Diagnosis

Diagnostic Reasoning

Management Plan

Step 1 - Urgent Assessment and Investigations

• Renal biopsy - confirm pauci-immune crescentic GN, assess proportion of viable crescents vs. sclerotic glomeruli (guides prognosis and intensity of treatment)
• Urine microscopy (confirm RBC casts), 24-hour urine protein
• ANCA titres (confirm C-ANCA/PR3 by ELISA), anti-GBM antibodies (already done), ANA, complement levels (C3/C4)
• FBC, LFTs, LDH, coagulation screen
• Chest X-ray/HRCT chest - rule out pulmonary involvement, nodules, or haemorrhage (pulmonary-renal syndrome)
• ENT/sinus CT - document extent of upper airway disease
• Hepatitis B, C, and HIV serology (before immunosuppression)
• Blood cultures if infection suspected
• Monitor urine output and fluid balance closely
• Assess dialysis requirement (oliguria + rising creatinine)

Step 2 - Induction Therapy (Remission Induction)

• IV methylprednisolone 500-1000 mg/day x 3 days (pulse) - given first to achieve rapid anti-inflammatory effect
• Followed by oral prednisolone 1 mg/kg/day (max ~60-80 mg/day)
• Taper to target of ≤5 mg/day prednisolone equivalent within 4-5 months (EULAR 2022 recommendation to reduce cumulative steroid exposure)

1. Rituximab 375 mg/m² IV weekly x 4 doses (preferred in many centres, especially for relapsing or fertile-age patients) - RAVE and RITUXVAS trials showed non-inferiority to cyclophosphamide for remission induction, with superiority in relapsing disease
2. IV cyclophosphamide 15 mg/kg (or 500-750 mg/m²) every 2-3 weeks x 6 pulses - traditional standard, still widely used; pulse IV preferred over daily oral to reduce cumulative dose and side effects (bladder toxicity, myelosuppression)

• Rituximab is often favoured given the patient's age and the desire to limit cyclophosphamide-related toxicity (infection risk, bladder toxicity, gonadal toxicity)
• If cyclophosphamide is used, reduce dose by 25-50% for eGFR <30 ml/min; use with MESNA for bladder protection

• 30 mg orally twice daily - may be added as a steroid-sparing adjunct to rituximab or cyclophosphamide (ADVOCATE trial; approved by FDA/EMA for GPA/MPA)
• Particularly useful to reduce glucocorticoid burden in a diabetic patient (helps avoid steroid-driven hyperglycaemia)

• Consider in patients with RPGN and dialysis-dependent or near-dialysis AKI (creatinine rising rapidly, oliguria)
• EULAR 2022: "Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis" - though the PEXIVAS trial (2020) showed PLEX did not significantly reduce end-stage renal disease or death at 2 years, it may still be offered on a case-by-case basis, particularly if there is concurrent pulmonary haemorrhage
• If alveolar haemorrhage is found on imaging, PLEX is more strongly indicated

Step 3 - Supportive / Adjunctive Measures

Step 4 - Maintenance Therapy (once remission achieved, typically at 3-6 months)

• Rituximab is first-line for maintenance in GPA (500 mg IV every 6 months x 2 years, then review) - per EULAR 2022
• Alternatives: azathioprine 2 mg/kg/day or mycophenolate mofetil 2-3 g/day (less preferred in PR3-ANCA GPA due to higher relapse rates)
• Methotrexate is an alternative but should be avoided with significantly reduced GFR
• Continue low-dose prednisolone taper; aim for steroid-free maintenance with rituximab if possible
• Monitor ANCA titres (rising titres may predict relapse), renal function, urinalysis
• Duration of maintenance: minimum 24 months; many centres continue 3-5 years given high relapse risk in PR3-positive GPA

Prognosis Note

GPA (Wegener's Granulomatosis) - Quick Reference

Clinical Features

• Chronic sinusitis, epistaxis, nasal crusting/ulceration
• Saddle-nose deformity, subglottic stenosis, otitis media

• Cough, haemoptysis, dyspnoea
• Nodules, cavities, infiltrates on CXR

• Haematuria, RBC casts, proteinuria
• RPGN → oliguria → AKI

• Eye: proptosis, scleritis
• Skin: purpura, ulcers
• Systemic: fever, weight loss, arthralgia

Investigations

Management

Induction (remission induction)

• IV methylprednisolone 500-1000 mg x 3 days → oral prednisolone 1 mg/kg/day (taper to ≤5 mg by 4-5 months)
• Rituximab (preferred) OR IV cyclophosphamide x 6 pulses
• Avacopan 30 mg BD - steroid-sparing add-on (especially useful in diabetics)
• Plasma exchange - consider if dialysis-dependent RPGN or pulmonary haemorrhage

Maintenance (once remission at ~3-6 months)

• Rituximab 500 mg IV every 6 months (first-line)
• Alternatives: azathioprine or MMF
• Duration: minimum 24 months (longer in PR3-positive)

Supportive

• PCP prophylaxis (co-trimoxazole)
• PPI + bone protection
• Tight glycaemic control (diabetic patient)
• Dialysis if needed (may recover with treatment)

Key point: PR3/C-ANCA GPA has a high relapse rate - long-term ANCA monitoring is mandatory.

Sickle Cell Anemia - Quick Reference

Clinical Features

Chronic (Baseline)

• Haemolytic anaemia - pallor, jaundice, splenomegaly (early), pigment gallstones
• Autosplenectomy by adulthood (repeated microinfarcts) → functional asplenia → susceptibility to encapsulated organisms (Strep pneumoniae, H. influenzae)
• Cardiomegaly, systolic murmur (high-output)
• Growth retardation, delayed puberty

Acute Crises

Organ Complications

• Renal: haematuria, papillary necrosis, renal failure
• Eye: proliferative retinopathy
• Bone: avascular necrosis (femoral head), osteomyelitis (Salmonella)
• Skin: chronic leg ulcers
• Priapism

Investigations

Management

Preventive / Long-term

• Hydroxyurea (hydroxycarbamide) - increases HbF, reduces sickling and crisis frequency; first-line disease-modifying drug
• Penicillin V prophylaxis - from infancy until age 5 (functional asplenia)
• Vaccinations - pneumococcal, H. influenzae type b, meningococcal, annual flu
• Folic acid 5 mg daily (compensate for increased erythropoiesis)
• Regular transfusion programme - for stroke prevention in high-risk children (TCD velocity >200 cm/s)

Acute Vaso-Occlusive Crisis

• Analgesia - paracetamol/NSAIDs first; opioids (IV/oral morphine) for severe pain - aim to give within 30 min
• IV fluids - correct dehydration (avoid over-hydration)
• O₂ - only if SpO₂ <95%
• Treat precipitant - antibiotics if infection, warming if cold

Acute Chest Syndrome

• O₂, IV fluids (not aggressive), incentive spirometry
• Empiric broad-spectrum antibiotics (atypicals covered)
• Simple or exchange transfusion if severe
• ITU if deteriorating

Other Crises

• Aplastic crisis: transfusion support
• Splenic sequestration: urgent transfusion
• Stroke: exchange transfusion (not simple transfusion)
• Priapism: hydration, analgesia, aspiration if >4 hours

Curative

• Allogeneic haematopoietic stem cell transplant (HSCT) - only curative option; best outcomes in children with matched sibling donor
• Gene therapy - emerging (betibeglogene, lovo-cel); approved in some centres

Key point: Acute chest syndrome is the #1 cause of death. Hydroxyurea is underused - offer to all patients with moderate-severe disease regardless of crisis frequency.

1. Event Causing Deterioration

Diagnosis: Acute Anaphylactic Transfusion Reaction (Severe Anaphylaxis)

Justification - symptom by symptom

2. Immediate Measures (Simultaneous, in order of priority)

1. STOP the transfusion immediately - disconnect IV line, keep IV access open with normal saline
2. Call for emergency help - anaesthetics, resuscitation team
3. IM adrenaline (epinephrine) 0.5 mg (1:1000 = 1 mg/mL) into anterolateral thigh - do not delay; this is the single most important intervention
4. Position: supine with legs elevated (unless stridor worsens - semi-recumbent if airway concern predominates)
5. High-flow oxygen 15 L/min via non-rebreather mask
6. Secure large-bore IV (16-18 G) - begin rapid isotonic crystalloid (normal saline 1000 mL in first 5 min, then titrate)
7. Continuous monitoring: ECG, pulse oximetry, BP every 2-5 min
8. Prepare for emergency airway - endotracheal intubation or surgical airway (cricothyroidotomy) if stridor worsens and airway is lost; SpO₂ of 75% demands immediate escalation

3. Treatment Plan

A. First-Line: Epinephrine (Adrenaline) - NON-NEGOTIABLE

• IM adrenaline 0.5 mg (0.5 mL of 1:1000) into anterolateral thigh
• Repeat every 5-10 minutes if no improvement (up to 3 doses IM)
• If refractory hypotension persists after 2-3 IM doses + IV fluids → IV adrenaline infusion 1-10 μg/min (1 mg in 1000 mL saline = 1 μg/mL; titrate to BP)
• Mechanism: α1 = vasoconstriction + reduces mucosal oedema; β1 = increased cardiac output; β2 = bronchodilation + mast cell stabilisation

B. Airway Management

• SpO₂ 75% with stridor = imminent airway loss - anaesthetics must be at bedside
• Attempt RSI (rapid sequence intubation) early before complete oedema occludes airway
• If intubation fails → surgical cricothyroidotomy
• High-flow O₂ throughout

C. Second-Line Agents (after adrenaline, not instead of it)

D. Fluid Resuscitation

• Normal saline 1-2 L rapidly IV - massive vasodilation causes relative hypovolaemia
• Titrate to MAP >65 mmHg and clinical improvement
• This patient already has haemorrhagic shock from femoral fracture - fluid resuscitation is critical

E. If Refractory / Beta-blocker taken

• IV adrenaline infusion (as above)
• Glucagon 1-5 mg IV over 5 min if patient is on beta-blockers (glucagon bypasses β-receptor blockade)
• Vasopressors (noradrenaline/dopamine) as adjuncts

F. Observation and Follow-up

• Admit to ICU/HDU - biphasic anaphylaxis can occur 1-72 hours later in up to 20% of cases
• Observe minimum 12-24 hours after severe reaction
• Serum mast cell tryptase - draw at 1-2 hours post-reaction (elevated confirms anaphylaxis, useful for medicolegal and diagnostic purposes)
• Report transfusion reaction to blood bank - return remaining blood product for analysis
• Allergy/immunology referral - test for IgA deficiency (if IgA-deficient, future transfusions require IgA-depleted/washed blood products)
• Supply patient with adrenaline auto-injector (EpiPen) on discharge + medic-alert bracelet

Key point: Adrenaline is the only life-saving drug in anaphylaxis. Antihistamines and steroids are adjuncts only - delayed or omitted adrenaline is the leading cause of death in anaphylaxis. - Rosen's Emergency Medicine, Chapter 106