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110-2 SECTION 14 Dermatologic Disorders • There are excoriations on the trunk and extremities resulting from severe itching and scratching related to psoriasis. 1.c. What risk factors for developing psoriasis or experiencing a disease flare-up are present in this patient? Risk factors for developing psoriasis: • There is relevant family history: His younger brother also has psoriasis. Psoriasis and psoriatic arthritis have complex genetic associations and generally result from an interplay between multiple genetic and environmental factors. There is a polygenic inheritance pattern. 5 There are psoriasis susceptibility genes and variants that reside on various chromosomes. The psoriasis susceptibility 1 (PSORS1) gene on chromosome 6 is considered the most important susceptibility locus and is associated with up to 50% of cases of psoriasis. 2 Other chromosomes with psoriasis susceptibility loci include 1p (PSORS7), 1q21 (PSORS4), 3q21 (PSORS5), 4q34 (PSORS3), 7p, 8, 11, 16q, 17q25 (PSORS2), 19p13 (PSORS6), and 20p, and others are being found. 1,2,5 For patients with known genetic-linked psoriasis, there is a strong tendency that the disease onset occurs in early adulthood. 4 • Twin studies have shown a 3-fold increased risk of psoriasis in monozygotic twins versus fraternal twins, with environmental factors also playing a role. 1,2,5 In addition, based on a study of 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. 1,2 Gene identification and linkage studies are ongoing. • Smoking cigarettes has recently been shown in two international studies to be a risk factor for psoriasis. 4 The patient is an ex-smoker who used to smoke heavily in his 20s and 30s. He was diagnosed with plaque psoriasis at age 23. There is also an increased prevalence of smoking associated with patients with psoriasis, seen in numerous countries. 4 Risk factors for experiencing a psoriasis flare: • The patient complains of feeling jumpy and appears to be under some stress in his work with the school board. The increasing stress could explain the frequent flare-ups of his psoriasis in the past year. • Although physical trauma or infections (particularly streptococcal upper respiratory tract infections) may trigger an exacerbation of psoriasis, 1,2 there are no indications of these in the patient. 1.d. What comorbidities does this patient have? • Comorbidities associated with psoriasis may be medical or psychiatric/psychological. Medical comorbidities include hypertension, hypertriglyceridemia, impaired glucose regulation, and obesity; autoimmune diseases such as psoriatic arthritis, Crohn’s disease, and multiple sclerosis; and malignancies such as cutaneous T-cell lymphoma. 4 Psychiatric/ psychological comorbidities include depression/suicidal ideation and suicide, anxiety, and poor self-esteem. 4 This patient is undergoing some stress and anxiety. He has a positive family history for cardiovascular disorders: a father with hypertension and type 2 diabetes. Thus, it would be prudent to routinely screen this patient for the above medical and psychiatric/psychological comorbidities. The importance of screening for comorbidities in psoriatic patients cannot be overemphasized. 1.e. Could the signs and symptoms be caused by any drug therapy he is receiving? • He is not receiving any drugs known to precipitate psoriasis (e.g., lithium, β-blockers, indomethacin, antimalarials such as chloroquine, and fluoxetine). Molecular mechanisms for druginduced flares of psoriasis are not completely understood. It is thought that lithium may elevate proinflammatory cytokines, thereby stimulating cutaneous leukocyte recruitment. β-Blockers may induce epidermal hyperproliferation associated with a decrease in intraepidermal cyclic adenosine monophosphate. Chloroquine blocks epidermal transglutaminase, involved in the terminal differentiation of keratinocytes. 1 • Withdrawal of corticosteroids after prolonged use and hypocalcemia may also exacerbate psoriasis; neither of these is a cause in this patient. Desired Outcome 2. What are the goals of pharmacotherapy for this patient’s plaque psoriasis? • Eliminate plaquelike skin lesions and achieve remission if possible. • Relieve the severe itching accompanying the psoriasis flare-up. • Prevent future flare-ups (relapses) of the psoriasis. • Relieve his work-related stress through nonpharmacologic and/or pharmacologic means. • Minimize drug-related toxicity and ensure no significant drug interactions with current medications. Therapeutic Alternatives 3.a. What nonpharmacologic alternatives are available for managing the patient’s psoriasis and its related symptoms? • Stress reduction (e.g., psychotherapy that includes stress management, guided imagery, and relaxation techniques) has been shown to improve the extent and severity of psoriasis. • Oatmeal baths such as Aveeno Oilated in tepid water may help soothe the itching with less need for systemic antipruritic agents. • Nonmedicated moisturizers used liberally several times daily may help prevent skin dryness. Maintaining adequate skin moisture helps control the scaling associated with psoriasis. Fragrancefree products should be selected when available. 1 • Avoid irritant chemicals on the skin (e.g., harsh soaps or detergents). Cleansing should be done preferably with lipid- and fragrance-free cleansers, using tepid water. • Avoid skin trauma. Sunburns can induce a flare-up of psoriasis; thus, sunscreens with a sun protection factor of at least 15 (preferably a sun protection factor of 30 or higher) should be routinely applied when outdoors. 1 • Climatotherapy is a complementary and alternative medicine (CAM) treatment for psoriasis that involves bathing in the Dead Sea, or using Dead Sea salts (DSS) or saline spa water combined with phototherapy (see discussion below). Limited studies using DSS or saline spa water appeared efficacious. 6 3.b. What feasible pharmacotherapeutic alternatives are available for controlling the patient’s disease and its related symptoms at this point? • Pharmacotherapy for plaque psoriasis consists of topical treatments, phototherapy, photochemotherapy, and systemic therapies. Between 2008 and 2010, both the American Academy Copyright © 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
110-3 of Dermatology (AAD) and the Canadian Dermatology Association (CDA) updated their treatment guidelines for psoriasis. The AAD guidelines were published in five sections, whereas the CDA published an entire guideline book. 3,4,7–9 In addition, the National Psoriasis Foundation held consensus conferences and published updated guidelines for use of methotrexate and cyclosporine. 10,11 • Topical treatments are most effective for mild to moderate or limited disease, or used as adjunct for extensive disease 4,7 and include the following options: ✓ ✓ Corticosteroids are available in a variety of potencies, strengths, and vehicles; selection depends on disease severity and lesion location. Low-potency agents (e.g., hydrocortisone) are used on the face and skin folds, and very-highpotency agents (e.g., clobetasol propionate) are generally reserved for thickly hyperkeratotic areas such as palms and soles. Refer to the textbook chapter for a table comparing corticosteroid potencies. Topical corticosteroids may cause topical side effects such as striae, skin atrophy, acne, telangiectasia, and rosacea. Systemic side effects from topical corticosteroids can also occur, including hypothalamic– pituitary–adrenal axis (HPA) suppression, hyperglycemia, and glaucoma. Tachyphylaxis can occur after prolonged use, and sensitization can develop. 1,4,7 ✓ ✓ Calcipotriol is a vitamin D 3 analogue that inhibits keratinocyte proliferation and promotes normal keratinization. It may cause hypercalcemia secondary to excessive absorption or use, or if underlying renal disease or impaired calcium metabolism exists. 4,7 It can be combined with ultraviolet B (UVB) phototherapy but is inactivated by UVA. 7 ✓ ✓ Calcipotriol plus betamethasone dipropionate is available in some countries (e.g., Canada) as a combination product (Dovobet). Dovobet ointment is effective for psoriasis when applied once daily in combination with thrice-weekly UVB therapy. 4 ✓ ✓ Tazarotene (0.05% or 0.1% gel) is a retinoid with antiinflammatory and antiproliferative effects. 4,7 It may cause skin irritation especially initially; concomitant use of products with a strong drying effect, whether topical preparations or cosmetics, should be avoided when possible. It can be used with phototherapy for enhanced effect. 4,7 ✓ ✓ Anthralin including SCAT with high anthralin concentrations (2–4%) for 20 minutes to 2 hours daily is effective, especially on thicker plaques, but may be highly irritating, especially if SCAT treatments are misused. 1 It is not as commonly used as the topical agents discussed previously. It can be used with phototherapy for enhanced effect. 4,7 ✓ ✓ Crude coal tar (liquor carbonis detergens) in various preparations is also not as commonly used today. It is keratolytic and may have antiproliferative and anti-inflammatory effects. 1,7 It may have similar efficacy as calcipotriol but has a slower onset. These preparations may precipitate folliculitis, as well as being cosmetically unappealing and may stain clothing. It can be used with phototherapy for enhanced effect. 4,7 ✓ ✓ Keratolytic agents such as salicylic acid are often added to bath oil or shampoos for scalp psoriasis. 1,7 ✓ ✓ M. aquifolium 10% topical cream or lotion (Relieva) is a topical herbal product standardized to contain 10% berberine, which may have limited potency for psoriasis. It inhibits keratinocyte growth and reduces keratinocyte proliferation and may be beneficial to some patients. 6 However, clinical trials are still limited, and there is a paucity of pharmacokinetic information such as systemic absorption data. In animal studies, berberine has uterine-contracting actions and anticonvulsant activity, and may depress cardiac function and respiration. ✓ ✓ Vehicles play a role in absorption and hence affect drug potency. A drug in an ointment base is more potent than in a cream base since ointments are occlusive and increase skin hydration. 1 Refer to the corticosteroid potency table in the textbook for some examples of potency changes due to different vehicles used. • Phototherapy and photochemotherapy are used for moderate to severe psoriasis, or when a patient fails topical therapy. Photochemotherapy is the concurrent use of phototherapy together with topical or systemic agents. 1,9 Phototherapy uses either UVB or UVA. UVB treatment modalities include broadband UVB or narrowband UVB (NB-UVB) used alone, or UVB with topical crude coal tar (Goeckerman regimen), UVB with topical anthralin (Ingram technique), NB-UVB with oral retinoids such as acitretin (RE-UVB), or UVB with methotrexate. UVA treatment modalities include UVA with oral or bath psoralens (psoralens with UVA phototherapy [PUVA]) used alone, or PUVA with oral retinoids (RE-PUVA), and PUVA with calcipotriol. 1,9 There may be an increased risk of skin cancers after prolonged use of phototherapy or photochemotherapy, and their use is contraindicated in patients with a history of melanoma or multiple nonmelanoma skin cancers. Carcinogenic risks are significantly greater with PUVA than UVB. In addition, there are other contraindications associated with either UVB or PUVA therapy. 9 Targeted phototherapy using excimer lasers that selectively target psoriatic lesions without affecting normal skin is an option being studied and early results appear promising, although blistering and burning of treated lesions are more common, and long-term safety has not been established. 9 • Traditional systemic therapies are seldom used for mild to moderate psoriasis and are generally reserved for patients with moderate to severe psoriasis. 1,4,7 However, a subset of patients with limited disease but debilitating symptoms may benefit from systemic treatment. First-line systemic therapies include methotrexate, acitretin, and cyclosporine. Although systemic therapies may be optimally used in a rotating fashion to minimize drug toxicities in patients requiring long-term systemic treatments, this is not routine practice for most dermatologists. However, rotational therapy to minimize cyclosporine toxicity (e.g., methotrexate → cyclosporine or methotrexate → acitretin → cyclosporine) may be helpful 10 as the appropriate duration of use for cyclosporine is not established. Current guidelines recommend either intermittent use in periods up to 12 weeks 4 to minimize nephrotoxicity 7 or continuous use up to 2 years. 10 ✓ ✓ Methotrexate (variable dosage range of 2.5–25.0 mg once per week) is generally considered the gold standard for traditional systemic therapies. 11 The combination of methotrexate and UVB appears to be synergistic. 1,9,11 Methotrexate carries a risk of hepatotoxicity, which is more significant in patients with other coexisting conditions: type 2 diabetes, alcoholism, obesity, and preexisting hepatic dysfunction. 11 Monitoring for psoriatic patients on long-term methotrexate use has traditionally included regular liver biopsies; however, the risks and benefits were recently reevaluated, and there is some evidence that this may not be routinely necessary for all patients. 11 Recent studies also seem to indicate that methotrexate-induced hepatic fibrosis and cirrhosis are rarer than initially reported. 11 Current AAD guidelines recommend the following: for low-risk patients, no baseline CHAPTER 110 Psoriasis Copyright © 2011 by The McGraw-Hill Companies, Inc. All rights reserved.
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