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168 AMYLOIDOSIS

168 AMYLOIDOSIS
Harrison’s Manual of Medicine

168

AMYLOIDOSIS

Definition
Classification
Clinical Manifestations
Diagnosis
Prognosis
Bibliography

Definition
A disease characterized by deposition of the fibrous protein amyloid in one or more sites of the body. Clinical manifestations depend on anatomic distribution and intensity of amyloid protein deposition and range from local deposition with little significance to involvement of virtually any organ system with consequent severe pathophysiologic changes.
Classification
Chemical characterization reveals several varieties of amyloid fibrils associated with different clinical situations (see Table 319-1, p. 1975, in HPIM-15):

Light chain amyloidosis (AL): most common form of systemic amyloidosis seen in clinical practice; occurs in primary idiopathic amyloidosis and amyloid associated with multiple myeloma.

Amyloid A amyloidosis (AA): occurs in secondary amyloidosis as a complication of chronic inflammatory disease and in familial Mediterranean fever (FMF).

Heredofamilial amyloidoses

Ab2M: Chronic hemodialysis-related amyloid; identical to b2 microglobulin.

Localized or organ-limited amyloidoses: includes Ab: found in neuritic plaques and cerebrovascular walls of pts with Alzheimer’s disease and Down’s syndrome.
Clinical Manifestations
Clinical features are varied and depend entirely on biochemical nature of the fibril protein. Frequent sites of involvement:

Kidney—seen with AA and AL; proteinuria, nephrosis, azotemia.

Liver—occurs in AA, AL, and heredofamilial; hepatomegaly.

Skin—characteristic of AL but can be seen in AA; raised waxy papules.

Heart—common in AL and heredofamilial; CHF, cardiomegaly, arrhythmias.

GI—common in all types; GI obstruction or ulceration, hemorrhage, protein loss, diarrhea, macroglossia, disordered esophageal motility.

Joints—usually AL, frequently with myeloma; periarticular amyloid deposits, “shoulder pad sign”: firm amyloid deposits in soft tissue around the shoulder, symmetric arthritis of shoulders, wrists, knees, hands.

Nervous system—prominent in heredofamilial; peripheral neuropathy, postural hypotension, dementia. Carpal tunnel syndrome may occur in AL and Ab2M.

Respiratory—lower airways can be affected in AL, localized amyloid can cause obstruction along upper airways.

Hematologic—selective clotting factor deficiency.
Diagnosis
Requires demonstration of amyloid in a biopsy of affected tissue using appropriate stains (e.g., Congo red). Aspiration of abdominal fat pad or biopsy of rectal mucosa may demonstrate amyloid fibrils. Electrophoresis and immunoelectrophoresis of serum and urine may assist in detecting paraproteins.
Prognosis
Outcome is variable and depends on type of amyloidosis and organ involvement. Average survival of AL amyloid is ~12 months; prognosis is poor when associated with myeloma. Renal failure and heart disease are the major causes of death.

TREATMENT
There is no specific therapy for any variety of amyloidosis. If present, an underlying disorder should be treated. Primary amyloidosis may respond to regimens incorporating prednisone and alkylating agents, presumably because of the effects of these agents on synthesis of the AL amyloid protein. Colchicine (1–2 mg/d) may prevent acute attacks in FMF and thus may block amyloid deposition. Renal transplantation may be effective in selected pts.

Bibliography

For a more detailed discussion, see Sipe JD, Cohen AS: Amyloidosis, Chap. 319, p. 1974, in HPIM-15.

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