Neonatal Dermatology — Approach & Transient Eruptions

• A wide variety of conditions can cause vesicles, pustules, bullae, erosions, and ulcerations during the newborn period and infancy.
• Accurate and prompt diagnosis is important — some underlying disorders represent potentially LIFE-THREATENING INFECTIONS; conversely, many are benign and self-limited.
• Essential to develop a systematic approach to evaluation and treatment (algorithm).
• Most infectious etiologies are also covered in Chapters 74–82.

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• Primarily EOSINOPHILS:
• Widespread / waxing & waning → likely ERYTHEMA TOXICUM NEONATORUM
• Linear streaks → likely INCONTINENTIA PIGMENTI
• Mainly on scalp with pruritus → consider EOSINOPHILIC PUSTULAR FOLLICULITIS
• Primarily NEUTROPHILS, with NEGATIVE Gram stain and NEGATIVE KOH:
• Widespread superficial pustules present AT BIRTH → likely TRANSIENT NEONATAL PUSTULAR MELANOSIS
• Localized to hands and feet with pruritus → consider ACROPUSTULOSIS OF INFANCY (typically in infants ≥3–4 weeks of age)
• OTHER cells:
• Large histiocytes with RENIFORM nuclei → likely LANGERHANS CELL HISTIOCYTOSIS → skin biopsy to confirm
• Immature MYELOID cells, especially if high WBC and Down syndrome → consider TRANSIENT MYELOPROLIFERATIVE DISORDER

• + Bacteria → BACTERIAL INFECTION (e.g. staphylococcal)
• Bacterial culture of skin and additional sites as indicated
• Begin empiric therapy based on Gram stain findings and clinical context

• + Pseudohyphae & budding yeast → CANDIDIASIS, congenital or neonatal
• Culture skin and other relevant sites (e.g. mouth, perianal area)
• For congenital candidiasis: culture BLOOD, CSF, and URINE if premature with birth weight <1000 g, and as indicated if signs of systemic infection
• Begin antifungal treatment (topical, oral, IV) depending on clinical context

• + MULTINUCLEATED GIANT CELLS → intrauterine/neonatal HSV vs neonatal varicella
• OR negative but high clinical suspicion of HSV/varicella
• Confirmatory testing with DFA/PCR/culture
• If HSV suspected: PCR of CSF to EXCLUDE CNS INVOLVEMENT
• Begin treatment for HSV/varicella

• + Mites, eggs, feces → SCABIES
• Treat INFANT AND ENTIRE FAMILY with permethrin 5% cream

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• Staphylococcal diseases: pyoderma and bullous impetigo (Ch. 74) — few days to weeks or older | pustules, bullae, occasionally vesicles; superficial erosions with COLLARETTES of scale, crusts; furuncles | favors DIAPER and PERIUMBILICAL areas | Gram stain: Gram-positive cocci in CLUSTERS; bacterial culture | may occur in OUTBREAKS
• Group A streptococcal infection (Ch. 74) — few days to weeks or older | isolated pustules, honey-colored crusts; moist, foul-smelling, FIERY RED intertriginous erythema | any body region; may affect moist umbilical stump or skin folds | Gram stain: Gram-positive cocci in CHAINS; rapid antigen test, bacterial culture | occasionally cellulitis, meningitis, pneumonia
• Group B streptococcal infection — birth to first few days | vesicles, bullae, erosions, pustules, honey-colored crusts | any body region | Gram stain: Gram-positive cocci in chains; bacterial culture | pneumonia, bacteremia, meningitis
• Listeria monocytogenes infection (Ch. 74) — birth to first few HOURS | hemorrhagic pustules and petechiae | generalized, especially trunk and extremities | Gram stain: Gram-positive RODS; bacterial culture | sepsis, respiratory distress; history of MATERNAL FEVER and PREMATURE LABOR
• Haemophilus influenzae infection (Ch. 74) — birth to first few days | vesicles, crusted papules | any body region | Gram stain: Gram-negative BACILLI; bacterial culture | bacteremia, meningitis
• Pseudomonas aeruginosa infection (Ch. 74) — days to weeks or older | erythema, pustules, hemorrhagic bullae, necrotic ulcerations | any region, especially anogenital area | Gram stain: Gram-negative rods; bacterial culture | prematurity, low birth weight, immunodeficiency
• Congenital candidiasis — birth to first few days | erythema, small papules and pustules, fine scaling; "BURN-LIKE" if extremely premature | any region; PALMS/SOLES often involved; nails may be affected | KOH: budding yeast; fungal culture; PLACENTAL/UMBILICAL CORD lesions may be present | prematurity, foreign body in cervix/uterus are risk factors; ASCENDING IN UTERO infection
• Neonatal candidiasis — 1–2 weeks of age | beefy red patches with scale, SATELLITE pustules and papules | diaper area, other intertriginous zones, face | KOH: budding yeast, pseudohyphae; fungal culture | usually otherwise healthy; acquisition during delivery or postnatally; oral thrush
• Aspergillus infection (Ch. 77) — few days to weeks | pustules (often CLUSTERED) rapidly evolve to NECROTIC ULCERS | any region, especially macerated skin in the diaper area and under adhesive tape/occlusive dressings | skin biopsy: SEPTATE HYPHAE; tissue fungal culture | extreme prematurity
• Neonatal HSV infection (Ch. 80) — birth to 2 weeks, usually AFTER 5 DAYS | vesicles, pustules, crusts, erosions | any region, especially scalp, torso; may involve mucosa | Tzanck preparation, PCR, DFA or immunoperoxidase slide test, viral culture | signs of sepsis, irritability, lethargy; MUST EXCLUDE herpes meningitis/encephalitis
• Intrauterine HSV infection — BIRTH | vesicles, pustules, widespread erosions, SCARS, areas of ABSENT SKIN | any body region | Tzanck, PCR, DFA or immunoperoxidase slide test, viral culture | low birth weight, MICROCEPHALY, CHORIORETINITIS; may MIMIC congenital erosive and vesicular dermatosis
• Neonatal varicella (Ch. 80) — birth to 2 weeks | vesicles on an erythematous base | generalized | Tzanck, PCR, DFA, viral culture | maternal primary varicella infection 7 DAYS BEFORE to 2 DAYS AFTER delivery
• Herpes zoster (Ch. 80) — typically 2 weeks or older | vesicles on an erythematous base | DERMATOMAL pattern | Tzanck, PCR, DFA, viral culture | maternal primary varicella during pregnancy or up to a few days after delivery, or neonatal varicella
• Scabies (Ch. 84) — typically 3–4 weeks or older | papules, nodules, crusted areas, vesicles, pustules, BURROWS | any region including head and neck; especially axillae, groin, palms/soles, and wrists | mineral oil preparation, dermoscopy | family members may have pruritus and similar lesions

• Erythema toxicum neonatorum — typically 24–48 hours but can be birth to 2 weeks | erythematous macules, papules, pustules > vesicles, wheals | any region, EXCEPT almost always SPARES PALMS/SOLES | clinical; Wright's stain: EOSINOPHILS | term infants >2500 g
• Transient neonatal pustular melanosis — BIRTH | pustules WITHOUT erythema; collarettes of scale; hyperpigmented macules | any region; most often forehead, neck, lower back, shins; may affect palms/soles | clinical; Wright's stain: NEUTROPHILS, occasional eosinophils, cellular debris | term infants; MORE COMMON in infants of AFRICAN DESCENT
• Miliaria crystallina (Ch. 39) — birth to early infancy | fragile vesicles WITHOUT erythema | forehead, upper trunk, arms most common | clinical | sometimes history of overheating or fever
• Miliaria rubra (Ch. 39) — typically ≥1 week | erythematous papules with superimposed pustules | forehead, neck, upper trunk; OCCLUDED areas most common | clinical; Wright's stain: variable inflammatory cells but NOT prominent eosinophils | sometimes history of overheating or fever
• Neonatal cephalic pustulosis (neonatal "acne") — ~5 days to 3 weeks | papules and pustules on erythematous base | cheeks, forehead, chin, eyelids; less commonly neck, upper chest, scalp | clinical; Giemsa stain: YEAST FORMS, neutrophils | otherwise well

• Acropustulosis of infancy — typically 3–6 months, occasionally birth to weeks | vesicles and pustules | hands and feet; occasionally scalp, trunk | clinical; assess for scabies infestation; skin biopsy: intraepidermal vesicle/pustule with neutrophils and occasionally eosinophils | SEVERE PRURITUS; lesions recur in CROPS; subset with PRIOR SCABIES
• Eosinophilic pustular folliculitis of infancy — birth to 14 months, MEAN 6 months | papules and pustules | scalp > face > trunk, extremities | skin biopsy: dense mixed infiltrate with EOSINOPHILS, often but NOT INVARIABLY centered on hair follicles | pruritus; lesions recur in crops; often PERIPHERAL EOSINOPHILIA; neonatal eosinophilic pustulosis variant favors the FACE in PREMATURE BOYS
• Congenital and neonatal Langerhans cell histiocytosis (Ch. 91) — birth to weeks | vesicles, crusts, papules, nodules, petechiae | any body region, especially flexural sites, palms/soles, scalp | skin biopsy: S100+/CD1a+ histiocytes with RENIFORM nuclei, focal invasion of epidermis | occasional mucosal or extracutaneous involvement; pure cutaneous form often resolves spontaneously, but later cutaneous and systemic RELAPSES possible
• Incontinentia pigmenti (Ch. 62) — birth to weeks | vesicles, hyperkeratotic papules along the LINES OF BLASCHKO | vesicular lesions most common on the extremities | skin biopsy: EOSINOPHILIC SPONGIOSIS with NECROTIC KERATINOCYTES; genetic analysis (IKBKG/NEMO) | ocular, CNS, and dental involvement common but often NOT evident at birth; X-LINKED DOMINANT, patients usually FEMALE
• Autosomal dominant hyper-IgE syndrome (Ch. 60) — birth to weeks | single and grouped vesicles or papulopustules | face, scalp, upper trunk, axillae, diaper area | skin biopsy: intraepidermal vesicle with eosinophils, eosinophilic folliculitis; genetic analysis (STAT3) | eosinophilia with VARIABLY elevated IgE levels; abscesses, pneumonias, and pneumatoceles often develop AFTER the neonatal period
• Vesiculopustular eruption of transient myeloproliferative disorder in Down syndrome — days to weeks | vesicles and pustules | face > trunk, extremities, sites of ADHESIVE DRESSINGS, MINOR TRAUMA | intraepidermal spongiotic vesiculopustules, infiltrate containing IMMATURE MYELOID CELLS | trisomy 21 or MOSAICISM for trisomy 21; severe leukocytosis with immature myeloid cells; INCREASED RISK OF MYELOID LEUKEMIA
• Erosive pustular dermatosis of the scalp — weeks to months | pustules, erythema with scale-crust, erosions; alopecia and scarring | "HALO SCALP RING" pattern, VERTEX of scalp | clinical, skin biopsy: alopecia, scarring, mixed dermal infiltrate | prolonged labor and delivery, NECROTIC CAPUT SUCCEDANEUM at birth
• Neonatal Behçet disease (Ch. 26) — first week | vesiculopustular, purpuric and necrotic skin lesions; oral and genital ulcers | lesions favor hands and feet as well as oral and genital mucosae | clinical | MATERNAL history of Behçet disease; diarrhea, vasculitis
• Pustular psoriasis, including deficiency of interleukin-36 receptor antagonist (DITRA; AR) and CARD14-mediated pustular psoriasis (CAMPS; AD) (Chs 8 & 45) — weeks to months or older | pustules and PUSTULAR LAKES within areas of erythema | often generalized with ERYTHRODERMA; pustules in any region, especially palms/soles | skin biopsy: SPONGIFORM PUSTULES and microabscesses within the epidermis, parakeratosis, dilated dermal capillaries; genetic analysis (IL36RN, CARD14) | occasional fever; often RESISTANT to therapy, although DITRA often responds to IL-36 and IL-17 inhibitors
• Deficiency of interleukin-1 receptor antagonist (DIRA) (Ch. 45) — birth to weeks | pustules within areas of erythema | often generalized with erythroderma; ORAL lesions | skin biopsy: neutrophilic microabscesses within ACANTHOTIC epidermis, parakeratosis, dilated dermal capillaries; genetic analysis (IL1RN) | STERILE OSTEOLYTIC or HYPERPLASTIC BONE LESIONS, neonatal distress, DRAMATIC RESPONSE TO IL-1 ANTAGONISTS
• Perforating neutrophilic and granulomatous dermatitis associated with immunodeficiency — birth to weeks | papules evolve into vesicles, pustules, crusts, and ulcers | varies: face, extremities, perineum | skin biopsy: granulomas, neutrophilic infiltrate, TRANSEPIDERMAL ELIMINATION of degenerated collagen and debris through HAIR FOLLICLES | primary immunodeficiencies, including APLAID (autoinflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation)

• Additional etiologies: irritant contact dermatitis, dermatophyte infection, Sweet syndrome, and intrauterine coxsackievirus or Chikungunya virus infection.
• The vesicular eruption of LIPOID PROTEINOSIS tends to develop AFTER 1 year of age (see Ch. 48).

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• Staphylococcal scalded skin syndrome (Ch. 74) — few days to weeks; RARELY congenital | erythematous patches, fragile bullae, superficial erosions, PEELING IN SHEETS | generalized with PERIORIFICIAL and INTERTRIGINOUS accentuation | biopsy: epidermal separation at the GRANULAR CELL LAYER; culture positive ONLY at primary site(s) of infection (TOXIN-MEDIATED) | irritability, temperature instability; high risk of secondary sepsis, fluid/electrolyte abnormalities
• Group B streptococcal infection — see Table 34.1
• Pseudomonas aeruginosa infection — see Table 34.1
• Congenital syphilis (Ch. 82) — birth to first few days | bullae or erosions; erythema and desquamation | any region, especially perioral, palms/soles | DARKFIELD examination of serous exudates, DFA; serologic studies (treponemal and non-treponemal) | SNUFFLES, hepatosplenomegaly, PERIOSTITIS with PSEUDOPARALYSIS
• "Invasive fungal dermatitis" due to candidiasis > other fungi in very-low-birth-weight premature newborns — birth to 2 weeks | "BURN-LIKE" erythema with desquamation and erosions; intertriginous maceration | any region | KOH: budding yeast; fungal culture; placental/umbilical cord lesions may be present | risk factors: birth weight <1000 g, VAGINAL DELIVERY, systemic corticosteroid administration, prolonged hyperglycemia; HIGH RISK of disseminated systemic infection
• Aspergillus infection — see Table 34.1
• Zygomycosis, trichosporonosis (Ch. 77) — days to weeks | generalized peeling and skin breakdown; cellulitis evolving into NECROTIC ULCER | any body region | skin biopsy and tissue fungal culture | extreme prematurity
• Intrauterine HSV infection — see Table 34.1
• Congenital (fetal) varicella syndrome (Ch. 80) — BIRTH | erosions, ulcers, scarring, APLASIA CUTIS CONGENITA | any region, especially extremities; may have DERMATOMAL pattern | variably positive Tzanck, PCR, DFA, viral culture | maternal varicella in the FIRST or EARLY SECOND TRIMESTER; LIMB ATROPHY, CNS/eye abnormalities

• Sucking blisters — BIRTH | flaccid bulla or LINEAR erosion, most often SOLITARY | radial forearm, wrist, hand, fingers, occasionally foot | clinical | due to sucking on affected areas IN UTERO
• Irritant contact dermatitis — first few days to weeks or older | glazed erythema, vesiculation, PUNCHED-OUT erosions | diaper area, especially on CONVEX surfaces | usually clinical | severe form = JACQUET EROSIVE DIAPER DERMATITIS
• Perinatal trauma/iatrogenic injury — birth or neonatal period | erosions, ulcerations, scars, atrophic lesions | depends on cause of trauma | usually clinical | perinatal history of fetal scalp electrode monitor, prolonged labor and/or vacuum or forceps delivery, history of amniocentesis, etc.
• Perinatal gangrene of the buttock — days | sudden-onset erythema and CYANOSIS, then GANGRENOUS ULCERS | buttocks | clinical | umbilical artery catheterization in some cases

• Erosions overlying large congenital melanocytic nevi (Ch. 112) — birth to first few days | erosions, ulcerations | superimposed on the congenital melanocytic nevus, most often on the BACK | clinical, skin biopsy to EXCLUDE MELANOMA if persistent or other unusual features | neurocutaneous melanosis present in a subset
• Ulcerated infantile hemangioma (Ch. 103) — birth to first few weeks or months | ulcer, often with a bright red or pale, VASOCONSTRICTED border | any site, but diaper area and lip most common | clinical | cause often NOT clinically apparent until the hemangioma begins to PROLIFERATE
• Aplasia cutis congenita (Ch. 64) — BIRTH | "BULLOUS" form: round/oval, sharply demarcated with overlying MEMBRANE; other types with raw, full-thickness ulcer; scar | scalp (especially VERTEX) or face most common; other sites depending on etiology (e.g. shins in BART SYNDROME) | usually clinical; imaging studies to evaluate underlying bone, CNS | possible associations: CNS defects, SAGITTAL SINUS THROMBOSIS, TRISOMY 13, limb-reduction abnormalities
• Linear porokeratosis, porokeratotic eccrine ostial and dermal duct nevus (PEODDN) (Chs 62, 109, 111) — birth or weeks to years later | occasionally eroded at birth; usually erythema and KERATOTIC BORDER or (in PEODDN) SPINES | often extremities, but any site | skin biopsy: CORNOID LAMELLA (may NOT be evident in the newborn period) | risk of SQUAMOUS CELL CARCINOMA; MOSAIC GJB2 mutations in PEODDN

• Mastocytosis (Ch. 118) — birth to weeks or months | discrete lesions ("maculopapular", mastocytoma): papules, plaques or nodules with intermittent superimposed wheals, bullae, erosions; often hyperpigmented. DIFFUSE: blistering and erosions superimposed on infiltrated skin with "PEAU D'ORANGE" appearance | any body region | positive DARIER SIGN; skin biopsy: increased mast cells in dermis | variably present: flushing, irritability, diarrhea, abdominal pain
• Epidermolysis bullosa (Ch. 32) — birth to first few days or older | mechanically induced blisters and erosions; depending on type: mucosal erosions, aplasia cutis congenita of ANTERIOR LEGS, scarring, milia, nail dystrophy | widespread or limited; most often extremities, especially hands/feet | biopsy of INDUCED blister for immunofluorescence antigen mapping ± electron microscopy; genetic analysis | difficulty feeding, failure to thrive; occasionally ocular, respiratory tract or GI (e.g. PYLORIC ATRESIA) involvement; anemia
• Kindler syndrome (Ch. 32) — birth to weeks or older | trauma-induced blisters and erosions; PROGRESSIVE POIKILODERMA | bullae most common in ACRAL sites; poikiloderma widespread with SKIP AREAS | skin biopsy: immunostaining with anti-kindlin-1 antibody, genetic analysis (FERMT1) | photosensitivity, gingivitis, colitis, mucosal stenoses (esophageal, urethral), acquired syndactyly (toes, proximal fingers); AR inheritance
• Epidermolytic ichthyosis (Ch. 57) — BIRTH | erythroderma with blisters and erosions | generalized | skin biopsy: EPIDERMOLYTIC HYPERKERATOSIS; genetic analysis (KRT1, KRT10) | risk of sepsis, fluid and electrolyte imbalances; AD inheritance
• Maternal autoimmune bullous disease — BIRTH | depends on type of maternal disease: tense or flaccid bullae, erosions | variable, often widespread | skin biopsy with DIF usually diagnostic | maternal history of blistering disease, but occasionally INACTIVE during pregnancy
• Bullous pemphigoid (Ch. 30) — usually ≥2 months of age | tense bullae | favor HANDS AND FEET but may be generalized | skin biopsy: subepidermal bullae with EOSINOPHILS; DIF: LINEAR IgG at DEJ
• Linear IgA bullous dermatosis (Ch. 31) — rarely at birth, usually later infancy or childhood | tense blisters often forming ROSETTE or SAUSAGE shapes | widespread but often concentrated in the GIRDLE area; usually SPARES MUCOSA | skin biopsy: subepidermal bullae with NEUTROPHILS; DIF: LINEAR IgA at DEJ
• Neonatal lupus (Ch. 41) — birth (~20%) to weeks or months | congenital erosions/ulcers, crusting, rarely bullae, as well as classic ANNULAR erythematous plaques; atrophy, scarring, background of LIVEDO RETICULARIS | FACE favored, especially the PERIORBITAL area, but can be more widespread | skin biopsy: epidermal atrophy, VACUOLAR INTERFACE dermatitis, variable mucin | mother and infant with antibodies to SSA/Ro, SSB/La, and/or U1RNP; variable HEART BLOCK, cardiomyopathy, hepatobiliary disease, cytopenias
• Toxic epidermal necrolysis (TEN) (Ch. 20) or TEN-like GVHD (Chs 52 & 60) — usually ≥6 weeks of age, EXCEPT for intrauterine GVHD | tender erythema, bullae, epidermal sloughing/erosions | often widespread, evolving rapidly over hours to days; MUCOSAL involvement | skin biopsy: subepidermal blister with epidermal necrosis (usually FULL THICKNESS) | typically in the setting of GRAM-NEGATIVE SEPSIS or due to maternofetal or transfusion-associated GVHD in infants with SEVERE COMBINED IMMUNODEFICIENCY
• Intrauterine epidermal necrosis — BIRTH | widespread erosions and ulcerations WITHOUT vesicles or pustules | generalized, SPARES mucous membranes | skin biopsy: epidermal necrosis and CALCIFICATION of PILOSEBACEOUS UNITS | prematurity, brain infarcts, cardiomegaly, renal tubular necrosis; RAPID MORTALITY
• Congenital erosive and vesicular dermatosis — BIRTH | erosions, vesicles, crusts, "scalded skin" | generalized with relative SPARING of face, palms/soles | clinical diagnosis, often retrospective; skin biopsy (nonspecific): epidermal necrosis, neutrophils or mixed infiltrate; EXCLUDE HSV via PCR | prematurity; heals with SUPPLE RETICULATED SCARRING; CNS/developmental abnormalities
• Pyoderma gangrenosum (Ch. 26) — rare reports of congenital or neonatal onset | sharply demarcated ulcerations with UNDERMINED borders | any site, especially groin and buttocks | clinical; exclusion of other etiologies; skin biopsy: infiltration of neutrophils WITHOUT primary vasculitis or infection | associations include inflammatory bowel disease, chronic recurrent multifocal osteomyelitis; consider immunodeficiency and autoinflammatory syndromes
• Acrodermatitis enteropathica\* (Ch. 51) — weeks to months | sharply demarcated, ERODED erythematous plaques with scale-crust; occasionally intact vesicles/bullae | PERIORIFICIAL (around mouth, nose, eyes, anus, genitalia), neck folds, hands/feet | LOW serum ZINC and ALKALINE PHOSPHATASE levels | irritability, diarrhea, failure to thrive; onset classically AFTER WEANING if breastfed; acquired zinc deficiency: low maternal breast milk zinc or prematurity; genetic form AR (SLC39A4)
• Methylmalonic acidemia, other organic acidemias/aminoacidopathies\* — days to weeks | erythema with or without erosions | periorificial or more widespread | urine organic acid analysis; plasma ISOLEUCINE level (if restricted diet); often included in newborn screening; genetic analysis | lethargy, hypotonia, neutropenia, metabolic acidosis; skin findings may result from THERAPEUTIC RESTRICTIONS of dietary amino acids
• Restrictive dermopathy — BIRTH | RIGID TENSE skin with LINEAR erosions, tears | generalized; skin tears most common in FLEXURAL CREASES | clinical; distinguish from NEU–LAXOVA syndrome (intrauterine growth retardation, microcephaly, abnormal brain development, edema, parchment-like or ichthyosiform skin); genetic analysis (ZMPSTE24 > LMNA) | joint contractures, micrognathia, FIXED FACIAL EXPRESSION, restrictive pulmonary disease, EARLY MORTALITY
• Focal dermal hypoplasia (Ch. 62) — BIRTH | occasional blisters, but more often HYPOPLASIA or APLASIA of skin in LINEAR and WHORLED pattern; also FAT "HERNIATION", telangiectasias | any body region | clinical; skin biopsy: dermal hypoplasia with FAT ABUTTING EPIDERMIS; genetic analysis (PORCN) | skeletal, eye, and CNS abnormalities to varying degrees
• Absent dermal ridges and congenital milia (Basan syndrome) (Ch. 64) — BIRTH | bullae, ABSENT DERMAL RIDGE PATTERNS, multiple milia | fingers, plantar surface of feet | clinical; genetic analysis (SMARCAD1) | AD inheritance
• Porphyrias (Ch. 49) — days to months | photosensitive erythema, blistering, erosions, scarring | sun-exposed areas, or more generalized if PHOTOTHERAPY for hyperbilirubinemia | transient form: elevated PLASMA porphyrins; heritable forms: elevated urine, fecal, and/or plasma porphyrins ± PINK/FLUORESCENT URINE | transient form usually related to HEMOLYTIC DISEASE; heritable forms rarely present with blistering in infancy, e.g. congenital erythropoietic porphyria
• Neonatal purpura fulminans — days | initially purpura or cellulitis-like areas evolving to necrotic bullae or ulcers | buttocks, extremities, trunk, and scalp | prolonged PT/PTT, LOW fibrinogen, ELEVATED FDPs, LOW protein C or S levels | related to sepsis or inherited protein C or S deficiency
• Ankyloblepharon–ectodermal dysplasia–clefting (AEC) syndrome (Ch. 63) — BIRTH | erythroderma, peeling skin, superficial erosions | generalized, with prominent SCALP involvement | clinical; genetic analysis (TP63) | ankyloblepharon, ectodermal dysplasia, cleft lip/palate

• \*An acrodermatitis enteropathica-LIKE eruption (periorificial or more widespread), often associated with EDEMA and HYPOALBUMINEMIA, can occur in infants (typically 3–5 months of age) with CYSTIC FIBROSIS as well as those with organic acidemias/aminoacidopathies (see Ch. 51).

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Synonyms: Erythema toxicum • Toxic erythema of the newborn

• Vesiculopustular eruption characterized by an EOSINOPHILIC infiltrate.
• Affects nearly HALF of full-term neonates and resolves spontaneously over a few days.
• Often involves the trunk as well as the face, proximal limbs, and buttocks.
• ALMOST ALWAYS SPARES THE PALMS AND SOLES.
• Small wheals, inflammatory papules, pustules, and/or vesicles surrounded by BLOTCHY ERYTHEMA.

• Originally described by Netlinger in 1472, known as "toxic erythema of the newborn"; renamed erythema toxicum neonatorum by LEINER in 1912.
• Occurs in approximately HALF of full-term neonates, possibly favoring those delivered VAGINALLY.
• Only rarely seen in premature infants or those weighing LESS THAN 2500 g.
• Most commonly observed in infants with Fitzpatrick types I–II skin — although this may relate to the difficulty in perceiving erythema in infants with darker skin — and may be more prevalent in MALES.

• Rarely presenting at birth; usually begins 24 to 48 hours after delivery, followed by a WAXING AND WANING course over the next few days.
• Onset may be as late as 1–2 weeks of age, but additional diagnoses need to be considered in these cases.
• FIVE distinct components may be present in various combinations: erythematous macules, wheals, small papules, vesicles, and pustules — usually measuring 1–2 mm.
• The characteristic central papule with a surrounding erythematous flare is reminiscent of a FLEA BITE.
• Mechanical irritation may precipitate new lesions.
• Most frequently affects the trunk, but can also involve the face, buttocks, and proximal extremities; almost always SPARES the palms and soles.
• Individual lesions RARELY PERSIST FOR MORE THAN A DAY.
• Asymptomatic and self-limited; requires NO therapy.

• Usually made on CLINICAL grounds.
• When necessary, numerous EOSINOPHILS via WRIGHT STAIN of pustular contents confirms the diagnosis.
• Peripheral eosinophilia is occasionally present.
• Histologically, pustules are INTRAFOLLICULAR, SUBCORNEAL, or INTRAEPIDERMAL, composed of eosinophils and occasional neutrophils; an eosinophilic infiltrate may also be present in the UPPER DERMIS.
• Pathogenesis is UNKNOWN — an inflammatory response to MICROBIAL COLONIZATION OF THE FOLLICLE in the first days of life has been postulated.

• Transient neonatal pustular melanosis (TNPM) — primarily NEUTROPHILIC, present AT BIRTH, usually affects infants with darkly pigmented skin, and resolves as pigmented macules lasting weeks to months; overlap between ETN and TNPM has been observed.
• Acropustulosis of infancy — an ACRAL, rather than truncal, eruption that usually appears after the neonatal period.
• Eosinophilic pustular folliculitis of infancy — favors the SCALP; lesions often become crusted and recur in crops over months to years.
• HSV infection — discrete vesicular lesions with progression to HEMORRHAGIC CRUSTING.
• Staphylococcus aureus infections — more well-developed superficial pustules or bullae that rapidly rupture, resulting in an erythematous base with a surrounding COLLARETTE.
• Congenital candidiasis — multiple tiny pustules and desquamation, with budding yeast and pseudohyphae on KOH.
• Both staphylococcal and candidal infections result in MORE PERSISTENT lesions that do NOT undergo the rapid spontaneous resolution characteristic of ETN.
• Miliaria rubra (prickly heat) — usually concentrated on the forehead and upper torso, with somewhat longer-lived lesions that LACK a prominent erythematous flare or eosinophilic infiltrate.

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Synonyms: Transient neonatal pustulosis • Lentigines neonatorum

• Develops in ~5% of newborns with darkly pigmented skin.
• Prominent SUPERFICIAL PUSTULES WITHOUT ERYTHEMA that rupture, leaving a collarette of scale and hyperpigmentation that may last several months.
• STERILE SUBCORNEAL NEUTROPHILIC infiltrate.
• Favors the forehead, chin, neck, back, and shins but may be widespread.

• Originally described in 1961 as "lentigines neonatorum"; the full spectrum was not recognized until 15 years later (1976).
• Most common in infants with darker skin phototypes; NO sexual predilection.
• Lesions are VIRTUALLY ALWAYS PRESENT AT BIRTH and have THREE different morphologies that can coexist or occur sequentially:
• At delivery: superficial, 2–10 mm vesiculopustules at the chin, forehead, nape of the neck, lower back, buttocks, and shins, and less often the remainder of the face, trunk, palms, and soles.
• These may go UNDETECTED — the fragile INTRA- and SUBCORNEAL pustules can be subtle or WIPED AWAY DURING THE FIRST BATH.
• Second phase: slightly hyperpigmented macules with FINE COLLARETTES OF SCALE at sites of ruptured and resolving pustules.
• Finally: residual BROWN MACULES may persist for SEVERAL MONTHS.
• The name "LENTIGINES" is a MISNOMER — these lesions result from POSTINFLAMMATORY HYPERPIGMENTATION.
• Sometimes only the brown macules are noted at birth, suggesting a previous pustular phase occurred IN UTERO.
• Less commonly, infants present at a few weeks of age with extensive pigmented macules but NO history of preceding pustules.

• Histologic examination is RARELY necessary.
• Early lesions: intra- or subcorneal pustules containing primarily NEUTROPHILS and occasionally some eosinophils.
• Pigmented macules show INCREASED MELANIN WITHIN BASAL KERATINOCYTES.
• Pathogenesis is UNKNOWN; differential diagnosis similar to ETN.
• NO treatment is necessary; reassure parents of the benign, self-limited nature.

• Postulated that TNPM is simply a VARIANT of ETN, based on overlapping clinical and histologic features and reports of the two coexisting in the same patient.
• The term "sterile transient neonatal pustulosis" has been proposed to encompass the ETN–TNPM spectrum.
• However, MOST AUTHORS consider TNPM and ETN to represent SEPARATE ENTITIES.

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• Caused by VIGOROUS SUCKING of the affected region IN UTERO.
• Common locations: radial forearm, wrist, hands, and fingers.
• May present with an intact bulla, erosion, callus, or superficial ulceration on a NON-INFLAMED base.
• Usually an ISOLATED finding without associated abnormalities.
• Resolves over days to weeks; therapy is supportive.

• Found in 1 of every 250 newborns, although they may be small and go unnoticed.
• Flaccid bullae occur on a non-inflamed base and rupture easily, leading to linear or round erosions.
• Lesions are usually 5–15 mm in diameter and may be unilateral or bilateral.
• Diagnosis usually straightforward — suggested by a non-inflammatory and, in most cases, SOLITARY lesion in a typical location in a HEALTHY infant.
• Lesions resolve in days to weeks WITHOUT treatment.

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Synonym: Infantile acropustulosis

• Onset usually between 3 and 6 months of age in the classic form.
• A POSTSCABETIC variant also occurs.
• PRURITIC ACRAL vesiculopustular eruption.
• Recurs in CROPS, typically every 3–4 weeks, with decreased frequency and severity over time; the classic form usually resolves completely by ~3 YEARS of age.
• Symptomatic therapy with POTENT TOPICAL CORTICOSTEROIDS and ORAL ANTIHISTAMINES.

• Uncommon, of UNKNOWN etiology; usually develops around 3–6 months of age, occasionally earlier.
• Affects all races but is MORE COMMON in BLACK infants and BOYS.
• An association with ATOPY has been observed.
• More commonly, the same clinical findings occur following SCABIES INFESTATION — particularly frequent in INTERNATIONAL ADOPTEES; referred to as "POSTSCABETIC ACROPUSTULOSIS" or, especially in younger patients, AI.
• Characterized by outbreaks of pruritic vesicles and pustules in ACRAL sites: in particular the palms, soles, dorsal aspects of the hands and feet, lateral fingers and toes, and less often wrists and ankles.
• Occasionally lesions also on the scalp, trunk, or proximal extremities.
• Vesiculopustules typically appear in crops LASTING 7–14 DAYS and RECUR EVERY 3–5 WEEKS.
• In both classic AI and the postscabetic variant, flares DECREASE in frequency and severity over time; spontaneous involution of classic AI usually occurs by 3 years of age.

• Smear of pustular contents: numerous NEUTROPHILS, occasional eosinophils, and NO bacteria or fungal elements.
• Histology (generally unnecessary): SUBCORNEAL pustules filled primarily with NEUTROPHILS; some mononuclear cells and eosinophils may be present.
• MAJOR CHALLENGE: distinguishing from ACTIVE SCABIES (see Ch. 84).
• LINEAR BURROWS are PATHOGNOMONIC of active scabies; genital or more widespread lesions and pruritic eruptions in FAMILY MEMBERS are also suggestive.
• Mineral oil examination of skin scrapings for mites, eggs, and scybala should be performed in ALL infants or toddlers with acral vesicles and pustules.
• Dermoscopy can be used for in vivo visualization of mites and to increase the efficiency of skin scrapings.
• In uncertain cases, EMPIRIC TREATMENT for scabies may be warranted.
• Other conditions with clinical overlap: dyshidrotic eczema and pustulosis palmaris et plantaris — both RARE in infancy.
• Congenital candidiasis is usually NOT limited to acral skin; TNPM is NOT pruritic, does NOT favor acral locations, and does NOT recur.

• Symptoms usually controlled with intermittent application of POTENT or SUPERPOTENT topical corticosteroids and oral antihistamines.

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Synonym: Bloch–Sulzberger syndrome

• X-LINKED DOMINANT multisystem disease, usually LETHAL IN MALE FETUSES.
• Cutaneous lesions characterized by FOUR PHASES: vesicular, verrucous, hyperpigmented, and hypopigmented/atrophic.
• Extracutaneous manifestations most commonly DENTAL, OPHTHALMOLOGIC, and NEUROLOGIC.

• Uncommon; presents within the first 2 weeks of life in 90% of patients.
• Lethal in male fetuses UNLESS they have X CHROMOSOME ANEUPLOIDY (e.g. Klinefelter syndrome) or GENOMIC MOSAICISM (see Ch. 62).
• Caused by mutations in IKBKG (inhibitor of NF-κB kinase regulatory subunit γ), also known as NEMO (NF-κB essential modulator).
• Its protein product confers PROTECTION AGAINST APOPTOSIS induced by the TUMOR NECROSIS FACTOR family of cytokines.

• 1st — VESICULAR phase: usually lasts 1–2 weeks, with intermittent recurrences for up to a YEAR and occasionally later in childhood in association with FEBRILE ILLNESSES.
• Streaks of vesicles most often develop on the EXTREMITIES and SCALP but can also appear on the trunk; the FACE is usually SPARED.
• 2nd — VERRUCOUS phase: hyperkeratotic linear plaques.
• 3rd — HYPERPIGMENTED phase: linear and whorled GRAYISH-BROWN hyperpigmentation, most often on the TRUNK; in some patients this represents the ONLY cutaneous feature.
• 4th — HYPOPIGMENTED/ATROPHIC phase: subtle atrophic, hypopigmented THIN STREAKS favoring the CALVES; may PERSIST INDEFINITELY.
• The first three phases typically resolve during infancy or childhood.
• Clinical stages can OVERLAP, occur IN UTERO, or occasionally be SKIPPED ENTIRELY.

• Patchy scarring alopecia (typically at the VERTEX), areas of WOOLLY HAIR, nail dystrophy, and ANHIDROSIS within atrophic linear streaks.
• Most common extracutaneous manifestations:
• (1) DENTAL abnormalities such as hypodontia and CONICAL TEETH
• (2) CNS involvement → seizures, delayed psychomotor development, or spastic paralysis
• (3) OCULAR disease — RETINAL VASCULAR abnormalities with potential for BLINDNESS
• During the vesicular phase, patients often have peripheral blood LEUKOCYTOSIS and EOSINOPHILIA.

• Skin biopsy is often helpful: vesicular stage shows EOSINOPHILIC SPONGIOSIS with SCATTERED or GROUPED NECROTIC KERATINOCYTES; a dermal infiltrate composed predominantly of EOSINOPHILS is also present.
• Cutaneous lesions generally do NOT require therapy.
• All affected infants should be referred for BASELINE and LONGITUDINAL OPHTHALMOLOGIC examinations, and should have periodic NEURODEVELOPMENTAL and DENTAL evaluations.
• Genetic testing is available.

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• Reported in neonates with trisomy 21 or MOSAICISM for trisomy 21.
• Begins during the first few days to weeks of life (RARELY beyond 1 month) in the setting of transient myeloproliferative disorder — a congenital LEUKEMOID REACTION due to somatic GATA1 mutations that affects ~10% of neonates with Down syndrome.
• Vesicles and pustules develop initially and most prominently on the FACE, but usually spread to involve the trunk and extremities.
• As a consequence of PATHERGY, lesions have a predilection for sites of MINOR TRAUMA or ADHESIVE DRESSINGS.
• Histology: intraepidermal SPONGIOTIC VESICULOPUSTULES with a perivascular infiltrate that includes IMMATURE MYELOID CELLS — which may be evident in a TZANCK SMEAR and are usually also present in the PERIPHERAL BLOOD.
• Skin lesions tend to resolve spontaneously within weeks to months as the leukemoid reaction subsides; however, affected patients are at INCREASED RISK for MYELOID LEUKEMIA during the first few years of life and should be followed by a pediatric oncologist.
• Because infants MOSAIC for trisomy 21 may NOT have phenotypic features of Down syndrome, an unexplained pustular eruption in a neonate accompanied by LEUKOCYTOSIS should prompt evaluation for transient myeloproliferative disorder and MOSAIC TRISOMY 21.

• ~40 cases reported since first described by Cohen and colleagues in 1985.
• At birth, the neonates — almost all PREMATURE — have widespread erosions, vesicles, crusting and "scalded skin"-like erythematous areas affecting UP TO 75% of the body surface area.
• Reported associated findings: collodion-like membrane, transparent areas of skin, LIVEDO RETICULARIS-like vascular patterns, and ulcerations.
• The FACE, PALMS, and SOLES are usually relatively SPARED.
• Lesions heal in 1 to 2 MONTHS with characteristic SUPPLE and RETICULATED SCARS that often cover large areas.
• Later findings: scarring alopecia of the scalp and eyelashes, scarring of the TONGUE, absent or hypoplastic nails, and HEAT INTOLERANCE with HYPOHIDROSIS; mild ongoing blistering is occasionally observed.
• Neurodevelopmental abnormalities, brain atrophy, hemiparesis, sensorineural hearing loss, and retinal scars have also been reported.
• Cause remains UNKNOWN, but an intrauterine infection has been suspected.
• CEVD is diagnosed after EXCLUSION of other etiologies; intrauterine HSV infection can MIMIC CEVD and likely accounted for a significant subset of reported cases, many of which predated widespread clinical use of HSV PCR.
• The extracutaneous findings of CEVD OVERLAP with those of congenital HSV infection, and recurrent HSV outbreaks during the first year of life were noted in 20% of reported CEVD cases.
• Biopsy — acute phase: epidermal necrosis, subepidermal vesiculation, or an eroded epidermis with a neutrophilic or mixed dermal infiltrate, and NO evidence of vasculitis or thrombosis.
• Biopsy — later course: scar formation with LOSS OF ECCRINE STRUCTURES.
• Differential diagnosis (besides HSV, confirmable via PCR): other intrauterine infections, epidermolysis bullosa, epidermolytic ichthyosis, acute intrauterine GVHD, and intrauterine epidermal necrosis.
• Infants with CEVD should be followed for evidence of DIMINISHED SWEATING and NEUROLOGIC DEFECTS.
• Treatment is SUPPORTIVE with meticulous wound care — no specific therapy is available.

• Rare disease characterized by RIGID, TENSE skin with erosions and LINEAR TEARS, most commonly in FLEXURAL CREASES.
• Results in a FETAL AKINESIA or HYPOKINESIA DEFORMATION SEQUENCE: multiple flexion joint contractures, dysmorphic facies with a FIXED FACIAL EXPRESSION, and POLYHYDRAMNIOS with reduced fetal movements.
• The latter results in PREMATURE DELIVERY, most often at 30–33 WEEKS' GESTATION.
• Other features: translucent skin with prominent vessels, micrognathia, sparse/absent eyelashes, NATAL TEETH, LARGE FONTANELLES, DYSPLASIA OF THE CLAVICLES, and POORLY EXPANDED LUNGS as a result of the restrictive skin changes.
• Most affected newborns DIE FROM RESTRICTIVE PULMONARY DISEASE WITHIN THE FIRST WEEK OF LIFE.
• Represents a LETHAL NEONATAL LAMINOPATHY, typically caused by either:
• Dominant DE NOVO mutations in LMNA (encodes nuclear lamin A/C proteins), or
• MORE COMMONLY, RECESSIVE NULL mutations in ZMPSTE24 (encodes a zinc metallopeptidase essential for lamin A processing) (see Ch. 63).

• Rare; characterized by the sudden onset of ERYTHEMA and CYANOSIS of the BUTTOCKS, followed by progressive development of GANGRENE and ULCERATION.
• Some cases associated with UMBILICAL ARTERY CATHETERIZATION; others were spontaneous.
• OCCLUSION or SPASM of the INTERNAL ILIAC ARTERY has been postulated as a potential cause.
• Considerations when evaluating a neonate with hemorrhagic bullae and gangrenous soft tissue infarction also include PURPURA FULMINANS due to congenital coagulopathies (e.g. PROTEIN C or S DEFICIENCY) or INFECTION.

• NEONATAL PERIOD: FIRST 4 WEEKS OF EXTRAUTERINE LIFE.
• INFANCY: FIRST 1 YEAR OF EXTRAUTERINE LIFE.
• PREMATURE (PRETERM): BORN BEFORE THE 37th WEEK OF GESTATION.
• FULL TERM: BORN IN WEEKS 37–42 OF GESTATION.
• POSTMATURE: BORN AFTER THE 42nd WEEK OF GESTATION.
• LOW BIRTH WEIGHT: BORN UNDER 2500 g.
• INTRAUTERINE GROWTH RETARDATION: BIRTH WEIGHT LOW FOR GESTATIONAL AGE (SMALL FOR DATES).

• FROM THE MOMENT OF BIRTH, THE SKIN OF A NEWBORN BEGINS A PERIOD OF ADAPTATION. DURING THIS PERIOD VARIOUS SKIN MANIFESTATIONS OCCUR THAT MAY BE TRANSIENT OR MARKERS OF UNDERLYING DISEASE.
• IN THE FIRST FEW HOURS OF LIFE NEWBORN SKIN UNDERGOES ADAPTATIVE CHANGES TO ACCOMMODATE THE TRANSITION FROM THE WET, ASEPTIC, THERMOREGULATED UTERINE ENVIRONMENT TO A DRY ATMOSPHERE WITH TEMPERATURE OSCILLATION AS WELL AS BEING SURROUNDED BY MICROORGANISMS.
• THE SKIN OF THE NEWBORN PERFORMS SEVERAL VITAL FUNCTIONS:

1. BEING A BARRIER TO WATER LOSS, LIGHT AND IRRITANTS.
2. INFECTION CONTROL AND IMMUNOSURVEILLANCE.
3. RESILIENCE TO MECHANICAL TRAUMA.
4. SENSATION AND TACTILE DISCRIMINATION.
5. THERMAL REGULATION.

• THE SKIN'S BARRIER FUNCTION IS MAINLY DUE TO THE STRATUM CORNEUM.
• HISTOLOGICAL ANALYSIS SUGGESTS THAT EPIDERMAL DEVELOPMENT BECOMES COMPLETELY NEUTRAL AT APPROXIMATELY 34 GESTATION WEEKS BUT WILL ONLY BECOME FUNCTIONAL IN THE FIRST WEEK OF LIFE.
• NEONATES BORN BEFORE 30 WEEKS HAVE REDUCED CORNIFIED LAYERS AND THEY ARE AT RISK OF INCREASED PERMEABILITY TO EXOGENOUS MATERIALS, ADDITIONAL SKIN DAMAGE, DELAYED BARRIER MATURATION AND INFECTION.
• THE THICKNESS OF THE PROTECTIVE EPIDERMAL BARRIER IS A POTENTIAL MARKER OF PREGNANCY DATING.
• TERM INFANTS HAVE A THICKER STRATUM CORNEUM THAN ADULTS AS THE EPIDERMIS IS NOT ADEQUATELY SLOUGHED IN UTERO, AS IT IS IN POSTNATAL LIFE.
• IT CAN TAKE ABOUT 2 WEEKS FOR A PRETERM INFANT TO DEVELOP SKIN THAT RESEMBLES THAT OF A TERM INFANT. THIS PROCESS CAN TAKE EVEN LONGER IN ULTRA LOW-BIRTH-WEIGHT INFANTS WHO ARE EXTREMELY PRETERM.
• THE PRETERM DERMIS IS DEFICIENT IN STRUCTURAL PROTEINS, AND HAS REDUCED MECHANICAL PROPERTIES AND INCREASED FRAGILITY.
• POST-TERM INFANTS ARE OFTEN OBSERVED TO HAVE SIGNIFICANT XEROSIS AND DESQUAMATION, PARTICULARLY IF THEY HAVE BEEN FOUND TO HAVE LOW AMOUNTS OF VERNIX AT BIRTH.
• AGE-RELATED TRANSEPIDERMAL WATER LOSS (TEWL) STUDIES INDICATE THAT INFANT SKIN BARRIER FUNCTION AT BIRTH OR VERY SOON THEREAFTER (WITHIN 2–4 WEEKS) IS IN THE SAME RANGE AS THAT OF HEALTHY ADULTS.

• TOXICITY RESULTING FROM PERCUTANEOUS ABSORPTION IN THE FULL-TERM NEONATE APPEARS LESS DEPENDENT ON IMPAIRED BARRIER FUNCTION BUT IS MORE OFTEN RELATED TO ONE OR MORE OF THE FOLLOWING:

1. THE GREATLY INCREASED RATIO OF SURFACE AREA TO VOLUME.
2. THE FREQUENT PRESENCE OF OCCLUSIVE CONDITIONS, SUCH AS EXIST UNDER WATERPROOF NAPPIES.
3. HIGH AMBIENT TEMPERATURES AND HUMIDITY.

• PERCUTANEOUS ABSORPTION IS INCREASED IN PRETERM INFANTS WHERE THERE IS EVIDENCE OF IMPAIRED BARRIER FUNCTION.
• ABSORPTION CORRELATES INVERSELY WITH GESTATIONAL AGE, BUT BARRIER FUNCTION APPEARS TO IMPROVE RAPIDLY AFTER BIRTH IN THE PRETERM INFANT AND WILL GENERALLY BE NORMAL BY THE END OF THE SECOND OR THIRD WEEK AFTER BIRTH.
• PRETERM NEWBORNS HAVE A VERY THIN EPIDERMIS AND A LESS DEVELOPED FUNCTIONAL BARRIER THAN FULL-TERM NEWBORNS.
• PRETERM NEONATES NURSED IN HUMIDIFIED INCUBATORS HAVE LOWER FLUID REQUIREMENTS, IMPROVED ELECTROLYTE BALANCE, HIGHER URINE OUTPUT AND INCREASED GROWTH VELOCITY.
• IN THE NEONATAL INTENSIVE CARE UNIT (NICU) THE FOLLOWING INTERVENTIONS HAVE BEEN SHOWN TO BE BENEFICIAL IN PRETERM NEONATES:
• SHORT-TERM APPLICATION OF NON-ADHESIVE POLYETHYLENE WRAPS WITHIN 10 MINUTES OF BIRTH.
• PLACEMENT IN HUMIDIFIED INCUBATORS.
• LONGER-TERM APPLICATION OF SEMIPERMEABLE, TRANSPARENT DRESSINGS.
• AIR-DRYING THE STUMP OF THE UMBILICAL CORD RATHER THAN CLEANSING WITH ANTISEPTICS.
• THE RISK OF TOXICITY VIA PERCUTANEOUS ABSORPTION IN THE NEONATE, PARTICULARLY IN PRETERM BABIES, IS HIGH.
• EVIDENCE FOR TOXICITY HAS BEEN REPORTED FOR: ANILINE DYES; HEXACHLOROPHENE AND RELATED ANTISEPTICS; ALCOHOL; AND CORTICOSTEROIDS.
• SUBSTANCES THAT SHOULD ALWAYS BE AVOIDED IN NEONATES AND ESPECIALLY IN PRETERM NEONATES: NEOMYCIN; BORIC ACID; RESORCINOL (IN CASTELLANI PAINT); γ-BENZENE HEXACHLORIDE; BENZYL ALCOHOL; UREA; AND SALICYLIC ACID.
• ANTISEPTICS SUCH AS CHLORHEXIDINE AND IODINE SHOULD BE USED WITH CAUTION AND ALCOHOL-BASED PRODUCTS SHOULD BE AVOIDED IN VIEW OF THE RISK OF 'CHEMICAL BURNS'.
• HOWEVER, LOW-DOSE (0.25%) AQUEOUS CHLORHEXIDINE APPLIED TO TERM BABIES HAS BEEN SHOWN TO DECREASE MORTALITY FROM SEPSIS IN A COMMUNITY-BASED STUDY OF 17 500 LOW-BIRTH-WEIGHT NEONATES FROM NEPAL, BUT NO DIFFERENCES WERE SEEN IN THOSE WITH BIRTH WEIGHTS OVER 2500 g.
• MULTIPLE STUDIES SHOW AN INCREASED RISK OF SEPSIS WITH THE APPLICATION OF PETROLATUM OINTMENT TO PRETERM NEONATES.
• SUNFLOWER SEED OIL HAS BEEN SHOWN TO REDUCE THE INCIDENCE OF NOSOCOMIAL INFECTIONS AND TO IMPROVE SKIN CONDITION IN STUDIES CONDUCTED IN BANGLADESH AND OTHER DEVELOPING COUNTRIES.
• THE USE OF VIRGIN COCONUT OIL HAS BEEN STUDIED IN 2294 PRETERM INFANTS AND WAS OBSERVED TO REDUCE THE INCIDENCE OF HYPOTHERMIA AND APNOEA. SKIN MATURITY WAS NOTED TO BE IMPROVED WITH A BETTER NEURODEVELOPMENTAL OUTCOME.
• NO DATA YET EXIST ON THE USE OF EMOLLIENTS IN PRETERM INFANTS WITH SEVERE SKIN DISEASE, SUCH AS NETHERTON SYNDROME OR HARLEQUIN ICHTHYOSIS, WHERE NOSOCOMIAL INFECTION IS A COMMON PROBLEM AND OFTEN LETHAL.
• TEWL IS GREATLY INCREASED IN PRETERM COMPARED WITH FULL-TERM BABIES. A RECENT STUDY ESTABLISHED NORMAL VALUES FOR TEWL IN EARLY LIFE USING DATA FROM THE CORK BASELINE BIRTH COHORT STUDY.
• THE RESULTING OUTWARD PASSAGE OF WATER CAN LEAD TO HIGH RATES OF HEAT LOSS BY EVAPORATION, WHICH MAY EVEN EXCEED THE BABY'S RESTING RATE OF HEAT PRODUCTION.
• THESE LOSSES CAN BE REDUCED BY INCREASING THE AMBIENT HUMIDITY (ALTHOUGH THIS LEADS TO AN INCREASED RISK OF INFECTION), BY COVERING THE CHILD WITH A PLASTIC BUBBLE BLANKET OR A PERSPEX SHIELD, OR BY APPLYING A LIPID BARRIER.
• IT IS POSSIBLE THAT IMMATURITY OF THE SKIN ALSO PREDISPOSES THE PREMATURE NEONATE TO PENETRATION OF THE SKIN BY MICROORGANISMS, LEADING TO SYSTEMIC INFECTION. THIS MAY BE THE REASON THAT THE PREMATURE INFANT WITH CONGENITAL CUTANEOUS CANDIDIASIS IS AT GREATER RISK OF DISSEMINATED CANDIDIASIS.
• THERE IS VERY LITTLE SCIENTIFIC EVIDENCE ON WHICH TO BASE RECOMMENDATIONS FOR PARENTS ON ROUTINE NEONATAL SKIN CARE IN TERMS OF CLEANSING AND/OR MOISTURISING, AND ADVICE VARIES CONSIDERABLY BETWEEN DOCTORS, HEALTH VISITORS AND MIDWIVES.
• A STUDY UNDERTAKEN IN THE USA SEVERAL YEARS AGO REVEALED THAT PARENTS HAD APPLIED OVER 48 DIFFERENT CHEMICALS IN OVER-THE-COUNTER PREPARATIONS TO THE SKIN OF THEIR 1-MONTH-OLD BABIES.
• A RECENT STUDY LOOKING AT CLEANSERS SUGGESTED THERE WAS NO DIFFERENCE BETWEEN USING PLAIN WATER AND A COMMERCIALLY AVAILABLE WASH PRODUCT FOR BABIES.
• THE SAME GROUP HAS ALSO SHOWN THAT OLIVE OIL (OFTEN USED IN NEONATAL UNITS OR FOR BABY MASSAGE) CAN DAMAGE THE SKIN BARRIER IN ADULTS SO PROBABLY SHOULD BE AVOIDED IN NEONATES.
• THE SUNFLOWER OIL USED IN THE LATTER STUDY DID NOT SHOW THE SAME DELETERIOUS EFFECT BUT SUNFLOWER OILS VARY CONSIDERABLY IN COMPOSITION AND SOME ARE INDEED HARMFUL. AS COMMERCIALLY AVAILABLE SUNFLOWER OILS ARE NOT 'PRODUCT LABELLED' THEY CANNOT BE RECOMMENDED FOR NEONATAL SKIN.
• BACTERIAL COLONISATION OF THE UMBILICAL STUMP MAY RESULT IN INVASIVE PATHOGENIC INFECTION AND REPRESENTS A MAJOR CAUSE OF NEONATAL MORBIDITY AND MORTALITY WORLDWIDE.
• SINCE 1998, THE WORLD HEALTH ORGANIZATION (WHO) HAS ADVOCATED THE USE OF DRY UMBILICAL CORD CARE IN HIGH-RESOURCE SETTINGS. THIS INCLUDES KEEPING THE CORD CLEAN AND EXPOSED TO AIR.
• IF IT DOES BECOME SOILED THE CORD SHOULD BE CLEANED WITH SOAP AND STERILE WATER OR CHLORHEXIDINE.
• A META-ANALYSIS PROVIDED NO EVIDENCE FOR ANTISEPTIC TREATMENT OF THE CORD WITH CHLORHEXIDINE.

• BY THE 28th WEEK OF GESTATION A FULL COMPLEMENT OF ANATOMICALLY NORMAL ECCRINE SWEAT GLANDS IS PRESENT.
• THESE APPEAR TO BE FUNCTIONALLY IMMATURE IN NEONATES BORN BEFORE THE 36th WEEK IN TERMS OF THEIR RESPONSES TO INTRADERMAL INJECTION OF ACETYLCHOLINE AND EPINEPHRINE (ADRENALINE), AND TO THERMAL STRESS.
• HOWEVER, RESPONSIVENESS USUALLY DEVELOPS IN SUCH BABIES BY 2 WEEKS AFTER BIRTH.
• NEONATES BORN AFTER THE 36th WEEK OF GESTATION SWEAT IN RESPONSE TO THERMAL STRESS FROM BIRTH, ALTHOUGH SUCH SWEATING IS INITIALLY RELATIVELY INEFFICIENT AS A THERMOREGULATORY MECHANISM.
• CARE MUST THEREFORE BE TAKEN NOT TO OVERHEAT ANY NEONATE, PARTICULARLY THE PRETERM NEONATE; ALTHOUGH SEVERE OVERHEATING LEADING TO HYPERPYREXIA IS PROBABLY RARE, LESSER DEGREES OF IATROGENIC OVERHEATING APPEAR TO BE COMMON AND MAY EVEN INDUCE APNOEIC ATTACKS.
• THE FOREHEAD APPEARS TO BE THE PRINCIPAL SITE OF THERMALLY INDUCED SWEATING IN THE NEONATE.
• THE PALMS AND SOLES, HOWEVER, ARE SITES OF 'EMOTIONAL' SWEATING, OCCURRING IN RESPONSE TO AROUSAL, WHICH APPEARS TO BE WELL DEVELOPED AT BIRTH IN FULL-TERM BUT NOT PRETERM NEONATES.
• SKIN CONDUCTANCE MEASUREMENTS (AS A MEASURE OF INCREASED SWEATING) MAY BE HELPFUL IN ASSESSING PAIN LEVELS IN NEONATES.

• THE SECRETIONS OF THE FETAL SEBACEOUS GLANDS MAKE A SIGNIFICANT CONTRIBUTION TO THE VERNIX CASEOSA.
• VERNIX CASEOSA ACTS AS A NATURALLY OCCURRING 'BARRIER CREAM' THAT ALSO CONTAINS ANTIMICROBIAL PEPTIDES AND IS FORMED FROM WEEK 24 OF GESTATION.
• THE PRESENCE OF VERNIX AT BIRTH IS ASSOCIATED WITH BETTER HYDRATION OF THE EPIDERMIS. ONE GROUP HAS EVEN STUDIED IT AS A 'NATURAL' BARRIER CREAM TO AID HEALING IN A CONTROLLED WOUND MODEL.
• SEBUM SECRETION RATES ARE HIGH IN NEONATES COMPARED WITH OLDER PREADOLESCENT CHILDREN, AND IT IS ASSUMED THAT THIS SEBACEOUS GLAND ACTIVITY REFLECTS STIMULATION BY PLACENTALLY TRANSFERRED MATERNAL ANDROGEN, PARTICULARLY BY DEHYDROEPIANDROSTERONE.
• SEBACEOUS GLAND ACTIVITY DECREASES FROM ABOUT THE END OF THE FIRST MONTH TO REACH A STABLE LEVEL BY THE END OF THE FIRST YEAR.

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• A VARIETY OF SKIN LESIONS COMMONLY SEEN IN THE NEWBORN ARE REGARDED AS 'PHYSIOLOGICAL'. THEIR FREQUENCY VARIES SOMEWHAT IN DIFFERENT RACIAL GROUPS.
• VERNIX CASEOSA:
• AT BIRTH THE SKIN IS COVERED WITH A WHITISH, GREASY FILM, THE VERNIX CASEOSA.
• AN ACIDIC LIPID MANTLE PRODUCED BY FETAL SEBACEOUS GLANDS, COMPOSED OF WATER (81%), LIPIDS (19%) AND PROTEIN (10%) NATURALLY ADHERED TO THE SKIN.
• VERNIX MAY COVER THE ENTIRE SKIN SURFACE, OR IT MAY BE PRESENT ONLY IN BODY FOLDS SUCH AS THE GROINS. IT USUALLY DRIES RAPIDLY AND STARTS TO FLAKE OFF WITHIN A FEW HOURS OF BIRTH.
• THE VERNIX ALSO CONTAINS ANTIMICROBIAL PEPTIDES SO IT MAY PLAY SOME ROLE IN KEEPING THE SKIN HYDRATED AND IN INNATE IMMUNITY.
• ITS COLOUR MAY REFLECT INTRAUTERINE PROBLEMS, SUCH AS HAEMOLYTIC DISEASE OF THE NEWBORN AND POSTMATURITY, BOTH OF WHICH RESULT IN GOLDEN YELLOW STAINING.
• FETAL DISTRESS IN UTERO MAY LEAD TO STAINING OF THE VERNIX BY THE BILE PIGMENTS PRESENT IN MECONIUM.
• PERIPHERAL CYANOSIS (ACROCYANOSIS):
• A FEATURE OF THE NEWBORN, PARTICULARLY THE FULL-TERM NEWBORN, AND IS USUALLY PARTICULARLY MARKED ON THE PALMS AND SOLES AND AROUND THE MOUTH.
• IN THE ABSENCE OF CYANOSIS OF WARM CENTRAL PARTS SUCH AS THE TONGUE, THIS MAY BE REGARDED AS NORMAL DURING THE FIRST 48 h OR SO.
• IT IS MADE MORE OBVIOUS BY HYPOTHERMIA, AND IS IMPROVED BY WARMING.
• ERYTHEMA NEONATORUM: A FEW HOURS AFTER BIRTH, MANY BABIES DEVELOP A STRIKING, GENERALISED HYPERAEMIA, WHICH FADES SPONTANEOUSLY WITHIN 24–48 h.
• HARLEQUIN COLOUR CHANGE:
• UP TO 15% OF NEONATES SHOW A VIVID COLOUR DIFFERENCE ALONG THE MIDLINE AT SOME TIME DURING THE FIRST WEEK OF LIFE.
• OCCURS WHEN THE BABY IS LYING ON ITS SIDE: THE UPPER HALF OF THE BODY IS PALE, THE LOWER HALF A DEEP RED COLOUR.
• THE DURATION OF THE ATTACK IS HIGHLY VARIABLE, BUT GENERALLY IS BETWEEN 30 s AND 20 min. IF THE BABY IS TURNED ON THE OTHER SIDE, THE COLOUR CHANGE MAY REVERSE.
• AN INDIVIDUAL NEONATE MAY HAVE ONLY A SINGLE EPISODE, OR IT MAY RECUR ON SEVERAL OCCASIONS.
• APPEARS TO HAVE NO PATHOLOGICAL SIGNIFICANCE IN THE GREAT MAJORITY OF CASES, AND IS CONSIDERED TO REFLECT IMMATURITY OF THE HYPOTHALAMIC CENTRES RESPONSIBLE FOR THE CONTROL OF PERIPHERAL VASCULAR TONE.
• IF IT PERSISTS BEYOND THE END OF THE FOURTH WEEK, IT MAY BE ASSOCIATED WITH HYPOXIA DUE TO CARDIOVASCULAR ANOMALIES.
• CUTIS MARMORATA:
• NEWBORN INFANTS WHO ARE SUBJECTED TO COOLING WILL SHOW DISTINCT MARBLING OF THE SKIN.
• ALTHOUGH THIS MORE OR LESS DISAPPEARS ON REWARMING, MANY NORMAL NEONATES DEMONSTRATE FAINT MARBLING, EVEN UNDER OPTIMAL ENVIRONMENTAL CONDITIONS.
• THE MARBLING COMPRISES A RETICULATE BLUE VASCULAR PATTERN. THIS RESPONSE IS A PHYSIOLOGICAL ONE, AND MAY BE SEEN THROUGHOUT INFANCY.
• CUTIS MARMORATA TELANGIECTATICA CONGENITA IS A DISTINCT VASCULAR DEVELOPMENTAL DISORDER, AND IS EASILY DISTINGUISHED AS IT IS FIXED (Chapter 71) AND MAY BE ASSOCIATED WITH A VARIETY OF OTHER ABNORMALITIES, FOR EXAMPLE OF LIMB GROWTH OR RENAL ANOMALIES.
• DESQUAMATION:
• RATHER SUPERFICIAL CUTANEOUS DESQUAMATION (PHYSIOLOGICAL SCALING OF THE NEWBORN) OCCURS IN UP TO 75% OF NORMAL NEONATES.
• USUALLY FIRST APPEARS AROUND THE ANKLES ON THE FIRST DAY OF LIFE, AND IS MORE OR LESS CONFINED TO THE HANDS AND FEET.
• IT MAY REMAIN LOCALISED OR MAY GRADUALLY BECOME WIDESPREAD, USUALLY REACHING ITS MAXIMUM EXTENT AND INTENSITY BY THE EIGHTH DAY.
• IT TENDS ALWAYS TO BE MORE SEVERE IN NEONATES WHO ARE SMALL FOR DATES, WHATEVER THEIR GESTATIONAL AGE.
• MILD VARIANTS OF ICHTHYOSIS SUCH AS ICHTHYOSIS VULGARIS MAY BE HARD TO DISTINGUISH FROM PRONOUNCED PHYSIOLOGICAL SCALING.
• X-LINKED HYPOHIDROTIC ECTODERMAL DYSPLASIA MAY PRESENT WITH SCALING OF THE SKIN IN THE NEONATAL PERIOD.
• SUCTION BLISTERS:
• SMALL BLISTERS OR EROSIONS MAY BE PRESENT IN 0.5% OF NEWBORNS.
• THEY TYPICALLY AFFECT THE BACK OF THEIR HANDS, FINGERS, ARMS AND LIPS AND ARE BELIEVED TO BE CAUSED BY VIGOROUS ORAL SUCTION IN UTERO; HENCE THE TERM SUCKING BLISTER.
• THE BLISTERS HEAL RAPIDLY WITHOUT SEQUELAE.
• NEONATAL OCCIPITAL ALOPECIA:
• THE SCALP HAIR IS SHED SYNCHRONOUSLY DURING THE FIFTH MONTH OF FETAL LIFE.
• AFTER REGROWING, THE HAIR THEN ENTERS A TELOGEN PHASE IN WAVE FROM FRONT TO BACK, STARTING ABOUT 12 WEEKS BEFORE TERM.
• AFTER SHEDDING OF THE TELOGEN HAIRS FROM THE FRONTAL AND PARIETAL AREAS, THE ROOTS AGAIN ENTER THE ANAGEN PHASE IN A SIMILAR WAVE FROM FRONT TO BACK.
• THE ROOTS IN THE OCCIPITAL AREA DO NOT ENTER TELOGEN UNTIL TERM, AND AS A RESULT ALOPECIA MAY APPEAR AT THIS SITE AT BIRTH OR WITHIN THE FIRST 2 MONTHS.
• TRAUMA FROM LYING ON THIS AREA MAY ALSO CONTRIBUTE.
• NEONATAL ALOPECIA HAS BEEN REPORTED TO OCCUR DUE TO BIRTH TRAUMA. TRICHOSCOPY ELUCIDATES PURPLE DOTS THAT CORRESPOND TO BLOOD EXTRAVASATION AND FOLLICULAR OSTIA.
• HAIR SHEDDING IN INFANCY:
• THERE APPEAR TO BE TWO PHASES OF HAIR LOSS AND REGROWTH FROM FRONT TO BACK DURING EARLY INFANCY, BUT BY THE END OF THE FIRST YEAR THE TYPICAL MOSAIC PATTERN OF HAIR GROWTH IS ESTABLISHED.
• IN SOME BABIES, THERE IS UNUSUALLY SYNCHRONOUS HAIR LOSS DURING THE NEONATAL PERIOD, RESULTING IN OBVIOUS DIFFUSE ALOPECIA (TELOGEN EFFLUVIUM OF THE NEWBORN), BUT, BY 6 MONTHS OF LIFE, MOST BABIES HAVE A FULL HEAD OF HAIR.
• AT THIS STAGE, THE HAIRLINE OFTEN EXTENDS TO THE LATERAL ENDS OF THE EYEBROWS, BUT THE TERMINAL HAIRS COMPRISING THIS EXTENSION GRADUALLY CONVERT TO VELLUS HAIRS DURING THE REMAINDER OF THE FIRST YEAR OF LIFE, CAUSING THE HAIRLINE TO RECEDE TO ITS CHARACTERISTIC CHILDHOOD POSITION.
• SEBACEOUS GLAND HYPERTROPHY / MILIA:
• SEBACEOUS GLAND HYPERPLASIA IS A PHYSIOLOGICAL EVENT IN THE NEWBORN, REFLECTING THE INFLUENCE OF MATERNAL ANDROGENS.
• VISIBLE TO THE NAKED EYE IN THE GREAT MAJORITY OF INFANTS AS MULTIPLE, UNIFORM, PINPOINT, YELLOWISH PAPULES THAT ARE MOST PROMINENT ON THE NOSE, CHEEKS, UPPER LIP AND FOREHEAD, BUT MAY ALSO BE VISIBLE ON THE UPPER TRUNK, ESPECIALLY THE AREOLAE, GENITALIA AND LIMBS.
• THE PHENOMENON IS ASSOCIATED IN ABOUT 40% OF INFANTS WITH MILIA, WHICH REPRESENT MINUTE FOLLICULAR EPIDERMAL CYSTS.
• THE NUMBERS OF MILIA MAY VARY FROM ONE OR TWO TO MANY HUNDREDS. THEY COMPRISE 1–3 mm DIAMETER, WHITE, GLOBULAR PAPULES, WHICH OCCUR AT THE SAME SITES AS SEBACEOUS GLAND HYPERPLASIA.
• RATHER LARGER AND USUALLY SINGLE MILIA, OFTEN TERMED PEARLS, ARE SEEN SOMETIMES ON THE AREOLAE, SCROTUM AND LABIA MAJORA.
• BOTH THE SEBACEOUS GLAND HYPERPLASIA AND THE MILIA TEND TO DISAPPEAR SPONTANEOUSLY DURING THE FIRST WEEKS OF LIFE, ALTHOUGH A FEW MAY PERSIST LONGER.
• MILIA THAT ARE EXCEPTIONALLY EXTENSIVE OR PERSISTENT, OR WHOSE DISTRIBUTION IS ATYPICAL, MAY BE FEATURES OF: THE ORO-FACIO-DIGITAL SYNDROME TYPE I (Chapters 65 and 66); MARIE–UNNA-TYPE CONGENITAL HYPOTRICHOSIS (Chapter 66); OR THE X-LINKED BAZEX–DUPRÉ–CHRISTOL SYNDROME, WHICH FEATURES HYPOTRICHOSIS AND MILIA (Chapter 140).
• 'MINIATURE PUBERTY' — THE INFLUENCE ON THE FETUS OF MATERNAL AND PLACENTAL HORMONES MAY GIVE RISE TO:
• AN ENLARGED CLITORIS.
• MUCOID VAGINAL DISCHARGE.
• ENLARGED WELL-DEVELOPED GENITALIA (BOYS AND GIRLS).
• HYPERTROPHY OF THE MAMMARY GLANDS (BOYS AND GIRLS), WHICH RESOLVES IN 2–4 WEEKS.
• DESQUAMATION OF THE HYPERPLASTIC VAGINAL EPITHELIUM (A FEW DAYS AFTER BIRTH).
• FRANK WITHDRAWAL BLEEDING, WHICH MAY OCCUR FROM THE UTERUS ON DAY 3/4, USUALLY LASTING FOR 2 OR 3 DAYS.
• LACTATION ('WITCH'S MILK') ON DAY 2/3 — IF PERSISTENT THIS CAN PREDISPOSE TO MASTITIS/BREAST ABSCESS IN GIRLS.
• HYPERPIGMENTARY DISORDERS:
• A LINEA ALBA OCCURS IN 8% OF BABIES AND MAY PERSIST FOR 2–3 MONTHS.
• MONGOLIAN BLUE SPOTS OCCUR IN UP TO 85% OF CHINESE BABIES, ARE COMMON IN BLACK BABIES BUT ONLY OCCUR IN ABOUT 3% OF WHITE BABIES.
• HYPERPIGMENTATION OF THE SCROTUM MAY OCCUR ESPECIALLY IN CHINESE BABIES (UP TO 30%).
• LINEAR/RETICULATE PIGMENTARY ANOMALIES HAVE BEEN DESCRIBED IN BLACK NEWBORNS.
• ORAL FINDINGS:
• EPSTEIN PEARLS ARE 1–2 mm DIAMETER, YELLOWISH WHITE, KERATINOUS CYSTS SEEN IN THE MOUTHS OF UP TO 85% OF ALL NEONATES, ALONG THE ALVEOLAR RIDGES AND/OR IN THE MIDLINE AT THE JUNCTION OF THE HARD AND SOFT PALATE. THESE GENERALLY DISAPPEAR WITHOUT TREATMENT WITHIN A FEW WEEKS.
• SUCCULENT GUMS, ANALOGOUS TO THE HYPERTROPHIC GINGIVITIS OFTEN SEEN IN PREGNANT WOMEN, ARE COMMON IN NEONATES.
• A WHITISH HUE TO THE ORAL MUCOSA ('LEUKOEDEMA') IS ALSO COMMON. THIS IS PROBABLY SYNONYMOUS WITH WHAT OTHER AUTHORS HAVE CALLED 'SUCKLING PADS'.

• THE SKIN OF THE PRETERM NEONATE TENDS TO HAVE A RATHER TRANSLUCENT, GELATINOUS QUALITY, AND THE SO-CALLED MINIATURE PUBERTY FEATURES ARE MUCH LESS PROMINENT.
• CUTANEOUS VESSELS ARE EASILY VISIBLE.
• PRETERM INFANTS ARE OFTEN COVERED IN LANUGO HAIRS, WHICH TEND TO BE MOST DENSE ON THE FACE, LIMBS AND TRUNK.
• THIS HAIR WOULD NORMALLY BE SHED IN UTERO ABOUT 1 MONTH BEFORE TERM, TO BE REPLACED BY A SECOND COAT OF SHORTER LANUGO, WHICH IS PRESENT AT BIRTH IN FULL-TERM INFANTS.
• LIKE THE TERMINAL SCALP HAIR, THIS DOWNY LANUGO IS SHED DURING THE FIRST MONTHS OF LIFE AND IS ITSELF REPLACED BY VELLUS HAIR.

• THE SMALL-FOR-DATES OR DYSMATURE NEONATE PRESENTS A CHARACTERISTIC APPEARANCE DUE TO RELATIVE PRENATAL MALNUTRITION.
• THE BABY IS SMALL AND THE MOST STRIKING DERMATOLOGICAL FEATURE IS THE LACK OF SUBCUTANEOUS FAT, WHICH CAUSES THE BABY TO LOOK THIN AND WRINKLED.
• VERNIX IS ABSENT IN THE EXTREMELY IMMATURE INFANT, BUT MAY BE PROFUSE NEARER TO TERM.
• THE SKIN AND VERNIX ARE OFTEN STAINED YELLOWISH GREEN BY MECONIUM.
• AFTER BIRTH, THE SKIN DRIES QUICKLY AND BECOMES 'CRAZED' WITH LONG TRANSVERSE SPLITS ON THE TRUNK. IT THEN PEELS OFF TO REVEAL MORE NORMAL-APPEARING SKIN BENEATH.
• THE FINGERNAILS ARE OFTEN LONG.
• THE POSTMATURE INFANT IS LONGER BUT OF OTHERWISE SIMILAR APPEARANCE TO THE SMALL-FOR-DATES NEONATE, HAVING ALSO EXPERIENCED INTRAUTERINE MALNUTRITION DUE TO PLACENTAL INSUFFICIENCY. VERNIX IS OFTEN ABSENT.

---

• DEFINITION: A COMMON, TRANSIENT, BLOTCHY, RED MACULAR RASH (SOMETIMES WITH SMALL PUSTULES) SEEN IN THE FIRST FEW DAYS OF LIFE.
• THE MOST WIDELY USED TERM FOR THIS CONDITION IS INAPPROPRIATE IN VIEW OF THE COMPLETE ABSENCE OF ANY EVIDENCE OF A TOXIC CAUSE.
• SYNONYM: ERYTHEMA TOXICUM NEONATORUM.
• EPIDEMIOLOGY:
• A DEGREE OF TOXIC ERYTHEMA DEVELOPS IN 30–50% OF CHILDREN.
• IT IS HARDLY EVER SEEN IN PRETERM INFANTS OR THOSE WEIGHING LESS THAN 2.5 kg.
• A HIGH PREVALENCE IS FOUND IN HIGHER-BIRTH-WEIGHT NEWBORNS. IT IS ALSO FOUND TO OCCUR MORE FREQUENTLY DURING THE SUMMER.
• AGE: IT USUALLY APPEARS IN THE FIRST 24–48 h OF LIFE.
• SEX: EQUAL PREVALENCE IN MOST STUDIES. ETHNICITY: OCCURS IN ALL RACIAL GROUPS.
• ASSOCIATED DISEASES: BLOOD EOSINOPHILIA IS ASSOCIATED.
• PATHOPHYSIOLOGY:
• THE CAUSE IS UNKNOWN. THERE IS FREQUENTLY AN ASSOCIATED BLOOD EOSINOPHILIA.
• THIS PROBABLY DOES NOT REFLECT AN ALLERGIC RESPONSE AS TISSUE EOSINOPHILIA IS A NON-SPECIFIC FEATURE OF INFLAMMATORY RESPONSES IN NEONATES.
• THE INTRAFOLLICULAR LOCATION OF MATURE PUSTULES HAS LED TO THE SUGGESTION THAT THE INFLAMMATORY RESPONSE IS ELICITED BY SOME COMPONENT OF SEBUM.
• SCANNING ELECTRON MICROSCOPY OF NEONATAL SKIN SHOWS THAT COLONISATION OF HAIR FOLLICLE EPITHELIUM BY STAPHYLOCOCCI IS COMMON IN EARLY LIFE.
• THE ACCUMULATION OF TRYPTASE-EXPRESSING MAST CELLS AROUND THE HAIR FOLLICLES IN LESIONAL SKIN HAS RECENTLY BEEN DEMONSTRATED BUT ITS RELATION TO THE STAPHYLOCOCCI AND ITS SIGNIFICANCE REMAIN UNCLEAR.
• NO PREDISPOSING FACTORS ARE KNOWN. NO PATHOGENIC BACTERIA HAVE BEEN ISOLATED FROM PUSTULES. NO ENVIRONMENTAL FACTORS HAVE BEEN DEMONSTRATED.
• PATHOLOGY:
• HISTOLOGICALLY, THE MACULAR REDNESS SHOWS OEDEMA IN THE UPPER DERMIS, ASSOCIATED WITH A SPARSE AND LARGELY PERIVASCULAR INFLAMMATORY INFILTRATE COMPOSED PRINCIPALLY OF EOSINOPHILS.
• PAPULAR LESIONS ARE CHARACTERISED, IN ADDITION, BY EOSINOPHIL INFILTRATION OF THE OUTER ROOT SHEATH OF ONE OR MORE HAIR FOLLICLES, ABOVE THE POINT OF ENTRY OF THE SEBACEOUS DUCT.
• PUSTULAR LESIONS SHOW INTRAFOLLICULAR ACCUMULATION OF EOSINOPHILS IMMEDIATELY BELOW THE STRATUM CORNEUM.
• SMEARS OF THE PUSTULE CONTENTS DEMONSTRATE INFLAMMATORY CELLS, MORE THAN 90% OF WHICH ARE EOSINOPHILS.
• THERE IS AN ASSOCIATED BLOOD EOSINOPHILIA OF UP TO 20% OF THE WHITE CELL COUNT IN AROUND HALF THE CASES, GENERALLY MORE MARKED WHEN THERE IS A PROMINENT PUSTULAR ELEMENT.
• CLINICAL FEATURES:
• SOME DEGREE OF TOXIC ERYTHEMA WILL MANIFEST IN 30–50% OF FULL-TERM INFANTS OF ALL RACIAL TYPES DURING THE FIRST FEW DAYS OF LIFE.
• IN MOST CASES THE ONSET IS DURING THE FIRST 48 h AFTER BIRTH, BUT IT MAY OCCUR AT ANY TIME UNTIL ABOUT THE FOURTH DAY. IT VERY RARELY PRESENTS AT BIRTH.
• PRESENTATION: MOST COMMONLY, A BLOTCHY, MACULAR REDNESS, THE NUMBER OF INDIVIDUAL LESIONS VARYING FROM ONE OR TWO TO SEVERAL HUNDRED.
• MOST PROFUSE ON THE TRUNK, PARTICULARLY THE ANTERIOR TRUNK, BUT ALSO COMMONLY ON THE FACE AND PROXIMAL PARTS OF THE LIMBS, ESPECIALLY THE THIGHS.
• LESIONS HAVE BEEN RECORDED AT ALMOST ANY SITE EXCEPT THE PALMS AND SOLES. IN THE MILDEST CASES, THESE MACULES FADE WITHIN A DAY.
• CLINICAL VARIANTS: IN MORE SEVERE CASES, URTICARIAL PAPULES ARISE WITHIN THE RED AREAS OR, OCCASIONALLY, INDEPENDENTLY OF THEM (PARTICULARLY ON THE BACK AND BUTTOCKS). THESE PAPULES ARE, IN ABOUT 10% OF CASES, SURMOUNTED BY SMALL PUSTULES 1–2 mm IN DIAMETER. PRESENTATION WITH SCROTAL PUSTULES PRESENT AT BIRTH HAS BEEN REPORTED.
• DIFFERENTIAL DIAGNOSIS: MUST BE DISTINGUISHED FROM OTHER DISORDERS FEATURING PUSTULAR LESIONS DURING THE NEONATAL PERIOD, PARTICULARLY MILIARIA, TRANSIENT NEONATAL PUSTULAR MELANOSIS, INCONTINENTIA PIGMENTI AND, MOST IMPORTANTLY, HSV INFECTION, VARICELLA, IMPETIGO NEONATORUM AND MALASSEZIA FURFUR PUSTULOSIS. OF THESE, PUSTULAR MILIARIA IS THE ONE MOST OFTEN CONFUSED CLINICALLY.
• COMPLICATIONS: THE INFANT APPEARS WELL, AND UNPERTURBED BY THE ERUPTION. THERE ARE NO COMPLICATIONS.
• DISEASE COURSE: SPONTANEOUS RECOVERY OCCURS RAPIDLY, USUALLY WITHIN 3 DAYS, BUT RECURRENCES ARE OCCASIONALLY SEEN AND HAVE BEEN REPORTED AS LATE AS THE SIXTH WEEK OF LIFE.
• INVESTIGATIONS: RARELY NEEDED AS IT IS A CLINICAL DIAGNOSIS. IF THERE IS ANY DIAGNOSTIC DOUBT, IT CAN BE RAPIDLY DIAGNOSED BY MICROSCOPIC EXAMINATION OF A SMEAR OF PUSTULE CONTENTS (STAINED WITH GIEMSA) TO SHOW THE EOSINOPHILS AND BY NEGATIVE BACTERIAL AND VIRAL CULTURES.
• MANAGEMENT: NO TREATMENT IS NEEDED.

• DEFINITION: MILIARIA CRYSTALLINA IS A SELF-LIMITING ECCRINE GLAND DISORDER DUE TO BLOCKAGE OF SWEAT GLANDS RESULTING IN RAPIDLY EVOLVING NON-INFLAMMATORY VESICLES THAT EASILY BREAK (Chapter 92).
• THREE SUBTYPES DEPENDING ON THE LEVEL OF BLOCKAGE:
• MILIARIA CRYSTALLINA (STRATUM CORNEUM).
• MILIARIA RUBRA (MID-EPIDERMAL).
• MILIARIA PROFUNDA (DERMAL–EPIDERMAL JUNCTION).
• SYNONYM: PRICKLY HEAT (FOR MILIARIA RUBRA).
• EPIDEMIOLOGY: MILIARIA OCCURS IN ABOUT 3–8% OF NEONATES. MAY OCCUR AT ANY AGE BUT MILIARIA RUBRA AND MILIARIA CRYSTALLINA ARE COMMON IN NEONATES. EQUAL SEX PREVALENCE; ALL RACIAL GROUPS.
• ASSOCIATED DISEASES: VERY RARELY HYPERNATRAEMIA OR HYPERALDOSTERONISM.
• PREDISPOSING FACTORS: IMMATURE SWEAT DUCTS ARE AN IMPORTANT FACTOR IN NEONATES ALTHOUGH HIGH LEVELS OF HEAT AND HUMIDITY ARE IMPORTANT AT ANY AGE. OCCLUSIVE CLOTHING IS PROBABLY MORE RELEVANT TO ADULTS. HYPERNATRAEMIA AND/OR HYPERALDOSTERONISM IS A VERY RARE UNDERLYING FACTOR.
• PATHOLOGY: MILIARIA CRYSTALLINA IS CHARACTERISED BY THE PRESENCE OF INTRACORNEAL OR SUBCORNEAL VESICLES IN COMMUNICATION WITH THE SWEAT DUCTS.
• IN MILIARIA RUBRA, FOCAL AREAS OF SPONGIOSIS AND SPONGIOTIC VESICLE FORMATION ARE SEEN IN CLOSE PROXIMITY TO THE SWEAT DUCTS, WHICH OFTEN CONTAIN AN AMORPHOUS, PERIODIC ACID–SCHIFF (PAS) STAIN-POSITIVE PLUG.
• CAUSATIVE ORGANISMS: THERE IS A POSSIBLE LINK WITH STAPHYLOCOCCUS EPIDERMIDIS AND S. AUREUS.
• ENVIRONMENTAL FACTORS: HEAT, HUMIDITY, OCCLUSIVE CLOTHES AND PLASTIC SHEETS.
• PRESENTATION:
• MILIARIA CRYSTALLINA PRESENTS AS CROPS OF CLEAR, THIN-WALLED, SUPERFICIAL VESICLES 1–2 mm IN DIAMETER, WITHOUT ASSOCIATED REDNESS, RESEMBLING DROPS OF WATER.
• EXCEEDINGLY DELICATE AND GENERALLY RUPTURE WITHIN 24 h, FOLLOWED BY BRAN-LIKE DESQUAMATION. LESIONS ARE ASYMPTOMATIC.
• ARISE MOST FREQUENTLY DURING THE FIRST 2 WEEKS OF LIFE, AND ARE PARTICULARLY LIKELY TO BE SEEN ON THE FOREHEAD, SCALP, NECK AND UPPER TRUNK.
• ALTHOUGH RARE DURING THE FIRST 4 DAYS, CONGENITAL CASES HAVE BEEN REPORTED.
• MILIARIA RUBRA ('PRICKLY HEAT') COMPRISES RED PAPULES AND PAPULOVESICLES ABOUT 1–4 mm IN DIAMETER, ON A BACKGROUND OF MACULAR REDNESS. SOMETIMES, QUITE LARGE, WEAL-LIKE LESIONS OCCUR.
• FREQUENTLY, SOME OF THE LESIONS ARE PUSTULAR (MILIARIA PUSTULOSA), BUT THIS DOES NOT NECESSARILY INDICATE SECONDARY INFECTION.
• NEVERTHELESS, STAPHYLOCOCCAL SECONDARY INFECTION OF MILIARIA (PERIPORITIS) IS NOT INFREQUENT, AND MAY LEAD TO SWEAT GLAND ABSCESSES.
• COMMON AND, ALTHOUGH IT MAY BE SEEN THROUGHOUT INFANCY, IT PROBABLY OCCURS MOST FREQUENTLY DURING THE NEONATAL PERIOD.
• CROPS OF LESIONS ARISE FAIRLY SYMMETRICALLY, MOST OFTEN IN FLEXURAL AREAS, ESPECIALLY AROUND THE NECK AND IN THE GROINS AND AXILLAE. THE FACE, SCALP AND UPPER TRUNK ARE ALSO FREQUENTLY AFFECTED.
• MAY ALSO OCCUR RATHER LOCALLY AT SITES THAT HAVE BEEN OCCLUDED, FOR EXAMPLE WHERE THERE HAS BEEN DIRECT CONTACT BETWEEN THE SKIN AND A PLASTIC MATTRESS COVER OR PLASTIC PANTS.
• LESIONS CAN BE ITCHY OR SORE. WHERE THE ERUPTION IS PROFUSE, THE CHILD MAY BE RESTLESS AND DISTRESSED.
• EACH CROP OF LESIONS WILL SUBSIDE WITHIN 2–3 DAYS, BUT RECURRENCES ARE COMMON UNLESS THE PROVOCATIVE ENVIRONMENTAL CONDITIONS ARE MODIFIED.
• RECURRENT BOUTS OF MILIARIA PUSTULOSA ARE A COMMON FINDING IN TYPE 1 PSEUDOHYPOALDOSTERONISM.
• MILIARIA PROFUNDA IS VERY UNCOMMON IN NEONATES AS IT USUALLY OCCURS IN ADULTS WHERE THERE HAVE BEEN REPEATED EPISODES OF MILIARIA RUBRA.
• HOWEVER, A GRANULOMATOUS VARIANT OF GIANT CENTRIFUGAL MILIARIA PROFUNDA WAS RECENTLY DESCRIBED IN TWO 3-MONTH-OLD BABIES. THIS PRESENTS WITH PAPULES AND GEOGRAPHIC AND ANNULAR PLAQUES OVER THE EXTENSOR ASPECTS OF THE LIMBS AND THE TRUNK.
• DIFFERENTIAL DIAGNOSIS:
• MILIARIA CRYSTALLINA IS DISTINGUISHABLE FROM VIRAL INFECTIONS OF THE SKIN (e.g. HERPES SIMPLEX) BY THE LACK OF BACKGROUND REDNESS, AND BY THE ABSENCE OF INFLAMMATORY CELLS OR GIANT KERATINOCYTES ON CYTOLOGICAL EXAMINATION OF VESICLE CONTENTS.
• WHEN IT OCCURS DURING THE FIRST FEW DAYS OF LIFE, MILIARIA RUBRA IS OFTEN CONFUSED WITH TOXIC ERYTHEMA, ESPECIALLY IF IT HAS BECOME PUSTULAR.
• HOWEVER, MILIARIA RUBRA CAN GENERALLY BE DISTINGUISHED BY ITS FLEXURAL PREDOMINANCE, BY THE FREQUENT PRESENCE OF VESICULAR LESIONS AND BY ITS TENDENCY TO RECUR.
• IF IN DOUBT, A SMEAR OF A VESICLE/PUSTULE WILL SHOW AN ABSENCE OF EOSINOPHILS (LARGE NUMBERS ARE SEEN IN TOXIC ERYTHEMA).
• MILIARIA PUSTULOSA MAY ALSO BE CONFUSED WITH INFANTILE ACNE OR FOLLICULITIS, BUT THE LESIONS ARE NOT FOLLICULAR.
• COMPLICATIONS: STAPHYLOCOCCAL INFECTION AND SWEAT GLAND ABSCESS RARELY OCCUR.
• DISEASE COURSE: MILIARIA CRYSTALLINA IMPROVES SPONTANEOUSLY AS THE SWEAT DUCTS MATURE. MILIARIA RUBRA IMPROVES IF THE PREDISPOSING AETIOLOGICAL FACTORS (HIGH HEAT/HUMIDITY AND OCCLUSION) ARE REMOVED.
• INVESTIGATIONS: THE DIAGNOSIS IS USUALLY CLINICAL. OCCASIONALLY, A SMEAR FROM A VESICLE OR PUSTULE IS USEFUL TO EXCLUDE HSV INFECTION OR TOXIC ERYTHEMA.
• MANAGEMENT: MILIARIA CRYSTALLINA SPONTANEOUSLY IMPROVES WITHOUT THERAPY OVER A FEW WEEKS AS THE SWEAT DUCTS MATURE.
• FIRST LINE — MILIARIA RUBRA WILL IMPROVE IN A FEW WEEKS WITHOUT MEDICAL TREATMENT IF THE CHILD IS REMOVED FROM CONDITIONS OF HIGH HEAT/HUMIDITY AND ANY OCCLUSIVE CLOTHING OR BEDDING IS REMOVED.
• SECOND LINE — ANTIBIOTICS MAY BE NEEDED IF STAPHYLOCOCCAL INFECTION OCCURS BUT THIS IS RARE.

• SYNONYM: TRANSIENT NEONATAL PUSTULAR MELANOSIS.
• DESPITE HAVING FIRST BEEN DESCRIBED MORE THAN 40 YEARS AGO, ITS AETIOLOGY REMAINS UNKNOWN.
• FIRST REPORTED IN BLACK AMERICANS, AND APPEARS TO BE COMMONER IN, BUT NOT CONFINED TO, BLACK NEONATES (4.4% IN BLACK US NEONATES AGAINST 0.6% IN WHITE US NEONATES).
• IT HAS BEEN SUGGESTED THAT IT IS MERELY AN EARLY-ONSET VARIANT OF TOXIC ERYTHEMA OF THE NEWBORN.
• LESIONS ARE USUALLY PRESENT AT BIRTH.
• THE MOST CHARACTERISTIC COMPONENT IS 1–3 mm FLACCID, SUPERFICIAL, FRAGILE PUSTULES, WITH NO SURROUNDING REDNESS.
• THESE PUSTULES MAY OCCUR AT ANY SITE, BUT FAVOUR THE CHIN, NECK, FOREHEAD, BACK AND BUTTOCKS.
• SITES WHERE THEY HAVE RUPTURED ARE MARKED INITIALLY BY A DETACHABLE BROWN CRUST, AND SUBSEQUENTLY BY A SMALL COLLARETTE OF SCALE, WHICH MAY SURMOUNT A PIGMENTED MACULE.
• SOMETIMES, PIGMENTED MACULES ARE ALREADY PRESENT AT BIRTH.
• THE PIGMENTED MACULES ARE A PROMINENT ELEMENT IN BLACK INFANTS, AND ARE SEEN MORE RARELY IN OTHER RACES. THE PIGMENTATION MAY PERSIST FOR ABOUT 3 MONTHS.
• AFFECTED INFANTS ARE OTHERWISE ENTIRELY WELL. DIAGNOSIS CAN USUALLY BE MADE ON CLINICAL GROUNDS WITHOUT THE NEED FOR A BIOPSY OR SMEAR.
• PATHOLOGY: A SKIN BIOPSY OF A PUSTULE SHOWS INTRA- OR SUBCORNEAL COLLECTIONS OF NEUTROPHILS AND A FEW EOSINOPHILS.
• THE UNDERLYING DERMIS MAY SHOW NO ABNORMALITY, OR A SPARSE PERIVASCULAR AND PERIFOLLICULAR INFLAMMATORY INFILTRATE, ALSO MAINLY OF NEUTROPHILS WITH A FEW EOSINOPHILS.
• THE PIGMENTED MACULES DEMONSTRATE BASAL AND SUPRABASAL INCREASES IN PIGMENTATION ONLY, APPARENTLY WITHOUT PIGMENTARY INCONTINENCE.
• SMEARS OF PUSTULAR CONTENTS SHOW PREDOMINANTLY NEUTROPHILS, AND BACTERIAL CULTURE IS NEGATIVE.
• MANAGEMENT: NO TREATMENT IS NEEDED FOR THIS SELF-RESOLVING CONDITION.

• CONGENITAL OR NEONATAL CANDIDIASIS.
• CONGENITAL SYPHILIS.
• EOSINOPHILIC PUSTULOSIS.
• HERPES SIMPLEX VIRUS INFECTION.
• IMPETIGO.
• INFANTILE ACROPUSTULOSIS.
• LANGERHANS CELL HISTIOCYTOSIS.
• MALASSEZIA PUSTULOSIS.
• MILIARIA.
• NEONATAL ACNE.
• NEONATAL LISTERIOSIS.
• NEONATAL PUSTULOSIS OF TRANSIENT MYELOPROLIFERATIVE DISORDER.
• PUSTULAR PSORIASIS.
• SCABIES.
• TOXIC ERYTHEMA OF THE NEWBORN.
• TRANSIENT PUSTULAR MELANOSIS.

• AN UNCOMMON DISORDER OF UNKNOWN AETIOLOGY. OCCURS IN ALL RACES ALTHOUGH IT WAS FIRST DESCRIBED IN BLACK INFANTS.
• IT HAS BEEN SUGGESTED THAT EOSINOPHILIC PUSTULAR FOLLICULITIS AND INFANTILE ACROPUSTULOSIS MAY BE DIFFERENT MANIFESTATIONS OF THE SAME DISEASE.
• IT HAS ALSO BEEN SUGGESTED THAT, AT LEAST IN SOME CASES, INFANTILE ACROPUSTULOSIS OCCURS FOLLOWING SUCCESSFUL TREATMENT OF SCABIES.
• IT HAS BEEN REPORTED IN SIBLINGS AND IN ONLY ONE OF A PAIR OF IDENTICAL TWINS.
• PRESENTATION:
• RECURRENT CROPS OF INTENSELY ITCHY, 1–4 mm VESICOPUSTULES THAT APPEAR PRINCIPALLY ON THE SOLES AND SIDES OF THE FEET, AND ON THE PALMS, BUT MAY ALSO OCCUR ON THE DORSA OF THE FEET, HANDS AND FINGERS, AND ON THE ANKLES, WRISTS AND FOREARMS.
• SCATTERED LESIONS MAY ALSO BE SEEN ON THE FACE, SCALP AND TRUNK, BUT A PREDOMINANTLY ACRAL DISTRIBUTION IS CHARACTERISTIC. MUCOSAL LESIONS DO NOT OCCUR.
• INDIVIDUAL LESIONS APPEAR TO START AS TINY, RED PAPULES, WHICH EVOLVE INTO VESICLES AND THEN PUSTULES OVER ABOUT 24 h.
• EXCORIATION RESULTS IN EROSIONS AND THEN CRUSTS. HEALING IS FREQUENTLY SUCCEEDED BY MACULAR POSTINFLAMMATORY HYPERPIGMENTATION.
• COURSE: IN THE MAJORITY OF CASES, THE ONSET IS IN THE FIRST YEAR OF LIFE, PARTICULARLY DURING THE FIRST 6 MONTHS. LESIONS RARELY PRESENT AT BIRTH.
• EACH CROP LASTS FOR 7–14 DAYS. THEY TEND TO OCCUR AT INTERVALS OF 2–4 WEEKS IN MOST CASES, OFTEN BEING MORE FREQUENT AND MORE NUMEROUS IN THE SUMMER MONTHS.
• DIFFERENTIAL DIAGNOSIS: THE PREDILECTION FOR THE PALMS AND SOLES AND THE RECURRENT ATTACKS DIFFERENTIATE THIS DISORDER FROM MOST OTHER PUSTULAR ERUPTIONS SEEN IN THE NEONATAL PERIOD, PARTICULARLY TOXIC ERYTHEMA, MILIARIA AND TRANSIENT PUSTULAR MELANOSIS.
• SCABIES MAY INITIALLY BE EXTREMELY DIFFICULT TO EXCLUDE, AND WHERE THERE IS ANY DOUBT A THERAPEUTIC TRIAL OF AN APPROPRIATE ACARICIDE IS JUSTIFIED.
• PATHOLOGY: SKIN BIOPSY OF A PUSTULE WILL SHOW WELL-CIRCUMSCRIBED SUBCORNEAL OR INTRAEPIDERMAL AGGREGATIONS OF NEUTROPHILS, WITH A SPARSE PERIVASCULAR LYMPHOHISTIOCYTIC INFILTRATE IN THE UNDERLYING PAPILLARY DERMIS.
• BIOPSY OF A PRE-PUSTULAR LESION SHOWS FOCAL INTRAEPIDERMAL VESICULATION WITH KERATINOCYTE NECROSIS. THIS INTRAEPIDERMAL VESICLE IS SUBSEQUENTLY INVADED BY NEUTROPHILS AND/OR EOSINOPHILS.
• THE PUSTULE STARTS ITS LIFE DEEP IN THE EPIDERMIS, BUT DOES NOT BECOME CLINICALLY FULLY DEVELOPED UNTIL IT REACHES A SUBCORNEAL LOCATION.
• DIRECT AND INDIRECT IMMUNOFLUORESCENCE STUDIES ARE NEGATIVE.
• STAINED SMEARS OF PUSTULE CONTENTS GENERALLY SHOW A PREDOMINANCE OF NEUTROPHILS, BUT THERE MAY BE A PREPONDERANCE OF EOSINOPHILS EARLY IN THE COURSE OF THE DISORDER. SOMETIMES PERIPHERAL BLOOD EOSINOPHILIA IS PRESENT.
• MANAGEMENT: TREATMENT IS WITH POTENT TOPICAL CORTICOSTEROIDS WITH OR WITHOUT OCCLUSION.
• DAPSONE HAS BEEN USED IN A FEW SEVERE CASES, AS HAS TOPICAL MAXACALCITOL.
• THE ATTACKS OCCUR WITH GRADUALLY DIMINISHING NUMBERS OF LESIONS, AND WITH DECREASING FREQUENCY, UNTIL THEY CEASE ALTOGETHER, USUALLY WITHIN 2 YEARS OF THE ONSET.

• THERE HAVE BEEN SEVERAL REPORTS OF NEONATES WITH TRISOMY 21 (AND MOSAIC TRISOMY 21) DEVELOPING PUSTULES AND VESICLES (ON A REDDISH BACKGROUND), PREDOMINANTLY ON THE FACE, AS PART OF CONGENITAL LEUKAEMIA OR TRANSIENT MYELOPROLIFERATIVE DISORDER (TMD).
• THEY MAY PUSTULATE AT SITES OF TRAUMA, SUCH AS VENEPUNCTURE SITES OR UNDER ADHESIVE TAPE.
• THE PATIENTS MAY ALSO HAVE HEPATOSPLENOMEGALY. THERE IS AN ASSOCIATED HIGH WHITE BLOOD CELL COUNT, OFTEN WITH THE PRESENCE OF BLASTS.
• SKIN BIOPSY SHOWS INTRAEPIDERMAL PUSTULES WITH A PERIVASCULAR DERMAL INFILTRATE OF NEUTROPHILS, EOSINOPHILS AND ATYPICAL MONONUCLEAR CELLS.
• THE LESIONS OFTEN RESOLVE SPONTANEOUSLY OVER A FEW WEEKS PARALLELED BY A DECREASING WHITE CELL COUNT.
• MUTATIONS IN THE TRANSCRIPTION FACTOR GATA1 SEEM TO UNDERLIE TMD BUT A SECOND GENETIC HIT IS NEEDED TO DEVELOP LEUKAEMIA.
• UP TO 20% OF PATIENTS WITH TMD WILL GO ON TO DEVELOP AN ACUTE MEGAKARYOBLASTIC LEUKAEMIA WITHIN THE FIRST 4 YEARS OF LIFE SO FOLLOW-UP IS MANDATORY.

• DEFINITION: PRESENTS IN NEONATES AS EROSIONS, ULCERATIONS, VESICLES AND RED SKIN AFFECTING AROUND 75% OF SKIN SURFACE AREA, WHICH HEAL TO LEAVE DISTINCTIVE RETICULATE SCARRING.
• TO DATE, THERE ARE FEWER THAN 40 CASES REPORTED IN THE LITERATURE.
• SYNONYM: EXTENSIVE CONGENITAL EROSIONS AND VESICLES HEALING WITH RETICULATE SCARRING.
• A RARE, SELF-LIMITING, BLISTERING DISORDER OF UNKNOWN AETIOLOGY FIRST DESCRIBED IN 1985 BY COHEN ET AL.
• EPIDEMIOLOGY: VERY RARE. OCCURS AT BIRTH AND THE MAJORITY OF AFFECTED INFANTS HAVE BEEN PREMATURE. OCCURRENCE IS GREATER IN BOYS THAN IN GIRLS.
• PATHOLOGY:
• BIOPSIES OF VESICULAR AREAS HAVE SHOWN SPONGIOSIS OR EPIDERMAL NECROSIS WITH DERMAL HAEMORRHAGE AND INFLAMMATION.
• IN ONE REPORT, AN ERODED AREA SHOWED LOSS OF THE EPIDERMIS WITH A SUPERFICIAL AND DEEP DERMAL INFLAMMATORY INFILTRATE COMPRISING MOSTLY NEUTROPHILS. PARAKERATOTIC SCALE MAY BE PRESENT.
• SCARRED AREAS HAVE SHOWN AN INCREASED DENSITY OF DERMAL COLLAGEN, AND ABSENCE OF ECCRINE SWEAT GLANDS.
• DIRECT IMMUNOFLUORESCENCE DOES NOT SHOW ANY SPECIFIC PATTERN OF DEPOSITION OF IMMUNOGLOBULINS, C3 OR FIBRIN.
• ELECTRON MICROSCOPY AND IMMUNOHISTOCHEMICAL MAPPING OF PERILESIONAL SKIN HAVE SHOWN NOTHING TO SUGGEST THAT THIS IS A VARIANT OF EPIDERMOLYSIS BULLOSA.
• PRESENTATION:
• EXTENSIVE, SUPERFICIAL EROSIONS, WITH SCATTERED VESICLES AND BULLAE, AFFECTING UP TO 75% OF THE BODY SURFACE. THESE EROSIONS MAY EXTEND IN THE FIRST FEW DAYS.
• THE TRUNK AND LIMBS TEND TO BE MORE SEVERELY AFFECTED THAN THE FACE AND SCALP. HANDS AND FEET MAY BE SPARED.
• PATIENTS ARE PRONE TO INFECTION PRIOR TO THE SKIN HEALING. BACTERIAL, FUNGAL AND HSV INFECTIONS HAVE BEEN DESCRIBED.
• THE BLISTERS/EROSIONS HEAL FAIRLY QUICKLY WITHIN THE FIRST FEW WEEKS OF LIFE, LEAVING RATHER CHARACTERISTIC SOFT, RETICULATED SCARRING.
• FOLLOWING HEALING, THERE MAY BE RESIDUAL LOSS OF ECCRINE SWEATING IN THE SCARRED AREAS, WITH THE POTENTIAL FOR HYPERTHERMIA, PATCHY ALOPECIA, PARTIAL LOSS OF EYELASHES AND THE ABSENCE OR HYPOPLASIA OF NAILS. TEETH ARE NORMAL.
• MILD, LOCALISED, RECURRENT VESICULATION MAY OCCUR.
• THE LARGEST PUBLISHED REVIEW OF 18 CASES REVEALED THE FOLLOWING ASSOCIATIONS:
• PRETERM BIRTH (79%).
• NAIL DYSTROPHIES (46%).
• HYPERTHERMIA/HYPOHIDROSIS (46%).
• MATERNAL CHORIOAMNIONITIS (43%).
• NEUROLOGICAL DISORDERS (MICROCEPHALY, CONVULSIONS, DEVELOPMENTAL DELAY) — 36%.
• OPHTHALMOLOGICAL COMPLICATIONS (LACRIMAL DUCT OBSTRUCTION, MACULAR OR CORNEAL SCARS) — 36%.
• TONGUE ATROPHY (29%).
• DIFFERENTIAL DIAGNOSIS: INFECTIVE BLISTERS (e.g. HERPES SIMPLEX), EPIDERMOLYSIS BULLOSA, BULLOUS ICHTHYOSIFORM ERYTHRODERMA, INCONTINENTIA PIGMENTI, APLASIA CUTIS CONGENITA, FOCAL DERMAL HYPOPLASIA AND STAPHYLOCOCCAL SCALDED SKIN SYNDROME.
• COMPLICATIONS: POSTNATAL INFECTION IS A RISK. IT IS UNCLEAR IF THE DISEASE ASSOCIATIONS ARE CAUSED BY CEVD ITSELF OR BY PREMATURITY OR AN UNIDENTIFIED INTRAUTERINE PATHOLOGY.
• DISEASE COURSE: SPONTANEOUS HEALING OCCURS WITHIN 2 WEEKS TO 3 MONTHS.
• INVESTIGATIONS: SKIN SWABS AND BLOOD CULTURE ARE NEEDED TO INVESTIGATE FOR INFECTIONS (VIRAL, BACTERIAL AND FUNGAL). SKIN BIOPSY MAY BE USEFUL.
• MANAGEMENT: THE BABY WILL NEED TO BE NURSED ON AN APPROPRIATE NEONATAL UNIT FOR THE MANAGEMENT OF FLUID BALANCE, TEMPERATURE CONTROL AND ANY INFECTION.
• NON-ADHESIVE DRESSINGS (e.g. SILICONE DRESSINGS) WILL BE NEEDED FOR THE FIRST FEW WEEKS OF LIFE UNTIL HEALING OCCURS. THERE IS NO SPECIFIC TREATMENT.

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• ANETODERMA IS CHARACTERISED BY FOCAL LOSS OF ELASTIC TISSUE IN THE MID-DERMIS, RESULTING IN LOCALISED AREAS OF MACULAR DEPRESSIONS OR POUCH-LIKE HERNIATIONS.
• ANETODERMA MAY OCCUR IN PRETERM BABIES APPEARING AT, OR SOON AFTER, BIRTH. ITS EARLY ONSET DIFFERENTIATES IT FROM ANETODERMA OF PREMATURITY CAUSED BY ELECTROCARDIOGRAM (ECG) ELECTRODES.
• EPIDEMIOLOGY: INCIDENCE UNKNOWN BUT VERY RARE. FOUND IN EXTREMELY PREMATURE BABIES (<29 WEEKS). EQUAL SEX INCIDENCE.
• PATHOPHYSIOLOGY: THE UNDERLYING CAUSE IS UNKNOWN ALTHOUGH IT IS FOUND IN PREMATURE BABIES.
• A SKIN BIOPSY OF A LESION SHOWS REDUCED OR ABSENT ELASTIC TISSUE, CONSISTENT WITH ANETODERMA.
• THERE MAY BE AN UNDERLYING GENETIC PREDISPOSITION. ANETODERMA HAS BEEN DESCRIBED IN TWO IDENTICAL PREMATURE TWINS BUT ALL OTHER CASES HAVE BEEN SPORADIC.
• PRESENTATION: NUMMULAR AREAS OF CUTANEOUS ATROPHY APPEARING ON THE TRUNK AND/OR PROXIMAL LIMBS WITHIN A FEW WEEKS OF BIRTH.
• ALL PATIENTS HAVE BEEN BORN BETWEEN THE 24th AND 29th WEEKS OF GESTATION AND IN ALMOST ALL CASES THE LESIONS FIRST APPEARED WHILE THE CHILD WAS STILL IN THE NEONATAL INTENSIVE CARE UNIT.
• RARELY, ANETODERMA MAY BE PRESENT AT BIRTH.
• CASES THAT PRESENT LATER AT 2–3 MONTHS OF AGE ARE MORE LIKELY A CONSEQUENCE OF TRAUMA FROM GEL ECG ELECTRODES.
• DIFFERENTIAL DIAGNOSIS: ANETODERMA FROM TRAUMA AND APLASIA CUTIS CONGENITA TYPE 5.
• DISEASE COURSE: IT IS NON-PROGRESSIVE AND PERSISTENT.
• INVESTIGATIONS: SKIN BIOPSY SHOULD BE DONE.
• MANAGEMENT: THERE IS NO KNOWN TREATMENT FOR ANETODERMA.

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• AMNIOCENTESIS NEEDLES — PUNCTATE SCARS AND DIMPLES (PREVALENCE DECREASED WITH REAL-TIME ULTRASOUND).
• ANTENATAL BIOPSIES (SKIN, LIVER, TUMOURS) — PUNCTATE SCARS AND DIMPLES.
• INTRAUTERINE RED CELL TRANSFUSION (USED IN HAEMOLYTIC DISEASE/RHESUS INCOMPATIBILITY) — GANGRENE ABDOMINAL WALL.
• SCALP ELECTRODES (USED FOR MONITORING FETAL HEART RATE) — SCARRING ALOPECIA/CEPHALOHAEMATOMA; NEONATAL HSV AT THE SITE OF ELECTRODES (CUTANEOUS BLISTERS/ENCEPHALITIS).
• SCALP BLOOD SAMPLING (MONITORING ACID–BASE BALANCE) — SCALP ABSCESS (IN 4% OF NEONATES; RARELY DEEP TISSUE INFECTIONS).
• FORCEPS DELIVERY — SUBCUTANEOUS FAT NECROSIS.
• SCALPEL INJURY DURING CAESAREAN SECTION — LACERATIONS/SCARS.
• VENTOUSE EXTRACTION — SCARRING ALOPECIA (USUALLY AFTER SEVERE CAPUT SUCCEDANEUM) (VERY RARE); ANNULAR BLISTERS OF THE SCALP ('VESICULAR ERUPTION OF VACUUM-ASSISTED DELIVERY') CAN BE TRAUMATIC OR DUE TO HSV.

• UMBILICAL ARTERY CATHETERISATION — AORTIC THROMBOSIS/SPASM, ARTERIAL EMBOLISM (LOWER LIMB ISCHAEMIA/GANGRENE).
• TRANSCUTANEOUS OXYGEN MONITORING (HEATED ELECTRODE) — SUPERFICIAL BURN (REDNESS/VESICULATION) — LESS RISK WITH UNHEATED PULSE OXIMETRY.
• ELECTROCARDIOGRAPH ELECTRODES — ANETODERMA SECONDARY TO TRAUMA (MAY BE PURPURIC INITIALLY).
• TRANSILLUMINATION (MORE COMMON IF INFRARED FILTERS ARE SWITCHED OFF) — BLISTERS: 2–4 mm IN DIAMETER, OFTEN AT ACRAL SITES.
• EXTRAVASATION INTRAVENOUS MEDICATION — CUTANEOUS NECROSIS.
• HEEL PRICKS — CUTANEOUS CALCIFICATION (LOCALISED).
• EXTRAVASATION WITH CALCIUM-CONTAINING SOLUTIONS — CUTANEOUS CALCIFICATION (LOCALISED).
• SCALP ELECTROENCEPHALOGRAPH ELECTRODES (CALCIUM CHLORIDE-CONTAINING PASTE) — CUTANEOUS CALCIFICATION (LOCALISED).
• NEEDLE INSERTIONS (REPEATED)/CHEST DRAIN INSERTIONS — PUNCTATE WHITE SCARS (SPECKLED SCARRING).
• CHEMICAL BURNS FROM ANTISEPTICS/ALCOHOL-BASED CLEANSERS — CUTANEOUS NECROSIS (OFTEN ON THE BACK OR BUTTOCKS WHERE THE CLEANSER HAS POOLED).
• ADVERSE CONSEQUENCES OF MEDICAL PROCEDURES ON THE NEONATE ARE MORE COMMON IF THE BABY IS PREMATURE.

• PHOTOTHERAPY IS MOSTLY USED FOR NEONATAL JAUNDICE AND CAN LEAD TO VARIOUS COMPLICATIONS.
• RED RASH — MACULAR RED RASH (AS BILIRUBIN FALLS); ULTRAVIOLET-INDUCED REDNESS ('BURN').
• HYPERPIGMENTATION — SKIN TANNING (ESPECIALLY TYPE VI SKIN); BRONZE BABY SYNDROME (UNDERLYING HEPATIC DISEASE). (DIFFERENTIAL DIAGNOSIS: CENTRAL CYANOSIS, 'CARBON BABY' AND 'GREY BABY' SYNDROME.)
• BULLOUS ERUPTIONS — DRUG PHOTOTOXICITY (FUROSEMIDE, METHYLENE BLUE); CONGENITAL PORPHYRIAS.
• EPIDERMOLYSIS BULLOSA-LIKE ERUPTIONS — TRANSIENT PORPHYRINAEMIA (AFTER REPEATED TRANSFUSIONS FOR SEVERE HAEMOLYTIC DISEASE OF THE NEWBORN).
• LOCALISED PURPURA ON 'EXPOSED' SITES — TRANSIENT PORPHYRINAEMIA (SECONDARY TO TRANSFUSIONS).

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• MORPHOEA.
• ATROPHIC DERMATOFIBROSARCOMA PROTUBERANS.
• CUTIS MARMORATA TELANGIECTATICA CONGENITA.
• APLASIA CUTIS CONGENITA.
• ANETODERMA OF PREMATURITY.
• CONGENITAL EROSIVE AND VESICULAR DERMATOSIS HEALING WITH RETICULATED SUPPLE SCARRING.
• MEDALLION-LIKE DERMAL DENDROCYTE HAMARTOMA.
• CONGENITAL INFECTION (HSV AND VZV; MAY BE ZOSTERIFORM).
• FOCAL DERMAL HYPOPLASIA OF GOLTZ.
• NEONATAL LUPUS ERYTHEMATOSUS.

• A BENIGN ATROPHIC LESION PRESENTING AT BIRTH AND FIRST DESCRIBED IN 2004 IN FEMALE NEONATES.
• EPIDEMIOLOGY: VERY RARE WITH FEWER THAN 15 CASES DESCRIBED. CONGENITAL PRESENTATION. MORE COMMON IN FEMALES.
• PATHOPHYSIOLOGY: THE UNDERLYING CAUSE IS UNKNOWN.
• PATHOLOGY: SHOWS EPIDERMAL ATROPHY, SPINDLE CELL PROLIFERATION IN THE DERMIS AND TO A LESSER DEGREE THE SUBCUTIS, AND REDUCED ADNEXAL STRUCTURES.
• SPINDLE CELLS STAIN POSITIVE FOR CD34, FACTOR XIIIa, VIMENTIN AND FASCIN, SUGGESTING A DERMAL DENDRITIC ORIGIN.
• ATROPHIC DERMATOFIBROSARCOMA PROTUBERANS IS ALSO CD34 POSITIVE, BUT IS FACTOR XIIIa NEGATIVE.
• PRESENTATION: A REDDISH BROWN, SLIGHTLY INDURATED, CONGENITAL, ATROPHIC LESION OF THE SKIN OFTEN ON THE SIDE OF THE NECK OR ON THE UPPER TRUNK.
• LESIONS ARE TYPICALLY ROUND OR OVAL, MEASURE 2–6 cm ACROSS AND PERSIST UNALTERED INTO ADULTHOOD.
• THEY MAY SHOW A SLIGHT INCREASE IN HAIR GROWTH AND VISIBLE UNDERLYING BLOOD VESSELS BENEATH A WRINKLED EPIDERMIS.
• DIFFERENTIAL DIAGNOSIS: CONGENITAL DERMATOFIBROSARCOMA PROTUBERANS, APLASIA CUTIS CONGENITA, ANETODERMA OF PREMATURITY, NEUROFIBROMA (ATROPHIC BLUE-RED MACULE VARIANT) AND CUTIS MARMORATA TELANGIECTATICA CONGENITA.
• THERE APPEARS TO BE SOME OVERLAP WITH FIBROBLASTIC CONNECTIVE TISSUE NAEVI, WHICH ALSO PRESENT AS CD34-POSITIVE SOLITARY PAINLESS PLAQUES OR NODULES.
• DISEASE COURSE: THE COURSE IS PERSISTENT BUT THERE IS NO RECORDED CASE OF MALIGNANT TRANSFORMATION.
• INVESTIGATIONS: SKIN BIOPSY AND IMMUNOSTAINING ARE USEFUL.
• MANAGEMENT: THERE IS NO KNOWN MEDICAL THERAPY. LESIONS CAN BE SAFELY LEFT OR EXCISED (USUALLY BY A PLASTIC SURGEON, DEPENDING ON THE SIZE).

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• CLINICAL MANIFESTATIONS IN THE NEONATE HAVE BEEN REPORTED IN A NUMBER OF MATERNAL DISORDERS BELIEVED TO BE INDUCED BY CIRCULATING AUTOANTIBODIES: PEMPHIGUS VULGARIS, PEMPHIGUS FOLIACEUS, HERPES GESTATIONIS AND LUPUS ERYTHEMATOSUS.
• BECAUSE IgA, IgM AND IgE ANTIBODIES DO NOT CROSS THE PLACENTA IN SIGNIFICANT AMOUNTS, THIS PHENOMENON IS RESTRICTED TO DISEASES CAUSED BY AUTOANTIBODIES OF IgG CLASS.
• PLACENTAL TRANSFER OF IgG IS A MECHANISM FOR PROTECTING THE NEONATE WHILE THEIR IMMUNE SYSTEM IS IMMATURE AND INEFFECTIVE.
• WHERE COMPLEMENT IS ALSO INVOLVED IN PATHOGENESIS, THIS MUST BE PROVIDED BY THE FETUS AS IT DOES NOT PASS ACROSS THE PLACENTA. COMPLEMENT CAN BE DETECTED IN THE FETUS FROM ABOUT THE 11th WEEK OF GESTATION.
• MATERNAL IgG IS CATABOLISED MORE OR LESS COMPLETELY WITHIN THE FIRST 3–6 MONTHS OF LIFE, AND ANTIBODY-MEDIATED TRANSPLACENTAL DISEASES CAN BE EXPECTED TO REMIT SPONTANEOUSLY WITHIN THIS PERIOD.

• PEMPHIGUS VULGARIS IS UNUSUAL IN PREGNANCY BECAUSE IT IS LARGELY A DISEASE OF AN OLDER AGE GROUP AND BECAUSE AFFECTED INDIVIDUALS RECEIVING SYSTEMIC TREATMENT RARELY BECOME PREGNANT.
• NEVERTHELESS, SEVERAL CASES OF TRANSPLACENTALLY TRANSMITTED PEMPHIGUS VULGARIS HAVE BEEN REPORTED (Chapter 50).
• NOT ALL MOTHERS HAVE HAD CLINICALLY APPARENT DISEASE DURING PREGNANCY; IN OTHER CASES THE DISEASE HAS BEEN MILD.
• IT IS RARE THAT PREGNANCY IS CONSIDERED AS A TRIGGERING FACTOR FOR PEMPHIGUS.
• AFFECTED INFANTS HAVE HAD CUTANEOUS AND/OR MUCOSAL EROSIONS OR BULLAE; SEVERAL HAVE BEEN STILLBORN.
• APPROXIMATELY ONE-THIRD OF NEONATES BORN TO MOTHERS WITH PEMPHIGUS ARE UNAFFECTED AT BIRTH.
• DIRECT IMMUNOFLUORESCENCE HAS BEEN POSITIVE IN SKIN BIOPSIES FROM ALL AFFECTED INFANTS, AND CIRCULATING IgG PEMPHIGUS ANTIBODIES HAVE BEEN FOUND IN THE MAJORITY.
• THERE ARE NO CASES OF INFANTS BORN TO MOTHERS WITH PEMPHIGUS REQUIRING TREATMENT.
• LESIONS HAVE RESOLVED SPONTANEOUSLY WITHIN ABOUT 3 WEEKS AND NO NEW LESIONS HAVE OCCURRED AFTER BIRTH.
• CIRCULATING IgG ANTIBODIES BECOME UNDETECTABLE BY THE END OF THE SECOND MONTH OF LIFE.
• TRANSPLACENTAL TRANSMISSION OF PEMPHIGUS FOLIACEUS HAS BEEN SIMILARLY DESCRIBED.

• CUTANEOUS LESIONS OCCUR IN ABOUT 10% OF INFANTS BORN TO MOTHERS WITH PEMPHIGOID GESTATIONIS, ALTHOUGH MATERNAL IgG ANTIBASEMENT MEMBRANE AUTOANTIBODY CAN BE FOUND IN ALL INFANTS OF AFFECTED MOTHERS (Chapter 113).
• THE LESIONS MAY BE PRESENT AT BIRTH OR THEY MAY APPEAR AT ANY TIME UP TO THE THIRD DAY OF LIFE.
• THESE LESIONS MAY VARY FROM EVANESCENT, NON-SPECIFIC, RED OR URTICARIAL PAPULES TO FULLY DEVELOPED BULLAE. LESIONS IN THE INFANT MAY BE EXTENSIVE.
• SPONTANEOUS REGRESSION OF LESIONS WITHIN 3 WEEKS IS THE RULE.
• DIRECT IMMUNOFLUORESCENCE IS NORMAL BY THE END OF THE FIRST MONTH, AND CIRCULATING IgG ANTIBASEMENT MEMBRANE ZONE ANTIBODY CAN NO LONGER BE FOUND.
• THE RISK OF FETAL AND INFANT MORBIDITY AND MORTALITY IN MOTHERS WITH PEMPHIGOID GESTATIONIS IS DEBATED AND HAS NOT BEEN CONFIRMED, ALTHOUGH THERE ARE SOME REPORTS OF FETAL GROWTH RESTRICTION AND PRE-ECLAMPSIA.
• HOWEVER, THERE DOES APPEAR TO BE AN INCREASED RISK OF PREMATURE DELIVERY.
• THE RISK OF ADRENAL INSUFFICIENCY SHOULD BE CONSIDERED IN NEONATES WHOSE MOTHERS HAVE REQUIRED LONG-TERM ORAL PREDNISOLONE TREATMENT.

• A RARE SYNDROME COMPRISING TRANSIENT SKIN LESIONS RESEMBLING SUBACUTE CUTANEOUS LE AND/OR CONGENITAL HEART BLOCK (Chapter 51).
• OCCURS IN THE BABIES OF MOTHERS WITH CLINICAL OR SUBCLINICAL AUTOIMMUNE CONNECTIVE TISSUE DISEASE, AND IS ASSOCIATED WITH THE TRANSPLACENTAL PASSAGE OF MATERNAL AUTOANTIBODIES TO THE RIBONUCLEOPROTEINS (RNPs) Ro-SSA (>90%), La-SSB OR RARELY U1-RNP.
• EPIDEMIOLOGY:
• ONLY 1–2% OF Ro-POSITIVE/La-POSITIVE MOTHERS WILL HAVE BABIES WITH NEONATAL LE, BUT BABIES FROM SUBSEQUENT PREGNANCIES HAVE A 20–25% RISK OF SKIN OR CARDIAC DISEASE.
• AGE: OCCURS IN NEONATES UP TO 3 MONTHS OLD. EQUAL SEX INCIDENCE. DESCRIBED IN ALL RACIAL GROUPS.
• ASSOCIATED DISEASES: THE RISK OF CONNECTIVE TISSUE DISEASE LATER IN LIFE IS INCREASED.
• PATHOPHYSIOLOGY:
• PROVOKED IN THE FETUS OR NEWBORN INFANT BY MATERNAL IgG AUTOANTIBODIES THAT HAVE CROSSED THE PLACENTA.
• IN 95% OF CASES, THESE ARE OF IgG1 CLASS AND ARE DIRECTED AGAINST THE Ro RNP ANTIGEN.
• THESE ANTIBODIES ARE RELATIVELY PREVALENT IN YOUNG WOMEN, AND OFTEN APPEAR TO BE COMPATIBLE WITH APPARENTLY NORMAL HEALTH.
• ANTI-La, ANTI-NATIVE DNA, ANTICARDIOLIPIN OR ANTINUCLEAR ANTIBODIES, OR RHEUMATOID FACTOR MAY BE PRESENT IN ADDITION TO Ro ANTIBODIES.
• A SMALL PROPORTION OF AFFECTED INFANTS DO NOT HAVE DETECTABLE Ro ANTIBODIES BUT DO HAVE La AND U1-RNP ANTIBODIES.
• THE PRESENCE OF Ro AND La ANTIGENS HAS BEEN DEMONSTRATED IN FETAL SKIN AND CARDIAC CONDUCTING TISSUE.
• UP TO 60% OF THE MOTHERS OF INFANTS WITH NEONATAL LE HAVE NO CLINICAL EVIDENCE OF CONNECTIVE TISSUE DISEASE AT THE TIME OF BIRTH. HOWEVER, THERE IS A SUBSTANTIAL RISK OF A SUBSEQUENT DEVELOPMENT OF SYMPTOMS.
• ABOUT 40% OF MOTHERS HAVE SIGNS OR SYMPTOMS OF SYSTEMIC LE, SUBACUTE CUTANEOUS LE OR THE SICCA SYNDROME, ALTHOUGH THESE MAY BE MINIMAL.
• ABOUT 5% OF WOMEN OF CHILD-BEARING AGE WHO PRESENT WITH LEUKOCYTOCLASTIC VASCULITIS WILL HAVE Ro ANTIBODIES, AND IT IS PROBABLE THAT ABOUT 5% OF BABIES WITH NEONATAL LE HAVE MOTHERS WITH LEUKOCYTOCLASTIC VASCULITIS.
• PREDISPOSING FACTORS: THERE APPEARS TO BE A GENETIC PREDISPOSITION TO DEVELOP THE CARDIAC COMPLICATIONS.
• ENVIRONMENTAL FACTORS: SUNLIGHT MAY INDUCE SKIN LESIONS.
• PATHOLOGY: SKIN BIOPSY SPECIMENS GENERALLY DEMONSTRATE THE FEATURES OF LE: EPIDERMAL ATROPHY, LIQUEFACTION DEGENERATION OF BASAL KERATINOCYTES, COLLOID BODIES AND A PERIVASCULAR AND PERIAPPENDAGEAL LYMPHOHISTIOCYTIC INFLAMMATORY INFILTRATE IN THE DERMIS.
• DIRECT IMMUNOFLUORESCENCE IS POSITIVE IN ABOUT 50% OF CASES, SHOWING DERMAL–EPIDERMAL JUNCTION AND PERIVASCULAR DEPOSITION OF IgG, IgM AND C3.
• PRESENTATION:
• MOST INFANTS HAVE EITHER SKIN LESIONS (90%) OR CARDIAC LESIONS (1%); APPROXIMATELY 8% HAVE BOTH.
• IN ABOUT TWO-THIRDS OF THOSE INFANTS WHO DEVELOP CUTANEOUS LESIONS, THESE ARE ALREADY PRESENT AT BIRTH. IN THE REMAINDER, THE LESIONS APPEAR DURING THE FIRST 2–3 MONTHS (SOMETIMES SUN-INDUCED), ALTHOUGH THEIR APPEARANCE MAY BE DELAYED FOR AS LONG AS 5 MONTHS.
• THE SKIN LESIONS GENERALLY TAKE THE FORM OF WELL-DEFINED AREAS OF MACULAR OR SLIGHTLY ELEVATED REDNESS, FREQUENTLY ANNULAR, OCCURRING PREDOMINANTLY ON THE FACE, PARTICULARLY THE FOREHEAD, TEMPLES AND UPPER CHEEKS, AND ON THE SCALP AND NECK.
• A 'SPECTACLE-LIKE' DISTRIBUTION OF LESIONS AROUND THE EYES IS ESPECIALLY CHARACTERISTIC. THE CHEST, BACK OR LIMBS MAY ALSO BE AFFECTED.
• PROVOCATION OR EXACERBATION OF LESIONS BY SUN EXPOSURE HAS BEEN REPORTED IN SOME CASES.
• FOLLICULAR PLUGGING IS NOT PROMINENT, BUT SCALING IS A COMMON EARLY FEATURE.
• A DEGREE OF ATROPHY AND/OR TELANGIECTASIA ARE FREQUENT LONG-TERM SEQUELAE. PERMANENT HAIR LOSS MAY OCCUR.
• IN MOST CASES, THE SKIN LESIONS HAVE RESOLVED WITHIN THE FIRST YEAR, BUT AREAS OF ATROPHY AND/OR TELANGIECTASIA MAY BE MORE PERSISTENT.
• LONGSTANDING DEPRESSIONS HAVE FOLLOWED SUBCUTANEOUS LESIONS. THE MOST FREQUENT SITES FOR SUCH LESIONS ARE THE TEMPLES AND SCALP.
• CLINICAL VARIANTS:
• LESS COMMONLY, LESIONS TAKE THE FORM OF ANNULAR PATCHES OF REDNESS WITHOUT AN EPIDERMAL COMPONENT; THIS TYPE OF PRESENTATION HAS PREDOMINANTLY BEEN REPORTED IN JAPANESE INFANTS.
• SUBCUTANEOUS LESIONS HAVE ALSO BEEN DESCRIBED.
• OCCASIONALLY, NEONATAL LE PRESENTS AS EXTENSIVE RETICULATE REDNESS WITH ATROPHY, CLOSELY RESEMBLING CUTIS MARMORATA TELANGIECTATICA CONGENITA.
• DEPIGMENTATION MAY BE VERY PROMINENT IN INFANTS WITH SKIN OF COLOUR. LESIONS RESEMBLING MORPHOEA HAVE BEEN REPORTED.
• DIFFERENTIAL DIAGNOSIS:
• THE LESIONS OF CONGENITAL RUBELLA OR CYTOMEGALOVIRUS INFECTION MAY NEED TO BE CONSIDERED, ALTHOUGH THESE ARE OF PURPLISH COLOUR AND PURPURA IS GENERALLY PROMINENT.
• CONGENITAL SYPHILIS MAY ALSO NEED TO BE EXCLUDED, BUT WHEREAS MUCOSAL, PERIORIFICIAL AND PALMAR AND PLANTAR LESIONS ARE COMMON IN CONGENITAL SYPHILIS, THESE FEATURES ARE RARE IN NEONATAL LE.
• CONFUSION MAY BE CAUSED BY THE FALSE POSITIVE ANTIBODY TESTS THAT ARE AS MUCH A FEATURE OF NEONATAL AS OF ACQUIRED LE.
• ATROPHY AND TELANGIECTASIA OF THE CHEEKS IS SEEN WITH PHOTOSENSITIVITY IN BLOOM SYNDROME (Chapter 77), AND WITHOUT PHOTOSENSITIVITY (IN MOST CASES) IN THE ROTHMUND–THOMSON SYNDROME (Chapter 75). IN THESE DISORDERS, SKIN LESIONS ARE NOT PRESENT AT BIRTH AND GENERALLY APPEAR LATER THAN IN NEONATAL LE.
• COMPLICATIONS AND CO-MORBIDITIES:
• SYSTEMIC FEATURES ARE DETECTABLE IN OVER HALF OF ALL AFFECTED INFANTS, OF WHICH CARDIAC INVOLVEMENT IS THE COMMONEST.
• CONGENITAL HEART BLOCK (DUE TO FIBROSIS OF THE CONDUCTING TISSUE) OCCURS IN ABOUT 1–2% OF Ro-POSITIVE PREGNANCIES, PROBABLY DUE TO GENETIC SUSCEPTIBILITY. IN THESE FAMILIES IT WILL RECUR IN 20% OF SUBSEQUENT PREGNANCIES.
• ANTI-Ro ANTIBODIES CAN BIND TO CARDIAC CONDUCTION CELLS DURING MID TO LATE FETAL DEVELOPMENT, LEADING TO ALTERED MEMBRANE REPOLARISATION AND SELECTIVE DAMAGE TO THE ATRIOVENTRICULAR NODE.
• CONGENITAL HEART BLOCK CAN BE DETECTED AS EARLY AS THE 18th WEEK OF GESTATION BY ULTRASOUND OR ELECTROCARDIOGRAPHY.
• THE BLOCK IS GENERALLY PERMANENT, AND IS NOT ASSOCIATED WITH STRUCTURAL CARDIAC ABNORMALITIES SUCH AS SEPTAL DEFECTS. ABOUT A HALF OF AFFECTED INFANTS REQUIRE PACEMAKERS.
• A SMALLER PROPORTION OF INFANTS HAVE COMBINATIONS OF HEPATOMEGALY, SPLENOMEGALY, LYMPHADENOPATHY AND PNEUMONITIS, WHICH ARE GENERALLY MILD IN DEGREE AND FAIRLY TRANSIENT.
• AUTOIMMUNE HAEMOLYTIC ANAEMIA AND THROMBOCYTOPENIA ARE SEEN IN A SMALL PROPORTION OF AFFECTED INFANTS.
• THE CENTRAL NERVOUS SYSTEM MAY BE INVOLVED AND THIS CAN CAUSE AN ASYMPTOMATIC VASCULOPATHY OR A MORE SERIOUS CEREBRAL VASCULITIS.
• DISEASE COURSE AND PROGNOSIS:
• INFANTS WITH SKIN LESIONS ALONE, OR WITH SKIN LESIONS AND SYSTEMIC FEATURES OTHER THAN HEART BLOCK, GENERALLY SHOW LITTLE SIGN OF RESIDUAL DISEASE AFTER THE AGE OF 1 YEAR.
• HOWEVER, THEIR LONG-TERM PROGNOSIS MUST REMAIN SLIGHTLY AT RISK IN THE LIGHT OF REPORTS OF THE LATER DEVELOPMENT BY SOME OF FULL-BLOWN CONNECTIVE TISSUE DISEASE.
• CONDUCTION DEFECTS OF THE HEART TEND TO BE PERMANENT, AND WHEN SEVERE ARE ASSOCIATED WITH A SIGNIFICANT MORTALITY.
• THE RISK OF RECURRENCE IN FURTHER PREGNANCIES APPEARS TO BE ABOUT 20–25%.
• SPONTANEOUS ABORTION AND STILLBIRTH DO NOT APPEAR TO BE MORE FREQUENT IN FURTHER PREGNANCIES OF MOTHERS WHO HAVE HAD A PREVIOUS CHILD WITH NEONATAL LE.
• NEONATAL LE ANTIBODIES DISAPPEAR FROM THE INFANT'S SERUM WITHIN ABOUT 6 MONTHS.
• INVESTIGATIONS: A SKIN BIOPSY WILL USUALLY ALLOW AN ACCURATE DIAGNOSIS, PARTICULARLY IF COMBINED WITH DIRECT IMMUNOFLUORESCENCE STUDIES, AND TESTS FOR THE APPROPRIATE CIRCULATING AUTOANTIBODIES IN BOTH THE MOTHER AND THE CHILD.
• MANAGEMENT:
• THE SKIN LESIONS REQUIRE NO TREATMENT, BUT SUN PROTECTION IS ESSENTIAL.
• OCCASIONALLY, THROMBOCYTOPENIA, HAEMOLYTIC ANAEMIA OR HEPATITIS MAY WARRANT SYSTEMIC STEROID THERAPY.
• UP TO 50% OF INFANTS WITH CARDIAC INVOLVEMENT WILL REQUIRE A PACEMAKER.
• THE PREGNANCY OF A WOMAN WHO HAS Ro, La OR U1-RNP ANTIBODIES SHOULD BE MONITORED TO DETECT A SLOW FETAL HEART RATE.
• TREATMENT WITH HIGH-DOSE SYSTEMIC STEROIDS MAY BE INDICATED FOR FETAL BRADYCARDIA WHERE THERE ARE SIGNS OF HEART FAILURE.

• FORTUNATELY EXTREMELY RARE, DESPITE THE FACT THAT MALIGNANCY OCCURS IN 1 IN 1000 PREGNANCIES, AND IT IS WELL ESTABLISHED THAT MATERNAL CELLS REGULARLY REACH THE FETUS.
• MELANOMA ACCOUNTS FOR APPROXIMATELY 90% OF TRANSPLACENTALLY TRANSFERRED MALIGNANT DISEASE, ALTHOUGH THIS PARTICULAR MALIGNANCY ACCOUNTS FOR ONLY ABOUT 8% OF THOSE OCCURRING IN PREGNANT WOMEN.
• MELANOMA TRANSMITTED IN THIS WAY MAY RESULT IN THE APPEARANCE OF NODULAR SKIN DEPOSITS IN THE NEONATE.
• FETAL MELANOMA METASTASIS IS REPORTED IN MOTHERS ALREADY KNOWN TO HAVE METASTATIC MELANOMA, AND THERE WAS PLACENTAL INVOLVEMENT IN ALL CASES.
• PLACENTAL INVOLVEMENT DOES NOT ALWAYS SIGNIFY METASTATIC DISEASE IN THE NEONATE.
• ALTHOUGH THE PROGNOSIS IS GENERALLY POOR, SPONTANEOUS REGRESSION OF TRANSPLACENTALLY TRANSFERRED MELANOMA HAS BEEN REPORTED.
• IN CASES WHERE PLACENTAL METASTASIS IS DETECTED WITH NO EVIDENCE OF FETAL METASTASIS THE INFANT SHOULD BE MONITORED UNTIL 24 MONTHS WITH SKIN EXAMINATION, IMAGING (CHEST X-RAY AND LIVER ULTRASOUND) AND BLOOD MONITORING (LACTATE DEHYDROGENASE AND LIVER ENZYMES).
• TRANSPLACENTAL TRANSMISSION OF ACUTE MONOCYTIC LEUKAEMIA, NATURAL KILLER CELL LYMPHOMA AND CHORIOCARCINOMA HAS ALSO BEEN REPORTED.
• CHECKING THE MATERNAL ORIGIN OF A TUMOUR IN A NEONATE CAN BE DONE QUICKLY BY A QUANTITATIVE POLYMERASE CHAIN REACTION (PCR) TECHNIQUE.

• WHEN CONSIDERING THE CAUSE OF ANY RASH IN A YOUNG INFANT, THE POSSIBILITY THAT IT REFLECTS EXPOSURE OF THE MOTHER TO A TOXIC SUBSTANCE THAT HAS BEEN TRANSFERRED IN HER MILK NEEDS TO BE BORNE IN MIND.
• A GOOD EXAMPLE IS PROVIDED BY TWO REPORTS OF BROMODERMA OCCURRING IN NEONATES WHOSE MOTHERS HAD TAKEN BROMIDE MEDICINALLY OR HAD BEEN ACCIDENTALLY EXPOSED IN A PHOTOGRAPHIC LABORATORY.

---

• FOUR SEPARATE CONDITIONS ARE DESCRIBED — COLD PANNICULITIS, NEONATAL COLD INJURY, SUBCUTANEOUS FAT NECROSIS OF THE NEWBORN AND SCLEREMA NEONATORUM — BUT THERE IS SOME CLINICAL AND PATHOLOGICAL OVERLAP.

• A DISTINCTIVE FORM OF PANNICULITIS PROVOKED DIRECTLY BY COLD EXPOSURE, TO WHICH INFANTS APPEAR PARTICULARLY PREDISPOSED.
• THE FAT OF THE NEWBORN APPEARS TO BE MORE HIGHLY SATURATED THAN THAT OF OLDER CHILDREN AND ADULTS, WITH THE EFFECT THAT IT SOLIDIFIES AT A HIGHER TEMPERATURE.
• APPLYING ICE FOR 50 s CAUSES PANNICULITIS IN ALL NEWBORN INFANTS, IN ONLY 40% OF 6-MONTH-OLD INFANTS AND ALMOST NEVER IN 9-MONTH-OLD INFANTS.
• COLD PANNICULITIS IN INFANCY HAS MOST OFTEN FOLLOWED EXPOSURE OF THE CHEEKS TO:

1. EXTREMELY COLD AIR.
2. ICE BAGS APPLIED AS A THERAPY FOR SUPRAVENTRICULAR TACHYCARDIA.
3. FROZEN LOLLIES (POPSICLES).

• INDURATED, WARM, RED, SUBCUTANEOUS PLAQUES AND NODULES APPEAR WITHIN HOURS OR DAYS OF APPROPRIATE COLD EXPOSURE.
• SKIN BIOPSY IS NOT USUALLY NEEDED BUT IF DONE EARLY IT SHOWS A LYMPHOHISTIOCYTIC INFILTRATE AROUND BLOOD VESSELS AT THE JUNCTION OF THE DERMIS AND SUBCUTANEOUS FAT.
• AFTER A FEW DAYS, LIPOCYTE RUPTURE LEADS TO THE FORMATION OF CYSTIC CAVITIES SURROUNDED BY AREAS OF MARKED INFILTRATION BY LYMPHOCYTES AND HISTIOCYTES, WITH A FEW NEUTROPHILS AND EOSINOPHILS.
• THE INDURATION RESOLVES OVER A PERIOD OF A WEEK OR SO, OFTEN LEAVING SOME RESIDUAL POSTINFLAMMATORY HYPERPIGMENTATION. NO TREATMENT IS REQUIRED.

• A DISORDER, NOW RARE IN DEVELOPED COUNTRIES, IN WHICH COLD EXPOSURE OF A SMALL-FOR-DATES NEONATE CAUSES HYPOTHERMIA ASSOCIATED WITH LETHARGY AND GENERALISED PITTING OEDEMA OF THE SKIN, CLINICALLY AND PATHOLOGICALLY DISTINCT FROM SCLEREMA NEONATORUM.
• A LOW ENVIRONMENTAL TEMPERATURE HAS BEEN THE PRINCIPAL CAUSE OF VIRTUALLY ALL REPORTED CASES.
• OTHER PREDISPOSING FACTORS: INTRAUTERINE GROWTH RETARDATION, WHICH RESULTS IN A RELATIVELY THIN PANNICULUS, AND TIGHT WRAPPINGS, WHICH RESTRICT MUSCULAR ACTIVITY.
• THE INFANT IS USUALLY A FULL-TERM NEONATE, BORN AT HOME, BUT SMALL FOR GESTATIONAL AGE.
• IN THE GREAT MAJORITY OF CASES, PRESENTATION IS WITHIN THE FIRST 4 DAYS OF LIFE, AND USUALLY DURING THE FIRST 24 h.
• THE MOST STRIKING FEATURES ARE INTENSE REDNESS OR CYANOSIS OF THE FACE AND EXTREMITIES, AND FIRM, PITTING OEDEMA BEGINNING AT THE EXTREMITIES AND SPREADING CENTRALLY, AND BECOMING PROGRESSIVELY MORE INDURATED IN A PROPORTION OF CASES.
• PETECHIAE HAVE OCCASIONALLY BEEN OBSERVED. THE SKIN FEELS COLD, AND THE BABY IS USUALLY HYPOTHERMIC WITH A LOW CORE TEMPERATURE.
• ASSOCIATED NON-CUTANEOUS FEATURES OF COLD INJURY ARE GENERALLY PRESENT, AND MAY OCCUR IN THE ABSENCE OF SKIN CHANGES: IMMOBILITY, DROWSINESS, POOR FEEDING, VOMITING, OLIGURIA AND GASTROINTESTINAL BLEEDING WITH VOMITING OF ALTERED BLOOD OR MELAENA.
• SKIN BIOPSY SHOWS A THIN PANNICULUS; OTHERWISE THERE IS LITTLE OBVIOUS ABNORMALITY APART FROM DILATATION OF THE DERMAL BLOOD VESSELS.
• PROFUSE EXUDATION OF CLEAR FLUID FROM THE CUT SURFACE AT POSTMORTEM SUGGESTS THAT THE INDURATION IS DUE TO OEDEMA.
• THE MORTALITY RATE OF HISTORICAL CASES WAS ABOUT 25% (USUALLY DUE TO MASSIVE PULMONARY HAEMORRHAGE).
• FORTUNATELY, THE CONDITION SEEMS TO BE MUCH LESS COMMON IN THE UK NOW THAN IT WAS 40 YEARS AGO, PROBABLY BECAUSE OF IMPROVED HEATING IN HOMES, REDUCED FREQUENCY OF HOME DELIVERY AND ABANDONMENT OF THE PREVIOUS HABIT OF BATHING BABIES AT BIRTH.
• CARE SHOULD BE TAKEN WHEN REWARMING IN CASES OF ACCIDENTAL HYPOTHERMIA AS RAPID REWARMING IN PROLONGED HYPOTHERMIA IS ASSOCIATED WITH FATAL THROMBOCYTOPENIA.

• DEFINITION: A RARE AND USUALLY TRANSIENT FORM OF PANNICULITIS WHICH MOSTLY AFFECTS FULL-TERM INFANTS USUALLY WITHIN THE FIRST FEW WEEKS OF LIFE.
• EPIDEMIOLOGY: THE INCIDENCE IS UNKNOWN BUT THE DISEASE IS RARE.
• AGE: GENERALLY OCCURS IN FULL-TERM OR POST-TERM INFANTS OF NORMAL BIRTH WEIGHT DURING THE FIRST 6 WEEKS OF LIFE.
• SEX: EQUAL SEX INCIDENCE. ETHNICITY: UNKNOWN INFLUENCE.
• ASSOCIATED DISEASES: MATERNAL PRE-ECLAMPSIA, DIABETES, PERINATAL ASPHYXIA AND HYPOTHERMIA, INCLUDING THERAPEUTIC WHOLE BODY COOLING.
• PREDISPOSING FACTORS: THE PRECISE CAUSE IS UNESTABLISHED, BUT A VARIETY OF INSULTS APPEAR TO HAVE CONTRIBUTED IN INDIVIDUAL CASES: BIRTH ASPHYXIA, MATERNAL PRE-ECLAMPSIA, MATERNAL DIABETES, OBSTETRIC TRAUMA, HYPOTHERMIA AND HYPOTHERMIC CARDIAC SURGERY.
• THE MOST IMPORTANT PREDISPOSING FACTORS APPEAR TO BE THE COMBINATION OF LOCAL TISSUE HYPOXIA AND COLD INJURY.
• THIS MIGHT EXPLAIN THE PREDOMINANT LOCATION OF LESIONS ON THE SHOULDERS AND BUTTOCKS, CUTANEOUS AREAS WHERE MECHANICAL PRESSURE MIGHT COMPROMISE THE CIRCULATION AND CONTRIBUTE TO HYPOXIA.
• A PRIMARY ABNORMALITY IN BROWN FAT HAS ALSO BEEN POSTULATED.
• PATHOLOGY: CHARACTERISED BY GRANULOMATOUS REACTION, LOBULAR PANNICULITIS AND MULTINUCLEATED GIANT CELLS.
• THE COMPOSITION OF NEONATAL FAT WITH INCREASED SATURATED FATTY ACIDS AND ITS HIGHER MELTING POINT COMPARED WITH ADULT FAT HAVE BEEN ASSOCIATED WITH THE TENDENCY FOR SOLIDIFICATION AND CRYSTALLISATION.
• BOTH THE FAT CELLS AND THE GIANT CELLS CONTAIN NEEDLE-SHAPED CLEFTS, WHICH MAY BE RADIALLY ARRANGED.
• FIBROTIC OBLITERATION OF SMALL ARTERIOLES HAS ALSO BEEN OBSERVED. CALCIUM DEPOSITS ARE COMMONLY FOUND IN THE NECROTIC FAT.
• ULTRASTRUCTURAL EXAMINATION HAS SHOWN PARALLEL AGGREGATIONS OF ELECTRON-LUCENT, NEEDLE-SHAPED SPACES WITHIN THE ADIPOCYTES.
• SIMILAR CHANGES IN VISCERAL ADIPOSE TISSUE HAVE BEEN REPORTED IN POSTMORTEM STUDIES. WIDESPREAD CALCIUM DEPOSITION IN INTERNAL ORGANS HAS ALSO BEEN SHOWN IN POSTMORTEM SPECIMENS FROM HYPERCALCAEMIC CASES AND NEPHROCALCINOSIS HAS BEEN OBSERVED IN SUCH INFANTS DURING LIFE.
• ENVIRONMENTAL FACTORS: HYPOXIA, COLD AND TRAUMA ALL SEEM TO PLAY A ROLE.
• PRESENTATION:
• INFANTS ARE GENERALLY FULL-TERM OR POST-TERM NEONATES OF NORMAL WEIGHT.
• THERE IS AN ASSOCIATION WITH PERINATAL ASPHYXIA, THERAPEUTIC HYPOTHERMIA, MECONIUM ASPIRATION AND OBSTETRIC TRAUMA.
• IT IS GENERALLY FELT THAT SOME FORM OF NEONATAL DISTRESS CAN REDUCE THE BLOOD SUPPLY TO NEONATAL FATTY TISSUE, RESULTING IN NECROSIS IN AN ATTEMPT TO SHUNT BLOOD FROM THE SKIN AND ADIPOSE TISSUE TO THE VITAL ORGANS.
• NODULAR THICKENING OF THE SUBCUTANEOUS TISSUES IS USUALLY FIRST DETECTED BETWEEN THE 2nd AND 21st DAYS OF LIFE. SOMETIMES THE CHANGES ARE PRESENT AT BIRTH AND, RARELY, THEY MAY APPEAR AS LATE AS THE SIXTH WEEK.
• THE NODULES TEND TO BE SYMMETRICALLY DISTRIBUTED AND SHOW A PREDILECTION FOR THE BUTTOCKS, THIGHS, SHOULDERS, BACK, CHEEKS AND ARMS.
• LESIONS MAY BE SINGLE OR MULTIPLE, ROUNDED OR OVAL, AND PEA-SIZED OR MANY CENTIMETRES IN DIAMETER. INITIALLY DISCRETE, BUT MAY FUSE TO FORM LARGE PLAQUES.
• THE OVERLYING SKIN IS OFTEN RED OR BLUISH RED. THE NODULES FEEL RUBBERY OR HARD, AND ARE NOT ATTACHED TO DEEPER STRUCTURES. THE LESIONS MAY BE PAINFUL.
• NEW NODULES MAY CONTINUE TO DEVELOP FOR A WEEK OR MORE.
• THERE HAS BEEN A SINGLE REPORT OF SCFN BEING COMPLICATED BY A HAEMATOMA, REQUIRING SURGICAL DEBRIDEMENT.
• IN MOST CASES, THE CHILD'S HEALTH IS NOT SUBSTANTIALLY IMPAIRED, AND WITHIN A FEW MONTHS THE NODULES DISAPPEAR.
• WHERE CALCIUM DEPOSITION IS MARKED, THE LESIONS MAY TAKE RATHER LONGER TO RESOLVE. USUALLY NO TRACE OF THE NODULES REMAINS BUT THERE MAY BE SLIGHT ATROPHY.
• RARELY, THE NODULES MAY ULCERATE, DISCHARGE THEIR FATTY CONTENTS AND LEAVE SCARS.
• THE CONDITION HAS OCCASIONALLY BEEN FATAL, PARTICULARLY WHEN VISCERAL FAT HAS BEEN INVOLVED, OR WHERE THERE HAS BEEN COMPLICATING HYPERCALCAEMIA.
• CLINICAL VARIANTS: SEVERAL REPORTS OF LESIONS ANALOGOUS TO SCFN IN CHILDREN WHO HAVE HAD HYPOTHERMIC CARDIAC SURGERY.
• THE CUTANEOUS APPLICATION OF ICE TO INDUCE HYPOTHERMIA, TRAUMA AND/OR HYPOXIA MAY ALL HAVE CONTRIBUTED.
• NOTEWORTHY THAT THESE CHILDREN APPEAR TO HAVE DEVELOPED LESIONS OF SUBCUTANEOUS FAT NECROSIS RATHER THAN COLD PANNICULITIS.
• THE AGES OF THE CHILDREN AT THE TIME OF SURGERY VARIED FROM 12 DAYS TO 20 MONTHS. LESIONS APPEARED BETWEEN 14 AND 30 DAYS LATER, PRINCIPALLY AT THE SITES SUBJECTED TO THE GREATEST COLD EXPOSURE. THE LESIONS RESOLVE WITHIN A FEW WEEKS AND NO TREATMENT IS USUALLY REQUIRED.
• DIFFERENTIAL DIAGNOSIS: NEONATES DELIVERED BY FORCEPS MAY DEVELOP SUBCUTANEOUS NODULES WHERE THE FORCEPS WERE APPLIED, PRESUMABLY AS A RESULT OF TRAUMATIC FAT NECROSIS.
• SCFN WAS IN THE PAST FREQUENTLY CONFUSED WITH SCLEREMA NEONATORUM. OCCASIONALLY, THE TWO CONDITIONS MAY OCCUR SIMULTANEOUSLY.
• COMPLICATIONS:
• SCFN MAY BE ASSOCIATED WITH HYPERCALCAEMIA, WHICH TENDS TO OCCUR IN AROUND A QUARTER OF ALL CASES, APPEARS MORE FREQUENTLY IN INFANTS WITH EXTENSIVE DISEASE, AND ALMOST EXCLUSIVELY WHEN THE TRUNK IS AFFECTED.
• THE CAUSE OF THE HYPERCALCAEMIA IS UNKNOWN. IT MAY BE DUE TO INCREASED CALCIUM ABSORPTION DUE TO EXTRARENAL PRODUCTION OF 1,25-DIHYDROXYVITAMIN D, WHICH HAS BEEN OBSERVED IN OTHER GRANULOMATOUS DISORDERS INCLUDING SARCOIDOSIS.
• THE FINDING OF INCREASED URINARY EXCRETION OF PROSTAGLANDIN E1 LED TO THE SUGGESTION THAT INCREASED BONE CALCIUM RESORPTION MIGHT BE RESPONSIBLE.
• TRANSIENT THROMBOCYTOPENIA HAS BEEN REPORTED DURING THE PERIOD OF INITIAL DEVELOPMENT OF THE LESIONS, POSSIBLY DUE TO SEQUESTRATION OF PLATELETS.
• PLASMA LIPID ABNORMALITIES HAVE BEEN REPORTED IN A NEONATE WITH SCFN, BUT THEIR RELEVANCE WAS UNCLEAR.
• ALL INFANTS WHO HAVE EXPERIENCED SCFN SHOULD HAVE THEIR SERUM CALCIUM MEASURED ON PRESENTATION AND EVERY 2–3 WEEKS FOR UP TO 3 MONTHS AS THE INCREASE IN CALCIUM CAN BE DELAYED.
• IF HYPERCALCAEMIA IS PRESENT, ITS CAUSE REQUIRES THOROUGH INVESTIGATION TO EXCLUDE DISORDERS SUCH AS PRIMARY HYPERPARATHYROIDISM AND VITAMIN D INTOXICATION.
• NEPHROCALCINOSIS IS A COMMON PERSISTENT FINDING EVEN IN THOSE CHILDREN WHO HAVE UNDERGONE TREATMENT FOR HYPERCALCAEMIA, BUT FORTUNATELY RENAL IMPAIRMENT IS VERY RARE.
• DISEASE COURSE: THE SKIN CONDITION RESOLVES OVER SEVERAL WEEKS ALTHOUGH THE HYPERCALCAEMIA CAN PERSIST FOR A FEW MONTHS.
• INVESTIGATIONS: SKIN BIOPSY IS REQUIRED TO CONFIRM THE DIAGNOSIS (Chapter 97). SERUM CALCIUM NEEDS TO BE MONITORED FOR 3 MONTHS.
• MANAGEMENT:
• NO TREATMENT IS GENERALLY REQUIRED AS THE CONDITION SPONTANEOUSLY RESOLVES OVER SEVERAL WEEKS. ANALGESIA MAY OCCASIONALLY BE REQUIRED.
• HYPERCALCAEMIA SHOULD BE TREATED AGGRESSIVELY TO PREVENT SOFT-TISSUE CALCIFICATION.
• TREATMENTS INCLUDE DIURETICS, DIETARY RESTRICTION OF CALCIUM AND VITAMIN D, AND SOMETIMES ORAL CORTICOSTEROIDS.
• IN RESISTANT CASES BISPHOSPHONATES CAN BE USED, AND A CASE OF HYPERCALCAEMIA TREATED WITH CALCITONIN HAS BEEN REPORTED.
• THESE MEASURES SHOULD BE INSTITUTED AS EARLY AS POSSIBLE WITH MAINTENANCE OF ADEQUATE HYDRATION WITH INTRAVENOUS NORMAL SALINE.
• FUROSEMIDE HAS BEEN USED TO ACHIEVE INCREASED CALCIUM EXCRETION BY INHIBITING CALCIUM REABSORPTION, BUT A RISK OF DEHYDRATION AND CONSEQUENT WORSENING OF HYPERCALCAEMIA EXISTS.
• PREDNISOLONE INTERFERES WITH THE METABOLISM OF VITAMIN D TO ITS ACTIVE FORM AND ALSO INHIBITS THE PRODUCTION OF 1,25-DIHYDROXYVITAMIN D3 BY THE MACROPHAGES INVOLVED IN THE INFLAMMATORY PROCESS.

• AN UNCOMMON PANNICULITIS WITH AN INVARIABLY HIGH MORTALITY.
• PREDOMINANTLY AFFECTS GRAVELY ILL, PRETERM NEONATES IN THE FIRST WEEK OF LIFE.
• MANIFESTS AS DIFFUSE HARDENING OF SKIN AND SUBCUTANEOUS ADIPOSE TISSUE TO SUCH AN EXTENT THAT IT HINDERS FEEDING AND RESPIRATION, AND USUALLY CULMINATES IN DEATH.
• EPIDEMIOLOGY: VERY RARE, PREVALENCE UNKNOWN.
• AGE: ALMOST ALWAYS APPEARS DURING THE FIRST WEEK OF LIFE, ALTHOUGH IT HAS OCCASIONALLY BEEN RECORDED LATER IN INFANTS BORN PRETERM.
• SEX: EQUAL SEX INCIDENCE. ASSOCIATED DISEASES: THERE IS UNDERLYING SEVERE ILLNESS.
• PREDISPOSING FACTORS: PREMATURITY AND SMALLNESS FOR DATES APPEAR TO BE FREQUENT PREDISPOSING FACTORS.
• RECORDED AS ALREADY PRESENT AT BIRTH IN INFANTS SUBJECTED TO PLACENTAL INSUFFICIENCY.
• THE DISORDER DOES NOT SEEM TO OCCUR IN OTHERWISE HEALTHY INFANTS, AND MOST CHARACTERISTICALLY DEVELOPS DURING THE COURSE OF ONE OF A WIDE VARIETY OF SEVERE ILLNESSES, PARTICULARLY SERIOUS INFECTIONS, CONGENITAL HEART DISEASE AND OTHER MAJOR DEVELOPMENTAL DEFECTS.
• A PROPORTION OF THESE INFANTS HAVE BEEN HYPOTHERMIC, AND OCCASIONALLY SCLEREMA HAS BEEN DESCRIBED AS A COMPLICATION OF NEONATAL COLD INJURY. NEVERTHELESS, COLD DOES NOT APPEAR TO BE AN IMPORTANT AETIOLOGICAL FACTOR IN THE MAJORITY OF CASES.
• LIPOLYTIC MECHANISMS ARE POORLY DEVELOPED IN THE NEWBORN, PARTICULARLY IN THOSE BORN PRETERM. THE MATURATION OF THESE ENZYME SYSTEMS MIGHT BE FURTHER COMPROMISED BY MAJOR INFECTION OR HYPOXIA.
• IT HAS BEEN SUGGESTED THAT SCLEREMA MIGHT REFLECT DEFECTIVE LIPOLYSIS WITHIN ADIPOSE TISSUE, WHICH WOULD RESULT IN FAILURE OF FAT MOBILISATION AND AN IMPAIRED CAPACITY TO MAINTAIN BODY TEMPERATURE.
• THE RATIO OF SATURATED TO UNSATURATED FATTY ACIDS IS RELATIVELY HIGH IN THE ADIPOSE TISSUE OF ALL NEONATES, AND THIS RATIO WAS EVEN HIGHER IN AN INFANT WITH SCLEREMA. THIS WOULD LEAD TO A RAISED MELTING POINT, AND THE INDURATION MIGHT REFLECT SOLIDIFICATION DUE TO A FALL IN THE TEMPERATURE OF THE ADIPOSE TISSUE DURING PERIPHERAL CIRCULATORY COLLAPSE.
• PATHOLOGY: IN MOST CASES THE SUBCUTANEOUS FAT LAYER APPEARS TO BE THICKENED DUE TO AN INCREASED SIZE OF THE INDIVIDUAL LIPOCYTES AND TO AN INCREASED WIDTH OF THE INTERSECTING BANDS OF CONNECTIVE TISSUE, PROBABLY DUE TO OEDEMA.
• THERE IS VERY LITTLE EVIDENCE OF FAT NECROSIS AND, GENERALLY, ONLY THE SLIGHTEST INDICATION OF INFLAMMATION.
• THE MOST CHARACTERISTIC HISTOLOGICAL FEATURE IS THE PRESENCE OF RADIALLY ARRANGED, NEEDLE-SHAPED CLEFTS IN ADIPOCYTES AND, OCCASIONALLY, IN MULTINUCLEATE GIANT CELLS, REFLECTING THE PRESENCE OF CRYSTALS PRIOR TO PROCESSING (Chapter 97).
• HISTORY: FIRST DESCRIBED BY UNDERWOOD IN 1784 AND WAS CALLED 'SKINBOUND DISEASE'. IN 1817, ALIBERT INTRODUCED THE TERM SCLEREMA, DERIVED FROM THE GREEK WORD SKLEROS, MEANING HARD.
• PRESENTATION:
• ALMOST ALWAYS APPEARS DURING THE FIRST 1–2 WEEKS OF LIFE. PREDOMINANTLY AFFECTS PRETERM NEONATES, ALTHOUGH THERE ARE SOME CASE REPORTS OF TERM BABIES.
• GENERALLY CONSIDERED A NON-SPECIFIC SIGN OF SEVERE ILLNESS AND HAS BEEN ASSOCIATED WITH A MORTALITY RANGING FROM 82% TO 98%.
• THE AFFECTED INFANT IS GENERALLY VERY ILL AT THE TIME OF ONSET.
• WOODY INDURATION OF THE SKIN STARTS ON THE BUTTOCKS, THIGHS OR CALVES AND EXTENDS RAPIDLY AND SYMMETRICALLY TO INVOLVE ALMOST THE WHOLE SURFACE, WITH THE EXCEPTION OF THE PALMS, SOLES AND GENITALIA.
• THE SKIN IS BOUND TO ADJACENT SUBCUTANEOUS TISSUE INCLUDING MUSCLE AND BONE AND THEREFORE IT CANNOT BE PITTED BY PRESSURE OR PINCHED INTO A FOLD.
• THIS SKIN IS HARD AND COLD TO TOUCH, AND YELLOWISH WHITE IN COLOUR, OFTEN WITH PURPLISH MOTTLING. MOBILITY IS LIMITED AND THIS CAN RESULT IN A TYPICAL FACIAL APPEARANCE.
• DIFFERENTIAL DIAGNOSIS:
• THE MAIN AREA OF DIAGNOSTIC CONFUSION HAS BEEN BETWEEN SCLEREMA AND SUBCUTANEOUS FAT NECROSIS. THE TWO DISORDERS ARE DISTINCT PATHOLOGICALLY AND CLINICALLY, ALTHOUGH RARELY THEY CAN OCCUR TOGETHER.
• SCLEREDEMA HAS BEEN REPORTED IN AN INFANT AT 2 WEEKS OF AGE, AND WAS DISTINGUISHED FROM SCLEREMA PRINCIPALLY ON HISTOLOGICAL GROUNDS.
• TURNER SYNDROME IS OFTEN RECOGNISABLE AT BIRTH BY THE PRESENCE IN A FEMALE OF FIRM, NON-PITTING LYMPHOEDEMA OF THE DORSA OF THE HANDS AND FEET, ASSOCIATED WITH LOW BIRTH WEIGHT AND LOOSE FOLDS OF SKIN AROUND THE NECK.
• WHERE PRIMARY LYMPHOEDEMA OCCURS IN NEONATES, IT WILL ALREADY BE CLINICALLY EVIDENT AT BIRTH. THE CONDITION MAY BE FAMILIAL, AND GENERALLY FIRST AFFECTS THE LEGS, PARTICULARLY THE LOWER LEGS. THE PRESENCE OF OEDEMA AT BIRTH, AND ITS VERY SLOW PROGRESSION IN AN OTHERWISE HEALTHY NEONATE, DISTINGUISHES PRIMARY LYMPHOEDEMA FROM SCLEREMA.
• COMPLICATIONS: RESPIRATORY INSUFFICIENCY OCCURS DUE TO RESTRICTED MOVEMENT OF THE CHEST WALL.
• DISEASE COURSE AND PROGNOSIS: THE PROGNOSIS IS POOR, AND IS LARGELY DETERMINED BY THE NATURE OF THE UNDERLYING DISEASE.
• IN SPITE OF ADVANCES IN THE TREATMENT OF MANY OF THE PREDISPOSING DISORDERS, PARTICULARLY SEPSIS, THE MORTALITY PROBABLY REMAINS IN EXCESS OF 50%.
• IN INFANTS WHO SURVIVE, THE APPEARANCE OF THE SKIN RETURNS TO NORMAL WITHOUT LONG-TERM COMPLICATIONS SUCH AS CALCIFICATION.
• INVESTIGATIONS: SKIN BIOPSY IS THE MOST USEFUL TEST.
• MANAGEMENT: FIRST LINE — TREATMENT OF THE UNDERLYING MEDICAL CONDITION(S) IN A NEONATAL UNIT IS THE KEY TO SURVIVAL.
• SECOND LINE — SYSTEMIC CORTICOSTEROIDS ARE PROBABLY NOT EFFECTIVE BUT THERE IS EVIDENCE THAT REPEATED EXCHANGE TRANSFUSIONS AND INTRAVENOUS IMMUNOGLOBULIN MAY BE HELPFUL IN SOME CASES.

• FREQUENCY — COLD INJURY: PREVIOUSLY COMMON, NOW RARE. SCLEREMA: RARE, USUALLY SEEN IN NEONATAL INTENSIVE CARE UNITS. SCFN: UNCOMMON.
• PATIENT — COLD INJURY: FULL-TERM NEONATES, OFTEN SMALL FOR DATES, BORN AT HOME. SCLEREMA: USUALLY SEVERELY ILL NEONATES, OFTEN PRETERM OR SMALL FOR DATES OR POST-TERM. SCFN: HEALTHY INFANTS, USUALLY FULL-TERM.
• ONSET — COLD INJURY: DURING THE FIRST WEEK. SCLEREMA: ALMOST ALWAYS DURING THE FIRST WEEK. SCFN: 1–6 WEEKS.
• SITES — COLD INJURY: EXTREMITIES, SPREADING CENTRALLY. SCLEREMA: LOWER LIMBS INITIALLY, BECOMING GENERALISED. SCFN: TRUNK, BUTTOCKS, THIGHS, ARMS, FACE.
• APPEARANCE — COLD INJURY: PITTING OEDEMA INITIALLY WITH REDNESS OR CYANOSIS OF THE FACE AND EXTREMITIES. SCLEREMA: DIFFUSE, YELLOW-WHITE, WOODY INDURATION WITH IMMOBILITY OF LIMBS. SCFN: FIRM, REDDISH VIOLET, SUBCUTANEOUS NODULES.
• HISTOLOGY — COLD INJURY: THIN PANNICULUS. SCLEREMA: SUBTLE; THICKENED CONNECTIVE TISSUE TRABECULAE, RADIAL NEEDLE-LIKE CLEFTS. SCFN: GRANULOMATOUS INFLAMMATION, FAT NECROSIS.
• PROGNOSIS — COLD INJURY: MORTALITY AROUND 25%. SCLEREMA: POOR; MORTALITY GREATER THAN 50% IN PAST. SCFN: GENERALLY EXCELLENT.

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• DEFINITION: RAISED BANDS FOUND ON THE SKIN, USUALLY OF THE LEGS, IN THE FIRST FEW MONTHS AFTER BIRTH.
• SYNONYMS: PERSISTENT LINEAR BANDS OF INFANCY; ACQUIRED RAISED BANDS OF INFANCY.
• FIRST DESCRIBED IN 2002 IN TWO PREMATURE BABIES. THIRTEEN CASES HAVE SINCE BEEN DESCRIBED IN BOTH PREMATURE AND TERM BABIES.
• EPIDEMIOLOGY: INCIDENCE UNKNOWN BUT VERY RARE. ONSET USUALLY AT 1–2 MONTHS OF AGE. FEMALE TO MALE RATIO OF 8 : 5.
• ASSOCIATED DISEASES: IN A FEW CASES AMNIOTIC BAND SYNDROME MAY BE PRESENT WITH POTENTIAL LIMB DEFECTS OBVIOUS FROM BIRTH.
• PATHOPHYSIOLOGY: THE CAUSE IS UNKNOWN BUT VARIOUS THEORIES HAVE BEEN POSTULATED REVOLVING AROUND THE POSSIBILITY OF AN ABNORMAL REACTION TO PRESSURE ON THE SKIN.
• IN THE FIRST FOUR CASES DESCRIBED, THREE OF THE CHILDREN WERE BORN PREMATURELY (28–31 WEEKS) AND THERE WAS DOCUMENTED EVIDENCE OF AMNIOTIC BANDS OR PLACENTAL ABRUPTION/PLACENTAL TEARS. SHORT TOES AND A CLUB FOOT WERE DESCRIBED IN TWO OF THESE CHILDREN.
• HOWEVER, OF THE 13 CASES DESCRIBED, 9 WERE IN TERM CHILDREN WITH NO DOCUMENTED EVIDENCE OF AMNIOTIC BANDS OR LIMB CONSTRICTION/DEFECTS.
• MARQUE ET AL. POSTULATED IN THEIR THREE CASES THAT THE LESIONS AROSE EXACTLY UNDER WHERE TIGHT SOCKS HAD BEEN WORN AND THE PRESSURE EFFECT OF CLOTHING MAY BE RELEVANT.
• HOWEVER, LESIONS HAVE BEEN DESCRIBED ON THE TRUNK, THE BUTTOCKS AND MUCH HIGHER UP THE LEG WHERE IT SEEMS LESS LIKELY THAT OCCLUSIVE CLOTHING IS AN AETIOLOGICAL FACTOR.
• PATHOLOGY: SKIN BIOPSY IS USUALLY UNREMARKABLE. THERE MAY BE A LITTLE OEDEMA IN THE DERMIS AND FAT, BUT THE COLLAGEN AND ELASTIN ARE NORMAL.
• THERE ARE NO SIGNS OF SMOOTH MUSCLE OR LIPOMATOUS NAEVUS.
• ONE AUTHOR HAS DESCRIBED A DERMAL INFILTRATE OF ADIPOCYTES ALONG BLOOD VESSELS AND ECCRINE DUCTS IN TWO CASES AND SUGGESTED A SIMILAR AETIOLOGY TO POST-TRAUMATIC PIEZOGENIC PEDAL PAPULES.
• GENETICS: IT IS NOT KNOWN IF THERE IS AN UNDERLYING GENETIC CAUSE. TWO FAMILIAL CASES HAVE BEEN DESCRIBED (BROTHER AND SISTER) BUT NO CONSANGUINITY HAS BEEN RECORDED.
• CLINICAL FEATURES: THE RAISED BANDS TYPICALLY PRESENT IN THE FIRST FEW MONTHS OF LIFE.
• THEY ARE OFTEN MULTIPLE AND CAN BE SYMMETRICAL. COMMON ON THE LEGS BUT MAY BE FOUND ON THE UPPER LIMBS AND RARELY THE TRUNK. THEY VARY FROM 1 TO 3 mm ACROSS.
• THE LESIONS ARE PALPABLE AND FIRM BUT NOT HARD.
• DIFFERENTIAL DIAGNOSIS: AMNIOTIC BAND SYNDROME/CONGENITAL PSEUDOAINHUM.
• THE AMNIOTIC BAND SYNDROME IS A SEPARATE, MORE SEVERE ENTITY PRESENTING WITH CONSTRICTIONS AT BIRTH. THESE MAY LEAD TO LIMB MALFORMATIONS, LYMPHOEDEMA AND EVEN ISCHAEMIA AND AUTOAMPUTATION (CONGENITAL PSEUDOAINHUM).
• CONSTRICTION BANDS MAY ALSO OCCUR IN OTHER CONDITIONS SUCH AS MICHELIN TYRE BABY SYNDROME.
• IF THE AMNIOTIC BAND SYNDROME OCCURS EARLY IN UTERO MALFORMATIONS TEND TO BE MORE EXTENSIVE AND INCLUDE ALOPECIA, APLASIA CUTIS, NEURAL TUBE DEFECTS AND CRANIO-FACIAL DEFECTS AS WELL AS LIMB CONSTRICTION BANDS.
• ULTRASOUND AND DOPPLER ARE USED TO ASSESS LIMBS. TREATMENT IS DIFFICULT AND IS BY FETOSCOPIC SURGERY WHEN POSSIBLE.
• CLASSIFICATION OF SEVERITY: IT IS A BENIGN, NON-PROGRESSIVE BUT PERSISTENT CONDITION.
• DISEASE COURSE: THE CONDITION PERSISTED IN ALL BUT ONE CASE (LONGEST FOLLOW-UP TO DATE IS 18 YEARS).
• INVESTIGATIONS: MOST CASES CAN BE DIAGNOSED CLINICALLY BUT A SKIN BIOPSY (WHICH IS ESSENTIALLY NORMAL) MAY OCCASIONALLY BE REQUIRED TO EXCLUDE OTHER CONDITIONS LIKE MICHELIN TYRE BABY SYNDROME.
• MANAGEMENT: REASSURANCE IS USUALLY ALL THAT IS REQUIRED AND EXPLAINING THAT THE LESIONS WILL PROBABLY PERSIST LIFELONG.
• ONE CASE FAILED TO RESPOND TO ORAL ANTIHISTAMINES.
• ONE CASE WAS TREATED WITH TOPICAL ANTIHISTAMINES AND THE LESIONS RESOLVED WITHIN 3 MONTHS. THIS CASE WAS NOT BIOPSIED AND HAD SOME ATYPICAL FEATURES IN THAT IT PRESENTED LATE, AT 6 MONTHS (MUCH LATER THAN THE USUAL 1–3 MONTHS), IN A CHILD WITH MARKED DERMOGRAPHISM.

• SOLITARY, SELF-HEALING, POLYPOID LESIONS HAVE BEEN OBSERVED IN SOME 4% OF NEONATES IN A JAPANESE SURVEY; THEIR OCCURRENCE IN OTHER RACIAL GROUPS HAS YET TO BE DOCUMENTED.
• THESE LESIONS ARE FIRM, PINK, POLYPOID NODULES, ABOUT 1 mm IN DIAMETER, USUALLY FOUND CLOSE AND MEDIAL TO ONE OR OTHER NIPPLE.
• THEY HAVE ALSO BEEN REPORTED TO OCCUR ON THE SCROTUM, LABIA MAJORA, CHEEKS, CHIN AND ARMS.
• HISTOLOGY SHOWS A NORMAL EPIDERMIS, A VASCULAR DERMIS CONTAINING PROMINENT HAIR FOLLICLES WITH VESTIGIAL SEBACEOUS GLANDS AND WELL-DEVELOPED ECCRINE GLANDS.
• THESE LESIONS GENERALLY SEPARATE FROM THE SKIN SPONTANEOUSLY AFTER A FEW DAYS BUT THEY MAY PERSIST IN EARLY LIFE.

• A DESCRIPTIVE TERM THAT REFERS TO AN INFANT WHO IS BORN ENCASED IN A TIGHT SHINY MEMBRANE.
• IT MAY REPRESENT THE FIRST EXPRESSION OF SOME FORMS OF ICHTHYOSIS, THE COMMONEST OF WHICH ARE THE AUTOSOMAL RECESSIVE ICHTHYOSES.
• EPIDEMIOLOGY: THE INCIDENCE IS APPROXIMATELY 1 PER 100 000 DELIVERIES. PRESENTS AT BIRTH. SLIGHT PREDOMINANCE IN MALES. EQUAL ETHNIC DISTRIBUTION.
• ASSOCIATED DISEASES:
• UP TO 10% OF BABIES BORN WITH A COLLODION MEMBRANE WILL LATER DEVELOP ENTIRELY NORMAL SKIN — 'SELF-HEALING' COLLODION BABY.
• ALMOST 90% WILL, HOWEVER, GO ON TO DEVELOP A SEVERE FORM OF AUTOSOMAL RECESSIVE ICHTHYOSIS IN THE FIRST FEW WEEKS OF LIFE: LAMELLAR ICHTHYOSIS AND NON-BULLOUS ICHTHYOSIFORM ERYTHRODERMA (SYNONYM CONGENITAL ICHTHYOSIFORM ERYTHRODERMA) ARE THE MOST COMMON (Chapter 63).
• IT IS DIFFICULT TO PREDICT WHICH CHILDREN WILL GO ON TO HAVE NORMAL SKIN OR LATER DEVELOP A VARIANT OF ICHTHYOSIS.
• THE COLLODION BABY PHENOTYPE IS ALSO REPORTED IN THE RARER AUTOSOMAL DOMINANT FORM OF LAMELLAR ICHTHYOSIS AND IN BATHING SUIT ICHTHYOSIS; IT IS ALSO CHARACTERISTIC OF THE TRICHOTHIODYSTROPHY–ICHTHYOSIS SYNDROME.
• OTHER ICHTHYOSES IN WHICH AN INITIAL COLLODION BABY PHASE HAS OCCASIONALLY BEEN REPORTED: NETHERTON SYNDROME, NEUTRAL LIPID STORAGE DISEASE, LORICRIN KERATODERMA (SYN. CAMISA KERATODERMA) AND SJÖGREN–LARSSON SYNDROME — BUT THE GREAT MAJORITY OF NEONATES WITH THESE DISORDERS DO NOT DEMONSTRATE THE COLLODION BABY PHENOTYPE.
• A TRANSIENT COLLODION MEMBRANE HAS ALSO BEEN REPORTED IN GAUCHER DISEASE.
• IN ABOUT 10% OF CASES, THE COLLODION BABY PHASE IS FOLLOWED BY A RELATIVELY MILD ICHTHYOSIS OF LAMELLAR TYPE OR INDEED NORMAL SKIN (SELF-HEALING ICHTHYOSIS).
• PATHOLOGY: SKIN BIOPSY IS NOT NECESSARY FOR THIS CLINICAL DIAGNOSIS. HISTOPATHOLOGY DOES NOT HELP PREDICT THE OUTCOME.
• HISTOLOGICALLY THE MEMBRANE IS A COMPACT, THICKENED, ORTHOKERATOTIC STRATUM CORNEUM; THE EPIDERMIS AND DERMIS ARE BOTH RELATIVELY NORMAL.
• GENETICS: AS THE COLLODION BABY IS NOT A DISEASE ENTITY BUT IS THE FIRST EXPRESSION OF SOME FORMS OF ICHTHYOSIS, EARLY GENETIC TESTING IS NOT ADVISED.
• AN UNDERLYING ICHTHYOSIS PHENOTYPE WILL USUALLY REVEAL ITSELF OVER THE FIRST FEW WEEKS OF LIFE AFTER THE COLLODION MEMBRANE HAS SHED. AT THAT POINT SPECIFIC GENETIC TESTING CAN HELP CONFIRM A DIAGNOSIS.
• PRESENTATION:
• IN SEVERE PRESENTATIONS THE BABY WILL APPEAR ERYTHRODERMIC AND ENCASED IN A RIGID, SHINY, GLISTENING, YELLOWISH, TRANSLUCENT COVERING RESEMBLING CLEAR PLASTIC FILM.
• THE TIGHTNESS OF THE MEMBRANE MAY CAUSE THE EYELIDS TO TURN OUT REVEALING THE PINK INNER LID — ECTROPION.
• ECLABIUM, THE TURNING OUT OF THE LIPS DUE TO THE TIGHTNESS OF THE MEMBRANE, MAY ACCOMPANY ECTROPION, AND MAY INTERFERE WITH FEEDING. THE NOSTRILS MAY ALSO BE BLOCKED.
• RESTRICTION OF THE SKIN OVER THE FINGERS, HANDS, TOES AND FEET MAY RESULT IN IMMOBILITY AND COULD INTERFERE WITH BLOOD FLOW, OCCASIONALLY RESULTING IN THE LOSS OF PARTS OF THE DIGITS.
• SURGERY MAY BE REQUIRED IN CASES OF ACUTE ISCHAEMIA TO FREE THE CONSTRICTIVE BANDS RESPONSIBLE. IN THE ABSENCE OF SURGERY, THE CONSTRICTIVE BANDS CAN LEAD TO AMPUTATION (PSEUDOAINHUM).
• WITHIN A FEW HOURS OF BIRTH, THE MEMBRANE USUALLY DRIES AND CRACKS, AND BLEEDING MAY OCCUR ALONG THE RESULTING FISSURES.
• WITHIN 1 OR 2 DAYS, IT STARTS TO SHED, EITHER IN EXTENSIVE SHEETS OR AS LARGE, LIGHT BROWN SCALES, BUT IT MAY REFORM SEVERAL TIMES. THE SHEDDING WILL GENERALLY BE MORE OR LESS COMPLETE WITHIN 4 WEEKS.
• SUBSEQUENTLY, THE TYPICAL FEATURES OF ONE OF SEVERAL VARIETIES OF ICHTHYOSIS WILL BE REVEALED OVER THE NEXT FEW WEEKS OR MONTHS.
• DURING THE FIRST DAY OR TWO, TIGHTNESS OF THE SKIN ON THE THORAX MAY IMPEDE RESPIRATION, AND VERY OCCASIONALLY RESPIRATORY DISTRESS MAY ALSO BE INDUCED BY NASAL OBSTRUCTION.
• CLINICAL VARIANTS: RARELY, THE COLLODION PHENOTYPE MAY BE CONFINED TO ACRAL SITES ONLY. THIS USUALLY HEALS SPONTANEOUSLY ('ACRAL SELF-HEALING COLLODION BABY').
• DIFFERENTIAL DIAGNOSIS:
• THE APPEARANCE OF THE COLLODION BABY IS UNMISTAKABLE. HOWEVER, A BABY WITH A SEVERE COLLODION PHENOTYPE (MARKED ECTROPION AND ECLABIUM) MAY BE CONFUSED WITH HARLEQUIN ICHTHYOSIS AS THE FACIAL APPEARANCES CAN BE SIMILAR (Chapter 63).
• HOWEVER, A CHILD WITH HARLEQUIN ICHTHYOSIS HAS MUCH THICKER SKIN, WHICH TYPICALLY ENCASES THE BABY LIKE A SUIT OF ARMOUR WITH DEEP FISSURES.
• HARLEQUIN ICHTHYOSIS SHOWS ALMOST FUSION OF THE FINGERS AND TOES WITH THICK PALMOPLANTAR SKIN.
• FINALLY, THE EARS ARE USUALLY BOUND DOWN TO THE SCALP IN HARLEQUIN ICHTHYOSIS WHEREAS THEY ARE NORMALLY 'FREE' IN COLLODION BABIES.
• RESTRICTIVE DERMOPATHY ALSO RESULTS IN A NEONATE WITH TIGHT AND IMMOBILISING SKIN, BUT IN THIS CONDITION THE SKIN APPEARS THIN AND TRANSPARENT, WITH PROMINENT UNDERLYING BLOOD VESSELS. THE MOUTH IS ALSO OPEN, BUT ECTROPION IS NOT PRESENT. THE SKIN DOES NOT DRY OUT AND COME AWAY. DEATH OCCURS RAPIDLY AS A CONSEQUENCE OF RESPIRATORY FAILURE.
• NEONATES WITH THE LETHAL AUTOSOMAL RECESSIVE NEU–LAXOVA SYNDROME MAY HAVE SKIN CHANGES CLOSELY RESEMBLING A COLLODION MEMBRANE. THE CONDITION IS CHARACTERISED BY INTRAUTERINE GROWTH RETARDATION, AND CENTRAL NERVOUS SYSTEM, SKELETAL AND CRANIAL ABNORMALITIES.
• COMPLICATIONS — THE COLLODION BABY IS AT RISK, LARGELY BECAUSE OF THE CONSEQUENCES OF LOSING THE SKIN BARRIER FUNCTION:
• IMPAIRED TEMPERATURE REGULATION.
• INCREASED INSENSIBLE WATER LOSS, HYPERNATRAEMIC DEHYDRATION AND ACUTE RENAL FAILURE.
• SEPTICAEMIA (BACTERIAL, CANDIDA).
• PERCUTANEOUS TOXICITY FROM TOPICAL MEDICAMENTS (INCREASED ABSORPTION).
• RESPIRATORY FAILURE — RESPIRATION MAY BE IMPAIRED AS A RESULT OF INTRAPARTUM ASPIRATION OF SQUAMOUS DEBRIS SHED INTO THE AMNIOTIC FLUID. IMMOBILITY OF THE CHEST MAY ALSO COMPROMISE RESPIRATORY FUNCTION, AND PREDISPOSE TO PNEUMONIA.
• WITH GOOD NEONATAL CARE MORTALITY FIGURES HAVE FALLEN FROM 50% IN THE 1960s TO LESS THAN 5% TODAY IN THE WESTERN WORLD.
• DISEASE COURSE AND PROGNOSIS: THE LONGER-TERM OUTLOOK DEPENDS ON WHICH TYPE OF ICHTHYOSIS DEVELOPS, AND THERE IS NO CORRELATION BETWEEN INITIAL SEVERITY IN A COLLODION BABY AND THE GRAVITY OF THE ICHTHYOSIS THAT FOLLOWS.
• WHILE ADVANCES IN GENETICS SHOULD SOON ALLOW ROUTINE GENETIC SCREENING OF COLLODION BABIES, THE GENOTYPE DOES NOT ALWAYS CORRELATE WELL WITH PHENOTYPE, SO A 'WAIT AND SEE' POLICY IS STILL REQUIRED.
• MANAGEMENT:
• THE MOST IMPORTANT ELEMENT IN TREATMENT IS AN AWARENESS OF THE POSSIBLE MEDICAL COMPLICATIONS FROM SKIN BARRIER FAILURE.
• THE BABY SHOULD BE NURSED IN AN INCUBATOR IN A HIGH-HUMIDITY ATMOSPHERE, WITH CAREFUL MONITORING OF BODY TEMPERATURE (OVERHEATING CAN ALSO BE AN ISSUE).
• GREAT ATTENTION NEEDS TO BE GIVEN TO FLUID AND ELECTROLYTE BALANCE. IN SEVERE CASES FLUID THERAPY SHOULD BE GIVEN INTRAVENOUSLY, BUT IN LESS SEVERE CASES ORAL OR NASOGASTRIC FLUID SUPPLEMENTATION WILL SUFFICE.
• PERITONEAL DIALYSIS MAY BE INDICATED IF RENAL FAILURE OCCURS.
• FLUID LOSS IS SIGNIFICANTLY REDUCED BY FREQUENT APPLICATIONS OF LIPID; A 50%/50% MIXTURE OF WHITE SOFT PARAFFIN AND LIQUID PARAFFIN IS IDEAL FOR THIS PURPOSE.
• FREQUENT OILING OF THE SKIN INCREASES MOBILITY AND COMFORT, ACCELERATES HEALING OF FISSURES AND MAY REDUCE THE RISK OF INFECTION.
• SUPPLEMENTAL FEEDS MAY BE NEEDED VIA A NASOGASTRIC TUBE.
• AVOID TOPICAL PRODUCTS THAT CONTAIN ACTIVE COMPOUNDS (e.g. UREA OR SALICYLIC ACID) AS TOXICITY IS A REAL RISK DUE TO ABSORPTION.
• PREVENTION OF INFECTION IS OF THE GREATEST IMPORTANCE IN SAVING THESE BABIES. SKIN PUNCTURES SHOULD BE KEPT TO A MINIMUM, AND VASCULAR ACCESS SHOULD BE AVOIDED AS FAR AS POSSIBLE.
• DEEPER FISSURES ARE MORE LIKELY TO BECOME INFECTED ESPECIALLY IF INFLAMED, SO REGULAR SWABS SHOULD BE DONE FOR BACTERIA AND CANDIDA AS SEPTICAEMIA IS A COMMON COMPLICATION.
• BANDS OF TIGHT SKIN CONSTRICTING THE DIGITS, HANDS OR FEET MAY OCCASIONALLY REQUIRE SURGICAL DIVISION.

• THIS TERM HAS BEEN USED TO DESCRIBE A CHARACTERISTIC ERUPTION IN NEONATES, OFTEN PRESENT AT BIRTH, COMPRISING WIDESPREAD, PURPLE-RED, OVAL OR CIRCULAR MACULES, PAPULES AND NODULES REFLECTING DERMAL ERYTHROPOIESIS.
• THERE MAY BE FRANK PETECHIAE ON THE SURFACE OF SOME OF THE LESIONS.
• FAVOURED SITES INCLUDE THE TRUNK, HEAD AND NECK. THE LESIONS GENERALLY FADE INTO LIGHT BROWN MACULES WITHIN A FEW WEEKS OF BIRTH.
• PERIORBITAL SWELLING CAN BE OBSERVED IN NEUROBLASTOMA, AND LESS FREQUENTLY IN CONGENITAL LEUKAEMIA.
• HISTOLOGICALLY THE LESIONS SHOW FOCI OF DERMAL ERYTHROPOIESIS. THE RETICULAR DERMIS CONTAINS AGGREGATES OF NUCLEATED AND NON-NUCLEATED ERYTHROCYTE PRECURSORS, BUT GENERALLY NO CELLS OF MYELOID OR MEGAKARYOCYTIC TYPE.
• IT IS POSSIBLE THAT THIS PROCESS REPRESENTS PERSISTENCE AND EXAGGERATION OF THE DERMAL ERYTHROPOIESIS THAT IS A NORMAL OCCURRENCE IN EARLY FETAL DEVELOPMENT.
• CAUSES OF 'BLUEBERRY MUFFIN' BABY:
• CONGENITAL INFECTIONS: RUBELLA, CYTOMEGALOVIRUS, COXSACKIE B2, SYPHILIS, TOXOPLASMOSIS.
• HAEMATOLOGICAL: HEREDITARY SPHEROCYTOSIS, RHESUS HAEMOLYTIC ANAEMIA, ABO BLOOD GROUP INCOMPATIBILITY, TWIN–TWIN TRANSFUSION SYNDROME, SEVERE MATERNAL ANAEMIA.
• DRUG INDUCED: ERYTHROPOIETIN.
• NEOPLASIA: CONGENITAL LEUKAEMIA, NEUROBLASTOMA, CONGENITAL RHABDOMYOSARCOMA, LANGERHANS CELL HISTIOCYTOSIS.
• INFLAMMATORY: NEONATAL LUPUS ERYTHEMATOSUS.
• LYSOSOMAL STORAGE DISEASE: GAUCHER DISEASE.
• (NEOPLASIA AND INFLAMMATORY CAUSES SHOW 'BLUEBERRY MUFFIN-LIKE' LESIONS BUT DERMAL ERYTHROPOIESIS IS NOT ALWAYS PRESENT HISTOLOGICALLY.)

• A RARE BUT POTENTIALLY LETHAL DISORDER CHARACTERISED BY A RAPIDLY PROGRESSIVE HAEMORRHAGIC NECROSIS OF THE SKIN ASSOCIATED WITH CUTANEOUS VASCULAR THROMBOSIS.
• IT IS PROBABLY BEST REFERRED TO AS A FORM OF DISSEMINATED INTRAVASCULAR COAGULATION (DIC) WITH ASSOCIATED PURPURA AND HAEMORRHAGIC INFARCTION OF THE SKIN.
• IT MAY RESULT FROM GENETICALLY TRANSMITTED THROMBOPHILIC DISORDER, MOST COMMONLY HOMOZYGOUS DEFICIENCY OF PROTEIN C OR, LESS FREQUENTLY, PROTEIN S.
• PROTEIN C RESISTANCE HAS ALSO BEEN REPORTED DUE TO MUTATIONS IN THE FACTOR V GENE.
• IN THE OLDER CHILD, PURPURA FULMINANS IS A HIGHLY CHARACTERISTIC FEATURE OF MENINGOCOCCAL SEPTICAEMIA, WHERE IT RESULTS FROM ACQUIRED DEFICIENCY OF PROTEIN C OR S.
• IT MAY ALSO OCCUR AS A RESULT OF ACQUIRED CONDITIONS (DIC, ANTIPHOSPHOLIPID ANTIBODIES, GALACTOSAEMIA, SEVERE CONGENITAL HEART DISEASE, WARFARIN THERAPY).
• NEONATAL PURPURA FULMINANS CAN ALSO RARELY OCCUR DUE TO INFECTION, SUCH AS WITH GROUP B STREPTOCOCCUS, METICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS, VARICELLA, MEASLES, KLEBSIELLA, ENTEROBACTER AND CITROBACTER.
• PRESENTATION:
• THE EARLIEST CUTANEOUS CHANGES ARE REDNESS AND ECCHYMOSIS, WHICH TYPICALLY APPEAR WITHIN THE FIRST 12 h OF LIFE BUT THEIR INITIAL DEVELOPMENT MAY OCCASIONALLY BE DELAYED.
• THE LESIONS RAPIDLY PROGRESS INTO MORE OR LESS SYMMETRICAL AND WELL-DEFINED 'LAKES' OF CONFLUENT ECCHYMOSIS, WITHOUT PETECHIAE.
• THE LESIONS OCCUR MOST OFTEN ON THE LIMBS, PARTICULARLY AT SITES OF PRESSURE, BUT MAY ALSO APPEAR ON THE TRUNK AND ON THE FACE AND SCALP.
• THE ONSET IS SUDDEN, AND THE LESIONS ENLARGE RAPIDLY, WITH COALESCENCE AND THE DEVELOPMENT OF HAEMORRHAGIC BULLAE AND CENTRAL NECROSIS.
• THERE IS SURROUNDING REDNESS AND THE LESIONS ARE TENDER. THE PATIENT IS FREQUENTLY FEBRILE.
• THESE INFANTS ARE ALSO AT RISK OF THROMBOSIS IN THE CENTRAL NERVOUS SYSTEM AND IN THE RETINAL VESSELS. THERE IS A SUBSTANTIAL DANGER OF INTERNAL HAEMORRHAGE, SHOCK AND DEATH.
• MANAGEMENT:
• TREATMENT SHOULD BE CARRIED OUT IN A SPECIALIST NEONATAL UNIT.
• THE EARLY INSTITUTION OF EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) WITH AGGRESSIVE INTENSIVE CARE MANAGEMENT HAS LED TO IMPROVED OUTCOMES.
• INITIALLY, FRESH FROZEN PLASMA SHOULD BE GIVEN URGENTLY IN A DOSE OF 10–15 mL/kg/12 h.
• IF PROTEIN C DEFICIENCY IS CONFIRMED, ONWARD THERAPY WITH PROTEIN C CONCENTRATE SHOULD CONTINUE UNTIL THE SKIN LESIONS HAVE HEALED.
• LONGER-TERM TREATMENT IS WITH ORAL ANTICOAGULANTS. LIVER TRANSPLANTATION CAN BE CURATIVE. ANY CONCOMITANT INFECTION NEEDS TO BE TREATED AS WELL.

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• HSV INFECTION IN THE NEWBORN IS GENERALLY A SERIOUS DISEASE WITH A HIGH MORTALITY (Chapter 25).
• THE WORLDWIDE INCIDENCE IS ESTIMATED AT ABOUT 10/100 000 LIVE BIRTHS AND UP TO 40% OF SUCH INFANTS ARE PREMATURE.
• THE MAJORITY OF INFECTIONS ARE A RESULT OF PERIPARTUM TRANSMISSION OF HSV TYPE 1 (20%) AND HSV TYPE 2 (80%) THROUGH CONTACT WITH AN INFECTED GENITAL TRACT DURING DELIVERY.
• HOWEVER, INTRAUTERINE HSV INFECTION OCCURS RARELY (5% OF ALL NEONATAL HSV INFECTIONS), DUE EITHER TO TRANSMISSION ACROSS THE PLACENTA OR TO ASCENDING INFECTION RELATED TO PROLONGED RUPTURE OF THE FETAL MEMBRANES.
• INTRAUTERINE HSV IS USUALLY DUE TO HSV TYPE 2 AND THE RISK IS HIGHER WHEN HSV IS A PRIMARY AND/OR DISSEMINATED INFECTION IN THE MOTHER.
• INFECTION MAY ALSO OCCUR POSTNATALLY BY CONTACT WITH NON-GENITAL SITES, BOTH MATERNAL AND NON-MATERNAL.
• MOST INFANTS WITH NEONATAL HSV INFECTION ARE BORN TO MOTHERS WHO HAVE NO PREVIOUS HISTORY OF GENITAL HSV AND WHO SHOW NO OVERT CLINICAL SIGNS OF HERPES AT DELIVERY.
• UP TO TWO-THIRDS OF WOMEN WHO ACQUIRE GENITAL HSV DURING PREGNANCY MANIFEST NO SYMPTOMS OR DEVELOP NON-SPECIFIC SYMPTOMS.
• OVER 70% OF ALL INFANTS WITH NEONATAL HSV INFECTION HAVE SKIN OR MUCOSAL LESIONS, BUT ONLY IN ABOUT 10–20% OF CASES WILL THE DISEASE BE CONFINED TO THE SKIN OR MUCOUS MEMBRANES.
• THE SKIN LESIONS APPEAR BETWEEN DAYS 2 AND 20, UNLESS INTRAUTERINE INFECTION HAS OCCURRED, IN WHICH CASE THEY WILL GENERALLY ALREADY BE PRESENT AT BIRTH.
• PRESENTATION:
• ISOLATED OR GROUPED VESICLES ARE THE MOST COMMON TYPE OF LESION, AND THE SCALP AND FACE ARE THE MOST COMMONLY AFFECTED SITES, ALTHOUGH LESIONS CAN OCCUR AT VIRTUALLY ANY SITE.
• OCCASIONALLY, THE ERUPTION MAY BE GENERALISED AND BULLOUS, AND WIDESPREAD EROSIONS MAY OCCUR WITHOUT OBVIOUS VESICLES OR BULLAE, MIMICKING EPIDERMOLYSIS BULLOSA.
• WHEN INFECTION IS ACQUIRED DURING BIRTH, THE INITIAL LESIONS HAVE A PREDILECTION FOR THE SCALP IN VERTEX PRESENTATIONS, AND THE PERIANAL AREA IN BREECH PRESENTATIONS.
• LESIONS MAY ALSO BE LOCALISED TO AREAS OF INTRAUTERINE OR INTRAPARTUM SKIN DAMAGE, SUCH AS THE AREA IN WHICH A FETAL SCALP ELECTRODE WAS SITED.
• AREAS OF CUTANEOUS ATROPHY OR SCARRING ARE NOT INFREQUENT IN THE INTRAUTERINE FORM, AND VESICULAR LESIONS MAY CONTINUE TO APPEAR WITHIN OR AT THE PERIPHERY OF THESE AREAS.
• A ZOSTERIFORM PATTERN HAS ALSO BEEN DESCRIBED AND, IN SOME CASES, LOCALISED OR GENERALISED NON-VESICULAR RED MACULES.
• CONGENITAL CUTANEOUS CALCIFICATION HAS BEEN REPORTED IN A CHILD WITH INTRAUTERINE HSV INFECTION.
• ORAL LESIONS ARE ALSO FREQUENT, AND TAKE THE FORM OF EROSIONS ON THE TONGUE, PALATE, GINGIVAE AND BUCCAL MUCOSA.
• IT MAY ALSO PRESENT WITH WIDESPREAD APLASIA CUTIS.
• PROGNOSIS AND MANAGEMENT:
• A FATAL OUTCOME IS UNUSUAL WHEN INFECTION IS LIMITED BUT MORTALITY IS HIGH IN DISSEMINATED OR CENTRAL NERVOUS SYSTEM INFECTIONS EVEN WITH APPROPRIATE THERAPY. MORTALITY IS ALSO HIGHER WITH HSV TYPE 2 INFECTION.
• EARLY RECOGNITION AND ADEQUATE EARLY TREATMENT WITH ACICLOVIR APPEAR TO PROTECT INFANTS FROM DISSEMINATION OF INFECTION WHERE THIS IS INITIALLY CONFINED TO THE SKIN.
• HSV INFECTION IN PREMATURE INFANTS IS EVEN MORE SEVERE IN TERMS OF CLINICAL OUTCOMES. IN ONE STUDY, 9 OF 12 INFANTS DIED AND THE OTHER 3 HAD NEUROLOGICAL SEQUELAE.
• IT IS ALSO MORE DIFFICULT TO DIAGNOSE AS VESICULAR LESIONS ARE FOUND IN LESS THAN HALF OF CASES. IT OFTEN PRESENTS WITH RESPIRATORY DISTRESS AND THROMBOCYTOPENIA.
• NON-SPECIFIC SIGNS SUCH AS LETHARGY, HYPOTENSION, RAISED ASPARTATE TRANSAMINASE AND FITS HAVE ALSO BEEN OBSERVED.
• DIAGNOSIS IS BY CULTURE/PCR BUT TREATMENT WITH INTRAVENOUS ACICLOVIR SHOULD NOT BE DELAYED IF HSV IS SUSPECTED.
• GANCICLOVIR (NEED TO MONITOR FOR NEUTROPENIA) AND FOSCARNET HAVE ALSO OCCASIONALLY BEEN USED IN TREATMENT.
• THERE IS INSUFFICIENT EVIDENCE TO SUGGEST THAT ACICLOVIR PROPHYLAXIS IN THE THIRD TRIMESTER OF HIGH-RISK PREGNANCIES AFFECTS THE INCIDENCE OF NEONATAL HSV ALTHOUGH IT WILL LESSEN THE NEED FOR CAESAREAN SECTION.

• APPROXIMATELY 90% OF ADULTS ARE SEROPOSITIVE FOR THE VARICELLA-ZOSTER VIRUS (VZV) ANTIBODY.
• IF A WOMAN IS SERONEGATIVE, SHE MAY DEVELOP CHICKENPOX DURING PREGNANCY (Chapter 25); THIS OCCURS IN UP TO 10 PER 10 000 PREGNANCIES.
• THE INFECTION MAY BE TRANSMITTED TO THE FETUS IN ABOUT 25% OF CASES.
• SUCH TRANSMISSION OF VZV TO THE FETUS IS VERY RARE IN MOTHERS WHO DEVELOP HERPES ZOSTER (SHINGLES) DURING PREGNANCY.
• WHEN A MOTHER DEVELOPS VARICELLA BETWEEN THE 7th AND 20th WEEK OF PREGNANCY, SPONTANEOUS ABORTION MAY FOLLOW, OR THE CHILD MAY BE BORN WITH A VARIETY OF ABNORMALITIES CONSIDERED CHARACTERISTIC OF FVS.
• THIS APPEARS TO OCCUR MOST FREQUENTLY WHEN MATERNAL INFECTION HAS OCCURRED BETWEEN WEEKS 13 AND 20.
• HOWEVER, MOST CHILDREN OF SUCH MOTHERS ARE BORN WITH NO DETECTABLE ABNORMALITY, DESPITE LABORATORY CONFIRMATION OF INTRAUTERINE INFECTION.
• FVS THEREFORE APPEARS TO BE A RELATIVELY RARE COMPLICATION OF MATERNAL VARICELLA EARLY IN PREGNANCY, WITH A FETAL RISK OF APPROXIMATELY 2%.
• SOME AUTHORS HAVE ARGUED THAT OCCASIONALLY FVS CAN OCCUR AS LATE AS 28 WEEKS INTO THE PREGNANCY.
• PRINCIPAL CLINICAL FEATURES OF THE FETAL VARICELLA SYNDROME:
• LOW BIRTH WEIGHT.
• CUTANEOUS LESIONS: LOCALISED ABSENCE OF SKIN, USUALLY ON A LIMB; SCARS, OFTEN OF DERMATOMAL OUTLINE; PAPULAR LESIONS RESEMBLING CONNECTIVE TISSUE NAEVI.
• HYPOPLASIA OF ONE OR MORE LIMBS (USUALLY THE LIMB AFFECTED BY LOCALISED ABSENCE OF SKIN OR SCARRING) AND/OR MALFORMED DIGITS.
• OCULAR ANOMALIES, INCLUDING CHORIORETINITIS, CATARACTS, MICROPHTHALMIA, HORNER SYNDROME.
• CENTRAL NERVOUS SYSTEM ABNORMALITIES, INCLUDING SEIZURES, MENTAL RETARDATION, HYDROCEPHALUS, CORTICAL ATROPHY, ENCEPHALITIS, ENCEPHALOMYELITIS, DORSAL RADICULITIS.
• LOCALISED SCARRING, PRESUMED TO BE THE SEQUEL TO INTRAUTERINE ULCERATION, IS THE MOST COMMON CUTANEOUS FEATURE OF FVS.
• THE LARGER SINGLE LESIONS CHARACTERISTICALLY OCCUR ON A LIMB, AND HAVE FREQUENTLY BEEN ASSOCIATED WITH HYPOPLASIA OF THAT LIMB; THESE LESIONS HAVE GENERALLY FOLLOWED INFECTIONS OCCURRING IN EARLY PREGNANCY.
• THEIR SEGMENTAL OUTLINE MAY BE A DIRECT CONSEQUENCE OF DAMAGE TO THE FETAL NERVOUS SYSTEM, AS VZV IS KNOWN TO BE STRONGLY NEUROTROPIC, OR TO FETAL HERPES ZOSTER.
• THE OCCURRENCE OF LARGER NUMBERS OF SMALLER LESIONS APPEARS TO RESULT MAINLY FROM VARICELLA LATER IN THE PREGNANCY; THEIR ANTECEDENTS SEEM LIKELY TO BE VESICULAR LESIONS, ESSENTIALLY THE SAME AS THOSE OCCURRING IN POSTNATAL VARICELLA.
• IF FETAL INFECTION HAS OCCURRED IN THE LAST TRIMESTER, THESE SMALLER SKIN LESIONS, REFLECTING FETAL VARICELLA, MAY STILL BE ULCERATED AT BIRTH.
• AREAS OF CONGENITAL LOCALISED ABSENCE OF SKIN, WITHOUT ASSOCIATED LIMB HYPOPLASIA OR OTHER NEUROLOGICAL ABNORMALITIES, HAVE BEEN A LESS WELL-RECOGNISED CONSEQUENCE OF INTRAUTERINE VARICELLA AND MAY REFLECT FETAL HERPES ZOSTER INFECTION LATER IN GESTATION.
• SKIN-COLOURED PAPULAR LESIONS AND MORE VERRUCOUS LESIONS HAVE ALSO BEEN DESCRIBED IN CHILDREN WITH FVS.
• IF A CHILD IS BORN WITH 'FULL-BLOWN FVS' THE MORTALITY IS ABOUT 25% IN THE FIRST 3 MONTHS OF LIFE.
• HERPES ZOSTER INFECTION IN EARLY INFANCY IS LIKELY TO INDICATE THAT THE CHILD HAS BEEN INFECTED WITH VZV IN UTERO.
• MANAGEMENT:
• PREGNANT WOMEN WHO ARE NOT IMMUNE (ON THE BASIS OF HISTORY AND, PREFERABLY, SEROLOGY), AND WHO EXPERIENCE EXPOSURE TO VZV, SHOULD BE GIVEN VARICELLA-ZOSTER IMMUNE GLOBULIN (VZIg).
• ALTHOUGH THIS CAN PREVENT OR MODIFY CLINICAL VARICELLA IF GIVEN UP TO 3 DAYS AFTER CONTACT, THERE IS NO DEFINITE EVIDENCE THAT IT PREVENTS FETAL INFECTION OR DAMAGE.
• GIVING VZIg TO NEONATES OF MOTHERS WHO HAVE CHICKENPOX AT THE TIME OF DELIVERY DOES NOT APPEAR TO REDUCE THE INCIDENCE OF CLINICAL INFECTION BUT MAY REDUCE ITS SEVERITY.
• AS THE RISK OF FETAL DAMAGE IS SMALL, TERMINATION OF PREGNANCY IS NOT INDICATED.
• ULTRASOUND EXAMINATIONS CAN BE PERFORMED TO DETECT SOME OF THE ABNORMALITIES THAT OCCUR IN THE CARDIOVASCULAR SYSTEM, BUT SEVERAL OF THE IMPORTANT OCULAR AND NEUROLOGICAL SEQUELAE CANNOT BE DIAGNOSED IN THIS WAY.
• THERE ARE NO REPORTS THAT ESTABLISH A ROLE FOR ACICLOVIR THERAPY IN THE PREVENTION OF FVS. THE DECISION WHETHER TO TREAT THE MOTHER SHOULD BE BASED SOLELY ON THE SEVERITY OF HER ILLNESS.
• A POTENTIALLY DANGEROUS SITUATION RELATES TO MATERNAL DEVELOPMENT OF VARICELLA IN THE 4 DAYS EITHER SIDE OF DELIVERY. IN THIS CASE, NEONATAL VARICELLA MAY ALSO OCCUR, BUT, IN THE ABSENCE OF THE PROTECTION OFFERED BY THE MATERNAL IMMUNE SYSTEM, MORTALITY MAY BE AS HIGH AS 30%.
• WHERE MATERNAL INFECTION OCCURS AT THIS TIME, VZIg IS RECOMMENDED FOR THE NEWBORN. IF OVERT VARICELLA DEVELOPS IN THE CHILD, INTRAVENOUS ACICLOVIR SHOULD BE ADDED TO THE VZIg.

• RUBELLA CONTRACTED BY THE FETUS BEFORE THE 20th WEEK OF GESTATION MAY RESULT IN DISSEMINATED INFECTION, CAUSING INTRAUTERINE GROWTH RETARDATION, MICROCEPHALY, MICROPHTHALMIA AND A WIDE VARIETY OF OTHER ABNORMALITIES (Chapter 25).
• CUTANEOUS LESIONS ARE AMONG THE MOST PROMINENT CLINICAL FEATURES.
• THE TYPICAL LESIONS ARE PRESENT AT BIRTH, OR MAKE THEIR APPEARANCE DURING THE FIRST 48 h.
• THEY COMPRISE DISCRETE, ROUNDED, RED OR PURPLE INFILTRATED MACULES, 3–8 mm IN DIAMETER.
• ALTHOUGH SUCH LESIONS MAY BE SEEN AT ANY SITE, THEY GENERALLY OCCUR IN THE LARGEST NUMBERS ON THE FACE, SCALP, BACK OF THE NECK AND TRUNK. OCCASIONALLY, THE LESIONS ARE SLIGHTLY RAISED. THEY TEND TO FADE OVER A PERIOD OF WEEKS.
• THESE LESIONS HAVE OFTEN BEEN DESCRIBED AS 'PURPURIC' AND HAVE GENERALLY BEEN ATTRIBUTED TO THROMBOCYTOPENIA, WHICH IS ANOTHER COMMON FEATURE.
• HOWEVER, HISTOLOGICAL EXAMINATION HAS SHOWN THEM TO COMPRISE FOCI OF DERMAL ERYTHROPOIESIS ('BLUEBERRY MUFFIN' LESIONS). GENUINE THROMBOCYTOPENIC PURPURA IS PROBABLY RATHER UNCOMMON.
• OTHER REPORTED SKIN MANIFESTATIONS: CUTIS MARMORATA, SEBORRHOEA AND HYPERPIGMENTATION OF THE FOREHEAD, CHEEKS AND UMBILICAL AREA, AND DISCRETE DEEP DIMPLES OVER BONY PROMINENCES, PARTICULARLY THE PATELLAE.
• FEWER CASES ARE SEEN TODAY AND COMPREHENSIVE VACCINATION PROGRAMMES SHOULD ALLOW FOR ERADICATION OF THIS CONDITION.

• HIV INFECTION MAY BE TRANSMITTED TO THE INFANT IN UTERO, DURING DELIVERY OR THROUGH BREASTFEEDING (Chapter 31).
• BECAUSE MOST INFECTIONS ARE PROBABLY TRANSMITTED AROUND THE TIME OF BIRTH, CLINICAL MANIFESTATIONS ARE NOT COMMONLY SEEN FOR THE FIRST FEW MONTHS, AND SOME INFECTED INFANTS WILL REMAIN ASYMPTOMATIC FOR MANY YEARS BEFORE MANIFESTATIONS FIRST APPEAR.
• MUCOCUTANEOUS MANIFESTATIONS ARE COMMON IN INFANT HIV INFECTION AND FREQUENTLY HAVE AN INFECTIVE AETIOLOGY.
• IN A STUDY IN ETHIOPIA UP TO 75% OF HIV-POSITIVE CHILDREN HAD ONE OR MORE MUCOCUTANEOUS DISORDERS — AGAIN SHOWING INFECTION TO BE MORE COMMON THAN INFLAMMATORY DISORDERS. STUDIES IN TANZANIA AND THAILAND HAVE SHOWN SIMILAR RESULTS.
• SKIN DISEASE IS MORE PREVALENT WHEN THERE IS A HIGHER DEGREE OF IMMUNOSUPPRESSION.
• PERSISTENT MUCOCUTANEOUS CANDIDIASIS IS THE COMMONEST OF ALL. IN ADDITION TO INFECTION OF THE ORAL AND NAPPY AREAS, THERE MAY BE EXTENSIVE CUTANEOUS INVOLVEMENT.
• DERMATOPHYTE FUNGAL INFECTIONS ARE ALSO CHARACTERISTIC, AND INFECTION WITH MORE UNUSUAL FUNGI MAY OCCUR, INCLUDING ASPERGILLUS.
• BACTERIAL INFECTIONS INCLUDE UNUSUALLY SEVERE OR RECURRING IMPETIGO, FOLLICULITIS, CELLULITIS AND ABSCESSES.
• PROBLEMS WITH VIRUSES INCLUDE ATYPICAL CHICKENPOX, HERPES ZOSTER, HERPES SIMPLEX AND UNUSUALLY SEVERE MOLLUSCUM AND HUMAN PAPILLOMAVIRUS INFECTIONS. NORWEGIAN SCABIES MAY PRESENT IN INFANCY.
• A WIDE VARIETY OF NON-INFECTIOUS MANIFESTATIONS MAY ALSO OCCUR. IN A STUDY OF ETHIOPIAN CHILDREN, 'PAPULAR PRURITIC ERUPTION OF HIV' WAS THE MOST COMMON INFLAMMATORY DISORDER, SEEN IN 30% OF CASES.
• SEBORRHOEIC DERMATITIS (SOMETIMES SEVERE) WAS ALSO COMMON, AFFECTING 8% OF CHILDREN.
• DRUG ERUPTIONS ARE MORE FREQUENT, ESPECIALLY WITH TRIMETHOPRIM–SULFAMETHOXAZOLE.

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• AS IN OLDER CHILDREN AND ADULTS, STAPHYLOCOCCUS AUREUS CAUSES A WIDE VARIETY OF CUTANEOUS LESIONS IN NEONATES.
• OTHER BACTERIAL SOURCES ARE IMPORTANT TOO, SUCH AS STREPTOCOCCI, LISTERIA MONOCYTOGENES, PSEUDOMONAS AERUGINOSA AND NEISSERIA MENINGITIDIS.

• THE NEONATE IS PECULIARLY LIABLE TO THE DEVELOPMENT OF BULLOUS IMPETIGO, WHICH IS MOST OFTEN CAUSED BY PHAGE GROUP II STRAINS OF S. AUREUS; METICILLIN-RESISTANT S. AUREUS HAS BEEN REPORTED AS A CAUSATIVE ORGANISM (Chapter 26).
• THE DISORDER IN NEONATES DIFFERS IN NO SIGNIFICANT WAY FROM THAT IN OLDER CHILDREN AND ADULTS, ALTHOUGH IT WAS FORMERLY DISTINGUISHED BY THE RATHER CONFUSING TERM PEMPHIGUS NEONATORUM.
• EPIDEMICS OF BULLOUS IMPETIGO, IN WHICH SOME INFANTS MAY DEVELOP STAPHYLOCOCCAL SCALDED SKIN SYNDROME, HAVE OCCURRED IN NEONATES DUE TO TRANSMISSION OF INFECTION IN THE NURSERY PRINCIPALLY VIA NURSING OR MEDICAL STAFF.
• ALTHOUGH THE INFECTION IS ACQUIRED IN HOSPITAL FOLLOWING DELIVERY, THE LESIONS DO NOT GENERALLY APPEAR UNTIL THE SECOND WEEK OF LIFE, WHEN THE CHILD WILL USUALLY HAVE LEFT HOSPITAL.
• THE PERINEUM, PERIUMBILICAL AREA AND NECK CREASES ARE PREDILECTION SITES FOR THE INITIAL LESIONS.
• RAPIDLY ENLARGING BULLAE WITH THIN, DELICATE WALLS AND A NARROW, RED AREOLA CONTAIN CLEAR FLUID AT FIRST, WHICH MAY LATER BECOME TURBID OR FRANKLY PURULENT.
• THE CONDITION MAY REMAIN LOCALISED OR BECOME WIDESPREAD.
• UNTREATED GENERALISED BULLOUS IMPETIGO IN THE NEONATE IS ASSOCIATED WITH A SIGNIFICANT MORTALITY; SERIOUS COMPLICATIONS INCLUDING LUNG ABSCESS, STAPHYLOCOCCAL PNEUMONIA AND OSTEOMYELITIS HAVE BEEN REPORTED, EVEN IN CASES TREATED WITH ANTIBIOTICS.

• MORE COMMON DISORDERS: MILIARIA CRYSTALLINA; BULLOUS IMPETIGO; THERMAL OR CHEMICAL BURNS; SUCKING BLISTERS.
• RARE DISORDERS:
• MASTOCYTOSIS.
• INFECTIONS: NEONATAL HERPES SIMPLEX, FETAL VARICELLA SYNDROME, HERPES ZOSTER, CONGENITAL SYPHILIS.
• PASSIVELY TRANSFERRED: PEMPHIGUS VULGARIS, PEMPHIGOID GESTATIONIS.
• BULLOUS PEMPHIGOID.
• PORPHYRIAS: CONGENITAL ERYTHROPOIETIC PORPHYRIA, TRANSIENT PORPHYRINAEMIA.
• TRANSIENT MYELOPROLIFERATIVE DISORDER (DOWN SYNDROME).
• CONGENITAL ABSENCE OF SKIN.
• LANGERHANS CELL HISTIOCYTOSIS.
• EXTENSIVE CONGENITAL EROSIONS AND VESICLES HEALING WITH RETICULATE SCARRING.
• GENODERMATOSES: EPIDERMOLYSIS BULLOSA, AEC SYNDROME (ANKYLOBLEPHARON/ECTODERMAL DYSPLASIA/CLEFT LIP AND PALATE), WEARY–KINDLER SYNDROME, ECTODERMAL DYSPLASIA–SKIN FRAGILITY SYNDROME (PLAKOPHILIN-1 DEFICIENCY), BULLOUS ICHTHYOSIFORM ERYTHRODERMA, INCONTINENTIA PIGMENTI.

• FIRST DESCRIBED IN NEONATES BY A GERMAN, RITTER VON RITTERSHAIN.
• CAUSED BY EPIDERMOLYTIC TOXINS A AND/OR B, WHICH ARE ELABORATED BY CERTAIN STRAINS OF S. AUREUS, MOST COMMONLY OF PHAGE GROUP II, PARTICULARLY STRAINS 71 AND 55 (Chapter 26).
• THESE TOXINS REACH THE SKIN VIA THE CIRCULATION FROM A DISTANT FOCUS OF INFECTION, USUALLY IN THE UMBILICUS, BREAST, CONJUNCTIVA OR SITE OF CIRCUMCISION OR HERNIORRHAPHY.
• TRANSMISSION OF THE CAUSATIVE TOXIN THROUGH HUMAN MILK HAS BEEN REPORTED.
• BOTH THESE TOXINS ATTACK DESMOGLEIN 1 (A DESMOSOMAL PROTEIN), SO MUCOSAL INVOLVEMENT DOES NOT OCCUR (THIS IS ANALOGOUS TO PEMPHIGUS FOLIACEUS, WHICH HAS THE SAME TARGET ANTIGEN).
• MOST OFTEN SEEN IN YOUNG CHILDREN, PARTICULARLY IN NEONATES. THE VERY MUCH GREATER INCIDENCE IN NEONATES IS BELIEVED TO REFLECT LESS EFFICIENT METABOLISM AND EXCRETION OF THE TOXIN.
• MULTIPLE CASES CAN OCCUR IN A NEONATAL UNIT. CASES OCCURRING IN LATER CHILDHOOD TEND TO BE ASSOCIATED WITH UNDERLYING DISEASE, ESPECIALLY IMMUNOSUPPRESSION AND RENAL FAILURE.
• PRESENTATION:
• IT DOES NOT PRESENT AT BIRTH, ALTHOUGH IT MAY APPEAR WITHIN THE FIRST FEW HOURS THEREAFTER.
• THE FIRST SIGN IS A FAINT, MACULAR, ORANGE-RED, SCARLATINIFORM ERUPTION.
• THE ERUPTION GENERALLY BECOMES MORE EXTENSIVE, AND OVER THE NEXT 24–48 h TURNS TO A MORE CONFLUENT, DEEP REDNESS WITH OEDEMA.
• THE SURFACE THEN BECOMES WRINKLED BEFORE STARTING TO SEPARATE, LEAVING RAW, RED EROSIONS.
• SITES OF PREDILECTION FOR THE DEVELOPMENT OF EROSIONS ARE THE CENTRAL PART OF THE FACE, THE AXILLAE AND THE GROINS. IT CAN RESULT IN WIDESPREAD SKIN DENUDATION.
• EXTREME TENDERNESS OF THE SKIN IS AN EARLY FEATURE, AND MAY OCCUR AT A STAGE WHERE CUTANEOUS SIGNS ARE NOT YET STRIKING.
• THE CHILD IS PYREXIAL AND DISTRESSED. THESE FEATURES CAN LEAD TO A SUSPICION THAT THE CHILD HAS ARTHRITIS OR AN ACUTE ABDOMEN.
• THE PRESENCE OF IMPETIGINOUS CRUSTING AROUND THE NOSE AND MOUTH CAN BE DIAGNOSTICALLY HELPFUL.
• RECOVERY IS USUALLY RAPID, EVEN WITHOUT ANTIBIOTIC THERAPY, ALTHOUGH INFANTS OCCASIONALLY DIE IN SPITE OF SUCH TREATMENT. HEALING OCCURS WITHOUT SCARRING.
• DIFFERENTIAL DIAGNOSIS:
• THE SCALDED APPEARANCE OF THE SKIN DIFFERENTIATES THE DISEASE FROM BULLOUS IMPETIGO, AND THE RAPID ONSET WITH MARKED CUTANEOUS TENDERNESS DISTINGUISHES IT FROM MOST OF THE OTHER CAUSES OF ERYTHRODERMA IN INFANCY.
• THE RARITY OF CLINICALLY APPARENT BULLAE AND THE CONFLUENT NATURE OF THE RASH HELP DIFFERENTIATE IT FROM THOSE BULLOUS DISORDERS LIKELY TO BE SEEN IN YOUNG CHILDREN.
• MILDER FORMS OF SSSS HAVE BEEN DESCRIBED WHERE THE SAME TOXIN-PRODUCING S. AUREUS IS ISOLATED BUT WHERE CLINICALLY THE RASH STARTS AS IMPETIGO ON THE FACE FOLLOWED BY AN EXANTHEM WITH PEELING MOSTLY CONFINED TO THE SKIN FOLDS. THE CHILDREN HAVE MILD PYREXIA BUT NO SHOCK OR FLUID DISTURBANCE.
• THE MAIN DIFFERENTIAL DIAGNOSIS IS TOXIC EPIDERMAL NECROLYSIS BUT THIS CONDITION SHOWS MUCOSAL INVOLVEMENT.
• IF THERE IS ANY DOUBT, THE TWO CONDITIONS MAY BE DISTINGUISHED BY HISTOLOGY; A FROZEN SECTION PROVIDES RAPID DIFFERENTIATION. THE LEVEL OF SPLIT IN TOXIC EPIDERMAL NECROLYSIS IS LOWER AT THE SUBEPIDERMAL LEVEL, BUT IS INTRAEPIDERMAL IN SSSS.
• MANAGEMENT:
• TREATMENT IS WITH EITHER A PENICILLINASE-RESISTANT PENICILLIN ANALOGUE, SUCH AS CO-AMOXICLAV, OR WITH A CEPHALOSPORIN OR SODIUM FUSIDATE.
• A RECENT STUDY FOUND THAT SSSS-ASSOCIATED ISOLATES DEMONSTRATED SIGNIFICANTLY HIGHER RATES OF CLINDAMYCIN RESISTANCE AND LOWER RATES OF NESTLING RESISTANCE COMPARED WITH OVERALL STAPHYLOCOCCAL INFECTIONS.
• CLINDAMYCIN, A RIBOSOMAL INHIBITOR, IS FREQUENTLY RECOMMENDED AS A FIRST LINE AGENT IN SSSS TO REDUCE TOXIN PRODUCTION. CEPHALOSPORINS ARE NOW FAVOURED FOR EMPIRICAL THERAPY.
• IF THE ATTACK IS SEVERE, THE DRUG SHOULD INITIALLY BE GIVEN INTRAVENOUSLY.
• SYSTEMIC CORTICOSTEROIDS ARE CONTRAINDICATED AS THEY AGGRAVATE THE DISEASE.
• APPROPRIATE COMPENSATION MUST BE MADE FOR HEAT AND FLUID LOSSES AND HYPONATRAEMIA.
• PAIN WILL ALSO REQUIRE TREATMENT, AND AFFECTED INFANTS WILL GENERALLY BE MUCH MORE COMFORTABLE IF THE LESIONS ARE DRESSED RATHER THAN LEFT OPEN.
• IN SEVERE CASES, IT MAY OCCASIONALLY BE JUSTIFIABLE TO VENTILATE THE PATIENT IN ORDER TO OBTAIN ADEQUATE RELIEF OF PAIN. PNEUMONIA ITSELF CAN BE A COMPLICATION.
• EVEN WITH TREATMENT MORTALITY IS 2–10% IN CHILDREN, BUT THIS USUALLY REFLECTS LATE DIAGNOSIS.

• PERIPORITIS STAPHYLOGENES IS THE TERM APPLIED TO PUSTULAR LESIONS APPEARING IN NEONATAL SKIN AS A RESULT OF SECONDARY INFECTION OF MILIARIA BY S. AUREUS.
• SUCH LESIONS MAY PROGRESS TO SWEAT GLAND ABSCESSES, ALTHOUGH IT IS NOT CLEAR WHETHER SWEAT GLAND ABSCESSES ARE ALWAYS A COMPLICATION OF MILIARIA.
• THESE DISORDERS HAVE IN THE PAST BEEN INCORRECTLY CALLED 'FOLLICULITIS AND FURUNCULOSIS OF THE NEWBORN'.
• SWEAT GLAND ABSCESSES ARE DISTINGUISHED FROM FURUNCLES CLINICALLY BY A LACK OF ANY TENDENCY TO 'POINT', 'COLDNESS' AND THE ABSENCE OF TENDERNESS.
• OUTBREAKS CAUSED BY MEDICAL STAFF IN NEONATAL UNITS HAVE BEEN DESCRIBED.
• PERIPORITIS MUST BE DISTINGUISHED FROM MILIARIA PUSTULOSA, WHICH IS NOT AN INFECTIVE DISORDER, AND FROM BACTERIAL FOLLICULITIS, WHICH IN THE NEONATE IS USUALLY CAUSED BY S. AUREUS.
• CANDIDA ALBICANS AND MALASSEZIA FURFUR MAY ALSO CAUSE PUSTULOSIS IN THE NEONATE, AND A NUMBER OF NON-INFECTIVE CONDITIONS MAY CAUSE CONFUSION SUCH AS EOSINOPHILIC PUSTULOSIS.

• INFECTION OF THE BREAST IS COMMON AND IS USUALLY ASSOCIATED WITH S. AUREUS, BUT A VARIETY OF OTHER BACTERIA MAY BE RESPONSIBLE INCLUDING ACINETOBACTER BAUMANNII AND FOENICULUM VULGARE.
• IT IS ALMOST ALWAYS UNILATERAL; IT OCCURS WITHIN THE FIRST 8 WEEKS OF LIFE, MOST COMMONLY IN THE SECOND OR THIRD WEEK OF LIFE.
• IT OCCURS MORE OFTEN IN GIRLS THAN BOYS, AND ONLY VERY RARELY IN THE PRETERM INFANT.
• THE AFFECTED BREAST IS SWOLLEN AND OFTEN RED AND HOT. SYSTEMIC TOXICITY IS USUALLY ABSENT.
• FLUCTUATION IMPLIES ABSCESS FORMATION, WHICH WILL REQUIRE SURGICAL DRAINAGE.
• COLOUR FLOW DOPPLER ULTRASOUND HELPS DISTINGUISH MASTITIS FROM AN ABSCESS.
• THE DEVELOPMENT OF A BREAST ABSCESS MAY LEAD TO THE LOSS OF BREAST TISSUE IN THE LONGER TERM.

• A NUMBER OF NEONATES HAVE BEEN DESCRIBED PRESENTING WITH 'COLD' ABSCESSES IN THE SKIN FOLDS (GROINS AND AXILLAE) SHORTLY AFTER BIRTH.
• THESE CHILDREN ARE WELL WITH NO ASSOCIATED FEVER OR MALAISE ALTHOUGH THE LESIONS MAY FISTULATE.
• LESIONS HAVE ALSO BEEN SEEN IN OCCIPITAL, SUBMANDIBULAR AND SUPRACLAVICULAR AREAS. THERE MAY BE AN ASSOCIATED OMPHALITIS.
• CULTURE OF PUS FROM THESE LESIONS GROWS S. AUREUS.
• TREATMENT WITH ORAL ANTIBIOTICS IS USUALLY SUFFICIENT AND LEADS TO RAPID RESOLUTION OF THE LESIONS, ALTHOUGH SOME CHILDREN MAY REQUIRE AN INCISION AND DRAINAGE PROCEDURE.

• OMPHALITIS IS RARE IN THE DEVELOPED WORLD (0.7% OF BIRTHS) BUT IS MORE OF A PROBLEM FOR DEVELOPING COUNTRIES (UP TO 6% OF BIRTHS).
• THE MEAN AGE OF DEVELOPMENT IS 3.2 DAYS.
• CHARACTERISED BY REDNESS, OEDEMA AND DISCHARGE OF THE UMBILICAL 'STUMP'. CASES CAN PROGRESS TO CELLULITIS AND DEEPER TISSUE INFECTION.
• MORE COMMON IN PROTRACTED LABOUR, NON-STERILE DELIVERY AND CORD CARE, PREMATURITY, LOW BIRTH WEIGHT AND SOME CULTURAL PRACTICES SUCH AS THE APPLICATION OF TOBACCO ASH.
• THE UMBILICAL CORD MAY BECOME COLONISED BY A VARIETY OF POTENTIALLY PATHOGENIC BACTERIA, AND AN EQUALLY WIDE VARIETY OF TOPICAL ANTISEPTICS AND ANTIBIOTICS HAVE BEEN USED IN AN ATTEMPT TO REDUCE THIS COLONISATION.
• THE USE OF HEXACHLOROPHANE WAS POPULAR UNTIL IT BECAME APPARENT THAT THIS COULD LEAD TO SERIOUS NEUROTOXICITY, PARTICULARLY IN THE PRETERM INFANT.
• THE BEST SUBSTITUTE MAY BE CHLORHEXIDINE, APPLIED AS A DUSTING POWDER OR AQUEOUS SOLUTION RATHER THAN AS AN ALCOHOLIC SOLUTION.
• IN DEVELOPING COUNTRIES, 4% CHLORHEXIDINE HAS BEEN SHOWN TO REDUCE OMPHALITIS AND TO REDUCE NEONATAL MORTALITY.
• SINCE 1998, THE WHO HAS ADVOCATED THE USE OF DRY UMBILICAL CORD CARE WHERE POSSIBLE. A RECENT META-ANALYSIS PROVIDED NO EVIDENCE FOR ANTISEPTIC TREATMENT OF THE CORD WITH CHLORHEXIDINE.
• OCCASIONALLY, INFECTION OF THE UMBILICAL CORD BECOMES DISSEMINATED, EITHER BY BLOODSTREAM INVASION OR BY DIRECT EXTENSION VIA THE UMBILICAL VESSELS TO THE PERITONEAL CAVITY.
• TETANUS, DIPHTHERIA AND NECROTISING FASCIITIS MAY ALSO OCCUR AS COMPLICATIONS OF UMBILICAL INFECTION. SUCH INFECTIONS ARE STILL RESPONSIBLE FOR A HIGH PROPORTION OF DEATHS IN THE NEONATAL PERIOD IN DEVELOPING COUNTRIES.

• PREORBITAL CELLULITIS IS RESTRICTED TO THE PART OF THE ORBIT ANTERIOR TO THE ORBITAL SEPTUM AND IS MANIFEST BY EYELID SWELLING.
• ORBITAL CELLULITIS INVOLVES THE STRUCTURES DEEP TO THE SEPTUM AND PRESENTS WITH PAINFUL PROPTOSIS, EYELID OEDEMA AND CONJUNCTIVAL REDNESS.
• A VARIETY OF BACTERIA CAN CAUSE THESE INFECTIONS, SUCH AS S. AUREUS, INCLUDING METICILLIN RESISTANT STRAINS, AND GROUP A AND OTHER STREPTOCOCCI.
• ONE SHOULD ALWAYS BE ALERT TO THE POSSIBILITY OF GROUP B STREPTOCOCCUS AS A RARE CAUSE OF PERIORBITAL CELLULITIS OR ANY FORM OF CELLULITIS IN A NEONATE IN VIEW OF THE HIGH RISK OF SEPTICAEMIA WITH THIS ORGANISM.
• TREATMENT IS WITH INTRAVENOUS ANTIBIOTICS AND OCCASIONALLY SURGERY.

• A DISTINCTIVE FORM OF CELLULITIS IN WHICH INFECTION TRACKS ALONG THE FASCIAL PLANES, CAUSING THROMBOSIS OF THE BLOOD VESSELS RUNNING THROUGH THE FASCIA WITH RESULTING NECROSIS OF THE SKIN, SUBCUTANEOUS FAT AND EVEN MUSCLE (Chapter 26).
• IN NEONATES, IT MAY ARISE SPONTANEOUSLY, BUT MOST OFTEN IS A COMPLICATION OF PHYSICAL BIRTH TRAUMA, OMPHALITIS, BREAST ABSCESS OR IATROGENIC SKIN WOUNDS SUCH AS RESULT FROM SCALP ELECTRODES OR CIRCUMCISION.
• THE MOTHER'S GENITAL TRACT MAY ALSO BE THE SOURCE OF THE INFECTION.
• INITIALLY, THE INFANT DEVELOPS WHAT APPEARS TO BE STRAIGHTFORWARD CELLULITIS, USUALLY AFFECTING THE ABDOMINAL WALL.
• HOWEVER, THE CHILD BECOMES DISPROPORTIONATELY TOXIC, AND THE AREA AFFECTED BECOMES INDURATED, DISCOLOURED AND EXTENDS PROGRESSIVELY.
• THE SURFACE MAY SHOW A PEAU D'ORANGE APPEARANCE.
• PURPURA AND, OCCASIONALLY, BULLAE MAY DEVELOP IN THE CENTRE OF THE INDURATED AREA, OFTEN FOLLOWED QUITE RAPIDLY BY FRANK NECROSIS.
• THE DESTRUCTION OF SUPERFICIAL NERVES RESULTS IN LOCAL CUTANEOUS ANAESTHESIA.
• GAS AND CREPITATION MAY BE CLINICALLY APPARENT, OR MAY BE SEEN RADIOLOGICALLY. FEVER IS NOT INVARIABLY PRESENT.
• A WIDE VARIETY OF BACTERIA HAVE BEEN ASSOCIATED, MOST COMMONLY GROUP A STREPTOCOCCI, BUT ALSO GROUP B STREPTOCOCCI, STAPHYLOCOCCUS AUREUS AND ESCHERICHIA COLI.
• IN MANY CASES, A SYNERGISTIC INFECTION BY AEROBIC AND ANAEROBIC ORGANISMS APPEARS TO BE RESPONSIBLE. OCCASIONALLY, FUNGI HAVE BEEN RESPONSIBLE.
• ANTIBIOTIC (AND ANTIFUNGAL) THERAPY APPEARS TO BE OF LIMITED VALUE IN THIS POTENTIALLY LETHAL SITUATION.
• THE MOST IMPORTANT ASPECT OF TREATMENT IS EARLY SURGICAL EXCISION OF THE NECROTIC TISSUE. THIS 'GOLD STANDARD' HAS BEEN CHALLENGED BY SOME AUTHORS WHO ADVISE A MORE CONSERVATIVE APPROACH, BUT MOST DOCTORS WOULD STILL ADVISE EARLY SURGICAL DEBRIDEMENT.
• CULTURED EPIDERMAL AUTOGRAFTS HAVE ALSO BEEN USED SUCCESSFULLY.

• UNCOMMON, BUT DANGEROUS. THE RESPONSIBLE ORGANISM, LISTERIA MONOCYTOGENES, MAY BE TRANSMITTED TO HUMANS PRINCIPALLY THROUGH CONTAMINATED FOODS.
• IN PREGNANCY, IT CAUSES A NON-SPECIFIC, MILD, INFLUENZA-LIKE ILLNESS IN THE MOTHER, BUT IT MAY LEAD TO TRANSPLACENTAL INFECTION OF THE FETUS.
• MATERNAL HIV INFECTION MAY PREDISPOSE TO NEONATAL LISTERIOSIS.
• ADULT LISTERIOSIS HAS INCREASED IN A NUMBER OF EUROPEAN COUNTRIES DURING THE EARLY 21st CENTURY, BUT MOSTLY IN THE ELDERLY AND NOT AS YET IN PREGNANCY-RELATED CASES.
• ATTENTION TO FOOD HYGIENE AND RECALL OF CONTAMINATED PRODUCTS HAVE REDUCED THE PREVALENCE OF NEONATAL LISTERIOSIS BY 44% IN THE USA. PRODUCTS MADE WITH UNPASTEURISED MILK ARE A COMMON SOURCE OF INFECTION.
• A LARGE EPIDEMIC OF L. MONOCYTOGENES OCCURRED IN SOUTH AFRICA IN 2017; EPIDEMIC NEONATAL LISTERIOSIS WAS ASSOCIATED WITH A PREDOMINANCE OF BACTERAEMIC, EARLY-ONSET DISEASE. LISTERIOSIS-ASSOCIATED MORTALITY RATES WERE HIGHER THAN PREVIOUSLY PUBLISHED.
• CLINICALLY, THERE ARE EARLY-ONSET AND LATE-ONSET FORMS:
• THE EARLY-ONSET FORM RESULTS FROM THE DEVELOPMENT OF MILIARY GRANULOMAS FOLLOWING BLOOD-BORNE DISSEMINATION OF INFECTION.
• SEVERELY AFFECTED BABIES TEND TO BE BORN PREMATURELY AND THERE IS A HIGH MORTALITY. POSTMORTEM STUDIES REVEAL MILIARY GRANULOMAS IN MANY ORGANS.
• A FEW INFANTS WILL HAVE ANALOGOUS MILIARY SKIN LESIONS DURING LIFE, MANIFEST AS SCATTERED, DISCRETE, GREY OR WHITE PAPULES OR PUSTULES ABOUT 1–2 mm IN DIAMETER, WITH A RED MARGIN, WHICH WILL PROVIDE A SOURCE OF ORGANISMS FOR CULTURE.
• THE BACK APPEARS TO BE THE SITE OF PREDILECTION FOR SUCH LESIONS, WHICH ARE ALSO SEEN IN THE MOUTH AND ON THE CONJUNCTIVA.
• OTHER CUTANEOUS LESIONS INCLUDE PURPURA AND MORBILLIFORM RASHES. HOWEVER, IN THE MAJORITY OF CASES THE SKIN IS NOT INVOLVED IN THE INITIAL CLINICAL PRESENTATION.
• THE LATE FORM OF THE DISEASE IS COMMONER, TAKING THE FORM OF MENINGITIS, OCCURRING A WEEK OR TWO AFTER BIRTH.
• DIAGNOSIS IS BY CULTURING THE ORGANISM FROM A VARIETY OF SITES, INCLUDING CEREBROSPINAL FLUID, BLOOD, URINE AND FROM BIOPSY MATERIAL, INCLUDING THE SKIN.
• TREATMENT IS USUALLY WITH A COMBINATION OF PARENTERAL AMPICILLIN WITH GENTAMICIN OR TOBRAMYCIN, FOLLOWED BY A PROLONGED 3–4-WEEK COURSE OF ORAL AMPICILLIN.

• PSEUDOMONAS AERUGINOSA IS COMMON IN THE HOSPITAL ENVIRONMENT AND INFECTIONS ARE ENCOURAGED BY THE WIDESPREAD USE OF BROAD-SPECTRUM ANTIBIOTICS (Chapter 26).
• A WEAK MECHANICAL DEFENCE BARRIER AND UNDERDEVELOPED CELLULAR OR HUMORAL IMMUNITY INCREASE THE RISK OF INFECTION FROM THIS PATHOGEN IN NEWBORNS.
• MOST, BUT NOT ALL, NEONATES WHO DEVELOP THE SKIN LESIONS HAVE P. AERUGINOSA SEPTICAEMIA, USUALLY IN THE CONTEXT OF PREDISPOSING FACTORS THAT INCLUDE PREMATURITY, RENAL FAILURE, NEUTROPENIA AND OTHER IMMUNODEFICIENCIES, NECROTISING ENTEROCOLITIS AND BOWEL SURGERY.
• OCCASIONALLY, THE LESIONS DEVELOP AT THE SITE OF DIRECT INOCULATION OF THE CAUSATIVE ORGANISM.
• OTHER BACTERIA HAVE BEEN IMPLICATED SUCH AS E. COLI AND KLEBSIELLA.
• HISTOLOGICALLY, THE PRESENCE OF VASCULITIS, DUE TO BACTERIAL INFILTRATION OF THE VESSEL WALLS, IS CHARACTERISTIC, TOGETHER WITH HAEMORRHAGE AND NECROSIS. FOR THIS REASON SKIN BIOPSY CAN BE VERY HELPFUL IN DIAGNOSIS.
• CLINICALLY, LESIONS INITIALLY TAKE THE FORM OF PAINFUL MACULAR RED SKIN OR PURPLE ECCHYMOSIS.
• THE CENTRE THEN GENERALLY DEVELOPS EITHER VESICLES (OR LESS COMMONLY BULLAE) OR PUSTULES, WHICH RAPIDLY ULCERATE.
• SUBSEQUENTLY ONE OR MORE ULCERS OCCUR, EACH WITH A DEPRESSED, NECROTIC, OFTEN BLACK, CRUSTED CENTRE AND A RAISED EDGE.
• THE PERIORAL AND PERIANAL AREAS MAY SHOW GROUPED LESIONS.
• THIS INFECTION IS POTENTIALLY DANGEROUS WHEN IT OCCURS IN THE SETTING OF SEPTICAEMIA. APPROPRIATE PARENTERALLY ADMINISTERED COMBINATION ANTIBIOTIC THERAPY WILL BE REQUIRED.
• AWARENESS OF THIS PRESENTATION IN NEONATES IS CRITICAL SINCE ITS PRESENCE PROMPTS THE NEED FOR EARLY TREATMENT, AS PSEUDOMONAS INFECTIONS CARRY A HIGH MORTALITY RATE.

• A GANGRENOUS DISORDER. THE PRIMARY SITE OF INVOLVEMENT IS THE ORAL CAVITY.
• OTHER SITES HAVE INCLUDED THE NOSE, EYELIDS, UMBILICUS, SCROTUM AND GROIN.
• REPORTED ONSET IS FROM THE THIRD POSTNATAL DAY TO 120 DAYS OF AGE.
• OCCURS IN LOW-BIRTH-WEIGHT AND/OR PREMATURE NEONATES, ALMOST EXCLUSIVELY IN DEVELOPING COUNTRIES.
• FREQUENTLY CAUSED BY P. AERUGINOSA AND IS ALMOST INVARIABLY LETHAL IN THE ABSENCE OF APPROPRIATE ANTIBIOTIC TREATMENT.
• A SIMILAR CONDITION MAY BE SEEN IN OLDER CHILDREN AND ADULTS IN THE CONTEXT OF POOR NUTRITION, DELAYED GROWTH AND IMMUNODEFICIENCY. IT WAS ALSO SEEN IN CONCENTRATION CAMP VICTIMS IN THE SECOND WORLD WAR.
• TREATMENT IS WITH PARENTERAL ANTIBIOTICS AND OFTEN REQUIRES PLASTIC SURGERY LATER TO REPAIR LARGE FACIAL DEFECTS. SURGICAL REPAIR IS GENERALLY DELAYED FOR 1 YEAR POST RESOLUTION.

• ALTHOUGH IN THE NEWBORN THIS CONDITION IS MOST OFTEN A REFLECTION OF GENETICALLY TRANSMITTED THROMBOPHILIC DISORDER, IT MAY BE CAUSED BY ACUTE INFECTIONS, PARTICULARLY WITH ENDOTOXIN-ASSOCIATED, GRAM-NEGATIVE BACTERIA SUCH AS NEISSERIA MENINGITIDIS.

• DESCRIBED IN DETAIL IN Chapter 29.
• ABOUT 15% OF CHILDREN BORN TO MOTHERS WITH UNTREATED SYPHILIS WILL CONTRACT CONGENITAL SYPHILIS, BUT FETAL LOSS/STILLBIRTH OCCURS IN ABOUT 20% OF SUCH PREGNANCIES.
• THE SKIN IS CLINICALLY AFFECTED IN ABOUT 40% OF NEONATES WITH CONGENITAL SYPHILIS.
• IN SUCH CASES, THE SKIN IS USUALLY OF NORMAL APPEARANCE AT BIRTH, THE INITIAL LESIONS OCCURRING BETWEEN THE SECOND AND EIGHTH WEEK, AND OCCASIONALLY LATER.
• SITES OF PREDILECTION ARE THE ANO-GENITAL AREA, THE FACE AND THE PALMS AND SOLES.
• THE LESIONS ARE REDDISH BROWN IN COLOUR; THEY MAY BE MACULAR OR PAPULAR, AND TEND TO BE LARGER AND FIRMER THAN THOSE SEEN IN ACQUIRED SECONDARY SYPHILIS.
• IN ABOUT 3% OF CASES THE LESIONS ARE BULLOUS; KERATODERMA AND DESQUAMATION OF THE EXTREMITIES HAVE BEEN DESCRIBED.
• PARONYCHIA IS COMMONLY PRESENT.
• SMALL, ROUND, MOIST, PAPULAR LESIONS, TRADITIONALLY TERMED MUCOUS PATCHES, ARE FREQUENTLY PRESENT IN THE MOUTH AND ON OTHER MUCOSAL SURFACES.
• CONDYLOMATA LATA MAY BE PRESENT IN THE ANO-GENITAL FLEXURES OR AT OTHER FLEXURAL SITES, FOR EXAMPLE BETWEEN THE TOES OR IN THE ANGLES OF THE MOUTH.
• BIRTH WEIGHT IS BELOW 2500 g IN APPROXIMATELY 50% OF AFFECTED INFANTS.
• APART FROM THE CUTANEOUS FEATURES, THE MOST FREQUENT CLINICAL MANIFESTATIONS ARE HEPATOMEGALY, SPLENOMEGALY, JAUNDICE, PNEUMONIA AND RHINITIS, OFTEN WITH A BLOOD-STAINED DISCHARGE.
• THE RECENT RESURGENCE IN THE INCIDENCE OF SYPHILIS IN MANY COUNTRIES MAY LEAD TO AN INCREASE IN CASES OF CONGENITAL DISEASE, ESPECIALLY WHERE ANTENATAL CARE IS POOR.

• TUBERCULOSIS IN THE NEWBORN DUE TO TRANSMISSION OF INFECTION IN UTERO IS RELATIVELY RARE (Chapter 27).
• THE LUNGS AND/OR LIVER TEND TO BE THE PREDOMINANT SITES OF INVOLVEMENT, AND SKIN MANIFESTATIONS ARE UNUSUAL.
• HOWEVER, CUTANEOUS LESIONS HAVE OCCASIONALLY OCCURRED, IN THE FORM OF SMALL NUMBERS OF DISCRETE, UMBILICATED, RED PAPULES UP TO 4 mm IN DIAMETER.
• CONGENITAL TUBERCULOSIS HAS A HIGH MORTALITY RATE. IN A RECENT RETROSPECTIVE REVIEW FROM CHINA THE MORTALITY RATE WAS 43.48%.

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• BOTH CANDIDA AND MALASSEZIA SPECIES CAN CAUSE NEONATAL FUNGAL DISEASE.
• THERE ARE TWO DISTINCT FORMS OF NEONATAL CANDIDIASIS, PRESENT AT BIRTH OR SEEN IN THE FIRST WEEKS OF LIFE.

• A RELATIVELY COMMON DISORDER THAT OCCURS IN THE EARLY WEEKS AFTER BIRTH, IN THE FORM OF ORAL CANDIDIASIS WITH OR WITHOUT CANDIDIASIS IN THE NAPPY AREA (Chapter 32).
• THE RASH IS USUALLY FOCUSED IN THE PERIANAL AREA AND IS A DEEP 'BEEFY' RED COLOUR, WITH A MOIST APPEARANCE, OFTEN WITH PUSTULES AT THE PERIPHERY, WHICH IS OFTEN SCALLOPED IN OUTLINE.
• JUST BEYOND THE MARGIN, IN AS YET UNAFFECTED SKIN, THERE MAY BE PUNCTATE RED LESIONS, SOMETIMES PUSTULAR ('SATELLITE' LESIONS).
• IT IS ASSUMED THAT THE INFECTION IS ACQUIRED DURING DELIVERY FROM THE MOTHER'S GENITAL TRACT, AND THE FREQUENCY OF VAGINAL CANDIDIASIS AT THE TIME OF DELIVERY IS BETWEEN 20% AND 25%.
• OCCASIONALLY, THE RASH MAY BECOME MORE GENERALISED.
• THE OCCURRENCE OF LOCALISED PALMAR PUSTULES IN AN INFANT WITH NEONATAL ORAL CANDIDIASIS WAS BELIEVED TO REFLECT THE INOCULATION OF CANDIDA FROM THE MOUTH INTO THE SKIN AS A RESULT OF SUCKING.
• TREATMENT IS WITH TOPICAL ANTICANDIDAL CREAMS AND ORAL GELS.
• SYSTEMIC NEONATAL CANDIDIASIS IS A PARTICULAR PROBLEM FOR PRETERM BABIES ON INTENSIVE CARE UNITS WHERE IT CAN CAUSE SEPTICAEMIA AND DEATH. OFTEN THERE ARE NO ASSOCIATED SKIN LESIONS. TREATMENT IS WITH INTRAVENOUS ANTIFUNGAL THERAPY.

• A RARER CONDITION, SEEN AT BIRTH, WHICH IS GENERALLY BELIEVED TO REFLECT MATERNAL CANDIDA CHORIOAMNIONITIS RESULTING FROM ASCENDING INFECTION FROM THE GENITAL TRACT.
• A TOTAL OF 10–35% OF WOMEN SUFFER FROM CANDIDAL VAGINITIS DURING PREGNANCY, BUT LESS THAN 1% OF THEM DEVELOP CANDIDAL CHORIOAMNIONITIS THAT CAN AFFECT THE FETUS.
• IT APPEARS THAT CANDIDA IS, HOWEVER, ABLE TO FIND ITS WAY INTO THE AMNIOTIC FLUID WITHOUT PRIOR RUPTURE OF MEMBRANES.
• FOREIGN BODIES IN THE UTERUS OR THE CERVIX INCREASE THE RISK, PARTICULARLY INTRAUTERINE CONTRACEPTIVE DEVICES.
• THERE IS NO EVIDENCE THAT MATERNAL ANTIBIOTIC THERAPY OR IMMUNODEFICIENCY IN THE INFANT PLAYS A ROLE IN PREDISPOSITION.
• PRESENTATION:
• AN EXTENSIVE ERUPTION OF SCATTERED PINKISH RED MACULES AND PAPULES IS PRESENT AT BIRTH OR APPEARS WITHIN A FEW HOURS.
• THE LESIONS GENERALLY PROGRESS TO A VESICULAR PHASE, AND THEN EITHER TO A PUSTULAR OR A BULLOUS PHASE, OVER A PERIOD OF 1–3 DAYS.
• MORE OR LESS ANY PART OF THE SKIN SURFACE MAY BE AFFECTED, INCLUDING THE NAILS, PALMS AND SOLES.
• IN FACT, PALMAR AND PLANTAR PUSTULES ARE REGARDED AS A HALLMARK OF CONGENITAL CUTANEOUS CANDIDIASIS.
• PARONYCHIA MAY OCCUR AND ISOLATED INVOLVEMENT OF THE NAIL PLATES HAS BEEN DESCRIBED.
• ORAL INVOLVEMENT IS USUALLY ABSENT, AND THE NAPPY AREA TENDS TO BE SPARED, AT LEAST INITIALLY.
• VERY LOW-BIRTH-WEIGHT INFANTS MAY HAVE A SCALDED APPEARANCE, AND ARE PARTICULARLY AT RISK OF SYSTEMIC INFECTION.
• COURSE AND MANAGEMENT:
• WHEN INFECTION IS CONFINED TO THE SKIN, AFFECTED INFANTS ARE GENERALLY WELL, AND THE RASH CLEARS WITHIN A WEEK WITH APPROPRIATE TOPICAL ANTIFUNGAL THERAPY, FOR EXAMPLE WITH TOPICAL KETOCONAZOLE. USUALLY THERE IS PROMINENT POSTINFLAMMATORY DESQUAMATION.
• SKIN AND MUCOSAL INVOLVEMENT MAY BE COMPLICATED BY SYSTEMIC CANDIDIASIS, PARTICULARLY IN THE PREMATURE BABY.
• THE LUNGS MAY BE AFFECTED; HEPATOSPLENOMEGALY AND ABNORMAL LIVER FUNCTION HAVE ALSO BEEN RECORDED. CANDIDAL MENINGITIS IS ANOTHER POTENTIAL COMPLICATION.
• CRITERIA HAVE BEEN PROPOSED THAT INDICATE A HIGH RISK OF SYSTEMIC INVOLVEMENT. SYSTEMIC ANTIFUNGAL THERAPY SHOULD BE CONSIDERED IN AT-RISK INFANTS; AMPHOTERICIN B IS PROBABLY THE DRUG OF CHOICE.
• STUDIES HAVE SHOWN THAT INTRAVENOUS FLUCONAZOLE PROPHYLAXIS IN VERY LOW-BIRTH-WEIGHT INFANTS CAN REDUCE BOTH INVASIVE CANDIDIASIS AND MORTALITY RATES, BUT A COCHRANE REVIEW USING ORAL ANTIFUNGAL PROPHYLAXIS IN PRETERM INFANTS HAS NOT SHOWN A DEFINITIVE BENEFIT.

• COLONISATION OF THE SKIN BY MALASSEZIA FURFUR STARTS SOON AFTER BIRTH AND PROGRESSES UNTIL THE AGE OF ABOUT 3 MONTHS, PROBABLY REFLECTING THE ACTIVITY OF THE SEBACEOUS GLANDS DURING THIS PERIOD.
• THIS YEAST HAS BEEN A CAUSE OF SYSTEMIC INFECTIONS IN INFANTS RECEIVING INTRAVENOUS LIPIDS, AND IT IS PRESUMED THAT THE SOURCE OF ORGANISMS IN SUCH CASES IS THE SKIN.
• IT IS NOW BELIEVED THAT M. FURFUR AND M. SYMPODIALIS MAY BE A FREQUENT CAUSE OF RED PAPULOPUSTULAR ERUPTIONS OCCURRING ON THE FACE AND SCALP IN NEONATES, A CONDITION NOW WIDELY TERMED NEONATAL CEPHALIC PUSTULOSIS, ALTHOUGH NOT ALL NEONATES WITH THIS CLINICAL PRESENTATION HAD DETECTABLE MALASSEZIA IN THE LESIONS.
• THIS TYPE OF RASH WAS REPORTED TO HAVE A FREQUENCY OF 10% IN NEONATES SEEN AS OUT-PATIENTS IN A PAEDIATRIC DERMATOLOGY DEPARTMENT, WITH PUSTULE CONTENTS SHOWING M. FURFUR YEASTS IN OVER HALF OF THESE.
• A GOOD THERAPEUTIC RESPONSE TO THE TOPICAL APPLICATION OF 2% KETOCONAZOLE CREAM FOR 15 DAYS WAS SEEN IN ALMOST EVERY CASE.
• A FREQUENCY OF 66% WAS REPORTED IN ONE STUDY, WITH 62% BEING CULTURE POSITIVE FOR MALASSEZIA.
• DIFFERENTIAL DIAGNOSIS INCLUDES EOSINOPHILIC PUSTULOSIS OF THE SCALP, TRANSIENT PUSTULAR MELANOSIS, SCABIES, NEONATAL ACNE AND INFECTIONS WITH CANDIDA OR STAPHYLOCOCCUS AUREUS.

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• Occurs in ~1/4 to under half of healthy full-term newborns, usually 2nd-3rd day of life.
• Broad erythematous flare much more prominent than the small follicular papule/pustule it surrounds.
• Involves face, trunk, proximal extremities; rare on soles/palms. NO fever. Generally disappears by the 10th day.
• Distinguish from miliaria, bacterial folliculitis, neonatal herpes, scabies. Smears of pustules show eosinophils; rarely biopsy needed (folliculitis with eosinophils and neutrophils).

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• Originally described for congenital rubella purpuric lesions; associated with disorders producing extramedullary erythropoiesis
• Generalized dark-blue to magenta, nonblanchable, indurated, round-oval hemispheric papules 1-7mm; favors head, neck, trunk
• Etiologies: congenital infections (toxoplasmosis, rubella, CMV, HSV, parvovirus B19), hemolytic disease of newborn (Rh incompatibility, blood group incompatibility), hereditary spherocytosis, twin transfusion syndrome, recombinant erythropoietin administration, neuroblastoma, rhabdomyosarcoma, extraosseous Ewing sarcoma, Langerhans cell histiocytosis/congenital self-healing indeterminate cell histiocytosis, congenital leukemia
• Multiple vascular disorders (hemangiopericytoma, hemangioma, blue rubber bleb nevus, glomangioma) may mimic
• Evaluation: peripheral blood count, hemoglobin, TORCH serologies, viral cultures, Coombs test; skin biopsy may help determine cause

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