CASE 4 A RARE CASE OF INTRALUMINAL GLOMERULAR CAPILLARY DEPOSITS
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1 CASE 4 A RARE CASE OF INTRALUMINAL GLOMERULAR CAPILLARY DEPOSITS DR ANNIE JOJO, Dr Seethalekshmy N V, Dr Nanda Kachare DEPARTMENT OF PATHOLOGY, AMRITA INSTITUTE OF MEDICAL SCIENCES, KOCHI.
2 54 yrs female, with an episode of fever, arthralgia, myalgia, pedal edema, decreased urine output since July 2007 Treated symptomatically Readmitted with h/o hemoptysis, epistaxis and oliguria in September 2007
3 No H/O macro hematuria, HT, DM On admission BP-150/80mm of Hg On examination Hepatosplenomegaly was present No lymphadenopathy
4 Investigations Hb 8.3g/dl, TC-3800/cu mm, DC:P70%,L30% Platelet count-1.8lac/cu mm ESR-64mm/1hr PS s/o Dimorphic anemia, no evidence of hemolytic anemia S. Creatinine- 4.3mg % S. Alb S. cholesterol- 126mg%.
5 Investigations-cont S. C3- low Urine- Albumin ++, 24hrs UP-1.3 gms Urine Micro: 8-10 RBCs, 2-4 WBCs/hpf, granular casts present Rheumatoid factor- Positive ANA-4.14, dsdna- Negative USG s/o renal parenchymal disease & hepatosplenomegaly Clinical diagnosis- Rapidly Progressive Renal Failure? SLE
6 H&E 40X
7 H&E,x100
8 H&EX400
9 H&EX400
10 PASX100
11 PASX100
12 PASX400
13 SILVERX400
14 MTX400
15 Immunofluroscent Microscopy 2+ granular capillary wall IgG 1+/2+ IgM, 1+ C3, 1+Gcw + M -IgA, C1q- Negative
16 Differential Diagnosis Idiopathic MPGN Hyaline thrombus Proliferative III/IV LN- large subendothelial deposits bulge into the glomerular capillary lumen Fibrin thrombi:less homogenous & diff- IHC & special stains Luminal immune deposits- cryoglobulinemia
17 case discussed with the clinician asked for further investigations including serum cryoglobulin levels & HCV status. HCV, HBsAg, HIV Negative Rheumatoid Factor- Positive Qualitative assesment for cryoglobulin Positive
18 Diagnosis: Cryoglobulinemic Glomerulonephritis
19 Treatment Methyl prednisolone 3 pulses 1g each/3 days Oral prednisolone-1/2 gm/kg 3 weeks Recovered completely & Discharged Continued with oral prednisolone 3 weeks Follow up after 3 weeks-normal renal functions
20 Cryoglobulinemic Glomerulitis Definition Classification Type I-composed of single monoclonal Ig usually IgM, 10-15% of people c cryoglobulinemia. Lymphoproliferative disorder- Immunocytoma/Waldenstrom Macglo, MM Asymptomatic- acrocyanosis,raynaud pheno, gangrene
21 Type II & III cryoglobulinemia (MC) 2 Igs polyclonal IgG & mono Ig usually IgM with reactivity to anti IgG RF 50-60% of pts Monoclonal IgMs contain kappa light chain Type III polyclonal IgG/IgM antibody 30-40% pts, Cryoprecipitation property : reduced solubility of IgM-IgG complex
22 Mixed Cryoglobulins Connective tissue disease Infections Lymphoproliferative disorders Hepatobiliary diseases Immunologically mediated glomerular diseases (SLE)
23 Sensitive Methods for detection Immunoblotting, two dimensional polyacrylamide gel electrophoresis. Another serological type of MC, oligoclonal or microheterogenous type are characterized Defined by more than 2 heterogenous bands of heavy chain Intermediate stage in the course of type III evolving into type II MC
24 Essential mixed cryoglobulinemia syndrome Systemic vasculitis c/o cutaneous purpura, urticaria, weakness, arthralgias, 10-60% of cases renal disease
25 Microscopic Examination Large glomerular intracapillary deposits Glomerular accumulation of monocytes Vasculitis in small & medium sized arteries with out features of segmental necrotizing glomerulonephritis More diffuse thickening of GCBM Crescents- uncommon, smaller, seen in a few glomeruli
26 10% cases- Mild segmental mesangial proliferation without monocyte infilteration or GBM alterations 10% have severe mesangial sclerosis with Mesangial hypercellularity
27 Electron Microscopy Microtubular, fibrillar or crystalloid organized structure of deposits Subendothelial location in glomerular capillaries Intraluminal thrombi in GC Occasionally in an intramembranous or subepithelial location
28 Cryoglobulin test Positive (at 4C) Negative (at 4C)
29 References 1. Cryoglobulinemia : Enrica Morra; pages: , American society of Hematology 2. Cryoglobulinemia :Article by Colin C Edgerton; pages:1-21,updated Jan 26,2006, emedicine 3. Atlas of renal pathology: William F Kern et.al 4. Hepstinstall s pathology of the kidney: 5 th edition vol1 & vol 2
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