Incontinentia pigmenti (IP)
- Prevalence: 1 : 140 000
- Female/male: 20 : 1
- Usually, antenatally lethal in boys except rare conditions such as Klinefelter syndrome or post zygotic mutation or affecting half chromatic.
- XLD mutation in IKBKG (NEMO) gene located at Xq28
- NEMO (NF-kB essential modulator): protects against TNF-α-induced apoptosis, disease explained by TNF- α mediated inflammation and apoptosis
- Milder hypomorphic NEMO mutations, hypohidrotic ectodermal dysplasia with immune deficiency (HED-ID) in boys
Variable distribution depends on X chromosome silencing in females, 4 stages
- Stage 1: days to weeks, possible recurring inflammation, linear erythema and blisters (vesicular)
- Stage 2: 2-8 weeks, verrucous linear plaques
- Stage 3: infancy to adolescence, hyperpigmentation
- Stage 4: (hypopigmented/atrophic/lack of adnexa), teen onwards, hypopigmented
- Possible recurring inflammatory with intercurrent febrile illness
H&E:
- Inflammatory phase: eosinophilic spongiosis + scattered dyskeratotic keratinocyte, most helpful stage to bx
- Verrucous phase: acanthosis + hyperkeratosis + foci of dyskeratosis
- Hyperpigmentation: pigmentary incontinence ± vacuolization
- Hypopigmented: thinned epidermis, dermis devoid of adnexa
- Multidisciplinary care depending on structures affected – eyes, neurologic, breast, other ectodermal (hair, teeth, nails, sweat), orthopedic
- Genetic diagnosis (diagnostic criteria and confirmatory genetic testing) and genetic counseling
- Unless extracutaneous disease, the prognosis is good
- Risk of transmission in affected female is 1/3 healthy female, 1/3 affected female, 1/3 healthy male