Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura (HSP), is a systemic, small-vessel, IgA immune complex-mediated leukocytoclastic vasculitis characterized by a tetrad of palpable purpura, GI symptoms (colicky abdominal pain, GI bleed), renal disease, and arthritis/arthralgias.

Henoch-Schönlein purpura (HSP)

Anaphylactoid purpura

Allergic purpura

∼1.2 to 2:1 male:female ratio. Seen mostly from ages 3 to 12 with peak incidence between 4 and 6 yr. This disorder can be seen in older adolescents and young adults; however, 90% of cases are in patients <10 yr.^2,4,5

• Palpable purpura (Fig. E1) of dependent areas, especially lower extremities (palms and soles) and areas subjected to pressure, such as the beltline in adults or buttocks in toddlers. Facial involvement is rare.
• GI symptoms are seen in up to two thirds of patients. Common findings are abdominal pain, nausea, vomiting, diarrhea, cramping, hematochezia, and melena. Complications include GI bleeding (20% to 30%), bowel ischemia, intussusception (1% to 5%), and bowel perforation (<1%). Pancreatitis and acalculous cholecystitis are rare complications.
• Subcutaneous edema in dependent and periorbital areas.
• Arthralgias and arthritis in 60% to 85%. Typically, oligoarticular, affecting lower extremity and large joints. Periarticular swelling and tenderness also noted.
• Renal involvement is seen in as many as 80% of older children, usually within the first month of illness. Fewer than 5% progress to end-stage renal failure, which is a major cause of morbidity. Renal manifestations may range from isolated hematuria, proteinuria, or severe crescentic glomerulonephritis.
• Genitourinary involvement is seen between 2% and 38% of male children that can present with pain and edema of the scrotum, epididymitis, or orchitis that can mimic testicular torsion.⁸
• Central nervous system (CNS) involvement is rare, but can manifest as confusion, weakness, visual deficits, or impaired consciousness.

• Presumptive etiology is exposure to a trigger antigen that causes antibody formation.
• Antigen-antibody (immune) complex deposition, complement factor, and neutrophil infiltration then occurs in arteriole and capillary walls of skin, renal mesangium, and GI tract. IgA deposition is most common.
• Abnormal IgA1 glycosylation is a leading cause of the elevated serum galactose-deficient IgA1 levels seen in the disease. Notably, this is a trait shared with IgA nephropathy indicating a similar pathogenesis or, perhaps, two variants of the same disease.
• Antigen triggers include drugs, foods, immunizations, upper respiratory, or other viral illnesses. Group A β-hemolytic streptococcal infection is the most common precipitant in children, seen in up to one third of cases. Of childhood cases, 30% to 65% are preceded by an unspecified upper respiratory infection. Various precipitants have been described in case reports including parvovirus B19, Helicobacter pylori, intravesical bacille Calmette Guérin (BCG), and COVID-19.
• Emerging data suggests that COVID-19 precipitation of IgA vasculitis is caused by rapid IgA activation and subsequent immune complex deposition; occurring as early as two days after initial symptom onset.⁹
• Development of IgA vasculitis may be associated with exposure to medications, including antibiotics, antitumor necrosis factors, or chemotherapeutic agents or vaccines.¹
• All vaccine subtypes have been identified as a potential precipitant of drug-induced IgA vasculitis. It is hypothesized that vaccine-mediated immune responses mimic the disease-mediated immune responses that would otherwise trigger IgA vasculitis.¹⁰

The diagnosis is made more difficult if the presenting symptoms exclude skin manifestations, wherein the differential will include alternative causes for abdominal pain, arthritis/arthralgia, and renal disease.

• Polyarteritis nodosa
• Meningococcemia
• Rocky Mountain spotted fever
• Cryoglobulinemia thrombocytopenic purpura
• Hypersensitivity vasculitis
• Microscopic polyangiitis

• Acute abdomen
• Intussusception
• Inflammatory bowel disease

• Poststreptococcal glomerulonephritis
• Granulomatosis with polyangiitis (Wegener granulomatosis)

• Connective tissue diseases (e.g., systemic lupus erythematosus)
• Juvenile rheumatoid arthritis

History, physical examination, laboratory testing, skin or renal biopsy

• Laboratory abnormalities are not specific for IgA vasculitis but may help identify complications and rule out other diseases.
  1. Electrolytes, blood urea nitrogen, and creatinine
  2. Urinalysis
  3. Urine albumin: Urine creatinine or urine protein: Urine creatinine ratio to screen for renal involvement
  4. CBC
  5. Prothrombin time, fibrinogen, and fibrin degradation products
  6. Blood cultures
  7. Skin or renal biopsy
• Leukocytosis and eosinophilia may be seen.
• IgA levels are elevated in ∼50% of patients.
• Glomerulonephritis may be present (microscopic hematuria, proteinuria, and red blood cell casts).
• Pathologic examination may aid diagnosis.
  1. Characteristic skin biopsy findings include hemorrhage below the epidermis, as well as necrotic, thickened small vessels with IgA/C3 deposits. Notably, the absence of IgA immunofluorescence staining does not exclude the diagnosis of IgA vasculitis.
  2. There is no one characteristic renal lesion, although mesangial IgA deposition is often seen.

• Imaging studies are generally not diagnostic of IgA vasculitis, although certain studies may be useful to narrow the differential diagnosis and/or screen for complications.
• One important example of this is the use of ultrasound to screen for intussusception in those with IgA vasculitis and severe abdominal pain.

Supportive care with pain management, adequate hydration, and nutrition is the primary intervention as up to 94% of cases in children and 87% cases in adults will resolve spontaneously.

• Prednisone 1 to 2 mg/kg/day PO for 2 wk is typically given for severe arthritis and/or abdominal pain. An equivalent dose of methylprednisolone can be used with same efficacy.
  1. A double-blind, randomized, controlled trial (RCT) found that early treatment with prednisone reduced abdominal pain and joint symptoms but did not prevent development of renal disease. It was effective in the treatment of renal disease once it was established.⁴
• Kidney disease: Improving Global Outcomes (KDIGO) guidelines¹² recommend the same treatment for nephritis related to IgA vasculitis in children and adults.
  1. ACE inhibitor or ARB therapy is suggested for nephritis with persistent proteinuria and monitor urine protein excretion to assess for progression.¹³ If initial therapies are unsuccessful and glomerular filtration rate (GFR) >50 ml/min/1.73m², treatment is similar to IgA nephritis where a prolonged (6-mo) glucocorticoid regimen is suggested along with RAAS inhibition and strict blood pressure control (<130/80 mm Hg).¹⁴
  2. Patients with crescentic glomerulonephritis with deteriorating renal function or nephrotic syndrome related to IgA vasculitis should be treated as if they have crescentic IgA nephritis; such treatment includes corticosteroids and cyclophosphamide.
  3. Children requiring kidney biopsy to guide management should have the procedure performed within 3 wk of proteinuria onset to help prevent the permanent kidney damage that often manifests within that timeframe.¹⁵
  4. In a 2018, study of 22 adult patients with IgA vasculitis, treatment with rituximab resulted in a 91% remission rate that appeared to be sustained for 6 mo post treatment.¹⁶
  5. Mycophenolate mofetil has been shown to be noninferior to glucocorticoid therapy in patients with nephrotic-range proteinuria.¹⁷
  6. An RCT of 24 children with nephrotic range proteinuria or crescentic HSPN on biopsy were treated with methylprednisolone or cyclosporine. All 11 patients treated with cyclosporine had resolution of proteinuria within 3 mo, compared to seven of the 13 patients treated with methylprednisolone. The six from the methylprednisolone group without resolution were subsequently treated with cyclosporine with five showing a response.¹⁸
  7. In a 2019 systematic review of 17 cases of patients with IgA vasculitis and severe or treatment-resistant purpura who were treated with dapsone, rash was resolved in each case. However, dapsone was associated with a high relapse rate (∼50%) and does not improve nonskin symptoms of IgA vasculitis.¹⁹
  8. Not all patients with nephritis or nephrotic-range proteinuria respond to these treatments; they eventually may require renal transplantation.
  9. Fig. E1 illustrates follow-up of IgA vasculitis patients with or without renal involvement.
• Severe GI involvement (defined by intense pain, GI bleeding, and protein losing enteropathy) improved with intravenous immunoglobulin (IVIG) in eight pediatric patients with IgA vasculitis. IVIG was found to slow or stop effects on estimated GFR (eGFR) in patients with nephritis. A case series postulated an efficacious addition of plasma exchange to adults with severe renal and extrarenal complications.

• Even if renal involvement is not present after the initial episode, urinalysis and blood pressure should be checked every 2 to 4 wk for first 6 mo to detect development and progression of kidney disease.
• Azathioprine may allow earlier corticosteroid discontinuation in patients with relapsing symptoms of IgA vasculitis.²⁰

• Prognosis excellent, with spontaneous recovery within 4 wk in most patients.
• Hospitalization is often required for significant GI or renal involvement.
• Increased age of onset generally correlates with morbidity. While end-stage renal disease (ESRD) occurs in 10% to 30% of adult patients with IgA vasculitis at 15 years, chronic renal insufficiency is the most common long-term morbidity and affects adults more than children.
• Recurrence occurs in approximately one third of patients, typically within first 4 to 6 mo after the initial episode, and most commonly affects patients with prior renal involvement. Recurrent episodes are generally less severe than the initial episode. For those with a relapsing course, immunosuppression may be required depending on the severity of symptoms.

No complementary or alternative treatment modalities proven to be effective for IgA vasculitis.

Rheumatology, nephrology, dermatology, or general surgery consultation based on clinical manifestations

• Organ systems involved in IgA vasculitis are skin, joints, GI tract, and kidneys.
• Palpable purpura, abdominal pain, arthritis, and renal involvement are common clinical manifestations.
• GI symptoms and arthritis may precede rash. Skin and renal manifestations occur at the same time.
• Most with spontaneous recovery within 4 wk of onset of symptoms.
• End-stage renal disease occurs in only 5% of all patients with IgA vasculitis.

• See https://www.vasculitisfoundation.org/.

Henoch-Schönlein Purpura (Patient Information)

IgA Nephropathy (Related Key Topic)