• Users Online: 414
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 11  |  Issue : 2  |  Page : 80-87

Immune-mediated lesions of the oral cavity: A scrupulously researched review


Department of Oral Medicine and Radiology, Maulana Azad Institute of Dental Sciences, New Delhi, India

Date of Submission06-Sep-2021
Date of Decision20-Oct-2021
Date of Acceptance30-Sep-2021
Date of Web Publication11-Feb-2022

Correspondence Address:
Dr. Sunita Gupta
Department of Oral Medicine and Radiology, Maulana Azad Institute of Dental Sciences, New Delhi
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijohs.ijohs_23_21

Rights and Permissions
  Abstract 


Oral mucosa may be the first site to manifest protean signs and symptoms in immune mediated diseases. Therefore, it is of paramount importance to have a thorough and vast knowledge about various diseases. It is the role of oral and maxillofacial diagnostician to diagnose the lesions according to their salient features. In this review article, we aim to describe the immune-mediated oral lesions, their clinical features, investigations, and management.

Keywords: Autoimmune, immune mediated, immunoflouresence, lichen planus, pemphigus, scleroderma


How to cite this article:
Khera S, Gupta S. Immune-mediated lesions of the oral cavity: A scrupulously researched review. Int J Oral Health Sci 2021;11:80-7

How to cite this URL:
Khera S, Gupta S. Immune-mediated lesions of the oral cavity: A scrupulously researched review. Int J Oral Health Sci [serial online] 2021 [cited 2022 Jun 26];11:80-7. Available from: https://www.ijohsjournal.org/text.asp?2021/11/2/80/337497




  Introduction Top


Immunology is the study of the molecular cells, organs, and system for the identification and removal of foreign materials. Immunological response is variable and can be due to difference in age, nutrition, and genetic factors. The confirmation of the lesion can be done by performing a biopsy.[1],[2]


  Classification of Immune Mediated and Autoimmune Diseases Top


The oral immune mediated and autoimmune lesions can be classified as follows:[3]

  • Hypersensitive reaction
  • Pemphigus vulgaris
  • Cicatricial or mucocutaneous pemphigoid
  • Cutaneous, bullous pemphigoid
  • Linear IgA Disease
  • Epidermolysis bullosa Acquisita
  • Erythema multiforme
  • Systemic Lupus erythematosus
  • Scleroderma
  • Bechets syndrome
  • Sjogren's Syndrome
  • Lichen planus.



  Hypersensitive Reaction Top


The surface of oral mucosa is continuously exposed to many infectious agents; however, the immune system does not react to it. This unresponsiveness/tolerance is due to energy or functional unresponsiveness, apoptosis, and the suppression of immune system by regulatory T-cells. The most serious, life-threatening hypersensitive reaction that initiates immediately after exposure to the allergen is known as anaphylaxis. It presents as swelling of the lips, tongue, cheek or ulcerations, and formation of blisters or erythema on the oral mucosa.[4],[5]

Treatment

It is primarily treated by intramuscular application of a dose of 0.3–0.5 mg adrenaline (body weight range 30–50 kg) at the outer upper thigh. In an unstable patient, i.e., in case of respiratory and/or circulatory arrest, intravenous administration of adrenaline should be given. Other management modalities include administration of dopamine, noradrenaline, and vasopressin. H1 antihistaminics such as dimetindene (0.1 mg/kg bw) and clemastine (0.05 mg/kg bw) and glucocorticoids are also used in the management of anaphylaxis.[6],[7],[8],[9],[10]


  Pemphigus Vulgaris Top


Pemphigus vulgaris is an immune-mediated disorder affecting the skin ad mucosa.

Etiopathogenesis

Etiology is multifactorial and can be associated with stress, genetic susceptibility, hormones or drug induced. The presence of immunoglobulin G antibody against desmosomal components such as desmoglein-1 and desmoglein-1 is seen in patients with pemphigus leading to alteration in adhesion of the cell molecules causing intraepithelial blisters.[11],[12] The disease predominantly involves females and in the 4th–5th decades of life.[11],[13],[14]

Clinical features

Oral mucosal lesions precede the cutaneous lesions. The buccal mucosa is most commonly involved followed by soft palate, lower lip, tongue, and gingiva. It appears as superficial vesicles or blisters which break rapidly due to masticatory forced leading to erosion of the oral mucosa causing burning sensation. Nikolsky phenomenon is positive which is detachment of large area of the surface with the formation of blisters by exerting a slight pressure on the epithelium.[14]

Diagnosis

Pemphigus can be easily confused with aphthae, lichen planus, candidiasis, and pemphigoid. Hence, it is mandatory to perform an indirect immunoflourescence in which the antibodies are detected in patient's serum and is seen as “Chicken wire” pattern. Direct immunoflourescence helps in detecting intercellular deposits of IgGMA and C3 protein. Laboratory methods for diagnosis include tzanck smear to detect acantholytic cells.[14],[15]

Treatment

Pemphigus is managed by local and systemic corticosteroids. The treatment is aimed in two phases: Loading phase to control the disease and a maintenance phase. The treatment is initially started with application of paste, ointment, or a mouthwash either alone or in conjunction with systemic treatment. In severe and extensive cases, systemic corticosteroids are the first line of treatment starting with 0.5–2 mg/kg of prednisone. Depending upon the response, the dose is altered to a minimum therapeutic dose to avoid side effects.[16],[17] To avoid long-term complications of steroids, immunomodulatory drugs such as azathioprine, cyclophosphamide, cyclosporine, and methotrexate can be added in the treatment regimen. The response to Rituximab 1 g I. V at 2 week interval has shown promising results.[18],[19] Titration of the circulating antibodies should be done to evaluate the response to treatment and progression of disease.[20]


  Mucous Membrane Pemphigoid Top


Mucous membrane pemphigoid is an immune-mediated blistering disease.

The oral mucosa is involved along with genitals, eyes, and skin. The disease shows autoantibodies mostly IgA and IgG along with C3 Complement C3 against mucosae and epithelial basal membranes.[11],[12]

Oral findings

Gingiva is most commonly affected giving rise to a clinical condition of desquamative gingivitis. However, it is not diagnostic. The oral mucosa shows erythema or true ulcerations involving the attached gingival. Erythematous lesions are also seen on palate, buccal mucosae, lips, tongue, and pharynx.[11] The patient may experience burning and inability to chew and eat food. The bullae in pemphigoid are less brittle; therefore, they may remain in the oral cavity for more than 48 h.[12],[21]

Diagnosis

The diagnosis is based on clinical and histological samples. The histologic examination reveals detachment of the epithelium from the underlying connective tissue. Immunoflourscence can be used to distinguish between lichen planus, pempphigus, periodontal diseases, and SLE. It reveals intense inflammatory infiltration of plasma cells and eosinophils in the connective tissue.[11]

Treatment

The treatment of the disease depends on the area of involvement. In minor or less extensive lesions, topical corticosteroids gel application can be advised. Along with corticosteroids, dapsone can be given. In severe cases, pulse therapy can also given. It is important to monitor and follow up the patient on a regular basis to assess the presence of eye lesions to prevent the ocular damage.[11],[21]

Linear IgA disease

Linear IgA disease is a mucocutaneous autoimmune disease that shows linear deposition of IgA and disruption of the dermoepidermal junction causing tense blisters.[22] The disease shows a bimodal occurrence, first occurring within the first 10 years and adult occurrence between 60 and 65 years.[23]

It could be idiopathic or drug induced. Drugs involved are antibiotics, antihypertensives, and nonsteroidal anti-inflammatory agents. Most commonly involved is vancomycin.[24] In addition, associations with lymphoproliferative disorders, infections, ulcerative colitis, and systemic lupus erythematosis have been reported.[25],[26],[27],[28],[29],[30],[31]

Diagnosis

The disease can be confirmed with clinical, histopathological, and immunological data. Direct immunofluorescence demonstrates the presence of IgA deposits along the basement membrane zone in a linear pattern.[32]

Treatment

Management varies with the degree of involvement and identification of inciting factors. The mainstay treatment modality is to remove the offending drug agent, which alone can help in gradual resolution of the skin lesions.[33] The drug therapy includes dapsone which is the first line of treatment with the dose of 50–150 mg/d in adults. It shows resolution of symptoms within 72 h. Dapsone is given after assessment of Glucose-6-phosphate dehydrogenase as deficit patients carry a risk of developing hemolytic anemia. Therefore, a complete blood cunt with differential and liver function tests should be obtained before the initiation of therapy.[34] Other treatment options are less substantiated and include sulfonamides, prednisone, colchicine, tetracyclines, and nicotinamide.[32],[35],[36],[37] Systemic therapy is required until patients show clinical remission with gradual tapering toward treatment cessation.


  Epidermolysis Bullosa Acquisita Top


It is an acquired, autoimmune, cutaneous subepidermal blistering disease that primarily involves the skin and sometimes mucous membranes. The disease exhibits no racial or gender predilection and often presents in the fourth to fifth decades of life.[38]

Clinical findings

It is characterized by formation of blisters following mild mechanical trauma. It can also present systemic complications such as ocular, genital and oropharyngeal infections, involving difficulty in swallowing.[24],[39]

Diagnosis

The hallmark of the disease shows the presence of autoantibodies (mainly IgG class) to Type VII collagen, a major component of anchoring fibrils at the dermal-epidermal junction. The disease occurs in approximately 5% of unselected patients with basement membrane zone antibodies.[38]

Treatment

Children respond to high dose of corticosteroids and steroid sparing drugs. The cutaneous lesions respond to dapsone alone.[40]


  Erythema Multiforme Top


This is a self-limiting disease characterized by target lesions on the mucous membrane and skin.[41]

Etiology

It is an immune-mediated disorder presenting hypersensitive reactions to viral and fungal infections and medication such as nonsteroidal antiinflammatory drugs (NSAIDSs), penicillins, alopurinol, barbiturates, chemotherapeutic agents, carbamazepines, and cephalosporins.[42]

Oral findings

It manifests as multiple irregular ulcers or vesicles are surrounded by erythematous margin and covered with white or yellow exudates. They usually affect the lingual, buccal, and/or labial mucosa, and less frequently the floor of the mouth, palate, and the gingivae. Patients may complain of trismus, dysphonia, dysarthria, and/or dysphagia. Painful crusting ulcerations are seen on the lips.[41],[43] Severe forms of EM are Steven−Johnson syndrome, toxic epidermal necrolysis that shows extensive mucosal involvement.

Histopathological section shows intercellular edema of superficial connective tissue with subepidermal vesicle. Liquefaction degeneration with superficial epithelium or corneal areas. Basal cell degeneration is seen.

Diagnosis

Blood investigation shows raised erythrocyte sedimentation rate and decrease CD4+ cells.[44]

Treatment

The treatment is aimed at treating the underlying cause. In case of lesions due to herpes simplex virus infection, antiviral agents may be indicated in herpes-associated EM, and a 5-day course of acyclovir 200 mg five times daily at the first sign of lesions, or 400 mg four times daily for 6 months, or continuous treatment using valacyclovir, 500 mg twice a day, is useful for prophylaxis. Tetracycline 250 mg four times a day for at least 1 week may be indicated in EM related to Mycoplasma pneumoniae.

Mouthwashes containing local anesthetic and mild antiseptic compounds may help in relieving painful oral symptoms. Patients with severe EM should be treated with systemic corticosteroids (prednisolone 0.5–1.0 mg/kg/day tapered over 7–10 days) or azathioprine, or both or other immunomodulatory drugs such as cyclophosphamide, dapsone, cyclosporine, levamisole, thalidomide or interferon-α.[45],[46]


  Systemic Lupus Erythematosus Top


Systemic lupus erythematosus is a severe autoimmune inflammatory disease with various clinical presentations affecting predominantly females.[47]

Etiopathogenesis

The disease involves cell-mediated immunity followed by humoral immunity leading to deposition of immune complex triggering an inflammatory reaction causing functional impairment of the organs.[11],[48]

Clinical features

It may appear as erythema on the sun-exposed areas. A characteristic butterfly or malar rash is located on the nose and cheek is seen. Healing is seen as a central scar. Multiple organs are involved leading to arthralgia and arthritis of the joints, eyes show retinal damage due to vasculitis leading to retinal nerve damage. Renal involvement leads to kidney damage thereby compromising patient's health.[49],[50]

Oral findings

Oral lesions show a central erythema with a border forming radiating white striae and peripheral telangiectasia appearing as discoid lesions. It may also appear as desquamative gingivitis, marginal gingivitis, or erosive mucosal lesions.[48],[51]

Diagnosis

Serum can be used to assess the presence of antinuclear antibodies. Blood stream shows LE cells. These are mature neutrophils with spherical inclusions. It has to be differentiated with erythema multiforme, lichen planus, vesiculobullous lesions, traumatic or smoker's keratosis, verrucous carcinoma, lichenoid reactions to restorations. This can be distinguished through histological and immunohistochemical confirmation as a standard criteria for a definitive diagnosis.[51],[52]

Treatment

Salicyclates can be advised in mild cases. Drugs such as steroids, hydroxychloroquine, steroid sparing drugs such as azathioprine and cyclosporine can be used to maintain the states of remission and alleviation of symptoms and reversal of inflammation.[47],[53]


  Sjogren's Syndrome Top


Sjogren's syndrome affects salivary and lacrimal glands leading to lymphocytic infiltration and destruction of the exocrine glands.[11]

Etiology

The disease triggers humoral and cell-mediated immunity leading to activation of B-cells followed by immune complex formation and autoantibody production. It affects females predominantly (9:1). It has bimodal peak of occurrence, just after the menarche and after the menopause.[10],[54],[55],[56]

Clinical features

The manifestations may be only confined to mouth and eyes, and it could also be associated autoimmune damage. Fifty percent is associated with rheumatoid arthritis and systemic lupus erythematosus.[10] The involvement of eyes and oral is primary Sjogren's syndrome, the addition of any other autoimmune issues is secondary Sjogren's syndrome.

Oral symptoms include dry mouth, lack of saliva leading to the development of cavities which can build up plaque accumulation can cause opportunistic infections leading to bacterial and fungal infection like candida. Gingival inflammation and ulcerations are also seen.[10],[57],[58]

Oral signs include dryness of eyes causing xerophthalmia and keratoconjunctivities leading to ocular infections. Patients also present with Raynaud's phenomenon, a condition causing bluish discoloration of the tips of fingers and toes in cold water due to vasoconstriction.[10]

Diagnosis

The diagnosis is primarily clinical, supported by oral presentation and laboratory investigations. The classification made by Shiboski et al. is most commonly used and is endorsed by the American College of Rheumatology.[59],[60] The diagnosis can be confirmed when two out of the listed conditions are identified: Xerostomia, keratoconjunctivitis sicca, and rheumatoid arthritis. Assessment of salivary flow rate and biopsy of the minor salivary glands are basic investigations to confirm the syndrome.[10],[61] Ophthalmic evaluation such as Rose Bengal test and BUT test are necessary to detect keratoconjunctivitis sicca. Regular follow-ups should be made mandatory as patients with Sjogren's syndrome are prone to developing lymphoma and Waldenstrom macroglobulinemia.[10],[61] Laboratory findings show 90% positive rheumatoid Factor, anti-Sjogren A/Anti-Ro, and antiSjogren B/Anti-La.[61]

Treatment

The treatment is aimed at treating clinical signs. Most commonly, corticosteroid and immunosupressive therapy is given for alleviation of symptoms. The salivary substitutes such as pilocarpine 5 mg three times a day and cevimiline 30 mg three times a day, installation of an air humidifier and salivary substitute mouthwashes can be prescribed to stimulate salivary production. Antifungal medications can be given in case of opportunistic candidal infections. Periodic follow with the dentist is recommended for the evaluation of hard and soft-tissue changes.[62],[63],[64]


  Behcet's Syndrome Top


First described by Hulusi Behcet in 1937 as an inflammatory disease of unknown etiology. It is characterized by recurrent aphthae, genital ulcerations, uveitis and cutaneous lesions. It may be associated with less frequent systemic manifestations such as gastrointestinal, central nervous system (CNS), vascular, and joint infections.[10],[65]

Etiopathogenesis

Altered immunoregulation causes activation of T-lymphocytes and macrophages in association with natural-killer cells which leads to both cellular and humoral immunity leading to Type III hypersensitivity reactions.[66],[67]

It usually affects individuals in their 30s and shoes no gender predilection. Topographically, it is commonly seen to affect the Mediterranean and Asian population with marked prevalence in Turkey. The disease shows the presence of autoantibodies in association with HLAB5 and B51.[10],[68]

Clinical features

Oral lesions manifest before involvement of any other organ. The lesions appear as aphthous ulcers in multiple numbers on the soft palate occurring on the soft palate, lips, tongue, gingiva, oral mucosa, and oropharynx. The ulcers appear with a necrotic yellowish base with raised edges with surrounding erythema. Ulcers persist for several days and heal without scarring.[69],[70]

Genital lesions appear in females mainly and appear on the vulva and vaginal wall. Cutaneous manifestations present as erythematous nodules, papules, vesicles, pustules, folliculitis and are positive in the pathergy test, a nonspecific hypersensitivity skin reaction induced by needle prick within 1–2 days. The orbital involvement show posterior uveitis, retinal vasculitis, conjunctivitis, optic neuritis, and retinal arthritis. Involvement of the articular joints such as knees, ankles, and wrists, which manifest as inflammatory episodes. The syndrome may involve the CNS leading to convulsions and meningoencephalitis in advanced cases.[68],[71],[72],[73]

Treatment

The main goal of therapy in patients with BD is to induce and maintain remission and improve patients' quality of life. Selecting treatment is based on the organ involved and the assessment of the severity of the disease.

For oral ulcers, the treatment can be started with topical colchicines and dapsone. If sufficient response is not observed, oral thalidomide, predisone, and methotrexate can be prescribed but the patient should be kept on regular follow-up to assess the degree of toxicity. Severe cases can be treated with cyclosprorines, azathioprine, cyclophosphamide, and interferon-alpha. The treatment requires a multidisciplinary approach due to systemic involvement.[72],[73]


  Oral Lichen Planus Top


Lichen planus is a mucocutaneous disease involving the skin and mucous membrane. The cutaneous lesions are self-limiting, whereas the oral lesions are chronic, exhibits periods of remission, and exacerbation is a potentially malignant disorder.[74]

Etiopathogenesis

It is believed that an abnormal T-cell-mediated immune response against the basal cells of the epithelium that are recognized foreign by the body due to antigenic variation. The antigen binds toCD8+ T-cells through MHC II present on the surface of keratinocytes. Other factors include psychological stress, systemic medications such as beta blockers, NSAID's, oral hypoglycemics, genetics, hepatitis C virus and dental amalgam, resinous dental materials, composite restorations that can cause lichenoid reactions.[75],[76],[77],[78],[79]

Clinical features

It is seen predominantly affecting females from the third to seventh decade. It mostly involves the buccal mucosa, gingival, and tongue. Clinically, six types are present: Reticular (fine white striae cross each other in the lesion), atrophic (areas of erythematous lesion surrounded by reticular components), papular type, bullous type, plaque type, erosive or ulcerative type. The reticular type of oral lichen planus is often asymptomatic, only can be seen clinically. Ulcerative type in which erythematous areas are seen surrounded by reticular elements. Grayish white lines can be seen around the surface of the lesion known as Wickham's striae.[80],[81],[82],[83],[84]

Oral findings

It presents as whitish gray radiating lines mostly bilateral presentation. Mostly, 80% buccal mucosa is involved, 65% tongue, 20% lips, <10% floor of the mouth and palate. The reticular form has a better prognosis as 40% of cases has spontaneous remission, the erosive type being long standing and with frequent exacerbations and severe pain and complications.[85],[86]

Investigations

Clinical examination with a thorough history, followed by tissue biopsy is routinely sufficient for the diagnosis of oral lichen planus. Histopathological examination from the biopsy of the site of lesion reveals the diagnosis of lichen planus. The direct immunofluorescence of lichen planus shows “Linear pattern” in the basement zone and exhibit positive fluorescence with antifibrinogen. IgA, IgG, complement C3 were seen on colloid bodies. Indirect immunofluorescence aids in the detection of antibodies in the circulating blood of the lichen planus patient. The circulating antibodies that react and bind to the basal cells of the epithelium gives rise to the “annular fluorescence” or the “string of pearls” appearance.[87],[88]

Treatment

Different drugs have been used in the form of topical and systemic application for the treatment of OLP. Topical application of corticosteroids, immunosuppressives, retinoids, and immunomodulators are used for the management of the localized lesion. In severe cases, systemic administration of metronidazole, griseofulvin, and hydroxychloroquine, some retinoids and corticosteroids is recommended. Holistic treatment modalities such as Tulsi, Green tea, Honey, and Aloe vera have shown remarkable results in the management of OLP.[89],[90],[91]

High dysplastic or severe cases can be managed by surgical excision, cryotherapy, CO2 laser, and ND: YAG laser.[92]


  Conclusion Top


Oral lesions secondary to immune dysregulation can affect the psychological, economic, and the quality of living in the patients. It is of utmost importance to diagnose and treat them to reduce the morbidity of the affected patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kharodawala M. Grand Rounds Presentation The University of Texas Medical Branch Department of Otolaryngology; April 26. 2006.  Back to cited text no. 1
    
2.
Urban Jonsson. Approach to Development Programming; 2003.  Back to cited text no. 2
    
3.
Robert E, Marx, Diane, Stern Oral and Maxillofacial Pathology: A Rationale for Diagnosis and Treatment. Vol. 1. United Nations: Quintessence Books; 2012.  Back to cited text no. 3
    
4.
Vojdani A, Bryan O, Kellerman G. The immunology of immediate and delayed hypersensitivity reaction to gluten. Eur J Inflamm 2008;6:1-10.  Back to cited text no. 4
    
5.
Jimson S, Balachader N, Anita N, Babu R. Immunologically mediated oral diseases. J Pharm Bioallied Sci 2015;7:S209-12.  Back to cited text no. 5
    
6.
Nolan JP, Soar J, Zideman DA, Biarent D, Bossaert LL, Deakin C, et al. European Resuscitation Council guidelines for resuscitation 2010 section 1. Executive summary. Resuscitation 2010;81:1219-76.  Back to cited text no. 6
    
7.
Friedrich JO, Adhikari N, Herridge MS, Beyene J. Meta-analysis: Low-dose dopamine increases urine output but does not prevent renal dysfunction or death. Ann Intern Med 2005;142:510-24.  Back to cited text no. 7
    
8.
Gronemeyer W. Norepinephrine instead of epinephrine in anaphylactic shock. Dtsch Med Wochenschr 1977;102:101-2.  Back to cited text no. 8
    
9.
Schummer C, Wirsing M, Schummer W. The pivotal role of vasopressin in refractory anaphylactic shock. Anesth Analg 2008;107:620-4.  Back to cited text no. 9
    
10.
Choo KJ, Simons E, Sheikh A. Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. Allergy 2010;65:1205-11.  Back to cited text no. 10
    
11.
Ibsen OA, Phelan JA. Oral Pathology for Dental Hygienist. 5th ed. Saunders (W.B.) Co Ltd.; 2009.  Back to cited text no. 11
    
12.
Cizenski JD, Michel P, Watson IT, Frieder J, Wilder EG, Wright JM, et al. Spectrum of orocutaneous disease associations: Immune-mediated conditions. J Am Acad Dermatol 2017;77:795-806.  Back to cited text no. 12
    
13.
Bascones-Martínez A, García-García V, Meurman JH, Requena-Caballero L. Immune-mediated diseases: What can be found in the oral cavity? Int J Dermatol 2015;54:258-70.  Back to cited text no. 13
    
14.
Shamim T, Varghese VI, Shameena PM, Sudha S. Pemphigus vulgaris in oral cavity: Clinical analysis of 71 cases. Med Oral Patol Oral Cir Bucal 2008;13:E622-6.  Back to cited text no. 14
    
15.
Ali S, Kelly C, Challacombe SJ, Donaldson AN, Dart JK, Gleeson M, et al. Salivary IgA and IgG antibodies to bullous pemphigoid 180 noncollagenous domain 16a as diagnostic biomarkers in mucous membrane pemphigoid. Br J Dermatol 2016;174:1022-9.  Back to cited text no. 15
    
16.
Arpita R, Monica A, Venkatesh N, Atul S, Varun M. Oral pemphigus vulgaris: Case report. Ethiop J Health Sci 2015;25:367-72.  Back to cited text no. 16
    
17.
Chrysomallis F, Ioannides D, Teknetzis A, Panagiotidou D, Minas A. Treatment of oral pemphigus vulgaris. Int J Dermatol 1994;33:803-7.  Back to cited text no. 17
    
18.
Anandan V, Jameela WA, Sowmiya R, Kumar MMS, Lavanya P. Rituximab: A magic bullet for pemphigus. J Clin Diagn Res 2017;11:C01-6.  Back to cited text no. 18
    
19.
Heelan K, Al-Mohammedi F, Smith MJ, Knowles S, Lansang P, Walsh S, et al. Durable remission of pemphigus with a fixed-dose rituximab protocol. JAMA Dermatol 2014;150:703-8.  Back to cited text no. 19
    
20.
Cutolo M, Sulli A, Capellino S, Villaggio B, Montagna P, Seriolo B, et al. Sex hormones influence on the immune system: Basic and clinical aspects in autoimmunity. Lupus 2004;13:635-8.  Back to cited text no. 20
    
21.
Bertram F, Bröcker EB, Zillikens D, Schmidt E. Prospective analysis of the incidence of autoimmune bullous disorders in lower Franconia, Germany. J Dtsch Dermatol Ges 2009;7:434-40.  Back to cited text no. 21
    
22.
Wojnarowska F, Marsden RA, Bhogal B, Black MM. Chronic bullous disease of childhood, childhood cicatricial pemphigoid, and linear IgA disease of adults. A comparative study demonstrating clinical and immunopathologic overlap. J Am Acad Dermatol 1988;19:792-805.  Back to cited text no. 22
    
23.
Fortuna G, Marinkovich MP. Linear immunoglobulin A bullous dermatosis. Clin Dermatol 2012;30:38-50.  Back to cited text no. 23
    
24.
Scheidt L, Sanabe ME, Diniz MB. Oral manifestations and dental management of epidermolysis bullosa simplex. Int J Clin Pediatr Dent 2015;8:239-41.  Back to cited text no. 24
    
25.
Fortuna G, Salas-Alanis JC, Guidetti E, Marinkovich MP. A critical reappraisal of the current data on drug-induced linear immunoglobulin A bullous dermatosis: A real and separate nosological entity? J Am Acad Dermatol 2012;66:988-94.  Back to cited text no. 25
    
26.
Jouan N, Plantin P, Berthou C, Gavanou J, Le Roy JP, Schollhammer M, et al. Association of IgA linear dermatitis and non-Hodgkin's malignant lymphoma. Rev Med Interne 1992;13:153-5.  Back to cited text no. 26
    
27.
Usmani N, Baxter KF, Child JA, Sheehan-Dare R. Linear IgA disease in association with chronic lymphocytic leukaemia. Br J Dermatol 2004;151:710-1.  Back to cited text no. 27
    
28.
Baldari U, Raccagni AA, Celli B, Righini MG. Chronic bullous disease of childhood following Epstein-Barr virus seroconversion: A case report. Clin Exp Dermatol 1996;21:123-6.  Back to cited text no. 28
    
29.
Simon JC, Dietrich A, Kapp A, Schöpf E. Chronic bullous dermatosis in childhood. Association with salmonella enteritis. Hautarzt 1995;46:485-9.  Back to cited text no. 29
    
30.
Taniguchi T, Maejima H, Saito N, Katsuoka K, Haruki S. Case of linear IgA bullous dermatosis-involved ulcerative colitis. Inflamm Bowel Dis 2009;15:1284-5.  Back to cited text no. 30
    
31.
Tobón GJ, Toro CE, Bravo JC, Cañas CA. Linear IgA bullous dermatosis associated with systemic lupus erythematosus: A case report. Clin Rheumatol 2008;27:391-3.  Back to cited text no. 31
    
32.
Guide SV, Marinkovich MP. Linear IgA bullous dermatosis. Clin Dermatol 2001;19:719-27.  Back to cited text no. 32
    
33.
Navi D, Michael DJ, Fazel N. Drug-induced linear IgA bullous dermatosis. Dermatol Online J 2006;12:12.  Back to cited text no. 33
    
34.
Wojnarowska F. Linear IgA dapsone responsive bullous dermatosis. J R Soc Med 1980;73:371-3.  Back to cited text no. 34
    
35.
Jabłońska S, Chorzelski TP, Rosinska D, Maciejowska E. Linear IgA bullous dermatosis of childhood (chronic bullous dermatosis of childhood). Clin Dermatol 1991;9:393-401.  Back to cited text no. 35
    
36.
Benbenisty KM, Bowman PH, Davis LS. Localized linear IgA disease responding to colchicine. Int J Dermatol 2002;41:56-8.  Back to cited text no. 36
    
37.
Pulimood S, Ajithkumar K, Jacob M, George S, Chandi SM. Linear IgA bullous dermatosis of childhood: Treatment with dapsone and co-trimoxazole. Clin Exp Dermatol 1997;22:90-1.  Back to cited text no. 37
    
38.
Zhu XJ, Niimi Y, Bystryn JC. Epidermolysis bullosa acquisita. Incidence in patients with basement membrane zone antibodies. Arch Dermatol 1990;126:171-4.  Back to cited text no. 38
    
39.
Babaee N, Zabihi E, Mohseni S, Moghadamnia AA. Evaluation of the therapeutic effects of Aloe vera gel on minor recurrent aphthous stomatitis. Dent Res J (Isfahan) 2012;9:381-5.  Back to cited text no. 39
    
40.
Mehren CR, Gniadecki R. Epidermolysis bullosa acquisita: Current diagnosis and therapy. Dermatol Reports 2011;3:e38.  Back to cited text no. 40
    
41.
Kazmierowski JA, Wuepper KD. Erythema multiforme: Clinical spectrum and immunopathogenesis. Springer Semin Immunopathol 1981;4:45-53.  Back to cited text no. 41
    
42.
Scully C, Bagan JV. Adverse drug reactions in the orofacial region. Crit Rev Oral Biol Med 2004;15:221-39.  Back to cited text no. 42
    
43.
Ayangco L, Rogers RS 3rd. Oral manifestations of erythema multiforme. Dermatol Clin 2003;21:195-205.  Back to cited text no. 43
    
44.
Howland WW, Golitz LE, Weston WL, Huff JC. Erythema multiforme: Clinical, histopathologic, and immunologic study. J Am Acad Dermatol 1984;10:438-46.  Back to cited text no. 44
    
45.
Siegel MA, Balciunas BA. Oral presentation and management of vesiculobullous disorders. Semin Dermatol 1994;13:78-86.  Back to cited text no. 45
    
46.
Stewart MG, Duncan NO 3rd, Franklin DJ, Friedman EM, Sulek M. Head and neck manifestations of erythema multiforme in children. Otolaryngol Head Neck Surg 1994;111:236-42.  Back to cited text no. 46
    
47.
Albilia JB, Lam DK, Clokie CM, Sándor GK. Systemic lupus erythematosus: A review for dentists. J Can Dent Assoc 2007;73:823-8.  Back to cited text no. 47
    
48.
Lourenço SV, de Carvalho FR, Boggio P, Sotto MN, Vilela MA, Rivitti EA, et al. Lupus erythematosus: Clinical and histopathological study of oral manifestations and immunohistochemical profile of the inflammatory infiltrate. J Cutan Pathol 2007;34:558-64.  Back to cited text no. 48
    
49.
Fessler BJ, Boumpas DT. Severe major organ involvement in systemic lupus erythematosus. Diagnosis and management. Rheum Dis Clin North Am 1995;21:81-98.  Back to cited text no. 49
    
50.
Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004;15:241-50.  Back to cited text no. 50
    
51.
Jonsson R, Heyden G, Westberg NG, Nyberg G. Oral mucosal lesions in systemic lupus erythematosus – A clinical, histopathological and immunopathological study. J Rheumatol 1984;11:38-42.  Back to cited text no. 51
    
52.
Schiodt M. Oral manifestations of lupus erythematosus. Int J Oral Surg 1984;3:101-47.  Back to cited text no. 52
    
53.
Ranginwala AM, Chalishazar MM, Panja P, Buddhdev KP, Kale HM. Oral discoid lupus erythematosus: A study of twenty-one cases. J Oral Maxillofac Pathol 2012;16:368-73.  Back to cited text no. 53
[PUBMED]  [Full text]  
54.
Both T, Dalm VA, van Hagen PM, van Daele PL. “Reviewing primary Sjögren's syndrome: Beyond the dryness – From pathophysiology to diagnosis and treatment. Int J Med Sci 2017;14:191-200.  Back to cited text no. 54
    
55.
Willeke P, Gaubitz M, Schotte H, Becker H, Mickholz E, Domschke W, et al. Clinical and immunological characteristics of patients with Sjögren's syndrome in relation to alpha-fodrin antibodies. Rheumatology (Oxford) 2007;46:479-83.  Back to cited text no. 55
    
56.
Liquidato BM, Soler Rde C, Bussoloti Filho I. Evaluation of the concordance of sialometry and salivary glands scintigraphy in dry mouth patients. Braz J Otorhinolaryngol 2006;72:116-9.  Back to cited text no. 56
    
57.
Margaix-Muñoz M, Bagán JV, Poveda R, Jiménez Y, Sarrión G. Sjögren's syndrome of the oral cavity. Review and update. Med Oral Patol Oral Cir Bucal 2009;14:E325-30.  Back to cited text no. 57
    
58.
Radfar L, Shea Y, Fischer SH, Sankar V, Leakan RA, Baum BJ, et al. Fungal load and candidiasis in Sjögren's syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol 2003;96:283-7.  Back to cited text no. 58
    
59.
Hamburger J. Orofacial manifestations in patients with inflammatory rheumatic diseases. Best Pract Res Clin Rheumatol 2016;30:826-50.  Back to cited text no. 59
    
60.
Shiboski SC, Shiboski CH, Criswell L, Baer AN, Challacombe S, Lanfranchi H, et al. American College of Rheumatology classification criteria for Sjögren's syndrome: A data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance Cohort. Arthritis Care Res 2012;64:475-87.  Back to cited text no. 60
    
61.
Fox RI. Sjögren's syndrome. Lancet 2005;366:321-31.  Back to cited text no. 61
    
62.
Vitali C, Bombardieri S, Moutsopoulos HM, Coll J, Gerli R, Hatron PY, et al. Assessment of the European classification criteria for Sjögren's syndrome in a series of clinically defined cases: Results of a prospective multicentre study. The European study group on diagnostic criteria for Sjögren's syndrome. Ann Rheum Dis 1996;55:116-21.  Back to cited text no. 62
    
63.
Torres SR, Peixoto CB, Caldas DM, Silva EB, Akiti T, Nucci M, et al. Relationship between salivary flow rates and Candida counts in subjects with xerostomia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:149-54.  Back to cited text no. 63
    
64.
Gottenberg JE, Seror R, Miceli-Richard C, Benessiano J, Devauchelle-pensec V, Dieude P, et al. Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sjögren's syndrome. Data at enrollment in the prospective ASSESS cohort. PLoS One 2013;8:e59868.  Back to cited text no. 64
    
65.
Marinho KC, Caputo BV, Noro-Filho GA, Giovani EM. Behçet's syndrome: Literature review and clinical case report. Rev Esp Cir Oral Maxilofac 2016;38:105-10.  Back to cited text no. 65
    
66.
Gül A, Esin S, Dilsen N, Koniçe M, Wigzell H, Biberfeld P. Immunohistology of skin pathergy reaction in Behçet's disease. Br J Dermatol 1995;132:901-7.  Back to cited text no. 66
    
67.
Maldini C, La Valley MP, Cheminant M, Menthon M, Mahr A. Relationships of HLA-B51 or B5 genotype with Behçet's disease clinical characteristics: Systematic review and meta-analyses of observational studies. Rheumatology 2012;51:887-900.  Back to cited text no. 67
    
68.
Greco A, De Virgilio A, Ralli M, Ciofalo A, Mancini P, Attanasio G, et al. Behçet's disease: New insights into pathophysiology, clinical features and treatment options. Autoimmun Rev 2018;17:567-75.  Back to cited text no. 68
    
69.
Krause I, Rosen Y, Kaplan I, Milo G, Guedj D, Molad Y, et al. Recurrent aphthous stomatitis in Behçet's disease: Clinical features and correlation with systemic disease expression and severity. J Oral Pathol Med 1999;28:193-6.  Back to cited text no. 69
    
70.
Alpsoy E, Elpek GO, Yilmaz F, Ciftcioglu MA, Akman A, Uzun S, et al. Androgen receptor levels of oral and genital ulcers and skin pathergy test in patients with Behcet's disease. Dermatology 2005;210:31-5.  Back to cited text no. 70
    
71.
Ozluk E, Balta I, Akoguz O, Kalkan G, Astarci M, Akbay G, et al. Histopathologic study of pathergy test in Behçet's disease. Indian J Dermatol 2014;59:630.  Back to cited text no. 71
[PUBMED]  [Full text]  
72.
Demiroglu H, Ozcebe OI, Barista I, Dündar S, Eldem B. Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Behçet's disease: A randomised trial. Lancet 2000;355:605-9.  Back to cited text no. 72
    
73.
Saenz A, Ausejo M, Shea B, Wells G, Welch V, Tugwell P. Pharmacotherapy for Behcet's syndrome. Cochrane Database Syst Rev. 2000;1998:CD001084. doi: 10.1002/14651858.CD001084.  Back to cited text no. 73
    
74.
Okade D, Nagaraj T, Sahu P, Saxena S, Biswas A, Kongbrailatpam S. Oral lichen planus: A case series. J Adv Clin Res Insights 2019;6:53-6.  Back to cited text no. 74
    
75.
Krupaa RJ, Sankari SL, Masthan KM, Rajesh E. Oral lichen planus: An overview. J Pharm Bioallied Sci 2015;7:S158-61.  Back to cited text no. 75
    
76.
Edwards PC, Kelsch R. Oral lichen planus: Clinical presentation and management. J Can Dent Assoc 2002;68:494-9.  Back to cited text no. 76
    
77.
Hamburger J, Potts AJ. Non-steroidal anti-inflammatory drugs and oral lichenoid reactions. Br Med J (Clin Res Ed). 1983;287:1258.  Back to cited text no. 77
    
78.
Ivanovski K, Nakova M, Warburton G, Pesevska S, Filipovska A, Nares S, et al. Psychological profile in oral lichen planus. J Clin Periodontol 2005;32:1034-40.  Back to cited text no. 78
    
79.
Thornhill MH, Pemberton MN, Simmons RK, Theaker ED. Amalgam-contact hypersensitivity lesions and oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:291-9.  Back to cited text no. 79
    
80.
Lowe NJ, Cudworth AG, Woodrow JC. HL-A antigens in lichen planus. Br J Dermatol 1976;95:169-71.  Back to cited text no. 80
    
81.
Carrozzo M, Brancatello F, Dametto E, Arduino P, Pentenero M, Rendine S, et al. Hepatitis C virus-associated oral lichen planus: Is the geographical heterogeneity related to HLA-DR6? J Oral Pathol Med 2005;34:204-8.  Back to cited text no. 81
    
82.
Lind PO. Oral lichenoid reactions related to composite restorations. Preliminary report. Acta Odontol Scand 1988;46:63-5.  Back to cited text no. 82
    
83.
Ingafou M, Leao JC, Porter SR, Scully C. Oral lichen planus: A retrospective study of 690 British patients. Oral Dis 2006;12:463-8.  Back to cited text no. 83
    
84.
Rajendran R, Sivapadasundaram B. Shafer's Textbook of Oral Pathology. 7th ed., New Delhi, India: Elsevier; 2012. p. 808-12.  Back to cited text no. 84
    
85.
Eisen D. The evaluation of cutaneous, genital, scalp, nail, esophageal, and ocular involvement in patients with oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:431-6.  Back to cited text no. 85
    
86.
Andreasen JO. Oral lichen planus. 1. A clinical evaluation of 115 cases. Oral Surg Oral Med Oral Pathol 1968;25:31-42.  Back to cited text no. 86
    
87.
Daniels TE, Quadra-White C. Direct immunofluorescence in oral mucosal disease: A diagnostic analysis of 130 cases. Oral Surg Oral Med Oral Pathol 1981;51:38-47.  Back to cited text no. 87
    
88.
McQueen A, Behan WM. Immunofluorescence microscopy. The “string of Pearls” phenomenon-an immunofluorescent serological finding in patients screened for adverse drug reactions. Am J Dermatopathol 1982;4:155-9.  Back to cited text no. 88
    
89.
Lavanya N, Jayanthi P, Rao UK, Ranganathan K. Oral lichen planus: An update on pathogenesis and treatment. J Oral Maxillofac Pathol 2011;15:127-32.  Back to cited text no. 89
  [Full text]  
90.
Patil A, Gunjal S, Latif AA. Tulsi: A medicinal herb for oral health.Galore Int J Health Sci Res 2018;3:37-9.  Back to cited text no. 90
    
91.
Sanatkhani M, Mosannen Mozafari P, Amirchaghmaghi M, Najafi Fathi M, Sanatkhani M, Sarjami N, et al. Effect of cedar honey in the treatment of oral lichen planus. Iran J Otorhinolaryngol 2014;26:151-61.  Back to cited text no. 91
    
92.
Choonhakarn C, Busaracome P, Sripanidkulchai B, Sarakarn P. The efficacy of aloe vera gel in the treatment of oral lichen planus: A randomized controlled trial. Br J Dermatol 2008;158:573-7.  Back to cited text no. 92
    




 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
   Abstract
  Introduction
   Classification o...
   Hypersensitive R...
  Pemphigus Vulgaris
   Mucous Membrane ...
   Epidermolysis Bu...
  Erythema Multiforme
   Systemic Lupus E...
   Sjogren's Sy...
   Behcet's Syn...
  Oral Lichen Planus
  Conclusion
   References

 Article Access Statistics
    Viewed657    
    Printed18    
    Emailed0    
    PDF Downloaded97    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]