Henoch-Schönlein purpura
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| ICD-10 | D69.0 (ILDS D69.010) |
|---|---|
| ICD-9 | 287.0 |
| DiseasesDB | 5705 |
| MedlinePlus | 000425 |
| eMedicine | derm/177 |
In medicine (rheumatology and pediatrics) Henoch-Schönlein purpura (HSP, also known as allergic purpura) is a systemic vasculitis characterized by prominent tissue deposition of IgA-containing immune complexes, especially in the skin and kidney. It has a prominent cutaneous involvement similarly seen in mixed cryoglobulinemia and hypersensitivity vasculitis: palpable petechiae or purpura is a major finding in these disorders. The pathogenesis is similar to that of IgA nephropathy, with similar histologic findings in the kidney.
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[edit] Epidemiology
HSP occurs more often in children than in adults, and usually follows an upper respiratory tract infection. Half of affected children are below the age of five. When adults are affected, the disease progression is more severe, with more renal involvement, and requiring more aggressive treatment, including corticosteroids and cytotoxic therapy. The incidence of HSP is about 1:7,000 in the United States. The median age is 6 years at disease onset, and 90% is under 10 years old. Boys tend to be more often affected than girls.
[edit] Signs and symptoms
The symptoms of HSP are usually preceded by a viral upper respiratory tract infection. The classic tetrad of HSP --- which can occur in any order at any time --- are, in order to decreasing frequency:
- (100%) rash --- typically purpuric with normal clotting times and usually in lower legs and arms. As purpura are small haemorrhages, they are non-blanching (i.e. they do not disappear on pressure), which can lead to confusion with the petechiae of meningococcal sepsis.
- (82%) arthralgia/arthritis --- usually affecting knees and ankles, are transient and cause no permanent damage
- (63%) abdominal pain
- (40%) renal disease.
GI bleed may occur in 33% of patients, nephritis and hematuria in 40%, and proteinuria in 25%. Other organs such as the CNS and lung can also be affected. 33% will develop recurrence of the syndrome. 1% will progress to chronic renal failure. Both recurrence and renal complications are more frequent in older children and adults.
GI disease is present in most HSP patients. Symptoms include colicky abdominal pain associated with vomiting, lower GI bleeding (melena or hematochezia), intussusception (usually in the ileum), pancreatitis, cholecystitis, and a protein-losing enteropathy. GI endoscopy may show purpuric lesions.
Renal disease is common in HSP patients, with 30-70% developing hematuria and/or proteinuria as shown by red cell and casts in the urinalysis. Other renal findings may include the nephrotic syndrome, hypertension, and acute renal failure. HSP nephritis accounts for about 15% of all glomerulopathies in childhood. The findings on renal biopsy correlates with the severity of symptoms: asymptomatic hematuria may only have focal mesangial proliferation while those with proteinuria may have marked cellular proliferation or even crescent formation. The number of crescentic glomeruli is an important prognostic factor in determining whether the patient will develop chronic renal disease or end-stage renal disease.
[edit] Diagnosis
The presence of the classic tetrad is virtually pathognomonic of HSP in children. It can be confirmed with evidence of IgA deposition in skin or kidney by biopsy with immunofluorescence. Biopsy will reveal inflammation of the small blood vessels, termed leukocytoclastic vasculitis, mostly in the postcapillary venules. Renal biopsy is an invasive procedure and should be reserved for those whose diagnosis is uncertain.
The differential diagnosis in children include antiphospholipid syndrome and sepsis. In adults, one must distinguish HSP from other vasculitis such as hypersensitivity vasculitis, SLE, Wegener's granulomatosis, or Goodpasture's disease. Clinical judgment as well as lab tests should be ordered to distinguish the various vasculitis. For a more detailed overview on the approach to vasculitis, see:
A clinical criteria is used to distinguish HSP from hypersensitivity vasculitis. The presence of 3 or more yields a sensitivity of 87% for HSP while the presence of 2 or less yields a sensitivty of 74% for hypersensitivity vasculitis:
- palpable purpura
- bowel angina
- GI bleeding(intussusception must be ruled out,as is common)
- hematuria
- onset < 20 years of age
[edit] Prognosis
Overall prognosis is good in most patients, with one study showing recovery occurring in 94% and 89% of children and adults, respectively. Only a minority have persistent disease, which was closely associated with the presence of nephrotic syndrome at the time of diagnosis, and may lead to chronic renal failure or end-stage renal disease. HSP accounts for about 3% of ESRD in children. Renal prognosis is poor in those with nephrotic syndrome, renal insufficiency, and tubulointerstitial nephritis. The renal prognosis is excellent in most patients, especially those who have focal glomerular involvement with transient hematuria or proteinuria that resolves over several months. Spontaneous recovery can also occur in those with more severe renal involvement.
Recurrence occurs in about 1/3 of patients, usually within four months of resolution of initial symptoms and are less severe. It is more common in those with nephritis (as opposed to nephrotic syndrome).
[edit] Treatment
Most patients do not receive therapy because of high recovery rate. Corticosteroids may enhance rate of recovery from arthritis or abdominal pain but does not prevent recurrence.
Renal disease. Treatment is only considered in those with marked proteinuria and/or impaired renal function and patients in this setting should get a renal biopsy since the amount of crescentic glomeruli is a prognostic factor. In those with crescentic nephritis (> 50% of glomeruli), a pulse IV methylprednisolone 250-1000 mg/day for three days followed by oral prednisone (1 mg/kg/day for three months) is used. This regimen is used to reverse the inflammation rather than the IgA deposition itself. Plasmapheresis (exchange of plasma) may be curative but data is inconclusive. Intravenous immunoglobulin has also been tried in patients with heavy proteinuria and decrease in glomerular filtration rate.
Renal transplant. Can be considered in those with end-stage renal disease, although recurrence is common, as evidenced by mesangial hypercellularity and IgA deposition in the graft. It occurs in about 35% of transplant patients at 5 years with 10% of patients experiencing graft loss due to recurrence. It is recommended that transplantation be delayed for 12-24 months after the disappearance of purpura.
[edit] Pathophysiology
HSP is a form of vasculitis that is mediated by antibodies of the subclass IgA1. These are found in the cutaneous lesions, as well as other inflammatory patches in the kidney (mesangium) and the intestine. IgA nephritis has many parallel symptoms, and is also often preceded by an infection, raising the suspicion that the nephritis may be a form of HSP limited to the kidney.
HSP can develop after infections with streptococci (Group A, β-haemolytic), hepatitis B, herpes simplex virus, parvovirus B19, Coxsackievirus, adenovirus and Helicobacter pylori. Certain medications have been reported to cause HSP as an idiosyncratic reaction.
In the 1990s, it was discovered that an abnormality of the IgA1 may be the causative factor of this disease. IgA1 and IgD differ from the other classes of antibody through an 18 amino acid-long hinge region between complement-fixating region 1 and 2. Of the amino acids, half is proline, while the other ones are mainly serine and threonine. The majority of the serines and the threonines have elaborate sugar chains, connected through oxygen atoms (O-glycosylation). This process is thought to stabilise the IgA molecule and make it less prone to proteolysis. The first sugar is always N-acetyl-galactosamine (GalNAc), followed by other galactoses and sialic acid.
In HSP and IgA nephritis, it appears that these sugar chains are deficient. The cause for this abnormalty is thought to be viral neuraminidase, which removes sialic acid. This abnormality leads to polymerisation of IgA1, mainly in the renal mesangium. While the local mechanism that leads to the vasculitis is not completely understood, recent findings seem to confirm this theory.
[edit] History
The disease carries the name of Eduard Heinrich Henoch (1820-1910), a German pediatrician, and his teacher Johann Lukas Schönlein (1793-1864), who described it in the 1860s.
The English physician William Heberden (1710-1801) and the dermatologist Robert Willan (1757-1812) had already described the disease in 1802 and 1808, respectively, but the name Heberden-Willan disease has fallen in disuse. William Osler would be the first to see HSP as a form of allergy.
[edit] External links
- Whonamedit.com page on HSP
only 14 people out of 10,000 people get this a year in each state
