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Ichthyosis

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Skin Presentations/Cornification

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Generalized scaling of the skin from a disorder of cornification. Severity ranges from mild dry "fish-scale" skin in a healthy school-age child (ichthyosis vulgaris) to a neonate encased in armor-like plates at birth (harlequin ichthyosis). The clinical sort is along two axes: time of onset (present at birth as a collodion baby or harlequin phenotype versus evolving in infancy and childhood) and isolated versus syndromic (skin only versus skin + hair + neurologic + ocular + immune + hepatic features). "Collodion baby" is a phenotype, not a diagnosis; the membrane peels in the first weeks and the underlying ichthyosis declares itself.

  1. Onset: at birth (severe congenital forms) versus after birth (ichthyosis vulgaris emerges in infancy/early childhood; X-linked ichthyosis emerges in the first months).
  2. Severity and morphology: mild dry scale on extensor surfaces (vulgaris) versus dark thick plate-like scales (lamellar) versus blistering plus scaling (epidermolytic) versus armor-like plates with ectropion/eclabium (harlequin).
  3. Extracutaneous features: isolated skin disease versus the syndromic ichthyoses (Netherton, Sjögren-Larsson, trichothiodystrophy, Chanarin-Dorfman, others).

Common, non-syndromic

  • Ichthyosis vulgaris (FLG, AD, very common, ~10% of the population carries an FLG loss-of-function variant): mild fine "fish-scale" scaling on extensor surfaces, hyperlinear palms, keratosis pilaris. Same gene as atopic dermatitis risk, so atopy, asthma, and food allergy track with this group. Manageable with emollients.
  • X-linked ichthyosis (STS, X-linked recessive, steroid sulfatase deficiency): dirty-looking dark polygonal scales on the neck, trunk, and extensor surfaces in boys; spares face and palms/soles. Maternal pregnancy often shows low unconjugated estriol on the quad screen and poor labor progression (placental sulfatase deficiency); the prenatal screen is sometimes how the diagnosis is first suggested. Increased risk of cryptorchidism and corneal opacities; contiguous-gene deletions on Xp22.3 can extend to Kallmann syndrome and X-linked ichthyosis combined.

Severe congenital (present at birth)

  • Autosomal recessive congenital ichthyosis (ARCI), lamellar form (TGM1 most common, also ALOXE3, ALOX12B, NIPAL4, others): collodion membrane at birth that peels to reveal large dark plate-like scales over the entire body, often with ectropion and eclabium. Distinct from congenital ichthyosiform erythroderma (also under ARCI; finer scale on erythematous background).
  • Epidermolytic ichthyosis (epidermolytic hyperkeratosis) (KRT1, KRT10, AD): blistering and erosions at birth with progression to thick verrucous hyperkeratosis in flexures; not a collodion phenotype. Caused by defective keratin filament assembly.
  • Harlequin ichthyosis (ABCA12, AR): the most severe form. Thick armor-like plates separated by deep red fissures, severe ectropion, eclabium, restricted respiration, and limb constriction at birth. Historically fatal in early days; survival has improved with neonatal intensive care + early systemic retinoids. Recurrence risk 25% in subsequent pregnancies.

Syndromic ichthyoses

  • Netherton syndrome (SPINK5, AR): trichorrhexis invaginata ("bamboo hair") + ichthyosis linearis circumflexa (serpiginous double-edged erythematous plaques) + severe atopy + failure to thrive + immune dysregulation. Neonates can present with collodion-like erythroderma + life-threatening dehydration and infection.
  • Sjögren-Larsson syndrome (ALDH3A2, AR): ichthyosis + spastic di/tetraplegia + intellectual disability + glistening white retinal dots. Defect in fatty aldehyde dehydrogenase.
  • Trichothiodystrophy (ERCC2, ERCC3, GTF2H5, others, AR): sulfur-deficient brittle hair (tiger-tail banding on polarized light microscopy) + ichthyosis + photosensitivity + intellectual disability + short stature (the IBIDS / PIBIDS acronym). Nucleotide excision repair defect; subset have increased UV sensitivity without melanoma risk.
  • Chanarin-Dorfman syndrome (ABHD5/CGI-58, AR): non-bullous congenital ichthyosiform erythroderma + vacuolated leukocytes on smear (Jordan's anomaly) + hepatomegaly + myopathy. Neutral lipid storage disease.
  • Conradi-Hünermann (X-linked chondrodysplasia punctata) (EBP, X-linked dominant): ichthyosiform skin lesions following Blaschko lines + punctate calcifications of epiphyses on infant X-ray + asymmetric short stature + cataracts.
  • Collodion baby is a syndrome bucket, not a diagnosis. Peel reveals the underlying ichthyosis: most often lamellar/ARCI (TGM1), occasionally Netherton, occasionally a self-healing collodion baby.
  • Boy with dirty dark polygonal scales sparing face and palms/soles + mother had low estriol on quad screen + poor labor progression → X-linked ichthyosis (steroid sulfatase deficiency).
  • Atopic, asthmatic child with hyperlinear palms and mild scaling → ichthyosis vulgaris (FLG); same biology as atopic dermatitis.
  • Blistering at birth that evolves into thick verrucous scale, especially in flexures → epidermolytic ichthyosis (KRT1/KRT10); biopsy shows epidermolytic hyperkeratosis. Half of severe cases are de novo dominant variants.
  • Newborn with armor plates, deep red fissures, ectropion, and eclabium → harlequin ichthyosis; start systemic retinoid + intensive supportive care in the NICU.
  • Ichthyosis + atopy + failure to thrive + bamboo hair on light microscopy → Netherton syndrome.
  • Ichthyosis + spastic diplegia + ID + glistening retinal dots → Sjögren-Larsson.
  1. Full skin exam under good light: scale morphology (fine vs plate-like vs blistering), distribution, palmar hyperlinearity, ectropion/eclabium, presence of erythroderma.
  2. Hair shaft microscopy (light + polarized): trichorrhexis invaginata (Netherton); tiger-tail banding (trichothiodystrophy).
  3. Maternal pregnancy history: low estriol on quad screen and poor labor progression suggest X-linked ichthyosis in a male infant; collodion membrane history in older siblings.
  4. Biopsy (when phenotype is ambiguous): epidermolytic hyperkeratosis pattern, paucity of granular layer in vulgaris.
  5. Peripheral smear for vacuolated leukocytes (Chanarin-Dorfman / Jordan's anomaly).
  6. Targeted gene panel or exome: a "congenital ichthyosis panel" covers FLG, STS, TGM1, KRT1, KRT10, ABCA12, SPINK5, ALDH3A2, ERCC2, ABHD5, EBP, and others.
  7. STS enzyme activity or STS deletion / array CGH for X-linked ichthyosis (most are deletions on Xp22.3).
  8. Multidisciplinary baseline: ophthalmology (ectropion, cataracts in Conradi), neurology (Sjögren-Larsson, trichothiodystrophy), GI/hepatology (Chanarin-Dorfman), audiology, and dermatology for chronic skin care planning.
  • A collodion baby is not a diagnosis; it is a starting point. Counsel the family that the membrane will peel in 2-4 weeks and the underlying ichthyosis (most commonly ARCI from TGM1) will then declare.
  • Harlequin ichthyosis is a neonatal emergency. Skin barrier failure plus restricted breathing plus dehydration is the killing combination; NICU with humidified environment, IV fluids, ophthalmology for ectropion, and early oral retinoids.
  • Low maternal estriol on the quad screen in a boy with scaly skin is X-linked ichthyosis until proven otherwise. The prenatal screen finding precedes the rash.
  • The same FLG variants that cause ichthyosis vulgaris are the strongest known genetic risk factor for atopic dermatitis. When you see hyperlinear palms in a child with eczema, the link is direct.
  • Hair shaft microscopy is a fast, cheap, and high-yield test for the syndromic ichthyoses. Don't move to a gene panel before you've looked at the hair under the microscope.