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Case Report

Oral pemphigus vulgaris: A case report with direct

immunofluorescence study
Sangeetha Jeevan Kumar, SP Nehru Anand1, Nandhini Gunasekaran, Rajkumar Krishnan
Departments of Oral Pathology and 1Oral Medicine, SRM Dental College, Chennai, Tamil Nadu, India

Abstract Pemphigus vulgaris (PV) is a chronic, autoimmune, intraepidermal blistering disease of the skin and mucous
membranes. The initial clinical manifestation is frequently the development of intraoral lesions, and later,
the lesions involve the other mucous membranes and skin. The etiology of this disease still remains obscure
although the presence of autoantibodies is consistent with an autoimmune disease. These antibodies are
targeted against the adhesion proteins of keratinocytes, leading to acantholysis (disruption of spinous layer,
leading to intraepidermal clefting) and blister formation. Because only oral lesions are present initially, the
chances of misdiagnosing the disease as another condition are increased, leading to inappropriate therapy.
In this article, we report a case of PV with only oral manifestations in a 36‑year‑old male.

Key Words: Autoantibodies, immunofluorescence, intra epithelial vesicle, pemphigus, ulceration

Address for correspondence:

Dr. Sangeetha Jeevan Kumar, Department of Oral Pathology, SRM Dental College, Ramapuram, Chennai ‑ 600 089, Tamil Nadu, India.
E‑mail: [email protected]
Received: 29.06.2015, Accepted: 26.08.2016

INTRODUCTION one of the cell adhesion molecules being targeted by IgG

autoantibodies, leading to acantholysis. Dsg‑1 is expressed
Pemphigus refers to a group of autoimmune, mucocutaneous in all layers of the epidermis, with a higher concentration in
blistering diseases, in which the keratinocyte antigens are the the more superficial layers, whereas Dsg‑3 is expressed in the
target of the autoantibodies, leading to acantholysis and blister parabasal and basal layers. The presence of a suprabasilar split
formation.[1] The word pemphigus originates from Greek reflects the expression of Dsg‑3 and relative lack of Dsg‑1 in
pemphix, which translates as blister or bubble. Pemphigus can the oral mucosa. The presence of antibodies to both, Dsg‑1
be classified into five major groups: Pemphigus vulgaris (PV), and Dsg‑3, is seen in patients who develop skin lesions.
pemphigus foliaceus, paraneoplastic pemphigus (PNP), Another theory, known as the multiple hit hypothesis, suggests
drug‑induced pemphigus and immunoglobulin A (IgA) that pemphigus occurs as an effect of anti‑acetylcholine
pemphigus. Oral lesions have been associated with only PV receptor antibodies, triggering acantholysis by weakening the
and PNP.[2] cohesion of adjacent keratinocytes due to inhibition of the
physiological control of their polygonal shape and intercellular
The cause of the disease remains obscure and many theories attachment.[1]
had been put forward. One commonly accepted theory is the
loss of cell adhesion caused by the loss of desmoglein (Dsg); This is an open access article distributed under the terms of the Creative Commons
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DOI: H o w t o c i t e t h i s a r t i c l e : K u m a r S J , N e h r u A n a n d S P,
10.4103/0973-029X.190979 Gunasekaran N, Krishnan R. Oral pemphigus vulgaris: A case report with
direct immunofluorescence study. J Oral Maxillofac Pathol 2016;20:549.

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Kumar, et al.: Oral pemphigus vulgaris

CASE REPORT had a characteristic “tombstone” appearance on the floor of

the bulla. The epithelium also showed prominent spongiosis
A 36‑year‑old male reported to the Department of Oral with acantholysis, Tzanck cells and focal influx of neutrophils,
Medicine with a history of painful ulcerations involving the eosinophils and lymphocytes. The superficial papillary
palate and gingiva for the past 2 weeks. History revealed that connective tissue was edematous and supported inflammatory
the ulcerations started initially as blisters and were associated cell infiltrate consisting of lymphocytes and plasma cells, in
with pain that was aggravated on chewing food. The ulcerations addition to neutrophils and eosinophils [Figures 3 and 4].
caused considerable discomfort, affecting his normal oral
functions. Personal and family histories were uneventful. DIF showed prominent intercellular deposition of antibodies
directed against IgG and C3 [Figures 5 and 6].
Intraoral examination revealed areas of erosions on the palate
and the lower vestibule [Figure 1a and b]. The gingivae appeared A definitive diagnosis of PV was made based on clinical,
erythematous and showed numerous erosions on the marginal histopathological and DIF findings. Initially, the patient was
gingiva [Figure  1a]. The gingival mucosa exhibited a positive prescribed prednisolone tablets 20 mg, which were to be taken
Nikolsky sign. Extraoral examination revealed no skin lesions. twice daily. Topical application of Kenacort (triamcinolone
gel, 0.1%) was recommended to be used twice daily on the
Based on the history and clinical examination, a provisional oral sores. The patient was given calcium and Vitamin D
diagnosis of PV was made although the differential diagnosis supplements. A gradual reduction of the areas of ulcerations
included mucous membrane pemphigoid and erosive lichen on the palate and lower vestibule and complete absence of
planus. erosions in the marginal gingiva was seen. The oral hygiene of
the patient was monitored and scaling and root planing was
An exfoliative cytological preparation from the labial gingiva done once the condition improved. After 2 months, the dose
showed desquamated cells along with a few acantholytic was tapered to 10 mg, twice daily. Over the past 6 months,
cells (Tzanck cells), the latter having a round shape with prednisolone was gradually tapered down as there was complete
prominent nuclei. The smear also showed mixed inflammatory regression of the lesions.
cells, predominantly composed of polymorphonuclear
neutrophils [Figure 2]. DISCUSSION

A gingival biopsy was obtained from a perilesional site under Pemphigus is a potentially life‑threatening, autoimmune,
local anesthesia and submitted for routine histopathological intraepithelial blistering disease of the skin and mucous
examination and direct immunofluorescence (DIF) testing. membranes. There are five major categories of pemphigus: PV,
pemphigus foliaceus, PNP, drug‑induced pemphigus and IgA
The histopathological sections showed surface epithelium pemphigus. The oral mucosa is the initial site of involvement
in association with fibrous connective tissue. The surface in 70%–90% of the cases before involvement of the skin and
epithelium exhibited suprabasilar clefting and basal cell layer other mucosal sites.[3] Nasal, conjunctival, pharyngeal, laryngeal,

a b
Figure 1: (a) Intraoral view showing generalized desquamative gingivitis with ragged shallow erosions, (b) intraoral view showing irregular
erosions in the palate

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Kumar, et al.: Oral pemphigus vulgaris

Figure 2: Cytological preparation showing presence of Tzanck Figure 3: Photomicrograph showing epithelium exhibiting spongiosis,
cells (PAP stain, ×200) tombstone appearance, suprabasilar split and dense inflammatory
infiltrate (H&E stain, ×100)

Figure 4: Suprabasilar cleft showing acantholysis of the keratinocytes,

Tzanck cells, red blood cells and inflammatory cells (H&E stain, ×400) Figure 5: Immunoglobulin G deposited in the intercellular regions of the
keratinocytes of the epithelium (direct immunofluorescence stain, ×100)
esophageal and genital mucosa are the other mucosal sites that
may be affected. 23.6%, respectively, and PV is the least common cause of
DG (2.3%).[5]
Clinically, the lesion appears as short‑lived blisters that have
a thin roof, are very fragile and rupture easily, giving rise to PV is believed to occur as a result of autoantibodies directed
painful and hemorrhagic erosions. In our case, the oral lesions against the components of epithelial desmosomes. The
of the palate and the gingiva were the first manifestation of the desmosomes consist of two membrane‑bound adhesion
disease. The final diagnosis was based on the histopathological molecules, Dsg[6] and desmocollin, which are linked to the
features and DIF studies. cytoskeleton through intracellular plakoglobin, plakophilin
and desmoplakin.[7] Dsg consists of two subtypes, Dsg‑1 and
PV is the form of pemphigus that is most commonly seen in Dsg‑3, which are expressed variably in the skin and oral mucosa.
the oral cavity. The gingival lesions usually appear as erosions Dsg‑3 is expressed in the basal layers of the epidermis while
or blisters on the unattached gingiva. Epithelial desquamation, the superficial epidermal cells predominantly express Dsg‑1. In
erythema and erosive lesions of the gingival tissue are the oral mucosa, Dsg‑3 expression predominates over Dsg‑1.
collectively described as desquamative gingivitis (DG). [4] Thus, the oral epithelial integrity is exclusively dependent on
Mucous membrane pemphigoid and erosive lichen planus are Dsg‑3, which is targeted by the autoantibodies in cases of PV
the most frequent causes of DG, accounting for 48.9% and affecting the oral cavity.[8]

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Kumar, et al.: Oral pemphigus vulgaris

Clinical examination along with other diagnostic modalities such

as routine biopsy and direct and indirect immunofluorescence
helps in differentiating the disease from the other bullous
lesions.

CONCLUSION

PV is a serious disease, and if left untreated, it could lead to

patient’s death. Often the oral mucosa is the first involved site
even before the skin and other mucosal sites are affected, so
the dentist may have the opportunity to play an important role
in diagnosing the disease. With early detection, PV is more
easily managed.

Financial support and sponsorship

Figure 6: C3 deposited in the areas of autoantibodies in the
epithelium (direct immunofluorescence stain, ×200) Nil.

The IgG antibodies which target Dsg‑3 are deposited at the Conflicts of interest
periphery of the epithelial cells, resulting in an appearance that There are no conflicts of interest.
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