U06-16108

#652660020

• 2 month history of being unwell

• Vasculitic lesions on lower limbs

• ANCA positive

• Likely Wegener’s vs MPA

A 14 y/o male with 2 month history of intermittent purpuric lower limb rash. Seen by pediatrician and dx with HSP.

Other symptoms include: wt loss of 20 lbs, general malaise and fatigue. Denies any cough or hemoptysis, sinus or visual problems.

Physical exam reveals a cachetic looking young teenager with normal vitals with normal bp, evidence of chronic papilledema (indicative of optic neuritis), and lower limb purpuric rash with arthritis in right ankle.

Lab investigations shows :– normal Cr of 60, – presence of hematuria/proteinuria (urine pr/cr ratio of 95)– normal C3, C4, IgA. – Both p and c-ANCA were positive. – DsDNA normal at 2%.

Patient was biopsied to r/o vasculitis - probably Wegener's Granulomatosis.

IF• IgG- Mild mesangial staining.• IgA- Mild to moderate mesangial staining.• IgM- Mild mesangial staining.• C3- Mild to strong vascular staining. Trivial to mild punctate

mesangial staining.• C1q- Negative.• Kappa- Mild mesangial staining.• Lambda- Mild to moderate mesangial staining.• Fibrin- Moderate interstitial staining. Moderate focal irregular

staining of necrotizing foci within glomeruli.• Albumin- Moderate hyaline droplet change in tubular

cytoplasm.

IgG

IgA

IgM

C3

C3

Kappa

Lambda

Fibrin

Fibrin

Albumin

Diagnosis

Renal Biopsy:Focal proliferative and necrotizing glomerulonephritis with crescent formation consistent with Henoch-Schönlein purpura.

Pathologic differential diagnosisFor Against

Henoch-Schonlein

•Presence of necrosis, crescents and fibrin deposits in glomeruli is more frequent than in IgA nephropathy

•Dominant IgA on IF and IC deposits on EM

•Clinical features …

•+ANCABut cases of IgA nephropathy (10-20%) and of Henoch-Schonlein (esp IgA ANCA) with positive ANCA are found in the literature (NDT 1999, 14:1266-1267)

Wegener’s (pauci-immune GN)

•Clinical features …

•+ANCA

•Severe necrotizing and crescentic GN can have slight IgA+

But in this case we have only 25% crescents and IgA is moderate

•Dominant IgA on IFBut up to 18% of ANCA a/a crescentic GN were found to have IC deposits, most often IgA (NDT 2003, 18:524-531)

•IC deposits on EM

Underlying low grade IgA nephropathy with superimposed Wegener’s

• « Although crescents and necrosis may be caused by severe IgA nephropathy alone, when they are conspicuous, the possibility of concurrent IgA nephropathy and ANCA disease should be considered. The likelihood of concurrent ANCA disease is highest when there are numerous crescents but only mild endocapillary hypercellularity. »

Atlas of non tumor pathology, non-neoplastic kidney diseases, D’Agati et al. 2005.

Elements in favor of the diagnosis

• Relative paucity of IC deposits on EM

• Absence of mesangial or endocapillary proliferation in remaining glomeruli

Underlying low grade IgA nephropathy with superimposed Wegener’s

Am J Kidney Dis, Oct 2000, vol 36(4):709-718.