Oral ulceration and vesiculobullous conditions in the paediatric patient

Traumatic ulceration

Ulceration as a result of oral mucosal trauma is frequently reported in children. Similarly to adult patients, traumatic ulceration can be categorized into physical or chemical causes, with the former being the most common.⁴ Physical trauma is often caused by sharp teeth, mamelons, orthodontic wires or appliances, with the most common site of traumatic ulceration being the non-keratinized mucosa. Traumatic ulceration can often present following accidental biting of the tissues after local anaesthetic has been administered (Figure 1).⁵ Therefore, it is important to provide optimal post-operative instructions to the child and parent/carer.

Factitious trauma is self-harm to the tissues by the patient themselves and can present due to behavioural disturbances (Figures 2 and 3).⁶ This is more commonly seen in children and adolescents with the lower lip and tongue being the most frequently affected sites. Because it can pose a clinical challenge to diagnose factitious ulceration, a structured approach to establishing the cause and effect relationship is advised. Factitious trauma may be a sign of underlying psychological stress, therefore if required, the dentist needs to liaise with the general medical practitioner (GMP) to ensure that a multi-disciplinary approach is adopted to assess the patient's wellbeing.⁵

Ulcers that are traumatic in origin are most likely to heal or have significant resolution within 10–14 days of the cause being removed or habit stopped. Any ulcer lasting longer than this time requires onward referral and investigation.

Recurrent aphthous stomatitis

Recurrent aphthous stomatitis (RAS) is the most common oral mucosal disease, affecting up to 40% of selected groups of children.⁷ It usually presents in childhood or adolescence with a peak age of 10–19, and is believed to have a genetic predisposition, with up to 40% of patients reporting a family history.⁸ However, no specific human leukocyte antigen (HLA) haplotype has yet been identified.⁷

Clinical features of RAS include recurrent bouts of shallow, painful ulcers that are usually round or oval in shape with a yellowish centre, surrounded by an erythematous border.⁹ A young child may describe the pain from the ulceration as toothache. There can be single or multiple ulcers at any episode. The defining feature of aphthous ulceration is that the ulcers are recurrent, present in intervals from a few days to months with ulcer-free periods depending on severity. There are three recognized forms of RAS: minor, major and herpetiform.¹⁰

Minor RAS is the most common subtype representing 80% of children with RAS (Figures 4 and 5).⁷ It is characterized by its size being less than 10 mm across and affecting the non-keratinized mucosal surfaces. These heal in less than 14 days without scarring.¹¹ Major RAS is less common and comprises much larger irregular ulcers, measuring over 10 mm across (Figures 6 and 7). They affect any part of the oral mucosa, including keratinized tissue, last up to 12 weeks and cause scarring.⁵ Finally, herpetiform RAS presents as multiple small ulcers (1–2 mm), which can coalesce to form irregular ulcers (Figures 8 and 9).¹¹ Herpetiform ulcers are the least common in children, representing only 5–10% of those with RAS.¹²

The aetiology of RAS is unclear and is believed to be multifactorial with a number of precipitating factors. For children, these include trauma, stress, hormonal factors and exposure to certain foods.¹²

Preventive

To help prevent an episode of ulceration, any source of trauma should be removed, for example, sharp teeth should be smoothed and orthodontic wires covered with wax. Haematological deficiencies should be corrected with the appropriate supplementation. An ulcer diary is a useful tool for the child and their parents to complete.²¹ This may highlight factors such as precipitating foods, which should be excluded from the diet.

Symptomatic

Suppressive

Many RAS patients can be treated in primary care, with the GMP supporting investigations. For some patients however, following referral to oral medicine clinics, suppressive treatment is required and topical corticosteroids are prescribed with their use closely monitored. There is a range of different topical steroids that can be used in a variety of preparations, including sprays or mouthwashes. It is important that, if topical steroids are used as a mouthwash, the child is able to rinse and spit the solution.⁵ A further topical adjunct that can be used as a mouthwash is doxycycline, which may aid healing. This should only be used for children over the age of 12 owing to the effects of tetracycline on the developing dentition. For severe non-responsive cases, systemic corticosteroids, such as a short course of oral prednisolone, may be required to control a flare up. Steroid-sparing immunosuppressant agents may be needed because long-term use of systemic corticosteroids can cause multiple complications, including stunted growth, elevated blood pressure and a reduction of bone density.

Management needs to be tailored to the specific child's needs and, at the time of writing, there is no evidence of a superior therapy.²³ If an underlying systemic condition has been diagnosed, appropriate multidisciplinary care of the child is required via liaison between specialities and oral medicine. The treatment of the underlying condition will aid the management of the oral manifestations.

Herpes simplex virus

Many infections, mainly viral in origin (Table 3), can present with oral ulceration after the associated blisters break down, with herpes simplex 1 (HSV-1) being the most common precipitant. Ulcers caused by viral infection can present similarly to herpetiform RAS; however, they can be easily distinguished because they often do not recur, and are usually accompanied by systemic symptoms of fever and restlessness.

Primary HSV-1 infection is mainly regarded as an infection of childhood with the majority of affected patients aged 6 months to 5 years.⁵ In most cases, infection with HSV-1 is subclinical, or can cause a mild pharyngitis. Others present with primary herpetic gingivostomatitis, which involves numerous small vesicles, affecting the oral mucosa and lips followed by ulceration (Figure 14). The gingivae are erythematous, and other clinical features include malaise, fever and lymphadenopathy.²⁴ The oral lesions resolve after approximately 7–10 days, and management includes symptomatic relief with antipyretics/analgesics, rest and encouragement of fluid intake. Chlorhexidine gluconate mouthwashes and gels may reduce secondary infection, and some patients may require analgesic mouthwashes to reduce pain. Plain-ice popsicles or iced water may provide some relief. Antiviral medication is not usually required, but should be considered if the disease is severe, atypical²⁵ or if the patient is immunocompromised.

Approximately 5% of patients previously infected by primary HSV-1 can develop recurrent herpes simplex infections whereby the virus is reactivated.⁴ Triggers for reactivation include stress, exposure to sunlight and an immunocompromised state.²⁶ Recurrent HSV classically affects the mucocutaneous junction whereby vesicles rupture to form a crusted lesion, more commonly known as a cold sore. Recurrent HSV infections can also occasionally present intra-orally, usually affecting the hard palate or gingivae and are usually unilateral. Topical antiviral cream, for example 5% aciclovir, can be of benefit and has been shown to decrease the duration of lesion pain.²⁷ Systemic antiviral treatment, eg aciclovir suspension is helpful for frequent episodes of recurrent HSV ulceration.

Varicella-zoster virus

Varicella-zoster virus (VZV) is another member of the herpes virus family. The primary viral infection causes chickenpox (varicella), which is a highly contagious disease, common in childhood. Skin lesions are characterized by maculopapular, pruritic lesions, which are followed by vesicles. Oral lesions are similar to those caused by HSV, and systemic symptoms are also present. Supportive treatment is all that is required for a child with chickenpox. Antiviral medications may be considered for immunocompromised patients.²⁶ Reactivation of the virus presents as shingles (herpes zoster). Most patients with herpes zoster, however, are middle age or older, and therefore, it is less common in children. Initial symptoms include pain and tenderness along the distribution of the sensory nerve, and the trunk is the most common site to be affected. When the facial skin or oral mucosa is involved, the virus affects the peripheral branches of the trigeminal nerve and vesicular lesions erupt unilaterally. High-dose systemic antivirals are required and can accelerate healing,²⁸ in addition to symptomatic treatment of any intra-oral lesions. Assessment by an ophthalmologist is required to assess any corneal scarring if the ophthalmic branch is involved.

Epstein–Barr virus

Epstein–Barr virus (EBV) plays a role in the aetiology of infectious mononucleosis (glandular fever), but is also linked to several malignancies, including nasopharyngeal carcinoma and lymphomas (non-Hodgkin and Burkitt's).

Most EBV infections in younger children are asymptomatic or associated with mild symptoms, whereas infectious mononucleosis tends to affect adolescents. Symptoms include fever, lymphadenopathy, pharyngitis and fatigue.²⁹ Non-specific oral ulceration and palatal petechiae may also be present. The severity of symptoms can vary and the disease is usually self-limiting and supportive measures are sufficient.²⁴

Coxsackievirus

Hand foot and mouth disease is caused by coxsackie A viruses, usually type 16 and enterovirus 71. It is highly contagious and tends to occur in mini-epidemics, typically in primary school children.³⁰ Affected individuals display a macular rash with vesiculation on the palmar surfaces of the hands and the plantar surfaces of the feet, in addition to oral vesicles and ulceration. General malaise and discomfort accompanies the disease and the symptoms resolve after approximately 14 days. Isolation of children is required to avoid the spread of infection.

Herpangina is a further condition caused by coxsackie A viruses and predominately affects children. It is characterized by grey-white vesicular lesions that present on the posterior regions of the oral cavity, usually the soft palate, tonsillar or pharyngeal regions (Figure 15). The patient may also have mild to moderate malaise, headache or back pain. The condition is short-lived, lasting up to 1 week.

Paramyxovirus

Paramyxoviruses include the mumps orthorubulavirus and also the morbillivirus that causes measles, both of which are transmitted via direct contact and droplet spread.

Mumps can occur at any age, but most commonly affects children. It is usually characterized by a prodromal illness of malaise and pyrexia followed by bilateral swellings of the parotid glands, with unilateral swellings occurring less frequently.³¹ The duct of the parotid salivary glands appear inflamed, with trismus and tenderness in the glandular region. Diagnosis is made on clinical presentation and the management is symptomatic and supportive in nature. Complications of infection with mumps virus can lead to encephalitis, pancreatitis, orchitis and oophoritis.³²

Prior to vaccination, measles affected 95–98% of children under the age of 18.³³ It usually affects infants and young children, and presents systemically with a fever and nasal discharge, followed by a maculopapular rash which lasts up to 7 days. Blue-white pinpoint spots on an erythematous base can appear on the buccal mucosa. These lesions, known as Koplik's spots, usually appear prior to the skin rash and resolve after 2–3 days. Management is symptomatic and supportive because the disease is self-limiting. There are, however, serious complications resulting from infection, including encephalitis and pneumonia.

The measles, mumps and rubella (MMR) vaccination is included in the World Health Organization's ‘Expanded programme on immunization’ and, since its introduction, there has been a significant reduction in the incidence of the diseases worldwide.³⁴ Questions regarding the progress of the child's immunization programme should be asked as part of the medical history, with direction to the GMP if needed.

Bacterial infections

Tuberculosis is usually a pulmonary disease, but rarely there can be extra-pulmonary manifestations. Oral tuberculosis (TB) lesions are uncommon and usually present as a painless ulcer, due to secondary infection of the oral mucosa from pulmonary disease. Primary oral TB is extremely rare, but when present, it affects younger patients, and usually affects the gingivae or buccal sulcus accompanied by cervical lymphadenopathy.³⁵

Syphilis is also a rare systemic bacterial cause of oral ulceration. Acquired primary syphilis can present with a chancre affecting the lips or tongue. It is particularly important from a paediatric safeguarding perspective because of the risks of transmission during sexual abuse.³⁶

Pemphigus

Pemphigus is a rare group of autoimmune disorders caused by the development of autoantibodies, which target intra-epithelial or intercellular desmosomal complexes, leading to acanthylosis (loss of intercellular connections and separation of desmosomes, resulting in loss of cohesion between keratinocytes) and the formation of intra-epithelial bullae. Clinically this presents as blisters, followed by ulcers of the skin and mucous membranes, with the oral mucosa being the most frequently affected mucosal site.³⁷ Pemphigus usually affects middle-aged patients and is extremely rare in children. Similarly to adults, pemphigus vulgaris is the most common type of vesiculobullous disease in the paediatric patient and childhood cases accounts for approximately 1.4–3.7% of total cases of pemphigus vulgaris.³⁷ There is a significantly higher involvement of genital mucosa in children when compared to affected adults.³⁸ Pemphigus can be life threatening and urgent referral for investigation is required. Immunosuppression with steroids or steroid-sparing agents is the mainstay of treatment.

Pemphigoid

Pemphigoid is another group of autoimmune vesiculobullous conditions causing blistering of the mucocutaneous surfaces. However, unlike in pemphigus, the autoantibodies target proteins in the basement membrane, thus causing subepithelial bullae. Again this condition is rare in childhood because it is normally seen in elderly patients. Specialist investigation and steroid treatment is required with steroid-sparing immunosuppression being important in the longer term.³⁹

Dermatitis herpetiformis

Dermatitis herpetiformis presents with pruritic rashes and blisters affecting the skin of young adults and occasionally children. It is a subepidermal autoimmune disease that is strongly associated with gluten hypersensitivity because most patients have some abnormality of the jejunal mucosa.⁴⁰ Oral manifestations are uncommon, but can include erythematous areas or erosions, affecting the oral mucosa. A gluten exclusion diet should be part of patient management. Diaminodiphenyl sulfone (dapsone) is a sulphonamide antibacterial medication. It acts as an anti-inflammatory drug and is a valid therapeutic option.

Chronic bullous dermatosis of childhood

This is another rare immune sub-epidermal blistering disease and is on the spectrum between pemphigoid and dermatitis herpetiformis. At the electron microscopic level there is linear deposition of IgA autoantibodies seen at the basement membrane zone. This results in linear IgA disease in adults and chronic bullous dermatosis of children.⁴¹ It usually presents in pre-school children (average onset at age 5 years), there are skin and oral vesicles/bullae, or ulcers, and there can sometimes be scarring. Most patients respond to corticosteroids or dapsone.

Erythema multiforme

Erythema multiforme (EM) is an acute-onset disease, which is variable in its clinical features. It can present with mucosal (including oral) vesicles and bullae leading to ulceration and circumoral haemorrhagic crusting. Skin lesions include erythematous maculopapular rashes and a classical target lesion, especially on extremities. EM usually affects young adults with approximately 20% of cases affecting children.⁴² It is thought that EM is a hypersensitivity reaction to infective agents, particularly herpes viruses, drugs (eg sulphonamides, anticonvulsants, such as phenytoin, and rarely anti-pyretic analgesics have been reported), in addition to food containing benzoates. Diagnosis is usually made clinically and treatment is mainly symptomatic, antivirals (if the suspected aetiology is viral) and topical and systemic corticosteroids may be helpful.⁴³

Epidermolysis bullosa

This is a rare genetic group of blistering mucocutaneous conditions that are characterized by exacerbated skin and or mucosal fragility. It is caused by a mutation in genes coding for keratins in basal epithelial cells, collagens or other attachment proteins in the basement membrane. Over 30 subtypes have been reported, ranging in severity. The most severe forms can have variable survival of birth because of the severe sloughing of skin during passage through the birth canal and only those with milder forms survive to adulthood. Skin bullae form at birth or shortly afterwards owing to friction/mechanical trauma, or they can arise spontaneously. Peripheral limbs and pressure points are the most common sites affected, leading to scarring and limb deformity.⁴⁴ Intra-oral bullae, which rupture resulting in painful erosions, may occur in babies when feeding and simple toothbrushing can present a challenge. Patients often develop multiple carious teeth because of their soft and high calorific diet, added to the difficulties with mechanical cleaning of plaque.⁴⁵ A comprehensive and enhanced oral health preventive programme is essential. Special precautions and a multidisciplinary approach to complete dental treatment should be adopted, in addition to genetic counselling.