A Red, Scaly Rash: How to Recognize and Treat Psoriasis CASE-BASED REVIEW

CASE-BASED REVIEW
A Red, Scaly Rash: How to Recognize and Treat
Psoriasis
Case Study and Commentary, Kimberly A. Cayce, MD, Christie L. Carroll, MD, Daniel J. Pearce, MD, and
Steven R. Feldman, MD, PhD
Abstract
• Objective: To review the diagnosis and treatment of
psoriasis.
• Methods: Qualitative assessment of the literature.
• Results: Psoriasis is a common, chronic cutaneous
disorder distinguished by erythematous, scaling
plaques characteristically distributed in the scalp and
the extensor surfaces of the elbows and knees. Inflammation and hyperproliferation are key findings
along with associated symptoms of pruritus, pain,
and in 10% to 30% of patients, a form of arthritis.
Psoriasis has negative effects on quality of life as
great as those seen with other major medical disorders. The pathogenesis of psoriasis is considered to
be multifactorial with a known genetic predisposition;
evidence for the prominent role of T cells recently
has emerged. Treatment modalities include topical,
oral, or injectable medications and phototherapy or
lasers. Localized disease usually can be controlled
with topical medications and can easily be managed
by primary care providers. For patients with generalized disease or those with associated psoriatic arthritis, evaluation and management by a dermatologist
is recommended. All patients with psoriasis (and the
physicians who care for them) should be encouraged
to use the resources of the National Psoriasis Foundation (www.psoriasis.org) to help address both psychosocial and educational issues.
• Conclusion: Patients with psoriasis are likely to
present in the primary care setting. Physicians
should be able to recognize psoriasis and manage
localized disease.
P
soriasis is a common, chronic skin disease with an estimated U.S. prevalence of approximately 2% to 5%
[1–3]. Psoriasis affects men and women equally and
occurs in all races, although it occurs most frequently in
whites. There are 2 peaks in age of onset, one between 20 and
30 years of age and another between 50 and 60 years [4].
However, psoriasis can begin at any age.
Plaque-type psoriasis is the most common form, representing 80% of cases. Itching, burning, and soreness may be
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associated with the lesions, and up to one third of patients
may experience joint pains or arthritis [5]. Psoriasis has negative effects on quality of life that are as great as those seen
with other major medical disorders.
Triggering factors such as infection, winter weather,
stress, and certain drugs along with a genetic predisposition
have long been known to play a role in the pathogenesis of
psoriasis. However, advancements have been made in our
understanding of the immunologic factors involved in the
development of psoriasis, particularly the role of T cells.
These advances have led to the development of biological
medications that interfere with specific steps in the pathogenesis of the disease. Topical therapies remain effective
modalities for localized disease and such treatment can be
managed by a primary care physician. For patients with generalized disease or those with associated psoriatic arthritis,
referral to a dermatologist or rheumatologist is warranted.
Primary care physicians are likely to encounter patients with
psoriasis and should know how to recognize it, how to manage localized disease, and when to refer.
CASE STUDY
Initial Presentation
A 21-year-old white male athlete presents to his primary care physician for his annual sports physical
exam. The patient asks the physician to examine a rash that
he recently developed on his elbows and knees. He says that
his teammates are concerned about his “contagiousness,”
which is making him feel self-conscious. The patient also
complains of a dry, flaky, itchy scalp.
• What are the clinical presentations of psoriasis?
• What other entities might be considered in the differential diagnosis?
From the Center for Dermatology Research, Wake Forest University School of
Medicine, Winston-Salem, NC.
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PSORIASIS
A
B
Figure 1. Plaque-type psoriasis. Note the well-demarcated, erythematous plaques with overlying silvery-white scale on
the (A) scalp and (B) elbows.
Figure 2. Guttate psoriasis. Note the multiple, small, erythematous plaques with overlying silvery-white scale.
Clinical Features
In most cases, the diagnosis of psoriasis is based solely on
clinical history and examination, and only rarely is biopsy
required. There are 5 forms of psoriasis: plaque-type, guttate,
inverse, erythrodermic, and pustular. Plaque-type psoriasis
is the most common form (Figure 1), occurring in more than
80% of the psoriatic population [6]. This variant presents
with the classic well-demarcated, erythematous, thick papules and plaques with overlying silvery scale. The scalp,
elbows, knees, and intergluteal cleft are most commonly
involved, although the palms, soles, and nails also may be
affected. Characteristic nail changes that can occur with any
form of psoriasis include pitting of the nail plate and the nail
plate lifting up from the nail bed (onycholysis).
Guttate psoriasis (Figure 2) is seen most commonly in
children and accounts for 10% of cases [6]. It often occurs following an upper respiratory tract infection, especially strep464 JCOM July 2004 Vol. 11, No. 7
Figure 3. Erythrodermic psoriasis. Note the generalized
erythema with scale.
tococcal pharyngitis. The lesions appear as numerous, small,
scaly, erythematous papules and plaques widely distributed
over the trunk and extremities. Inverse psoriasis occurs on
the flexural surfaces, armpit, and groin, under the breast,
and in the skin folds and is characterized by smooth, inflamed lesions without scaling. The other 2 forms of psoriasis, erythrodermic (Figure 3) and pustular (Figure 4), each
account for less than 3% of cases [6]. Erythrodermic psoriasis is characterized by generalized erythema and scaling covering up to 100% of the body surface area. This serious form
of psoriasis decreases the skin’s innate ability to protect from
infection and loss of fluids and to control temperature.
Pustular psoriasis involves the development of sterile pustules, and it can be generalized or localized. Severe cases of
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CASE-BASED REVIEW
Table 1. Differential Diagnosis of Psoriasis
Disorder
Distinguishing Features
Seborrheic
dermatitis
Scale is yellow and greasy. Characteristic distribution over the scalp, forehead, eyebrows,
nasolabial folds, and beard; does not involve
the elbows, knees, or nails
Generally not as scaly as lesions of psoriasis;
distributed commonly on the neck and legs,
not in areas characteristically associated with
psoriasis
Configured in an annular pattern with central
clearing and peripheral scale
Purplish, flat-topped papules or plaques, generally not located in areas characteristically
associated with psoriasis; oral involvement is
common
Psoriasiform type is rare; lesions are usually
atrophic, annular papules/plaques; distribution typically is confined to sun-exposed
areas
Distributed in characteristic “Christmas tree”
pattern; usually resolves in approximately
6 weeks
Thickened palms and soles with yellowish to
orange hue; characteristic islands of sparing
Less scale than psoriasis lesions; not distributed in areas characteristically associated
with psoriasis
Lichen simplex
chronicus
Tinea corporis
Lichen planus
Figure 4. Pustular psoriasis. Note the pustules with surrounding area of erythema.
SCLE
generalized pustular psoriasis can cause loss of the skin’s
protective functions as well. The localized variant typically
involves the hands and feet and can be quite debilitating due
to pain and functional disability.
Differential Diagnosis
The clinical manifestations of several skin disorders are similar to those seen in psoriasis and should be considered in the
differential. These disorders include seborrheic dermatitis,
lichen simplex chronicus, tinea corporis, lichen planus, subacute cutaneous lupus erythematosus (SCLE), pityriasis rosea,
pityriasis rubra pilaris, and mycosis fungoides (Table 1).
Seborrheic dermatitis (Figure 5) often presents in the
scalp as a yellowish, greasy scale over an erythematous base
and can be confused with the plaques of psoriasis. Other
body surfaces characteristically affected in seborrheic dermatitis include the eyebrows, beard, forehead, nasolabial
fold, glabella, retroauricular region, concha of the ear and ear
canal, axilla, groin, sternum, submammary areas, and umbilicus. Differentiating between the 2 diseases can be difficult, but close inspection of the nails can provide clues to the
diagnosis. Nail abnormalities such as pitting, onycholysis,
and discoloration are present in up to 50% of psoriasis
patients but are not a feature of seborrheic dermatitis. It is
not uncommon for psoriasis and seborrheic dermatitis to
coexist.
Lichen simplex chronicus (Figure 6) also may be associated with psoriasis, but it can accompany any pruritic cutaneous disease, such as atopic dermatitis, xerosis, and venous
insufficiency. The condition results from chronic scratching or
rubbing and appears as thickened, often scaly, leathery, red to
brown colored plaques in areas that are easily reached by
scratching. The lesions of tinea corporis (Figure 7) are usually erythematous and configured in an annular pattern with
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Pityriasis
rosea
Pityriasis rubra
pilaris
Mycosis
fungoides
SCLE = subacute cutaneous lupus erythematosus.
Figure 5. Seborrheic dermatitis. Note the erythema and
scaling behind the ear and along the hairline.
central clearing and peripheral scale. The fungus may affect
any part of the body. When the diagnosis is unclear by visual inspection, microscopic examination of a potassium hydroxide preparation of skin scrapings to identify hyphae is a
quick and simple aid to diagnosis. Lichen planus (Figure 8)
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PSORIASIS
Figure 6. Lichen simplex chronicus. Note the thickened
(lichenified), erythematous plaque with scale.
Figure 8. Lichen planus. Note the purplish, flat-topped
plaques on the wrist.
Figure 7. Tinea corporis. Note the annular, erythematous
plaque with peripheral scale.
presents as pruritic, reddish-purple, flat-topped papules or
plaques most commonly located on the wrists and ankles;
however, the lower back, neck, legs, and genitals can be involved. While oral involvement is rare in psoriasis, oral
lesions are common in lichen planus and appear as patches of
fine white lines (Wickham’s striae). Wickham’s striae also are
present on the surface of the skin lesions.
The lesions of SCLE (Figure 9) typically are distributed in
areas of sun exposure. They initially appear as erythematous
papules and plaques with slight scale. As the lesions progress, they can become more psoriasiform with increased
scale (less common), although more often the lesions take on
an annular configuration. Patients with SCLE may have sys466 JCOM July 2004 Vol. 11, No. 7
Figure 9. Subacute cutaneous lupus erythematosus.
Note the atrophic, erythematous plaques on the arm.
temic symptoms such as fatigue or arthralgias, and serologic abnormalities are common [7]. In fact, tests for antinuclear
antibody (ANA) are positive in most patients with SCLE.
Anti-Ro (SS-A) antibodies occur in 80% to 95% of these patients, while anti-La (SS-B) antibodies occur less frequently
[7]. The presence of anti-double-stranded DNA antibodies
usually reflects systemic disease.
The history of pityriasis rosea (Figure 10) helps differentiate it from psoriasis. The initial lesion (herald patch) erupts
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CASE-BASED REVIEW
Figure 11. Pityriasis rubra pilaris. Note the patchy, salmoncolored plaques with islands of sparing.
Figure 10. Pityriasis rosea. Note the multiple, oval, salmoncolored plaques with fine scale.
acutely as an oval or circular, salmon-colored plaque with a
collarette of fine scale. Within 1 to 2 weeks, a more generalized rash consisting of multiple, smaller, symmetrical lesions
similar to the primary plaque appears in a “Christmas tree”
pattern, primarily on the trunk. Pityriasis rosea typically
resolves spontaneously in approximately 6 weeks, unlike
psoriasis, which has a chronic course.
Pityriasis rubra pilaris (Figure 11) is a rare condition that
presents as a pruritic, patchy, salmon-colored rash, characteristically with follicular papules, and first affects the scalp,
face, or chest. Often the rash eventually extends downward
covering most of the body, although it may affect only the
elbows and knees. The palms and soles also become thickened with a yellow to orange hue (palmoplantar keratoderma). Small areas of unaffected skin (islands of sparing) are
characteristic.
Mycosis fungoides (Figure 12) is an uncommon, slowly
progressive, cutaneous lymphoma of T-cell origin. The disease usually affects adults over age 50 years but can occur in
childhood and adolescence. It appears in 3 forms (patches,
plaques, and tumors) and often is mistaken for other cutaneous diseases in the initial phases. The patches (flat) and
plaques (raised) are erythematous, fine-scaling lesions with
irregular borders. Annular or serpiginous patterns are common. Any area of the body can be affected, but the hips, buttocks, groin, lower trunk, axillae, and breasts are frequently
involved. Tumors are red-violet nodules that may be domeshaped, exophytic, or ulcerated. Other systems, such as the
lymph nodes, liver, and lungs, also can be affected in later
stages.
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Figure 12. Mycosis fungoides. Note the erythematous,
fine-scaling plaque with irregular borders.
Further Evaluation
Upon further questioning, the patient says that the
rash has been present for approximately 3 to 4 weeks
and is getting worse. He notices that the rash becomes worse
particularly after he has scraped his elbow on the football
field. He has tried some over-the-counter moisturizers, but
these have not helped. The patient uses “whatever shampoo
is around the house.” He is otherwise healthy and does not
take any medications. He denies any other complaints or
family history of skin disease.
Physical examination reveals large, erythematous plaques
with thick, white, silvery scale in the scalp and on the bilateral elbows and knees. The remainder of the skin examination is normal. No oral lesions are found, and the nails
appear normal. The rest of the physical examination is within normal limits.
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Table 2. Susceptibility Loci Identified in Psoriasis
Locus Name
Location
PSORS1
6p21.3
6q
7
8q24
10q22–q23
11p13
14q31–q32
15q
17q24–q25
19p13
20p
4q34
1q21
2p
3q21
4q13
4q21
1p35–p34
16q12–q13
PSORS2
PSORS3
PSORS4
PSORS5
PSORS7
PSORS8
Adapted with permission from Bowcock AM, Barker JN. Genetics
of psoriasis: the potential impact on new therapies. J Am Acad
Dermatol 2003;49(2 Suppl):S51–6. Copyright © 2003, American
Academy of Dermatology.
Diagnosis
Based on these findings, the physician makes a diagnosis of
psoriasis. She informs the patient that he has psoriasis and
reassures him that his skin condition is not contagious. The
patient wants to know how he got this disease.
• What factors are known to lead to the development of
psoriasis?
Pathogenesis
Multiple factors are involved in the pathogenesis of psoriasis.
A genetic predisposition combined with environmental triggers appears to play a part in disease development. The complex genetics of psoriasis are not yet fully understood but are
best described as a polygenic inheritance model. PSORS1, a
human leukocyte antigen (HLA)-associated allele, is considered to be a major component of the genetic basis of psoriasis
[8]. However, many other genes and HLAantigens have been
associated with psoriasis (Tables 2 and 3). Environmental
triggers such as mechanical, ultraviolet (UV), and chemical
injury can trigger the onset of psoriasis or worsen an existing
case. Koebner’s phenomenon, in which psoriatic lesions
manifest at a site of injury to the skin, occurs in approximate468 JCOM July 2004 Vol. 11, No. 7
Table 3. Human Leukocyte Antigens Associated with
Psoriasis
HLA-B13
HLA-B17
HLA-B37
HLA-Bw16
HLA-Cw6 (associated more with early onset disease)
HLA-DR7
HLA-B27 (associated with sacroiliitis of psoriatic arthritis)
HLA-Aw19
HLA-Bw35
HLA-DRB1*0701/2 (associated more with early-onset disease)
Information from reference 8.
ly 25% of patients [9]. Various infections (particularly streptococcal pharyngitis), psychological stress, smoking, and certain medications (ie, lithium, β blockers, antimalarials, and
interferon) also are known triggers for the disease [10].
The important role of T cells in the pathogenesis of psoriasis has become more evident in recent years. The T lymphocyte is the predominant cell in the infiltrate of psoriatic
lesions, and it is already present in early pinpoint lesions [9].
CD4+ cells predominate in the dermis and are most prevalent in early lesions, whereas CD8+ cells predominate in the
epidermis and are most prevalent in resolving lesions [9]. In
the presence of unidentified antigens, antigen-presenting
cells mature and interact with naive T cells, causing T-cell
activation. This process requires at least 2 signals: (1) recognition of the antigen on the antigen-presenting cell by the
T-cell receptor and (2) a costimulatory signal from the
antigen-presenting cell to the T cell. Following this signaling,
the T cells proliferate, and some become memory T cells [6].
Through the interaction between lymphocyte function associated antigen-1 (LFA-1) on the T cell and intercellular adhesion molecule-1 on the endothelium, T cells migrate to the
site of inflamed skin. Binding of T cells to endothelial cells
also is facilitated by the interaction between cutaneous
lymphocyte-associated antigen on T cells and E-selectin on
endothelial cells. Once in the inflamed skin, T cells encounter
the initiating antigen and secrete type-1 cytokines (Th1), particularly interferon-α and interleukin (IL)-2, as well as tumor
necrosis factor-α (TNF-α), leading to proliferation and decreased maturation of epidermal keratinocytes [6]. IL-8, produced by most cells of the body, also plays a role in psoriasis
by attracting neutrophils and T cells and promoting epidermal proliferation [9].
Further Discussion with Patient
The physician explains the causes of psoriasis and
its triggering factors to the patient. The patient
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confirms that he understands this information and asks
what the diagnosis means for him in the long-term and what
therapies are used to treat it.
• What is the impact of psoriasis on patients’ quality of
life?
Psoriasis is a chronic condition, although complete remissions do occur. Approximately 5% of patients have reported
remission times of 5 or more years [9]. In the absence of such
remission, many patients experience periods of wellcontrolled disease with episodic flares as they cycle through
various treatments. Some patients who achieve treatment
success can flare when therapy is tapered or discontinued;
maintenance therapy is the norm. The disease itself, along
with the therapies used to treat it, can have a dramatic effect
on patients’ lives, including career, finances, leisure activities, relationships, and physical intimacy [4]. For patients
with psoriasis, the appearance of their skin is the most concerning aspect of having the disease [11]. Other commonly
cited bothersome features of psoriasis include pruritus,
physical irritation, and physical pain or soreness [4]. The
severity of psoriasis is correlated with the disease’s negative
impact on health-related quality of life [12,13]. Physicians
frequently underestimate the psychological morbidity associated with skin disease [14]. The physical and mental functioning of psoriasis patients are comparable to patients with
other chronic diseases, such as cancer, arthritis, hypertension, heart disease, diabetes, and depression [15].
Management of the psychosocial aspects of psoriasis is
just as important as management of the physical disease.
Various coping strategies have been reported in the literature, including educating others, covering lesions, and social
avoidance [16]. Telling others that the disease is not contagious may lessen the negative impact of psoriasis [16]. In
addition to talking with the patient, it is imperative for the
physician to use body language that conveys openness and
acceptance. Physically touching the skin lesions can be particularly beneficial and communicates to the patient that the
psoriasis is not contagious. One of the most important
aspects of psoriasis management is patient referral to the
National Psoriasis Foundation (NPF), which offers great
psychosocial support and educational resources to patients
suffering from psoriasis. The NPF’s goal is to improve
the quality of life of those with psoriasis and promote psoriasis research. The organization provides brief, topic-specific
brochures to address patients’ most commonly asked
questions, and more information can be found on their
Web site at www.psoriasis.org. The foundation can be contacted by mail (6600 SW 92nd Ave., Suite 300, Portland, OR
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97223-7195), phone (800-723-9166), fax (503-245-0626), or
e-mail ([email protected]).
• What is the approach to selecting therapy for psoriasis
patients?
Definitions of Psoriasis Severity
A first step in treatment planning for a psoriasis patient is
evaluation of the extent and impact of disease. There are
2 major arms in psoriasis therapy: (1) localized therapy with
topical agents and (2) phototherapy or systemic therapy,
which is considered a more aggressive approach. For patients with mild or localized psoriasis, topicals are the firstline of treatment. Practically all topical medications available
for psoriasis are safe and have efficacy when used appropriately. A good rule of thumb is that if a patient has greater
than 10% body surface area (BSA) involved, application of
topicals may be cumbersome and poor adherence is almost
guaranteed. For such patients, systemic agents or phototherapy is likely more appropriate. This strategy essentially creates 2 classes of disease severity based on the appropriateness of topical versus systemic treatment (mild versus
moderate-to-severe). The BSA can be estimated using the
palm rule—1 palm equals about 1% BSA. Objective measures for assessing psoriasis severity such as the Psoriasis
Area and Severity Index (PASI) and Physician Global Assessment have been developed; however, these measures
can be cumbersome and subject to significant intraevaluator
variability if not used frequently. These measures are most
useful in clinical trials.
The impact of the disease on the patient’s quality of life
should factor into treatment planning. For example, if a
patient with 7% BSA involvement is devastated and is not
able to carry out her activities of daily living, aggressive therapy with a systemic agent may be warranted. Conversely,
some patients with relatively extensive disease are impacted
very little, and it may be appropriate to spare them exposure
to potentially toxic agents. Another instance when BSA does
not necessarily predict morbidity is in patients with psoriasis of the palms and soles. Because of the significant physical
burden of this psoriasis variant, systemic therapy often is
first-line.
• What therapies are used to treat localized disease?
Treatment of Localized Disease
The case patient has localized disease and would likely benefit from treatment with topical therapy, an approach that
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avoids some of the risks associated with systemic treatment.
Topical corticosteroids have been a long-standing treatment
modality for psoriasis. Superpotent steroids (class I) such as
clobetasol, halobetasol, and betamethasone (optimized vehicle) sometimes are used initially to penetrate through the
scaly, thickened lesions. As a class, these medications have
similar efficacy and often are applied twice daily. To further
enhance penetration, application of occlusive dressings
(even plastic kitchen wrap) is sometimes beneficial. Ointments or creams work well for lesions on the body, but solution or foam formulations generally are preferred for scalp
involvement [17]. Lesion improvement in the form of decreased scale and erythema may prompt substitution of a
lower-potency steroid in order to avoid long-term sequelae
associated with high-potency steroid use. The high-potency
steroids should be avoided on the face, axilla, and groin
region because of the increased risk of skin atrophy and permanent changes in dermal blood vessels, although lowstrength steroids are acceptable. Combination or sequential
therapy often is preferred to minimize steroid use.
Topical calcipotriol, a vitamin D analogue, is a safe and
effective treatment alternative for mild-to-moderate psoriasis and often is used in combination with topical corticosteroids or other treatment modalities, even in severe cases.
The combination of calcipotriol and corticosteroid has been
shown to be more effective in the treatment of psoriasis than
either agent used alone [18]. Calcipotriol is usually applied
twice daily. Common steroid-sparing schedules include
application of each medication once daily (eg, calcipotriol in
the morning and the corticosteroid at night), or use of calcipotriol during the week and corticosteroid on the weekends. Calcitriol and tacalcitol are other vitamin D analogues
available in ointment formulations for the treatment of
psoriasis. Fewer studies have been performed with these
agents, but efficacy has been demonstrated in placebocontrolled trials [19,20]. As a class, the vitamin D analogues
can clear approximately 50% of psoriasis plaques when used
twice daily [19–21]. If a vitamin D analogue is combined
with phototherapy, it should be applied after UV exposure
because the drug is inactivated by UV light [22]. Additionally, products that contain acid, such as salicylic acid,
inactivate vitamin D analogues [23]. Skin irritation is the
most common side effect reported with the use of these
agents.
Topical agents that are used less frequently for the treatment of psoriasis include coal tar, anthralin, and tazarotene.
Coal tar exhibits anti-inflammatory properties and is particularly effective for the pruritus associated with psoriasis;
however, many patients will not tolerate its unpleasant smell
and messiness. Anthralin and tazarotene also have disadvantages and are second-line treatment options. Anthralin is
messy and stains nearly everything with which it comes in
470 JCOM July 2004 Vol. 11, No. 7
contact. Clinical trials have demonstrated modest improvement of psoriasis with the use of tazarotene, although it may
be slow to work [9]. Furthermore, the drug can be irritating,
often limiting its use [5].
Another approach to localized psoriasis therapy is UV
light. Light can be delivered via specialized hand and foot
units for disease of the palms and soles. For other locations,
delivery of UV light can be done with specialized laser
devices. Laser delivery systems are able to deliver light of a
limited wavelength in order to maximize UV efficacy. The
308-nm excimer laser has shown promise in the treatment of
localized disease [24,25].
• What steps can be taken to improve patient adherence
to treatment?
A major challenge in treating localized psoriasis is patient
adherence to the recommended treatment regimens. Low
adherence is related to use of topical therapies, which can be
messy and irritating as well as time consuming to apply [26].
Studies evaluating patient compliance have reported a 40%
nonadherence rate with topical therapy for psoriasis [27].
Additionally, highly motivated patients participating in a
clinical trial had only about a 50% adherence rate after
8 weeks of treatment [28]. Because reduced adherence is
associated with poorer outcomes, physicians must be very
aggressive in promoting adherence to the topical therapies,
especially over the chronic course of psoriasis. Educational
materials from the NPF help encourage patients to be more
adherent to recommended treatment regimens. In addition,
vehicle choice is an important factor in improving patient
adherence [29]. Patients generally prefer less messy topical
formulations such as solutions, foams, and lotions [30].
Choosing the topical therapies or vehicles that are most
appealing to patients can improve adherence and therefore
improve treatment outcomes. Additionally, investigation
into the patient’s use of the medications is important, as
changes in the regimen can be made to improve adherence.
Initiation of Topical Therapy
Because the patient has localized disease, the physician prescribes him sequential therapy with a topical steroid and calcipotriol. She advises him of the benefits
and risks of sun exposure and refers him to the NPF for additional information and support. On follow-up visits, the
patient is asked about his ability to comply with the current
regimen. He reports that he misses a dose a few times a
week. Importantly, he is pleased overall with his response to
treatment and no alterations in his regimen are needed. The
patient improves over the first 6 weeks and is scheduled for
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twice-yearly visits for medication refills and monitoring for
adverse events. For the next several years, he is able to
control his psoriasis; there are periods of waxing and waning, but increases in his dosing regimen effectively combat
the flares.
• What therapies are used for generalized disease?
Therapeutic Options for Generalized Disease
Topical therapies alone will not suffice for the management
of generalized psoriasis. Adherence is likely a major reason
that extensive psoriasis cannot be treated with topical
agents. Time commitment, messiness, and the ability to
reach certain plaques are important factors when considering the suitability of a topical regimen. Referral to a dermatologist is appropriate for treatment of generalized disease as
screening and regular laboratory tests are required with systemic therapies. Blood counts, liver function, and lipid levels
have to be monitored; at times liver biopsy is required even
in the absence of laboratory abnormalities. Furthermore,
adverse events, both clinically significant and occult, must
be closely monitored.
Phototherapy
Ultraviolet B (UVB) light is a reasonably safe therapy that
can lead to prolonged remissions. Treatments typically are
administered 3 to 5 times per week. Patients may receive the
light treatments in the office or obtain a home UVB device.
In fact, sunlight itself can be highly effective and is often recommended. If patients do not respond to UVB therapy,
higher-risk therapies may be employed. A combination of
UVA light with an oral or topical psoralen medication
(PUVA therapy) is a classic treatment for psoriasis patients.
The psoralen sensitizes the patient to UVA light, intensifying
the treatment. However, use of psoralen increases the risk of
severe burns as well as nonmelanoma skin cancer [31]. These
risks must be considered prior to initiation of treatment, and
precautions must be taken to avoid treatment in areas of
chronic sun exposure.
Systemic Agents
Systemic medications can be highly effective for the treatment of psoriasis but often are accompanied by side effects.
Oral medication options include acitretin, methotrexate, and
cyclosporine. Acitretin is a retinoid and works by inhibiting
epidermal proliferation [9]. It is particularly useful in the
treatment of generalized pustular psoriasis, with rapid resolution of lesions usually achieved within 10 days [32]. When
acitretin is used as monotherapy for other forms of psoriasis,
including chronic plaque-type, response time is generally
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slower [33]. In a study of patients with plaque-type psoriasis, 70% of subjects on acitretin monotherapy achieved an
approximately 50% reduction in severity measures [9]; however, efficacy rates are typically lower in clinical practice.
Combination therapy with UV light or vitamin D3 analogues
has been shown to be substantially more effective [9].
Acitretin is highly teratogenic, and this must be carefully
considered before this drug is prescribed to women with
childbearing potential. The half-life of acitretin is extremely
long, and pregnancy must be avoided for 3 years after discontinuation of the drug. Additional possible side effects
include mucocutaneous dryness, alopecia, increased serum
triglycerides, and rarely hepatotoxicity. Despite the potential
side effects of acitretin, the drug has been shown to be effective and generally well-tolerated as maintenance therapy
[34]. Regular monitoring with serum chemistries, measurement of triglycerides, and liver function tests must be done
throughout the treatment period. Prior to initiating therapy
in women, a pregnancy test should be performed and definitive birth control measures initiated.
Methotrexate is a folic acid antagonist and primarily
works by reducing cutaneous inflammation [5]. In a clinical trial involving 248 patients, 90% of the patients on
methotrexate had at least a 75% reduction in disease severity [35]. In addition, long-term therapy with methotrexate
has been shown to result in prolonged remissions [36].
Although methotrexate is highly efficacious in the management of psoriasis, adverse events typically limit its use to
moderate-to-severe disease resistant to topical medications
and/or UV light therapy or situations in which these therapies are contraindicated. The most worrisome side effects
associated with methotrexate are its potential for bone marrow and liver toxicity. Because methotrexate can suppress
the bone marrow, complete blood counts should be monitored while on therapy. Liver function tests also should be
performed every 1 to 2 months, and liver biopsies are
required periodically to screen for subclinical hepatotoxicity. Patients may also complain of nausea, vomiting, abdominal pain, fatigue, and headache. Administration of folic
acid once daily (except on methotrexate days) may reduce
these subjective symptoms as well as the risk of hematologic adverse events.
Cyclosporine is a cyclic undecapeptide that ultimately
works by inhibiting the activity of T cells [9]. Efficacy rates are
high and results are seen rapidly. Within 4 weeks, a reduction
of 60% to 70% in severity and area of involvement has been
achieved [37]. However, treatment with the drug is recommended for no longer than 1 year because of potential
adverse events, most importantly, renal impairment. Other
associated adverse events include hypertension, hyperkalemia, hypomagnesemia, hyperuricemia, and elevated
cholesterol and triglycerides. Thus, regular monitoring of
Vol. 11, No. 7 July 2004 JCOM 471
PSORIASIS
blood pressure, renal function, liver function, cholesterol, triglyceride, and uric acid levels, and serum chemistries is needed. Additionally, cyclosporine may cause gastrointestinal discomfort, hypertrichosis, paresthesias, gingival hyperplasia,
headache, vertigo, muscle cramps, and tremor [9].
Biological Agents
A new category of injectable medications known as biologic
response modifiers, or biologicals, recently has been used in
the treatment of psoriasis. Engineered from proteins produced by living cells, these drugs target key steps in the
pathogenesis of psoriasis.
Alefacept was approved by the U.S. Food and Drug Administration (FDA) for treating psoriasis in 2003. It is a fusion
protein of the CD2 binding domain of LFA-3 and the Fcportion of human immunoglobulin G1. Alefacept blocks the
costimulatory pathway between LFA-3 on the antigen presenting cell and CD2 on the T lymphocyte, inhibiting T-cell
activation and proliferation [38]. A selective reduction in
memory T cells occurs because CD2 expression is higher on
activated memory T cells than on naive T cells [38]. It is
administered as a weekly intramuscular injection in the
office over a 12-week period; this regimen may be repeated
after a 12-week treatment-free period, if necessary. Clinical
trials have demonstrated a 75% reduction in disease severity
as measured by the PASI in 21% of patients treated with alefacept versus 5% with placebo [39]. The drug appears to be
relatively safe with no increased risk of infection; however,
routine laboratory monitoring of lymphocytes is recommended [38]. Also, there is no long-term safety data available for alefacept or any of the biologicals.
Three TNF-α inhibitors are available for managing psoriasis; only etanercept is FDA-approved for psoriasis. Etanercept is a recombinant human protein that competitively
binds to TNF-α, preventing interactions with its cell surface
receptors [40]. In efficacy trials, nearly 30% of treated patients
achieved a 75% reduction in PASI scores [41]. It is administered at home as a twice weekly subcutaneous injection and
is considered a relatively safe treatment option. Injection site
reactions were the most frequently sited adverse events in
clinical trials [40]. Infections and central nervous system demyelinating disorders are potential concerns with the use of
etanercept and, patients should be screened appropriately.
Infliximab is a chimeric monoclonal antibody that binds
to soluble and transmembrane TNF-α molecules in the plasma and diseased tissue, disabling activation of the TNF-α
receptor [42]. In fact, some authors speculate that infliximab
also could bind to TNF-α that is already bound to the receptor, turning off the activated cell [40,43]. Most experience
with infliximab has come from its use in patients with
Crohn’s disease and rheumatoid arthritis, but infliximab has
proved to be efficacious in the treatment of psoriasis as well.
472 JCOM July 2004 Vol. 11, No. 7
Up to 88% of patients in phase 2 clinical trials achieved a 75%
improvement in severity [44]. The drug is administered via
intravenous infusion over 2 to 3 hours. The most common
adverse events reported in clinical trials were infusionrelated reactions (dyspnea, urticaria, hypotension, flushing,
and headache) [42]. Patients should be screened for tuberculosis prior to treatment initiation and also should be monitored for infections during and after treatment [42]. Patients
with moderate to severe congestive heart failure should not
receive infliximab, and those with mild disease should be
monitored carefully with discontinuation at the first signs of
worsening heart failure. Careful monitoring also is advised
in patients with preexisting or recent-onset central nervous
system demyelinating or seizure disorders and those with
renal or hepatic insufficiency [42].
Adalimumab is the third and newest TNF inhibitor introduced and is given by subcutaneous injection. Approved for
rheumatoid arthritis, preliminary data have shown efficacy
in psoriasis [45]. A humanized monoclonal antibody, adalimumab may have less immunogenicity (ie, development of
autoantibodies to the non-native proteins) than infliximab.
Adalimumab carries the same black-box warning as infliximab regarding tuberculosis, and a tuberculin skin test
screen is recommended.
Efaluzimab is a humanized form of a murine antibody
directed against CD11a, the α subunit of LFA-1. By binding to
CD11a, it inhibits T-cell activation, cutaneous T-cell trafficking, and T-cell adhesion to keratinocytes [46]. In phase 3 trials,
30% of subjects achieved a 75% reduction in PASI scores [45].
It is administered via subcutaneous injection weekly at home.
However, significant disease flares have been reported in psoriasis patients after starting or abruptly discontinuing the
medication [47]. Thrombocytopenia was rare in clinical trials;
therefore, occasional monitoring of platelet counts (2 to
4 times per year) is recommended. Side effects most frequently reported include headache, nonspecific infection (ie, common cold), nausea, chills, pain, and fever [46].
Case Patient: 10 Years Later
The patient arrives for an office visit 10 years after
the psoriasis diagnosis was made. He has been seen
1 or 2 times per year for refills, flares, and adverse event
monitoring. He states that he has noticed new lesions arising
more frequently and complains of severe joint pains, particularly in the fingers on his right hand. Physical examination
reveals large, erythematous, silvery scaling plaques on his
scalp, elbows, and knees. In addition, the plaques have extended down onto his forearms and fingers as well as his
back and lower legs. His nails have deep pits and appear to
be lifting away from the nail bed. Range of motion testing is
within normal limits, although there is boggy edema involving the second and third digits of the right hand.
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CASE-BASED REVIEW
• How frequently does psoriatic arthritis occur in patients with psoriasis?
Dermatology and Pathology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, [email protected]
wfubmc.edu.
Financial disclosures: None.
This patient now appears to have psoriatic arthritis, an erosive, debilitating arthritis found in an estimated 10% to 30% of
all psoriasis patients [1]. Although cutaneous lesions generally appear well before the arthritis, 10% to 15% of patients
report the arthritis developed first [47]. The clinical manifestations of psoriatic arthritis are similar to rheumatoid arthritis,
but serologic testing can be negative in psoriatic arthritis. The
arthritis is an asymmetrical oligoarthritis and most commonly
affects the interphalangeal joints. The spine also may be involved. However, unlike rheumatoid arthritis, the metacarpophalangeal joint typically is spared in psoriatic arthritis.
Nail involvement and skin lesions adjacent to the affected
joints are almost always present. Radiologic findings vary by
patient and stage of disease but characteristically demonstrate
erosion and mutilation of the distal finger joints and of the
interphalangeal joints of the toes [48]. As with cutaneous psoriasis, T cells play a prominent role in psoriatic arthritis, particularly the Th1 cytokines, interferon-α and IL-2, as well as
the macrophage cytokines, TNF and IL-1β [49].
A crucial aspect of treatment for psoriatic arthritis is early
identification and aggressive intervention to avoid or minimize joint damage. All patients with psoriasis should be
asked about joint pains. Referral to a dermatologist and/or a
rheumatologist should be prompt if symptoms are uncovered.
Conclusion
Psoriasis is a common, chronic cutaneous condition affecting
both men and women of all ages and races. The classic lesions present as sharply demarcated, erythematous papules
and plaques with a silvery scale distributed on the scalp,
elbows and knees, and commonly the intergluteal cleft. Patients frequently experience a decrease in quality of life, not
only because of the physical appearance of the lesions, but
also because of the associated pruritus and pain. Although a
genetic predisposition exists, the genetics are not yet completely understood. Advancements in the understanding of
the important role of T cells, particularly Th1 cytokines, have
improved the outlook for psoriasis patients, with new therapies that target specific steps in the pathogenesis. Topical
therapies remain effective treatment modalities for localized
disease and can easily be managed by a primary care physician. For patients with generalized disease or those with
associated psoriatic arthritis, referral to a dermatologist or
rheumatologist is warranted.
Corresponding author: Steven R. Feldman, MD, PhD, Depts. of
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Author contributions: conception and design, KAC, CLC, DJP, SRF;
drafting of the article, KAC, CLC, DJP, SRF; critical revision of the
article, CLC, DJP, SRF; provision of study materials or patients,
KAC; obtaining of funding, SRF; administrative, technical, or logistic
support, KAC, CLC, DJP, SRF; collection and assembly of data, SRF.
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Copyright 2004 by Turner White Communications Inc., Wayne, PA. All rights reserved.
474 JCOM July 2004 Vol. 11, No. 7
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