The diagnosis and treatment of skin disease depend on the health care provider’s familiarity with dermatology terms. Fitzpatrick and Bernhard (1993) summed it up best when they said, “To read words, one must recognize letters; to read the skin, one must recognize the basic lesions.” A barrier to communication among providers exists because of the lack of any standardization of basic dermatologic terminology. The International League of Dermatologic Societies has published a glossary of basic lesions in an attempt to standardize the definitions. To prevent confusion in the standard of measurement of lesions, a metric ruler is an essential tool for the provider to ensure accurate documentation of lesion size.

Primary Lesions

Microscopic examinations are used frequently in dermatology and include Gram stains, cultures (both bacterial and fungal), potassium hydroxide preparations, Tzanck tests, and hair pluck evaluation.

A serological test for syphilis should always be considered for a patient with generalized erythematous and scaling eruptions.

Biopsy of the skin is a useful diagnostic tool to obtain more information about the lesion or rash. The two most common techniques for biopsying the skin are a punch biopsy, using a tool called a punch (a small, sterile, disposable tubular knife); or a shave biopsy (using a single- or double-sided flexible razor) under local anesthesia. The site of the biopsy is very important and usually depends on the stage of the eruption.

Elliptical excisions and scalpel wedge excisions can also be performed and sent for examination. The excision method used should be based on the practitioner’s experience and the laboratory’s requirements for the requested tests.

COMMON SKIN CONDITIONS

ACNE

PATHOLOGY AND ETIOLOGY

Increased Sebum Production

The main factor influencing sebum production is the hormone androgen. Research has found that androgens are essential for the development of acne and women with hyperandrogenic states are more prone to develop acne, as well as hirsuitism and menstrual irregularities (James et al., 2011). For this reason, medicines that influence this hormone can do well at controlling acne.

Abnormal Keratinization of the Follicular Epithelium

Abnormal or disordered shedding of the cells that line the sebaceous follicles is central to the pathogenesis of acne. This process is also known as follicular plugging (Arndt, 1995). The result of this abnormal shedding is comedo formation. If the plug is formed within a dilated opening, it develops into a whitehead. If the comedonal mass protrudes from the sebaceous follicle, it develops into a blackhead. A whitehead is considered a closed comedo, whereas a blackhead is considered an open comedo (James et al., 2011).

Proliferation of P. acnes and Inflammation

P. acnes is a gram-positive anaerobic diphtheroid that colonizes sebaceous follicles (Thiboutot, 1996). This organism, combined with keratin, sebum, and other microorganisms in the skin, promotes the release of inflammatory mediators. This then leads lymphocytes, neutrophils, and foreign-body giant cells to accumulate and triggers the formation of papules, pustules, nodules, and cysts—all features of inflammatory acne (James et al., 2011).

Epidemiology

Options, Expected Outcomes, and Comprehensive Management

Acne vulgaris is rarely misdiagnosed. It may, however, become confused with folliculitis, rosacea, or any other acneiform eruption. The diagnosis is usually based on the finding of comedones, pustules, papules, nodules, or cysts on the back, chest, or face. When initially evaluating a child or a woman with acne, hormonal imbalance should be considered. Women with hirsuitism, central obesity, irregular or decrease in menses, and problems with fertility should be tested for excess levels of androgen as should those women whose acne is recalcitrant to treatment. Acne is one common symptom of polycystic ovarian syndrome (PCOS) and treatment of this underlying condition will help clear acne.

There are many myths regarding factors that may aggravate or alleviate acne. The most common myth is that various foods such as chocolate and fatty foods aggravate acne. There is no clear evidence to support the value of eliminating these foods (James et al., 2011). For patients who attribute their acne flare-ups to their dietary intake, it is best to encourage them to cut back on the foods they think produce the flare-up.

A few factors can aggravate acne. One of these is skin trauma and frictional forces. Providers should counsel patients to avoid scrubbing the face when washing it, and also avoid harsh chemicals and drying agents on the skin. Chin straps, tape, collars, hats, and other causes of friction should be avoided if possible. Occlusive makeups and oil-based products are another cause of acne. Non-comedogenic cosmetics should be recommended (James et al., 2011).

Acne vulgaris has a very favorable prognosis, but can take months to years to fully treat. Management of acne should be directed toward a combination of the four factors associated with acne. Scarring, which can be minimized with proper treatment, is the only sequelae of acne. With the exception of isotretinoin, most therapies are prescribed on a long-term basis. Many treatment options are available; however, the best treatment in the end will be the one that the patient can adhere to the most. It should be tailored to the patient’s preferences, habits/routines, and based on the psychosocial impact the acne creates for the individual, as well as treatment costs.

Topical Therapy

Topical therapy is initially prescribed for patients with mild to moderate inflammatory acne and should be used for 6 to 8 weeks to judge its effectiveness (James et al., 2011). Topical therapies include comedolytic agents, antibiotics, and anti-inflammatory drugs.

Comedolytic Agents

TOPICAL RETINOIDS

Topical retinoids (vitamin A) have been available for use in the United States for at least 30 years and were initially marketed in the 1970s for the treatment of acne vulgaris as Retin-A. It was later discovered by its maker that women were noticing its other advantages to the skin—it decreased the appearance of fine lines and wrinkles (Wolverton, 2007). Today many different topical retinoids are available to treat both photoaging and acne. Because of their teratogenic potential, topical retinoids should be avoided in pregnancy.

Tretinoin • Tretinoin is an effective first-line comedolytic agent. It normalizes desquamation of the follicular epithelium by thinning out the stratum corneum and promotes drainage of preexisting comedones and with continued use prevents the development of new comedones (James et al., 2011).

There are various dosage forms and vehicle bases of tretinoin. It is usually applied once daily at bedtime after the face has been cleansed and adequate time allowed for it to dry. The mildest cream formulation should be prescribed first and the concentration increased depending on the clinical response. If the patient has excessively oily skin or lives in a humid climate, the gel formulation may be preferable. Dosage forms of tretinoin cream include 0.025%, 0.05%, and 0.1%. Gel formulation dosages include 0.01% and 0.025%. A 0.05% solution also exists. In terms of potency, the 0.05% cream and the 0.01% gel are roughly equivalent, as are the 0.1% cream and the 0.025% gel. The 0.05% solution is the most potent form of tretinoin. There are also newer vehicles available including microsphere (0.1% and 0.04% gel), which is more photostable than regular gel as well as polymerized (0.05% and 0.1%).

Patients should always be informed of potential side effects, which include desquamation, burning, erythema, and exacerbation of inflammatory acne lesions. This irritation can be minimized by selecting the appropriate starting dose, combining it with a moisturizer, and increasing the concentration gradually. Tretinoin does not possess antimicrobial or anti-inflammatory activity.

Adapalene • Adapalene is a retinoid-like compound that has good photostability and is similar in efficacy to lower concentrations of tretinoin (James, Berger, & Elston, 2006). It comes in 0.1% cream, gel, solution, and pledgets. Its main side effects are dryness, erythema, scaling, pruritus, and a burning sensation. It is in pregnancy category X (James et al., 2011).

Azelaic Acid Cream • Azelaic acid cream (20%) is another topical therapy for acne. It is a naturally occurring compound that serves as an effective monotherapy in mild to moderate forms of acne (Graupe, Cunliffe, Gollnick, & Zaumseil, 1996). The therapeutic benefits result from its ability to decrease the hyperproliferation of keratinocytes in the follicular infundibulum, an antibacterial effect against P. acnes, and direct anti-inflammatory properties. Azelaic acid cream has been found to have an overall efficacy comparable to that of 0.05% tretinoin, 5% benzoyl peroxide, and 2% topical erythromycin (Graupe et al., 1996). It has a similar efficacy to oral tetracycline and its maximal improvement with use occurs at about 4 months (Wolverton, 2007). It has also been used for melasma as well as rosacea under the trade names Azalex (20% cream) and Finacea (15% gel).

Anti-Inflammatory Agents • P. acnes is one of the stimuli for inflammatory acne and topical antibiotics can decrease the formation of this gram-positive anaerobe. Antimicrobial agents, such as tetracycline and erythromycin, may also decrease the inflammatory potential of P. acnes (Webster, 1995). Benzoyl peroxide is a potent bactericidal agent effective against P. acnes and is a common first agent to use in mild to moderate inflammatory acne. It may have some comedolytic effects as well (James et al., 2011). Benzoyl peroxide is formulated as a wash, cream, lotion, foam, or gel. It is available in concentrations of 2%, 5%, 10%, and 20%. It may be used once or twice daily. The more common side effects include erythema and dryness. It may also bleach clothing, which is an important consideration when the benzoyl peroxide is applied to the chest or back.

The more commonly used topical antibiotics include clindamycin, erythromycin, and sulfur. They are available in various formulations, including gels, lotions, solutions, and pads. In general, lotions are less drying to the skin than gels or pads; solutions tend to be more drying to the skin. The provider must always consider allergies that the patient may have and prescribe a topical antibiotic accordingly. Side effects include local irritation and the development of resistant bacteria (especially with erythromycin). Topical antibiotics are effective against mild to moderate inflammatory acne, especially when used in combination with another topical agent such as benzoyl peroxide as well as a topical retinoid.

Topical clindamycin and erythromycin are available as solutions, lotions, and gels. They may be used once or twice daily, depending on whether they are prescribed alone or with a comedolytic agent.

Topical sulfur is available as a lotion, cream, wash, and gel. It can be used once or twice daily, depending on whether it is prescribed alone or in combination with a comedolytic agent. It is known to be an anti-acne therapy as well as a treatment for other conditions including seborrheic dermatitis, rosacea, scabies, and tinea versicolor (Wolverton, 2007). It should be avoided in patients with a sulfur allergy. Sulfur, resorcin, and salicyclic acid are commonly found in over-the-counter preparations and, while older and less used, can be helpful when newer medications are not available (James et al., 2011).

Combination Therapy

Studies have been carried out to test the efficacy and safety of various combinations. Tretinoin has been found to increase the penetration of other topical agents by thinning out the stratum corneum and therefore increasing absorption. It has also been found that when all lesion types are considered, the concurrent use of topical clindamycin and tretinoin, or clindamycin and benzoyl peroxide, is clinically superior to either of the agents used alone (Berson & Shalita, 1995). These combinations also make the treatment better tolerated because the irritant effects of one agent are decreased with the addition of the other.

Systemic Therapy

Systemic drugs are usually added to the treatment regimen when an inflammatory disease, whether mild, moderate, or severe, does not respond to topical combinations. The more commonly used oral antibiotics include tetracycline, erythromycin, minocycline, and doxycycline. The mechanism of action common among these antibiotics is their antibacterial effect against P. acnes. They are most often used in combination with topical acne agents and should be used for 6 to 8 weeks to judge efficacy. Often a typical length of treatment time is 3 to 6 months, often starting at a high dose and decreasing the dosage as acne is controlled, for 1 to 2 months at a time (James et al., 2011).

TETRACYCLINES AND ERYTHROMYCIN

Tetracyclines are the mainstay of acne therapy. Tetracycline itself does not directly alter sebum production, but it does decrease the concentration of free fatty acids, which has a direct effect on the secretion of other proinflammatory products (Strauss, 1993). Common side effects of tetracycline manifest in the gastrointestinal system: nausea, vomiting, epigastric burning, and abdominal upset. Because dairy products and iron can decrease the absorption of tetracycline, it should be taken on an empty stomach, preferably with a glass of water, 30 minutes before meals or 2 hours afterward but not right before bedtime, to avoid esophagitis (James et al., 2011). Tetracyclines have the ability to mineralize tissues rapidly and are deposited in developing teeth; this may cause irreversible yellow-brown staining. Also, they should never be prescribed for pregnant women, children, or babies. The initial dose given is 250 to 500 mg one to four times/d (James et al., 2011).

Doxycycline is another type of tetracycline. It is commonly used for treatment of the combination of acne and rosacea as well as rickettsial infections such as Lyme disease. It can be taken with food and has a long half-life (18–22 hours). One of the main side effects with doxycycline is an increase in cutaneous photosensitivity, especially at doses of 100 mg/d and higher (Wolverton, 2013). It is important to warn patients and to have them protect their skin when outdoors.

Erythromycin is less efficacious than tetracycline and other antibiotics (James et al., 2011). However, it can be given to patients who cannot tolerate tetracyclines or pregnant women. Erythromycin is a good alternative for photosensitive patients as well. It should be taken with food or milk to decrease the possibility of gastrointestinal upset, which is common (including nausea, abdominal pain, and diarrhea). It can be given initially at 250 to 500 mg two to four times/d (James et al., 2011).

The dosages of tetracycline and erythromycin are usually 250 to 1,500 mg/d. Minocycline is given at a dosage of 50 to 200 mg/d. Doxycycline comes in 20 to 100 mg individual tablets or capsules and can be given once or twice daily depending on the indication. It is important to inform patients that there is usually little improvement within the first month of therapy. As improvement of the acne condition is noted, the dosage of the oral antibiotic is decreased. Long-term use of oral antibiotics should be avoided and can change the body’s normal flora, decreasing resistance to staph and strep. Using a topical retinoid and/or benzoyl peroxide in combination with an antibiotic can help limit resistance and an oral antibiotic should be stopped after 8 weeks if no improvement is seen. Patients should always be informed of the possibility of restarting the oral antibiotic if an exacerbation occurs.

HORMONE THERAPY

For females with or without androgen excess, hormone therapy can be beneficial in treating their acne. The medications most often used will take longer to work (at least 3 months) and are successful with women who have late-onset acne, acne occurring along the jawline and neck, acne that has relapsed soon after completing isotretinoin, and acne that has not responded well to other interventions. In particular, women with PCOS, late-onset adrenal hyperplasia, androgen excess, and others with endrocrine disorders are good candidates (James et al., 2011).

The two most commonly used hormone therapies for acne are oral contraceptives (OCPs) and spironolactone. OCPs that block both adrenal and ovarian androgens are the best. Yaz, Ortho Tri-Cyclen, and Estrostep are Food and Drug Administration (FDA) approved for this purpose (James et al., 2011). Spironolactone can be given in starting doses of 50 to 100 mg/d (maximum of 150–200 mg/d) and is normally prescribed along with an OCP due to the known side effects in pregnancy (feminization of the male fetus). Common side effects are headache, dizziness, light-headedness, diuresis, breast tenderness, irregular menstrual periods, and fatigue (James et al., 2011). Spironolactone should not be used in people with known renal and/or cardiac disease.

ISOTRETINOIN

Isotretinoin is a synthetic oral retinoid. It is an analog of vitamin A and was approved by the FDA in 1982. The indication for isotretinoin is inflammatory acne or cystic acne that does not respond to conventional therapy. Isotretinoin is the only form of therapy that directly affects all four of the pathogenic factors of acne (Berson & Shalita, 1995). It has a direct influence on the abnormal keratinization of the follicle. A decrease in sebum production occurs as a result of sebaceous gland activity inhibition.

Before starting this medication, patient counseling by the provider is extremely important. The provider should talk to the patient about effectiveness, usual length of treatment, and chances of remission. The provider should also review contraindications to taking this medication (pregnancy, frequent follow-up needed, avoiding alcohol, etc.) and lastly serious side effects related to isotretinoin.

The use of isotretinoin must be carefully monitored. Its half-life is 10 to 20 hours; it is metabolized in the liver and excreted in the bile and urine. A complete blood count (CBC); serum chemistries; and levels of hepatic enzymes, cholesterol, and triglycerides should be obtained before initiating therapy and monthly thereafter. Taking this with food is recommended (ideally a high-fat, high-caloric meal) for better absorption. Isotretinoin should not be taken with tetracycline or vitamin A supplementation.

Every patient taking isotretinoin will develop some degree of mucocutaneous side effects, which may be controlled with the use of emollients. The most common of these is cheilitis. Secondary infection of the skin with Staphylococcus aureus may complicate the mucocutaneous side effects. Some less common side effects include elevation of serum lipids, dry eyes, photophobia, and elevated transaminases. Other side effects are dermatitis, photosensitivity, acne flare, and exuberant granulation tissue. There are some reports of worsening depression and an association between isotretinoin and inflammatory bowel disease, but these are not firmly established.

PSORIASIS

Not only does psoriasis have an effect on well-being, it also has an economic impact. In one study, approximately 60% of psoriasis patients missed an average of 26 days of work a year due to their illness (Horn et al., 2007).

Control of this lifelong disease poses a great challenge to the patient, family, provider, and community. “Psoriasis is a disease that, in attacking the skin, attacks the very identity of the individual. Many patients have to deal on a daily basis with shame, guilt, anger, and fear of being thought dirty and infectious by others” (Ginsburg, 1995).

Clinical Presentation

Because of the dynamic nature of psoriasis and the varied presentations of this disease, it is often confused with other dermatologic conditions. Psoriasis typically reveals itself in five different variations (Lowe, 1993):

More than one pattern of psoriasis may be present at the same time. Each person with psoriasis is unique and his or her course of disease is unpredictable. A thorough skin examination is the crucial first step in diagnosing and managing patients with psoriasis.

PLAQUE PSORIASIS

PUSTULAR PSORIASIS

Pustular psoriasis can be localized or generalized and is subtyped accordingly. It is often found on the palms or at the edges of plaques. Instead of thickened scaling plaques, this type of psoriasis presents as erythematous plaques studded with pustules and develops suddenly. Some cases of pustular psoriasis may resolve spontaneously with supportive treatment only; in other cases, flare-ups and complications occur repeatedly. Patients can have mucocutaneous involvement and have fevers, erythroderma, and hypocalcemia. Some systemic complications such as respiratory distress syndrome, pneumonia, congestive heart failure, and hepatitis can occur (James et al., 2006).

GUTTATE PSORIASIS

ERYTHRODERMIC PSORIASIS

When psoriasis completely covers the body, it is referred to as exfoliative, generalized, or erythrodermic psoriasis. This is a severe, life-threatening eruption that most often manifests as intense pruritus, generalized erythema, and scaling. Fever, chills, pruritus, malaise, difficulty in regulating body temperature, and fatigue are systemic symptoms associated with this condition. Fortunately, this type of psoriasis occurs in fewer than 10% of patients (Lowe, 1993). Erythroderma may be a complication associated with pustular or plaque psoriasis, or it may even be the initial manifestation of psoriasis. After the erythrodermic flare subsides, patients usually revert to their original pattern of disease (Stern & Wu, 1996).

PSORIATIC ARTHRITIS

Trigger Factors

A variety of stimuli can trigger the onset of psoriasis. A genetic predisposition should always be taken into consideration, as multifactorial inheritance is likely. Certain genes are being linked to the development of psoriasis as well as human leukocyte antigen (HLA) types (James et al., 2011). Pharmacologic triggers may include beta-blockers, antimalarial agents, lithium, calcium channel blockers, terbinafine, glyburide, systemic corticosteroids, and others. Other stimuli include infection by Streptococcus pyogenes and HIV, weather, and skin injury. Cutaneous trauma, also referred to as the Koebner phenomenon, is seen mainly in unstable psoriasis, and is the development of psoriasis in response to cutaneous injury.

Treatment Options, Expected Outcomes, and Comprehensive Management

Psoriasis follows an irregular, chronic course marked by exacerbations of unpredictable onset and duration, as well as spontaneous remissions. Patients with newly developed psoriasis often become disenchanted with their treatment; if they do not accept that there is no cure, they may switch providers in the hope of finding one. Although there is no cure, treatment usually offers significant temporary relief and sometimes clears the rash. Because psoriasis is a lifelong disorder, optimal therapy should be simple and inexpensive, whenever possible. The severity of the disease and its impact, as perceived by the patient and provider together, can serve as a guide in developing a rational treatment plan. Seriously considering the way psoriasis affects the patient physically, socially, and psychologically should increase the patient’s participation in developing and maintaining the treatment plan. This in turn will be the best indicator of the effectiveness of the treatment plan.

The aim of treatment is to help clear the skin and reverse inflammatory joint disease, if present. All too often, however, treatments that have kept the psoriasis in check will stop working. In cases where the condition becomes resistant, new therapeutic modalities are required.

TOPICAL CORTICOSTEROIDS

Topical corticosteroids are frequently prescribed as the initial therapy for mild to moderate plaque psoriasis with limited number of plaque involvement. They are available in a variety of strengths and vehicles are categorized according to potency. Topical therapy is usually begun with a medium-strength agent. Higher-potency corticosteroids are most often reserved for plaques that are resistant to a weaker corticosteroid or are prescribed for short-term use in a patient with limited areas of involvement. Even with the high-potency agents, complete clearance occurs in only a minority of patients (Stern & Wu, 1996). Less-potent steroids should be used for the face and intertriginous areas. By doing so, the risk of side effects is decreased.

Topical steroids are odorless, colorless, and relatively simple to use. The choice of vehicle is very important. Ointments are more potent than creams and provide the best delivery of the medication by acting as an occlusive agent. Ointments, however, have a greasy consistency and may be unpleasant. Creams are more tolerable but less effective. They are the vehicle of choice for intertriginous areas. Lotions and solutions penetrate less well but are more practical for hairy areas. Foams, solutions, and spray forms are more acceptable to use on the scalp.

Topical steroids are generally applied twice a day. Use of ultrapotent steroids is limited to 2- to 3-week courses. Occlusive dressings enhance the delivery and increase the effectiveness of topical steroids. In general, however, occlusive dressings are only used with low- to medium-potency steroids.

Side effects of topical steroids increase with the potency, amount, length, and site of treatment; the risk is also increased if they are used under occlusion. Local side effects, which may be seen after several weeks of treatment, include skin atrophy and striae, telangiectasias, steroid acne, miliaria, and a rebound worsening after discontinuing use. Tachyphylaxis (development of a tolerance to the medication) can also occur. A rosacea-like syndrome may develop after long-term use of steroids on the face.

ANTHRALIN

This medication has a direct effect on keratinocytes and leukocytes by suppressing neutrophil superoxide generation and inhibiting IL-6, IL-8, and tumor necrosis factor (TNF)-alpha (James et al., 2006). Anthralin should be used only to treat stable plaque psoriasis; the irritation it produces may aggravate erythrodermic and pustular psoriasis.

Anthralin is available in paste, cream, and ointment formulas. The paste allows the most precise application. The ointment and cream are easier to apply, but they may smear and therefore cause irritation of unaffected skin. A significant limitation to the use of anthralin is its staining properties. Staining of the skin and clothing is primarily caused by the oxidation of anthralin. Byproducts of oxidation bind to keratin, stain natural and synthetic fibers, and are increased by alkalis.

TAR PREPARATIONS

Tars are the products of the distillation of oil. The main type of tar used in psoriasis therapy is coal tar. Tar preparations have been used for many years as an adjunctive therapy with UVB. They are messy and smelly; this limits their acceptability by patients. However, liquor carbonis detergens (LCD) is a modified form of coal tar that is generally more acceptable to patients and can be found as a shampoo. Coal tar can come in concentrations ranging from 5% to 20% and is often compounded in creams, ointments, and pastes (Wolverton, 2007). Tar has been reported to suppress epidermal hyperplasia in psoriasis (Silverman, Menter, & Hairston, 1995) but is rarely used as monotherapy.

VITAMIN D₃ ANALOGS

The identification of a high-affinity receptor in most skin cells for vitamin D has led to both oral and topical use of vitamin D analogs in the treatment of psoriasis. Epidermal keratinocytes produce vitamin D₃, metabolize it to its most active form, and respond with a decrease in proliferation and an increase in differentiation (Kragballe, 1995). Calcipotriene is the most common of these vitamin D₃ analogs and is best used for the treatment of plaque and scalp psoriasis. Cream, ointment, and solution forms are available. Even though calcipotriol usually decreases plaque thickness, some residual thickness often remains. Calcipotriene is most often used in combination with higher-potency steroids in order to minimize the side effects and maximize benefits. Calcipotriene degrades when exposed to UV light and is unstable in the presence of other topical agents (James et al., 2011).

Phototherapy and Photochemotherapy

Phototherapy is the use of UV radiation to treat skin disorders. Light is absorbed by molecules in the skin, triggering a sequence of photochemical events that may alter the structure and function of the skin (Stern & Wu, 1996). Sunlight exposure has long been known to improve the symptoms of psoriasis. UVB may be used as a monotherapy or in combination with other therapies. UVA is used with topical or systemic photosensitizers. The use of exogenous photosensitizing agents to enhance the therapeutic effect of UV radiation is termed photochemotherapy.

UVB PHOTOTHERAPY

PHOTOCHEMOTHERAPY (PUVA)

PUVA, or psoralen used topically or orally in conjunction with UVA light, is used to treat severe psoriasis. The mechanism of action is unknown. Treatment consists of oral ingestion of a potent photosensitizer (8-methoxypsoralen) 2 hours before exposure to high-intensity long-wave UV exposure. Treatments are given two or three times a week. In most patients, clearing occurs after 19 to 25 treatments (Christophers & Sterry, 1993), with subsequent maintenance therapy needed with some. PUVA results in rapid pigmentation of the skin. To protect the eyes, UVA-blocking wraparound glasses should be worn while outdoors for 24 hours after ingestion of the photosensitizing agent. Ophthalmologic examinations should be performed before the initiation of PUVA and at yearly intervals thereafter, due to the risk of cataracts. Long-term side effects make it necessary to restrict PUVA to patients with widespread and severe psoriasis. A major early side effect is pruritus. Late sequelae include long-term actinic skin damage (solar elastosis, dry and wrinkled skin) and hyper- and hypopigmentation. Skin cancers may also develop. All of these side effects are of considerable importance when deciding whether to begin PUVA therapy.

Systemic Therapy

Systemic therapy can produce substantial to complete clearance of psoriatic lesions and psoriatic arthritis. Side effects of and contraindications to systemic therapy must be carefully considered before prescribing it. This type of therapy is most often reserved for refractory or severe cases of psoriasis.

SYSTEMIC CORTICOSTEROIDS

The mechanism of action is thought to be anti-inflammatory. Despite a transient relief of symptoms, systemic corticosteroid therapy is often followed by a severe flare of disease. There is a higher risk of rebound psoriasis in which onset of pustular lesions can occur; thus, use of systemic corticosteroids is generally not recommended.

METHOTREXATE

Methotrexate is a folic acid antagonist and has been a standard systemic treatment for psoriasis for more than 50 years. Some indications for use include psoriasis with widespread body surface involvement, psoriatic erythroderma, psoriatic arthritis, and acute pustular psoriasis (James et al., 2011). Because of the possible severe systemic side effects, patients should be thoroughly screened beforehand. The most recent guidelines recommend the following relative contraindications: any abnormalities in renal function, significant abnormalities in liver function, hepatitis (active or recurrent), cirrhosis, excessive alcohol consumption, concomitant use of hepatotoxic drugs, chronic and active infectious disease (especially untreated tuberculosis [TB] and advanced HIV), immunosuppression, conception, recent live vaccination, obesity (body mass index [BMI] <30), diabetes, and an unreliable patient. Because of the risk of hepatotoxicity, some clinicians have suggested in the past that a baseline liver biopsy should be obtained. Recent data suggest that in the presence of normal lab findings, history and physical examination in a patient with low risk of liver disease overall, the decision to perform a liver biopsy (baseline or during therapy with methotrexate) should be made on a case-by-case basis after weighing the relative risk of the procedure itself (Kalb, Strober, Weinstein, & Lebwohl, 2008). In this lower-risk group, data suggest that patients who reach a cumulative dose of 3.5 to 4.0 g of methotrexate could be considered for an initial liver biopsy. Before starting therapy, it is recommended that baseline labwork be performed, including CBC and platelet count, renal function tests, liver chemistries (with hepatitis B and C serology tests when indicated), pregnancy test (if indicated in females of childbearing age), HIV antibody in patients at risk, and a baseline purified protein derivative (PPD). In patients with history of significant liver disease, clinicians should consider baseline liver biopsy.

Once the medication is initiated, liver function tests (LFTs) should be monitored monthly for the first 6 months and then every 1 to 2 months thereafter.

Methotrexate is given as a weekly oral, intravenous, or intramuscular dose or as a weekly divided dose over 24 hours (Stern & Wu, 1996). Salicylates and nonsteroidal anti-inflammatory agents interact with methotrexate by decreasing its renal excretion, and the result is an increase in methotrexate toxicity. Co-trimoxazole (Bactrim) should also be avoided while taking methotrexate because of an increased risk of myelosuppression and severe pancytopenia. The most common side effects of methotrexate therapy include malaise, headache, nausea, and anorexia. Stomatitis, diarrhea, and myelosuppression suggest acute toxicity to the rapidly proliferating cells of the gastrointestinal mucosa and bone marrow (Stern & Wu, 1996). Chronic hepatotoxicity is the most serious complication of long-term therapy. Concomitant use of folic acid supplementation (1 mg daily) is suggested.

RETINOIDS

CYCLOSPORINE

This medication, which was discovered in 1970 and is also known as cyclosporin A (CsA), is a powerful immunesuppressant medication (Wolverton, 2007). It is indicated for erythrodermic and pustular psoriasis as well as severe psoriatic flares and cases of psoriasis recalcitrant to other therapies. It helps by downregulating the proinflammatory epidermal cytokines (James et al., 2006) and divided doses between 2 and 5 mg/kg/d are given daily. Treatment duration is usually limited to 6 to 12 months because of its renal toxicity. Serum creatinine as well as blood pressure must be closely monitored. Cyclosporine can suppress the immune system and patients on this medication should not receive live vaccinations. This medication is contraindicated in patients with renal impairment, uncontrolled hypertension, cutaneous T-cell lymphoma, and malignancy. When taking a patient off this medication, it should be done with a gradual taper using supplementary therapy for psoriasis.

BIOLOGICS

Biologics are a relatively newer class of systemic, psoriatic treatments that can give complete clearance but are very expensive and can have serious adverse effects. They take advantage of the evidence that psoriatic skin has increased TNF-α (a cytokine) and IL-12/23, among others. There are currently three TNF inhibitors (that block TNF-α): etanercept, adalimumab, and infliximab. Each of these medications has a different mechanism of action as well as a unique delivery system. Primary care providers can help by identifying psoriasis patients who would benefit from a biologic medication. Patients without adequate control of their skin on topical or systemic medications like methotrexate, with significant body surface area involvement, or with concomitant arthritis, may be appropriate candidates and should be referred to a dermatologist and/or a rheumatologist to consider starting a biologic.

Etanercept (Enbrel) is a TNF inhibitor that is FDA approved for the treatment of plaque psoriasis. It is also approved for the treatment of ankylosing spondylitis and rheumatoid arthritis (RA). It is usually given initially as a 50 mg subcutaneous injection twice/wk (or 3–4 days apart), then decreased to 25 to 50 mg once/wk depending on the clinical response. An initial set of lab work, including Quantiferon gold (or PPD), CBC, complete metabolic panel, LFTs, screening for hepatitis B and C, and potentially HIV, is recommended. After starting treatment, follow-up labwork is generally performed every 3 to 6 months, but there are no standardized guidelines for this. Etanercept is pregnancy Category B and can be used in patients with active hepatitis C infection (Wolverton, 2007). One contraindication includes active or chronic infections. Common adverse side effects include injection site reactions (14% of patients) and development of autoantibodies (6%). There are ongoing studies looking at whether there is a higher relative risk for developing a malignancy; none of these has been proven to be higher than the risk expected for patients with RA and psoriasis (Wolverton, 2007).

Infliximab (Remicade) is another TNF-α inhibitor that is FDA approved for RA, ankylosing spondylitis, Crohn’s disease, and psoriatic arthritis. Contraindications include hypersensitivity to murine proteins, active or chronic infections, and use with an IL-I receptor antagonist. Relative contraindications include congestive heart failure and a family history of demyelinating disease (including multiple sclerosis). Common side effects include infusion reactions (headache, flushing, nausea, dyspnea), and there have been case reports of reactivation of latent TB. Some patients develop anti-drug antibodies to infliximab, especially those being treated for Crohn’s disease and RA. Others on infliximab can develop acute liver failure, jaundice, and autoimmune hepatitis, but this is rare (Wolverton, 2007). Getting baseline labwork, including CBC, LFTs, and a PPD, is recommended, as is monitoring labwork every three to six months. Infliximab is given as an infusion, often starting at 3 mg/kg with maintenance infusions every 8 weeks.

Adalimumub (Humira), the third approved TNF-α inhibitor, is a human IgG recombinant antibody to TNF-α and is given as a single subcutaneous dose of 40 mg every other week (Wolverton, 2007). It is FDA approved for psoriatic arthritis, plaque psoriasis, RA, juvenile idiopathic arthritis, Crohn’s disease, and most recently ulcerative colitis. Its use is contraindicated for patients with active and chronic infections and a relative contraindication for those with a family history of demyelinating disease. There are no specific monitoring guidelines, but as with the others in its class, baseline labwork, including CBC, electrolytes, LFTs, and a PPD, is recommended before beginning therapy and then repeated every 3 to 6 months. An initial loading dose of 80 mg the first week is often given at week 1, then 40 mg at week 2, and then 40 mg every other week.

Newer systemic biologic medications have been developed and have come onto the market, including ustekinumab (Stelara). It is a human monoclonal antibody directed against IL-12 and IL-23 and was approved by the FDA for plaque psoriasis. It is given as a subcutaneous injection of 45 or 90 mg, with the first two injections given 4 weeks apart, then every 3 months. It should not be given to patients with active or chronic infections including TB. Common side effects include upper respiratory infection, headaches, and fatigue. Ustekinumab increases the risk of developing an infection and certain types of cancer. There is one case report of reversible posterior leukoencephalopathy syndrome (RPLS).

Studies have shown a higher risk of developing skin cancer in patients with psoriasis (Lee, Lin, Chang, & Lai, 2012). Many of the psoriatic treatments, including PUVA, cyclosporine, and biologics, can increase the risk even more, so frequent skin checks are sometimes recommended in this group of patients.

PITYRIASIS ROSEA