Incontinentia Pigmenti

  • Inheritance pattern
    • X linked dominant
    • X-inactivation leads to blaschkoid distribution
      • Severe phenotypes have random X-inactivation whereas mild have skewed inactivation
    • Lethal in males, unless XXY karyotype (Klinefelter)
    • Both sexes may have mosaic form
  • Mutation → leads to abnormal apoptosis regulation
    • Loss of function of NF-kB essential modulator (NEMO)/IKBKG leads to inactivation of the NF-kB
    • IKBKG deficient keratinocytes are suscetible to apoptosis/necrosis due to the loss of protection against cell death
    • Immune cell activation and eosinophil recruitment
    • Endothelial inflammation and further damage (colateral damage)
      • notion image
      DOI doi:10.1038/nrdp.2016.35
      DOI doi:10.1038/nrdp.2016.35
  • Clinical manifestations
    • 4 stages: pathology varies with stage, patient may have multiple stages at one time
      • Vesicular
        • 0-4 months
        • eosinophilic spongiosis/vesicles, apoptotic keratinocytes
      • Verrucous
        • 2-6 months
        • papillomatosis, hyperkeratosis and acanthosis of the epidermis; apoptotic cells
      • Hyperpigmented
        • 6 months - adult
        • pigment incontinence
      • Hypopigmented: atrophic, epidermal atrophy
    • Other manifestations of IP are highly variable
      • Skin - scarring alopecia in blaschkoid distribution, subungueal tumors (resemble SCC)
      • Eyes - retinal vascular anomalies (blidness)
      • Teeth - hypodontia, anodontia, peg-shaped
      • CNS - seizures, intellectual delay
      • Breast - hypoplasia, supernumerary nipples
  • Diagnóstico
      • notion image
  • Abordagem
    • Pedir oftalmologia, neurologia, estomatologia