Pediatric dermatology updates

This has been an exciting year in pediatric dermatology and many new strides forward have been made.

Pediatric psoriasis patients finally have improved access to biologic agents with the approval late last year of etanercept (Enbrel, Amgen), a TNF inhibitor for psoriasis patients as young as four years old. Ustekinumab (Stelara, Janssen), an IL-12 and IL-23 inhibitor, which requires injections only four times a year, was approved in October 2017 for pediatric psoriasis patients 12 years of age and older. The approval of these biologic agents significantly broadens the options available for pediatric patients with moderate-to-severe psoriatic disease requiring systemic treatment.

Clinicians should feel comfortable counseling patients and their families about the use of systemic agents. A recent review by Bronckers et al. published in JAMA Dermatology in November 2017 highlighted the overall excellent safety profile of systemic agents in the treatment of pediatric psoriasis and showed that biologic agents have fewer medication- associated adverse effects.¹ (Read more in Insights into treatment safety).

The risk of serious co-morbidities in adult patients with psoriasis is well understood and screening of adult patients is the standard of care, however until recently no guidelines existed for pediatric patients. It has been speculated that since up to one-third of psoriasis begins in childhood, early identification of risk may be critical to help minimize future health effects.

The first evidence based guidelines for comorbidity screening of pediatric psoriasis patients were published last year in JAMA Dermatology. They recommend screening of obesity and hypertension in patients as young as two years of age and screening for dyslipidemia, type II diabetes and nonalcoholic fatty liver disease starting at about 10 years of age, with earlier screening in the presence of additional risk factors, particularly obesity. ^2,3 (Read more Pediatric psoriasis guidelines).

Advances in the field of atopic dermatitis have been especially exciting this year. Focus in the last year has been on both new treatment options and on the larger health implications of atopic dermatitis.

Multiple studies have cited the association between atopic dermatitis and attention deficit hyperactivity disorder (ADHD), and a recent paper by Schmidt et al. has confirmed that association, and posited that early antihistamine exposure may be a risk factor.⁴ (Read more in AD therapy linked to ADHD).

It has been well known that psoriasis is associated with serious comorbidities, however a recent review article from Anderson et al. proposed that atopic dermatitis patients may also have an increased risk of cardiovascular disease, as well as an increased risk of autoimmune diseases, certain malignancies and neuropsychiatric disease.⁵ Evolving knowledge of comorbidities and understanding that poor disease control leads to poorer quality of life should encourage physicians to push for improved disease control to minimize disease impact with close follow up of atopic dermatitis flares.

After years with few new products available for atopic dermatitis there has been a recent flurry of activity regarding pharmacologic treatments for atopic dermatitis. Crisaborole (Eucrisa, Pfizer), a topical phosphodiesterase 4 inhibitor, was approved in December 2016 as a safe and effective topical treatment for pediatric patients as young as two years old. The advent of crisaborole provides an alternative steroid-sparing agent that is readily acceptable to parents, as it does not carry the black box warning seen with topical calcineurin inhibitors. (Read more in Atopic dermatitis in 2018).

Dupilumab (Dupixent, Sanofi and Regeneron), an IL-4 receptor alpha antagonist that inhibits both IL-4 and IL-13, was approved for adult patients in March 2017 as the first biologic to target atopic dermatitis. (Read more in Atopic dermatitis and psoriasis as spectrum conditions).

Phase II trials are currently ongoing for pediatric patients from ages 12 to 17. Younger patients are being actively enrolled at numerous sites and studies will soon be underway for patients two to 12 years old. JAK inhibitors are being studied for both topical and systemic use in atopic dermatitis and pediatric trials evaluating topical tofacitinib, a JAK1 and 3 inhibitor, will be opening soon.

Probiotics have long been proposed for the prevention and treatment of atopic dermatitis and a RCT published in JAMA Dermatology in January 2018 showed that atopic dermatitis severity score and topical corticosteroid use were decreased in patients treated with oral probiotics.⁶ (Read more in the cover story, Probiotics may improve pediatric AD symptoms).

The field of complicated vascular anomalies has always been difficult to classify due to the enormous phenotypic variability seen. The increased availability of next generation genetic sequencing has lead to a reconceptualization of vascular anomaly classification and patients are increasingly being categorized, not by their phenotypic appearance, but instead by their specific genetic mutation.

A recent multi-center study published in the Journal of Investigative Dermatology demonstrated that most vascular anomalies with overgrowth harbor a post zygotic mutation in oncogenes. Despite the presence of oncogene mutations, the prevalence of cancer remains low in patients with vascular stain and overgrowth.⁷

Genotyping has the potential to assist in determination of treatment options and is an area of significant interest to pediatric dermatologists, most notably in the use of sirolimus, which has been used with moderate benefit in several patients with PIK3CA mutations.⁸

Teledermatology has been receiving a lot of attention in recent months as patient care evolves in the digital age. Long waits and limited access to pediatric dermatology specialty clinics make teledermatology an attractive option. A recent study from Children’s Hospital of Philadelphia showed there is good correlation of diagnosis via teledermatology versus live patient evaluation, which may lead more sites to offer these services, allowing pediatric dermatology to broaden its influence and availability.⁹

REFERENCES

1. Bronckers IMGJ, et al. “Safety of Systemic Agents for the Treatment of Pediatric Psoriasis”. JAMA Dermatol. 2017 Nov 1;153(11):1147-1157.

2. Osier E, Et al. “Pediatric Psoriasis Comorbidity Screening Guidelines”. JAMA Dermatol. 2017 Jul 1;153(7):698-704

3. Tollefson MM, et al. “Comorbidity Development in Children With Psoriasis”. JAMA Dermatol. 2018, Jan 10

4. Schmitt J, et al. “Increased attention-deficit/hyperactivity symptoms in atopic dermatitis are associated with history of antihistamine use”. Allergy. 2017 Oct 4.

5. Anderson YMF, et al. “Comorbidities of Atopic Dermatitis: Beyond Rhinitis and Asthma”. Curr Dermatol Rep. 2017; 6(1): 35–41.

6. Navarro-Lopez V, et al. “Effect of Oral Administration of a Mixture of Probiotic Strains on SCORAD Index and Use of Topical Steroids in Young Patients With Moderate Atopic Dermatitis: A Randomized Clinical Trial”. JAMA Dermatol. 2018 Jan 1;154(1):37-43.

7. Siegel DH, et al. “Analyzing the Genetic Spectrum of Vascular Anomalies With Overgrowth Via Cancer Genomics” J Invest Dermatol. 2017 Nov 22.

8. Adams DM, et al. “Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies”. Pediatrics. 2016 Feb;137(2):e20153257.

9. O’Connor DM, et al. “Diagnostic Accuracy of Pediatric Teledermatology Using Parent-Submitted Photographs: A Randomized Clinical Trial”. JAMA Dermatol. 2017; 153(12):1243-1248.