Flow chart for typing amyloidoses. The crucial division is made from typing the amyloid deposits. This can be accomplished with immunohistochemistry or immunoelectron microscopy27 or by biochemical methods which are applicable also to formalin-fixed tissue samples.28 If a variant protein is identified, the specific mutation can be rapidly detected by DNA analysis. Genetic testing is also necessary for the diagnosis of familial autoinflammatory diseases (FADs) causing reactive amyloidosis (AA) in patients with characteristic clinical features.29 Immunohistochemistry is usually reliable for identifying or ruling out AA amyloidosis but is frequently not diagnostic with respect to AL amyloidosis.30 Immunoelectron microscopy (EM) and biochemical methods provide definitive results; however, they are labor intensive and require expertise. If these techniques are not available, the DNA analysis should be performed upfront to exclude the hereditary amyloidoses whose clinical presentation is consistent with the patient's manifestations. Illustration by Marie Dauenheimer.
