A Successful Treatment of Pemphigus Foliaceus Patient with

Systemic Corticosteroid

Widyaningsih Oentari

, Irma D. Roesyanto-Mahadi

Department of Dermatology and Venereology, Faculty of Medicine,

Universitas Sumatera Utara, Haji Adam Malik General Hospital, Medan

Keywords: Pemphigus foliaceus, diagnosis, treatment

Abstract: Pemphigus is a group of IgG-related autoimmune disease of skin and mucous membrane. It cause

acantholysis with blisters and erosion as the clinical manifestation. There are three main groups of

pemphigus, which is vulgaris, foliaceus, and paraneoplastic. Female 68 years old, came with chief complain

of blisters that were spreading on her face, body, and both extremities since 1 year ago. From

dermatological examination, we found multiple bullae and erosions sized lenticular to plaque with

erythematous base and multiple hyperpigmented maculae with crusts on the face, body and both extremities.

Biopsy was taken from newly formed vesicle and histopathological examination supported characteristics of

pemphigus foliaceus. The patient was treated with NaCl 0,9% compress for 15 minutes every 4-6 hours,

fusidic acid cream twice a day, 32 mg methylprednisolone every morning, and clarithromycin 500 mg once

a day. After control, the patients showed improvement in her skin lesions.

1 INTRODUCTION

Pemphigus is a group of IgG-related autoimmune

disease of skin and mucous membrane resulting

acantholysis with clinical manifestation of blisters

and erosion (Payne et al, 2012; Kasperkiewicz et al,

2017). Pemphigus can be classified into three main

groups, such as vulgaris, foliaceus, and

paraneoplastic (Kasperkiewicz et al, 2017). In

pemphigus vulgaris (PV), the blisters can be found

on the suprabasal layer, whereas in pemphigus

foliaceus (PF) on granular layer (Payne et al, 2012;

Kasperkiewicz et al, 2017). Patients with

paraneoplastic pemphigus usually have neoplasm

associated with lymphoid tissues and caused by

combination of autoimmune humoral and cellular

reaction (Kasperkiewicz et al, 2017). Both PV and

PF have their variants. Variants of PV usually

appear locally, such as pemphigus vegetans of

Hallopeau and pemphigus vegetans of Neumann.

While, PF that appear locally is pemphigus

eritematosa (Payne et al, 2012).

Epidemiology of pemphigus varies throughout

the world (Payne et al, 2012; Kasperkiewicz et al,

2017). The incidence is quite rare, which is 2-10

cases per one million population in some areas of the

world and the prevalence is 0,1-0,7 per 100.000

population (Dimarco, 2016). Pemphigus vulgaris is

a subtype that often found in Europe, United States

and Japan, especially in women aged 50-60 years

old. Pemphigus foliaceus is less common compare to

PV and commonly found as endemic disease in

South America and North Africa (Kasperkiewics et

al, 2017; Pollmann et al, 2018). The age of onset of

PF is 40 to 60 years old. However, the endemic form

of PF can appear in second or third decades (James

et al, 2011). Paraneoplastic pemphigus is less

common that PV and PF, usually can be found in

adult aged 45 to 70 years old (Kasperkiewicz et al,

2017). Pemphigus seldom found in children (Payne

et al, 2012). The different onset of age is related to

genetic, hormonal, and environmental factors

(Kasperkiewicz et al, 2017).

In addition to anamnesis and physical

examination, the diagnosis of pemphigus can be

supported by histopathology and serology

examination. Direct immunofluorescence

examination can also be done to detect IgG antibody

on the surface of keratinocytes. Also, measurement

of IgG antibody titers to desmoglein can be done

through enzyme-linked immunosorbant assay

(ELISA) (Dimarco, 2016; Pollmann et al, 2018).

Through this case report, we would like to present

patient with pemphigus foliaceus.

Oentari, W. and Mahadi, I.

A Successful Treatment of Pemphigus Foliaceus Patient with Systemic Corticosteroid.

DOI: 10.5220/0009990804250429

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 425-429

ISBN: 978-989-758-469-5

425

2 CASE

The patient, female 68 years old, came with chief

complain of blisters that were spreading on her face,

body, and both extremities since 1 year ago. At first,

the blisters were only found on her left hand, then

after a couple of months it started spreading to her

legs and body. One month ago, the blisters are also

appeared on her face. The blisters especially appear

after being exposed to friction and scratch, easily

ruptured, leaving painful erosion. There were no

blisters on her mouth, eyes, or genital area. The

patient denied any drug allergy and similar lesion in

family. She also denied any other medical condition

or consumes any medication.

Physical examination generally was within

normal limits. From dermatological examination, we

found multiple bullae and erosions sized lenticular to

plaque with erythematous base and multiple

hyperpigmented maculae with crusts on the face,

body and both extremities. We then carried out

punch biopsy on patient’s bulla for histopathology

examination. According to several examination that

was done in the patients, we have differential

diagnoses of pemphigus vulgaris, pemphigus

foliaceus, and bullous pemphigoid. The patient was

treated with NaCl 0,9% compress for 15 minutes

every 4-6 hours, fusidic acid cream twice a day, 32

mg methylprednisolone every morning, and

clarithromycin 500 mg once a day.

Figure 1. In generalized area, there were multiple bullae and erosions sized lenticular to plaque with erythematous base and

hyperpigmented maculae with crust

Figure 2. Multiple papule in lenticular to plaque sized with erosion, hyperpigmented maculae with crusts in her back, chest,

and lower extremities

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

426

Histopathological examination showed stratified

squamous epithelial cell with hyperkeratosis and

thickening on stratum granulosum and acanthosis.

There are subcorneal blister surrounded by

lymphocyte infiltrate. It was concluded that the

diagnosis was pemphigus foliaceus. After control,

the patients showed improvement in her skin lesions.

3 DISCUSSION

Pemphigus is caused by autoantibody, especially

IgG

, against its antigen, which is desmoglein, a

trans membrane glycoprotein of desmosome.

Desmoglein is part of cell’s adhesion molecule

cadherin. (Payne et al, 2012; Pollmann et al, 2018).

Pemphigus is mainly caused by antibodies to

desmoglein 1 (Dsg1, 160-kDa) in PF, desmoglein 3

(Dsg3, 130-kDa) in PV that predominantly in

mucosal membrane, or both in muco-cutaneous PV.

(Payne et al, 2012;Dimarco, 20 et al,2016);Hammers

et al, 2016) Dsg1 and 3 are found in varying

amounts in the skin and mucous membrane. Dsg1 is

found more in upper layer of epidermis, while Dsg3

is found in lower layer of epidermis. This causes

different clinical manifestation in PV and PF.

(Dimarco, 2016; Pollmann et al, 2018;Ruocco et

al,2013). There are two main types of PF, which is

idiopathic PF, that are found universally and appears

sporadically, and fogo selvagem (FS) which is an

endemic form of PF associated with several

geographic areas.(James et al,2011)

IgG autoantibody of PV and PF bound NH

domain of Dsg ectodomain. This domain is the same

area as the area that plays a role in desmoglein

intercellular adhesion, which directly caused

acantholysis. In addition, studies on keratinocytes

show that loss of intercellular adhesion due to

autoantibodies causes desmoglein internalization

and degradation. (Payne et al, 2012; Pollmann et al,

2018). Pathogenic antibodies to desmoglein tend to

bind to matured desmoglein on keratinocytes.

(Pollmann et al, 2018). In PF, pathogenic IgG binds

to Dsg1, causes phosphorylation of p-38 mitogen-

activated protein kinase (MPAK) thus encouraging

apoptosis in keratinocytes.(James et al,2011)

Clinical manifestation of PF and PV can

resemble one another, which is superficial blisters

that rupture easily causing erosions. (Pollmann et al,

2018;James et al,2011) Patients usually complain

about pain and burning sensation on their skin

lesions. (Payne et al, 2012;James et al,2011) It can

be located on chest, face, scalp, upper back and

traumatized area. (Pollmann et al, 2018) Skin lesions

in PV can be found on the entire surface of the skin,

but rarely on palms and feet. There are several clues

that can help us distinguish PF from PV. Skin

lesions of PF are initially found locally and spread

on seborrheic location. This condition can expand to

entire body and can be aggravated by ultraviolet

light. (Payne et al, 2012) Bullae in PF is more prone

to rupture than PV, therefore the clinical

manifestation of PF usually are small erosions with

crusts. (Hammers et al, 2016) Also, PF rarely

involves the mucous membrane. (Dimarco, 2016)

Both V and PF show a positive Nikolsky sign.

(Hammers et al, 2016) Initially in our patient, skin

lesions appeared on her left hand, which lasted for

several weeks, then spreads slowly throughout her

body. There are no similar lesions that were reported

on mucous area, therefore we considered PF as one

of differential diagnoses. However, given the similar

clinical manifestation of PV and PF, we still could

not eliminate PV as differential diagnosis.

Another differential diagnosis from this patient is

bullous pemphigoid. It usually found in adult age

more than 60 years old and caused by IgG

autoantibody against antigen in dermo-epidermal

junction causing subepidermal blister. Skin lesions

that are usually found are tense skin blisters on

normal or erythematous skin on flexors, lower thighs

and abdomen. Sometimes, skin lesions can be found

in the mucous membrane. Nikolsky sign is negative

in patients with bullous pemphigoid. (Culton et

al,2012)

Our patient complained about easily rupture

blisters with erosions that appeared after friction.

Therefore, based on anamnesis and physical

examination, we concluded that bullous pemphigoid

could be excluded from differential diagnoses.

The diagnosis of pemphigus should be supported

by histopathology and laboratory tests. Biopsy

samples are usually taken from newly formed

vesicle or edge of blister. Moreover, direct

immunofluorescent should be carried out by taking

biopsy at least 1 cm from blisters or inflamed skin.

Enzyme-linked immunosorbent assay (ELISA) is

also useful to measure IgG antibody titers against

desmoglein in patient’s serum. (Dimarco, 2016;

Pollmann et al, 2018). In this patient, we taken

biopsy sample from newly formed vesicle from her

back.

Histopathologically, pemphigus shows loss of

intraepidermic cell adhesion. (Pollmann et al, 2018).

While in PV, histopathological examination shows

suprabasal blister with acantholysis with “row of

tombstones” that sign of bad prognosis. In PF,

acantholysis can be found right under stratum

corneum and in stratum granulosum. Other finding

A Successful Treatment of Pemphigus Foliaceus Patient with Systemic Corticosteroid

427

include subcorneal pustules contains neutrophil.

(Payne et al, 2012; Hammers et al, 2016) Old PF

lesion usually shows papillomatosis, acanthosis,

hyperkeratosis, parakeratosis and follicular plug.

Increase pigment formation can also be found in

melanocytes of basal layer and there is capillary

dilatation in papilla dermis. There are also infiltrates

consist of neutrophils, eosinophils, and lymphocytes.

(James et al,2011) Histopathological characteristics

of PF is often difficult to differentiate with bullous

impetigo or staphylococcal scalded skin syndrome.

(Payne et al, 2012) According to this informations,

we concluded that histopathological examination of

this patient support diagnosis of pemphigus

foliaceus. Differential diagnosis of bullous

pemphigoid could be eliminated because usually the

blisters are located in subepidermis with eosinophils,

neutrophils and monosit infiltrate in superficial

dermis.(Culton et al,2012)

Immunofluorescence examination of pemphigus

showed IgG autoantibody on the surface of

keratinocytes. In patients with PV and PF, direct and

indirect immunofluorescence can give similar

findings, which is IgG on epidermal cell surface

with netlike intraepidermal staining pattern (Payne

et al, 2012; Pollmann et al, 2018). Biopsy samples

for direct immunofluorescence can be taken from

perilesion area and stored on Michel’s transport

media before examination. While in indirect

immunofluorescence, patient’s serum was incubated

with tissues obtained from esophagus of monkey,

human skin, or bladder epithelium from mice or

rabbit.(Pollmann et al, 2018). We could not perform

this examination on this patient because it is not

available in our healthcare facilities.

Serological examination such as ELISA can be

used to identify and monitor IgG antibody serum

level in pemphigus. According to the type of

autoantigen, such as Dsg1 and Dsg3, we can identify

different type of pemphigus in patients (Pollmann et

al, 2018). Unfortunately, this modalities also not yet

available and routinely tested at our healthcare

facilities so that this examination is not carried out in

this patient.

There has been no FDA-approved therapy for

pemphigus. (Payne et al, 2012) General

recommendation for treatment of pemphigus remain

inconclusive because of various research designs

and different outcomes from previous studies.

(Pollmann et al, 2018;Singh et al,2011) Initial

therapy for pemphigus is high dose of systemic

corticosteroid equivalent 0,5-1,5 mg/kg/day of

prednisone with adjuvant immunosuppressive

medication. (Pollmann et al, 2018;Singh et

al,2011;Hertl et al,2015) Patients that unresponsive

to initial therapy or have contraindication for high

dose of corticosteroid can be given second line

therapy, which is intravenous immunoglobulin 2

g/kg/cycle. Monoclonal antibody of anti CD20 is

also useful in patients with refractory pemphigus

(Pollmann et al, 2018 (Pollmann et al, 2018;Singh et

al,2011) Pemphigus foliaceus with local skin

eruption can be treated with topical corticosteroid.

However, if the disease is active and widespread, we

can use similar therapy as pemphigus vulgaris(Payne

et al, 2012) Our patient were given NaCl 0,9%

compress for 15 minutes every 4-6 hours, fucidic

acid cream twice a day, methylprednisolone 32 mg

every morning, and clarithromycin 500 mg once a

day. After control, there were improvements in

patient complaints.

4 CONCLUSION

Pemphigus is group of autoimmune disease

associated with IgG to desmosome of stratified

squamous epithelial skin and mucous membrane,

causing acantholysis with clinical manifestation of

easily rupture blisters and erosions. We reported 68

years old female patient with blisters on her face,

body and extremities since 1 year ago. Differential

diagnosis includes pemphigus vulgaris, pemphigus

foliaceus, and bullous pemphigoid. Anamnesis,

physical examination and histopathological

examination are important for diagnosis and in this

case, we concluded patients as pemphigus foliaceus.

Immunofluorescence examination is also important

for diagnosis but still unavailable in our health

facility. Treatment with systemic corticosteroid

provides benefits for clinical improvement of

patients.

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