What are the discriminant factors for starting Wysolone (Prednisolone) in a patient with a history of inflammatory or autoimmune disease?

Discriminant Factors for Starting Wysolone (Prednisolone)

Start Wysolone when AST/ALT exceeds 10-fold the upper limit of normal, or when AST/ALT is 5-fold elevated with gamma-globulin at least 2-fold elevated, or when histology shows bridging/multilobular necrosis—these are the absolute indications for immunosuppressive therapy in autoimmune hepatitis. 1

Absolute Indications for Starting Prednisolone

The following criteria mandate immediate corticosteroid therapy:

• Serum aminotransferases (AST or ALT) >10-fold upper limit of normal (ULN) 1
• Serum aminotransferases ≥5-fold ULN AND gamma-globulin ≥2-fold ULN 1
• Histological evidence of bridging necrosis or multilobular necrosis 1

These criteria represent severe disease with high mortality risk without treatment, where untreated 10-year survival may be significantly compromised. 1

Relative Indications Requiring Individualized Assessment

Asymptomatic patients with mild disease present a more nuanced decision:

• Asymptomatic patients with mild laboratory and histological changes may benefit from treatment, but this must be balanced against steroid-related risks 1
• Untreated asymptomatic patients with mild disease have lower 10-year survival compared to treated patients (67% versus 98%, P < 0.01) 1
• Spontaneous improvement occurs in only 12% of untreated patients versus 63% in treated patients (P < 0.006) 1
• In young individuals who tolerate medication well, favor corticosteroid therapy even for mild disease 1

Contraindications to Starting Prednisolone

Do not start immunosuppressive therapy in the following situations:

• Minimal or no disease activity, or inactive cirrhosis (though close monitoring every 3-6 months is required) 1
• Severe pre-existing comorbidities including vertebral compression, psychosis, brittle diabetes, or uncontrolled hypertension—unless disease is severe and progressive with adequate comorbidity control measures 1
• Severe pretreatment cytopenia (WBC <2.5 × 10⁹/L or platelets <50 × 10⁹/L) if considering azathioprine combination 1

Disease-Specific Considerations

Inflammatory Bowel Disease

• Prednisolone 40 mg daily is appropriate when prompt response is required or when mesalazine has failed in mild-to-moderate disease 1
• Steroid dependency (inability to wean below 10 mg within 3 months) or steroid excess (≥2 courses per year) indicates need for alternative immunosuppression 1
• Prolonged steroid use (>3 months continuous) carries increased mortality risk and should be avoided 1

Rheumatic Immune-Related Adverse Events

• High-dose systemic glucocorticoids (1-2 mg/kg/day, median 70 mg/day) are first-line for severe myositis, especially with dyspnea, bulbar symptoms, severe weakness, or myocarditis 1
• For Grade 2 inflammatory arthritis: initiate prednisolone 10-20 mg/day for 4-6 weeks if NSAIDs inadequate 1
• For Grade 3-4 arthritis: initiate oral prednisone 0.5-1 mg/kg 1

Pediatric Autoimmune Hepatitis

• All children with confirmed autoimmune hepatitis should be treated at diagnosis 1
• Disease appears more severe in children, with >50% having cirrhosis at presentation 1
• Only children with advanced cirrhosis without inflammatory activity are unlikely to benefit 1

Initial Dosing Regimens

Two equally effective regimens for severe autoimmune hepatitis in adults: 1

1. Combination therapy (preferred):

   • Prednisolone 30 mg/day (Week 1) → 20 mg/day (Week 2) → 15 mg/day (Weeks 3-4) → 10 mg/day maintenance
   • Plus azathioprine 50 mg/day throughout
   • Lower corticosteroid-related side effects (10% vs 44%) 1

2. Monotherapy:

   • Prednisolone 60 mg/day (Week 1) → 40 mg/day (Week 2) → 30 mg/day (Weeks 3-4) → 20 mg/day maintenance
   • Reserved for patients with cytopenia, thiopurine methyltransferase deficiency, pregnancy, or malignancy 1

Critical Pitfalls to Avoid

• Never use corticosteroids for maintenance therapy in IBD—they are effective only for inducing remission, not preventing relapse 1
• Avoid abrupt discontinuation after long-term therapy—withdraw gradually to prevent adrenal insufficiency 2
• Do not delay alternative immunosuppression in steroid-dependent patients—prolonged steroid use (>3000 mg prednisolone equivalent/year) increases mortality 1
• Screen for osteoporosis risk in patients requiring prolonged (>3 months) or repeated corticosteroid courses 1
• Monitor closely for disease progression in patients with pre-existing autoimmune disease, as flares occur in approximately 50% but are usually manageable 1