What secondary dermatology conditions can occur with azathioprine (immunosuppressive medication) and prednisolone (corticosteroid)?

Secondary Dermatological Conditions with Azathioprine and Prednisolone

The combination of azathioprine and prednisolone significantly increases the risk of viral, bacterial, and fungal infections manifesting in the skin, with potentially fatal outcomes, especially in elderly patients with immunobullous disorders. 1

Infection-Related Dermatological Conditions

Viral Infections

• Varicella zoster virus (VZV) infections occur more commonly in patients receiving azathioprine 1

  • Primary infection (chickenpox) can be severe in immunosuppressed patients
  • Reactivation (shingles) may be more extensive and prolonged
  • Management recommendation: Consider temporary withdrawal of azathioprine and prompt use of antivirals 1

• Viral warts (verrucae)

  • Significantly more common in patients on long-term therapy 2
  • Increase in frequency with longer duration of treatment
  • More prevalent in transplant recipients than non-transplant patients on the same medications 2

Fungal and Bacterial Infections

• Various cutaneous fungal and bacterial infections may occur due to immunosuppression
• Risk increases when azathioprine is combined with corticosteroids 1

Malignancy-Related Dermatological Conditions

• Skin malignancies

  • Significantly increased rate in transplant recipients compared to general population 1
  • Risk factors include:
    • Pale skin type
    • Excess sun exposure
    • Duration of treatment 3
  • Reports of skin malignancy with azathioprine monotherapy are rare 1
  • Recommendation: Advise skin photoprotection for all patients 1

• Dysplastic skin lesions

  • Incidence increases with:
    • Increasing age
    • Pale skin type
    • Excess sun exposure
    • Duration of treatment 3

Hypersensitivity Reactions

• Azathioprine hypersensitivity syndrome (occurs in approximately 2-5% of patients)
  • Cutaneous manifestations in 49% of cases 4
  • Most common presentation (76%) is a neutrophilic dermatosis 4
  • Other manifestations include:
    • Urticarial rashes
    • Maculopapular eruptions
    • Vasculitic rashes 1
  • May be accompanied by fever, rigors, and even circulatory collapse 1
  • Important: Rechallenge should be avoided as reactions are typically more severe and potentially life-threatening 1

Direct Drug Side Effects on Skin

• Nausea-related manifestations (common side effect)
  • May manifest as facial flushing
  • Often self-limiting but can be severe enough to require treatment discontinuation 1

Monitoring and Prevention

Monitoring Protocol

• Weekly monitoring of FBC and LFTs for first 4 weeks of therapy
• Continue monitoring at least every 3 months for duration of therapy 1
• More frequent monitoring in:
  • Elderly patients
  • Those with hepatic or renal impairment
  • After dose increases 1

Prevention Strategies

1. Infection prevention:

   • Screen for previous chickenpox/VZV exposure before starting therapy
   • Advise patients to seek immediate attention if exposed to chickenpox/shingles 1
   • Avoid live vaccines during treatment 1

2. Skin cancer prevention:

   • Regular skin examinations
   • Sun protection advice (sunscreen, protective clothing)
   • Avoid excessive sun exposure 1, 3

Clinical Pitfalls to Avoid

1. Failing to recognize azathioprine hypersensitivity syndrome

   • Often mistaken for infection or disease exacerbation 4
   • Early recognition is crucial as continued treatment can be life-threatening

2. Overlooking early signs of myelosuppression

   • Unexplained infections, throat ulceration, bruising, or bleeding may indicate bone marrow suppression 1

3. Underestimating infection risk in elderly patients

   • Infection in elderly patients with bullous pemphigoid treated with azathioprine and prednisolone has been identified as a significant cause of mortality 1

4. Neglecting skin cancer surveillance

   • Regular skin examinations are essential, especially in fair-skinned patients with significant sun exposure history

By understanding these potential dermatological complications and implementing appropriate monitoring and preventive strategies, clinicians can optimize the safety profile of azathioprine and prednisolone combination therapy.