AA (Inflammatory) Amyloidosis Clinical Presentation

Updated: Dec 30, 2018
  • Author: Richa Dhawan, MD, CCD; Chief Editor: Herbert S Diamond, MD  more...
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Presentation

History

The most common presentation of amyloid A (AA) amyloidosis is renal. Renal involvement is found in as many as 90% of patients. Thus, signs and symptoms reflect the appearance of proteinuria, progressive development of renal insufficiency, or nephrotic syndrome. [26] Weakness, weight loss, and peripheral edema are the most common manifestations.

In patients with active rheumatoid arthritis (RA), some of those symptoms may be incorrectly attributed to progression of the inflammatory disease or to adverse effects of drugs. However, the development of proteinuria in patients with RA should always raise the suspicion of AA amyloidosis.

Amyloid deposits also occur in the spleen and liver, but even a significant splenic and hepatic load may remain asymptomatic for long periods. Splenic involvement might be suspected if Howell-Jolly bodies are found in a peripheral blood smear of a nonsplenectomized patient, or if frequent episodes of infection occur.

Rarely, evidence of bowel involvement dominates the presentation. GI involvement may lead to motility disorders and pseudo-obstruction. Amyloid accumulations in the small intestine can cause generalized malabsorption. The weakened bowel wall can rupture, leading to peritonitis. Blood vessel wall and tissue amyloid predispose to bleeding. [27]

Again, in patients with inflammatory joint disease, the GI symptoms can also be secondary to treatment, particularly with nonsteroidal anti-inflammatory drugs.

Goiter has also been reported as a possible feature of symptomatic AA amyloidosis.

Cardiac AA deposits may be revealed with echocardiography in about 10% of patients. Clinical evidence of cardiac involvement occurs in as many as 50% of patients with L chain–type (AL) amyloidosis compared with less than 5% with AA amyloidosis. Amyloid accumulation in the heart may be suggested by the following:

  • Decreased voltage in the electrocardiogram limb leads
  • Pseudoinfarction pattern in form of Q waves in the anterior chest leads
  • Thickening of the left ventricular wall disproportionate to the degree of current or prior hypertension

The hypomotile and pathological heart wall and failing heart predispose to mural thrombosis and embolic complications. Such right-sided heart involvement is a major prognostic determinant in AL amyloidosis, but is uncommon in AA amyloidosis. Amyloid in the conduction pathways can lead to high-grade blocks. [28]

Congestive heart failure, peripheral neuropathy, or carpal tunnel syndrome occasionally occurs during the course of AA amyloidosis. In contrast to AL amyloidosis and other amyloidoses, however, they are rarely, if ever, a presenting manifestation.

In patients with familial Mediterranean fever (FMF), the history of periodic fever, arthritis, serositis, and the presence of the same disorder in other family members are characteristic. Some instances have been reported in which febrile episodes are not apparent, and renal amyloid is the first manifestation of disease.

In patients with atrial myxoma or renal carcinoma, the appearance of symptoms consistent with nephrotic syndrome or renal failure due to amyloidosis may be the first evidence of the primary neoplastic disease.

In general, the appearance of symptoms suggesting renal disease in a patient with chronic infectious or noninfectious inflammation should raise a warning flag with respect to the presence of AA amyloidosis as a complication.

Rarely, a more specific symptom, such as abdominal fullness or right upper quadrant discomfort (reflecting hepatomegaly), might bring the patient to the physician.

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Physical Examination

Patients with amyloid renal disease are commonly hypertensive, although whether the hypertension is associated with the renal amyloidosis or is a coincidental finding is not always clear. Sallow complexion and peripheral edema are the main physical findings in individuals with either renal failure or nephrotic syndrome.

The major physical findings may be those associated with the primary inflammatory disease. The appearance of hepatosplenomegaly in a patient with ongoing inflammation should prompt investigation for amyloidosis, although some patients with severe RA develop splenomegaly with subsequent Felty syndrome (splenomegaly and neutropenia or pancytopenia in the course of RA). These patients with Felty syndrome generally have normal renal function, although they might have a renal disease other than AA deposition.

The purpura and macroglossia observed in AL amyloidosis are not features of AA amyloidosis. Nor is the orthostatic hypotension associated with AL amyloidosis or the familial amyloidoses, unless gastrointestinal bleeding or other forms of hypovolemia associated with renal dysfunction are present.

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