What is the step-by-step management strategy for a patient presenting with Henoch-Schönlein Purpura (HSP)?

Henoch-Schönlein Purpura (HSP): Causes, Manifestations, and Step-by-Step Management

Definition and Etiology

HSP is an IgA-mediated systemic small-vessel vasculitis affecting primarily the skin, gastrointestinal tract, joints, and kidneys, with the fundamental cause remaining unknown but clearly involving abnormal IgA1 glycosylation and immune complex deposition. 1, 2, 3

• The disease involves leukocytoclastic vasculitis with IgA deposition in vessel walls and renal mesangium 3
• Most cases (>90%) follow an antecedent upper respiratory infection 2
• Abnormal O-linked oligosaccharide glycosylation of IgA1 molecules appears central to pathogenesis 3
• Incidence is 10-20 cases per 100,000 children annually, with peak age 4-7 years 4, 5

Clinical Manifestations

All patients develop palpable purpura (100%), with the classic tetrad including arthritis (75-82%), abdominal pain (60-65%), and renal involvement (40-50%). 2, 4, 3

Cutaneous Features

• Non-thrombocytopenic palpable purpura, typically on lower extremities and buttocks 1, 2
• Purpuric lesions are non-blanchable and may be preceded by urticarial lesions 6

Musculoskeletal Involvement

• Arthritis or arthralgia affecting knees and ankles predominantly 1, 4
• Joint symptoms are typically self-limited and non-deforming 2

Gastrointestinal Manifestations

• Diffuse abdominal pain (63% of cases) 3
• Gastrointestinal bleeding (33% of cases), which may include hematemesis 6, 3
• Erosive gastropathy and duodenal erosions on endoscopy 6

Renal Disease

• Hematuria and/or proteinuria (40-50% of cases) 2, 4
• Initial renal inflammation occurs in 46% of patients 5
• End-stage renal disease develops in 1-5% of patients 2

Diagnostic Approach

Diagnosis requires palpable purpura plus at least one of: renal involvement (hematuria/proteinuria), arthralgia/arthritis, or abdominal pain. 1, 4

Essential Initial Testing

• Urinalysis with microscopy looking for proteinuria, red blood cell casts, and dysmorphic red blood cells 1
• Basic metabolic panel including BUN, serum creatinine 1
• Complete blood count with platelets to rule out thrombocytopenia 1
• Blood pressure measurement (hypertension indicates severe renal involvement) 1

Confirmatory Testing

• Skin biopsy showing IgA deposition within superficial dermal vessel walls is the gold standard 6, 4
• Renal ultrasound if severe nephritis is suspected or biopsy is being considered 1

Monitoring Protocol

• Day 7 urinalysis is critical: a normal result has 97% negative predictive value for normal renal outcome 5
• Six-month monitoring period for all patients, with intensive monitoring for those with abnormal day 7 urine findings 5

Step-by-Step Management Strategy

Step 1: Initial Assessment and Supportive Care

Supportive treatment is the primary intervention, as HSP spontaneously resolves in 94% of children and 89% of adults. 2

• Provide patient/family education about disease course and expected duration (average 4 weeks) 4
• Use acetaminophen (paracetamol) as first-line analgesic, avoiding NSAIDs like ketorolac due to renal injury risk 1
• Ensure adequate hydration and rest 2

Step 2: Treatment of Joint and Cutaneous Symptoms

For significant arthritis or severe cutaneous symptoms, oral prednisone 1-2 mg/kg daily for two weeks is recommended. 1, 2

• Corticosteroids hasten resolution of joint pain and abdominal symptoms but do not prevent recurrences 3
• For persistent purpura and pain beyond initial treatment, consider colchicine 1 mg/day for at least six months 1
• A low-antigen-content (LAC) diet for 4-8 weeks may improve symptoms when strictly followed 1

Step 3: Management of Gastrointestinal Complications

Oral corticosteroids (prednisone 1-2 mg/kg daily) should be used for severe gastrointestinal pain and hemorrhage. 4

• Corticosteroids reduce mean time to resolution of abdominal pain 2
• Upper endoscopy may be needed if hematemesis occurs to assess for erosive gastropathy 6
• If incomplete response to steroids, add mycophenolate mofetil 1000 mg twice daily for three months 6

Step 4: Renal Disease Management Algorithm

This is the most critical aspect of management as renal involvement determines long-term prognosis. 1, 2

For Persistent Proteinuria (Any Level):

• Start ACE inhibitor or ARB therapy targeting proteinuria to <1 g/day/1.73 m² 1
• Do NOT attempt complete normalization to <0.5 g/day/1.73 m² (increases side effects without benefit) 1

For Persistent Proteinuria >1 g/day/1.73 m² After ACE Inhibitor/ARB Trial:

• If GFR >50 ml/min/1.73 m², add 6-month course of oral corticosteroids 1
• Reserve corticosteroids for nephrotic syndrome (proteinuria >3.5 g/day) or nephritic syndrome unresponsive to ACE inhibitor/ARB 1

For Crescentic HSP with Nephrotic Syndrome and/or Deteriorating Kidney Function:

• High-dose intravenous methylprednisolone PLUS cyclophosphamide 1, 3
• Alternative immunosuppressants include azathioprine, cyclosporine, tacrolimus, or mycophenolate mofetil/mycophenolic acid 1
• Cyclophosphamide is used less frequently due to side effects but remains indicated for severe disease 1

For Adults with HSP Nephritis:

• Use the same treatment approach as children, though adults have worse prognosis 1

Step 5: What NOT to Do

Do NOT use prophylactic corticosteroids at HSP onset to prevent nephritis—moderate quality evidence shows no benefit. 1, 4

• Do not start corticosteroids for mild proteinuria without adequate ACE inhibitor/ARB trial 1
• Do not use corticosteroids in usual doses for established nephritis (ineffective) 3
• Avoid NSAIDs in patients with any renal involvement 1

Step 6: Long-Term Monitoring

All patients require six-month monitoring with prioritization based on day 7 urinalysis results. 5

• Monitor for persistent hematuria and proteinuria as indicators of ongoing disease activity 1
• Older patients (mean age 12.3 years vs. 6.0 years) are at higher risk for renal referral 5
• One-third of patients will have recurrences requiring repeat evaluation 3
• Long-term follow-up for hypertension and chronic kidney disease in those with significant renal involvement 4

Common Pitfalls to Avoid

• Starting corticosteroids too early for mild proteinuria increases side effects without proven benefit 1
• Delaying aggressive immunosuppression in crescentic disease worsens renal outcomes 3
• Using NSAIDs for pain control in patients with renal involvement risks acute kidney injury 1
• Inadequate monitoring duration—the six-month period is essential even if initial presentation is mild 5
• Assuming GI symptoms always precede rash—hematemesis can be the initial presenting symptom 6