Incontinentia pigmenti (Bloch-Sulzberger) Q82.3

X-linked dominant hereditary neuroectodermal disease of childhood, present at birth or occurring within the first week of life (almost 100%), affecting the skin, nails, hair, teeth and eyes. Initially, an inflammatory skin disease is impressive, which in the later "non-inflammatory stage IV" leaves spatter-like pigmentation and atrophy.

Incidence: 1/50.000 births/year.

X-linked dominant inheritance of mutations of the NF-kappa-B essential modulator gene(IKBKG gene formerly known as NEMO gene; gene locus: Xq28). In 64% of cases, this is a new mutation. This gene encodes a protein that is responsible for the regulation of various cytokines, chemokines and adhesion molecules. It is essential for protection against TNF-alpha-induced apoptosis.

The mutations are only compatible with life if they are present as a genetic mosaic. Mosaics develop most frequently in women in the context of X-linked inactivation. Affected male fetuses usually die in utero. Genetic mosaics rarely occur in male patients due to Klinefelter syndrome, chromatid mutations or early somatic mutations.

Mainly extremities, lateral trunk areas.

• The disease progresses in phases and presents itself on the integument in different clinical forms, which can be divided into 4 (partly overlapping) stages:
  • Stage 1 (birth to 4th month): Red vesicles, blisters, (eosinophilic) pustules, papules, plaques in a striped or girdle-shaped, sometimes also whorled arrangement ( Blaschko's lines).
  • Stage 2 (2nd-6th month): Healing of the acute manifestations. Formation of hyperkeratotic, yellow-brownish, verrucous plaques
  • Stage 3 (7th month - 12th year of life): dirty brown or steel to slate gray, spatter-like, striped or garland-like, also annular patches.
  • Stage 4 (6th year of life to adulthood): Lesions are pale. Development of hypopigmented, atrophic scars with hair abnormalities (in 50% of cases), alopecia and loss of sweat glands.
  • Note: In rare cases, a reactivation of vesicular stage 1 may occur, e.g. in the context of an infection (Juan CK et al. 2015). Stages 1-3 may already be complete at birth (Sigl J et al. 2020)
• Malformations of other organs:
  • Tooth and jaw (67-90% of patients): Tooth hypoplasia, hypodontia, peg teeth, microdontia, prognathism
  • Eyes (20-70% of patients): Strabismus (about 20%), pseudoglioma retinae, corneal and lens opacities, pigmentary dystrophy and retinal detachment, optic atrophy, microphthalmia, blue sclera, ptosis
  • CNS (20- 30% of patients) microcephaly, debility, spastic diplegia, seizures (most common neurological symptom) intellectual deficits (approx. 10% of patients), ataxia
  • Skeleton (sporadic): hip joint dysplasia, syndactyly
  • Heart (sporadic): Endomyocardial fibrosis, tetralogy of Fallot
  • Nails (sporadic): dimples, onychogryposis
• Concomitant:
  • Blood- (stage 1: 35% of patients. Blood eosinophilia can be excessive up to 80% of peripheral leukocytes). Blood eosinophilia reduced in later stages (in stage 4 only in 10% of patients)
  • Tissue eosinophilia

High blood and tissue eosinophilia (blood eosinophilia in about 35% of patients).

Intraepidermal and subcorneal blisters with abundant eosinophilic cells, acanthotic widened, spongiotically loosened epidermis with single cell keratinization. In stages 3 and 4: considerable accumulations of melanin (pigment incontinence) in the dermis. There in melanophages.

Epidermolysis bullosa group: no arrangement in the Blaschko lines

ILVEN: usually manifested at a later age.

Incontinentia pigmenti, Franceschetti-Jadassohn type

Melanodermitis toxica: no arrangement in the Blaschko lines

Urticaria pigmentosa: no arrangement in the Blaschko lines, Darier's sign can be triggered

Lichen planus: no phased development since birth. Histology is diagnostic.

Schimmelpenning-Feuerstein-Mims syndrome: The skin lesions are already present at birth and arranged in a linear pattern. No inflammatory signs. Histology is diagnostic: nevi sebacei; head and neck preferred.

In the inflammatory stage short-term potent glucocorticoids such as prednicarbate (e.g. Dermatop cream). In case of blister formation, moist compresses with antiseptic additives such as potassium permanganate (light pink).

Skin symptoms regress until adulthood, possibly slight hypopigmentation and partial scars. Otherwise depending on the accompanying diseases (especially seizure disorders).

Only in exceptional cases does a recurrence of the inflammatory phases occur in later stages (e.g. infection-associated)

It is recommended to arrange for a genetic examination of the mother!

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