What is the approach to diagnosis and management of a pediatric patient with Henoch-Schönlein purpura (HSP)?

Diagnosis and Management of Henoch-Schönlein Purpura in Pediatric Patients

Diagnostic Approach

Diagnose HSP clinically when palpable purpura is present plus at least one of the following: renal involvement (hematuria and/or proteinuria), arthralgia/arthritis, or abdominal pain. 1, 2

Essential Clinical Criteria

• The diagnosis requires palpable purpura (non-thrombocytopenic) plus at least one additional feature: diffuse abdominal pain, arthritis or arthralgia, renal involvement (hematuria and/or proteinuria), or biopsy showing predominant IgA deposition 1, 2
• The clinical triad of hematuria, purpuric lesions, and ankle pain is diagnostic of HSP 1
• Approximately 78% present with typical form (purpura first), while 22% present atypically with joint involvement preceding purpura 3

Mandatory Initial Laboratory Evaluation

• Urinalysis with microscopy is essential to assess for glomerulonephritis, specifically looking for proteinuria, red blood cell casts, and dysmorphic red blood cells indicating glomerular involvement 1
• Complete blood count with platelets to confirm non-thrombocytopenic purpura and rule out other causes 1, 2
• Basic metabolic panel including BUN and serum creatinine to assess renal function, with creatinine levels interpreted relative to age in pediatric patients 4, 1
• Blood pressure measurement is mandatory as hypertension indicates more severe renal involvement 1

Role of Skin Biopsy

• Skin biopsy should be performed when the clinical picture is incomplete or atypical to confirm IgA deposits in vessel walls, which is sine qua non for diagnosis 5
• Biopsy prevents both missed diagnoses (patients developing silent chronic renal failure) and overdiagnosis (unnecessary follow-up) 5
• The finding of IgA deposits with characteristic small-vessel vasculitis on histology and immunofluorescence confirms HSP and distinguishes it from other leukocytoclastic vasculitides 5, 6
• Skin biopsy is particularly important when renal signs become manifest years after initial presentation, as the clinical picture is often incomplete 5

Imaging Considerations

• Renal ultrasound is the preferred initial imaging modality to assess kidney size and anatomy, particularly if renal biopsy is being considered for severe nephritis 1

Management Strategy

General Supportive Care

Most cases of HSP are self-limited with an average disease duration of 4 weeks, requiring only supportive care. 2

• The majority of HSP cases resolve spontaneously without specific treatment 2, 7
• Pain management with acetaminophen (paracetamol) is recommended as first-line analgesic, avoiding NSAIDs due to potential renal toxicity 1
• Do NOT use NSAIDs (including ketorolac/Toradol) in HSP patients due to risk of acute kidney injury, especially with pre-existing renal impairment 1

Management of Renal Involvement

For children with HSP nephritis and persistent proteinuria 0.5-1 g/day per 1.73 m², start ACE inhibitors or ARBs as first-line therapy. 4, 1

Mild to Moderate Renal Disease

• ACE inhibitors or ARBs are recommended for persistent proteinuria 0.5-1 g/day per 1.73 m² despite optimized supportive care 4, 1
• Target proteinuria to <1 g/day/1.73 m² rather than attempting complete normalization, which increases medication side effects without proven benefit 1
• For persistent proteinuria >1 g/day per 1.73 m² after ACE inhibitor/ARB trial and GFR >50 ml/min per 1.73 m², add a 6-month course of corticosteroid therapy 4, 1

Severe Renal Disease

• For crescentic HSP with nephrotic syndrome and/or deteriorating kidney function, treat with high-dose intravenous methylprednisolone plus cyclophosphamide, following the same protocol as crescentic IgA nephropathy 4, 1
• Reserve corticosteroid therapy for nephrotic syndrome (proteinuria >3.5 g/day) or nephritic syndrome that has not improved with ACE inhibitor/ARB therapy 4
• Alternative immunosuppressive options for severe nephritis include steroids combined with azathioprine, cyclosporine, tacrolimus, or mycophenolate mofetil, with cyclophosphamide used less frequently due to side effects 4

Management of Gastrointestinal Symptoms

• Oral corticosteroids (prednisone 1-2 mg/kg daily for two weeks) may be considered for severe gastrointestinal pain and gastrointestinal hemorrhage 1, 2
• Do NOT use corticosteroids prophylactically at HSP onset to prevent nephritis, as moderate quality evidence (Level 1B) shows no benefit in preventing nephritis or reducing risk of severe persistent nephritis 4, 1

Management of Joint and Cutaneous Symptoms

• For joint pain and cutaneous symptoms, oral prednisone at 1-2 mg/kg daily for two weeks may be beneficial 1
• Colchicine (1 mg/day) may be considered for persistent purpura and pain, with treatment for at least six months 1
• Dapsone has beneficial effects on cutaneous, gastrointestinal, and articular manifestations, especially in chronic forms 6

Dietary Considerations

• A low-antigen-content (LAC) diet may improve symptoms and laboratory abnormalities when strictly followed for 4-8 weeks, and can be considered as supportive treatment in all symptomatic patients 1
• The LAC diet can be used in conjunction with other treatments, such as colchicine, for chronic or persistent symptoms 1

Monitoring Protocol

All children with HSP require follow-up for at least 6 months with regular urine testing for proteinuria and hematuria plus blood pressure measurement. 7

Timing of Renal Involvement

• Among patients with renal involvement, 68% experience it in the first month after onset 3
• However, renal signs can become manifest years after initial presentation, necessitating prolonged monitoring 5, 7
• Monitor for persistent hematuria and proteinuria, as these indicate ongoing disease activity 1

Recurrence Risk

• Recurrences occur in approximately 15% of patients 3
• The average duration of disease is 4 weeks, though chronic forms may persist 2

Critical Pitfalls to Avoid

• Do NOT start corticosteroids too early for mild proteinuria without adequate trial of ACE inhibitor/ARB therapy, as this increases side effects without proven benefit 1
• Do NOT attempt to normalize proteinuria to <0.5 g/day/1.73 m², which increases side effects without proven benefit 1
• Do NOT use corticosteroids prophylactically to prevent HSP nephritis, as this has no benefit based on strong evidence 4, 1
• Avoid NSAIDs including ketorolac due to nephrotoxicity risk 1
• Do not discontinue monitoring after initial resolution, as renal involvement can develop late 5, 7

Long-Term Prognosis and Special Considerations

• Most cases have excellent outcomes, with renal involvement being the most important prognostic factor determining morbidity and mortality 2
• Long-term complications are rare but include persistent hypertension and end-stage kidney disease 2
• Approximately 2% of children with HSP progress to renal failure, and up to 20% of children with nephritis treated in specialized centers require hemodialysis 6
• The risk of chronic renal failure is maximal (>50%) when initial signs are a combination of nephrotic and nephritic syndromes 5
• Women with a history of HSP during childhood are at increased risk of complications (proteinuria and hypertension) during pregnancy and should be monitored closely 7
• Adult HSP nephritis should be treated using the same approach as children, though adults have worse prognosis and higher risk of progression to end-stage renal disease 4, 1