Updates In Pediatric Dermatology

Dr. Adena Rosenblatt MD PhD Assistant Professor of Pediatric

Dermatology University of Chicago Medicine

Disclosures

• I have no relevant financial relationships with the manufacturers(s) of any commercial products(s) and/or provider of commercial services discussed in this CME activity.

• I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation.

Learning Objectives

• Present new therapies for common pediatric dermatologic conditions

• Describe how to overcome barriers to implementing in practice

Acne

• 85% of adolescents and young adults between 12-24yo develop acne

Types of Acne

Guidelines of Care for Acne

Journal of the American Academy of Dermatology 2016 74, 945-973.e33DOI: (10.1016/j.jaad.2015.12.037)

Antibiotic Resistance Prevention

• Recent retrospective cohort study in the United Kingdom

• 62% of general practitioners (GP) prescribing oral antibiotics for acne did so without also prescribing a retinoid

• 29% of GPs prescribed oral antibiotics for greater that 6 mo course for acne

New Acne Treatments in Trial

• Topical minocycline foam appears to be effective and safe for the treatment of moderate to severe inflammatory acne in Phase 2 clinical trials.

• Olumacostat glasaretil (OG) inhibits sebocyte lipid production is an effective and safe topical treatment for moderate to severe acne in Phase 2 clinical trials

• Of note, Differin (adapalene) 0.1% cream is now available over the counter

Fig 1. Acetyl coenzyme A carboxylase (ACC) effect on sebum production. CoA, Coenzyme A; HMG CoA, 3-hydroxy-3-methyl-

glutaryl-coenzyme A; OG, olumacostat glasaretil; TOFA, 5-(tetradecyloxy)-2-furancarboxylic acid.

Robert Bissonnette, Yves Poulin, Janice Drew, Hans Hofland, Jerry Tan

Olumacostat glasaretil, a novel topical sebum inhibitor, in the treatment of acne vulgaris: A phase IIa, multicenter,

randomized, vehicle-controlled study

Journal of the American Academy of Dermatology, Volume 76, Issue 1, 2017, 33–39

http://dx.doi.org/10.1016/j.jaad.2016.08.053

Periorificial Dermatitis

• Common condition in children

• Exacerbated by topical steroids

• +/- burning sensation • Standard treatment is

erythromycin x6wk, sometimes topical metronidazole or calcineurin inhibitors

• New study looks at efficacy of topical ivermectin (may be 2/2 demodex)

Atopic Dermatitis

• Most common chronic inflammatory skin condition

• Occurs in 10-15% of children

• Multifactorial pathogenesis but it is TH2 mediated

• Atopic Triad: AD, asthma, allergic rhinitis

Atopic Dermatitis

Types of Atopic Dermatitis

Atopic Dermatitis

• Guidelines of care for the management of atopic dermatitis in JAAD

• Emollients are mainstay for the treatment and maintenance of atopic dermatitis

• Bathing should be performed daily with mild, fragrance free soap

• Topical steroids are the mainstay for first line treatment in AD and topical calcineurin inhibitors can also be effective

• Refractory AD can be treated with phototherapy (ie nbUVB) or systemic treatment (ie cyclosporine, azathioprine, methotrexate)

• Probiotics may be mildly helpful but food avoidance is not recommended

New Treatment for Atopic Dermatitis

• Topical crisaborole 2% oint, a PDE 4 inhibitor, is effective for mild to moderate AD in Phase 3 clinical trial for children and adults

• Dupilumab, a human monoclonal antibody to IL-4 receptor alpha, is effective for moderate to severe AD in Phase 3 clinical trials in adults

• 5 year randomized trial found that pimecrolimus (elidel) cream was safe and effective for long term management of mild to moderate AD in infants

Contact Dermatitis In Children With Atopic Dermatitis

• Patch tested children with AD were younger and had a longer history of dermatitis compared to those without AD

• Increase frequency of reactions to:

– cocamidopropyl betaine (ie acne cleansers- panoxyl, clearasil, biore)

– wool alcohol/lanolin (ie Aquaphor)

– tixocortol pivalate

– Parthenolide (extract of feverfew, in Aveeno products)

2014 ISSVA Classification of Vascular Anomalies

Vascular Anomalies

Vascular

Tumors

Vascular Malformations

Simple Combined Of Major

Named

Vessels

Associated

With Other

Anomalies

Benign CM See Table 5 See text See Table 6

Locally

aggressive or

borderline

LM

VM

Malignant

AVM

Arteriovenou

s fistula

Vascular Lesions Benign vascular tumors

Infantile hemangioma/hemangioma of

infancy

Congenital hemangioma

Rapidly involuting CH (RICH)a

Noninvoluting CH (NICH)

Partially involuting CH (PICH)

Tufted angiomaa,b

Spindle cell hemangioma

Epithelioid hemangioma

Pyogenic granuloma (or lobular

capillary hemangioma)

Others

Locally aggressive or borderline

vascular tumors

Kaposiform hemangioendotheliomaa,b

Retiform hemangioendothelioma

Papillary intralymphatic

angioendothelioma, Dabska tumor

Composite hemangioendothelioma

Kaposi sarcoma

Others

Malignant vascular tumors

Angiosarcoma

Epithelioid hemangioendothelioma

Others

CMs

Cutaneous and/or mucosal CM (“port

wine” stain)

CM with bone and/or soft tissue

overgrowth

CM with CNS and/or ocular

anomalies (Sturge-Weber syndrome)

CM of CM-AVM

CM of microcephaly-CM (MICCAP)

CM of megalencephaly-CM-

polymicrogyria (MCAP)

Telangiectasia

Hereditary hemorrhagic

telangiectasia (HHT; different types)

Others

Cutis marmorata telangiectatica

congenita (CMTC)

Nevus simplex/salmon patch/ “angel

kiss,” “stork bite”

Others

LMs

Common (cystic) LMs

Macrocystic LM

Microcystic LM

Mixed cystic LM

Generalized lymphatic anomaly (GLA)

LM in Gorham-Stout disease

Channel-type LM

Primary lymphedema

Others

VMs

Common VM

Familial VM cutaneo-mucosal

(VMCM)

Blue rubber bleb nevus (Bean)

syndrome VM

Glomuvenous malformation

(GVM)

Cerebral cavernous

malformation (CCM; different

types)

Others

AVMs

Sporadic

In HHT

In CM-AVM

AVFs

Sporadic

In HHT

In CM-AVM

Others

Infantile Hemangiomas

• Benign vascular tumor

• Most present in the first few weeks of life (1/3 present at birth)

• More common in premature infants, females, mothers of AMA or with placental problems during pregnancy

• Growth phase (in 1st 6mo of life) plateau phase (1st few years of life) involution phase (3-10yo)

Types of Hemangiomas

Complications of Hemangiomas

• Functional compromise – Eye – Ear – Airway – Anogenital

• Ulceration • Permanent disfigurement

– Lip, tip of nose, parotid, anogenital

• Visceral lesions • Hypothyroidism • Associated syndromes or features

Management of Hemangiomas: Interventions

• Parental support and careful observation • Wound care when ulcerated • Propranolol is treatment of choice for

complicated lesions – Topical timolol gel: Might moderate proliferation;

might help heal ulcers • 2nd line options:

– Systemic corticosteroids, intralesional corticosteroids – Vincristine

– Pulsed dye laser – Embolization – Surgical excision

Infantile Hemangiomas

• Topical timolol is a safe and effective treatment for superficial, thin IH

• Oral propranolol has a safe profile with minimal AE if pt are screened properly for contraindications

• ~25% of patients on oral propranolol have rebound growth after d/c

Vascular Malformations

New Treatments for Vascular Anomalies

• Sirolimus (rapamycin) was efficacious and well tolerated for treatment of a variety of vascular anomalies in a phase 2 clinical trial

• Propranolol may be effective at low doses for the treatment of lymphatic anomalies in a recent retrospective case series

Psoriasis

• Chronic inflammatory skin condition affecting 4-5% of US population

• Multifactorial but it is TH1 mediated

• Guttate type is more common in children often following strep infection

• May be associated with arthritis and/or nail findings

Types of Psoriasis

Psoriasis Treatment

• Topical treatment: – Topical steroids – Topical vitamin D analogs – Topical calcineurin inhibitors – Tazorac (retinoid)

• Phototherapy: – nbUVB – Excimer laser – PUVA (not commonly used b/c risk of skin cancer)

• Systemic treatment: – Methotrexate – Cyclosporine – Acitretin – Biologics

Psoriasis

• Study showed a decrease in QOL of parents of children with psoriasis (ie sleep disruption, sadness, frustration, burden of care)

• Increased rates of psychiatric comorbid conditions in children with psoriasis (ie depression, substance abuse, eating disorders)

• Increased rates of metabolic syndrome in children with psoriasis

Psoriasis treatments and trials

• Approval for etanercept in children

• Investigation of biosimilars and other biologics in adults Guselkumab (anti IL 23 monoclonal ab) highly effective including adalimumab nonresponders

• Clinical trial is starting to investigate the efficacy of ixekizumab, (anti IL 17A monoclonal ab) for treatment of moderate to severe plaque psoriasis in children (approved in adults)

Alopecia areata

• Most common non-scarring alopecia

• T cell mediated autoimmune condition

• May have associated nail findings

• Clinical course is unpredictable

• May be associated with other autoimmune conditions

• Current treatments include: topical or intralesional steroids, squaric acid topical tx

Types of Alopecia areata

New Treatments for alopecia areata

• Tofacitinib, a JAK kinase inhibitor, was found to be effective in the treatment of alopecia areata in adolescents

• Clinical trial is underway to evaluate efficacy of topical JAK kinase inhibitor in adults with alopecia areata

Teledermatology

• Provides pediatric dermatology care remotely

• Dermatologist are able to identify the correct diagnosis most of the time through teledermatology

• It is best utilized with standardized history taking and photography

• Teledermatology is best for characteristic presentations of skin conditions and for follow up of previously diagnosed conditions

References • Puttgen K et al. Topical timolol maleate treatment of infantile hemangiomas. Pediatrics. Sept 2016 Vol 138 (3) • Leaute-Labreze C et al. Safety of oral propranolol for the treatment of infantile hemangiomas: as systematic review. Pediatrics. Oct 2016 138(4). • Shah SD et al. Rebound growth of infantile hemangiomas after propranolol therapy. Pediatrics Apr 2016 Vol 137 (4) • Wassef M et al. Vascular anomalies classification: recommendations from the international society for the study of vascular anomalies. Pediatrics Jul

2015 Vol 136 (1) • Tollefson MM et al. Impact of childhood psoriasis on parents of affected children. J Am Acad Dermatol. Feb 2017. 76 (2) • Todberg T et al. Psychiatric comorbidities in children and adolescents with psoriasis- a population-based cohort study. Br J Dermatol. Sept 2016. • Noguera-Morel L et al. Ivermectin therapy for papulopustular rosacea and periorificial dermatitis in children: A series of 15 cases. JAAD. Mar 2017 Vol

76 (3) 567-570. • Reich K et al. Efficacy and safety of guelkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of

patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator- controlled VOYAGE 2 trial. JAAD. Mar 2017 Vol 76(3) 418-431

• Strober B. et al. Short and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis> Etanercept comparisons and integrated data. JAAD. Mar 2017. Vol 76 (3) 432-440.

• Craiglow BG et al. Tofacitinib for the treatment of alopecia areata and variants in adolescents. JAAD. Jan 2017. Vol 76 (1) 29-32. • Bissonnette R et al. Olumacostat glasaretil, a novel topical sebum inhibitor, in the treatment of acne vulgaris: A phase IIa, multicenter, randomized,

vehicle-controlled study. JAAD. Jan 2017 Vol 76 (1). • Zaenglein AL et al. Guidelines of care for the management of acne vulgaris. JAAD. May 2016 Vol 74 (5) 945-973. • Shermer A et al. Topical minocycline foam for moderate to severe acne vulgaris: Phase 2 randomized double-blind, vehicle-controlled study results.

JAAD. June 2016. Vol 74 (6) • Barbieri JS et al. Duration of oral tetracycline-class antibiotic therapy and use of topical retinoids for the treatment of acne among general

practitioners (GP): A retrospective cohort study. JAAD. Dec 2016. Vol 75 (6) 1142-1150. • Jarnagin K et al. Crisaborole topical ointment, 2%: a nonsteroidal, topical, anti-inflammatory phosphodiesterase 4 inhibitor in clinical development for

the treatment of atopic dermatitis. JDD. Apr 2016 15 (4) 390-396. • Sidbury R et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic

agents. JAAD Aug 2014. 71 (2) 327-49 • Eichenfield LF et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. JAAD. Feb

2014 70(2) 338-51 • Sidbury R et al. Guidelines of care for the management of atopic dermatitis: section 4. Prevention of disease flares and use of adjunctive therapies

and approaches. JAAD Dec 2014 71 (6) 1218-1233 • Eichenfield LF et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with

topical therapies. JAAD Jul 2014 71(1) 116-32 • Simpson EL et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. Dec 2016. Vol 375 (24) 2335-2348 • Sigurgeirsson B et al. Safety and efficacy of pimecrolimus in atopic dermatitis: a 5-year randomized trial. Pediatrics. Apr 2015. Vol 135 (4) 597-606 • Adams DM et al. Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies. Pediatrics. Feb 2016. Vol 137 (2) • Wu JK et al. Initial experience with propranolol treatment of lymphatic anomalies: a case series. Pediatrics. Sep 2016. Vol 138 (3) • Philp JC et al. Pediatric teledermatology consultation: relationship between provided data and diagnosis. Pediatr Dermatol. Sept 2013. Vol 30 (5) 561-

7 • Fogel AL and Teng JM. Pediatric teledermatology: a survey of usage, perspective, and practice. Pediatr Dermatol. May 2015. Vol 32 (3) 363-8