NEW YORK – Kidney function may be the single best determinant of outcome in Henoch-Schönlein purpura, according to Dr. Philip Kahn.
Although only 1%-3% of patients develop end-stage renal disease, Henoch-Schönlein purpura (HSP) accounts for up to 20% of children on dialysis, Dr. Kahn said at a meeting sponsored by New York University.
The most common form of vasculitis in children, HSP is generally self-limiting. "Most renal manifestations of HSP will resolve spontaneously. A minority of patients with HSP will develop nephrotic-range proteinuria and elevated creatinine, with or without hypertension," according to Dr. Kahn, a pediatric rheumatologist affiliated with the New York University Langone Medical Center. "This increases the risk of progressive disease, and necessitates dialysis for a small minority of these patients."
About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.
HSP may account for about one-half of all vasculitis cases in the United States. A full 90% of HSP cases present during childhood, with a mean age of onset of 4-7 years. The characteristic clinical features of HSP are nephritis, purpura, arthritis/arthralgia, and abdominal pain. Symptoms typically last for about 4 weeks.
Between 20% and 54% of HSP patients have glomerulonephritis, said Dr. Kahn. Many patients will have asymptomatic hematuria, with mild or no proteinuria. "We see a gamut of urinalysis abnormalities: 14% have isolated hematuria, 9% have isolated proteinuria, 56% have both hematuria and proteinuria, 20% have nephrotic syndrome, and 1% have nephrotic-nephritic syndrome," said Dr. Kahn. For 85% of patients, nephritis develops within the first 4 weeks.
Patients with transient hematuria and proteinuria generally have an excellent prognosis, he said, and renal symptoms usually resolve spontaneously. However, counterintuitively up to 20% of patients who develop mild proteinuria may still have a poor outcome with advanced renal disease on biopsy, emphasizing that the biopsy may not mirror the clinical symptoms. Of those with nephrotic-range proteinuria and elevated creatinine levels, with or without hypertension, 1%-3% develop progressive disease. "Studies have shown that long-term persistent renal abnormalities are more likely to present with nephrotic syndrome, yet symptoms do resolve for half of these patients, no matter what the treatment," said Dr. Kahn.
A recent report indicated that 8 years after HSP, those with nephritis at the onset of HSP had more than a threefold increased risk of hypertension and/or urine abnormalities, as well as an increased risk of pregnancy-related proteinuria.
Typically, patients with overt renal disease are managed by nephrologists. About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.
To monitor renal involvement in HSP patients, Dr. Kahn recommended doing urinalysis dipstick and blood pressure monitoring weekly for the first 1-2 months after diagnosis, then monthly for the next 6 months, followed by every other month until the completion of 1 year. Neither biopsy nor symptoms reliably predict outcome, said Dr. Kahn. Pathologic findings of HSP appear identical to those of IgA nephropathy, with histologic findings including mesangial proliferation, focal and segmental proliferation, and severe crescentic glomerulonephritis. Electron dense deposits can be seen in mesangial areas under electron microscopy. Immunofluorescence can reveal large, globular mesangial IgA deposits, which occasionally also include IgG and IgM. The presence of crescents may not necessarily foretell poor prognosis, although generally patients with greater than 50% crescents do not recover fully.
There is no well-accepted treatment for HSP-related nephritis. Most evidence comes from small retrospective cohort studies, with marked differences in the definitions of renal involvement, dosing regimens, and glucocorticoid modes of delivery. Variable results have been reported for cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, antiplatelet therapy, and plasmapheresis.
Whether glucocorticoids can be used to treat or prevent HSP-related nephritis is controversial. A meta-analysis of patients treated between 1956 and 2007 comparing outcomes of prednisone treatment versus supportive care suggested that the use of corticosteroids early in the disease reduced the risk of developing persistent renal disease (Pediatrics 2007;120:1079-87). On the other hand, a Cochrane review of 10 randomized, controlled trials that included 1,230 patients failed to demonstrate any benefit of prednisone in preventing serious long-term kidney disease in HSP (Arch. Dis. Child. 2009;94:132-7).
HSP may recur in about one-third of patients within 4 months, with the second bout being milder and briefer than the first. There is some evidence that the risk of recurrence increases in those with more severe disease, including patients who have had nephritis, an elevated erythrocyte sedimentation rate, or steroid treatment.