BASICS
Description
- Small vessel vasculitis with IgA immune complex deposition.
- Multisystem: skin, joints, GI tract, kidneys.
- Formerly known as Henoch-Schönlein purpura; increasingly termed immunoglobulin-A vasculitis (IgAV).
- Self-limited in most cases, but renal damage causes morbidity and mortality.
Epidemiology
- Annual incidence: 29.9/100,000 children; 0.1-1.8/100,000 adults.
- Peak age: 4-6 years; 90% under 10 years.
- Male predominance: M:F ratio ~1.2-1.8:1.
- More common in Caucasians and Asians.
- Seasonal: fall and winter predominance.
ETIOLOGY AND PATHOPHYSIOLOGY
- Triggered by increased IgA1 production leading to immune complex deposition and complement activation.
- Small vessel inflammation causes tissue necrosis and fibrosis in affected organs.
- Likely multihit pathogenesis; infectious triggers common (URI prodrome).
- Associated infections: Group A Streptococcus, parvovirus B19, Bartonella, Helicobacter pylori, adenovirus, others.
- Drug triggers more common in adults (e.g., acetaminophen, ACEI/ARB, antibiotics, NSAIDs).
- Rare vaccine associations reported.
- Genetic predisposition: associations with α1-antitrypsin deficiency, familial Mediterranean fever, HLA subtypes, renin-angiotensin polymorphisms.
COMMONLY ASSOCIATED CONDITIONS
- Rare associations with solid tumors, lymphomas, and other malignancies.
- Possible links with H. pylori infection, immune disorders (food/drug allergies, IBD).
DIAGNOSIS
Clinical Criteria
- Mandatory: palpable purpura without thrombocytopenia.
- Plus at least one of:
- Diffuse abdominal pain
- Biopsy showing predominant IgA deposition
- Arthralgia or arthritis
- Renal involvement (hematuria or proteinuria)
- Direct immunofluorescence for IgA may aid diagnosis.
History
- Recent infection or drug exposure.
- Rash: palpable, nonblanching purpura; typically symmetric on lower extremities/buttocks.
- GI symptoms: abdominal pain, nausea, vomiting, GI bleeding.
- Joint symptoms: symmetric polyarthritis, mainly knees and ankles.
- Renal: hematuria, oliguria.
- Rare: CNS symptoms, scrotal swelling/orchitis.
Physical Exam
- Palpable purpura, petechiae, possible ecchymoses/bullae.
- Abdominal tenderness; rectal exam for GI bleeding.
- Joint tenderness without erythema or effusion.
- Orchitis with scrotal swelling.
- Hypertension with renal involvement.
- Rare CNS or pulmonary findings.
Differential Diagnosis
- Infectious: meningococcemia, Rocky Mountain spotted fever, bacterial endocarditis, EBV, sepsis.
- Vasculitis: polyarteritis nodosa, granulomatosis with polyangiitis, lupus, Kawasaki disease.
- Others: IBD, thrombocytopenic purpura, juvenile arthritis, leukemia, hereditary hemorrhagic telangiectasia, child abuse.
DIAGNOSTIC TESTS
Initial Labs
- CBC: leukocytosis, thrombocytosis; eosinophilia common; thrombocytopenia suggests alternative diagnosis.
- Blood cultures if sepsis suspected.
- Renal function: serum chemistries, urinalysis for hematuria/proteinuria.
- Coagulation studies: typically normal in HSP.
- Inflammatory markers: ESR, CRP.
- IgA levels: often elevated but nonspecific.
- Complement levels: normal or decreased.
- Antistreptolysin-O titer for recent streptococcal infection.
Imaging
- Abdominal X-rays or ultrasound to assess for intussusception or GI complications.
- CT angiography for GI bleeding localization if indicated.
Biopsy
- Renal biopsy if diagnosis uncertain or severe nephritis.
- Skin biopsy shows leukocytoclastic vasculitis with IgA deposition.
TREATMENT
General Measures
- Supportive care: rest, elevation, hydration, nutrition.
Medications
- Most cases self-limited; supportive care often sufficient.
- NSAIDs for arthralgia (caution if renal involvement).
- Corticosteroids:
- For severe joint, abdominal pain, cerebral vasculitis, pulmonary hemorrhage, orchitis, or severe renal disease.
- Oral prednisone 1-2 mg/kg/day or IV methylprednisolone pulses.
- Early steroids may reduce symptom duration but do not prevent long-term renal involvement.
- Immunosuppressants (cyclosporine, mycophenolate, cyclophosphamide, rituximab, plasmapheresis) for severe or steroid-resistant renal disease—clinical consensus lacking.
Adjunct Therapy
- ACE inhibitors or ARBs for persistent proteinuria.
ISSUES FOR REFERRAL
- Nephrology: for renal biopsy, nephrotic-range proteinuria, or persistent proteinuria >100 mg/mmol after 3 months.
INPATIENT CONSIDERATIONS
- Admit for:
- Severe abdominal pain, GI bleeding
- Renal insufficiency
- Altered mental status
- Severe arthritis limiting mobility
- Hypertension or nephrotic syndrome
ONGOING CARE
Follow-up
- Weekly during acute illness: history, physical exam, BP, urinalysis.
- Monthly for ≥6 months to monitor for renal involvement.
- Monitor pregnant women for proteinuria and hypertension.
- Evaluate for occult malignancy in adult-onset HSP.
PATIENT EDUCATION
- Resources: National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC): IgAV.
PROGNOSIS
- Dependent on renal involvement severity.
- Usually self-limited: 94% children, 89% adults.
- Most resolve in 4 weeks; recurrence rate ~33% within 6 months.
- Poor prognostic factors: age >8 years, fever at presentation, purpura above waist, elevated ESR/IgA, severe renal histology.
- Chronic renal disease in up to 20% children, 50% adults with nephritis.
- Long-term renal failure risk ≤5%.
COMPLICATIONS
- Nephrotic/nephritic syndrome, renal failure, hypertension.
- GI: hemorrhage, intussusception, infarction, obstruction.
- Pulmonary: alveolar hemorrhage.
- CNS: cerebral hemorrhage, seizures.
- Others: orchitis, testicular torsion, myocarditis, anterior uveitis.
CLINICAL PEARLS
- Classic tetrad: palpable purpura, abdominal pain, arthralgia, renal involvement.
- Supportive care mainstay; steroids for severe complications.
- Close renal monitoring essential for all patients up to 6 months.
REFERENCES
- Pohl M. Henoch-Schönlein purpura nephritis. Pediatr Nephrol. 2015;30(2):245-252.
ADDITIONAL READING
- Kawasaki Y. The pathogenesis and treatment of pediatric Henoch-Schönlein purpura nephritis. Clin Exp Nephrol. 2011;15(5):648-657.