Incontinentia Pigmenti: A Case Report

Dyah Ayu Pitasari, Iskandar Zulkarnain

Departement of Dermatology and Venereology Faculty of Medicine, Universitas Airlangga / Dr. Soetomo General Hospital

Surabaya, Indonesia

Keywords: incontinentia, pigmenti.

Abstract: Incontinentia pigmenti (IP) is an uncommon X-linked dominant genodermatosis, can affects the skin, eyes,

teeth, and may be associated with neurological defects. Changes of skin that are always present are usually

combined with anomalies in skin appendages and in other organs. A 2 month female baby, with chief

complaint brown patches on her body. Her mother said that brown patches on her body since 1 month, at first

it was red patch with blister, then dry and left rough mark. Dermatological examination on regio thoracalis

anterior et posterior, brachii dextra et sinistra, femoralis dextra et sinistra found linear hiperpigmentation

macule, along blaschko line, no scale, no verucosa. Histopathological examination on epidermis there were

hiperkeratosis basal cell, no spongiosis and on dermis there were melanin within macrophage along superficial

dermis. In this case, there was a skin anomali but with no other organ involvement. This patient is female,

with history of her mother miscarriage in second child. Although the skin lesions of IP appear impressive,

little treatment is needed as they will gradually clear on their own. Parents should be appropriately counseled

about the expected course of the disease. A bland emollient can be applied to inflammatory lesions to prevent

ulceration.

1 INTRODUCTION

Incontinentia pigmenti (IP) is an uncommon X-linked

dominant genodermatosis, can affects the skin, eyes,

teeth, and may be associated with neurological

defects. It affects predominantly females and is lethal

in utero in male fetuses. Cutaneous manifestations are

classically subdivided into four stages:

vesiculobullous, verrucous, hyperpigmented, and

atrophic.The diagnosis of IP was based on clinical

findings and on histopathological analysis of biopsy

specimen. IP is a single-gene disorder caused by

mutation in the NEMO (nuclear factor kB essential

modulator) gene located at chromosome Xq28, which

is required for activation of a transcription factor

involved in immune, inflammatory, and apoptotic

pathways. More than 90% of patients will present in

the newborn period with inflammatory vesicles, often

following a linear pattern (V-shaped pattern on the

back and S-shaped pattern on the anterior trunk)

corresponding to the migration of embryonic cells

during fetal development (the lines of Blaschko).

Classically, these vesicles will subsequently evolve

through a verrucous stage, a hyperpigmented stage,

and finally, a stage of dermal atrophy and

hypopigmentation. The identification of NF-kB

essential modulator (NEMO) as the disease-causing

gene, and the skewing of X-chromosome

inactivation, are powerful tools for the diagnosis of

unusual forms of IP. In 80% of IP cases, the disease

is caused by a large-scale deletion of NEMO exons 4

to 10. Nevertheless, the diagnosis of IP is based on a

thorough clinical examination. Landy and Donnai

have defined criteria that are useful for the clinical

diagnosis of IP (Hegde et al., 2006; Hadj-Rabia et al.,

2013).

2 CASE

A 2 month female baby, with chief complaint brown

patches on her body. Her mother said that brown

patches on her body since 1 month, at first it was red

patch with blister, then dry and left rough mark.There

was no itchy, no pain at the brown patches. There was

no history of trauma at the site of the lesion before.

History of giving topical, family having the same

complaint, eye abnormalities, seizure or epilepsy

were denied. No history of having other disease. She

is third child, history normal childbirth, 38 weeks of

Pitasari, D. and Zulkarnain, I.

Incontinentia Pigmenti: A Case Report.

DOI: 10.5220/0008157203510354

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 351-354

ISBN: 978-989-758-494-7

351

pregnancy, 3kg birth weight, 50 cm lenght, no history

of having other disease. Her mother said that during

pregnancy, she routinly control to the doctor and there

were no abnormality. History of consanguineous

marriages was denied. Her first brother was not

affected. History of consuming drug or medicinal

herbs during pregnancy was denied. History of

consuming drug or medicinal herbs during pregnancy

was denied. Her mother have thin white mark on her

wrist. History of mother miscarriage in second child.

General examination revealed compos mentis

condition, look well with no sign of anemic, icterus,

cyanosis, or respiratory distress, no lymph node

enlargement. Body weight 3,5 kg, and lenght 55cm.

The pulse rate was 100 per minute, respiratory rate 20

per minute, and body temperature 36.8

C. There was

no abnormality on thorax and abdomen examintion.

Dermatological examination on regio thoracalis

anterior et posterior, brachii dextra et sinistra,

femoralis dextra et sinistra found linear

hiperpigmentation macule, along blaschko line, no

scale, no verucosa. Blood examination, hemoglobin

was 12g/dl, leucocyte was 11.700/cmm with

eosinophil 0%, basophil 0%, neutrophyl stab 0%,

segmen 47%, lymphocyte 44%, monocyte 9%,

trombhocyte 266.000 and erytrocyte 3,88.

Histopathological examination on epidermis there

were hiperkeratosis basal cell, no spongiosis and on

dermis there were melanin within macrophage along

superficial dermis. Patient consult to pediatric

departement, there were normal growth and

development. Consult to ophthalmology

departement, neurology departement, and dentist

with no abnormalities found. Patient give therapy

emolient baby cream two times daily, and education

about patient’s condition, posibility of opthalmologic

or neurologic condition, consult if there’s any

complain and not manipulate the lesion.

3 DISCUSSION

Incontinentia pigmenti [Bloch–Sulzberger syndrome]

is a rare X-linked genodermatosis with an estimated

prevalence of 0.7/100,000. Changes of skin that are

always present are usually combined with anomalies

in skin appendages and in other organs. IP appears

almost exclusively in females and is usually lethal in

males (Hilde et al., 2012; Zhang et al., 2013).

The

absence of severe systemic complications was noted

in 43 of 96 (44.8%) patients with generalized IP and

39 of 43 (90.7%) IP patients with minor cutaneous

symptoms (Hadj-Rabia et al., 2011).

In this case,

there was a skin anomali but with no other organ

involvement. This patient is female, with history of

her mother miscarriage in second child.

The cutaneous lesions in the first stage represent

the population of NEMO-deficient cells that fail to

activate NF-κB, leading to apoptosis, as NF-κB

normally protects against tumor necrosis factor-

induced apoptosis. Epidermal cells expressing the

defective NEMO gene give rise to typical skin lesions

along the lines of Blaschko, reflecting the embryonic

migration path of the affected keratinocytes. The

number of NEMO-deficient cells decreases

secondary to apoptosis and is replaced by cells

expressing the normal allele. Subsequently, the

inflammatory and vesicular stage ends. The

hyperproliferation in the second stage is likely due to

compensatory proliferation of normal NEMO

keratinocytes. Hyperpigmentation in the third stage

results from incontinence of melanin pigment from

the destroyed epidermis into the dermis (Hilde et al.,

2012).

The differences in effect that are found among

tissues in an individual, and among the same tissues

in different individuals, point out the profound effect

of selection for cells in which the normal X-

chromosome escapes inactivation and becomes the

active X-chromosome in this disease. Some tissues

appear to undergo this selection early in development

and are therefore spared any apparent phenotype at

the time of birth. Other tissues, such as hair roots and

tooth bulbs, undergo selection after birth during

proliferation. This leads to abnormalities such as

anodontia and alopecia, in which cells harboring the

NEMO mutation fail to proliferate. These cells are

apparently unaffected by the NEMO mutation until

directed to generate teeth or hair, which they are

unable to do. Those cells with an active normal X-

chromosome contribute to these tissues, resulting in

patchy alopecia, and oddly shaped when the tooth bud

is made up of a mix of mutant and normal cells or

normal teeth (Hadj-Rabia et al., 2011).

Recently, NEMO was implicated as the primary

effector molecule for signaling the presence of DNA

damage to the NFkB complex. Cells that undergo

DNA damage must determine whether to undergo

apoptosis, a decision that is mediated by a number of

components of the DNA damage-sensing and repair

pathway. Huang et al. recently determined that

NEMO is the principal molecule that provides this

signaling from the nucleus to the cytoplasm, thereby

enabling the release of NFkB released into the

nucleus to stimulate transcription of anti-apoptotic

genes. The ATM (ataxia telangiectasia mutated)

kinase phosphorylates NEMO and assists its

association with the IKK complex in the cytoplasm.

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

352

The details of NEMO alteration in the nucleus are

also being explored; it has been found to be associated

with PIDD (p53-inducible death-domain-containing

protein) and RIP1 (receptor-interacting protein 1) in

a complex that facilitates its sumoylation, a mark of

activation. The cell death causes lethality in male

embryos and skewed X-inactivation in female

patients, as a result of elimination of cells with an

active mutant X-chromosome. In order to explain the

survival of some male patients with IP, three

mechanisms have been proposed (Nelson, 2006).

Cutaneous manifestations: Stage 1, inflammatory

or vesicular stage: development of papules, vesicles

and pustules on an erythematous base, distributed

linearly along the lines of Blaschko. Stage 2,

verrucous stage, is characterized by plaques and

warty papules linearly arranged over an erythematous

base, also following the lines of Blaschko. Stage 3 or

hyperpigmented stage : development of linear or

whorled lesions, with a brownish pigmentation,

which may be accompanied by atrophy, occurs in 90-

98% . Stage 4, known as atrophic or hypopigmented,

is characterized by areas of hypopigmentation,

atrophy and absence of hair.develop during

adolescence, persist into adulthood (Berlin et al.,

2002).

On this case, histopathological examination

showed on epidermis there were hiperkeratosis basal

cell, no spongiosis. On dermis there were melanin

within macrophage along superficial dermis. There

were some lymphocyte. No eosinophil. This is more

like the third stage of IP.

Other dermatologic findings, the inflammatory

lesions of IP can produce scarring alopecia, primarily

of the vertex of the scalp. Up to 38% of affected

individuals report this finding. Like atrophic skin

lesions, vertex alopecia is a persistent marker for IP

(Zou et al., 2007).

Laboratory findings, perhaps one of the most

striking findings during the first cutaneous stage of IP

is the marked peripheral blood leukocytosis and

eosinophilia. Eventually, the counts return to normal

during the subsequent stages. Immunoglobulin levels

and lymphocyte subpopulation counts are within

normal limits (Zou et al., 2008).

Although the skin lesions of IP appear impressive,

little treatment is needed as they will gradually clear

on their own. Parents should be appropriately

counseled about the expected course of the disease. A

bland emollient can be applied to inflammatory

lesions to prevent ulceration. If ulceration occurs,

antibiotic ointment and non-adherent sterile dressings

should be used to cover the affected areas. Subungal

tumors may spontaneously resolve, but can be treated

with surgical excision or curretage to ameliorate the

associated pain (Bruckner, 2004; Julie et al., 2013;

Mini'c et al., 2014).

Parents should also be counseled about the

possibility of delayed eruption of the teeth and other

dental abnormalities. Significant absence of the teeth

may impact not only the ability to eat and speak, but

also facial development and cosmesis. The early

involvement of a dental team familiar with these

problems is important (Bruckner, 2004; Julie et al.,

2013; Mini'c et al., 2014).

4 CONCLUSION

Incontinentia pigmenti (IP) is an uncommon X-linked

dominant genodermatosis, can affects the skin, eyes,

teeth, and may be associated with neurological

defects. It affects predominantly females and is lethal

in utero in male fetuses. Cutaneous manifestations are

classically subdivided into four stages:

vesiculobullous, verrucous, hyperpigmented, and

atrophic. The diagnosis of IP was based on clinical

findings and on histopathological analysis of biopsy

specimen. IP is a single-gene disorder caused by

mutation in the NEMO (nuclear factor kB essential

modulator) gene located at chromosome Xq28, which

is required for activation of a transcription factor

involved in immune, inflammatory, and apoptotic

pathways.

A 2 month female baby, with chief complaint

brown patches on her body. Her mother said that

brown patches on her body since 1 month, at first it

was red patch with blister, then dry and left rough

mark.There was no itchy, no pain at the brown

patches. There was no history of trauma at the site of

the lesion before. History of giving topical, history of

family having the same complaint, history of eye

abnormalities, history of seizure or epilepsy were

denied. No history of having other disease. She is

third child, history normal childbirth, 38 weeks of

pregnancy, 3kg birth weight, 50 cm lenght, no history

of having other disease. Her mother said that during

pregnancy, she routinly control to the doctor and there

were no abnormality. History of consanguineous

marriages was denied. Her first brother was not

affected. History of mother miscarriage in second

child. Dermatological examination on regio

thoracalis anterior et posterior, brachii dextra et

sinistra, femoralis dextra et sinistra found linear

hiperpigmentation macule, along blaschko line, no

scale, no verucosa. Histopathological examination on

epidermis there were hiperkeratosis basal cell, no

spongiosis and on dermis there were melanin within

Incontinentia Pigmenti: A Case Report

353

macrophage along superficial dermis. Patient give

therapy emolient baby cream two times daily, and

education about patient’s condition, posibility of

opthalmologic or neurologic condition, consult if

there’s any complain and not manipulate the lesion.

The absence of severe systemic complications

was noted in 43 of 96 (44.8%) patients with

generalized IP and 39 of 43 (90.7%) IP patients with

minor cutaneous symptoms (Hadj-Rabia et al., 2011).

In this case, there was a skin anomali but with no

other organ involvement. This patient is female, with

history of her mother miscarriage in second child.

Cutaneous manifestations: Stage 1, inflammatory

or vesicular stage: development of papules, vesicles

and pustules on an erythematous base, distributed

linearly along the lines of Blaschko. Stage 2,

verrucous stage, is characterized by plaques and

warty papules linearly arranged over an erythematous

base, also following the lines of Blaschko. Stage 3 or

hyperpigmented stage : development of linear or

whorled lesions, with a brownish pigmentation,

which may be accompanied by atrophy, occurs in 90-

98% . Stage 4, known as atrophic or hypopigmented,

is characterized by areas of hypopigmentation,

atrophy and absence of hair.develop during

adolescence, persist into adulthood.

On this case, histopathological examination

showed on epidermis there were hiperkeratosis basal

cell, no spongiosis. On dermis there were melanin

within macrophage along superficial dermis. There

were some lymphocyte. No eosinophil. This is more

like the third stage of IP.

Although the skin lesions of IP appear impressive,

little treatment is needed as they will gradually clear

on their own. Parents should be appropriately

counseled about the expected course of the disease. A

bland emollient can be applied to inflammatory

lesions to prevent ulceration. If ulceration occurs,

antibiotic ointment and non-adherent sterile dressings

should be used to cover the affected areas. Subungal

tumors may spontaneously resolve, but can be treated

with surgical excision or curretage to ameliorate the

associated pain (Brucker, 2004; Julie et al., 2013).

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