Amyloidosis/Fibrillary GN/Immunotactoid GN

Question 1

Amyloidosis

Clinical Manifestations

Answer 1

Depends on the type of amyloid. Typically there is waxy skin, easy bruising, enlarged muscles, liver, tongue, heart failure, abnormal cardiac conduction, proteinuria, peripheral, autonomic neuropathy, and coagulopathy.

Primary AL predominantly due to monoclonal IG light chain fragments and secondary AA due to chronic inflammatory diseases. You can have periodic fever syndromes for example familial Mediterranean fevers.

AL Monoclonality

Question 2

Amyloidosis

Histopathology

Answer 2

Light Microscopy unit and nodular or diffuse pink deposits of amorphous materials in Mesangial matrix and basement membranes of capillary loops, arterial walls. Nodular lesions resemble diabetic Kimmelstiel-Wilson nodules.

Question 3

Amyloidosis

Histopathology

Answer 3

Immunofluorescence microscopy you do not see anything

Electron Microscopy you see 10 nm fibrils

Question 4

Amyloidosis

Histopathology

Answer 4

Congo red stain is positive and also maybe negative in very early disease. You also see negative congo red staining in heavy chain amyloidosis.

Question 5

Amyloidosis

Management

Answer 5

Serum Free Light Chains you treat the underlying disease. You do dialysis support if needed.
Kidney Transplant and Dialysis related Amyloidosis.
Liver Transplant in certain hereditary and Amyloidosis.

Question 6

Amyloidosis

Answer 6

Note that fat pad biopsy is recommended over biopsies of liver or kidneys due to lowest bleeding complications.

Question 7

Fibrillary Glomerulonephritis

Clinical manifestations

Answer 7

Mean age is 50 years. You see hematuria, proteinuria, nephrotic syndrome, hypertension, and elevated serum creatinine.

Question 8

Fibrillary Glomerulonephritis

Clinical associations

Answer 8

Are idiopathic or it may be associated with malignancy, there is low association with Monoclonal (15%). It can be also associated with autoimmune diseases, and hepatitis C.

Question 9

Fibrillary Glomerulonephritis

Clinical associations

Answer 9

Monoclonality

It could be Oligotypic, for example IG G1 and IgG4

Question 10

Fibrillary Glomerulonephritis

Histopathology

Answer 10

On light microscopy you see focal residential or diffuse proliferative, or member no proliferative or membranous glomerulonephritis.

Question 11

Fibrillary Glomerulonephritis

Histopathology

Answer 11

On Immunofluorescent Microscopy you see mesangial or glomerular capillary wall deposits for IgG, C3, both kappa and lambda light chains. C1q deposition is also possible.

Question 12

Fibrillary Glomerulonephritis

Histopathology

Answer 12

In terms of Electron Microscopy you see randomly arranged fibrils about 16 to 24 nm.

They are more randomly arranged than immunotactoid

Congo red staining this is negative

Question 13

Fibrillary Glomerulonephritis

Management

Answer 13

Annual screening for associated diseases. The screening includes complete blood count with differential, serum Immunofixation and free light chains, hepatitis C.

Question 14

Fibrillary Glomerulonephritis

Management

Answer 14

Treat underlying disease. Use of ACEi or ARBs are necessary. Use of immunosuppressive therapy per findings on light microscopy. Dialysis support if needed. Renal transplant is an option also controversial in those with monoclonal the myopathy.

Question 15

Fibrillary Glomerulonephritis

Management

Answer 15

Recurrence in graft is common, but rate of progression in idiopathic cases may be slower than that observed in native kidneys.

Question 16

Immunotactoid Glomerulonephritis

Clinical manifestations

Answer 16

You see this in older populations compared to fibrillary glomerulonephritis. One third of patients have hypocomplementemia.

Question 17

Immunotactoid Glomerulonephritis

Clinical Associations

Answer 17

This could be idiopathic; there is frequent association with chronic lymphocytic leukemia or CLL and B-cell lymphomas. 60% to 70% with monoclonal gammopathy.
Cryoglobulinemia and Lupus has to be considered.

Question 18

Immunotactoid Glomerulonephritis

Clinical Associations

Answer 18

Monoclonality

This is predominantly monoclonal

Question 19

Immunotactoid Glomerulonephritis

Histopathology

Answer 19

On Light microscopy you see the same thing as Fibrillary glomerulonephritis where it is focal mesangial or diffuse proliferative or membranoproliferative or member no glomerulonephritis.

Question 20

Immunotactoid Glomerulonephritis

Histopathology

Answer 20

On immunofluorescence microscopy you see monoclonal immunoglobulin deposition with a restricted light chain either kappa or lambda.

Question 21

Immunotactoid Glomerulonephritis

Histopathology

Answer 21

Congo red stain is negative

Question 22

Immunotactoid Glomerulonephritis

Management

Answer 22

Annual screening for associated diseases is necessary. You do a complete blood count with differential, serum immunofixation and free light chains, and hepatitis C.

Question 23

Immunotactoid Glomerulonephritis

Management

Answer 23

Always treat the underlying disease. Use of ACEi or ARBs are necessary. Use of immunosuppressive therapy per findings on light microscopy is also necessary. Dialysis support if needed.

Question 24

Immunotactoid Glomerulonephritis

Management

Answer 24

Renal transplant is an option although controversial in those with monoclonal gammopathy.
Recurrence in graft is common, but rate of progression in idiopathic cases may be slower than that observed in native kidneys.