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: is important for proper treatment planning contributing to better prognosis and better quality of life of patient. Dr. Sudha Jimson, E‑mail: omfpsudhajim@ gmail.com

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

mmune‑mediated diseases along with lesions in oral cavity. • Systemic drug reaction I Immunology is defined as the study of the molecular cells, • Lupus erythematosus organs and system for the recognition and disposal of foreign • 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, swelling of lips, tongue, cheek or ulcers and blisters. Access this article online 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 Direct immunoflourescence helps in detecting lines with an erythematous border. The striae are typically intercellular deposits of IgGMA and C3 protein. Indirect located bilaterally on the buccal mucosa, mucobuccal fold, immunoflourescenceaids to detect pemphigus antibodies in gingiva. Erosive lichen planus is second most common type. serum. Immunoprecipitation and immunoblotting techniques The differential diagnosis of erosive lichen planus includes confirm, where others are in doubt [Table 1].[9] squamous cell carcinoma, discoid lupus erythematosus, chroniccandidiasis, benign mucous membrane pemphigoid, Linear IgA lichenoid reactions.[6] It is an acquired blistering disorder which is of two types Histopathology represents liquefaction of the basal cell layer one of which is chronic dermatitis of childhood, occurring accompanied by apoptosis of the keratinocytes, dense band like within the first 10 years and adult linear IgA occurring later lymphocytic infiltrate at the interface between the epithelium between 60 and 65 years. Both of them share the target and connective tissue. A characteristic saw‑toothed reteridges, lesions. Human leukocyte antigen‑B8 has been associated civatte bodies, which represent degenerating keratinocytes, are with childhood IgA. Laboratory investigation reveals elevated viewed in the lower half of the surface epithelium. erythrocyte sedimentation rate. Lesions resolve with scarring. Histological appearance seems to show micro abscess and Diagnosis is based on histopathology, however erosive type is infiltration of eosinophilic in superficial corneum. Lymphocytes challenging. Treatment needs excellent oral hygiene, which will are seen surrounding small vessels. Diagnosis is based on minimize the severity of symptoms, topical corticosteroids to immunoflouresence.[10] the modulate immune response. Other treatment modalities include retinoids, Vitamin A analogs, cyclosporine rinse, Epidermolysis Bullosa immunomodulating agent levamisole psoralens and long wave ultraviolet A treatment.[7] It is a developmental blister disease with reversal pressure, ring shaped atrophic scars on the surface of the limbs and Pemphigus Vulgaris articulations. Major is classified based on tissue separation:[11] 1. Simplex – above stratum basale Pemphigus Vulgaris is an autoimmune blistering disease 2. Junctional – within dermal‑epidermal junction involving skin and mucosal membrane. The pathogenesis behind 3. Dystrophies – beneath entire dermal epidermal junction. is that the formation of autoantibodies to the desmosomes involved in the cell‑cell adhesion leads to destruction of cellular Sever cases reveal scaring, microstomia, obliteration of oral cohesion.[1] 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 It is typical, self‑limiting and recurring mucocutaneous reaction localize in any part of oralmucosa but frequently subjected to characterized by the target or iris lesions of skin and mucous frictional areas such as the soft palate, buccal mucosa, ventral membrane. tongue, gingival and lower lip. Blisters rupture leading to chronic painful ulcer and erosions that take a long window for healing. Erythema multiforme is an immune mediated disease with Diagnosis is on three major criteria, that is, clinical features, hypersensitive reaction to infection and medications. Herpes histology and immunological.[8] Another diagnostic approach is simplex virus, fungal infections and drugs like barbiturates to test for the nikolskys sign. Laboratory methods for diagnosis nonsteroidal antiinflammatory drug s pencillins, etc., are include tzanck smear to detect acantholytic cells. Histology of considered to be the etiology.[12] It presents as mild self‑limiting fresh blister specimen aids in detecting the accantholysis in the with mild oral involvement to progressive fulminating variant stratiformspinous layer. Steven Johnson syndrome.

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

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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 inflammatory disorder characterized by oral aphthous ulcers, Systemic lupus erythematosus is an autoimmune disease with genital ulcer, skin lesions, ocular lesions.[15] Etiopathogenesis a wide range of clinical presentation involving all organs and include genetic and environmental. Diagnosis can be made tissues. Etiology includes both genetics and environmental according to clinical criteria proposed by international study with higher incidence in females. Toll like receptors and group for Behcet’s disease.[16] Recurrent oral ulcers which are Type I interferon signaling pathways play a major role.[13] difficult to distinguish between recurrent aphthous stomatitis Environmental factors are ultraviolet light, demethylating drugs and recurrent oral ulcers in Bechet syndrome. and infections or endogenous virus. Hormonal factors include estrogen and prolactin have high incidence in favor. 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 • Renal disorders. 1. Kharodawala M. Grand Rounds Presentation The University of Texas Medical Branch Department of Otolaryngology; April 26, 2006. 2. Jonsson U. Human Rights Approach to Development 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. Histopathological shows hyperortho/parakeratosis, liquefaction 6. Regezi JA, Sciubba JJ, Jordan RCK. Oral Pathology: Clinical Pathologic 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

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autoimmune bullous diseases. J Cell Mol Med 2007;11:462‑81. 14. Jaovisidha K, Csuka ME, Almagro UA, Soergel KH. Severe 10. O’Regan E, Bane A, Flint S, Timon C, Toner M. Linear IgA disease gastrointestinal involvement in systemic sclerosis: Report of presenting as desquamative gingivitis: A pattern poorly recognized five cases and review of the literature. Semin Arthritis Rheum in medicine. Arch Otolaryngol Head Neck Surg 2004;130:469‑72. 2005;34:689‑702. 11. Wright JT, Fine JD, Johnson L. Hereditary epidermolysis bullosa: Oral 15. Kovacova E, Salmas J, Stenova E, Bedeova J, Duris I. Behcet’s manifestations and dental management. Pediatr Dent 1993;15:242‑8. syndrome. Bratisl Lek Listy 2005;106:386‑9. 12. Kazmierowski JA, Wuepper KD. Erythema Multiforme: 16. Neurol L. Criteria for diagnosis of Behçet’s disease. International Clinical Spectrum and Immunopathogenesis. Springer Semin: Study Group for Behçet’s Disease Lancet 1990;335:1078‑80. 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; Source of Support: Nil, Conflict of Interest: None declared. 20:476-505.

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