Clinical Pearls

Richard Brandt, PA-C, MPAS^a
Metroplex Dermatology
Arlington, Texas

Richard Brandt, PA-C, MPAS, is a dermatologic physician assistant and has practiced medical and surgical dermatology for over 12 years. At various times, he has also served as a peer-to-peer lecturer, a sub-investigator (Sub-I) for pharmaceutical research, an adjunct PA faculty member, a moderator for educational meetings and a clinical instructor. His practice philosophy: better patient education usually leads to better medication compliance!

Psoriasis vulgaris, or chronic plaque psoriasis (CPP), is an immune disorder with a complex, multifactorial pathogenesis and an equally convoluted armamentarium of treatment modalities.^1-3 Despite the multitude of specially focused therapeutic options, an antiquated dichotomy of medication selection has developed among some clinicians; for those prescribers, it consists of a "topical corticosteroid versus other" ideology. Topical therapy is a critical component of overall psoriasis management—a survey of 895 patient records in the US found that 86% of patients with psoriasis receive topical medications.⁴ Thus, it is important that we, as clinicians, retool our topical decision making to better manage mild to moderate psoriatic disease and ameliorate the widely accepted default philosophy of using a corticosteroid as monotherapy.

Once considered primarily an epidermal disease, we now have a greater understanding of a complex cascade of events leading to psoriatic lesion formation, including abnormal leukocyte activation, an accumulation of T cells with proinflammatory cytokine secretion, keratinocyte hyperproliferation and altered keratinocyte differentiation.^2,3 Residual genetic and structural changes persist after clinical resolution of a plaque, suggesting that a "molecular scar" remains and may contribute to disease recurrence.⁵ Hence, our management regimens must be chronic and multifaceted, which is ultimately more commensurate with the disease that we are trying to treat.

In appropriate patients, the initiation of a super-potent topical corticosteroid as monotherapy is common and is implemented for its many immunosuppressive and anti-inflammatory effects.¹ However, continuous use of super-potent topical corticosteroids is generally limited to 2-4 weeks because of the potential for adverse events (AEs) such as hypothalamic-pituitary-adrenal (HPA) axis suppression, tissue atrophy, cutaneous striae and tachyphylaxis.^1,6 Disease relapse is likely within 1-2 months of corticosteroid cessation.^7,8 The astute clinician appreciates the potential undulating and relapsing pattern of plaque formation that may soon develop, and should consider chronic management medication. Topical Vitamin D₃ may be a beneficial option for the chronic management of psoriasis, as it has been shown to exert effects on the epidermis such as restoring the granular layer; reducing acanthosis, parakeratosis and epidermal inflammatory cells; decreasing hyperproliferation; and normalizing keratinization.^9,10 However, the slower onset of action associated with topical Vitamin D₃ derivatives may leave a disjointed gap in therapy between topical corticosteroid cessation and full activation of the Vitamin D₃ derivative if it is not initiated concomitantly at the start of therapy (Figure 1). In my opinion, there is a strong possibility of plaque recurrence during this reprieve from therapy (Figure 1, Weeks 4-10).

Figure 1. Initiating Vitamin D₃ therapy after cessation of steroid therapy.

*Indicates approved length of use.

However, the initiation of a topical corticosteroid that is approved for up to 4 weeks of use and a Vitamin D₃ derivative simultaneously at the start of therapy may significantly lessen the rate of plaque recurrence¹¹ because the benefits of topical Vitamin D₃ can be appreciated sooner after corticosteroid cessation (Figure 2).

Figure 2. Initiating Vitamin D₃ derivatives earlier in therapy.

*Indicates approved length of use.

I understand the allure of prescribing a fast-acting medication that offers seemingly immediate benefits to the patient; however, the early initiation of concomitant topical Vitamin D₃ may afford the patient more optimal long-term disease management and therefore should be implemented. In an effort to increase compliance and enrich the patient's understanding of these concepts, I often paraphrase Dr. John Koo's analogy of the tortoise and the hare, and implore the patient to choose the synergistic effect of both together.

^aRichard Brandt, PA-C, MPAS, has been compensated by Galderma for the authorship of this Clinical Pearl.

Paul Yamauchi, MD, PhD^a
David Geffen School of Medicine at UCLA
Los Angeles, California

Psoriasis afflicts an estimated 2% of the US population.¹ Understanding the factors that may induce, trigger or exacerbate psoriatic flares is very important in clinical practice, as certain psoriasis patients may be at risk for more frequent plaque recurrence and this may ultimately affect treatment decisions.²

There is growing evidence that certain factors may have a stronger association with disease induction or exacerbation than others. For example, many family studies have provided compelling evidence that there is a genetic predisposition to psoriasis, although the inheritance pattern remains unclear.³ Early onset of the disease and a positive family history appear to be associated with a more severe disease course.⁴ Furthermore, medications taken for other conditions can both exacerbate preexisting psoriasis and precipitate new-onset disease.² In a 2011 US survey of 103 dermatologists who prescribed Vectical^® (calcitriol) Ointment 3 µg/g to 302 patients with psoriasis, more than two-thirds of patients had at least one comorbidity.⁵ Of these comorbidities, the most common were hypertension and obesity, at 40% and 33% of patients, respectively, followed by dyslipidemia (23%) and diabetes (19%). Among patients with comorbidities, 78% used one or more medications for these conditions, the most common of which were cholesterol-lowering and antihypertensive medications such as atorvastatin, hydrochlorothiazide, lisinopril, and simvastatin, as well as metformin, a treatment for type 2 diabetes.⁵ The molecular mechanisms underlying drug-induced flares of psoriasis are not completely understood, although mechanisms for certain medications have been partially delineated. Both beta-blockers and lithium are thought to induce keratinocyte proliferation and decrease differentiation via alterations in intracellular calcium homeostasis.² There have been reports showing that lithium may also elevate proinflammatory cytokines in the skin, thereby stimulating cutaneous leukocyte recruitment.²

Frequent and severe plaque recurrence often leads to frustration and has negative effects on patients' quality of life, with many patients believing that physicians underestimate the burden they face.⁶ Successful management of psoriasis depends on appropriate treatment. Certain patients may have risk factors for more frequent plaque recurrence, and discussing these issues with them may promote better adherence.⁷ It is important to consider treatment options for these patients that may help delay disease recurrence and prevent further exacerbation of the disease.

^aDisclosure: Paul Yamauchi, MD, PhD, was compensated for the authorship of this Clinical Pearl.

Fran Cook-Bolden, MD^a
Skin Specialty Dermatology
New York, New York

The scalp is one of the most common sites affected by plaque psoriasis, with as many as 90% of patients with plaque psoriasis having scalp involvement.¹ Although scalp psoriasis involves only a small portion of the total body surface area, it can be burdensome to patients and difficult to treat.¹ In one survey study, 97% of subjects reported that the condition was disruptive to their daily routines.¹ Treatments that are easy to use and highly efficacious may help to alleviate the burden of this condition. A clinical trial was conducted to evaluate the efficacy, safety and patient satisfaction associated with Clobex^® (clobetasol propionate) Spray, 0.05%, compared to its vehicle in the treatment of moderate to severe plaque psoriasis of the scalp. This was a randomized, double-blind study undertaken at 4 investigative sites.² Seventy-eight percent of study subjects identified themselves as Caucasian and 22% as African-American, Asian, Pacific Islander or other.³ Subjects used Clobex^® Spray (n=41) or vehicle spray (n=40) twice daily for up to 4 weeks and were evaluated at baseline and at Weeks 2 and 4. Study products were provided in the newly designed bottle with a directional nozzle applicator, the function of which was assessed by a subject satisfaction questionnaire.²

The primary endpoint was the Global Severity Score (GSS) of scalp psoriasis after 4 weeks of treatment with either Clobex^® Spray or vehicle.² Treatment success was defined as achieving a GSS of 0 (clear) or 1 (almost clear).³ The secondary endpoint was GSS of scalp psoriasis after 2 weeks of treatment. Patients who had a GSS of 0 (clear) at Week 2 were considered to have completed the study early and did not receive further treatment.²

At Week 2, 80% of subjects (33/41) in the Clobex^® Spray group had achieved a GSS of clear or almost clear as compared to 8% of subjects (3/40) in the vehicle group. Treatment success at Week 4 was achieved by 85% of the Clobex^® Spray group (35/41) and 13% of the vehicle spray group (5/40). The inter-group difference was statistically significant (P<.001), favoring the Clobex^® Spray treatment group, at both Weeks 2 and 4.²

Three reported adverse events (AEs) (2 burning sensation, 1 alopecia) were deemed related to Clobex^® Spray, and 2 AEs (one report of application site burning and one report of application site irritation) were deemed related to the vehicle spray. These AEs were considered moderate in severity; there were no reports of serious AEs in this study.^2,3

At the end of treatment, subjects were given a 13-item questionnaire designed to elicit their opinions regarding the use of the study product and its directional nozzle applicator. Both the Clobex^® Spray group and the vehicle spray group reported the product easy to apply and to incorporate into their daily routine.^2,3 Both groups also felt that the directional nozzle aided application to the scalp and facilitated delivery of the product to psoriatic plaques, suggesting high subject satisfaction rates.^2,3

Previous studies evaluating the use of Clobex^® Spray have demonstrated its powerful efficacy for the treatment of moderate to severe plaque psoriasis on the body.⁴ This is the first clinical trial evaluating Clobex^® Spray specifically for the treatment of scalp psoriasis in a relatively diverse patient population. The outcomes of this study were consistent with what has been seen previously for Clobex^® Spray: 85% of subjects were clear or almost clear within 4 weeks of treatment initiation.² Clobex^® Spray is a highly efficacious and easy-to-use treatment for moderate to severe plaque psoriasis of the scalp.²

^aDisclosure: Fran Cook-Bolden, MD, was compensated for the authorship of this Clinical Pearl.

Robert Greenberg, MD^a
East Bay Psoriasis Treatment Center
San Ramon, CA

Psoriasis is a chronic disease that is challenging to treat; as such, its optimal management requires the patient to be fully cooperative and actively involved in treatment.¹ Better adherence to prescribed therapeutic regimens can result in desired reductions in the severity of psoriasis.² Efficacy, safety, cost and complexity of treatment protocols are key factors affecting adherence to treatment regimens.³ Interestingly, treatment adherence has not been found to correlate with disease severity or quality of life (QOL): contrary to what one might expect, patients with the most severe disease or lowest QOL often have the poorest adherence with treatment regimens.^3-5 Consequently, effective therapy for many patients may result from facilitating adherence to existing treatment rather than switching to more aggressive therapies.^3,4

Every patient with psoriasis has his or her own definition of treatment success.⁶ Additionally, dermatologists and patients do not always agree on treatment goals and protocols. One study found that whereas dermatologists' treatment goals generally included a 30%–40% improvement in skin condition and an enhanced QOL, patients typically desire rapid, visible results, followed by complete resolution of symptoms.⁶ Dermatologists and patients may also disagree about long-term treatment regimens: in contrast to their dermatologists' advice, many patients report using their medications when first diagnosed and to treat succeeding flares, but do not think it is necessary to continue treatment during remission.⁶

Patients' adherence to treatment regimens is affected by their personal experience and treatment history, as well as their level of satisfaction with their dermatologist consultation.¹ Patient satisfaction may be determined by the dermatologist's interpersonal/listening skills, the amount of time spent with the patient, and the patient's own preferences and expectations and ability to access care.¹

Once patient expectations have been identified, a frank educational discussion about reasonable and clear treatment goals will help patients understand and reach therapeutic objectives, which is very important, because failure to meet anticipated outcomes can result in decreased adherence.^1,6-9 Other strategies that may help set patient expectations and improve compliance include:

• Tailor therapeutic regimens to meet patient's needs^4,8
  • Consider the use of multiple treatment modalities that can help manage psoriasis over the long term¹⁰
  • Consider patient lifestyle1,¹¹ (eg, retirees vs full-time employees)
  • Use cues to support adherence (eg, instruct patient to administer treatment after showering)¹
• Increase the number of follow-up visits³
  • Compliance increases around the time of doctor visits¹²
• Use education to ensure that patients understand the disease and medication instructions^1,13
  • Knowledgeable patients are more likely to participate in treatment decisions⁹
• Recognize and manage the psychological needs and emotional concerns of patients¹

One way that dermatologists can extend patient contact time and enhance patient satisfaction with clinical care is to utilize nurses,¹³ and possibly other staff such as nurse practitioners and physician assistants. These members of the healthcare team can play an important role in educating patients about their disease and treatment regimens, and can issue patient telephone reminders and facilitate access to services.^1,3,13 The medical team can also promote participation in support groups and encourage family and friends to help.⁸ The National Psoriasis Foundation (www.psoriasis.org) sponsors educational and advocacy programs that empower patients with psoriasis and extend the initiatives begun by the dermatologist and office staff.¹⁴ Enlisting family members and friends to act as advocates for adherence,^3,8 perhaps by inviting them to accompany patients on office visits to provide support, can help improve compliance.

Dermatologists have a duty to offer hope to patients with psoriasis,⁷ because the disease can have an extensive psychological impact, and patient outlook can have profound effects on treatment success. Adherence to therapeutic regimens is most affected by patients' perceptions of care, which depend on the quality of the doctor-patient relationship, optimism concerning the treatment process and an understanding of how treatment will impact daily life.¹

^aDisclosure: Robert Greenberg, MD, was compensated for the authorship of this Clinical Pearl.

Jerry Bagel, MD^a
Psoriasis Treatment Center of Central New Jersey
Princeton, New Jersey

Psoriasis is a chronic disease that significantly affects patients because of its recurrences and comorbidities.¹ Severe psoriasis may affect 5% to 100% of a patient's body surface area (BSA), including sensitive areas such as hands, feet, face, and genitals.^1-3 Psoriasis may be disfiguring and impair activities of daily living, including sleeping, sexual activity, using hands, walking, sitting or standing for long periods, and performing job duties.⁴ The negative impact of psoriasis on patient quality of life (QOL) is comparable to heart disease, lung disease, depression, arthritis, cancer, type 2 diabetes, and other serious medical conditions.⁵ The National Psoriasis Foundation (NPF) surveyed its patient members to identify their QOL concerns, and found that they suffer from anxiety about the worsening of their disease, frustration with treatment efficacy, embarrassment, and feelings of unattractiveness.⁴

Patients with psoriasis experience a continuous, life-altering burden of disease. A newly proposed term, cumulative life course impairment (CLCI), describes the cumulative impact of psoriasis on patients due to its physical and psychological comorbidities, stigma, and economic and social ramifications.^6,7 This descriptor underscores the common belief of patients with psoriasis that they have not achieved their "full life potential."⁶ The social consequences for psoriasis patients can be derived from the misconceptions others may have about their condition such as that psoriasis is contagious. As a result psoriasis patients often feel that they receive unequal treatment or are excluded from facilities such as public pools or health clubs.⁴ The psychiatric ramifications include a greater propensity toward depression.^8-11 One study demonstrated that more extensive psoriatic manifestations correlate with greater depression.¹⁰ Additionally, patients with psoriasis frequently exhibit suicidal ideation: one study showed that 10% of psoriasis patients between the ages of 18 and 34 years have contemplated suicide.⁴ Studies have shown that patients with more severe psoriasis, as indicated by their Psoriasis Area and Severity Index (PASI) scores, have higher levels of anxiety.^11,12 Other studies have indicated that successful treatment of psoriatic skin leads to a significant improvement in patients' depression and QOL.^13-16

The CLCI of psoriasis also results from the significant physiological comorbidities and health care expenses associated with the disease. Studies showed that patients with psoriasis have significantly higher health care costs and use more medical services than those who do not have the disease.^17,18 These findings are likely due to the common comorbidities of psoriasis, including cardiovascular disease and metabolic syndrome, as well as the risk factors associated with the disease, such as alcoholism and smoking.^1,8,19-21 Further, patients with psoriasis experience greater sleep disturbance, daytime somnolence, and inadequate sleep, resulting in part from the pruritus caused by psoriatic plaques.^22,23 Their significant medical expenses are compounded by the difficulty many patients with psoriasis experience in obtaining and maintaining employment.⁴ Patients with psoriasis are more likely to miss work for health-related reasons, especially when symptoms affect patients' hands and/or feet.^24,25 Psoriasis has been shown to negatively affect overall work productivity, as individuals with psoriasis frequently go to work despite feeling ill, termed presenteeism.^22,24,25 Taken together, the cumulative effects of psoriasis on patients' QOL cannot be overstated. Thus, physicians who care for patients with psoriasis must address their QOL issues as a means of treating the whole patient.^6-8

^aDisclosure: Jerry Bagel, MD, was compensated for the authorship of this Clinical Pearl.

Emil A. Tanghetti, MD^a
Center for Dermatology and Laser Surgery
Sacramento, CA

Dermatologists frequently choose therapies that target the acute components of psoriasis because patients urgently want rapid clearance of their plaques. Treatments like topical steroids can address patients' needs by clearing psoriatic plaques quickly and effectively.¹

However, psoriasis is a chronic disease that requires long-term therapeutic management, and long-term use of topical steroids is usually not indicated because of the potential for adverse effects.¹ Available data for high-potency steroids indicate that more than 2 to 4 weeks of continuous use is associated with the development of both cutaneous and systemic effects, while the end point for lower-potency steroids is not known.² Skin atrophy is one cutaneous adverse effect that may occur with the use of steroids, albeit to varying degrees, due to their antiproliferative effects on keratinocytes and their inhibitory effects on collagen synthesis.³ Skin atrophy typically presents as striae and/or increased transparency of the skin³; however, full clinical manifestation of atrophy is relatively rare.^4,5 Despite the fact that skin atrophy may not be readily apparent on the surface, signs of atrophy—including epidermal thinning and a reduction in collagen—are frequently observed even after short-term use of steroids. Numerous studies evaluating the atrophogenic potential of topical steroids have demonstrated a significant reduction in skin thickness, a significant reduction in collagen production, or significant reductions in both. The length of treatment in these studies ranged from 3 days to 1 year, yet early signs of atrophy were significant in all the studies, suggesting that adverse effects of topical steroids occur relatively quickly.^6-11

In light of the well-established adverse effects of long-term steroid use, is the clinical benefit worth the risk? Patients may not necessarily experience substantial clinical benefit from long-term topical steroid treatment. However, as psoriasis is a chronic disease, long-term management is critical to optimizing treatment success. Studies have shown that stopping therapy with treatments such as topical steroids can result in treatment failure as early as 4 weeks post-treatment,¹² suggesting the need for therapies that can be utilized continuously. In light of these considerations, one could argue in favor of "pulsing" the steroid as an alternative to continuous steroid use. A study comparing PRN use of Taclonex^® (calcipotriene 0.005% and betamethasone dipropionate 0.064%) ointment to PRN use of calcipotriene ointment showed considerable benefit for both therapies over 52 weeks: 76.9% of patients in the Taclonex^® group and 69.7% of patients in the calcipotriene group achieved a satisfactory response based on the investigator's assessment.¹³ Given that the efficacy of both treatments was similar, one might ask — what added benefit do patients receive by using a therapy containing a steroid, and what other treatment options are available to help patients avoid treatment failure soon after stopping steroid treatment?

Unlike topical steroids, which are used primarily to effectively treat the acute aspects of psoriasis, topical Vitamin D₃ agents provide benefits that are unique and that can help manage psoriasis over the long term without inducing the side effects associated with steroids. Clinical studies have evaluated the use of Vitamin D₃ agents for 6 to 12 months. One study assessed weekend application of halobetasol ointment in conjunction with weekday application of either calcipotriene ointment or vehicle ointment: 76% of patients who used the calcipotriene ointment on weekdays and the halobetasol ointment on weekends for 24 weeks maintained treatment success, compared to only 40% of those using halobetasol in conjunction with vehicle ointment.¹⁴ Furthermore, a study evaluating continuous, twice-daily treatment with Vectical^® (calcitriol) Ointment 3 µg/g for up to 52 weeks (n=324), in which the primary end points were localized and systemic safety, demonstrated that Vectical^® was well tolerated and had no clinically relevant effects on systemic calcium homeostasis over the long term. Secondary end points, all of which evaluated clinical efficacy, included the investigator-rated Global Severity Score (GSS), change in affected body surface area (BSA), and the patient-rated Global Assessment of Improvement (GAI). A marked improvement in GAI rating was noted in 52.6% of patients (131/249) at Week 26 and 63.8% of patients (83/130) at Week 52.¹⁵ A recent retrospective analysis evaluated changes in affected BSA in the 130 patients who participated in the study for the entire 52 weeks, and it was found that 94% of patients were stable or improved after 26 weeks and 98% were stable or improved after 52 weeks of treatment with Vectical^®.¹²

These studies indicate that continuous use of topical Vitamin D₃ therapy is a safe^b and effective method for managing mild to moderate plaque psoriasis over the long term without the systemic and cutaneous side effects of chronic topical steroids.^1,12,14,15

^aDisclosure: Emil Tanghetti, MD, was compensated for the authorship of this Clinical Pearl.

^bVectical^® has not been evaluated in patients with disorders relating to calcium metabolism. Vectical^® should be used with caution in individuals with known or suspected disturbances in calcium homeostasis, such as renal impairment, those who are taking calcium or Vitamin D supplements, and those who are taking diuretics.¹⁶

The scalp is one of the most common sites of psoriasis. As many as 40%-90% of patients with plaque psoriasis have scalp involvement.¹ Although the scalp represents a small percentage of total body surface area, psoriasis in this location is associated with a disproportionately high level of burden to the patient: A survey evaluating the impact of scalp psoriasis found that 97% of patients reported that the disorder caused disruption of their daily routines.¹

According to the Medical Board of the National Psoriasis Foundation, which convened to develop a consensus for scalp psoriasis therapy, topical treatments for scalp psoriasis are considered effective first-line therapies.² Topical treatments are available in a variety of modalities and formulations, including sprays, ointments, lotions, shampoos, and foams. The vehicle itself can be as important as the choice of therapy, especially in scalp psoriasis, because patient compliance and tolerability can play a significant role in efficacy.² Considerations when choosing a vehicle for the scalp include the application of the active ingredient, as plaques hidden by hair are less accessible and require targeted delivery. Ultimately, the choice of vehicle should be tailored to each individual's needs. Key considerations for choosing the appropriate vehicle for your scalp psoriasis patient may include:

• Delivery of the drug to the target site³
• Appropriate formulation to reach the anatomic site effectively³
• Release of the drug so it can migrate freely to the site of action³
• Encouraging patient compliance, which is facilitated by treatments that are⁴:
  • Minimally irritating, easy to apply, and free of odors and tackiness
  • Non-interfering with clothing, easily incorporated into daily activities, portable
• Providing minimal discomfort and lowest risk of adverse events³

Topical therapies continue to be a mainstay of scalp psoriasis treatment; thus, prescribers are challenged to select the proper topical treatment to meet patients' therapeutic needs and optimize adherence. Vehicle selection is an important component in achieving these goals.⁴