Rebecca M.T. Law
LEARNING OBJECTIVES
Upon completion of this chapter, the reader will be able to:
1. Discuss the etiology of psoriasis including genetic and immune changes.
2. Describe the pathophysiology of psoriasis including the types of psoriasis and clinical presentations.
3. Describe the comorbidities and risks in patients with psoriasis.
4. Compare and contrast the treatment modalities for psoriasis, that is, topical therapies, systemic therapies including biologics, and phototherapies.
5. Recommend an appropriate treatment plan for a patient with psoriasis.
6. Recommend appropriate monitoring parameters for a patient with psoriasis.
7. Provide appropriate counseling information to a patient with psoriasis.
KEY CONCEPTS
Patients with psoriasis have a lifelong illness that may be very visible and emotionally distressing. There is a strong need for empathy and a caring attitude in interactions with these patients.
Psoriasis is a T-lymphocyte–mediated inflammatory disease that results from a complex interplay between multiple genetic factors and environmental influences. Genetic predisposition coupled with some precipitating factor triggers an abnormal immune response, resulting in the initial psoriatic skin lesions. Keratinocyte proliferation is central to the clinical presentation of psoriasis.
Diagnosis of psoriasis is usually based on recognition of the characteristic plaque lesion, and not based on lab tests.
Treatment goals for patients with psoriasis are to minimize signs such as plaques and scales, alleviate symptoms such as pruritus, reduce the frequency of flare-ups, and ensure appropriate treatment of associated conditions such as psoriatic arthritis or clinical depression, and minimize treatment-related morbidity.
Management of patients with psoriasis generally involves both nonpharmacologic and pharmacologic therapies.
Nonpharmacologic alternatives such as stress reduction and the liberal use of moisturizers may be extremely beneficial and should always be considered and initiated when appropriate.
Pharmacologic alternatives for psoriasis include topical agents, phototherapy, and systemic agents including the use of biologic response modifiers (BRMs).
In initiating pharmacologic treatment, the choice of therapy is generally guided by the severity of disease: topical agents would be appropriate for mild to moderate disease while a systemic agent would be a more appropriate choice for moderate to severe disease. Phototherapy or photochemotherapy are used for patients with moderate to severe psoriasis, generally when topical therapies alone are inadequate. Patient-specific concerns such as existing comorbid conditions (e.g., renal impairment or hepatic disease) must also be taken into consideration in the choice of therapy. Once the disease is under control, it would be important to step down to the least potent, least toxic agent(s) that maintain control.
Rotational therapy (i.e., rotating systemic drug interventions in a sequential manner) is a means to minimize drug-associated toxicities, since systemic agents for psoriasis often have differing toxicities. This may be considered for psoriasis patients who require systemic treatments long-term to manage their condition.
Some BRMs have proven efficacy for psoriasis; however, there are differences among these agents, including mechanism of action, duration of remission, and adverse-effect profile. In general, due to their immunosuppressive effects, there is an increased risk of infection with most of these agents. The use of live or live-attenuated vaccines during therapy is generally not recommended. Currently, BRMs are often considered for patients with moderate to severe psoriasis when other systemic agents are inadequate or relatively contraindicated. It has also been recommended that BRMs be considered as first-line therapy, alongside conventional systemic agents, for patients with moderate to severe psoriasis; however, in practice, cost may be a limiting factor. They may be appropriate if comorbidities exist.
INTRODUCTION
Psoriasis is a disease that waxes and wanes. It is a chronic illness that is never cured; however, the signs and symptoms of psoriasis may subside totally (go into remission) and then return again (flare-up, exacerbation, or reactivation). Remission may last for years in some patients, while in others exacerbations may occur every few weeks. Triggers include stress, seasonal changes, and some drugs. Disease flare-ups may also occur at times of life crises. Disease severity may vary from mild to disabling. Thus, management of this condition is necessarily long-term, and management modalities may change according to the severity of illness at the time.
Patients with psoriasis have a lifelong illness that may be very visible and emotionally distressing. There is a strong need for empathy and a caring attitude in interactions with these patients.
EPIDEMIOLOGY AND ETIOLOGY
Psoriasis is a common inflammatory skin disorder which is estimated to affect 1.5% to 3% of the Caucasian population.1,2 It may present at any age.3,4 Ethnic factors influence disease prevalence. In the United States, prevalence among blacks (0.45% to 0.7%) is lower than in the remainder of the U.S. population (1.4% to 4.6%).1 Between 10% and 30% of patients with psoriasis will also have psoriatic arthritis.5 In 10% to 15% of psoriatic patients with arthritis, joint symptoms actually appear prior to skin involvement.3 Our understanding about comorbidities associated with psoriasis is growing. Associated conditions include well known psychiatric/psychological comorbidities such as depression, anxiety and poor self-esteem; as well as more recently found medical comorbidities, such as inflammatory bowel disease, diabetes, cardiovascular disease, and lymphoma.6 In 2008 the National Psoriasis Foundation published a clinical consensus on psoriasis comorbidities and recommendations for screening, addressing issues such as cardiovascular risk, metabolic syndrome, and obesity.7
Clinical depression may be present in up to 60% of patients with psoriasis.6 The depression may be severe enough that patients contemplate suicide; one study showed that 10% reported a wish to be dead and 5% reported active suicidal ideation. Other psychopathologies include poor self-esteem, anxiety and sexual dysfunction. The emotional and psychological impact of psoriasis may not be reflected by the severity of the psoriatic skin condition, and it is important to ensure that the psychosocial aspects of the disease is always considered for the patient.6
The incidence of inflammatory bowel diseases, such as Crohn’s and ulcerative colitis, may be 3.8 to 7.5 times higher in psoriatic patients than in the general population.6 This has been attributed to shared or closely linked genetic susceptibility traits, with individual susceptibility localized to a similar region of chromosome 16, among others.6 There may also be a link to multiple sclerosis.6
Recent research has shown that psoriatic patients have an increased risk of cardiovascular diseases.7, 8 There is a higher than normal incidence of myocardial infarction. The risk is increased in patients with both mild and severe psoriasis, with the highest risk in younger patients with severe disease.8 These findings persist even when corrected for the cardiovascular risk factors of smoking, diabetes, obesity, hypertension, and hyperlipidemia.6,8 Psoriatic patients also have an increased incidence of diabetes, obesity, hypertension, and an atherogenic lipid profile.6–8 In a recent study in hospitalized patients, the metabolic syndrome is significantly more prevalent in patients with psoriasis than those without.6,7 Several large epidemiologic studies have shown an increased Body Mass Index (BMI) in psoriatic patients, with the relative risk of developing psoriasis highest in those with the highest BMIs.6
With regard to increased cancer risk, although there is ongoing controversy, some studies are showing an increased risk of lymphoma, with one study demonstrating a significantly increased risk of cutaneous T-cell lymphoma (relative risk of 10.75) or Hodgkin’s lymphoma (relative risk of 3.18) in patients with severe disease.6 Some psoriatic treatments with a known lymphoma risk may be confounding factors. Increased cancer risk may be limited to subpopulations: Caucasian with more than 250 PUVA (psoralens + UVA) treatments have a 14-fold greater risk of cutaneous squamous cell carcinoma than those with fewer treatments.6 However, the risk of melanoma and nonmelanoma skin cancer appears to be equivalent to the general population.6
Psoriasis is a T-lymphocyte–mediated inflammatory disease that results from a complex interplay between multiple genetic factors and environmental influences.1 Genetic predisposition coupled with some precipitating factor triggers an abnormal immune response, resulting in the initial psoriatic skin lesions. Other risk factors may exacerbate pre-existing psoriasis and cause disease flare-ups. Precipitating factors include skin trauma such as a horse-fly bite (known as the Koebner phenomenon),6 an environmental change such as cold weather, stress, a viral or streptococcal infection, or use of a β-adrenergic blocker.2 Factors exacerbating psoriasis include drugs (e.g., lithium, nonsteroidal anti-inflammatory drugs, antimalarials, β-adrenergic blockers, and withdrawal of corticosteroids), and psoriatic patients commonly have exacerbations during times of stress.2
There is a polygenic inheritance pattern which may account for disease susceptibility and expression.9 Family linkage studies have identified several genetic loci that are potentially responsible: the PSOR1gene on chromosome 6p21.3, the PSOR2 gene on chromosome 17q25, the PSOR3 gene on chromosome 4q34, the PSOR4 gene on chromosome 1q21, the PSOR5 gene on chromosome 3q21, the PSOR6 gene on chromosome 19p13, the PSOR7 gene on chromosome 1p, the PSOR8 gene on chromosome 16q12–13 (which links to both psoriasis and Crohn’s disease), and the PSOR9 gene on chromosome 4q31.1,4,6,8There are possibly other genetic loci. PSOR1 (the HLA-Cw6 allele)6has been considered the major gene locus for psoriasis;1,4,6 it appears to be associated with up to 50% of cases of psoriasis.1
Studies conducted in twins show a threefold increased risk of psoriasis in monozygotic twins versus fraternal twins.9 In addition, based on a study in 3,095 families with psoriasis, the calculated lifetime risk of developing psoriasis if no parent, one parent, or both parents have psoriasis was found to be 0.04, 0.28, and 0.65, respectively. If there was already one affected child in the family, the risks were increased to 0.24, 0.51, and 0.83, respectively.9As many as 71% of patients with psoriasis during childhood have some positive family history.1 Similarly, psoriatic arthritis is heritable, with a prevalence 19 times higher in first-degree relatives of patients with psoriatic arthritis than in the general population.9
PATHOPHYSIOLOGY
Keratinocyte proliferation is central to the clinical presentation of psoriasis.Keratinocytes are skin cells producing keratin which act as a skin barrier. Increased keratinocyte cell turnover (hyperkeratosis) results in the characteristic thick scaly skin lesions seen in patients with psoriasis.10 Hyperkeratosis results from immune derangements. The abnormal immune response seen in psoriasis is mediated primarily by T lymphocytes (T cells).1 In patients with psoriasis, certain types of T cells are overactive and migrate to the skin in large numbers. T cells access the skin by binding to activated endothelial cells via intracellular cell adhesion molecules (ICAM-1).1,11 These naïve T cells then encounter antigens in the skin, which are presented to the T cells by antigen-presenting cells (APCs), and become activated. There is an LFA-3–CD2 signal which plays an important part in T-cell activation: LFA-3 is the leukocyte function–associated antigen type 3 found on APCs; CD2 is a cell-surface glycoprotein expressed on T-cell subtypes.1 When LFA-3 interacts with CD2, there is an increased proliferation of T cells.12
Activated T cells begin releasing cytokines including interleukin-2 (IL-2), interferon-γ (IFN-γ), tumor necrosis factor- α (TNF-α), and others.4,12 Cytokine activity leads to a rapid proliferation and turnover of skin cells, triggering the inflammatory process and the development of psoriatic skin lesions.4,12,13 TNF- α may have a role in disease severity; it upregulates endothelial and keratinocyte expression of ICAM-1, activates T cells, enhances T-cell infiltration, and augments keratinocyte proliferation.11
Treatment of psoriasis is based on an understanding of the underlying pathophysiology. Agents that modulate the abnormal immune response, such as corticosteroids and biologic response modifiers (BRMs), are important treatment strategies for psoriasis. In addition, topical therapies that affect cell turnover are effective for psoriasis. Clinically, a treatment regimen should always be individualized, taking into consideration severity of disease, patient responses, and tolerability of various interventions.
CLINICAL PRESENTATION
Diagnosis of psoriasis is usually based on recognition of the characteristic plaque lesion, and not based on lab tests.
Patient Encounter, Part 1
A 25-year-old Caucasian man presents with itchy lesions on his scalp, chest, back, elbows, and knees. He says these lesions started about a month ago, and seem to be spreading. Upon examination, the lesions are well demarcated and are reddish-violet in color—easily distinguished from normal skin. They appeared raised and are covered with loose scales. Scales are silvery in color. Removing the scales caused pinpoints of bleeding to show up. There are signs of excoriation on the patient’s chest.
What information is consistent with psoriasis in this patient?
Clinical Presentation and Diagnosis of Plaque Psoriasis
General
• Patients have small discrete to generalized confluent lesions over the entire body.
Symptoms
• Patients may complain of severe itching.
Signs
• Lesions are raised and are red to violet in color (commonly known as plaques).
• Lesions have sharply demarcated borders except where confluent.
• Lesions are loosely covered with silvery-white scales, which if lifted off, show small pinpoints of bleeding (Auspitz’s sign).
• Plaques appear most commonly on the elbows, knees, scalp, umbilicus, and lumbar areas, and often extend to involve the trunk, arms, legs, face, ears, palms, soles, and nails.
• Nail involvement presents as pitting, discoloration (“oil spots”), crumbling, splinter hemorrhages, growth arrest lines, or tissue build-up around the nails.
Clinical Presentation and Diagnosis of Other Types of Psoriasis
Inverse psoriasis spares the areas commonly involved in plaque psoriasis and instead appears in intertriginous areas, where scaling is minimal.
Guttate psoriasis presents as a sudden eruption of small, disseminated erythematosquamous papules and plaques, and is often preceded by a streptococcal infection 2 to 3 weeks prior.
Pustular psoriasis may be localized or generalized and may be an acute emergency requiring systemic therapy.
Generalized pustular psoriasis is characterized by disseminated deep-red erythematous areas and pustules, which may merge to become “lakes of pus.”
Erythrodermic psoriasis is a generalized, life-threatening condition that presents with erythema, desquamation, and edema, and may require life support measures as well as systemic therapy.
Psoriatic diaper rash is the most common type of psoriasis in children under 2 years old. This usually affects inguinal folds and greater than 90% of psoriatic diaper rash cases may have involvement outside the diaper area.
Patient Encounter, Part 2
Additional relevant information was obtained from the patient, including the following history.
FH: His father and one of his brothers have psoriasis; his only sister has atopic dermatitis
SH: He works as an assistant copywriter in a busy publishing house, and is constantly struggling with multiple deadlines; he is an occasional social drinker and nonsmoker; he is a single father to a 6-year-old boy with asthma
PE:
He appears anxious and embarrassed about the lesions
VS: BP 125/70 mm Hg, P 72 bpm, RR 16/min, T 37°C (98.6°F)
Abd: Soft, nontender; bowel sounds present
Exts: Within normal limits; no joint pains
Skin: Multiple lesions on the scalp, chest, back, elbows, and knees; evidence of excoriation on the chest.
What risk factors does he have for psoriasis?
Identify your treatment goals for the patient.
TREATMENT
Desired Outcomes and Goals
Since psoriasis is a chronic illness with no known cure, the goals of treatment focus on controlling the signs and symptoms of disease, including:
• Minimizing or eliminating the signs of psoriasis such as plaques and scales.
• Alleviating pruritus and minimizing excoriations.
• Reducing the frequency of flare-ups.
• Ensuring appropriate treatment of associated conditions such as psoriatic arthritis, clinical depression, or itching.
• Avoiding or minimizing adverse effects from topical or systemic treatments used.
• Providing cost-effective therapy.
• Providing guidance or counseling as needed (e.g., stress-reduction techniques).
• Maintaining or improving the patient’s quality of life.
General Approach to Treatment
Management of patients with psoriasis generally involves both nonpharmacologic and pharmacologic therapies. Pharmacologic alternatives for plaque psoriasis include topical treatments, phototherapy, photochemotherapy, and systemic therapies alone (orally or by injection). The choice of treatment is usually dictated by the severity of disease.14,15 In some cases, a combination of treatment options may be preferred. Topical therapies can be used in patients with limited or mild to moderately severe disease. Phototherapy and photochemotherapy are used in moderate to severe disease. Systemic therapies are used for patients with extensive or moderate to severe disease. To minimize drug toxicities in these patients, systemic therapies are often used in rotation, or used in conjunction with topical or phototherapy.14,15BRMs are becoming incorporated into the same category as other systemic agents and are currently recommended for consideration as first-line therapies alongside conventional systemic agents for moderate to severe disease.15 However, since there is a significant cost difference, biologic agents are often reserved for cases in which traditional systemic agents provide inadequate control or for patients with comorbidities (e.g., where traditional systemic agents may be inappropriate due to potential adverse effects). There are four recently published treatment guidelines including a 2008 guidelines of care for the management of psoriasis and psoriatic arthritis6 and a 2003 general consensus on psoriasis treatments,14 both by the American Academy of Dermatology, a 2009 Canadian Guidelines for the Management of Plaque Psoriasis endorsed by the Canadian Dermatology Association at www.dermatology.ca/psoriasisguidelines.html and a consensus on moderate to severe psoriasis by the Canadian Psoriasis Expert Panel.15 In addition, it would be important to ensure appropriate screening and treatment of any comorbid illnesses such as depression or diabetes,7 and to ensure appropriate management of symptoms such as itching.
Efficacy Assessment
Although there are tools to evaluate the efficacy of a psoriasis treatment, these are used primarily in clinical trials and rarely in clinical practice. These include the Psoriasis Area and Severity Index (PASI), the Physician’s Global Assessment (PGA), and the National Psoriasis Foundation—Psoriasis Score (NPF-PS). The PASI is the most well known and measures the overall extent and severity of psoriasis, assessing areas of coverage, erythema, induration, and scaling. Clinical efficacy will be reported as a decrease in the PASI score, or an improvement (e.g., 75% improvement or PASI-75).6
In clinical practice, subjective qualitative assessments of disease severity is generally used to determine the efficacy of a treatment. In addition, an assessment of the patient’s quality of life (QOL) is important in the management of psoriasis. The impact of psoriasis on a patient’s psychological well-being may differ substantially from the severity of disease. Various QOL instruments validated for dermatologic diseases include the Dermatology Quality of Life Scales, Dermatology Life Quality Index (DLQI), Dermatology Specific Quality of Life Instrument, and Skindex-29.
Nonpharmacologic Treatment
Nonpharmacologic alternatives may be extremely beneficial in the patient with psoriasis and complement pharmacologic therapies; thus should always be considered and initiated when appropriate.These include the following management strategies:10
• Stress reduction techniques. Psychotherapy including stress management, guided imagery, and relaxation techniques are being used more frequently as adjunctive therapies for patients with psoriasis. Stress reduction has been shown to improve both the extent and severity of psoriasis.
• Oatmeal baths. Regular use of oatmeal baths in tepid water may help soothe the itching associated with psoriasis and reduce the need for systemic antipruritic agents.
• Nonmedicated moisturizers. Maintaining adequate skin moisture helps to control the scaling associated with psoriasis. Emollients restore skin pliability, reduce skin shedding, reduce pruritus, and help prevent painful cracking and bleeding.2 Nonmedicated moisturizers may be liberally applied several times daily to help prevent skin dryness. Fragrance-free products should be selected when available.
• Avoid irritant chemicals on the skin. Harsh soaps or detergents should not be used. Cleansing should be done with tepid water, preferably using lipid-free and fragrance-free cleansers.
• Avoid skin trauma. Sunburns can induce a flare-up of psoriasis. Sunscreens with a sun protection factor of at least 15 should be routinely used when outdoors; often a sun protection factor of 30 is recommended. Avoid scratching the skin, which could lead to excoriations and exacerbate psoriasis. Loose-fitting cotton garments should be worn to minimize skin irritation.
Patient Encounter, Part 3
The diagnosis is that the patient has new-onset mild to moderate plaque psoriasis.
What are the drug-related problems in this patient?
What nonpharmacologic alternatives are appropriate for this patient?
What pharmacologic treatments would be appropriate as initial therapy for this patient?
FIGURE 64–1. Treatment algorithm for mild to moderate psoriasis.
FIGURE 64–2. Treatment algorithm for moderate to severe psoriasis.
Pharmacologic Treatment
Pharmacologic alternatives for psoriasis include topical agents, phototherapy, and systemic agents including the use of BRMs. See Figures 64–1 and 64–2 for treatment algorithms.
Topical Therapy for Psoriasis Topical therapy is the initial drug treatment strategy for patients with mild to moderate psoriasis. It is estimated that approximately 70% to 80% of all patients with psoriasis can be treated adequately with use of topical therapy.1 Topical therapies include corticos-teroids, coal tar products, anthralin, vitamin D3 analogues such as calcipotriol, retinoids such as tazarotene, and topical immunomodulators such as tacrolimus and pimecrolimus.16 Vitamin D3 analogues and topical retinoids all affect kera-tinocyte functions and the immune response. Currently, these are in wider use than is either anthralin or coal tar preparations.
Topical agents may be incorporated into various vehicles including ointments, creams, gels, lotions, foams, pastes, and shampoos. Ointments provide occlusion, which may increase drug penetration and enhance efficacy. Creams and lotions are easier to spread, especially in hairy areas. Gels may have drying and cooling effects in addition to easy spreadability. Foams may have enhanced delivery and/or efficacy in comparison to lotions or creams and become a cosmetically elegant liquid upon skin contact, with good patient acceptance.16 Shampoos incorporating tar distillates or salicylic acid are useful for scalp psoriasis. Pastes such as Lasar’s paste have an inherent stiffness, which minimizes the spread of medication and are useful for incorporating drugs, such as anthralin. Anthralin, especially in higher concentrations used in short-contact methods, may cause skin irritation and burning if in contact with normal skin. The selection of an appropriate vehicle is often an important consideration.
For mild to moderate psoriasis, mid-potency corticosteroids such as betamethasone valerate (0.05% to 1%) are most frequently selected first, with escalation to higher-potency corticosteroids, if needed, and stepping down to lower-potency corticosteroids when the psoriasis improves. High-potency corticosteroids may be used initially in thicker plaque areas such as palms and soles, but should be considered for short-term use only. These include fluocinonide, clobetasol, halobetasol, and betamethasone dipropionate in optimized base. Low-potency corticosteroids such as hydrocortisone (0.5% to 2%) are appropriate choices if treatment of the face or flexures is necessary. Topical corticosteroids are available as ointments, creams, lotions including scalp lotions, and a few foam products, and should be applied in a thin layer on the skin. Intralesional triamcinolone may be useful for specific lesions, such as nail matrix psoriasis. Tachyphylaxis, due to down-regulation of steroid receptors, can occur with prolonged use, making the treatment regimen ineffective.2,16 Using a potent corticosteroid for only 1 to 2 days per week (“weekend therapy”) has been shown to lengthen the duration of effectiveness.16 Combining this regimen with calcipotriol used during the week may provide greater efficacy.16
It is important to remember that adverse effects of topical corticosteroids may be systemic in nature and hypothalamic–pituitary–adrenal axis suppression can occur, especially when high-potency corticosteroids are used. Infants and small children may be more susceptible due to their increased skin surface:body mass ratio.16 Topical corticosteroids may also cause striae, skin atrophy, acne, telangiectasias, and rosacea.2,10,16 Atrophy can result in thin, fragile, easily lacerated skin. Striae are caused by tearing of dermal connective tissue and are irreversible.16 Due to their significant adverse-effect profile, it has been recommended that no topical corticosteroid be used regularly for more than 4 weeks without review and reassessment.2
Vitamin D analogues (calcipotriol, calcitriol, and tacalcitol) are also frequently selected as initial pharmacotherapy in the management of mild to moderate psoriasis.2 These inhibit keratinocyte differentiation and proliferation and may be anti-inflammatory.2 Unlike corticosteroids, tachyphylaxis does not occur with prolonged use. Clearance of lesions should occur after 4 to 6 weeks of treatment.2 Lack of response by 8 weeks indicates treatment failure.2These analogues may cause skin irritation leading to erythema, dryness, stinging, or burning. They may also cause hypercalcemia secondary to excessive absorption or use.2,10,16 Calcipotriol (50 mcg/g) is currently available in the United States and Canada as ointment, cream, and solution. Topical calcitriol has been studied for treatment of psoriasis and appears almost as effective as betamethasone dipropionate in clearance of lesions, with a longer remission period.2 It is less irritating than calcipotriol and can be used for the face and flexures.2 Calcipotriol plus betamethasone is available as a combination product in Canada.10 In contrast, salicylic acid can completely inactivate calcipotriol on contact.16 Tacalcitol is a newer vitamin D3 analogue available in the UK.1
Keratolytic agents, such as salicylic acid, are often added to bath oil or shampoos (typically 3% to 4%) for scalp psoriasis.10 Salicylic acid can also be added to topical corticosteroid preparations to enhance steroid penetration (salicylic acid breaks down keratin).
Coal tar is keratolytic and may have antiproliferative and anti-inflammatory effects.2 Coal tar products include crude coal tar and tar distillates (liquor carbonis detergens) available as ointments, creams, and shampoos in various strengths. Preparations containing coal tar may precipitate folliculitis,10 will stain clothing, and have an unpleasant odor. They are also photosensitizing and can be combined with ultraviolet B (UVB) phototherapy (Goekermann’s regimen) to increase treatment response.17
Anthralin (dithranol) has a direct antiproliferative effect on epidermal keratinocytes2 and is generally used only on thick plaque areas. It can be used continuously or as short-contact anthralin therapy (SCAT): 1% to 4% applied for minutes to up to 2 hours.16 Anthralin, including SCAT with high anthralin concentrations, may be highly irritating, especially if SCAT treatments are misused or used continuously.10 It is important to remember when compounding anthralin preparations that prescribed concentrations can range from 0.1% (meant for continuous use) to 1% to 4% (meant for short-contact use).16 Normal skin surrounding the psoriasis plaques should be protected by using nonmedicated paste or zinc oxide. People who handle the dry anthralin powder should avoid skin contact (e.g., by wearing gloves while compounding).
Tazarotene is a topical retinoid used for mild to moderate psoriasis and is also effective for acne. It normalizes keratinocyte differentiation and has antiproliferative and anti-inflammatory effects.2 Tazarotene is available commercially as a 0.05% or 0.1% gel. It may cause significant skin irritation including erythema, pruritus, and burning, especially upon initial use.2,10,16 Combining tazarotene use with a topical corticosteroid in an alternate-day regimen or morning corticosteroid–evening tazarotene dosing fashion may minimize skin irritation and steroid-induced skin atrophy, and enhance efficacy.16 Avoid its use in women of child-bearing age unless effective contraception is being used; there is a potential risk of systemic drug absorption2 and systemic retinoids are known teratogens. Concomitant use of other topical preparations or cosmetics with a strong drying effect should be avoided when possible.10
Phototherapy for Psoriasis Phototherapy or photochemotherapy is used for patients with moderate to severe psoriasis, generally when topical therapies alone are inadequate. Photochemotherapy is the concurrent use of phototherapy together with topical agents16,18 or systemic drugs.1,18 Phototherapy of psoriasis involves the use of either ultraviolet A (UVA) or UVB. UVA is a longer wavelength, and therapy with UVA is always combined with psoralens (e.g., methoxsalen or trioxsalen), which are used as photosensitizers to increase efficacy. There may be an increased risk of skin cancers after prolonged use of phototherapy and risks are greater with PUVA than UVB.10,18In particular, long-term PUVA treatments in Caucasians is associated with an increased risk of squamous cell carcinoma and possibly malignant melanoma.6
There is a bath PUVA and an oral PUVA. Bath PUVA therapies involve soaking in a bath of psoralens liquid for 15 minutes prior to UVA treatment. Oral PUVA involves taking an oral psoralens capsule the day prior to a UVA treatment. Oral psoralens, such as methoxsalen, cause nausea in many patients.6 Other adverse effects of PUVA include photosensitivity, which necessitates the use of eye protection and UVA-blocking sunscreen for 24 hours after a PUVA treatment; macular melanosis at exposed sites (PUVA lentigines); and increased risk of skin cancers, especially squamous cell carcinoma.18
PUVA has been used in conjunction with other topical agents to increase treatment efficacy. Calcipotriol when added to a regimen of PUVA may reduce the number of PUVA treatments and the total UVA dosage needed for clearing lesions.16,19,20 The rate ratio for marked improvement in patients receiving PUVA plus calcipotriol versus PUVA alone was 1.2 in a recent meta-analysis of 11 controlled studies.21 If calcipotriol and PUVA are used together, calcipotriol must be applied after PUVA, since irradiation with UVA will inactivate calcipotriol.22 Use with other topical agents has been limited. One small study of PUVA with tazarotene in 12 patients with extensive plaque psoriasis showed a statistically significant improvement after 3 weeks;23 however, UVA doses should be reduced by at least one-third if tazarotene is added, since it increases the risk for immediate pigment darkening caused by UVA.24 Coal tars are photosensitizing16 and are not generally used with PUVA,18 and PUVA plus topical corticosteroids have yielded conflicting results.18
Patient Encounter, Part 4
The patient’s psoriatic condition remains well controlled with topical treatments for about 10 years, then flare-ups become a frequent occurrence. Phototherapy with NB-UVB was initiated. The patient did not respond well to NB-UVB therapy used alone. He is currently presenting with fairly extensive plaque psoriasis, affecting about two-thirds of his body surface area. There are signs of excoriation as well.
What are the drug-related problems in this patient?
What pharmacologic treatments would be appropriate for this patient now?
UVA can be used with other systemic agents including oral retinoids (RePUVA) and methotrexate. This will be discussed later in greater detail.
UVB treatments are often used alone and are effective and cost-effective.6 Narrowband UVB (NB-UVB) is moreeffective than broadband UVB and avoids some of the adverse effects of PUVA, but is slightly less effective than PUVA.6 UVB treatments have also been given in combination with topical or systemic agents to increase treatment efficacy. Topical regimens include UVB with tazarotene,18 UVB with crude coal tar (Goekermann’s regimen),17,18UVB with anthralin (Ingram’s regimen),18 and UVB with calcipotriol.18 UVB with tazarotene (a retinoid) may be synergistic; the effect of each agent seems to be enhanced when used together. However, all retinoids can cause skin thinning, which may allow for easier burning to occur. The erythema induction threshold is lowered by about 25%.18 Therefore, doses of UVB should be reduced by at least one-third when tazarotene is added.16,18 UVB with crude coal tar is a regimen developed early in the twentieth century that is still considered one of the most effective regimens available.18 However, many patients consider it messy and time-consuming. UVB with SCAT may not be consistently effective, and UVB with topical steroids may actually shorten the remission period.19,25
Several UVB and systemic therapy combinations have shown efficacy. These include UVB with acitretin (ReUVB) and UVB with methotrexate, and will be discussed later.
Systemic Therapy for Psoriasis Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.15,26 Oral agents include sulfasalazine, acitretin, methotrexate, cyclo-sporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the BRMs alefacept, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis.
Rotational therapy (i.e., rotating systemic drug interventions in a sequential manner) is a means to minimize drug-associated toxicities, since systemic agents for psoriasis often have differing toxicities. This may be considered for psoriasis patients who require systemic treatments long-term to manage their condition. Systemic therapies are optimally used in a rotating fashion to minimize drug toxicities (e.g., methotrexate–acitretin–cyclosporine or methotrexate–PUVA–acitretin).10 Sequential therapy (i.e., starting with systemic therapy followed by topical therapy) is another method that minimizes toxicities.
Sulfasalazine has variable efficacy and is of limited potency. However, its side-effect profile is better than other systemic therapies and it is sometimes tried as an initial systemic agent for moderate to severe psoriasis. Usual doses are 2 to 4 g/day in divided doses.10
Acitretin is an oral retinoid that is likely safer than methotrexate or cyclosporine, especially when considering continuous use over many years.18 It has the advantage of not being immunosuppressive.6 The initial dose is 25 mg/day which can be increased to a maximum of 75 mg/day if needed.15 When acitretin is used concurrently with phototherapy (ReUVB or RePUVA), there appears to be a synergistic treatment effect, and the number and duration of phototherapy sessions needed to achieve clearance is reduced.18 RePUVA is a well-established treatment regimen for psoriasis.1,6 When acitretin is used with calcipotriol, improvement and clearance of lesions may be achieved with significantly lower cumulative acitretin dosages.18,27 However, acitretin is teratogenic and relatively contraindicated in women of childbearing potential. It must not be used in pregnant women, those with unreliable contraception, or those who intend to become pregnant at any time during or for 3 years after discontinuation of therapy.6,10,26 Ethanol should be avoided during therapy and for 2 months after drug discontinuation, since it causes the transesterification of acitretin to etretinate, which has a much longer elimination half-life.10,26 Other side effects include ophthalmologic, neuromuscular, hyperlipidemic, and hepatic enzyme changes.10,26 Long-term continuous use has caused a syndrome of disseminated idiopathic skeletal hyperostosis and mild osteoporosis, found in a few case reports.18,28
Methotrexate used in low doses is one of the mainstays of systemic therapy in the treatment of psoriasis. An initial test dose of 2.5 to 5 mg (single dose once weekly) is recommended.15 If lab values are normal after 1 week, the dose can be increased to a range of 7.5 to 30 mg once weekly.15 This dosage can be given as a single dose or split into two or three doses given 12 hours apart to minimize GI side effects. Always titrate to the lowest effective dosage for maintenance. Methotrexate is contraindicated in pregnancy, individuals with renal impairment, hepatitis, cirrhosis, alcoholics, unreliable patients, and patients with leukemia or thrombocytopenia.6 There is a significant risk of hepatotoxicity which is greater than that seen in patients with rheumatoid arthritis given similar cumulative doses of methotrexate.26In psoriatic patients with no hepatic risk factors, a liver biopsy is suggested when the cumulative dose of methotrexate reaches 1.5 g.6 In high-risk psoriatic patients, it is preferable to also perform a biopsy during initial therapy with methotrexate.10,15,26,29 Monitoring PIIINP (the aminoterminal propeptide of type III procollagen) at least three times yearly may reduce the number of repeat liver biopsies required.10,26 Liver biopsies are not recommended in the elderly, those with limited life expectancy, or those with significant medical problems.26 Besides hepatoxicity, methotrexate, even in low doses used in psoriasis, may cause leukopenia, megaloblastic anemia, pneumonitis and pulmonary fibrosis. Periodic complete blood cell counts (CBCs), renal and liver function tests (LFTs), and pulmonary toxicity testing should also be conducted.10,26
The combination of methotrexate and UVB seems to be synergistic; responses may occur with lower cumulative doses of both methotrexate and UVB. However, stopping methotrexate may cause rebound18,30and there is some concern about photosensitivity.18 Methotrexate and PUVA have been used together in patients refractory to other treatments; however, there is additive carcinogenesis (especially increasing the risk of squamous cell cancer) and subacute phototoxicity.18
Methotrexate has been used successfully with cyclosporine, either concurrently31 or in rotation. Rotational therapy is particularly effective since it minimizes the serious adverse effects of both agents: hepatotoxicity from methotrexate and hypertension and nephrotoxicity from cyclosporine. Having an overlapping treatment period may not be necessary and patients have been successfully switched after a 1-week washout period.18,32 This is a very useful combination of systemic agents in the long-term management of this chronic disease.
Cyclosporine is used in low doses whether alone or in combination with other agents. The usual dose range is 2 to 2.5 mg/kg/day, given orally in two divided doses, for patients with stable generalized psoriasis or for moderate to severe disease. For patients with severe inflammatory flares of psoriasis, or recalcitrant cases who fail to respond to numerous other therapies, or for a highly distressed patient in a crisis situation, the starting dose is higher at 5 mg/kg/day in two divided doses.26 This dose should not be exceeded15 and, once there is a clear response, should be decreased by 0.5 to 1 mg/kg/day at weekly or longer periods, to the lowest effective maintenance dose. If started at 2.5 mg/kg/day, and the response is inadequate, it is recommended to wait at least 1 month before considering a dosage increase. If necessary, the dosage may be increased by 0.5 to 1 mg/kg per day9,25,32 monthly15 to a maximum of 5 mg/kg/day.15 Always titrate to the lowest effective dose for maintenance.15 Cyclosporine is contraindicated in psoriatic patients with abnormal renal function, uncontrolled hypertension, malignancy (except nonmelanoma skin cancer), uncontrolled infection, primary or secondary immunodeficiency excluding autoimmune disease.
Blood pressure and serum creatinine (SCr) should be assessed prior to beginning cyclosporine therapy to obtain accurate baselines, and should be reassessed biweekly once therapy is started for at least the first 12 weeks of therapy (until values stabilize), and then closely monitored during therapy (bimonthly for doses up to 2.5 mg/kg/day, and monthly for patients receiving higher doses). If SCr increases to 30% above the patient’s baseline, the cyclosporine dosage needs to be decreased and SCr rechecked in a month. If the SCr is still above 30% of the patient’s baseline, cyclosporine should be discontinued and only resumed when the SCr returns to within 10% of the patient’s baseline. Cyclosporine should also be discontinued for inadequate response after 3 months’ use at the maximum dose.10,33 Besides impaired renal function and hypertension, cyclosporine may increase the risk of lymphomas and cutaneous malignancies after long term treatment.6 Patients should have a careful physical exam for tumors prior to initiation of therapy.
The combination of cyclosporine with calcipotriol may be more efficacious than either agent used alone.18,34 Cyclosporine and SCAT may also be effective.18,35 However, cyclosporine should not be used concurrently with PUVA; there is a well-documented increased risk of squamous cell cancer and the combination may have a negative effect on lesion clearance.18 The combination of cyclosporine with metho trexate is extremely effective and minimizes toxicity from either agent as discussed. Cyclosporine has also been used successfully with mycophenolate mofetil35 and etanercept.26
Mycophenolate mofetil in doses of 1 to 1.5 g twice daily (maximum dose 3 g/day) is effective as adjunctive therapy in patients with resistant psoriasis on cyclosporine.26,35 As monotherapy, there may be some benefit in patients with moderate psoriasis and psoriatic arthritis, but not in severe psoriasis.26
Hydroxyurea is an older agent still used occasionally today for patients with psoriasis; however, there have been recent precautions about its use in the elderly and cutaneous vasculitic toxicities in patients with myeloproliferative disorders.26 Toxicity associated with tacrolimus has limited its use in psoriasis. Azathioprine has a slow onset and significant toxicity.26 Oral corticosteroids are reserved for severe or life-threatening conditions such as severe psoriatic arthritis or exfoliative psoriasis; prolonged oral steroid use should be avoided.10
Biologic Response Modifiers
Based on the recent advances in our understanding of the pathogenesis and pathophysiology of psoriasis, there was accompanying research into the development and use of BRMs for psoriasis and psoriatic arthritis. Some BRMs have proven efficacy for psoriasis; however, there are differences among these agents, including mechanism of action, duration of remission, and adverse-effect profile. Currently, BRMs are often considered for patients with moderate to severe psoriasis when other systemic agents are inadequate or relatively contraindicated. It has also been recommended that BRMs be considered as first-line therapy, alongside conventional systemic agents, for patients with moderate to severe psoriasis; 15 however, in practice, cost may be a limiting factor. They may be appropriate if comorbidities exist. BRMs with proven efficacy for psoriasis include alefacept, etanercept, adalimumab, and infliximab.6 These agents employ the following targeted immunosuppressive strategies: alefacept inhibits T-cell activation by targeting LFA-3–CD2 and inducing apoptosis in memory T cells;1 etanercept, adalimumab, and infliximab are all TNF- α inhibitors and efalizumab inhibits T-cell activation by targeting CD11a, the α subunit of LFA-1 (ICAM-1).1,6,10,36 Other biologic agents in clinical trials for psoriasis include HuMax-CD4, siplizumab, daclizumab, and denileukin diftitox.10,36 In general, due to their immunosuppressive effects, there is an increased risk of infection with most of these agents. In particular, efalizumab has recently been suspended from use in Canada and has been voluntarily withdrawn in the United States by the company (in consultation with the FDA) due to serious adverse CNS effects from viral causes. The use of live or live-attenuated vaccines during therapy is generally not recommended.
The most promising types of BRMs are monoclonal antibodies, cytokines, and fusion proteins.1 Monoclonal antibodies may be chimeric (fused mouse and human segments; designated “-ximab”), humanized with intermittent murine sequences (designated “-zumab”), human backbone with monkey sequences, or fully human.37
Alefacept is a recombinant dimeric fusion protein composed of the extracellular CD2-binding portion of lymphocyte function–associated antigen (LFA)-3 linked to the constant portion of human IgG.6,37,38Alefacept inhibits T-cell activation by binding to their CD2 sites, thus impairing costimulatory signals; and alefacept also interacts with natural killer cells to destroy already activated T cells.1,10 This agent is useful for moderate to severe chronic plaque psoriasis. About one-third of alefacept-treated patients enter prolonged remissions ranging from 6 to 18 months. Alefacept appears to spare helper T-cell function and does not significantly impair primary or secondary antibody responses (e.g., the ability to combat infections or respond to vaccinations). There is a significant risk of malignancy and common side effects include lymphopenia, myalgias and chills, pharyngitis, cough, nausea, and for IM injections pain and inflammation at the injection site.10,39 The dosage recommended is 15 mg IM once weekly for 12 weeks provided the CD4+ T-cell count is normal (defined as greater than or equal to 250 cells/mm3).10 Biweekly monitoring of CD4 counts is required during treatment.6 Dosing should be held for counts less than 250 cells/mm3 and discontinued if the CD4+ count remains below 250 cells/mm3 for four consecutive weeks.6 The maximum response to alefacept generally occurred 6 to 8 weeks after the last IM injection of the 12-week course.6,40 The regimen may be repeated in 12 weeks if needed and CD4 counts are normal.10 Patients who responded to alefacept may achieve additional benefit from successive 12-week treatment courses.6 Although predictive markers for which patients will respond are currently unknown, those who achieve a PASI-75 or greater tend to maintain a 50% of greater reduction in PASI for a median duration of 10 months.6 Alefacept is contraindicated in HIV+ve patients due to the potential for accelerating disease progression from CD4 count reduction.6
Etanercept is a fully human dimeric fusion protein composed of human TNF-α p75 receptor fused to the Fc portion of human IgG1.38 It acts as a TNF-α inhibitor by binding to and inactivating soluble and membrane-bound TNF-α, thus preventing interactions with its cell surface receptors.6,38 This agent is useful for chronic moderate to severe plaque psoriasis and for psoriatic arthritis. Dosing in psoriasis is different from its other indications (rheumatoid arthritis, juvenile rheumatoid arthritis, and ankylosing spondylitis).6 The approved regimen in psoriasis is 50 mg subcutaneously twice weekly for the first 12 weeks followed by 50 mg weekly thereafter, dosing being continuous.6 In clinical trials, 49% of patients given 50 mg subcutaneously twice weekly achieved a 75% improvement in PASI by 12 weeks.10,41Clinical responses continue to improve with longer treatment,6,41 but some patients will show a loss of response after 12 weeks when the dose is reduced to once weekly6 The drug appears to be well tolerated; common side effects include mild injection site reactions, headache, increased respiratory tract infections (colds and sinusitis), and GI symptoms.6,10,41 There is an increased risk of tuberculosis6 and hepatitis B reactivation. Serious infections including fatalities have been reported with etanercept and there were reports of worsening congestive heart failure (CHF) and new-onset CHF.10 Due to rare reports of blood disorders (anemia, aplastic anemia, leukopenia, neutropenia, pancytopenia, and thrombocytopenia), patients are advised to contact their doctor if they experience persistent fever, bruising, bleeding, or paleness.10 A systemic lupus erythematosus (SLE)-like syndrome without renal or CNS complications has been rarely reported.6 Monitoring includes a baseline tuberculin purified protein derivative (PPD) skin test, LFTs, and CBC. Yearly PPD and periodic CBC and LFTs are recommended while on treatment.6
Etanercept has been found to be effective in children and adolescents (aged 4-17) with plaque psoriasis. 57% of patients receiving etanercept 0.8 mg/kg once weekly (to a maximum of 50 mg) achieved PASI-75.6,42
Efalizumab provides an example of a drug where serious toxicity has been discovered in the postmarketing phase, leading to product withdrawal. Efalizumab is a recombinant humanized murine monoclonal IgG antibody directed against CD1 1a, the α subunit of leukocyte function-associated antigen type 1 (LFA-1). This inhibits T-cell activation, cutaneous T-cell trafficking, and T-cell adhesion to keratinocytes. Efalizumab is effective for patients with moderate to severe plaque psoriasis and is self-administered subcutaneously by the patient.6 It is not effective for psoriatic arthritis; and psoriatic arthritis may develop or recur in a small percentage of patients during efalizumab treatment of psoriasis.6 Recommended dose prior to drug withdrawal was 0.7 mg/kg for the initiation dose followed by weekly 1 mg/kg doses thereafter.6 Efalizumab has a rapid onset of action with symptom improvement seen in about 4 weeks. About 25% of psoriatic patients receiving either 1 or 2 mg/kg/week improved by at least 75% at 12 weeks of treatment.11,43,44 Treatment needed to be continued; with cessation of therapy, the median time to relapse is 60 to 80 days. Although with continued therapy patients will continue to improve, with 44% to 50% of patients achieving and maintaining PASI-75 after 6 to 36 months of continuous efalizumab therapy,6,45 the possibility for serious adverse effects outweighed the benefits. Efalizumab has recently been suspended from use in Canada, and on April 8, 2009, the FDA issued a statement that efalizumab has been voluntarily withdrawn by the company in the United States. This withdrawal is due to reports of progressive multifocal leukoencephalopathy (PML). There have been 3 confirmed cases and one possible case of PML in patients 47 to 73 years of age with moderate to severe plaque psoriasis who had been using efalizumab continuously for over three years. PML is a rare, serious, progressive neurologic disease caused by a virus that affects the CNS and there is no known effective treatment. The reader is directed to the following FDA website for further information about the issue and the phased-in withdrawal process: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149561.htm
Common side effects include headache, fever, chills, nausea, and myalgias, which usually diminish after the third week of treatment.6 Thrombocytopenia, hemolytic anemia, pancytopenia, and peripheral demyelination have also been reported; and a CBC is recommended monthly for the first 3 months and every 3 months during therapy.6 Worsening psoriasis may occur during treatment or after drug discontinuation and it was recommended that treatment not be discontinued abruptly unless it is essential as rebound may develop.6 There is an increased risk of infections (other than viral leading to PML) and caution should be exercised in patients at risk for or have a history of malignancy or infection.6,43,44
Infliximab is a chimeric human/murine monoclonal antibody against TNF-α which binds to both soluble and transmembrane TNF-α molecules. It is approved for both psoriasis and psoriatic arthritis. Dosing for these patients is 5 mg/kg IV over 2 to 3 hours at weeks 0, 2, and 6 and continued every 8 weeks thereafter.6 Approximately 80% of patients achieved PASI-75 by 10 weeks (after 3 doses of inflixamab) however by week 50 only about 60% of patients maintained PASI-75.46,47 Infliximab is also approved for rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, and ulcerative colitis. Significant adverse effects from postmarketing experience and clinical trials have included hematologic abnormalities (leukopenia, neutropenia, thrombocytopenia, and pancytopenia), hepatotoxicity (rarely: acute liver failure, jaundice, hepatitis, and cholestasis), hypersensitivity reactions (anaphylaxis, urticaria, and serum sickness), ocular toxicity (optic neuritis and optic neuropathy), CHF exacerbation and new onset CHF, and increased infections (tuberculosis, hepatitis B reactivation, Listeria monocytogenes infections, fungal infections, and sepsis). There is an increased risk of infection by live vaccines and vaccination with live vaccines while receiving infliximab therapy is not recommended. Patients should be evaluated for active or latent tuberculosis (tuberculin PPD skin test) prior to therapy.6 Recommended baseline and ongoing monitoring include yearly PPD, LFTs, and CBC.6
Adalimumab is a fully human TNF-α inhibitor initially approved for the treatment of rheumatoid arthritis in 2003. It is approved for treatment of psoriasis and psoriatic arthritis. Other approved indications include juvenile rheumatoid arthritis, ankylosing spondylitis, adult rheumatoid arthritis, and Crohn’s disease.6 The dosage in psoriasis is 80 mg subcutaneously in the first week, followed by 40 mg the following week, and 40 mg subcutaneously every 2 weeks thereafter continuously.6 With this regimen, 71% of patients achieved PASI-75 by 16 weeks of treatment.48 Patients should be evaluated for active or latent TB infection (tuberculin PPD skin test) prior to therapy. There is an increased risk of serious infections (in particular, respiratory infections including pneumonia and tuberculosis, and hepatitis B reactivation), of exacerbation in patients with heart failure, and increased risk of lymphoma. Hematologic abnormalities (pancytopenia, thrombocytopenia, and leukopenia) have been rarely reported. Positive antinuclear antibody titers and a lupus syndrome have been reported. Anti-ds DNA antibody determinations are recommended in patients presenting with lupus-like symptoms during adalimumab therapy. A pruritic urticarial eruption that lessens in severity with each subsequent injection has been reported. Rebound does not usually occur.6
Patient Encounter, Part 5
was decided to begin systemic therapy with either methotrexate or cyclosporine to control the flare ups. Both alternatives were presented to the patient and discussed with the patient.
What lab tests or other measurements would be important to perform prior to starting therapy with methotrexate? With cyclosporine?
What dosage regimen would be appropriate for methotrexate? For cyclosporine?
What monitoring plan would be appropriate for methotrexate? For cyclosporine?
Natural Health Products
There are several natural health products which are considered possibly effective for psoriasis. The most promising is Mahonia aquifolium (Oregon grape). This is not a grape, but a plant with blue-violet berries which is native to southern British Columbia, western Oregon and northern Idaho, and is the state flower of Oregon. An extract from the medicinal part of the plant, the rhisome and root, has been formulated into a 10% topical cream/lotion (Relieva, Apollo Pharmaceuticals) and is marketed in Canada for the treatment of psoriasis. This product has been shown in several recent clinical trials to modestly decrease the severity of psoriasis and improve the quality of life for patients with mild to moderate psoriasis.49 Preliminary research suggests that it is as effective as calcipotriene cream for some patients.49Adverse effects include a burning sensation, irritation, redness and itching, and possible allergic reactions.
Other natural health products which are possibly effective include an aloe vera extract 0.5% hydrophilic cream applied topically three times daily, and an omega-3 fatty acid based lipid infusion (with both DHA and EPA) given intravenously. Oral supplementation with dietary fish oils containing DHA and EPA did not appear to be effective. More research into these natural health products is required before they can be recommended for use in psoriasis.
OUTCOME EVALUATION
• Monitor the patient for clearance of skin lesions. Depending on the agent(s) used and site of lesions it may take 2 to 6 weeks or longer to see a response. Complete clearance may not be achieved for all patients.
• Monitor the patient for specific adverse effects, depending on agent(s) used. Some agents are discussed below, and others are discussed earlier in this chapter.
• Methotrexate: Monitor CBC and liver function tests at baseline and regularly, and consider liver biopsy prior to treatment and at a cumulative dose of 1.5 g. If available, monitor PIIINP at least three times yearly.
• Cyclosporine: Monitor SCr, blood urea nitrogen, and blood pressure at baseline and reassess biweekly for at least 12 weeks (or longer until values stabilize), then regularly. Adjust doses when needed in response to SCr changes as discussed above.9,32
• Acitretin: Monitor serum lipids and liver function tests.
Patient Care and Monitoring
With respect to pharmacologic therapies, it is important to:
• Provide patients with an approximate time frame for improvement based on the patient’s areas of involvement and type of drug therapy. For example, a statement such as: “There should be less scaling and redness of your scalp lesions and a reduction in the thickly crusted areas within 1 to 2 weeks. You should notice a general improvement in your condition by 6 to 12 weeks. Your palms, soles, elbows, and knees may take longer to clear.”9
• Provide appropriate advice about drug regimens including how to apply a specific topical agent, how to use a specific systemic agent, and precautions and possible toxicities of any drug therapy, remembering that topical therapies can have significant systemic adverse effects.
• Check the patient profile and talk with the patient to ensure that there are no significant drug interactions with other concurrent medications and therapies.
• Reinforce the importance of adherence to therapies and specific drug regimens.
• Reinforce the importance of regular follow-up with the patient’s health care providers including all appointments for follow-up care and lab work (if any).
• Interact with the patient’s other health care providers as needed to discuss patient concerns or issues detected including drug interactions, nonadherence, and adverse effects.
• Topical corticosteroids: Monitor for skin thinning, telangiectasias, and possible hypothalamic–pituitary–adrenal axis suppression.
• Interact with the patient’s other health care providers as needed to discuss patient concerns or issues.
SUMMARY
It is important to remember that psoriasis is a lifelong illness with no known cure and often has a significant psychosocial component. Author John Updike has said about his own psoriatic condition, that “my torture is skin deep” and that “we hate to look upon ourselves,” calling himself a “leper.”50 This disease may be very visible and emotionally distressing, and can cause significant disability both physically and psychologically, affecting psychosocial functioning and quality of life. Empathy and a caring attitude can go a long way in the care of these patients.50
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
ACKNOWLEDGMENTS
In the first edition, portions of this chapter had been adapted from the following article: Law RM. Psoriasis: An update. Pharmacy Practice 2005:21(12):CE 1–7. With permission from the publisher.
REFERENCES
1. Schon MP, Boehncke WH. Psoriasis. N Engl J Med 2005;352: 1899–1912.
2. Clarke C. Psoriasis—First-line treatments. Pharm J 2005;274:623–626.
3. Christophers E. Psoriasis—Epidemiology and clinical spectrum. Clin Exp Dermatol 2001;26:314–320.
4. Godic A. New approaches to psoriasis treatment. A review. Acta Dermatovenerol Alp Panonica Adriat 2004;13(2):50–57.
5. Kruger JG, Bowcock A. Psoriasis pathophysiology: Current concepts of pathogenesis. Ann Rheum Dis 2005;64(suppl II):ii30–ii36.
6. Menter A. Gottlieb A, Feldman SR 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 2008;58:826–850.
7. Kimball AB, Gladman D, Gelfand JM et al. National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening. J Am Acad Dermatol 2008;58: 1031–1042.
8. Kremers HM, McEvoy MT, Dann FJ et al. Heart disease in psoriasis. J Am Acad Dermatol 2007;57:347–354.
9. Rahman R, Elder JT. Genetic epidemiology of psoriasis and psoriatic arthritis. Ann Rheum Dis 2005;64(suppl II):ii37–ii39.
10. Law RM, Gulliver WP. Psoriasis: The harried school teacher. Section 14: Dermatologic disorders, no. 100. In: Schwinghammer TL, ed. Pharmacotherapy Casebook: A Patient-Focused Approach. 6th ed: 271–273. And in: Instructor’s Guide [to accompany] Pharmacotherapy Casebook: A Patient-Focused Approach. 6th ed: 1183–1194. New York: McGraw-Hill;2005.
11. Veale DJ, Ritchlin C, FitzGerald O. Immunopathology of psoriasis and psoriatic arthritis. Ann Rheum Dis 2005;64(suppl II):ii26-ii29.
12. Ellis CN, Krueger GG. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 2001;345:248–255.
13. Lui H, Langley R, Poulin Y, et al. Incorporating biologics into the treatment of psoriasis. J Cutan Med Surg 2004;8(suppl):8–13.
14. Callen JP, Krueger GG, Lebwohl M, et al. AAD consensus statement on psoriasis therapies. J Am Acad Dermatol 2003;49:897–899.
15. Guenther L, Langley RG, Shear NH, et al. Integrating biologic agents into management of moderate-to-severe psoriasis: A consensus of the Canadian Psoriasis Expert Panel. J Cutaneous Med Surg 2004; 8:321–337. http://www.springerlink.com/content/p30qnput52xh1648/fulltext.pdf.
16. Lebwohl M, Ali S. Treatment of psoriasis. Part 1. Topical therapy and phototherapy. J Am Acad Dermatol 2001;45:487–498.
17. Lebwohl M. Innovations in the treatment of psoriasis. J Am Acad Dermatol 2004;51(1):S40–S41.
18. Lebwohl M, Menter A, Koo J, Feldman SR. Combination therapy to treat moderate to severe psoriasis. J Am Acad Dermatol 2004;50: 416–430.
19. Speight EL, Farr PM. Calcipotriol improves the response of psoriasis to PUVA. Br J Dermatol 1994;130:79–82.
20. Frappaz A, Thivolet J. Calcipotriol in combination with PUVA: A randomized double blind placebo study in severe psoriasis. Eur J Dermatol 1993;3:351–354.
21. Ashcroft DM, Li WPA, Williams HC, Griffiths CE. Combination regimens of topical calcipotriene in chronic plaque psoriasis: Systematic review of efficacy and tolerability. Arch Dermatol 2000;136: 1536–1543.
22. Lebwohl M, Hecker D, Martinez J, et al. Interactions between calcipotriene and ultraviolet light. J Am Acad Dermatol 1997;37: 93–95.
23. Behrens S, Grundmann-Kollmann M, Peter RU, et al. Combination treatment of psoriasis with photochemotherapy and tazarotene gel, a receptor-selective topical retinoid. Br J Dermatol 1999;141:177.
24. Hecker D, Worsley J, Yueh G, et al. Interactions between tazarotene and ultraviolet light. J Am Acad Dermatol 1999;41:927–930.
25. Horwitz SN, Johnson RA, Sefton J, et al. Addition of a topically applied corticosteroid to a modified Goeckerman regimen for treatment of psoriasis: Effect on duration of remission. J Am Acad Dermatol 1985;13:784–791.
26. Yamauchi PS, Rizk D, Kormeili T, et al. Current systemic therapies for psoriasis: Where are we now? J Am Acad Dermatol 2003;49:S66–S77.
27. van de Kerkhof PC, Cambazard F, Hutchinson PE, et al. The effect of addition of calcipotriol ointment (50 micrograms/g) to acitretin therapy in psoriasis. Br J Dermatol 1998;138:84–89.
28. Saurat JH. Side effects of systemic retinoids and their clinical management. J Am Acad Dermatol 1992;27(6 pt 2):S23–S28.
29. Zachariae H. Liver biopsies and methotrexate: A time for reconsideration? J Am Acad Dermatol 2000;42:531–534.
30. Paul BS, Momtaz K, Stern RS, et al. Combined methotrexate—ultraviolet B therapy in the treatment of psoriasis. J Am Acad Dermatol 1982;7:758–762.
31. Clark CM, Kirby B, Morris AD, et al. Combination treatment with methotrexate and cyclosporin for severe recalcitrant psoriasis. Br J Dermatol 1999;141:279–282.
32. Koo J, Liao W. Update on psoriasis therapy: A perspective from the USA. Keio J Med 2000;49:20–25.
33. Lebwohl M, Ellis C, Gottlieb A, et al. Cyclosporine consensus conference: With emphasis on the treatment of psoriasis. J Am Acad Dermatol 1998;39:464–475.
34. Grossman RM, Thivolet J, Claudy A, et al. A novel therapeutic approach to psoriasis with combination calcipotriol ointment and very low-dose cyclosporine: Results of a multicenter placebo-controlled study. J Am Acad Dermatol 1994;31:68–74.
35. Ameen M, Smith HR, Barker JN. Combined mycophenolate mofetil and cyclosporin therapy for severe recalcitrant psoriasis. Clin Exp Dermatol 2001;26:480–483.
36. Gottlieb A. Immunobiologic agents for the treatment of psoriasis. Arch Dermatol 2003;139:791–793.
37. Walsh SRA, Shear NH. Psoriasis and the new biologic agents: Interrupting a T-AP dance. Can Med Assoc J 2004;170(13):1933–1941.
38. Kormeili T, Lowe NJ, Yamauchi PS. Psoriasis: Immunopathogenesis and evolving immunomodulators and systemic therapies; U.S. experiences. Br J Dermatol 2004;151:3–15.
39. Gottlieb G, Casale TB, Frankel E, et al. CD4+ T-cell-directed antibody responses are maintained in patients with psoriasis receiving alefacept: Results of a randomized study. J Am Acad Dermatol 2003(Nov);49:816–825.
40. Menter A, Cather JC, Baker D et al. The efficacy of multiple courses of alefacept in patients with moderate to severe chronic plaque psoriasis. J Am Acad Dermatol 2006;54:61–63.
41. Leonardi CL, Powers JL, Matheson RT, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med 2003;349:2014–2022.
42. Paller AS, Siegfried EC, Langley RG et al. Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med 2008;358:241–251.
43. Lebwohl M, Tyring SK, Hamilton TK, et al. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med 2003;349:2004–2013.
44. Gordon KB, Papp KA, Hamilton TK, et al. Efalizumab for patients with moderate to severe plaque psoriasis: A randomized controlled trial. J Am Med Assoc 2003;290:3073–3080.
45. Gottlieb AB, Hamilton T, Caro I et al. Long-term continuous efalizumab therapy in patients with moderate to severe chronic plaque psoriasis: Updated results from an ongoing trial. J Am Acad Dermatol 2006;54(Suppl):S154-S163.
46. Reich K, Nestle FO, Papp K et al. Infiximab induction and maintenance therapy for moderate-to-severe psoriasis: A phase III, multicenter, double-blind trial. Lancet 2005;366:1367–1374.
47. Menter A, Feldman SR, Weinstein GD et al. A randomized comparison of continuous vs intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. J Am Acad Dermatol 2007;56(31):e1–e15.
48. Menter A, Tyring SK, Gordon K et al. Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trial. J Am Acad Dermatol 2007;58:106–115.
49. Gulliver W P, Donsky HJ. A report on three recent clinical trials using Mahonia aquifolium 10% topical cream and a review of the worldwide clinical experience with Mahonia aquifolium for the treatment of plaque psoriasis. Am J Ther 2005;12:398–406.
50. Updike J. From the journal of a leper. Northridge, CA: Lord John Press; 1978:21.