Thread by @WUNephrology

@VijayanMD @Charbel_Khoury @GMatzumura #Tweetorial Reveal of this week's pathology case from @WUNephrology consults #FOAMed

@VijayanMD @Charbel_Khoury @GMatzumura The cortical tubulointerstitial tissue had an expansile interstitial fibrosis without significant tubular atrophy.  With diffuse mixed interstitial inflammatory infiltrate composed of eosinophils, plasma cells and mononuclear cells.

@VijayanMD @Charbel_Khoury @GMatzumura Immunohistochemical stain for IgG4 highlights numerous positive cells within the interstitium

The patient's serum IgG4 was elevated 185.0 (2.4 - 121.0) mg/dL

@VijayanMD @Charbel_Khoury @GMatzumura IgG4 related disease is a systemic fibroinflammatory dz, once believed to be separate organ-specific clinical entities.

@VijayanMD @Charbel_Khoury @GMatzumura Humoral and cell-mediated immunity seem to have roles in the pathophysiology of IgG4-RD
Fibrosis might be caused by activation of innate immune cells by polarized CD4+ T cells.

@VijayanMD @Charbel_Khoury @GMatzumura IgG-4 RD can affect the kidney in 15% of patients and present in 2 distinct patterns:
- Tubulointerstitial nephritis (TIN): most common
- Membranous glomerulonephropathy (MGN)

@VijayanMD @Charbel_Khoury @GMatzumura IgG4 TIN is classically
-male predominant
-common in older age (+/- 65 years)
-with insidious rise in creatinine
-variable proteinuria (nephrotic range proteinuria rare) and absence of RBC casts.
-Commonly diagnosed in association with extrarenal manifestations.

@VijayanMD @Charbel_Khoury @GMatzumura Suggestive lab and imaging findings include
-hypocomplementemia (60%) ✔️
- peripheral eosinophilia (40%)
-weakly positive ANA but negative specific Abs✔️
-Hypodense renal cortical lesions (40%)
-diffuse renal enlargement (20%)✔️

@VijayanMD @Charbel_Khoury @GMatzumura What are the caveats when checking IgG4 levels?

Substantial elevation IgG-4 level (6-8 fold higher) is present in IgG4-RD but mild elevation can be seen in other diseases.

Normal IgG-4 level does NOT exclude IgG4-RD
IgG-4 level loosely correlates w activity and response

@VijayanMD @Charbel_Khoury @GMatzumura Hallmark features on renal pathology
- Diffuse or multifocal lymphoplasmacytic interstitial infiltrate (eosinophils frequently present)
- Whorled Storiform fibrosis

@VijayanMD @Charbel_Khoury @GMatzumura Positive immunostaining for IgG4 + plasma cells (> 10 per hpf) is characteristic. (Pauci-immune glomerulonephritis can have IgG4 + staining but necrotizing GN is a distinguishing feature)

@VijayanMD @Charbel_Khoury @GMatzumura MGN IgG4-RKD is rare, presents with nephrotic range proteinuria and can have concomitant IgG4 TIN. Subepithelial deposits in membranous pattern are seen on biopsy

@VijayanMD @Charbel_Khoury @GMatzumura Steroids are the first line of treatment and have good initial clinical response but relapse following cessation of steroids is frequent (20%).

Rituximab is a promising agent but remains unproven.

@VijayanMD @Charbel_Khoury @GMatzumura This tweetorial was prepared by our fellow on the case @GMatzumura with @VijayanMD and @Charbel_Khoury

Ref: pubmed.ncbi.nlm.nih.gov/25481618/
pubmed.ncbi.nlm.nih.gov/26122730/

#FOAMed #Nephpearls

--Fin