A 33-year-old woman presents with uncontrolled psoriasis for 20 years. In addition to the plaque psoriasis (Figure 158-1), she has inverse psoriasis (Figure 158-2). Topical ultrahigh-potency steroids and topical calcipotriene have not controlled her psoriasis. The options for phototherapy and systemic therapy were discussed. The patient chose to try narrowband UVB treatment in addition to her topical therapy.
Typical plaque psoriasis on the elbow and arm. (Reproduced with permission from Richard P. Usatine, MD.)
Inverse psoriasis in the inframammary folds of the patient in Figure 158-1. This is not a Candida infection. (Reproduced with permission from Richard P. Usatine, MD.)
Psoriasis is a chronic inflammatory papulosquamous and immune-mediated skin disorder. It is also associated with joint and cardiovascular comorbidities. Psoriasis can present in many different patterns from the scalp to the feet and cause psychiatric distress and physical disabilities. It is crucial to be able to identify psoriasis in all its myriad presentations so that patients receive the best possible treatments to improve their quality of life and avoid comorbidities.
Psoriasis affects approximately 1% to 8% of the world population.1 In the United States, 3.7% of non-Hispanic white patients have psoriasis compared to 2.0% of African American patients and 1.6% of Hispanic patients.2 Psoriasis affects men and women equally, but occurs earlier in women. While psoriasis can begin at any age, it has two peak incidences: ages 20–29 and 50–59 among women and ages 30–39 and 60–69 among men.1
ETIOLOGY AND PATHOPHYSIOLOGY
Psoriasis is an immune-mediated disease in which T cells play a pivotal role. Evidence suggests that foreign antigens in the skin first trigger antigen-presenting cells to release cytokines, including interleukin (IL)-23 and IL-1β. These cytokines trigger dermal T cells and helper T cells that release more cytokines, including IL-17 and tumor necrosis factor (TNF)-α, promoting keratinocyte hyperproliferation. This inflammatory immune response attracts more immune cells to the skin, which release further cytokines and chemokines. An escalated positive feedback loop results in psoriatic plaques. Greater understanding of the pathophysiology has led to the development of effective treatments targeted at TNF-α, IL-17, and IL-23.
Table 158-1 lists the factors that trigger and exacerbate psoriasis.
TABLE 158-1Factors that Trigger and Exacerbate Psoriasis ||Download (.pdf) TABLE 158-1 Factors that Trigger and Exacerbate Psoriasis
Physical trauma to the skin (Koebner phenomenon)
Cold dry weather
Sun or hot weather
Infections (including strep throat and HIV)
Medications (e.g., biologics, ACE-inhibitors, corticosteroids, lithium, antimalarials, β-blockers, NSAIDs)
Family history: 60% of patients report a family history of psoriasis.3 The psoriasis-susceptibility (PSORS) locus on chromosome 6p21 is a major genetic source of susceptibility to psoriasis.4 Other identified loci include IL-12 and IL-23 related genes, which code for the interleukin receptors. Mutations in the IL36RN gene have been found in patients with generalized pustular psoriasis.
Obesity: Obesity is associated with more severe psoriasis (odds ratio [OR] mild psoriasis 1.46 (95% confidence index [CI] 1.17–1.82) vs severe psoriasis 2.23 (95% CI 1.63–3.05).5
Smoking and environmental smoke: Current and former smoking are associated with psoriasis (OR 1.78, 95% CI 1.52–2.06) with a dose-dependent effect on incidence.6
Alcohol use: A large, prospective study found an increased risk of developing psoriasis among women who regularly drank alcohol (relative risk [RR] 1.72, 95% CI 1.15–2.57).7 Alcohol use is associated with increased risk of psoriasis among both women and men.
Medications: Many medications are associated with worsening psoriasis or a psoriasis-like skin changes, including beta-blockers, lithium, and anti-malarial drugs.
Psoriasis manifests in many forms and locations. These nine categories were used to describe psoriasis in a consensus statement of the American Academy of Dermatology (AAD)8:
Plaque (80% of patients with psoriasis)9 (Figures 158-1 and 158-3).
Scalp psoriasis (Figure 158-4).
Guttate psoriasis (Figure 158-5).
Inverse psoriasis (Figures 158-2 and 158-6).
Palmar-plantar psoriasis (Figure 158-7). Also known as palmoplantar psoriasis.
Erythrodermic psoriasis (Figure 158-8).
Pustular psoriasis—localized and generalized (Figure 158-9).
Nail psoriasis (Figure 158-10) (see Chapter 203, Psoriatic Nails).
Psoriatic arthritis (Figure 158-11).
Well-demarcated plaques of plaque psoriasis in a 44-year-old man with severe psoriasis and psoriatic arthritis. (Reproduced with permission from Richard P. Usatine, MD.)
Scalp psoriasis visible at the hairline. (Reproduced with permission from Richard P. Usatine, MD.)
Two cases of guttate psoriasis that started 2 weeks after strep pharyngitis. A. Note the typical drop-like (guttate) lesions on the arm of this 11-year-old girl. B. The salmon patches of guttate psoriasis in a 7-year-old boy with prominent neck, ear, and scalp involvement. (Reproduced with permission from Richard P. Usatine, MD.)
Inverse psoriasis in the axilla of this middle-aged woman. There is considerable erythema and very little scale. Prior to this visit her condition was misdiagnosed as fungal in origin. (Reproduced with permission from Richard P. Usatine, MD.)
A. Palmoplantar psoriasis with pustulosis that started 3 months ago on the hands of a 62-year-old woman. B. Note the erythema, scale, brown macules (mahogany spots), and pustules that are typical of this condition. This is considered to be a localized form of pustular psoriasis. (Reproduced with permission from Richard P. Usatine, MD.)
Erythrodermic psoriasis covering most of the body surface. (Reproduced with permission from Richard P. Usatine, MD.)
Pustular psoriasis on the back that occurred when oral prednisone was stopped. (Reproduced with permission from Jack Resneck, Sr., MD.)
Nail pitting from psoriasis. (Reproduced with permission from Richard P. Usatine, MD.)
Psoriatic arthritis that has become crippling to this 44-year-old man. The shortening of the fingers fits the psoriatic arthritis mutilans subtype.(Reproduced with permission from Richard P. Usatine, MD.)
The most common areas involved are listed in Table 158-2. Patients frequently present with more than one subtype.
TABLE 158-2The Most Common Locations of Lesions in Patients with Psoriasis9 ||Download (.pdf) TABLE 158-2 The Most Common Locations of Lesions in Patients with Psoriasis9
|Location ||% of Psoriasis Patients |
|Scalp ||42 |
|Elbows and/or knees ||35 |
|Limbs and/or legs ||35 |
|Trunk ||19 |
|Face ||11 |
|Intragluteal/perianal ||10 |
|Genital ||7 |
|Palms and/or soles ||7 |
|Groin ||3 |
Plaques tend to be symmetrically distributed along the elbows, knees, and other extensor surfaces. Extent can vary from localized to widespread involvement. Most patients experience some pruritus.
White scale on an erythematous raised base with well-demarcated borders (see Figures 158-1 and 158-3).
Silvery scale with hyperpigmentation may be seen in patients with darker skin (Figures 158-12 and 158-13).
Plaques can appear in different colors including hypopigmented (Figure 158-14) and silvery gray (Figure 158-15). A tricolored presentation occurs when the inflammation leads to leukoderma or when there is coexisting vitiligo (Figure 158-16).
The thickness and extent of the scale is variable (see Figure 158-15).
A positive Auspitz sign is when peeling of a plaque's scale produces pinpoint bleeding on the underlying skin.
The plaques can be found from head to toe including the penis (Figure 158-17).
Plaques can be annular with central clearing (Figure 158-18).
When plaques occur at a site of skin trauma, it is known as the Koebner phenomenon (Figure 158-19).
Plaque psoriasis with silvery scale on a black man. (Reproduced with permission from Richard P. Usatine, MD.)
Psoriasis on the knee of a Hispanic man showing postinflammatory hyperpigmentation. (Reproduced with permission from Richard P. Usatine, MD.)
Plaque psoriasis with hypopigmentation in this 12-year-old obese boy. (Reproduced with permission from Richard P. Usatine, MD.)
Thick plaque psoriasis covering the lower legs of this obese man. Note the silver gray color to his plaques. (Reproduced with permission from Richard P. Usatine, MD.)
Plaque psoriasis that has caused hypopigmentation in a band across the back. His original skin color is brown so that the brown, white, and pink colors produce the appearance of Neapolitan ice cream. (Reproduced with permission from Richard P. Usatine, MD.)
Plaque psoriasis on the penis, covering the glans and part of the shaft. (Reproduced with permission from Richard P. Usatine, MD.)
Plaque psoriasis with an annular configuration. (Reproduced with permission from Richard P. Usatine, MD.)
Linear distribution of psoriasis on the arm secondary to the Koebner phenomenon. (Reproduced with permission from Richard P. Usatine, MD.)
Plaque on the scalp that may be seen at the hairline and around the ears (see Figure 158-4).
The thickness and extent of the plaques are variable, as seen in plaque psoriasis.
Small round plaques that resemble water drops (guttate means like a water drop) (Figure 158-20).
Classically described as occurring after strep pharyngitis or another bacterial infection. More often occurs in children and young adults without a prior history of psoriasis.
Typical distribution includes the trunk and extremities, but may include the face and neck (Figure 158-21).
Guttate psoriasis in a 17-year-old young man following an episode of strep pharyngitis. (Reproduced with permission from Richard P. Usatine, MD.)
This young boy developed guttate psoriasis after an upper respiratory infection. A. Note the droplike pink plaques on the face and neck. B. Droplike plaques on the arms and trunk. (Reproduced with permission from Richard P. Usatine, MD.)
Found in the intertriginous areas of the axilla, groin, and inframammary and intergluteal folds (Figures 158-2, 158-6, and 158-22). It can also be seen below the pannus or within adipose folds in obese individuals.
The term inverse refers to the fact that the distribution is not on extensor surfaces but in areas of body folds.
Lesions are flat and well-demarcated and have little to no visible scale.
Color is generally pink to red but can be hyperpigmented in dark-skinned individuals.
Inverse psoriasis in the inguinal area. This was mistaken for tinea cruris for a long time. (Reproduced with permission from Richard P. Usatine, MD.)
Palmar-plantar (palmoplantar) psoriasis:
Psoriasis that mainly occurs on the plantar aspects of the hands and feet (palms and soles) (Figure 158-23), but can involve other parts of the hands and feet.
Patients with this type of psoriasis often experience severe foot and hand pain that can impair walking and other daily activities of living. Hand involvement can result in pain with many types of work.
Lesions may be plaque-like, vesicular, or pustular (Figure 158-24). Brown macules or flat papules ("mahogany spots") are characteristic of palmar-plantar psoriasis, but not uniformly present. Exfoliation of the skin can occur.
Palmar-plantar psoriasis that was biopsy proven. Note the widespread erythema and scale that could be mistaken for tinea pedis and tinea manus. The patient does not have pustules or mahogany spots, but those lesions are often not present in palmar-plantar psoriasis. (Reproduced with permission from Richard P. Usatine, MD.)
Palmar-plantar psoriasis with extensive pustules and mahogany spots. (Reproduced with permission from UTHSCSA dermatology.)
Erythrodermic psoriasis is widespread and erythematous, covering most of the skin (Figure 158-25).
Morphologically, it can have plaques and erythema or the erythroderma can appear with the desquamation of pustular psoriasis.
Widespread distribution can impair the important functions of the skin, and this can be a dermatologic urgency requiring hospitalization and IV fluids. Chills, fever, tachycardia, and orthostatic hypotension are all signs that the patient may need hospitalization.
Erythrodermic psoriasis in a 45-year-old man. Note the extensive exfoliation of the skin along with the deep erythema. (Reproduced with permission from Richard P. Usatine, MD.)
Pustular psoriasis comes in localized and generalized types. One example of the local type is pustular psoriasis on the feet (see Figure 158-24).
In the generalized type, the skin initially becomes fiery red and tender and the patient experiences constitutional signs and symptoms such as headache, fever, chills, arthralgia, malaise, anorexia, and nausea (Figure 158-26). The desquamation that occurs in the generalized form can impair the important functions of the skin, predisposing to dehydration and sepsis. This is a dermatologic emergency requiring hospitalization and IV fluids, preferably in an ICU or monitored bed with good nursing care.
Typical distribution: Flexural and anogenital (Figure 158-27). Less often, facial lesions occur. Pustules may occur on the tongue and subungually, resulting in dysphagia and nail shedding, respectively.
Time course: Within hours, clusters of non-follicular, superficial 2- to 3-mm pustules may appear in a generalized pattern. These pustules coalesce within 1 day to form lakes of pus that dry and desquamate in sheets, leaving behind a smooth erythematous surface on which new crops of pustules may appear. These episodes of pustulation may occur for days to weeks, causing the patient severe discomfort and exhaustion. Upon remission of the pustular component, most systemic symptoms disappear; however, the patient may be in an erythrodermic state or may have residual lesions.1
Generalized pustular psoriasis in a 47-year-old man with fever, exfoliation, and dehydration. This is the twentieth time for this patient in his life. His siblings also get severe generalized pustular psoriasis. (Reproduced with permission from Richard P. Usatine, MD.)
Localized pustular psoriasis in the groin. (Reproduced with permission from Jeffrey Meffert, MD.)
Nail involvement in psoriasis can lead to pitting, onycholysis, subungual keratosis, splinter hemorrhages, oil spots, and nail loss (see Figure 158-10 and Chapter 203, Psoriatic Nails).
Psoriatic arthritis (PsA) is an inflammatory seronegative spondyloarthropathy that presents as stiffness, pain, and swelling of the joints and surrounding soft tissues. Stiffness is worse in the morning and after prolonged inactivity, lasting more than 30 minutes. Most patients have a polyarticular arthritis involving the hands, feet, and knees, which can resemble rheumatoid arthritis.10 However, the spectrum of PsA is variable and can involve axial to peripheral disease. Distal interphalangeal joint (DIP) involvement is a classic finding, but DIP predominance is present in the minority of cases. The fingers may be swollen like sausages, which is called dactylitis (Figure 158-28). See Table 97-1 in Chapter 97, Arthritis Overview, for a description of the five types of psoriatic arthritis.
Hand involvement can be disabling (see Figure 158-11). X-rays should be ordered when a person with psoriasis has joint pains suggesting psoriatic arthritis. Typical findings are juxtaarticular erosions, bony proliferation, and osteolysis, including the "pencil in cup" deformity (Figure 158-29).
There may be inflammation at the insertion of tendons onto bone (enthesopathy). This may occur at the Achilles tendon.
Nail involvement is common and correlates with the severity of arthritis.
Patients with psoriatic arthritis need to be treated earlier with systemic agents (methotrexate or biologics) to prevent permanent joint damage and disability, often in conjunction with a rheumatologist.
Dactylitis with sausage-shaped fingers in this middle-aged woman with plaque psoriasis and psoriatic arthritis. Note the nail involvement along with distal interphalangeal joint involvement. (Reproduced with permission from Richard P. Usatine, MD.)
Radiograph showing the pencil-in-cup deformity at the distal interphalangeal joint of the second and third digits. (Reproduced with permission from Richard P. Usatine, MD.)
Moderate-to-severe disease is defined by psoriasis of the palms, soles, head and neck, or genitalia, and in patients with more than 5% body surface area (BSA) involvement.11 A person's palm with fingers extended and abducted is approximately 1% BSA.
Another grading system for severity uses percent BSA:
Mild: Up to 3% BSA
Moderate: 3% to 10% BSA
Severe: >10% BSA
Patients with psoriatic arthritis may have limited skin disease but require more aggressive systemic therapies.
Note that palmoplantar psoriasis is considered moderate-to-severe even if the BSA involved is not above 5% (Figure 158-30).
Palmoplantar psoriasis in a 31-year-old man with erythema, pustules, and lakes of pus. Note the typical brown macules that are called mahogany spots. High-potency topical steroids did not help at all. It is painful for him to walk and systemic therapy has just been started. This is a localized form of pustular psoriasis. (Reproduced with permission from Jeff Meffert, MD.)
Laboratory studies are rarely needed for diagnosis. A punch biopsy or scoop shave is used for evaluating atypical cases. For pustular psoriasis, a 4-mm punch around an intact pustule is preferred (Figure 158-31). A KOH prep is useful for ruling out tinea. A complete blood count (CBC) with differential, renal and hepatic function testing, electrolytes, and blood and skin cultures should be obtained in cases of erythroderma or acute generalized pustular psoriasis.
Pustular psoriasis in a 41-year-old woman. A 4-mm punch biopsy including at least one pustule helped to confirm the clinical diagnosis. The patient was stable for outpatient treatment and was started on cyclosporine and acitretin together with the plan to stop the cyclosporine once the pustules have cleared. A. Arm involvement. B. Close-up of pustules on the leg. (Reproduced with permission from Robert T. Gilson, MD.)
Plain films should be ordered when a person with psoriasis has joint symptoms suggesting psoriatic arthritis (see Figure 158-29). Early psoriatic arthritis often has no findings on plain films, but if history and physical exam suggest the diagnosis, one should not wait for irreversible visible joint damage to initiate therapy.
Cutaneous T-cell lymphoma (CTCL) can have plaques that resemble psoriasis. In most cases of psoriasis, the distribution and nail changes will help to differentiate between these diseases. Plaque-type CTCL tends to be more central and truncal, whereas psoriasis often involves the extremities along with the trunk. If needed, a punch biopsy can help to differentiate between these two conditions (see Chapter 180, Cutaneous T- Cell Lymphoma).
Lichen planus is another papulosquamous disease. Classic findings include polygonal purple and pink pruritic papules/plaques. Patients may have fine white lines on the buccal mucosa ("Wickham striae"). Lichen planus occurs on flexor surfaces and around the wrists and ankles rather than the elbows and knees. (see Chapter 160, Lichen Planus).
Lichen simplex chronicus is the end result of repeated scratching from a variety of causes, manifesting as a hyperkeratotic plaque with lichenification. It is typically found on the posterior neck, ankle, wrist, or lower leg where the patient can reach and scratch. There is usually more lichenification than thick scale, and it is always pruritic (see Chapter 155, Psychocutaneous Disorders).
Nummular eczema presents with coinlike plaques ranging from 1 to 10 cm in diameter, typically on the legs. Lesions are usually not as thick as the plaques of psoriasis, have less scale, and are more pruritic. Nummular eczema may have vesicles and bullae. The face and scalp are spared (see Chapter 151, Atopic Dermatitis).
Pityriasis rosea is a self-limited process that has papulosquamous plaques and may be confused with guttate psoriasis. These plaques are less keratotic, have a fine collarette of scale, and follow skin lines. Pityriasis rosea frequently has a herald patch (see Chapter 159, Pityriasis Rosea).
Seborrheic dermatitis of the scalp can closely resemble psoriasis of the scalp, especially when it is severe. Psoriasis generally has thicker plaques on the scalp, and the plaques often cross the hairline. Seborrhea and psoriasis can both involve the ear. Both conditions respond to topical steroids (see Chapter 157, Seborrheic Dermatitis).
Syphilis is the great imitator, and secondary syphilis can have a papulosquamous eruption similar to guttate psoriasis. Secondary syphilis often involves the palms and soles, and the rapid plasma reagin (RPR) will be positive (see Chapter 225, Syphilis).
Tinea corporis or cruris can resemble inverse psoriasis in the intertriginous areas, as both conditions tend to have erythema and thinner plaques without central clearing in these regions. Tinea corporis in non-intertriginous areas presents with annular plaques with central clearing and peripheral scale. Psoriasis can do this, as seen in Figure 158-18. Tinea corporis usually does not have as many plaques as psoriasis, but a KOH preparation can be obtained if needed (see Chapter 144, Tinea Corporis). Onychomycosis can be confused with psoriatic nail changes, and a nail clipping may be sent for fungal culture to distinguish this from psoriasis (see Chapter 201, Onychomycosis). However, it is possible to have a fungal infection in nails affected by psoriasis.
Cutaneous candidiasis appears similar to inverse psoriasis when found in intertriginous areas, but often has satellite lesions (see Chapter 142, Candidiasis).
Reactive arthritis (see Chapter 161, Reactive Arthritis) is a noninfectious acute oligoarthritis that occurs in response to an infection, most commonly in the GI or urogenital tract. Patients present 1 to 4 weeks after the triggering infection, with joint pain in asymmetric large joints, eye disease such as conjunctivitis, and skin changes including erythema nodosum, keratoderma blennorrhagicum, and circinate balanitis. Diagnosis is based on the clinical presentation plus evidence of associated infection. The skin lesions closely resemble psoriasis, so the diagnosis depends on the constellation of the clinical involvement and the history.
When caring for a patient with psoriasis, physicians should consider goals of treatment, disease severity, disease pattern, response to prior treatments, patient comorbidities, family planning, and individual preferences. Patients' perception of their disease and expectations for improvement are as important as the following evidence-based recommendations. Some patients are willing to live with some continued skin changes rather that start systemic treatment, whereas others desire maximal therapy with a goal of 100% clearance. Further, patients may prefer different vehicles of topical treatment or the convenience of some regimens compared to others. One of the most important factors in successful treatment is patient adherence. The most effective treatment is often the one that is most acceptable to the patient.
All patients should apply daily emollients to keep skin soft, thereby limiting pruritus and irritation. Address lifestyle changes that can affect psoriasis, including:
Avoid or minimize alcohol use.
Weight loss for obese patients.
Address depression and offer stress management techniques.
Avoid known precipitants.
Choice of topical vehicles:
An ointment has a petrolatum base and will penetrate thick scale best.
An emollient cream has some of the advantages of an ointment but is cosmetically more appealing to patients who find a basic ointment to be too greasy.
Some patients prefer cream to avoid the oily feel of ointment. The most effective vehicle is the one the patient will use.
Lotions and foams are good for hair-bearing areas when some moisturizing is desired.
Steroid solutions work well for psoriasis of the scalp.
New foam and spray preparations have rapid absorption and are cosmetically appealing. These tend to be more expensive at this time.
Very potent topical corticosteroids are the single most effective topical agent for psoriasis. A meta-analysis of 34 randomized controlled trials (RCTs) found that very potent corticosteroids applied twice daily resulted in 78.2% of patients reporting clear or nearly clear disease.12 SORⒶ
Topical vitamin D analogs available include calcipotriene, calcitriol, and tacalcitol. They are as effective as potent corticosteroids, but are more likely to cause side effects including irritation and burning.13 SORⒶ Calcitriol may be less irritating than calcipotriene.
Topical vitamin D analogs have slower onset of action compared to topical corticosteroids, but result in longer disease-free periods after cessation.14
Combined treatment with topical vitamin D and potent corticosteroid is more effective than either alone and is as well tolerated as potent corticosteroids.13 SORⒶ Although this is available in combination products, it is less expensive to prescribe each component separately in their generic formulations.
Tazarotene is a topical retinoid applied once daily with comparable efficacy to vitamin D analogs.13 SORⒷ Applying in combination with a corticosteroid is recommended to improve efficacy and reduce irritation. A double-blind RCT comparing a combination of halobetasol propionate 0.01% and tazarotene 0.045% lotion to either component alone found increased efficacy and reduced irritation with the combination compared to tazarotene alone.15
Topical calcineurin inhibitors are less effective than potent topical steroids, but are useful for sensitive areas such as the face and skin folds due to increased risk of irritation and skin atrophy from topical vitamin D and corticosteroids, respectively.11,13 SORⒷ
Maintenance with weekend potent corticosteroid use, with or without weekday topical vitamin D, increases likelihood of remission.16 SORⒷ
UV-based treatment with narrow-band UVB (NB-UVB) or psoralen-UVA (PUVA) are highly effective, safe treatments for widespread psoriasis or psoriasis not responding to topical therapy. A meta-analysis of UV-based therapies found that PUVA resulted in clearance rates of 79% (95% CI 69–88) and NB-UVB resulted in clearance rates of 68% (95% CI 57–78).17 SORⒶ
Narrow-band UVB is more effective than broadband UVB with fewer side effects.17,18 SORⒷ
Evidence is controversial regarding the relative efficacy of NB-UVB directly compared to PUVA.18 A systematic review of 5 low-quality, head-to-head RCTs found that oral PUVA resulted in longer-lasting clearance and required fewer treatments compared to NB-UVB, but had similar relapse rates at 6 months.18 SORⒷ
NB-UVB offers several advantages over PUVA, including lack of need for pretreatment with a photosensitizing medication, lower long-term risk of skin cancer, and safety in pregnancy.11 Therefore, it may be considered as a first choice, with PUVA reserved for treatment failures.
PUVA is associated with increased risk of squamous (SCC) and basal cell carcinomas. A 30-year prospective cohort study of 1380 patients treated with PUVA found that undergoing more than 350 treatments greatly increased risk of developing SCC (incidence rate ratio 20.9, 95% CI 14.0–31.1).19
Targeted phototherapy, with high energy 308-nm excimer laser, delivers UV radiation to localized areas of skin. A trial of 124 patients receiving twice weekly treatments for 10 weeks found that 84% of patients (95% CI 79%-87%) reported 75% or better improvement in their psoriasis.20 SORⒷ
Combining systemic agents with UV-based therapy can increase response rates, improve tolerance, and reduce UV exposure. Effective combinations include methotrexate and acitretin.17 SORⒷ Cyclosporine should not be combined with UV treatments because of increased risk of skin cancer.11
When topical agents and/or phototherapy fail, systemic agents are the next step (Table 158-4). Systemic agents include acitretin, apremilast, cyclosporine, methotrexate, and the biologics. Systemic agents (excluding acitretin and apremilast) have immunosuppressant effects and therefore require baseline evaluation, including:
TABLE 158-3Strength of Recommendations for the Treatment of Psoriasis Using Topical Therapies ||Download (.pdf) TABLE 158-3 Strength of Recommendations for the Treatment of Psoriasis Using Topical Therapies
|Agent ||Strength of Recommendation ||Level of Evidence |
|Class I corticosteroids (highest potency) ||A ||I |
|Class II corticosteroids ||B ||II |
|Classes III/IV corticosteroids (medium potency) ||A ||I |
|Classes V/VI/VII corticosteroids (lowest potency) ||A ||I |
|Vitamin D analogs ||A ||I |
|Tazarotene ||A ||I |
|Tacrolimus and pimecrolimus ||B ||II |
|Anthralin ||C ||III |
|Coal tar ||B ||II |
|Combination corticosteroid and salicylic acid ||B ||II |
|Combination corticosteroid and vitamin D analog ||A ||I |
|Combination corticosteroid and tazarotene ||A ||I |
|Combination tacrolimus and salicylic acid ||B ||II |
TABLE 158-4Systemic Drugs Used in Treatment of Psoriasis41 ||Download (.pdf) TABLE 158-4 Systemic Drugs Used in Treatment of Psoriasis41
|Drug Name ||Classification/Mechanism of Action ||Comments |
|Acitretin ||Oral retinoid || |
First-line systemic drug for chronic palmoplantar or pustular psoriasis in patients of non-childbearing potential.
Limited benefit for plaque psoriasis.
|Cyclosporine ||Oral calcineurin inhibitor || |
Fast-acting systemic drug that is often used first-line for pustular psoriasis or erythrodermic psoriasis.
For intermittent use in periods up to 12 wk as a short-term agent to control a flare of psoriasis.
|Methotrexate sodium ||Inhibitor of folate biosynthesis || |
May be used as a first-line systemic drug for plaque psoriasis and psoriatic arthritis.
Compared with cyclosporine, has a more modest effect, but can be used continuously for years or decades.
|Adalimumab ||TNF inhibitor || |
May be used as first-line systemic treatment of plaque psoriasis and psoriatic arthritis.
Has higher efficacy and lower rate of adverse effects compared with methotrexate.
|Etanercept ||TNF inhibitor ||Commonly used as a first-line systemic drug for chronic plaque psoriasis and psoriatic arthritis. |
|Infliximab ||TNF inhibitor || |
Intravenous infusion with high rates of effectiveness.
Fast-acting drug that is often used as a second- or third-line biological for chronic plaque psoriasis.
|Ustekinumab ||Monoclonal antibody that binds the shared p40 protein subunit of IL-12 and IL-23 || |
Favorable results when compared with etanercept in terms of efficacy and safety.
May be used as first-line systemic treatment for chronic plaque psoriasis.
|Secukinumab ||Monoclonal antibody targeting IL-17A ||Effective for moderate-severe psoriasis, greater efficacy compared to ustekinumab |
|Ixekizumab ||Monoclonal antibody targeting IL-17A ||Recently approved for moderate-severe psoriasis, highest efficacy of all the biologics |
|Apremilast ||PDE-4 inhibitor ||Oral medication taken twice daily. Similar in efficacy to methotrexate, similar in cost to biologics. Second-line for moderate-severe psoriasis. May be used in psoriatic arthritis. |
CBC with differential, renal and hepatic function testing.
Tuberculosis screening with purified protein derivative (PPD) or QuantiFERON-TB Gold.
Hepatitis and HIV serologies to exclude chronic hepatitis B, C and HIV.
Vaccination status, preferably completing required vaccinations prior to treatment.
Pregnancy test in women of childbearing age (methotrexate and cyclosporine).
Psoriasis Area and Severity Index (PASI) is the most widely used tool for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease)
A 75% reduction in the PASI score (PASI-75) is the current benchmark of primary endpoints for most clinical trials
Methotrexate has been used for over 50 years in the treatment of psoriatic skin, nail and arthritic disease. A meta-analysis of 11 RCTs found that 45.2% (95% CI 34.1–60.0) of patients achieve PASI-75 after 16 weeks of treatment.21 SORⒶ
Methotrexate (MTX) is given as a weekly dose of 5 to 25 mg/week depending on response and side effects. The starting dose is between 5 and 10 mg/week for the first week, then escalated with monitoring to obtain a therapeutic target dose of 15 to 25 mg/week. Oral dosing is preferred, but intravenous, intramuscular, and subcutaneous delivery is available in cases of intolerable GI side effects (same dosing as oral).
Major side effects include hepatotoxicity, pulmonary fibrosis, bone marrow suppression, and fetal malformations. Folic acid 1 mg daily helps mitigate hepatotoxic and hematologic side effects. Women of childbearing age should be counseled and use effective contraception. A CBC and complete metabolic panel (CMP) should be monitored regularly. Expert consensus recommends liver biopsy after a cumulative dose of 3.5 g in low-risk patients and 1.5 g in high-risk patients.22 SORⒸ Risk factors for hepatotoxicity include diabetes mellitus, obesity, excessive alcohol use, and history of liver disease such as chronic hepatitis B or C. Noninvasive markers of liver fibrosis include the serum tests FibroSURE and procollagen III peptide, and transient elastography (FibroScan). One small study suggested that 2 of these 3 tests be abnormal before requiring liver biopsy.23 SORⒷ Still, the question of whether or when to do a liver biopsy and/or stop MTX is controversial.
Methotrexate is less effective than biologic agents.24 An RCT of 271 patients comparing methotrexate to adalimumab found that 36% vs. 80%, respectively, reached PASI-75 after 16 weeks of treatment.25
Cyclosporine is a T-cell inhibitor and is an effective, rapid treatment for psoriasis. The recommended starting dose is 2.5 to 5 mg/kg/day orally divided twice a day.11 SORⒷ
Major side effects include renal toxicity and hypertension, which are dose-related. Serum creatinine and blood pressure should be measured monthly, along with CBC, uric acid, potassium, lipids, liver function tests (LFTs), and magnesium. Cyclosporine is associated with increased risk of premature birth but not major fetal malformations, and it may be used in pregnancy.
Cyclosporine is very effective for treating psoriasis flares, but can be used for maintenance with up to a 1-year maximum per U.S. guidelines and 2-year maximum per European guidelines.26,27
Cyclosporine is comparable in efficacy to methotrexate doses of 15 mg/week.28 SORⒷ
Acitretin is a potent oral retinoid used for psoriasis. As monotherapy, acitretin may be particularly effective in pustular psoriasis, including palmoplantar, compared with plaque-type psoriasis.29 SORⒷ
Major side effects include hepatotoxicity and hypertriglyceridemia; therefore lipid levels and LFTs should be monitored. Because acitretin is a known teratogenic medication than can remain in the body for 3 years after cessation, it contraindicated in women of childbearing age. Low-dose acitretin (25 mg/day) is better tolerated with fewer adverse effects than 50 mg/day.30 SORⒷ
Acitretin may be added to phototherapy to improve clearance and reduce UV exposure.18 SORⒷ
Biologic agents have become a mainstay of treatment for moderate to severe psoriasis in the past 10 years, and several new agents are available. Treatments approved by the U.S. Food and Drug Administration (FDA) include the TNF-α inhibitors (etanercept, adalimumab, and infliximab) and the anti-interleukin monoclonal antibodies (ustekinumab—IL-12/23, secukinumab—IL-17A, and ixekizumab—IL-17A) (Table 158-5).
Biologic agents are administered either via the subcutaneous route or as an intravenous infusion at regular intervals, ranging from twice a week to every 12 weeks (see Table 158-5).
Safety concerns for biologics include risk of serious infection and cytopenia. TNF-a inhibitors have been associated with increased risk of autoimmune conditions (lupus, demyelinating disease), congestive heart failure, and malignancy (lymphoma).10 Therefore, in addition to the baseline evaluation discussed, a CBC with differential, LFTs, creatinine, and electrolytes should be monitored every 6 months and tuberculosis (TB) screening yearly. Patients should be offered participation in long-term safety registries (Psoriasis Longitudinal Assessment and Registry [PSOLAR]). An observational study of more than 12,000 patients from PSOLAR found no increased risk of death, malignancy, or major cardiovascular events among patients treated with biologic compared to nonbiologic agents.31
A meta-analysis of 27 RCTs found that infliximab was the most effective short-term biologic for psoriasis, followed by secukinumab and ustekinumab (PASI-75 95.9%, 90.9%, and 73.6%, respectively). Ustekinumab had the best safety profile.32 SORⒶ
Infliximab has a faster onset of action than other biologic agents, but the highest incidence of serious infection.32,33 SORⒶ
Interleukin-17A antibody. 300 mg SQ weekly × 5 weeks then every 4 weeks. Comparable to ustekinumab in efficacy and tolerability. Jabbar-Lopez ZK, et al. Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis. J Invest Dermatol. 2017.24
Ixekizumab is a recently approved IL-17A antibody with high levels of efficacy. Two large RCTs found that at 12 weeks of treatment, PASI-75 rates of ixekizumab vs etanercept were 87–90% and 42–53%, respectively.34 Up to 75% of patients maintained PASI-75 at 60 weeks of continued treatment with ixekizumab.35 SORⒶ A recent meta-analysis of 41 RCTs found that ixekizumab was the highest ranked in terms of efficacy and tolerability compared to all other biologic therapies.24 SORⒶ
Biologic agents are effective for psoriatic arthritis and should be considered early for patients with severe, erosive PsA.11 SORⒶ
Although the biologic agents are all very expensive, insurance often pays, and there are patient assistance programs for uninsured patients with limited resources. Prior authorization forms may require the prescribing physician to be a dermatologist.
TABLE 158-5FDA-Approved Biologic Agents for Treating Psoriasis ||Download (.pdf) TABLE 158-5 FDA-Approved Biologic Agents for Treating Psoriasis
| ||Adalimumab (Humira) ||Etanercept (Enbrel) ||Infliximab (Remicade) ||Ixekizumab (Taltz) ||Secukinumab (Cosentyx) ||Ustekinumab (Stelara) |
|Mechanism of Action ||TNF-α inhibitor ||TNF-α inhibitor ||TNF-α inhibitor ||Monoclonal antibody targeting IL-17A ||Monoclonal antibody targeting IL-17A ||Monoclonal antibody targeting IL-12 and IL-23 |
|Dose ||SQ every 2 weeks ||SQ 1-2 times a week ||IV infusion every 8 weeks ||SQ every 2 weeks for three months, then every 4 weeks ||SQ every 4 weeks ||SQ every 12 weeks |
|Clear/nearly clear (PASI 90) at 12–16 weeks24 (95% CI) ||34% (23–46) ||23% (17–29) ||45% (30–61) ||68% (58–77) ||58% (48–68) ||41% (34–39) |
Apremilast is a phosphodiesterase-4 (PDE-4) inhibitor recently approved for psoriasis, given as an oral dose of 30 mg twice daily.36 SORⒶ Its theoretical mechanism of action is to block cytokine production, thereby improving psoriasis.
Diarrhea is a common side effect, and it is recommended to titrate up the dose during the first week. Patients may also experience weight loss, nausea, headaches, and depression.
Apremilast is similar in cost to the biologics, but similar in efficacy to methotrexate with one study reporting 28.8% of patients reaching PASI-75 at 16 weeks.36,37 SORⒶ It is useful for patients with PsA who are not candidates for methotrexate, but do not require biologics.
THERAPY BY TYPE OF PSORIASIS
First-line options include the following topical treatments: corticosteroids, vitamin D analogs, tazarotene, calcineurin inhibitor (flexures and face), and targeted phototherapy (see Table 158-3).11
Most patients may be started with a very potent topical corticosteroid, such as clobetasol, twice daily for 2–4 weeks. Once controlled, topical vitamin D can be applied twice daily during the week and corticosteroid on the weekend for maintenance.
Another option is to apply a very potent topical corticosteroid in the morning and topical vitamin D in the evening.
Second-line treatment includes the short-term use of a systemic agent and older agents such as anthralin and coal tar.11
Systemic agent may be considered for patients who fail topical treatments, or who wish to gain rapid control (for example, who have an upcoming wedding).11
Intralesional steroids may be effective for small plaques (Figure 158-32). Typically, triamcinolone acetonide 5 to 10 mg/mL is injected using a 27-gauge needle directly into the plaque. SORⒸ
Intralesional injection of small plaques over the knee that were resistant to treatment with high-potency topical steroids. A 27-gauge needle was employed with 5 mg/mL triamcinolone. (Reproduced with permission from Richard P. Usatine, MD.)
Moderate to severe plaque psoriasis:
First-line options for patients with more significant disease include UV-based and systemic treatments. Additional indications include failed topical treatment; those with affected vulnerable areas, such as the face, hands, feet, or genitals; and those with poor quality of life.
Patients with access to UV-based therapy should be offered UV treatment.11
NB-UVB therapy may be combined with methotrexate or acitretin,11 and PUVA may be combined with acitretin.
Patients without access to UV treatment may be offered systemic agents.
Topical therapies are generally continued during systemic treatment for symptomatic relief.
Biologics should be considered if methotrexate and cyclosporine have failed, are not tolerated, or are contraindicated.11
Second-line treatments of moderate to severe disease include infliximab, acitretin monotherapy, and apremilast.
A recent meta-analysis of nearly 12,000 patients found that potent topical corticosteroids are the most effective treatment for scalp psoriasis.38 SORⒶ Topical vitamin D preparations are less effective than corticosteroids and cause more irritation. Although combination corticosteroid–vitamin D products are available, the benefit is small compared to potent corticosteroids alone.
Fluocinonide solution applied daily
Derma-smooth, a combination product of a high-potency steroid and peanut oil
Second-line therapies alone or in combination with a first-line therapy:
UV therapy is the first-line treatment for guttate psoriasis, mainly based on experience with plaque psoriasis and the widespread nature of disease.8 SORⒸ NB-UVB is preferred because of its safety and efficacy profile, especially in children and young adults.11 SORⒸ Topical therapies can be used if phototherapy is not available.8 SORⒸ Although there is an association between recent streptococcal pharyngitis and guttate psoriasis, evidence is lacking to support routine antibiotics.39
Effective topical treatments for inverse psoriasis include mid- to high-potency steroids, vitamin D analogs, and calcineurin inhibitors.13 SORⒷ Topical corticosteroids should be limited because of increased penetration in skin folds and risk of skin atrophy. Topical calcineurin inhibitors have similar efficacy to vitamin D analogs.13 SORⒷ Patients may find topical vitamin D preparations irritating, especially in the skin folds. Topical calcineurin inhibitors may cause a warm sensation or pruritus with initial application, and patients should be counseled that this may improve with time. Applying an emollient to affected areas after bathing may also be beneficial.11 SORⒸ
All patients should be encouraged to quit smoking because of the strong association of palmar-plantar psoriasis with smoking.40 SORⒸ Topical treatments, as in plaque psoriasis, are a first-line treatment for mild disease and should be applied under occlusion.11 For moderate to severe cases, first-line options include acitretin and PUVA, alone or in combination. Second-line options cases include MTX and the biologics.
Treatment considerations include hospitalization for dehydration, close monitoring, and broad-spectrum antibiotics for secondary infection and sepsis. Cyclosporine is a first-line treatment option that is very effective in rapidly treating the most severe erythrodermic psoriasis (see Figure 158-25).41 SORⒸ Other options include MTX, acitretin, and the biologics—in particular infliximab due to its rapid onset of action.11,42 Topical corticosteroids and emollients applied under occlusion provide symptomatic relief and restore the skin barrier.11
Acitretin is the preferred first-line treatment for relatively stable pustular psoriasis.43 SORⒷ Additional options include MTX and cyclosporine. For patients with severe, acute flares of pustular psoriasis, hospitalization may be required. Cyclosporine has a long history as an effective, rapid treatment of acute pustular psoriasis, with marked improvement occurring within a few days of initiating treatment. SORⒸ Infliximab may also be used in acute flares. SORⒸ One strategy is to start cyclosporine and acitretin together and to stop the cyclosporine once the pustules have cleared. Second-line options include the other biologics, PUVA + acitretin or cyclosporine, or a combination of a first-line agent and biologic.43 Systemic corticosteroid therapy should be avoided in all patients with psoriasis, as it can provoke life-threatening pustular flares (see Figure 158-26). SORⒸ
Pregnancy. Approximately 50% of women will note spontaneous improvement of their psoriasis during pregnancy, and others will note no change or worsening.44 Topical emollients and corticosteroids are the mainstay of treatment, and potent corticosteroids should be limited because of association with low birth weight. NB-UVB is preferred for women who need additional control. Biologic agents have shown safety in pregnancy, with the most data for anti-TNF-a agents and cyclosporine.45 Pustular psoriasis of pregnancy is a generalized pustular psoriasis that occurs in pregnant women, usually without a prior history of psoriasis, and is associated with poor fetal outcomes. Prompt systemic treatment and close fetal monitoring are required.
Hepatitis C. UVB is preferred in patients with moderate to severe disease, in additional to topical therapies.46 Methotrexate should be avoided due to the potential for liver toxicity.
Tonsillectomy. A systematic review of 20 low-quality trials found that 70% of patients reported improvement in psoriasis after tonsillectomy.47 Because of the low quality of the studies, tonsillectomy should be considered only for patients with recalcitrant psoriasis in association with episodes of tonsillitis.
Prognosis depends on several factors, including psoriasis subtype. Palmar-plantar psoriasis is the most difficult to treat. Although erythrodermic and generalized pustular psoriasis are the most immediately dangerous types, the response to treatment may vary from excellent to disappointing. Widespread plaque psoriasis is challenging—the prognosis is not easily predictable, and patient adherence is a very important factor. New biologic agents have the potential to control previously severe, recalcitrant disease.
Patients with moderate to severe psoriasis should be followed initially at 3 months after treatment initiation and then every 6 months. Patients should be assessed for adequate treatment response, medication side effects, and appropriate laboratory monitoring. A recent expert consensus panel defined an adequate treatment response as <3% BSA or 75% improvement in BSA involvement from baseline, with a target response of <1% BSA.48 Patients should be asked about joint symptoms, including morning stiffness lasting more than 30 minutes, to screen for PsA. Well-controlled psoriasis on topical agents does not require frequent follow-up.
Patients should be counseled that psoriasis cannot be cured, but can be managed effectively. Time should be taken to listen to patients, develop shared treatment goals, and educate patients so that they feel empowered to take control of their disease. Physicians should emphasize skin care, importance of adherence to topical medications, and lifestyle changes such as smoking cessation and weight management. Patients need to develop a trusting relationship with a family physician or dermatologist to control the psoriasis for maximum quality of life. Table 158-6 lists discussion points.
TABLE 158-6Discussion Points for Healthcare Provider and Patient at Initial Visits ||Download (.pdf) TABLE 158-6 Discussion Points for Healthcare Provider and Patient at Initial Visits
Exacerbating and ameliorating factors
Past treatment responses
Range of therapeutic options
Chronic long-term disease
Optimism for tomorrow based on rapid research developments
Support/services available from the National Psoriasis Foundation
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