Atypical Intra‐Oral Lesions in a Young Epileptic Patient: A Case Report

ABSTRACT

This case report describes a 16‐year‐old boy with a history of generalized idiopathic epilepsy who developed severe intraoral lesions. Initial antiepileptic medications and the dosage adjustments to stabilize the disease triggered a recurrent grade 1 thrombocytopenia accompanied by debilitating oral lesions. Symptomatic treatment was provided to alleviate the patient's symptoms, drug adjustments were made by the neurologists, and a regular hematological monitoring was implemented. This case highlights the importance of recognizing rare adverse effects of anticonvulsant medications on the oral mucosa.

Dorsal surface of the tongue in a young epileptic patient showing depapillated erythematous areas, illustrating atypical intraoral lesions.

1. Introduction

Epilepsy, characterized by abnormal paroxysmal electrical activity of nerve cells in the cerebral cortex, is one of the most common neurological disorders worldwide [1]. Anticonvulsant medications, which form the cornerstone of epilepsy treatment, can cause numerous adverse effects. Hematological consequences (anemia, thrombocytopenia), neurological effects (tremors, drowsiness) [2], gastrointestinal, dermatological (drug‐induced skin reactions) [3, 4], and oral effects (gingival hypertrophy, drug eruptions, macroglossia) [5, 6, 7] are well documented. However, rare adverse effects on the oral mucosa are mostly not well known by dental practitioners, who are the first to be consulted for oral diseases.

The consequences can be serious if the symptoms affect quality of life or are misdiagnosed.

This case report focuses on a young epileptic patient who developed severe intraoral lesions during treatment with lamotrigine.

The aim is to highlight the importance of early detection of these rare adverse effects to improve the multidisciplinary management of patients.

2. Case History

A 16‐year‐old boy was referred to the oral dermatology consultation in December 2019 due to intraoral lesions that had appeared 4 months earlier and progressively worsened, affecting his ability to eat. The patient had a history of generalized idiopathic epilepsy diagnosed at the age of 14 and had previously experienced thrombocytopenia during prior epilepsy treatments. He also had long‐standing eating disorders, consuming only cheese, bread, and dairy products since the age of three while avoiding meat, fruits, and vegetables.

His epilepsy treatment initially included sodium valproate (1 g/day in two doses) and midazolam (10 mg as needed for seizures). However, the patient developed a grade 3 thrombocytopenia (39,000 platelets/mm³), detected during hospitalization for acute pyelonephritis in November 2018. Consequently, a change in medication to clobazam (5 mg in the morning and 10 mg in the evening) was attempted for 1 month. This modification triggered an increase in the platelet numbering but proved to be ineffective in controlling the seizures. In December 2018, his treatment was changed to lamotrigine, with gradually increased dosages (25 mg morning and evening in January 2019, 50 mg morning and 75 mg evening in July 2019, and 100 mg morning and evening in December 2019) (Figure 1).

FIGURE 1.

Timeline summarizing the patient's management.

In August 2019, while on lamotrigine (100 mg twice daily), the patient exhibited grade 1 thrombocytopenia (Common Terminology Criteria for Adverse Events) (platelet count: 88,000/mm³) (Figure 2), accompanied by increasingly debilitating oral lesions (Figure 1). These lesions were characterized by intense pain (VAS score 6), vesicles and tingling triggered by eating and chewing, leading to feeding difficulties and significant weight loss (3.8 kg in < 6 months) (Figure 3).

FIGURE 2.

Evolution of platelet count during the patient's drug treatment.

FIGURE 3.

Patient's weight progression shown on the body mass index curve for boys.

Given this clinical presentation and the appearance of a right submandibular lymphadenopathy, additional hematological investigations were initiated.

3. Methods (Investigations, Differential Diagnosis, and Treatment)

The patient subsequently presented at our clinic. Intraoral examination (Figure 4) revealed petechiae on the palatal mucosa (A), multiple sub‐centimeter ulcers along the bite line with surrounding erythematous areas localized in the buccal mucosa of the right cheek (B). The tongue was depapillated with diffuse erythematous macules (C) on the ventral and dorsal surfaces, homogeneous erosions (D, E), and occasional macroglossia were also found. Periodontal inflammation and gingival bleeding were also observed. The patient reported initial vesicular lesions that later ulcerated, although these were not observed during consultation. Additionally, the neurologist reported lingual petechiae in the addressing letter of December 2019.

FIGURE 4.

Intraoral photographs of the patient taken during the initial consultation in our oral dermatology department (early 2020 by Dr. Taihi). (A) Palatal petechiae. (B) Right buccal mucosa with sub‐centimetric ulcerations along the bite line. (C) Dorsal surface of the tongue, depapillated with erythematous areas. (D) Multiple erosions on the left ventral surface of the tongue. (E) Multiple erosions on the right ventral surface of the tongue.

Hematological investigations in January 2020 revealed a severe anemia and a grade 1 thrombocytopenia (97,000 platelets/mm³) associated with a thromboxane A2 pathway defect. Antibodies were not tested. However, platelet aggregometry was performed, showing a reduced response to collagen and arachidonate, and an absent response to ADP, with a normal response to U46619, suggesting a defect in the TXA2/aspirin‐like pathway. C‐reactive protein levels were within the normal range. The Platelet function analyzer (PFA) closure time was below the normal range with CEPI (139 s) and slightly prolonged with CADP (122 s).

As the patient had undergone circumcision at 1 year of age without hemorrhagic complications, an acquired thrombopathy was considered likely.

In February 2020, the patient experienced another epileptic seizure. As a result, lamotrigine (100 mg morning and evening) was supplemented with levetiracetam (750 mg twice daily). However, as epileptic seizure control did not improve, the dosage was initially increased to 1000 mg in the morning and 1500 mg in the evening before being gradually discontinued and replaced with lacosamide (150 mg twice daily), while continuing lamotrigine (100 mg morning and evening).

At the stage of the diagnostic workup, alternative aetiologies unrelated to pharmacological exposure were progressively excluded through detailed clinical assessments, physical examinations, and extensive laboratory investigations.

Considering the rapid weight loss, the development of right submandibular lymphadenopathy, and the association of petechiae with ulcerative mucosal lesions, a malignant hematological disorder—particularly leukemia—was initially considered. This hypothesis was promptly refuted based on the hematological and biochemical test results. Aphthous stomatitis was also excluded as the clinical features were not consistent with this diagnosis. Likewise, in the absence of pyrexia and given the chronicity of the lesions (persisting for nearly 5 months), viral infections like Herpes Simplex Virus (HSV) and Cytomegalovirus (CMV) were ruled out. A PCR test performed on a buccal swab was also negative for both viruses, further supporting this exclusion. Moreover, microbiological analysis did not provide evidence of a severe candidal infection.

Only minor hematological abnormalities, such as anemia and deficiencies in vitamins B9, B12, and D, were additionally identified.

Concerning the oral lesions, symptomatic treatments were prescribed, consisting of local anesthetic and antiseptic gels for ulcers, and a 7/100 soft toothbrush with analgesic toothpaste for periodontal care. Vitamin supplements and nutritional counseling were also suggested to address deficiencies related to the patient's restrictive diet. Regular follow‐ups and frequent correspondence with the neurology department have also been established.

4. Conclusion and Results (Outcome and Follow‐Up)

Since the last medication adjustments, thrombocytopenia/thrombopathy has been progressively managed, and no new epileptic seizures have occurred since April 2021. The four‐year follow‐up showed no further oral lesions and a significantly improved quality of life. Considering these findings and according to the Naranjo classification [8], it can be concluded that lamotrigine is probably responsible for the observed oral and platelet‐related adverse effects (Figure 5).

FIGURE 5.

Naranjo adverse drug reaction probability scale.

5. Discussion

This case report highlights the clinical presentation of a young patient with a history of epilepsy who developed severe intraoral lesions associated with underlying thrombocytopenia and thrombopathy related to drug adjustments.

Although some anti‐convulsant treatment effects on oral mucosa are widely known, such as gingival hyperplasia associated with phenytoin intake, rare effects associated with thrombocytopenia are not well defined, making this diagnosis more difficult to make.

In this case, the aetiological hypothesis for the observed oral mucosal lesions may be considered through two primary mechanisms. Firstly, these lesions could represent a direct adverse reaction to lamotrigine. Similar oral manifestations have been documented in the literature, with several case reports describing mucosal involvement following lamotrigine administration. Malčić et al. [9] reported a case involving a 35‐year‐old woman who developed extensive erosive lesions of the oral mucosa after initiating lamotrigine therapy—the same antiepileptic agent taken by our patient.

Mucocutaneous adverse effects—including oral ulcerations and petechiae—are well characterized and most frequently occur during the early titration phase, especially when dose escalation is rapid [10]. Such mucosal involvement is likely related to a lamotrigine‐induced hypersensitivity reaction. These reactions are typically immune‐mediated, ranging from mild mucosal lesions to severe conditions such as Stevens‐Johnson syndrome. The underlying pathophysiology involves complex immune responses, notably the activation of drug‐specific T lymphocytes [4, 10, 11]. In this case, the chronological correlation between the initiation of lamotrigine and the appearance of oral lesions further reinforces a drug‐induced etiology.

Alternatively, the lesions may be secondary to a hematological abnormality triggered by lamotrigine. Thrombocytopenia is a recognized, though rare, adverse effect of lamotrigine [12] and is listed in the drug's Summary of Product Characteristics. Lamotrigine‐induced thrombocytopenia is considered to be immune‐mediated, resulting from the formation of drug‐dependent antibodies that target platelets for peripheral destruction. This mechanism is similar to that described with other drug‐induced thrombocytopenias [13, 14] and typically presents within the first few weeks of therapy. In contrast, platelet dysfunction (thrombopathy) would be possible, potentially due to interference with intracellular signaling pathways or granule release mechanisms. These effects may lead to impaired primary hemostasis, even in the presence of normal platelet counts. This condition could account for the presence of petechiae, particularly on the palate and tongue.

However, to date, our case is the first reporting thrombopathy associated with thrombopenia induced by antiepileptic treatment.

The association between hematological disorders and antiepileptic treatments was also reported in other cases [12]. Pollack et al. [4] reported a case of a 9‐year‐old patient who developed erosions of the oral mucosa 2 weeks after starting phenobarbital. This patient also suffered from thrombocytopenia (associated with leukocytosis) and presented oral erosions. Finally, the authors made the diagnosis of polymorphic bullous erythema because of the more evocative clinical aspects: fever, generalized bullae, conjunctival involvement, photophobia, and remission after corticosteroid therapy.

Anticonvulsants are widely used to treat neurological disorders, including epilepsy, but their adverse effects on the skin and mucosa are common. Lack of awareness among dental practitioners for oral lesions delays diagnosis and management. In cases of severe oral lesions, this can lead to reduced quality of life, decreased adherence to medication, and even failure to detect severe drug reactions such as Stevens‐Johnson syndrome and toxic epidermal necrolysis [15]—serious conditions that can be fatal if curative treatment is delayed [3, 16, 17, 18].

Regarding long‐term use of antiepileptic drugs, some authors have suggested the existence of a “threshold effect,” beyond which cumulative toxicity on the platelet lineage may occur, linked to progressive alterations either at the medullary or peripheral level. Although this hypothesis remains debated, it raises the question of whether measuring plasma levels of lamotrigine might have been informative. Similarly, one might wonder whether the platelet toxicity initially induced by valproate—which was the first documented episode of platelet involvement in this patient—could have evolved into a latent process, later reactivated or exacerbated by lamotrigine.

Analyzing of the profiles of reporters of adverse events recorded in the National Pharmacovigilance Database (BNPV) in France in the 2020 annual report of the Agence Nationale de la Sécurité du Medicament (ANSM) reveals that reports by dentists accounted for only 0.07% of all declarations for this year (Figure 6) [19]. These practitioners should be encouraged to report drug‐related adverse effects to enhance knowledge of these rare oral reactions.

FIGURE 6.

Profiles of reporters of adverse event cases recorded in the French National Pharmacovigilance Database in 2020 [18].

Although not performed in this case, genetic testing could play a key role in preventing severe adverse drug reactions [20] caused by antiepileptic medications. Several studies have highlighted significant associations between specific Human Leukocyte Antigen (HLA) alleles (notably HLA‐B58:01 and HLA‐A31:01) and an increased risk of developing serious cutaneous reactions such as Stevens‐Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) [21]. For instance, HLA‐A31:01 has been linked to carbamazepine‐induced DRESS [22], while HLA‐B58:01 is associated with a significant risk of SJS/TEN [23, 24]. These conditions, with mortality rates ranging from 5% to 20% [22], represent a significant public health concern. Yet, genetic screening remains underutilized in clinical practice (15%) [20], despite its potential to tailor treatment choices to individual risk profiles (particularly in populations with a high prevalence of these alleles).

Rare oral adverse drug reactions are difficult to diagnose. Awareness and educational efforts must be directed toward dental practitioners, neurologists, general practitioners, and pediatricians to increase their awareness.

Author Contributions

Guillaume Loridon: conceptualization, data curation, formal analysis, methodology, project administration, software, supervision, validation, visualization, writing – original draft, writing – review and editing. Marine Mansencal: data curation, investigation, resources, software, visualization, writing – original draft. Mohamed Kadri: data curation, investigation, resources, software, writing – original draft. Ihsène Taihi‐Nassif: conceptualization, formal analysis, methodology, project administration, resources, supervision, validation, writing – original draft, writing – review and editing.

Ethics Statement

The authors have nothing to report.

Consent

Authors obtained written patient consent for the use of their photographs and medical information to be published online with the understanding that this information may be publicly available and discoverable via search engines.

Conflicts of Interest

The authors declare no conflicts of interest.

Loridon G., Mansencal M., Kadri M., and Taihi‐Nassif I., “Atypical Intra‐Oral Lesions in a Young Epileptic Patient: A Case Report,” Clinical Case Reports 13, no. 10 (2025): e70946, 10.1002/ccr3.70946.

Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.