Incontinentia Pigmenti Neurocutaneous Syndromes

1. INCONTINENTIA PIGMENTI
Dr. Pawan Kumar Barolia
MBBS MD (pediatrics)
Fellowship in intensive care pediatrics

2. CASE REPORT
 Newborn female, 20 days old, affected by a diffuse vesciculo-
bullous rash showed up to our clinic.
 The baby was born at term by a spontaneous vaginal delivery,
which was carried out after 3 hours by the membranes rupture.
 The entire pregnancy had taken place regularly, without any
complication.
 The patient’s mother was an otherwise healthy single woman of 31
years old. She did not have previous pregnancies or abortions.
During her childhood, the woman had suffered from varicella,
rubeola, parotitis and rubella.
 The woman told us to be affected by epilepsy. Her medical
treatment, also during the pregnancy, consisted of carbamazepine.
No other diseases or drugs assumptions had been reported. Her
familial history was insignificant

3.  At the mother’s clinical evaluation we did not observe any form of
cutaneous, nail or hair alterations. Maternal serology was negative
for VDRL, HIV, HBV, HCV.
 Unfortunately, no news about the newborn’s father had been
reported to us.
 During the clinical evaluation, the young patient was 48 cm in
height, and 2.6 kg of weight, which is less than normal. She had
normal blood pressure, pulse rate and breathing.
 The musculoskeletal system was normal, except for an hypoplastic
mandible. She did not have ocular or abdominal alterations.

4.  From birth, the newborn suffered from seizures. The EEG
showed a severely abnormal pattern with frequent multi-focal
spikes; the head ultrasound showed a pattern of immature
neurological development.
 Even if, in a first moment, the neurologist thought how
seizures could be the result of the carbamazepine abstinence,
seizures never stopped as they were a primary disease.
 During the dermatologic examination, we observed clear,
tense blister and bullae, on inflammatory base. Lesions
were localised on the extremities and the trunk, in a linear
arrangement which followed the lines of Blaschko, and
seemed to be asymptomatic.
 The Nikolsky test was negative. No other lesions were
observed in the other cutaneous or mucosal areas.

5.  Hairs were less than normal, wiry and coarse. Nails were
dystrophic
 Routine blood testing for inflammation, infections and autoimmune
diseases were negative, except for a peripheral eosinophilia (>
20%).
 CRP and PCT were normal.
 A punch biopsy performed on a lesion showed, in the epidermis, a
mild acanthosis, foci of eosinophilic spongiosis and occasional
dyskeratotic keratinocytes.
 In the same time, the dermis showed an infiltrate of lymphocytes,
eosinophils and nuclear dust derived from eosinophilic
karyorrhexis. (destructive fragement of nucleaus of dying cell)

6.  On the basis of the patient’s clinical pattern and of the
histological examination, we made the diagnosis of IP.
 Because of the spontaneous improvement and resolution of
skin lesions, we prescribed only an antibiotic therapy to avoid
secondary infections of the lesions.
 Two weeks later, during a follow-up,
 the dermatologic manifestations
had been changed,
as the classic evolution of IP.
Linear warty lesions appeared
on the side of the previous
vesicular-bullous rash.

7. Histology: The epidermis shows mild
acanthosis, foci of eosinophilic
spongiosis and occasional dyskeratotic
keratinocytes. The dermis is
characterised by an infiltrate of
lymphocytes, many eosinophils and
nuclear dust derived from eosinophilic
karyorrhexis
Acanthosis – benign overgrowth of
stratum spongiosum.
Dyskeratosis – keratinization of
individual cell

8. INCONTINENTIA PIGMENTI
 Heritable, x-linked dominant
 multisystem ectodermal disorder features dermatologic, dental, and
ocular abnormalities
 The phenotype is produced by functional mosaicism
 Random x-inactivation of an x-linked dominant gene that is lethal in
males (ikk-gamma/NEMO gene)
 The paucity of affected males
 The occurrence of female-to-female transmission,
 An increased frequency of spontaneous abortions in carrier females
support this supposition.

9. CLINICAL MANIFESTATIONS AND DIAGNOSIS
 This disease has 4 phases, not all of which may occur
 The 1st phase is evident at birth or in the 1st few weeks of life
 Consists of erythematous linear streaks and plaques of vesicles
 Most pronounced on the limbs and circumferentially on the trunk.
 The lesions may be confused with those of herpes simplex,
bullous impetigo, or mastocytosis, but the linear configuration is
unique
 Histopathologically, epidermal edema and eosinophil-filled
intraepidermal vesicles
 Eosinophils also infiltrate the adjacent epidermis and dermis.
 Blood eosinophilia as high as 65% of WBC count

10. CLINICAL MANIFESTATIONS AND DIAGNOSIS
 The 1st stage resolves by 4 mo of age, but mild, short-lived
recurrences of blisters may develop during febrile illnesses
 In the 2nd phase, as blisters on the distal limbs resolve, they
become dry and hyperkeratotic, forming verrucous plaques
 The verrucous plaques rarely affect the trunk or face and
generally involute within 6 mo
 Epidermal hyperplasia,
 Hyperkeratosis
 Papillomatosis are characteristic.

11. CLINICAL MANIFESTATIONS AND DIAGNOSIS
 The 3rd or pigmentary stage is the hallmark of IP
 It generally develops over weeks to months
 May overlap the earlier phases, be evident at birth, or, more
commonly, begin to appear in the 1st few weeks of life
 Hyperpigmentation is on the trunk > the limbs
 Distributed in macular whorls, reticulated patches, flecks, and linear
streaks that follow blaschko lines
 The axillae and groin are invariably affected

12.  The sites of involvement are not necessarily those of the preceding
vesicular and warty lesions
 The pigmented lesions, once present, persist throughout childhood
 Begin to fade by early adolescence & often disappear by age 16 yr
 Occasionally, the pigmentation remains permanently, particularly in
the groin
 The lesion, histopathologically, shows vacuolar degeneration of the
epidermal basal cells
 Melanin in melanophages of the upper dermis as a result of
incontinence of pigment

13. CLINICAL MANIFESTATIONS AND DIAGNOSIS
 In the 4th stage, hairless, anhidrotic, hypopigmented patches
or streaks occur
 late manifestation of IP
 they may develop, however, before the hyperpigmentation of
stage 3 has resolved
 The lesions develop mainly on the flexor aspect of the lower
legs and less often on the arms and trunk.

14.  Approximately 80% of affected children have other defects
 Alopecia (40%) which may be scarring and patchy or diffuse,
MC on the vertex
 Hair may be lusterless, wiry, and coarse
 Dental anomalies (80%) - persistent throughout life
 consist of late dentition, hypodontia, conical teeth, and impaction
 CNS (1/3) - motor and cognitive developmental retardation,
seizures, microcephaly, spasticity, and paralysis

15.  Ocular (30%) - neovascularization, microphthalmos,
strabismus, optic nerve atrophy, cataracts, and retrolenticular
masses
 > 90% of patients have normal vision
 Less common abnormalities include dystrophy of nails
(ridging, pitting) and skeletal defects.

16. DIAGNOSIS OF INCONTINENTIA PIGMENTI
 clinical grounds
 Although major and minor criteria have been established
 Wood lamp examination - highlight pigmentary abnormalities
 Clinical molecular testing is available
 80% of the affected patients a deletion that removes exons 4
through 10 of NEMO can be detected.
 D/D - hypomelanosis of Ito, which presents with similar skin
manifestations and is often associated with chromosomal
mosaicism.

17. MANAGEMENT
 The choice of investigative studies and the plan of
management depend on the occurrence of particular
noncutaneous abnormalities since the skin lesions are benign
 The high incidence of associated major anomalies warrants
genetic counseling.

18.  thank you