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Psoriasis

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Psoriasis
Author: Jeffrey Meffert, MD; Cief Editor: Robert E OConnor,MD, MPH more Updated: Sep 23, 2011

Background
Psoriasis is a chronic, noncontagious, multisystem, inflammatory disorder. Patients with psoriasis have a genetic predisposition for the illness, which most commonly manifests itself on the skin of the elbows, knees, scalp, lumbosacral areas, intergluteal clefts, and glans penis. The joints are also affected by psoriasis in up to 30% of patients with the disease. (See Pathophysiology and Etiology.) Psoriasis has a tendency to wax and wane with flares related to systemic or environmental factors, including life stress events and infection. It impacts quality of life and potentially longterm survival. There should be a higher clinical suspicion for depression in the patient with psoriasis. (See Prognosis.) Multiple types of psoriasis are identified, with plaque-type psoriasis, also known as discoid psoriasis, being the most common type. Plaque psoriasis usually presents with plaques on the scalp, trunk, and limbs (see the image below). These plaques appear as focal, raised, inflamed, edematous lesions covered with silvery-white micaceous scales. (See Clinical Presentation.)

Psoriasis pictures. Plaque psoriasis is most common on the extensor surfaces of the knees and elbows. Contributed by Randy Park, MD. Ocular signs occur in approximately 10% of psoriasis patients, and they are more common in men than in women. Patients with ocular findings almost always have psoriatic skin disease; however, it is rare for the eye to become involved before the skin.[1, 2, 3]

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Psoriasis

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The diagnosis of psoriasis is clinical. (See Workup.) Management of psoriasis may involve topical or systemic medications, light therapy, stress reduction, climatotherapy, and various adjuncts such as sunshine, moisturizers, and salicylic acid. (See Treatment and Management.) For more information, see the following:

Guttate Psoriasis Nail Psoriasis Plaque Psoriasis Pustular Psoriasis Psoriatic Arthritis Imaging of Psoriatic Arthritis Parapsoriasis

Pathophysiology
Psoriasis is a complex, multifactorial disease that appears to be influenced by genetic and immune-mediated components. This is supported by the successful treatment of psoriasis with immune-mediating, biologic medications. The pathogenesis of this disease is not completely understood. Multiple theories exist regarding triggers of the disease process including an infectious episode, traumatic insult, and stressful life event. In many patients, no obvious trigger exists at all. However, once triggered, there appears to be substantial leukocyte recruitment to the dermis and epidermis resulting in the characteristic psoriatic plaques. Specifically, the epidermis is infiltrated by a large number of activated T cells, which appear to be capable of inducing keratinocyte proliferation. This is supported by histologic examination and immunohistochemical staining of psoriatic plaques revealing large populations of T cells within the psoriasis lesions. One report calculated that a patient with 20% body surface area affected with psoriasis lesions has around 8 billion blood circulating T cells compared with approximately 20 billion T cells located in the dermis and epidermis of psoriasis plaques. [4] Ultimately, a ramped-up, deregulated inflammatory process ensues with a large production of various cytokines (eg, tumor necrosis factor- *TNF-+, interferon-gamma, interleukin-12). Many of the clinical features of psoriasis are explained by the large production of such mediators. Interestingly, elevated levels of TNF- specifically are found to correlate with flares of psoriasis. One study adds further support that T-cell hyperactivity and the resulting proinflammatory mediators (in this case IL-17/23) play a major role in the pathogenesis of psoriasis.[5]

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Key findings in the affected skin of patients with psoriasis include vascular engorgement due to superficial blood vessel dilation and altered epidermal cell cycle. Epidermal hyperplasia leads to an accelerated cell turnover rate (from 23 d to 3-5 d), leading to improper cell maturation. Cells that normally lose their nuclei in the stratum granulosum retain their nuclei, a condition known as parakeratosis. In addition to parakeratosis, affected epidermal cells fail to release adequate levels of lipids, which normally cement adhesions of corneocytes. Subsequently, poorly adherent stratum corneum is formed leading to the flaking, scaly presentation of psoriasis lesions, the surface of which often resembles silver scales. Conjunctival impression cytology demonstrated a higher incidence of squamous metaplasia, neutrophil clumping, and nuclear chromatin changes in patients with psoriasis.[6, 7]

Etiology
Psoriasis involves hyperproliferation of the keratinocytes in the epidermis, with an increase in the epidermal cell turnover rate. (See Pathophysiology.) The cause of the loss of control of keratinocyte turnover is unknown. However, environmental, genetic, and immunologic factors appear to play a role.

Environmental factors
Many factors besides stress have also been observed to trigger exacerbations, including cold, trauma, infections (eg, streptococcal, staphylococcal, human immunodeficiency virus), alcohol, and drugs (eg, iodides, steroid withdrawal, aspirin, lithium, beta-blockers, botulinum A, antimalarials). Hot weather, sunlight, and pregnancy may be beneficial, although the latter is not universal. Perceived stress can exacerbate psoriasis. Some authors suggest that psoriasis is a stress-related disease and offer findings of increased concentrations of neurotransmitters in psoriatic plaques.

Genetic factors
Patients with psoriasis have a genetic predisposition for the disease. The gene locus is determined. The triggering event may be unknown in most cases, but it is likely immunologic. The first lesion commonly appears after an upper respiratory infection. Psoriasis is associated with certain human leukocyte antigen (HLA) alleles, particularly human leukocyte antigen Cw6 (HLA-Cw6). In some families, psoriasis is an autosomal dominant trait. A multicenter meta-analysis confirmed that deletion of 2 late cornified envelope (LCE) genes, LCE3C and LCE3B, is a common genetic factor for susceptibility to psoriasis in different populations.[8]

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Obesity is another factor associated with psoriasis. Whether it is related to weight alone, genetic predisposition to obesity, or a combination of the 2 is not certain. Onset or worsening of psoriasis with weight gain and/or improvement with weight loss is observed.

Immunologic factors
Evidence suggests that psoriasis is an autoimmune disease. Studies show high levels of dermal and circulating TNF-. Treatment with TNF- inhibitors is often successful. Psoriatic lesions are associated with increased activity of T cells in the underlying skin. Psoriasis is related to excess T-cell activity. Experimental models can be induced by stimulation with streptococcal superantigen, which cross-reacts with dermal collagen. This small peptide has been shown to cause increased activity among T cells in patients with psoriasis but not in control groups. Some of the newer drugs used to treat severe psoriasis directly modify the function of lymphocytes. Also of significance is that 2.5% of those with HIV develop worsening psoriasis with decreasing CD4 counts. This is paradoxical, in that the leading hypothesis on the pathogenesis of psoriasis supports T-cell hyperactivity and treatments geared to reduce T-cell counts help reduce psoriasis severity. This finding is possibly explained by a decrease in CD4 T cells, which leads to overactivity of CD8 T cells, which drives the worsening psoriasis. The HIV genome may drive keratinocyte proliferation directly. HIV associated with opportunistic infections may see increased frequency of superantigen exposure leading to similar cascades as above mentioned. Guttate psoriasis often appears following certain immunologically active events, such as streptococcal pharyngitis, cessation of steroid therapy, and use of antimalarial drugs.

Epidemiology
According to the National Institutes of Health (NIH), approximately 2.2% of the United States population has psoriasis. Internationally, the incidence of psoriasis varies dramatically. A study of 26,000 South American Indians did not reveal a single case of psoriasis, whereas in the Faeroe Islands, an incidence of 2.8% was observed. Overall, approximately 2-3% of people are affected by psoriasis worldwide. Psoriasis can begin at any age. Approximately 10-15% of new cases begin in children younger than 10 years. The median age at onset is 28 years. Psoriasis appears to be slightly more prevalent among women than among men; however, men are thought to be more likely to experience the ocular disease. Psoriasis is slightly more common in women than in men.

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The incidence of psoriasis is dependent on the climate and genetic heritage of the population. It is less common in the tropics and in dark-skinned persons. Psoriasis prevalence in African Americans is 1.3% compared with 2.5% in whites.[9]

Prognosis
Although psoriasis is usually benign, it is a lifelong illness with remissions and exacerbations and is sometimes refractory to treatment. It progresses to arthritis in about 10% of cases. About 1755% of patients experience remissions of varying lengths. Mild psoriasis does not appear to increase risk of death.[10] However, men with severe psoriasis died 3.5 years earlier compared with men without the disease. Women with severe psoriasis died 4.4 years earlier compared with women without the disease.[10] Psoriasis is associated with cardiovascular disease, smoking, alcohol, metabolic syndrome, lymphoma, depression, suicide, potentially harmful drug and light therapies, and possibly melanoma and nonmelanoma skin cancers. A systematic review of 90 studies confirmed that patients with psoriasis had a higher risk of ischemic heart disease, stroke, and peripheral arterial disease but also a greater prevalence of risk factors for cardiovascular disease, compared with controls. The authors concluded that large prospective studies with long-term followup are required to determine whether psoriasis is an independent risk factor for vascular disease or is merely associated with known risk factors.[11] Psoriasis can significantly influence a persons quality of life. One study suggests that the physical and mental disability experienced with this disease was comparable or in excess of that found in patients with other chronic illnesses such as cancer, arthritis, hypertension, heart disease, diabetes, and depression.[12] A study by Kurd et al further supports the notion that psoriasis impacts quality of life and potentially long-term survival.[13] There should be a higher clinical suspicion for depression in the patient with psoriasis. Studies show that psoriasis of the palms and soles tend to have greater impact on the patients quality of life compared to those with more extensive psoriatic involvement not involving the palms and soles.[14, 15]

Patient Education
Dry eye and its manifestations may be present. Avoiding drying conditions and using lubricants can be effective. Patient recognition of these symptoms is vital for effective early treatment of this disease. Most cases of psoriasis can be controlled at a tolerable level with the regular application of care measures.

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For patient education resources, see the Psoriasis Center, as well as Psoriasis, What Is Psoriasis?, Types of Psoriasis, Nail Psoriasis, and Understanding Psoriasis Medications.

History
Symptoms of psoriasis may include the following:

Worsening of a long-term erythematous scaly area Sudden onset of many small areas of scaly redness Recent streptococcal throat infection, viral infection, immunization, use of antimalarial drug, or trauma Family history of similar skin condition Pain (especially in erythrodermic psoriasis and in some cases of traumatized plaques or in the joints affected by psoriatic arthritis) Pruritus (especially in eruptive, guttate psoriasis) Afebrile (except in pustular or erythrodermic psoriasis in which the patient may have high fever) Dystrophic nails Long-term rash with recent presentation of joint pain Joint pain without any visible skin findings

The skin almost always is affected before the eyes. Ocular findings occur in approximately 10% of patients. The most common ocular symptoms are redness and tearing due to conjunctivitis or blepharitis. The nonocular symptoms are related to rash and psoriatic arthritis. The rash can be uncomfortable or even painful. Psoriatic arthritis can cause stiffness, pain, throbbing, swelling, or tenderness of the joints. The distal joints, such as the fingers, toes, wrists, knees, and ankles, are most often affected.

Physical Examination
Findings on physical examination depend on the type of psoriasis present. The most common skin manifestations are scaling erythematous macules, papules, and plaques. Typically, the macules are seen first, and these progress to maculopapules and ultimately well-demarcated, noncoherent, silvery plaques overlying a glossy homogeneous erythema. The area of skin involvement varies with the form of psoriasis. Chronic stationary psoriasis (psoriasis vulgaris) is the most common type of psoriasis. This involves the scalp, extensor surfaces, genitals, umbilicus, and lumbosacral and retroauricular regions.

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Plaque psoriasis is characterized by raised, inflamed lesions covered with a silvery white scale. The scale may be scraped away to reveal inflamed skin beneath. This is most common on the extensor surfaces of the knees, elbows, scalp, and trunk. Guttate psoriasis presents as small salmon-pink papules, 1-10 mm in diameter, predominately on the trunk; the lesions may be scaly (see the image below). It frequently appears suddenly, 23 weeks after an upper respiratory infection (URI) with group A beta-hemolytic streptococci.

Psoriasis pictures. Guttate psoriasis erupted in this patient after topical steroid therapy was withdrawn during a pregnancy. Contributed by Randy Park, MD. Inverse psoriasis occurs on the flexural surfaces, armpit, groin, under the breast, and in the skin folds. It is characterized by smooth, inflamed lesions without scaling due to the moist nature of the area where this type of psoriasis is located. Pustular psoriasis presents as sterile pustules appearing on the palms and soles or diffusely over the body. Pustular psoriasis may cycle through erythema, pustules, then scaling. The diffuse variant is termed von Zumbusch variant, which is accompanied by fever and intense ill feeling in addition to the widespread pustules. Acrodermatitis continua of Hallopeau is considered a form of pustular psoriasis that affects the hands and feet. It may prove resistant to topical and other therapies. Erythrodermic psoriasis presents as generalized erythema, pain, itching, and fine scaling; various pustular forms also exist. It typically encompasses nearly the entire body surface area. It may be accompanied by fever, chills, hypothermia, and dehydration secondary to the large body surface area involvement. Patients with severe pustular or erythrodermic psoriasis may require hospital admission for metabolic and pain management. Older patients with erythrodermic psoriasis may experience cardiac instability and hypotension due to massive vascular shunting in the skin. Scalp psoriasis affects approximately 50% of patients. It presents as erythematous raised plaques with silvery white scales on the scalp. Nail psoriasis may cause pits on the nails, which often become thickened and yellowish in color. Nails may separate from the nail bed. Psoriatic nails may be indistinguishable from fungal nails and, at the same time, may be more prone to developing onychomycosis because of the nail separation and subungual debris.
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Psoriatic arthritis affects approximately 10-30% of those with skin symptoms. The arthritis is usually in the hands and feet and, occasionally, the large joints. It produces stiffness, pain, and progressive joint damage. Oral psoriasis may present with whitish lesions on the oral mucosa, which may appear to change in severity daily. It may also present as severe cheilosis with extension onto the surrounding skin, crossing the vermillion border. Geographic tongue is considered by many to be an oral form of psoriasis. Eruptive psoriasis involves the upper trunk and upper extremities. Most often, it is seen in younger patients.

Ocular Manifestations
In addition to skin manifestations, psoriasis may also affect the lid, conjunctiva, or cornea and give rise to ocular manifestations, including ectropion and trichiasis, conjunctivitis and conjunctival hyperemia, and corneal dryness with punctate keratitis and corneal melt.[16, 17] Blepharitis is the most common ocular finding in psoriasis. Erythema, edema, and psoriatic plaques may develop, and they can result in madarosis, cicatricial ectropion, trichiasis, and even loss of the lid tissue. A chronic nonspecific conjunctivitis is fairly common. It usually occurs in association with eyelid margin involvement. Psoriatic plaques can extend from the lid onto the conjunctiva. Chronic conjunctivitis can lead to symblepharon, keratoconjunctivitis sicca, and trichiasis. Nodular episcleritis and limbal lesions resembling phlyctenules also can be seen. Corneal disease is relatively rare. Most often, it is secondary to lid or conjunctival complications, such as dryness, trichiasis, or exposure. The most common finding is punctate keratitis. Filaments, epithelial thickening, recurrent erosions, vascularization, ulceration, and scarring can occur. The vascularization tends to be superficial, peripheral, and interpalpebral or inferior. Rarely, peripheral infiltration and melting can occur in the absence of trichiasis and exposure.[18] In one case, recurrent nasolacrimal duct occlusion was observed, presumably caused by washing of the scales into the lacrimal sac. Usually, anterior uveitis can be seen in association with psoriatic arthritis. Acute psoriatic uveitis tends to be bilateral, prolonged, and more severe than nonpsoriatic cases.[19, 20]

Complications
Complications of psoriasis may include the following:
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Secondary infections Possible increased risk of lymphoma Possible increased risk of cardiovascular and ischemic heart disease Psoriatic arthritis Mitral valve prolapse

Diagnostic Considerations
Conditions to be considered include the following:

Seborrheic dermatitis Diaper dermatitis Onychomycosis Squamous cell carcinoma Nummular eczema Lichen planus Lichen simplex chronicus Mycosis fungoides Subcorneal pustulosis Pustular eruptions

Differentials

Adult Blepharitis Atopic Dermatitis Atopic Keratoconjunctivitis Contact Dermatitis Dry Eye Syndrome Gout and Pseudogout Pityriasis Alba Pityriasis Rosea Reactive Arthritis Sicca Keratoconjunctivitis Syphilis Tinea

Approach Considerations
The diagnosis of psoriasis is clinical. The differentiation of psoriatic arthritis from rheumatoid arthritis and gout can be facilitated by the absence of the typical laboratory findings of those conditions.
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Lab Studies
Laboratory studies and findings for patients with psoriasis may include the following:

Test result for rheumatoid factor (RF) is negative. Erythrocyte sedimentation rate (ESR) is usually normal (except in pustular and erythrodermic psoriasis). Uric acid level may be elevated in psoriasis (especially in pustular psoriasis), causing confusion with gout in psoriatic arthritis. Fluid from pustules is sterile with neutrophilic infiltrate. Perform fungal studies. (This is especially important in cases of hand and foot psoriasis that seem to be worsening with the use of topical steroids.)

If starting systemic therapies such as immunological inhibitors, consider obtaining baseline laboratory studies (ie, complete blood count [CBC], blood urea nitrogen [BUN]/creatinine, liver function tests [LFTs], hepatitis panel, tuberculosis [TB] screening).

Other Tests
Although most cases of psoriasis are diagnosed clinically, some, particularly the pustular forms, can be difficult to recognize. In these cases, dermatologic biopsy can be used to make diagnosis. Biopsy of the skin lesion may reveal basal cell hyperplasia, proliferation of subepidermal vasculature, absence of normal cell maturation, and keratinization. A large number of activated T cells are present in the epidermis. Lesions from other inflammatory conditions may be rubbed and scratched until they develop psoriasiform histological changes. Radiographs of affected joints can be helpful in differentiating types of arthritis. Joint x-rays can facilitate the diagnosis of psoriatic arthritis. Bone scans can identify joint involvement early. Conjunctival impression cytology has demonstrated an increased incidence of squamous metaplasia, neutrophil clumping, and snakelike chromatin. When the scales are removed, small droplets of blood appear within a few seconds; this is known as the Auspitz sign.

Approach Considerations
Management of psoriasis may involve drugs, light therapy, stress reduction, climatotherapy, and various adjuncts such as sunshine, moisturizers, and salicylic acid. The American Academy of Dermatology (AAD) is developing a series of recommendations under the umbrella title, Guidelines of Care for the Management of Psoriasis and Psoriatic Arthritis. The most recent addition was Section 6 (published online in November 2010; in print 2011.) All
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6 sections are available online at the AAD website.[21, 22, 23, 24, 25] Section 6 of the AAD guideline recommends that psoriasis treatment be personalized for each patients clinical situation and discusses examples of this approach to treatment.[25]

Treatment of Skin Lesions


Patients with guttate, erythrodermic, or pustular psoriasis may present to the emergency department. In each of these cases, restoration of the barrier function of the skin is of prime concern. This can be performed with cleaning and bandaging. Plaque and scalp lesions are frequently encountered in patients seeking care for other problems, and initial treatment of the lesions should be offered. The simplest treatment of psoriasis is daily sun exposure, sea bathing, topical moisturizers, and relaxation. Moisturizers, such as petrolatum jelly, are helpful. Daily application of moisturizing cream to the affected area is inexpensive and successful adjunct to psoriasis treatment. Application immediately after a bath or shower helps to minimize itching and tenderness. Section 3 (2009) of the AAD guideline discusses topical agents and recommends their use adjunctively but not as monotherapy if the disease is extensive or recalcitrant.[22] Nonprescription tar preparations are available and have therapeutic success, especially when used in conjunction with topical corticosteroids; the newer foams are less messy preparations than some of the older ones. Anthralin, topical corticosteroids, salicylic acid, phenolic compounds, and calcipotriene (a vitamin D analog) also may be effective. Systemic corticosteroids are generally ineffective, and they can significantly exacerbate the disease upon withdrawal. Combination therapy with a vitamin D analog (calcipotriol and calcipotriene) or a retinoid such as tazarotene and a topical corticosteroid is more effective than therapy with either agent alone.[26] Oatmeal baths may be helpful. Solar or ultraviolet radiation may be helpful. Various ultraviolet light treatments are used most commonly, psoralen-ultraviolet A (PUVA) therapy. Among phototherapy options, Section 5 (2010) of the AAD guideline gives the highest recommendation to oral PUVA or a combination of PUVA and topical agents.[24] Psoralen is a photosensitizer that is ingested prior to light exposure. PUVA treatment results in conjunctival hyperemia and dry eye, particularly if sun protection is not used. With proper eye protection, there does not appear to be a risk of cataract. Psoralens for either topical (bath) or systemic use may occasionally be difficult to obtain because of stocking shortages. According to the AAD guidelines, PUVA can result in long remissions, but long-term use of PUVA in Caucasians may increase the risk of squamous cell carcinoma and possibly malignant melanoma.[21, 24] Narrow-band ultraviolet B (UVB) therapy has always been accepted as a good treatment modality of psoriasis and the AAD guidelines recommend it over broad-band (UVA), although
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both are less effective than PUVA.[21, 24] As with PUVA, the guidelines also recommend treatment with combinations of UVB and topic or systemic agents.[24] However, a study by Keaney and Kirsner gives objective reasoning for the benefit of narrow-band UV therapy by showing decreases in T cells, dendritic cells, and interleukins within responsive psoriatic plaques compared with plaques that did not respond to therapy.[5] Gutate psoriasis may prove especially responsive to phototherapy. Therapies such as UVB and PUVA have low efficacy for the treatment of nail psoriasis because of the blockage of the UV radiation by the intervening nail plate.[27] Patients with psoriasis should avoid injury to skin, including sunburn and other physical trauma, as these areas may develop psoriasis. The appearance of psoriatic lesions in previously uninvolved areas after irritation or trauma is known as the Kbner phenomenon. Patients with psoriasis should also avoid drugs known to worsen the problem (eg, chloroquine, beta-blockers, aspirin or other NSAIDs). In severe cases, retinoids (acitretin), methotrexate, cyclosporine, 6-thioguanine, azathioprine, a biologic, or hydroxyurea may be used. Retinoids have been reported to cause dry eye, blepharitis, corneal opacities, cataracts, and decreased night vision.[28, 29] All of these may be associated with gastrointestinal intolerance, hepatic damage (acitretin, 6-thioguanine, azathioprine, methotrexate), marrow suppression (6-thioguanine, methotrexate, azathioprine, hydroxyurea) or renal damage (cyclosporine). The use of these systemic medications, with appropriate safety considerations, is supported by Section 4 (2009) of the AAD guidelines. [23] In addition, systemic retinoids and hydroxyurea may interfere with proper wound healing and elective procedures, including dental surgery, which are best performed before the start of the medications. Acitretin appears more effective than isotretinoin in psoriasis and does not require enrollment in the IPledge program. On the other hand, there is a 3-year pregnancy prohibition after its use, and many will not use this medication in any patient capable of ever becoming pregnant. Combination therapies, such as a biologic plus another immunosuppressive medication, have been used with good effect but data detailing the safest way to do this are scant. All of the systemic medications except acitretin may increase the risk of infection. Abruptly stopping steroid therapy in psoriasis or adding known irritant drugs can result in the sudden worsening of psoriasis or appearance of a new form. Commonly, this new form is guttate psoriasis, which is much more severe and cosmetically problematic than the preexisting plaque type. It may also present with a more threatening pustular or erythrodermic psoriatic flare. The use of biologic agents (proteins with pharmacologic activity) is discussed in Section 1 (2008) and reviewed, with updated safety information, in Section 6 of the AAD guidelines. The AAD recommends a set of baseline laboratory studies before starting treatment with a biologic agent to ensure any underlying conditions or risk factors are understood.[21, 25]

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Many of the therapies for psoriasis manipulate the function of the immune system and expose the patient to risk of severe infections while blunting the bodys response. In these patients, findings suggestive of minor infections must be taken seriously, and the risk versus the benefit of continuing the drug in the face of the infection must be weighed.

Treatment of Ocular Complications


Keratoconjunctivitis sicca can be treated with ocular lubricants and punctal occlusion. Trichiasis and cicatricial ectropion usually require surgical treatment. Conjunctival, corneal, and anterior chamber inflammation can be treated with topical corticosteroids. Nonsteroidal antiinflammatory agents or oral corticosteroids are occasionally necessary. Whether systemic immunosuppression is effective for ocular disease is not clear. Corneal melting, inflammation, and vascularization can be difficult to treat. A bandage contact lens may retard the melting. Topical corticosteroids can control the infiltration and delay the vascularization. In some cases, progression can occur in spite of these treatments and can lead to the need for lamellar or penetrating keratoplasty.

Consultations
Psoriasis is a chronic problem, and consultation for follow-up with a dermatologist or a rheumatologist is appropriate. Close follow-up is necessary to design an optimal treatment plan in accordance with the severity of disease. Severity of psoriasis can be classified as follows:

Mild - Less than 2% of the body is affected Moderate - From 3-10% of the body is affected Severe - More than 10% of the body is affected

Of note, the palm of the patients hand is equal to 1% body surface area. Determining the severity of psoriasis requires combining objective measures, such as body surface area involvement; disease location; symptoms; and presence of psoriatic arthritis with subjective measures such as the physical, financial, and emotional impact of the disease. Patients with infectious diseases and psoriasis may be using drugs that modify immunologic response and render them immunocompromised. Investigation into the type of therapy is important and, if such an agent is identified, referral and close follow-up is needed.

Medication Summary

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Many drugs that affect the rate of skin cell production are used in psoriasis therapy alone or in combination with light therapy, stress reduction, and climatotherapy. Adjuncts to treatment include sunshine, moisturizers, and salicylic acid as a scale-removing agent. Generally, these therapies are used for patients with less than 20% of body surface area involved, unless the lesions are physically, socially, or economically disabling. Treatments for more advanced psoriasis include narrow-band ultraviolet B (UVB) light, psoralen with ultraviolet A (UVA) light retinoids (eg, isotretinoin [Accutane, Claravis], acitretin [Soriatane]), methotrexate (particularly for arthritis), cyclosporine (Neoral, Sandimmune), infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), and alefacept (Amevive). The AAD guidelines recommend treatment with methotrexate, cyclosporine, and acitretin, with consideration of the contraindications and drug interactions noted in the discussion of each medication below.[23]

Topical Corticosteroids
Class Summary
Topical corticosteroids are used to reduce plaque formation. These agents have antiinflammatory effects and may cause profound and varied metabolic activities. In addition, they modify the bodys immune response to diverse stimuli. Several examples are provided, but no topical corticosteroids are superior in efficacy or adverse effects to others in the same class. Some formulations such as foams and solutions are easier to use in the scalp than either creams or ointments. A patient who has been doing well on a topical steroid who begins to have worsening, especially with itching, should be evaluated for either a concomitant fungal infection or the development of allergic contact dermatitis to a steroid or vehicle component. View full drug information

Triamcinolone acetonide (Aristocort, Kenalog) 0.025-0.1% cream

Triamcinolone treats inflammatory dermatosis responsive to steroids. It decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. It has mild potency and is the first drug of choice for most patients. View full drug information

Betamethasone (Diprolene, Diprosone) 0.025-0.1% cream


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Betamethasone treats inflammatory dermatosis responsive to steroids. It decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. It is a potent topical steroid and is the drug of choice if psoriasis is resistant to milder forms.

Ophthalmic Corticosteroids
Class Summary
Ophthalmic corticosteroids treat conjunctival, corneal, and anterior chamber inflammation. These agents help control infiltration and delay vascularization. View full drug information

Prednisolone acetate 1% ophthalmic (Pred Forte)

Prednisolone decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. In cases of bacterial infections, concomitant use of anti-infective agents is mandatory; if signs and symptoms do not improve after 2 days, reevaluate patient. Dosing may be reduced, but advise patients not to discontinue therapy prematurely.

Dexamethasone 0.1% ophthalmic

Dexamethasone is used for various allergic and inflammatory diseases. It decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Coal Tar
Class Summary
Coal tar is an inexpensive treatment that is available over the counter in shampoos, lotions, creams, or foam for use in widespread areas of involvement. It is particularly useful in hairbearing areas. Some recent research has shown the 1% concentration may be superior in control of lesions to more concentrated preparations. Tar preparations may be especially useful
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when combined with topical corticosteroids. This may be accomplished by applying the products sequentially or, when available, obtaining them from a compounding pharmacy. View full drug information

Coal tar 0.5-33% (DHS Tar, Doctar, Theraplex T)

Coal tar is antipruritic and antibacterial and inhibits deregulated epidermal proliferation and dermal infiltration. It does not injure the normal skin when applied widely, and it enhances the usefulness of phototherapy. It generally is used as a second-line drug therapy due to messy application, except for shampoos, which may be used and rinsed at once.

Keratolytic Agents
Class Summary
Keratolytic agents are used to remove scale, to smooth the skin, and to treat hyperkeratosis. Removing the thick scale allows topical corticosteroids and other topical medications to better reach the target tissues and achieve better results. This is especially important on the scalp. Many over-the-counter preparations can be used for this, most of which contain salicylic acid. Lactic acid, ammonium lactate, and urea are other ingredients that may be applied before or at the same time as other topical medications. Urea preparations stronger than 30% require a prescription, a variety of creams, lotions, and foams are available for this. Many foot creams contain combinations of keratolytics and may be applied to any area of the body needing scale removal. Anthralin is also considered to be in the antipsoriatic therapeutic class.

Anthralin 0.1-1% (Drithocreme, Anthra-Derm)

Anthralin reduces the rate of cell proliferation. Its chemically reducing properties may also upset the oxidative metabolic processes, further reducing epidermal mitosis. It is not the first or second drug of choice due to irritation problems of normal skin surrounding lesions and staining of the skin.

Vitamin D Analogs
Class Summary
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Vitamin D analogs are used in patients with lesions resistant to topical therapy or with lesions on the face or exposed areas where thinning of the skin would pose cosmetic problems. These come as ointments, solutions, and foams. The latter 2 are especially useful for scalp treatments. View full drug information

Calcitriol (Vectical) Ointment

Calcitriol is a topical vitamin D analog similar to calcipotriene but seems to be less irritating in sensitive areas of skin. View full drug information

Calcipotriene (Dovonex, Sorilux)

Calcipotriene is a synthetic vitamin D-3 analog that regulates skin cell production and development. It is used in the treatment of moderate plaque psoriasis. This treatment does not cause long-term skin thinning or systemic effects. Sorilux is a newer foam version of this medication. View full drug information

Calcipotriene and betamethasone topical ointment (Taclonex)

Calcipotriene is a synthetic vitamin D-3 analog that regulates skin cell production and development. It inhibits epidermal proliferation, promotes keratinocyte differentiation, and has immunosuppressive effects on lymphoid cells. Betamethasone is a corticosteroid that decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. The combination is available as a topical ointment and as a scalp solution containing calcipotriene 0.005% and betamethasone dipropionate 0.064%. The product is quite expensive and the same results may be obtained by using a generic corticosteroid sequentially in combination with one of the other vitamin D analog products.

Topical Retinoids
Class Summary
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Psoriasis

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Aqueous gel formulations are odorless and colorless, and no long-term skin damage has been noted with topical retinoids. There is also no threat of worsening if the therapy is withdrawn, as with steroids. These drugs should not be used in women if pregnancy is a possibility. View full drug information

Tazarotene (Tazorac) aqueous gel and cream 0.05% and 0.1%

Tazarotene is a retinoid prodrug that is converted to its active form in the body and modulates differentiation and proliferation of epithelial tissue and perhaps has anti-inflammatory and immunomodulatory activities. It may be the drug of choice for those with facial lesions who are not at risk of pregnancy. Tazarotene, although topical, is a category X medication. Topical tretinoin is of less use in psoriatic patients. A strategy that may be tried in patients who experience unacceptable irritation is to use short contact times. There are several protocols, but the least irritating is to apply the medication for 15-20 min and then wash off. The total time on may be increased by 15-20 minutes every few weeks until clinical efficacy or adverse cutaneous effects are seen. This short-contact method may be especially useful when one is using it in skin folds but is less effective for the plaque with very thick scale.

Antimetabolites
Class Summary
Antimetabolites inhibit cell growth and proliferation. View full drug information

Methotrexate (Trexall)

Methotrexate inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one-carbon groups in the synthesis of nucleotides and thymidylate. Subsequently, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues are in general more sensitive to this effect of methotrexate.

Immunomodulators
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Psoriasis

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Class Summary
Immunomodulators regulate key factors responsible for inflammatory response. View full drug information

Tacrolimus topical 0.1% (Protopic)

Topical tacrolimus has been used in the past for management of refractory atopic dermatitis. However, multiple studies have shown effectiveness with psoriasis affecting intertriginous regions as well as the face. Generally, it seems to be effective in thin-skinned areas. However, it has become somewhat of a second-line agent given other studies showing topical steroids may be more effective and potential serious disease association. View full drug information

Cyclosporine (Sandimmune, Neoral)

Cyclosporine is an 11-amino acid cyclic peptide and natural product of fungi. It acts on T-cell replication and activity. Cyclosporine is a specific modulator of T-cell function and an agent that depresses cellmediated immune responses by inhibiting helper T-cell function. Preferential and reversible inhibition of T lymphocytes in the G0 or G1 phase of cell cycle is suggested. The drug binds to cyclophilin, an intracellular protein, which, in turn, prevents formation of interleukin (IL)-2 and the subsequent recruitment of activated T cells. Cyclosporine has about 30% bioavailability, but there is marked interindividual variability. It specifically inhibits T-lymphocyte function with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that the drug be present during first 24 h of antigenic exposure. Cyclosporine suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease) for a variety of organs. Cyclosporine is used in extensive disease refractory to other treatments, especially when used at 5 mg/kg/d. Remission is usually rapid with this therapy; however, skin lesions tend to recur within days to weeks after treatment is stopped (although patients do not usually have the

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severe rebound that patients withdrawing from therapy may have). Maintenance therapy (3 mg/kg/d) usually is required with lower doses of this drug. View full drug information

Alefacept (Amevive)

Alefacept is a recombinant dimeric fusion protein that binds to CD2 on memory-effector T lymphocytes, thereby inhibiting the activation of these cells and reducing the number of these cells. It is indicated for moderate to severe psoriasis. This drug usually is administered intramuscularly. View full drug information

Ustekinumab (Stelara)

Ustekinumab is a human monoclonal antibody directed against IL-12 and IL-23, thereby interfering with T-cell differentiation and activation and subsequent cytokine cascades. It is indicated for moderate-to-severe plaque psoriasis.

Tumor Necrosis Factor Inhibitors


Class Summary
These agents neutralize the effects of tumor necrosis factor- (TNF-). View full drug information

Infliximab (Remicade)

Infliximab is a chimeric antibody that binds both the soluble and transmembrane TNF- molecules, thereby neutralizing the effects of TNF-. It is indicated for chronic severe (ie, extensive and/or disabling) plaque psoriasis in adults who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. It is also indicated to reduce signs and symptoms, and to improve physical function of patients with psoriatic arthritis. Screen patients for tuberculosis (TB) and hepatitis B, as reactivation of both illnesses is associated with TNF- inhibitors.
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This drug is delivered by infusion only. View full drug information

Etanercept (Enbrel)

Etanercept is a recombinant human TNF- receptor protein fused with the Fc portion of IgG1 that binds to soluble and membrane-bound TNF-, thereby neutralizing the effects of TNF-. It is indicated for moderate-to-severe psoriasis and moderate-to-severe psoriatic arthritis. Screen patients for TB and hepatitis B, as reactivation of both illnesses is associated with TNF- inhibitors. View full drug information

Adalimumab (Humira)

Adalimumab is a fully human antiTNF- monoclonal antibody. It binds specifically to soluble and membrane-bound TNF-, thereby neutralizing the effects of TNF-. It is used to treat moderate-to-severe psoriasis and moderate-to-severe psoriatic arthritis. Screen patients for TB and hepatitis B, as reactivation of both illnesses is associated with TNF- inhibitors.

Artificial Tears
Class Summary
Artificial tears are used to treat dry eye irritation. Many types of artificial tears are available over the counter. In mild cases, preserved tears can be used. In severe cases, only nonpreserved tears should be used. Preserved tears include GenTeal, Refresh Tears, and Tears Naturale II. Nonpreserved tears include Refresh, Refresh Plus, OcuCoat, Bion, and Hypo Tears PF. View full drug information

Artificial tears

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Artificial tears contain the equivalent of 0.9% NaCl and are used to maintain ocular tonicity. They act to stabilize and thicken precorneal tear film and prolong tear film breakup time, which occurs with dry eye states.

Injectable Corticosteroids
Class Summary
Intramuscular corticosteroids are not recommended for the management of psoriasis because of the risk of flare upon withdrawal. On the other hand, isolated plaques may be injected intralesionally, as may the nail matrix in cases of severe psoriatic nails.

Triamcinolone 10 mg/mL

For inflammatory dermatosis responsive to steroids; decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Many other topical steroids also are available. Up to 0.4 mL may be injected, after ring block, into the nail bed and matrix to improve psoriatic dystrophy. Results may be long lasting but more than one treatment may be required.

References
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8. Riveira-Munoz E, He SM, Escarams G, et al. Meta-Analysis Confirms the LCE3C_LCE3B Deletion as a Risk Factor for Psoriasis in Several Ethnic Groups and Finds Interaction with HLA-Cw6. J Invest Dermatol. May 2011;131(5):1105-9. [Medline]. 9. Gelfand JM, Stern RS, Nijsten T, Feldman SR, Thomas J, Kist J, et al. The prevalence of psoriasis in African Americans: results from a population-based study. J Am Acad Dermatol. Jan 2005;52(1):23-6. [Medline]. 10. Gelfand JM, Troxel AB, Lewis JD, Kurd SK, Shin DB, Wang X, et al. The risk of mortality in patients with psoriasis: results from a population-based study. Arch Dermatol. Dec 2007;143(12):1493-9. [Medline]. 11. Patel RV, Shelling ML, Prodanovich S, Federman DG, Kirsner RS. Psoriasis and vascular disease-risk factors and outcomes: a systematic review of the literature. J Gen Intern Med. Sep 2011;26(9):1036-49. [Medline]. 12. Rapp SR, Feldman SR, Exum ML, Fleischer AB Jr, Reboussin DM. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol. Sep 1999;41(3 Pt 1):401-7. [Medline]. 13. Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol. Aug 2010;146(8):891-5. [Medline]. [Full Text]. 14. Pettey AA, Balkrishnan R, Rapp SR, Fleischer AB, Feldman SR. Patients with palmoplantar psoriasis have more physical disability and discomfort than patients with other forms of psoriasis: implications for clinical practice. J Am Acad Dermatol. Aug 2003;49(2):271-5. [Medline]. 15. Sampogna F, Tabolli S, Sderfeldt B, Axtelius B, Aparo U, Abeni D. Measuring quality of life of patients with different clinical types of psoriasis using the SF-36. Br J Dermatol. May 2006;154(5):844-9. [Medline]. 16. Catsarou-Catsari A, Katambus A, Theodorpoylos P. Ophthalmological manifestations in patients with psoriasis. In: Acta Derm Venereol (Stock). 64. 1984:557-559. 17. Huynh N, Cervantes-Castaneda RA, Bhat P, Gallagher MJ, Foster CS. Biologic response modifier therapy for psoriatic ocular inflammatory disease. Ocul Immunol Inflamm. May-Jun 2008;16(3):89-93. [Medline]. 18. Moadel K, Perry HD, Donnenfeld ED, Zagelbaum B, Ingraham HJ. Psoriatic corneal abscess. Am J Ophthalmol. Jun 1995;119(6):800-1. [Medline]. 19. Durrani K, Foster CS. Psoriatic uveitis: a distinct clinical entity?. Am J Ophthalmol. Jan 2005;139(1):106-11. [Medline]. 20. Takahashi H, Sugita S, Shimizu N, Mochizuki M. A high viral load of Epstein-Barr virus DNA in ocular fluids in an HLA-B27-negative acute anterior uveitis patient with psoriasis. Jpn J Ophthalmol. Mar-Apr 2008;52(2):136-8. [Medline]. 21. [Guideline] Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. May 2008;58(5):826-50. [Medline]. 22. [Guideline] Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3.

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Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. Apr 2009;60(4):643-59. [Medline]. 23. [Guideline] Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. Sep 2009;61(3):451-85. [Medline]. 24. [Guideline] Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol. Jan 2010;62(1):114-35. [Medline]. 25. [Guideline] Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis Section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: Case-based presentations and evidence-based conclusions. J Am Acad Dermatol. Feb 7 2011;[Medline]. 26. Mason AR, Mason J, Cork M, Dooley G, Edwards G. Topical treatments for chronic plaque psoriasis. Cochrane Database Syst Rev. Apr 15 2009;CD005028. [Medline]. 27. Stern DK, Creasey AA, Quijije J, Lebwohl MG. UV-A and UV-B Penetration of Normal Human Cadaveric Fingernail Plate. Arch Dermatol. Apr 2011;147(4):439-41. [Medline]. 28. Lerman S. Ocular side effects of accutane therapy. Lens Eye Toxic Res. 1992;9(3-4):42938. [Medline]. 29. Brelsford M, Beute TC. Preventing and managing the side effects of isotretinoin. Semin Cutan Med Surg. Sep 2008;27(3):197-206. [Medline].

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