Single Case Report: Diffuse Cutaneous Mastocytosis with

Generalized Bullae Mimicking Bullous Pemphigoid

Muhammad Ridlo

, Irma D. Roesyanto-Mahadi

, Remenda Siregar

Department of Dermatology & Venereology, University of Sumatera Utara, Faculty of medicine, Universitas Sumatera

Utara Hospital - H.Adam Malik Hospital, Medan

Department of Dermatology & Venereology, University of Sumatera Utara, Faculty of medicine, Universitas Sumatera

Utara Hospital - Dr.Pirngadi Medan

Keywords: Diffuse cutaneous mastocytosis, mastocytosis bullous, bullous pemphigoid

Abstract: Introduction:Mastocytosisis a rare disease; it is defined as mast cells infiltration in some organs. Skin is the

most commonly involved organ.Diffuse cutaneous mastocytosisis a form of skin mastocytosiswhich can be

manifested as bullous lesions. Case: A 3-month-old male infant is presentedwith generalized dermatosis,

characterized by multipleblisters and brownish spots all over his bodysince one month ago.On dermatologic

examination, multiple tense bullae of various sizes with brownmacules and plaques are located throughout

the body.Some bullae rupture to form an erosion.Darier sign showserythema/mild urticaria lesions(positive).

Routine blood tests within normal limits. The histopathologic examination reveals sub-epidermal bullae

with aninflammatory cell and the dermis is filled with inflammatory cells and mast cells. Patients were

diagnosed with diffuse cutaneous bullous mastocytosis. The patient was treated with 0.9% NaCl

compresses, 2% mupirocin cream, and 0.1% betamethasone cream. Monitoring therapy is done routinely to

evaluate the prognosis of the disease.Discussion:Diffuse cutaneous bullous mastocytosis is one of the rarest

forms of skin mastocytosis. Cutaneous mastocytosis in children who persist until adolescence develops

systemic mastocytosis in 15-30% cases so early diagnosis of mastocytosis in children is very important to

get a goodprognosis. Conclusion: Diagnosisdiffuse cutaneous mastocytosis is not easy because the

prevalence is difficult to determine and often misdiagnosed. Here,we report this case due to the similarity

clinical manifestation of bullous diseases, especially in a newborn with scattered blisters and erosions.

1 INTRODUCTION

Mastocytosisisa diseasewhich shows a large number

of abnormal proliferation and accumulation of mast

cells in one or more organ systems including the

skin, bone marrow, liver, spleen, lymph nodes and

digestive tract with various variants of clinical

manifestations (Dines et al, 2014). There are two

types of mastocytosis that arecutaneous

mastocytosis (CM) and systemic mastocytosis

(SM). CM is often found in children, whereas SM is

more common in adults (Lange et al, 2015).

According to the 2017 World Health Organization

(WHO) classification, CM encompassesurticaria

pigmentosa or maculopapular cutaneous

mastocytosis (UP), diffuse cutaneous mastocytosis

(DCM), and mastocytoma in the skin.The bullous

eruption is most commonly associated with DCM,

although bullae can occur in all forms of cutaneous

mastocytosis (Hans et al, 2018). In patients with

DCM, bullous eruptions are widespread during the

early stages of life. The blisters present in a variety

of sizes and initially contain clear fluid that may

become hemorrhagic with time and can leave a

hyperpigmented brown macula. Bullous lesions

may occur in linear or grouped fashion and often

develop on the trunk, scalp, and extremities. The

bullous lesions typically resolve by 3-5 years of

age. A small number of patients have been reported

with yellow-orange infiltrated. Over time, the skin

becomes thickened and has a doughy consistency.

Other cutaneous manifestations may include

pruritus, urticaria, a positive Darier's sign and

marked dermographism (Metcalfe et al, 2016; Eui et

al, 2010).

The prevalence of mastocytosis is still

challenging to determine, but it is estimated that the

incidence of mastocytosis is around 5-10 per

1,000,000 inhabitants per year. This disease can

occur at any age.Approximately 50% of the onset of

436

Ridlo, M., Mahadi, I. and Siregar, R.

Single Case Report: Diffuse Cutaneous Mastocytosis with Generalized Bullae Mimicking Bullous Pemphigoid.

DOI: 10.5220/0009991004360440

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 436-440

ISBN: 978-989-758-469-5

mastocytosis that occurs in children can appear

during infancy, especially in the neonatal period

until the age of 2 years. There is no racial difference

and sexual dominance in this disease (Metcalte et

al, 2016).

Spontaneous resolution of 50-60% of bullous

lesions can occur in most patients with DCM until

before the age of 5 years. However,reliable

prognostic clues are lacking, especially for

predicting the risk of systemic involvement with

life-threatening manifestations that they should

undergo annual investigations and careful follow-up

(Lange et al, 2015; Magliacanel et al, 2014).

2 CASE

A 3-month-old male infant is checked in a

polyclinic with generalized dermatosis

characterized by multiple blisters and brownish

spots all over his bodysince one month ago.

According to his mother, since the age of 1

month,the blisters appear for the first time in the

abdominal area. One month later, blistersspread

overthe limbs, trunk, and scalp. When the blister

bursts, it will leave behind red which then becomes

brownish spots. History of flushing, complaints of

vomiting, and diarrhea in patients are denied. Due

to the distance of health facilities are far from where

they live, patients have never been taken to a health

facility and have never received treatment. The

patient was the third child with a history of normal

birth, spontaneous crying with a birth weight of

2900 grams. There is no history of the same

complaints in previous births. There is no history of

asthma and allergies in the patient's family.

Physical examination within normal limits, and

there are no abnormalities or congenital disabilities

experienced by the patient. Dermatologic

examination revealed skin was dry and facial skin is

thickened with numerous tense bullous vary in size

over normal skin et regio temporoocipital, oralis,

mentalis, medial antebrachii sinistra, and femoralis

dextra posterior. Multiple erosions vary in size are

seen on regio infraclavicularis, lateral dextra brachii

posterior and vertebralis. Brownish plaques and

macules vary in size circumscribed multiple discrete

et regio abdominals, antebrachii dextra et sinistra,

vertebralis and anterior-posterior femoralis dextra et

sinistra (Figure 1). Darier sign shows

erythemalesions (positive). Examination of the

Nikolsky sign is negative. Based on the anamnesis

and physical examination, we considered diffuse

cutaneous mastocytosis bullous, bullous

pemphigoid, and bullous epidermolysis as a

differential diagnosis. Routine blood tests within

normal limits. Patients were then biopsied on bullae

lesions which are newly formed less than 24 hours

located in the medial region of the left antebrachii.

Histopathologic examination results with staining of

hematoxylin-eosin, showing sub-epidermal blister

with a dome consist of squamous epithelial cells, an

inflammatory cell eosinophils in bullae. Mast cells

densely filling the dermis below the blister

accompanied by vascular congestion and dilatation

(Figure 2). Examination of spinal cord aspiration

was not carried out in these patients because they did

not get the consent of the patient's parents.To assess

the extent and activity of skin lesions, the SCORMA

Index was applied with result 51.8.

The diagnosis of DCM was made based on these

clinical and histopathological findings. Patients were

given 0.9% NaCl compress therapy in erosion

lesions for 15-20 minutes every 6 hours a day, 2%

mupirocin cream and 0.1% betamethasone cream

every 12 hours a day.

3 DISCUSSION

The diagnosis of CM, in this case, is based on

history, clinical manifestations, histopathologically

examination, and the absence of signs of systemic

mastocytosis. Organomegaly examination

(hepatomegaly, splenomegaly, lymphadenopathy) is

needed to look for systemic involvement. A

peripheral blood examination is needed to look for

hematologic abnormalities related to bone marrow

involvement.(Lange et al., 2015;Eui et al., 2010)

The most common variant of CM is UP, that it

manifests as 0,5- 1 cm yellowish-tan to red-brown

macules or slightly raised papules. The affected

areas include the trunk and extremities, while the

face, scalp, palms, and soles tend to be free of

lesions. DCM is an unusual variant of the mast cell

disease characterized by widespread bullae as its

main cutaneous feature. DCM can appear at birth

(congenital and neonatal) or in early infancy.

Widespread involvement of the skin with blistering

and bullae may be the presenting symptoms. The

skin may be leathery and thickened (‘‘peaud'

orange'') due to infiltration with mast cells.

Hyperpigmentation may persist into adulthood, and

dermographism may be prominent.6,7We diagnosed

our case as DCMsince there were multiple bullae all

over his body including face, scalp, trunk and limb

as its main cutaneous feature andwithout systemic

involvement.

Single Case Report: Diffuse Cutaneous Mastocytosis with Generalized Bullae Mimicking Bullous Pemphigoid

437

Figure 1. Three-month-old infant with numerous tense bullousvary in size over normal skin et regio temporoocipital, oralis,

mentalis, medial antebrachii sinistra and femoralis dextra posterior (red arrow)(A),(B),(C),(D) and the facial skin is

thickened especially forehead (green arrow) (E). Multiple erosionsvary in size are seen on regio infraclavicularis, lateral

dextra brachii posterior and vertebralis (blue arrow) (G),(H) and (I). Brownish plaques and macules vary in size

circumscribed multiple discrete et regio abdominal, antebrachii dextra et sinistra, vertebralis and anterior posterior femoralis

dextra et sinistra.

Figure 2. Sub-epidermal blister with a dome consists of squamous epithelial cells, an inflammatory cell eosinophils in

bullae (black arrows) (A), (C) and (D).Mast cells densely filling the dermis below the blister accompanied by vascular

congestion and dilatation (red arrows) (A), (B), (D), and (E).

The clinical manifestations of various bullous

diseases in children are almost the same, so clinical

diagnosis is not enough. To confirm mastocytosis in

bone marrow or in blood, the mast cell count should

be more than 20% of the nucleated cells in the bone

marrow or >10% peripheral blood leukocytes.

However, systemic investigations such as bone

marrow aspiration/biopsy or serum total tryptase

level could not be performed because of the

reluctance of the parents.Histopathological and

immunofluorescence exams, particularly DIF (direct

immunofluorescence) are needed for diagnosis.

(Heide et al., 2009).

According to WHO (2017), the

terminology of mastocytosis on the skin can be

established from the results of histopathological

biopsy exams that prove the infiltration of mast cells

in the dermis, and there is no involvement of other

organs or signs of SM. Usually, because no bone

marrow examination was performed and/or clinical

information is lacking.Tran et al. reported that in the

case of CM there was a large amount of infiltration

of eosinophil cells originating from chemotactic

eosinophils a factor secreted by neoplastic mast cells

in the dermis.(Hans-Peter e al., 2018;Arber et al.,

2016)

There are two important biological findings as

markers related to the pathogenesis of

mastocytosisdisease; the presence of somatic

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

438

mutations in KIT genes (usually KIT Asp816Val

D816V mutations) and the presence of

immunophenotype deviations associated with CD25

and c-KIT gene expression CD117 which plays a

role in differentiation, maturation, and proliferation

of mast cells.(Arock et al., 2015;Walker et al.,2006)

Mutations from oncogenic KIT D816V are usually

detected in almost 80% of patients with SM.

Mutations KIT D816V is rarely found in CM

patients.As a result of mutations in the c-KIT gene,

this will result in an increase in abnormal

proliferative activity of mast cells.Mast cell

degranulation causes the release of various

mediators such as histamine, the slow-releasing

substance of anaphylaxis (SRSA), eosinophil

chemotactic activating factor (ECAF), heparin and

other mediators that play a role in the Darier sign

mechanism. Darier's sign, which is defined by

wheeling and reddening of lesions upon mechanical

stroking or rubbing, is usually demonstrable. It is not

always positive in adult patients but usually positive

in pediatric patients. The Darier's sign is often not

elicited correctly, resulting in false-negative or false-

positive results.(Tran et al., 2014)

In bullous pemphigoid, IgG autoantibodies are

attached to BP180 antigen (transmembrane

glycoprotein hemidesmosome).The IgG bond and

BP180 antigen will activate complement. The

complement will cause degranulation of mast cells

and withdrawal of neutrophils and eosinophils,

which will release various inflammatory mediators

and proteinases that cause subepidermal domes.

However, there is no histopathological infiltration of

mast cells in the dermis in the bullous pemphigoid,

and the Darier sign does not show erythema/urticaria

lesions (negative).(Wada et al., 2016)

Because there is still no curative treatment for

mastocytosis, the available therapeutic options are

mostly palliative and symptomatic. In the treatment

of CM that occurs in children, it is recommended to

give topical medium-class steroids immediately.

Topical steroid applications in CM that occur in

children have been shown to eliminate local skin

symptoms, and Darier's sign becomes very weak

until it disappears. Treatment with topical steroids is

still better and effective in the case of cutaneous

mastocytosis considering the long time required for

the spontaneous disappearance.(Annalisa et al.,

2015)

Hartmann et al. in a randomized study of

multiple parallel and case-control trials, it was

explained that the topical use of clobetasol for two

weeks in 39 patients with CM had a significant

effect on reducing the size of lesions and the number

of mast cells in the upper dermis.(Hartman et al.,

2010)

In our case patient giving 0.1% betamethasone

creamand 2% mupirocin cream every 12 hours a

dayto prevent secondary infections in open wounds.

In the treatment of mastocytosis in addition to

medical treatment, it is essential to maintain nutrient

intake, which can trigger the release of mast cell

mediators. We can see some food ingredients that

must be watched out for sufferers of mastocytosis

such as; Monosodium Glutamate (MSG), alcohol,

shellfish, artificial food dyes and flavorings, food

preservatives, pineapples, tomatoes & tomato-based

products, and chocolate. .(Annalisa et al., 2015;

Hartman et al., 2010). In our case, we educate the

patient's mother so that after entering the

complementary stage of breastfeeding, it can be

more attentive and careful about food ingredients

that can trigger the release of histamine mediators.

There are still many controversies in defining

and evaluating mastocytosis. One of the aspects that

are missing is a system for clinical evaluation of

mastocytosis of the skin. The clinical use of the

scoring index of mastocytosis (SCORMA). The

scoring of the SCORMA Index was designed in

order to assess the extent and activity of skin lesions.

It is based on a semi-quantitative analysis of the

extent, intensity, and subjective complaints, and it

ranges from 5.2 to 100.(M.Lange et al.,2012)

Despite progress in understanding the

pathogenesis, genetics, and diagnostic criteria of

mastocytosis, reliable prognostic clues are lacking,

especially for predicting the risk of systemic

involvement. According to some, most DCM cases

about 50% of patients tend to improve with time,

whereas others concluded that DCM patients are at

higher risk of developing SM or life-threatening

events such as hypotension or bronchospasm.

Cutaneous mastocytosis in children who persist until

adolescence develops SM in 15-30% cases.

Therefore, evaluation of the prognosis assessment of

cutaneous mastocytosis in children is essential to

determine whether or not an attempt is made to seek

systemic involvement. (Hartman et al., 2010;

M.Lange et al.,2012).

4 CONCLUSION

Due to the similarity between bullous

pemphigoidand CM, we must be considered in the

differential diagnoses of bullous eruptions,

especially in a newborn with scattered blisters and

erosions. It could be concluded that pediatricians

and dermatologists should remain aware of varied

forms of cutaneous mastocytosis because of its rarity

Single Case Report: Diffuse Cutaneous Mastocytosis with Generalized Bullae Mimicking Bullous Pemphigoid

439

and the distinctive management of each individual

case. Our case helps to document the diagnosis of

CM in the pediatric patient population.

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