Diagnosis and treatment
Oral ulcers: Differential diagnosis and treatment
Úlceras orales: diagnóstico diferencial y tratamiento
Mayra Schemel-Suárez, José López-López, Eduardo Chimenos-Küstner
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Facultad de Odontología, Universidad de Barcelona, Spain
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PFAPA, <span class="elsevierStyleItalic">periodic fever, aphtae, pharyngitis and cervical adenopathies</span>.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Oral ulcers are usually very painful and are a frequent reason for consultation. Infectious processes, neoplasms, gastrointestinal diseases, blood disorders, rheumatic diseases, immunological diseases, trauma lesions and other factors are among its causes.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">1,2</span></a> An appropriate differential diagnosis is necessary due to the various factors that can cause them.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Ulcers can be primary, when not preceded by a previous lesion (in the case of canker sores) or secondary (aphthoid) to trauma or a ruptured blister or vesicle.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">canker sores</span>, described by Hippocrates in 400 BC, are usually located in the oral mucosa (lips, tongue, floor of the mouth, soft palate, uvula, etc.) and pharyngeal mucosa; they can also be observed in the genital region.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">4</span></a> The primary lesion is neither a vesicle or a blister, but direct ulceration due to epithelial necrosis which exceeds the basement membrane, exposing nerve endings and causing discomfort or pain.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">2,4</span></a> If they become large, they can leave a scar after healing. Clinically, they present with painful ulcerations, of different sizes, round or oval and clean edges. The necrotic fundus is covered by a yellowish-white fibrinous exudate and its periphery is framed by a border or red halo of hyperaemic origin and have a tendency to relapse.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">4</span></a> The <span class="elsevierStyleItalic">aphthoid</span> are secondary ulcers, usually infectious, which begin with a major lesion: vesicles or vesicular-pustules, clinically and histologically different from the true canker sores. Other aphthoid ulcers have a trauma-related origin, with acute or chronic progression, in response to a repeated and persistent mucosal trauma. Some tend to chronicity and may be recurrent (e.g. herpetic stomatitis).<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">5</span></a> The <span class="elsevierStyleItalic">aphtosis</span> are certain processes that occur with canker sores or aphthoid ulcers and usually with systemic repercussions. In these processes, ulcers may be located in the oral mucosa and in others such as genital, anal or conjunctival.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Differential diagnosis</span><p id="par0020" class="elsevierStylePara elsevierViewall">The first step in making a correct differential diagnosis is the medical record. The patient's medical history provides essential data to identify the type of lesion. The medical history (family and personal history of systemic or skin disease, drugs, allergies, food and toxic habits) should be investigated.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">1</span></a> The following should be established with the case history questioning: time of appearance of the first lesion; progression period or, if recurrent, duration of lesions; affected oral mucosa area; coexistence of similar or concomitant lesions in other areas (genital, skin); the presence of accompanying symptoms (pain, fever, burning); association with any traumatic lesion of the oral mucosa or some other situation (stress, menstrual cycle, smoking cessation); and if there are any medications that relieve symptoms.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The clinical examination will complete the case history, through a systematic inspection of the oral mucosa. This step should take into account the type of lesion (vesicles, blisters, ulcers), number of lesions, size, appearance, location (keratinized mucosa, nonkeratinized mucosa or both), and their relationship with sharp teeth edges or prosthesis.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">After collecting all this data, a presumptive diagnosis of the lesion can be established. Its confirmation may require additional procedures or tests (blood tests,<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> biopsy<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">3,7</span></a>). <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a> show the main clinical features behind oral ulcers. These should prompt a differential diagnosis.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Treatment</span><p id="par0035" class="elsevierStylePara elsevierViewall">Depending on the established diagnosis and according to the data collected in the clinical history, the most appropriate treatment may be considered. We pay special attention to therapy against canker sores, which stand out as being the most frequent.</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Treatment of aphthoid ulcers</span><p id="par0040" class="elsevierStylePara elsevierViewall">In the case of viral ulcers, treatment is symptomatic (analgesics and antipyretics) to reduce fever and pain control, as this type of lesion has a short duration and resolve spontaneously. An adequate fluid intake is very important, especially in children, and a bland diet if chewing is limited by pain.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a> Mouthwashes with local anaesthetics can also be used as adjunctive therapy.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Treatment of specific ulcers</span><p id="par0045" class="elsevierStylePara elsevierViewall">If the presumptive diagnosis of an ulcer caused by <span class="elsevierStyleItalic">Treponema pallidum</span>, an incisional biopsy and blood tests should be performed, including VDRL, RPR and FTA-ABS. If the diagnosis is positive, the indicated antibiotic treatment should be established.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a> In the case of a suspected ulcer infection by <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>, one incisional<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a> biopsy will be taken and if the histopathological diagnosis is suggestive of tuberculosis, the study of the patient should be completed with adequate complementary examinations (PPD, culture and chest radiography), so that the appropriate treatment can be established.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">10,11</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Treatment of traumatic ulcers</span><p id="par0050" class="elsevierStylePara elsevierViewall">In oral ulcers caused by traumatic factors, treatment will depend on the identification of the irritant agent and its elimination (polishing of sharp cusps, adjustment of prosthesis, correct brushing techniques, change in oral hygiene products for less irritating ones, etc.).<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Treatment of neoplastic ulcers</span><p id="par0055" class="elsevierStylePara elsevierViewall">If a neoplastic ulcer is suspected, an incisional biopsy of the lesion should be performed; if the histopathological result confirms the suspected diagnosis of squamous cell carcinoma, the patient will be immediately referred to his/her centre, where different specialists (oncologists, oral and maxillofacial surgeons, radiation therapists, chemotherapists, dentists, psychologists and nutritionists) will provide the most appropriate treatment according to the stage (TNM) of the tumour.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Treatment of canker sores</span><p id="par0060" class="elsevierStylePara elsevierViewall">These are usually part of a recurrent clinical condition, known as recurrent aphthous stomatitis (RAS). Faced with this pathological process, a complete blood analysis is recommended, including blood count, folic acid, ferritin and vitamin B<span class="elsevierStyleInf">12</span>, to rule out systemic causes or underlying diseases such as vitamin deficiencies, gastrointestinal diseases or immune deficiencies (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) and, eventually treat them.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">5,13</span></a> The treatment to prescribe (which could be extrapolated largely to other types of ulcers, such as those described above) depend on the severity and painful symptomatology of the disease, the frequency of episodes with ulcers and patient tolerance to medication (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> It often begins with topical treatment; the first line of treatment includes antiseptic and anti-inflammatory/analgesic drugs. Chlorhexidine 0.12% in mouthwashes or gel is very useful. The duration of the treatment will last until the resolution of the lesions (usually a few days). Triclosan can also be used in gel or mouthwashes, providing an analgesic, anti-inflammatory and antiseptic effect.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> Some authors propose the use of amlexanox 5% (oral patches, tablets or adhesive pastes) as a topical treatment of ulcers. It is an anti-inflammatory and antiallergic drug, which inhibits the formation and release of histamine and leukotrienes from mast cells, neutrophils and mononuclear cells in the affected area. Several studies have shown it accelerates healing of ulcers and resolves erythema, pain and lesion size in the RAS.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">13,14</span></a> Topical antibiotics are another treatment option. Among them, mouthwashes with tetracycline hydrochloride, minocycline 0.2% or doxycycline in adhesive base, which help improve the painful symptoms of patients.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">13,15</span></a> Topical glucocorticoids are very useful in the treatment of RAS. The most popular are, in order, from lowest to highest potency: triamcinolone acetonide, fluocinolone acetonide, and clobetasol propionate, in the appropriate proportion, depending on lesion severity.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> These 3 drugs can be administered as ointments on adhesive excipient when lesions are localized or mouthwashes in aqueous or aqueous-alcoholic solutions when lesions are diffuse or very numerous.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">16</span></a> Triamcinolone acetonide is particularly indicated in patients with small and moderate erosions. Fluocinolone acetonide provides a medium to high potency and is used in patients with more aggressive lesions. Finally, clobetasol propionate is reserved for major lesions. In this context, it is considered a pre alternative to prescribing systemic glucocorticoids. To help with the healing process it is advisable to keep the medication in direct contact with the lesion as long as possible, not eating or drinking during 20<span class="elsevierStyleHsp" style=""></span>min after drug application, avoiding touching the treated area. If the drug is administered in the form of mouthwashes, keep the solution in the mouth during the specified time without swallowing.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> Another therapeutic option for RAS is the systemic treatment, when the topical treatment is not effective because of the lesion severity degree. Glucocorticoids are the first choice. Prednisone has been used, achieving the disappearance of pain and re-epithelialization of lesions during the first month of treatment. The long-term treatment with glucocorticoids can have side effects. Immunomodulators such as thalidomide are also used as a treatment for RAS, obtaining good results in the remission of lesions, but with many side effects such as teratogenicity, polyneuropathy, drowsiness, constipation, increased appetite, nausea and stomach pain.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">In the case of ulcers associated with other syndromes (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>), measures (topical treatment) to alleviate the symptoms will be adopted and patients will be referred to complete their study.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">In summary, oral ulcers occur with great frequency in the population and can be the first sign of a systemic disease. These lesions can affect the patient's daily life, as they are very painful, they hinder normal chewing, swallowing and speaking, and is thus a frequent reason for consultation. Because they can have multiple causes, it is very important to emphasize performing a correct case history, taking into account the clinical characteristics of the ulcer, its location and progression time. In this way it will be possible to make a differential diagnosis, which will contribute to an effective treatment for the patient.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflict of interests</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Differential diagnosis" ] 2 => array:3 [ "identificador" => "sec0015" "titulo" => "Treatment" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Treatment of aphthoid ulcers" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Treatment of specific ulcers" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Treatment of traumatic ulcers" ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Treatment of neoplastic ulcers" ] 4 => array:2 [ "identificador" => "sec0040" "titulo" => "Treatment of canker sores" ] ] ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interests" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-03-14" "fechaAceptado" => "2015-04-27" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Schemel-Suárez M, López-López J, Chimenos-Küstner E. Úlceras orales: diagnóstico diferencial y tratamiento. Med Clin (Barc). 2015;145:499–503.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2052 "Ancho" => 3244 "Tamanyo" => 413226 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Diagram for clinical diagnosis of oral ulcers. EBV, Epstein–Barr virus; HSV, herpes simplex virus; VZV, varicella-zoster virus.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1854 "Ancho" => 3240 "Tamanyo" => 384924 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Diagram for clinical diagnosis of recurrent oral ulcers. PFAPA, <span class="elsevierStyleItalic">periodic fever, aphtae, pharyngitis and cervical adenopathies</span>.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">RAS, recurrent aphthous stomatitis.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hereditary \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The presence of canker sores in parents significantly influences the risk of RAS development in their children.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a> Genetic risk factors include several polymorphisms in the DNA of the human genome<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">18</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nutritional deficiencies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Low blood levels of iron, folate, zinc, or vitamins B<span class="elsevierStyleInf">1</span>, B<span class="elsevierStyleInf">2</span>, B<span class="elsevierStyleInf">6</span> and B<span class="elsevierStyleInf">12</span>. These deficiencies can be secondary to other diseases such as malabsorption syndrome or gluten sensitivity, with or without enteropathy<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hormonal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The levels of sex hormones in the blood can exacerbate the frequency of RAS mainly in the luteal phase of the menstrual cycle and during the menopause, while remissions often occur during pregnancy and in women taking contraceptives<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Local trauma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In individuals predisposed to RAS, lesions in the oral mucosa will appear shortly after mechanical irritation of the area 6. There is a low incidence of RAS in smokers, this may be due to hyperkeratinisation of the oral mucosa in response to tobacco consumption, making it less sensitive to irritation and trauma<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stress \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Stress triggers episodes of RAS but does not influence their duration<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">It has been observed that the RAS symptoms are more severe in patients infected with Helicobacter pylori compared to those that are not. The action of the bacteria in the onset and recurrence of canker sores will be associated with anaemia caused by gastric diseases positive to Helicobacter pylori.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1037625.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Factors that may influence the onset of recurrent aphthous stomatitis.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drugs \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Posology \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Topical</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chlorhexidine 0.12% in mouthwashes or gel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Three times a day until the ulcers disappears \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Triclosan gel or mouthwashes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Three times a day until the ulcers disappears \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Amlexanox 5% (oral patches, tablets or adhesive pastes) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Two to four times a day until the ulcers disappear \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Doxiciclina 100<span class="elsevierStyleHsp" style=""></span>mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dissolve in 10<span class="elsevierStyleHsp" style=""></span>ml of water, rinsed 4 times daily for 3 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Triamcinolone acetonide (aqueous solution or orabase) at concentrations of 0.05–0.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Applied 3–10 times a day for 3–5<span class="elsevierStyleHsp" style=""></span>min, until the ulcers disappear \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fluocinolone acetonide (or aqueous solution orabase) in concentrations 0.025–0.05% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Applied 3–10 times a day for 3–5<span class="elsevierStyleHsp" style=""></span>min, until the ulcers disappear \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Clobetasol propionate (aqueous or orabase solution) 0.025% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Applied 3–10 times a day for 3–5<span class="elsevierStyleHsp" style=""></span>min, until the ulcers disappear \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Systemic</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Prednisone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25<span class="elsevierStyleHsp" style=""></span>mg dose/day at the beginning, followed by a dose reduction for the next two months \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Thalidomide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50–100<span class="elsevierStyleHsp" style=""></span>mg dose/day for 2–3 months \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Levamisole \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">150<span class="elsevierStyleHsp" style=""></span>mg dose a day, 3 times a week, for 6 months \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1037626.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Treatment of recurrent aphthous stomatitis.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PFAPA syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Acronym for <span class="elsevierStyleItalic">periodic fever, aphtae, pharyngitis and cervical adenopathies</span>. It is one of the causes of periodic fever in paediatrics and is characterized by recurrent febrile episodes (every 3–6 weeks), accompanied in 65–80% of cases of sore throat, canker sores and cervical lymphadenopathies<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Behcet syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Inflammatory, multigenetic, systemic disorder of unknown aetiology. Clinical features include oral and genital ulcers, ocular inflammation, skin lesions as well as joint, vascular, neurological, pulmonary, gastrointestinal and genitourinary manifestations<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">23</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sweet syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Disorder characterized by fever, erythematosus infiltrative type skin lesions, neutrophilic leukocytosis and dense dermis infiltration of mature neutrophils<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1037624.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Syndromes associated with oral ulceration.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib0125" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Úlceras orales" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. 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