IgA vasculitis

IgA vasculitis (IgAV), formerly known as Henoch-Schonlein purpura (HSP), is an acute immune complex-mediated small vessel vasculitis that most commonly occurs in children. It is often preceded by an upper respiratory tract infection and typically presents with a tetrad of symptoms: palpable purpura, arthritis/arthralgia, abdominal pain, and renal disease. However, in any individual patient, only some of the classic tetrad of symptoms may be present. IgAV is a clinical diagnosis, but in particularly unclear or atypical cases a biopsy may be used to confirm the diagnosis. Because the disease course is usually self-limiting, treatment is generally supportive. Severe cases may require glucocorticoids, antihypertensive drugs, and possibly dialysis. IgAV has an excellent prognosis, usually resolving within one month when not complicated by significant renal disease.

• Sex: : ♂ > ♀
• Age: more common in children
  • 90% of cases < 10 years ^[1]
  • Peak incidence: 6 years ^[2]

Epidemiological data refers to the US, unless otherwise specified.

The exact pathogenesis is unknown and assumed to be multifactorial. Factors that likely play a role include:

• Preceding infection
  • Up to 90% of cases preceded by viral or bacterial infection 1–3 weeks prior ^[3]
  • Most commonly an upper respiratory tract infection caused by group A Streptococcus ^[4]
  • GI infections also possible
  • Many other organisms have also been associated with IgAV
• IgA nephropathy
• Genetic predisposition
• Drugs (especially β-lactam antibiotics and antiarrhythmics) and vaccines (e.g., yellow fever, cholera)

• Hypothesized pathophysiological mechanism: exposure to allergen/antigen (e.g., infection, drugs) → stimulation of IgA production → deposition of IgA immune complexes in vascular walls (e.g., in the skin, GI tract, joints, kidneys) → activation of complement → vascular inflammation and damage

History

• Symptom onset often 1–3 weeks after an infection, typically affecting the upper respiratory tract ^[3]

Manifestations ^[1][5]

• Skin: (∼ 100% of cases)
  • Symmetrically distributed, raised, erythematous macules or urticarial lesions that coalesce into palpable purpura (nonblanching skin lesions)
  • Most common sites: the lower extremities, buttocks, and other areas of pressure or constraint (e.g., from socks or clothing)
• Joints: (∼ 75% of cases) arthritis/arthralgia, most common in the ankles and knees
• Gastrointestinal tract (∼ 60% of cases)
  • Colicky abdominal pain (may be severe enough to mimic an acute abdomen)
  • Can cause intussusception
  • Bloody stools or melena
  • Nausea/vomiting
• Kidneys: (∼ 50% of cases): IgAV nephritis with signs and symptoms of nephritic syndrome
• Other organs
  • Scrotum (scrotal swelling, pain, and tenderness)
  • Central and peripheral nervous system (e.g., headaches, seizures, focal neurologic deficits, ataxia, intracerebral hemorrhage, central and peripheral neuropathy)
  • Respiratory tract (e.g., mild interstitial changes, pulmonary hemorrhage)
  • In rare cases: eyes (e.g., keratitis, uveitis)

IgAV is characterized by PAPAH: purpura, abdominal pain, arthritis/arthralgia, and hematuria.

IgAV is one of the important differential diagnoses to consider in pediatric limp.

IgAV is a clinical diagnosis; , laboratory tests are not essential to IgAV diagnosis. However, they may be useful for excluding differential diagnoses in patients exhibiting only one or two of the IgAV tetrad of symptoms, as is often the case in the first few days. Laboratory tests are also useful for monitoring the extent of renal involvement, which helps determine the prognosis. Definitive diagnosis in uncertain cases is made via biopsy. ^[1][6]

Laboratory tests

• Indications: useful in patients with an incomplete or unusual presentation
• Complete blood cell count with differential
  • ↑ Platelet count
  • ↑ White blood cell count
  • ↓ Hemoglobin
• Coagulation profile: usually normal
• Serum antibodies and complement
  • ↑ IgA in serum
  • Evidence of circulating IgA immune complexes
  • ↓ Complement
  • In case of preceding streptococcal infection: antistreptolysin O (ASO) titers
• Serum chemistry
  • ↑ Creatinine and/or BUN
  • Electrolyte imbalances
• Urinalysis to assess possible renal disease
  • Hematuria; , often with RBC casts
  • Possibly proteinuria
• Inflammatory markers
  • ↑ ESR
  • ↑ CRP
• In case of GI involvement: positive stool guaiac

The platelet count in IgAV is normal or elevated, as opposed to other causes of purpura.

Imaging

• Indication: performed in patients with marked abdominal symptoms or suspected complications
• Modalities: abdominal ultrasound/CT

Biopsy

• Indications: reserved for patients with unusual skin presentations or severe renal involvement (e.g., persistent nephritic syndrome)
• Skin: leukocytoclastic vasculitis with IgA and C3 immune complex deposition (hallmark) in small vessels of the superficial dermis
• Kidney
  • Mesangial IgA deposition
  • C3 complement and fibrin
  • Crescent formation in more severe cases

IgAV is a unique cause of purpura without thrombocytopenia.

The differential diagnoses listed here are not exhaustive.

Most cases of IgAV are self-limiting and only require supportive care; (e.g., pain management) with regular outpatient follow-up. Severe IgAV requires hospitalization and intensive medical therapy.

Mild disease

• Outpatient treatment
• Usually no treatment necessary
• NSAIDs for pain management, rest, and adequate hydration
• Discontinuation of suspected precipitating drug, if applicable

Severe disease ^[7]

• Inpatient treatment
• Systemic glucocorticoids for severe abdominal pain not relieved by NSAIDs
• IV fluids to maintain hydration
• In case of severe renal disease
  • IV methylprednisolone pulse therapy ^[8]
  • Renal transplantation in end-stage renal disease (ESRD)
  • Acute dialysis in the case of acute kidney injury (AKI)
  • Consider antihypertensive agents if hypertension is present.
  • Reduce salt intake

• Renal ^[9]
  • In some cases, IgAV nephritis may progress to nephrotic syndrome.
  • Serious complication: rapid-progressive glomerulonephritis (RPGN) with crescent formation
• Gastrointestinal
  • Small bowel infarction or perforation
  • Intussusception

We list the most important complications. The selection is not exhaustive.

• All patients
  • Blood pressure monitoring and urinalysis
  • Timing
    • Symptomatic patients: weekly or biweekly testing
    • After symptoms subside: monthly testing for the first 6 months, then every other month for an additional 6 months
    • Symptom-free for > 12 months: perform tests at subsequent well-child visits
• In patients with abnormal blood pressure or urinalysis
  • Measure serum creatinine
  • Referral to a pediatric nephrologist if serum creatinine levels are abnormal

• Usually resolves with full recovery, however, relapse is likely in patients with previous renal involvement.
• The prognosis is worse in patients with nephrotic range proteinuria. In rare cases (∼ 1%), ESRD may occur.