Download 11 BENIGN MUCOUS MEMBRANE

Clinical Report
BENIGN MUCOUS MEMBRANE
PEMPHIGOID
PARUL BHATIA* , BHAVIN DUDHIA** , PURV S. PATEL*** , MAULIKA PATEL****
ABSTRACT
Benign Mucous Membrane Pemphigoid (BMMP) is an uncommon, chronic autoimmune subepithelial disease that
primarily affects the mucous membranes of the oral cavity & eyes. It also affects the skin, though less frequently. It is
more commonly seen in female patients over the age of 50 years. It is believed to be caused by autoantibodies, usually
of IgG class, directed against proteins of the basement membrane complex resulting in mucosal ulceration &
subsequent scarring. Topical &/or systemic corticosteroids form the mainstay of treatment. Here, a case of 27 year old
male patient has been presented who, inspite of having severe form of disease, responded well to topical corticosteroid
therapy.
Key Words: Benign Mucous Membrane Pemphigoid (BMMP), CicatricialPemphigoid (CP), Ocular Pemphigoid.
INTRODUCTION
Benign Mucous Membrane Pemphigoid (BMMP),
also called Cicatricial Pemphigoid (CP), is an
uncommon, chronic immune mediated
1-6
subepithelial vesiculobullous disease. The term
cicatricial is derived from word 'cicatrix' meaning
scar, as it heals with scarring. 7It is a part of the group
of autoimmune subepidermal/subepithelial bullous
disorders, recognized by the term “immune
mediated subepithelial blistering diseases”
7-9
(IMSEBD). This family of diseases constitutes a
spectrum: at one end are bullous pemphigoid (BP)
& pemphigoid - herpes gestationis (HG), which
generally affects the skin, with minimal and
infrequent involvement of the mucous membranes,
while at the other end is cicatricial pemphigoid
(CP), which mainly involves the mucous
membranes most frequently of oral cavity & eyes
along with less frequent involvement of mucous
membranes of nasal cavity, pharynx, larynx,
esophagus & genitalia & occasional involvement of
1, 3-5, 8-13
the skin.
Wichmann (1794) first reported a female patient
with ocular and oral involvement as well as skin
lesions. In 1896, Thost introduced the original
nomenclature chronic pemphigus of the mucous
membrane &, in 1911; he described the mucous
membrane pemphigus with its salient features. On
the basis of histologic studies in 1951, Lever
distinguished CP from pemphigus vulgaris (PV).
The disease was then referred to as benign mucous
membrane pemphigoid (BMMP). 8
BMMP is usually of unknown cause but
occasionally triggered by drugs (such as clonidine,
indomethacin, D-penicillamine & some topical
ocular medications). Other suggested etiological
factors are viruses, UV light & genetic
predisposition or occasional association with other
autoimmune diseases. They are characterized by the
in vivo linear deposition of immunoglobulins,
complement or both, mainly IgG & C3 along the
8, 9, 14, 15
basement membrane zone (BMZ).
There may
be an immunogenetics background & an association
with HLA DQB1*0301, which is especially notable
8-10, 13, 16, 17
in ocular pemphigoid.
The pathogenesis of
BMMP probably includes an autoantibody induced,
complement mediated sequestration of leukocytes
which results in release of cytokine & leukocytes
causing detachment of basal cells from BMZ. 7, 9,
15
However, BP180 epidermal antigen is a major
*Reader (Oral Medicine & Radiology Department ) **reader (Oral Medicine & Radiology Department )
***Postgraduate Student (part II) (Oral Medicine & Radiology Department ) ****Postgraduate Student (part I) (Oral Medicine & Radiology Department )
AHMEDABAD DENTAL COLLEGE & HOSPITAL, BHADAJ-RANCHHODPURA ROAD, TA:- KALOL DIST:-GANDHINAGAR.
ADDRESS FOR AUTHOR CORROSPONDENCE : DR. PARUL BHATIA, PHONE:- 98254 98409
The Journal of Ahmedabad Dental College and Hospital; 2(1), March 2011 - August 2011
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PARUL BHATIA et. al. : Benign Mucous Membrane Pemphigoid
antigenic target of IgG autoantibodies produced by
BMMP patients. 2, 6, 15BMMP autoantibodies localize
to an extracellular site in lower lamina lucida &
upper lamina densa region of lamina propria. 3, 11, 15
Dermatologic data suggest that BMMP is
approximately 7 times less common than BP. On the
other hand, it is up to 3 times more frequent than
pemphigus, which itself has an annual incidence of
9
0.5 to 3.2 per 100000 people. There are no known
8-10, 13, 16,17
racial or geographic predilections.
Most patients ranged from 23 to 75 years age;
maximum being 50 to 60 years old.3, 4, 6-10, 13, 15-18The
female/male ratio was 1.8:1. The oral mucosal
involvement is seen in all patients, the initial site of
3, 4, 6presentation being oral in 48% & ocular in 30%.
10, 13,15, 16
In the oral cavity, gingival involvement was
8, 9, 16
seen in 100% cases.
There are several variants of BMMP, each with
distinctive clinical features, pattern of
immunopathology and antigenic specificity of
autoantibodies. They are oral pemphigoid, anti
epiligrin pemphigoid, anti BP antigen mucosal
pemphigoid, ocular pemphigoid & multiple
9
antigens.
Commonly, patients with BMMP have oral, in
particular, gingival lesions. It is one of the main
known causes of desquamative gingivitis (DG).
Hence, dentists could be the first health
professionals to recognize this rare disease.3-5, 7, 9, 10,13,
15, 16
The clinical appearance is of gingival erythema
& loss of stippling, extending apically from the
gingival margins to the alveolar mucosae. The
desquamation may vary from mild, almost
insignificant small patches to widespread erythema
with a glazed appearance. Chronic soreness is
common, being especially worse when acidic foods
9
are eaten. The time between the onset of symptoms
and diagnosis is relatively short, probably because
of the patient's discomfort caused by bullae,
ulcerations & subsequent pain. 18 Vesicles or bullae
may also occur elsewhere on the oral mucosa in
5, 6,
BMMP & there can be a positive Nikolsky's sign.
9,
18,
19
The relatively tense oral blisters rupture
quickly, leading to pseudomembrane covered,
irregularly shaped erosions, which are the most
common manifestation after DG.9, 10, 12 Erosions have
a yellowish slough and are surrounded by an
inflammatory halo. The hard and soft palate, buccal
mucosae, alveolar ridge & tongue may also be
9
involved, whereas lip lesions are uncommon.
Ocular manifestations have been quite common,
ranging from 3 to 48 % and they may culminate in
blindness. Eye involvement usually begins as
chronic conjunctivitis with symptoms of burning,
irritation and excess tearing.9 Scarring after
repeated fibrosis can lead to the fusion of the sclera
and palpebral conjunctivae (symblepheron) or of
the superior and inferior palpebrae
(ankyloblepheron). The conjunctiva may contract
& invert the eyelid margins (entropion) leading to
inversion of eyelashes onto the corneal surface with
subsequent irritation (trichiasis). However, scarring
is less common in the oral cavity.3, 4, 6, 7, 9, 10, 12, 13, 15The
skin lesions are characteristically hemispherical &
tense bullae which are usually asymptomatic until
12
they rupture.
The diagnosis is based on the history, examination
& biopsy with histologic and direct
immunofluorescent (DIF) examination. The most
appropriate area to biopsy is not the erosion, which
will show loss of the epithelium one wishes to study,
but a vesicle or perilesional tissue. Gingival biopsy
is best avoided, as gingival chronic inflammation
may lead to confusion. 7, 9, 18
Histologically, there is loss of attachment &
separation of the full thickness of the epithelium
from the connective tissue at basement membrane
level. Epithelium, though separated, remains for a
time intact and forms the roof of a bulla. The floor of
the bulla is formed by connective tissue alone,
infiltrated with inflammatory cells. A
histopathologic feature distinguishing BMMP from
BP is that the inflammatory infiltrate in former
contains predominantly neutrophils with fewer
4-7, 9, 12,18
eosinophils.
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PARUL BHATIA et. al. : Benign Mucous Membrane Pemphigoid
Direct immunofluorescence (DI) findings include
linear IgG, C3 &, less commonly, other
immunoglobulins deposited at the basement
membrane zone. Investigation of presence of
circulating antibodies in the patient's serum using
indirect immunofluorescence (IDI) is not always
4
reliable for diagnosis or monitoring of BMMP.
In some patients, the disease is localized and has a
slowly progressive course without complications;
in others, it is devastating, with severe morbidity.
Treatment should be individualized for each patient
depending on disease severity, age and general state
of health & associated medical problems. The main
treatment is immunosuppressive & includes the
topical & systemic corticosteroids, as well as other
immunosuppressive agents such as dapsone,
3-6, 9, 10, 12, 15
sulphapyridine & azathioprine.
Topical
corticosteroids remain the mainstay treatment of
BMMP, especially for localized oral lesions, though
some investigators advocate dapsone, tetracycline
or mild to moderate strength systemic
corticosteroids. For gingival lesions, topical
corticosteroids are typically more effective when
used in a vacuum formed custom tray or veneer.
Candidiasis may complicate treatment, but it can be
prevented by adding antimycotic therapy. If oral
lesions continue to develop or extend or new oral
lesions, progressive ocular disease or laryngeal or
oesophageal lesions appear, treatment with a short
plasma half-life systemic corticosteroid should be
initiated, accompanied by systemic
immunosuppressant & immunoglobulin. Topical
antibiotics are advisable for resolution of eye
9, 20, 21
lesions.
Radiology Department of Ahmedabad Dental
College & Hospital (ADCH) for the complain of
multiple painful ulcers in the oral cavity since a
week.
Patient first noticed multiple painful ulcers in the
oral cavity before 6 months, for which he was
prescribed some topical ointment by a local general
practitioner. The ointment provided some
symptomatic relief but complete remission was not
achieved. Then before a week, his condition got
aggravated with appearance of multiple new ulcers
in oral cavity and fluid filled vesicles on the upper
lip. He also noticed fluid filled blisters on extensor
surfaces of left forearm & leg which subsequently
ruptured in few days. Before 3 days, he noticed a
burning & itching sensation at medial canthus of
right eye accompanied by continuous watering. So
he visited a local dental practitioner, who diagnosed
the condition as a viral infection and prescribed
systemic acyclovir. With no relief, patient visited
Civil Hospital, Sola before 4 days from where he
was referred to ADCH.
Patient had no other significant medical or dental
history. He reported inability to eat due to painful
ulcers. He had habit of placing tobacco, betelnut &
slaked lime quid in lower labial vestibule 5 to 6
times a day since last one year.
On extraoral examination, there was a laceration of
palpebral conjunctiva at medial canthus of right eye
with some scarring.
Here, we present a case of a 27 year old male with
typical oral, eye & skin lesions of benign mucous
membrane pemphigoid who responded well to
topical treatment.
CASE REPORT
A 27 year old male Hindu mill worker residing at
Chandlodiya, was referred from Skin Department
of Civil Hospital, Sola to Oral Medicine &
Fig.-1: Extraoral photo showing crusted lesion at medial canthus of right eye
The Journal of Ahmedabad Dental College and Hospital; 2(1), March 2011 - August 2011
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PARUL BHATIA et. al. : Benign Mucous Membrane Pemphigoid
Fig.-2: Extraoral photo showing crusted lesion of left half of upper lip
There was crusting of entire left half of upper lip.
There were single, round, 5 mm diameter sized
crusted lesions on extensor surface of left forearm
as well as left leg.
Fig.-4: Intraoral photo showing depapillation of
attached gingiva in mandibular right canine premolar region
There were multiple, round, 4 to 5 mm diameter
ulcers with yellowish white floor and erythematous
halo scattered over the dorsum & ventral surface of
tongue as well as hard & soft palate.
Fig.-5: Intraoral photo showing multiple ulcers on
dorsum & ventral surface of surface of tongue, hard & soft palate
Fig.-3:
Photos showing crusted lesion of extensor surface of left forearm & leg
There were large, irregular shaped ulcers in
posterior half of right & left buccal mucosa.
On intraoral examination, patient had full
complement of 32 teeth present with partially
erupted 38 & 48. There were generalized extrinsic
tobacco stains, more severe in relation with the
labial surfaces of mandibular anterior teeth. The
marginal and attached gingiva in mandibular
anterior and right quadrants was erythematous and
had a tendency to bleed as well as peel off on
pressure.
Fig.-6: Intraoral photo showing multiple ulcers on ventral surface of tongue
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PARUL BHATIA et. al. : Benign Mucous Membrane Pemphigoid
On scraping the anterior border of the ulcer on left
buccal mucosa, there was an extension of the ulcer
to involve a normal mucosal surface anterior to the
ulcer.
Based on the clinical findings, history & positive
Nikolsky's sign, a provisional diagnosis of Benign
Mucous Membrane Pemphigoid was placed.
Bullous Pemphigoid, Erythema Multiforme (EM)
& Epidermolysis Bullosa Acquisita were kept as
differential diagnosis. An exfoliative cytology slide
was prepared from affected areas on gingiva &
buccal mucosa which showed chronic
inflammatory cell infiltration but was negative for
Tzanck cells.
Fig.-8: Photo of healed lesion of lip at 1 week follow up
The patient was given topical antiseptic &
anaesthetic gel application along with topical
steroid application with the objective of relief of
symptoms. He was also advised topical
sulfonamides for skin & eye lesions from skin
department of Civil Hospital, Sola. The patient was
recalled after a week for follow up and further
investigations. However, on 1 week follow up,
patient showed nearly complete remission of
majority of oral & lip lesions as well as skin & eye
lesions.
Fig.-9: Photos of healing lesions of left forearm & leg at 1 week follow up
Fig.-7: Photo of healed lesion of right eye at 1 week follow up
Fig.-10: Photo of healed lesions of gingiva at 1 week follow up
The Journal of Ahmedabad Dental College and Hospital; 2(1), March 2011 - August 2011
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PARUL BHATIA et. al. : Benign Mucous Membrane Pemphigoid
However, it does occur in males & occasional cases
have been reported even in children & young
10, 16
adults,
as in our patient who was a 27 year old
male.
Oral & ocular lesions occur most commonly in
BMMP with gingiva as the initial site of
presentation.3-5, 7, 9, 10, 13, 15, 16This is in accordance with
the present case.Lip & skin involvement also occurs
rarely in BMMP,1, 3-5, 8-13 which is in accordance to the
present case.
Fig.-11: Photos of healed lesions of dorsum & ventral surface of
tongue & hard & soft palate at 1 week follow up
There is a tendency for oral lesions to appear as
vesicles, which rupture quickly to form ulcers in
9, 10, 12
BMMP.
Nikolsky's sign may be positive for
5, 6, 9, 18, 19
BMMP.
This is in accordance with the present
case.
Based on clinical findings, multiple mucosal
involvements and positive Nikolsky's sign, a
provisional diagnosis of Benign Mucous
Membrane Pemphigoid was placed.
Fig.-12: Photo of healed lesions of left buccal mucosa at 1 week follow up
There was complete relief of symptoms & patient
was able to eat comfortably. The patient is under
routine follow up recalls with no reported
recurrence within the two month follow up period.
DISCUSSION
Benign Mucous Membrane Pemphigoid (BMMP)
mainly involves the mucous membranes of oral
cavity & eyes along with less frequent involvement
of mucous membranes of nasal cavity, pharynx,
larynx, esophagus & genitalia & occasional skin
1, 3-5, 8-13
involvement.
This was a case of Benign
Mucous Membrane Pemphigoid in a young male.
Literature suggests that it is more common in
females with peak in fifth decade.3, 4, 6-10, 13, 15-18
Such cases demand due attention and differentiation
from all Immune mediated subepithelial blistering
diseases (IMSEBD) based on histopathologic
examination, direct & indirect
Immunofluorescence testing & antigen testing.
Hence, the differential diagnosis included Bullous
Pemphigoid (BP), Erythema Multiforme (EM) &
Epidermolysis Bullosa Acquisita (EBA). Oral
lesions are more common in BMMP than in BP. The
distinction continues to be based on the clinical
presentation; if the disease is predominantly
cutaneous with healing without scarring, a
diagnosis of BP is made, whereas if it is
predominantly mucosal which heals with scarring, a
1, 2, 8, 10,
diagnosis of BMMP is more appropriate.
11
Erythema Multiforme most commonly presents at
hands & feet & target or iris lesion is
pathognomonic for this entity. Gingival
involvement is rare in EM. 15Epidermolysis Bullosa
Acquisita (EBA) also predominantly affects skin,
especially over the trauma prone extensor surfaces,
with scar & milia formation; presenting
histopathologic & immunopathologic features
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PARUL BHATIA et. al. : Benign Mucous Membrane Pemphigoid
indistinguishable from those of BMMP. 8, 10, 15
Classic histopathologic features include a
subepithelial split with a chronic inflammatory
infiltrate containing eosinophils in the lamina
propria and immunostaining that shows deposits of
4-7, 9, 12, 18
IgG and C3 in a linear manner in the BMZ.
However, being already in grave pain, the patient
was not willing to undergo biopsy. As he responded
well to topical therapy, further investigations were
not advisable.
BMMP with oral &/or skin involvement is
considered low risk case which responds to topical
steroids. However, ocular, genital, oral & skin
involvement falls in high risk category requiring
systemic steroids along with dapsone & intravenous
immunoglobulin for control of symptoms and rapid
progression.3-6, 9, 10, 12, 15However, the current case
responded well to topical steroid & antibiotic
therapy with satisfactory healing of oral & eye
mucosal lesions as well as skin lesions after a week.
CONCLUSION
BMMP, being a part of a group of autoimmune
subepithelial vesiculobullous diseases, has clinical
& histopathologic similarities with a variety of
diseases. Since the means of differentiation of all
these diseases are special & costly investigations
which are not routinely used, this entity demands
thorough clinical & histopathologic evaluation
combined with vigilant long term follow up of the
patient to ensure prevention of further attacks.The
gingival involvement often being the initial
presentation of this entity, the dentist often plays a
vital role in early detection & prevention of eye
complications.
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