AA (Inflammatory) Amyloidosis Clinical Presentation

Updated: Jan 08, 2021
  • Author: Jefferson R Roberts, MD; 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. Signs and symptoms reflect the appearance of proteinuria, progressive development of renal insufficiency, or nephrotic syndrome. [35]  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 for underlying AA amyloidosis.

Amyloid deposits also occur in the spleen and liver, but even a significant splenic and hepatic load may remain clinically asymptomatic for long periods of time. Rarely, abdominal fullness or right upper quadrant discomfort (reflecting hepatomegaly), might bring the patient to the physician. Hepatic dysfunction will eventually present itself on physican examination, but may also not be evident on laboratory analysis for long periods of time. Splenic involvement might be suspected if Howell-Jolly bodies are found on a peripheral blood smear of a nonsplenectomized patient, or if frequent episodes of infection occur.

Rarely, evidence of bowel involvement dominates the presentation. Gastrointestinal (GI) involvement may lead to motility disorders and pseudo-obstruction. Amyloid accumulations in the small intestine can cause generalized malabsorption, manifesting as a variety of nutrient deficiencies and the complications associated with specific nutrients (eg, iron deficiency anemia, macrocytic anemia in vitamin B12/folate deficiency). GI involvement can result in weakening of the intestinal wall, which can rupture and lead to peritonitis. Amyloid deposition in blood vessel walls and tissue  predispose patients to bleeding. [36]

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. [37]

 Clinical evidence of cardiac involvement occurs in less than 5% with AA amyloidosis, compared with as many as 50% of patients with L chain–type (AL) amyloidosis. 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.  [38]

In general, the appearance of symptoms suggesting kidney disease in a patient with chronic infectious or noninfectious inflammation should raise a warning flag for possible underlying AA amyloidosis.

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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 if it 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. 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 kidney function, although they might have a renal disease other than AA deposition. [39]

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.  In summary, the physical examination manifestations that will appear in a patient with AA amyloidosis depend on the organ system involved. The following are possible patient presentations depending on the organ system involved:

  • Renal involvement: edema of extremities (due to proteinuria)
  • Hepatic involvement: hepatomegaly
  • Gastrointestinal involvement: diarrhea or constipation, bleeding
  • Splenic involvement: splenomegaly
  • Cardiac involvement: chest pain, edema, shortness of breath, palpitations
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Complications

Complications of AA amyloidosis focus on the organ system involved. Renal dysfunction and consequently the progression to end-stage-renal-disease and dialysis are the most common complications. Hepatic dysfunction manifesting as liver failure, splenic dysfunction with more frequent infections, gastrointestinal dysfunction with malabsoprtion and possible bowel rupture, and cardiac dysfunction with heart failure are all possible outcomes, but less common than the renal disease progression. 

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