January 2019
Volume 40, Issue 1

Recalcitrant Gingival Lesions in a Patient Previously Diagnosed With Behçet’s Disease

Eric T. Stoopler, DMD; Sahar Mirfarsi, DDS; Faizan Alawi, DDS; and Thomas P. Sollecito, DMD

Abstract: Oral mucosal lesions are frequently encountered in a variety of healthcare settings and often present as a diagnostic and management challenge. Several immune-mediated disorders present with overlapping oral and/or cutaneous manifestations. Healthcare providers must establish a specific diagnosis to guide effective disease management. This article describes the case of a patient previously diagnosed with Behçet's disease who presented with recalcitrant gingival lesions. The case report underscores the need for healthcare providers to have a fundamental knowledge of mucocutaneous disorders.

An individual with chronic mucocutaneous lesions may present as a diagnostic dilemma for the clinician. Several disorders may be included in the differential diagnosis due to the complex nature and symptomatology of these diseases.1 Lichen planus, pemphigus vulgaris, and mucous membrane pemphigoid (MMP) are among the most common immune-mediated disorders that cause chronic oral mucosal lesions, with desquamative gingivitis as a possible presenting sign of all three conditions.2 Additional oral manifestations of these diseases include striae, erythema, and/or ulceration of varying severity and extent.2

While oral disease may be the only manifestation of these disorders, cutaneous lesions such as vesicles or bullae are often associated with these conditions and patients may require multidisciplinary management depending on the extent and severity of disease. Chronic mucocutaneous lesions may be a clinical feature of systemic disorders such as lupus erythematosus and Behçet's disease (BD) (also referred to as Behçet's syndrome).3 A thorough review of the patient's medical history and clinical examination findings will enable healthcare providers to establish an appropriate differential diagnosis. Serologic evaluation and/or tissue analysis is often sought in patients with chronic mucocutaneous disorders to aid in establishing a specific diagnosis, which will permit development of appropriate management strategies and determination of disease prognosis. Pharmacologic management typically includes use of topical and/or systemic immunosuppressants and other disease-specific agents to treat underlying systemic diseases as necessary.2,3

This article describes a case of a patient with recalcitrant gingival lesions who was previously diagnosed with BD, a systemic vasculitis disorder that affects multiple organ systems.

Case Report

A 64-year-old Caucasian man with a 20-year history of BD was referred by a rheumatologist for evaluation of recalcitrant gingival lesions. The patient reported symptom onset 10 years prior to diagnosis of BD and described the condition as recurrent episodes of painful oral and cutaneous blisters. He was unaware of the results of a previous oral biopsy. Prior treatment included corticosteroids (topical and systemic) and colchicine without benefit.

Upon presentation, the patient was using dapsone 75 mg daily, which effectively managed his cutaneous lesions. He denied any history of genital lesions, ocular lesions, or pathergy testing. In addition to BD, the patient's medical history was significant for esophageal reflux, eosinophilic esophagitis, and generalized osteoarthritis. Review of systems was positive for tinnitus bilaterally and joint/muscle pain. In addition to dapsone, medications included dexlansoprazole and fexofenadine.

Physical examination revealed a well-nourished, well-developed individual. Extraoral examination did not show lymphadenopathy, salivary gland enlargement, or cutaneous lesions. Intraoral examination revealed generalized erythema of the maxillary and mandibular gingiva (Figure 1). Focal ulcerations in various stages of healing were observed on the maxillary gingiva (Figure 2).

Differential diagnosis of the oral lesions included MMP, pemphigus vulgaris, and erosive lichen planus. The patient underwent testing for human leukocyte antigen (HLA)-B51 with negative results. An incisional biopsy of the mandibular gingiva for routine staining revealed stratified squamous epithelium exhibiting subepithelial cleavage from the underlying connective tissue with an infiltrate of lymphocytes, plasma cells, and neutrophils in the lamina propria (Figure 3). Direct immunofluorescence (DIF) analysis of labial mucosa revealed a linear band of immunoglobulin G (IgG) and complement 3 (C3) deposition at the mucosal-submucosal interface.

The patient's history, physical examination, and histopathologic findings supported the diagnosis of oral MMP. It was unclear if the patient's cutaneous lesions were consistent with BD, as none were present at the time of presentation; however, the authors favored an overall diagnosis of MMP based on the current oral findings, the patient's description of the cutaneous lesions as "blisters," and favorable treatment response to dapsone. The patient was prescribed fluocinonide gel 0.05% twice daily to the affected oral tissues and clotrimazole 10 mg three times daily with nearly complete resolution of the gingival lesions. At the time of this writing, the patient continues to use dapsone 75 mg daily to manage his cutaneous lesions.


Behçet's disease is a chronic multisystem disorder that often is challenging to diagnose and manage. Disease prevalence is highest in the region extending from the Mediterranean to the Far East (along the so-called Silk Road), with substantially lower prevalence in Northern and Western Europe and the United States.4 Age of BD onset is typically between 20 and 50 years, although individuals at any age may be affected.4,5 While the exact etiology of BD is unknown, the condition represents a systemic inflammatory vasculitis of varying severity and clinical presentation.6 HLA-B51 is the genetic risk factor most closely associated with BD, with prevalence ranging from 15% to 80% in patients with the condition; however, the role of HLA-B51 in the pathogenesis of BD is unknown.4,7

Multiple classification systems for BD have been proposed, and the criteria suggested by the International Study Group are commonly used to diagnose the condition.8 Diagnostic criteria include recurrent oral ulceration at least three times annually and two of the following: (1) recurrent genital ulceration; (2) ocular lesions, such as uveitis; and/or (3) positive pathergy.7 The international criteria for BD incorporate a scoring system and include neurologic and vascular manifestations as conditions for diagnosis of the disease.4,8 Individuals with BD may also experience gastrointestinal, pulmonary, and/or articular manifestations of the disease.4

Oral lesions associated with BD present as symmetrical, round-ovoid ulcers with pseudomembrane surrounded by erythema (aphthous ulcers) (Figure 4) and have been reported to be present in 98% of BD cases.4,6 Recurrent aphthous stomatitis (RAS) is a common condition that is more often associated with a genetic predisposition toward the disorder rather than having an association with a systemic disease such as BD.2 Minor RAS, the most common presentation of this condition, is characterized by ulcer(s) smaller than 1 cm that heal within 2 weeks without scarring.2 In contrast, major RAS presents with ulcer(s) larger than 1 cm in diameter that may appear asymmetric, are present for more than 2 weeks, and typically heal with scarring.2 Aphthous ulcers may present in clusters, rendering a herpetiform appearance to the lesions.4,6 The gingival lesions in the present case did not clinically resemble typical BD-associated aphthous ulcers.

Management of BD is highly variable depending on severity of disease and extent of involvement. Topical corticosteroids, such as fluocinonide gel 0.05% applied to the lesion(s) twice daily and which is often prescribed concomitantly with topical antifungal prophylaxis, such as clotrimazole troches 10 mg three times daily, may be useful for limited mucocutaneous disease. Systemic therapies, such as colchicine, dapsone, prednisone, and/or azathioprine, are used for controlling multi-organ involvement owing to BD.5,9 Newer agents, such as tumor necrosis factor (TNF)-alpha inhibitors (eg, etanercept) and novel immunomodulators (eg, apremilast), have demonstrated benefit in the management of BD.5,9

MMP is an autoimmune vesiculobullous disease with local and/or systemic involvement with incidence estimated to be 1.3 to 2 per million per year.2 MMP has no known geographical or racial predilection and predominantly affects individuals between 60 to 80 years of age with a female:male ratio of 2:1.10 Autoantibodies, such as IgG and IgA, are directed against targets in the basement membrane zone of the dermal-epidermal junction, most commonly bullous pemphigoid antigen 180 (BP-180, BPAg2) in MMP, causing subepithelial separation.10,11 Clinical manifestations of MMP include tense blister formation and ulceration, which can affect any mucosal surface and most often involves the oral mucosa (85% of cases), ocular mucosa (65% of cases), and nasal mucosa (up to 40% of cases).10,12 A common oral manifestation of MMP is peeling of the gingival epithelium (ie, desquamative gingivitis). Scarring typically occurs when MMP lesions heal, and scarring of the ocular conjunctiva may result in development of symblepharon, which may lead to blindness if left untreated.

Diagnosis of MMP incorporates clinical findings and histopathologic analysis, including biopsy of affected tissue for routine evaluation and normal tissue for DIF analysis.10,12 Routine tissue analysis (hematoxylin and eosin) typically demonstrates complete subepithelial separation with presence of eosinophils, neutrophils, and lymphocytes, while DIF reveals continuous linear deposition of IgG and/or C3 along the mucosal-submucosal interface in patients with MMP.2 Indirect immunofluorescence analyzing the patient's serum for circulating autoantibodies also may be used to aid in the diagnosis of MMP.10 Topical corticosteroids prescribed concomitantly with antifungal prophylaxis, as previously described, are considered first-line therapy for management of oral MMP lesions.10,12 Systemic therapy, which includes tetracycline, dapsone, corticosteroids, and/or biologics such as rituximab, may be necessary when oral MMP lesions are not responsive to topical therapy or there is widespread involvement of other tissues.10,12,13 Patients on any medications for MMP must be monitored closely for therapeutic benefit, medication side-effects, and disease progression. Patients with MMP should routinely undergo ophthalmologic evaluations.


This case illustrates the importance of understanding systemic disorders with mucocutaneous manifestations to establish an appropriate diagnosis and guide therapeutic management to ensure optimal clinical outcomes.

About the Authors

Eric T. Stoopler, DMD
Professor of Oral Medicine, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania; Fellowship in Dental Surgery of the Royal College of Surgeons of Edinburgh and England (FDSRCS); Fellowship inDental Surgery of the Royal College of Physicians and Surgeons of Glasgow (FDSRCPS)

Sahar Mirfarsi, DDS
Assistant Professor, College of Dental Medicine, Western University of Health Sciences, Pomona, California

Faizan Alawi, DDS
Associate Professor of Pathology, Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania

Thomas P. Sollecito, DMD
Professor and Chairman of Oral Medicine, Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania; Fellowship in Dental Surgery of the Royal College of Surgeons of Edinburgh (FDSRCSEd)


1. Rogers RS III. Pseudo-Behçet's disease. Dermatol Clin. 2003;21(1):49-61.

2. Stoopler ET, Sollecito TP. Oral mucosal diseases: evaluation and management. Med Clin North Am. 2014;98(6):1323-1352.

3. Mays JW, Sarmadi M, Moutsopoulos NM. Oral manifestations of systemic autoimmune and inflammatory diseases: diagnosis and clinical management J Evid Based Dent Pract.2012;12(3 suppl):265-282.

4. Wanat KA, Kim B, Rosenbach M. Multisystem diseases affecting the skin and eye. Clin Dermatol. 2016;34(2):214-241.

5. Mazzoccoli G, Matarangolo A, Rubino R, et al. Behçet syndrome: from pathogenesis to novel therapies. Clin Exp Med. 2016;16(1):1-12.

6. Hamburger J. Orofacial manifestations in patients with inflammatory rheumatic diseases. Best Pract Res Clin Rheumatol. 2016;30(5):826-850.

7. Dalvi SR, Yildirim R, Yazici Y. Behçet's syndrome. Drugs. 2012;72(17):2223-2241.

8. Davatchi F, Sadeghi Abdollahi B, Chams-Davatchi C, et al. The saga of diagnostic/classification criteria in Behçet's disease. Int J Rheum Dis. 2015;18(6):594-605.

9. Ozguler Y, Hatemi G. Management of Behçet's syndrome. Curr Opin Rheumatol. 2016;28(1):45-50.

10. Xu HH, Werth VP, Parisi E, Sollecito TP. Mucous membrane pemphigoid. Dent Clin North Am. 2013;57(4):611-630.

11. Schmidt E, Zillikens D. Pemphigoid diseases. Lancet.2013;381(9863):

12. Shetty S, Ahmed AR. Critical analysis of the use of rituximab in mucous membrane pemphigoid: a review of the literature. J Am Acad Dermatol. 2013;68(3):499-506.

13. Taylor J, McMillan R, Shephard M, et al. World Workshop on Oral Medicine VI: a systematic review of the treatment of mucous membrane pemphigoid. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120(2):161-171.

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