Can allopurinol be used in patients with bullous pemphigoid?

Allopurinol Use in Bullous Pemphigoid

Allopurinol should not be used in patients with bullous pemphigoid due to the significant drug interaction with azathioprine, which is commonly used as a steroid-sparing agent in bullous pemphigoid treatment. 1

Rationale for Contraindication

• Allopurinol inhibits xanthine oxidase, which is one of three enzymes involved in azathioprine metabolism, leading to decreased metabolism of 6-mercaptopurine to inactive metabolites and increased generation of immunosuppressant 6-thioguanine nucleotides 1
• This interaction creates the same effect as deficiency in thiopurine methyltransferase (TPMT), potentially causing significant myelosuppression 1
• The British Association of Dermatologists explicitly states that concurrent treatment with allopurinol and azathioprine "results in an important drug interaction which may cause significant myelosuppression, and should therefore be avoided" 1

Treatment Options for Bullous Pemphigoid

First-Line Treatment

• Superpotent topical corticosteroids (e.g., clobetasol propionate) are recommended as first-line treatment for bullous pemphigoid 2, 3
• For localized disease, apply topical corticosteroids directly to lesions; for widespread disease, apply to the entire body except the face 2
• Topical steroids provide better disease control with significantly lower mortality compared to systemic corticosteroids 2, 4

Second-Line and Adjunctive Treatments

• If topical corticosteroids fail, oral prednisone at 0.5 mg/kg/day may be considered 2
• Azathioprine is a key adjunctive therapy that allows reduction of steroid dose by approximately 45% 2, 4
• Other steroid-sparing options include tacrolimus for topical treatment 5

Management of Gout in Bullous Pemphigoid Patients

If a patient with bullous pemphigoid requires treatment for gout:

Alternative ULT Options

• Febuxostat can be considered as an alternative to allopurinol for urate-lowering therapy in patients who cannot take allopurinol 1
• Uricosuric agents may also be appropriate alternatives 1
• When initiating any ULT, start at a low dose and titrate upward until the serum uric acid target is reached 1

Monitoring and Precautions

• Target serum uric acid level should be maintained at <6 mg/dL (360 μmol/L) 1
• For patients with cardiovascular disease history, febuxostat should be used with caution due to potential cardiovascular risks 1
• Consider testing for HLA-B*5801 before starting allopurinol in patients of Southeast Asian descent or African American patients due to increased risk of severe cutaneous adverse reactions 1

Potential Drug-Induced Bullous Pemphigoid

• Be aware that some medications can induce or exacerbate bullous pemphigoid 6, 7
• Strongest evidence for drug-associated bullous pemphigoid is seen with gliptins, PD-1/PD-L1 inhibitors, loop diuretics, and penicillin derivatives 6
• Diuretics, particularly aldosterone antagonists, have been associated with increased risk of bullous pemphigoid 7

Key Clinical Considerations

• Bullous pemphigoid is a self-limiting disease that usually remits within 5 years 2
• Regular follow-up is essential: every 2 weeks for the first 3 months, then monthly for the next 3 months, then every 2 months 2
• Monitor for disease activity and consider testing anti-BP180 IgG by ELISA at days 0,60, and 150 2
• Consider discontinuing treatment after 12 months if the patient has been symptom-free for at least 1-6 months on minimal therapy 2

Conclusion

The concurrent use of allopurinol and azathioprine in bullous pemphigoid patients poses a significant risk of myelosuppression and should be avoided. Alternative urate-lowering therapies should be considered for gout management in these patients.