Department of Pharmacy Practice, Ezhuthachan College of Pharmaceutical Sciences, Marayamuttom, Thiruvananthapuram, Kerala, India 695124
Methotrexate is a widely used disease-modifying antirheumatic drug (DMARD) in the treatment of rheumatoid arthritis due to its immunosuppressive and anti-inflammatory properties. However, inappropriate dosing can result in severe toxicity. This article propose a clinically relevant case of MTX toxicity complicated by oral ulcers, highlighting the need for clear communication between doctors, patients and caregivers regarding duration and dosage, especially in older adults on using complex treatment regimens. MTX is commonly prescribed for RA and Psoriasis, as well as in cancer treatment. However, inappropriate use may result in severe adverse effects such as GI issues (nausea, vomiting, diarrhea, oral ulcers), hepatotoxicity, pulmonary toxicity, nephrotoxicity and bone marrow suppression. We present the case of a 68-year-old women presented with the history of seropositive RA, systemic hypertension, and prediabetes, who had found to have ulcer-oral cavity and systemic symptoms due to an inadvertent overdose of MTX daily for 5 consecutive days by her caregiver. Dermatology evaluation confirmed MTX induced oral ulcers. She was promptly treated with Leucovorin (a methotrexate antidote), fluids, antibiotics, steroids, and oral care. Within few days her condition was gradually started to improve. This case reminds the need for careful monitoring of MTX dosing schedule by educating not only the patient but also the families and ensuring regular follow-up can help prevent such avoidable yet dangerous medication errors.
Case Report
A 68-years-old female patient was admitted to the General Medicine Department with the complaints of ulcer-oral cavity, right leg ulcer, left knee pain and bilateral foot pain. The patient had a past medical history of Systemic Hypertension-managed with TAB. TELMISARTAN 40mg P/O 1-0-0 and she was diagnosed with RA (predominant Lower limb symptoms) 5 months ago, since then she had been managed with TAB. HYDROXYCHLOROQUINE 300mg 0-0-1, TAB. METHYLPREDNISOLONE 4mg 1-0-0, TAB. CALCIUM CITRATE + VITAMIN D3 + ZINC SULFATE + MAGNESIUM SULPHATE 1000mg + 200IU + 4mg + 100mg 1-0-0, TAB. RABEPRAZOLE + DOMPERIDONE 20mg+10mg 1-0-0, TAB. ETORICOXIB 90mg 0-0-1, TAB. PREDNISOLONE 10mg 1-0-1 for 2 weeks and 1-0-0 for next 2 weeks, TAB. FOLIC ACID 5mg twice weekly, TAB. METHOTREXATE 20mg intended for once weekly which she has been taken everyday for 5 days, which was given to her by the bystander.
The patient was conscious, heart sounds were heard, chest was clear, was able to move all limbs, and GI series showed no abnormalities. During admission, she had a Pulse Rate of 88 beats/min, Respiratory Rate of 24 breaths/min, Blood Pressure of 130/70mmHg.
Table 1(a): Laboratory Investigation – Elevated Parameters
|
PARAMETERS |
TEST VALUE |
|
ESR |
60mm/hr |
|
HbA1C |
6.1% |
|
Urea |
50mg/dL |
|
CRP |
49.1mg/L |
Table 1(b): Laboratory Investigation – Declined Parameters
|
PARAMETERS |
TEST VALUES |
|
Hb |
10.8g/dL |
|
PCV |
32.7% |
|
WBC Count |
3640cells/mm3 |
|
Polymorphs |
38.5% |
|
Lymphocytes |
55.5% |
|
Monocytes |
0.5% |
|
Sodium |
134mEq/L |
|
Serum Methotrexate |
<0.04µmol/L |
Arterial doppler study of right and left lower limb showed, diffuse atherosclerotic changes in the form of intimo medial thickening and luminal irregularity in right lower limb and left lower limb arteries showing no hemodynamic stenosis/occlusion. Venous doppler study of right and left lower limb showed, no deep venous thrombosis in right lower limb and left lower limb (Figure 1).Initially Dermatology consultation was done and withheld the TAB. METHOTREXATE, validated the intervention and diagnosed as METHOTREXATE toxicity-induced oral ulcer and advised with INJ. LEUCOVORIN CALCIUM (an antidote to MTX toxicity) 50mg with 100ml NORMAL SALINE IV over 2 hours as stat given initially and then converted to 25mg IV Q6H for the next two days, CHLORHEXIDINE MOUTH WASH L/A 1-1-1, METRONIDAZOLE ORAL GEL L/A BD, TRIAMCINOLONE ACETONIDE BUCCAL PASTE L/A 1-0-1, LIOVIN CREAM L/A BD for treating hyperpigmentation in the leg. General Surgery consultation was done in view of right leg ulcer, venous doppler had been taken, no DVT and advised with TAB. COUMARIN 200mg P/O 1-0-1, TAB. VERICOLYTE FORTE P/O 1-0-1. Other supportive measures were INJ. HYDROCORTISONE 50mg IV BD to control systemic inflammation, INJ. PIPERACILLIN + TAZOBACTUM 4.5g IV TID for treating infection conditions, SYP. SUCRALFATE + OXETACAINE 10mL P/O 1-1-1 for gastric mucosal protection, TAB. TELMISARTAN 40mg P/O 1-0-0 for treating systemic hypertension, INJ. BIPHASIC INSULIN S/C 14 UNIT 0-0-1 to treat prediabetes, NORMAL SALINE INFUSION 500ml along with INJ. SODIUM BICARBONATE 3 AMPOULES to eliminate MTX through urine by alkalinizing the urine. After 4 days of admission patient got symptomatically better, laboratory parameters are gradually returned back to normal and was discharged with TAB. PREDNISOLONE 10mg P/O 1-0-0, TRIAMCINOLONE ACETONIDE BUCCAL PASTE L/A 1-0-1, TAB. FOLIC ACID 10mg P/O 1-0-0, CHLORHEXIDINE MOUTH WASH L/A 1-1-1, TAB. TELMISARTAN 40mg P/O 1-0-0, TAB. COUMARIN P/O 200mg 1-0-1, TAB.VERICOLYTE FORTE P/O 1-0-1, METRONIDAZOLE ORAL GEL L/A BD, LIOVIN CREAM L/A BD, TAB. HYDROXYCHLOROQUINE 200mg P/O 0-0-1.
Figure 1 : Doppler Study
DISCUSSION
Methotrexate has recently become the mostly used drug treatment for disorders like psoriasis and rheumatoid arthritis-used as low dose, once a week therapy. It is used because of its immunosuppressive and anti-inflammatory properties. However, inappropriate dosing of even low dose MTX can lead to serious but reversible side effects; the most common is oral ulcers-reported in most of the clinical trials which are encountered by dental practitioners [7].In this case, the patient’s unintended daily intake of low-dose Methotrexate had led to Methotrexate toxicity induced oral ulcers. In elderly patients with multiple comorbidities such medication errors are noted when the caregivers misunderstand the dosing regimens. Methotrexate toxicity cases observed from daily rather than weekly dosing in older age has confirmed in a retrospective observational study conducted on non-oncologic outpatients [8]. Likewise, Dorji et al., in a clinical study with similar case reports had observed, early mucocutaneous toxicity with painful mucositis which has been identified as a sentinel warning sign [9].
Comparison with other Case Reports
The results in this instance align with multiple previously documented cases of methotrexate toxicity, especially those associated with dosing mistakes. In a recent series by Dugad et al., the majority of patients who experienced toxicity had incorrectly taken methotrexate every day instead of weekly, akin to the current case. Oral ulcers were noted as a common initial sign, frequently occurring before more severe issues like pancytopenia [10]. This aligns closely with our patient, where mucositis served as the initial clinical warning sign. Likewise, Schelzel et al., reported on an elderly individual receiving low-dose methotrexate who exhibited painful oral lesions and blood-related issues. The research highlighted that even typical doses can result in serious toxicity when extra risk factors like kidney dysfunction or older age are involved [11]. In contrast, our case illustrates how a medication error by itself, even in the absence of considerable comorbid decline, can lead to toxicity.
Prognosis
The patient had a positive outlook primarily because of the swift identification of methotrexate toxicity and the quick start of suitable treatment. After discontinuing the problematic medication and administering supportive treatment, such as leucovorin rescue, the patient demonstrated consistent clinical progress. The mouth sores started to heal slowly and related symptoms diminished after a few days. No lasting complications were detected throughout the recovery period. This case indicates that if detected early, methotrexate induced toxicity especially affecting the mucosa can be successfully reversed through suitable intervention and careful observation.
CONCLUSION
This case underlines how a frequently prescribed medication can cause serious damage when dosage guidelines are misinterpreted. The onset of oral ulcers acted as an early indicator of underlying toxicity and facilitated the prompt initiation of treatment. More significantly, it highlights a preventable issue medication mistakes. Effective communication, adequate counselling and the engagement of caregivers are essential in promoting safe medication use, particulary in elderly individuals undergoing long-term treatment. Enhancing these elements in everyday clinical practice can significantly help minimize preventable adverse drug reactions and boost patient safety.
Patient Consent
The complete written informed consent was obtained from patient and by stander for the publication in this study.
REFERENCES
Rishika S., Reshma Babu, Shaiju Dharan, Methotrexate Induced Oral Ulcers in an Elderly Patient with Rheumatoid Arthritis and Comorbidities: A Sporadic Case Report, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 4, 1443-1448, https://doi.org/10.5281/zenodo.19480583
10.5281/zenodo.19480583
