Psoriasis is hyperproliferation of epidermal keratinocytes combined with inflammation of the epidermis and dermis. It affects about 1 to 5% of the population worldwide; light-skinned people are at higher risk, and blacks are at lower risk. Peak onset is roughly bimodal, most often at ages 16 to 22 and at ages 57 to 60, but the disorder can occur at any age.
Etiology of Psoriasis
The cause of psoriasis is unclear but involves immune stimulation of epidermal keratinocytes; T cells seem to play a central role. Family history is common, and certain genes and human leukocyte antigens (Cw6, B13, B17) are associated with psoriasis. Genomewide linkage analysis has identified numerous psoriasis susceptibility loci; the PSORS1 locus on chromosome 6p21 plays the greatest role in determining a patient's susceptibility of developing psoriasis. An environmental trigger is thought to evoke an inflammatory response and subsequent hyperproliferation of keratinocytes.
Well-identified triggers include
Injury (Koebner phenomenon)
Beta-hemolytic streptococcal infection (leading to guttate psoriasis)
Drugs (especially beta-blockers, chloroquine, lithium, angiotensin-converting enzyme inhibitors, indomethacin, terbinafine, and interferon-alfa)
Symptoms and Signs of Psoriasis
Lesions are either asymptomatic or pruritic and are most often localized on the scalp, extensor surfaces of the elbows and knees, sacrum, buttocks (commonly the gluteal cleft), and genitals. The nails, eyebrows, axillae, umbilicus, and perianal region may also be affected. The disease can be widespread, involving confluent areas of skin extending between these regions. Lesions differ in appearance depending on type.
Among the various psoriasis subtypes Subtypes of Psoriasis Psoriasis is an inflammatory disease that manifests most commonly as well-circumscribed, erythematous papules and plaques covered with silvery scales. Multiple factors contribute, including... read more , plaque psoriasis (psoriasis vulgaris or chronic plaque psoriasis) accounts for about 90%; lesions are discrete, erythematous papules or plaques covered with thick, silvery, shiny scales. Lesions appear gradually and remit and recur spontaneously or with the appearance and resolution of triggers.
Arthritis develops in 5 to 30% of patients and can be disabling (psoriatic arthritis Psoriatic Arthritis Psoriatic arthritis is a spondyloarthropathy and chronic inflammatory arthritis that occurs in people with psoriasis of the skin or nails. The arthritis is often asymmetric, and some forms involve... read more ); joint destruction may ultimately occur.
Psoriasis is rarely life-threatening but can affect a patient’s self-image. Besides the patient's appearance, the sheer amount of time required to treat extensive skin or scalp lesions and to maintain clothing and bedding may adversely affect quality of life.
Diagnosis of Psoriasis
Diagnosis of psoriasis is most often by clinical appearance and distribution of lesions.
Differential diagnosis includes
Dermatophytoses Overview of Dermatophytoses Dermatophytoses are fungal infections of keratin in the skin and nails (nail infection is called tinea unguium or onychomycosis). Symptoms and signs vary by site of infection. Diagnosis is by... read more (potassium hydroxide wet mount should be done for any scaly plaques, especially if they do not have a classic appearance of eczema or psoriasis)
Squamous cell carcinoma in situ (Bowen disease Bowen Disease Bowen disease is a superficial squamous cell carcinoma in situ. (See also Overview of Skin Cancer.) Bowen disease is most common in sun-exposed areas but may arise at any location. Lesions can... read more , especially when on the trunk; this diagnosis should be considered for isolated plaques that do not respond to usual therapy)
Biopsy is rarely necessary and may not be diagnostic; however, it may be considered in cases where the clinical findings are not classic.
Disease is graded as mild, moderate, or severe based on the body surface area affected and how the lesions affect the patient's quality of life. To be considered mild, usually < 10% of the skin surface should be involved. There are many more complex scoring systems for disease severity (eg, the Psoriasis Area and Severity Index), but these systems are useful mainly in research protocols.
Treatment of Psoriasis
Ultraviolet (UV) light therapy
Other systemic treatments
Treatment options are extensive and range from topical treatments (eg, emollients, salicylic acid, coal tar, anthralin, corticosteroids, vitamin D3 analogs, calcineurin inhibitors, tazarotene) to UV light therapy to systemic treatments (eg, methotrexate, oral retinoids, cyclosporine, immunomodulatory agents [biologics]). (See the American Academy of Dermatology's clinical guideline for psoriasis.)
Corticosteroids are usually used topically but may be injected into small or recalcitrant lesions. (CAUTION: Systemic corticosteroids may precipitate exacerbations or development of pustular psoriasis and should not be used to treat psoriasis.) Topical corticosteroids are used twice daily. Corticosteroids are most effective when used overnight under occlusive polyethylene coverings or incorporated into tape; a corticosteroid cream is applied without occlusion during the day. Corticosteroid potency Anti-inflammatory agents Topical dermatologic treatments are grouped according to their therapeutic functions and include Cleansing agents Moisturizing agents (emollients, skin hydrators, and softeners) Drying agents... read more is selected according to the extent of involvement.
As lesions abate, the corticosteroid should be applied less frequently or at a lower potency to minimize local atrophy, striae formation, and telangiectases. Ideally, after about 3 weeks, an emollient, vitamin D3 analog, or calcineurin inhibitor should be substituted for the corticosteroid for 1 to 2 weeks (as a rest period); this substitution limits corticosteroid dosage, reduces risk of topical corticosteroid adverse effects (eg, skin atrophy, telangiectasias, easy bruising, striae), and prevents tachyphylaxis (diminishing response to an agent after successive dosing). Topical corticosteroid use can be expensive because large quantities (about 1 oz or 30 g) are needed for each application when a large body surface area is affected. Topical corticosteroids applied for long duration to large areas of the body may cause systemic effects and exacerbate psoriasis. For small, thick, localized, or recalcitrant lesions, high-potency corticosteroids are used with an occlusive dressing or flurandrenolide tape; these dressings are left on overnight and changed in the morning. Relapse after topical corticosteroids are stopped is often faster than with other agents.
Vitamin D3 analogs (eg, calcipotriol [calcipotriene], calcitriol) are topical vitamin D analogs that induce normal keratinocyte proliferation and differentiation; they can be used alone or in combination with topical corticosteroids. Some clinicians have patients apply calcipotriol on weekdays and corticosteroids on weekends.
Calcineurin inhibitors (eg, tacrolimus, pimecrolimus) are available in topical form and are generally well-tolerated. They are not as effective as corticosteroids but may avoid the complications of corticosteroids when treating facial and intertriginous psoriasis. It is not clear whether they increase the risk of lymphoma and skin cancer.
Tazarotene is a topical retinoid. It is less effective than corticosteroids as monotherapy but is a useful adjunct.
Other adjunctive topical treatments include emollients, salicylic acid, coal tar, and anthralin.
Emollients include emollient creams, ointments, petrolatum, paraffin, and even hydrogenated vegetable (cooking) oils. They reduce scaling and are most effective when applied twice daily and immediately after bathing. Lesions may appear redder as scaling decreases or becomes more transparent. Emollients are safe and should probably always be used for mild to moderate plaque psoriasis.
Salicylic acid is a keratolytic that softens scales, facilitates their removal, and increases absorption of other topical agents. It is especially useful as a component of scalp treatments; scalp scale can be quite thick.
Coal tar preparations are anti-inflammatory and decrease keratinocyte hyperproliferation via an unknown mechanism. Ointments or solutions are typically applied at night and washed off in the morning. Coal tar products can be used in combination with topical corticosteroids or with exposure to natural or artificial broad-band UVB light (280 to 320 nm) in slowly increasing increments (Goeckerman regimen). Shampoos should be left in for 5 to 10 minutes and then rinsed out.
Anthralin is a topical antiproliferative, anti-inflammatory agent. Its mechanism of action is unknown. Effective dose is 0.1% cream or ointment increased to 1% as tolerated. Anthralin may be irritating and should be used with caution in intertriginous areas; it also stains. Irritation and staining can be avoided by washing off the anthralin 20 to 30 minutes after application. Using a liposome-encapsulated preparation may also avoid some disadvantages of anthralin.
UV light therapy is typically used in patients with extensive psoriasis. The mechanism of action is unknown, although UVB light reduces DNA synthesis and can induce mild systemic immunosuppression. In psoralen plus ultraviolet A (PUVA), oral methoxypsoralen, a photosensitizer, is followed by exposure to long-wave UVA light (330 to 360 nm). PUVA has an antiproliferative effect and also helps to normalize keratinocyte differentiation. Doses of light are started low and increased as tolerated. Severe burns can result if the dose of drug or UVA is too high.
Although the treatment is less messy than topical treatment and may produce remissions lasting several months, repeated treatments may increase the incidence of UV-induced skin cancer and melanoma. Less UV light is required when used with oral retinoids (the so-called re-PUVA regimen). Narrowband UVB light (311 to 312 nm), which is used without psoralens, is similar in effectiveness to PUVA. Excimer laser therapy is a type of phototherapy using a 308-nm laser directed at focal psoriatic plaques.
Methotrexate taken orally is an effective treatment for severe disabling psoriasis, especially severe psoriatic arthritis or widespread erythrodermic or pustular psoriasis unresponsive to topical agents or UV light therapy (narrowband UVB) or PUVA. Methotrexate seems to interfere with the rapid proliferation of epidermal cells. Hematologic, renal, and hepatic function should be monitored. Dosage regimens vary, so only physicians experienced in its use for psoriasis should undertake methotrexate therapy.
Cyclosporine can be used for severe psoriasis. It should be limited to courses of several months (rarely, up to 1 year) and alternated with other therapies. Its effect on the kidneys and potential long-term effects on the immune system preclude more liberal use.
Mycophenolate mofetil can be an alternative option for patients who do not respond to methotrexate or cyclosporine or those who develop toxicity from the above medications.
Other immunosuppressants (eg, hydroxyurea, 6-thioguanine) have narrow safety margins and are reserved for severe, recalcitrant psoriasis.
Other systemic treatments
Systemic retinoids (eg, acitretin, isotretinoin) may be effective for severe and recalcitrant cases of psoriasis vulgaris, pustular psoriasis (in which isotretinoin may be preferred), and hyperkeratotic palmoplantar psoriasis. Because of the teratogenic potential and long-term retention of acitretin in the body, women who use it must not be pregnant and should be warned against becoming pregnant for at least 2 years after treatment ends. Pregnancy restrictions also apply to isotretinoin, but the agent is not retained in the body beyond 1 month. Long-term treatment may cause diffuse idiopathic skeletal hyperostosis Diagnosis Ankylosing spondylitis is the prototypical spondyloarthropathy and a systemic disorder characterized by inflammation of the axial skeleton, large peripheral joints, and digits; nocturnal back... read more (DISH).
Immunomodulatory agents (biologics—see Immunotherapeutics Immunotherapeutics Immunotherapeutic agents use or modify immune mechanisms. Use of these agents is rapidly evolving; new classes, new agents, and new uses of current agents are certain to be developed. A number... read more ) include tumor necrosis factor (TNF)–alpha inhibitors (etanercept, adalimumab, infliximab, certolizumab [which does not cross the placenta]). TNF-alpha inhibitors lead to clearing of psoriasis, but their safety profile is still under study. Efalizumab is no longer available in the US due to increased risk of progressive multifocal leukoencephalopathy Progressive Multifocal Leukoencephalopathy (PML) Progressive multifocal leukoencephalopathy (PML) is caused by reactivation of the JC virus. The disease usually occurs in patients with impaired cell-mediated immunity, particularly patients... read more . Ustekinumab, a human monoclonal antibody that targets IL-12 and IL-23, can be used for moderate to severe psoriasis. IL-23 inhibitors include tildrakizumab, risankizumab, and guselkumab. IL-17 inhibitors (secukinumab, ixekizumab, brodalumab) are now being used for moderate to severe psoriasis. Tofacitinib (a Janus kinase inhibitor) is available for patients with psoriatic arthritis; however, it is not approved for skin-limited psoriasis. Apremilast (inhibitor of phosphodiesterase 4) is the only available oral drug for psoriasis; however, early post-marketing data suggest it is not as effective as the TNF-alpha inhibitors. There are several new drugs under development for treatment of psoriasis, including an IL-36 inhibitor for generalized pustular psoriasis (also see drugs in development from the National Psoriasis Foundation).
Choice of therapy
Choice of specific agents and combinations requires close cooperation with the patient, always keeping in mind the untoward effects of the treatments. There is no single ideal combination or sequence of agents, but treatment should be kept as simple as possible. Monotherapy is preferred, but combination therapy is the norm. First-line treatment for psoriasis includes topical corticosteroids and topical vitamin D3 analogs (either as monotherapy or in combination).
Rotational therapy refers to the substitution of one therapy for another after 1 to 2 years to reduce the adverse effects caused by chronic use and to circumvent disease resistance. Sequential therapy refers to initial use of potent agents (eg, cyclosporine) to quickly gain control followed by use of agents with a better safety profile. Immunomodulatory agents achieve clearance or near clearance of lesions more often than methotrexate or narrowband UVB.
Mild plaque psoriasis can be treated with emollients, keratolytics, tar, topical corticosteroids, vitamin D3 analogs, or anthralin alone or in combination. Moderate exposure to sunlight is beneficial, but sunburn can induce exacerbations.
Moderate to severe plaque psoriasis should be treated with topical agents and either phototherapy or systemic agents. Immunosuppressants are used for quick, short-term control (eg, in allowing a break from other modalities) and for the most severe disease. Immunomodulatory agents are used for moderate to severe disease unresponsive to other agents.
Scalp plaques are notoriously difficult to treat because they resist systemic therapy, and because hair blocks application of topical agents and scale removal and shields skin from UV light. A suspension of 10% salicylic acid in mineral oil may be rubbed into the scalp at bedtime manually or with a toothbrush, covered with a shower cap (to enhance penetration and avoid messiness), and washed out the next morning with a tar (or other) shampoo. More cosmetically acceptable corticosteroid solutions can be applied to the scalp during the day. These treatments are continued until the desired clinical response is achieved.
Resistant skin or scalp patches may respond to local superficial intralesional injection of triamcinolone acetonide suspension diluted with saline to 2.5 or 5 mg/mL, depending on the size and severity of the lesion. Injections may cause local atrophy, which is usually reversible.
Special treatment needs for subtypes of psoriasis Subtypes of Psoriasis Psoriasis is an inflammatory disease that manifests most commonly as well-circumscribed, erythematous papules and plaques covered with silvery scales. Multiple factors contribute, including... read more are described above.
For psoriatic arthritis Psoriatic Arthritis Psoriatic arthritis is a spondyloarthropathy and chronic inflammatory arthritis that occurs in people with psoriasis of the skin or nails. The arthritis is often asymmetric, and some forms involve... read more , treatment with systemic therapy is important to prevent joint destruction; methotrexate or a TNF-alpha inhibitor may be effective.
Psoriasis is a common inflammatory disorder affecting the skin that has a genetic component and several triggers (eg, trauma, infection, certain drugs).
The most common skin findings are usually well-circumscribed, erythematous papules and plaques covered with silvery scales in plaque psoriasis, but lesions differ between the other less common subtypes of psoriasis.
Psoriatic arthritis develops in 5 to 30% of patients and can cause joint destruction and disability.
Diagnose based on the appearance and distribution of lesions.
Use topical treatments (eg, emollients, salicylic acid, coal tar preparations, anthralin, corticosteroids, vitamin D3 analogs, calcineurin inhibitors, tazarotene), particularly for mild disease.
Use ultraviolet (UV) light therapy, usually for moderate or severe psoriasis.
For extensive psoriasis, use systemic treatments, such as immunomodulatory (biologic) agents, methotrexate, cyclosporine, retinoids, and/or other immunosuppressants.
The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Psoriasis Area and Severity Index (PASI): An online calculator to determine a patient's PASI score
American Academy of Dermatology: Psoriasis Clinical Guidelines: Joint guidelines from the American Academy of Dermatology and the National Psoriasis Foundation
National Psoriasis Foundation: A resource providing information about treatments and community support