What is the definition of steroid refractory and steroid resistant in Juvenile Crohn's (Jc) disease and Crohn's disease?

Definitions of Steroid Refractory and Steroid Resistant in Crohn's Disease

In Crohn's disease, steroid refractory disease is defined as active disease despite an adequate dose and duration of prednisolone (>20 mg/day for >2 weeks), while steroid dependence is defined as a relapse when the steroid dose is reduced below 20 mg/day, or within 6 weeks of stopping steroids. 1

Steroid Refractory Disease

Definition and Criteria

• Steroid refractory disease: Active disease persisting despite:
  • Prednisolone dose >20 mg/day (or equivalent)
  • Treatment duration of at least 2 weeks
  • No clinical improvement observed

Management Approach

1. Rule out complications:

   • Evaluate for coexistent infections (C. difficile, cytomegalovirus)
   • Consider abscess formation or stricturing disease
   • Exclude malignancy

2. Treatment options:

   • First-line: Anti-TNF therapy (infliximab, adalimumab) preferably combined with thiopurines 1, 2
   • Second-line: Methotrexate (25 mg weekly parenteral) 1
   • Third-line: Consider vedolizumab or ustekinumab in anti-TNF refractory cases 2
   • Surgical evaluation: If medical therapy fails or complications are present

Steroid Dependent Disease

Definition and Criteria

• Steroid dependence: Either:
  • Relapse occurs when steroid dose is reduced below 20 mg/day
  • Relapse occurs within 6 weeks of stopping steroids
  • Inability to taper steroids without disease flare

Management Approach

1. Steroid-sparing strategies:

   • First-line: Azathioprine (1.5-2.5 mg/kg/day) or mercaptopurine (0.75-1.25 mg/kg/day) 1
   • Alternative: Methotrexate (15-25 mg weekly, preferably parenteral) 1, 2
   • Biologic therapy: Anti-TNF agents with or without immunomodulators 1, 2

2. Monitoring response:

   • Evaluate for steroid-free remission within 12-16 weeks 1
   • If no response, modify therapy (dose adjustment or switch class)

Special Considerations for Juvenile Crohn's Disease

While specific definitions for juvenile Crohn's disease are not explicitly different in the provided evidence, management approaches include:

• Earlier consideration of biologic therapy in children with moderate-severe disease 3
• Greater emphasis on growth and nutritional parameters in assessment
• Exclusive enteral nutrition as first-line therapy for induction of remission 3
• Similar steroid-sparing strategies as in adults

Important Clinical Pitfalls

• Prolonged steroid use: Corticosteroids are ineffective for maintenance of remission and associated with significant adverse effects including bone loss, metabolic complications, infections, and growth failure in children 2, 4, 5

• Delayed escalation: Failure to escalate therapy promptly in steroid-refractory or steroid-dependent patients can lead to disease progression and complications 2

• Inadequate assessment: Relying solely on symptoms without objective markers of inflammation can lead to inappropriate management decisions 2

• Overlooking complications: Always consider abscess, stricture, or perforation in patients with persistent symptoms despite therapy 2

Monitoring Recommendations

• Regular assessment of objective markers of inflammation (CRP, fecal calprotectin)
• Endoscopic evaluation to assess mucosal healing in unclear cases
• Laboratory monitoring specific to each medication (CBC, liver function tests)
• Screening for tuberculosis and other infections before initiating biologic therapy

By understanding these definitions and implementing appropriate management strategies, clinicians can optimize outcomes and minimize steroid-related complications in patients with Crohn's disease.