Can Imuran (azathioprine) cause hair loss?

Can Imuran (Azathioprine) Cause Hair Loss?

Yes, azathioprine (Imuran) can cause hair loss (alopecia), though it occurs in less than 10% of patients and is listed as a recognized adverse effect in the FDA drug label. 1

Evidence from FDA Drug Label

The official FDA prescribing information for azathioprine explicitly lists alopecia among the additional side effects of low frequency that have been reported with the medication. 1 This represents the highest quality evidence as it comes directly from the regulatory-approved drug label.

Clinical Context and Frequency

• Hair loss from azathioprine is classified as an uncommon adverse effect, occurring in the minority of treated patients 1
• In clinical practice, mild hair loss was observed in several patients treated with azathioprine in combination with corticosteroids for insulin-dependent diabetes mellitus 2
• The British Association of Dermatologists guidelines acknowledge azathioprine's side effect profile but do not emphasize hair loss as a major concern compared to more serious toxicities like bone marrow suppression 3

Genetic Risk Factors

Patients with NUDT15 R139C polymorphism are at dramatically increased risk for severe hair loss from azathioprine:

• All patients (5/5) who were homozygous (T/T) for NUDT15 R139C developed severe hair loss, compared to zero patients with other genotypes (odds ratio = 212, p = 3.82 × 10⁻¹⁶) 4
• This severe alopecia typically occurs early in treatment (within the first 8 weeks) and is associated with concurrent leukopenia 4
• Case reports document severe alopecia and agranulocytosis within 4 days of starting azathioprine in patients homozygous for this polymorphism 5
• This genetic variant is more common in East Asian populations (Japanese, Korean) 4, 5

Clinical Recommendations

For patients experiencing hair loss on azathioprine:

• Do not discontinue the medication without medical guidance, as benefits may outweigh this reversible cosmetic side effect 6
• Contact the prescribing physician immediately to report the symptom 6
• Consider genetic testing for NUDT15 polymorphism, particularly in patients of East Asian descent or those with early-onset severe alopecia 4, 5
• Evaluate alternative causes including thyroid dysfunction, nutritional deficiencies (iron, zinc, vitamin D), or the underlying disease itself 6, 7

For patients with confirmed NUDT15 T/T genotype:

• Azathioprine should be avoided entirely due to extremely high risk of severe complications 4
• Alternative immunosuppressive agents should be selected 4

For heterozygous carriers (C/T genotype):

• Low-dose 6-mercaptopurine (0.2-0.3 mg/kg/day) may be preferable to standard-dose azathioprine to allow continuation of thiopurine therapy with reduced toxicity 4

Important Caveats

• Hair loss is far less concerning than azathioprine's serious hematologic toxicities (leukopenia, thrombocytopenia) which occur in >50% of transplant recipients and 28% of rheumatoid arthritis patients 1
• The temporal association between starting a medication and hair loss does not prove causation, as telogen effluvium can result from fever, severe illness, stress, or the underlying disease being treated 8
• Cosmetic changes from corticosteroids (often co-administered with azathioprine) are extremely common, affecting 80% of patients after 2 years, and may be confused with azathioprine effects 3