Neonate Dermatology · 2020-01-06 · Section of Pediatric Dermatology; The Hospital for Sick...

Neonate Dermatology

Elena Pope, Namita Deodhare, and Irene Lara-Corrales

Contents1 Transient Lesions of the Newborn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.1 Milia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.2 Miliaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31.3 Erythema Toxicum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41.4 Transient Pustular Melanosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51.5 Cephalic Pustulosis (Neonatal Acne) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51.6 Dermal Melanocytosis (Mongolian Spot or Blue-Slay Nevus) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61.7 Cutis Marmorata (Marbled Skin) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2 Developmental Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72.1 Branchial Cysts and Sinuses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72.2 Thyroglossal Duct Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82.3 Perineal Median Raphe Cysts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82.4 Neural Tube Dysraphism (Spina Bifida or Sinus Pericranii) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82.5 Neuroglial Heterotopia (Rudimentary Encephalocele) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92.6 Aplasia Cutis Congenita . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92.7 Dermoid Cysts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

3 Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113.1 Viral Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113.2 Bacterial Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123.3 Fungal Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

4 Atopic Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

5 Vesiculobullous Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155.1 Autoimmune Blistering Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155.2 Diffuse Cutaneous Mastocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165.3 Self-Healing Langerhans Cell Histiocytosis (Hashimoto-Pritzker Syndrome) . . . . . . . . . . . . . . . . . . . . . . . . 175.4 Epidermolysis Bullosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185.5 Porphyria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205.6 Epidermolytic Ichthyosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215.7 Incontinentia Pigmenti . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

6 Nodules/Tumors/Neoplastic Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226.1 Nevus Sebaceous and Epidermal Nevus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226.2 Neurofibroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246.3 Hemangioma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

E. Pope (*) · I. Lara-CorralesSection of Pediatric Dermatology; The Hospital for Sick Children,University of Toronto, Toronto, Canadae-mail: [email protected]; [email protected]

N. DeodhareMcMaster University, Hamilton, ON, Canadae-mail: [email protected]

# Springer Nature Switzerland AG 2018B. Smoller, N. Bagherani (eds.), Atlas of Dermatology, Dermatopathology and Venereology,https://doi.org/10.1007/978-3-319-45134-3_25-1

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6.4 Hemangioendothelioma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266.5 Myofibroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286.6 Rhabdomyosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286.7 Fibrosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296.8 Subcutaneous Fat Necrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306.9 Blueberry Muffin Baby . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316.10 Vascular Malformation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326.11 Xanthogranuloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326.12 Congenital Melanocytic Nevi (Bathing Trunk Nevus) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

7 Papulosquamous Eruptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377.1 Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377.2 Pustular Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387.3 Ichthyosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

8 Disorders of Pigmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408.1 Oculocutaneous Albinism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408.2 Piebaldism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 418.3 Nevus Anemicus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428.4 Nevus Depigmentosus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428.5 Nevus of Ota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428.6 Café-Au-Lait Macules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 438.7 Mosaic Pigmentary Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

9 Vascular Anomalies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459.1 Vascular Stains (Nevus Simplex, Angel’s Kiss, Stork Bite, or Capillary Malformation) . . . . . . . . . . . . . 459.2 Vascular Tumors (See Sect. 6.4) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459.3 Vascular Malformations (See Sect. 6.10) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459.4 Cutis Marmorata Telangiectatica Congenita . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

AbstractThis chapter is an overview of common and uncommondermatological diseases with emphasis on presentations inthe neonatal period. Whenever possible, differential diag-noses based on morphological presentation were offered.

KeywordsMilia · Milium · Milia in plaque · Miliaria · Miliariacrystallina · Miliaria rubra · Miliaria pustulosa · Miliariaprofunda · Erythema toxicum neonatorum · Erythematouspapule · Pseudovesicle · Pustule · Transient pustularmelanosis · Collarette of scales · Pigmentary changes ·Cephalic pustulosis · Neonatal acne · Malassezia ·Mongolian spot · Dermal melanocytosis · Blue-slaynevus · Cutis marmorata · Marbled skin · Branchial cyst ·Branchial sinus · Squamous epithelial · Ciliatedcolumnar · Sistrunk procedure · Thyroglossal duct cyst ·Squamous type · Thyroidal acinar · Perineal median raphecyst · Sebaceous glad cyst · Stratified squamous epitheliallining · Neural tube dysraphism · Spina bifida · Spinabifida occulta · Neural tube defect · Sinus pericranii ·Neuroglial heterotopia · Rudimentary encephalocele ·Nasal glioma · Aplasia cutis congenita · Hair collar sign ·Dermoid cyst · Ectodermal structure · Subcutaneousmasses · Hypertrophic hair collar · Herpes simplex virusinfection · Grouped vesicles eosinophilic intranuclear

inclusion · Chickenpox · Varicella · Hemorrhagic crust ·Ballooning of cell · Impetigo · Bullous impetigo ·Folliculitis · Staphylococcus scalded skin syndrome ·Yeast infection · Candida infection · Candida albicans ·Candida parapsilosis · Atopic dermatitis · Xerosis · Skindryness · Neonatal pemphigus vulgaris · Neonatal bullouspemphigoid · Bullous neonatal lupus · Linear IgA bullousdermatosis · Mastocytosis · Diffuse cutaneousmastocytosis · Pachyderma · Dermographism ·Histiocytosis · Langerhans cell histiocytosis · Hashimoto-Pritzker syndrome · Epidermolysis bullosa · Blistering ·Junctional epidermolysis bullosa · Herlitz non-Herlitz ·Dystrophic epidermolysis bullosa · Kindler syndrome ·Bart syndrome · Porphyria · Congenital erythropoieticporphyria · Photosensitivity · Skin fragility ·Epidermolytic ichthyosis · Increased odor · Vacuolardegeneration · Incontinentia pigmenti · X-linkeddominant · IKBKG mutation · Nevus sebaceous ·Epidermal nevus · Hamartomas · Nevus sebaceoussyndrome · Schimmelpenning syndrome · Neurofibroma ·Neurofibromatosis type 1 · Plexiform neurofibroma ·Schwann cell · Hemangioma · Congenital hemangioma ·Infantile hemangioma · Vascular tumor · GLUT-1marker · Hemangioendothelioma · Tufted angioma ·Kasabach-Merritt phenomenon · Cannonball ·Glomeruloid pattern · Myofibroma · Fibrous tumor ·Fibroblast · Myofibroblast · Rhabdomyosarcoma ·

2 E. Pope et al.

Embryonal · Alveolar · Desmin · Myogenin · Myoglobin ·MYOD1 · Fibrosarcoma · Zigzag · Herring-boneconfiguration · Vimentin · Smooth muscle actin · CD31 ·Ki-67 · Subcutaneous fat necrosis · Crystal-like structure ·Hypercalcemia · Blueberry muffin baby · TORCH ·Extramedullary erythropoiesis · Capillary malformation ·Port-wine stain · Venous malformations · Lymphaticmalformation · Arteriovenous malformation ·Xanthogranuloma · Non-Langerhans histiocytosis ·Foaming histiocytes · Touton giant cells · Congenitalmelanocytic nevus · Bathing trunk nevus ·Hypertrichosis · Melanoma · Pediatric psoriasis · Diaperpsoriasis · Napkin psoriasis · Erythematous plaque · Gray-silvery scale · Pustular psoriasis · Deficiency ofinterleukin-1 receptor antagonist · Deficiency ofinterleukin-36 receptor antagonist · CARD14 medicatedpsoriasis · Ichthyosis · Collodion baby · Harlequinichthyosis · Lamellar ichthyosis · Congenitalichthyosiform erythroderma · Oculocutaneous albinism ·Melanin · Strabismus · Nystagmus · Piebaldism ·Leukoderma · Poliosis · White forelock · Nevusanemicus · Hypopigmentation · Decreased vascularity ·Nevus depigmentosus · Geographical margin · Nevus ofOta · Hyperpigmentation · Trigeminal distribution · Irisheterochromia · Café-au-lait macules · Uniformpigmentation · Pigmentary disorders · Pigmentarymosaicism · Genetic heterogeneity · Nevus simplex ·Angel’s kiss · Stork bite · Cutis marmorata telangiectaticacongenital · Vascular anomaly · Skin atrophy ·Glaucoma · Skeletal changes

1 Transient Lesions of the Newborn

1.1 Milia

– Definition: Milia are benign cysts filled with keratinresulting from a blocked sebaceous gland. It can be pri-mary (spontaneous) or secondary (associated with anotherprocess) (Berk and Bayliss 2008). Secondary milia arecommonly seen in areas of trauma, particularly in patientswith epidermolysis bullosa.

– Clinical feature: Milia present as asymptomatic, white,pin-sized papules without erythema or inflammation.They are most commonly found on the chin, cheeks,nose, and forehead (Fig. 1). Milia en plaque is a specifictype of primary milia which is characterized by a cluster oflesions on an erythematous base.

– Pathological manifestation: Histologically presents as athick wall of stratified squamous epithelial tissue includ-ing a layer of granular cells. Milia en plaque can bedistinguished by the presence of lymphocytic infiltrateand keratinous cysts (Berk and Bayliss 2008).

– Prognosis and treatment: Primary milia self-resolvewithin the first few months following birth. Secondarymilia may take longer to resolve and may require a topicalretinoid or extraction (Berk and Bayliss 2008).

– Differential diagnosis: Limited; nevus comedonicus formilia en plaque.

1.2 Miliaria

– Definition: Miliaria is a common condition characterizedby the blockage of eccrine glands causing the retention ofsweat in the dermis or epidermis. It often occurs due to anexposure to high heat or humidity (Ghosh 2015). It isclassified into four subtypes: miliaria crystallina (sub-corneal or intracorneal obstruction), miliaria rubra(intraepidermal obstruction), miliaria profunda (obstruc-tion at dermal-epidermal junction), and miliaria pustulosa(pustular progression of vesicles) (Reginatto et al. 2016).

– Clinical feature: The most common type seen in theneonatal period is miliaria crystalline, presenting assmall vesicles, 1–3 mm in size, with clear fluid (Fig. 2).They are easily deroofed releasing trapped sweat. Miliariarubra presents as small vesicles on an erythematous base.The other forms are rarely seen in neonatal period (Haaset al. 2002).

– Pathological manifestation: The histological presenta-tion of miliaria differs based on subtype. Miliariacrystallina has subcorneal vesicles with occasional neutro-philic infiltrate. Miliaria rubra contains intraepidermalspongiotic vesicles and miliaria profunda displaysspongiosis within the dermis of the sweat gland alongwith chronic inflammation (Ghosh 2015).

Fig. 1 Milia; multiple white pinpoint papules on the forehead. (Takenby Drs. Elena Pope and Irene Lara-Corrales, The Hospital for SickChildren, Toronto, Canada)

Neonate Dermatology 3

– Prognosis and treatment:Miliaria is self-resolving eitherspontaneously or following removal of the humid envi-ronment. Topical calamine agents can be used to relievesymptoms (Ghosh 2015).

– Differential diagnosis: Several vesicular disordersincluding herpes simplex, varicella, erythema toxicumneonatorum, neonatal pustular melanosis, acropustulosisof infancy, staphylococcal infections, incontinentiapigmenti, and epidermolysis bullosa (Haas et al. 2002).

1.3 Erythema Toxicum

– Definition: Erythema toxicum is a common skin condi-tion, of unknown etiology, affecting up to 50% of new-borns. The lesions are not present at birth and appear in thefirst days of life (O’Connor et al. 2008).

– Clinical feature: Clinically it presents as small erythem-atous papules/pseudovesicles or pustules on an erythema-tous background (Figs. 3 and 4). The lesions are transientand migratory. The most common location is head andneck area and the trunk, less commonly on the extremities(Morgan et al. 2009).

– Pathological manifestation: Histologically, edema canbe seen in the upper dermis along with a marked presenceof eosinophils (Freeman et al. 1960).

Fig. 2 Miliaria rubra; multiple red papule/pseudovesicles on the lateraltrunk. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospitalfor Sick Children, Toronto, Canada)

Fig. 3 Erythema toxicum neonatorum anterior chest; multiple scatteredred papules/vesicles on an erythematous patch. (Taken by Drs. ElenaPope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

Fig. 4 Erythema toxicum neonatorum on the posterior chest; multiplelarge erythematous patches with central papule/pseudovesicles. (Takenby Drs. Elena Pope and Irene Lara-Corrales, The Hospital for SickChildren, Toronto, Canada)

4 E. Pope et al.

– Prognosis and treatment: There is a regression of thelesions after about 2–3 weeks, and thus no treatment isrequired.

– Differential diagnosis: Other transient dermatoses, can-dida infection, listeria infection, chicken pox, and herpessimplex virus infections.

1.4 Transient Pustular Melanosis

– Definition: Transient pustular melanosis is a commontransient dermatosis, present at birth, primarily in darkerskin individuals (O’Connor et al. 2008).

– Clinical feature: Transient pustular melanosis is charac-terized by the presence of pustular lesions, with no back-ground erythema that are easily ruptured leaving acollarette of scales at the periphery. Pigmented brown-colored macules take the place of the primary lesionsand persist for several months. Lesions can be found onall areas of the body (Ghosh 2015).

– Pathological manifestation: Polymorphic neutrophilsand few eosinophils are seen upon histological examina-tion (Figs. 5 and 6).

– Prognosis and treatment: Lesions resolve spontaneouslyover 3 to 4 weeks, and thus no treatment is needed.Pigmentary changes may persist for months.

– Differential diagnosis: Candidiasis, erythema toxicum,miliaria, milia, herpes simplex virus infection and Staphy-lococcus aureus infection.

1.5 Cephalic Pustulosis (Neonatal Acne)

– Definition: Cephalic pustulosis is a transient pustulardermatosis caused by Malassezia species (sympodialis,furfur). It presents in the first week of life and resolvesover several weeks.

– Clinical feature: Cephalic pustulosis presents with redpapules, pustules, and sebaceous hyperplasia. The typicallocation is the face, although more extensive cases in thescalp and trunk involvement may be seen (Fig. 7). Incontrast with infantile acne, the presence of comedones,big inflammatory nodules, and cysts are not seen (Serna-Tamayo et al. 2014).

Fig. 5 Transient pustular melanosis; multiple flaccid pustules on thegroin; deroofed lesions leave a collarette appearance of the scale. (Takenby Drs. Elena Pope and Irene Lara-Corrales, The Hospital for SickChildren, Toronto, Canada)

Fig. 6 Transient pustular melanosis; multiple flaccid pustules arm andtrunk with no erythema. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 7 Cephalic pustulosis; multiple red papules and pustules, noevidence of comedones. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)


– Pathological manifestation: The main histological markerof cephalic pustulosis is the presence of Malassezia furfurwithin the pustule.

– Prognosis and treatment: Cephalic pustulosis is a self-resolving within weeks to months. Persistent or moresevere presentation may benefit from a topical antifungal.

– Differential diagnosis: Folliculitis, herpetic infections,dermatitic eruptions.

1.6 Dermal Melanocytosis (Mongolian Spotor Blue-Slay Nevus)

– Definition: Dermal melanocytosis is described as tran-sient skin pigmentation occurring primarily in dark skinindividuals. It is the result of a collection of melanocytesin the dermis during neural crest migration (Franceschiniand Dinulos 2015; Gupta and Thappa 2013).

– Clinical feature: Dermal melanocytosis is more commonlyseen in Asian and African population. Color varies fromdark blue to gray or black in darker skin tones (Figs. 8 and9). Although it can appear anywhere in the body, the mostcommon location is the lower back (lumbar, sacral, andgluteal areas) (Franceschini and Dinulos 2015).

– Pathological manifestation: Upon histological examina-tion, deep dendritic melanocytes are seen with melaningranules dissecting bundles of dermal collagen.

– Prognosis and treatment: Dermal melanocytoses self-resolve within the first few years of life. Since they arerarely permanent, no treatment is required. Persistent orwidespread lesions should raise the suspicion of a storagedisease or phacomatosis pigmentovascularis.

– Differential diagnosis: Blue nevi, dermal melanocytehamartoma, nevus of Ota, nevus of Ito, bruising, café-au-lait macules, and congenital melanocytic nevus.

1.7 Cutis Marmorata (Marbled Skin)

– Definition: Cutis marmorata is a transient vascularresponse characterized by mottling of the skin in responseto ambient temperature changes.

– Clinical feature: The classical appearance is of a reticularpattern of the extremities and less commonly of the rest ofthe body created by normal skin interspersed byred-violaceous discoloration (Fig. 10). The color improveswith rewarming (Hulsmann and Oranje 2014).

Fig. 8 Dermal melanocytosis; blue-gray flat discoloration on the lum-bar sacral area. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)

Fig. 9 Dermal melanocytosis in the context of storage disease; wide-spread, persistent, blue-gray discoloration. (Taken by Drs. Elena Popeand Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

Fig. 10 Physiologic cutis marmorata; marbled-like pattern due toprominent vessels. (Taken by Drs. Elena Pope and Irene Lara-Corrales,The Hospital for Sick Children, Toronto, Canada)

6 E. Pope et al.

– Pathological presentation: Histopathologically, cutismarmorata presents with increased vascular pattern dueto dilated dermal vessels.

– Prognosis and treatment: Prognosis is favorable withthis phenomenon disappearing over several months. Per-sistent cutis marmorata may be seen in certain syndromessuch as Down syndrome and Cornelia de Lange.

– Differential diagnosis: Cutis marmorata telangiectaticacongenita, reticulated capillary malformation, sepsis, andparvovirus infection.

2 Developmental Defects

2.1 Branchial Cysts and Sinuses

– Definition: Branchial anomalies are characterized by con-genital cystic masses or skin indentations found on thehead and neck due to incomplete obliteration of the bran-chial apparatus during the embryonic phase. They arecategorized as first, second, third, and fourth cysts,sinuses, and fistulae (LaRiviere and Waldhausen 2012).

– Clinical feature: See Table 1 and Figs. 11 and 12 (Goffet al. 2012).

– Pathological manifestation: Histological examinationreveals respiratory or squamous epithelial lining. Cystsare lined with squamous epithelium, while sinuses and

fistulas are more commonly lined with ciliated columnarepithelium.

– Prognosis and treatment: Surgical excision is the treat-ment of choice for branchial cysts and sinuses. Specifi-cally, the Sistrunk procedure involves the removal of thecyst through neck incision with dissection up to thehyoid bone. This procedure reduces the chances ofrecurrence. Infected cysts can also be treated withantibiotics.

– Differential diagnosis: Vascular anomalies, hemangiomaof infancy, cystic hygroma, and ectopic thyroid or salivarytissue.

Table 1 Classification and clinical features of branchial cysts andsinuses (Goff et al. 2012)

Type LocationClinicalpresentation Complications

1st Right side around theretro auricular andparotid areas andextends down to thecervical region

Masscausingpain andrednessDraining pit

Infection

2nd(mostcommon)

Anterior border of theupper thirdsternocleidomastoidmuscle

PainlessmassFistula

Increase insize with viralinfections

3rd Mid and lower third ofthesternocleidomastoidmuscle, penetrates thethyroid membrane inclose proximity withthe superior andrecurrent laryngealnerves

Mass onimagingFistula

4th Same as 3rd but foundbetween recurrent andsuperficial nerve morecommon on the leftside and

Mass onimagingFistula

Fig. 11 Ear pit with depression in the skin; may be isolated or a sign ofa sinus. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hos-pital for Sick Children, Toronto, Canada)

Fig. 12 Second branchial cleft cyst; well-defined mass in the anteriorcervical area. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)


2.2 Thyroglossal Duct Cyst

– Definition: Thyroglossal duct cyst is the most commonanomaly of the neck, accounting for more than two thirdsof anterior neck masses. It may be present at birth butbecomes more evident with age. It is a developmentaldefect resulting from persistent epithelial remnants of thethyroglossal duct during the descent of thyroid gland(Ducic et al. 1998; Allard 1982).

– Clinical features: Thyroglossal duct cyst presents as apainless mass in the midline neck that moves withswallowing. Occasionally, the lesion may get infectedand present as an abscess.

– Pathological presentation: The histological picture con-sists of a cystic structure with an epithelial lining thatvaries in terms of location (squamous type near foramencecum and thyroidal acinar in the proximity to the thyroidgland location) (Chou et al. 2013).

– Prognosis and treatment: Prognosis is favorable. Surgi-cal excision using a Sistrunk procedure is curative withlow risk of recurrences.

– Differential diagnosis: Branchial cleft cysts, vascularlesions, and abscess.

2.3 Perineal Median Raphe Cysts

– Definition: Perineal median raphe cysts are characterizedby sebaceous glad cysts that appear on the foreskin oranywhere between the tip of the penis and the anus(Amaranathan et al. 2013).

– Clinical feature: They present as small, white or yellow,firm papules arranged in a linear configuration (Fig. 13).

– Pathological manifestation: Median raphe cysts histo-logically present with stratified squamous epithelial lining.At times, mucous secreting cells may also be present.

– Prognosis and treatment:Median raphe cysts are benignand asymptomatic; however, enlargement can occurthroughout infancy. If size of the cyst is too large, thensurgical removal is recommended.

– Differential diagnosis: Urethral diverticulum, pilonidalcyst, epidermal inclusion cyst, and dermoid cyst.

2.4 Neural Tube Dysraphism (Spina Bifida orSinus Pericranii)

– Definition: Congenital abnormalities characterized by animpaired development of craniospinal structures duringthe formation of the brain and spinal cord. Can be openneural tube dysraphism (open spina bifida) or closed one(e.g., spina bifida occulta or sinus pericranii) (Adzick2013; Copp et al. 2013).

– Clinical feature: Open spina bifida is characterized byprotruding portions of the meninges and spinal cordthrough vertebral arches. Both open (Fig. 14) and closed

Fig. 13 Median raphe cyst; multiple yellow papules on the midline,some draining mucous. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 14 Open spina bifida repaired; midline defect with a scar, evidenceof cleft deviation, lipomatous mass, and vascular changes. (Taken byDrs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Chil-dren, Toronto, Canada)

8 E. Pope et al.

neural tube dysraphisms (Fig. 15) may be accompanied bycutaneous stigmata that carry different risks for the pres-ence of a spinal defect. The high-risk lesions are >2 oflipoma, acrochordon, pseudotail, tail, aplasia cutis,dermoid cyst or sinus, and hemangioma > 2.5 cm. Atyp-ical dimples (>5 mm in diameter and > 2.5 cm from analverge), smaller infantile hemangiomas, and hypertrichosishave an intermediate risk, while pigmentary changes, con-genital nevi, simple dimple, teratomas, and port-winestains carry a low risk (Sewell et al. 2015).

– Sinus pericranii is characterized by the connection of theintracranial dural sinuses with the epicranial veins. Com-pressible swelling is usually found on the midline orfrontal portion of the head at birth and is worse withValsalva maneuvers. It may be associated with a vascularstain and/or a bony defect (Kamble et al. 2010).

– Pathological manifestation: Pathological picture is vari-able depending on the type of tissue that is excised (lipo-matous, cyst, neural, etc.)

– Prognosis and treatment: Spina bifida has a high asso-ciation with lifelong morbidity. Surgical closing of thedefect can reduce the chances of infection, thus decreasingthe long-term morbidity.

– Sinus pericranii are generally benign but can be surgicallyor endovascularly treated to avoid further complicationssuch as hemorrhage, infection, etc.

– Differential diagnosis: Sacrococcygeal teratomas,hamartoma, lumbosacral lipoma and SACRAL/LUM-BAR syndrome for open spina bifida and dural fistula,arteriovenous malformation, dermoid cyst, nasal glioma,lipoma, and encephalocele for sinus pericranii.

2.5 Neuroglial Heterotopia (RudimentaryEncephalocele)

– Definition: Neuroglial heretopias are developmentalanomalies that consist of glial tissue that lost its connec-tion with the intracranial contents. The location varies, butmost are in the nasal area (nasal gliomas).

– Clinical feature: They present at birth as skin-colored orred masses, firm to palpation (Fig. 16). There may be somehypertrichosis associated with the mass. In up to 25% ofcases, there may be a skull defect and a connection withthe dura (Rogers et al. 2005).

– Pathological manifestation: The pathology is that ofneuroglial tissue (Patterson et al. 1986).

– Prognosis and treatment: Prognosis is favorable withcure after surgical excision.

– Differential diagnosis: Vascular tumors anddermoid cyst.

2.6 Aplasia Cutis Congenita

– Definition: Aplasia cutis congenita is a rare congenitalcondition characterized by localized or widespreadabsence of the skin, appendages, and subcutaneous tissue.It is isolated or associated with other anomalies(Silberstein et al. 2014; Frieden 1986).

– Clinical feature: Aplasia cutis congenita is often locatedon the scalp; however, the face, trunk, extremities, and

Fig. 15 Sinus pericranii; erythematous background, tuft of dark haircovering a small defect in the skin; there is bulging with Valsalvamaneuver suggesting connection with draining sinuses. (Taken by Drs.Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children,Toronto, Canada)

Fig. 16 Nasal glioma; firm mass, off midline nasal root, with faint reddiscoloration. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)


buttocks can also be affected (Figs. 17, 18, 19, and 20).Scalp aplasia cutis congenita may be accompanied by acollar of hypertrichosis – “hair collar” sign – heraldingdeeper abnormalities of the brain. Aplasia cutis can pre-sent as either superficial erosion, deep ulceration, healedscar, or a thin, translucent membranous cover. Occasion-ally, a hemorrhagic blister may develop due to fragility ofthe affected area (Browning 2013).

– Pathological manifestation:Histologically, a fibrovascularand/or edematous stroma is seen, and for nonbullous aplasiacutis congenita, thin layers of dermal collagen are present.

– Prognosis and treatment: Treatment options depend onthe appearance, extent of the lesion, and associated anom-alies. Open wounds require wound care. Large defects(> 15 cm) require skin grafts, flap reconstruction, andscar revisions (Silberstein et al. 2014).

– Differential diagnosis: Nevus sebaceous and traumaticscars.

Fig. 17 Aplasia cutis with a hemorrhagic blister; large hemorrhagicblister covering a scalp defect. (Taken by Drs. Elena Pope and IreneLara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 18 Large aplasia cutis; large patch of absent skin and hair. (Takenby Drs. Elena Pope and Irene Lara-Corrales, The Hospital for SickChildren, Toronto, Canada)

Fig. 19 Aplasia cutis on the neck; round patch of full-thickness absentskin with visible vessels. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

10 E. Pope et al.

2.7 Dermoid Cysts

– Definition: Dermoid cysts are benign lesions containingectodermal structures (skin, hair follicles, sweat, and seba-ceous glands) resulting from defects along the embryonicfusion lines. Approximately 40% are noted at birth(Orozco-Covarrubias et al. 2013; McAvoy andZuckerbraun 1976).

– Clinical feature: Dermoid cysts are most commonlyfound on the head (the outer edge of the eyebrow),scalp, neck, intracranially, spine, or abdomen (Figs. 21and 22). They are small, non-tender, gradually growingsubcutaneous masses covered with normal-appearing

skin. Focal alopecia or hypertrophic hair collar may alsobe present.

– Pathological manifestations: The histology shows a cys-tic structure with stratified squamous epithelium lining,keratin debris, hair follicles, sweat glands, and sebaceousglands. A giant cell reaction to hair and keratin may alsobe noted (Orozco-Covarrubias et al. 2013).

– Prognosis and treatment: Midline lesions (along thenose or scalp) need imaging to assess extent and relation-ship with brain structures. Surgery is conducted to reducethe risk of further infections or for cosmetic purposes.There is a good prognosis following surgery with rarerecurrence risk (Sorenson et al. 2013; Orozco-Covarrubiaset al. 2013).

– Differential diagnosis: Epidermoid cysts, glioma, sinuspericranii, meningocele, sebaceous cysts, and aplasia cutiscongenita.

3 Infections

3.1 Viral Infections

3.1.1 Herpes Simplex Virus– Definition: Herpes simplex virus(HSV) can be transmit-

ted to contact skin and mucosal areas and remain latent inthe neural tissue. This virus can be passed down from themother to newborn neonatally or postnatally and can bedivided into three subtypes: HSV localized to the skin,eye, and mouth area (SEM), HSV encephalitis, and dis-seminated HSV resulting in multi-organ failure (Wanget al. 2017).

Fig. 20 Aplasia cutis with “hair collar” sign; absent skin surrounded bya tuft of darker, coarser hair. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 21 Eyebrow dermoid cyst; well-defined, skin color nodule on theouter edge of the eyebrow. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 22 Dermoid cyst on the forehead; well-defined, skin color nodule,firm to palpation, not mobile, on the forehead. (Taken by Drs. ElenaPope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)


– Clinical feature: Newborns present the classical lesions,grouped vesicles on an erythematous base, either at birthor within the first month of life (Fig. 23). Various degreesof fever and lethargy as well as mucosal erosions, neuro-logical findings, and other organ involvement may beseen. The lesions may be localized or disseminated, caus-ing diagnostic challenges, particularly if classical clusterlesions are not seen (Wang et al. 2017; Wauters et al.2012).

– Pathological manifestation: Histologically, multi-nucleated giant cells and eosinophilic intranuclear inclu-sion are seen.

– Prognosis and treatment: Prognosis for infants withHSV is poor; without prompt recognition and therapy,the mortality reaches 80% (Wang et al. 2017). Treatmentof choice is acyclovir. The dosage and duration dependson the disease severity, extent, and comorbidities.

– Differential diagnosis: Other infections, such as candida,varicella, cytomegalovirus, incontinentia pigmenti, andHashimoto-Pritzker (self-healing histiocytosis).

3.1.2 Varicella Zoster– Definition: Chickenpox is an infection caused by a vari-

cella zoster virus. Exposure before 20-week gestationleads to a congenital presentation with a syndrome similarto other TORCH infections. Exposure after 20 weeks orafter birth causes neonatal varicella (Hussain et al. 2013).

– Clinical feature: The rash of neonatal varicella evolvessimilarly to older age presentation, starting with papules,progressing to vesicles (Fig. 24) and hemorrhagic crusts.In contrast with other forms, the distribution is preferentialto the head and neck due to contamination through the

cervical canal. Overtime, the classical polymorphic erup-tion adds to the diagnosis.

– Pathological manifestation: Early lesions present withballooning of the epidermal cells. Later on, vesiclescontaining proteinaceous material and giant cells andintranuclear inclusions of the epidermal cells are seen(Grayson 2008).

– Prognosis and treatment: Prognosis is good, providedprompt recognition and treatment with antivirals. Passiveimmunization with varicella immunoglobulins may begiven to newborns whose mothers developed chickenpoxwithin 5 days before and 2 days after delivery or forpremature infants (Carter et al. 1986).

– Differential diagnosis: Other infections, such as candida,herpes simplex, cytomegalovirus, incontinentia pigmenti,and Hashimoto-Pritzker (self- healing histiocytosis).

3.2 Bacterial Infections

3.2.1 Staphylococcus– Definition: Staphylococcus pyodermas encompass a

group of conditions that range from impetigo, pustularfolliculitis due to direct effect of the bacteria on the skin,to bullous impetigo and staphylococcal scalded skin syn-drome (SSSS) caused by a staphylococcal toxin. Thecondition is more common in younger children due toabsence of antitoxin antibodies or poor renal toxin excre-tion. The source of the infection is in the conjunctiva,nares, umbilicus, perineum, and perioral areas; therefore,cultures should be performed from these areas. The fluid

Fig. 23 Herpes simplex infection; multiple vesiculobullous lesions onthe face of a newborn. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 24 Chickenpox (early): tense blisters on an erythematous base.(Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital forSick Children, Toronto, Canada)

12 E. Pope et al.

blister is sterile as it is the result of the toxin (Hussain et al.2013).

– Clinical feature: Impetigo presents shortly after birthwith pustules causing erosions with yellow crusting. Typ-ically, the lesions are on the neck, groin, and axilla. Bul-lous impetigo progresses to large, flaccid bulla that leaveslarge erosions (Fig. 25). The erosions tend to clusteraround the source of infections (e.g., umbilicus, groin).In SSSS, there is significant background erythema, ten-derness of the skin, with periorificial crusting and devel-opment over several days of large bulla and skinsloughing. In contrast with bullous impetigo, infantshave systemic symptoms (Fig. 26) (Li et al. 2014).

– Pathological manifestation: SSSS lesions show epider-mal detachment at the granular level (Handler andSchwartz 2014). Impetigo shows subcorneal pustulesmade of neutrophils and bacteria. Folliculitis may have asimilar presentation; however, the infiltrate is localized tothe follicular ostium.

– Prognosis and treatment: Prognosis of localized forms isvery favorable with complete recovery with topical orsystemic antibiotics. SSSS requires intravenous antibi-otics and care of the denuded skin. The mortality innormal hosts is low.

– Differential diagnosis: Streptococcal, listeria, fungal andherpetic infections as well as other transient dermatosespresenting with vesicles/pustules for localized staphylo-coccal forms and other acquired and congenitalvesiculobullous conditions for SSSS.

3.3 Fungal Infections

3.3.1 Candida– Definition: A fungal infection most often caused by Can-

dida albicans and Candida parapsilosis causing differentpresentations depending on the time of infection, birthweight, gestational age, and mechanism of infection(Hussain et al. 2013).

– Clinical feature: Congenital candidiasis presents with amonomorphous, papulovesicular eruption on erythema-tous background that progresses rapidly to pustules,crusting, and peeling (Fig. 27). Initially the lesions are inthe folds and progress to widespread involvement. Peri-ungual and nail involvement as well as mouth involve-ment may be seen (López-Martínez 2010).

– Pathological manifestation: Silver methenamine andperiodic acid-Schiff stains will reveal the presence of thehyphae. Smear samples that are gram stained will also bepositive.

– Prognosis and treatment: Prognosis depends on theseverity of infection and host’s characteristics. Topicalagents can be used against localized cutaneous candidainfections. Systemic antifungals are needed for wide-spread disease, premature, and low birth weight babies(Greenberg et al. 2012).

Fig. 25 Bullous impetigo; flaccid bulla and pustules on the groin on abackground of erythema, large erosion on the chest, crusting on theumbilicus. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)

Fig. 26 Staphylococcal scalded skin syndrome; large area of exfolia-tion on an erythematous background in the axilla. (Taken by Drs. ElenaPope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)


– Differential diagnosis: Viral and bacterial infections andtransient pustular eruptions.

4 Atopic Dermatitis

– Definition: Atopic dermatitis is a chronic inflammatorycondition characterized by erythema, edema, excoriations,and crusting on a background of xerosis. Neonatal onsetoccurs in the first few weeks of life, but classical presen-tation may not be apparent for a few months (Grey andMaguiness 2016).

– Clinical feature: The first affected site is face and scalp.The facial presentation consists of raised, red plaques withlinear or circumscribed erosions on the perioral region(Fig. 28). Diffuse scalp scaling with an erythematousbackground is typical for early scalp presentation. Thereare various degrees of skin dryness. The presence ofpustules or widespread involvement in the context oftypical lesions should raise concern for dermatitis ofimmunodeficiency as seen in patients with hyper IgEsyndrome or combined immunodeficiencies (Fig. 29).Similarly, widespread involvement with prominent scal-ing and fold involvement should point toward seborrheicdermatitis (Fig. 30) (Grey and Maguiness 2016; SillevisSmitt and Kuijpers 2013).

– Pathological manifestation: The pathology is non-specific, demonstrating spongiosis with a perivascularlymphocytic infiltrate (Guttman-Yassky et al. 2011).

– Prognosis and treatment: The disease has a chroniccourse with frequent flare-ups. Treatment targets control-ling xerosis, inflammation, and pruritus. Environmentalmodifications are helpful in reducing potential triggers(Baron et al. 2012).

Fig. 28 Infected atopic dermatitis; typical periorificial dermatitic changeswith excoriation, oozing, and crusting. (Taken by Drs. Elena Pope andIrene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 27 Candidiasis; multiple pustules on an erythematous backgroundon the neck areas and scalp. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 29 Dermatitis of immunodeficiency; pustular lesions on the scalpand face in the context of dermatitis (patient with hyper IgE syndrome).(Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital forSick Children, Toronto, Canada)

14 E. Pope et al.

– Differential diagnosis: Seborrheic dermatitis, ichthyosis,psoriasis, nutritional deficiencies, and dermatitis ofimmunodeficiency.

5 Vesiculobullous Disorders

Vesiculobullous disorders are a group of conditions that maypresent in the neonatal period with vesicles/bulla on the skin.These entities may be acquired, secondary to other processes,or represent the primary manifestation of inherited dermato-ses where the main pathogenic process is skin fragility. SeeTable 2 for their differential diagnoses.

5.1 Autoimmune Blistering Disorders

– Definition: Neonatal autoimmune blistering disorders are agroup of extremely rare entities resulting from transfer ofmaternal autoantibodies through the placenta that targetproteins in the skin of the baby. The most common entityis pemphigus vulgaris, followed by pemphigoid gestationis,the rest being exceedingly rare (Zhao et al. 2016).

– Clinical feature: All affected newborns have lesions atbirth. However, the extent and the severity of the clinicalfeatures are variable; typically, pemphigus vulgaris maypresent with blisters and erosions only, while bullouspemphigoid’s manifestations range from erosions andblisters to urticarial plaques (Fig. 31). Linear IgA bullousdermatosis has a particular appearance with blisters takingan annular configuration. All body parts may be affected,although mucosal involvement (erosions and ulcerations)

is seen in less than 50% of cases (Zhao et al. 2016). Whilemouth involvement is most common, other membranes(e.g., eyes) may be affected with potential for scarring.Neonatal Behcet’s syndrome can be presented byerythematous-violaceous macules/papules on the scalpand annular plaques with central scarring (Fig. 32).

– Pathological manifestation: In the absence of maternalhistory of autoimmune blistering disease, a skin biopsyshould be performed from lesional skin (for H&E) and

Fig. 30 Generalized seborrheic dermatitis; large areas of erythema andscaling in an otherwise well-looking child. (Taken by Drs. Elena Popeand Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

Table 2 Differential diagnoses of vesiculobullous disorders

Acquired Inherited Developmental

Infections (see above)Viral (e.g., HSV)Bacterial (e.g., bullous

impetigo, SSSS, listeria)Candida

Autoimmune blisteringdisordersNeonatal bullous

pemphigoidNeonatal pemphigus

foliaceusBullous neonatal lupusLinear IgA bullous

dermatosisNeonatal pemphigus

vulgarisNonimmune inflammatoryconditionsDrug eruption (e.g.,

Stevens-Johnsonsyndrome)Proliferative disordersDiffuse cutaneous

mastocytosisSelf-healing

Langerhans Histiocytosis(Hashimoto-Pritzkersyndrome)

Epidermolysis bullosaKindler syndromePorphyriaEpidermolyticichthyosis(Epidermolytichyperkeratosis, bullousIchthyosiformerythroderma)Superficialepidermolytichyperkeratosis (bullousichthyosis of Siemens)Incontinentia pigmenti

Bullous aplasiacutis

Fig. 31 Neonatal pemphigus; large, superficial bulla on an erythema-tous background. (Taken by Drs. Elena Pope and Irene Lara-Corrales,The Hospital for Sick Children, Toronto, Canada)


perilesional skin (for DIF). The pathological picture issimilar to older age presentations and depends on the par-ticular entity. The H&E demonstrates subepidermal blisterswith a mixed inflammatory infiltrate consisting of neutro-phils and eosinophils. Serum IIF and antibody titers fordesmoglein 1 and 3 and BP-180 are recommended.

– Prognosis and treatment: Prognosis is favorable withresolution of the blisters within the first few weeks oflife. However, close monitoring for complications relatedto prematurity, sepsis, electrolyte imbalances, and muco-sal sequelae is important.Treatment depends on the severity of the presentation andprogression and ranges from supportive treatment, topicaltherapy, and systemic anti-inflammatories (steroids,steroid-sparing agents, and intravenous immunoglobulins)(Zhao et al. 2016).

– Differential diagnosis: Infections, other autoimmuneblistering disorders, and inherited bullous disorders.

5.2 Diffuse Cutaneous Mastocytosis

– Definition: Diffuse cutaneous mastocytosis is a general-ized form of mastocytosis, a group of disorders character-ized by clonal expansion of mast cells in different organs,often due to a KIT activating mutation (Valent et al. 2017).

– Clinical feature: Patients present at birth or shortly afterwith diffuse erythema widespread blistering in the contextof thickened skin (pachyderma) (Fig. 33). The color of theskin is darker than normal skin, although this feature maynot be easily apparent at birth. The blistering occurs withminimal trauma (rubbing) Fig. 34 and may be easilyconfused with other skin fragility disorders. In older sur-vivors, the clue to the diagnosis may be the persistent andpronounced dermographism. Prolonged bleeding from theskin lesions may also be seen (Hartmann et al. 2016).

– Pathological manifestation: A dermal infiltrate withincreased number of mast cells, at least fourfold over

Fig. 32 Neonatal Behcet’s syndrome; healing lesions of ulceration onthe neck of a newborn with Behcet’s syndrome. (Taken by Drs. ElenaPope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

Fig. 33 Diffuse cutaneous mastocytosis; infiltrated skin with skin-colored to brown plaques (pachyderma). (Taken by Drs. Elena Pope andIrene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

16 E. Pope et al.

baseline, is easily demonstrable on Giemsa or toluidineblue stains. Staining with anti-tryptase antibody may helpcases where there is hypogranulation. Cell markers are nothelpful (Hartmann et al. 2016).

– Prognosis and treatment: Prognosis is guarded. The neo-natal period is extremely difficult due to constant blisteringresulting in electrolyte imbalance, risk of infection, respira-tory symptoms, and bleeding. Prompt recognition andappropriate management may allow survival. If complica-tions in early neonatal period are overcome, patients dem-onstrate decreased blistering with age, despite persistenceof pachyderma and persistent dermatographism. There is nospecific treatment apart from supportive, local skin care andantihistamines. Imatinib mesylate has been reported asbeneficial (Morren et al. 2013).

– Differential diagnosis: Infections, other autoimmuneblistering disorders, and inherited bullous disorders (seeTable 2).

5.3 Self-Healing Langerhans CellHistiocytosis (Hashimoto-PritzkerSyndrome)

– Definition: Hashimoto-Pritzker syndrome is a rare pre-sentation of Langerhans cell histiocytosis, characterizedby typical skin lesions resulting from histiocytic infiltratebut with a spontaneous resolution in the first few monthsafter birth (Larralde et al. 1999).

– Clinical feature: Classical presentation of Langerhanscell histiocytosis is a polymorphic eruption consistent ofpapules and vesicles, including hemorrhagic lesions,crusts, and nodules (Figs. 35, 36, and 37). In Hashimoto-Pritzker syndrome, the eruption is more monomorphous

with vesicles or ulcerative lesions, easily confused withother more common entities (Yu et al. 2017).

– Pathological manifestation: The microscopy shows aheavy, mixed lichenoid infiltrate with histiocytic predom-inance. The epidermis is usually ulcerated. Staining forS100, CD1A, and Langerin are positive.

– Prognosis and treatment: Prognosis is favorable withspontaneous resolution in the first few months of life.Topical steroids may be used. Patients require long-termfollow-up to monitor for transformation into systemicLangerhans cell histiocytosis (Lau et al. 2006).


Fig. 35 Self-healing histiocytosis; red-brown nodular lesion in thegroin area in a patient with self-healing histiocytosis. (Taken by Drs.Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children,Toronto, Canada)

Fig. 34 Darier sign; infiltrated, red plaque after stroking a mastocytosislesion. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospitalfor Sick Children, Toronto, Canada)

Fig. 36 Langerhans cell histiocytosis groin; polymorphic eruptionconsisting of red-brown papules, hemorrhagic crusts, and petechiae.(Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital forSick Children, Toronto, Canada)


5.4 Epidermolysis Bullosa

– Definition: Epidermolysis bullosa is a group of inheritedskin diseases that have in common various degrees of skinand mucous membrane fragility. The severity of the skinand other organ involvement is dependent on the degree ofprotein abnormality (absent, reduced, abnormal, etc.) andthe level of the abnormal protein’s location in the skinlayers. Deeper locations are typically associated with moresevere clinical presentations.

– Clinical feature: Clinical presentation in the newbornperiod is very variable and, as such, should dissuade

clinicians from making subtype diagnostic predictionsuntil there is pathological and/or molecular conformation(Fine et al. 2014) (Figs. 38, 39, 40, 41, 42, and 43).Epidermolysis bullosa simplex: It is the result of abnormalproteins called keratins (KRT5 or KRT14). There areseveral subtypes even within this grouping accountingfor various degrees of blistering. Newborns may presentwith blisters at the site of trauma (leads, heel prick) orhave a more generalized distribution. Typically, there is nomucosal involvement at this age and no nail changes.Patients with Dowling-Meara epidermolysis bullosa sim-plex have more skin involvement with blisters that expandat the edge causing a “string of pearl” appearance. Laterthey tend to develop keratoderma.

Fig. 37 Langerhans cell histiocytosis generalized; diffuse papular erup-tion with hemorrhagic crusts and scattered petechiae. (Taken by Drs.Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children,Toronto, Canada)

Fig. 38 Bart syndrome (aplasia cutis in association with epidermolysisbullosa); large areas of full thickness absence of the skin present at birth.(Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital forSick Children, Toronto, Canada)

Fig. 39 Bart syndrome and fetus papyraceus due to epidermolysisbullosa lethal type; widespread areas of full-thickness absent skin.(Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital forSick Children, Toronto, Canada)

Fig. 40 Epidermolysis bullosa tense blistering; large, tense bulla on thehands with no inflammatory changes. (Taken by Drs. Elena Pope andIrene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

18 E. Pope et al.

Junctional epidermolysis bullosa: It is the result ofproteins that present at dermoepidermal junction. Junc-tional epidermolysis bullosa, Herlitz type (resulting frommutations in three genes encoding laminin 332, LAMA3,LAMB3, and LAMC2), consists of severe skin fragilityresulting in widespread blistering and erosions. These maynot be apparent at birth but becomes significant in the firstfew weeks of life. Mucosal fragility is very significant inthis subtype; hoarseness develops soon after birth and is apathognomonic feature. Periorificial and periungual blis-tering are also common presentations. Non-Herlitz junc-tional epidermolysis bullosa may result from the samelaminin gene mutation and additionally from mutationsin the type XVII collagen gene (COL17A1), genesencoding α6 or β4 integrin (ITGA6 or ITGB4) or, veryrarely, plectin. The clinical presentation is similar toHerlitz variant but less severe.

Dystrophic epidermolysis bullosa: It is either domi-nantly or recessively inherited, but all forms are causedby mutations in the gene that encodes type VII collagen(COL7A1) affecting the integrity of anchoring fibrils.Recessive dystrophic epidermolysis bullosa is character-ized by a wide spectrum of severity, due to variable skinand mucosal membrane involvement. The newborn pre-sentation may be deceptively mild, but deep blisters thatdemonstrate poor healing and scarring formation becomethe norm in the first few months of life. Blisters of the oralcavity are also common, creating feeding difficulties.Dominant dystrophic epidermolysis bullosa have a milderpresentation, with blisters in high-friction areas that healwith scarring and milia formation.

Kindler syndrome: It is a rare autosomal recessivegenodermatosis also presenting with skin fragility earlyin life. Kindler syndrome presents blistering at differentlevels of the skin, so some blisters might heal withoutscarring, while others might heal leaving scars behind. Inthe neonatal period, this syndrome cannot be differenti-ated clinically from other skin fragility problems.

Bart syndrome: It consists of large areas of missingskin (aplasia cutis) at birth in the context of epidermolysisbullosa. Most commonly, this occurs on the lower extrem-ities, presumably due to increased intrauterine friction andresulting blistering. The presence of Bart syndrome is notepidermolysis bullosa type specific; however, it is morefrequently encountered in junctional epidermolysisbullosa and dystrophic epidermolysis bullosa.

– Pathological manifestation: The purpose of the skinbiopsy is to rule out other entities that cause blistering,to determine the split level, and to direct the moleculartesting. The H&E shows a split in the absence or paucityof an inflammatory infiltrate. Immunofluorescence map-ping shows the location of the abnormal protein inrelationship with other normal structures and the inten-sity of the staining using antibodies against knownaffected proteins compared to normal controls. Thedefinitive diagnosis is made by molecular testing(Murrell 2013).

Fig. 42 Epidermolysis bullosa: blistering after heel prick; tense blisterson the heel developing at the site of the heel prick. (Taken by Drs. ElenaPope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

Fig. 41 Epidermolysis bullosa: mucosal blistering; large erosion on thepalate with a rim of erythema. (Taken by Drs. Elena Pope and IreneLara-Corrales, The Hospital for Sick Children, Toronto, Canada)


– Prognosis and treatment: Prognosis is dependent on theepidermolysis bullosa subtype. Herlitz type ofepidermolysis bullosa may progress very rapidly in thefirst few weeks of life with significant morbidity (airwaycompromise, sepsis, anemia, etc.) and high mortality.Treatment is supportive, directed at skin care and preven-tion of blistering and complications.


5.5 Porphyria

– Definition: Porphyrias are an inherited group of entitiescharacterized by abnormal porphyrin metabolismresulting in toxic metabolites that lead to cutaneous pho-tosensitivity and skin fragility. The subtype most likely topresent shortly after birth is congenital erythropoietic pro-toporphyria and autosomal recessive condition caused bydeficiency of uroporphyrinogen III synthase (Desnick andAstrin 2002).

– Clinical feature: Cutaneous photosensitivity to both arti-ficial and natural light leading to blistering, skin fragility,edema, and pain are common features on congenital eryth-ropoietic protoporphyria (Fig. 44). Symptoms can presentshortly after birth but become increasingly more commonwith increased light exposure. The skin manifestationsmay be preceded by red urine, hematological abnormali-ties, and hepatosplenomegaly. Diagnosis may be delayeddue to a lag between light exposure and clinical manifes-tations (Katugampola et al. 2012b). Typical mutilatingfeatures, erythrodontia, and hypertrichosis become evi-dent later in life.

– Pathological manifestation: Pathology is helpful to ruleout other blistering conditions. A biopsy from the affected

skin reveals a subepidermal blister with minimal or noinflammatory infiltrate. Older lesions may demonstratescarring and hyalinization (Fritsch et al. 1998).

– Prognosis and treatment: Congenital erythropoietic pro-toporphyria has a very poor prognosis causing skin muti-lation and multiple system involvement. Preventativetherapies such as photoprotection and systemic medica-tion with potential alteration of porphyrin metabolism areof limited benefit to improve long-term prognosis andquality of life. Bone marrow transplantation is the onlydisease-modifying modality that showed some benefit(Katugampola et al. 2012a).

Fig. 44 Congenital erythropoietic porphyria; tense blisters on the faceof a newborn. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)

Fig. 43 Epidermolysis bullosa;multiple body parts affected byblisters and aplasia cutis affectingthe left leg. (Taken by Drs. ElenaPope and Irene Lara-Corrales, TheHospital for Sick Children,Toronto, Canada)

20 E. Pope et al.


5.6 Epidermolytic Ichthyosis

– Definition: Autosomal dominant condition ofepidermolytic ichthyosis is caused by KRT1 and KRT10mutations and characterized by erythroderma, widespreadblistering, and desquamation at birth followed byimprovement of the blistering over time and worseninghyperkeratosis with flexural predilection.

– Clinical feature: Affected neonates present shortly atbirth with diffuse erythroderma with large bulla formation(Fig. 45). Increased odor is a pathognomonic feature ofthis condition even shortly after birth. The blistering issuperficial and leads to large areas of denuded skin andheals without scarring (Lacz et al. 2005).

– Pathological manifestation: Hyperkeratosis with contin-uous vacuolar degeneration involving the granular andspinous layers is a characteristic feature. Focal hyperker-atosis, commonly seen in older children, may be absent inthe neonatal period (Ross et al. 2008).

– Prognosis and treatment: Epidermolytic ichthyosis is achronic skin condition.With time the skin fragility improvesand hyperkeratosis becomes more prominent. The appear-ance and constant malodor are causing significant psycho-social problems. Treatment modality in the neonatal periodconsists of skin and supportive care alone. Topical andsystemic retinoids may be helpful in the hyperkeratoticphase, although it may lead to more blistering formation.

– Differential diagnosis: Infections, other autoimmuneblistering disorders, inherited bullous disorders (see

Table 2), and superficial epidermolytic ichthyosis (bullousichthyosis of Siemens) (Cervantes et al. 2013).

5.7 Incontinentia Pigmenti

– Definition: Incontinentia pigmenti is a rare, X-linkeddominant genodermatosis caused by an IKBKG mutation,leading to typical skin manifestations and abnormalities inother ectodermal structures.

– Clinical feature: The skin findings go through four dif-ferent stages including vesiculobullous, verrucous, hyper-pigmented, and hypopigmented (Figs. 46, 47, and 48).

Fig. 45 Epidermolyticichthyosis; large areas ofdesquamation leaving backgrounderythema. (Taken by Drs. ElenaPope and Irene Lara-Corrales, TheHospital for Sick Children,Toronto, Canada)

Fig. 46 Incontinentia pigmenti vesiculobullous phase; linear distribu-tion of vesicles and hemorrhagic crusting. (Taken by Drs. Elena Popeand Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)


The first stage, vesiculobullous, presents at birth, orshortly after, with tense vesicles/bulla on an erythematousbase in a linear configuration following Blaschko’s lines.Rarely, this stage may overlap with the verrucous stage ormiss completely. Other manifestations include alopecia,particularly of the vertex, nipple abnormalities (absence,hypoplasia, supranumerary), and CNS and eye anomalies(Minić et al. 2014).

– Pathological manifestation: The first stage has markedeosinophilic spongiosis with formation of anintraepidermal vesicle containing eosinophils. There is avariable degree of keratinocyte apoptosis.

– Prognosis and treatment: Prognosis is dictated by theextent of the non-cutaneous manifestations (particularlyCNS). Skin lesions evolve over time through the fourstages, resulting in adulthood in hypopigmented, slightlyatrophic areas of minimal cosmetic significance. There isno specific treatment.

– Differential diagnosis: Herpes infection, autoimmuneblistering disorders, and epidermolysis bullosa for blister-ing phase (see Table 2), epidermal nevus and psoriasis forverrucous phase, pigmentary mosaicism for hyper-pigmented phase, and morphea, blaschkitis, and pigmen-tary mosaicism for hypopigmented phase.

6 Nodules/Tumors/Neoplastic Processes

Nodules and tumors may occasionally present at birth. Adifferential approach, based on the color of the lesions, isoutlined in Table 3.

6.1 Nevus Sebaceous and Epidermal Nevus

– Definition: Nevus sebaceous is a hamartomatous growth,commonly occurring on the head, neck, and scalp,consisting of abnormalities of sebaceous and sweat glandsand hair follicles (Moody et al. 2012). Epidermal nevus isconsidered a variant of nevus sebaceous with less or

Fig. 47 Incontinentia pigmenti: tense blister; linear distribution oftense blisters. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)

Fig. 48 Incontinentia pigmenti resolving; linear distribution of residualerythema and peeling. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Table 3 Differential of nodule, tumors, and neoplastic processes

Color Entities

Yellow/tan LipomasNevus sebaceousEpidermal nevusNeurofibromas

Red Vascular tumors (infantile and congenitalhemangioma, hemangioendothelioma, and tuftedangioma)MyofibromasRhabdomyosarcomaFibrosarcomaSubcutaneous fat necrosis

Blue/violaceous

Blueberry muffin babyNeuroblastomaLeukemiaVascular malformations (venous, lymphatic, andcombined)

Yellow/brown

HistiocytosisXantogranulomaMelanocytic neviEpidermal nevi

22 E. Pope et al.

absent sebaceous glad hyperplasia, typically found outsideof the head and neck area.

– Clinical feature Nevus sebaceous presents at birth withan oval, round, or linear plaque with white-yellow discol-oration and no evidence of hair follicles (Figs. 49, 50, 51,52, and 53). Rarely, rather than a smooth surface, thenevus sebaceous may have a mammillated appearance.Epidermal nevus is mostly in a linear configuration, fol-lowing the Blaschko’s lines distribution (Fig. 54). Gener-alized presentation of both should raise the suspicion ofnevus sebaceous syndrome or Schimmelpenning syn-drome, with potential for cerebral, ocular, and skeletalanomalies (Happle 2010).

– Pathological manifestation: Although clinical diagnosisis sufficient, pathology may offer confirmatory findings

such as acanthosis, papillomatosis, and basal layer pig-mentation. Sebaceous gland hyperplasia and decreasedhair follicles are other pathognomonic features in nevussebaceous but are missing in epidermal nevus (Kamyab-Hesari et al. 2016).

– Prognosis and treatment: In the absence of nevus seba-ceous syndrome, prognosis is good. Increased rugosity isseen in puberty in both types of nevi. In nevus sebaceous,pubertal changes may lead to an increased incidence ofbenign proliferations such as syringocystadenomapapilliferum, trichoblastoma, etc. Malignant transforma-tion occurs in a very small percentage of patients with

Fig. 50 Nevus sebaceous on the scalp; linear yellow plaque with anuneven contour (cerebriform like). (Taken by Drs. Elena Pope and IreneLara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 51 Nevus sebaceous appearing like a bleeding lesion; nevussebaceous presenting as a polypoid hemorrhagic lesion at birth. (Takenby Drs. Elena Pope and Irene Lara-Corrales, The Hospital for SickChildren, Toronto, Canada)

Fig. 52 Nevoid hamartomas lesions presenting as hairless patch; skin-colored, well-defined plaque of hair loss with a mammillated appear-ance. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospitalfor Sick Children, Toronto, Canada)

Fig. 49 Nevus sebaceous on the scalp; yellow-pink papules forming aplaque on the scalp. (Taken by Drs. Elena Pope and Irene Lara-Corrales,The Hospital for Sick Children, Toronto, Canada)


nevus sebaceous during adulthood (Idriss and Elston2014). Surgical excision, whenever feasible, for cosmeticand/or medical indications is reasonable. Destructivelasers’ benefit is controversial.

– Differential diagnosis: Aplasia cutis.

6.2 Neurofibroma

– Definition: Neurofibroma is a benign proliferation ofSchwann cells arising from the fibrous tissue around thenerve fibers. Neurofibromas are a hallmark of neurofibro-matosis type 1 (NF1). Plexiform or diffuse neurofibromasoccur in 30–50% of patients with neurofibromatosis type 1

and may be present at birth (Tucker et al. 2009; Williamset al. 2009).

– Clinical feature: Plexiform neurofibromas present as soft,skin and subcutaneous masses with a classical “bag ofworms” feel on palpation (Fig. 55). They are typicallyskin colored or slightly hyperpigmented. Hypertrichosismay also be present. Sizes, as well as location, vary widely(Williams et al. 2009).

– Pathological manifestation: Plexiform neurofibromasshow a cellular infiltrate with various degree of atypiainvolving multiple nerve fascicles or the nerve plexus.The cells have enlarged, hyperchromatic, or “wavy”nuclei. Differentiating this from schwannoma and malig-nant tumors is difficult (Rodriguez et al. 2012).

– Prognosis and treatment: Neurofibromas tend to growover time causing cosmetic deformity and pain. They areconsidered premalignant due to the potential for develop-ment of malignant peripheral nerve sheaths tumors(~10%) (Tucker et al. 2009). Complete surgical excisionis rarely possible.

– Differential diagnosis: Congenital nevi and hamartomas.

6.3 Hemangioma

– Definition: Hemangiomas are benign vascular prolifer-ations that affect ~5% of infants. There are two majorcategories: Infantile hemangioma, characterized with aproliferative phase after birth and involution in thechildhood years, and congenital hemangioma, wherethe proliferation occurs in utero (Luu and Frieden2013).

Fig. 54 Linear epidermal nevus; linear configuration, respecting mid-line of multiple skin to pink-colored papules. (Taken by Drs. Elena Popeand Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

Fig. 55 Neurofibroma: pink-brown plaque, soft to palpation. (Taken byDrs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Chil-dren, Toronto, Canada)

Fig. 53 Sebaceous nevus on the face; red-yellow papules forming aplaque in a Blaschko’s line distribution on the face of a newborn. (Takenby Drs. Elena Pope and Irene Lara-Corrales, The Hospital for SickChildren, Toronto, Canada)

24 E. Pope et al.

– Clinical feature: Infantile hemangioma may be present atbirth. The typical appearance is flat, red papules or plaquesthat proliferate over the ensuing weeks. This presentationmay be preceded by a hypoanemic, bruise-like, or telan-giectatic patch (premonitory sign) that delineates the ter-ritory where ultimately the infantile hemangioma willproliferate. Congenital hemangioma, in contrast, presentsas a tumor growth with coarse telangiectasias and aperipheral rim of white discoloration (“halo”). Largelesions could display various degrees of ulceration. It isimpossible to differentiate at birth the lesions that willhave rapid involution or no involution (Figs. 56, 57, 58,59, 60, 61, 62, 63, 64, and 65) (Luu and Frieden 2013;Mulliken and Enjolras 2004).

– Pathological presentation: Pathological picture consistsof multiple lobules containing endothelial cells and peri-cytes mixed with mast cells. Infantile hemangioma lesionsare differentiated from congenital hemangioma by thepresence normal septi between the lobules, lack of encap-sulation, and strong positivity to GLUT-1 marker (Northet al. 2000, 2001).

– Prognosis and treatment: Prognosis is favorable withvery few patients experiencing complications (ulceration,functional compromise, and bad cosmetic outcome). Theinterventions range from expectant management, medicaland surgical treatment depending on the size, location,

Fig. 57 Early infantile hemangioma in a patient with PHACES syn-drome; segmental patch of red-violaceous discoloration, coarse telangi-ectasias, circular ulceration on the hemiface and scalp. (Taken by Drs.Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children,Toronto, Canada)

Fig. 56 Premonitory sign of infantile hemangioma; pale patch withpinpoint erythematous papules. (Taken by Drs. Elena Pope and IreneLara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 58 Multiple hemangiomas; multiple, disseminated, red papulesand nodules. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)


potential or existent functional impairment, and ultimatedeforming potential.

– Differential diagnosis: Myofibromas, hemangioen-dothelioma, tufted angioma, and vascular malformations.

6.4 Hemangioendothelioma

– Definition: Hemangioendothelioma is a benign tumor butwith a locally aggressive behavior and the potential todevelop a consumptive coagulopathy (Kasabach-Merrittphenomenon). Tufted angioma is a more superficial andless aggressive variant of hemangioendothelioma with atypical pathological picture.

Fig. 62 Congenital hemangioma; coarse telangiectasias overlying abluish mass with a white halo. (Taken by Drs. Elena Pope and IreneLara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 59 Early proliferative mixed infantile hemangioma; red tumorwith a deep and superficial component. (Taken by Drs. Elena Popeand Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

Fig. 60 Scalp congenital hemangioma; large mass with minimal super-ficial component, multiple feeding vessels, highly vascularized on imag-ing. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospitalfor Sick Children, Toronto, Canada)

Fig. 61 Congenital hemangioma on the leg; large mass with no evidentvascularity and a white surrounding halo. (Taken by Drs. Elena Popeand Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

26 E. Pope et al.

– Clinical feature: Hemangioendothelioma lesions may bepresent at birth as raised, firm masses, with a violaceousdark color, typically affecting the skin, subcutaneous tis-sue with extension into the deeper tissues (Figs. 66, 67,and 68). If Kasabach-Merritt phenomenon develops,lesions enlarge rapidly and display signs of bleeding

(bruising, petechiae). Tufted angioma lesions have a sim-ilar discoloration but are flatter with a minimal subcutane-ous component (Croteau and Gupta 2016).

– Pathological manifestation: Hemangioendothelioma hasa nodular appearance created by a conglomeration ofmultiple lobules of endothelial and spindle cells. A “can-nonball” or glomeruloid pattern has been described. Elon-gated, slit-like lymphatics are present at the periphery ofthe lesion. GLUT-1 stains are negative, but lymphatic

Fig. 65 Deep nodular hemangioma; large tumor with minimal viola-ceous discoloration over the eyelid. (Taken by Drs. Elena Pope and IreneLara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 64 Telangiectatic hemangioma; flat patch with telangiectasiasrepresenting either a premonitory sign of an infantile hemangioma oran abortive hemangioma. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 66 Hemangioendothelioma on the leg; large, circumferentialtumor, red-violaceous, firm to touch. (Taken by Drs. Elena Pope andIrene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 63 Ulcerated congenital hemangioma; large mass, highly vascularwith a white halo and a central ulceration healing. (Taken by Drs. ElenaPope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)


stains (LYVE-1 and D2–40) are positive (Putra and Gupta2017).

– Prognosis and treatment: Prognosis depends on theextent of the tumor and the presence of Kasabach-Merrittphenomenon. Long term, they demonstrate partial involu-tion. There is potential for recurrence of the Kasabach-Merritt phenomenon later in life and chronic pain anddeformity of the affected area. Treatment for complicatedcases consists of combination steroids plus vincristine or,more recently, sirolimus (Ji et al. 2017; Drolet et al. 2013).

– Differential diagnosis: Hemangiomas, vascularmalformations, rhabdomyosarcoma, fibrosarcoma, peri-cytoma, and myofibroma.

6.5 Myofibroma

– Definition: Myofibroma is a rare, benign fibrous tumor ofinfancy, consisting of proliferation of fibroblasts andmyofibroblasts.

– Clinical features: Myofibroma is a red-purple, hard nod-ule/tumor, often presenting as a solitary lesion at birth(Fig. 69). Multiple lesions are possible raising the concernfor systemic involvement. The lesions are commonly pre-sent on the head and neck but can occur elsewhere(Stanford and Rogers 2000).

– Pathological manifestation: Myofibroma shows an infil-trate composed of spindle cells organized in fascicles andnodules. The immunohistochemical stains for smoothmuscle actin are positive (Friedman et al. 2013).

– Prognosis and treatment: The prognosis is favorable,with most lesions involuting spontaneously over the ensu-ing months. Systemic involvement carries a more guardedprognosis.

– Differential diagnosis: Hemangioma, hemangioen-dothelioma, and fibrosarcoma.

6.6 Rhabdomyosarcoma

– Definition: Rhabdomyosarcoma is a rare malignant tumorof mesenchymal origin with skeletal muscle differentia-tion. The most common subtypes seen in the pediatric agegroup are embryonal and alveolar tumors.

– Clinical feature: Rhabdomyosarcoma may be present atbirth as nonspecific red, firm tumors (Figs. 70, 71, and 72).

Fig. 68 Hemangioendothelioma on the face; large, red-violaceous,infiltrated, firm plaque consisting of multiple nodules. (Taken by Drs.Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children,Toronto, Canada)

Fig. 69 Myofibroma: red-purple, firm nodule on the back, poorlydemarcated. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)

Fig. 67 Hemangioendothelioma on the arm; large, violaceous, firm totouch. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospitalfor Sick Children, Toronto, Canada)

28 E. Pope et al.

Rapid growth and firmness and tendency to ulcerate arefeatures that differentiate rhabdomyosarcoma from othermore benign vascular tumors (Brecher et al. 2003). Typi-cal locations are head and neck area, followed by extrem-ities and genitourinary area.

– Pathological manifestation: The classical picture is thatof a neoplastic infiltrate with small, blue and round cellswith hyperchromatic nuclei. Muscle-specific actin anddesmin are positive as there are myogenin, myoglobin,and MYOD1 stains (Marburger et al. 2012).

– Prognosis and treatment: Prognosis is guarded anddepends on the staging at diagnosis. A combination ofchemotherapy to reduce the bulk of the tumor followed bysurgical excision may offer longer survivals. Genitouri-nary and orbit involvement carry a more favorableprognosis.

– Differential diagnosis: Benign vascular tumors,hemangioendothelioma, fibrosarcoma, and pericytoma.

6.7 Fibrosarcoma

– Definition: Fibrosarcoma is a rare neoplasm, with aggres-sive local behavior but less propensity to metastasize,representing the most common soft tissue sarcoma in theinfantile period (Bellfield and Beets-Shay 2014).

– Clinical feature: Fibrosarcoma presents as a pink-redtumor, firm to palpation with a rapid growth phase afterbirth and potential for ulceration (Fig. 73). Typical loca-tions are on extremities and less commonly on the headand neck region.

– Pathological manifestation: Classical appearance ofspindle cell proliferation in a zigzag or herring-bone con-figuration in conjunction with endothelial vessel hyper-plasia. Stains are positive for vimentin, smooth muscleactin, CD31, and Ki-67. Immunofluorescence is diagnos-tic showing a translocation t(12;15) (p13;q25) (Kerl et al.2012).

– Prognosis and treatment: Fibrosarcoma has a good prog-nosis. Chemotherapy before surgery reduces the mass andenables complete resection of the tumor. Recurrences are

Fig. 70 Rhabdomyosarcoma of the philtrum; pink, firm mass present atbirth, rapidly growing mistaken for an infantile hemangioma. (Taken byDrs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Chil-dren, Toronto, Canada)

Fig. 71 Rhabdomyosarcoma of the face; large pedunculated, rapidlygrowing mass with ulceration. (Taken by Drs. Elena Pope and IreneLara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 72 Rhabdomyosarcoma of the face; large, firm, rapidly growingmass. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospitalfor Sick Children, Toronto, Canada)


common, especially for partially resected tumors (Lohet al. 2002).

– Differential diagnosis: Hemangioma, hemangioen-dothelioma, and rhabdomyosarcoma.

6.8 Subcutaneous Fat Necrosis

– Definition: Subcutaneous fat necrosis is a rare type of tran-sient panniculitis seen only in the neonatal period. Its riskfactors are maternal and newborn factors such as neonatalhypoxia, infection, macrosomia leading to birth trauma, andfamilial risk factors for thrombosis (Mahé et al. 2007).

– Clinical feature: Typical lesions occur a few days afterbirth and consist of skin color or violaceous, firm nodulesor subcutaneous tumors (Figs. 74, 75, and 76). The distri-bution is variable, but trunk, cervical areas, and arms arethe most common locations (Mahé et al. 2007). Recently,the cooling blankets have been implicating, causing arectangular plaque matching the contact areas with theblanket (Tognetti et al. 2015). Occasionally, the lesionsare painful. Liquefaction may occur over time causingsoftening of the lesions, increasing the chances of lesionsbeing diagnosed as a vascular anomaly.

Fig. 73 Congenital fibrosarcoma; large, firm tumor with evidence ofulceration/necrosis. (Taken by Drs. Elena Pope and Irene Lara-Corrales,The Hospital for Sick Children, Toronto, Canada)

Fig. 74 Subcutaneous fat necrosis back; violaceous, firm nodules,some appear ready to open up. (Taken by Drs. Elena Pope and IreneLara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 75 Subcutaneous fat necrosis; red-violaceous, firm nodules/plaques on the shoulders and arms. (Taken by Drs. Elena Popeand Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

30 E. Pope et al.

– Pathological manifestation: Classical pathologic pictureconsists of adipocyte necrosis, a lymphohistiocytic infil-trate, and crystal-like structures (Friedman andWinkelmann 1989).

– Prognosis and treatment: Prognosis is favorable withcomplete resolution within months. The most commoncomplication is hypercalcemia, developing after an aver-age of 24 days, in >60% of patients. There is a small riskof nephrocalcinosis (Del Pozzo-Magaña and Ho 2016;Mahé et al. 2007).

– Differential diagnosis: Hemangiomas, vascularmalformations, hemangioendothelioma, hamartomas, andmyofibromatosis.

6.9 Blueberry Muffin Baby

– Definition: Blueberry muffin baby is a clinical phenotypeconsisting of multiple bluish nodules in a newbornresulting from both neoplastic and nonneoplastic pro-cesses. In the nonneoplastic process resulting from infec-tions (TORCH), hemolytic processes, and twin-twintransfusion, the nodules represent extramedullary hemato-poiesis as a compensatory mechanism for the underlyingcondition. In the neoplastic group, the blue nodules rep-resent metastatic spread. The most common underlyingentities are leukemia, Langerhans cell histiocytosis, neu-roblastoma, rhabdomyosarcoma and other rhabdoidtumors, and primitive neuroectodermal tumors (Isaacs2011).

– Clinical feature: Clinically all babies have typical infil-trative nodules, red-violaceous in color (Figs. 77, 78, and79). Signs, such as blanching of the lesion with stroking(due to epinephrine/norepinephrine release) seen in neu-roblastoma, associated bruising or bleeding diathesis in

leukemia/lymphoma, or other skin lesions such as pete-chiae and hemorrhagic crusting in a typical “seborrheicdistribution” seen in Langerhans cell histiocytosis, allowto narrow the diagnostic possibilities on the clinical pre-sentation alone (Shaffer et al. 2005).

– Pathological manifestation: Skin biopsies show a dermalinfiltrate. The cellularity, pattern, and cell markers dependon the underlying diagnosis.

– Prognosis and treatment: Prognosis and treatment aredependent on the underlying diagnosis.

Fig. 76 Subcutaneous fat necrosis due to cooling blanket; violaceous,firm, irregular mass in a rectangular configuration mistaken as a vascularmalformation. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)

Fig. 78 Blueberry muffin baby due to extramedullary hematopoiesis;multiple red, violaceous and blue papules and nodules. (Taken by Drs.Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children,Toronto, Canada)

Fig. 77 Blueberry muffin baby due to leukemic metastases; multiplered-violaceous nodules and bruise-like lesions. (Taken by Drs. ElenaPope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)


– Differential diagnosis: Hemangiomas, mastocytosis,blue rubber bleb syndrome, and multifocallymphangiomatosis with thrombocytopenia.

6.10 Vascular Malformation

– Definition: Vascular malformations comprise a largegroup of heterogeneous conditions that represent abnor-malities of the angiogenesis. They are classified as simple(composed of only one type of vessel – capillaries, veins,lymphatics, and arteriovenous malformations), combinedmalformations (any combinations of the main vessels),malformations of the major vessels, malformations asso-ciated with other abnormalities (e.g., overgrowth), andunclassified lesions (Wassef et al. 2015).

– Clinical feature: See Table 4 and Figs. 80, 81, 82, 83, 84,85, 86, 87, 88, 89, and 90.

– Pathological manifestation: Although clinical diagnosisis sufficient in most case, pathology may be helpful todifferentiate from other vascular anomalies, such astumors. The biopsies of vascular malformations showonly ectatic vessels in the papillary dermis with blandendothelial cells. Vascular malformations have irregularvenous type of channels, characterized by flat endothelialcells surrounded by smooth muscle. The stains are posi-tive for CD31. Lymphatic malformation is characterizedby thin- to thick-walled channels with variable depth ofinvolvement. These findings are accompanied by variousdegree of fibrosis. They are positive for LYVE-1 andD2-40 stains (Gupta and Kozakewich 2011).

– Prognosis and treatment: Prognosis and treatment variesdepending on the size, location, associated complications,

etc. Capillary malformations may be amenable to lasertreatment. Venous and lymphatic malformations mayrequire no intervention, single (sclerotherapy) or com-bined modalities (sclerotherapy plus medical interventionssuch as rapamycin). Arteriovenous malformations are dif-ficult to manage; to date, no intervention can successfullymanage progression.

– Differential diagnosis: Vascular tumors and subcutane-ous fat necrosis.

6.11 Xanthogranuloma

– Definition: Xanthogranulomas are histiocytic prolifera-tions occurring primarily in children and adolescents.

Fig. 79 Blueberry muffin baby due to neuroblastoma; multiple skin-colored and bluish nodules; when struck they develop a halo. (Taken byDrs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Chil-dren, Toronto, Canada)

Table 4 Classification and clinical features of vascular malformations

Type of vessel Clinical presentations

Capillarymalformations

Flat, red-violaceous patches; could be diffuse,reticulated, circumscribed, or telangiectatic

Venousmalformations

Blue/violaceous flat patchesSoft, compressible subcutaneous massesPhleboliths

Lymphaticmalformations

Microcysts: Skin color, red, blue vesicles, “frogspawn,” or “grape-like”Macrocysts: Large skin color, translucentmasses

Fig. 80 Capillary malformation face; segmental red flat patch in a childwith Sturge-Weber syndrome. (Taken by Drs. Elena Pope and IreneLara-Corrales, The Hospital for Sick Children, Toronto, Canada)

32 E. Pope et al.

They are the most common form of non-Langerhanshistiocytosis (Emile et al. 2016).

– Clinical feature: Most common presentation is of a sin-gle, well-demarcated, raised, yellow or orange-brownishpapule (Figs. 91, 92, and 93). Most occur on the head andneck, less commonly on the trunk and extremities. Singlelesions coalescing into a plaque or multiple lesions are rareoccurrences.

– Pathological manifestation: The pathological picturedepends on the stage of progression from early to latetransitional xanthogranulomas. The classical pathologi-cal picture is of an infiltrate containing foaming histio-cytes and Touton giant cells. The non-Langerhanshistiocytosis cell lineage markers (CD68, FXIIIa) are

positive, while CD1A and S100 are negative (Janssenand Harms 2005).

– Prognosis and treatment: Xanthogranuloma has a favor-able prognosis with spontaneous resolution over severalyears. Large lesions may resolve with anetoderma thatrequire further treatment. Ocular xanthogranulomas areseen in less than 1% of cases of disseminate lesions.Systemic involvement is unusual.

– Differential diagnosis: Spitz nevus, Langerhans cellhistiocytosis, benign cephalic histiocytosis, andxanthoma.

Fig. 82 Superficial venous malformation; patch of blue discoloration.(Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital forSick Children, Toronto, Canada)

Fig. 83 Venous malformation of the face; irregular blue violaceouspatch representing the superficial component of a complex venousmalformation. (Taken by Drs. Elena Pope and Irene Lara-Corrales,The Hospital for Sick Children, Toronto, Canada)

Fig. 84 Complex venous malformation with associated anomalies;deep venous malformation causing asymmetry of the lumbosacral areawith dysraphism and buttock asymmetry. (Taken by Drs. Elena Pope andIrene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 81 Diffuse capillary malformation with overgrowth; widespreadreticulated red discoloration. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)


6.12 Congenital Melanocytic Nevi (BathingTrunk Nevus)

– Definition: Congenital melanocytic nevi are due to anabnormal but benign proliferation of melanocytes. Mostare present at birth or shortly after. Single congenitalmelanocytic nevi are found in 1% of newborns (Alperand Holmes 1983). These are a form of mosaicism givenby post-zygotic mutations in NRAS, BRAF, MC1R,TP53, or GNAQ. Multiple congenital melanocytic nevican be associated with extracutaneous associations and are

Fig. 88 Mixed capillary-lymphatic malformation causing deformity ofthe fingers; soft tissue swelling with bluish-red discoloration. (Taken byDrs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Chil-dren, Toronto, Canada)

Fig. 89 Complex capillary-venous malformation with overgrowth;large violaceous mixed blue discolored patches. (Taken by Drs. ElenaPope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

Fig. 87 Complex capillary-venous malformation; intense violaceous-blue patch. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)

Fig. 86 Microcystic lymphatic malformation; multiple clear fluid col-ored or red papules. (Taken by Drs. Elena Pope and Irene Lara-Corrales,The Hospital for Sick Children, Toronto, Canada)

Fig. 85 Vascular malformation of the tongue; large mass causingtongue involvement and interfering with feeding. (Taken by Drs. ElenaPope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

34 E. Pope et al.

Fig. 90 Phacomatosis pigmentovascularis; widespread flat patches ofoverlapping vascular stain and dermal melanocytosis. (Taken by Drs.Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children,Toronto, Canada)

Fig. 91 Juvenile xanthogranuloma face; yellow-orange papules on thecheeks. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hos-pital for Sick Children, Toronto, Canada)

Fig. 92 Juvenile xanthogranuloma perineal area; orange-brown, softnodule. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hos-pital for Sick Children, Toronto, Canada)

Fig. 93 Juvenile xanthogranuloma en plaque; multiple yellow papulesforming a plaque in the axilla. (Taken by Drs. Elena Pope and IreneLara-Corrales, The Hospital for Sick Children, Toronto, Canada)


linked to NRAS mutations in 80% of cases (Kinsler et al.2017).

– Clinical feature: Congenital melanocytic nevi present asround to oval, pigmented skin lesions (Figs. 94, 95, 96,and 97). Most are palpable and can have hypertrichosis.Depending on their projected size in adulthood, congenitalmelanocytic nevi are classified into small (<1.5 cm),medium (1.5–19.9 cm), and large (>20 cm). Particularlylarger ones can present satellite lesions that are smallermelanocytic lesions on the periphery of a larger one.Larger lesions can also become itchy and sometimes pre-sent benign proliferative nodules.

– Pathological manifestation: Histopathology typicallyreveals a nodular lesion composed of nevus cells that extenddeep into the dermis, subcutaneous tissues, and some deeperstructures. It is common to see nevus cells clustered aroundother skin structures like blood vessels or hair follicles.Cytologic atypia, architectural disorder, and pagetoid spreadhave been reported to be common in benign congenitalmelanocytic nevi in children (Simons et al. 2017).

– Prognosis and treatment: Treatment of congenitalmelanocytic nevi depends on age, location, depth, risk ofmalignant melanoma, and patient preference. Some nevimay be excised if they pose a cosmetic concern, there is a

risk or clinical suspicion of melanoma, if recent changesare appreciated or location is difficult to observe andmonitor. In the absence of these concerns, most nevi justrequire monitoring and observation at intervals that aredetermined by their size. Pictures and dermoscopy areuseful tools for monitoring nevi.Lifetime risk of melanoma is higher in larger nevi withdifferent studies reporting that the risk of small/mediumnevi is <1% and for large nevi from 2.2% to 8% (Kinsleret al. 2017). The risk of melanoma is higher not only in

Fig. 96 Irregular color giant congenital melanocytic nevus; flatmelanocytic patch with irregular coloration but no nodularity. (Takenby Drs. Elena Pope and Irene Lara-Corrales, The Hospital for SickChildren, Toronto, Canada)

Fig. 94 Medium- to large-size congenital melanocytic nevus; well-defined pigmented lesion with uniform coloration. (Taken by Drs.Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children,Toronto, Canada)

Fig. 95 Giant congenital melanocytic nevus; giant nevus covering theentire back, mixed flat pigmentation with nodularity. (Taken by Drs.Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children,Toronto, Canada)

36 E. Pope et al.

large/giant nevi but also in those that have axial/para-vertebral location, if multiple satellites are seen or ifthere is neurocutaneous melanosis (proliferation of mela-nocytes in the central nervous system).

– Differential diagnosis: Café-au-lait macules, pigmentarydisorders, and other tumors.

7 Papulosquamous Eruptions

7.1 Psoriasis

– Definition: Psoriasis is a chronic, immune-mediated, sys-temic, inflammatory disease that affects all age groups.About one third of psoriasis cases present in childhood.Neonatal presentation is extremely rare (Rogers 2002).

– Clinical feature: All forms of psoriasis can present inchildren (Figs. 98, 99, 100, and 101), but in the first2 years of life, diaper psoriasis or napkin psoriasis ismore common (Bhutani et al. 2012).Diaper psoriasis presents as large, bright to dull, erythem-atous plaques with dry or minimal scaling due to thehumidity of the diaper area. Approximately 4% of diaperpsoriasis is localized, while 13% may present dissemi-nated disease with more typical erythematous plaqueswith gray-silvery scale elsewhere in the body (Morriset al. 2001). The most common sites of disseminationare the trunk, limbs, scalp, and face.

– Pathological manifestation: Histology reveals epidermalthickening, acanthosis with elongated rete ridges, reten-tion of nuclei in the stratum corneum (parakeratosis), and

mononuclear infiltrate with focal collection of neutrophilsin the stratum corneum or subcorneal layer.

– Prognosis and treatment: Given the chronic nature ofpsoriasis, patients can present with frequent flares of thedisease. Topical medications such as low-potency topicalcorticosteroids, calcipotriene ointment, and calcineurininhibitors may be used to control inflammation (Afsaret al. 2016).

– Differential diagnosis: Seborrheic dermatitis, irritant andallergic contact dermatitis, candidal dermatitis, and atopicdermatitis.

Fig. 98 Generalized psoriasis; large coalescent plaques consisting ofredness and scaling. (Taken by Drs. Elena Pope and Irene Lara-Corrales,The Hospital for Sick Children, Toronto, Canada)

Fig. 99 Generalized psoriasis causing erythroderma; large desqua-mated area on the background of erythema. (Taken by Drs. Elena Popeand Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

Fig. 97 Giant congenital melanocytic nevus with Spitzoid features;giant bathing trunk nevus consisting of light background pigmentationand multiple color nodules of various colors (from red-pink to brown).(Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital forSick Children, Toronto, Canada)


7.2 Pustular Psoriasis

– Definition: Pustular psoriasis is a rare, debilitating, andoften life-threatening inflammatory disease that presentswith episodic infiltration of neutrophils into the skin lead-ing to formation of pustules and accompanied by systemicinflammation (Johnston et al. 2017). Specific syndromespresenting as pustular psoriasis have been described: defi-ciency of interleukin-1 receptor antagonist, deficiency ofinterleukin-36 receptor antagonist, and CARD14-mediated psoriasis (Almeida de Jesus and Goldbach-Mansky 2013).

– Clinical feature: Pustular psoriasis is characterized bygeneralized, sheeted, pinhead-sized, sterile, subcorneal

pustules (Fig. 102). These pustules can be seen on theborders of expanding erythematous plaques or withinerythrodermic skin. Systemic symptoms are common.Patients with deficiency of interleukin-1 receptor antago-nist can also present multifocal osteomyelitis andperiostitis.

– Pathological manifestation: The typical histologic find-ing is the presence of spongiform, epidermal pustules(pustules of Kogoj). These are the result of neutrophilinfiltration into necrotic epidermis in which the cell wallspersist as a sponge-like network (Sugiura 2014).

– Prognosis and treatment: Pustular psoriasis is a lifelongskin disorder. Medication options are acitretin, cyclospor-ine, and methotrexate, but response to treatment variesamong patients, and long-term safety and efficacy data islacking. (Posso-De Los Rios et al. 2014). Biologics maybe indicated.

– Differential diagnosis: Bacterial infections (impetigo),fungal infections, and acute generalized exanthematouspustulosis.

7.3 Ichthyosis

– Definition: Ichthyoses are disorders of cornification dueto mutations in various genes important for keratin differ-entiation and epidermal barrier function (Schmuth et al.2013). These are divided into non-syndromic and syn-dromic (if there is other organ involvement) (Oji et al.2010).

– Clinical feature: Autosomal recessive congenitalichthyoses that comprise harlequin ichthyosis, lamellarichthyosis, and congenital ichthyosiform erythrodermapresent in the newborn period (Figs. 103, 104, 105, 106,107, and 108) (Oji et al. 2010).

Fig. 100 Psoriasis in the diaper area; well-defined plaques of intenseerythema and scaling. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 101 Generalized psoriasis; large coalescent plaques consisting ofredness and scaling. (Taken by Drs. Elena Pope and Irene Lara-Corrales,The Hospital for Sick Children, Toronto, Canada)

Fig. 102 Pustular psoriasis; large coalescent plaques redness scalingstudded with pustules. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

38 E. Pope et al.

The two most prominent clinical features of patients withichthyosis are scaling and hyperkeratosis. Autosomalrecessive congenital ichthyosis typically presents as acollodion baby that refers to a parchment-like membranethat covers the baby’s body surface in its totality or par-tially. Other clinical features such as ectropion, eclabium,sparse hair, and pseudo-contractures may be seen.

– Pathological manifestation: A thick, hyperkeratotic stra-tum corneum is seen in different types of ichthyosis. Fewtypes of ichthyoses have pathognomonic histological fea-tures. With lamellar ichthyosis, histology reveals lamellarbody “ghosts.”

– Prognosis and treatment: Ichthyoses are lifelong skindisorders. The prognosis depends on the type, with harle-quin ichthyosis being the most severe subtype.

Fig. 103 Collodion baby; generalized erythema and a tight membranecovering the body in a restrictive fashion. (Taken by Drs. Elena Popeand Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

Fig. 105 Collodion membrane on the face; large membrane peeling offthe face. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)

Fig. 104 Harlequin baby; large constrictive bands of thickened collo-dion membrane. (Taken by Drs. Elena Pope and Irene Lara-Corrales,The Hospital for Sick Children, Toronto, Canada)

Fig. 106 Lamellar ichthyosis; generalized plate-like scaling. (Taken byDrs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Chil-dren, Toronto, Canada)


Collodion babies need intensive care with close monitor-ing of temperature, electrolytes, and water balance as wellas caloric supplementation (NG tube), monitoring forinfection, and pain management.

Liberal use of emollients is recommended in allpatients. Severe phenotypes may require systemic

treatments such as oral retinoids, retinoic acid metabolismblocking agents, and antibiotics (Prado et al. 2012).

– Differential diagnosis: Ichthyosis prematurity syndrome,Sjogren-Larsson syndrome, Netherton syndrome, andimmunodeficiencies.

8 Disorders of Pigmentation

8.1 Oculocutaneous Albinism

– Definition: Oculocutaneous albinism is an autosomalrecessive condition causing diluted pigmentation of theskin, hair, and eyes. It can be classified into differentcategories depending on severity. Oculocutaneous albi-nism 1A is the most severe type distinguished by a com-plete lack of melanin formation. Types 1B, 2, 3, and 4 aremilder and show some pigmentation (Levin and Stroh2011).

– Clinical feature: The clinical features depend on thesubtype of oculocutaneous albinism (Fig. 109). Type1 has no skin pigmentation, white hair, andred-appearing eyes at birth with prominent nystagmus. Inthe following years, the hair will turn more yellow and canbecome light brown in adulthood. Type 2 will have pig-ment in the hair ranging from white to golden, reddishblond, and brown. At birth, the skin will appear creamierin color rather than milky. Through adulthood, those diag-nosed with type 2 will begin to gain some pigmentation intheir skin and develop freckles in sun-exposed areas(Okulicz et al. 2003).

Fig. 108 Erythroderma in immunodeficiency syndromes (combinedimmunodeficiency syndromes); widespread erythema and scaling.(Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital forSick Children, Toronto, Canada)

Fig. 107 Bullous ichthyosis of Siemens; widespread erosions resultingfrom superficial blisters. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)

Fig. 109 Oculocutaneous albinism type 1; white platinum hair andwhite skin. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)

40 E. Pope et al.

– Pathological manifestation: Histological examinationreveals melanocytes as suprabasal clear cells. Type2 will display some melanin; however, type 1 will have acomplete absence of melanin (Okulicz et al. 2003).

– Prognosis and treatment: There is no cure foroculocutaneous albinism. Patients are at high risk for mela-noma and non-melanoma skin cancer due to lack of protec-tive melanin. Surgery may be required to control associatedstrabismus and nystagmus (Levin and Stroh 2011).

– Differential diagnosis: Hermansky-Pudlak syndrome,Chediak-Higashi syndrome, Elejalde syndrome, and vitiligo.

8.2 Piebaldism

– Definition: Piebaldism is defined as an autosomal domi-nant hypopigmentation disorder caused by mutations inthe KIT gene (Oiso et al. 2013).

– Clinical feature: It is clinically characterized by the pres-ence of patches of leukoderma interspersed by the normalskin, with symmetrical distribution on the trunk andextremities and white hair (poliosis or “white forelock”)on the scalp and forehead (Figs. 110, 111, and 112) (Oisoet al. 2013).

– Pathological manifestation: Melanocyte count is signif-icantly decreased in hypopigmented areas (Thomas et al.2004).

– Prognosis and treatment: The leukoderma present inpiebaldism is quite stable; however, camouflaging andgrafting have been used to improve appearance (Oisoet al. 2013).

– Differential diagnosis: Waardenburg syndrome, vitiligo,nevus depigmentosus, oculocutaneous albinism, pigmen-tary mosaicism, and neurofibromatosis type 1 (Oisoet al. 2013).

Fig. 110 White forelock; tuft of depigmented hair in the middle of theforehead. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)

Fig. 111 Piebaldism legs; symmetrical depigmented patches. (Takenby Drs. Elena Pope and Irene Lara-Corrales, The Hospital for SickChildren, Toronto, Canada)

Fig. 112 “Ash leaf” hypopigmentation in tuberous sclerosis; leaf-likehypopigmented patch. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto, Canada)


8.3 Nevus Anemicus

– Definition: Nevus anemicus is due to decreased vascular-ity, causing the skin to appear hypopigmented. It is acommon occurrence in patients with neurofibromatosistype 1 (Marque et al. 2013).

– Clinical feature: Clinically, nevus anemicus can be dis-tinguished by the presence of confluent macules forminga patch on the trunk at birth or in early childhood(Fig. 113). There is an enhancement of paleness afterstroking surrounding skin areas and the presence of ery-thema that spares the actual patch (Ahkami and Schwartz1999).

– Pathological manifestation: Histologically, the skinappears normal with melanocytes in the lower part of theepidermis.

– Prognosis and treatment: Prognosis of nevus anemicusis good; however, cosmetic products can be used to coverup the hypopigmented areas of the skin.

– Differential diagnosis: Vitiligo, nevus depigmentosus,and depigmented macules of tuberous sclerosis.

8.4 Nevus Depigmentosus

– Definition: Nevus depigmentosus is a rare skin disorderthat can be characterized by the presence of hypopigmentedpatches; however, the source of this disease is still unknown

(Deb et al. 2014). Many consider nevus depigmentosus as alocalized form of pigmentary mosaicism.

– Clinical feature: The main clinical diagnostic features fornevus depigmentosus are the presence of an isolated patchwith geographical margins (Fig. 114), circumscribed bandwith a block-like formation along Blaschko’s lines, andgeneralized whorls or streaks. Leukoderma is also presentat birth, and no alteration of its distribution is seen (Debet al. 2014).

– Pathological manifestation: Melanocyte count is normalwith no obvious changes in shape and number; however,functional defects, such as reduced melanin, are prevalentin melanocyte cultures (Deb et al. 2014).

– Prognosis and treatment: No treatment is curative. Cos-metic camouflage is an acceptable method. Phototherapy,excimer laser, surgical grafting methods, and melanocyte-keratinocyte transplantation have been used as treatmentoptions (Mulekar et al. 2011).

– Differential diagnoses:Nevus anemicus, ash leaf macule,vitiligo, hypomelanosis of Ito, incontinentia pigmenti, andpiebaldism.

8.5 Nevus of Ota

– Definition: Nevus of Ota refers to the sporadic occurrenceof oculodermal melanocytosis. In contrast to dermalmelanocytosis, the affected areas are not limited to theskin but also to the eye (Plateroti et al. 2017). Mutations in

Fig. 113 Nevus anemicus; white discolored irregular patch surroundedby normal skin. (Taken by Drs. Elena Pope and Irene Lara-Corrales, TheHospital for Sick Children, Toronto, Canada)

Fig. 114 Nevus depigmentosus; hypo/depigmented patch with well-demarcated borders. (Taken by Drs. Elena Pope and Irene Lara-Corrales,The Hospital for Sick Children, Toronto, Canada)

42 E. Pope et al.

GNAQ and GNA11 have been reported in nevus of Ota(Van Raamsdonk et al. 2009).

– Clinical feature: Nevus of Ota is more commonly seen inAsian populations and in females. Most are noticed atbirth, following a trigeminal distribution, and notextending beyond the nasolabial fold (Fig. 115)(Franceschini and Dinulos 2015). Typically, these areunilateral, but some can be bilateral. Coloration of thesebirthmarks has been described as brown/violet, violet/blue, or blue/green. The most common ocular sign is irisheterochromia, and 2/3 of patients will have affectedsclera (Plateroti et al. 2017).

– Pathological manifestation: A biopsy of a nevus of Otawould reveal melanocytes in the dermis.

– Prognosis and treatment:No treatment is necessary for thepigmentation of the skin. Natural history of the nevus is toget darker pigmentation with age. Some may seek cosmeticprocedures to lighten the area, and few lasers have shown toimprove the pigmentation, although there are reports ofrecurrence after successful laser treatment. The use of cos-metic camouflage can also be used to hide the pigmentation.In patients with nevus of Ota, close follow-up by ophthal-mology is recommended to screen for glaucoma and uvealmelanoma. Other less common associations that havebeen reported are central nervous system problems andcutaneous malignant transformation.

– Differential diagnosis: Congenital melanocytic nevus,bathing trunk nevus, café-au-lait macules, and dermalmelanocytosis.

8.6 Café-Au-Lait Macules

– Definition: Café-au-lait macules refer to a common typeof birthmark that present as hyperpigmented macules orpatches. These are seen in 1.3% of newborns (Haveri andInamadar 2014) and in about 25% of all Caucasian school-aged children (Burwell et al. 1982). Having more thanthree café-au-lait macules with no underlying diagnosis isuncommon (0.3%) and more than six even more rare(<0.1%) (Whitehouse 1966).

– Clinical feature: Café-au-lait macules are round to oval,tan to brown, hairless, non-palpable areas in the skin(Fig. 116). These have uniform pigmentation, well-demarcated borders, and various sizes. They can be iso-lated findings or can be seen in association with systemicdiseases. More than three macules in a Caucasian or morethan five in an African-American may warrant furtherinvestigations to rule out other possible syndromes.

– Pathological manifestation: Isolated café-au-lait mac-ules present increased number of melanosomes with anormal number of epidermal melanocytes. In contrast,those café-au-lait macules associated with neurofibroma-tosis type 1 present an increase in epidermal melanocytes.

– Prognosis and treatment: No treatment is necessary forcafé-au-lait macules. Some lasers have been used to fadesome of the pigmentation, but this is more for cosmetics.Specific syndromic associations determine prognosis.Infants with six or more macules should be followedclosely as the majority will eventually meet criteria for

Fig. 116 Café-au-lait patch; uniform café-au-lait color on the abdo-men; if isolated it has no medical significance. (Taken by Drs. ElenaPope and Irene Lara-Corrales, The Hospital for Sick Children, Toronto,Canada)

Fig. 115 Nevus of Ota; well-defined dark blue-gray pigmentationaffecting the face and sclera. (Taken by Drs. Elena Pope and IreneLara-Corrales, The Hospital for Sick Children, Toronto, Canada)


neurofibromatosis type 1, particularly if the morphologicappearance of their café-au-lait macules is classic (Nunleyet al. 2009).

– Differential diagnosis: Congenital melanocytic nevi, post-inflammatory hyperpigmentation, pigmentary mosaicism,and other localized hyperpigmented lesions for isolatedcafé-au-lait macules and neurofibromatosis type 1, Legiussyndrome, McCune-Albright syndrome, RASopathies,Watson syndrome, Bloom syndrome, ataxia-telangiectasiasyndrome, Russell-Silver syndrome, tuberous sclerosis,Gaucher disease, constitutional mismatch repair deficiencysyndrome, piebaldism, PTEN hamartoma syndromes, andFanconi anemia for multiple café-au-lait macules.

8.7 Mosaic Pigmentary Disorders

– Definition: Pigmentary mosaicism refers to a group ofpigmentation (hypo- and hyperpigmentation) patterns thatare caused by genetic heterogeneity. A variety of disordersfit into the category of mosaic hypopigmentation includinghypomelanosis of Ito and nevus depigmentosus, while thehyperpigmentation includes conditions previously describedas linear and whorled hyperpigmentation, McCune-Albrightsyndrome, segmental neurofibromatosis, segmental pigmen-tary disorders, etc. (Lombillo and Sybert 2005).

– Clinical features: This disorder is characterized by hypo-pigmentation or hyperpigmentation in whorls and streaksthat follow Blaschko’s lines (Figs. 117 and 118). They canbe unilateral or bilateral, localized, or generalized, affecting any body part. There is no palpable component

(Molho-Pessach and Schaffer 2011).– Pathological manifestation: Hyperpigmented lesions

demonstrate increased basal cell hyperpigmentation dueto increased melanocytes. Hypopigmented lesions showreduction of melanosomes both in the melanocytes andkeratinocytes (Devillers et al. 2011).

– Prognosis and treatment: The prognosis is dependent onthe associated abnormalities as extensive lesions may haveother ectodermal structures that are affected. The pigmenta-tion is permanent and may cause psychological impairment.

– Differential diagnosis: Melanocytic nevi, urticariapigmentosa, post-inflammatory hyperpigmentation, caf-é-au-lait macules, and incontinentia pigmenti for hyper-pigmentary disorders and vitiligo, post-inflammatoryhypopigmentation, incontinentia pigmenti, tuberous scle-rosis, nevus depigmentosus, and nevus anemicus forhypopigmentary disorders.

Fig. 118 Pigmentary mosaicism hyperpigmented type, generalized.(Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital forSick Children, Toronto, Canada)

Fig. 117 Pigmentary mosaicism (hypopigmentation); irregular patchesof hypopigmentation in a Blaschko’s line distribution. (Taken by Drs.Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children,Toronto, Canada)

44 E. Pope et al.

9 Vascular Anomalies

9.1 Vascular Stains (Nevus Simplex, Angel’sKiss, Stork Bite, or CapillaryMalformation)

– Definition: Nevus simplex is a common birthmark affect-ing over 80% of newborns. It is typically seen on theforehead (in “V” shape), glabella, upper eyelids, and occi-put. Less frequently, other areas such as the tip of the nose,philtrum, and lumbosacral area may also be affected(Rozas-Muñoz et al. 2016).

– Clinical feature: Nevus simplex presents as pink to redflat discoloration with irregular borders (Figs. 119 and120). The lesion completely or partially blanches withpressure and increases with extreme temperatures orValsalva maneuvers. It can be differentiated from otherbirthmarks on the typical location, limited surface area,lack of associated features, and fading over the ensuingyears (Juern et al. 2010).

– Pathological manifestation: Pathology shows ectaticcapillaries.

– Prognosis and treatment: Most nevus simplex, particu-larly the facial lesions, fade over time. In contrast, occipital,scalp, and lower trunk areas tend to persist. Persistence ofthe facial lesions can be seen in the context of a familialpredisposition or if associated with syndromes such asBeckwith-Wiedemann, macrocephaly-capillary malforma-tion syndrome, Nova syndrome, etc. Laser treatment maybe offered for persistent lesions (Juern et al. 2010).

– Differential diagnosis: Port-wine stains, other vascularmalformations, and hemangiomas.

9.2 Vascular Tumors (See Sect. 6.4)

9.3 Vascular Malformations (See Sect. 6.10)

9.4 Cutis Marmorata TelangiectaticaCongenita

– Definition: Cutis marmorata telangiectatica congenita isan uncommon vascular anomaly characterized by persis-tent reticulated discoloration of the skin. The diagnostic ismade on meeting all major criteria (congenital reticulatederythema, absence of venectasia, and lack of response to

Fig. 119 Nevus simplex face; typical location in the central forehead,eyelids and philtrum of ill-defined red patches that blanch to pressure.(Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospital forSick Children, Toronto, Canada)

Fig. 120 Nevus simplex occiput; well-defined, non-blanchable redpatch. (Taken by Drs. Elena Pope and Irene Lara-Corrales, The Hospitalfor Sick Children, Toronto, Canada)

Fig. 121 Cutis marmorata of leg; violaceous vascular pattern withreticular configuration and areas of atrophy, crusting. (Taken by Drs.Elena Pope and Irene Lara-Corrales, The Hospital for Sick Children,Toronto, Canada)


rewarming) and two or more of the minor criteria (fadingof the color within the first 2 years, telangiectasias, port-wine stain, ulceration, atrophy of the affected areas)(Kienast and Hoeger 2009).

– Clinical feature: Cutis marmorata telangiectaticacongenita can be localized or generalized. The classicalfeatures are reticulated flat or depressed patches with deepviolaceous color that are not blanching to pressure(Figs. 121, 122, and 123). Additional features are promi-nent veins, various degrees of skin atrophy, ulceration, andtelangiectasias. The affected body area may be hypo-trophic. Approximately 50% of affected infants have alimb length discrepancy. Skeletal changes and glaucomaare associated anomalies (Memarzadeh et al. 2014).

– Pathological manifestation: Pathology shows dilatedcapillaries and veins in the dermis.

– Prognosis and treatment: Prognosis is dependent on theassociated anomalies. Because of the risk of ocular anom-alies, regular ophthalmological follow-up isrecommended. Although color may fade overtime, theabnormality is persistent into adulthood and exacerbatedby ambient temperature changes. Laser treatment offerslittle benefit.

– Differential diagnosis: Physiologic cutis marmorata,macrocephaly-capillary malformation syndrome, diffusecapillary malformation with overgrowth, reticulated cap-illary malformation, and healed arterial injuries.

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Neonate Dermatology · 2020-01-06 · Section of Pediatric Dermatology; The Hospital for Sick...

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