways of psoriasis involveTh9,Th17,Th1 lymphocytes, andIL-22. The aforementioned biologic agents hinder different aspects of these pathways.[citation needed]
Another set of treatments for moderate to severe psoriasis arefumaric acid esters (FAE), which may be similar in effectiveness tomethotrexate.[107]
Apremilast (Otezla, Celgene) is an oral small-molecule inhibitor of the enzymephosphodiesterase 4, which plays an important role in chronic inflammation associated with psoriasis.[108]
It has been theorized thatantistreptococcal medications may improve guttate and chronic plaque psoriasis; however, limited studies do not show thatantibiotics are effective.[109]
Uncontrolled studies have suggested that individuals with psoriasis or psoriatic arthritis may benefit from a diet supplemented withfish oil rich ineicosapentaenoic acid (EPA) anddocosahexaenoic acid (DHA).[112] A low-calorie diet appears to reduce the severity of psoriasis.[43] Diet recommendations include consumption of cold water fish (preferably wild fish, notfarmed) such assalmon,herring, andmackerel; extra virgin olive oil; legumes; vegetables; fruits; and whole grains; and avoid consumption of alcohol, red meat, and dairy products (due to their saturated fat). The effect of caffeine consumption (including from coffee,black tea, mate, and dark chocolate) remains to be determined.[113]
Many patients report improvements after consuming less tobacco, caffeine, sugar,nightshades (tomatoes, eggplant, peppers,paprika and white potatoes) and takingprobiotics and oral Vitamin D.[114]
Most people with psoriasis experience nothing more than mild skin lesions that can be treated effectively with topical therapies.[78] Depending on the severity and location of outbreaks, people may experience significant physical discomfort and some disability, affecting the person'squality of life.[34] Itching and pain can interfere with basic functions, such as self-care and sleep.[52] Participation in sporting activities, certain occupations, and caring for family members can become difficult activities for those with plaques located on their hands and feet.[52] Plaques on the scalp can be particularly embarrassing, as flaky plaque in the hair can be mistaken fordandruff.[118]
Individuals with psoriasis may feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection andpsychosexual concerns. Psoriasis has been associated with low self-esteem, anddepression is more common among those with the condition.[3] People with psoriasis often feel prejudiced against due to the commonly held incorrect belief that psoriasis is contagious.[52] Psychological distress can lead to significantdepression andsocial isolation; a high rate ofthoughts about suicide has been associated with psoriasis.[21] Many tools exist to measure the quality of life of people with psoriasis and other dermatological disorders. Clinical research has indicated that individuals often experience a diminished quality of life.[119] Children with psoriasis may encounterbullying.[120]
Several conditions are associated with psoriasis, includingobesity,cardiovascular, andmetabolic disturbances. These occur more frequently in older people. Nearly half of individuals with psoriasis over the age of 65 have at least threecomorbidities (concurrent conditions), and two-thirds have at least two comorbidities.[121]
Psoriasis has been associated withobesity[3] and several other cardiovascular and metabolic disturbances. Thenumber of new cases per year of diabetes is 27% higher in people affected by psoriasis than in those without the condition.[122] Severe psoriasis may be even more strongly associated with the development of diabetes than mild psoriasis.[122] Younger people with psoriasis may also be at increased risk for developing diabetes.[121] Individuals with psoriasis or psoriatic arthritis have a slightly higher risk of heart disease andheart attacks when compared to the general population. Cardiovascular disease risk appeared to be correlated with the severity of psoriasis and its duration. There is no strong evidence to suggest that psoriasis is associated with an increased risk of death from cardiovascular events.Methotrexate may provide a degree of protection for the heart.[42][121]
The odds of havinghypertension are 1.58 times( i.e. 58%) higher in people with psoriasis than those without the condition; these odds are even higher with severe cases of psoriasis. A similar association was noted in people who have psoriatic arthritis—the odds of having hypertension were found to be 2.07 times( i.e., 107%) greater when compared to the odds of the general population. The link between psoriasis and hypertension is not currently[when?] understood. Mechanisms hypothesized to be involved in this relationship include the following: dysregulation of therenin–angiotensin system, elevated levels ofendothelin 1 in the blood, and increasedoxidative stress. The number of new cases of the heart rhythm abnormalityatrial fibrillation is 1.31 times( i.e. 31%) higher in people with mild psoriasis and 1.63 times( i.e. 63%) higher in people with severe psoriasis.[123] There may be a slightly increased risk ofstroke associated with psoriasis, especially in severe cases.[42][124] Treatinghigh levels of cholesterol withstatins has been associated with decreased psoriasis severity, as measured by PASI score, and has also been associated with improvements in other cardiovascular disease risk factors such as markers ofinflammation.[125] Thesecardioprotective effects are attributed to ability of statins to improve bloodlipid profile and because of their anti-inflammatory effects. Statin use in those with psoriasis andhyperlipidemia was associated with decreased levels ofhigh-sensitivity C-reactive protein andTNFα as well as decreased activity of the immune proteinLFA-1.[125] Compared to individuals without psoriasis, those affected by psoriasis are more likely to satisfy the criteria formetabolic syndrome.[16][123]
The rates ofCrohn's disease andulcerative colitis are increased when compared with the general population by a factor of 3.8 and 7.5, respectively.[3] People with psoriasis also have a higher risk ofceliac disease.[113][117] Few studies have evaluated the association ofmultiple sclerosis with psoriasis, and the relationship has been questioned.[3] Psoriasis has been associated with a 16% increase in overall relative risk for non-skin cancer, thought to be attributed to systemic therapy, particularly methotrexate.[42] People treated with long-term systemic therapy for psoriasis have a 52% increased riskcancers of the lung and bronchus, a 205% increase in the risk of developingcancers of the upper gastrointestinal tract, a 31% increase in the risk of developingcancers of the urinary tract, a 90% increase in the risk of developingliver cancer, and a 46% increase in the risk of developingpancreatic cancer.[42] The risk for the development of non-melanoma skin cancers is also increased. Psoriasis increases the risk of developingsquamous cell carcinoma of the skin by 431% and increases the risk ofbasal cell carcinoma by 100%.[42] There is no increased risk ofmelanoma associated with psoriasis.[42] People with psoriasis have a higher risk of developing cancer.[126]
Psoriasis is estimated to affect 2–4% of the population of the Western world.[7] The rate of psoriasis varies according to age, region, and ethnicity; a combination of environmental and genetic factors is thought to be responsible for these differences.[7] Psoriasis is about five times more common in people of European descent than in people of Asian descent,[127] more common in countries farther from theequator,[49] relatively uncommon in African Americans, and extremely uncommon in Native Americans.[50] Psoriasis has been estimated to affect about 6.7million Americans.[5]
Psoriasis can occur at any age, although it is more frequent in adults and commonly appears for the first time between the ages of 15 and 25 years.[5] Approximately one-third of people with psoriasis report being diagnosed before age 20.[128] Psoriasis affects bothsexes equally.[62]
People withinflammatory bowel disease, such as Crohn's disease or ulcerative colitis, are at an increased risk of developing psoriasis.[49]
Scholars believe psoriasis to have been included among the various skin conditions calledtzaraath (translated asleprosy) in theHebrew Bible.[129] The person was deemed "impure" (seetumah and taharah) during their affected phase and is ultimately treated by thekohen.[130] However, it is more likely that this confusion arose from the use of the same Greek term for both conditions. The Greeks used the termlepra (λέπρα) for scaly skin conditions. They used the termpsora (ψώρα) to describe itchy skin conditions.[130] It became known asWillan's lepra in the late 18th century when EnglishdermatologistsRobert Willan and Thomas Bateman differentiated it from other skin diseases.Leprosy, they said, is distinguished by the regular, circular form of patches, while psoriasis is always irregular. Willan identified two categories:leprosa graecorum andpsora leprosa.[131]
Psoriasis is thought to have first been described inAncient Rome byCornelius Celsus.[132] The British dermatologistThomas Bateman described a possible link between psoriasis and arthritic symptoms in 1813.[132] AdmiralWilliam Halsey missed out on theBattle of Midway because he contracted psoriasis while out at sea in the early months of American participation ofWorld War II. AdmiralChester Nimitz medically ordered Halsey to recover at a hospital inHawaii.
The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. In the 18th and 19th centuries,Fowler's solution, which contains apoisonous andcarcinogenicarsenic compound, was used by dermatologists as a treatment for psoriasis.[130]Mercury was also used for psoriasis treatment during this time.[130]Sulfur,iodine, andphenol were also commonly used treatments for psoriasis during this era, when it was incorrectly believed that psoriasis was an infectious disease.[130]Coal tars were widely used withultraviolet light irradiation as a topical treatment approach in the early 1900s.[130][133] During the same time, psoriatic arthritis cases were treated withintravenously administered gold preparations in the same manner asrheumatoid arthritis.[133]
The International Federation of Psoriasis Associations (IFPA) is the global umbrella organization for national and regional psoriasis associations and also gathers the leading experts in psoriasis and psoriatic arthritis research for scientific conferences every three years.[134] The Psoriasis International Network, a program of the Fondation René Touraine, gathers dermatologists,rheumatologists, and other caregivers involved in the management of psoriasis. Non-profit organizations like theNational Psoriasis Foundation in the United States, the Psoriasis Association in the United Kingdom, Association France Psoriasis[135] and Psoriasis Australia offer advocacy and education about psoriasis in their respective countries. October 29 is World Psoriasis Day.[136]
The annual cost of treating psoriasis in the United States is estimated as high as $32.5billion, including $12.2billion in direct costs. Pharmacy costs are the main source of direct expense, with biologic therapy the most prevalent. These costs increase significantly when co-morbid conditions such as heart disease, hypertension, diabetes, lung disease, andpsychiatric disorders are factored in. Expenses linked to co-morbidities are estimated at an additional $23,000 per person per year.[137]
The role ofinsulin resistance in the pathogenesis of psoriasis is under investigation. Preliminary research has suggested thatantioxidants such aspolyphenols may have beneficial effects on the inflammation characteristic of psoriasis.[138]
^LeMone P, Burke K, Dwyer T, Levett-Jones T, Moxham L, Reid-Searl K (2015).Medical-Surgical Nursing. Pearson Higher Education AU. p. 454.ISBN978-1-4860-1440-8.Archived from the original on 14 January 2023. Retrieved8 May 2020.
^Colledge NR, Walker BR, Ralston SH, eds. (2010).Davidson's principles and practice of medicine (21st ed.). Edinburgh: Churchill Livingstone/Elsevier. pp. 1260–1.ISBN978-0-7020-3084-0.
^abJames W, Berger T, Elston D (2005).Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. pp. 191–7.ISBN978-0-7216-2921-6.
^Robinson A, Van Voorhees AS, Hsu S, Korman NJ, Lebwohl MG, Bebo BF, Kalb RE (August 2012). "Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation".Journal of the American Academy of Dermatology.67 (2):279–88.doi:10.1016/j.jaad.2011.01.032.PMID22609220.
^abZattra E, Belloni Fortina A, Peserico A, Alaibac M (May 2012). "Erythroderma in the era of biological therapies".European Journal of Dermatology.22 (2):167–71.doi:10.1684/ejd.2011.1569.PMID22321651.
^Greenberg MS, Glick M, Ship JA (2008).Burket's oral medicine (11th ed.). Hamilton, Ont: BC Decker. pp. 103–4.ISBN978-1-55009-345-2.
^González-Álvarez L, García-Martín JM, García-Pola MJ (May 2019). "Association between geographic tongue and psoriasis: A systematic review and meta-analyses".Journal of Oral Pathology & Medicine.48 (5):365–372.doi:10.1111/jop.12840.hdl:10651/52321.ISSN1600-0714.PMID30739339.
^Krueger G, Ellis CN (July 2005). "Psoriasis--recent advances in understanding its pathogenesis and treatment".Journal of the American Academy of Dermatology.53 (1 Suppl 1): S94–100.doi:10.1016/j.jaad.2005.04.035.PMID15968269.
^abClarke P (July 2011)."Psoriasis"(PDF).Australian Family Physician.40 (7):468–73.PMID21743850.Archived(PDF) from the original on 27 June 2019. Retrieved4 March 2014.
^"Images of Memorable Cases: Case 34".Connexions. Rice University.Archived from the original on 10 July 2012. Retrieved21 December 2009.This AIDS patient presented with a pruritic eruption over most of his body
^abcGuerra I, Gisbert JP (January 2013). "Onset of psoriasis in patients with inflammatory bowel disease treated with anti-TNF agents".Expert Review of Gastroenterology & Hepatology.7 (1):41–8.doi:10.1586/egh.12.64.PMID23265148.S2CID207210831.
^abcOuyang W (December 2010). "Distinct roles of IL-22 in human psoriasis and inflammatory bowel disease".Cytokine & Growth Factor Reviews.21 (6):435–41.doi:10.1016/j.cytogfr.2010.10.007.PMID21106435.
^abcdParrish L (November 2012). "Psoriasis: symptoms, treatments and its impact on quality of life".British Journal of Community Nursing.17 (11):524–528.doi:10.12968/bjcn.2012.17.11.524.PMID23124421.
^abcMudigonda P, Mudigonda T, Feneran AN, Alamdari HS, Sandoval L, Feldman SR (October 2012). "Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis".Dermatology Online Journal.18 (10): 1.doi:10.5070/D33N39N8XM.PMID23122008.
^Griffiths CE, Christophers E, Barker JN, Chalmers RJ, Chimenti S, Krueger GG, Leonardi C, Menter A, Ortonne JP, Fry L (February 2007). "A classification of psoriasis vulgaris according to phenotype".The British Journal of Dermatology.156 (2):258–62.doi:10.1111/j.1365-2133.2006.07675.x.PMID17223864.S2CID45917573.
^Mease PJ (November 2011). "Measures of psoriatic arthritis: Tender and Swollen Joint Assessment, Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), Modified Nail Psoriasis Severity Index (mNAPSI), Mander/Newcastle Enthesitis Index (MEI), Leeds Enthesitis Index (LEI), Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht Ankylosing Spondylitis Enthesis Score (MASES), Leeds Dactylitis Index (LDI), Patient Global for Psoriatic Arthritis, Dermatology Life Quality Index (DLQI), Psoriatic Arthritis Quality of Life (PsAQOL), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Joint Activity Index (PsAJAI), Disease Activity in Psoriatic Arthritis (DAPSA), and Composite Psoriatic Disease Activity Index (CPDAI)".Arthritis Care & Research.63 (Supplement 11): S64–85.doi:10.1002/acr.20577.PMID22588772.
^Louden BA, Pearce DJ, Lang W, Feldman SR (October 2004). "A Simplified Psoriasis Area Severity Index (SPASI) for rating psoriasis severity in clinic patients".Dermatology Online Journal.10 (2): 7.doi:10.5070/D318W9J736.PMID15530297.
^abSamarasekera EJ, Sawyer L, Wonderling D, Tucker R, Smith CH (May 2013). "Topical therapies for the treatment of plaque psoriasis: systematic review and network meta-analyses".The British Journal of Dermatology.168 (5):954–967.doi:10.1111/bjd.12276.PMID23413913.S2CID21979785.
^Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, Gottlieb A, Koo JY, Lebwohl M, Lim HW, Van Voorhees AS, Beutner KR, Bhushan R (April 2009). "Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies".Journal of the American Academy of Dermatology.60 (4):643–59.doi:10.1016/j.jaad.2008.12.032.PMID19217694.
^Soleymani T, Hung T, Soung J (April 2015). "The role of vitamin D in psoriasis: a review".International Journal of Dermatology.54 (4):383–92.doi:10.1111/ijd.12790.PMID25601579.S2CID1688553.
^abcKatz U, Shoenfeld Y, Zakin V, Sherer Y, Sukenik S (October 2012). "Scientific evidence of the therapeutic effects of dead sea treatments: a systematic review".Seminars in Arthritis and Rheumatism.42 (2):186–200.doi:10.1016/j.semarthrit.2012.02.006.PMID22503590.
^Medical College of Georgia at Augusta University. "Glycerin is safe, effective in psoriasis model." ScienceDaily. [www.sciencedaily.com/releases/2021/10/211004104229.htm] (accessed 9 July 2023).
^Lapolla W, Yentzer BA, Bagel J, Halvorson CR, Feldman SR (May 2011). "A review of phototherapy protocols for psoriasis treatment".Journal of the American Academy of Dermatology.64 (5):936–49.doi:10.1016/j.jaad.2009.12.054.PMID21429620.
^Dunn LK, Gaar LR, Yentzer BA, O'Neill JL, Feldman SR (July 2011). "Acitretin in dermatology: a review".Journal of Drugs in Dermatology.10 (7):772–82.PMID21720660.
^abDogra S, Mahajan R (August 2013). "Systemic methotrexate therapy for psoriasis: past, present and future".Clinical and Experimental Dermatology.38 (6):573–88.doi:10.1111/ced.12062.PMID23837932.S2CID11207097.
^Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH, Durez P, Tak PP, Gomez-Reino JJ, Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD, Rose K, Haider A, Di Padova F (October 2010). "Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis".Science Translational Medicine.2 (52): 52ra72.doi:10.1126/scitranslmed.3001107.PMID20926833.S2CID10132276.
^Leffler DA, Green PH, Fasano A (October 2015). "Extraintestinal manifestations of coeliac disease".Nature Reviews. Gastroenterology & Hepatology (Review).12 (10):561–71.doi:10.1038/nrgastro.2015.131.PMID26260366.S2CID15561525.
^Dessinioti C, Katsambas A (2013). "Seborrheic dermatitis: etiology, risk factors, and treatments: facts and controversies".Clinics in Dermatology.31 (4):343–351.doi:10.1016/j.clindermatol.2013.01.001.PMID23806151.
^abcHabif TP (2010)."8".Clinical dermatology a color guide to diagnosis and therapy (5th ed.). Edinburgh: Mosby Elsevier.ISBN978-0-323-08037-8.Archived from the original on 14 January 2023. Retrieved8 May 2020.
^abTablazon IL, Al-Dabagh A, Davis SA, Feldman SR (February 2013). "Risk of cardiovascular disorders in psoriasis patients: current and future".American Journal of Clinical Dermatology.14 (1):1–7.doi:10.1007/s40257-012-0005-5.PMID23329076.S2CID207482092.
^abGhazizadeh R, Tosa M, Ghazizadeh M (May 2011). "Clinical improvement in psoriasis with treatment of associated hyperlipidemia".The American Journal of the Medical Sciences.341 (5):394–8.doi:10.1097/MAJ.0b013e3181ff8eeb.PMID21233693.S2CID12519829.
^E. V. Hulse, "The Nature of Biblical 'Leprosy' and the Use of Alternative Medical Terms in Modern Translations of the Bible,"Palestine Exploration Quarterly 107.2 (1975): 87-105.
^abcdefGruber F, Kastelan M, Brajac I (2004). "Psoriasis treatment--yesterday, today, and tomorrow".Acta Dermatovenerologica Croatica.12 (1):30–4.PMID15072746.
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