Methotrexate and Photosensitivity: Side Effects & Sun Protection

Methotrexate (MTX) is an antimetabolite drug widely used for rheumatoid arthritis, psoriasis, inflammatory bowel disease, ectopic pregnancy, and various cancers. It causes a distinctive and clinically important drug-induced photosensitivity — particularly the methotrexate UV recall phenomenon — that requires careful management in any patient receiving this drug.

Types of Methotrexate Photosensitivity

Arm showing methotrexate UV recall phenomenon: severe erythema and blistering reappearing at site of prior sunburn after MTX administration

1. Acute methotrexate photosensitivity — phototoxic reaction similar to severe sunburn on UV-exposed skin. Occurs in a minority of patients and is dose-related.

2. UV recall reaction (methotrexate recall phenomenon) — the most clinically significant and unique form. MTX causes previously sun-damaged (sunburned) skin to re-react when the drug is given, even if no new UV exposure occurs. This happens because methotrexate preferentially targets rapidly dividing cells — including the already-damaged, repairing skin cells from a recent sunburn. The result can be severe:

• Intense erythema, blistering, and erosion at the site of a previous sunburn
• Can occur days to weeks after the original sun exposure
• Severity correlates with degree of prior UV damage

3. Psoriasis flare with photosensitivity — paradoxically, methotrexate (used to treat psoriasis) can occasionally cause sunlight-induced psoriasis flares at photosensitive doses.

Mechanism

MTX inhibits dihydrofolate reductase (DHFR), blocking purine synthesis and rapidly inhibiting proliferating cells. In skin:

• UV radiation damages DNA and triggers a repair response that accelerates keratinocyte proliferation
• MTX preferentially targets these UV-damaged, rapidly proliferating keratinocytes
• The resulting cell death produces the recall erythema/blistering pattern

MTX also reduces folate levels systemically, impairing DNA repair capacity and potentially increasing UV-induced DNA damage.

Clinical Implications for Psoriasis Patients

Psoriasis is treated with both methotrexate AND phototherapy (PUVA, narrowband UVB). This combination requires careful management:

• Phototherapy doses must be carefully calibrated when switching to or from MTX
• The MTX UV recall can be triggered by phototherapy sessions
• Dermatologists managing this combination carefully monitor for reactions

Prevention and Management

For all methotrexate patients:

• Apply broad-spectrum SPF 50+ sunscreen daily before any sun exposure
• Avoid sun exposure, especially during the first months of treatment when skin sensitivity is being established
• Critically: If you experience sunburn while on MTX, notify your prescriber immediately — the recall reaction can cause severe skin damage requiring dose adjustment or interruption

After sunburn on MTX:

• Notify the prescribing rheumatologist, oncologist, or dermatologist
• The MTX dose may need to be held or reduced at the next cycle
• Cool compresses, topical steroids for immediate burn care

Key patient counseling point: Patients starting methotrexate should be explicitly warned that even a “mild” sunburn can cause a severe delayed skin reaction when the next MTX dose is taken.

Sources

1. Litt JZ. “Drug Eruption Reference Manual.” Taylor & Francis. 2012.
2. Roenigk HH, et al. “Methotrexate in psoriasis.” J Am Acad Dermatol. 1998;38(3):478-485.
3. Burrows NP, et al. “Methotrexate and photosensitivity.” Br J Dermatol. 1994;130(6):800-802.