In medicine (rheumatology and pediatrics) Henoch-Sch๖nlein purpura (HSP, also known as allergic purpura) is a form of vasculitis that mainly affects children. Its course is generally benign, although some serious complications can develop, mainly of the kidney and intestine.
Signs and symptoms
The purpura that are mentioned in the name of the disease are present in all patients. They are located on the legs and arms, and progress to the trunk. 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. Often, the symptoms are preceded by a viral upper respiratory tract infection.
Other symptoms are: arthritis (75%, non-erosive, often present before all other symptoms), abdominal pain (65%), intestinal bleeding (35%), nephritis and hematuria (40%) and proteinuria (25%). Many other symptoms have been reported, but their specificity for HSP is limited.
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.
Some patients can present with intusseception; this complication is the folding of a segment of the intestine into its own lumen, leading to hematochezia and severe abdominal pain. It requires urgent surgery, before the intestinal tissue becomes necrotic and dies.
Diagnosis
There is no definitive test for HSP, but blood tests are commonly performed. These include: full blood count, electrolytes, renal function, C-reactive protein and erythrocyte sedimentation rate. Immunoglobulin levels show elevated IgA in 50% of the cases. Complement levels are normal (in other vasculitis syndromes these can be consumed and therefore low).
Rarely, a renal biopsy has to be performed to arrive at a full diagnosis. This shows mesangial proliferation and is indistinguishable from IgA nephritis.
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 neuramidase, which removes sialic acid. This abnormalty leads to polymerisation of IgA1, mainly in the renal mesangium. While the local mechanism that leads to the vasculitis is not compltely understood, recent findings seem to confirm this theory.
Treatment
Many cases are self-limiting and don't require any therapeutic intervention. Steroids suppress the joint pain and the abdominal pain, but does not affect the progression of the purpura. The prognosis depends mainly on the seriousness of the renal involvement: hematuria, nephrotic syndrome, decreased renal function and hypertension predict future development of chronic renal failure.
As most patients are children, a renal biopsy is only performed when there are concerns about long-term renal prognosis. If over 50% of the glomeruli show crescenteric changes, more aggressive treatment may be required.
Second-line therapy consists of methylprednisolone pulse therapy. Other therapies, most of which have not been compared systematically, are DMARDs (disease-modifying antirheumatic drugs, e.g. azathioprine or methotrexate), cyclophosphamide or plasmapheresis.
Epidemiology
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. Nevertheless, it has been described in adults. Boys tend to be more often affected than girls.
History
The disease carries the name of Eduard Heinrich Henoch (1820-1910), a German pediatrician, and his teacher Johann Lukas Sch๖nlein (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.
Source
Saulsbury FT. Henoch-Sch๖nlein purpura. Curr Opin Rheumatol 2001;13:35-40.
|
