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Amyloidosis, AA (Inflammatory): Treatment & Medication
Updated: Nov 21, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
At present, the major therapeutic strategy in amyloid A (AA) amyloidosis is treatment of the primary inflammatory disease in order to reduce the circulating levels of the amyloid precursor protein SAA. Intensive treatment that lowers SAA levels to less than 10 mg/L may halt disease progression and induce a slow progressive recovery of renal function. Accounts exist of the disappearance of the amyloid deposits associated with tuberculosis or chronically infected burns with appropriate treatment of the infection. Similarly, case reports exist of the disappearance of amyloid deposition associated with chronic inflammatory bowel disease after resection of the affected section of bowel.
Data from a randomized prospective series of patients with juvenile chronic arthritis who were treated with chlorambucil or cyclophosphamide show that the occurrence of amyloidosis is markedly reduced.2 The tradeoff for the aggressive use of alkylating agents is an increased incidence of leukemia.
Treatment with tumor necrosis factor-a inhibitors and interleukin-1 inhibitors has recently proved effective in controlling the progression of renal amyloid in patients with inflammatory arthritides and hereditary periodic fevers. The application of these agents will possibly achieve similar therapeutic effects without the additional risk, thus lowering the incidence of amyloidosis without increasing mortality.
- The use of colchicine (0.6 mg tid) by patients with FMF has been shown to reduce or eliminate the febrile episodes and to prevent the appearance of renal amyloidosis. The mechanism of action is not clear, although the elimination of AA deposition is likely mediated through the suppression of the inflammatory response and SAA production, rather than having a primary effect on amyloidogenesis.
- Based on observations of people with FMF and mice with experimental AA amyloidosis, individual patients with the nephrotic syndrome secondary to renal AA amyloidosis in the course of inflammatory bowel disease, ankylosing spondylitis, and psoriatic arthritis were treated with colchicine and had clinical pictures consistent with the resolution of the nephrotic syndrome.
- While none of these reports contained follow-up renal biopsies, the clinical information supports the conclusion; however, many unreported instances in which colchicine has been used unsuccessfully in similar circumstances also are likely to exist. The only attempt at a randomized prospective trial of colchicine has been carried out in AL disease, and it showed no effect on that process.
- The following are new approaches to the treatment of AA amyloidosis that are currently undergoing clinical trials:
- A low–molecular-weight sulfonated molecule has been developed that interferes with fibril formation and deposition of amyloid by inhibiting interaction of SAA with glycosaminoglycans. In experimentally induced murine AA amyloidosis, this drug (NC-503) has been shown to reduce the amount of amyloid deposits.
- Dimerization of human SAP molecules in vivo with a palindromic compound (CPHPC) triggers very rapid clearance of the complexed protein by the liver, depleting SAP from the circulation within a few hours of drug administration.
- Anti–IL-6R therapy appears promising for the treatment of AA amyloidosis.3
- A case report exists of severe protein-losing enteropathy with intractable diarrhea due to systemic AA amyloidosis successfully treated with corticosteroids and octreotide4 .
- A single patient with AA amyloidosis secondary to Hodgkin disease was administered 4'-iodo-4'deoxydoxorubicin as antitumor therapy (see the treatment section in Amyloidosis, Immunoglobulin-Related); this patient has been reported to show a reduction in proteinuria and the liver amyloid burden on biopsy. The response was not complete and the resolution on liver biopsy may have been the result of sampling differentially infiltrated portions of tissue; nonetheless, the result is potentially exciting.5
- A more experimentally and theoretically based approach uses the observation that anionic sulphonates interfere with the deposition of AA fibrils in a murine model of inflammatory amyloidosis. One of these compounds is in clinical trials, the results of which should be available over the next 2 years. Little or no toxicity was shown in the preclinical testing.
- In patients with AA amyloidosis who were treated before 1990, the major cause of death was renal failure, generally accounting for 35-70% of mortality, with infection responsible for an additional 10-20%. The mean survival was 2-4 years, with the degree of renal insufficiency present at the time of diagnosis correlating with longevity. In a series of patients with AA amyloidosis presenting from 1985-1999, the median survival was 53 months, and the median renal survival (time alive and independent of renal replacement) was 18 months.6 Because of the increased availability of renal replacement, renal failure was the cause of death in only 12.5% of people, and infection became dominant (42%). Nonetheless, the results of dialysis in patients with renal amyloid and an underlying inflammatory disease are worse than the results in those undergoing dialysis for other chronic renal diseases.
Surgical Care
Renal transplantation is an option in these patients, with some successes reported; however, data suggest that patients who have amyloidosis do not have as favorable a prognosis as patients transplanted for other forms of renal failure. Nonetheless, results have been improving, and transplantation is a reasonable option, particularly if the primary inflammatory disease has been treated successfully.
Consultations
- Because AA amyloidosis is usually a complication of a primary chronic infectious or inflammatory disease, consultations with specialists in infectious diseases concerning antibiotics, surgical resection, and other diagnostic and therapeutic modalities are appropriate.
- Consult a rheumatologist with regard to newer modes of anti-inflammatory treatment before assuming that the patient will inevitably follow a downhill course.
- Nephrologic and surgical management of the chronic renal failure also requires a coordinated team approach for an optimal outcome.
- Cardiac complications at the time of transplantation seem to be more common in patients with amyloidosis than in those with other forms of renal failure.
Diet
No specific dietary recommendations for patients with amyloid disease exist.
- Patients with chronic renal failure should be managed by a nutritionist who has experience with such patients, maintaining appropriate levels of sodium and protein intake.
- Occasionally, patients have significant gastrointestinal symptomatology, and attention should be paid to maintaining caloric intake with minimal gastrointestinal distress.
Activity
Encourage as much activity as the patient can tolerate in order to maintain muscle mass and a positive outlook.
Medication
No specific therapeutic agents are recommended for the treatment of amyloid A (AA) amyloidosis. Therapy for the underlying inflammatory disorders should be as aggressive as possible.
Anti-inflammatory agents
Colchicine is a disaggregator of microtubules, not a member of any of the traditional categories of anti-inflammatory agents.
Colchicine
Decreases leukocyte motility and phagocytosis in inflammatory responses. Effective in the treatment of acute gout, pseudogout, and the prophylaxis of acute febrile episodes of FMF. The latter effect probably is responsible for the reduced frequency of renal amyloidosis when treatment is adequate.
Adult
0.6 mg bid PO unless not tolerated or renal insufficiency occurs; in these cases, lower doses will be used
Pediatric
Not established
Sympathomimetic agent toxicity and effect of CNS depressants are significantly increased with colchicine
Documented hypersensitivity; severe renal, hepatic, GI, or cardiac disorders; blood dyscrasias
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Risk of renal failure, hepatic failure, permanent hair loss, bone marrow suppression, numbness or tingling in hands and feet, disseminated intravascular coagulopathy, and decreased sperm count; associated with idiosyncratic reactions; overdose results in bone marrow and gastrointestinal toxicity and death from overwhelming sepsis secondary to intestinal ulceration; decrease dose in patients with renal impairment
More on Amyloidosis, AA (Inflammatory) |
| Overview: Amyloidosis, AA (Inflammatory) |
| Differential Diagnoses & Workup: Amyloidosis, AA (Inflammatory) |
 Treatment & Medication: Amyloidosis, AA (Inflammatory) |
| Follow-up: Amyloidosis, AA (Inflammatory) |
| References |
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References
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Further Reading
Keywords
amyloidosis, secondary amyloidosis, amyloid A amyloidosis, AA amyloidosis, inflammatory amyloidosis, systemic amyloidosis, inflammation-associated amyloidosis, tissue amyloid deposition, AA deposition, renal amyloidosis, amyloid renal disease, amyloid nephropathy, rheumatoid arthritis, RA, familial Mediterranean fever, FMF, serum amyloid A protein, SAA protein
