Légeret and Furlano Italian Journal of Pediatrics (2021) 47:144 https://doi.org/10.1186/s13052-021-01097-2 REVIEW Open Access Oral ulcers in children- a clinical narrative overview Corinne Légeret1,2* and Raoul Furlano1,2 Abstract The prevalence of oral ulcers in children is reported to be 9%, however diagnosis of oral lesions can be challenging, being an unspecific symptom of several diseases. Differential diagnosis can range from classic infectious disease of childhood (e.g. herpangina, hand-foot-and-mouth-disease) over nutritional deficiencies, gastrointestinal disorders, inflammations (e.g. pemphigus vulgaris, lichen planus, mucous membrane pemphigoid) to side effects of medications (Stevens-Johnson Syndrome) or chronic dieseases (e.g. sarcoidosis, systemic Lupus erythematodes, familial Mediterrenean fever). Therefore, children with oral ulcers are treated by many different specialists such as dentists, family doctors, paediatricians, rheumatologists, haematologists, gastroenterologists and otorhinolaryngologists. A systematic literature search and a narrative literature review about the potential 48 diseases connected to oral ulcers were performed. According to the duration of symptoms and size of the lesions, a tabular overview was created to support the clinician in making a correct diagnosis, additionally different treatment options are presented. Keywords: Oral ulcers, Stomatitis, Children, Overview What is known Background The term ‘aphthous’ is derived from the Greek word 9% of all children are affected from oral ulcers aphthi, which is translated with ‘to set on fire’ or ‘to in- many different specialists see and treat children with flame’ and is thought to have been first mentioned by ulcers, which might be the reason that no uniform the philosopher Hippocrates to describe the pain associ- clinical guidelines exist ated with a frequent disorder of the mouth during this time (equals aphthous stomatitis [1]). The term ‘aph- thous stomatitis’ has been used interchangeably with What is new ‘aphthous ulcers’, but at present, the term aphthous sto- matitis is preferred [2]. It is a common disease, affecting we have created a narrative review of all differential about 20% of the general population, in children the es- diagnosis of oral ulcers in children timated prevalence is 9% [2]. Due to the high prevalence a tabular overview, according to duration and size of medical and dental professionals are repeatedly con- ulcers, is provided to support clinicians in making a fronted with paediatric patients complaining about oral correct diagnosis ulcers, but the diversity of causative factors can make a diagnosis challenging. Causes can range from infections to allergies, nutritional deficiencies, autoinflammation, * Correspondence: [email protected] 1University Children’s Hospital of Basel, Spitalstrasse 33, 4056 Basel, genetics or can be drug induced, therefore children with Switzerland oral ulcers are often treated by general paediatricians, 2University Children’s Hospital Basel, Spitalstrasse 31, 4055 Basel, Switzerland © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Légeret and Furlano Italian Journal of Pediatrics (2021) 47:144 Page 2 of 9 dentists, rheumatologist, allergologists and many more possible underlying infection, a background of an auto- specialists. immune process, immunosuppression or the involve- Although oral ulcers are common in childhood, there ment of the gastrointestinal tract, or whether it is just a is only sparse literature published describing the diag- local problem. Figure 1 provides a summary of all poten- nostic approach. Our aim was to introduce a narrative tial differential diagnosis of oral ulcers, whilst Table 1 review and create a decision flowchart for diagnosing gives a tabular overview of diseases according to the children with oral ulcers, supporting clinicians in the timely occurrence and size of the ulcers. diagnostic pathway. Traumas might be the easiest causes to be identified: They may be thermal, chemical or mechanical and arise Methods and results from direct application of heat, acidity or pressure. Re- A systematic literature search was carried out using petitive traumatic ulcers or bite injuries can be observed PubMed Science databases between January 1965 and in children with an Autism Spectrum disorder and intel- December 2020 using the following MeSH terms: ‘Oral lectual disability [7] or in the context of a seizure. Other ulcers’, ‘oral stomatitis’ and ‘children’. causes for repetitive local, traumatic ulcers can be ill- A total of 199 articles were published since 1965 in- fitting dental braces or aggressive toothbrushing. Pa- cluding case reports, cross-sectional studies, retrospect- tients with a nighttime habit of grinding teeth (bruxism) ive cohort studies and case series. Eighty one articles may also suffer from recurrent ulcers in the cheeks, were excluded because full text was not available any- whilst having other symptoms such as a damaged tooth more or being duplicates. Studies were restricted to enamel or a deformation of the tongue. Risk factors for humans and conference abstracts, and non-English lit- bruxism are excessive anxiety, beverages containing caf- erature was excluded. feine, mental retardation, hyperactivity and cerebral palsy [8]. Mucosal damage is the most common acute Classification side effect experienced by patients undergoing radiation An ulcer is defined as a complete breach of the epithe- therapy of the head and neck. Clinically it presents as lium, which becomes covered with a fibrin slough and erythema, mucosal atrophy and ulceration with or with- appears as a white lesion surrounded by erythema. If a out pseudomembranes [9]. mucosal lesion lasts over 14 days, it is considered Eosinophilic ulcer also known as traumatic ulcerative chronic, otherwise it is regarded as an acute ulcer [3]. granuloma, oral traumatic granuloma or traumatic ulcer Recurrent ulcers are defined as similar episodes with is a benign, self-limited oral condition which often oc- intermittent healing [4] and are described as recurrent curs on the lateral tongue but may also be seen in gin- aphthous stomatitis (RAS). RAS are subdivided into gival and other areas of the oral mucosa [10]. It appears minor, major and herpetiform aphthae [5]: Minor aph- as a sharp, punched-out ulcer, often in association with thae represent the most common variety of RAS (80– a trauma, particularly in young children when teething. 85%), which vary between 3 and 10 mm in size and typ- ically involve nonkeratinized oral mucosa (lips, cheeks, Viral/bacterial infections floor of the mouth, ventral and lateral surface of tongue). Herpetic gingivostomatitis is a manifestation of herpes During an episode of minor aphthae, a maximum of 5 simplex virus type 1 (HSV-1), it is the most common ulcers occur and last for 10–14 days before they heal viral cause of oral ulcers and occurs in children from 6 without scarring. months to 5 years. The initial sign is hyperemia of the Major aphthae are larger (exceeding 10 mm) and dee- oral and perioral mucosa, patients are typically febrile per as minor aphthae, they persist longer (over 6 weeks) with widespread superficial fluid-filled vesicles which and can leave a scar after healing. Clinically they impress rapidly break down to form a cluster of small ulcers of with substantial pain, fever, dysphagia and malaise. both keratinized and non-keratinized mucosa. On phys- 10% of RAS classify as herpetiform aphthae, the least ical examination, they may appear as flat, yellowish in common type. It is defined as multiple recurrent crops color and approximately 2-5 mm in size, they are quick of at least 10 (up to 100 ulcers may be present at the to bleed and heal without scarring within 18 days [11]. same time) small ulcers of 2-3 mm but may fuse into lar- Approximately a third of those patients will develop re- ger ulcers (as seen in viral infections, thus the name). current episodes of herpes labialis. Ulcers due to Herpes Furthermore, oral ulcers are classified as solitary and simplex virus 2 (HSV-2) look similar to those of primary multiple ulcerative lesions [6]. HSV-1 infections and are a consequence of orogenital or vertical (from mother to baby) transmission. Local and systemic etiologies of oral ulcers Herpangina affects mainly children under 5 years of A detailed history of the patient is essential to identify age, who present with sudden pharyngeal pain, fever, whether there are other symptoms present indicating a and multiple ulcers in the posterior pharyngeal wall. It is Légeret and Furlano Italian Journal of Pediatrics (2021) 47:144 Page 3 of 9 Fig. 1 Overview: Oral lesions mainly caused by enteroviruses, particularly coxsackie- disease is mostly seen in patients receiving immunosup- virus, and presents with epidemic peaks in the summer pression or HIV (human immunodeficiency virus) posi- months [12]. Hand-foot-and-mouth-disease (HFMD) is tive, they may develop recurrent aphthous oral caused by the same group of virus and clinically presents ulceration. with multiple oral blisters after a prodromal phase of Primary oral tuberculosis lesions are rare, but do occur fever and sore throat.