Can methimazole (antithyroid medication) induce a skin rash?

Methimazole-Induced Skin Rash

Yes, methimazole commonly causes skin rash, occurring in approximately 1.5-12% of patients, and the FDA label explicitly warns patients to report skin eruptions immediately. 1

Incidence and Clinical Presentation

• Skin rash is one of the most common adverse effects of methimazole, typically presenting as an erythematous, maculopapular eruption that may be accompanied by pruritus. 1, 2
• The rash usually develops within the first few weeks to months of initiating therapy, with most cases occurring within the first 2 months of treatment. 3, 4
• Patients should be instructed to report any skin eruptions immediately, as this may herald more serious complications or require treatment modification. 1

Mechanism and Associated Features

• The rash may occur as an isolated finding or as part of a more severe hypersensitivity syndrome that can include fever, hepatotoxicity, and cholestatic jaundice. 3, 4
• In rare cases, methimazole can trigger a lupus-like syndrome characterized by joint pains, skin rash, and positive antinuclear antibodies, which resolves upon drug discontinuation. 5
• Severe pruritus often accompanies the rash and may precede the development of cholestatic liver injury, requiring immediate discontinuation of the medication. 3, 4

Management Algorithm

Immediate Actions

• Discontinue methimazole immediately if rash develops, particularly if accompanied by fever, jaundice, pruritus, or systemic symptoms. 1, 4
• Obtain complete blood count with differential to rule out agranulocytosis, and liver function tests to assess for hepatotoxicity. 1, 4

Treatment Options After Rash Resolution

Option 1: Switch to Propylthiouracil (PTU)

• PTU is the most straightforward alternative for patients who develop rash on methimazole. 2, 4
• PTU has successfully controlled hyperthyroidism in patients with prior methimazole-induced rash without recurrence of adverse reactions. 4

Option 2: Methimazole Desensitization

• Under allergist supervision, desensitization to methimazole is feasible for patients who experienced rash (but not agranulocytosis or hepatotoxicity). 2
• In a case series of 7 patients with methimazole-induced side effects, all successfully tolerated methimazole after desensitization, either for continued medical therapy or as a bridge to definitive treatment. 2
• This approach requires close monitoring and should only be attempted with allergist involvement. 2

Option 3: Definitive Therapy

• Consider radioactive iodine ablation or thyroidectomy as definitive treatment options, particularly if the patient cannot tolerate either thionamide. 2, 4

Symptomatic Management During Acute Phase

• Administer antihistamines for pruritus and rash. 4
• If cholestatic liver injury is present, provide hepatoprotective agents until liver function normalizes (typically 11 days to 2 years depending on severity). 3, 4

Alternative Formulation

• Topical methimazole ointment (5%) applied to skin around the thyroid has similar efficacy to oral tablets but causes significantly fewer systemic adverse effects, including rash (1.5% vs 12.3%). 6
• This formulation may be considered for patients at high risk for systemic adverse effects, though it is not widely available. 6

Critical Monitoring Points

• Monitor for vasculitis symptoms including new rash, hematuria, decreased urine output, dyspnea, or hemoptysis, as methimazole can cause severe vasculitic complications. 1
• Watch for warning signs of cholestatic jaundice: severe pruritus, jaundice, dark urine, and light-colored stools. 3
• Genetic predisposition may exist, as familial cases of thioamide-induced lupus syndrome have been reported, suggesting HLA-DR locus involvement. 5

Common Pitfalls to Avoid

• Do not continue methimazole if rash develops with systemic symptoms (fever, jaundice, severe pruritus), as this may progress to serious hepatotoxicity or vasculitis. 1, 3, 4
• Do not assume all patients with methimazole rash will tolerate PTU—close monitoring is still required after switching. 4
• Do not attempt desensitization in patients who experienced agranulocytosis or hepatotoxicity, as these are absolute contraindications. 2