Five pearls guide pediatric psoriasis systemic therapy

SAN FRANCISCO – Five practice tips can help physicians consider systemic therapy for the subset of children with psoriasis who develop severe disease at some point, Dr. Kelly M. Cordoro said.

The key is to weigh the risks and benefits to decide which is worse, the treatment or the disease, in terms of how it affects the patient medically, psychosocially, and physically, she said at the annual meeting of the Pacific Dermatologic Association.

Approximately a quarter of the physicians in the audience had treated patients younger than 18 years with systemic therapy for psoriasis, an informal poll showed.*"

The exact approach varies per patient, and not all cases of severe pediatric psoriasis need systemic treatment. "It’s an art as much as it is a science," said Dr. Cordoro of the University of California, San Francisco.

It’s often a good idea to start with nonimmunosuppressive systemic agents for psoriasis in children, such as phototherapy or acitretin, before trying immunosuppressive treatments such as cyclosporine, methotrexate, or biologics, she suggested. Systemic therapy should be added to a multimodal care plan that includes identification and treatment of triggers and comorbidities, topical therapy, lifestyle modifications, education, and support. Keep in mind that no systemic medications are approved to treat psoriasis in children, and management is based on expert opinion, Dr. Cordoro noted.

Dr. Cordoro offered the following five pearls and principles to guide physicians managing severe pediatric psoriasis:

• Don’t just do something, stand there! Treat these children conservatively at first and observe the response, especially in patients with new-onset psoriasis and in particular if they have a family history of psoriasis, said Dr. Cordoro. It’s also a good approach in patients who’ve had a recent infection – group A streptococcal infection is a very common trigger of pediatric psoriasis, for example – or a recent viral illness or skin trauma.

"If you can find the trigger" and treat it, "you may be able to prevent the use of systemic therapy" for the psoriasis, she said. Conservative, yet aggressive, treatment might include a combination of topical therapy, wet wraps, itch control, and managing the triggers. Let the disease evolve for a few days to weeks before moving to systemic therapy, she suggested.

• Don’t just stand there, do something! The psychological impact of chronic disease can be as disabling as the physical impact, and uncontrolled inflammation can cause long-term health consequences, Dr. Cordoro said. No systemic therapies are approved for pediatric psoriasis because of a lack of studies, "but I encourage you to treat these kids" with severe disease who fail topical and other treatment strategies, she said.

Off-label use of methotrexate can help children with any form of psoriasis, in a dose range of 0.2-0.7 mg/kg per week, with a maximum of 25 mg/week, said Dr. Cordoro. Consider this a rescue phase, and then try to taper to the lowest effective dose or off of systemic therapy.

"Methotrexate doesn’t have to be forever," Dr. Cordoro emphasized. In children, methotrexate’s side effects commonly include GI symptoms and anorexia, and the drug very rarely causes pulmonary and hepatotoxicity. Dr. Cordoro recommended a supplemental folate dose of 1-5 mg every day, except methotrexate dose days, to ameliorate some of the GI side effects and the potential bone marrow toxicity. Monitoring is less intense than in adults, and involves frequent lab evaluations but no liver biopsies. Drug interactions with NSAIDs or trimethoprim/sulfamethoxazole can cause bone marrow toxicity, so be sure to send a letter to the child’s pediatrician and parents to alert them, she said.

For severe, diffuse plaque psoriasis in children, any of the conventional systemic or biologic treatments can be effective, and the choice depends on patient and clinical factors, Dr. Cordoro said. The goal is to gain control, taper the systemic treatment, and hold it at the lowest effective dose or transition to topical therapy or phototherapy.

• Don’t forget oral retinoids. Often a forgotten choice for therapy, short-term oral retinoids can be the best first systemic treatment for severe guttate psoriasis if phototherapy is not indicated or unavailable, or for palmoplantar psoriasis or pustular psoriasis, Dr. Cordoro said. In some cases, there can be synergistic effects from combining a low-dose retinoid with low-dose narrow-band UVB phototherapy.

Acitretin is not immunosuppressive but is teratogenic, so it should be avoided in girls older than 8 years, Dr. Cordoro noted. Reversible, dose-dependent side effects include mucocutaneous effects, dyslipidemia, or transaminitis. "Kids cannot tolerate high doses of retinoids, so 1 mg/kg per day or less is where you need to be," she said. Much-feared potential skeletal effects are very rare at doses that low when the medication is used for no more than a year or two, she added.

• When you need speed, try cyclosporine. Cyclosporine acts rapidly. An initial high dose of 5 mg/kg per day can take control of refractory plaque psoriasis, rapidly moving pustular psoriasis, or severe, rapidly progressive psoriasis. No more than a year of continuous use is the guideline, so you don’t want to start low and go slow. "Kids and typically tolerate and need higher doses" compared with adults, Dr. Cordoro said. Use the modified form (Neoral) for better oral bioavailability and better sustained drug levels, she suggested.

This, too, is a rescue treatment intended to control and stabilize the disease, followed by tapering and transitioning to other therapies. The most serious potential side effects include nephrotoxicity, hypertension, and immunosuppression. The most common side effects include nausea, vomiting and diarrhea, anorexia, and headache. Less often, cyclosporine can cause myalgia, arthralgia, paresthesia, gingival hyperplasia, or hypertrichosis. "My colleagues in oncology assure me that at the doses we’re using for psoriasis, we’re not at risk for giving these kids carcinomas down the road," she said.

• Biologics play an important role. Biologics are potent, but wouldn’t be the first choice for systemic therapy because they don’t have prolonged efficacy, said Dr. Cordoro. Their precise place in the therapeutic armamentarium is yet to be defined. "I like to reserve a biologic for when I don’t necessarily have a better choice, because I know I have a finite period of time for biologics," she said.

Nonetheless, anti–tumor necrosis factor agents can play a role in treating refractory plaque psoriasis, severe or refractory generalized pustular psoriasis, or psoriatic arthritis, Dr. Cordoro said. Anecdotal reports suggest that IL-12 and IL-23 inhibitors may help with pediatric psoriasis, but there are no study data yet.

The potential advantages of using biologics include less frequent dosing, less laboratory monitoring, and targeted treatment. On the other hand, biologics are expensive, require injection or infusion, have as-yet-unknown long-term risks, and are not approved for treating pediatric psoriasis (so insurance coverage is a battle), said Dr. Cordoro. Questions remain about standardized dosing and monitoring protocols, and about the endpoints of biologic therapy in this setting, although experience with biologics and evidence of their efficacy and safety in children are accumulating, she said.

Dr. Cordoro recommended two articles that she coauthored that provide expert consensus guidelines, tables, and charts for systemic treatment and monitoring of children with psoriasis (Dermatol. Clin. 2013;31:267-88 and Skin Therapy Lett. 2013;18:1-4).

Dr. Cordoro reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

*CORRECTION, 11/4/2013: An earlier version of this article imprecisely stated the results of the informal study.

SAN FRANCISCO – Five practice tips can help physicians consider systemic therapy for the subset of children with psoriasis who develop severe disease at some point, Dr. Kelly M. Cordoro said.

The key is to weigh the risks and benefits to decide which is worse, the treatment or the disease, in terms of how it affects the patient medically, psychosocially, and physically, she said at the annual meeting of the Pacific Dermatologic Association.

Approximately a quarter of the physicians in the audience had treated patients younger than 18 years with systemic therapy for psoriasis, an informal poll showed.*"

The exact approach varies per patient, and not all cases of severe pediatric psoriasis need systemic treatment. "It’s an art as much as it is a science," said Dr. Cordoro of the University of California, San Francisco.

It’s often a good idea to start with nonimmunosuppressive systemic agents for psoriasis in children, such as phototherapy or acitretin, before trying immunosuppressive treatments such as cyclosporine, methotrexate, or biologics, she suggested. Systemic therapy should be added to a multimodal care plan that includes identification and treatment of triggers and comorbidities, topical therapy, lifestyle modifications, education, and support. Keep in mind that no systemic medications are approved to treat psoriasis in children, and management is based on expert opinion, Dr. Cordoro noted.

Dr. Cordoro offered the following five pearls and principles to guide physicians managing severe pediatric psoriasis:

• Don’t just do something, stand there! Treat these children conservatively at first and observe the response, especially in patients with new-onset psoriasis and in particular if they have a family history of psoriasis, said Dr. Cordoro. It’s also a good approach in patients who’ve had a recent infection – group A streptococcal infection is a very common trigger of pediatric psoriasis, for example – or a recent viral illness or skin trauma.

"If you can find the trigger" and treat it, "you may be able to prevent the use of systemic therapy" for the psoriasis, she said. Conservative, yet aggressive, treatment might include a combination of topical therapy, wet wraps, itch control, and managing the triggers. Let the disease evolve for a few days to weeks before moving to systemic therapy, she suggested.

• Don’t just stand there, do something! The psychological impact of chronic disease can be as disabling as the physical impact, and uncontrolled inflammation can cause long-term health consequences, Dr. Cordoro said. No systemic therapies are approved for pediatric psoriasis because of a lack of studies, "but I encourage you to treat these kids" with severe disease who fail topical and other treatment strategies, she said.

Off-label use of methotrexate can help children with any form of psoriasis, in a dose range of 0.2-0.7 mg/kg per week, with a maximum of 25 mg/week, said Dr. Cordoro. Consider this a rescue phase, and then try to taper to the lowest effective dose or off of systemic therapy.

"Methotrexate doesn’t have to be forever," Dr. Cordoro emphasized. In children, methotrexate’s side effects commonly include GI symptoms and anorexia, and the drug very rarely causes pulmonary and hepatotoxicity. Dr. Cordoro recommended a supplemental folate dose of 1-5 mg every day, except methotrexate dose days, to ameliorate some of the GI side effects and the potential bone marrow toxicity. Monitoring is less intense than in adults, and involves frequent lab evaluations but no liver biopsies. Drug interactions with NSAIDs or trimethoprim/sulfamethoxazole can cause bone marrow toxicity, so be sure to send a letter to the child’s pediatrician and parents to alert them, she said.

For severe, diffuse plaque psoriasis in children, any of the conventional systemic or biologic treatments can be effective, and the choice depends on patient and clinical factors, Dr. Cordoro said. The goal is to gain control, taper the systemic treatment, and hold it at the lowest effective dose or transition to topical therapy or phototherapy.

• Don’t forget oral retinoids. Often a forgotten choice for therapy, short-term oral retinoids can be the best first systemic treatment for severe guttate psoriasis if phototherapy is not indicated or unavailable, or for palmoplantar psoriasis or pustular psoriasis, Dr. Cordoro said. In some cases, there can be synergistic effects from combining a low-dose retinoid with low-dose narrow-band UVB phototherapy.

Acitretin is not immunosuppressive but is teratogenic, so it should be avoided in girls older than 8 years, Dr. Cordoro noted. Reversible, dose-dependent side effects include mucocutaneous effects, dyslipidemia, or transaminitis. "Kids cannot tolerate high doses of retinoids, so 1 mg/kg per day or less is where you need to be," she said. Much-feared potential skeletal effects are very rare at doses that low when the medication is used for no more than a year or two, she added.

• When you need speed, try cyclosporine. Cyclosporine acts rapidly. An initial high dose of 5 mg/kg per day can take control of refractory plaque psoriasis, rapidly moving pustular psoriasis, or severe, rapidly progressive psoriasis. No more than a year of continuous use is the guideline, so you don’t want to start low and go slow. "Kids and typically tolerate and need higher doses" compared with adults, Dr. Cordoro said. Use the modified form (Neoral) for better oral bioavailability and better sustained drug levels, she suggested.

This, too, is a rescue treatment intended to control and stabilize the disease, followed by tapering and transitioning to other therapies. The most serious potential side effects include nephrotoxicity, hypertension, and immunosuppression. The most common side effects include nausea, vomiting and diarrhea, anorexia, and headache. Less often, cyclosporine can cause myalgia, arthralgia, paresthesia, gingival hyperplasia, or hypertrichosis. "My colleagues in oncology assure me that at the doses we’re using for psoriasis, we’re not at risk for giving these kids carcinomas down the road," she said.

• Biologics play an important role. Biologics are potent, but wouldn’t be the first choice for systemic therapy because they don’t have prolonged efficacy, said Dr. Cordoro. Their precise place in the therapeutic armamentarium is yet to be defined. "I like to reserve a biologic for when I don’t necessarily have a better choice, because I know I have a finite period of time for biologics," she said.

Nonetheless, anti–tumor necrosis factor agents can play a role in treating refractory plaque psoriasis, severe or refractory generalized pustular psoriasis, or psoriatic arthritis, Dr. Cordoro said. Anecdotal reports suggest that IL-12 and IL-23 inhibitors may help with pediatric psoriasis, but there are no study data yet.

The potential advantages of using biologics include less frequent dosing, less laboratory monitoring, and targeted treatment. On the other hand, biologics are expensive, require injection or infusion, have as-yet-unknown long-term risks, and are not approved for treating pediatric psoriasis (so insurance coverage is a battle), said Dr. Cordoro. Questions remain about standardized dosing and monitoring protocols, and about the endpoints of biologic therapy in this setting, although experience with biologics and evidence of their efficacy and safety in children are accumulating, she said.

Dr. Cordoro recommended two articles that she coauthored that provide expert consensus guidelines, tables, and charts for systemic treatment and monitoring of children with psoriasis (Dermatol. Clin. 2013;31:267-88 and Skin Therapy Lett. 2013;18:1-4).

Dr. Cordoro reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

*CORRECTION, 11/4/2013: An earlier version of this article imprecisely stated the results of the informal study.

SAN FRANCISCO – Five practice tips can help physicians consider systemic therapy for the subset of children with psoriasis who develop severe disease at some point, Dr. Kelly M. Cordoro said.

The key is to weigh the risks and benefits to decide which is worse, the treatment or the disease, in terms of how it affects the patient medically, psychosocially, and physically, she said at the annual meeting of the Pacific Dermatologic Association.

Approximately a quarter of the physicians in the audience had treated patients younger than 18 years with systemic therapy for psoriasis, an informal poll showed.*"

The exact approach varies per patient, and not all cases of severe pediatric psoriasis need systemic treatment. "It’s an art as much as it is a science," said Dr. Cordoro of the University of California, San Francisco.

It’s often a good idea to start with nonimmunosuppressive systemic agents for psoriasis in children, such as phototherapy or acitretin, before trying immunosuppressive treatments such as cyclosporine, methotrexate, or biologics, she suggested. Systemic therapy should be added to a multimodal care plan that includes identification and treatment of triggers and comorbidities, topical therapy, lifestyle modifications, education, and support. Keep in mind that no systemic medications are approved to treat psoriasis in children, and management is based on expert opinion, Dr. Cordoro noted.

Dr. Cordoro offered the following five pearls and principles to guide physicians managing severe pediatric psoriasis:

• Don’t just do something, stand there! Treat these children conservatively at first and observe the response, especially in patients with new-onset psoriasis and in particular if they have a family history of psoriasis, said Dr. Cordoro. It’s also a good approach in patients who’ve had a recent infection – group A streptococcal infection is a very common trigger of pediatric psoriasis, for example – or a recent viral illness or skin trauma.

"If you can find the trigger" and treat it, "you may be able to prevent the use of systemic therapy" for the psoriasis, she said. Conservative, yet aggressive, treatment might include a combination of topical therapy, wet wraps, itch control, and managing the triggers. Let the disease evolve for a few days to weeks before moving to systemic therapy, she suggested.

• Don’t just stand there, do something! The psychological impact of chronic disease can be as disabling as the physical impact, and uncontrolled inflammation can cause long-term health consequences, Dr. Cordoro said. No systemic therapies are approved for pediatric psoriasis because of a lack of studies, "but I encourage you to treat these kids" with severe disease who fail topical and other treatment strategies, she said.

Off-label use of methotrexate can help children with any form of psoriasis, in a dose range of 0.2-0.7 mg/kg per week, with a maximum of 25 mg/week, said Dr. Cordoro. Consider this a rescue phase, and then try to taper to the lowest effective dose or off of systemic therapy.

"Methotrexate doesn’t have to be forever," Dr. Cordoro emphasized. In children, methotrexate’s side effects commonly include GI symptoms and anorexia, and the drug very rarely causes pulmonary and hepatotoxicity. Dr. Cordoro recommended a supplemental folate dose of 1-5 mg every day, except methotrexate dose days, to ameliorate some of the GI side effects and the potential bone marrow toxicity. Monitoring is less intense than in adults, and involves frequent lab evaluations but no liver biopsies. Drug interactions with NSAIDs or trimethoprim/sulfamethoxazole can cause bone marrow toxicity, so be sure to send a letter to the child’s pediatrician and parents to alert them, she said.

For severe, diffuse plaque psoriasis in children, any of the conventional systemic or biologic treatments can be effective, and the choice depends on patient and clinical factors, Dr. Cordoro said. The goal is to gain control, taper the systemic treatment, and hold it at the lowest effective dose or transition to topical therapy or phototherapy.

• Don’t forget oral retinoids. Often a forgotten choice for therapy, short-term oral retinoids can be the best first systemic treatment for severe guttate psoriasis if phototherapy is not indicated or unavailable, or for palmoplantar psoriasis or pustular psoriasis, Dr. Cordoro said. In some cases, there can be synergistic effects from combining a low-dose retinoid with low-dose narrow-band UVB phototherapy.

Acitretin is not immunosuppressive but is teratogenic, so it should be avoided in girls older than 8 years, Dr. Cordoro noted. Reversible, dose-dependent side effects include mucocutaneous effects, dyslipidemia, or transaminitis. "Kids cannot tolerate high doses of retinoids, so 1 mg/kg per day or less is where you need to be," she said. Much-feared potential skeletal effects are very rare at doses that low when the medication is used for no more than a year or two, she added.

• When you need speed, try cyclosporine. Cyclosporine acts rapidly. An initial high dose of 5 mg/kg per day can take control of refractory plaque psoriasis, rapidly moving pustular psoriasis, or severe, rapidly progressive psoriasis. No more than a year of continuous use is the guideline, so you don’t want to start low and go slow. "Kids and typically tolerate and need higher doses" compared with adults, Dr. Cordoro said. Use the modified form (Neoral) for better oral bioavailability and better sustained drug levels, she suggested.

This, too, is a rescue treatment intended to control and stabilize the disease, followed by tapering and transitioning to other therapies. The most serious potential side effects include nephrotoxicity, hypertension, and immunosuppression. The most common side effects include nausea, vomiting and diarrhea, anorexia, and headache. Less often, cyclosporine can cause myalgia, arthralgia, paresthesia, gingival hyperplasia, or hypertrichosis. "My colleagues in oncology assure me that at the doses we’re using for psoriasis, we’re not at risk for giving these kids carcinomas down the road," she said.

• Biologics play an important role. Biologics are potent, but wouldn’t be the first choice for systemic therapy because they don’t have prolonged efficacy, said Dr. Cordoro. Their precise place in the therapeutic armamentarium is yet to be defined. "I like to reserve a biologic for when I don’t necessarily have a better choice, because I know I have a finite period of time for biologics," she said.

Nonetheless, anti–tumor necrosis factor agents can play a role in treating refractory plaque psoriasis, severe or refractory generalized pustular psoriasis, or psoriatic arthritis, Dr. Cordoro said. Anecdotal reports suggest that IL-12 and IL-23 inhibitors may help with pediatric psoriasis, but there are no study data yet.

The potential advantages of using biologics include less frequent dosing, less laboratory monitoring, and targeted treatment. On the other hand, biologics are expensive, require injection or infusion, have as-yet-unknown long-term risks, and are not approved for treating pediatric psoriasis (so insurance coverage is a battle), said Dr. Cordoro. Questions remain about standardized dosing and monitoring protocols, and about the endpoints of biologic therapy in this setting, although experience with biologics and evidence of their efficacy and safety in children are accumulating, she said.

Dr. Cordoro recommended two articles that she coauthored that provide expert consensus guidelines, tables, and charts for systemic treatment and monitoring of children with psoriasis (Dermatol. Clin. 2013;31:267-88 and Skin Therapy Lett. 2013;18:1-4).

Dr. Cordoro reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

*CORRECTION, 11/4/2013: An earlier version of this article imprecisely stated the results of the informal study.