Aphthous Ulcers Clinical Presentation
- Author: Crispian Scully, MD, MRCS, PhD, MDS, CBE, FDSRCS(Eng), FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FSB, DSc, DChD, DMed(HC), Dr(HC); Chief Editor: Arlen D Meyers, MD, MBA more...
The 3 main clinical types of recurrent aphthous stomatitis (RAS) are as follows:
(1) Minor aphthous ulcers (MiAUs, 80% of all RAS)
(2) Major aphthous ulcers (MjAUs)
(3) Herpetiform ulcers.
However, any significance of these distinctions is unclear (ie, they could just be 3 distinct disorders). Diagnosis is based on history and clinical features.
Characteristics of MiAUs (ie, Mikulicz ulcers) include the following:
- They occur mainly in persons 10-40 years of age.
- They often cause minimal symptoms.
- They are small round or ovoid ulcers 2-4 mm in diameter. (MiAUs are round or ovoid in most situations but are often more linear when in the buccal sulcus, a common site.)
- They have an ulcer floor that is initially yellowish but assumes a gray hue as healing and epithelialization proceeds.
- They are surrounded by an erythematous halo and some edema.
- They are found mainly on the nonkeratinized mobile mucosa of the lips, cheeks, floor of the mouth, sulci, or ventrum of the tongue; they are uncommonly seen on the keratinized mucosa of the palate or dorsum of the tongue.
- They occur in groups of only a few ulcers (ie, 1-6) at a time.
- They heal in 7-10 days.
- They recur at intervals of 1-4 months.
- They leave little or no evidence of scarring.
Characteristics of MjAUs (ie, Sutton ulcers, periadenitis mucosa necrotica recurrens [PMNR]) include the following:
- They are larger, of longer duration, of more frequent recurrence, and often more painful than MiAUs.
- They are round or ovoid like MiAUs but are larger and associated with surrounding edema.
- They reach a large size, usually about 1 cm in diameter or even larger.
- They are found on any area of the oral mucosa, including the keratinized dorsum of the tongue or palate.
- They occur in groups of only a few ulcers (ie, 1-6) at one time.
- They heal slowly over 10-40 days.
- They recur extremely frequently.
- They may heal with scarring.
- They occasionally are found with a raised erythrocyte sedimentation rate or plasma viscosity.
Characteristics of herpetiform ulceration (HU) include the following:
- They are found in a slightly older age group than the other RAS.
- They are mainly found in females.
- They begins with vesiculation that passes rapidly into multiple, minute, pinhead-sized, discrete ulcers.
- They involve any oral site, including the keratinized mucosa, increase in size, and coalesce to leave large round ragged ulcers.
- They heal in 10 days or longer.
- They are often extremely painful.
- They recur so frequently that ulceration may be virtually continuous.
Most patients with RAS appear to be otherwise well, but a minority have etiologic/precipitating factors that can be identified by the history. These factors may include the following:
- Dentifrices containing sodium lauryl sulfate
- Cessation of smoking
- Menstrual cycle association
- Food allergy
Aphthous-like ulcers may appear in the following diseases and states:
- Hematinic deficiency (eg, iron, folate, vitamin B-12)
- Celiac disease
- Crohn disease
- Behçet syndrome, which may include genital, cutaneous, ocular, or other lesions (The mouth ulcers in Behçet syndrome often mimic major aphthae, with frequent episodes and long duration to healing.)
- Immunodeficiencies such as human immunodeficiency virus (HIV) infection, and neutropenia (Ulcers appearing on a regular 3-week cycle may indicate cyclic neutropenia.)
- Auto-inflammatory syndromes, such as periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) in children
- Malignancy (Ulcers appearing for the first time in an older individual may reflect underlying systemic disease [eg, colonic carcinoma with chronic hemorrhage].)
- Drug use (eg, nicorandil, NSAIDs, others)
- Sweet syndrome, a rare immunologically mediated condition that belongs to the group of neutrophilic dermatoses and must be differentiated, particularly from Behçet disease
- Sweet syndrome is characterized by red-brown plaques and nodules that are frequently painful and occur primarily on the head, neck, and upper extremities.
- Patients often also have neutrophilia and fever and may have oral ulceration.
RAS ulcers are recurrent small, round, or ovoid ulcers with circumscribed margins, erythematous haloes, and yellow or gray floors. No specific investigations exist for RAS; the other causes of recurrent mouth ulceration noted above, should be excluded.
Some RAS cases involve a familial and genetic basis; approximately 40% of patients with RAS have a familial history, but inheritance may be polygenic with penetrance dependent on other factors.
Most relevant studies have found hematinic (eg, iron, folic acid, vitamin B-12) deficiencies in as many as 20% of patients with recurrent ulcers. In addition, deficiencies of vitamins B-1, B-2, and B-6 have been noted in some patient cohorts.
The previously proposed association between recurrent ulcers and celiac disease (gluten-sensitive enteropathy [GSE]) is tenuous, despite some evidence that the haplotype of HLA-DRW 10 and DQW1 may predispose patients with GSE to RAS.
Hypersensitivity reactions to exogenous antigens other than gluten do not have a significant etiologic role in RAS, and associations with atopy are inconsistent. Moreover, a consistent association between aphthous ulceration and psychological illness, zinc deficiency, or sex hormone levels is unlikely.
Local physical trauma may initiate ulcers in susceptible people, and RAS is uncommon where mucosal keratinization is present or in patients who smoke tobacco.
Various microorganisms have been examined for a causal association. Latterly, Helicobacter pylori has been detected in lesional tissue of ill-defined oral ulcers, but the frequency of serum immunoglobin G (IgG) antibodies to H pylori is not increased in RAS. On the other hand, a study by Gülseren et al indicated that H pylori may play a role in the etiology of RAS. The rapid urease test was used to find the bacterium in dental plaque samples from 34 of 38 patients with RAS (89.5%), compared with 24 of 43 controls (55.8%).
A study by Hijazi et al also suggested that the development of idiopathic RAS is associated with changes in the mucosal microbiome. The investigators found, for example, that species of the bacterial family Porphyromonadaceae related to periodontal disease were more abundant in ulcerated areas in the mucosae of patients with RAS than in the mucosae of healthy controls. In contrast, species of the bacterial family Streptococcaceae that are associated with oral health were more abundant in the healthy controls than in the ulcerated areas of RAS patients.
Similarly, a study by Kim et al suggested that dysbiosis contributes to the development of RAS. In an analysis of the oral mucosa and saliva from RAS patients and controls, the investigators found that the patients with RAS had reductions in healthy core microbiota and increases in rare microbial species. These changes included decreases in Streptococcus salivarius and increases in Acinetobacter johnsonii.
Little evidence suggests an etiologic association between viruses and RAS. Human herpesvirus (HHV)–6 and HHV-7 DNA has not been demonstrated in RAS, but HHV-8 DNA is present in HIV-related oral ulcers.
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