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Psoriasis

By Shinjita Das, MD, Instructor in Dermatology;Assistant in Dermatology, Harvard Medical School;Massachusetts General Hospital

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Psoriasis is an inflammatory disease that manifests most commonly as well-circumscribed, erythematous papules and plaques covered with silvery scales. Multiple factors contribute, including genetics. Common triggers include trauma, infection, and certain drugs. Symptoms are usually minimal, but mild to severe itching may occur. Cosmetic implications may be major. Some people develop severe disease with painful arthritis. Diagnosis is based on appearance and distribution of lesions. Treatment can include topical treatments (eg, emollients, vitamin D analogs, retinoids, coal tar, anthralin, corticosteroids), phototherapy, and, when severe, systemic drugs (eg, methotrexate, oral retinoids, cyclosporine, immunomodulatory agents [biologics]).

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

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 HLA 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)

  • Sunburn

  • HIV infection

  • Beta-hemolytic streptococcal infection

  • Drugs (especially beta-blockers, chloroquine, lithium, ACE inhibitors, indomethacin, terbinafine, and interferon-alfa)

  • Emotional stress

  • Alcohol consumption

  • Tobacco smoking

  • Obesity

Symptoms and Signs

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, 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); 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.

Subtypes of Psoriasis

Subtype

Description

Treatment and Prognosis

Plaque psoriasis

Gradual appearance of discrete, erythematous papules or plaques covered with thick, silvery, shiny scales

Lesions that remit and recur spontaneously or with appearance and resolution of triggers

Treatment: Topical corticosteroids of minimal effective potency, with or without vitamin D3 analogs (eg, calcipotriol)

Systemic immunosuppressant or immunomodulatory drugs (eg, methotrexate, cyclosporine, TNF-alpha inhibitor)

Prognosis: Waxes and wanes, without cure

Inverse psoriasis

Psoriasis of intertriginous areas (usually the inguinal, gluteal, axillary, inframammary, and retroauricular folds and the glans of the uncircumcised penis)

Possibly formation of cracks or fissures in the center or edge of involved areas

Possibly absence of scales

Treatment: Topical corticosteroids of minimal effective potency, with or without vitamin D3 analogs (eg, calcipotriol)

Possibly tacrolimus 0.1% ointment in recalcitrant cases

Tar and anthralin possibly irritating

Prognosis: Waxes and wanes

Guttate psoriasis

Abrupt appearance of multiple plaques 0.5 to 1.5 cm in diameter, usually on the trunk in children and young adults after streptococcal pharyngitis

Treatment: Antibiotics for underlying streptococcal infection

Prognosis: Excellent, often with permanent cure

May progress to plaque psoriasis

Palmoplantar psoriasis

Hyperkeratotic, discrete plaques on palms and/or soles that tend to become confluent

Treatment: Systemic retinoids, topical corticosteroids, vitamin D3 analogs (eg, calcipotriol), systemic immunosuppressant or immunomodulatory drugs (eg methotrexate, cyclosporine, TNF-alpha inhibitor)

Prognosis:

Waxes and wanes

Rarely resolves completely, even with treatment

Nail psoriasis

Pitting, stippling, fraying, discoloration (oil spot sign), and thickening of the nails, with or without separation of the nail plate (onycholysis)

May resemble a fungal nail infection

Affects 30–50% of patients with other forms of psoriasis

Treatment: Responds best to systemic therapy

For brave or stoic patients, possibly intralesional injection with corticosteroids

Prognosis: Often unresponsive to treatment

Pustular psoriasis of the palms and soles

Gradual appearance of deep pustules on palms and soles

Flare-ups that may be painful and disabling

Typical psoriatic lesions possibly absent

Treatment: Systemic retinoids or psoralen plus ultraviolet A (PUVA) therapy

Prognosis: Waxes and wanes

Acrodermatitis continua of Hallopeau

Pustular psoriasis confined to distal fingers or toes, sometimes just one digit

Replaced by scale and crust when it resolves

Treatment: Systemic retinoids, vitamin D3 analogs (eg, calcipotriol), topical corticosteroids

Prognosis: Waxes and wanes

Generalized pustular psoriasis

Explosive onset of widespread erythema and sterile pustules

Treatment: Systemic retinoids or methotrexate

Prognosis: If untreated, can be fatal due to high-output heart failure

Erythrodermic psoriasis

Gradual or sudden onset of diffuse erythema, usually in patients with plaque psoriasis (possibly the first manifestation of erythrodermic psoriasis); typical psoriatic plaques less prominent or absent

Most commonly triggered by inappropriate use of topical or systemic corticosteroids or light therapy

Treatment: Potent systemic drugs (eg, methotrexate, cyclosporine, TNF-alpha inhibitor) or intense topical therapy, sometimes as inpatient therapy

Tars, anthralin, and phototherapy likely to exacerbate the condition

Prognosis: Good with elimination of triggering factors

Diagnosis

  • Clinical evaluation

  • Rarely biopsy

Diagnosis of psoriasis is most often by clinical appearance and distribution of lesions.

Differential diagnosis includes

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

  • Topical treatments

  • Ultraviolet (UV) light therapy

  • 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.)

Topical treatments

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 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 wk, an emollient should be substituted for the corticosteroid for 1 to 2 wk (as a rest period); this substitution limits corticosteroid dosage and prevents tachyphylaxis. 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 min 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 min after application. Using a liposome-encapsulated preparation may also avoid some disadvantages of anthralin.

Phototherapy

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 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). NBUVB 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.

Systemic treatments

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 [NBUVB]) or psoralen plus ultraviolet A (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.

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 yr after treatment ends. Pregnancy restrictions also apply to isotretinoin, but the agent is not retained in the body beyond 1 mo. Long-term treatment may cause diffuse idiopathic skeletal hyperostosis (DISH).

Immunosuppressants can be used for severe psoriasis. Cyclosporine is a commonly used immunosuppressant. It should be limited to courses of several months (rarely, up to 1 yr) and alternated with other therapies. Its effect on the kidneys and potential long-term effects on the immune system preclude more liberal use. Other immunosuppressants (eg, hydroxyurea, 6-thioguanine, mycophenolate mofetil) have narrow safety margins and are reserved for severe, recalcitrant psoriasis.

Immunomodulatory agents (biologics—see Immunotherapeutics) include TNF-alpha inhibitors (etanercept, adalimumab, infliximab). 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. Ustekinumab, a human monoclonal antibody that targets IL-12 and IL-23, can be used for moderate to severe psoriasis. IL-17 inhibitors (secukinumab and ixekizumab) are the most recently available biologics for moderate to severe 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.

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 yr 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 NBUVB.

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 are described above.

For psoriatic arthritis, treatment with systemic therapy is important to prevent joint destruction; methotrexate or a TNF-α inhibitor may be effective.

Key Points

  • Psoriasis is a common inflammatory disorder affecting the skin that has a genetic component and several triggers (eg, trauma, infection, certain drugs).

  • Skin findings are usually well-circumscribed, erythematous papules and plaques covered with silvery scales.

  • 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.

More Information

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • LAMISIL
  • ENBREL
  • REMICADE
  • HUMIRA
  • CORDRAN
  • LITHOBID
  • DOVONEX
  • SORIATANE
  • OTREXUP
  • KENALOG
  • PROGRAF
  • ARALEN
  • No US brand name
  • STELARA
  • INDOCIN
  • OTEZLA
  • NEORAL, SANDIMMUNE
  • ELIDEL
  • AVAGE, TAZORAC
  • ROCALTROL
  • HYDREA
  • SOTRET