Pediatric Psoriasis: ‘An Area Ripe for Study’

Pediatric psoriasis is uncommon, with an annual prevalence of up to only 1% in the United States. However, since many children and adolescents are misdiagnosed or untreated, the true prevalence of this disease may not be well understood.

The most common clinical form in this age group is chronic plaque psoriasis, followed by guttate, pustular and erythrodermic psoriasis. Pediatric psoriasis presents itself differently from that in adults, predominantly appearing on the face and scalp, as well as on the elbows and knees and, not uncommonly, on the axillae.

A 2021 study published in Cureus showed that more than half of pediatric patients with psoriasis had a documented family history of psoriasis among a first relative. Other predisposing factors include prior streptococcal infection and direct trauma to the skin.

Current treatments for pediatric psoriasis are based heavily on expert consensus and experience, as formal data have been scarce in this patient population — until now.

Pediatric psoriasis is more poorly understood than other inflammatory disorders, such as atopic dermatitis, which has been much more extensively studied in children, Amy S. Paller, MD, Walter J. Hamlin Professor and Chair of dermatology at Northwestern University Feinberg School of Medicine and pediatric dermatologist at the Ann and Robert H. Lurie Children’s Hospital of Chicago, said during an interview with Healio Psoriatic Disease.

“Many pediatric patients go years without a correct diagnosis because pediatricians do not receive much training about psoriasis and the disease does not look like what is classically described in adults,” Paller added. “In children, psoriasis often fails to show the sharp borders and thick scaling seen in adults — and psoriasis is often found on the face, including around the eyes. Given the delay in diagnosis and in referral to dermatologists, our therapies have been slower to roll out in the pediatric population. However, it is an area ripe for study and the hope is that researchers engage in the effort.”

Healio Psoriatic Disease spoke with experts about the predisposing factors associated with pediatric psoriasis, the burden on quality of life for children and their caregivers, the latest treatment options available for pediatric patients and what future research is needed.

Predisposing factors

Family history of psoriasis can be a key feature in children who develop the condition, Joy Wan, MD, MSCE, pediatric dermatologist at Johns Hopkins University, said during an interview with Healio Psoriatic Disease.

“Other triggers include prior infection, which is particularly relevant in pediatric populations. Streptococcal infections are the most common type of infection that trigger the first flare of psoriasis, and for some children, it leads to subsequent flares,” Wan said. “We also know that direct trauma to the skin can bring about psoriasis in a particular spot where trauma has been induced. This is seen in adults as well and is known as the Koebner phenomenon. Environmental factors, including emotional stressors or other physical stressors and illness, can also trigger psoriasis flares.”

Data have indicated an association between pediatric psoriasis and systemic conditions, including high BMI, obesity, arthritis, inflammatory bowel disease and metabolic abnormalities.

“We know that psoriasis is associated with other systemic conditions, with the most well-studied falling under the ‘umbrella’ of cardiometabolic diseases for both children and adults,” Wan said. “These are not necessarily causes of psoriasis, but they have certainly been associated with psoriasis and are important comorbidities to be mindful of among our pediatric patients.”

The prospective, case-control, cross-sectional study published in Cureus compared 150 children and adolescents with psoriasis vs. 150 age- and sex-matched controls. Data indicated that significantly more patients with psoriasis were overweight (26.7% vs. 11%) and obese (40% vs. 8%). Researchers additionally found that significantly more pediatric patients had abnormal lipid profiles compared with controls (62% vs. 30%; P < .05).

“Obesity is by far the most common comorbidity that we see in patients with psoriasis,” Paller said. “In studies with moderate to severe disease, about 35% of patients are obese and there is a high percentage who are overweight as well. This common comorbidity almost always precedes the development of psoriasis in children and adolescents. Psoriatic arthritis occurs much less often in children than in adults, but occurs in 1% to 4% of the pediatric population with psoriasis.”

‘Invisible effects’

Pediatric psoriasis can be a highly visible, uncomfortable and burdensome disease that affects quality of life for many patients and their families.

“The burden of psoriasis on quality of life is an important question to ask all of our pediatric patients and their caregivers,” Wan said. “Psoriasis can have a burdensome impact on quality of life and that impairment can stem from physical impairment in terms of discomfort on the skin — pain and itch are common — and for the children who develop psoriatic arthritis, that can impact physical function as well.”

Psoriasis has also been linked to depression and anxiety.

“There can be a lot of social stigma attached to having a skin condition like this as a child, especially during the important socio-developmental phases of their life,” Wan said. “Patients have described to me that other children feared their skin disease and that it might be contagious. The scaling and flaking of the skin that can happen with psoriasis has an impact on social relationships and all of this has a tremendous effect on children. We need to focus on quality of life in our patients and their families. For some, this is a very burdensome disease but hopefully we can develop interventions to adequately address the issue. The first step is identifying those concerns when they arise.”

Data from a cross-sectional study published in Anais Brasileiros de Dermatologia showed that psoriasis had a negative impact on the quality of life among children, adolescents and their families — even for those with mild disease.

Salman and colleagues found that among 58 patients (median age, 11 years; median duration of psoriasis, 36 months) with a median Psoriasis Area and Severity Index score of 1.8 at baseline, the median Children’s Dermatology Life Quality Index score was 5, with 21% of patients reporting a moderate or greater effect of psoriasis on their quality of life. Moreover, the median Family Dermatology Life Quality Index score was 10 among caregivers.

“Considering that difficulties in school, family life and personal relationships during pediatric ages may cause long-term sequelae such as psychiatric morbidities, integration of assessment of quality of life in patients with psoriasis and their families into medical treatments might be beneficial for prevention of invisible effects of psoriasis,” the researchers wrote.

Psoriasis has a significant impact on quality of life for patients, Lara Wine Lee, MD, PhD, pediatric dermatologist at Medical University of South Carolina, said during an interview with Healio Psoriatic Disease.

“This has been shown in a lot of research that has been done in general about different skin diseases as well as what we see in our day-to-day practice with our own patients. Psoriasis is a chronic disease that is very visible, significantly impacts social functioning, emotional growth and development — just the appearance of it affects quality of life,” Wine Lee said. “Treatment planning sessions need to include discussion about this. There is also a lot of comorbid depression and anxiety in patients with psoriasis and to be holistic about it, we need to consider all of this when treating our patients with psoriasis.”

‘Therapeutic ladder’

Various societies have devoted attention to pediatric psoriasis in recent years. In 2020, the American Academy of Dermatology and National Psoriasis Foundation published a joint guideline of care for the management and treatment of pediatric psoriasis. The guideline recognized the unique physiology, pharmacokinetics and patient-parent-provider interactions of the disease.

The “therapeutic ladder” of treatment options for pediatric psoriasis most commonly begins with topicals, followed by phototherapy and then systemic therapies.

“At the ‘bottom rung of the ladder’ are the creams and ointments that are applied directly on the skin. They serve as the first-line treatment option, especially for children with mild disease and include topical steroids, retinoids and others,” Wan said. “The next ‘rung up’ is phototherapy. We most commonly use ultraviolet B therapy, which can be delivered to the whole body in a booth, or it can be targeted to certain spots on the skin with a handheld laser device. For children who have failed topicals or have extensive or severe enough disease where topicals may not be practical to apply all over the body, phototherapy may be recommended.”

However, there are downsides to phototherapy.

“Accessibility and convenience are issues. Treatment involves coming into the office two to three times per week and depending on where patients live, this can be very difficult,” Wine Lee said. “It can also be expensive for patients with high copays. Many phototherapy centers also find it difficult and uncomfortable to treat children with phototherapy, but the treatment has excellent safety and efficacy in pediatric patients. We have used phototherapy for years and it has become better from a safety standpoint — children as young as 3 years can undergo phototherapy. The problem is that insurance does not always cover it and so depending on insurance type, treatment may or may not be accessible. Home phototherapy can be an affordable option if covered by insurance and is perfect for the child who is in school, with parents who work. I am hoping that more insurance companies will cover home phototherapy soon.”

Systemic therapies are at the top of the “therapeutic ladder” — both oral agents and injectables.

“At first, we relied heavily on the traditional systemic oral therapies, such as methotrexate, acitretin and cyclosporine,” Wan said. “Within the past decade or so, many biologics have become available for psoriasis. As they are approved in adults, they trickle down to children and are the most effective of all treatments.”

‘Arsenal of biologics’

Biologics have shown significant promise in pediatric psoriasis.

Physicians who treat pediatric psoriasis have seen a shift in treatment on the therapeutic ladder, Lawrence F. Eichenfield, MD, pediatric dermatologist at Rady Children’s Hospital-San Diego, said during an interview with Healio Psoriatic Disease.

“I don’t think that step or ladder analogies are necessarily the appropriate guide to determine whether a patient is appropriate for a systemic therapy as compared to topical treatments,” Eichenfield said. “The disease severity is really important. Some patients may have rapid relief with topicals, and others with phototherapy, where others are so severe that treatment with biologic or systemic therapies shouldn’t be withheld.”

There are currently four biologics that have gained FDA approval for pediatric psoriasis.

“It is heartening to see that biologics have gained formal FDA approval for pediatric patients,” Wan said. “The earliest approval was etanercept [Enbrel, Amgen], then ustekinumab [Stelara, Janssen] and more recently we have had biologics targeting the interleukin [IL]-17 pathway, including ixekizumab [Taltz, Lilly] and secukinumab [Cosentyx, Novartis]. We now have this ‘arsenal of biologics’ approved for use in children.”

Wine Lee agreed.

“Pediatric psoriasis has lagged far behind adult psoriasis — just as much as pediatric treatments have,” Wine Lee said. “A lot of new and exciting work is now being done in biologic systemic treatments for pediatric patients. This is exciting, because for adult psoriasis, we cannot keep up with treatment approvals, but within the past decade there has been a huge amount of research and therapeutic advances that has occurred in pediatric psoriatic disease. As a pediatric dermatologist with so much interest in pediatric psoriasis, my patients were left out for so long, but we are now starting to see some of the trials pick up in this patient group. There are still a lot of limitations in terms of what we can use based on insurance, but we have some tools, finally, in our pocket.”

In a 2020 study published in JAMA Dermatology, Paller and colleagues found that biologics were associated with a greater decrease in psoriasis severity scores and higher decrease in psoriasis severity scores and increased treatment-associated survival compared with treatment with methotrexate among 234 pediatric patients with psoriasis.

As Healio previously reported, researchers observed a PASI 75 psoriasis severity score in 40% of patients treated with methotrexate vs. 71.4% of patients treated with biologics (P = .02). Moreover, the overall treatment survival with biologics was 83.4% at 1 year, 64.3% at 3 years and 57.1% at 5 years compared with 1-year survival of 77.5%, 3-year survival of 50.3% and 5-year survival of 35.9% with methotrexate.

“Fortunately, there is increasing availability of biologic agents that are becoming more effective and more targeted against psoriasis than traditional therapies,” Paller said. “Other agents are in trials now, bringing the promise of more choices to patients — and their families — with moderate to severe psoriasis.”

Looking ahead

Experts with whom Healio spoke said more comparative effectiveness data are needed for the traditional systemic treatments as well as for biologics in pediatric psoriasis.

“It is still uncertain what the best biologic treatment is for a child who begins with cutaneous psoriasis and during the course develops psoriatic arthritis, for example,” Eichenfield said. “There are many different factors that come into play with this disease in children. The preference for having less frequent injections may move a patient toward a set of biologic agents compared with other agents that may require monthly or more frequent injections. This is one reason why we need comparative effectiveness research.”

Paller agreed.

“More research is definitely needed looking into therapeutic approaches for our patients. There is a lot to be understood about the comorbidities and implications the systemic immune abnormalities of psoriasis have on children who still have decades of life ahead of them,” Paller said. “Similarly, the research that has been done looking at arthritis risk issues and the cardiovascular risk issues related to psoriasis in adults has not been performed in children. These will be hard studies to conduct and will require many more years, but it is important to try and understand the long-term risks and the potential role for all therapeutic agents in pediatric patients.”

There are several areas of need in pediatric psoriasis, according to Wine Lee, including the need for advanced treatments and accessibility to those treatments.

“The ‘elephant in the room,’ that we do not want in the room, is the health insurance companies. There has been difficulty in patient/physician treatment planning because everything is influenced by the insurance companies,” Wine Lee said. “For children, a medical injection may be worse than the disease itself. It is difficult to have the outside influence of an insurance company that doesn’t take into consideration these complex details. It is different with pediatrics than it is with adults because it is not only the impact of the disease but the impact of treatment as well.”

Research is definitely needed in a few areas, Wan said.

“There are a growing number of studies about quality of life burden but a number of them are fairly small and may not be inclusive of the most representative populations of children. Having research that uses consistent measures of quality of life and a systematic way to use these measurements in our patient population will be extremely helpful,” Wan said.

Going beyond the patient, research is needed to examine the impact on the family as well, Wan added.

“We need to understand the impact on family members and caregivers because oftentimes, especially when children are young, caregivers are providing most of the care. They are the ones to apply topicals, take the patient to frequent phototherapy appointments, help them manage injectable biologic medications and the risks associated with them. There is a significant family impact that we haven’t quite measured in research yet,” Wan said. “We need to develop, but also test interventions that may improve quality of life in this patient population. It is important to identify the impact, but then what are we going to do once we identify the impact? We need an understanding of what interventions are most effective so that we can reach both our patients and their families. This is critical and will become more critical in the coming years.”

• References:
Bronckers IMGJ, et al. JAMA Dermatol. 2020;doi:10.1001/jamadermatol.2019.4835.
Dhaher SA, et al. Cureus. 2021;doi:10.7759/cureus.18397.
Menter A, et al. J Am Acad Dermatol. 2020;doi:10.1016/j.jaad.2019.08.049.
Salman A, et al. An Bras Dermatol. 2018;doi:10.1590/abd1806-4841.20186981.

• For more information:
• Lawrence F. Eichenfield, MD, can be reached at Rady Children’s Hospital, 3020 Children’s Way, San Diego, CA 92123; email: leichenfield@rchsd.org.
• Amy S. Paller, MD, can be reached at the Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N. St. CLair, Suite 1600, Chicago, IL 60611; email: apaller@northwestern.edu.
• Joy Wan, MD, MSCE, can be reached at Johns Hopkins Medicine, 200 N. Wolfe Street, Baltimore, MD 21287; email: jwan7@jhmi.edu.
• Lara Wine Lee, MD, PhD, can be reached at MUSC Health University Medical Center, 135 Rutledge Ave., Floor 3, Charleston, SC 29425; email: winelee@musc.edu.