Henoch-Schönlein Purpura (HSP)

Henoch-Schönlein Purpura (HSP) / IgA Vasculitis (IgAV)

Definition and Epidemiology

Henoch-Schönlein Purpura (HSP), also known as IgA Vasculitis (IgAV), is the most common vasculitis of childhood, characterized as a small vessel vasculitis.

• Pathogenesis: Involves increased serum IgA and IgA immune complexes, with IgA1-dominant deposits in vessel walls.
• Incidence: 20/100,000 children/year; 90% of cases occur between ages 3 and 15 (mean age 6–7 years).
• Epidemiology: More common in winter/spring and in boys (1.8:1 ratio).
• Triggers: Preceded by Upper Respiratory Tract Infection (URTI) in 50% of cases. Common triggers include:
  • Group A Streptococcus, S. aureus, Mycoplasma, Adenovirus.
  • Vaccines (MMR, COVID-19).
  • COVID-19 infection.
  • Certain drugs (including biologics).
• Associated Conditions: Higher incidence of kidney involvement and recurrent rash observed in patients with allergic rhinitis and chronic rhinosinusitis.

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Pathology

• Skin: Vasculitis of dermal capillaries and postcapillary venules with neutrophil/monocyte infiltration (leukocytoclastic vasculitis).
• Kidney: Endocapillary proliferative glomerulonephritis (ranging from focal segmental to crescentic).
• Immunofluorescence: Identifies IgA deposition in small vessel walls, along with C3, fibrin, and IgM.
• Genetics: Associated with HLA-B35 and HLA-DRB1 alleles.

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Clinical Manifestations

HSP is characterized by a classic tetrad of symptoms:

1. Skin: Palpable Purpura

• Hallmark: Occurs in 75–100% of cases.
• Appearance: Starts as pink macules/wheals, evolving into petechiae, palpable purpura, or large ecchymoses.
• Distribution: Symmetrical, involving lower extremities and buttocks.
• Evolution: Erupts in groups (lasting 3–10 days); may recur for up to 4 months.
• Edema: Subcutaneous edema in hands, feet, periorbital area, and scrotum is common.

2. Musculoskeletal: Arthritis and Arthralgia

• Frequency: 50–75%.
• Characteristics: Transient, migratory, oligoarticular (1–4 joints), and non-deforming.
• Location: Mainly hips, knees, and ankles.
• Presentation: Periarticular swelling and tenderness, usually without joint effusion or erythema.

3. Gastrointestinal (GIT) Manifestations

• Frequency: 50%.
• Symptoms: Nausea, vomiting, and abdominal pain.
• Complications: Intussusception (most common severe GIT complication), mesenteric ischemia, or perforation.
• Markers: Guaiac-positive stool (56%), increased fecal alpha-1-antitrypsin, and hypoalbuminemia.
• Timing: Typically follows the rash within 8 days, but precedes it in 15–35% of cases.

4. Renal Involvement

• Frequency: 25–50%; more prevalent in older children. Z
• Presentation: Microscopic hematuria (most common) with/without red blood cell casts and mild proteinuria.
• Risk Factors: Nephrotic-range proteinuria, elevated creatinine, and hypertension increase the risk of progressive disease.
• Prognosis: Progression to end-stage renal disease (ESRD) occurs in 1–2% of children. Z

Other Systemic Involvement

• Urologic (2–30%): Scrotal pain, swelling (epididymitis/orchitis). Scrotal edema may cause testicular torsion.
• Neurologic: Headaches, seizures, encephalopathy (PRES), or stroke (rare).
• Respiratory: Impaired lung diffusion capacity is common; pulmonary hemorrhage is rare.
• Eyes: Keratitis and uveitis (rare).

Central & peripheral nervous system – headaches, seizures, encephalopathy (including hypertensive encephalopathy and posterior reversible encephalopathy syndrome PRES), focal neurologic deficits, ataxia, intracerebral hemorrhage, and neuropathy. Most CNS findings are transient; occasional permanent sequelae may follow hemorrhagic stroke.

Respiratory tract – In hospitalized IgA‑vasculitis patients, impaired lung diffusion (~97 %) and mild interstitial changes on chest X‑ray (~69 %) are common even without notable respiratory symptoms. Pulmonary hemorrhage is rare.

Ocular – Keratitis and uveitis occur rarely as sequelae.

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Clinical Manifestations

Diagnosis

The diagnosis is primarily clinical and usually straightforward when palpable purpura is present. In ≈ 25 % of cases the rash appears after other manifestations, making early recognition challenging.

Classification criteria – Palpable purpura (in the absence of coagulopathy or thrombocytopenia) plus at least one of the following:

• Abdominal pain (acute, diffuse, colicky)
• Biopsy of affected tissue showing predominant IgA deposition
• Arthritis or arthralgia
• Renal involvement (proteinuria > 3 g/24 h, hematuria, or red‑cell casts)

Laboratory clues

• Serum IgA elevated in ~50 % of patients; higher levels are associated with kidney involvement.
• Normochromic anemia due to occult or overt gastrointestinal bleeding.
• Leukocytosis and ↑ ESR when IgAV follows bacterial infection.
• PT, aPTT, bleeding time, and platelet count are typically normal.
• Initial urinalysis often normal, though proteinuria/hematuria may develop over time.
• Renal assessment includes blood‑pressure measurement, urinalysis, and serum creatinine.
• Hypocomplementemia (C3, C4) is reported in a significant proportion of children, often linked to recent streptococcal infection.
• ANA and ANCA are usually negative.

Differential Diagnosis Comparison

Criteria	ITP	Acute Leukemia	Aplastic Anemia	HSP
Hb / RBC	Normal	Decreased	Decreased	Normal
WBC Count	Normal	Highly Increased	Decreased	Normal/Increased in some cases
Platelets	Decreased	Decreased	Decreased	Normal

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Differential diagnosis for IgAV
The differential depends on the organ(s) involved:

• Purpura

  • Consider septicemia, immune thrombocytopenia (ITP), hemolytic uremic syndrome (HUS), leukemia, and coagulopathies (eg, hemophilia).
    • Normal platelet count and coagulation studies help differentiate IgAV from these conditions.
  • Other causes of purpura with normal platelets/coagulation: other small‑vessel vasculitides, hypersensitivity vasculitis, and acute hemorrhagic edema of infancy (AHEI).

• Arthritis / Arthralgia

  • Evaluate for alternative rheumatologic or septic causes when presentation is atypical or persistent.

• Abdominal pain

  • Consider surgical and non‑surgical gastrointestinal causes if pain is severe, prolonged, or accompanied by bleeding.

• Kidney disease

  • Differentiate from other causes of glomerulonephritis based on clinical course, labs, and urinalysis.

IgAV management (general principles)

• Most patients: outpatient care with adequate oral hydration, bed rest, and symptomatic relief for joint/abdominal pain.
• Analgesia: NSAIDs (eg, naproxen) for joint and/or abdominal pain when appropriate.
• Oral prednisone for severe abdominal pain that prevents oral intake, for patients who fail NSAIDs, or for other life‑threatening manifestations.
  • Important: prednisone reduces abdominal and joint pain but does not change overall prognosis nor prevent renal disease.
• Severe disease: intravenous immune globulin (IVIG) and plasma exchange are sometimes used.
• Chronic IgAV renal disease: immunosuppressants such as azathioprine, cyclophosphamide, cyclosporine, or mycophenolate may be employed.

Indications for hospitalization

• Inability to maintain adequate hydration orally
• Severe abdominal pain
• Significant gastrointestinal bleeding
• Altered mental status or respiratory compromise
• Severe pain or joint involvement limiting ambulation/self‑care
• Kidney insufficiency (elevated creatinine), hypertension, and/or nephrotic syndrome

Long‑term complications and monitoring

• Renal disease is the major long‑term complication. Incidence of chronic renal disease ≈ 1–2%.
• Nephritis can develop up to 6 months after diagnosis — serial monitoring of blood pressure and urinalysis for several months is recommended.

Prognosis

• Overall excellent for childhood IgAV; most cases are acute and self‑limited (average duration ~4 weeks).
• Recurrence in ~30% of children, typically within 4–6 months of diagnosis.
• Long‑term outcome depends largely on severity/duration of gastrointestinal or renal involvement.
• Of children who develop IgAV nephritis, ~8% may progress to end‑stage renal disease.
• Rarely, death can occur in the acute phase from bowel infarction, CNS involvement, or severe renal disease.