What Is Psoriasis and Who Is Affected?
By definition, psoriasis is a skin disorder marked by thickened and inflamed skin with silvery scales. Psoriasis is a common condition, affecting approximately 2.5% of Caucasians and 1.3% of African Americans in the United States. Worldwide prevalence of disease is hard to pinpoint because it appears to be more common in certain ethnic populations, such as the Japanese, aboriginal Australians, and South American Indians. Psoriasis is found in all age-groups and races; however, the disorder is more commonly seen in people between the ages of 20 and 30 and between 50 and 60 years. Psoriasis can negatively impact affected individuals, leading to low self-esteem, embarrassment, increased stress, depression, and even thoughts of suicide. Although there is no cure for psoriasis, many treatments are currently available to minimize symptoms.
What Causes Psoriasis?
Some people are genetically predisposed to developing psoriasis; individuals with family members affected by psoriasis are more likely to develop it themselves. In addition, the immune system has been implicated in the development of psoriasis, as demonstrated by infiltration of neutrophils in the dermis and epidermis and T-lymphocytes in the dermis, the presence of activated growth factors (ie, epidermal growth factor receptor, transforming growth factor type alpha), overexpression of cytokines, and activation of T-cells. Psoriasis has also be associated with infection, use of certain medications (beta blockers, lithium, angiotensin-converting enzyme inhibitors), and certain environmental or behavioral factors, including smoking, obesity and higher body mass index, increased stress level, and use of alcohol.
What Does Psoriasis Look Like?
Psoriasis can appear on several areas of the body, including the elbows, ears, face, back, feet, palms, and the trunk. Typically, psoriasis looks like dry, red skin with a silver, scaly appearance. Occasionally, the psoriatic rash may be raised or appear as small red dots on the skin. Psoriasis symptoms can also appear on the scalp, genitals, in the mouth or tongue, or in skin folds. Nail abnormalities, such as pitting, discoloration, or cracked nails may be seen as well. The rash may be associated with itching, burning, or joint aches and pains (ie, psoriatic arthritis). Distribution of the lesions is usually symmetric.
What Are the Types of Psoriasis?
There are several types of psoriasis: plaque psoriasis, guttate psoriasis, pustular psoriasis, inverse psoriasis, nail psoriasis, and erythrodermic psoriasis.
A majority of individuals with psoriasis present with plaque psoriasis, symmetric plaques on the scalp, elbows, knees, and back. The rash is red, raised, and scaly with a silvery appearance, with plaques ranging from 1 to 10 cm in diameter. Plaque psoriasis is typically found in young adults.
Guttate psoriasis is the sudden appearance of many small lesions of psoriasis on the trunk of the body that are less than 1 cm in diameter. Children and young adults are most commonly affected. There is a strong association between guttate psoriasis and recent infection with Streptococcus species.
Pustular psoriasis is a rare type of psoriasis that is incredibly severe and unstable and may be fatal if not properly managed. This form of psoriasis is seen after discontinuation of systemic corticosteroids, infection, or in pregnancy. Patients have widespread inflammation and red, painful skin with pustules that spread into sheets across the body. Additional symptoms include weakness, fever, and diarrhea.
Patients with inverse psoriasis present with opposite symptoms of classic plaque psoriasis. Specifically, the rash appears on inner areas prone to rubbing or chafing, including the inguinal, perineal, genital, and intergluteal regions of the body. Unlike plaque psoriasis, there is typically no scaling. Sometimes this type of psoriasis is misdiagnosed as a fungal or bacterial infection.
Nail psoriasis involves pitting, discoloration, and nail crumbling and usually occurs in conjunction with plaque psoriasis. Several tiny pits may be found on the nail plate. Discoloration of the nail, termed the "oil drop sign," looks like the brownish color of motor oil. Nails can also appear yellow. Nail crumbling is found in severe cases of nail psoriasis.
Erythrodermic psoriasis is also relatively rare and involves a scaly rash from head to toe. Because of the severity of the rash, patients with erythrodermic psoriasis should be treated in the hospital because of the risk of infection and dehydration.
How Is Psoriasis Treated?
Several psoriasis treatments, both topical and systemic, are available. Appropriate treatment is determined based on severity of psoriasis (classified as mild-to-moderate or moderate-to-severe), location of the disease (elbows, trunk, face, etc), patient preference, and overall effectiveness of psoriasis medications. Most often, patients are started on topical medications and then proceed to more aggressive therapies based on disease response.
For mild-to-moderate psoriasis, topical psoriasis medicines and emollients are tried first. Most cases of mild-to-moderate psoriasis respond relatively well to topical glucocorticoids, which are first-line treatment for psoriasis and applied twice daily to the affected areas. Other psoriasis treatments for limited disease include tar, topical retinoids, and calcipotriene. Occasionally, combinations of topical medications may be used in conjunction with UV radiation in the form of phototherapy. Emollients (eg, petroleum jelly, heavy creams) are recommended because it is important to keep the skin soft and moist to decrease itching and tenderness. Emollients should be applied after a bath or shower for the best effect. If patients comply with the recommended psoriasis treatment regimen, results can be seen within several weeks.
Patients with moderate-to-severe disease often require more aggressive therapy with phototherapy (UVB or UVA) or systemic treatment, including retinoids, methotrexate, cyclosporine, alefacept, efalizumab, etanercept, or infliximab. The type of psoriasis treatment will depend on the type and severity of disease. For instance, systemic retinoids are commonly used for rarer types of psoriasis, including pustular or erythrodermic psoriasis. Methotrexate and cyclosporine are typically reserved for very severe cases of psoriasis. The biologic agents (alefacept, efalizumab, etanercept, and infliximab) are increasingly being used to treat moderate-to-severe disease and have demonstrated effectiveness in multiple studies. The decision of which biologic agent to use is difficult, and patient response varies. Additionally, biologic agents are more expensive than older therapies and may have more side effects and require more monitoring by a physician.
Although there is no cure for psoriasis, symptoms can be managed with a variety of available psoriasis medicines. Psoriasis symptoms resolve and recur; therefore, it is essential that patients with psoriasis be followed by a physician, particularly a dermatologist if psoriasis is moderate-to-severe.
Guidelines For Managing Psoriasis With Systemic Medications
Based on an extensive review of scientific literature on psoriasis and the opinion of recognized psoriasis experts, the American Academy of Dermatology (Academy) has released new guidelines of care for the management and treatment of psoriasis with traditional systemic therapies. Recommendations, efficacy and safety for the use of the three U.S. Food & Drug Administration (FDA) approved and most commonly used traditional systemic agents – methotrexate, cyclosporine and acitretin – were outlined.
Published online in the Journal of the American Academy of Dermatology, this is the Academy’s fourth of six sections of the guidelines of care for psoriasis, with three previously published sections focusing on general recommendations for the treatment of psoriasis and psoriatic arthritis, as well as the use of biologics and topical therapies.
“While in recent years biologics have changed the treatment of psoriasis, traditional systemic therapies – which are easily administered orally and less expensive than biologics – continue to play an important role in treating psoriasis,” said dermatologist David M. Pariser, MD, FAAD, president of the Academy. “The Academy’s new evidence-based guidelines are intended as a guide for physicians so the best treatment can be determined for each individual patient. The guideline also discussed any potential side effects or risk factors that need to be evaluated prior to treatment.”
Psoriasis is a chronic skin condition, which usually begins before age 35 and is characterized by thick, red, scaly patches that itch and bleed. Although it is a genetic disease, it is not completely understood how it is inherited. However, there are at least eight chromosomes to date that researchers have identified as being linked to the genetic transmission of the disease.
Although a prerequisite to starting a systemic therapy traditionally has been whether a patient is affected by psoriasis over a minimum body surface area of about 10 percent, a subset of patients with limited psoriasis have debilitating symptoms on their palms, soles or scalp that can significantly impact their quality of life – making systemic treatments an appropriate option for them.
As the most commonly prescribed traditional systemic therapy for psoriasis, methotrexate can be very effective with even the most severe cases of psoriasis. Methotrexate works by competitively inhibiting the enzyme dihydrofolate reductase, which decreases the production of folic acid thus blocking DNA synthesis and cell division.
Efficacy & Dosage
In the only placebo-controlled trial of methotrexate for psoriasis, 36 percent of patients treated with a low weekly dosage of 7.5 mg of methotrexate – which was increased as needed up to 25 mg per week – achieved a 75 percent or greater improvement in their Psoriasis Area and Severity Index (PASI) score after 16 weeks. In general, methotrexate is administered as a single weekly oral dose that can be increased gradually until an optimal response is achieved. Although there are no established maximum or minimum dosages of methotrexate, weekly dosages usually range from 7.5 mg to 25 mg.
“Some patients can be gradually tapered off treatment and restarted when the psoriasis recurs, and it is important for physicians to minimize the total cumulative dose of methotrexate while maintaining adequate control of psoriasis and the patient’s tolerance of the medication,” said Dr. Pariser.
Toxicities & Contraindications
Because of the known organ toxicities of traditional systemic medications, proper patient selection and appropriate monitoring are crucial to minimize the toxicity of any therapy. For example, the most common and generally minor side effects of methotrexate that most often occur at the time it is administered include nausea, fatigue, inflammation of the mucous membranes of the mouth and anorexia. The most serious toxicities associated with methotrexate are white blood cell and platelet deficiency, liver damage and lung scarring.
Since methotrexate can cause birth defects or terminate a pregnancy, it is not prescribed to women attempting to conceive. In addition, methotrexate should not be prescribed to nursing mothers, those with chronic liver disease, alcoholics, or patients with immunodeficiency syndromes, among others.
Cyclosporine is one of the most effective treatments for psoriasis and induces immunosuppresion by inhibiting the first phase of T-cell activation.
When the medication is used long-term (i.e., three to five years), a significant number of patients will develop some degree of glomerulosclerosis, scarring of the kidney’s blood vessels. For this reason, Dr. Pariser noted that published guidelines in the United States limit the use of cyclosporine to one year.
Efficacy & Dosage
Numerous clinical trials have demonstrated the efficacy of cyclosporine used as a short-term treatment for psoriasis, with minimal toxicities in healthy patients. Specifically, studies show at 3 mg/kg and 5 mg/kg per day, 36 percent and 65 percent of patients, respectively, achieved a clear or almost clear result after eight weeks. In addition, after eight to 16 weeks, 50 to 70 percent of patients achieved a 75 percent or greater improvement in their PASI score. Cyclosporine is generally prescribed to adult, non-immunocompromised patients with severe psoriasis who have not responded to at least one systemic therapy or in patients who cannot tolerate other systemic medications.
Generally, dosing of cyclosporine is given as 2.5 mg/kg to 5.0 mg/kg a day in two divided doses, and physicians should make decreased dose adjustments by 0.5 mg/kg to 1.0 mg/kg when psoriasis is cleared or when high blood pressure or decreased kidney function test results are observed.
Toxicities & Contraindications
The most serious side effects associated with cyclosporine are kidney damage and high blood pressure, which is why it requires careful patient selection and subsequent monitoring to be used safely. A number of drug interactions can occur with this medication, and the FDA advises that it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
“Studies also show that patients with psoriasis taking cyclosporine may be at increased risk of developing squamous cell carcinoma, particularly those with a history of more than 200 PUVA treatments,” said Dr. Pariser. “Due to these known toxicities and contraindications, a careful assessment of a psoriasis patient’s disease severity is critical when assessing the risk-benefit ratio of treatment with cyclosporine.”
Acitretin is an oral retinoid, which is derived from vitamin A. Although the exact way retinoids work in the treatment of psoriasis is not completely understood, they are known to inhibit excessive cell growth and stimulate differentiation of the epidermis (outermost layer of the skin). Etretinate was the first retinoid introduced for the treatment of severe psoriasis and was replaced by acitretin, the active metabolite of etretinate, in 1988.
Efficacy & Dosage
Clinical studies suggest that when used alone, acitretin is the least effective of the traditional systemic therapies and is therefore often used in conjunction with ultraviolet (UV) light. The effectiveness of acitretin is dose dependent, with dosing ranging from 10 mg to 50 mg per day administered as a single dose.
“Typically, it takes three to six months for acitretin to achieve the desired response in most psoriasis patients,” explained Dr. Pariser. “Appropriate dosing must take into account the balance among safety, tolerability and efficacy, as many patients may not be able to tolerate the higher dosages of acitretin needed for optimal efficacy.”
Toxicities & Contraindications
Several potential adverse effects are associated with acitretin, such as alopecia, nausea and abdominal pain, and joint and muscle pain, to name a few. However, Dr. Pariser explained that these can generally be minimized by appropriate patient selection, careful dosing and monitoring. As is the case with methotrexate, acitretin’s most serious side effect is its potential to cause birth defects. Therefore, its use is limited to male and female patients of non-childbearing potential. In addition, other increased risks include severely impaired liver or kidney function and chronic, abnormally elevated blood lipid values. For this reason, patients should be monitored with lipid profiles and liver enzymes once every two weeks after starting acitretin.
“These guidelines emphasize that the decision to prescribe methotrexate, cyclosporine, acitretin or any other traditional therapy must be individualized,” said Dr. Pariser. “Under the right circumstances, systemic therapies can significantly improve even the more severe cases of psoriasis. But every patient needs to be carefully evaluated in terms of disease severity, quality of life, and general medical and psychological history. Dermatologists and patients must work together to continually review the response to treatment and potential risks.”