COVID-19 Skin Symptoms in Children

Many new treatments for pediatric skin conditions have been either approved or have recently released new data. Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego and professor of dermatology and pediatrics and vice-chair of the Department of Dermatology at University of California San Diego School of Medicine, both in California, described these updates at the Fall Clinical Dermatology conference held October 21 to 24 in Las Vegas, Nevada.¹

Lawrence Eichenfield, MD

For atopic dermatitis (AD), Eichenfield described updates to the current pipeline.

The topical treatments mentioned were:

• Ruxolitinib (Opzelura; Incyte) a topical selective Janus kinase (JAK)1/JAK2 inhibitor which was approved by the FDA for the treatment of mild to moderate AD in patients 12 years and older on September 21, 2021.
• Tapinarof (DMVT-505; Dermavant) an investigational therapeutic aryl hydrocarbon receptor modulating agent that started dosing in its phase 3 for AD in September 2021 and has a new drug application (NDA) for the treatment of psoriasis is adults.
• Roflumilast (ARQ-151; Arcutis Biotherapuetics) a selective phosphodiesterase-4 inhibitor being studied in atopic dermatitis and psoriasis.
• FB-401, a live biotherapeutic that is made of specifically selected strains of commensal Roseomonas mucosa, that was being tested for mild to moderate AD. This treatment has failed to reach statistical significance.²
• Dupilumab (Dupixent), a fully human monoclonal antibody that inhibits the signaling of the interleukin (IL)-4 and IL-13 pathways, recently demonstrated safety and efficacy in pediatric AD patients ages 6 months to 5 years.

He briefly mentioned the status of systemic JAK inhibitors for pediatric patients—abrocitinib (PF-04965842; Pfizer), baricitinib (Olumiant; Eli Lilly and Company), and upadacitinib (Rinvoq; AbbVie)—of which abrocitinib and upadacitinib for adolescents is currently on hold for approval from the FDA for the treatment of AD, and baricitinib not yet filed.³

Eichenfield next tackled pediatric psoriasis, describing the newest treatments, such as:

• Ustekinumab (Stelara, Janssen Pharmaceutical Companies of Johnson & Johnson) a IL-12 and IL-23 inhibitor which was approved for moderate to severe plaque psoriasis in pediatric patients 6 to 11 years.
• Secukinumab (Cosentyx, Novartis) an IL-17A inhibitor approved in patients 6 years and older to treat moderate to severe plaque psoriasis in June 2021.
• Ixekizumab (Taltz, Eli Lilly and Company) monoclonal antibody is designed to selectively bind with interleukin 17A (IL-17A) cytokine while inhibiting its interaction with the IL-17 receptor. It was approved last year for pediatric patients with moderate to severe plaque psoriasis ages 6 to 17.

He presented a study⁴ that compared pediatric patients treated with methotrexate vs biologic agents. There were 234 patients with moderate to severe psoriasis treated with at least 3 months of either methotrexate or biologic. It was found that 71.4% of patients treated with biologics compared to 40% of methotrexate patients achieved Psoriasis Area and Severity Index (PASI)75. Also, the biologic medications had a longer drug survival than its comparator. This demonstrates the efficacy difference between treatments, according to Eichenfield.

Switching gears, he discussed pediatric specific COVID-19 skin symptoms.

COVID-19 skin symptoms, Eichenfield continued, are different in pediatric patients compared to adults. He explained that symptoms are usually milder in adults, with infants and the immunocompromised at a greater risk of becoming more ill from the virus. He gathered data from several studies,^5-7 that found the skin symptoms to include multiple rashes (extensive or localized) such as hives, petechial, psoriasiform, maculopapular, papulovesicular (varicella-like), livedoid, and mucositis. There may also be signs of Kawasaki-disease or vasculitis in pediatric patients.

Next, Eichenfield pondered on whether COVID toes was in relation to infection or an immune response?

The toes often show pernio-like lesions, according to Eichenfield, but there is usually no history of Raynaud’s syndrome or autoimmune disease. In some cases, skin biopsies reveal immunohistochemistry positive for COVID-19 in the tissue and both polymerase chain reaction (PCR) tests and serology were commonly negative. Other articles state that the lesions are not associated with COVID-19.^8-11

With COVID-19 research still underway, dermatology practices have completely changed in how they function, Eichenfield explained. With teledermatolgy, it has changed the way the patient and physician interact for both good and bad.

Eichenfield concluded his presentation, stating that in the future there will be new genome targeted interventions for genetic diseases and evolved therapies in inflammatory skin disorders.

Disclosures:

Eichenfield is an investigator or consultant for AbbVie, Almirall, Arcutis Biotherapeutics, Aslan, Dermavant Sciences, Dermira, Inc., Forte Biosciences, Galderma Laboratories, Ichnos Sciences, Incyte Corporation, Eli Lilly and Company, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, Ortho Dermatology, and Verrica Pharmaceuticals.

References:

1. Eichenfield L. Pediatric dermatology update. Presented at: Fall Clinical Dermatology Conference 2021; October 21 to October 24, 2021; Las Vegas, Nevada, and virtual.

2. Clinical trial of fb-401 for the treatment of atopic dermatitis fails to meet statistical significance. Published September 9, 2021. Accessed October 18, 2021. https://www.fortebiorx.com/investor-relations/news/news-details/2021/Clinical-Trial-of-FB-401-For-the-Treatment-of-Atopic-Dermatitis-Fails-to-Meet-Statistical-Significance/default.aspx

3. FDA requiring black box warning for certain jak inhibitors. Dermatology Times. September 2, 2021. Accessed October 19, 2021. https://www.dermatologytimes.com/view/fda-requiring-black-box-warning-for-certain-jak-inhibitors

4. Bronckers IMGJ, Paller AS, West DP, et al. A comparison of psoriasis severity in pediatric patients treated with methotrexate vs biologic agents. JAMA Dermatol. 2020;156(4):384-392. doi:10.1001/jamadermatol.2019.4835

5. Casas CG, Català A, Hernández GC, et al. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. British Journal of Dermatology. 2020;183(1):71-77. doi:10.1111/bjd.19163

6. Cordoro KM, Reynolds SD, Wattier R, McCalmont TH. Clustered cases of acral perniosis: Clinical features, histopathology, and relationship to COVID-19. Pediatric Dermatology. 2020;37(3):419-423. doi:10.1111/pde.14227

7. Hernandez C, Bruckner AL. Focus on “covid toes.” JAMA Dermatol. 2020;156(9):1003. doi:10.1001/jamadermatol.2020.2062

8. Colmenero I, Santonja C, Alonso-Riaño M, et al. SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven pediatric cases. Br J Dermatol. 2020;183(4):729-737. doi:10.1111/bjd.19327

9. Freeman EE, McMahon DE, Lipoff JB, et al. Pernio-like skin lesions associated with COVID-19: A case series of 318 patients from 8 countries. J Am Acad Dermatol. 2020;83(2):486-492. doi:10.1016/j.jaad.2020.05.109

10. Herman A, Peeters C, Verroken A, et al. Evaluation of chilblains as a manifestation of the covid-19 pandemic. JAMA Dermatol. 2020;156(9):998-1003. doi:10.1001/jamadermatol.2020.2368

11. McCleskey PE, Zimmerman B, Lieberman A, et al. Epidemiologic analysis of chilblains cohorts before and during the covid-19 pandemic. JAMA Dermatol. 2021;157(8):947-953. doi:10.1001/jamadermatol.2021.2120