Psoriasis, a chronic, proliferative skin disease, is one of the most common immune-
mediated disorders, occurring in 1.5% to 3% of the population worldwide, with
northern Europeans and Scandinavians affected most.
distinctive silvery scale. Of patients, 75% present with symptoms of psoriasis before
2 A family history of psoriasis is found in nearly half of patients.
At least 36 chromosomal loci have been identified that increase psoriasis
5–7 Modifiable triggers, such as tobacco and alcohol use, stress,
obesity, skin injury, and hormone changes, also play a major role in disease
Innate and adaptive immunity are both involved in the initiation and maintenance of
psoriatic plaques. Because the epidermis is the body’s main barrier to environmental
insult, epidermal hyperplasia forms a key component of the innate immune response.
Natural killer cells and natural killer T cells are part of the cutaneous inflammation
+ T-lymphocytic cells constitute most of the leukocyte
infiltrates found in plaques early in the development of lesions, current evidence
supports an autoimmune mechanism for psoriasis. Cytokines such as interferon-α2 or
interleukin-2 are also found in psoriatic plaques.
10 T cells in the cutaneous infiltrate
are positive for cutaneous lymphocyte–associated antigen, a marker for skin-homing
leukocytes. Pathogenesis also involves
vascular and inflammatory changes, which precede epidermal changes.
Alterations in the dermal vasculature also appear to be a result of angiogenesis, the
development of new blood vessels, similar to a number of other disease processes,
including tumor growth. Many commonly used therapeutic agents for psoriasis have
The epidermal changes of psoriasis are based on the time required for affected
epidermal cells to travel to the surface and be cast off, which is markedly reduced
(3–4 vs. 26–28 days in normal cells).
12 This sixfold to ninefold transit time decrease
does not allow the normal events of cell maturation and keratinization to take place
and is reflected clinically as diffuse scaling. T cells contribute to this keratinocyte
hyperproliferation through the secretion of various growth factors.
lymphocytes marked with cutaneous lymphocyte–associated antigen, to remember the
anatomic site where they first encountered antigen, migrate to the (epi)dermis by a
number of immunologic and inflammatory triggering mechanisms released from
keratinocytes after minor trauma. On entry into the skin, these T cells complex with
epidermal self-antigens presented by major histocompatibility complex molecules
that confer the risk of psoriasis. The subsequent release of T-cell cytokines results in
further inflammation, the recruitment of additional marked (i.e., with cutaneous
lymphocyte–associated antigen) T cells, and, ultimately, the development of psoriatic
lesions in susceptible persons.
Similar to those with diabetes, cancer, or heart disease, patients with psoriasis
experience a reduced quality of life related to an impairment of social,
psychological, and physical functioning.
15–17 Although psoriasis is a treatable
disease, there is no known cure. Optimism and encouragement are justified and make
it easier for patients to conscientiously apply sometimes awkward and messy topical
treatments or take medications that have significant adverse effects. The goal of
therapy should be to achieve complete clearing of psoriatic lesions, particularly
during emotionally critical times, such as the commencement of school, puberty, and
Clinical Presentation of Psoriasis
QUESTION 1: M.M., a 35-year-old man, presents with complaints of several thick, well-defined
rest of M.M.’s physical examination and laboratory results are within normal limits.
Laboratory values and vitalsigns include the following:
Blood Urea Nitrogen (BUN), 13 mg/dL
What classic signs and symptoms suggestive of psoriasis are demonstrated by M.M.?
Most psoriatic lesions are asymptomatic, but not always. Pruritus, for example, is
noted in 50% of patients, and it can be severe.
18 Patients also report stinging or
19 The primary psoriatic lesion is a relapsing eruption of scaling
papules that rapidly coalesce or enlarge to form circumscribed, erythematous, scaly
plaques. The scale is adherent and silvery white and may reveal bleeding points
when removed, called the Auspitz sign. Scales can become extremely dense on the
scalp or macerated and dispersed in intertriginous areas.
The development of lesions of active psoriasis at the site of epidermal trauma is
known as the Koebner phenomenon. Scratch marks, sunburn, or surgical wounds may
heal, leaving psoriatic lesions in their place. The elbows, knees, scalp, gluteal cleft,
fingernails, and toenails are favored areas of involvement. Extensor surfaces are
affected more than the flexor surfaces, but the disease usually spares the palms, soles,
and face. Nail beds may show punctate pitting, profuse collections of keratotic
material, yellow-brown discoloration (“oil spot”), or onycholysis (nail plate
separation) in approximately 50% of patients.
20 Psoriatic arthritis is a seronegative
inflammatory arthritis that occurs in approximately 25% of all patients with
psoriasis, with combined features of both rheumatoid arthritis and the seronegative
Most patients (90%) have chronic localized disease (plaque type or psoriasis
vulgaris), but several other presentations exist.
3 The most severe form of the disease
is erythrodermic psoriasis, a condition of acute inflammatory erythema and scales
involving greater than 90% of the BSA. Pustular psoriasis is generally localized to
palms and soles, but there is also a generalized version. Both generalized pustular
psoriasis and erythrodermic psoriasis can be accompanied by systemic symptoms
(i.e., hyperthermia, tachycardia, edema, dehydration, shortness of breath) and can
have life-threatening consequences (i.e., hypovolemia, electrolyte imbalance,
septicemia) if not promptly treated.
21 Lesions of Guttate psoriasis are small, fine,
and typically lacks scales and looks more like intertrigo.
is rarely secondarily infected, because of the overexpression of the endogenous
peptides cathelicidins and β-defensins.
Systemic disorders that can have a causative association with psoriasis include
type 2 diabetes mellitus, Chron’s disease, metabolic syndrome, depression, and
2,15–17 This increased risk is thought to be caused by the
presence of endothelial activation, proinflammatory cytokines, and
2,17,21 Disease severity is also thought to be a factor, because psoriatic
patients with more severe conditions have an increased risk of metabolic, coronary
heart disease or stroke compared with those with milder forms of psoriasis.
M.M. presents with many classic signs of psoriasis, including symmetric,
distinctive, chronic, and erythematous plaques covered with silvery scales on the
extensor surfaces of the elbows and knees as well as the flexural surface of his arms
and legs. He also shows scalp involvement, but does not appear to have plaques on
his trunk or nail or systemic involvement. He exhibits the Auspitz sign and evidence
of the Koebner phenomenon because
his lesions worsened after skin trauma from the sunburn. His report of pruritus is
consistent with the presentation in 50% of patients.
potential causes of M.M.’s psoriatic exacerbation?
A thorough medical history may reveal a cause of exacerbations of psoriatic
lesions. Most patients report that hot weather, sunlight, and humidity help clear
psoriasis, whereas cold weather has an adverse effect on its course. Anxiety or
psychological stress is believed to contribute adversely. Viral or bacterial infections,
especially streptococcal pharyngitis, may precipitate the onset or flare-up of
psoriasis. Cuts, burns, abrasions, injections, and other trauma can also elicit the
development of lesions. Any drug that causes a skin eruption to develop can
exacerbate psoriasis via this response.
A number of drugs have been reported to exacerbate preexisting psoriasis, induce
psoriatic lesions on apparently normal skin in patients with psoriasis, or precipitate
psoriasis in persons with or without a family history of psoriasis (Table 41-1).
Antimalarial agents, such as chloroquine (taken by M.M.), may have an adverse
effect on the course of psoriasis and can cause exfoliative erythroderma.
Hydroxychloroquine, however, has not shared this association (except for one case
report) and usually induces a beneficial response in 75% of patients with psoriatic
It is preferred over chloroquine in patients with psoriasis who need
prophylactic treatment for malaria when both are effective against the particular
plasmodium species in the area (see Chapter 81, Parasitic Infections).
Lithium also can precipitate psoriasis and contribute to resistance to treatment
through its effects on cell kinetics (increase in circulating neutrophils, accelerated
neutrophil turnover, increased epidermal cell proliferation).
general contraindication, however, to lithium therapy. More intensive psoriasis
treatment can be used if these reactions occur, and lithium must be continued.
β-Blockers and some nonsteroidal anti-inflammatory drugs (NSAIDs) also can
precipitate a psoriasiform state.
22 Because both lithium and propranolol inhibit cyclic
adenosine monophosphate (cAMP), cyclic nucleosides may play a role in the onset
and clinical course of psoriasis. Chemotactic substances, including 12-
hydroxyeicosatetraenoic acid and leukotrienes, may accumulate in the epidermis of
some patients taking indomethacin, thereby precipitating psoriasis.
When compared with other NSAIDs, indomethacin may selectively inhibit
cyclooxygenase more than lipoxygenase pathways of arachidonic acid metabolism.
As a result, indomethacin may have a more significant adverse psoriatic effect than
other NSAIDs that have been reported to ameliorate psoriasis.
Flare-ups of pustular psoriasis also can be precipitated by withdrawal from
systemic corticosteroids or withdrawal from high-potency topical corticosteroids
that are applied under occlusion to large areas.
25 Because of this problem and
because fatalities have been associated with systemic corticosteroid use and
withdrawal, systemic corticosteroids are not routinely used to treat psoriasis.
Chloroquine prophylaxis, a Caribbean sunburn, and triamcinolone tachyphylaxis
probably all contributed to the exacerbation of M.M.’s psoriasis.
CASE 41-1, QUESTION 3: How would you categorize M.M.’s psoriasis?
The Self-Administered Psoriasis Area and Severity Index (SAPASI) is a
validated, structured instrument that can be used for patient assessment of psoriasis
severity and the response to therapy. It closely correlates with the standard clinician
assessment instrument, Psoriasis Area and Severity Index (PASI), which includes
quantification of the percentage of body involvement and severity of lesions.
PASI of 75 (a ≥75% decrease in PASI score) at 3 months from baseline has become
the most prominent marker to assess systemic agent efficacy (see
http://escholarship.org/uc/item/18w9j736, which is Dermatol Online J.
2004;10(2):7, for a good reference to teach someone the PASI and SAPASI).
Drugs Reported to Induce Psoriasis
Antimicrobial agents Amoxicillin, ampicillin, imiquimod, penicillins, sulfonamides, terbinafine,
tetracyclines, vancomycin, voriconazole
Anti-inflammatory drugs Corticosteroids (after withdrawal), NSAIDs (indomethacin, salicylates),
Antimalarial agents Chloroquine, hydroxychloroquine
Cardiovascular drugs Acetazolamide, amiodarone, angiotensin-converting enzyme inhibitors
(enalapril, lisinopril), β-blockers (atenolol, metoprolol, propranolol, timolol),
calcium channel blockers (dihydropyridines, diltiazem, verapamil), clonidine,
digoxin, gemfibrozil, quinidine
-antagonists Cimetidine, ranitidine
Hormones Oxandrolone, progesterone
Lithium carbonate, venlafaxine, fluoxetine, carbamazepine, olanzapine,
gabapentin, oxcarbazepine, tigabine, valproic acid, zaleplon
NSAIDs, nonsteroidal anti-inflammatory drugs.
Source: Kim GK, Del Rosso JQ. Drug-provoked psoriasis: is it drug induced or drug
aggravated? J Clin Aesthet Dermatol. 2010;3:32–38; Basavaraj KH et al. The role of
drugs in the induction and/or exacerbation of psoriasis. Int J Dermatol.
2010;49:1351; Facts & Comparisons eAnswers. Accessed August 21, 2015, with
The National Psoriasis Foundation has released a clinical consensus statement on
the classification of severity of disease. Rather than using a mild (less than 5% BSA
affected) to moderate (5%–10%) to severe (greater than 10% BSA affected)
classification system, the statement recommends two categories for patients: those
who are candidates for topical therapy (less than 5% of BSA affected) and those who
are candidates for systemic or phototherapy (more than 5% of BSA affected).
M.M. would be categorized as having mild psoriasis and is a candidate for topical
therapy because less than 5% of his BSA is currently affected by psoriasis.
Many topical and systemic therapeutic agents are available, varying from simple
topical emollients to systemic, highly potent immunosuppressant drugs for more
recalcitrant conditions. Often, treatment modalities are chosen on the basis of disease
severity, cost, convenience, and patient response. Patients with mild disease can
generally be treated with topical therapy (Table 41-2). Patients with psoriasis
covering more than 5% of the body require more specialized systemic or
phototherapy treatment programs (Table 41-3). Nonpharmacologic treatment is also
very important and can range from spa therapy to support groups.
CASE 41-1, QUESTION 4: What role can emotional support play in the comprehensive management of
Psoriasis is often more emotionally or psychologically disturbing than is
recognized, and it may cause a reluctance from patients to participate in sports and
other outdoor activities that may expose their skin to sunlight. Although exposure to
sunlight helps most patients with psoriasis, there is an unwillingness to sunbathe if
the lesions can be seen. Furthermore, if the psoriatic lesions become pruritic and are
scratched, there can be further deterioration at the site. Many patients alter their
lifestyles or use nontraditional medications and modalities, often in desperation.
Emotional support should begin with explanation of the psoriatic condition. M.M.
needs to be reassured that many other people have the same condition, that the
disorder is not contagious or fatal, and that it can be controlled, although no cure
29 Patients usually are comforted in the knowledge that a wide range of
treatments are available. Psychological encouragement and support are justified and
make it easier for the patient to conscientiously apply messy topical treatments or to
Topical Agents for the Treatment of Psoriasis (Mild to Moderate; <5%Body
Treatment Modality Advantages Disadvantages
Emollients Basic adjunct for all treatments; safe,
inexpensive, reduces scaling, itching,
Keratolytics (salicylic acid, urea,
α-hydroxy acids [i.e., glycolic
Reduce hyperkeratosis; enable other
topical modalities to better penetrate;
Provide minimal relief individually;
nonspecific; salicylism (tinnitus,
nausea, vomiting) with salicylic acid if
Topical corticosteroids Rapid response; control inflammation
and itching; best for intertriginous
areas and face; convenient, not
messy; mainstay topical treatment
Temporary relief; less effective with
continued use (tachyphylaxis occurs);
withdrawal can produce flare-ups;
atrophy, telangiectasia, and striae with
continued use after skin returns to
normalized state; expensive; adrenal
Coal tar Particularly effective for “flaky” scalp
lesions; newer preparations are more
cosmetically appealing; efficacy
enhanced in combination with UVB
Effective only for mild psoriasis or
scalp psoriasis; inconvenient with
difficult application; stains clothing
and bedding, not skin; strong smelling;
folliculitis and contact allergy
(bronchospasm in atopic patient with
asthma after inhalation of vapor);
Anthralin Effective for widespread, refractory
plaques; produces long remissions;
preferred; enhanced efficacy in
combination with UVB (i.e., Ingram
Purple-brown staining (skin, clothing,
and bath fixtures); irritating to normal
skin and flexures; careful application
regimen) Calcipotriene and calcitriol As effective as topical corticosteroids,
although slower onset, without longterm corticosteroid adverse effects;
Slow onset; expensive; potential
(hypercalcemia); irritant dermatitis on
face and intertriginous areas;
contraindicated during pregnancy
Tazarotene Extended response; convenient
formulation); maintenance therapy;
effective on scalp and face; used in
Slow onset; local irritation and
pruritus; teratogenic (adequate
Ultraviolet B (UVB) Effective as maintenance therapy;
eliminates problems of topical
Expensive; office-based therapy;
sunburn (exacerbates psoriasis);
Agents for the Treatment of Severe Psoriasis (>5%Body Surface Area
Treatment Modality Advantages Disadvantages
Psoralens plus UVA (PUVA) 80% efficacy; “suntan” effect is
Time-consuming; expensive, officebased therapy (restrictive); sunburn
(exacerbates psoriasis); photoaging;
both nonmelanoma skin cancer and
melanoma; contraindicated during
Acitretin Not as effective as other systemic
agents; efficacy enhanced if given
with PUVA or UVB (i.e., RePUVA
or ReUVB); less hepatotoxic than
Teratogenic (contraception required);
contraindicated with liver or renal
dysfunction, drug or alcohol abuse,
hypertriglyceridemia, hypervitaminosis
Methotrexate Effective for both skin lesions and
arthritis, as well as psoriatic nail
Hepatotoxicity (liver biopsy may be
indicated); bone marrow toxicity; folic
acid protects against stomatitis (but
not against hepatic or pulmonary
contraindicated during pregnancy and
lactation, drug or alcohol abuse; use
with caution during acute infections
Cyclosporine Toxicities and short-lived remissions;
used in patients with extensive disease
who are unresponsive to other agents;
pathophysiology and increasing
increasing role in rotational therapy to
discontinued); increased risk of skin
cancer, lymphomas, and solid tumors;
phototoxic; contraindicated during
pregnancy and lactation, and with
induce remissions hyperkalemia, acute infections
Specific, targeted therapy; effective
for both moderate-to-severe skin
lesions and arthritis; maintains
Expensive; parenteral therapy (often
administered in an office-based
practice); long-term safety unknown;
increased risk of serious infections
CASE 41-1, QUESTION 5: What topical corticosteroid therapy is appropriate for M.M.?
Topical corticosteroids, the most widely prescribed treatment for psoriasis, are
effective in the treatment of psoriasis because of their anti-inflammatory, antimitotic,
immunosuppressant, and antipruritic properties.
25,30,31 These properties are explained
by a reduction in phospholipase A2
, DNA synthesis, and epidermal mitotic activity,
as well as their vasoconstrictive actions. They provide prompt relief, and patients
areas, or for maintenance therapy.
32 However, topical corticosteroids can, in a
process called tachyphylaxis, also become less effective with continued use, and
long-term use after the skin has returned to a normalized state leads to typical
corticosteroid adverse effects (atrophy, telangiectasia, and striae). Thin-skinned
areas (i.e., facial and intertriginous) are particularly susceptible.
Psoriasis is generally a relatively corticosteroid-resistant disease; therefore, the
more potent corticosteroids are frequently necessary, often with occlusion (e.g.,
plastic food wrap on top of the topical corticosteroid-treated area) (see Table 39-8
i n Chapter 39, Dermatotherapy and Drug-Induced Skin Disorders, for a listing of
topical corticosteroids by potency). Less-potent agents are more appropriate in
intertriginous areas, on the face, and for maintenance. Potent fluorinated
corticosteroid preparations should be used cautiously and only for short periods on
the face and flexures, if at all. Potent topical corticosteroids may clear psoriasis in
25% of patients in 3 to 4 weeks, with 75% clearing in 50% of treated patients.
Intermittent dosing or “pulse therapy” with several weeks between successive
courses appears to yield the best long-term results and minimizes tachyphylaxis and
adverse effects. An additional drawback of chronic corticosteroid therapy is an
associated acute flare-up of psoriasis when corticosteroid therapy is terminated.
Continuous application for more than 3 to 4 weeks should be discouraged in patients
with psoriasis, and systemic corticosteroids have no place in therapy.
corticosteroids occasionally can cause a reversible suppression of the hypothalamic–
pituitary–adrenal (HPA) axis, as indicated by a decrease in the morning plasma
33 For anything more extensive than mild disease and short duration of
therapy, topical corticosteroids are best used in an adjunctive role. During a flare-up,
corticosteroids help reduce inflammation, redness, and irritation and prepare the
involved area for initiation of other potentially irritating, but more appropriate,
maintenance topical treatments (e.g., coal tar, anthralin, calcipotriene, or tazarotene).
A short course of a potent topical corticosteroid is appropriate for this flare-up of
erythematous plaque psoriasis in M.M. This will help reduce inflammation, redness,
and irritation before possible initiation of more appropriate chronic topical
treatments, such as calcipotriene, coal tar, or anthralin with ultraviolet B (UVB).
Topical corticosteroids also may continue to be useful for M.M.
on the face and flexures, where the alternative topical agents are poorly tolerated.
His scalp psoriasis can be treated with corticosteroid preparations in gels, lotions,
or aerosol sprays. This will allow for a more effective treatment of scaling and
pruritus using an agent such as coal tar shampoo lathered into the scalp for 5 to 10
The response to once- or twice-daily corticosteroid application is as effective as
or better than that observed with more frequent regimens (owing to a corticosteroid
reservoir effect) and is much less expensive. M.M. should apply a topical
corticosteroid preparation after a bath, at bedtime with occlusion, and possibly again
during the day without occlusion. As the lesions subside, occlusion should be
decreased or omitted, emollient use should increase, and the corticosteroid potency
should decrease. After lesions have flattened, the topical corticosteroid products can
be continued intermittently (e.g., 1–2 weeks on, 1–2 weeks off; or on alternate days
ALTERNATIVE TOPICAL TREATMENTS
Effective alternative topical therapies available for patients with localized, mild
psoriasis include crude coal tar, anthralin, calcipotriene, calcitriol, and tazarotene.
Although anthralin has irritating properties and both coal tar and anthralin generally
stain clothing and skin and are somewhat inconvenient to apply, their efficacy is well
established and may be an option to consider for initial management. Tachyphylaxis
does not occur with chronic use of any of these alternative agents. Once the
is ineffective, calcipotriene ointment applied twice daily or tazarotene gel applied
once daily is effective in treating flare-ups and maintaining remission. Ointment
vehicles are favored because they help moisturize the plaques (in contrast to creams,
which dry the plaques further). Also, moisturizers or emollients are often helpful for
Crude coal tar is a complex mixture of thousands of hydrocarbon compounds.
a time-honored modality for treating psoriasis. It affects psoriasis by enzyme
inhibition and antimitotic action (antiproliferative and anti-inflammatory).
efficacy of the combination of tar and UVB light (i.e., Goeckerman regimen) led to its
increased popularity beginning in the 1920s. Tar preparations of 2% to 10% are
processed as creams, ointments, lotions, gels, oils, shampoos, and coal tar solution.
Newer purified preparations, using refined coal tar, are less messy and more
cosmetically acceptable, but perhaps not as effective.
patients with mild-to-moderate disease, and tar shampoos are useful for psoriasis of
the scalp. The potential severity of adverse drug effects from topical tar products is
less than that from anthralin and much less than that from topical corticosteroids.
Because tar, in every form, is messy, stains the skin, has an odor, and is low potency
compared with anthralin, it has been relegated to second-line therapy for most
patients, despite its moderate price and newer, more cosmetically appealing
Tar preparations generally are used once or twice daily, and a bedtime application
(as a shampoo or cream overnight) is particularly useful in psoriasis of the scalp.
Patients should be warned about the staining properties of tar on clothing and
bedding. Other adverse effects include photosensitivity, acneiform eruptions,
folliculitis, and irritation dermatitis. Care should be taken to avoid use of tar on the
face, flexures, and genitalia and with inflammatory psoriasis because of tar’s irritant
The polyaromatic hydrocarbons contained in coal tar may be metabolized to active
carcinogens by epidermal microsomal enzymes. The incidence of hyperkeratotic
lesions, including squamous cell carcinoma, is increased after prolonged industrial
exposure to tar; however, extensive reviews of patients who have used tar
preparations in psoriasis have not revealed an increased risk of carcinom
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