Vipawee S. Chat, MD

Psoriasis is a chronic inflammatory skin disease characterized by erythematous scaly plaques that can invoke substantial pain, pruritus, and quality-of-life disturbance in patients. Topical therapies are the most commonly used medications for treating psoriasis, with one study (N = 128,308) showing that more than 85% of patients with psoriasis were managed solely with topical medications. ¹ For patients with mild to moderate psoriasis, topical agents alone may be able to control disease completely. For those with more severe disease, topical agents are used adjunctively with systemic or biologic agents to optimize disease control in localized areas.

The American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) published guidelines in 2020 for managing psoriasis with topical agents in adults.² This review presents the most up-to-date clinical recommendations for topical agent use in adult patients with psoriasis and elaborates on each drug’s pharmacologic and safety profile. Specifically, evidence-based treatment recommendations for topical steroids, calcineurin inhibitors (CNIs), vitamin D analogues, retinoids (tazarotene), emollients, keratolytics (salicylic acid), anthracenes (anthralin), and keratoplastics (coal tar) will be addressed (Table 1). Recommendations for combination therapy with other treatment modalities including UVB light therapy, biologics, and systemic nonbiologic agents also will be discussed.

Selecting a Topical Agent Based on Disease Localization

When treating patients with psoriasis with topical therapies, clinicians should take into consideration drug potency, as it determines how effective a treatment will be in penetrating the skin barrier. Plaque characteristics, such as distribution (localized vs widespread), anatomical localization (flexural, scalp, palms/soles/nails), size (large vs small), and thickness (thick vs thin), not only influence treatment effectiveness but also the incidence of drug-related adverse events. Furthermore, preferred topical therapies are tailored to each patient based on disease characteristics and activity. Coal tar and anthralin have been used less frequently than other topical therapies for psoriasis because of their undesirable side-effect profiles (Table 1).³

Face and Intertriginous Regions—The face and intertriginous areas are sensitive because skin tends to be thin in these regions. Emollients are recommended for disease in these locations given their safety and flexibility in use for most areas. Conversely, anthralin should be avoided on the face, intertriginous areas, and even highly visible locations because of the potential for skin staining. Low-potency corticosteroids also have utility in psoriasis distributed on the face and intertriginous regions. Additionally, application of steroids around the eyes should be cautioned because topical steroids can induce ocular complications such as glaucoma and cataracts in rare circumstances.⁴

Off-label use of CNIs for psoriasis on the face and intertriginous areas also is effective. Currently, there is a level B recommendation for off-label use of 0.1% tacrolimus for up to 8 weeks for inverse psoriasis or psoriasis on the face. Off-label use of pimecrolimus for 4 to 8 weeks also can be considered for inverse psoriasis. Combination therapy consisting of hydrocortisone with calcipotriol ointment is another effective regimen.⁵ One study also suggested that use of crisaborole for 4 to 8 weeks in intertriginous psoriasis can be effective and well tolerated.⁶

Scalp—The vehicle of medication administration is especially important in hair-bearing areas such as the scalp, as these areas are challenging for medication application and patient adherence. Thus, patient preferences for the vehicle must be considered. Several studies have been conducted to assess preference for various vehicles in scalp psoriasis. A foam or solution may be preferable to ointments, gels, or creams.⁷ Gels may be preferred over ointments.⁸ There is a level A recommendation supporting the use of class 1 to 7 topical steroids for a minimum of 4 weeks as initial and maintenance treatment of scalp psoriasis. The highest level of evidence (level A) also supports the use of calcipotriol foam or combination therapy of calcipotriol–betamethasone dipropionate gel for 4 to 12 weeks as treatment of mild to moderate scalp psoriasis.

Nails—Several options for topical medications have been recommended for the treatment of nail psoriasis. Currently, there is a level B recommendation for the use of tazarotene for the treatment of nail psoriasis. Another effective regimen is combination therapy with vitamin D analogues and betamethasone dipropionate.⁹ Topical steroid use for nail psoriasis should be limited to 12 weeks because of the risk for bone atrophy with chronic steroid use.

Palmoplantar—The palms and soles have a thicker epidermal layer than other areas of the body. As a result, class 1 corticosteroids can be used for palmoplantar psoriasis for more than 4 weeks with vigilant monitoring for adverse effects such as skin atrophy, tachyphylaxis, or tinea infection. Tazarotene also has been shown to be helpful in treating palmoplantar psoriasis.

Resistant Disease—Intralesional steroids are beneficial treatment options for recalcitrant psoriasis in glabrous areas, as well as for palmoplantar, nail, and scalp psoriasis. Up to 10 mg/mL of triamcinolone acetonide used every 3 to 4 weeks is an effective regimen.¹⁰Pregnancy/Breastfeeding—Women of childbearing potential have additional safety precautions that should be considered during medication selection. Emollients have been shown to be safe during pregnancy and lactation. Currently, there is little known about CNI use during pregnancy. During lactation, CNIs can be used by breastfeeding mothers in most areas, excluding the breasts. Evaluation of the safety of anthralin and vitamin D analogues during pregnancy and lactation have not been studied. For these agents, dermatologists need to use their clinical judgment to weigh the risks and benefits of medication, particularly in patients requiring occlusion, higher medication doses, or treatment over a large surface area. Salicylic acid should be used with caution in pregnant and breastfeeding mothers because it is a pregnancy category C drug. Lower-potency corticosteroids may be used with caution during pregnancy and breastfeeding. More potent corticosteroids and coal tar, however, should be avoided. Similarly, tazarotene use is contraindicated in pregnancy. According to the US Food and Drug Administration labels for all forms of topical tazarotene, a pregnancy test must be obtained 2 weeks prior to tazarotene treatment initiation in women of childbearing potential because of the risk for serious fetal malformations and toxicity.

Recommendations, Risks, and Benefits of Topical Therapy for the Management of Psoriasis

Topical Corticosteroids—Topical corticosteroids (TCs) are widely used for inflammatory skin conditions and are available in a variety of strengths (Table 2). They are thought to exert their action by regulating the gene transcription of proinflammatory mediators. For psoriasis, steroids are recommended for 2 to 4 weeks, depending on disease severity. Although potent and superpotent steroids are more effective than mild- to moderate-strength TCs, use of lower-potency TCs may be warranted depending on disease distribution and localization.¹¹ For treatment of psoriasis with no involvement of the intertriginous areas, use of class 1 to 5 TCs for up to 4 weeks is recommended.

For moderate to severe psoriasis with 20% or less body surface area (BSA) affected, combination therapy consisting of mometasone and salicylic acid has been shown to be more effective than mometasone alone.^12,13 There currently is a level A recommendation for the use of combination therapy with class 1 TCs and etanercept for 12 weeks in patients with moderate to severe psoriasis who require both systemic and topical therapies for disease control. Similarly, combination therapy with infliximab and high-potency TCs has a level B recommendation to enhance efficacy for the treatment of moderate to severe psoriasis.¹⁴ High-quality studies on the use of TCs with anti–IL-12/IL-23, anti–IL-23, and anti–IL-17 currently are unavailable, but the combination is not expected to be unsafe.^14,15 Combination therapy of betamethasone dipropionate ointment and low-dose cyclosporine is an alternative regimen with a level B recommendation.

The most common adverse effects with use of TCs are skin thinning and atrophy, telangiectasia, and striae (Table 1). With clinical improvement of disease, it is recommended that clinicians taper TCs to prevent rebound effect. To decrease TC-related adverse effects, clinicians should use combination therapy with steroid-sparing agents for disease maintenance, transition to lower-potency corticosteroids, or use intermittent steroid therapy. Systemic effects of TC use include hypothalamic-pituitary-adrenal axis suppression, Cushing syndrome, and osteonecrosis of the femoral head.^16-18 These systemic effects with TC use are rare unless treatment is for disease involving greater than 20% BSA or occlusion for more than 4 weeks.

Calcineurin Inhibitors—Calcineurin inhibitors inhibit calcineurin phosphorylation and T-cell activation, subsequently decreasing the expression of proinflammatory cytokines. Currently, they are not approved by the US Food and Drug Administration to treat psoriasis but have demonstrated efficacy in randomized control trials (RCTs) for facial and intertriginous psoriasis. In RCTs, 71% of patients using pimecrolimus cream 0.1% twice daily for 8 weeks achieved an investigator global assessment score of clear (0) or almost clear (1) compared with 21% of placebo-treated patients (N=57).¹⁹ Other trials have shown that 65% of patients receiving tacrolimus ointment 0.1% for 8 weeks achieved an investigator global assessment score of 0 or 1 compared with 31% of placebo-treated patients (N=167).²⁰ Because of their efficacy in RCTs, CNIs commonly are used off label to treat psoriasis.

The most common adverse effects with CNI use are burning, pruritus, and flushing with alcohol ingestion (Table 1). Additionally, CNIs have a black box warning that use may increase the risk for malignancy, but this risk has not been demonstrated with topical use in humans.²¹Vitamin D Analogues—The class of vitamin D analogues—calcipotriol/calcipotriene and calcitriol—frequently are used to treat psoriasis. Vitamin D analogues exert their beneficial effects by inhibiting keratinocyte proliferation and enhancing keratinocyte differentiation. They also are ideal for long-term use (up to 52 weeks) in mild to moderate psoriasis and can be used in combination with class 2 and 3 TCs. There is a level A recommendation that supports the use of combination therapy with calcipotriol and TCs for the treatment of mild to moderate psoriasis.

For severe psoriasis, many studies have investigated the efficacy of combination therapy with vitamin D analogues and systemic treatments. Combination therapy with calcipotriol and methotrexate or calcipotriol and acitretin are effective treatment regimens with level A recommendations. Calcipotriol–betamethasone dipropionate ointment in combination with low-dose cyclosporine is an alternative option with a level B recommendation. Because vitamin D analogues are inactivated by UVA and UVB radiation, clinicians should advise their patients to use vitamin D analogues after receiving UVB phototherapy.²²

Common adverse effects of vitamin D analogues include burning, pruritus, erythema, and dryness (Table 1). Hypercalcemia and parathyroid hormone suppression are extremely rare unless treatment occurs over a large surface area (>30% BSA) or the patient has concurrent renal disease or impairments in calcium metabolism.

Tazarotene—Tazarotene is a topical retinoid that acts by decreasing keratinocyte proliferation, facilitating keratinocyte differentiation, and inhibiting inflammation. Patients with mild to moderate psoriasis are recommended to receive tazarotene treatment for 8 to 12 weeks. In several RCTs, tazarotene gel 0.1% and tazarotene cream 0.1% and 0.05% achieved treatment success in treating plaque psoriasis.^23,24

For increased efficacy, clinicians can recommend combination therapy with tazarotene and a TC. Combination therapy with tazarotene and a mid- or high-potency TC for 8 to 16 weeks has been shown to be more effective than treatment with tazarotene alone.²⁵ Thus, there is a level A recommendation for use of this combination to treat mild to moderate psoriasis. Agents used in combination therapy work synergistically to decrease the length of treatment and increase the duration of remission. The frequency of adverse effects, such as irritation from tazarotene and skin atrophy from TCs, also are reduced.²⁶ Combination therapy with tazarotene and narrowband UVB (NB-UVB) is another effective option that requires less UV radiation than NB-UVB alone because of the synergistic effects of both treatment modalities.²⁷ Clinicians should counsel patients on the adverse effects of tazarotene, which include local irritation, burning, pruritus, and erythema (Table 1).

Emollients—Emollients are nonmedicated moisturizers that decrease the amount of transepidermal water loss. There is a level B recommendation for use of emollients and TCs in combination for 4 to 8 weeks to treat psoriasis. In fact, combination therapy with mometasone and emollients has demonstrated greater improvement in symptoms of palmoplantar psoriasis (ie, erythema, desquamation, infiltration, BSA involvement) than mometasone alone.²⁸ Emollients are safe options that can be used on all areas of the body and during pregnancy and lactation. Although adverse effects of emollients are rare, clinicians should counsel patients on the risk for contact dermatitis if specific allergies to ingredients/fragrances exist (Table 1).

Salicylic Acid—Salicylic acid is a topical keratolytic that can be used to treat psoriatic plaques. Use of salicylic acid for 8 to 16 weeks has been shown to be effective for mild to moderate psoriasis. Combination therapy of salicylic acid and TCs in patients with 20% or less BSA affected is a safe and effective option with a level B recommendation. Combination therapy with salicylic acid and calcipotriene, however, should be avoided because calcipotriene is inactivated by salicylic acid. It also is recommended that salicylic acid application follow phototherapy when both treatment modalities are used in combination.^29,30 Clinicians should be cautious about using salicylic acid in patients with renal or hepatic disease because of the increased risk for salicylate toxicity (Table 1).

Anthralin—Anthralin is a synthetic hydrocarbon derivative that has been shown to reduce inflammation and normalize keratinocyte proliferation through an unknown mechanism. It is recommended that patients with mild to moderate psoriasis receive anthralin treatment for 8 to 12 weeks, with a maximum application time of 2 hours per day. Combination therapy of excimer laser and anthralin has been shown to be more effective in treating psoriasis than anthralin alone.³¹ Therefore, clinicians have the option of including excimer laser therapy for additional disease control. Anthralin should be avoided on the face, flexural regions, and highly visible areas because of potential skin staining (Table 1). Other adverse effects include application-site burning and erythema.

Coal Tar—Coal tar is a heterogenous mixture of aromatic hydrocarbons that is an effective treatment of psoriasis because of its inherent anti-inflammatory and keratoplastic properties. There is high-quality evidence supporting a level A recommendation for coal tar use in mild to moderate psoriasis. Combination therapy with NB-UVB and coal tar (also known as Goeckerman therapy) is a recommended treatment option with a quicker onset of action and improved outcomes compared with NB-UVB therapy alone.^32,33 Adverse events of coal tar include application-site irritation, folliculitis, contact dermatitis, phototoxicity, and skin pigmentation (Table 1).

Conclusion

Topical medications are versatile treatment options that can be utilized as monotherapy or adjunct therapy for mild to severe psoriasis. Benefits of topical agents include minimal required monitoring, few contraindications, and direct localized effect on plaques. Therefore, side effects with topical agent use rarely are systemic. Medication interactions are less of a concern with topical therapies; thus, they have better safety profiles compared with systemic therapies. This clinical review summarizes the recently published evidence-based guidelines from the AAD and NPF on the use of topical agents in psoriasis and may be a useful guiding framework for clinicians in their everyday practice.

Psoriasis is a chronic inflammatory skin disease characterized by erythematous scaly plaques that can invoke substantial pain, pruritus, and quality-of-life disturbance in patients. Topical therapies are the most commonly used medications for treating psoriasis, with one study (N = 128,308) showing that more than 85% of patients with psoriasis were managed solely with topical medications. ¹ For patients with mild to moderate psoriasis, topical agents alone may be able to control disease completely. For those with more severe disease, topical agents are used adjunctively with systemic or biologic agents to optimize disease control in localized areas.

The American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) published guidelines in 2020 for managing psoriasis with topical agents in adults.² This review presents the most up-to-date clinical recommendations for topical agent use in adult patients with psoriasis and elaborates on each drug’s pharmacologic and safety profile. Specifically, evidence-based treatment recommendations for topical steroids, calcineurin inhibitors (CNIs), vitamin D analogues, retinoids (tazarotene), emollients, keratolytics (salicylic acid), anthracenes (anthralin), and keratoplastics (coal tar) will be addressed (Table 1). Recommendations for combination therapy with other treatment modalities including UVB light therapy, biologics, and systemic nonbiologic agents also will be discussed.

Selecting a Topical Agent Based on Disease Localization

When treating patients with psoriasis with topical therapies, clinicians should take into consideration drug potency, as it determines how effective a treatment will be in penetrating the skin barrier. Plaque characteristics, such as distribution (localized vs widespread), anatomical localization (flexural, scalp, palms/soles/nails), size (large vs small), and thickness (thick vs thin), not only influence treatment effectiveness but also the incidence of drug-related adverse events. Furthermore, preferred topical therapies are tailored to each patient based on disease characteristics and activity. Coal tar and anthralin have been used less frequently than other topical therapies for psoriasis because of their undesirable side-effect profiles (Table 1).³

Face and Intertriginous Regions—The face and intertriginous areas are sensitive because skin tends to be thin in these regions. Emollients are recommended for disease in these locations given their safety and flexibility in use for most areas. Conversely, anthralin should be avoided on the face, intertriginous areas, and even highly visible locations because of the potential for skin staining. Low-potency corticosteroids also have utility in psoriasis distributed on the face and intertriginous regions. Additionally, application of steroids around the eyes should be cautioned because topical steroids can induce ocular complications such as glaucoma and cataracts in rare circumstances.⁴

Off-label use of CNIs for psoriasis on the face and intertriginous areas also is effective. Currently, there is a level B recommendation for off-label use of 0.1% tacrolimus for up to 8 weeks for inverse psoriasis or psoriasis on the face. Off-label use of pimecrolimus for 4 to 8 weeks also can be considered for inverse psoriasis. Combination therapy consisting of hydrocortisone with calcipotriol ointment is another effective regimen.⁵ One study also suggested that use of crisaborole for 4 to 8 weeks in intertriginous psoriasis can be effective and well tolerated.⁶

Scalp—The vehicle of medication administration is especially important in hair-bearing areas such as the scalp, as these areas are challenging for medication application and patient adherence. Thus, patient preferences for the vehicle must be considered. Several studies have been conducted to assess preference for various vehicles in scalp psoriasis. A foam or solution may be preferable to ointments, gels, or creams.⁷ Gels may be preferred over ointments.⁸ There is a level A recommendation supporting the use of class 1 to 7 topical steroids for a minimum of 4 weeks as initial and maintenance treatment of scalp psoriasis. The highest level of evidence (level A) also supports the use of calcipotriol foam or combination therapy of calcipotriol–betamethasone dipropionate gel for 4 to 12 weeks as treatment of mild to moderate scalp psoriasis.

Nails—Several options for topical medications have been recommended for the treatment of nail psoriasis. Currently, there is a level B recommendation for the use of tazarotene for the treatment of nail psoriasis. Another effective regimen is combination therapy with vitamin D analogues and betamethasone dipropionate.⁹ Topical steroid use for nail psoriasis should be limited to 12 weeks because of the risk for bone atrophy with chronic steroid use.

Palmoplantar—The palms and soles have a thicker epidermal layer than other areas of the body. As a result, class 1 corticosteroids can be used for palmoplantar psoriasis for more than 4 weeks with vigilant monitoring for adverse effects such as skin atrophy, tachyphylaxis, or tinea infection. Tazarotene also has been shown to be helpful in treating palmoplantar psoriasis.

Resistant Disease—Intralesional steroids are beneficial treatment options for recalcitrant psoriasis in glabrous areas, as well as for palmoplantar, nail, and scalp psoriasis. Up to 10 mg/mL of triamcinolone acetonide used every 3 to 4 weeks is an effective regimen.¹⁰Pregnancy/Breastfeeding—Women of childbearing potential have additional safety precautions that should be considered during medication selection. Emollients have been shown to be safe during pregnancy and lactation. Currently, there is little known about CNI use during pregnancy. During lactation, CNIs can be used by breastfeeding mothers in most areas, excluding the breasts. Evaluation of the safety of anthralin and vitamin D analogues during pregnancy and lactation have not been studied. For these agents, dermatologists need to use their clinical judgment to weigh the risks and benefits of medication, particularly in patients requiring occlusion, higher medication doses, or treatment over a large surface area. Salicylic acid should be used with caution in pregnant and breastfeeding mothers because it is a pregnancy category C drug. Lower-potency corticosteroids may be used with caution during pregnancy and breastfeeding. More potent corticosteroids and coal tar, however, should be avoided. Similarly, tazarotene use is contraindicated in pregnancy. According to the US Food and Drug Administration labels for all forms of topical tazarotene, a pregnancy test must be obtained 2 weeks prior to tazarotene treatment initiation in women of childbearing potential because of the risk for serious fetal malformations and toxicity.

Recommendations, Risks, and Benefits of Topical Therapy for the Management of Psoriasis

Topical Corticosteroids—Topical corticosteroids (TCs) are widely used for inflammatory skin conditions and are available in a variety of strengths (Table 2). They are thought to exert their action by regulating the gene transcription of proinflammatory mediators. For psoriasis, steroids are recommended for 2 to 4 weeks, depending on disease severity. Although potent and superpotent steroids are more effective than mild- to moderate-strength TCs, use of lower-potency TCs may be warranted depending on disease distribution and localization.¹¹ For treatment of psoriasis with no involvement of the intertriginous areas, use of class 1 to 5 TCs for up to 4 weeks is recommended.

For moderate to severe psoriasis with 20% or less body surface area (BSA) affected, combination therapy consisting of mometasone and salicylic acid has been shown to be more effective than mometasone alone.^12,13 There currently is a level A recommendation for the use of combination therapy with class 1 TCs and etanercept for 12 weeks in patients with moderate to severe psoriasis who require both systemic and topical therapies for disease control. Similarly, combination therapy with infliximab and high-potency TCs has a level B recommendation to enhance efficacy for the treatment of moderate to severe psoriasis.¹⁴ High-quality studies on the use of TCs with anti–IL-12/IL-23, anti–IL-23, and anti–IL-17 currently are unavailable, but the combination is not expected to be unsafe.^14,15 Combination therapy of betamethasone dipropionate ointment and low-dose cyclosporine is an alternative regimen with a level B recommendation.

The most common adverse effects with use of TCs are skin thinning and atrophy, telangiectasia, and striae (Table 1). With clinical improvement of disease, it is recommended that clinicians taper TCs to prevent rebound effect. To decrease TC-related adverse effects, clinicians should use combination therapy with steroid-sparing agents for disease maintenance, transition to lower-potency corticosteroids, or use intermittent steroid therapy. Systemic effects of TC use include hypothalamic-pituitary-adrenal axis suppression, Cushing syndrome, and osteonecrosis of the femoral head.^16-18 These systemic effects with TC use are rare unless treatment is for disease involving greater than 20% BSA or occlusion for more than 4 weeks.

Calcineurin Inhibitors—Calcineurin inhibitors inhibit calcineurin phosphorylation and T-cell activation, subsequently decreasing the expression of proinflammatory cytokines. Currently, they are not approved by the US Food and Drug Administration to treat psoriasis but have demonstrated efficacy in randomized control trials (RCTs) for facial and intertriginous psoriasis. In RCTs, 71% of patients using pimecrolimus cream 0.1% twice daily for 8 weeks achieved an investigator global assessment score of clear (0) or almost clear (1) compared with 21% of placebo-treated patients (N=57).¹⁹ Other trials have shown that 65% of patients receiving tacrolimus ointment 0.1% for 8 weeks achieved an investigator global assessment score of 0 or 1 compared with 31% of placebo-treated patients (N=167).²⁰ Because of their efficacy in RCTs, CNIs commonly are used off label to treat psoriasis.

The most common adverse effects with CNI use are burning, pruritus, and flushing with alcohol ingestion (Table 1). Additionally, CNIs have a black box warning that use may increase the risk for malignancy, but this risk has not been demonstrated with topical use in humans.²¹Vitamin D Analogues—The class of vitamin D analogues—calcipotriol/calcipotriene and calcitriol—frequently are used to treat psoriasis. Vitamin D analogues exert their beneficial effects by inhibiting keratinocyte proliferation and enhancing keratinocyte differentiation. They also are ideal for long-term use (up to 52 weeks) in mild to moderate psoriasis and can be used in combination with class 2 and 3 TCs. There is a level A recommendation that supports the use of combination therapy with calcipotriol and TCs for the treatment of mild to moderate psoriasis.

For severe psoriasis, many studies have investigated the efficacy of combination therapy with vitamin D analogues and systemic treatments. Combination therapy with calcipotriol and methotrexate or calcipotriol and acitretin are effective treatment regimens with level A recommendations. Calcipotriol–betamethasone dipropionate ointment in combination with low-dose cyclosporine is an alternative option with a level B recommendation. Because vitamin D analogues are inactivated by UVA and UVB radiation, clinicians should advise their patients to use vitamin D analogues after receiving UVB phototherapy.²²

Common adverse effects of vitamin D analogues include burning, pruritus, erythema, and dryness (Table 1). Hypercalcemia and parathyroid hormone suppression are extremely rare unless treatment occurs over a large surface area (>30% BSA) or the patient has concurrent renal disease or impairments in calcium metabolism.

Tazarotene—Tazarotene is a topical retinoid that acts by decreasing keratinocyte proliferation, facilitating keratinocyte differentiation, and inhibiting inflammation. Patients with mild to moderate psoriasis are recommended to receive tazarotene treatment for 8 to 12 weeks. In several RCTs, tazarotene gel 0.1% and tazarotene cream 0.1% and 0.05% achieved treatment success in treating plaque psoriasis.^23,24

For increased efficacy, clinicians can recommend combination therapy with tazarotene and a TC. Combination therapy with tazarotene and a mid- or high-potency TC for 8 to 16 weeks has been shown to be more effective than treatment with tazarotene alone.²⁵ Thus, there is a level A recommendation for use of this combination to treat mild to moderate psoriasis. Agents used in combination therapy work synergistically to decrease the length of treatment and increase the duration of remission. The frequency of adverse effects, such as irritation from tazarotene and skin atrophy from TCs, also are reduced.²⁶ Combination therapy with tazarotene and narrowband UVB (NB-UVB) is another effective option that requires less UV radiation than NB-UVB alone because of the synergistic effects of both treatment modalities.²⁷ Clinicians should counsel patients on the adverse effects of tazarotene, which include local irritation, burning, pruritus, and erythema (Table 1).

Emollients—Emollients are nonmedicated moisturizers that decrease the amount of transepidermal water loss. There is a level B recommendation for use of emollients and TCs in combination for 4 to 8 weeks to treat psoriasis. In fact, combination therapy with mometasone and emollients has demonstrated greater improvement in symptoms of palmoplantar psoriasis (ie, erythema, desquamation, infiltration, BSA involvement) than mometasone alone.²⁸ Emollients are safe options that can be used on all areas of the body and during pregnancy and lactation. Although adverse effects of emollients are rare, clinicians should counsel patients on the risk for contact dermatitis if specific allergies to ingredients/fragrances exist (Table 1).

Salicylic Acid—Salicylic acid is a topical keratolytic that can be used to treat psoriatic plaques. Use of salicylic acid for 8 to 16 weeks has been shown to be effective for mild to moderate psoriasis. Combination therapy of salicylic acid and TCs in patients with 20% or less BSA affected is a safe and effective option with a level B recommendation. Combination therapy with salicylic acid and calcipotriene, however, should be avoided because calcipotriene is inactivated by salicylic acid. It also is recommended that salicylic acid application follow phototherapy when both treatment modalities are used in combination.^29,30 Clinicians should be cautious about using salicylic acid in patients with renal or hepatic disease because of the increased risk for salicylate toxicity (Table 1).

Anthralin—Anthralin is a synthetic hydrocarbon derivative that has been shown to reduce inflammation and normalize keratinocyte proliferation through an unknown mechanism. It is recommended that patients with mild to moderate psoriasis receive anthralin treatment for 8 to 12 weeks, with a maximum application time of 2 hours per day. Combination therapy of excimer laser and anthralin has been shown to be more effective in treating psoriasis than anthralin alone.³¹ Therefore, clinicians have the option of including excimer laser therapy for additional disease control. Anthralin should be avoided on the face, flexural regions, and highly visible areas because of potential skin staining (Table 1). Other adverse effects include application-site burning and erythema.

Coal Tar—Coal tar is a heterogenous mixture of aromatic hydrocarbons that is an effective treatment of psoriasis because of its inherent anti-inflammatory and keratoplastic properties. There is high-quality evidence supporting a level A recommendation for coal tar use in mild to moderate psoriasis. Combination therapy with NB-UVB and coal tar (also known as Goeckerman therapy) is a recommended treatment option with a quicker onset of action and improved outcomes compared with NB-UVB therapy alone.^32,33 Adverse events of coal tar include application-site irritation, folliculitis, contact dermatitis, phototoxicity, and skin pigmentation (Table 1).

Conclusion

Topical medications are versatile treatment options that can be utilized as monotherapy or adjunct therapy for mild to severe psoriasis. Benefits of topical agents include minimal required monitoring, few contraindications, and direct localized effect on plaques. Therefore, side effects with topical agent use rarely are systemic. Medication interactions are less of a concern with topical therapies; thus, they have better safety profiles compared with systemic therapies. This clinical review summarizes the recently published evidence-based guidelines from the AAD and NPF on the use of topical agents in psoriasis and may be a useful guiding framework for clinicians in their everyday practice.

Psoriasis is a chronic inflammatory skin disease characterized by erythematous scaly plaques that can invoke substantial pain, pruritus, and quality-of-life disturbance in patients. Topical therapies are the most commonly used medications for treating psoriasis, with one study (N = 128,308) showing that more than 85% of patients with psoriasis were managed solely with topical medications. ¹ For patients with mild to moderate psoriasis, topical agents alone may be able to control disease completely. For those with more severe disease, topical agents are used adjunctively with systemic or biologic agents to optimize disease control in localized areas.

The American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) published guidelines in 2020 for managing psoriasis with topical agents in adults.² This review presents the most up-to-date clinical recommendations for topical agent use in adult patients with psoriasis and elaborates on each drug’s pharmacologic and safety profile. Specifically, evidence-based treatment recommendations for topical steroids, calcineurin inhibitors (CNIs), vitamin D analogues, retinoids (tazarotene), emollients, keratolytics (salicylic acid), anthracenes (anthralin), and keratoplastics (coal tar) will be addressed (Table 1). Recommendations for combination therapy with other treatment modalities including UVB light therapy, biologics, and systemic nonbiologic agents also will be discussed.

Selecting a Topical Agent Based on Disease Localization

When treating patients with psoriasis with topical therapies, clinicians should take into consideration drug potency, as it determines how effective a treatment will be in penetrating the skin barrier. Plaque characteristics, such as distribution (localized vs widespread), anatomical localization (flexural, scalp, palms/soles/nails), size (large vs small), and thickness (thick vs thin), not only influence treatment effectiveness but also the incidence of drug-related adverse events. Furthermore, preferred topical therapies are tailored to each patient based on disease characteristics and activity. Coal tar and anthralin have been used less frequently than other topical therapies for psoriasis because of their undesirable side-effect profiles (Table 1).³

Face and Intertriginous Regions—The face and intertriginous areas are sensitive because skin tends to be thin in these regions. Emollients are recommended for disease in these locations given their safety and flexibility in use for most areas. Conversely, anthralin should be avoided on the face, intertriginous areas, and even highly visible locations because of the potential for skin staining. Low-potency corticosteroids also have utility in psoriasis distributed on the face and intertriginous regions. Additionally, application of steroids around the eyes should be cautioned because topical steroids can induce ocular complications such as glaucoma and cataracts in rare circumstances.⁴

Off-label use of CNIs for psoriasis on the face and intertriginous areas also is effective. Currently, there is a level B recommendation for off-label use of 0.1% tacrolimus for up to 8 weeks for inverse psoriasis or psoriasis on the face. Off-label use of pimecrolimus for 4 to 8 weeks also can be considered for inverse psoriasis. Combination therapy consisting of hydrocortisone with calcipotriol ointment is another effective regimen.⁵ One study also suggested that use of crisaborole for 4 to 8 weeks in intertriginous psoriasis can be effective and well tolerated.⁶

Scalp—The vehicle of medication administration is especially important in hair-bearing areas such as the scalp, as these areas are challenging for medication application and patient adherence. Thus, patient preferences for the vehicle must be considered. Several studies have been conducted to assess preference for various vehicles in scalp psoriasis. A foam or solution may be preferable to ointments, gels, or creams.⁷ Gels may be preferred over ointments.⁸ There is a level A recommendation supporting the use of class 1 to 7 topical steroids for a minimum of 4 weeks as initial and maintenance treatment of scalp psoriasis. The highest level of evidence (level A) also supports the use of calcipotriol foam or combination therapy of calcipotriol–betamethasone dipropionate gel for 4 to 12 weeks as treatment of mild to moderate scalp psoriasis.

Nails—Several options for topical medications have been recommended for the treatment of nail psoriasis. Currently, there is a level B recommendation for the use of tazarotene for the treatment of nail psoriasis. Another effective regimen is combination therapy with vitamin D analogues and betamethasone dipropionate.⁹ Topical steroid use for nail psoriasis should be limited to 12 weeks because of the risk for bone atrophy with chronic steroid use.

Palmoplantar—The palms and soles have a thicker epidermal layer than other areas of the body. As a result, class 1 corticosteroids can be used for palmoplantar psoriasis for more than 4 weeks with vigilant monitoring for adverse effects such as skin atrophy, tachyphylaxis, or tinea infection. Tazarotene also has been shown to be helpful in treating palmoplantar psoriasis.

Resistant Disease—Intralesional steroids are beneficial treatment options for recalcitrant psoriasis in glabrous areas, as well as for palmoplantar, nail, and scalp psoriasis. Up to 10 mg/mL of triamcinolone acetonide used every 3 to 4 weeks is an effective regimen.¹⁰Pregnancy/Breastfeeding—Women of childbearing potential have additional safety precautions that should be considered during medication selection. Emollients have been shown to be safe during pregnancy and lactation. Currently, there is little known about CNI use during pregnancy. During lactation, CNIs can be used by breastfeeding mothers in most areas, excluding the breasts. Evaluation of the safety of anthralin and vitamin D analogues during pregnancy and lactation have not been studied. For these agents, dermatologists need to use their clinical judgment to weigh the risks and benefits of medication, particularly in patients requiring occlusion, higher medication doses, or treatment over a large surface area. Salicylic acid should be used with caution in pregnant and breastfeeding mothers because it is a pregnancy category C drug. Lower-potency corticosteroids may be used with caution during pregnancy and breastfeeding. More potent corticosteroids and coal tar, however, should be avoided. Similarly, tazarotene use is contraindicated in pregnancy. According to the US Food and Drug Administration labels for all forms of topical tazarotene, a pregnancy test must be obtained 2 weeks prior to tazarotene treatment initiation in women of childbearing potential because of the risk for serious fetal malformations and toxicity.

Recommendations, Risks, and Benefits of Topical Therapy for the Management of Psoriasis

Topical Corticosteroids—Topical corticosteroids (TCs) are widely used for inflammatory skin conditions and are available in a variety of strengths (Table 2). They are thought to exert their action by regulating the gene transcription of proinflammatory mediators. For psoriasis, steroids are recommended for 2 to 4 weeks, depending on disease severity. Although potent and superpotent steroids are more effective than mild- to moderate-strength TCs, use of lower-potency TCs may be warranted depending on disease distribution and localization.¹¹ For treatment of psoriasis with no involvement of the intertriginous areas, use of class 1 to 5 TCs for up to 4 weeks is recommended.

For moderate to severe psoriasis with 20% or less body surface area (BSA) affected, combination therapy consisting of mometasone and salicylic acid has been shown to be more effective than mometasone alone.^12,13 There currently is a level A recommendation for the use of combination therapy with class 1 TCs and etanercept for 12 weeks in patients with moderate to severe psoriasis who require both systemic and topical therapies for disease control. Similarly, combination therapy with infliximab and high-potency TCs has a level B recommendation to enhance efficacy for the treatment of moderate to severe psoriasis.¹⁴ High-quality studies on the use of TCs with anti–IL-12/IL-23, anti–IL-23, and anti–IL-17 currently are unavailable, but the combination is not expected to be unsafe.^14,15 Combination therapy of betamethasone dipropionate ointment and low-dose cyclosporine is an alternative regimen with a level B recommendation.

The most common adverse effects with use of TCs are skin thinning and atrophy, telangiectasia, and striae (Table 1). With clinical improvement of disease, it is recommended that clinicians taper TCs to prevent rebound effect. To decrease TC-related adverse effects, clinicians should use combination therapy with steroid-sparing agents for disease maintenance, transition to lower-potency corticosteroids, or use intermittent steroid therapy. Systemic effects of TC use include hypothalamic-pituitary-adrenal axis suppression, Cushing syndrome, and osteonecrosis of the femoral head.^16-18 These systemic effects with TC use are rare unless treatment is for disease involving greater than 20% BSA or occlusion for more than 4 weeks.

Calcineurin Inhibitors—Calcineurin inhibitors inhibit calcineurin phosphorylation and T-cell activation, subsequently decreasing the expression of proinflammatory cytokines. Currently, they are not approved by the US Food and Drug Administration to treat psoriasis but have demonstrated efficacy in randomized control trials (RCTs) for facial and intertriginous psoriasis. In RCTs, 71% of patients using pimecrolimus cream 0.1% twice daily for 8 weeks achieved an investigator global assessment score of clear (0) or almost clear (1) compared with 21% of placebo-treated patients (N=57).¹⁹ Other trials have shown that 65% of patients receiving tacrolimus ointment 0.1% for 8 weeks achieved an investigator global assessment score of 0 or 1 compared with 31% of placebo-treated patients (N=167).²⁰ Because of their efficacy in RCTs, CNIs commonly are used off label to treat psoriasis.

The most common adverse effects with CNI use are burning, pruritus, and flushing with alcohol ingestion (Table 1). Additionally, CNIs have a black box warning that use may increase the risk for malignancy, but this risk has not been demonstrated with topical use in humans.²¹Vitamin D Analogues—The class of vitamin D analogues—calcipotriol/calcipotriene and calcitriol—frequently are used to treat psoriasis. Vitamin D analogues exert their beneficial effects by inhibiting keratinocyte proliferation and enhancing keratinocyte differentiation. They also are ideal for long-term use (up to 52 weeks) in mild to moderate psoriasis and can be used in combination with class 2 and 3 TCs. There is a level A recommendation that supports the use of combination therapy with calcipotriol and TCs for the treatment of mild to moderate psoriasis.

For severe psoriasis, many studies have investigated the efficacy of combination therapy with vitamin D analogues and systemic treatments. Combination therapy with calcipotriol and methotrexate or calcipotriol and acitretin are effective treatment regimens with level A recommendations. Calcipotriol–betamethasone dipropionate ointment in combination with low-dose cyclosporine is an alternative option with a level B recommendation. Because vitamin D analogues are inactivated by UVA and UVB radiation, clinicians should advise their patients to use vitamin D analogues after receiving UVB phototherapy.²²

Common adverse effects of vitamin D analogues include burning, pruritus, erythema, and dryness (Table 1). Hypercalcemia and parathyroid hormone suppression are extremely rare unless treatment occurs over a large surface area (>30% BSA) or the patient has concurrent renal disease or impairments in calcium metabolism.

Tazarotene—Tazarotene is a topical retinoid that acts by decreasing keratinocyte proliferation, facilitating keratinocyte differentiation, and inhibiting inflammation. Patients with mild to moderate psoriasis are recommended to receive tazarotene treatment for 8 to 12 weeks. In several RCTs, tazarotene gel 0.1% and tazarotene cream 0.1% and 0.05% achieved treatment success in treating plaque psoriasis.^23,24

For increased efficacy, clinicians can recommend combination therapy with tazarotene and a TC. Combination therapy with tazarotene and a mid- or high-potency TC for 8 to 16 weeks has been shown to be more effective than treatment with tazarotene alone.²⁵ Thus, there is a level A recommendation for use of this combination to treat mild to moderate psoriasis. Agents used in combination therapy work synergistically to decrease the length of treatment and increase the duration of remission. The frequency of adverse effects, such as irritation from tazarotene and skin atrophy from TCs, also are reduced.²⁶ Combination therapy with tazarotene and narrowband UVB (NB-UVB) is another effective option that requires less UV radiation than NB-UVB alone because of the synergistic effects of both treatment modalities.²⁷ Clinicians should counsel patients on the adverse effects of tazarotene, which include local irritation, burning, pruritus, and erythema (Table 1).

Emollients—Emollients are nonmedicated moisturizers that decrease the amount of transepidermal water loss. There is a level B recommendation for use of emollients and TCs in combination for 4 to 8 weeks to treat psoriasis. In fact, combination therapy with mometasone and emollients has demonstrated greater improvement in symptoms of palmoplantar psoriasis (ie, erythema, desquamation, infiltration, BSA involvement) than mometasone alone.²⁸ Emollients are safe options that can be used on all areas of the body and during pregnancy and lactation. Although adverse effects of emollients are rare, clinicians should counsel patients on the risk for contact dermatitis if specific allergies to ingredients/fragrances exist (Table 1).

Salicylic Acid—Salicylic acid is a topical keratolytic that can be used to treat psoriatic plaques. Use of salicylic acid for 8 to 16 weeks has been shown to be effective for mild to moderate psoriasis. Combination therapy of salicylic acid and TCs in patients with 20% or less BSA affected is a safe and effective option with a level B recommendation. Combination therapy with salicylic acid and calcipotriene, however, should be avoided because calcipotriene is inactivated by salicylic acid. It also is recommended that salicylic acid application follow phototherapy when both treatment modalities are used in combination.^29,30 Clinicians should be cautious about using salicylic acid in patients with renal or hepatic disease because of the increased risk for salicylate toxicity (Table 1).

Anthralin—Anthralin is a synthetic hydrocarbon derivative that has been shown to reduce inflammation and normalize keratinocyte proliferation through an unknown mechanism. It is recommended that patients with mild to moderate psoriasis receive anthralin treatment for 8 to 12 weeks, with a maximum application time of 2 hours per day. Combination therapy of excimer laser and anthralin has been shown to be more effective in treating psoriasis than anthralin alone.³¹ Therefore, clinicians have the option of including excimer laser therapy for additional disease control. Anthralin should be avoided on the face, flexural regions, and highly visible areas because of potential skin staining (Table 1). Other adverse effects include application-site burning and erythema.

Coal Tar—Coal tar is a heterogenous mixture of aromatic hydrocarbons that is an effective treatment of psoriasis because of its inherent anti-inflammatory and keratoplastic properties. There is high-quality evidence supporting a level A recommendation for coal tar use in mild to moderate psoriasis. Combination therapy with NB-UVB and coal tar (also known as Goeckerman therapy) is a recommended treatment option with a quicker onset of action and improved outcomes compared with NB-UVB therapy alone.^32,33 Adverse events of coal tar include application-site irritation, folliculitis, contact dermatitis, phototoxicity, and skin pigmentation (Table 1).

Conclusion

Topical medications are versatile treatment options that can be utilized as monotherapy or adjunct therapy for mild to severe psoriasis. Benefits of topical agents include minimal required monitoring, few contraindications, and direct localized effect on plaques. Therefore, side effects with topical agent use rarely are systemic. Medication interactions are less of a concern with topical therapies; thus, they have better safety profiles compared with systemic therapies. This clinical review summarizes the recently published evidence-based guidelines from the AAD and NPF on the use of topical agents in psoriasis and may be a useful guiding framework for clinicians in their everyday practice.

Psoriasis is a chronic and relapsing systemic inflammatory disease that predisposes patients to a host of other conditions. It is believed that these widespread effects are due to chronic inflammation and cytokine activation, which affect multiple body processes and lead to the development of various comorbidities that need to be proactively managed.

In April 2019, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) released recommendation guidelines for managing psoriasis in adults with an emphasis on common disease comorbidities, including psoriatic arthritis (PsA), cardiovascular disease (CVD), inflammatory bowel disease (IBD), metabolic syndrome, and mood disorders. Psychosocial wellness, mental health, and quality of life (QOL) measures in relation to psoriatic disease also were discussed.¹

The AAD-NPF guidelines address current screening, monitoring, education, and treatment recommendations for the management of psoriatic comorbidities. The Table and eTable summarize the screening recommendations. These guidelines aim to assist dermatologists with comprehensive disease management by addressing potential extracutaneous manifestations of psoriasis in adults.

Screening and Risk Assessment

Patients with psoriasis should receive a thorough history and physical examination to assess disease severity and risk for potential comorbidities. Patients with greater disease severity—as measured by body surface area (BSA) involvement and type of therapy required—have a greater risk for other disease-related comorbidities, specifically metabolic syndrome, renal disease, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, uveitis, IBD, malignancy, and increased mortality.² Because the likelihood of comorbidities is greatest with severe disease, more frequent monitoring is recommended for these patients.

Psoriatic Arthritis

Patients with psoriasis need to be evaluated for PsA at every visit. Patients presenting with signs and symptoms suspicious for PsA—joint swelling, peripheral joint involvement, and joint inflammation—warrant further evaluation and consultation. Early detection and treatment of PsA is essential for preventing unnecessary suffering and progressive joint destruction.³

There are several PsA screening questionnaires currently available, including the Psoriatic Arthritis Screening Evaluation, Psoriasis Epidemiology Screening Tool, and Toronto Psoriatic Arthritis Screen. No significant differences in sensitivity and specificity were found among these questionnaires when using the Classification Criteria for Psoriatic Arthritis as the gold standard. All 3 questionnaires—the Psoriatic Arthritis Screening Evaluation and the Psoriasis Epidemiology Screening Tool were developed for use in dermatology and rheumatology clinics, and the Toronto Psoriatic Arthritis Screen was developed for use in the primary care setting—were found to be effective in dermatology/rheumatology clinics and primary care clinics, respectively.³ False-positive results predominantly were seen in patients with degenerative joint disease or osteoarthritis. Dermatologists should conduct a thorough physical examination to distinguish PsA from degenerative joint disease. Imaging and laboratory tests to evaluate for signs of systemic inflammation (erythrocyte sedimentation rate, C-reactive protein) also can be helpful in distinguishing the 2 conditions; however, these metrics have not been shown to contribute to PsA diagnosis.¹ Full rheumatologic consultation is warranted in challenging cases.

Cardiovascular Disease

The American Heart Association and the American College of Cardiology have identified chronic inflammatory states, such as psoriasis, as inducing factors that predispose patients to CVD. Many studies have found an association among psoriasis, coronary artery disease, myocardial infarction (MI), and stroke.^4-7 It is strongly recommended that dermatologists educate patients of their increased risk for CVD, given the association between psoriasis and major adverse cardiovascular events (eg, stroke, heart failure, MI) and cardiovascular health. However, patients with congestive heart failure were found to have an increased risk of mortality associated with use of tumor necrosis factor (TNF) α inhibitors (P=.016).⁸ Thus, TNF inhibitors are contraindicated in patients with New York Heart Association Class III or Class IV congestive heart failure.⁹

Primary care physicians (PCPs) are recommended to screen patients for CVD risk factors using height, weight, blood pressure, blood glucose, hemoglobin A_1C, lipid levels, abdominal circumference, and body mass index (BMI). Lifestyle modifications such as smoking cessation, exercise, and dietary changes are encouraged to achieve and maintain a normal BMI.

Dermatologists also need to give special consideration to comorbidities when selecting medications and/or therapies for disease management. Patients on TNF inhibitors have a lower risk for MI compared with patients using topical medications, phototherapy, and other oral agents.¹⁰ Additionally, patients on TNF inhibitors have a lower risk for occurrence of major adverse cardiovascular events compared with patients treated with methotrexate or phototherapy.^11,12

Metabolic Syndrome

Numerous studies have demonstrated an association between psoriasis and metabolic syndrome. Patients with increased BSA involvement and psoriasis area and severity index scores have a higher prevalence of metabolic syndrome.¹³ Patients with psoriasis have an increased risk for the following conditions compared to controls: obesity (38% vs 31%; odds ratio [OR], 1.38; 95% CI, 1.29-1.48), elevated triglycerides (36% vs 28%; OR, 1.49; 95% CI, 1.39-1.60), hypertension (31% vs 28%; OR, 1.20; 95% CI, 1.11-12.9), and elevated glucose levels (22% vs 16%; OR, 1.44; 95% CI, 1.33-1.56).¹⁴ Dermatologists are strongly recommended to inform patients about the risk for metabolic syndrome and to encourage the measurement of blood pressure, waist circumference, fasting blood glucose, hemoglobin A_1C, and fasting lipid levels with their PCP when indicated. Body mass index and waist circumference also should be measured annually in patients with moderate to severe psoriasis because of the association with disease severity.

The association between psoriasis and weight loss has been analyzed in several studies. Weight loss, particularly in obese patients, has been shown to improve psoriasis severity, as measured by psoriasis area and severity index score and QOL measures.¹⁵ Another study found that gastric bypass was associated with a significant risk reduction in the development of psoriasis (P=.004) and the disease prognosis (P=.02 for severe psoriasis; P=.01 for PsA).¹⁶ Therefore, patients with moderate to severe psoriasis are recommended to have their obesity status determined according to national guidelines. For patients with a BMI above 40 kg/m² and standard weight-loss measures fail, bariatric surgery is recommended. Additionally, the impact of psoriasis medications on weight has been studied. Apremilast has been associated with weight loss, whereas etanercept and infliximab have been linked to weight gain.^17,18

An association between psoriasis and hypertension also has been demonstrated by studies, especially among patients with severe disease. Therefore, patients with moderate to severe psoriasis are recommended to have their blood pressure evaluated according to national guidelines, and those with a blood pressure of 140/90 mm Hg or higher should be referred to their PCP for assessment and treatment. Current evidence does not support restrictions on antihypertensive medications in patients with psoriasis. Physicians should be aware of the potential for cyclosporine to induce hypertension, which should be treated, specifically with amlodipine.¹⁹

Many studies have demonstrated an association between psoriasis and dyslipidemia, though the results are somewhat conflicting. In 2018, the American Heart Association and the American College of Cardiology deemed psoriasis as an atherosclerotic CVD risk-enhancing condition, favoring early initiation of statin therapy. Because dyslipidemia plays a prominent role in atherosclerosis and CVD, patients with moderate to severe psoriasis are recommended to undergo periodic screening with lipid tests (eg, fasting total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides).²⁰ Patients with elevated fasting triglycerides or low-density lipoprotein cholesterol should be referred to their PCP for further management. Certain psoriasis medications also have been linked to dyslipidemia. Acitretin and cyclosporine are known to adversely affect lipid levels, so patients treated with either agent should undergo routine monitoring of serum lipid levels.

Psoriasis is strongly associated with diabetes mellitus. Because of the increased risk for diabetes in patients with severe disease, regular monitoring of fasting blood glucose and/or hemoglobin A_1C levels in patients with moderate to severe psoriasis is recommended. Patients who meet criteria for prediabetes or diabetes should be referred to their PCP for further assessment and management.^21,22

Mood Disorders

Psoriasis affects QOL and can have a major impact on patients’ interpersonal relationships. Studies have shown an association between psoriasis and mood disorders, specifically depression and anxiety. Unfortunately, patients with mood disorders are less likely to seek intervention for their skin disease, which poses a tremendous treatment barrier. Dermatologists should regularly monitor patients for psychiatric symptoms so that resources and treatments can be offered.

Certain psoriasis therapies have been shown to help alleviate associated depression and anxiety. Improvements in Beck Depression Inventory and Hamilton Depression Rating Scale scores were seen with etanercept.²³ Adalimumab and ustekinumab showed improvement in Dermatology Life Quality Index compared with placebo.^24,25 Patients receiving Goeckerman treatment also had improvement in anxiety and depression scores compared with conventional therapy.²⁶ Biologic medications had the largest impact on improving depression symptoms compared with conventional systemic therapy and phototherapy.²⁷ The recommendations support use of biologics and the Goeckerman regimen for the concomitant treatment of mood disorders and psoriasis.

Renal Disease

Studies have supported an association between psoriasis and chronic kidney disease (CKD), independent of risk factors including vascular disease, hypertension, and diabetes. The prevalence of moderate to advanced CKD also has been found to be directly related to increasing BSA affected by psoriasis.²⁸ Patients should receive testing of blood urea nitrogen, creatinine, and urine microalbumin levels to assess for occult renal disease. In addition, physicians should be cautious when prescribing nephrotoxic drugs (nonsteroidal anti-inflammatory drugs and cyclosporine) and renally excreted agents (methotrexate and apremilast) because of the risk for underlying renal disease in patients with psoriasis. If newly acquired renal disease is suspected, physicians should withhold the offending agents. Patients with psoriasis with CKD are recommended to follow up with their PCP or nephrologist for evaluation and management.

Pulmonary Disease

Psoriasis also has an independent association with COPD. Patients with psoriasis have a higher likelihood of developing COPD (hazard ratio, 2.35; 95% CI, 1.42-3.89; P<.01) than controls.²⁹ The prevalence of COPD also was found to correlate with psoriasis severity. Dermatologists should educate patients about the association between smoking and psoriasis as well as advise patients to discontinue smoking to reduce their risk for developing COPD and cancer.

Patients with psoriasis also are at an increased risk for obstructive sleep apnea. Obstructive sleep apnea should be considered in patients with risk factors including snoring, obesity, hypertension, or diabetes.

Inflammatory Bowel Disease

Patients with psoriasis have an increased risk for developing IBD. The prevalence ratios of both Crohn disease (2.49) and ulcerative colitis (1.64) are increased in patients with psoriasis relative to patients without psoriasis.³⁰ Physicians need to be aware of the association between psoriasis and IBD and the effect that their coexistence may have on treatment choice for patients.

Adalimumab and infliximab are approved for the treatment of IBD, and certolizumab and ustekinumab are approved for Crohn disease. Use of TNF inhibitors in patients with IBD may cause psoriasiform lesions to develop.³¹ Nonetheless, treatment should be individualized and psoriasiform lesions treated with standard psoriasis measures. Psoriasis patients with IBD are recommended to avoid IL-17–inhibitor therapy, given its potential to worsen IBD flares.

Malignancy

Psoriasis patients aged 0 to 79 years have a greater overall risk for malignancy compared with patients without psoriasis.³² Patients with psoriasis have an increased risk for respiratory tract cancer, upper aerodigestive tract cancer, urinary tract cancer, and non-Hodgkin lymphoma.³³ A mild association exists between PsA and lymphoma, nonmelanoma skin cancer (NMSC), and lung cancer.³⁴ More severe psoriasis is associated with greater risk for lymphoma and NMSC. Dermatologists are recommended to educate patients on their risk for certain malignancies and to refer patients to specialists upon suspicion of malignancy.

Risk for malignancy has been shown to be affected by psoriasis treatments. Patients treated with UVB have reduced overall cancer rates for all age groups (hazard ratio, 0.52; P=.3), while those treated with psoralen plus UVA have an increased incidence of squamous cell carcinoma.^32,33 Adalimumab was correlated with increased risk for NMSC in patients with psoriasis but did not have an increased risk for all cancers collectively when used for various immune-mediated inflammatory diseases.³⁵ In contrast, a meta-analysis of randomized clinical trials found no association with TNF inhibitor use and NMSC.³⁶ Ustekinumab had no association with malignancy.³⁷ Treatment history should be elucidated because of higher rates of squamous cell carcinoma in patients with prior psoralen plus UVA, cyclosporine, or methotrexate use.³³ To address malignancy risk, patients with psoriasis should undergo regular screenings for skin cancer and follow national guidelines for age-appropriate cancer screenings.

Lifestyle Choices and QOL

A crucial aspect of successful psoriasis management is patient education. The strongest recommendations support lifestyle changes, such as smoking cessation and limitation of alcohol use. A tactful discussion regarding substance use, work productivity, interpersonal relationships, and sexual function can address substantial effects of psoriasis on QOL so that support and resources can be provided.

Final Thoughts

Management of psoriasis is multifaceted and involves screening, education, monitoring, and collaboration with PCPs and specialists. Regular follow-up with a dermatologist and PCP is strongly recommended for patients with psoriasis given the systemic nature of the disease. The 2019 AAD-NPF recommendations provide important information for dermatologists to coordinate care for complicated psoriasis cases, but clinical judgment is paramount when making medical decisions. The consideration of comorbidities is critical for developing a comprehensive treatment approach, and this approach will lead to better health outcomes and improved QOL for patients with psoriasis.

Psoriasis is a chronic and relapsing systemic inflammatory disease that predisposes patients to a host of other conditions. It is believed that these widespread effects are due to chronic inflammation and cytokine activation, which affect multiple body processes and lead to the development of various comorbidities that need to be proactively managed.

In April 2019, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) released recommendation guidelines for managing psoriasis in adults with an emphasis on common disease comorbidities, including psoriatic arthritis (PsA), cardiovascular disease (CVD), inflammatory bowel disease (IBD), metabolic syndrome, and mood disorders. Psychosocial wellness, mental health, and quality of life (QOL) measures in relation to psoriatic disease also were discussed.¹

The AAD-NPF guidelines address current screening, monitoring, education, and treatment recommendations for the management of psoriatic comorbidities. The Table and eTable summarize the screening recommendations. These guidelines aim to assist dermatologists with comprehensive disease management by addressing potential extracutaneous manifestations of psoriasis in adults.

Screening and Risk Assessment

Patients with psoriasis should receive a thorough history and physical examination to assess disease severity and risk for potential comorbidities. Patients with greater disease severity—as measured by body surface area (BSA) involvement and type of therapy required—have a greater risk for other disease-related comorbidities, specifically metabolic syndrome, renal disease, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, uveitis, IBD, malignancy, and increased mortality.² Because the likelihood of comorbidities is greatest with severe disease, more frequent monitoring is recommended for these patients.

Psoriatic Arthritis

Patients with psoriasis need to be evaluated for PsA at every visit. Patients presenting with signs and symptoms suspicious for PsA—joint swelling, peripheral joint involvement, and joint inflammation—warrant further evaluation and consultation. Early detection and treatment of PsA is essential for preventing unnecessary suffering and progressive joint destruction.³

There are several PsA screening questionnaires currently available, including the Psoriatic Arthritis Screening Evaluation, Psoriasis Epidemiology Screening Tool, and Toronto Psoriatic Arthritis Screen. No significant differences in sensitivity and specificity were found among these questionnaires when using the Classification Criteria for Psoriatic Arthritis as the gold standard. All 3 questionnaires—the Psoriatic Arthritis Screening Evaluation and the Psoriasis Epidemiology Screening Tool were developed for use in dermatology and rheumatology clinics, and the Toronto Psoriatic Arthritis Screen was developed for use in the primary care setting—were found to be effective in dermatology/rheumatology clinics and primary care clinics, respectively.³ False-positive results predominantly were seen in patients with degenerative joint disease or osteoarthritis. Dermatologists should conduct a thorough physical examination to distinguish PsA from degenerative joint disease. Imaging and laboratory tests to evaluate for signs of systemic inflammation (erythrocyte sedimentation rate, C-reactive protein) also can be helpful in distinguishing the 2 conditions; however, these metrics have not been shown to contribute to PsA diagnosis.¹ Full rheumatologic consultation is warranted in challenging cases.

Cardiovascular Disease

The American Heart Association and the American College of Cardiology have identified chronic inflammatory states, such as psoriasis, as inducing factors that predispose patients to CVD. Many studies have found an association among psoriasis, coronary artery disease, myocardial infarction (MI), and stroke.^4-7 It is strongly recommended that dermatologists educate patients of their increased risk for CVD, given the association between psoriasis and major adverse cardiovascular events (eg, stroke, heart failure, MI) and cardiovascular health. However, patients with congestive heart failure were found to have an increased risk of mortality associated with use of tumor necrosis factor (TNF) α inhibitors (P=.016).⁸ Thus, TNF inhibitors are contraindicated in patients with New York Heart Association Class III or Class IV congestive heart failure.⁹

Primary care physicians (PCPs) are recommended to screen patients for CVD risk factors using height, weight, blood pressure, blood glucose, hemoglobin A_1C, lipid levels, abdominal circumference, and body mass index (BMI). Lifestyle modifications such as smoking cessation, exercise, and dietary changes are encouraged to achieve and maintain a normal BMI.

Dermatologists also need to give special consideration to comorbidities when selecting medications and/or therapies for disease management. Patients on TNF inhibitors have a lower risk for MI compared with patients using topical medications, phototherapy, and other oral agents.¹⁰ Additionally, patients on TNF inhibitors have a lower risk for occurrence of major adverse cardiovascular events compared with patients treated with methotrexate or phototherapy.^11,12

Metabolic Syndrome

Numerous studies have demonstrated an association between psoriasis and metabolic syndrome. Patients with increased BSA involvement and psoriasis area and severity index scores have a higher prevalence of metabolic syndrome.¹³ Patients with psoriasis have an increased risk for the following conditions compared to controls: obesity (38% vs 31%; odds ratio [OR], 1.38; 95% CI, 1.29-1.48), elevated triglycerides (36% vs 28%; OR, 1.49; 95% CI, 1.39-1.60), hypertension (31% vs 28%; OR, 1.20; 95% CI, 1.11-12.9), and elevated glucose levels (22% vs 16%; OR, 1.44; 95% CI, 1.33-1.56).¹⁴ Dermatologists are strongly recommended to inform patients about the risk for metabolic syndrome and to encourage the measurement of blood pressure, waist circumference, fasting blood glucose, hemoglobin A_1C, and fasting lipid levels with their PCP when indicated. Body mass index and waist circumference also should be measured annually in patients with moderate to severe psoriasis because of the association with disease severity.

The association between psoriasis and weight loss has been analyzed in several studies. Weight loss, particularly in obese patients, has been shown to improve psoriasis severity, as measured by psoriasis area and severity index score and QOL measures.¹⁵ Another study found that gastric bypass was associated with a significant risk reduction in the development of psoriasis (P=.004) and the disease prognosis (P=.02 for severe psoriasis; P=.01 for PsA).¹⁶ Therefore, patients with moderate to severe psoriasis are recommended to have their obesity status determined according to national guidelines. For patients with a BMI above 40 kg/m² and standard weight-loss measures fail, bariatric surgery is recommended. Additionally, the impact of psoriasis medications on weight has been studied. Apremilast has been associated with weight loss, whereas etanercept and infliximab have been linked to weight gain.^17,18

An association between psoriasis and hypertension also has been demonstrated by studies, especially among patients with severe disease. Therefore, patients with moderate to severe psoriasis are recommended to have their blood pressure evaluated according to national guidelines, and those with a blood pressure of 140/90 mm Hg or higher should be referred to their PCP for assessment and treatment. Current evidence does not support restrictions on antihypertensive medications in patients with psoriasis. Physicians should be aware of the potential for cyclosporine to induce hypertension, which should be treated, specifically with amlodipine.¹⁹

Many studies have demonstrated an association between psoriasis and dyslipidemia, though the results are somewhat conflicting. In 2018, the American Heart Association and the American College of Cardiology deemed psoriasis as an atherosclerotic CVD risk-enhancing condition, favoring early initiation of statin therapy. Because dyslipidemia plays a prominent role in atherosclerosis and CVD, patients with moderate to severe psoriasis are recommended to undergo periodic screening with lipid tests (eg, fasting total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides).²⁰ Patients with elevated fasting triglycerides or low-density lipoprotein cholesterol should be referred to their PCP for further management. Certain psoriasis medications also have been linked to dyslipidemia. Acitretin and cyclosporine are known to adversely affect lipid levels, so patients treated with either agent should undergo routine monitoring of serum lipid levels.

Psoriasis is strongly associated with diabetes mellitus. Because of the increased risk for diabetes in patients with severe disease, regular monitoring of fasting blood glucose and/or hemoglobin A_1C levels in patients with moderate to severe psoriasis is recommended. Patients who meet criteria for prediabetes or diabetes should be referred to their PCP for further assessment and management.^21,22

Mood Disorders

Psoriasis affects QOL and can have a major impact on patients’ interpersonal relationships. Studies have shown an association between psoriasis and mood disorders, specifically depression and anxiety. Unfortunately, patients with mood disorders are less likely to seek intervention for their skin disease, which poses a tremendous treatment barrier. Dermatologists should regularly monitor patients for psychiatric symptoms so that resources and treatments can be offered.

Certain psoriasis therapies have been shown to help alleviate associated depression and anxiety. Improvements in Beck Depression Inventory and Hamilton Depression Rating Scale scores were seen with etanercept.²³ Adalimumab and ustekinumab showed improvement in Dermatology Life Quality Index compared with placebo.^24,25 Patients receiving Goeckerman treatment also had improvement in anxiety and depression scores compared with conventional therapy.²⁶ Biologic medications had the largest impact on improving depression symptoms compared with conventional systemic therapy and phototherapy.²⁷ The recommendations support use of biologics and the Goeckerman regimen for the concomitant treatment of mood disorders and psoriasis.

Renal Disease

Studies have supported an association between psoriasis and chronic kidney disease (CKD), independent of risk factors including vascular disease, hypertension, and diabetes. The prevalence of moderate to advanced CKD also has been found to be directly related to increasing BSA affected by psoriasis.²⁸ Patients should receive testing of blood urea nitrogen, creatinine, and urine microalbumin levels to assess for occult renal disease. In addition, physicians should be cautious when prescribing nephrotoxic drugs (nonsteroidal anti-inflammatory drugs and cyclosporine) and renally excreted agents (methotrexate and apremilast) because of the risk for underlying renal disease in patients with psoriasis. If newly acquired renal disease is suspected, physicians should withhold the offending agents. Patients with psoriasis with CKD are recommended to follow up with their PCP or nephrologist for evaluation and management.

Pulmonary Disease

Psoriasis also has an independent association with COPD. Patients with psoriasis have a higher likelihood of developing COPD (hazard ratio, 2.35; 95% CI, 1.42-3.89; P<.01) than controls.²⁹ The prevalence of COPD also was found to correlate with psoriasis severity. Dermatologists should educate patients about the association between smoking and psoriasis as well as advise patients to discontinue smoking to reduce their risk for developing COPD and cancer.

Patients with psoriasis also are at an increased risk for obstructive sleep apnea. Obstructive sleep apnea should be considered in patients with risk factors including snoring, obesity, hypertension, or diabetes.

Inflammatory Bowel Disease

Patients with psoriasis have an increased risk for developing IBD. The prevalence ratios of both Crohn disease (2.49) and ulcerative colitis (1.64) are increased in patients with psoriasis relative to patients without psoriasis.³⁰ Physicians need to be aware of the association between psoriasis and IBD and the effect that their coexistence may have on treatment choice for patients.

Adalimumab and infliximab are approved for the treatment of IBD, and certolizumab and ustekinumab are approved for Crohn disease. Use of TNF inhibitors in patients with IBD may cause psoriasiform lesions to develop.³¹ Nonetheless, treatment should be individualized and psoriasiform lesions treated with standard psoriasis measures. Psoriasis patients with IBD are recommended to avoid IL-17–inhibitor therapy, given its potential to worsen IBD flares.

Malignancy

Psoriasis patients aged 0 to 79 years have a greater overall risk for malignancy compared with patients without psoriasis.³² Patients with psoriasis have an increased risk for respiratory tract cancer, upper aerodigestive tract cancer, urinary tract cancer, and non-Hodgkin lymphoma.³³ A mild association exists between PsA and lymphoma, nonmelanoma skin cancer (NMSC), and lung cancer.³⁴ More severe psoriasis is associated with greater risk for lymphoma and NMSC. Dermatologists are recommended to educate patients on their risk for certain malignancies and to refer patients to specialists upon suspicion of malignancy.

Risk for malignancy has been shown to be affected by psoriasis treatments. Patients treated with UVB have reduced overall cancer rates for all age groups (hazard ratio, 0.52; P=.3), while those treated with psoralen plus UVA have an increased incidence of squamous cell carcinoma.^32,33 Adalimumab was correlated with increased risk for NMSC in patients with psoriasis but did not have an increased risk for all cancers collectively when used for various immune-mediated inflammatory diseases.³⁵ In contrast, a meta-analysis of randomized clinical trials found no association with TNF inhibitor use and NMSC.³⁶ Ustekinumab had no association with malignancy.³⁷ Treatment history should be elucidated because of higher rates of squamous cell carcinoma in patients with prior psoralen plus UVA, cyclosporine, or methotrexate use.³³ To address malignancy risk, patients with psoriasis should undergo regular screenings for skin cancer and follow national guidelines for age-appropriate cancer screenings.

Lifestyle Choices and QOL

A crucial aspect of successful psoriasis management is patient education. The strongest recommendations support lifestyle changes, such as smoking cessation and limitation of alcohol use. A tactful discussion regarding substance use, work productivity, interpersonal relationships, and sexual function can address substantial effects of psoriasis on QOL so that support and resources can be provided.

Final Thoughts

Management of psoriasis is multifaceted and involves screening, education, monitoring, and collaboration with PCPs and specialists. Regular follow-up with a dermatologist and PCP is strongly recommended for patients with psoriasis given the systemic nature of the disease. The 2019 AAD-NPF recommendations provide important information for dermatologists to coordinate care for complicated psoriasis cases, but clinical judgment is paramount when making medical decisions. The consideration of comorbidities is critical for developing a comprehensive treatment approach, and this approach will lead to better health outcomes and improved QOL for patients with psoriasis.

Psoriasis is a chronic and relapsing systemic inflammatory disease that predisposes patients to a host of other conditions. It is believed that these widespread effects are due to chronic inflammation and cytokine activation, which affect multiple body processes and lead to the development of various comorbidities that need to be proactively managed.

In April 2019, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) released recommendation guidelines for managing psoriasis in adults with an emphasis on common disease comorbidities, including psoriatic arthritis (PsA), cardiovascular disease (CVD), inflammatory bowel disease (IBD), metabolic syndrome, and mood disorders. Psychosocial wellness, mental health, and quality of life (QOL) measures in relation to psoriatic disease also were discussed.¹

The AAD-NPF guidelines address current screening, monitoring, education, and treatment recommendations for the management of psoriatic comorbidities. The Table and eTable summarize the screening recommendations. These guidelines aim to assist dermatologists with comprehensive disease management by addressing potential extracutaneous manifestations of psoriasis in adults.

Screening and Risk Assessment

Patients with psoriasis should receive a thorough history and physical examination to assess disease severity and risk for potential comorbidities. Patients with greater disease severity—as measured by body surface area (BSA) involvement and type of therapy required—have a greater risk for other disease-related comorbidities, specifically metabolic syndrome, renal disease, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, uveitis, IBD, malignancy, and increased mortality.² Because the likelihood of comorbidities is greatest with severe disease, more frequent monitoring is recommended for these patients.

Psoriatic Arthritis

Patients with psoriasis need to be evaluated for PsA at every visit. Patients presenting with signs and symptoms suspicious for PsA—joint swelling, peripheral joint involvement, and joint inflammation—warrant further evaluation and consultation. Early detection and treatment of PsA is essential for preventing unnecessary suffering and progressive joint destruction.³

There are several PsA screening questionnaires currently available, including the Psoriatic Arthritis Screening Evaluation, Psoriasis Epidemiology Screening Tool, and Toronto Psoriatic Arthritis Screen. No significant differences in sensitivity and specificity were found among these questionnaires when using the Classification Criteria for Psoriatic Arthritis as the gold standard. All 3 questionnaires—the Psoriatic Arthritis Screening Evaluation and the Psoriasis Epidemiology Screening Tool were developed for use in dermatology and rheumatology clinics, and the Toronto Psoriatic Arthritis Screen was developed for use in the primary care setting—were found to be effective in dermatology/rheumatology clinics and primary care clinics, respectively.³ False-positive results predominantly were seen in patients with degenerative joint disease or osteoarthritis. Dermatologists should conduct a thorough physical examination to distinguish PsA from degenerative joint disease. Imaging and laboratory tests to evaluate for signs of systemic inflammation (erythrocyte sedimentation rate, C-reactive protein) also can be helpful in distinguishing the 2 conditions; however, these metrics have not been shown to contribute to PsA diagnosis.¹ Full rheumatologic consultation is warranted in challenging cases.

Cardiovascular Disease

The American Heart Association and the American College of Cardiology have identified chronic inflammatory states, such as psoriasis, as inducing factors that predispose patients to CVD. Many studies have found an association among psoriasis, coronary artery disease, myocardial infarction (MI), and stroke.^4-7 It is strongly recommended that dermatologists educate patients of their increased risk for CVD, given the association between psoriasis and major adverse cardiovascular events (eg, stroke, heart failure, MI) and cardiovascular health. However, patients with congestive heart failure were found to have an increased risk of mortality associated with use of tumor necrosis factor (TNF) α inhibitors (P=.016).⁸ Thus, TNF inhibitors are contraindicated in patients with New York Heart Association Class III or Class IV congestive heart failure.⁹

Primary care physicians (PCPs) are recommended to screen patients for CVD risk factors using height, weight, blood pressure, blood glucose, hemoglobin A_1C, lipid levels, abdominal circumference, and body mass index (BMI). Lifestyle modifications such as smoking cessation, exercise, and dietary changes are encouraged to achieve and maintain a normal BMI.

Dermatologists also need to give special consideration to comorbidities when selecting medications and/or therapies for disease management. Patients on TNF inhibitors have a lower risk for MI compared with patients using topical medications, phototherapy, and other oral agents.¹⁰ Additionally, patients on TNF inhibitors have a lower risk for occurrence of major adverse cardiovascular events compared with patients treated with methotrexate or phototherapy.^11,12

Metabolic Syndrome

Numerous studies have demonstrated an association between psoriasis and metabolic syndrome. Patients with increased BSA involvement and psoriasis area and severity index scores have a higher prevalence of metabolic syndrome.¹³ Patients with psoriasis have an increased risk for the following conditions compared to controls: obesity (38% vs 31%; odds ratio [OR], 1.38; 95% CI, 1.29-1.48), elevated triglycerides (36% vs 28%; OR, 1.49; 95% CI, 1.39-1.60), hypertension (31% vs 28%; OR, 1.20; 95% CI, 1.11-12.9), and elevated glucose levels (22% vs 16%; OR, 1.44; 95% CI, 1.33-1.56).¹⁴ Dermatologists are strongly recommended to inform patients about the risk for metabolic syndrome and to encourage the measurement of blood pressure, waist circumference, fasting blood glucose, hemoglobin A_1C, and fasting lipid levels with their PCP when indicated. Body mass index and waist circumference also should be measured annually in patients with moderate to severe psoriasis because of the association with disease severity.

The association between psoriasis and weight loss has been analyzed in several studies. Weight loss, particularly in obese patients, has been shown to improve psoriasis severity, as measured by psoriasis area and severity index score and QOL measures.¹⁵ Another study found that gastric bypass was associated with a significant risk reduction in the development of psoriasis (P=.004) and the disease prognosis (P=.02 for severe psoriasis; P=.01 for PsA).¹⁶ Therefore, patients with moderate to severe psoriasis are recommended to have their obesity status determined according to national guidelines. For patients with a BMI above 40 kg/m² and standard weight-loss measures fail, bariatric surgery is recommended. Additionally, the impact of psoriasis medications on weight has been studied. Apremilast has been associated with weight loss, whereas etanercept and infliximab have been linked to weight gain.^17,18

An association between psoriasis and hypertension also has been demonstrated by studies, especially among patients with severe disease. Therefore, patients with moderate to severe psoriasis are recommended to have their blood pressure evaluated according to national guidelines, and those with a blood pressure of 140/90 mm Hg or higher should be referred to their PCP for assessment and treatment. Current evidence does not support restrictions on antihypertensive medications in patients with psoriasis. Physicians should be aware of the potential for cyclosporine to induce hypertension, which should be treated, specifically with amlodipine.¹⁹

Many studies have demonstrated an association between psoriasis and dyslipidemia, though the results are somewhat conflicting. In 2018, the American Heart Association and the American College of Cardiology deemed psoriasis as an atherosclerotic CVD risk-enhancing condition, favoring early initiation of statin therapy. Because dyslipidemia plays a prominent role in atherosclerosis and CVD, patients with moderate to severe psoriasis are recommended to undergo periodic screening with lipid tests (eg, fasting total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides).²⁰ Patients with elevated fasting triglycerides or low-density lipoprotein cholesterol should be referred to their PCP for further management. Certain psoriasis medications also have been linked to dyslipidemia. Acitretin and cyclosporine are known to adversely affect lipid levels, so patients treated with either agent should undergo routine monitoring of serum lipid levels.

Psoriasis is strongly associated with diabetes mellitus. Because of the increased risk for diabetes in patients with severe disease, regular monitoring of fasting blood glucose and/or hemoglobin A_1C levels in patients with moderate to severe psoriasis is recommended. Patients who meet criteria for prediabetes or diabetes should be referred to their PCP for further assessment and management.^21,22

Mood Disorders

Psoriasis affects QOL and can have a major impact on patients’ interpersonal relationships. Studies have shown an association between psoriasis and mood disorders, specifically depression and anxiety. Unfortunately, patients with mood disorders are less likely to seek intervention for their skin disease, which poses a tremendous treatment barrier. Dermatologists should regularly monitor patients for psychiatric symptoms so that resources and treatments can be offered.

Certain psoriasis therapies have been shown to help alleviate associated depression and anxiety. Improvements in Beck Depression Inventory and Hamilton Depression Rating Scale scores were seen with etanercept.²³ Adalimumab and ustekinumab showed improvement in Dermatology Life Quality Index compared with placebo.^24,25 Patients receiving Goeckerman treatment also had improvement in anxiety and depression scores compared with conventional therapy.²⁶ Biologic medications had the largest impact on improving depression symptoms compared with conventional systemic therapy and phototherapy.²⁷ The recommendations support use of biologics and the Goeckerman regimen for the concomitant treatment of mood disorders and psoriasis.

Renal Disease

Studies have supported an association between psoriasis and chronic kidney disease (CKD), independent of risk factors including vascular disease, hypertension, and diabetes. The prevalence of moderate to advanced CKD also has been found to be directly related to increasing BSA affected by psoriasis.²⁸ Patients should receive testing of blood urea nitrogen, creatinine, and urine microalbumin levels to assess for occult renal disease. In addition, physicians should be cautious when prescribing nephrotoxic drugs (nonsteroidal anti-inflammatory drugs and cyclosporine) and renally excreted agents (methotrexate and apremilast) because of the risk for underlying renal disease in patients with psoriasis. If newly acquired renal disease is suspected, physicians should withhold the offending agents. Patients with psoriasis with CKD are recommended to follow up with their PCP or nephrologist for evaluation and management.

Pulmonary Disease

Psoriasis also has an independent association with COPD. Patients with psoriasis have a higher likelihood of developing COPD (hazard ratio, 2.35; 95% CI, 1.42-3.89; P<.01) than controls.²⁹ The prevalence of COPD also was found to correlate with psoriasis severity. Dermatologists should educate patients about the association between smoking and psoriasis as well as advise patients to discontinue smoking to reduce their risk for developing COPD and cancer.

Patients with psoriasis also are at an increased risk for obstructive sleep apnea. Obstructive sleep apnea should be considered in patients with risk factors including snoring, obesity, hypertension, or diabetes.

Inflammatory Bowel Disease

Patients with psoriasis have an increased risk for developing IBD. The prevalence ratios of both Crohn disease (2.49) and ulcerative colitis (1.64) are increased in patients with psoriasis relative to patients without psoriasis.³⁰ Physicians need to be aware of the association between psoriasis and IBD and the effect that their coexistence may have on treatment choice for patients.

Adalimumab and infliximab are approved for the treatment of IBD, and certolizumab and ustekinumab are approved for Crohn disease. Use of TNF inhibitors in patients with IBD may cause psoriasiform lesions to develop.³¹ Nonetheless, treatment should be individualized and psoriasiform lesions treated with standard psoriasis measures. Psoriasis patients with IBD are recommended to avoid IL-17–inhibitor therapy, given its potential to worsen IBD flares.

Malignancy

Psoriasis patients aged 0 to 79 years have a greater overall risk for malignancy compared with patients without psoriasis.³² Patients with psoriasis have an increased risk for respiratory tract cancer, upper aerodigestive tract cancer, urinary tract cancer, and non-Hodgkin lymphoma.³³ A mild association exists between PsA and lymphoma, nonmelanoma skin cancer (NMSC), and lung cancer.³⁴ More severe psoriasis is associated with greater risk for lymphoma and NMSC. Dermatologists are recommended to educate patients on their risk for certain malignancies and to refer patients to specialists upon suspicion of malignancy.

Risk for malignancy has been shown to be affected by psoriasis treatments. Patients treated with UVB have reduced overall cancer rates for all age groups (hazard ratio, 0.52; P=.3), while those treated with psoralen plus UVA have an increased incidence of squamous cell carcinoma.^32,33 Adalimumab was correlated with increased risk for NMSC in patients with psoriasis but did not have an increased risk for all cancers collectively when used for various immune-mediated inflammatory diseases.³⁵ In contrast, a meta-analysis of randomized clinical trials found no association with TNF inhibitor use and NMSC.³⁶ Ustekinumab had no association with malignancy.³⁷ Treatment history should be elucidated because of higher rates of squamous cell carcinoma in patients with prior psoralen plus UVA, cyclosporine, or methotrexate use.³³ To address malignancy risk, patients with psoriasis should undergo regular screenings for skin cancer and follow national guidelines for age-appropriate cancer screenings.

Lifestyle Choices and QOL

A crucial aspect of successful psoriasis management is patient education. The strongest recommendations support lifestyle changes, such as smoking cessation and limitation of alcohol use. A tactful discussion regarding substance use, work productivity, interpersonal relationships, and sexual function can address substantial effects of psoriasis on QOL so that support and resources can be provided.

Final Thoughts

Management of psoriasis is multifaceted and involves screening, education, monitoring, and collaboration with PCPs and specialists. Regular follow-up with a dermatologist and PCP is strongly recommended for patients with psoriasis given the systemic nature of the disease. The 2019 AAD-NPF recommendations provide important information for dermatologists to coordinate care for complicated psoriasis cases, but clinical judgment is paramount when making medical decisions. The consideration of comorbidities is critical for developing a comprehensive treatment approach, and this approach will lead to better health outcomes and improved QOL for patients with psoriasis.