Isolated Palatal Ulcer Induced by Methotrexate: A Case Report

M ethotrexate is an antimitotic drug that affects by competition with dihydrofolate reductase in the DNA synthesis.¹ It has anti-inflammatory and anti-arthritic effects by decreasing the proliferation of lymphocytes and changing the polymorphonuclear chemotaxis.² It acts as an anti-cancer drug in higher doses and as an anti-rheumatoid agent in lower doses.³ One study showed that methotrexate damages the epidermis by decreasing the proliferation of keratinocytes.⁴ Skin and mucous membrane reactions associated with methotrexate treatment were reported in previous studies. The adverse cutaneous effects of methotrexate are commonly seen during anti-cancer chemotherapies.⁵ Cutaneous ulcerations, erosions of psoriatic plaques, and skin ulcers on limbs caused by methotrexate were reported previously.^3,6–10 However, few studies about oral ulcerations induced by methotrexate are available.^11,12 The authors present a case of an isolated large ulceration on the palatal mucosa induced by methotrexate during the treatment of rheumatoid arthritis without psoriasis. In the literature, palatal ulceration has not been reported as an adverse effect of methotrexate. Case Report A 48-year-old woman was diagnosed with seronegative arthritis. She had no personal or familial history of psoriasis. She was treated with only methotrexate (25mg weekly) in the Department of Rheumatology. After four months, a nonpainful ulceration, which was slowly spreading, appeared on her palate. She was referred to the Department of Plastic Surgery. In the initial examination, a 2cm x 2.5cm dimension mucosal ulcer with a necrotic crust was seen on her palate (Figure 1). Bone was exposed in the center of the palatal ulcer. There were no other mucosal ulcers or oral lesions in her mouth. A biopsy was taken from the margins of the ulcer; the result was nonspecific inflammatory granulation tissue. Methotrexate toxicity was suspected, and this therapy was stopped by the Department of Rheumatology. The ulcer was curetted under local anesthesia. Topical wound care was carried out using an antimicrobial oral spray. The patient was followed up by the Departments of Plastic Surgery and Rheumatology. The wound bed granularized, and the bone exposure disappeared in four weeks. Epithelization was complete in six weeks. The patient was given two grams of vitamin C daily and soft foods without particles during wound healing. Discussion Oral and gastrointestinal ulcerations are signs of methotrexate toxicity.⁵ The most frequent mucocutaneous reactions to methotrexate treatment are ulcerations of the oral mucosa, burning sensation of the skin, photosensitivity, acral erythema, erythema multiforme, urticaria, and vasculitis.³ Skin ulcerations within psoriatic plaques on limbs were reported as an adverse effect of methotrexate.¹³ Several cutaneous ulcers had been reported in cases of non-psoriatic arthritis as a sign of drug toxicity in patients who were taking 25mg to 125mg of methotrexate weekly.^8,14 The most common risk factor in toxicity was a high dose of methotrexate and concomitant use of non-steroidal anti-inflammatory drugs. Other frequent risk factors for toxicity were renal failure, infection, and old age.³ The palatal mucosal ulceration in the authors’ case was probably caused by the high dose of methotrexate (25mg/week). She was 48 years old and had no renal diseases or signs of systemic infections. She was not taking non-steroidal anti-inflammatory medication, and no other risk factors were noted. Solitary drug-induced oral ulcers are resistant to conventional treatments but heal rapidly after cessation of the responsible drug.11 In this case, the mucosal ulcer healed upon the termination of methotrexate therapy.^3,9 Conclusion In summary, a high dose of methotrexate with additional anti-inflammatory drugs may cause mucosal ulcerations. It is considered that multiple drug interactions and individual properties of patients may have a role in methotrexate toxicity. To the authors’ knowledge, this is the first case of non-psoriatic arthritis where an isolated large ulceration on the palate was induced by methotrexate. The histopathological mechanism of the mucocutaneous ulcerations secondary to methotrexate therapy may be multifactorial.