Bullous Urticaria Pigmentosa in an Infant:

A Rare Form of Bullous Disorder

Lidwina Anissa

, Sarah Mahri

, Rinadewi Astriningrum

, Triana Agustin

Rahadi Rihatmadja

, Githa Rahmayunita

Department of Dermatology and Venereology Faculty of Medicine Universitas Indonesia/

Dr. Cipto Mangunkusumo National General Hospital, Indonesia

Corresponding author

Keywords: Bullous Urticaria Pigmentosa

Abstract: Mastocytosis is a rare, sporadic, and a heterogeneous group of hematopoietic disorder, characterized by an

enormous number and accumulation of mast cells in one or more organ systems. The prevalence of

mastocytosis is challenging to determine due to underdiagnosis. Pediatric-onset mastocytosis which was

commonly diagnosed before two years of age is generally a benign disease. The course of pediatric-onset

mastocytosis is variable, from birth to the first year of life, with an average of 2.5 months. Cutaneous

mastocytosis may manifest as urticaria pigmentosa, diffuse cutaneous mastocytosis, and telangiectasia

macularis eruptive perstans. Bullous urticaria pigmentosa is a rare variant of urticaria pigmentosa. Blistering

is considered to be an effect of free mediator activity. The symptoms are mostly in proportion to the mast cell

degranulating activities in tissues, which may appear in the first year of life. Although systemic involvement

is rare in pediatric cutaneous mastocytosis, blistering may promote secondary infection and electrolyte

imbalance. We report a four-month-old infant with bullous urticaria pigmentosa. The symptoms had appeared

since the second day of life. Routine hematology examination revealed mild microcytic hypochromic anemia.

Skin biopsy from the lesional skin revealed diffuse dermal infiltration of mast cells, some showing granules

and scanty cytoplasm which supported the diagnosis of urticaria pigmentosa. The patient was managed with

antihistamines. In two-month-period of follow up, the development of new lesions is slowing.

1 INTRODUCTION

A mastocytosis is a heterogeneous group of myeloid

neoplasms with abnormal proliferation and

accumulation of mast cell in one or more organ

systems. (Asati DP et al., 2014)

During 2015-2019,

there are 12 new cases of cutaneous mastocytosis in

Pediatric Dermatology Division, Department of

Dermatology and Venereology Faculty of Medicine

Universitas Indonesia/ Dr. Cipto Mangunkusumo

National General Hospital. (Data Kunjungan

Poiklinik Dermatologi Pediatri Departemen Ilmu

kesehatan Kulit dan Kelamin FKUI/RSCM, 2015-

2019). (Asati DP et al., 2014;Barros et al., 2014)

reported two cases of congenital urticaria pigmentosa

in twin babies. (Barros et al., 2014) Year 2005

Working Conference on Mastocytosis’ classified

mastocytosis into three major categories: cutaneous

mastocytosis, systemic mastocytosis and

extracutaneous mast cell proliferation.

(Van Gysel D et

al., 2011) The cutaneous form consists of urticaria

pigmentosa, mastocytoma, diffuse cutaneous

mastocytosis, and telangiectasia macularis eruptive

perstans in their order of their frequency.

(Asati DP et

al., 2014

)

The diagnosis of cutaneous mastocytosis

(CM) is based on clinical and histological findings in

the skin, together with the absence of criteria that

would allow the diagnosis of systemic mastocytosis.

In cutaneous mastocytosis, the visible cutaneous

abnormalities are most often of major concern to the

patient and their family.

(Van Gysel D et al., 2011)

Urticaria pigmentosa is by far the most common

variant (70-90%) of childhood mastocytosis. The

lesions commonly appear in the first year of life and

maybe present at birth. The eruption consists of

slightly elevated, skin-colored, brown-red or yellow

macules, plaques or nodules.

(Van Gysel D et al., 2011)

Urticaria pigmentosa presenting with a vesicular and

bullous lesion as the predominant feature is a rare

entity. (Chintagunta SR et al.,2017)

Anissa, L., Mahri, S., Astriningrum, R., Agustin, T., Rihatmadja, R. and Rahmayunita, G.

Bullous Urticaria Pigmentosa in an Infant: A Rare Form of Bullous Disorder.

DOI: 10.5220/0009986302670271

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 267-271

ISBN: 978-989-758-469-5

267

The lesions occur in a generalized distribution but

tend to be of highest density on the trunk. (Van Gysel

D et al., 2011).

Less affected are palms, soles, scalp,

and face, as well as sun-exposed body areas.

(Chintagunta SR et al.,2017)

In the first two years, Urtica and erythema may

occur spontaneously or after stroking a lesion

(Darier’s sign), although Darier’s sign is not always

present in all patients.

(Van Gysel D et al., 2011;Castells

M et al., 2011)

All pediatric cutaneous forms of mastocytosis can

rarely present with acute mast cell degranulating

events, such as anaphylaxis, whole body flushing,

dyspnea, wheezing, vomiting, diarrhea and

sometimes cyanotic spells (Castells M et al.,

2011;Tharp MD et al., 2012)

The diagnosis of cutaneous mastocytosis requires a

history of new-onset skin lesions with or without

systemic symptoms. A physical examination with a

positive Darier's sign, supported with increasing

serum tryptase and dermal infiltration of mast cell on

skin biopsy is essential for building the diagnosis.

Analysis of c-kit mutations is recommended. In

addition to the skin biopsy, bone marrow studies are

recommended if the tryptase is significantly elevated,

severe systemic symptoms are present, if there is

associated organomegaly or if there is no significant

response to initial symptomatic therapy. Parents

should be explained carefully about the possibility of

evolution to a systemic form in a small number of

cases.(Castells M et al., 2011;Chintagunta SR et

al.,2017)

We report a case of bullous urticaria pigmentosa,

which is a rare clinical manifestation and also an

extreme form of cutaneous mastocytosis to raise

awareness about the differential diagnosis of vesicle

and bullae in the infancy period.

2 CASE

A four-month-old boy was referred to our hospital

presented with multiple patches and blisters, which

began on the second day after birth. The lesions were

first observed on the trunk and spread to the scalp and

limbs within several days. The lesions started as

erythematous patches all over his body, and several

evolved to the vesicle. The vesicles were easily

ruptured and became scars. He was the second child,

and his brother was healthy. His birth and

development were normal. He was breastfed and

supplemented with formula. There was no history of

drug ingestion both in mother and patient — no

current episode of facial flushing, dyspnea, and

diarrhea.

On physical examination, there were

erythematous and hyperpigmentation plaques,

vesicles, and erosions covered by crust (Figure 1). No

lymph node enlargement found. Darier’s sign was

negative. At the first visit, gram staining from the

erosions revealed moderate numbers of leukocytes

and Gram-positive coccus.

Laboratory examination revealed mild microcytic

hypochromic anemia (hemoglobin 11.9 g/dL, MCV

91.1 fL, and MCH 32 pg). Histopathology

examination revealed rete ridges elongation of the

epidermis and dermal perivascular and interstitial

infiltration of lymphocytes, histiocytes, neutrophils,

and mast cell, which came to a conclusion as

cutaneous mastocytosis (Figure 2).

The patient was given topical antibiotics for a

short period of time due to secondary infection on

several lesions and oral cetirizine to reduce the

symptoms. The patient was also referred to the

Pediatric Department to find systemic involvement of

mastocytosis. Bone marrow studies were not done

due to parents’ disapproval. In one month follow up

period, the patient showed a slower progression of

new lesions. No systemic symptoms reported.

However, education and counseling about the

possibility of systemic mastocytosis include the

symptoms are done to prevent life-threatening

systemic involvement.

ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease

268

Figure 1. Clinical manifestation in patient. A. Lesions on face on the first visit, B. Lesion on the trunk on the first visit, C.

Bullae on the right thigh (blue arrow).

Figure 2. Histopathology findings. A. Epidermal rete ridges elongation (H&E,10x),

B. Interstitial mast cell infiltration (blue arrow, H&E, 100x), C. Perivascular mast cell infiltration (blue arrow, H&E,

100x)

3 DISCUSSION

There are many conditions which manifest as a blister

in the neonatal period. They can be caused by

infectious, traumatic, or inherited causes. Infectious

causes include bullous impetigo, staphylococcal

scalded skin syndrome, neonatal varicella,

candidiasis, etc.; meanwhile, non-infectious causes

include epidermolysis bullosa, epidermolytic

ichthyosis, incontinentia pigmenti, cutaneous

mastocytosis, Langerhans cell histiocytosis or

chronic bullous disease of the childhood.(Park MN et

al., 2014).

The diagnosis was established by excluding other

differential diagnoses. Since there was no sign of

infection, infectious etiologies were excluded. The

discrete distribution of lesion which was located on

non-traumatic region excluded epidermolysis

bullosa. Epidermolysis ichthyosis and incontinentia

pigmenti were excluded due to the difference in the

nature of the disease. Lastly, we excluded other types

of cutaneous mastocytosis. The clinical entity which

mimics initial clinical presentation, in this case, is

diffuse cutaneous mastocytosis. Diffuse cutaneous

mastocytosis (DCM) can be manifested initially as

two types: one with a minimal blistering and large

area of nodular and leathery skin and one with

extensive blistering and/or exfoliation, usually

accompanied by erythrodermic appearance. (Tharp

MD et al., 2012). Both features are not fulfilled in this

case; therefore, DCM was excluded. Telangiectasia

macularis eruptive perstants (TMEP) is the least

common form of cutaneous mastocytosis and rarely

manifests in childhood. The typical lesions are

telangiectatic macules in a tan or brown background

and may co-exist with urticaria pigmentosa. (Costa

DLM et al., 2011). In this patient, there was no

telangiectasia as well as telangiectatic macules, so

TMEP was also excluded.

The pathogenesis of pediatric cutaneous

mastocytosis is not well understood, and most

children do not present with mutations of c-kit in bone

A

C

A

C

Bullous Urticaria Pigmentosa in an Infant: A Rare Form of Bullous Disorder

269

marrow mast cells. (Castells M et al., 2011) An earlier

study by (Verzijl et al., 2007) found that a quarter of

pediatric patients presenting urticaria pigmentosa had

a D816V codon mutation. Unfortunately, genetic

testing has not been available yet in Indonesia.

Blistering of urticaria pigmentosa may happen

and is considered to be exaggerated of Darier's sign.

This is caused by the release of a mediator (mainly

chymase) upon mast cell degranulation, which binds

and cleaves the dermo-epidermal junction (DEJ). The

DEJ is slowly stabilizing over the first two years of

life, resulting in a reduction of vesiculobullous lesion

by the age of 3. (Briley LD et al., 2008)

In this case, the histopathology examination

showed diffuse dermal infiltration of mast cells which

verified the clinical diagnosis of urticaria pigmentosa.

Due to the presence of vesicles and bullae, the patient

was finally diagnosed as bullous urticaria

pigmentosa.

We referred the patient to the Child Health

Department to rule out systemic involvement.

Physical examination revealed no mucosal lesion and

no hepatosplenomegaly. Bone marrow

cytomorphology study was planned to confirm if the

mast cell count exceeded 20% of the nucleated cells

in the bone marrow. In this case, bone marrow

aspiration could not be performed due to parents’

disapproval. (Kettelhut et al., 1989) reported that the

initial evaluation of the bone marrow of 17 children

where 15 had urticaria pigmentosa and two had

diffuse cutaneous mastocytosis revealed no adult-

type mast aggregates. This finding is indicating that

in most cases, cutaneous mastocytosis in children

does not involve internal organs which precludes the

need for routine bone marrow aspiration.

(

Uzzaman

also con et al.,) cluded that only the persistent disease

might justify repeated bone marrow examination

aggressive systemic therapy. The clear majority of

cases could be managed satisfactorily by

symptomatic treatment. (Uzzaman A et al., 2000)

Management includes alleviation of the

symptoms and avoidance of potential mast cell

degranulating stimuli such as several drugs, food,

local or systemic anesthetics, heat, as well as

friction.(Asati DP et al., 2014).Patient was prescribed

oral cetirizine daily. Parents have been adhering to

periodic follow-up evaluation for the past two

months, and up to now our patient responded well to

oral antihistamines and had gradual reduction in new

lesions (both blisters and papules) development.

Although pediatric cutaneous mastocytosis is

generally benign and rarely involve other organs,

parents were counseled in detail about the possibility

of systemic involvement, the sign and the symptoms

of systemic involvement. Whole-body flushing,

shortness of breath, diarrhea may happen due to mast

cell mediator release.

Systemic mastocytosis in children is extremely

rare, and usually, the clinical symptoms could be

managed by medication. The majority of these lesions

and the severity of the symptom will resolve over

time. However, it is essential to do regular follow up

to detect systemic involvement.(Asati DP et al.,

2014;Briley LD et al., 2008)

4 CONCLUSION

It could be concluded that dermatologist should

remain aware of varied forms of pediatric cutaneous

mastocytosis because of its rarity. Diagnosis of

bullous urticaria pigmentosa should be thought in the

infant with lesions suspected as urticaria pigmentosa

accompanied by vesicle or bullae. Skin biopsy

became mandatory to build the diagnosis. Systemic

involvement screening, appropriate treatment, and

follow up are required as routine. Finally, education

and counseling also play an important role in the

management of this entity.

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