Dra. Lucía Quintana

DERMATOLOGÍA PEDIÁTRICA

HEMANGIOMAS y MALFORMACIONES VASCULARES

Haemangiomas

Do all haemangiomas have the same evolution?▪ 59 patients with IH growth at 3 years of age or later

▪ 85% females

▪ More common in head and neck

▪ 53% Phace

▪ Deep hemangiomas

▪ Almost all received systemic treatment

IH involute, but do not “disappear”Untreated haemangioma leave sequel in 56-69% cases!

Haemangiomas

Megha M. Tollefson, Ilona J. Frieden. Pediatrics Aug 2012, 130 (2) e314-e320

Haemangiomas

▪ Which IH will leave more sequel?

▪ How to identify them?

Location Size IH characteristics

DESFIGUREMENT

• Glabella• Nasal tip• Lip• Central face• Breast

• Larger • Ulcerated• Pedunculated• Mixed>Superf>Deep• Border/thickness

superficial component

Baselga E et al. JAMA Dermatol 2016;152:1239-1243

Treatment decisions have to be taken early.“Early referral and close follow/up during the early proliferative phase”

Megha M. Tollefson, Ilona J. Frieden. Pediatrics Aug 2012, 130 (2) e314-e320

PHACES SYNDROME (OMIM 606519)

90% OF PATIENTS WITH PHACEs > 1 EXTRACUTANEOUS MANIFESTATION

• Posterior fossa malformation• Large segmental Facial

Haemangioma• Arterail anormalities• Cardiac aorta coartation• Eye abnormalities• Sternal raphe

91%

45%

Peadiatrics 201 139:117-23Pediatrics 2010:126(2):418-26Arch Dermatol 1996:132:307

CNS structural and Cerebrovascular

▪ S1 more risk than others (but if extensive more risk)

▪ S1 was associated with significantly higher risk for ▪ Structural CNS anomalies

▪ Cerebrovascular anomalies

▪ Isolated S2 lower risk / just 1 case

▪ S1>S3<S4

Am J Med Genet A. 2018 January ; 176(1): 48–55Pediatrics. 2010 Aug;126(2):e418-26

EMERGENCIAS NEONATALES

DRESS

▪ Therapy syst corticosteroids and in viral infection/reactivation (VHS-6 y CMV)

plusantiviral therapy

▪ Ganciclovir iv 5mg/kg every 12h for 3wk and then low KS and Ganciclovir → healing

SÍNDROMES NEUROCUTÁNEOS

VITÍLIGO

Vitíligo

▪ Vitíligo y Tofacitinib: necesita luz

▪ Topical ruxolitinib 1,5% and vitíligo:▪ ≥12 años

ICTIOSIS

Novedades en manejo de ictiosis

▪ TRIFAROTENE 50 μg/g (Aklief®)

▪ Retinoide de 4 generación

▪ Aprobado acné cara y tronco >9 años

▪ Se unen selectivamente al RAR γ

▪ Rápida eliminación del torrente sanguíneo

TERAPIA SISTÉMICA EN PSORIASIS INFANTIL

Systemic therapy in pediatric psoriasis

▪ In the majority of cases children psoriasis is mild or moderateand therefore topical treatment and/or phototherapy are thefirst choice

▪ Overall, 13-27% of children have moderate to severe plaque type psoriasis (BSA>10%) and may need systemic treatment

▪ Nevertheless in children the visibility of the lesions (nails, face, hand) must be taken into consideration due to the high risk of lifelong psychosocial impairment and may lead to social withdrawal, stigma or bullying

Schwartz G; Paller A. Targeted therapies for pediatric psoriasis. Seminars in Cutaneous Medicine and Surgery. Sept 2018

T resident memory cells

▪ There is evidence of lesional memory, or the so called“immunologic scar”

▪ High levels of different inflammatory cytokines have beendetected such as IL-17, IL-22 and INFgamma in biopsies ofclinically healed lesiones

▪ There is and emerging role of the tissue resident memory T-cells playing an integral role in the chronic relapsing course of the disease

Schwartz G; Paller A. Targeted therapies for pediatric psoriasis. Seminars in Cutaneous Medicine and Surgery. Sept 2018Clark RA, J Invest Dermatol 2011, Park CO, Kupper TS Nat Med 2015

T resident memory cells

▪ There is evidence of lesional memory, or the so called“immunologic scar”

▪ High levels of different inflammatory cytokines have beendetected such as IL-17, IL-22 and INFgamma in biopsies of clinicaly healed lesiones

▪ There is and emerging role of the tissue resident memory T-cells playing an integral role in the chronic relapsing course of the disease

Schwartz G; Paller A. Targeted therapies for pediatric psoriasis. Seminars in Cutaneous Medicine and Surgery. Sept 2018Clark RA, J Invest Dermatol 2011, Park CO, Kupper TS Nat Med 2015

Schwartz G; Paller A. Targeted therapies for pediatric psoriasis. Seminars in Cutaneous Medicine and Surgery. Sept 2018

Is it probably time to reassed the use of systemic orbiologic drug early in the course of psorasis?

Targeted therapies for pediatric psoriasis

Target and structure Drug Mode FDA and EMA approval Dosage

TNFa receptor/IgG-FC fusión protein

Etanercept Sc FDA 4years (2016)EMA 6 years (2009)

0,8mg/kg/wk

Human high-affinityIgG1 anti-TNF

monoclonal antibody

Adalimumab Sc FDA not approvedEMA ≥4 years (2016)

0,8mg/kg week, and then every 2 weeks,

max 40mg

Human monoclonal IgG1 antibody targeting

Il-12/23 shared p40 subunit

Ustekinumab Sc FDA 12years (2016)EMA ≥12yeas(2015)

0,75mg/kg if ≥60kh45mg if >60 to 100kg90mg if >100kg week0,34 , then every 12

weeks

Schwartz G; Paller A. Targeted therapies for pediatric psoriasis. Seminars in Cutaneous Medicine and Surgery. Sept 2018

1. Infliximab is not currently approved for pediatric use by the FDA or EMA and ir rarely used for plaque psoriasis

2. It is a human IgG1 anti-TNF monoclonal antibody administred i.v. at a dosage of 3-5mg/kg at wk 0,2,6 and then every 8 wk

3. All biologics for pediatric use share the same profile of potential side effects; injection site reaction and pain, upper respiratory tract infection, risck of mycobacterial infection.

▪ At the present moment there are ongoing clinical trials in pediatric psoriasis with the following agents:

▪ Secukinumab (NCT02471144)

▪ Ixekizumab (NCT03073200)

▪ Brodalumab (NCT03240809)

▪ Guselkumab (NCT03451851)

▪ Risankizumab

▪ Apremilast

▪ *Ustekinumab is now investigated in clinical trials for 6-11 years old

Psoriasis in childhood - The role of IL-22

▪ In a recent study of the T-cell composition in the lesional skin of children versus adults, a predominance of cluster ofdifferentiation CD4+ and CD8+ IL-22 expressing T-cells in pediatric skin vs. the predominance of CD4+ and CD8+ IL17 T-cells in adults skin was found

▪ While the IL-22 therapy (fezakinumab) was not efficacious in adult psoriasis, the greater increase in the proportion of T-cellexpression IL-22 in children, compared with adults, suggeststhat the pediatric population may prove more responsive to anti IL-22 therapy

Schwartz G; Paller A. Targeted therapies for pediatric psoriasis. Seminars in Cutaneous Medicine and Surgery. Sept 2018

DERMATITIS ATÓPICA

Atopic Dermatitis

▪ Dupilumab (DUPIXENT®)

▪ Blocking IL-13: ▪ Lebrikizumab and Tralokinumab

▪ Targeting IL-22: ▪ Fezakinumab

▪ Anti-Interleukin 31 receptor A: ▪ Nemolizumab

▪ Topical Inh PDE-4: ▪ Crisaborole (Eucrisa®)

▪ Approved in US

Atopic Dermatitis

▪ Baricitinib (JAK1/3)▪ Phase III

▪ Upadacitinib (JAK1)▪ Phase 2▪ 167 patients, moderate – severe AD▪ 16 weeks▪ Dose finding: 7,5mg – 15mg – 30mg▪ Safety: increased risk for infections

▪ Topical tofacitinib:▪ Phase II: EASI reduction 82% vs 30% placebo group▪ No increased risk of infections, contact dermatitis, itch/pain at application

site

▪ Topical ruxolitinib▪ Phase III