BACKGROUND

A 12-year-old girl is referred to the general paediatrician with recurrent mouth ulcers. She has had three episodes in as many months, each lasting about a week, greatly limiting her intake of food and fluids for days and causing her to be so miserable that she cannot attend school or her favourite sporting and social activities. There is no apparent response to oral aciclovir therapy. Her parents are concerned as to the cause and about her falling behind at school should the episodes continue to recur.

Terminology tautology?

The term ‘aphthous ulcer’ is somewhat of a tautology: ‘aphtha’ originates from the Greek for eruption or ulcer; medical texts define them as ‘canker sores’ (not very illuminating in this day and age); Webster definitions dictionary descriptively states they are ‘roundish pearl-coloured specks or flakes in the mouth, lips etc, terminating in a white slough’1 describing thrush. Better then to use the terms recurrent aphthous stomatitis (RAS) or recurrent oral/mouth ulceration to signify what we recognise as a roundish breach in the integrity of the oral or lip mucosa.

What should you cover in the history?

Recurrent mouth ulceration is common, said to occur in between 1% and 10% of children.2 Most troublesome is usually the associated pain, such that oral intake may be so reduced that the child becomes dehydrated, but otherwise, there is typically little by way of systemic upset. While the majority of cases are idiopathic, they can be associated with an underlying systemic disease, including nutritional deficiencies and inflammatory conditions; so generalised complaints will be a clue. A focused history and examination are therefore crucial in order to reach a working differential diagnosis and to plan appropriate management.

The following points should be covered in the history.

• Onset, prodrome and disease pattern

Detailing the onset, progression and duration of individual lesions is important because it helps to distinguish localised aphthous ulcers from systemic causes of oral ulceration. In the absence of additional clinical features, recurrent ulcers that resolve with complete healing are suggestive of an idiopathic cause.

Age at first onset is important diagnostically; recurrent herpetiform ulcers are rare in children under the age of 5 years,3 while RAS associated with periodic fever syndromes such as periodic fever with aphthous ulcers pharyngitis and adenitis (PFAPA) tend to start before the age of 5 years.

Timing of ulcers emerging in relation to other symptoms can also be a guide to diagnosis. Ulcers appearing following a prodromal tingling and additional features such as generalised malaise may help in differentiating idiopathic or herpetic from non-herpetic lesions. Other prodromal features such as fever, coryza or lethargy before ulcers appear may indicate viral causes.

Focused examination in a child with RAS

Assessment for aetiological factors: Examination of skin, joints and assessment of growth should be undertaken with care to exclude serious underlying conditions such as autoimmune disease, malignancy and immunodeficiencies.

Lesions around the urethral opening may indicate Behcet's disease if infective causes (viral or bacterial) are excluded.

Idiopathic and herpetic ulceration: Once you have excluded systemic causes for recurrent aphthous ulceration, then it is important to make the distinction between idiopathic ulceration and herpetic ulcers.

Classification of ulceration by morphology: Lesions can be classified according to size, number, location, healing time and healing completeness; the categories are minor, major or herpetiform. Table 2 describes the features of each type of ulceration. Presence of clusters of intensely painful tiny lesions is suggestive of herpetic stomatitis. figures 1⇓–3 demonstrate different ulcer types.

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Figure 1

Major recurrent aphthous stomatitis on buccal mucosa.

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Figure 2

Minor recurrent aphthous stomatitis.

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Figure 3

Recurrent aphthous stomatitis on palate.

What investigations might you consider?

In the absence of systemic features, extensive investigation is rarely warranted; the child and parents can be reassured that the episodes are likely to be self-limiting. If episodes are severe, it might be helpful to substantiate your reassurance with basic tests, such as full blood count and blood film to exclude malignancy, neutropenia and infection, and viral swabs for culture or molecular diagnostics.

Where further investigation is warranted due to systemic features you may consider:

1. Haematological tests: Beyond the full blood count, haematinics may be useful to rule out nutritional deficiencies (iron, ferritin, folate, total iron-binding capacity, B vitamins, zinc and magnesium). Where there is suspicion of immunodeficiency, plasma immunoglobulins and lymphocyte subsets should be checked.

2. Serological testing: With systemic features, there should be a low threshold for excluding HIV infection (ensuring that both parent and child—as age/cognitively-appropriate—are advised of the intention to test beforehand). Additional tests such as erythrocyte sedimentation rate, antinuclear antibody and antineutrophil cytoplasmic antibodies should be considered to investigate autoimmune conditions. IgA anti-endomysial antibodies and IgA and IgG tissue transglutaminase antibodies may be useful if there is a history of poor weight gain or other clues such as diarrhoea, lethargy or abdominal distension that might point to inflammatory bowel disease.

3. Local infection tests: Swabs from the ulcer base (as tolerated) should be sent for bacterial and viral diagnostics (PCR, cultures etc.) where there is a suspicion of infectious aetiology: herpes simplex virus (HSV), tuberculosis, enteroviruses etc, although the yield is low. However, serology for Epstein–Barr virus and cytomegalovirus is rarely useful in determining the cause of RAS.

4. Histology: There is rarely need to biopsy ulcers, but unusual, persistent and recalcitrant lesions might warrant this, especially where there is suspicion of granulomatous conditions such as orofacial granulomatosis, tuberculosis or malignancy. Similarly, for typical but severe herpetiform ulcers, which are negative on infection screening, biopsy for tissue culture may be considered to confirm the diagnosis if the lesions are unresponsive to treatment.

What are the treatment options?

While the long-term management of recurrent ulceration depends on the diagnosis, acutely the principal goals are threefold:

1. to adequately manage any pain,

2. to ensure adequate hydration and

3. to promote healing.

Especially for infants and small children, careful assessment for decreased feeding, short-term weight loss and poor urine output are important. Dehydration can result insidiously, especially where reduced fluid intake is coupled with increased insensible losses from mouth breathing and drooling, particularly if the need for effective symptomatic relief is not appreciated.

Where an underlying cause is found, measures to prevent recurrence are considered where applicable, such as for herpes simplex ulceration or nutritional deficiencies.5

Evaluating severity and response to treatment

Disease severity scoring can be helpful to assess severity and response to treatment, and a recently devised system for ulcer severity scoring includes number, size, duration, ulcer-free period, site and associated pain.11 The reference has a useful clinical scoring tool for assessment of the disease course over time, such that the effectiveness of acute therapies, the need for prophylactic measures and its effect on the disease course can be evaluated with some objectivity over time. In younger children, where examination is difficult and a meaningful grading score is not achievable, observation of additional skin lesions and level of pain are important. Table 3 summarises the approach to children with RAS.