Does Methotrexate Change Skin Color? An Overview of Pigmentation Side Effects

October 13, 2025 •

4 min read

Although an uncommon side effect, methotrexate can cause changes in skin pigmentation, particularly in areas exposed to the sun. This occurs in a small percentage of patients, with cases reported in individuals treated for conditions like rheumatoid arthritis and psoriasis.

Quick Summary

Methotrexate can cause skin color changes like photosensitivity and hyperpigmentation, especially in sun-exposed areas. These effects are often reversible upon stopping the medication, but diligent sun protection is crucial during treatment. Other discoloration can signal more serious issues, such as liver problems.

Key Points

Photosensitivity is the most common skin reaction: Methotrexate increases skin sensitivity to UV light, causing severe sunburn-like reactions.
Hyperpigmentation is a documented, but less common, side effect: It presents as a darkening of the skin, most often on sun-exposed areas, and may be more likely in individuals with darker skin.
Mechanism involves interplay of immune factors and sun exposure: While not fully understood, direct hyperpigmentation may result from a drug-induced release of melanin-producing cell inhibition.
Management focuses on prevention and treatment: Strict sun protection is vital, while persistent hyperpigmentation can be addressed with topical treatments or laser therapy.
Other forms of discoloration can indicate serious issues: Yellow skin (jaundice) signals liver problems, while unexplained bruising or purplish patches may indicate a blood disorder.

Understanding Methotrexate's Effect on Skin Pigmentation

Methotrexate (MTX) is a widely used immunosuppressant and chemotherapy agent for treating conditions like rheumatoid arthritis, psoriasis, and certain cancers. While many patients tolerate it well, it can cause a range of side effects, including changes to skin color. These dermatological reactions can vary in severity and presentation, from increased sensitivity to sunlight to more localized dark patches.

The Primary Mechanism: Photosensitivity

One of the most common ways methotrexate can affect skin color is by increasing photosensitivity. This means the skin becomes highly sensitive to ultraviolet (UV) light from the sun or tanning beds, leading to severe reactions that can feel and look like an intense sunburn.

Common photosensitivity reactions include:

Redness and swelling
Blisters or papules
Severe rash, limited to sun-exposed areas
Reactivation of old sunburn or radiation sites (known as "recall reactions")

Healthcare providers emphasize that patients on methotrexate should take strict precautions to protect their skin from the sun, such as using high-SPF sunscreen and wearing protective clothing.

Less Common: Direct Hyperpigmentation

Beyond photosensitivity, methotrexate can also cause direct hyperpigmentation, or darkening of the skin. This is a documented, though less common, side effect. Case studies have reported this phenomenon, especially in individuals with a darker complexion who also have significant sun exposure. The exact mechanism is not fully understood, but it may involve a complex interplay between the drug, immune responses, and the skin's pigment-producing cells (melanocytes). This type of hyperpigmentation most often appears on sun-exposed areas, such as the face and the backs of the hands.

Other Types of Skin Discoloration

While less directly related to the drug's effect on melanin, other side effects of methotrexate can manifest as changes in skin color:

Jaundice: Methotrexate can cause liver damage in rare cases, which can lead to jaundice—a yellowing of the skin and whites of the eyes. This is a serious symptom that requires immediate medical attention.
Bruising and Purplish Patches: Methotrexate can lower platelet counts, potentially causing unusual bleeding or bruising, which may appear as pinpoint red spots or large, flat, purplish patches on the skin.

Factors Influencing Methotrexate-Induced Skin Changes

Several factors can influence the likelihood and severity of skin color changes while taking methotrexate:

Dose and Duration: Higher doses and longer duration of treatment can increase the risk of adverse effects, including dermatological issues.
Sun Exposure: UV radiation is a significant trigger for photosensitivity and can exacerbate hyperpigmentation.
Individual Skin Type: People with darker complexions may be more susceptible to hyperpigmentation, while those with lighter skin are more prone to photosensitive sunburn-like reactions.
Underlying Health Conditions: Pre-existing conditions, including liver or kidney impairment, can increase the risk of side effects.

How to Manage Skin Color Changes Caused by Methotrexate

Management depends on the type and severity of the discoloration. For photosensitivity and mild hyperpigmentation, preventative measures are key.

Prevention Strategies

Strict Sun Protection: Always use a high-SPF, broad-spectrum sunscreen (SPF 30 or higher) containing zinc oxide or titanium dioxide.
Protective Clothing: Wear wide-brimmed hats, sunglasses, and long-sleeved shirts and pants when outdoors.
Avoid Peak Sun Hours: Limit sun exposure, especially between 11 a.m. and 3 p.m..
No Tanning Beds: Avoid sunlamps and tanning equipment altogether.

Treatment Options for Existing Pigmentation

In some cases, the pigmentation may resolve on its own after the medication is discontinued, though this can take time. If the discoloration persists and is bothersome, a dermatologist can recommend treatments, though results can vary.

Topical Therapies: Creams with ingredients like hydroquinone, retinoids, or azelaic acid may help lighten dark spots.
Laser Therapy: Laser treatments, like Q-switched lasers, can sometimes be effective but carry a risk of complications, including post-inflammatory pigmentation changes. This should only be performed by an experienced professional.
Address Underlying Cause: If the discoloration is due to liver or kidney issues, addressing the underlying organ dysfunction is the priority. Discontinuing methotrexate may be necessary.

Comparison of Different Types of Skin Discoloration


Characteristic	Methotrexate-Induced Hyperpigmentation	Photosensitivity Reaction	Jaundice (Liver Dysfunction)
Appearance	Darkening, often brown patches	Redness, swelling, blister-like rash	Yellowing of the skin and eyes
Location	Typically sun-exposed areas (face, hands)	Sun-exposed areas	Entire body, including eyes and mucosal membranes
Primary Cause	Increased melanin production, possibly triggered by sun and immune factors	UV light activating the drug in the skin	Buildup of bilirubin due to liver damage
Speed of Onset	Gradual, over weeks or months	Rapid, shortly after sun exposure	Gradual or sudden, depending on severity of liver issue
Management	Sun protection, topical agents, laser therapy	Strict sun avoidance, protective clothing, high-SPF sunscreen	Immediate medical evaluation, may require stopping methotrexate

When to Contact a Healthcare Provider

While some skin changes may be benign, others can indicate a more serious issue. You should contact your healthcare provider immediately if you experience:

Yellowing of the skin or eyes: This can be a sign of liver problems.
Blistering, peeling, or severe rash: These are serious skin reactions.
Large, flat, blue, or purplish patches: This may indicate a blood disorder.
Any unusual or painful skin changes, ulcers, or erosions.
Signs of a severe allergic reaction: Including swelling of the face, throat, or tongue; or difficulty breathing.

Conclusion

Methotrexate can, in fact, change skin color, but the effects range from mild to severe. The most common reaction is photosensitivity, which can be managed with diligent sun protection. Less frequently, patients may develop hyperpigmentation in sun-exposed areas. In rare cases, more serious discoloration, such as jaundice from liver issues or bruising from low platelet counts, can occur. Patients should maintain an open dialogue with their healthcare providers, report any skin changes promptly, and adhere to sun safety guidelines. For individuals concerned about pigmentation, preventative measures are the first line of defense, and dermatological consultation can address persistent issues. More information about methotrexate can be found on the MedlinePlus website.

Frequently Asked Questions

The skin discoloration from methotrexate is often temporary and can slowly resolve after the medication is discontinued. However, in some cases, particularly with long-term use or intense sun exposure, some residual pigmentation may persist.

Yes, methotrexate can cause yellow skin, known as jaundice, which is a symptom of liver problems. If you notice yellowing of your skin or the whites of your eyes, you should contact a doctor immediately as this can indicate a serious side effect.

If you notice your skin getting darker, especially in sun-exposed areas, the most important step is to be extremely diligent with sun protection. Wear protective clothing, a wide-brimmed hat, and use a high-SPF sunscreen. You should also inform your healthcare provider about the change in pigmentation.

Yes, methotrexate can cause serious skin reactions, including blistering, peeling, and severe rashes. If you experience these symptoms, it's crucial to seek immediate medical attention, as they can be signs of a serious skin toxicity.

To protect your skin, avoid intense sun exposure, especially between 11 a.m. and 3 p.m.. Wear protective clothing, including a hat and long sleeves. Always use a broad-spectrum, high-SPF sunscreen (SPF 30 or higher) containing zinc oxide or titanium dioxide.

Yes, individuals with darker skin complexions, those with higher sun exposure, and patients on higher doses or longer-term treatment may have a higher risk of developing hyperpigmentation. Those with underlying liver or kidney issues also face higher risks of serious side effects.

While uncommon, some patients have reported changes in nail pigmentation while on methotrexate. Diffuse hair loss has also been noted, especially with higher cancer-treatment doses. Any unusual changes should be reported to your doctor.