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Manifestations and Management of Difficult-to-Treat Psoriasis

Aldredge, Lakshi M.; Higham, Robert C.

Journal of the Dermatology Nurses' Association: July/August 2018 - Volume 10 - Issue 4 - p 189–197
doi: 10.1097/JDN.0000000000000418

ABSTRACT Psoriasis is a common, immune-mediated skin disorder that can manifest as multiple clinical phenotypes. Although psoriasis affecting the scalp, face, nails, palms, soles, and intertriginous regions has not been studied as extensively as chronic plaque psoriasis in other body areas, these phenotypes can be associated with significant physical, psychosocial, and functional impairments, which impact quality of life. In addition, recent evidence has shown that psoriasis affecting these areas is more prevalent than traditionally thought. In this article, we discuss the clinical characteristics of these hard-to-treat areas and review newer treatment options, which have shown significant efficacy for psoriasis affecting these body regions. To provide optimal care to patients with difficult-to-treat psoriasis, nurses, nurse practitioners, and physician assistants should evaluate patients for scalp, facial, nail, palmoplantar, and inverse psoriasis to provide more effective therapeutic options.

Lakshi M. Aldredge, MSN, ANP-BC, DCNP, VA Portland Healthcare System, Portland, OR.

Robert C. Higham, MPAS, PA-C, American Skin Institute, Sherman Oaks, CA.

Technical assistance with editing and styling of the article for submission was provided by Oxford PharmaGenesis Inc. and was funded by Novartis Pharmaceuticals Corporation. The authors were fully responsible for all content and editorial decisions and received no financial support or other form of compensation related to the development of this article.

Lakshi M. Aldredge, MSN, ANP-BC, served as a speaker/consultant/advisory board member for AbbVie, Celgene, Novartis, Merck, Pfizer, Lilly, Amgen, Sanofi, Regeneron, and Galderma. Robert C. Higham, MPAS, PA-C, served as a speaker/consultant/advisory board member for AbbVie, Celgene, Novartis, Amgen, Taro, and Promius.

The authors declare no conflict of interest.

Correspondence concerning this article should be addressed to Lakshi M. Aldredge, MSN, ANP-BC, VA Portland Healthcare System, 3710 S. W. U.S. Veterans Hospital Road, Portland, OR 97239. E-mail:

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Psoriasis is an immune-mediated, inflammatory disease that can manifest in different body locations. Chronic plaque psoriasis is the most common disease manifestation and was the focus of most clinical and epidemiological studies conducted in recent years. Although the trunk and extremities are the most commonly affected areas, involvement of the scalp, face, nails, palms, soles, and intertriginous regions has a significant impact on quality of life (Merola, Li, Li, Cho, & Qureshi, 2016). To date, few studies have evaluated psoriasis affecting these particular locations. However, recent data indicate that psoriasis of these areas is highly prevalent and associated with significant physical, psychosocial, and functional impairments (Merola et al., 2016). Psoriasis that presents in these skin areas is often referred to as “difficult-to-treat psoriasis” because special considerations are needed to treat these areas effectively (Sánchez-Regaña et al., 2014).

This article discusses the epidemiology and clinical characteristics of these difficult-to-treat areas affected by psoriasis and provides practical advice for healthcare practitioners to optimize care for patients with psoriasis in these body regions. Therapeutic options for each type of difficult-to-treat psoriasis are reviewed, with guidance on how to overcome potential challenges associated with using traditional psoriasis treatments and when to consider newer therapies such as biologic agents.

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Scalp Psoriasis

The scalp is one of the most common locations of plaque psoriasis. A recent study found that, among patients with psoriasis, the prevalence of scalp psoriasis was between 45% and 56% (Merola et al., 2016). Other epidemiologic studies have noted that up to 90% of patients with psoriasis have scalp involvement at some point during their lifetimes (Frez et al., 2014 ; P. C. van de Kerkhof & Franssen, 2001).

Scalp psoriasis generally presents as erythematous patches and silvery white scales that flake and may be mistaken for dandruff (Figure 1a). Unlike dandruff, scalp psoriasis causes a silvery sheen, and affected areas are extremely dry, often to the point of cracking and bleeding. Scalp lesions are usually very pruritic, and many patients have reported experiencing sensations of burning or soreness (L. H. Kircik & Kumar, 2010 ; Wozel, 2008). Patients with scalp psoriasis are especially vulnerable to perpetual Koebnerization (reformation of the same lesions due to injury) because routine hair care (e.g., brushing and shampooing) and scratching or picking at lesions causes skin trauma and a cycle of worsening disease (Wozel, 2008). Scratching and scale removal can also cause secondary and temporary hair loss in these patients.



Scalp psoriasis has a significant negative impact on patients’ quality of life, with more than 70% of patients reporting difficulty with daily life (Sampogna et al., 2014). Patients often report feeling ashamed, embarrassed, or self-conscious about their scalp symptoms. More than 60% of patients report that flaking sometimes, often, or always affects their choice of clothing color, and about half of the surveyed patients say the disease affects how they wear their hair (Sampogna et al., 2014). Typically, patients with scalp psoriasis wear hats or grow their hair long to try to hide the disease (L. H. Kircik & Kumar, 2010). A significant correlation has been observed between scalp desquamation and impaired mental health among patients with moderate-to-severe plaque psoriasis (Heydendael et al., 2004).

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Facial Psoriasis

About one in five patients with plaque psoriasis has facial involvement, and facial psoriasis is more common in patients with longer disease duration, family history of psoriasis, and more severe psoriasis (Alpsoy et al., 2017 ; Canpolat, Cemil, Eskiog˘lu, & Akis, 2008 ; Kim, Ahn, Park, & Youn, 2016 ; Woo et al., 2008). The most commonly affected areas of the face include the upper forehead (76%), lower forehead (52%), periauricular area (46%), ears (39%), and cheeks (39%; Woo et al., 2008). Less common (<20%) areas of facial involvement include the nasolabial fold, perioral area, and eyelids (Woo et al., 2008). Almost all patients with facial psoriasis also have scalp involvement (Woo et al., 2008).

Facial psoriasis lesions are characterized by sharply demarcated, red scaly plaques that tend to be symmetrical (Figure 1b). Symptoms include itching, soreness, and skin sensitivity. The problem is often exacerbated by external factors, such as psychological stress, sun exposure, skin trauma, infection, and the presence of the yeast species Malassezia in skin flora (Keshavarz, Roknsharifi, Shirali Mohammadpour, & Roknsharifi, 2013 ; Wozel, 2008).

The stigma associated with facial psoriasis can be especially severe given the cosmetically apparent nature of the disease. People with facial psoriasis fear negative stereotypes and societal judgment, which can result in feelings of isolation, embarrassment, depression, and suicidality (Alpsoy et al., 2017). The negative effects of facial psoriasis can extend broadly to many activities of daily living (e.g., resulting in problems with intimacy and unemployment; Alpsoy et al., 2017 ; Malakouti et al., 2017).

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Nail Psoriasis

Reported nail psoriasis prevalence rates vary. Data from epidemiologic studies indicate that nails are affected in about 20%–40% of patients with plaque psoriasis (Augustin et al., 2010 ; Merola et al., 2016), but it is estimated that up to 90% of patients will develop nail involvement at some point during their lives (Jiaravuthisan, Sasseville, Vender, Murphy, & Muhn, 2007). Nail psoriasis usually affects several digits. Fingernail involvement is more common than toenail involvement, but more than half of patients show psoriasis in both (Rigopoulos, Papanagiotou, Daniel, & Piraccini, 2017).

Isolated nail psoriasis is uncommon. Nail involvement almost always occurs preceding or accompanying skin or joint involvement (Sánchez-Regaña et al., 2014). Among patients with psoriatic arthritis, roughly 80% have signs of nail psoriasis (Langley, Saurat, Reich, & Nail Psoriasis Delphi Expert Panel, 2012 ; Wozel, 2008). Characteristic features include pitting of the nail plate, leukonychia (i.e., areas of white nail plate), onycholysis (i.e., separation of the nail plate from the nail bed), oil-drop yellow–red discoloration in the nail bed, scaling under the nail as a result of subungual hyperkeratosis, appearance of transverse lines and ridges, nail plate crumbling, and splinter hemorrhages (Figure 1c; Crowley et al., 2015 ; Dogra & Arora, 2014 ; Jiaravuthisan et al., 2007 ; Wozel, 2008). Pain and tenderness are common symptoms in affected nails, which can lead to functional limitations (Crowley et al., 2015). Patients with nail psoriasis are also at an increased risk for secondary bacterial or fungal infections (Klaassen, Dulak, van de Kerkhof, & Pasch, 2014).

Typically, patients believe that nail psoriasis is unsightly or disfiguring, making them feel embarrassed or self-conscious in social settings. Among patients with psoriasis, those with nail involvement reported significantly greater negative effects of their disease on relationships, daily activities, leisure activities, and work or school activities than patients without nail involvement (Klaassen, van de Kerkhof, & Pasch, 2014). Substantial proportions (>20%) of patients with nail psoriasis reported having difficulty with activities, including putting on shoes and socks and performing household tasks. Adverse effects of nail psoriasis on quality of life were more common in women and in patients with more severe nail involvement (Klaassen, van de Kerkhof, et al., 2014).

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Inverse/Genital Psoriasis

Approximately 20%–30% of patients with psoriasis have inverse (intertriginous) involvement affecting inframammary, axillary, inguinal, intergluteal, or other skin folds (Merola et al., 2016). Comorbidities such as obesity, diabetes mellitus, and/or hypertension often occur in patients with inverse psoriasis (Wozel, 2008).

Inverse psoriasis has not been extensively studied, in part, because patients are often uncomfortable discussing disease affecting such intimate body regions with their healthcare providers. As such, inverse psoriasis is often referred to as “hidden psoriasis” (Cohen et al., 2016 ; Meeuwis et al., 2015 ; Meeuwis, de Hullu, Massuger, van de Kerkhof, & van Rossum, 2011 ; Merola et al., 2016).

Inverse psoriasis usually presents as well-demarcated, bright red plaques without extensive scaling because the skin in the intertriginous areas is soft (Figure 1d). If scales do form, they can be easily scraped off, which can result in pinpoint bleeding. In women, vulvar psoriasis is often symmetrical; glossy red or moist gray plaques can be observed, along with silvery patches adjacent to the outer parts of the labia majora (Meeuwis et al., 2011). In men, inverse psoriasis is most commonly observed on the glans penis, although the entire penis, scrotum, and inguinal folds can be affected. In both men and women, genital psoriasis can cause painful fissures or cracks, along with pruritus and burning sensations. Exposure to urine or feces can irritate genital lesions, as can tight-fitting clothing and sexual intercourse (Meeuwis et al., 2011).

In addition to making sexual interactions painful, 94% of patients with inverse psoriasis report that the disease negatively affects body self-image (Cohen et al., 2016). The combined physical and psychosocial effects of inverse psoriasis have a significant negative impact on patients’ sexual health throughout their lives, with many patients choosing to avoid physical/intimate contact altogether (Cohen et al., 2016 ; Malakouti et al., 2017). Inverse psoriasis can also negatively affect personal hygiene/toileting, daily activities, recreation, and overall interpersonal function (Cohen et al., 2016).

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Palmoplantar Psoriasis

Palmoplantar psoriasis occurs in 12%–16% of patients with psoriasis (Merola et al., 2016). Cigarette smoking, trauma, and exposure to irritants increase the risk for palmoplantar psoriasis (Engin et al., 2017). This clinical phenotype is characterized by red, dry, and thickened palms and/or soles that often have deep, painful fissures (Figure 1e). Lesions are usually sharply demarcated and symmetrical, with similar distribution patterns on both palms and/or both soles. Palmoplantar psoriasis is usually considered to be the most disabling form of psoriasis, and these patients experience greater physical discomfort than those without palmoplantar involvement (Pettey, Balkrishnan, Rapp, Fleischer, & Feldman, 2003). When a patient’s dominant hand or soles of the feet are affected, mobility may be limited and he or she may be unable to work or perform activities of self-care or daily living, which can have a significant impact on quality of life (Chung et al., 2014 ; Engin et al., 2017). The added stigmatization of having psoriasis on visible and sensitive areas such as the hands contributes further to the psychosocial burden associated with palmoplantar psoriasis (Hawro et al., 2017).

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It is well established that psoriasis can have profound negative effects on patients’ quality of life by interfering with daily activities such as dressing, bathing, sleeping, cooking, and other physical, leisure, and occupational activities (Pariser et al., 2016 ; Rapp et al., 1997). These effects and the social stigmas associated with having a highly visible and unsightly disease are associated with elevated levels of anxiety, depression, low self-esteem, and suicidal ideation among patients with psoriasis (Kurd, Troxel, Crits-Christoph, & Gelfand, 2010 ; Magin, Adams, Heading, Pond, & Smith, 2009 ; Rapp et al., 1997). In an analysis of survey data collected by the National Psoriasis Foundation, 94% of patients with psoriasis indicated that psoriasis was a problem in daily life, 88% believed that psoriasis affected their overall well-being, and 82% reported that psoriasis interfered with enjoyment of life (Armstrong, Schupp, Wu, & Bebo, 2012).

Physical and emotional burdens can be tremendous in patients with psoriasis and can be even greater in patients with difficult-to-treat psoriasis in sensitive and/or highly visible body areas such as the face, scalp, genitals, hands, and feet (Alpsoy et al., 2017 ; Chung et al., 2014 ; Cohen et al., 2016 ; Hawro et al., 2017 ; Heydendael et al., 2004). Many patients may be embarrassed and uncomfortable talking with healthcare practitioners about having psoriasis in sensitive areas and the impact of the disease on their social life, intimacy, and self-esteem (Merola et al., 2016). As such, it is especially important for nurse practitioners (NPs) and physician assistants (PAs) to develop strong, trusting relationships with patients with difficult-to-treat psoriasis so that they feel more comfortable having open and honest dialogues about how psoriasis affects their quality of life.

NPs and PAs can facilitate frank conversations about psoriasis burdens and treatment goals. Practitioners should explain to patients that psoriasis is a chronic disease and managing symptoms is a lifelong journey. Different treatments are associated with varying levels of efficacy and safety, so NPs and PAs should describe what may be realistic outcomes with each type of treatment and work with each patient to understand their treatment goals. As part of this process, it is helpful for practitioners to understand each patient’s treatment history so that they know what has and has not worked in the past and what patients liked and disliked about different treatments. Studies have shown that patients value practitioners who are knowledgeable about psoriasis, current treatment options, and ongoing research (Pariser et al., 2016). Many patients are eager to try new treatments and express frustration when providers seem unwilling to make changes to a suboptimal treatment regimen (Pariser et al., 2016).

Because patients may be uneasy about undergoing full-body skin examinations, NPs and PAs should discuss the importance of these examinations for the evaluation of psoriasis severity. NPs and PAs should explain that the appearance of psoriasis in sensitive areas of the body can be quite different from its appearance in other areas and may be mistaken as a different dermatosis, such as yeast or fungal infections. Determining psoriasis severity can be challenging because some definitions of severity rely on the percentage of body surface area (BSA) affected, with severe disease defined as >10% BSA (Pariser et al., 2007). However, for patients with psoriasis in difficult-to-treat areas, BSA is often not an accurate representation of the burden of disease. For example, the entire scalp is only 5% of a person’s BSA (L. H. Kircik & Kumar, 2010), as is the entire palmoplantar area (each hand is ~1% BSA; Engin et al., 2017 ; Pariser et al., 2007). Thus, other definitions of disease severity should be used when assessing difficult-to-treat phenotypes. Consensus recommendations define severe scalp psoriasis as disease affecting >50% of the scalp, with at least one of the following symptoms: severe erythema, severe scaling, very thick lesions, moderate-to-severe pruritus, hair loss with scarring, and hairline or forehead involvement (Ortonne et al., 2009). Similarly, an alternative scale, such as the palmoplantar psoriasis Investigator’s Global Assessment (IGA), can be used to define palmoplantar psoriasis severity. On the palmoplantar psoriasis IGA, severe disease is defined as bright to deep dark-red lesions with severe thickening and hard edges, and coarse scaling covering almost all lesions and containing numerous fissures (Armstrong, Vender, & Kircik, 2016). Patients with nail disease should be assessed using a nail-specific instrument, such as the Nail Psoriasis Severity Index (NAPSI; Rich & Scher, 2003), the simpler modified NAPSI (Cassell et al., 2007), the Physician’s Global Assessment (PGA) of Fingernail Psoriasis (Hudgens, Sundaram, & Williams, 2016), or a nail visual analog scale (Mease, Palmer, Litman, Karki, & Greenberg, 2016).

Several validated instruments, such as the Dermatology Life Quality Index and the Koo–Menter Psoriasis Instrument, can be used in clinical trials to evaluate the impact of psoriasis on patients’ quality of life (Heller et al., 2012). However, these tools are not frequently used in clinical practice. Rather, in our experience, we have found it helpful to incorporate questions such as those in Table 1 into conversations with patients.



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Topical Therapies

Topical treatments are generally used as first-line therapy for most types of psoriasis. However, application of topical therapy can be messy and time consuming, and some treatments have unpleasant odors and/or sticky or greasy textures (L. H. Kircik & Kumar, 2010 ; Zschocke, Mrowietz, Karakasili, & Reich, 2014). Topical agents can also stain clothing and may be slow to absorb into the skin (Lee & Maibach, 2006). For patients with scalp psoriasis, hair discoloration is another potential complication of some topical therapies. As a result of the many inconveniences and other drawbacks of topical therapies (e.g., cost, frequency of application, treatment duration), the rate for patient adherence to topical treatment is low, and clinical outcomes are often far from optimal (Zschocke et al., 2014).

When using topical therapies for patients with difficult-to-treat psoriasis, it is important to employ treatment vehicles that will work best on the specific body areas affected by the disease. The range of vehicles used for delivery of topical formulations is extensive, including oils, ointments, creams, sprays, tapes, lotions, gels, bath solutions, shampoos, and foams (Handa, 2010 ; Wozel, 2008). Sensitivity of affected skin areas and patient preferences should be considered when selecting topical agent vehicles. For example, some patients with scalp psoriasis may prefer to use products that can be washed off (e.g., shampoos), whereas others may prefer products that can be left on the scalp, such as gels, lotions, and ointments. Many patients prefer the newer foam formulations of some topical therapies because of ease of use, rapid absorption with minimal residue, and no odor (Handa, 2010 ; Wozel, 2008).

Potent corticosteroids, which are a mainstay of many topical psoriasis treatment regimens (Guenther, 2015), should be avoided in patients with psoriasis in sensitive areas, including the facial and intertriginous areas, because of increased risks of cutaneous side effects, such as skin thinning. In addition, because of increased percutaneous absorption of steroids, phenols, and alcohols, inverse psoriasis should be treated only with topicals that are odorless, cosmetically acceptable, chemically and physically stable, and nonirritating (e.g., certain low- or mid-potency corticosteroids, vitamin D3 analogues, and calcineurin inhibitors; Kalb et al., 2009 ; Wozel, 2008).

Treatment of nail psoriasis with topical therapies is especially challenging. In many cases, the anatomical structure and texture of the nail make it difficult to apply topical agents that can effectively penetrate the nail bed or nail matrix. In some cases, it is possible to inject corticosteroids directly into nail lesions, but such procedures are painful and can increase risk of atrophy, depigmentation, infection, subungual hemorrhage, and tendon rupture (Crowley et al., 2015 ; Wozel, 2008). If intralesional injections are administered, patients should be given nerve blockers or topical anesthetics to reduce pain sensitivity (Crowley et al., 2015). Systemic treatment is usually recommended for nail psoriasis, especially when the disease is severe (Sánchez-Regaña et al., 2014).

More than two-thirds of patients with palmoplantar psoriasis have a disease that is recalcitrant to topical therapies (Sarma, 2017). Given the inherent severity of this disease manifestation, systemic therapies are often preferred (Engin et al., 2017 ; Sánchez-Regaña et al., 2014). In cases causing significant reductions in quality of life, use of biologics as first-line therapy is justified (Sánchez-Regaña et al., 2014). In our experience, topical therapies are useful as adjunct therapies in patients receiving treatment with biologics.

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Although phototherapy is a commonly used treatment for psoriasis, its utility is limited for many difficult-to-treat disease manifestations. For scalp psoriasis, use of traditional phototherapy is impractical and, in many cases, impossible because of the physical dimensions and light-emitting properties of machines. Although handheld phototherapy devices are available, they must be moved quickly and constantly over the scalp to avoid burns, which is often not feasible (L. H. Kircik & Kumar, 2010). For facial psoriasis, broadband ultraviolet B therapy should be minimized to reduce risk of toxicity (Menter et al., 2010). In patients with nail psoriasis, the effectiveness of phototherapy is limited; thus, phototherapy is not recommended for the treatment of isolated nail psoriasis without skin involvement (Langley et al., 2012). Phototherapy is also not recommended for male patients with genital psoriasis because it is associated with increased risks for genital tumors (Menter et al., 2010).

Phototherapy, including psoralen plus ultraviolet A baths and oral psoralen plus ultraviolet A with 8-methoxypsoralen, has shown efficacy in palmoplantar psoriasis. However, many patients find the need for repeated clinic visits burdensome, and phototherapy increases the risks of skin cancer (Handa, 2010). Treatment with a 308-nm excimer laser has also shown efficacy in patients with palmoplantar and scalp psoriasis (Al-Mutairi & Al-Haddad, 2013 ; Goldberg, Chwalek, & Hussain, 2011).

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Oral Systemic Therapies

Systemic therapies are indicated for patients with moderate-to-severe disease, which may include severe nail involvement (e.g., NAPSI > 10) with or without skin symptoms (Sánchez-Regaña et al., 2014). Conventional systemic therapies for psoriasis include methotrexate, cyclosporine, and acitretin. Although these agents can be effective for some patients with psoriasis affecting these difficult-to-treat areas, they are also associated with noteworthy limitations. In patients with scalp psoriasis, methotrexate and acitretin exacerbate hair loss (L. H. Kircik & Kumar, 2010 ; P. C. van de Kerkhof & Franssen, 2001). Other certain side effects of conventional systemic therapies can also be especially troubling for patients with psoriasis affecting difficult-to-treat areas. Methotrexate can cause photosensitivity, oral ulcerations, and burning sensations in lesions; acitretin can lead to dry skin, photosensitivity, peeling fingertips, nail changes, depression, and thoughts of aggression or self-harm; and cyclosporine can cause tingling or burning, skin sensitivity, renal toxicity, and muscle or joint pain (Deeming, Collingwood, & Pemberton, 2005 ; Young, Aldredge, & Parker, 2017). These are only some of the safety considerations that should be taken into account when prescribing conventional systemic therapies for patients with psoriasis affecting difficult-to-treat areas. The detailed safety of these agents has been reviewed elsewhere (Young et al., 2017).

Subanalyses of Phase III trials of apremilast (phosphodiesterase-4 inhibitor) in patients with moderate-to-severe plaque psoriasis showed that, compared with placebo, treatment for 16 weeks significantly reduced the severity of nail, scalp, and palmoplantar psoriasis (Bissonnette et al., 2016 ; Rich et al., 2016). Across studies, apremilast was generally well tolerated. However, apremilast is associated with increased rates of new or worsening depression, suicidal thoughts, and other mood changes (“Otezla prescribing information,” 2017). Patients with psoriasis affecting difficult-to-treat areas should be monitored especially closely for these types of side effects, given the already high psychologic burden of these clinical phenotypes.

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Biologic Therapies

Currently, eight biologic therapies have been approved for the treatment of moderate-to-severe or severe plaque psoriasis (adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, secukinumab, brodalumab, and guselkumab). Dosage, administration, and safety characteristics of these agents are summarized in Table 2. Evidence-based guidelines for the management of difficult-to-treat psoriasis have shown that good or at least fair evidence is available to support the efficacy of the tumor necrosis factor-α inhibitors, adalimumab, etanercept, and infliximab, for treating nail, scalp, and palmoplantar involvement (Sánchez-Regaña et al., 2014). Specifically, these agents are recommended for psoriasis that is uncontrolled with topical or conventional systemic therapies, is causing extensive lesions or a NAPSI score > 10, is rapidly worsening, is associated with a Dermatology Life Quality Index score > 10, or is present with a concomitant psoriatic joint disease (Sánchez-Regaña et al., 2014). However, these guidelines are limited because most of the data used to evaluate the efficacy and safety of tumor necrosis factor inhibitors for difficult-to-treat psoriasis manifestations were from retrospective studies and case reports (Sánchez-Regaña et al., 2014). In addition, most other investigations of these drugs were performed in subanalyses of Phase III trials.



Treatment with ustekinumab, an interleukin (IL)-12/23 antagonist, was associated with significant improvements in nail psoriasis in patients with moderate-to-severe plaque psoriasis based on a subgroup analysis of a Phase III study (Rich et al., 2014). Evaluation of the efficacy and safety of ustekinumab for other difficult-to-treat areas (scalp, palmoplantar, and inverse disease) has been limited to case reports/series (Campos, Varela, Baptista, & Moreira, 2016 ; Papadavid et al., 2014 ; Sánchez-Regaña et al., 2014).

In a subanalysis of three Phase III studies of ixekizumab, an IL-17A inhibitor, in patients with moderate-to-severe psoriasis, patients with scalp psoriasis had significantly greater Psoriasis Scalp Severity Index 90 responses at Week 12 with ixekizumab 80 mg every 2 weeks (81.7%) than with etanercept (55.5%; p < .001) or placebo (7.6%; p < .001; Reich, Leonardi, et al., 2017). In the subpopulation of patients with palmoplantar psoriasis in these three studies, significant improvements in palmoplantar Psoriasis Area and Severity Index (PASI) 75 scores were seen at Week 12 with ixekizumab 80 mg every 2 weeks (69.3%) compared with etanercept (44.1%; p < .05) and placebo (18.8%; p < .05; Menter et al., 2017). Data from one Phase III trial showed improvements in fingernail psoriasis as measured by mean percentage of NAPSI improvement for treatment with ixekizumab 80 mg every 2 weeks (35.2%) compared with etanercept (20.0%; p = .048) and placebo (−34.3%; p < .001) at Week 12 (P. van de Kerkhof et al., 2017).

The largest volume of data on the efficacy and safety of biologic agents for psoriasis affecting difficult-to-treat areas has come from randomized controlled trials of secukinumab, an IL-17A inhibitor. In a prospective Phase IIIb study of secukinumab in 205 patients with moderate-to-severe palmoplantar psoriasis, 33.3% of the patients treated with secukinumab 300 mg and 22.1% of the patients treated with secukinumab 150 mg for 16 weeks achieved clear or almost clear palms and soles, compared with 1.5% with placebo (p < .001; Gottlieb et al., 2017). Both secukinumab doses were associated with significant improvements in quality of life compared with placebo (Gottlieb et al., 2017). In a prospective Phase IIIb study of moderate-to-severe scalp psoriasis, more than half (52.9%) of 102 patients receiving treatment with secukinumab 300 mg for 12 weeks achieved Psoriasis Scalp Severity Index 90 responses compared with 2% of the placebo group (p < .001; Bagel et al., 2017). Secukinumab 150 mg showed significant efficacy for nail psoriasis compared with placebo in a subanalysis of a Phase II trial (Paul et al., 2014), and preliminary results from congress proceedings of a prospective Phase IIIb trial of secukinumab in moderate-to-severe nail psoriasis were positive; formal publication of these findings is expected soon (Reich, Arenberger, et al., 2017). In addition, in a pooled analysis of data from four Phase III studies of secukinumab that evaluated efficacy in patients with head and neck PASI subscores of ≥12 at baseline, head and neck PASI 90 and PASI 100 response rates in the patients taking 300 mg of secukinumab were 76% and 69%, respectively (L. Kircik et al., 2016).

Brodalumab, an IL-17 receptor inhibitor, has not been evaluated in psoriasis affecting difficult-to-treat areas. Guselkumab, an IL-23 inhibitor, was evaluated in scalp, nail, and palmoplantar psoriasis in a subanalysis of a Phase III trial (Blauvelt et al., 2017). In patients with baseline scalp-specific Investigator’s Global Assessment (IGA) (ss-IGA) ≥ 2 and ≥2-grade improvement in ss-IGA, ss-IGA 0/1 response rates at Week 16 were achieved by 83.4% of patients receiving guselkumab 100 mg, 70.3% of patients receiving adalimumab, and 14.5% of patients receiving placebo (p < .001 for guselkumab vs. placebo). Among patients with NAPSI scores, there was a mean percent improvement at Week 16 of 34.4 with guselkumab 100 mg, 38.0 with adalimumab, and −0.9 with placebo (p < .001 for guselkumab vs. placebo). In patients with baseline hands and/or feet Physician’s Global Assessment (PGA) (hf-PGA) score ≥ 2, ≥2-grade improvement in ss-IGA and hf-PGA scores, and ≥1-grade improvement in f-PGA score, hf-PGA 0/1 response rates at Week 16 were achieved by 73.3% of patients receiving guselkumab 100 mg, 55.8% of patients receiving adalimumab, and 14.0% of patients receiving placebo (significant guselkumab vs. placebo, p value not provided; Blauvelt et al., 2017).

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Difficult-to-treat areas of plaque psoriasis (scalp, face, nails, genitals, and palms/soles) are more common than previously thought. These areas may not respond as well to traditional treatment algorithms for plaque psoriasis and are associated with disproportionately high physical and psychosocial burdens compared with chronic plaque psoriasis. NPs and PAs can provide valuable patient-centered care for these psoriasis manifestations and facilitate discussions about treatment goals that may be achievable using one or more agents from the diverse therapeutic armamentarium for psoriasis. Encouraging results from clinical trials of new biologic agents should provide hope to those patients with psoriasis affecting difficult-to-treat areas.

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      Difficult-to-Treat Psoriasis; Facial Psoriasis; Inverse Psoriasis; Nail Psoriasis; Palmoplantar Psoriasis; Scalp Psoriasis

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