Recent Advances in the Treatment of Psoriasis

Release Date: April 1, 2012

Expiration Date: April 30, 2014

FACULTY:

Kiran Panesar, BPharmS (Hons), MRPharmS, RPh, CPh
Consultant Pharmacist and Freelance Medical Writer
Orlando, Florida

FACULTY DISCLOSURE STATEMENTS:

Mr. Panesar has no actual or potential conflict of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

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Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge

TARGET AUDIENCE:

This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

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DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

GOAL:

To educate pharmacists about the different types of psoriasis and the current agents available for the management of this condition.

OBJECTIVES:

After completing this activity, the participant should be able to:

  1. Identify psoriasis and the different types of psoriasis.
  2. Describe various comorbidities associated with psoriasis.
  3. Discuss both traditional and more recent therapies used in the management of psoriasis.

Psoriasis is an autoimmune disorder that commonly presents as a dermatologic condition in which skin cells turn over much more quickly than normal and pile up as immature cells on the skin surface.1 The first description of psoriasis was documented in 1808 by Robert Willan, MD, in an attempt to distinguish this condition from leprosy. In his text On Cutaneous Diseases, Willan describes psoriasis as a "scaly psora."2

Psoriasis is seen in about 2% to 3% of the worldwide population, but the rates vary between ethnic populations (e.g., only 0.3% of the Chinese population has this condition).2,3 More than 35% of persons with psoriasis have moderate-to-severe psoriasis, i.e., psoriasis that affects between 2% and >10% of the body surface area (BSA).4

This skin disorder occurs equally in men and women, and the mean age for the onset of psoriasis is 33 years, with 75% of cases occurring before the age of 46 years.2,5 Some studies suggest a bimodal onset with peaks between 16 and 22 years and 57 and 60 years.2

TYPES OF PSORIASIS

Psoriasis has a number of clinical variants that differ in severity, location, longevity, shape, pattern, cause, and treatment. The different types of psoriasis are fairly distinct and are listed in TABLE 1. Patients may experience more than one type at the same time.


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Plaque Psoriasis (Psoriasis Vulgaris)
Plaque psoriasis is the most common variant, observed in about 90% of patients.5,6 The red or salmon-colored papulosquamous plaques are well delineated from the surrounding skin.2 They may be thick or thin, large or small.2 Classic sites of plaque involvement are the extensor aspects of elbows and knees, the scalp, shins, the lumbosacral region, and the umbilicus; plaques do not, however, occur on the face.2,7 The plaques can develop from small lesions that converge to form larger papules. In active psoriasis, the rim of the plaque expands and the center of it clears, forming a typical plaque known as annular psoriasis.7  With the inactive form of plaque psoriasis, lesions remain the same size even without treatment.7

The active form has a better prognosis than the inactive form.7 The Koebner phenomenon describes active inflammatory psoriasis where new lesions develop at sites of trauma and pressure.2

Flexural or Inverse
Flexural or inverse psoriasis is commonly found in the skin folds, particularly the axillae, submammary regions, groin, and natal cleft.7 The patient's skin is shiny, red, and typically devoid of scales, and the plaques are thin.2,7

Guttate or Eruptive
Guttate or eruptive psoriasis is characterized by lesions that are less than 1 cm in diameter and are found over the upper trunk and proximal extremities.2,7 This type of psoriasis typically occurs in children and adolescents and frequently appears following a bacterial or viral infection of the upper airways.7 The lesions appear suddenly and are self-resolving, clearing within 3 to 4 weeks. 2,7 While the long-term prognosis has not been established, one study concluded that one-third of individuals with guttate psoriasis develop classic plaque disease within 10 years.2,8

Pustular
Also known as von Zumbusch psoriasis, this is an acute form in which small, monomorphic, sterile pustules develop in painful inflamed skin.2 It is often caused by current infection and abrupt withdrawal of systemic and topical corticosteroids.2 Many smaller pustules may form from an erythematous base and join up to form a lake of pus.7 Patients often experience associated weakness, weight loss, and episodes of fever that correspond to new outbreaks of pustules.

Palmoplantar
Palmoplantar psoriasis resembles pustular psoriasis and is associated with yellowbrown sterile pustules on the palms and soles. It is predominantly found in women and/or current or previous smokers.2

Erythrodermic
Erythrodermic psoriasis affects the whole body, generally over 90% of the BSA.2,7 The skin appears bright red and is covered by superficial scales. This can lead to hypothermia, hypoalbuminemia, and high output cardiac failure.2,7 In this way, erythrodermic psoriasis is life threatening.2 It can be caused by atopic dermatitis, drug eruptions, and cutaneous T-cell lymphoma.2

Scalp
Scalp psoriasis is characterized by plaques on the scalp and along the hair margin, the plaques becoming thicker and crusted as the disease develops.7,9 The plaques may be described as a dandruff-like desquamation of the scalp.7 While the scalp is the major area involved, in some cases the lesions may extend to the forehead, neck, ear, and retroauricular areas.7,9 It is always encouraging for patients to know that scalp psoriasis does not cause alopecia.7

Nail
Psoriatic nail disease is frequently seen in patients, with approximately 50% of the fingernails and 35% of the toenails being affected.2,7 The changes range from minor alterations in the nail plate to severe defects and include pitting, onycholysis (nail plate separations), oil spots (orange-yellow subungual discoloration), dystrophy, and splinter hemorrhages.2,7,10

Acral
Acral psoriasis is seen only on the palms and soles. It is primarily characterized by hyperkeratosis, and some patients may present with variable redness.7

Seborrheic
Seborrheic psoriasis is a condition whereby seborrheic dermatitis and psoriasis co-exist. In many cases, the seborrheic dermatitis leads to psoriasis in the same areas.7

While all types of psoriasis are well defined, parameters to describe the severity of psoriasis have not yet been clearly laid out.5,11 Perhaps the largest drawback is that the description of severe psoriasis varies depending upon the judgment of the assessor. One patient may define it differently from another depending upon how it is affecting his or her quality of life. There are also a number of different techniques used to measure the severity of psoriasis (TABLE 2). Furthermore, clinicians need to establish whether the severity is comparative or absolute, or current or long term.


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EFFECTS OF PSORIASIS

Psoriasis is associated with a high morbidity and a great level of psychological stress. Females tend to be affected more than males.12 Socially, patients with psoriasis tend to have a lower income, reduced levels of employment, and a poorer quality of life. Generally, the greater the skin involvement, the lower the quality of life.6,12 Depressive illness in psoriasis is associated with a low self-image, a fear of public rejection, and psychosexual concerns.1,2

Although not much research has been conducted in this area, it has been shown that psoriasis also impacts the quality of life of family members and partners.13

Physical
A recent study concluded that psoriasis is associated with a range of medical comorbidities including coronary artery disease, metabolic disease, renal failure, liver disease, viral hepatitis B or C, asthma, peptic ulcers, and malignancies, whereby the extent of the comorbidity increases with the severity of the psoriasis.14-16 One study group has postulated that there might be a genetic link between psoriasis and these comorbidities.17 There also seems to be a relationship between inflammatory factors in psoriasis and those with streptococcal oropharyngeal infections, decreased responsiveness to allergens, and a decreased frequency of rheumatic fever and poststreptococcal nephritis.17

Psoriatic Arthritis
Psoriatic arthritis is a seronegative inflammatory arthritis that occurs in the presence of skin or nail psoriasis.2,7 It can be divided into five types: distal interphalangeal joint, asymmetrical oligoarthritis, polyarthritis, spondylitis, and arthritis mutilans.2 It resembles rheumatoid arthritis in its effects.

Cardiovascular Disease and Metabolic Syndrome
The risk of cardiovascular disease in psoriatic patients increases by threefold with moderate and severe disease, but there is no apparent risk in those with mild disease.2,17,18 It is thought that the chronic systemic inflammation associated with psoriasis results in coronary artery disease (CAD), because the inflammatory mediators of psoriasis are similar to those of CAD.19,20

Psoriatic patients also have an increased risk of developing metabolic syndromes, including obesity, diabetes, hyperlipidemia, and hypertension.21

Crohn's Disease
Crohn's disease is seen seven times more often in psoriatic patients.22 This may be due to overlapping inflammatory pathways common in both conditions or be a side effect of some of the biological agents used in the management of psoriasis, such as infliximab and adalimumab.23-25

Cancer
Some authors postulate that psoriasis may be associated with an increased risk of cancer; however, this could be a side effect of psoriasis treatments, including photochemotherapy.2,25

HISTOLOGY AND PATHOLOGY

For many years it was thought that psoriasis was purely a skin disorder, but more recent studies have shown that immunosuppressive agents reduce psoriasis.26 The current model is that psoriasis is a complex autoimmune disease in which T cells are mistakenly activated, triggering other immune responses.1-3 Various environmental triggers such as trauma, stress, infection, climate changes, and drugs, including beta-blockers and lithium (TABLE 3), activate the disease in genetically predisposed individuals.1,27 The genetic basis of the disease is well established. Studies have shown that 30% of psoriasis patients have a first-degree relative with the condition.2 In cases where both a parent and one child are affected, siblings have a 50% chance of developing psoriasis.2


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In the early stages of psoriasis, the blood vessels of the papillary dermis elongate and dilate.28 The rate of mitosis of the basal keratinocytes is increased. Hyperproliferation of the epidermis by these factors results in premature maturation of keratinocytes and incomplete cornification with retention of nuclei in the stratum corneum.6 As the disease progresses, the plaques become infiltrated by high numbers of immunoregulatory cells, namely T lymphocytes and dendritic cells, expressing multiple cytokine, chemokine, and growth factors involved in cell proliferation and inflammation.3,5 It has been observed that the lymphocytes are primarily CD8+ T cells in the epidermis, a mixture of CD4+ and CD8+ T cells in the dermis, and predominantly CD4+ in the peripheral blood.28

DIAGNOSIS

There is no diagnostic test for psoriasis, and currently its identification is made clinically. All symptoms have to be considered for a differential diagnosis, since a number of cutaneous disorders mimic the signs and symptoms of psoriasis.29

TREATMENT

There is no cure for psoriasis— therapy is aimed at limiting lesions and improving the patient's quality of life.30 The currently available treatments can be divided into topical therapies, systemic therapies, and biological agents (TABLE 4).


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Topical Therapies
Psoriasis covering less than 5% of BSA can be managed in most patients with the use of topical agents alone.5 These agents are the cornerstone of treatment for most patients with psoriasis.30 Formulated as creams, lotions, foams, sprays, ointments, and gels, they are effective and easy to use although compliance becomes an issue because application is time consuming.30 Creams and ointments are preferred over lotions since the latter are lighter and less occlusive.31

Topical therapies do not always work for nail psoriasis even though they are easy to administer and readily available.10 Patients should be counseled to keep nails as short as possible, avoid manicures of the cuticle, and prevent accumulation of any exogenous material under the nail.10 Any concomitant nail fungal infections should be treated appropriately.

Emollients: Emollients can have one or more of the following actions: occlusive, humectant, antipruritic, anti-inflammatory, rehydrant, and skin barrier restorant.32 In simple terms, they reduce water loss, prevent the skin from drying out, and create a barrier against the environment. TABLE 5 lists some of the agents in which these properties are found. Emollients are particularly useful in inflammatory and chronic plaque psoriasis as well as in acral psoriasis. In psoriasis, emollients offer relief from dryness, scaling, and cracking of the skin, and might also have an antiproliferative effect. Emollient monotherapy may be sufficient only in mild psoriasis. In most cases other adjuvants are required. Water-in-oil emollients have been shown to replace one of the doses of twice-daily corticosteroid therapy.32


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Some authors recommend a daily warm bath followed by liberal application of emollients together with one or two more moisturizing applications throughout the day.32 Full-body bath products that reduce scale load and improve stratum corneum hydration are of two types: dispersion bath oils and spreading bath oils. Similarly in scalp psoriasis, a shampoo that encourages desquamation of the scalp should be used followed by the application of a keratolytic lotion.32

The use of emollients is associated with side effects such as irritant dermatitis, allergic contact dermatitis, stinging, cosmetic acne, and pigmentation disorders.32

Keratolytics: Perhaps the most widely used and oldest keratolytic agent known today, salicylic acid is available in concentrations ranging from 0.5% to 60% in a number of vehicles.31 It is particularly useful in thick plaque or scaly plaque psoriasis.

In some patients salicylic acid may be useful as monotherapy. It can also be added to anthralin and zinc pastes to reduce the interaction between these two ingredients. Additionally, salicylic acid offers antioxidant properties to such preparations.31

Application on large areas and in concentrations greater than 10% results in toxicity.31 This manifests as oral mucosal burning, frontal headache, central nervous system symptoms, metabolic acidosis, tinnitus, nausea, vomiting, and gastric symptoms. Salicylic acid may reduce the action of other therapies for psoriasis, including calcipotriene.31

Urea has both emollient and keratolytic properties (TABLE 5). Furthermore, it can be combined with anthralin to improve its clinical efficacy.31 Urea combined with bifonazole is useful in the management of scalp psoriasis.31 It is used topically in concentrations of 5% to 25% in creams or lotions and up to 40% in nail preparations.33

Omega Fatty Acids: Abnormal serum fatty acid profile has been noted in psoriasis.31 Omega 3 and omega 6 fatty acid preparations may restore barrier properties.31 Olive oil has been particularly useful in this respect.

Corticosteroids: Corticosteroids are perhaps the most widely used treatment for psoriasis worldwide.30 There are a number of corticosteroids on the market that vary in their potency. The potency of earlier corticosteroids has been enhanced by chemical modification including halogenation, acetylation, and methylation. The penetration of corticosteroids can be enhanced by using occlusive dressings or changing the base they are formulated in. Potent and very potent steroids are more useful than mild-to-moderate steroids in psoriasis.30

Long-term effects include skin atrophy, telangiectasia, striae disease, purpura, iatrogenic Cushing's syndrome, and hypothalamic-pituitary-adrenal (HPA) axis suppression. Since most studies are not conducted for long periods of time, the effects of tachyphylaxis are not well documented.30 Regimens to minimize the long-term effects are yet to be recognized.

Shampoos and foams containing clobetasol propionate have shown improvement in 2 weeks in scalp psoriasis.9 Potent topical corticosteroids may be useful in subungual hyperkeratosis, especially in combination with salicylic acid, as well as in pitting and surface ridging. However, longterm use may result in skin and even phalanx atrophy.10

Intralesional corticosteroids, particularly triamcinolone, are administered via a 28-gauge needle and syringe or a 29-gauge insulin syringe.10 These agents are particularly useful in pitting, ridging, nail thickening, and subungual hyperkeratosis. In addition to pain, patients may experience periungual hypopigmentation, subungual hemorrhage, and reversible atrophy.10

Vitamin D Analogues: These analogues (i.e., calcitriol, calcipotriene, tacalcitol) affect cellular differentiation and proliferation.30,34 Additionally, they regulate apoptosis and demonstrate an immunomodulatory effect.34 All vitamin D analogues allow a reduction in the duration and potency of other treatments.30,34 They are odorless and nonstaining and therefore cosmetically more acceptable than anthralin.

Calcitriol is an active metabolite of vitamin D3, while used twice daily. In addition to the side effects associated tacalcitol and calcipotriene are synthetic derivatives.30 All three cause hypercalcemia but are safe if used according to their respective dosage regimens. A model vitamin D analogue that has minor calcemic activity is yet to be developed.30,33 Other side effects include pruritus, burning, edema, peeling, dryness, and erythema, which diminish with ongoing treatment.30

Calcipotriene (also known as calcipotriol internationally) is slightly more effective than calcitriol and tacalcitol and is as effective as potent (but not ultrapotent) topical corticosteroids.30 A combination of calcipotriene with betamethasone reduces the long-term side effects of each ingredient by 1 year.30 Furthermore, since the combination has a low systemic absorption, the localized anti-inflammatory and immunoregulatory effect is higher than that of either of the individual drugs used separately.35 The combination is also available as a topical solution that is useful in the management of scalp psoriasis, delivering better efficacy and less irritation.9 In nail psoriasis, an application of calcipotriene may be used on its own or in combination with corticosteroids, particularly to manage subungual hyperkeratosis.10

The concentration of calcipotriene used is 0.005%, and it should not be applied more than twice daily. The limit per week is 100 g of cream or ointment or 60 mL of scalp solution in adults.33 If both cream and scalp solution are used, the limit per week is either 60 g of cream and 30 mL of solution or 30 g of cream and 60 mL of solution. In children, the maximum dose is 50 g for those aged 6 to 12 years and 75 g for children above 12 years.33

About 10% of patients using calcipotriene may notice a mild dermatitis on the face as a side effect.34 Calcipotriene also has a limited effect on calcium homeostasis as compared to calcitriol and tacalcitol.30 Calcitriol is better tolerated than calcipotriene in the treatment of easily irritated areas such as the face, hairline, and flexural areas.30

Compliance is better with tacalcitol since it only needs to be used once daily as opposed to the others, which are used twice daily.30 In addition to the side effects associated with calcitriol, it can also cause paresthesias.33 Tacalcitol is not available in the U.S.

Tazarotene: This is a topical vitamin A derivative that is modified to tazarotenic acid through de-esterification in the skin.30 It appears to exert its beneficial effects in acne by modulating cell proliferation and differentiation. Tazarotene can only be used once daily and therefore has limited use in monotherapy. It is less potent than vitamin D analogues and moderate or potent local corticosteroids. Tazarotene is used in patients in whom over 20% of the BSA is affected. The starting dose is a 0.05% cream or gel that can be increased to 0.1% as needed. It is normally used for 12 weeks at a time.30

The use of tazarotene for psoriasis may exacerbate acne.33 Since tazarotene is teratogenic, it should not be used by individuals who are pregnant or planning a pregnancy.30,33

Anthralin: This drug has been used in the treatment of psoriasis for over 80 years, but due to its staining properties, it is not a cosmetically acceptable agent.30 It demonstrates lower efficacy than topical corticosteroids and vitamin D derivatives as monotherapy. It is thought to exert its effects through its action on mitochondria.30 Currently, anthralin is used for the management of subacute and chronic psoriasis in two ways—conventional and short-contact treatment.

Conventional treatment is initiated with 0.1% anthralin ointment or paste that is applied sparingly to the lesions only for a few hours and then washed off. If irritation occurs, the strength and contact time must be reduced. The strength is gradually increased to 0.5% and even up to 1%, and the contact period is extended to overnight.33Short-contact treatment involves applying anthralin to the lesion in strengths of 0.1% to 2% for up to 60 minutes daily and then washing it off.33

Treatment should be continued until the psoriasis clears.33 Since anthralin causes skin irritation and staining of the skin, clothing, and furniture, it is best used in day centers or hospitals.30 In many cases it is combined with coal tar to reduce irritation. Furthermore, it can be combined with phototherapy for better results.33

Anthralin ointment applied on nails and washed off after 30 minutes is useful in onycholysis and subungual hyperkeratosis. However, this treatment results in temporary staining of the nail and local irritation.10

Use of anthralin should be avoided on the face, skin flexures, and genitals; hands should be washed thoroughly after use. Anthralin should not be used in acute or pustular psoriasis or applied onto inflamed skin.33 It is useful to inform patients that staining slowly disappears upon discontinuation of treatment.

Coal Tar: Coal tar reduces the thickness of the epidermis and has a slightly antipruritic and antiseptic effect.33 It is particularly useful in the management of stable chronic plaque psoriasis. Coal tar is a mixture of thousands of compounds and is available as solutions, ointments, and crude coal tar as well as shampoos that can be used for scalp psoriasis.9,30 The crude form is less acceptable cosmetically, but is more effective than the purified preparations.30

Coal tar therapy is initiated with concentrations of 0.5% to 1% of crude coal tar and increased every few days up to no more than 10%. Phototherapy can be used to enhance the effect of coal tar therapy, with the coal tar being applied about 2 hours before the light therapy. The Ingram regimen includes the application of anthralin following coal tar and light therapy.33

Coal tar causes skin irritation, folliculitis, odor, and staining of clothing and can be quite messy to use.30 Coal tar has a carcinogenic potential, and gloves should be worn by anyone handling it, including individuals making coal tar extemporaneous preparations.33

Systemic Therapies

Methotrexate: This folic acid antagonist interferes with purine synthesis, thereby inhibiting DNA synthesis and cell replication.30 In psoriatic lesions it decreases RNA and DNA synthesis in activated T lymphocytes and keratinocytes and reduces the production of several cytokines with messenger proteins.5,36

The drug is administered as a single weekly dose or as three divided doses given every 12 hours over 36 hours once a week, starting at 7.5 mg and adjusting upward at 4-week intervals to a maximum of 25 mg per week.5 During methotrexate therapy, 1 mg folic acid is given in three doses over 36 hours starting 12 hours after the last methotrexate dose. This reduces the incidence of adverse gastrointestinal (GI), hematologic, and hepatotoxic effects such as stomatitis and macrocytic anemia, without decreasing the efficacy of methotrexate.5,30 The toxicity of methotrexate can be increased by nonsteroidal anti-inflammatory drugs (NSAIDs) and sulfa drugs. Since it can be teratogenic, pregnancy should be avoided for 3 months after discontinuing treatment.30 This also applies to men whose partners may conceive.30

Methotrexate can also cause pulmonary fibrosis and liver cirrhosis.30 It is recommended that a liver biopsy be carried out after every cumulative dose of 1.5 g. Patients should be monitored every 1 to 3 months for bone marrow suppression.30

Cyclosporine: This macrocyclic immunosuppressant binds immunophilin and inhibits the calcineurin phosphatase initiated translocation of activated T lymphocytes.5,30 It is useful in the treatment of moderate-to-severe psoriasis for the short term.30 The usual dosage is 3 mg/kg/day in 2 divided doses, which can be increased to 5 mg/kg/day for severe disease and reduced once a response is achieved.5 The duration of treatment should ideally be restricted to 12 weeks.30 Long-term treatment should be administered at doses of about 3 mg/kg/day to maintain remission.30

Cyclosporine is useful in treating pitting and onycholysis; however, a suitable vehicle for topical administration has not yet been found.10

The use of cyclosporine is associated with hypertension and nephrotoxicity requiring the addition of an antihypertensive or a calcium channel blocker or a reduction of the dosage.5 Additionally, there is an increased risk of nonmelanoma skin cancer, particularly in patients who have previously been treated with photochemotherapy (PUVA).30 Other side effects include hyperlipidemia, hypomagnesemia, hyperkalemia, hypertrichosis, gum hyperplasia, GI problems, and neurologic disturbances.30 Since cyclosporine is metabolized by CYP34A enzymes, it interacts with CYP34A inhibitors, including macrolides and grapefruit juice as well as CYP34A inducers.5

A combination of methotrexate and cyclosporine is particularly useful in psoriatic arthritis.30 Cyclosporine can also be combined with other agents such as mycophenolate mofetil, fumarates, sulfasalazine, and biological agents.30

Acitretin: This oral retinoid inhibits the induction of helper T lymphocytes by modulating gene expression through interleukin (IL)-6.5 It is particularly useful in the treatment of erythrodermic and pustular variants of psoriasis.30 Acitretin may also be useful in children, in patients with HIV infection, or in patients prone to cancers, since it does not have an immunosuppressive effect.30 Acitretin is administered in doses of 25 to 50 mg daily with maximal effect seen in 3 to 6 months.5 Since the effects of acitretin are delayed, patient compliance is poor.5

Acitretin is often used in combination with other treatments and phototherapy for better results and to reduce the number of phototherapy treatments required. Furthermore, combination therapy decreases the risk of cancer.30

Acitretin is teratogenic, and patients taking the drug should avoid pregnancy during treatment and for 3 years after discontinuing therapy.5,30 Other side effects include hyperlipidemia, osteoporosis, ligamentous calcifications, and skeletal abnormalities.30 Toxicity results in mucocutaneous side effects including cheilitis, skin dryness, conjunctivitis, and hair loss.30 Retinoid hepatitis and pseudotumor cerebri are rarer but more severe side effects.30

Fluorouracil: This antimetabolite is useful in treating pitting of the nails and subungual hyperkeratosis at the expense of worsening onycholysis.10 The recommended dosage of fluorouracil is 1% to 2% cream applied twice daily to the nails. Fluorouracil causes yellowing of the nails.37

Oral Vitamin D: While much attention has been paid to topical vitamin D analogues, some authors believe that oral vitamin D may be a useful agent in the management of psoriasis. Close monitoring and appropriate dosing may overcome its hypercalcemic side effects. Presently, oral vitamin D is not being used for psoriasis therapy.38

The National Psoriasis Foundation recommends that if the psoriasis covers more than 5% of the BSA, phototherapy and systemic biological agents should be initiated.5

Phototherapy: Ultraviolet (UV) light therapy induces T-lymphocyte apoptosis in psoriatic lesions of the dermis and epidermis, causing decreased keratinocyte proliferation.5,29 Patients who have moderate-to-severe disease or localized lesions are ideal candidates for UV therapy.29 Narrow band UVB (NBUVB) is used in younger patients with thin lesions and in those who respond positively to sunlight.5

Patients should be screened for photosensitizing medications, skin cancer risk factors and immunosuppression before being selected for phototherapy.29 Phototherapy is difficult to deliver in scalp psoriasis due to the high density of hair follicles as well as the difficulty in avoiding nonaffected areas.9

Photochemotherapy (PUVA): This combination of psoralens and phototherapy is useful for thicker lesions or lesions that do not respond to NBUVB.5 Myeloid dendritic cells that induce autoproliferation of T cells as well as production of type 1 helper T cell cytokines are increased in psoriatic lesions.6 Psoralens and light therapy exert their effects by reducing the number of dendritic cells. The psoralen is ingested prior to the UVA therapy.

Photochemotherapy has also found a place in the management of subungual hyperkeratosis, onycholysis, discoloration, and nail crumbing in nail psoriasis.10

Phototherapy is inconvenient since it can only be carried out at specialized sites. Furthermore, photochemotherapy is associated with a risk of developing skin cancer, and therefore patients need to be monitored regularly for their entire life.5 Particular care needs to be taken in pale-skinned patients. Photochemotherapy is associated with an immediate feeling of nausea and headache from psoralen as well as skin burning and photosensitivity.30 Some of these side effects can be reduced using the newer topical psoralens with UVA therapy.

Biological Agents
Systemic biological agents (biologics) have revolutionized psoriatic therapy. An appreciation of the immune pathways fundamental in psoriasis has highlighted the fact that T cells play an important role in this process.30 Biologics are recombinant molecules that target the action of T cells at different points.30,38 Fusion proteins, recombinant proteins, and monoclonal antibodies all fall under the category of biologics.30 These therapies are highly effective for moderateto-severe psoriasis but prove costly for most patients.30 Their specific usefulness in nail psoriasis has not yet been established.10

Three different groups of biologics are currently being used in psoriatic therapy: anticytokine therapies, T-cell– targeted therapies, and monoclonal antibodies.

Anticytokine Therapies (anti-TNFs): These agents target the proinflammatory cytokine, tumor necrosis factor (TNF)-alpha, which is released by the differentiated T cells.3

Infliximab is a murine/human immunoglobulin (Ig) G chimera that targets soluble and membrane-bound TNF-alpha and neutralizes its activity.5,30 It is given by IV infusion over 2 hours at a dosage of 3 or 5 mg/kg during weeks 0, 2, and 6, and then every 8 weeks.5 As the patient's body develops antibodies towards infliximab, a loss of activity is noted over time.30 Common side effects include nausea, abdominal pain, back pain, arthralgia, fatigue, and headaches. Patients may also experience infusion reactions and serum sickness.5 It is also important to screen patients for latent tuberculosis at baseline.39

Adalimumab is a fully human monoclonal IgG antibody that targets soluble and membrane-bound TNF-alpha.5 It is self-administered as a subcutaneous injection starting at a dose of 80 mg at week 0, then 40 mg every 2 weeks starting at week 25.5,30 Its efficacy improves through weeks 24 to 36.5 Patients may experience injection site reactions, and laboratory tests may show a positive antinuclear antibody (ANA).4 Adalimumab can be used concurrently with corticosteroids, salicylates, and NSAIDs.4

Etanercept is a soluble human recombinant dimeric fusion protein that links the p75 TNF receptor to the Fc portion of the IgG1.5 It is also self-administered subcutaneously at a dose of 50 mg twice weekly for 3 months, then 50 mg weekly.5 The peak effect of etanercept is seen at 24 to 48 weeks.5 Etanercept is unique in that it relieves fatigue and symptoms of depression in patients with moderate-tosevere psoriasis and reduces the signs and symptoms of joint disease in patients with psoriatic arthritis.30

T-cell–Targeted Therapies: These agents (alefacept, efalizumab) modulate the action of T cells and can be used in combination with methotrexate.3,4

Alefacept is a humanized recombinant fusion protein containing a leukocyte function-associated antigen fused to human IgG1 that binds on CD2+ on CD8+ memory effector T cells.5 It is the first biologic approved for the treatment of psoriasis, indicated for the management of moderate-to-severe plaque psoriasis in adults.4,30 It can be used concurrently in patients who are undergoing phototherapy.4 The recommended dosage is 15 mg injected IM once weekly for 12 weeks followed by a 12-week treatmentfree period. As the psoriasis improves, the number of memory effector CD4 T cells drops in the peripheral blood.30

The CD4+ cell count must be monitored every 2 weeks while the patient is on alefacept. If it falls below 250 cells/ µL the treatment should be suspended, and if it does not return to that level within 30 days, treatment should be discontinued.5 It is important that the patient's CD4+ cell count return to normal before the next 12-week treatment.

Chills are common following an injection.33 Patients may also complain of cough, dizziness, nausea, pharyngitis, myalgias, injection site reactions, and transaminitis.4 More serious side effects include lymphopenia, malignancies, serious infections, hypersensitivity, elevations of transaminase enzymes, and cardiovascular events.4 Alefacept should be used with caution in patients with a history of malignancy.4

Efalizumab is a humanized monoclonal IgG1 antibody that binds to the CD11a subunit of leukocyte function associated antigen-1.5 It was withdrawn from the market in 2009 by the manufacturer after four patients developed progressive multifocal leukoencephalopathy.5

Monoclonal Antibody Against IL-22 and IL-23: Ustekinumab is currently the only agent in this group. It is a fully human monoclonal IgG1 antibody generated in human immunoglobulin in transgenic mice.5 It is administered subcutaneously at a dosage of 45 mg at weeks 0 and 4 and then repeated every 12 weeks.5

Since all biologics suppress the immune system, they come with black box warnings about the development of bacterial, fungal, and viral infections.5 Biologics should be discontinued during periods of infection or during treatment with an antibiotic. They are not, however, associated with other organ toxicities that are observed with traditional systemic therapies. Injection site reactions have been reported to varying extents.5

CONCLUSION

In short, an ideal treatment for psoriasis has not been found. The disease cannot be cured at present, and researchers continue to search for effective therapies. A summary of the treatments discussed is listed in TABLE 4. Pharmacists need to stay abreast of these changes to ensure that their patients are undergoing the most appropriate treatment for their condition and to ensure compliance through appropriate counseling.

REFERENCES

  1. Psoriasis. National Institute of Arthritis and Musculoskeletal and Skin Diseases. www.niams.nih.gov/Health_Info/Psoriasis/default.asp. Accessed October 13, 2011.
  2. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370:263-271.
  3. Sobell JM, Kalb RE, Weinberg JM. Management of moderate to severe plaque psoriasis (part 2): clinical update on T-cell modulators and investigational agents. J Drugs Dermatol. 2009;8:230-238.
  4. Thomas VD, Yang FC, Kvedar JC. Biologics in psoriasis: a quick reference guide. J Am Acad Dermatol. 2005;53:346-351.
  5. Herrier RN. Advances in the treatment of moderate-to-severe plaque psoriasis. Am J Health Syst Pharm. 2011;68:795-806.
  6. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361:496-509.
  7. Ayala F. Clinical presentation of psoriasis. Reumatismo. 2007;59(suppl 1):40-45.
  8. Martin BA, Chalmers RJ, Telfer NR. How great is the risk of further psoriasis following a single episode of acute guttate psoriasis? Arch Dermatol. 1996;132:717-718.
  9. Crowley J. Scalp psoriasis. J Drugs Dermatol. 2010;9:912-918.
  10. Edwards F, de Berker D. Nail psoriasis. Drugs. 2009;69:2351-2361.
  11. Finlay AY. Current severe psoriasis and the rule of tens. Br J Dermatol. 2005;152:861-867.
  12. Gelfand JM, Feldman SR, Stern RS, et al. Determinants of quality of life in patients with psoriasis. J Am Acad Dermatol. 2004;51:704-708.
  13. Eghlileb AM, Davies EE, Finlay AY. Psoriasis has a major secondary impact on the lives of family members and partners. Br J Dermatol. 2007;156:1245-1250.
  14. Chen YJ, Wu CY, Chen TJ. The risk of cancer in patients with psoriasis. J Am Acad Dermatol. 2011;65:84-91.
  15. Yang YW, Keller JJ, Lin HC. Medical comorbidity associated with psoriasis in adults. Br J Dermatol. 2011;165:1037-1043.
  16. Henseler T, Christophers E. Disease concomitance on psoriasis. J Am Acad Dermatol. 1995;32:982-986.
  17. Sommer DM, Jenisch S, Suchan M, et al. Increased prevalence of the metabolic syndrome in patients with moderate to severe psoriasis. Arch Dermatol Res. 2006;298:321-328.
  18. Neimann AL, Shin DB, Wang X, et al. Prevalence of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol. 2006;55:829-835.
  19. Margolis DJ. Psoriasis and cardiovascular disease: an association or a reason to treat? Br J Dermatol. 2011;165:930.
  20. Warren RB. Psoriasis comorbidities: a worldwide problem? Br J Dermatol. 2011;165:929.
  21. Ghiasi M, Nouri M, Abbasi A, et al. Psoriasis and increased prevalence of hypertension and diabetes mellitus. Indian J Dermatol. 2011;56:533-536.
  22. Christophers E. Comorbidities in psoriasis. Clin Dermatol. 2007;25:529-534.
  23. Glenn CJ, Kobraei KB, Russo JJ. New-onset psoriasis associated with adalimumab: a report of two cases. Dermatol Online J. 2011;17:15.
  24. Iborra M, Beltrán B, Bastida G, et al. Infliximab and adalimumab-induced psoriasis in Crohn’s disease: a paradoxical side effect. J Crohns Colitis. 2011;5:157-161.
  25. Gelfand JM, Shin DB, Neimann AL, et al. The risk of lymphoma in patients with psoriasis. J Invest Dermatol. 2006;126:2194-2201.
  26. Lebwohl M. Psoriasis. Lancet. 2003;361:1197-1204.
  27. Monteleone G, Pallone F, MacDonald TT, et al. Psoriasis: from pathogenesis to novel therapeutic approaches. Clin Sci (Lond). 2011;120:1-11.
  28. De Rosa G, Mignogna C. The histopathology of psoriasis. Reumatismo. 2007;59(suppl 1):46-48.
  29. Patel RV, Lebwohl M. In the clinic. Psoriasis. Ann Intern Med. 2011;155:ITC2-1−ICT2-16.
  30. Menter A, Griffiths CE. Current and future management of psoriasis. Lancet. 2007;370:272-284.
  31. Fluhr JW, Cavallotti C, Berardesca E. Emollients, moisturizers and keratolytics. Clin Dermatol. 2008;26:380-386.
  32. Green L. Emollient therapy for dry and inflammatory skin conditions. Nurs Stand. 2011;26:39-46.
  33. Sweetman SC, ed. Martindale: The Complete Drug Reference. 34th ed. London, UK: Pharmaceutical Press; 2005 [electronic version].
  34. Trémezaygues L, Reichrath J. Vitamin D analogs in the treatment of psoriasis: where are we standing and where will we be going? Dermatoendocrinol. 2011;3:180-186.
  35. McCormack PL. Calcipotriol betamethasone dipropionate: a review of its use in the treatment of psoriasis vulgaris of the trunk, limbs and scalp. Drugs. 2011;71:709-730.
  36. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol. 2009;60:824-837.
  37. Fiallo P. Yellow nails as an adverse reaction to the topical use of 5-fluorouracil for the treatment of nail psoriasis. J Dermatolog Treat. 2009;20:299-301.
  38. Kamangar F, Koo J, Max Heller M, et al. Oral vitamin D, still a viable treatment option for psoriasis. J Dermatolog Treat. 2012;Jan 21 [Epub ahead of print].
  39. Sobell JM, Kalb RE, Weinberg JM. Management of moderate to severe plaque psoriasis (part I): clinical update on antitumor necrosis factor agents. J Drugs Dermatol. 2009;8:147-154.

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