Methotrexate toxicity

What it is

From: Orphanet

A rare intoxication characterized by acute renal tubular toxicity due to crystallization of methotrexate in the renal tubular lumen (which in turn leads to impaired methotrexate clearance and further deterioration of renal function and exacerbation of non-renal adverse events), myelosuppression with pancytopenia, gastrointestinal mucositis, maculopapular skin rash, chemical conjunctivitis, hepatotoxicity (reversible chemical hepatitis and hyperbilirubinemia), pulmonary toxicity, and, in severe cases, multiorgan failure. Central nervous system involvement, including headaches, seizures, and stroke-like symptoms, may also be observed.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abdominal pain · Frequent (79-30%)

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.

Decreased liver function · Frequent (79-30%)

Reduced ability of the liver to perform its functions.

Elevated circulating hepatic transaminase concentration · Frequent (79-30%)

Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.

Vomiting · Frequent (79-30%)

Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.

Alopecia · Occasional (29-5%)

A noncongenital process of hair loss, which may progress to partial or complete baldness.

Cirrhosis · Occasional (29-5%)

A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.

Confusion · Occasional (29-5%)

Lack of clarity and coherence of thought, perception, understanding, or action.

Drowsiness · Occasional (29-5%)

Abnormal feeling of sleepiness or difficulty staying awake.

Fatigue · Occasional (29-5%)

A subjective feeling of tiredness characterized by a lack of energy and motivation.

Fever · Occasional (29-5%)

Body temperature elevated above the normal range.

Gastrointestinal hemorrhage · Occasional (29-5%)

Hemorrhage affecting the gastrointestinal tract.

Headache · Occasional (29-5%)

Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.

Leukopenia · Occasional (29-5%)

An abnormal decreased number of leukocytes in the blood.

Megaloblastic anemia · Occasional (29-5%)

Anemia characterized by the presence of erythroblasts that are larger than normal (megaloblasts).

Other findings in the same source

From: Orphanet

Additional reported features include Nausea (Occasional (29-5%)); Oral ulcer (Occasional (29-5%)); Pancreatitis (Occasional (29-5%)); Renal insufficiency (Occasional (29-5%)); Seizure (Occasional (29-5%)); Vertigo (Occasional (29-5%)); Interstitial pneumonitis (Occasional (29-5%)); Conjunctivitis (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

All ages

Inheritance in the source

From: Orphanet

Not applicable

Frequency and the population described

From: Orphanet

Point prevalence: 1-9 / 100 000; Europe; Value and class.

Which doctor should you see?

The suggested department for discussing Methotrexate toxicity is Emergency Medicine, with a emergency physician as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• What is the immediate problem that needs stabilisation?
• Which results and discharge instructions should the family keep?
• What follow-up and return precautions are needed after emergency treatment?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Methotrexate toxicity. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.