BUENOS AIRES — Diagnosing Henoch-Schönlein purpura requires a small-vessel biopsy to confirm the presence of IgA, Dr. Thomas G. Cropley said at the 21st World Congress of Dermatology.
IgA deposits in vessel walls, along with prominent extracutaneous manifestations, are the hallmarks of Henoch-Schönlein purpura (HSP), a specific type of small-size vessel vasculitis that is the most common vasculitis syndrome in children, often occurring after a respiratory tract infection.
In recent years, three different sets of classification criteria have been proposed, the oldest of which does not list IgA deposition in its diagnostic criteria. In 1990, the American College of Rheumatology published its classification of Henoch-Schönlein purpura (Arthritis Rheum. 1990;33: 1114–21), requiring four diagnostic criteria:
▸ Palpable purpura, defined as slightly raised “palpable” hemorrhagic skin lesions not related to thrombocytopenia;
▸ Age less than 20 years at disease onset;
▸ Bowel angina, or diffuse abdominal pain, which might include bloody diarrhea;
▸ Presence of granulocytes in vessel walls.
“There is no mention of immunofluorescence or IgA here,” said Dr. Cropley. The ACR definition is based only on histo- pathology and clinical symptoms. Dermatologists were not involved in developing the classification system, which has been criticized for the “lack of dermatological insight,” said Dr. Cropley, professor of medicine in the division of dermatology at the University of Massachusetts, Worcester.
A group of physicians that included rheumatologists, nephrologists, and pulmonologists (but not dermatologists) convened in Chapel Hill, N.C., in 1994 and developed consensus guidelines for the diagnosis of various forms of vasculitis, including HSP (Arthritis Rheum. 1994;37:187–92). “[This] definition of Henoch- Schönlein purpura requires the presence of vasculitis with IgA-dominant immune deposits affecting small vessels, which they defined as capillaries, venules, or arterioles,” said Dr. Cropley. The definition noted that the vasculitis typically involves skin, gut, and glomeruli and that the condition is associated with arthralgias or arthritis. “IgA is part of the definition, but there are still many other areas of 'looseness' in this definition.”
In 2006, the European League Against Rheumatism and the Paediatric Rheumatology Society published Classification Criteria for Henoch-Schönlein purpura (Ann. Rheum. Dis. 2006;65:936–41). In their definition, the presence of palpable purpura is a mandatory criterion, and at least one of the following four features must be present: diffuse abdominal pain; biopsy-proved predominant IgA deposition; acute arthritis in any joint or arthralgia; and renal involvement (hematuria and/or proteinuria).
The epidemiology of HSP is well described. In the United States, the incidence is about 10 cases per 10,000. About 75% of cases begin in childhood, with an equal prevalence in males and in females. The disease is often preceded by a respiratory tract infection, but no typical or unique pathogen has been associated with it, said Dr. Cropley.
Adult cases are less likely to be associated with an antecedent infection, and the prevalence is higher in men than in women.
Differential diagnosis of Henoch-Schönlein purpura includes other forms of small-size vessel vasculitis causing palpable purpura, such as Wegener's granulomatosis, IgG leukocytoclastic vasculitis, and microscopic polyangiitis. Other IgA-associated vasculitides should also be considered, including IgA rheumatoid factor-associated small-vessel vasculitis and acute hemorrhagic edema of infancy.
The question of whether or not the presence of IgA predicts an increased likelihood of renal involvement is unanswered. An epidemiologic study of HSP showed renal involvement occurred in one-third of the children with the disease (Kidney Int. 1998;53:1755–9). Significant independent risk factors for chronic renal disease in these patients were severe abdominal symptoms, prolonged purpura, and decreased factor XIII activity. But the prognostic significance of IgA status could not be evaluated in the study, because the researchers used the 1990 ACR diagnostic criteria of Henoch-Schönlein purpura.
IgA deposition is a defining criterion of Henoch-Schönlein purpura in the two most recent diagnostic guidelines. Patients with the condition may have a poorer prognosis concerning renal involvement than patients with other forms of small-vessel vasculitis. As such, Dr. Cropley recommended a biopsy for immunofluorescence and histopathology, if possible, in patients who seem to have Henoch- Schönlein purpura. Serum IgA levels have been shown to correlate with the risk of IgA nephropathy in adults with Henoch-Schönlein purpura; thus, monitoring serum IgA level over time may help identify patients at particular risk of chronic renal disease. He reports no conflicts of interest.
Even in the presence of palpable lesions, vessel biopsy is required to diagnose Henoch-Schönlein purpura. Courtesy Dr. Lauren Alberta-Wszolek