5th ABC of Pediatric Friday 21 September 2018

Acneiform eruptions in childhood

Talia Kakourou MD Consultant Pediatric Dermatologist 1st Pediatric Dept, Athens University Aghia Sophia Children’s Hospital Athens, Greece Acneiform eruptions : a group of disorders that resemble vulgaris Acne vulgaris

• A chronic inflammatory disorder of the pilosebaceous unit • It is characterized by comedones, papules, pustules , nodules and/or Acne vulgaris location

• Face (99% of cases)

• Back (60% of cases)

• Chest (15% cases) Comedone

• Sine qua non lesion in acne vulgaris • Clinical classification – Closed – Opened – Macrocomedones (diameter >1mm)

Childhood Acne vulgaris (classification based on age of onset) • Neonatal 0 - 4 weeks • Infantile 1-12 months • Mid-childhood 1-7 years • Pre-adolescent 7-12 years

(Dermatol Ther (Heidelb) 2017; 7 (Suppl 1):S43–S52 Am J Clin Dermatol 2006; 7:281-290) Acne vulgaris vs acneiform eruption Acne vulgaris Acneiform eruption

Age Any age group Any age group

Area of Sebum reach Any site of the involvement areas of the skin skin Sine qua non Comedone Absence of lesion comedone True occurs rarely

• Acneiform eruptions may affect up to 20% of neonates

Neonatal acneiform eruptions

• Neonatal cephalic pustulosis • Acne venenata (use of topical oils and ointments) • Acneiform eruption due to maternal medication (lithium, phenytoin, steroids)

Neonatal Cephalic Pustulosis (NCP) • Benign entity • Sex:  ♂ • Location • Comedones are absent

• It is often referred as neonatal acne

NCP: pathogenesis • NCP: association with skin colonization of the Malassezia species ( M. sympodialis, M. globosa, M. dermatis) • The exact etiologic role of Malassezia remains unclear as Malassezia is part of the normal flora of neonatal skin • Lack of complete correlation between NCP and presence of Malassezia species

Ayhan M et al J Am Acad Dermatol 2007;57:1012-8 Bernier V Arch Dermatol 2002; 138: 215-8 Herane MA, Ando I. Dermatology 2003;206: 24-8 NCP: pathogenesis cont/ed)

NCP lesions may represent a hypersensitivity reaction to the presence of M. Species in predisposed neonates with more intense sebum production

(Niamba et al. Arch Dermatol 1998; 134:995) NCP: management • A self-limited disorder with spontaneous resolution in a few weeks up to 2 months of age • Reassurance of the parents • Use of a mild cleanser and water (once or twice daily) If lesions are numerous  topical treatment with ketoconazole cream (twice daily, 1 week)

Rapelanoro R et al. Arch Dermatol. 1996;132:190-3 Marcoux D et al. J Cutan Med Surg 1998:2: 2– 6 Neonatal acneiform eruptions

• Neonatal cephalic pustulosis • Acne venenata (use of topical oils and ointments) • Acneiform eruption due to maternal medication (lithium, phenytoin, steroids)

Neonatal acne venenata Neonatal acneiform eruptions

• Neonatal cephalic pustulosis • Acne venenata (use of topical oils and ointments) • Acneiform eruption due to maternal medication (lithium, phenytoin, steroids)

Infantile acne vs infantile acneiform eruptions (1-12 months) Acneiform eruption Infantile acneiform eruptions

• Acne venenata (use of topical oils and ointments) • Acneiform eruption due (use of topical or inhaled corticosteroids) monomorphic eruption

Mid childhood acne (1-7 years) vs mid- childhood acneiform eruptions

Mid- childhood acne Acneiform eruptions •

• Childhood granulomatous periorificial dermatitis

• Ιdiopathic Facial Aseptic Granuloma

Rosacea

• Common chronic facial dermatosis • Primarily affects the central face • Exacerbations and remissions • It affects both sexes • It usually presents after the age of 30 years Rosacea lesions • Facial flushing commonly in response to emotional or environmental stress) • Erythema • Telangiectasias • Papules • Pustules • Phymatous skin changes (e.g. ) • Ocular involvement • No comedones Rosacea - clinical classification • Erythematotelangiectatic (subtype 1)

• Papulopustular (subtype 2)

• Phymatous rosacea (subtype 3) • Ocular J Am Acad Dermatol 2002; 46:584

World J Dermatol. 2016; 5(2): 109-114 Blepharitis

Conjuctival injection,conjuctivitis

Meibomianitis

Recurrent chalazia

Telangiectasias and erythema of the lid margin

Keratitis , episcleritis,iritis, sclerokeratitis, corneal ulceration, Leukoma

Childhood vs Adulthood rosacea

Children may exhibit all subtypes except phymatous changes and symptoms may persist into adulthood

Thanopoulou I, Alexopoulos A, Chrousos G, Kakourou T. Rosacea an underestimated clinical entity in children (ESPD 2015; Lausanne Switzerland) • No of pts:18 • Sex: M:5, F: 13 • Mean age: 5.8yrs • Studied period: 2008-2014

Dermatologic and ophthalmologic criteria for childhood rosacea • Facial flushing with recurrent or permanent erythema • Facial telangiectasia with no other causative dis. • Papules and pustules without comedones • Preferential distribution of lesions on convex areas of the face • Ocular manifestations (1 of the following) – Relapsing chalazions – Ophthalmic hyperemia – Keratitis Two criteria are mandatory for diagnosis of childhood rosacea Labreze et al, Arch Dermatol. 2008; 144:167-71

Location: nose (16/18, 89%) Recurrent ocular manifestations (10/18, 55%). The ocular signs preceded the skin manifestations by an average of one year Pathogenesis of rosacea A dysregulation of the innate immune system (↑ Cathelicidins, LL-37) ► • Inflammatory reaction to: – Cutaneous microorganisms (Demodex species, Bacillus olenorium, Staph. epidermidis ) – Ultraviolet radiation • Vascular hyper reactivity • ↑ Mast cells → vasodilatation, angiogenesis

(Cutis 2016; 98:49; J Dermatol Sci 2009; 55:77 Nat Med 2007;13:975 Ital Dermatol Venereol 2009; 144:663)

Pathogenesis of rosacea

• Cathelicidins: antimicrobial peptides • Antimicrobial peptides: small molecular weight proteins , a part of the innate immune response, Cathelicidins: ↑ levels in patients with rosacea • LL-37: interacts with endothelial cells → angiogenesis, modulates the expression of VEGF • Injection of LL-37 into mice induced , erythema, and telangiectasia (Nat Med 2007;13:975 )

Rosacea- treatment

Treatment of childhood rosacea is similar to that in adult rosacea.

Treatment of childhood rosacea Avoidance of recognized trigger factors – strenuous exercise – extreme temperatures (e.g.hot and humid atmosphere) – emotional upset – sun exposure – intense rubbing of the skin – hot drinks, spicy food – topical agents that could be irritating (especially topical corticosteroids, cosmetics containing sodium lauryl sulfate, menthol, and camphor Sunprotection (physical blockers) J Am Acad Dermatol. 2004;51:499-512 Treatment of childhood rosacea Topical agents (mild to moderate disease) • Metronidazole (0.75% cream or lot, 1% gel) • Azelaic acid cream 20% • Benzoyl peroxide (wash or gel) • Clindamycin • Erythromycin • Tacrolimus ointment • Tretinoin cream • Ivermectin 1% cream Treatment of childhood rosacea • Systemic agents (moderate to severe disease) • Tetracycline (children > 8yrs old) • Erythromycin (30–50 mg/kg daily) • Clarithromycin (15 mg/kg twice daily for 4 weeks and then daily for 4 weeks) • Azithromycin (5–10 mg/kg daily)

Cutis. 2016 Jul;98(1):49-53 Br J Dermatol. 2015;172:1103-10 Treatment of childhood ocular rosacea • Daily warm compresses • Eyelid hygiene with neutral baby shampoo Topical agents (mild to moderate disease) – erythromycin ointment – azithromycin 1.5% eye drops Systemic agents (moderate to severe disease) – Tetracycline (children > 8yrs old) – Macrolides Inflammatory keratitis and episcleritis – Ocular corticosteroids (short term use) – Cyclosporine A 0.5% to 2% eye drops World J Dermatol. , 2016; 5(2): 109-114

Childhood granulomatous periorificial dermatitis

• Unknown etiology; A variant of rosacea??? • Afro-Caribbean children • Age: 1-13 years old • Yellow-brown papules or micro-nodules upon normal appearing skin • Location: primarily affects the periorificial areas • Monomorphic eruption • Histology: epithelioid granulomas without caseation • It has a self-limited course ; the disease may resolve with small pitted scars • Duration: a few months to 3 years J Am Acad Dermatol 2002; 46:584; Clinics in Dermatology 2014; 32:24

Ιdiopathic Facial Aseptic Granuloma (IFAG) Br J Dermatol 2007 ;156:705-8; Case Rep Dermatol 2016; 8: 197–201

• Painless facial nodule • Single lesion • Location:cheek • Course: prolonged • No response to antibiotics • (+ topical metroidazole, oral doxycycline) • Spontaneous healing • Granuloma in the spectrum of granulomatous rosacea

Pre- adolescent acne (7-12 years) vs pre- adolescent acneiform eruptions Pre- adolescent acne Acneiform eruptions • Childhood periorificial dermatitis

• Angiofibromas (Tuberous Sclerosis)

• Rosacea and its variants

Periorificial dermatitis • Unkown etiology • Age: young adult women (15-45 yrs) • More prevalent in pts with: – Atopic diathesis – Use of topical or inhaled corticosteroids • Clinical manifestations Periorificial (the vermillion is spared) clustered – erythematous papules – papulovesicles, – papulopustules (1-2mm) with or without mild scale – a mild eczematous dermatitis

Periorificial dermatitis

Nguyen V, Eichenfield LF. J Am Acad Dermatol. 2006;55:781-785 • No of pts: 79 • Age: 6months- 18 yrs • Exposure to steroids for treatment of AD:72% • Location of lesions Perioral : 70% Perinasal : 43% Periocular : 25% Perivulvar : 1% • Type of lesions Erythema with or without scaling: 86% Papules : 66 Pustules : 11%

Childhood periorificial dermatitis

Pediatric Periorificial Dermatitis Cutis. 2017;100:385-388, Pediatr Ann. 2015;44:188-193 • Discontinuation of topical corticosteroids • Avoidance of skin care products that may irritate or occlude the skin • Use of a mild cleanser ; non-occlusive moisturizer • Topical agents (moderate cases) – metronidazole cream, gel – Sodium sulfacetamide lotion • Systemic agents (if topical Tx is not effective) – Macrolides – Tetracyclines > 8yrs

Pediatric Periorificial Dermatitis Cutis. 2017;100:385-388

Prognosis: excellent (most pediatric patients show marked improvement within weeks to months)

Tuberous sclerosis. Angiofibromas (adenoma sebaceum) Pediatr Ann. 2015;44:188-193

• By the age of 9yrs:75% of pts have angiofibromas • Pink or skin-colored dome- shaped papules with tiny telangiectatic vessels • They are composed of vascular and fibrous tissue • Butterfly-shaped pattern • In the nasolabial folds • The upper lip is spared

Drug-induced acneiform eruptions

( can occur at any age) Drug-induced acneiform eruptions Am J Clin Dermatol 2011 ;12(4):233-45 • Appear after the administration of an inciting drug – (15 days to 2 months after starting treatment) • Location of lesions: trunk and upper arms • Papulopustules • Comedones are typically absent • Monomorphic eruption • (neutrophilic)

Drug-induced acneiform eruptions • Systemic glucocorticoids • Antiepileptic drugs – (phenytoin, carbamazepine, gabapentin) • Isoniazid • Lithium • Halogenated compounds – (iodides, radiopaque contrast materials, bromides in sedatives, analgesics) • Growth hormone • Εpidermal growth factor receptor inhibitors – (cetuximab) Drug-induced acneiform eruptions management • Drug withdrawal (when appropriate ) • Resolution of lesions usually occurs within 1 month. Childhood acneiform eruptions. D.D.

• Age of onset • History • Morphology • Location of the lesions Childhood acneiform eruptions Age period Entity

Neonatal Cephalic pustulosis, Acne venenata (0 - 4 weeks) Acneiform eruption due to maternal medication

Infantile Acne venenata (1-12 months) Acneiform eruption due to use of topical or inhaled corticosteroids

Mid-childhood Rosacea, Childhood granulomatous periorificial dermatitis (1-7 years) Ιdiopathic Facial Aseptic Granuloma

Pre-adolescent Childhood periorificial dermatitis (7-12 years) Angiofibromas (Tuberous Sclerosis) Rosacea and its variants

Any age Drug induced

Acne vulgaris vs acneiform eruption Acne vulgaris Acneiform eruption

Age Any age group Any age group

Area of Sebum reach Any site of the involvement areas of the skin skin Sine qua non Comedone Absence of lesion comedone Thank you for your attention