Dental Science - Review Article

Immunologically mediated oral diseases

Sudha Jimson, N. Balachader1, N. Anita1, R. Babu1

Department of Oral ABSTRACT

Pathology, 1Department
Immune mediated diseases of oral cavity are uncommon. The lesions may be self‑limiting and undergo remission
of Oral Pathology and
Microbiology, Sree spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus,
Balaji Dental College erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated
and Hospital, Bharath immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns.
University, Chennai, Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation
Tamil Nadu, India, and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through
a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis
Address for correspondence:
Dr. Sudha Jimson,
is important for proper treatment planning contributing to better prognosis and better quality of life of patient.
E‑mail: omfpsudhajim@
gmail.com

Received : 31-10-14
Review completed : 31-10-14
Accepted : 09-11-14 KEY WORDS: Immunoflourescence, lichenplanus, pemphigus

I mmune‑mediated diseases along with lesions in oral cavity.

Immunology is defined as the study of the molecular cells,
organs and system for the recognition and disposal of foreign
•
•
•
Systemic drug reaction
Lupus erythematosus
Scleroderma
materials.[1] Factor responsible for differences in immunity are • Crest syndrome
age, nutrition and genetic factors. Clinical appearance may • Bechets syndrome
not lead to a final diagnosis, but can be achieved by a biopsy of • Reiter’s syndrome.[3]
4 mm in diameter at the perimeter.[2]
Hypersensitve Reaction
Classification
Mucosal surfaces are exposed to many dietary proteins and
• Hypersensitive reaction infectious agents, the immune system normally will not react
• Pemphigus vulgaris to these antigens. Unresponsiveness or tolerance to these
• Paraneoplastic pemphigus antigens are maintained by three principle mechanism namely
• Cicatricial or mucocutaneouspemphigoid
energy or functional unresponsiveness; apoptosis; and immune
• Cutaneous, bullous pemphigoid
suppression by regulatory T‑cells.[4]
• LinearIgA
• Epidermolysisbullosa
Anaphylaxis is the most serious hypersensitive reaction, which
• Lichenplanus
• Erythemamultiforme commences immediately after the exposure to allergens. The
clinical presentation may be redness or whiteness of mucosa,
Access this article online
swelling of lips, tongue, cheek or ulcers and blisters.
Quick Response Code:
Website: Lichen planus
www.jpbsonline.org
Lichen planus is believed to result from an abnormal T‑cell
DOI: mediated immune response in which basal epithelial cells are
10.4103/0975-7406.155909 recognized as foreign because of changes in the antigenicity
of cell surface.[5] The reticular type is most common type of

How to cite this article: Jimson S, Balachader N, Anita N, Babu R. Immunologically mediated oral diseases. J Pharm Bioall Sci 2015;7:S209-12.

Journal of Pharmacy and Bioallied Sciences April 2015 Vol 7 Supplement 1 S209 
 Jimson, et al.: Immunologically and oral diseases

oral lichen planus. It presents as interlacing white keratotic
lines with an erythematous border. The striae are typically
located bilaterally on the buccal mucosa, mucobuccal fold,
gingiva. Erosive lichen planus is second most common type.
The differential diagnosis of erosive lichen planus includes
squamous cell carcinoma, discoid lupus erythematosus,
chroniccandidiasis, benign mucous membrane pemphigoid,
lichenoid reactions.[6]
Histopathology represents liquefaction of the basal cell layer
accompanied by apoptosis of the keratinocytes, dense band like
lymphocytic infiltrate at the interface between the epithelium
and connective tissue. A characteristic saw‑toothed reteridges,
civatte bodies, which represent degenerating keratinocytes, are
viewed in the lower half of the surface epithelium.
Diagnosis is based on histopathology, however erosive type is
challenging. Treatment needs excellent oral hygiene, which will
minimize the severity of symptoms, topical corticosteroids to
the modulate immune response. Other treatment modalities
include retinoids, Vitamin A analogs, cyclosporine rinse,
immunomodulating agent levamisole psoralens and long wave
ultraviolet A treatment.[7]
Pemphigus Vulgaris
Pemphigus Vulgaris is an autoimmune blistering disease
involving skin and mucosal membrane. The pathogenesis behind
is that the formation of autoantibodies to the desmosomes
involved in the cell‑cell adhesion leads to destruction of cellular
cohesion.[1]
Direct immunoflourescence helps in detecting
intercellular deposits of IgGMA and C3 protein. Indirect
immunoflourescenceaids to detect pemphigus antibodies in
serum. Immunoprecipitation and immunoblotting techniques
confirm, where others are in doubt [Table 1].[9]
Linear IgA
It is an acquired blistering disorder which is of two types
one of which is chronic dermatitis of childhood, occurring
within the first 10 years and adult linear IgA occurring later
between 60 and 65  years. Both of them share the target
lesions. Human leukocyte antigen‑B8 has been associated
with childhood IgA. Laboratory investigation reveals elevated
erythrocyte sedimentation rate. Lesions resolve with scarring.
Histological appearance seems to show micro abscess and
infiltration of eosinophilic in superficial corneum. Lymphocytes
are seen surrounding small vessels. Diagnosis is based on
immunoflouresence.[10]
Epidermolysis Bullosa
It is a developmental blister disease with reversal pressure,
ring shaped atrophic scars on the surface of the limbs and
articulations. Major is classified based on tissue separation:[11]
1. Simplex – above stratum basale
2. Junctional – within dermal‑epidermal junction
3. Dystrophies – beneath entire dermal epidermal junction.
Sever cases reveal scaring, microstomia, obliteration of oral
vestibule and ankyloglossia.

Intradermal blistering results in the epithelium where Erythema Multiforme

desmoglein one and three are present. Oral lesions are the
first manifestations of the disease in 50–90% of cases. Blisters
localize in any part of oralmucosa but frequently subjected to
frictional areas such as the soft palate, buccal mucosa, ventral
tongue, gingival and lower lip. Blisters rupture leading to chronic
painful ulcer and erosions that take a long window for healing.
Diagnosis is on three major criteria, that is, clinical features,
histology and immunological.[8] Another diagnostic approach is
to test for the nikolskys sign. Laboratory methods for diagnosis
include tzanck smear to detect acantholytic cells. Histology of
fresh blister specimen aids in detecting the accantholysis in the
stratiformspinous layer.
It is typical, self‑limiting and recurring mucocutaneous reaction
characterized by the target or iris lesions of skin and mucous
membrane.
Erythema multiforme is an immune mediated disease with
hypersensitive reaction to infection and medications. Herpes
simplex virus, fungal infections and drugs like barbiturates
nonsteroidal antiinflammatory drug s pencillins, etc., are
considered to be the etiology.[12] It presents as mild self‑limiting
with mild oral involvement to progressive fulminating variant
Steven Johnson syndrome.

Table 1: Diagnostic criteria

Disease Clinicalcharacteristics
Paraneoplastic Autoimmune syndromes associated with
lymphoproliferativeneoplasm of B cells
Autoantibody production of desmoplakin 1 and 2,
BP antigen
Cicatrical Oral and ocular mucosa can be affected. Oral lesions
pemphigoid present with erythematous patches, blister erosion,
scarring absent, BP 1 and 2, laminin, BP 180 involved
Bullosal Effective with elderly aged individuals with
pemphigoid morbidity. Itchy excoriated eczematosalpapular,
utricarial lesions persist for several weeks or months
BP: Bullous pemphigoid, ELISA: Enzyme‑linked immunosorbent assays
Histopathology
Intraepidermalacantholysis, necrotic
keratinocyte, vascular interface dermatitis
Separation of mucosal epithelium from
underlying tissue at the level of lamina lucida demonstrating linear IgG, IgA or C3
between basal cell layer and lamina densa
Subepidermal cleft with presence of
eosinophils in the dermis and bulbous
regions
Diagnosis
Mucocutaneouseruptions, direct
immunofluorescence IgG, complement
deposits, immunoprecipitation, indirect
presence of circulating antibodies
Direct immunoflourescence
Skin biopsy, direct
immunoflourescence, indirect
immunofluorescence BP‑180, ELISA

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 Jimson, et al.: Immunologically and oral diseases

Table 2: Clinical presentation

Type Pattern Distribution Presentation Mucosal Detachment
involvement %
Erythema multiforme Typical target raised, atypical targets Localized Yes <10
Steven-Johnson syndrome Blisters of macules, flat, a typical target Widespread Dusky red Yes <10
Steven-Johnson syndrome‑ten Blisters of macules, flat, a typical target Widespread Dusky red Yes 10-30
Ten Blisters of macules, flat, a typical target Widespread Poorly delineated erythematous Yes >30
plaques, atypical targets

Oral lesions are seen in 70% of patients with erythema multiforme • Xerostomia
as vesicles or bullae which rupture and leave a white or yellow • Telengectasia
exudate. Painful bloody crusting ulcerations are viewed on the lips. • Discordlupuserythematosus
• Fungal infection
Histopathological section shows intercellular edema of • Gingivitis
superficial connective tissue with subepidermal vesicle. • Ulcers.
Liquefaction degeneration with superficial epithelium or
corneal areas. Basal cell degeneration is seen. It is a disease of the multisystem involving the immune
system, blood vessels and connective tissue. The diagnosis
Diagnosis is based, clinically Steven Johnson syndrome/ can be made based on clinical symptoms, barium swallow,
toxic epidermal necrolysis  (TEN) there is raised in blood and endoscopy.[14]
sedimentation rate, transient decline in CD4+ T lymphocytes
may be noticed in TEN [Table 2]. Bechets Syndrome

Lupus Erythematosus It is characterized by chronic, relapsing multisystemic

Systemic lupus erythematosus is an autoimmune disease with
a wide range of clinical presentation involving all organs and
tissues. Etiology includes both genetics and environmental
with higher incidence in females. Toll like receptors and
Type I interferon signaling pathways play a major role.[13]
Environmental factors are ultraviolet light, demethylating drugs
and infections or endogenous virus. Hormonal factors include
estrogen and prolactin have high incidence in favor.
inflammatory disorder characterized by oral aphthous ulcers,
genital ulcer, skin lesions, ocular lesions.[15] Etiopathogenesis
include genetic and environmental. Diagnosis can be made
according to clinical criteria proposed by international study
group for Behcet’s disease.[16] Recurrent oral ulcers which are
difficult to distinguish between recurrent aphthous stomatitis
and recurrent oral ulcers in Bechet syndrome.
Conclusion

Criteria Oral lesions contribute to patients morbidity affecting the

psychological and economic functioning of the individual and
• Malar patch community. These lesions can cause pain, discomfort and other
• Oral ulcers symptoms and in most cases seek treatment.
• Hematological disorders
• Photosensitivity References
• Neurological disorders
1. Kharodawala M. Grand Rounds Presentation The University of Texas
• Renal disorders.
Medical Branch Department of Otolaryngology; April 26, 2006.
2. J o n s s o n   U. H u m a n R i g h t s A p p r o a c h t o D e v e l o p m e n t
Discoid Lupus Erythematosus Programming. United nations: Published by UNICEF; 2003.
3. Robert E, Marx, Diane, Stern. Oral and maxillofacial pathology: A
rationale for diagnosis and treatment Vol 1. ed. Quintessence Books:
The chronic dermatological disease leads to scarring. It is a United nations; 2012.
collagen vascular lesion. Oral lesions occur on labial mucosa, 4. Vojdani A, Bryan O, Kellerman G. The immunology of immediate
vermilion borders and buccal mucosa. Clinically present as and delayed hypersensitivity reaction to gluten. Eur J Inflamm
2008;6:1‑10.
white popular central erythema, a border forming radiating 5. Regezi JA, Sciubba JJ, Jordan RCK, Kazmierowski JA, Krik D,Sapp JP
white striae and peripheral telengactasia. et al. Contemporary Oral and Maxillofacial Pathology. St. Louis (MI):
2nd ed. Mosby; 2004.
6. Regezi JA, Sciubba JJ, Jordan RCK. Oral Pathology: Clinical Pathologic
Histopathological shows hyperortho/parakeratosis, liquefaction
Correlations. 3rd ed. Philadelphia: WB Saunders; 1999.
degeneration of basal layer infiltration of lymphocytes. 7. Carrozzo M, Gandolfo S. The management of oral lichen planus. Oral
Dis 1999;5:196‑205.
8. Shamim T, Varghese VI, Shameena PM, Sudha S. Pemphigus vulgaris
Scleroderma in oral cavity: Clinical analysis of 71 cases. Med Oral Patol Oral Cir
Bucal 2008;13:E622‑6.
• Microstomia 9. Mihai S, Sitaru C. Immunopathology and molecular diagnosis of

Journal of Pharmacy and Bioallied Sciences April 2015 Vol 7 Supplement 1 S211 
 Jimson, et al.: Immunologically and oral diseases
autoimmune bullous diseases. J Cell Mol Med 2007;11:462‑81.
10. O’Regan E, Bane A, Flint S, Timon C, Toner M. Linear IgA disease
presenting as desquamative gingivitis: A pattern poorly recognized
in medicine. Arch Otolaryngol Head Neck Surg 2004;130:469‑72.
11. Wright JT, Fine JD, Johnson L. Hereditary epidermolysis bullosa: Oral
manifestations and dental management. Pediatr Dent 1993;15:242‑8.
12. Kazmierowski JA, Wuepper KD. Erythema Multiforme:
Clinical Spectrum and Immunopathogenesis. Springer Semin:
Immunopathology 1981;4:45‑53.
13. Bertsias G, Cervera R, Bournpass DT. Systemic Lupus Erythematosus:
Pathogenesis and Clinical Features. J Clin Exp Dermatol Res 2012;
20:476-505.
 S212 Journal of Pharmacy and Bioallied Sciences April 2015 Vol 7 Supplement 1
14. Jaovisidha K, Csuka ME, Almagro UA, Soergel KH. Severe
gastrointestinal involvement in systemic sclerosis: Report of
five cases and review of the literature. Semin Arthritis Rheum
2005;34:689‑702.
15. Kovacova E, Salmas J, Stenova E, Bedeova J, Duris I. Behcet’s
syndrome. Bratisl Lek Listy 2005;106:386‑9.
16. Neurol L. Criteria for diagnosis of Behçet’s disease. International
Study Group for Behçet’s Disease Lancet 1990;335:1078‑80.
Source of Support: Nil, Conflict of Interest: None declared.
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