ORAL ULCERATION: AN OVERVIEW OF DIAGNOSIS AND MANAGEMENT PRIYA THAKRAR, SHAHID I CHAUDHRY Prim Dent J. 2016; 5(1): 30-33

and localised vasculitis results in ulceration ABSTRACT with a mixed inflammatory infiltrate of neutrophils, lymphocytes, plasma cells, Mouth ulcers are a common complaint by patients, with individuals regularly mast cells and macrophages. presenting to primary care practitioners for diagnosis and treatment. The aetiology and pathogenesis of oral ulceration is, however, both varied and complex. This Recurrent aphthous stomatitis is classified article highlights the importance of differentiating recurrent aphthous stomatitis phenotypically into minor, major and (RAS) in otherwise healthy individuals from recurrent oral ulceration (ROU) herpetiform subtypes predominantly secondary to known or unknown systemic disease. An overview of the diagnosis on whether the ulceration occurs on and management of such patients is provided as a framework to guide general keratinized or non-keratinized surfaces dental practitioners’ with clinical decision making on whether to treat or refer and the healing characteristics (i.e. to secondary care. scarring or non-scarring).

Minor This accounts for approximately 80% of cases of RAS, with patients often presenting with a history of oral ral ulceration is defined as ulceration having started in the second a break in the surface of the decade of life. Crops of two to five ulcers, Omucosal lining of the oral less than 10mm in diameter and oval mucosa. The aetiology and pathogenesis in shape, affecting the non-keratinized of oral ulceration is both varied and mucosa are typical (see Figure 1). Ulcers complex. A basic classification is shown heal within 14 days without scarring. in Table 1, and explained in further depth in this article. Major This subtype accounts for 10% of cases Recurrent aphthous of RAS and is defined by a few ulcers stomatitis (RAS) (typically one to five) affecting both Recurrent aphthous stomatitis (RAS) is keratinized and non-keratinized mucosal used to define recurrent episodes of surfaces and healing with scarring. The oral ulceration in the otherwise healthy latter is a result of the protracted acute-on- individual. It is a common condition chronic inflammatory response that occurs with a prevalence of around 20%. The and the depth of tissue destruction that onset of RAS is usually within the first ensues. Ulcers may exceed 10mm in three decades of life, but can persist diameter, take several weeks to resolve KEY WORDS into adulthood. 1 and are associated with significant Oral Ulceration, Recurrent Aphthous morbidity (see Figure 2). A major Stomatis, Behçet’s Syndrome, Reiter’s The aetiology of RAS is multifactorial, aphthous ulcer may mimic a squamous Syndrome, Therapy with antigenic sensitivity, genetic cell carcinoma in appearance. predisposition, hormonal influences, mucosal integrity, nutritional deficiencies Herpetiform 2,3 AUTHORS and stress being relevant. The Herpetiform aphthous ulceration is Priya Thakrar, BDS(Hons) underlying pathogenesis is a T characterised by recurrent crops of Specialty Doctor Oral Medicine lymphocyte cell-mediated immune multiple small ulcers which may look Guys Hospital, London SE1 9RT response involving the production of ‘herpetic’ in nature but do not have Shahid I Chaudhry, PhD MRCP (UK) tumour necrosis factor alpha (TNF- ) a viral aetiology (see Figure 3). They FDSRCS FDS (OM) RCS FHEA and interleukins. 4 In the pre-ulceratαive may involve any oral site and range Consultant in Oral Medicine, King’s College Hospital, Denmark Hill, London stage, the mucosa is characterised by from 0.5-3mm in diameter. These small the infiltration of lymphocytes. Oedema ulcers invariably coalesce to form

30 PRIMARY DENTAL JOURNAL TABLE 1 CLASSIFICATION OF ORAL ULCERATION

Recurrent oral ulceration • Recurrent aphthous stomatitis (RAS) • Oral Ulceration secondary to systemic disease • Dermatological Lichen planus Pemphigus vulgaris Mucous membrane pemphigoid (MMP) Erythema multiforme • Gastrointestinal Orofacial granulomatosis irregular areas of ulceration and, similar A patient should have one major and two 6 (OFG) to minor RAS, heal without scarring minor criterion to fulfil a diagnosis of BS. Crohn’s disease within 14 days. In reality, however, the diagnosis of BS Ulcerative colitis is not straightforward as the spectrum of • Haematological Oral ulceration and clinical presentation is complex and often Anaemia secondary Systemic Disease incomplete. 7 A multidisciplinary team to haematinic deficiencies Patients with systemic disease may is therefore required to adequately Neutropenia present with recurrent oral ulceration assess individuals for the condition. Leukaemia • Rheumatological (ROU). In such cases, the aetiology Vasculitides and pathogenesis is directly linked Oral disease in BS may be identical to Lupus erythematosus to the underlying medical disorder that of RAS. The ‘major’ phenotype is Mixed connective tissue and this should be used to define more common than in RAS, with patients disease the nature of the oral involvement. having more frequent episodes of Reactive arthritis (Reiter’s As previously discussed, the term ulceration and greater number of ulcers syndrome) aphthous ulceration should only be per crop. In addition, the soft palate and • Miscellaneous Behçet’s syndrome used in the context of RAS which relates oropharynx are more commonly involved, Drug-induced to healthy individuals who experience scarring is more pronounced and the MAGIC syndrome recurrent episodes of ulcers. ulcers are intrinsically more resistant PFAPA syndrome to treatment (see Figure 4). Sweet’s syndrome Behçet’s syndrome TUGSE Behçet’s syndrome (BS) is an auto- Reactive arthritis • Oral ulceration secondary inflammatory condition characterised (Reiter’s syndrome) to infectious disease by aphthous-like oro-genital ulceration This is an autoimmune condition • Viral and ocular disease, especially uveitis. characterised by an inflammatory arthritis Acute necrotizing It is a multi-system disorder which of large joints, inflammation of the eyes gingivitis (ANUG) Herpetic gingivostomatitis predominantly affects males and in the form of conjunctivitis or uveitis, Chickenpox usually presents in the third decade urethritis and mucocutaneous lesions. Infectious mononucleosis of life. There is a higher prevalence Individuals may present with aphthous- Herpangina in countries bordering the like oral ulceration. Hand, foot and mouth Mediterranean, especially Turkey, disease as well as in Japan. The racial Principles of diagnosis HIV infection distribution is indicative of a genetic To reach a differential and ultimately • Bacterial Tuberculosis predisposition with several tissue types a definitive diagnosis, a structured Syphilis (HLA-B12, HLA-DR2 and HLA-B51) approach to eliciting the pattern of • Fungal 5 being associated with the condition. ulceration is important. This should Deep mycoses include the following: The diagnosis of BS is based upon • Site, size and shape of ulcer(s). Single episode of ulceration the recognition of the following criteria. • Number of ulcers in one crop. • Trauma Major: • Frequency of ulcers, including • Burns Chemical • Recurrent oral ulceration. the number of ulcer-free days. Electric • Recurrent genital ulceration. • Duration. Radiation • Ocular disease. • Age of onset. Thermal • Cutaneous disease. • Any systemic features • Other at the time of ulceration. Iatrogenic Minor: Factitious • Sero-negative arthritis. In addition to this, a careful medical Non-accidental injury • Gastrointestinal disease. history and systemic enquiry should be Single persistent oral ulceration • Vascular complications. undertaken, making particular note of • Squamous cell carcinoma (SCC) • Central nervous system involvement. any dermatological, gastrointestinal,

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Figure 1: Figure 2: Recurrent aphthous stomatitis (minor) Recurrent aphthous stomatitis (major)

haematological, ophthalmological and First line therapy the reasons for doing so provided. rheumatological manifestations. Family First line therapies are: However, it is important for primary and drug histories should also be Mucosal protectants: care practitioners to be aware of the documented. • Carboxymethylcellulose (Orabase® use of medications in this way as they Protective Paste). will encounter patients commenced Special investigations may be needed on such therapy. to exclude underlying causes of oral Topical analgesics: ulceration such as anaemia to vitamin • 0.15% Benzydamine hydrochloride Listed in DPF: B12, folate or iron deficiency. Tissue (Difflam™ Oral Rinse or Spray). • 2.5mg Hydrocortisone biopsy must be performed if squamous • 1% Lidocaine ointment. muco-adhesive buccal tablets. cell carcinoma (SCC) is suspected. • 0.5mg soluble betamethasone Topical antimicrobials: phosphate tablets diluted in 5mls • Chlorhexidine digluconate of water as a mouthwash OD-QDS. Principles of management (Corsodyl® mouth rinse). RAS/ROU can be very painful, with • Dispersible doxycycline (100mg) ‘Off-licence’ preparations: a patient’s quality of life being severely as a mouthwash TDS. • 400mcg fluticasone propionate affected. 8 The principles of managing nasules (Flixonase®) diluted as a such individual’s involve diagnosing and Topical Corticosteroids: mouthwash in 5ml of water OD-TDS. treating the underlying cause, removing The intrinsic potency, concentration, • 50mcg fluticasone propionate aetiological factors and providing mode of delivery and frequency of (Flixonase®) nasal spray to symptomatic relief. Treatment should topical corticosteroid selected should ulcers TDS. ideally reduce the duration of ulcers by be based on the severity and pattern • 1% hydrocortisone ointment. facilitating healing and increasing the of ulceration and be tailored to the • 0.005% fluticasone propionate ulcer-free period thus minimising the individual depending on the manual ointment (Cutivate®). impact of the condition on the patient. dexterity and likelihood of compliance. • 0.05% clobetasol propionate The majority of these preparations are ointment (Dermovate®). There have been very few randomised used in an ‘off-licence’ or ‘off-label’ control trials for the treatment of RAS. way in the context of RAS/ROU and Second-line therapy A wide range of therapies have been cannot be prescribed by general Systemic corticosteroid and used, many of which have questionable dental practitioners. immunosuppressive treatment is efficacy. 9 None are curative and it is reserved for severe or refractory therefore important that any treatment Off-licence prescribing should usually disease due to the potential of adverse instituted is done so with the patient fully be instituted by consultant-level specialists side effects associated with these informed of the nature of the ‘agent’ familiar with the prevailing expert drugs. Such therapy should always be being prescribed and of any side-effects opinion. The patient must be informed consultant-led and cannot be prescribed or complications that may arise. of the drug being used off-licence and by general dental practitioners.

32 PRIMARY DENTAL JOURNAL Figure 3: Figure 4: Recurrent aphthous stomatitis (herpetiform) Scarring of the tongue secondary to Behçet’s syndrome

Azathioprine, clofazimine, colchicine, When to refer? Summary dapsone, levamisole, mycophenolate Individuals with the following Mouth ulcers are a common complaint mofetil, pentoxifylline and thalidomide presentation should be referred by patients. When assessing such have all been used in the management for a specialist opinion: individuals it is important to ascertain of RAS in an off-licensed way. However, • Single ulcers persisting for whether there is an underlying medical no single systemic agent has been longer than three weeks. condition that may account for the shown to be effective and should not be • Ulcers with an indurated border. ulceration. A careful structured history instituted without careful consideration. 9,10 • Recurrent oral ulceration of and examination will guide your initial uncertain aetiology. management. Referral to secondary As mentioned previously, general dental • Recurrent aphthous stomatitis care for clarification of the diagnosis practitioners will encounter patients on impacting on an individual’s and treatment is appropriate in cases such therapy and so an awareness of quality of life. where potent topical corticosteroids and these medications and their potential • Recalcitrant ulcers secondary systemic therapy is likely to be needed. side-effects is important. to known systemic disease.

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