By Allison Evans, staff editor, August 01, 2012
While psoriasis continues to be a popular research topic in the field of dermatology, treating pediatric psoriasis remains a challenge. According to a study published in the Archives of Dermatology, one of the primary obstacles is the scarcity of data and lack of approved therapies or standardized guidelines for the pediatric population (2012;148(1): 66-71).
Kelly M. Cordoro, MD, assistant professor of clinical dermatology and pediatrics at University of California San Francisco, spoke at the Academy’s 70th Annual Meeting in March about managing pediatric psoriasis as part of a symposium called “Pediatric Hotline.” Dr. Cordoro provided a wealth of information about the basic principles and advanced practices necessary to treat both mild and severe psoriasis in children.
Because of the lack of data in this specific field of dermatology, “We need to combine the best evidence we have with experience,” Dr. Cordoro said, prefacing her presentation by relating that there is vast experience with many, but not all, of the drugs she was going to talk about. Dermatologists treating children with psoriasis often use off-label treatments or treatments with the potential for side effects, so it becomes even more important to have an open dialogue with the family of the child and keep them informed about treatment options and possible side effects.
Because psoriasis is a chronic disease, children will endure a lifetime of the potential need for some form of therapy on and off, including systemic therapy, Dr. Cordoro said. “Management in children really requires both short- and long-term perspectives. What you decide now can impact not only now, but later. We need to anticipate the types of therapies that may be required in the future, and keep in mind the principles of rotational and combination therapy in order to minimize toxicities and maximize efficacy,” Dr. Cordoro said. [pagebreak]
Severity can be subjective, age a factor
Defining the severity of psoriasis can also prove challenging, Dr. Cordoro said. Clinicians can objectively define severity by body surface area of involvement or extra-cutaneous manifestations/systemic impact. Psoriasis, however, can also be defined subjectively.
“As we all know, a little bit of psoriasis, depending on location, may be considered severe, while diffuse psoriasis, if it’s covered by clothing and not bothering the patient physically or emotionally, may not be deemed as severe, by you or the patient,” she said. It’s important to ask the patient and the family to understand the impact of the disease. Treating psoriasis in pediatric patients goes beyond medical treatments — it’s also about managing emotional and psychological impacts of the disease.
A child who has been deemed “severe” according to various criteria doesn’t necessarily need systemic therapy. Some children with severe psoriasis have cleared after having been treated only with topical corticosteroids and topical vitamin D analogues. Dr. Cordoro reminded the audience that a physician’s treatment of pediatric psoriasis may differ from that of adult psoriasis because children have more inciting factors. “In children, we may need to let the disease evolve a bit before committing a child to systemic therapy,” Dr. Cordoro said. [pagebreak]
She then posed the question whether children with psoriasis experience some of the same comorbidities that adults can experience. “Will children with severe, unchecked inflammation from psoriasis develop cardiovascular and other diseases that we’re seeing in adults?” The answer is that physicians just don’t know the answer yet. This idea may seem to support treating children with systemic therapy early on because unchecked inflammation, like in patients with rheumatoid arthritis, can be associated with cardiovascular disease and premature death. Since there is a scarcity of data, Dr. Cordoro keeps the potential for comorbidities in mind. “Until we learn more, it’s something to consider and can be a rationale to aggressively treat inflammation,” she said.
A three-phase approach
Dr. Cordoro said that when dermatologists think about psoriasis, they typically think about a three-phase approach to treatment and management of the disease. First is the rescue phase, in which the patient is first diagnosed and prescribed treatment to control the disease. The next stage is the transition. For children, it’s important to start thinking relatively quickly about this second phase, when lesions begin to heal. At this point, dermatologists might think about weaning the patient off the more potentially toxic rescue medication and transitioning the agent or dose to something else, ideally combination topicals, although this isn’t always possible, Dr. Cordoro said. The last stage is one of maintenance, which comes after the patient has been stable or clear for a few months. “In maintenance phase, the least toxic combination or the lowest dose that will do the job is what the goal is, always.”
Children of any age can be treated with certain systemic therapies. “For example, cyclosporine is used in children in infancy,” she noted. However, Dr. Cordoro typically limits systemic treatments to “refractory disease, when combination topicals fail, or at times, on first presentation, depending on what the disease morphology and speed of progression is.” [pagebreak]
Systemic treatment options
According to Dr. Cordoro, phototherapy is a form of systemic therapy — and often serves as an entry point into systemic therapy, especially because it’s not immunosuppressive. Retinoids are also a good non-immunosuppressive choice for certain types of psoriasis in well-selected patients. Other systemic treatments, like methotrexate or biologics, target the immune system globally or in a targeted way, Dr. Cordoro said.
Phototherapy, or narrowband UVB, is an ideal treatment for children for its “ease of administration, low toxicity profile, and [the fact that] it does very well with diffuse plaque psoriasis, but the plaques need to be thin.” Narrowband UVB won’t penetrate thick plaques, she said. It’s important, however, to be cautious when using phototherapy because children have a vast amount of UV exposure ahead of them by way of natural sunlight. The necessary requirement for using phototherapy is that the child is able to comply with wearing ocular protection (for more about phototherapy, see story, p. 6).
Retinoids, like acitretin, can be used in children starting at six months old — and sometimes even younger, Dr. Cordoro said. Getting the medication prepped for infants and younger children requires working with a pharmacist to get the medication in liquid form. Fears of toxicity can be lessened by avoiding it in adolescent females and working with the correct dosage one milligram per kilogram per day or less. “In children with psoriasis, minimizing the dose is really going to minimize the risk of bone toxicity,” she said. Also, many children can’t tolerate higher doses of retinoids, which helps keep clinicians from pushing the dosage. If the patient experiences a flare-up, the dose can be increased, but once it’s under control, the therapy should be tapered back down.
The goal for psoriasis patients is to get them off systemic therapy once the disease is controlled, which is sometimes possible and sometimes not, Dr. Cordoro said. “Try to taper and discontinue medications if there’s been three months of clearance and observe to determine if you need them. If you don’t keep trying to taper, then you’ll never know if you’re overtreating.” [pagebreak]
Methotrexate works for all types and presentations of psoriasis. Ideally, in children the drug is meant to be used as a clearing drug, or a rescue therapy. “It’s important not to exceed 0.7 milligrams per kilogram per week because that increases the risk for toxicities tremendously,” Dr. Cordoro said. It’s always a good idea to start with a test dose to observe for bone marrow suppression. “Check a CBC in a week and look for bone marrow suppression.” If the cell counts are fine, then you can go ahead and slowly escalate the dose.
“I recommend supplementing [methotrexate] with folate always; it minimizes the GI toxicity and it also minimizes the risk of bone marrow suppression. It may have a small effect on efficacy, but in my opinion, the risk without folate isn’t worth it in children,” Dr. Cordoro advised.
Pulmonary and hepatic toxicity are the most feared side effects from using methotrexate, but Dr. Cordoro said these effects are rare in children. “What we really see in children more often is nausea and appetite suppression.” Dr. Cordoro pointed out that the drug has substantial drug interactions. It’s important to remember that when you write the methotrexate prescription, you need to coordinate with the child’s pediatrician or other doctors.
While the therapies that have already been discussed are effective, there is one therapy that works faster than the others — and that drug is cyclosporine. The range of cyclosporine dosing for children can be anywhere between one and a half to five milligrams per kilogram per day, whereas a standard adult dosing is between one and four milligrams per kilogram per day. “Because children have higher body surface area to weight ratios and age-dependent differences in pharmacokinetics, they often require higher doses than those recommended for adults,” Dr. Cordoro said. She also recommended obtaining a cyclosporine trough level from the blood to help determine whether sufficient levels have been achieved with the current dose. [pagebreak]
“It’s really important to remember that in children that have fast-moving psoriasis it’s okay to start at the higher end of the dose range of cyclosporine,” Dr. Cordoro said. She also confirmed that cyclosporine is primarily a rescue drug, with the goal being to control the disease, taper, and then transition to other therapies. Close monitoring of the blood pressure and renal function is imperative while patients are taking cyclosporine.
Dr. Cordoro made it clear that all patients on systemic therapies require close clinical and laboratory monitoring.
Treating children with biologics
The guidelines of care for treating adults with biologics are pretty straight forward, Dr. Cordoro noted. However, it’s not so clear when it comes to children. “Etanercept has the most evidence, including a placebo-controlled randomized trial and numerous case series and reports.” For pediatric patients who don’t respond well to conventional systemic therapies or phototherapy, Dr. Cordoro will prescribe biologics. And while biologics can be used first-line, she is still somewhat reluctant to use them as such “because of the inadequacy of long-term safety data in children with psoriasis.”
Although considerably controversial, biologics are printed with a black box warning about the possibility of causing cancer in the pediatric population. And while clinicians should be aware of this possibility, “all of the cases that were presented to the FDA of cancers in children, half of which were lymphomas, on biologics were for diseases other than psoriasis, and the children were on not only a biologic, but an additional immunosuppressive therapy as well,” Dr. Cordoro said. There have been rare reports in adolescents and young adults of hepatosplenic T-cell lymphoma in patients taking infliximab in combination with azathioprine or 6-mercaptopurine. While there have been no cases of malignancy reported in studies of pediatric psoriasis, this potential risk and the warning highlighting it warrant discussion with patients and their families prior to beginning treatment, she said. [pagebreak]
The newest biologic treatments for adults are IL-12/23 inhibitors. They’re an attractive option because they’re given every three months. While trials are currently being performed and a paper has been recently-submitted for publication, there is still a lack of data, Dr. Cordoro said.
The pros for treating children with biologics are less frequent dosing, fewer lab draws, and they’re targeted, so they’re not likely to cause the end organ damage of the other therapies, she said. “The unknown benefits may be to minimize the psoriatic march’ when you are treating unchecked inflammation — perhaps you’ll prevent comorbidities down the road. We’re not sure about that yet, but it’s an enticing possibility,” Dr. Cordoro said.
A few cons of using biologics for children are the exorbitant cost of treatment, the fact that you must give a child an injection or infusion, and the fact that there is no FDA approval, “which translates into real difficulty getting insurance policies to cover the drugs.” The biggest concern for Dr. Cordoro is the long-term unknown; no one knows how biologics will affect children 15 or 20 years from now. While treatment guidelines specific to pediatric psoriasis would be useful, formal evidence on which to base such guidelines is not yet available (Arch Dermatol 2012; 148(1): 66-71).
Dr. Cordoro wrapped up her presentation with one final point: “Let the disease evolve in children before you commit them to a systemic therapy; they actually may not end up needing it.”
For more in-depth information about childhood psoriasis, see Dr. Cordoro’s article, “Management of Childhood Psoriasis,” in Advances in Dermatology (2008; 24:125-169). A comprehensive review of using systemic therapies in children with psoriasis will be available in a chapter entitled “Systemic Treatments for Severe Pediatric Psoriasis: A Practical Approach” for an upcoming pediatric dermatology edition of Dermatologic Clinics.