Chapter 41  ·  Module 4
Corticosteroid Toxicity, Drug Interactions & Gout Pharmacology
Organ toxicity, infection prophylaxis, withdrawal, and gout from acute attack to urate-lowering therapy
Abbreviations: GC = glucocorticoid  ·  GIOP = glucocorticoid-induced osteoporosis  ·  AVN = avascular necrosis  ·  PJP = Pneumocystis jirovecii pneumonia  ·  TMP-SMX = trimethoprim-sulfamethoxazole  ·  TB = tuberculosis  ·  IGRA = interferon-gamma release assay  ·  HBV = hepatitis B virus  ·  MSU = monosodium urate  ·  NLRP3 = NOD-like receptor pyrin domain 3  ·  IL-1β = interleukin-1 beta  ·  XO = xanthine oxidase  ·  ULT = urate-lowering therapy  ·  eGFR = estimated glomerular filtration rate
Corticosteroid Toxicity by Organ System
Metabolic & Endocrine
Metabolic Effects
  • Hyperglycemia (postprandial)
  • Unmasks or worsens diabetes
  • Central adiposity, moon face, buffalo hump
  • Dyslipidemia, hypertension
Musculoskeletal
Bone & Muscle
  • GIOP — greatest loss in first 3–6 months
  • Bisphosphonate if ≥2.5 mg/day ≥3 months
  • AVN — can follow even short high-dose courses
  • Proximal myopathy — normal CK
Ophthalmic & Psychiatric
Eye & CNS Effects
  • Posterior subcapsular cataracts (irreversible)
  • Ocular hypertension → glaucoma (reversible)
  • Insomnia, mood elevation, mania, psychosis
  • Depression more common during tapering
Infection Risk & Mandatory Screening
Before chronic immunosuppressive doses
Pre-Therapy Screening
  • Latent TB: IGRA (preferred) or tuberculin skin test
  • HBV: surface antigen, core antibody, surface antibody
  • Vaccinations: live vaccines ≥4 weeks before; inactivated any time
  • Live vaccines contraindicated during ≥20 mg/day ≥2 weeks
≥20 mg/day for ≥4 weeks + immunosuppressants
PJP Prophylaxis
  • TMP-SMX single-strength daily (preferred)
  • Also covers toxoplasmosis, nocardiosis
  • Alternatives: dapsone, atovaquone, inhaled pentamidine
  • PJP mortality 30–50% if untreated in immunosuppressed
Distinguishing Three Tapering Syndromes
Entity Morning Cortisol Key Features Management
Adrenal insufficiency Low (<3 μg/dL) Hyponatremia, hypoglycemia possible Slow taper; stress dosing
Withdrawal syndrome Normal or elevated Arthralgia, myalgia, fatigue; no electrolyte changes Slower taper; reassurance
Disease relapse Normal Disease-specific symptoms; inflammatory markers rise Increase immunosuppression
Gout — NLRP3 Pathway and Acute Attack Drugs
Trigger
MSU crystals
→
Inflammasome
NLRP3 activation
→
Enzyme
Caspase-1 activated
→
Cytokine
IL-1β secreted
→
Outcome
Joint inflammation
Drug block points
Colchicine
Blocks neutrophil migration and NLRP3 assembly — must start within 36 h
NSAIDs
Block prostaglandin synthesis — first-line if no contraindications
Steroids / IL-1 inhibitors
Corticosteroids suppress inflammation; anakinra/canakinumab block IL-1β directly
Urate-Lowering Therapy
Agent Mechanism Key Points Cautions
Allopurinol XO inhibitor (purine analogue) First-line; start low (50–100 mg/day), titrate slowly Dose-adjust in CKD; hypersensitivity syndrome risk
Febuxostat XO inhibitor (non-purine) No dose adjust in mild–moderate CKD CV risk signal; use only if allopurinol fails/intolerated
Probenecid URAT1/GLUT9 blocker (uricosuric) Increases renal urate excretion Avoid eGFR <30; avoid with low-dose aspirin
Pegloticase Recombinant uricase Refractory tophi only; IV every 2 weeks Anti-drug antibodies → loss of effect + anaphylaxis risk; use with methotrexate
Gout Management Rules

Do NOT start ULT during acute attack — wait 2–4 weeks after resolution. Co-prescribe colchicine prophylaxis for first 3–6 months of ULT. Target serum urate <6 mg/dL (<5 mg/dL if tophi). Patients already on ULT who flare: do NOT stop ULT.