A 7-month-old girl with persistent erythroderma since the neonatal period presents with migratory, polycyclic, double-edged scaly plaques on the trunk and thighs. She has poor weight gain, recurrent skin infections, and severe pruritus. Exam also reveals diffuse scalp scaling. Serum studies demonstrate elevated IgE and eosinophilia. Trichoscopy of eyebrow hairs shows the following hair shaft deformity.

Which of the following is the most likely diagnosis?

A. X-linked ichthyosis
B. Netherton syndrome
C. Lamellar ichthyosis 
D. Hyper-IgE (STAT3) syndrome
E. Atopic dermatitis

Rationale:

In infants with congenital erythroderma, failure to thrive, and refractory “atopic-like” dermatitis, the diagnostic fork hinges on hair-shaft abnormalities and the pattern of ichthyosis. Netherton syndrome uniquely combines (1) ichthyosis linearis circumflexa (migratory, serpiginous plaques with double-edged scale), (2) hair-shaft fragility with trichorrhexis invaginata (“bamboo hair”) best seen in eyebrows/eyelashes or by trichoscopy/hair mount, and (3) atopic diathesis (very high IgE/eosinophilia) with barrier dysfunction leading to infections. Molecularly, SPINK5 (LEKTI) deficiency is associated with Netherton syndrome. 

Correct answer: B. Netherton syndrome

Incorrect answer choices:

A. X-linked ichthyosis is due to STS deficiency; presents in male infants with large, adherent brown scale (often neck/trunk/extensors) without erythroderma, migratory double-edged scale, or trichorrhexis invaginata. IgE/eosinophilia and severe atopic features are not typical.

C. Lamellar ichthyosis (ARCI/TGM1) presents as collodion baby at birth followed by generalized plate-like scale and ectropion/eclabium in some cases. It lacks the migratory serpiginous plaques with double-edged scale and does not feature bamboo hair or marked atopic diathesis.

D. Hyper-IgE (STAT3) syndrome is characterized by recurrent “cold” staph abscesses, pneumatoceles, coarse facies, retained primary teeth, fractures; skin shows eczema, but no pathognomonic hair-shaft abnormality and no ichthyosis linearis circumflexa. Hair fragility with trichorrhexis invaginata is not a feature.

E. Atopic dermatitis can be severe in infancy with high IgE, but the presence of bamboo hair and characteristic double-edged migratory scale strongly argues for Netherton. Primary AD does not cause congenital erythroderma with hair-shaft invagination.

Additional reading at Fitzpatrick's Dermatology Chapter 47: The Ichthyoses