IgA vasculitis (Henoch-Schönlein purpura)

Henoch-Schönlein purpura, also known as Henoch-Schönlein disease or IgA vasculitis, is a primary vasculitis of small vessels (arterioles, capillaries, venules) characterized by polymorphous perivascular infiltration, focal fibrinoid necrosis of the vascular wall, and the presence of granular deposits of IgA (+- C3, IgG, IgM, fibrin, properdin) in the wall of dermal capillaries and/or glomeruli, as well as in the mesangium. IgA deposits can also be found in the synovium and intestines.

It can occur at any age but affects children 20 to 40 times more often than adults. It is the most common vasculitis in children. Its prevalence is 0.5 per 100,000 people but rises to 20 per 100,000 among children. The average onset age is 5 to 7 years with a male-to-female ratio of 1.5:1. There is a predominance among Caucasians and an increased frequency in autumn and winter.

Some believe that Henoch-Schönlein purpura and Berger’s disease are two different clinical expressions of the same disease.

Etiopathogenesis

The etiology is unknown. However, in 25 to 90% of cases, a triggering factor is found: infection (streptococcus, mycoplasma pneumoniae, clostridium difficile, staphylococcus, parvovirus B19, EBV, adenovirus, mumps virus, HIV, rarely parasitic), intoxication (insect bite, cocaine) or iatrogenic (vaccines, antibiotics, NSAIDs, ACE inhibitors). Additionally, a particular predisposition may be present: allergies, complement/ IgG subclass deficiency, α-1-antitrypsin deficiency, Hodgkin's disease, Wiskott-Aldrich syndrome, certain liver diseases, gluten intolerance, Crohn's disease, etc.

Clinical Presentation

The onset usually occurs over a few hours to a few days. The course is variable, with one (usually lasting 2 to 3 weeks) or multiple episodes (over several months). Less than 5% develop a chronic course.

• General symptoms:
  • Moderate fever 50%
  • Fatigue 100%
• Skin involvement 95-100%
  • Vascular purpura (almost constant, presenting symptom in 50%): symmetrical, predominantly in dependent areas, worsened/ triggered by standing, petechial lesions coalescing to form a palpable purpura
  • Often preceded and accompanied by pruritic urticarial elements and painful edema.
  • Upon resolution, lesions become brown and then fade.
  • Sometimes atypical: nodular, ecchymotic, vesiculobullous, crusty, ulcerated
  • Typically appears within 1 week and resolves within 3 weeks
• Joint involvement 60-80%
  • Polyarthralgia, ++ symmetrical, not severe, transient, non-migratory, involving large joints (knees/ ankles ++)
  • Precedes skin syndrome in 25%
  • Disappears within a few days, without sequelae
• Gastrointestinal involvement 50-90%
  • +++ Moderate abdominal pain (+- nausea/ vomiting), often presenting as paroxysmal colic
  • Positive Hematest in 50%
  • Precedes skin syndrome in 10-30%
  • Sometimes mimics an acute surgical abdomen. Consider this in a child with unexplained acute abdomen.
• Renal involvement 20-50% (glomerular)
  • Hematuria ++ sometimes with mild proteinuria (< 1g/24h)/ leukocyturia
  • Transient AKI and hypertension are possible

Diagnosis

Diagnosis is primarily clinical → history and thorough clinical examination. Complementary tests are mainly useful to rule out differential diagnoses.

Laboratory tests have limited value. The abnormalities are non-specific and have no prognostic value:

• Normal or slightly elevated inflammatory markers
• Normal or slightly elevated platelets/ WBCs
• Possible normochromic normocytic anemia
• Elevated serum IgA in 50% of cases

A urine dipstick is useful. If there is diagnostic uncertainty: 24-hour proteinuria test.

A renal biopsy is rarely necessary (5%) and should be considered in cases of nephrotic syndrome, persistent or recurrent renal impairment, or persistent or recurrent urinary sediment abnormalities long after the initial episode. In case of abdominal complications, do not hesitate to perform an abdominal ultrasound to evaluate potential surgical indications.

Complications

Complications are rare and exceptionally fatal. Mortality from gastrointestinal or renal involvement is < 1%.

Gastrointestinal (10-15%)

++ in the proximal small intestine. Hemorrhage, hematomas, edema, intussusception, malabsorption, ulcerations, necrosis, perforations.

Renal (< 5%)

Rare but represents one of the most common causes of rare glomerulonephritis in children. In some cases, it can present late, so always conduct renal follow-up (urine dipstick and BP 1x/ week for 1 month, then 1x/ month for 3 months, then 1x/ 3 months for 1 year. In case of abnormalities: check creatinine levels. This nephropathy usually resolves within 2 years and progresses to ESRD in only 2% (1% of ESRD in children).

Others:

• Urogenital: stenosing ureteritis (+- nephrolithic colic or even obstructive AKI in bilateral involvement), hemorrhagic cystitis, hematomas
• Neurological (2-7%): multifactorial (vasculitis, hypertension, digestive-origin hyponatremia, stroke, etc.): most often simple headaches. Very rarely: seizures, focal deficits, retinal involvement, optic neuritis, confusion, coma
• Myo/ pericarditis (1-3%)
• Pleuro-pulmonary involvement (< 1%), muscular involvement, parotitis, hepatosplenomegaly, cholecystitis, etc.

Therapeutic Management

The prognosis under treatment is good (90% resolution without sequelae).

• Bed rest: only for severe cutaneous forms (cf role of orthostasis) or severe or very painful systemic forms
• For severe cutaneous involvement: antiseptic baths, local corticosteroids, systemic corticosteroids in case of isolated persistent cutaneous involvement (switch to colchicine in case of failure)
• Paracetamol 60 mg/kg/day for joint pain
• Brief corticosteroid therapy for abdominal pain: 2 mg/kg/day for 7 days with gradual discontinuation over the following 7 days
• In case of nephropathy with significant renal involvement (> 30% of glomeruli) on biopsy: intensive corticosteroid therapy (methylprednisolone 3 x 1g/1.73m² IV, each infusion lasting 6 hours and 48 hours between each infusion, then switch to prednisone 2 mg/kg/day for 1 month, then 2 mg/kg/ every 2 days, then gradual discontinuation over 1 month).
  • In case of failure: immunosuppressants (cyclophosphamide/ azathioprine/ cyclosporine) and/ or plasmapheresis
  • At the stage of CKD: ACE inhibitors, angiotensin II antagonists are preferred (control BP + reduce proteinuria)
  • Transplantation is rarely necessary
  • In case of isolated hypertension: calcium channel blockers/ ACE inhibitors +- furosemide

Management of complications is on a case-by-case basis (corticosteroids, surgery, transfusions, adapted enteral/ parenteral nutrition, etc.).

Henoch-Schönlein purpura in adults

Similar presentation except: fever is often absent, more pronounced inflammatory syndrome, more severe joint involvement, more frequent nephropathy leading to renal impairment in 10 to 15% of cases.

The treatment is more intensive, more frequently involving corticosteroids and immunosuppressants... but the prognosis is just as good with treatment.

Bibliography

EMC, traité de médecine AKOS, Elsevier, 2018

Jameson JL et al., Harrison's Principles of Internal Medicine, 20th edition, McGraw Hill Higher Education, 2018