First-Ever Guidelines for Pediatric Psoriasis Bring Unique Concerns to Forefront
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Despite the often-devastating impact of psoriasis on children, and a variety of unique issues distinguishing these patients from adults, there has, until recently, been a lack of guidelines that specifically cater to juveniles with the disease.
No more.
Released in November and published in the January issue of Journal of the American Academy of Dermatology, the new guidelines focus for the first time solely on pediatric patients with psoriasis. A joint venture between the American Academy of Dermatology and the National Psoriasis Foundation, they also offer a thorough examination of the physical and psychosocial impacts of psoriasis on children and adolescents and the unique challenges this patient population faces.
“Although psoriasis is less common in children, it can have a devastating impact on the physical and emotional well-being of those affected,” Joel M. Gelfand, MD, MSCE, co-author of the guidelines and professor of dermatology and epidemiology at University of Pennsylvania Perelman School of Medicine, said. “There have been tremendous advances in the management of pediatric psoriasis, with several biologic agents receiving FDA approval for this indication.”
According to Joy Wan, MD, MSCE, pediatric dermatologist at University of Pennsylvania Perelman School of Medicine, the guidelines provide counsel and instruction on comorbidity screening, and review available treatments for pediatric psoriasis including topical medications, phototherapy, oral systemic therapies and the relatively newer biologics.
“These guidelines not only guide current clinical practice, but they also highlight the need for more research in psoriasis focused on comorbidities and long-term treatment safety and efficacy particular to the pediatric population,” Wan said.
The guidelines also evaluate the state of research on treatments for this population.
Although three biologic agents are now approved for use in some children, experts hope the guidelines will prompt further research so children and their families will someday have an array of treatment options available, as adults with psoriasis do today.
R. Davis
“Psoriasis can be psychologically, medically and cosmetically concerning for all patients, pediatric or adult,” Dawn Marie R. Davis, MD, professor of dermatology and pediatrics at Mayo Clinic and co-author of the guidelines, said. “Pediatric patients are not small adults — kids have unique physiology, pharmacodynamics and patient-parent-provider relationship — relative to adult patients. Most adults can come see their provider independently.”
Unique physical and emotional effects of pediatric psoriasis
Children and adolescents with psoriasis often experience the physical aspects of the disease differently from adults. However, according to Davis, most of the measures used by physicians and researchers to study the disease’s impact on patients neglect the experiences of children.
For one, children are more likely than adults to experience pruritus with their psoriasis, which can lead to misdiagnosis, she said.
“It is important for providers to be aware that pediatric psoriasis plaques can itch. It does not necessarily mean that if it is itchy then it cannot be psoriasis,” Davis said.
Additionally, among the most important differences between adult and pediatric psoriasis is the impact of social stigma and the risk for bullying.
For example, one common quality of life measurement for psoriasis is the amount of body surface area involvement, and for adult patients this may be an accurate determination.
“However, some of the most common areas for children, and especially young children, to develop psoriasis are the face and the genitalia, as well as the scalp, hands and feet,” Davis said. “As you can imagine, if you have isolated facial involvement — while technically that is not a large body surface area — that can be very distressing because you walk around with an obvious rash on your face. Additionally, the rash is exposed to the environment all the time, increasing the risk of pain and itch.”
“A similar situation with regard to pain and quality of life could be said about isolated disease of genitalia, though it is a small body surface area,” she said. “Thus, quality of life impact can be out of proportion to the amount of body surface area involved.”
According to Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, and co-chair of the committee that developed the guidelines, children with psoriasis are also at a much greater risk for bullying due to the disease, greatly affecting their quality of life.
He added dermatologists and physicians should recognize how this aspect of psoriasis may affect other aspects of their young patients’ lives.
“Dermatologists should know that children with psoriasis get teased and bullied a lot more than people recognize, and many wish to drop out of school because of it,” Menter said.
Menter told the story of a young female patient, aged 10 years, who had significant disease and was facing so much bullying at school she came to his office in tears and wanting to drop out of school. He prescribed cyclosporine, which achieved clearance in 3 months.
Afterward, he prescribed etanercept, which maintained her skin clearance for the next 8 years. She graduated at the top of her class and earned a scholarship at a top university.
“We have to recognize that it’s important to get these children clear, safely,” Menter said. “A 70-year-old patient is going to be far less uncomfortable with their disease because they’ve had it for so long. A child with recent onset has to be treated appropriately and cleared in a safe way. It is important to recognize how much psoriasis impacts a younger child’s life and the comorbidities, particularly from an emotional and mental perspective.”
According to Davis, the new guidelines address these psychosocial impacts of psoriasis and the unique problems they present for children.
“Children with visible skin disease often have a poor quality of life, and it is highly stressful,” she said. In fact, its effects have been found to be comparable to those of diabetes, epilepsy or atopic dermatitis.
“Children with psoriasis state they often have stigmatization in the form of bullying, name-calling and shaming, and we have concerns this may result in behavioral changes such as depression, anxiety and risk-taking behavior,” she said. These behavioral changes are among the comorbidities for which practitioners should be screening patients with pediatric psoriasis, according to Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital and vice chair of the department of dermatology at the University of California, San Diego. Eichenfield co-authored the first paper to offer screening recommendations for children, which are referenced in the guidelines. Eichenfield said he looks forward to the potential impact the guidelines will have on practice.
“Studies have shown that guidelines implementation and use take a lot of work. I would say that the [number] of children who are actually getting screened for comorbidities is actually pretty low, so I am thrilled that these guidelines have come out, and I hope that they will help to influence practice both amongst dermatologists and primary care doctors,” he said.
Treatment options increasing; more research needed
Another problem unique to pediatric psoriasis is the lack of available treatment options for this age group relative to adults, according to Eichenfield.
“Children, unfortunately, have been about a decade behind adults in terms of the studies, acceptability and approval of anti-psoriasis agents,” he said.
The FDA has approved Enbrel (etanercept, Amgen) for children aged at least 4 years, Stelara (ustekinumab, Janssen) for adolescents aged at least 12 years and recently Taltz (ixekizumab, Lilly) for ages 6 years and older.
“Only in the last few years were any approved,” Eichenfield said. “So, instead of having these two decades of newer generations of agents coming, and people figuring out where is the right place to start patients on systemics, pediatric psoriasis has just been behind, which means there is a lot of psoriasis that is undertreated and a lot less systemic therapy than could be utilized to minimize the disease over time.”
In addition, according to Menter, physicians who prescribe treatments for juvenile patients need to be mindful of the unique impacts of both topical and systemic medications on children. Topical steroids in particular can be problematic for juveniles, he said.
“With topical steroids, we need to be more cautious,” Menter said. “They get absorbed and may cause systemic side effects more commonly in children than in adults. A lot of the discussion points were how comfortable do we feel with methotrexate and cyclosporine for children. I am much more comfortable with cyclosporine with young people than older patients because in children the risk of renal side effects and hypertension is significantly lower.”
More information is needed regarding both systemic treatment options for children and the use of combination therapies before robust recommendations can be made. As Davis noted, as children and adolescents are in a different phase of immunological maturity and development than adults, more research is needed to determine whether the impact of psoriasis therapies lessens over time in this patient population.
“We do not know if it is more common for children to develop antibodies to the drug or to have decreased efficacy from the drug relative to adults,” she said. “However, it is also well known there are certain cases of psoriasis — whether that be in a child or an adult — where the person begins with mild disease and over time progresses to have moderate to severe disease, and with the increasing severity of the disease we oftentimes have to increase the therapeutic ladder. This may have more to do with the maturation of the disease than the maturation of the individual.”
According to Menter, discussing moderate to severe psoriasis is especially difficult in the pediatric setting, as mild to moderate forms of the disease make up about 70% to 80% of cases, leading to issues when prescribing appropriate medications.
“We all get taken up with biologic drugs because they work so well, but the majority of patients have mild to moderate disease,” Menter said. “All of us treat children and adolescents all the time. What patients fear most is side effects. Once we tell them this drug is approved for children, they feel like it is even safer for adults.”
The co-authors of the guidelines “want to stress that biologic therapy is not first-line therapy for pediatric psoriasis,” Davis said. Instead, they recommend addressing comorbidities and using first-line therapies such as topical prescription medication. Then, if the child needs additional therapy, consider second-line therapies, including phototherapy; systemic immune suppressants that are non-biologics, such as methotrexate and other drugs; and then biologics in addition or as an alternative treatment, Davis said.
Eichenfield said he hopes to see future versions of the guidelines and future research address whether earlier intervention using aggressive systemic therapy may minimize systemic comorbidities in children.
“These are seminal research questions that we hope we can answer in the future,” he said. “For instance, in adult studies, it has been stated that there is an increase of 4% higher than the general population per year for cardiovascular problems if you have psoriasis.”
“So, it is 4% a year, and I’m looking at a 12-year-old boy with psoriasis and thinking, where will he be when he’s 42 and has 30 years of having a 4% increase per year?” he said. “What should we be doing from a counseling or general health standpoint to make sure we have more psoriasis control to try to minimize the secondary effects? Psoriasis clearly influences a lifetime of effects on the individual.”
Guidelines to evolve, fill in research gaps
According to Gelfand, the new guidelines “raise the bar for the standard of care treatment approach for children affected by psoriasis.”
However, although this first set of comprehensive pediatric psoriasis guidelines creates a baseline for best practice, Davis said the guidelines will not remain static; instead, they will be reviewed and updated every 5 years.
“The American Academy of Dermatology has wisely put forth a structure where all disease interest groups have a work group specifically to make guidelines, such as psoriasis, atopic dermatitis, acne and skin cancer,” she said. “Once a set of guidelines is published and complete, a 5-year time period passes, and then the work group reconvenes to publish updated guidelines of what has happened in medicine in the 5 years since the previous guidelines.”
Eichenfield looks forward to a future set of guidelines addressing more topical, systemic and biologic therapies for pediatric psoriasis as they are explored in research.
“One of the limitations of the guidelines is just the way the guidelines process works,” he said. “They always have to lag behind where the literature is developing. But the hope is that … more regular updates will allow the guidelines to keep up.” As for Davis, she hopes a future set of guidelines will have more research to work with regarding off-label treatments.
For pediatric psoriasis, these include topical corticosteroids with vitamin D and topical calcineurin inhibitors either as monotherapy or in combination with topical corticosteroids.
“I would like to see more research on the drugs that are commonly used for psoriasis in adults and children that are technically FDA off-label indications,” Davis said. “I would like to see more FDA-approved processing of these drugs, and I would love to see more research trials on the safety and efficacy of these drugs specifically for the psoriasis population, whether that be for children or adults.”
However, for now, the guidelines can be used as a tool to provide the best possible care for pediatric patients with psoriasis.
“It is nice that we have been able to take all of the current knowledge that we have about psoriasis in the pediatric population and summate it into one document for ease of review and educational purposes,” Davis said. “Hopefully it will serve as a best practice guide for the next few years. Providers are reaching out and asking questions now that the guidelines are published because they are learning from the document and they want to implement change in their practice.”
“Patients are also reaching out after hearing about the guidelines and reading about them to champion for themselves,” she said. “I am very glad providers and patients feel empowered to make proactive, positive change to help themselves or their patients with psoriasis.”
According to Eichenfield, guidelines are not just an academic process, but also a major influence on physicians, payers and patients alike. He added he is heartened these new guidelines will influence the field of dermatology to be more mindful when caring for juvenile patients.
“They tremendously influence the ability to access drugs, they influence payers and they influence patients, because when it is in the guidelines, they are more comfortable that it is within the standard of care,” Eichenfield said. “I have also seen how it moves people over time. I was very happy that we now have pediatric-specific guidelines that will help influence the field and get people more conscious of treating psoriasis as well as assessing for comorbidities.”– by Amanda Alexander and Jason Laday
References:
Menter A, et al. J Am Acad Dermatol. 2019;doi:10.1016/j.jaad.2019.08.049.
Osier E, et al. JAMA Dermatol. 2017;doi:10.1001/jamadermatol.2017.0499.
Disclosures: Davis reports no relevant financial disclosures. Eichenfield reports he has served as an investigator or consultant for AbbVie, Leo, Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi and UCB. Gelfand reports he served as a consultant for AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Dermira, Dr. Reddy, Glaxo-SmithKline, Janssen Pharmaceuticals, Menlo Therapeutics, Novartis Pharmaceuticals, Pfizer, Regeneron, Sanofi US Services, UB and Valeant Pharmaceuticals North America. Menter reports he served as a consultant for Abbott Labs, AbbVie, Amgen, Eli Lilly and Co., Galderma USA, Janssen Pharmaceuticals, Leo Pharma US, Menlo Therapeutics, Novartis, Sienna Biopharmaceuticals and Wyeth Labs. Wan reports she conducts research in inflammatory skin disease and has received funding from Pfizer and NPF.