PSORIASIS - McGraw-Hill Professional

110 

PSORIASIS 

The Harried School Teacher Level II 

Rebecca M.T. Law, BS Pharm, PharmD 

Wayne P. Gulliver, MD, FRCPC 

INSTRUCTOR’S GUIDE TO 

CHANGES IN THIS EDITION 

(Neoral) 75 mg twice daily for 3 months, alternating with acitretin 

25 mg once daily for 3 months; periodic flare-ups had been 

treated with short-contact anthralin therapy (SCAT). Because the 

patient has failed topical therapies and appears to be failing the 

cyclosporine/acitretin rotational therapy, the optimal treatment 

plan should involve replacing cyclosporine/acitretin with other 

systemic immunosuppressive therapies, preferably a biologic agent 

such as alefacept or an anti–tumor necrosis factor (anti-TNF) agent, 

rather than more traditional immunosuppressives such as azathioprine, 

tacrolimus, or hydroxyurea. Topical therapies such as salicylic 

acid in bath oil applied to the scalp and continuation of SCAT 

to heavily crusted lesions would be beneficial. Careful clinical and 

laboratory monitoring is required because of the potential toxicities 

of topical and systemic therapies. 

110-1 

CHAPTER 110 

Psoriasis 

CASEBOOK 

• Updated all learning objectives—in particular regarding the 

biologic response modifiers (BRMs) and other systemic therapies. 

• Added a past smoking history to the patient’s medical history. 

• New clinical pearl included. 

INSTRUCTOR’S GUIDE 

Problem Identification 

• Added new discussion about percent body surface area (BSA) 

as related to severity of psoriasis (consistent with new textbook 

chapter). 

• Added more specific information about psoriatic onychodystrophy. 

• Added new discussion about smoking as a risk factor. 

• Included a new question and answer about comorbidities associated 

with psoriasis. 

Therapeutic Alternatives 

• Included more discussion about complementary and alternatives 

drug therapies (Mahonia aquifolium, climatology). 

• Updated discussion about topical therapies, phototherapies, 

and photochemotherapies with updated guidelines. 

• Included more distinction between first- and second-line 

systemic therapies and where BRMs fit within the updated 

guidelines. 

• Updated the discussion about methotrexate hepatotoxicity and 

routine liver biopsies and provided updated guidelines. 

• Updated the discussion about cyclosporine duration of therapy 

and use with other agents and provided updated guidelines. 

• Updated the discussion about biologic therapies such as etanercept, 

alefacept, infliximab, and adalimumab with updated 

guidelines. Deleted all efalizumab information. Added information 

on ustekinumab. 

References 

• Revised and updated; nine new references added. 

CASE SUMMARY 

A 50-year-old man with a 25-year history of psoriasis is admitted 

with a stress-related extensive flare-up of plaque psoriasis with 

severe itching. He had been taking cyclosporine microemulsion 

QUESTIONS 

Problem Identification 

1.a. Create a list of this patient’s drug therapy problems. 

• Plaque psoriasis inadequately controlled with current treatments 

(cyclosporine alternating with acitretin, and SCAT for 

flare-ups). 

• Severe and generalized itching minimally responsive to moisturizers 

that requires drug or other treatments. 

• Work-related stress that may require evaluation and drug or 

other treatments. 

1.b. What signs and symptoms consistent with plaque psoriasis 

does this patient demonstrate? 

• The patient has confluent plaques with extensive lesions on his 

abdomen, arms, legs, back, and scalp. He also has thick, crusted 

lesions on his elbows, knees, palms, and soles. He is presenting 

with lesions covering 60–70% of his BSA. 

• The lesions are red to violet in color with sharply demarcated 

borders except where confluent, and loosely covered with silvery 

white scales. 

• The typical psoriatic lesion is a sharply demarcated erythematous 

plaque covered by silvery white scales. 1,2 The patient’s 

lesions are consistent with this, which is seen in plaque psoriasis. 

1,2 There are no pustules or vesicles to indicate this is pustular 

psoriasis. 

• Common areas of involvement include the elbows, knees, 

scalp, trunk, buttocks, and limbs. 1,3 Scalp involvement is seen 

in about 50% of patients with psoriasis. 1,2 Smaller plaques may 

coalesce into larger lesions, especially on the legs and trunk. 3 

Painful fissuring within plaques can occur when lesions are 

present over joint lines or on palms and soles. 3 The patient has 

areas of skin involvement much greater than 10% BSA, which 

is considered severe disease. 4 The other definitions of severe 

disease include a Psoriasis Area and Severity Index (PASI) of 

10 or greater or a Dermatology Life Quality Index (DLQI) of 

10 or greater. 4 Thus, the patient has skin lesions consistent with 

a severe flare-up of plaque psoriasis. 

• From 5% to 20% of patients with psoriasis have associated 

psoriatic arthritis. 2 Although nail involvement (psoriatic onychodystrophy) 

can occur with any type of psoriasis, it is seen in 

up to 90% of patients with psoriatic arthritis. 4 Fingernails are 

involved in about 50% of all patients with psoriasis and toenails 

are involved in 35% of patients. 4 There are no indications of psoriatic 

arthritis in this patient; even the patient’s nails are spared. 

Copyright © 2011 by The McGraw-Hill Companies, Inc. All rights reserved.

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 


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 


110-4 


liver biopsy, and consider liver biopsy after 3.5–4 g total 

cumulative dosage or consider switching to another agent; 

for high-risk patients, consider using another systemic agent 

altogether, or consider delayed baseline liver biopsy (after 

2–6 months of therapy to establish medication efficacy and 

tolerability), and repeat liver biopsies after approximately 

1–1.5 g of therapy. 11 Besides regular liver function tests 

(monthly for the first 6 months and then every 1–2 months), 

periodic complete blood counts (CBCs), renal function 

tests, and pulmonary toxicity tests should also be conducted. 

Pancytopenia is rare with doses used in psoriasis; however, 

it may still occur at any time during treatment, particularly 

in those with preexisting hematologic risk factors. Routine 

folic acid supplementation has been recommended to 

minimize hepatotoxicity, but this is currently controversial 

due to some evidence of slightly reduced efficacy of the 

methotrexate. 11 Some dermatologists would wait until signs 

of hematologic toxicity are seen before giving folate. There 

is also a risk of malignancy with methotrexate. 

✓ ✓ Acitretin is the free acid active metabolite of etretinate and 

is more potent when used with UVB or PUVA. It may produce 

a more rapid initial response than methotrexate for 

patients with severe inflammatory forms of psoriasis, and it 

has antineoplastic properties. The initial dose is 25–50 mg 

per day. Benefits should be visible within 10 days of drug 

initiation. Although not a problem in this case, 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. 8 Men should not donate 

blood for a similar time period. 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. Other 

side effects include ophthalmologic, neuromuscular, and 

hyperlipidemic changes. 1,8 

✓ ✓ Cyclosporine is a valuable option for management of psoriasis, 

but due to significant toxicities it is often reserved for 

treatment failures, in crisis management, and as a bridge 

to other therapies. 10 The combination of cyclosporine and 

calcipotriol may be more efficacious than either agent 

used alone. 1,10 Cyclosporine may also be successfully used 

with SCAT; however, it should not be used with PUVA 

due to reduced efficacy and the potential increased risk 

of cutaneous malignancies. 10 The risk of nephrotoxicity is 

higher in psoriatic patients than renal transplant recipients; 

drug-induced hypertension and possible carcinogenesis are 

also of concern. Intermittent cyclosporine used in 12-week 

cycles with other systemic agents such as a retinoid is useful 

in prolonging the disease-free period and in minimizing 

drug toxicities. The microemulsion formulation is more 

effective and is the recommended formulation. For patients 

with stable generalized psoriasis or when the severity of 

disease is moderate to severe, the recommended starting 

dose is 2.5 mg/kg per day given orally in two divided doses. 

Wait at least 4 weeks before considering increasing the dosage 

by 0.5 mg/kg per day every 2 weeks if the response is 

inadequate, to 4 mg/kg per day. 10 There may be patients 

who require more than 4 mg/kg per day for clearance, and a 

maximum dose of 6 mg/kg per day is recommended. 10 

For patients with severe inflammatory flares of psoriasis 

or recalcitrant cases who have failed to respond to numerous 

other therapies, or for a highly distressed patient in a crisis 

situation, the recommended starting dose is 4–6 mg/kg per 

day, to be decreased by 0.5–1.0 mg/kg per day at weekly or 

longer periods once the patient has a clear response, to the 

lowest effective maintenance dose. 

As mentioned earlier, optimal duration of therapy for 

cyclosporine in the treatment of plaque psoriasis has not 

been established. Intermittent short-course (75% in psoriasis severity, consistently over at least three 

treatment cycles. 4 When transitioning from cyclosporine 

to other systemic therapies, there should be an overlap 

period to allow tapering of the cyclosporine dosage. 

If transitioning to a biologic agent, the overlap period 

should be minimal to reduce the risk of opportunistic 

infections. 10 The National Psoriasis Foundation recommends 

the cyclosporine treatment duration be limited to 

2 years or less, and that in those patients on continuous 

therapy for longer than 1 year, a nephrologist be involved 

to assist with management of cyclosporine-associated 

nephrotoxicity. 10 

Blood pressure, serum creatinine, blood urea nitrogen, 

CBC, uric acid, potassium, magnesium, and lipids should 

be assessed prior to beginning therapy to obtain accurate 

baseline values, and reassessed biweekly once therapy is 

started for the first 12 weeks of therapy and then monthly 

during therapy. 10 If the serum creatinine increases to 25% 

above the patient’s baseline on two occasions (2 weeks 

apart), the cyclosporine dosage needs to be decreased by 

25–50% and serum creatinine rechecked as often as every 

other week for 1 month. If the serum creatinine does not 

return to within 10% of the patient’s baseline value, a further 

dose decrease of 25–50% should be considered. If the 

value continues to be greater than 10% above the patient’s 

baseline value, consider discontinuing cyclosporine therapy. 

10 (Note: A 25% above-baseline cutoff for dosage reduction 

is the manufacturer’s recommendation; the National 

Psoriasis Foundation consensus guidelines continue to 

recommend a 30% cutoff. 10 ) Cyclosporine should be discontinued 

if there is insufficient response after 3 months at 

the maximum dose. 1 

✓ ✓ Sulfasalazine has variable efficacy and is of limited potency, 

and psoriasis is not an approved indication for its use. 

However, its side-effect profile is better than other systemic 

therapies; side effects are common but generally not serious. 

Usual doses are 2–4 g per day in divided doses. 1,8 

✓ ✓ Azathioprine has been used in doses of 50 mg twice daily. 

However, the response time is slower than methotrexate or 

cyclosporine. 

✓ ✓ Tacrolimus (FK506) is an immunosuppressive agent used 

to prevent organ transplant rejection that has shown dramatic 

effectiveness for patients with psoriasis. However, side 

effects including nephrotoxicity, hypertension, GI intolerance, 

paresthesias, tremor, and palpitations have limited 

its use. 

✓ ✓ Hydroxyurea (500 mg twice daily) is an option in patients 

who have contraindications to methotrexate because of liver 

disease. However, there have been recent precautions about 


110-5 

its use in the elderly and cutaneous vasculitic toxicities in 

patients with myeloproliferative disorders. 1 

✓ ✓ Mycophenolate mofetil is not approved for psoriasis; however, 

it has been used effectively for recalcitrant moderate to 

severe psoriasis in limited studies. 1,8 

✓ ✓ Oral corticosteroids are reserved for severe or life-threatening 

conditions such as severe psoriatic arthritis or exfoliative 

psoriasis; prolonged steroid use should be avoided. 

• Biologic agents alefacept, etanercept, adalimumab, infliximab, 

ustekinumab, and others 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. 3,4 

In particular, they would be an appropriate first-line choice if 

comorbidities such as psoriatic arthritis are present. However, 

due to the significant cost difference, these agents are generally 

reserved for cases where traditional systemic agents are inadequate 

or if comorbidities exist. 1,3,4 Biologic agents employ 

various targeted immunosuppressive strategies: alefacept targets 

memory T cells; etanercept, infliximab, and adalimumab 

target TNF-α; and ustekinumab selectively targets IL-12 and 

IL-23. In general, due to their immunosuppressive effects, 

there is a significantly increased risk of infection with most 

of these agents, including serious infections such as sepsis, 

new-onset or reactivation of tuberculosis (TB), and opportunistic 

infections such as histoplasmosis, cryptococcosis, 

aspergillosis, candidiasis, and pneumocystis; the use of live 

or live-attenuated vaccines during therapy is generally not 

recommended. 3,4 

✓ ✓ Alefacept (Amevive) is a recombinant fusion protein that 

inhibits T-cell activation by binding to their CD2 sites and 

also interacts with natural killer cells to destroy already activated 

T cells. It was the first biologic agent approved by the 

FDA for the treatment of moderate to severe chronic plaque 

psoriasis, even in treatment-naive patients. Relative to other 

biologics, alefacept monotherapy provides limited control, 

but with long periods of complete or incomplete remission 

in some cases. 4 About one third of treated patients go into 

remissions that are prolonged (6–18 months). The dosage 

is 15 mg intramuscular (IM) once weekly for 12 weeks. The 

regimen may be repeated in 12 weeks only if needed (up to 

two more courses per year) and if the CD4 + T-cell count is 

normal (defined as greater than or equal to 250 cells/μL). 

Alefacept appears to spare helper T-cell function and does 

not significantly impair primary or secondary antibody 

responses (to fight infection or respond to vaccinations). 

There is a significant risk of malignancy, and common side 

effects include lymphopenia, myalgias, chills, pharyngitis, 

cough, and nausea, and for IM injections, pain and inflammation 

at the injection site. 3,4 Monitoring of the CD4 count 

is recommended. 3 

✓ ✓ Etanercept (Enbrel) is a fully human dimeric fusion protein 

composed of human TNF-α p75 receptor fused to the Fc 

portion of human immunoglobulin G1; it acts as a TNF-α 

inhibitor. 3 It binds to and inactivates TNF-α, preventing 

interactions with its cell surface receptors. It is useful for 

chronic moderate to severe plaque psoriasis and for psoriatic 

arthritis. The FDA-recommended dose is 50 mg subcutaneously 

twice weekly for 12 weeks, followed by 50 mg 

subcutaneously once weekly thereafter. Each dose is taken in 

two 25-mg injections within a 24-hour period or 3 or 4 days 

apart. Etanercept was studied in clinical trials using various 

regimens ranging from 50 mg twice weekly to 25 mg once 

weekly. In those given 50 mg subcutaneously twice weekly, 

49% of patients showed a 75% improvement in the PASI by 

12 weeks. 3 The drug was well tolerated, and common side 

effects included injection site reactions, headache, increased 

respiratory tract infections, and GI symptoms such as nausea. 

1 Serious infections (e.g., TB) including fatalities have 

been reported with etanercept but are rare when the drug is 

used alone. There have also been rare reports of worsening 

congestive heart failure (CHF) and new-onset CHF, lupus 

without renal or CNS complications, and multiple sclerosis. 

3 A small number of patients developed anti-etanercept 

antibodies that did not appear to affect drug efficacy. 1 

Due to rare reports of blood disorders such as aplastic 

anemia, leukopenia, and thrombocytopenia, patients are 

advised to contact their doctor if they experience persistent 

fever, bruising, bleeding, or paleness. 1,3,4 Among the TNF-α 

inhibitors, opportunistic infections are less common with 

etanercept than with infliximab or adalimumab 3 ; however, it 

is still recommended that patients be evaluated for active or 

latent TB prior to therapy and consider yearly PPD. 1,3,4 CBC 

and LFTs are also recommended prior to and periodically 

during therapy. 3 

✓ ✓ Infliximab (Remicade) is a chimeric human/murine monoclonal 

antibody against TNF-α. It is a highly effective 

treatment on initial exposure, even in severe, acute flares. 4 

However, on reinitiation or use beyond the first year of 

continuous treatment, efficacy becomes variable. 4 Patients 

with moderate to severe plaque psoriasis receive a standard 

dosing regimen of three IV infusions (5 mg/kg) over 

a 6-week induction period, followed by regular infusions 

every 8 weeks. 4 Adverse effects (primarily from experience 

in patients with rheumatoid arthritis) have included 

infusion reactions, hematologic abnormalities (leukopenia, 

neutropenia, thrombocytopenia, and pancytopenia), hepatotoxicity 

(rarely: acute liver failure, jaundice, hepatitis, and 

cholestasis), hypersensitivity reactions (anaphylaxis, urticaria, 

serum sickness), ocular toxicity (optic neuritis and optic 

neuropathy), demyelinating disorders, and increased infections 

(TB, hepatitis B reactivation, Listeria monocytogenes 

infections, fungal infections, sepsis). There is an increased 

risk of infections with live vaccines, so this is not recommended 

during therapy. Patients should be evaluated for 

active or latent TB prior to therapy and consider yearly PPD; 

a CBC, LFTs, and hepatitis profile should also be obtained at 

baseline and CBC and LFTs monitored periodically during 

therapy. 1,3,4 

✓ ✓ Adalimumab (Humira) is a TNF-α inhibitor that is a 

fully human anti–TNF-α antibody. 3 It binds specifically to 

soluble and membrane-bound TNF-α, thus blocking interactions 

with p55 and p75 cell surface TNF receptors. 3 It may 

also provide rapid control of psoriasis, which appears to 

be maintained for at least 1 year with continuous therapy. 4 

The dose is 40 mg subcutaneously every 2 weeks given on a 

continuous basis. 3 If adalimumab is discontinued, psoriasis 

over time will return to pretreatment severity, and there 

is loss of efficacy when adalimumab is restarted. 3 Adverse 

effects include injection site reactions, exacerbation of heart 

failure and new-onset CHF, hematologic abnormalities 

(pancytopenia, thrombocytopenia, and leukopenia), multiple 

sclerosis, and increased risk of serious infections (especially 

respiratory infections such as pneumonia and TB, and 

hepatitis B reactivation). Patients should be evaluated for 

active or latent TB infection prior to therapy and consider 

yearly PPD; a CBC, LFTs, and hepatitis profile should also be 

CHAPTER 110 

Psoriasis 


110-6 


obtained at baseline and CBC and LFTs monitored periodically 

during therapy. 1,3,4 

✓ ✓ Ustekinumab (Stelara) is an IL-12/23 monoclonal antibody 

that selectively targets IL-12 and IL-23, two cytokines that 

play a role in the pathogenesis of psoriasis. It binds to their 

shared p40 protein subunit, thus preventing interaction 

with their cell surface IL-12Rβ1 receptor. 12,13 It appears to 

provide a rapid response that is sustained for a year with 

continuous treatment. It is given subcutaneously at weeks 0 

and 4, and then every 12 weeks as maintenance therapy. The 

manufacturer recommends dosing by body weight, with 

patients weighing 220 lb (100 kg) or less receiving 45 mg 

and those weighing more than 220 lb (100 kg) receiving 90 

mg. Common side effects include upper respiratory infections, 

headache, and tiredness. Serious side effects include 

those seen with other BRMs such as serious infections (e.g., 

TB, fungal, viral) and cancer risk; in addition, a reversible 

posterior leukoencephalopathy syndrome (RPLS) has been 

reported. 

• Intralesional corticosteroid injections (triamcinolone acetonide 

5–10 mg/mL or triamcinolone hexacetonide 5 mg/mL) may be 

useful for small, localized, recalcitrant plaques. 

• Antihistamines such as hydroxyzine 10–25 mg po TID and 

50–75 mg po at bedtime should be given as adjunctive therapy 

to relieve the pruritus. Hydroxyzine also has anxiolytic properties 

that may be useful in this patient. 

• There are many natural health products/alternative treatments 

for psoriasis, including omega-3 fish oil supplements, 

cleansing diets, emu oil, lecithin, a protein extract 

XP-828L, and Kalawalla (Polypodium leucotomos 50:1 

standardized extract). Limited clinical studies with some of 

these treatments (e.g., omega-3 fish oil supplements) seem 

promising, and there is limited ongoing research. 6 At this time 

it is too early to make population-based recommendations 

for using these products (see the section “Clinical Course: 

Alternative Therapy” for more information about alternative 

therapies). 

Optimal Plan 

4. What drug regimen is best suited for treating this flare-up of 

the patient’s psoriasis and its related symptoms? 

• The patient has failed topical and photochemotherapies with 

the exception of SCAT for defined limited lesions, and his current 

regimen of cyclosporine alternating with acitretin appears 

to be inadequate. It is important to remember that the patient 

is on rotational systemic therapy in combination with topical 

and photochemotherapy. Although rotational systemic therapy 

is not currently used by most dermatologists, it has been useful 

in this case for minimizing cyclosporine toxicity. 

• It would be appropriate at this point to consider the use of a 

biologic agent, either as monotherapy or in combination with 

other therapies. Alefacept, adalimumab, infliximab, etanercept, 

and ustekinumab are approved by the US FDA and Health 

Canada for plaque psoriasis. 

✓✓ Etanercept, infliximab, and adalimumab appear to have a 

higher efficacy rate than alefacept. Adalimumab appears to 

provide sustained efficacy over at least 1 year, whereas efficacy 

becomes variable over time for infliximab. 

✓✓ Alefacept, although limited in efficacy, may lead to sustained 

complete or incomplete remissions in some patients. 

✓✓ Infliximab, although highly efficacious initially even for 

severe cases, may lose efficacy if discontinued and reinitiated, 

or if used beyond the first year of continuous treatment. 

✓✓ Etanercept, adalimumab, or infliximab would be more 

convenient to administer than alefacept since patients can 

be taught to self-inject the subcutaneous doses, whereas 

alefacept therapy would require weekly clinic visits for IM 

administration. 

✓✓ Three cost–efficacy analyses conducted in 2005, 2007, and 

2009 found that the cost–benefit of different biologics is 

quite variable. The most recent clinical and economic review 

was conducted in 2009 for adalimumab, etanercept, infliximab, 

ustekinumab, and efalizumab. 14 This review found 

that the cost per responder achieving a PASI 75 response at 

12 weeks was lowest for adalimumab and highest for alefacept, 

based on the pooled number needed to treat (NNT) 

to obtain benefit found at 1.3 (infliximab), 1.5 (ustekinumab 

90 mg), 1.6 (adalimumab and ustekinumab 45 mg), 

2.3 (etanercept), 4.1 (efalizumab—now off the market in the 

United States and Canada), and 5.6 (alefacept). The annual 

cost per patient was also lowest for adalimumab, followed 

by etanercept, ustekinumab, alefacept (two courses), and 

infliximab. This analysis suggests that there are favorable 

cost and benefits, particularly with some newer biologics 

such as adalimumab being the least expensive and most 

cost-effective. 

✓✓ With respect to adverse effects, alefacept may be the safest, 

but it commonly causes lymphopenia and CD4 counts 

must be monitored. The TNF-α inhibitors adalimumab, 

etanercept, and infliximab rarely cause hematologic side 

effects such as thrombocytopenia but have greater concerns 

regarding serious infections including reactivation of TB 

and opportunistic infections. Cases of multiple sclerosis 

and other central nervous system disorders have also been 

observed in association with etanercept and other medications 

that target TNF-α, as is the risk of worsening CHF and 

new-onset CHF. Infliximab has been associated rarely with 

cases of cholecystitis and autoimmune hepatitis, which may 

be a class effect for TNF-α inhibitors. None of the agents is 

nephrotoxic. 

✓✓ Based on the above considerations, adalimumab would be 

an appropriate choice for an initial trial of a biologic agent 

(as monotherapy) in this patient, due to its efficacy, lower 

maintenance cost, and ease of administration. 

✓✓ Administer adalimumab 80 mg subcutaneously in the first 

week, then 40 mg the following week, and thereafter 40 mg 

every other week continuously. 3,4 

✓✓ The patient could be taught to self-administer the adalimumab 

dose. 

• The cyclosporine could be tapered off over 1 month for a 

smoother transition. 

• If the patient fails to respond adequately after a 12-week trial 

of the first biologic agent used (i.e., adalimumab in this case), 

another biologic (either another anti-TNF agent or another 

biologic agent) should be tried. 

• Reverting to methotrexate and increasing its dose is not an 

appropriate option because a previous dosage increase had not 

been beneficial and he has already received a cumulative lifetime 

dose of 2.2 g, although a recent liver biopsy showed no 

hepatocellular changes as yet. 


110-7 

• In addition to systemic therapy, topical therapy for the scalp 

should be given. An appropriate regimen is salicylic acid 10% in 

bath oil applied nightly to the scalp and covered with a shower 

cap overnight plus a tar shampoo used three times weekly until 

the scalp lesions clear. An alternative therapy is betamethasone 

0.1% lotion or 0.12% foam (Luxiq) for the scalp applied twice 

daily. Because the foam melts only when it reaches body temperature, 

steroid delivery will be to the scalp and not hair. The 

foam is easy to apply and has high patient preference. If this 

is inadequately effective, topical clobetasol propionate 0.05% 

foam (Olux) could be tried. 

• Continuation of SCAT to thickly crusted lesions would be beneficial. 

A 4% anthralin paste is applied twice daily for 2 hours 

and then wiped off. This should be continued until improvement 

is seen. 

• Hydroxyzine 10–25 mg po TID and 50–75 mg at bedtime 

should be given as adjunctive therapy for its antipruritic and 

anxiolytic effects. 

Outcome Evaluation 

5. How should you monitor the therapy you recommended for 

efficacy and adverse effects? 

Efficacy monitoring: 

• Psoriatic lesions do not improve overnight. However, some 

improvement should be apparent within 1–2 weeks for topical 

therapies and within 2–8 weeks for systemic or biologic 

therapies. With certain agents, more rapid responses (e.g., 

2–4 weeks) are typical—this is true for cyclosporine, adalimumab, 

infliximab, and ustekinumab. Scalp lesions should 

have less scaling and erythema (as a result of salicylic acid and 

tar shampoo treatments), and the thickly crusted lesions on 

his body should be reduced (as a result of SCAT treatment) 

within 1–2 weeks. 

• He should see a definite overall improvement by 12 weeks. If 

not, the biologic agent is not effective. If this occurs, switching 

to another biologic agent may still be beneficial. 

• His pruritus should improve within 24–48 hours of starting 

hydroxyzine therapy. 

• General monitoring: If the drug is effective, and the patient’s 

skin is cleared of psoriatic lesions, it would be important at that 

point to provide routine dermatologic care. This would include 

examining the skin and screening for other skin lesions (e.g., 

skin cancers), especially in the patient who has received PUVA 

or UVB or has prolonged exposure to natural sunlight. 

Adalimumab adverse effects monitoring: 

• Monitor for TB. Baseline PPD is required. Annual PPD should 

be considered. 

• Monitor CBC and differential at baseline and periodically (e.g., 

every 2–3 months). 

• Monitor LFTs at baseline and periodically (e.g., every 2–3 

months). 

• Monitor for signs of infection during therapy. Some serious 

acute infections (e.g., opportunistic fungal infections) and 

reactivation of latent chronic infections (e.g., TB) have been 

reported. 

• Other possible adverse effects include mild constitutional symptoms 

(headache, chills, fever, nausea, and myalgia), worsening 

CHF or new-onset CHF, lupus without renal or CNS complications, 

and multiple sclerosis. 3 

• Periodic history and physical examination are recommended 

while on treatment. 3 

Hydroxyzine adverse effects: 

• Sedation is the most common side effect with first-generation 

antihistamines, especially with the phenothiazine and aminoalkyl 

ether subgroups. Hydroxyzine is a piperazine derivative 

with less marked sedating effects. If drowsiness is excessive, 

switch to a second-generation agent such as loratadine. 

• Other adverse effects include dizziness or incoordination, GI 

complaints, and anticholinergic effects such as dry mucous 

membranes, dysuria, and urinary retention. 

Patient Education 

6. What information should be provided to the patient to enhance 

compliance and ensure successful therapy? 

General information: 

• There should be less scaling and redness of your scalp lesions 

and a reduction in the thickly crusted areas within 1–2 weeks. 

You should notice a general improvement in your condition 

by 6–12 weeks. Your palms, soles, elbows, and knee areas may 

take longer to clear. 

• It is important to keep all follow-up appointments with your 

physician. 

Adalimumab: 

• You will be taught how to inject the dose subcutaneously 

(under the skin). 

• Some pain at the injection site may occur. 

• This medication may rarely cause white blood cells to decrease in 

number. You will have regular blood tests to monitor for this. 

• Headaches, chills, fever, nausea, and muscle pains can also 

occur; contact your physician if these become troublesome or 

persistent. 

• Because this drug suppresses your immune system, you may 

be at greater risk of infections, including TB or other serious 

infections. Let your physician know as soon as possible if you 

develop a persistent fever. 

• Other adverse effects can also happen but are rare. These include 

hepatitis, heart failure, multiple sclerosis, and lupus. You should 

keep regular clinic appointments and contact your physician if 

you have any concerns between appointments. 

Hydroxyzine: 

• Take one capsule three times daily and two capsules at bedtime 

for itching. 

• Itchiness should be relieved within several hours and definitely 

within 1–2 days. 

• This medication may cause drowsiness, dry mouth, and problems 

with urination. If you become too drowsy, other medications 

are available but they are more expensive. Contact the 

clinic if any of these effects are too bothersome or if the itchiness 

is not relieved. 

SCAT: 

• While wearing gloves, apply the anthralin paste only on the 

thickly crusted areas. Leave the paste on for 2 hours and then 

wipe it off. 

• Contact us if you notice severe burning. 

CHAPTER 110 

Psoriasis 


110-8 


Salicylic acid in bath oil: 

• Apply the oil to the roots of your hairs (i.e., your scalp) every 

night before sleeping. Cover with a shower cap overnight. The 

next morning shampoo it off. 

• Use the tar shampoo three times a week. 

m CLINICAL COURSE: ALTERNATIVE THERAPY 

Because of Mr Kent’s frustration with his increased psoriasis flareups 

despite his prescription treatments, he is very interested in trying 

anything to help decrease his symptoms. A friend who takes fish 

oil for eczema told him it might help the psoriasis, so he asks about 

the possibility of adding fish oil on a daily basis. For questions and 

answers related to the use of fish oil/omega-3 fatty acids for the treatment 

of psoriasis, please see Section 19 of this instructor’s guide. 

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