Monday, October 17, 2011

Heavy Chain Deposition Disease

As an intern, and I'm sure many can relate to this story, I remember trailing after the team, disheveled and exhausted as we rounded endlessly postcall one day. Our hospital had the county jail contract and as we walked by a patient room I caught a glimpse of a man in the characteristic orange jumpsuit sitting at the edge of the bed with his leg chain draped around the bedpost.

As I passed the doorway the attending at the head of the group spun on his heal, looked at me dramatically and asked, "what illness was that man suffering from?"

I wracked my brain, "had his hands looked arthritic? Did he have a chest tube?" I had no idea and shrugged.

"That," the attending declared, "was Heavy Chain Disease!" The team chuckled and moved on and I sighed and tried to remember what Heavy Chain Deposition Disease (HCDD) was. In the October issue of AJKD there's a nice case series of HCDD that had me reliving that day of internship.

HCDD falls under the banner of Monoclonal Ig Deposition Diseases (MIDD). There are three major types of MIDD, Light Chain deposition disease (LCDD), Light and Heavy Chain Deposition Disease (LHCDD) and HCDD. In the July NephSap on Renal Pathology (which is a must read if you haven't seen it yet) it's stated that 80 to 90% of MIDD cases are LCDD, 10 to 20% are LHCDD and less than 5% are HCDD with just 27 cases identified by the AJKD authors.

HCDD is characterized by glomerular and tubular basement membrane deposition of monoclonal heavy chains without associated light chains. In terms of the types of Ig that have been described IgG related disease has been most commonly reported with rare reports of IgA and IgM.

Clinically most patient's with HCDD present with hypertension, progressive renal failure, nephrotic range proteinuria and microhematuria. In the AJKD article the authors note that a conclusive diagnosis of a plasma cell dyscrasia was made in all cases of IgA related disease but in just 19% of IgG disease. They speculate that the reason for this is that the conformational abnormality of the monoclonal heavy chain in IgG disease is such that it has a very high avidity for renal parenchyma so that even small quantities produced by a clinically undetectable population of cells is enough to cause HCDD. The single case report of IgM disease did not have an associated plasma cell dyscrasia.

The predominant pattern seen on light microscopy in HCDD is nodular glomerulosclerosis and of note all the cases of IgA related disease additionally had crescents. Nodular glomerulosclerosis has its own interesting differential diagnosis that has been previously reviewed on RFN. Check out the nice table below on the subject from JASN.

Immunofluorescence is negative except for occasional complement deposition along with the pathologic heavy chain and electron microscopy shows fine, granular, punctate electron dense deposits that lack fibrillary structure (see Emily's great review of Organized Deposition Diseases for more on fibrillary deposits). The deposits are seen in the inner aspect the of the GBM, mesangium, outer tubular basement membranes and vessel walls.

Now if the attending hits you with a bad pun post call, you'll 1) be ready for the pun and 2) be ready to dazzle and amaze with knowledge about HCDD.