10 percent of patients who appear by all the usual criteria to have primary amyloidosis will be found to have a genetic type. However, as mentioned, only a small proportion of the latter group has a monoclonal gammopathy and it tends to be of low concentration (it has been estimated to occur in one-quarter of familial cases but we have not encountered it). This difference and the rapid progression of the primary acquired form assist in distinguishing it from the genetic type that is discussed further on.
In addition to the more slowly evolving familial types, the differential diagnosis of acquired amyloid neuropathy includes the myelomatous varieties, toxic and nutritional small-fiber neuropathies, diabetic polyneuropathy, paraneoplastic polyneuropathy, Sjögren disease, and an idiopathic small-fiber sensory neuropathy, all of which cause pain and which we have encountered more frequently than amyloidosis.
Treatment of Amyloid Neuropathy The prognosis of primary-acquired amyloidosis and its associated neuropathy has been poor. Attempts at immunomodulation, immunosuppression (which may help the renal disease), or removal of amyloid by plasma exchange have been marginally effective. Another approach has been bone marrow suppression with high doses of melphalan followed by stem cell replacement (previously harvested from the patient). Several such patients have survived for years with marked improvement in the neuropathy. Recently, several small molecules designed to prevent the aggregation of amyloid fibrils have shown benefit in the familial type of amyloid; see further on.
Pain is a serious problem in the amyloid neuropathies that may be treated with transcutaneous fentanyl patches or with oral narcotic medications. Orthostatic hypotension responds to the use of leg stockings, midodrine, and mineralocorticoids, as well as sleeping with the bed elevated at the head so that the patient’s entire body is angled down toward the feet.
This form of polyneuropathy was separated from acute inflammatory polyradiculopathy, or Guillain Barre syndrome, by Austin in 1958 on the basis of a prolonged and relapsing course, enlargement of nerves, and responsiveness to corticosteroids. Excluding the duration of evolution, the acute and chronic forms are similar in many ways. Both are widespread polyradiculoneuropathies, usually with cytoalbuminologic dissociation of the CSF (raised protein concentration with few or no cells); both exhibit nerve conduction abnormalities characteristic of a demyelinating neuropathy (reduced conduction velocity and partial conduction block in motor nerves), and pathologically, both show similar multifocal perivenous inflammatory infiltrates. But there are also important differences, the most evident of which are the modes of evolution, responses to treatment, and prognosis. As a rule, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) begins insidiously and evolves slowly, either in a steadily progressive or stepwise manner, attaining its maximum severity after several months. From the beginning it may be asymmetrical or involve the arms predominantly. However, in a small proportion of patients (16 percent in the series of McCombe et al [1987b] and a smaller proportion in our own series) the disease at first emerges from a mild or moderate case of GBS, in which case the illness becomes relapsing or simply worsens slowly and progressively.