Henoch-Schönlein purpura

01Definition and overview

IgA vasculitis (IgAV), the name the 2012 Chapel Hill nomenclature gave to Henoch-Schönlein purpura, is a vasculitis with IgA1-dominant immune deposits in small vessels: capillaries, venules and arterioles. It typically involves the skin, the gut and the joints, and it causes a glomerulonephritis that looks under the microscope exactly like IgA nephropathy. Both names are still used, and Henoch-Schönlein purpura remains common in paediatrics.

It is an immune complex small vessel vasculitis, one of the diseases introduced in vasculitis. In children it is mostly a short, self-limiting illness; the long-term risk lies in the kidneys, in a minority. In adults it is rarer and more often serious.

IgA vasculitis nephritis and IgA nephropathy are probably two expressions of one disease process: the same abnormal IgA1, the same mesangial deposits, and the occasional patient who has IgA nephropathy and later develops purpura, or the reverse. The difference is the systemic vasculitis.

02Etiology and pathophysiology

Abnormal IgA1

The process is best described as several hits, worked out mainly in IgA nephropathy and shared by IgA vasculitis:

1. 1

   Galactose-deficient IgA1

   The hinge region of IgA1 carries O-linked sugar chains. In susceptible people some of them lack galactose, and this galactose-deficient IgA1 rises in the blood; mucosal infections may boost its production.
2. 2

   Autoantibodies

   The exposed sugars are recognised as foreign, and IgG and IgA autoantibodies form against them.
3. 3

   Immune complexes

   Large IgA1-containing complexes circulate and are poorly cleared by the liver.
4. 4

   Deposition and injury

   The complexes lodge in the walls of small vessels and in the glomerular mesangium, activate complement through the alternative and lectin pathways, and draw in neutrophils, which damage the wall.

In the skin the result is a leucocytoclastic vasculitis of the dermal postcapillary venules, with neutrophils, nuclear dust, fibrinoid necrosis and red cells leaking out, and IgA and C3 on direct immunofluorescence. In the kidney it is a mesangial proliferative glomerulonephritis with IgA deposits, sometimes with endocapillary proliferation, necrosis and crescents in severe cases.

Triggers and risk

• Infections: an upper respiratory infection precedes many cases by 1 to 3 weeks; group A streptococcus is the commonest identified, and many viruses have been implicated. Cases cluster in autumn and winter.
• Drugs and vaccines occasionally, usually as single reports.
• Genetic background: HLA class II alleles (HLA-DRB1), and MEFV variants of familial Mediterranean fever in the eastern Mediterranean.
• In adults, solid tumours (lung, prostate and others) and haematological cancers in some series, so an older adult with IgA vasculitis is checked for cancer.

03Clinical features

The illness often starts with a few days of low fever and malaise. Purpura is the first sign in about three-quarters of children; joint pain or abdominal pain comes first in the rest, by a few days, which can make the diagnosis hard until the rash appears. The frequencies below are from a prospective study of 223 children followed for 6 months:

The gut

Bleeding and oedema in the bowel wall cause the pain. The complications to look for are:

• intussusception, the commonest surgical complication, most often ileo-ileal and then out of the reach of a reducing enema;
• bowel ischaemia and perforation, rare but life-threatening;
• protein-losing enteropathy, with oedema and a low albumin without proteinuria;
• pancreatitis and acute cholecystitis, rarely.

The kidney

Nephritis appears in about 85 per cent of the children who develop it within 4 weeks of the diagnosis, and in 97 per cent within 6 months. Most have isolated microscopic haematuria or mild proteinuria. A nephritic syndrome, nephrotic-range proteinuria, hypertension or a falling eGFR mark severe disease. Nephritis is more likely in older children and in those with persistent purpura, severe abdominal pain or relapses.

Rare features are seizures and encephalopathy (often with hypertension), alveolar haemorrhage, uveitis and ureteric involvement.

In adults

Adults present with the same features but differ in degree. The purpura more often becomes bullous or necrotic and spreads above the waist. Nephritis is more common and more severe: in a large French series of 250 adults with a kidney biopsy, nearly a third had a creatinine clearance below 50 mL/min at presentation, and over a median of 15 years about a tenth reached end-stage kidney disease.

04Diagnosis and management

Classification criteria

The EULAR/PRINTO/PRES criteria of 2010 were developed in children and are also used in adults. Purpura or petechiae, predominantly on the lower limbs, are mandatory, with at least one of four:

When the purpura is atypical in its distribution, IgA deposits must be shown on a biopsy. The criteria classified children with a sensitivity of 100 per cent and a specificity of 87 per cent, but like all classification criteria they assume that other causes of purpura have been excluded.

Tests

Differential diagnosis

• Meningococcal sepsis: a non-blanching rash in a febrile or unwell child is treated as meningococcal disease at once.
• Immune thrombocytopenia and leukaemia: flat petechiae and bruises with a low platelet count.
• Non-accidental injury: bruises in odd places and patterns.
• Acute haemorrhagic oedema of infancy: under 2 years, large target-like purpuric plaques on the face, ears and limbs in a well infant, without kidney disease.
• Other vasculitis in adults: ANCA-associated vasculitis, cryoglobulinaemic and urticarial vasculitis, drug-induced leucocytoclastic vasculitis, lupus and endocarditis.
• An acute surgical abdomen when pain comes before the rash.

When to biopsy the kidney

In children, the 2025 international paediatric nephrology recommendations, which build on the European SHARE ones (whose cut-offs are a little higher, 250 mg/mmol for severe proteinuria), advise a kidney biopsy for:

• nephrotic-range proteinuria, a urine protein-to-creatinine ratio above 200 mg/mmol;
• a reduced eGFR;
• persistent moderate proteinuria, 100 to 200 mg/mmol, for 2 to 4 weeks;
• and to consider it for persistent mild proteinuria, 20 to 100 mg/mmol, for about 3 months, or hypertension.

The biopsy is graded by the International Study of Kidney Disease in Children classes, from minimal change (I) through mesangial proliferation (II) to rising proportions of crescents (III to V), with a rare membranoproliferative pattern as VI; the Oxford MEST-C score of IgA nephropathy is often reported too, though it is less validated in IgA vasculitis. Adults are biopsied at a lower threshold: proteinuria of 0.5 g a day or more lasting over 4 weeks, or impaired kidney function.

Treatment of the illness

Most children are treated at home:

• rest and elevation of the legs while the purpura is active;
• paracetamol for pain; an NSAID for joint pain only when the kidney function is normal and there is no gut bleeding;
• prednisolone, about 1 to 2 mg/kg a day for 1 to 2 weeks and then tapered, for severe abdominal pain or gut bleeding once intussusception is excluded, orchitis, and other severe organ involvement (brain, lung); intravenous methylprednisolone for the most severe;
• surgery for an intussusception that does not reduce, or for perforation.

Glucocorticoids shorten the abdominal and joint pain, but placebo-controlled trials showed that they do not prevent nephritis, so they are not given to a child with normal urine to protect the kidneys. Chronic or relapsing skin disease sometimes responds to dapsone or colchicine.

Treatment of nephritis

Children are treated by severity, following the European SHARE recommendations, which rest almost entirely on expert opinion:

The 2025 international paediatric recommendations are more sparing with glucocorticoids: none for haematuria without proteinuria, an ACE inhibitor or angiotensin receptor blocker first for proteinuria, and a 3 to 6 month course of glucocorticoids, with another immunosuppressant if needed, for nephrotic-range proteinuria or rapidly progressive disease with at least class II changes on biopsy. The target is a protein-to-creatinine ratio below 20 mg/mmol, and the systolic blood pressure is kept below the 90th centile for age, sex and height.

In adults, the 2025 KDIGO guideline manages IgA vasculitis nephritis much as IgA nephropathy: lifestyle advice, blood pressure at or below 120/70 mmHg with an ACE inhibitor or angiotensin receptor blocker as the first drug, and that drug, an SGLT2 inhibitor or both to cut proteinuria. Glucocorticoids, for a patient who chooses them after hearing the risks, are given at the reduced dose used in IgA nephropathy, with prophylaxis against infection; the guideline finds too little evidence to base treatment on the number of crescents. Rapidly progressive disease is treated as ANCA vasculitis is, with glucocorticoids and cyclophosphamide or rituximab. The drugs newly approved for IgA nephropathy, such as targeted-release budesonide and sparsentan, have not been tested in IgA vasculitis. The guideline advises against glucocorticoids to prevent nephritis in patients whose vasculitis spares the kidneys.

Follow-up

of urine and blood pressure checks for every child, at least monthly after the first weeks

6monthsof urine and blood pressure checks for every child, at least monthly after the first weeks

at least, for a child who has had nephritis

5yearsat least, for a child who has had nephritis

of nephritis has appeared within 6 months

97per centof nephritis has appeared within 6 months

The checks are most frequent in the first month, when most nephritis appears. A child whose urine stays normal for 6 months can be discharged. Children who had nephritis have their blood pressure, urine and eGFR checked for at least 5 years, and for life if they needed treatment or did not fully remit, and women who had IgA vasculitis nephritis in childhood need close monitoring in pregnancy, when hypertension and proteinuria are common.

05Epidemiology

IgA vasculitis affects about 3 to 27 children per 100,000 a year, about 18 to 20 in most European studies, peaking at 4 to 6 years, when it reaches about 70 per 100,000. Nine in ten patients are under 10. Boys are affected slightly more often than girls, and the disease is commoner in autumn and winter; in a UK study it was commoner in children of South Asian ancestry and rarer in Black children, while Japan reports some of the lowest rates. In adults it is much rarer, by at least ten-fold, with a mean age at onset of about 50 and more men than women.

06Prognosis

In children the illness usually settles within about 4 weeks. A quarter to a third have one or more recurrences, usually within months, and recurrences are commoner in those over 8 and those with nephritis.

The kidney decides the long-term outlook:

Kidney impairment can appear decades later, especially in women and in pregnancy: in one Finnish cohort followed for 24 years, a third of those with severe nephritis in childhood had impaired kidney function as adults. IgA vasculitis nephritis causes a small share of end-stage kidney disease in children, and it can recur in a transplanted kidney.

Adults do worse. Complete remission of the nephritis is less common, chronic kidney disease frequent, and in the French series a tenth reached end-stage kidney disease. The main predictors are the eGFR and proteinuria at presentation and, on biopsy, interstitial fibrosis, sclerosed glomeruli and fibrinoid necrosis.