Psoriasis a common dermatologic condition that affects 2% to 4% of the world’s population.¹ It is characterized by red, scaly plaques that can affect any part of the body. The impact of psoriasis reaches well beyond the skin, affecting a person’s overall health, well-being and sense of self. Many patients with psoriasis become progressively isolated as they limit their activities to avoid the embarrassment caused by their skin’s appearance.

Case Presentation

“A.D.” presented to the dermatology clinic with worsening symptoms of itching and pain caused by multiple skin plaques. In the prior month, he had developed deepening fissures that covered his palms. This 55-year-old man had a 35-year history of psoriasis with sporadic but minimal periods of remission. He described his psoriasis as not well controlled and progressively worsening. He said the disease was limiting his ability to work around the house and that he had been experiencing pain and stiffness in his knees and hips.

The patient’s medical history included diagnoses of hypertension, hyperlipidemia, obesity, psoriasis and depression. A.D.’s father, who also had psoriasis, died after a heart attack at age 60.

A.D. is single, lives alone and has limited social support. He often isolates himself as a result of negative comments. The scaling skin on his scalp, which sloughs off onto his clothes, embarrasses him and attracts the attention of others. He is a cartographer and works at home. His activity level is low, partially as a result of his psoriasis. He smokes a pack of cigarettes daily.

Objective Findings

Seven types of psoriasis have been identified: plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, nail psoriasis and psoriatic arthritis. Plaque psoriasis accounts for approximately 80% of psoriasis cases. It is characterized by raised, inflamed red lesions covered by a silvery white scale. These typically occur on the elbows, knees, scalp and lower back. Guttate psoriasis appears as small red spots, typically on the trunk and extremities. Inverse psoriasis occurs in the armpits, groin, under the breasts and in other skinfolds around the genitals and buttocks. Pustular psoriasis is characterized by pustules surrounded by erythema. Erythrodermic psoriasis causes widespread skin redness and pain; it is the rarest form of the disease. Nail psoriasis causes noticeable changes in the shape and integrity of fingernails and toenails. Psoriatic arthritis develops later in the psoriasis progression. As its name implies, arthritis co-exists with the psoriasis.

Three indexes are commonly used to assess the severity of psoriasis: the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index (DLQI) and Body Surface Area (BSA). PASI is the most widely used tool. It combines the assessment of plaque severity and the area affected into a single score that ranges from 0 (no disease) to 72 (maximal disease). A score of 10 is considered severe.

The DLQI is a patient questionnaire that asks the patient to rate the impact of the skin condition on important aspects of his or her life, such as ability to work, maintain a home, attend leisure activities and sustain personal relationships, including sexual function. Scores range from 0 (no interference) to 30 (maximal interference). A score of 10 is considered severe. The BSA is a crude assessment of overall affected area by percentage. A BSA of 10% or greater is considered severe.

A.D. has widely dispersed red scaling and crusted plaques of varying sizes on his scalp, elbows, palms, buttocks, knees and the soles of his feet. A.D. reported a DLQI of 25 at this visit. His PASI score was 20, with 40% of his body surface area affected. All of his toenails and eight of his fingernails had yellowish discoloration, were hyperkeratotic and showed onycholysis. The fissures on the skin of his palms showed evidence of bleeding and were painful. A.D.’s knees and elbows had become increasingly stiff and sore with movement.

A.D.’s body mass index was 42 (obese). His complexion fit the criteria for Fitzpatrick skin type I. A.D.’s drug regimen included antihypertensives, a statin and, to treat his psoriasis, clobetasol propionate spray and calcipotriol betamethasone ointment. He did not have any known drug allergies.

Comorbidities

Differential Diagnosis

The morphology of raised, scaly plaques or erythematosquamous eruptions points to a variety of dermatologic diseases. The differential diagnoses for psoriasis can include plaque psoriasis, nummular eczema, pityriasis rubra pilaris, mycosis fungoides, Bowen disease, tinea corporis, porokeratosis, psoriasiform drug eruptions, lichen planus, pityriasis rosea, and secondary syphilis.

The most reasonable diagnosis for this patient is severe plaque psoriasis. Most cases of psoriasis can be diagnosed with findings from the patient’s medical history and physical examination. History alone can tease away some of the proposed diagnoses because of the chronic nature of this condition.

For example, pityriasis rosea most often affects teenagers and young adults and usually occurs after an upper respiratory infection. It presents with an erythematous scaly herald patch, usually 2 cm to 5 cm in diameter, 1 to 20 days before the general rash. This rash usually covers the chest and back, but it may progress to the extremities. It clears spontaneously after several weeks and therefore is not a reasonable diagnosis for this patient.²

The location of the plaques also shortens the list of possible diagnoses. Lichen planus, for example, rarely presents on the palmoplantar surfaces.³ Psoriasiform drug eruptions should also be considered if symptoms emerge and progress aggressively after adding a new medication. The medications commonly associated with this condition include amoxicillin, trimethoprim sulfamethoxazole, ampicillin, nonsteroidal anti-inflammatories, allopurinal, anticonvulsants, bumetanide, captopril, furosemide and thiazide diuretics.⁴

When the history reveals that the erythematosquamous plaques are chronic, a careful physical examination can rule out some of the other less likely diagnoses. For example, the plaques associated with porokeratosis have a characteristic lifted edge that is not seen in psoriasis.⁵

Microscopy may also help eliminate another common skin condition that can mimic psoriasis. Tinea infections in the skin can often present as hyperkeratotic crusted or scaly plaques. These usually occur on the scalp, similar to psoriasis. Under microscopy, skin scrapings will reveal fungal elements with hyphae, spores or both; these are not characteristic of psoriasis.

Certain other diseases can mimic psoriasis so closely that only histology can provide definitive diagnosis. Bowen disease presents as an erythematous, scaly and well-demarcated plaque, but it is squamous cell carcinoma in situ. Few indicators separate Bowen disease from an early form of psoriasis other than careful histologic review of a biopsy of the plaque.⁶

Despite the array of diagnostic tools available, pinning down the correct diagnosis can be difficult for several skin diseases. Pityriasis rubra pilaris, nummular eczema and mycosis fungoides are three diseases often mistaken for each other. Pityriasis rubra pilaris distinguishes itself from psoriasis by the presence of follicular hyperkeratosis, yellow coloring of the palmoplantar keratoderma, and chalky appearance of the face. However, these traits are not present in all cases and the histologic findings are not always diagnostic. Sometimes the only option is to monitor the progression of the disease.⁷

Mycosis fungoides is a great impersonator because it looks like many other skin diseases, including psoriasis. Diagnosis of mycosis fungoides is usually only possible through repeated biopsies because in its early stages it shares pathologic findings similar to chronic dermatoses.⁸

Nummular eczema is difficult to distinguish from psoriasis because the plaques can appear similarly. Nummular eczema is commonly found on the legs but it can also occur on the trunk, hands or feet; the face and scalp are usually spared.⁹

Plaque Psoriasis

Although psoriasis can begin at any age, two peaks in onset are recognized: one between ages 16 and 21 and one between ages 50 and 60.¹ A.D. first noticed his symptoms at age 20. Among first-degree relatives of people with psoriasis, the recurrence risk ratio for psoriasis is 30.4. In the general population it is estimated to be 4.10.¹⁰

The findings from A.D.’s physical examination support the diagnosis of plaque psoriasis. The typical plaques caused by this form of psoriasis usually have a symmetrical distribution involving the scalp, extensor elbows, knees and back. The Auspitz sign is the appearance of punctate bleeding after scales are scraped off; A.D. has experienced this on his palms. Intertriginous areas such as the umbilicus and intergluteal cleft can also be affected. The plaques are raised, erythematous and well demarcated. A thick, silvery scale is usually present. The plaques may or may not be associated with pruritus. Plaques can range in size from less than 1 cm to more than 10 cm in diameter.

The fissuring of the palms and soles is one of the most troubling common signs in psoriasis.¹ Close inspection may reveal pitting of the nail plates, onycholysis, and thickening and yellowing of the nails.

Diagnostic Testing

Psoriasis is usually diagnosed accurately by clinical information alone, but skin biopsy is useful in excluding some diagnoses. Histology can produce typical findings such as epidermal hyperplasia, parakeratosis, neutrophils in the stratum corneum and epidermis, a thin or absent granular cell layer of the epidermis, and thinning of the suprapapillary dermal plates. Recent plaques have histologic findings different from established plaques. Newly developed plaques may only show superficial perivascular lymphocytic infiltrates and dilated tortuous capillaries. Additionally, atypical or partially treated psoriasis can have histologic findings that are suggestive but not diagnostic. Therefore, histology alone cannot always diagnose psoriasis.

It is a reasonable assumption that the rest of the body is not impervious to the dysregulation of immunity responsible for creating psoriatic plaque, which may account for many of A.D.’s comorbidities. For example, 30% of people with psoriasis have psoriatic arthritis.¹¹

Emerging evidence shows that psoriasis is associated with the same sequelae found in other chronic inflammatory diseases, such as Crohn disease and rheumatoid arthritis. Other sequelae include obesity, dyslipidemia and depression.¹ A.D. displays each of these. Research has shown that 34% of patients with psoriasis are obese versus 18% of the general population.¹² Thirty percent of patients with psoriasis also have metabolic syndrome, versus 19.8% of general dermatology patients.¹³ An overproduction of TNF-α, IL-6 and IL-8 is found in patients with psoriasis and patients with metabolic disease.¹⁴

Research also has pinpointed a strong association (P < 0.05) between psoriasis and a variety of atherogenic dyslipidemias.¹⁵ A recent systematic review found an overall increased cardiovascular risk among patients with psoriasis.¹⁶ In a cross-sectional study of 265 psoriasis patients, 32% screened positive for depression compared to 8% of the general population.¹⁷

Treatment Planning

Treatment options can be categorized by level of associated risk. Lifestyle modifications have few risks and can be adopted by all patients. Topical medications carry a lower level of risk than systemic treatments, which carry the most risk. Medications are selected based on the classification of the psoriasis (mild to moderate or moderate to severe). Patients with less severe disease should be started on topical therapy, while patients with more severe disease can be treated aggressively – systemic therapy with topical therapy as an adjuvant. The onset of the disease should also guide treatment decisions.

Comorbidities also influence decision making about management. Many drugs used to treat the inflammatory features of psoriasis in the skin also treat the inflammatory joint symptoms that occur with psoriatic arthritis. Emerging evidence suggests that early treatment of psoriasis may decrease morbidity and mortality associated with metabolic syndrome.

Treatment choices for psoriasis encompass lifestyle changes, pharmacologic therapy and ultraviolet therapy. The table (opposite page) outlines these choices.

Lifestyle Changes

Lifestyle changes may improve the appearance of skin and decrease itch. Such changes integrate the concepts of health promotion and disease prevention and may result in a greater sense of control over the disease. Suggestions might include regular application of moisturizers, short periods of sun exposure, smoking cessation, weight loss, reduced alcohol consumption, stress managementand avoidance of skin trauma.

Moisturizer keeps the skin supple, which avoids fissuring and reduces itchiness. Small doses of sunlight decrease the severity of psoriasis. Ultraviolet (UV) radiation from the sun decreases the production of skin cells in the basal layer of the skin, which is upregulated in psoriasis. Brief exposure to UV light mutes the skin immunity by increasing the production of anti-inflammatory cytokines and decreasing the movement of inflammatory mediators toward the skin.¹⁸

Epidemiologic studies show that smoking is linked with the severity of psoriasis.¹⁹ Smoking causes an overproductionof IL-1 and increases the production of TNF and transforming growth factor.²⁰ Therefore, smoking cessation should be encouraged in patients with psoriasis who smoke. Reducing alcohol intake may also improve outcomes in this patient population, since alcohol intake has a negative effect on treatment response.

Evidence also shows that stress is associated with increased psoriasis severity. Stress stimulates the secretion of hormones such as cortisol, which interact with peripheral and central hypothalamic-pituitary-adrenal axis activity. This interference can activate mast cells in the skin, altering their barrier ability and inducing proin?ammatory cytokines.

Activities such as prayer, yoga and regular exercise may be useful in decreasing stress. Meditation can increase the effectiveness of psoriasis treatment.²⁰ These activities may also help manage the depression that is prevalent in psoriasis. Clinicians report that many patients are less depressed after their skin has cleared. The possibility that skin clearing can improve depression in patients with psoriasis is a subject for research.

It is also important to protect the skin from trauma due to the Koebner phenomenon, in which skin lesions develop or worsen as a result of scratching or other trauma. Habit reversal training can help reduce scratching in patients with pruritic skin conditions such as psoriasis.

Topical Therapies

Topical therapy is necessary for all patients with psoriasis. A wide range of topical products is available. Perhaps the most important factor in choosing a medication is ease of use, since patient adherence to topical therapy is low.

Corticosteroids are the cornerstone of topical treatment for psoriasis. Topical therapies exert anti-inflammatory, antiproliferative and immunosuppressive actions by affecting gene transcription. Steroids are effective when used as prescribed, but most patients find the required twice-a-day application time consuming and messy. Certain formulations can be expensive.

Ultra-potent steroids are best reserved for areas where the skin is thicker, such as the extensor surfaces, palms and soles. The scalp can be treated with steroid-containing shampoos and sprays. The parts of the body where skin is thin – the face and intertriginous areas – should be treated with low-potency creams. Common side effects related to potency and dose are dermal atrophy, tachyphylaxis and potential suppression of the hypothalamic axis; these are most often noted with overuse.

Keratolytic agents thin the skin by loosening cell adhesions, promoting sloughing. Common keratolytics include salicylic acid and urea. Both are painful if applied to skin that is fissured, excoriated or eroded. Salicylism is a risk when high-concentration topical salicylic acid is used.

Topical vitamin D analogs include calcipotriol and calcitriol. These medications inhibit keratinocyte proliferation, stimulate keratinocyte differentiation and inhibit T-cell proliferation and other inflammatory mediators.⁴² They can enhance the effects of topical steroids. When applied twice daily, topical vitamin D analogs reduce scaling and induration. But erythema often persists. These drugs are generally well tolerated, but they can cause stinging and irritant dermatitis, especially on areas where skin is thin. If the patient is using more than 100 g each week, calcium levels in blood and urine should be monitored for hypercalcemia.²¹

Tar has anti-inflammatory and antiproliferative effects and is used to treat psoriasis. Tar shampoo and ointments are less expensive than certain medications.

Tacrolimus, a topical calcineurin inhibitor, and tazarotene, a topical retinoid, are most useful on the face, neck, anogenital region and the acral areas of the extremities. Topical calcineurin inhibitors disrupt the activation of T cells, which reduces inflammation and plaque buildup. Topical retinoids down regulate epidermal proliferation. These medications can cause erythema, irritation and photosensitivity. Topical retinoids have been associated with birth defects.

Ultraviolet Therapies

In controlled doses, UV radiation is effective and relatively safe for the treatment of psoriasis. UV radiation has antiproliferative and anti-inflammatory effects and induces apoptosis of pathogenic T cells in psoriatic plaques. UV radiation treatment has the predictable risks of photodamage and increased skin cancer risk. Phototoxicity and photosensivity are additional risks.²²

Three UV light therapies that are therapeutic in psoriasis are UVB, narrowband UVB and photochemotherapy (PUVA). The range of UVB therapy is 290 nm to 320 nm, and psoriasis requires a dose that potentially induces erythema. Narrowband UVB therapy is 311 nm and is more effective at causing apoptosis of T cells without causing erythema.²² PUVA involves treatment with oral or bath psoralen to photosensitize skin, followed by UVA radiation with a range of 320 nm to 400 nm. This dose penetrates deeply into the dermis. Due to the skin cancer risk associated with UV therapy, a lifetime exposure limit is standard. UV therapy can be prohibitive for patients who cannot easily access light treatment centers. An alternative is an at-home product such as a light box.

Oral Systemic Therapies

The three oral systemic therapies most often prescribed for psoriasis are methotrexate, cyclosporine and acitretin. Methotrexate (MTX) is a folate antagonist and an antimetabolite that is moderately effective against psoriasis. MTX works by suppressing active T cells. It is available in oral, subcutaneous, intramuscular and intravenous formulations.²³

This drug has many side effects. The most common and troubling are ulcerative stomatitis, nausea and gastric distress. To counteract these effects, folic acid is taken on days that MTX is not dosed. MTX has a narrow therapeutic range and is associated with many toxicities. Hepatotoxicity is a known complication, and patients with active hepatitis are not candidates for this drug. Nephrotoxicity is also a known complication. Myelosuppression is a dose-limiting adverse effect and usually presents with macrocytic red blood cells. More rare but more concerning is the risk for pancytopenia. MTX is an abortifacient and therefore a pregnancy class X drug. Women who take this drug should have a confirmed method of birth control, and patients of either gender should discontinue the drug for a minimum of 3 months prior to conceiving a child.²⁴

MTX has restrictions on alcohol and beta-lactams use.

Due to the risk of hepatotoxicity, alcohol should not be ingested during therapy; this can often prompt nonadherence to treatment. Although MTX is the most appropriate choice for long-term oral systemic therapy, it can be troublesome for some patients.²⁵

Cyclosporine can produce complete clearing in 4 weeks, a rapid response compared to other therapies. Cyclosporine is a systemic calcineurin inhibitor, an immunosuppressant that suppresses T-cells. The two most serious side effects are nephrotoxicity and hypertension. Additional side effects include tremors, fatigue and paresthesias. Cyclosporine also has many drug-drug interactions.²⁶

Another oral systemic drug is acitretin, a derivative of vitamin A. It slows the proliferation of skin cells. A therapeutic response is noted in more than half of patients, but it usually takes several weeks. It is most effective as part of a combination treatment with UVB and PUVA. Common dose-related side effects are cheilitis and hair loss. Less common adverse effects are hepatotoxicity and serum lipid alterations. Women must avoid becoming pregnant for at least 2 years after discontinuing acitretin. Several drug interactions have been identified.²⁷

Biologic Therapies

Biologics are a group of immunomodulatory agents that treat inflammatory diseases. Patients require regular follow-up to review blood work results, ensure effectiveness and monitor for side effects. Biologic therapies can reactivate latent Mycobacterium tuberculosis so patients must get tested for TB. Rare side effects include demyelination or symptoms of multiple sclerosis.

Infrequently, blood work may show elevated antinuclear antibodies and the development of lupus-like syndrome. Early diagnosis and withdrawal from the drug resolves these risks. Due to the modulation of immunity imposed by biologics, patients should allow one half-life to pass before having surgery or receiving a live vaccine.

An unexpected benefit of biologics noted in European registries is a decreased risk of heart attack and stroke in patients with rheumatoid arthritis.²⁸

Case Outcome

Returning to A.D.’s case, the severity and treatment resistance of his psoriasis along with the positive finding of arthralgia suggested the need for rheumatologist referral and consideration of systemic therapy. His BMI of 42 and associated metabolic syndrome also supported aggressive therapy. An in-depth discussion with A.D. determined his goals for treatment, the degree of risk he was willing to take, the details of his prescription drug coverage, and his preferences for drug route.

The patient has 100% prescription drug coverage and wanted to pursue all possible means of clearing his skin. A.D. was screened for possible biologic therapy and received education about systemic therapy. After several months of biologic therapy, his skin had largely cleared. He now uses topical therapy to control breakthrough plaques. The patient is enjoying his life significantly more. He is able to care for his home, work with less pain, and exercise regularly at a gym, where he is becoming more social. His BMI has decreased, and he has an improved sense of well-being.

References

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Rebecca R. Cottrill is an adult nurse practitioner at L’Hôpital Montfort in Ottawa, Ontario, Canada. She is a member of the National Academy of Dermatology Nurse Practitioners. She has completed a disclosure statement and reports no relationships related to this article.