8 year old girl with gross hematuria, nephrotic proteinuria, and rash.

An 8-year-old Hispanic girl presented with gross hematuria, nephrotic proteinuria (10 g/24 hrs), edema, and hypertension, followed by rash, joint pain and abdominal pain. She was treated with steroids with resolution of edema, but serum albumin continued to fall. The duration of renal disease was 1 month. Past medical history included seizure disorder. At time of renal biopsy, serum creatinine was 0.5 mg/dL and urine protein/creatinine ratio was 5.0. Urinalysis showed 4+ protein, microhematuria and leukocyturia, and no cellular casts. Serologic tests revealed negative ANA, mildly reduced C3, normal C4, negative ASLO and ANCA. Serum albumin was 2.9 g/dL, hematocrit 33.6%, WBC 9K, and platelets 708K. Kidneys were echogenic by ultrasound.

BIOPSY FINDINGS

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PATHOLOGIC DIAGNOSIS
 
Diffuse proliferative glomerulonephritis, consistent with Henoch-Schonlein purpura nephritis

DISCUSSION

Henoch Schonlein purpura (HSP) is a systemic small vessel vasculitis affecting skin, gastrointestinal tract and kidney, and characterized by IgA deposits in vessel walls and glomeruli(1). HSP predominantly affects children but may occur at any age. Renal involvement (HSP nephritis) occurs in approximately 40% of pediatric cases(2) and is associated with a wide spectrum of clinical and pathologic features. HSP is typically an acute, self-limited disease with a good outcome, but recurrences occur in approximately one-third of childhood cases. Long-term sequelae are confined to cases with severe HSP nephritis.
 
HSP affects male patients more commonly than females, is uncommon among individuals of African descent, and usually presents in the autumn or winter months(3). Among children, the mean and median age of presentation is approximately 5 years. The clinical features of HSP include purpura, arthritis, abdominal pain, gastrointestinal bleeding, and nephritis; in addition, boys may present with orchitis(3). HSP nephritis typically manifests hematuria, either gross or microscopic. Approximately one-third of patients present with nephritic syndrome (hematuria, hypertension, and acute renal insufficiency). Proteinuria is variable, with nephrotic syndrome in up to 45% of patients. The prognosis for those with combined nephritic and nephrotic syndrome is poor, with ESRD or persistent renal disease resulting in 40% of these patients(4). Factors associated with increased risk of ESRD in an adults with HSP nephritis include proteinuria >1g/day, elevated serum creatinine >1.5 mg/dL, hypertension(5) and gross hematuria(6). The overall incidence of ESRD is less than for IgAN, and is higher in adults than in children. Recurrence in the renal allograft has been described, sometimes leading to graft failure.
 
The pathology of glomerular changes in HSP nephritis runs the gamut from minimal histologic alteration to diffuse crescentic glomerulonephritis. HSP nephritis is indistinguishable from IgA nephropathy (IgAN) but tends to have more severe proliferative glomerular lesions, including crescents. Worse outcomes are associated with more severe glomerular pathology, and with the degree of glomerulosclerosis and tubulointerstitial scarring. Necrotizing arteritis is rare in renal biopsy specimens but necrotizing capillaritis involving peritubular capillaries may be seen, particularly in the medulla.
 
The etiology and pathogenesis of HSP nephritis remain poorly understood, but share features with IgAN, including glomerular deposits of polymeric IgA1 which are abnormally glycosylated. The optimal clinical management of HSP nephritis is also unclear. To date, there are no proven strategies to prevent the development of nephritis in HSP. Therapy for HSP nephritis is generally predicated on the severity of glomerular disease, with use of steroids and other immunosuppressive agents in selected cases. Plasmapheresis may be beneficial in those with rapidly progressive glomerulonephritis and diffuse crescent formation.
 
REFERENCES

1.         Jennette JC, Falk RJ, Andrassy K, Bacon PA, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994; 37: 187-192.
2.         Sanders JT, Wyatt RJ. IgA nephropathy and Henoch-Schonlein purpura nephritis. Curr Opin Pediatr 2008; 20: 163-170.
3.         Saulsbury FT. Henoch-Schonlein purpura in children. Report of 100 patients and review of the literature. Medicine (Baltimore) 1999; 78: 395-409.
4.         Meadow SR, Glasgow EF, White RH, Moncrieff MW, et al. Schonlein-Henoch nephritis. Q J Med 1972; 41: 241-258.
5.         Coppo R, Mazzucco G, Cagnoli L, Lupo A, et al. Long-term prognosis of Henoch-Schonlein nephritis in adults and children. Italian Group of Renal Immunopathology Collaborative Study on Henoch-Schonlein purpura. Nephrol Dial Transplant 1997; 12: 2277-2283.
6.         Pillebout E, Thervet E, Hill G, Alberti C, et al. Henoch-Schonlein Purpura in adults: outcome and prognostic factors. J Am Soc Nephrol 2002; 13: 1271-1278.