Can methotrexate cause paresthesias?

Can Methotrexate Cause Paresthesias?

Paresthesias are not listed as a recognized side effect of methotrexate in major dermatology and rheumatology guidelines, though methotrexate can cause various neurological toxicities including stroke-like episodes, encephalopathy, and optic neuropathy.

Documented Neurological Side Effects of Methotrexate

The established neurological toxicities of methotrexate do not include paresthesias as a primary manifestation:

Central Nervous System Toxicity

• Methotrexate encephalopathy presents with hemiparesis, facial palsy, dysarthria, and altered mental status—not sensory symptoms like paresthesias 1, 2
• Stroke-like episodes can occur, characterized by focal motor deficits that typically resolve quickly 1
• Neurotoxicity can manifest as hypoactive delirium, marked lethargy, and ocular ataxia 2
• In rare cases, severe and fatal neurotoxicity has been documented, though this is uncommon 3

Peripheral Nervous System Effects

• Optic neuropathy has been reported with low-dose methotrexate, presenting with visual loss, central scotomas, and dyschromatopsia—not paresthesias 4
• The literature on methotrexate in rheumatoid arthritis mentions "neurological disorders" as potential adverse effects but does not specify paresthesias 5

Recognized Toxicities from Guidelines

The American Academy of Dermatology guidelines comprehensively list methotrexate toxicities and do not include paresthesias or sensory neuropathy 6:

Common Side Effects Listed

• Gastrointestinal: nausea, vomiting, diarrhea, ulcerative stomatitis 6, 7
• Hematologic: anemia, leukopenia, thrombocytopenia, pancytopenia 6, 7
• Hepatic: elevated liver enzymes, potential fibrosis/cirrhosis 6, 8
• Pulmonary: interstitial pneumonitis, pulmonary fibrosis 9, 8
• Constitutional: malaise, fatigue, chills, fever 6
• Dermatologic: alopecia, photosensitivity 6
• Neurologic: dizziness is mentioned, but not paresthesias 6

Clinical Interpretation

If a patient on methotrexate develops paresthesias, alternative etiologies should be investigated:

• Consider vitamin B12 deficiency (methotrexate affects folate, not B12 directly, but folate deficiency can mask B12 deficiency) 4
• Evaluate for concurrent medications that may cause neuropathy
• Assess for underlying conditions (diabetes, renal dysfunction) that predispose to peripheral neuropathy 6
• Rule out disease-related causes (e.g., rheumatoid arthritis can cause peripheral neuropathy independent of methotrexate)

Important Caveat

While methotrexate causes folate antagonism and low folate levels have been associated with neurological symptoms 4, the documented neurological manifestations are primarily central (encephalopathy, stroke-like episodes) rather than peripheral sensory symptoms like paresthesias 1, 2, 3.

The absence of paresthesias in comprehensive toxicity listings from major guidelines 6, 7, 8 suggests this is not a characteristic adverse effect of methotrexate therapy.