Methotrexate-associated Oral Diseases: Lymphoproliferative Disorder and Severe Stomatitis
Methtrexate (MTX) is called as “anchor drug” for the treatment of rheumatoid arthritis (RA). It is used as first choice medication for RA treatment. But it has the risk of MTX-associated oral diseases. These also include life threatening severe conditions like malignancies or multiple organ failure. We report severe cases of MTX-associated oral diseases with reviewing literatures.
Case summary 1:
A 54 year old woman visited general dental clinic with chief complaint of bilateral upper gum pain around of molar teeth. At the clinic, intraoral steroid ointment was administrated for gum ulcer. But there wasn’t any clear healing of mucous lesion. She was referred to our hospital and intraoral examinations revealed that bilateral 20mm-sized necrotic ulcer and bone exposure at peripheral gingiva of inside of upper second molar. Contrast-enhanced CT showed osteonecrosis in the posterior cortex. Furthermore, FDG-PET/CT revealed strong uptake bilaterally.
In clinical diagnosis, malignant lymphoma was suspected, and brood examination was performed. Although, it showed slight rising of CRP, monocyte and dropping of lymphocyte, s-IL2R level was in normal range.
In histological finding of incisional biopsy from ulcer, MTX-LPD was suspected. With consultation to hematologist, MTX was stopped and BP (risedronate sodium) that had medication history of over 3 years stopped additionally. After that stopping, bilateral ulcer were disappeared. But only ipsilaterally, bone exposure and FDG abnormal uptake was remained. The lesion was diagnosed as BRONJ and osteonecrotomy was performed.
Postoperatively, healing of the lesions were good and there was no recurrence.
Case summary 2:
A 81 year old woman visited a general clinic of internal medicine with chief complaint of bad appetite and gastric distress. After few week’s infusion therapy, her condition was getting worse and diagnosed as severe stomatitis.
Initially, oral candidiasis was suspected but miconazole ointment wasn’t effective. She was referred to our hospital to investigate and treat the stomatitis. Intra oral examination revealed extensive severe stomatitis in whole mouse. And she was administrated weekly MTX and prednisolone over 9 years. In labo-examinations, candida, anti-HSV Ab, anti-VZV Ab were negative. Anti-Dsg1/Dsg3 Ab were also negative. So, the stomatitis was suspected as MTX-associated epithelitis. With hospitalization, tube feeding was started and MTX was stopped. In addition, leucovorin rescue was also combined. Stomatitis was gradually recovered and after 2 week’s treatment Leucovorin could be finished. Finally, CRP became negative and oral ingestion was completely recovered.
Conclusions:
It must be considered about medication specific side effect. Especially, it is very important to recognize the possibility of drug-associated diseases in cases with “KEY-Drug” exsintence.
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