eMedicine Specialties > Dermatology > Internal Medicine

Amyloidosis, Primary Systemic: Treatment & Medication

Author: Judit Nyirady, MD, MBA, Adjunct Assistant Professor, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School
Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Contributor Information and Disclosures

Updated: Apr 29, 2009

Treatment

Medical Care

The treatment of primary systemic amyloidosis (PSA) is directed toward the affected organ and the specific type of the disease. In studies of different regimens of intermittent oral melphalan and prednisone, Skinner et al and Kyle et al reported that the response rates were low, with an increased survival from a median of approximately 7-9 months in patients who did not receive chemotherapy to approximately 12-18 months in those receiving chemotherapy.9,17

Shimojima et al reported a patient with primary systemic amyloidosis who achieved partial hematological response after 2 courses of the VAD (vincristine, doxorubicin [Adriamycin], and dexamethasone) chemotherapy regimen and subsequent high-dose melphalan followed by autologous peripheral blood stem cell transplantation despite involvement of multiple organs, including the heart.18 When amyloidosis-related dysfunction is seen in multiple organs, intensive chemotherapy might be a possible therapeutic option, although several modifications in the regimen and careful management are necessary.

  • The nephrotic syndrome requires supportive therapy and diuretics, and renal failure can be successfully treated with dialysis.
  • Congestive heart failure may respond to diuretics, but larger doses are often required as the disease progresses. The use of calcium channel blockers, beta-blockers, and digoxin are contraindicated in cardiac amyloidosis, because they may cause toxicity at therapeutic levels.
  • Gastrointestinal involvement and neuropathy are treated symptomatically.

Medication

The treatment of primary systemic amyloidosis is often unsatisfactory. No reliable method for the accurate assessment of the total amount of amyloid in the body exists. Investigations are limited to the evaluation of organ function and the measurement of monoclonal protein levels in the serum and urine.

The similarity between primary systemic amyloidosis and multiple myeloma suggests that chemotherapy may be useful. Using different regimens of intermittent oral melphalan and prednisone, 2 groups of investigators9,17 confirmed the effectiveness of this therapy compared with no therapy or therapy with colchicine alone. However, the response rate was low, with an increased survival from a median of approximately 7-9 months in patients who did not receive chemotherapy to approximately 12-18 months in those receiving chemotherapy.

In another trial, Kyle and Greipp reported the effectiveness of combined melphalan and prednisone therapy compared with placebo therapy.19 Although the nephrotic syndrome improved in a number of individuals receiving the active medications, overall survival rates for the active and placebo groups were not substantially different.

Colchicine has also been used in the treatment of primary systemic amyloidosis. Colchicine may inhibit amyloid deposition by blocking the formation of amyloid-enhancing factors, and it also inhibits the secretion of amyloid from hepatocytes.

Based on encouraging results in myeloma patients, Dispenzieri et al reported results of a clinical trial of lenalidomide therapy with or without dexamethasone in patients with primary systemic amyloidosis.20 As a single agent, lenalidomide had modest activity in primary systemic amyloidosis. This activity was significantly enhanced when lenalidomide was used in conjunction with dexamethasone.

Immunosuppressants

These agents inhibit key factors in the immune system that are responsible for inflammatory responses.


Prednisone (Deltasone, Orasone, Meticorten)

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.

Adult

5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve

Pediatric

4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve

Coadministration with estrogens may decrease clearance; concurrent digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Documented hypersensitivity; viral, fungal, tubercular, or connective tissue infection; peptic ulcer disease, hepatic dysfunction; GI disease

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use


Dexamethasone (Decadron)

Has many pharmacologic benefits but significant adverse effects. Stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines (eg, TNF-alpha, IL-6, IL-2, and IFN-gamma). The inhibition of chemotactic factors and factors that increase capillary permeability inhibits recruitment of inflammatory cells into affected areas. Suppresses lymphocyte proliferation through direct cytolysis and inhibits mitosis. Breaks down granulocyte aggregates, and improves pulmonary microcirculation. Important chemotherapeutic agent in the treatment of ALL. Used in induction and reinduction therapy and given as intermittent pulses during continuation therapy.
Adverse effects are hyperglycemia, hypertension, weight loss, GI bleeding or perforation synthesis, cerebral palsy, adrenal suppression, and death. Most of the adverse effects of corticosteroids are dose or duration dependent.
Readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Lacks salt-retaining property of hydrocortisone.
Patients can be switched from an IV to PO regimen in a 1:1 ratio.

Adult

6-8 mg/m2/d PO divided tid

Pediatric

Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; decreases effect of salicylates and vaccines used for immunization

Documented hypersensitivity; active bacterial or fungal infection

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications of glucocorticoid use

Antineoplastic agents

These agents inhibit cell growth and proliferation.


Melphalan (Alkeran)

Inhibits mitosis by cross-linking DNA strands.

Adult

0.15 mg/kg/d PO for 7 d or 0.25 mg/d for 4 d

Pediatric

4-20 mg/m2/d PO for 1-21 d

Concurrent administration with cyclosporine increases nephrotoxicity; cimetidine and H2 antagonists increase gastric pH decreasing effects; may exacerbate bone marrow suppression if administered 24 h before or 24 h after colony-stimulating factor; coadministration with zidovudine may contribute to bone marrow suppression

Documented hypersensitivity; severe bone marrow depression

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Amenorrhea may occur; caution in previously diagnosed myelosuppression

Uricosuric agents

These agents may inhibit the events involved in the inflammatory response associated with the disease.


Colchicine

Decreases leukocyte motility and phagocytosis in inflammatory responses.

Adult

0.5-1.2 mg PO initially, followed by 0.5-0.6 q1-2h or 1-1.2 mg q2h until a satisfactory response is attained; not to exceed 4 mg/d
1-3 mg IV initially, followed by 0.5 mg q6h until a satisfactory response is attained; not to exceed 4 mg/d

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Significantly increases sympathomimetic agent toxicity and effect of CNS depressants

Documented hypersensitivity; severe renal, hepatic, GI, or cardiac disorders; blood dyscrasias

Pregnancy

D - Fetal risk shown in humans; use only 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; dose-dependent GI upset and diarrhea common

Immunomodulators


Lenalidomide (Revlimid)

Structurally similar to thalidomide. Elicits immunomodulatory and antiangiogenic properties. Inhibits proinflammatory cytokine secretion and increases anti-inflammatory cytokines from peripheral blood mononuclear cells.

Adult

10 mg PO qd initially; dose adjustment required if renal impairment, thrombocytopenia, or neutropenia occurs

Pediatric

<18 years: Not established
>18 years: Administer as in adults

Documented hypersensitivity; pregnancy

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Available only through RevAssist, a risk management plan to prevent fetal exposure; only pharmacists and prescribers registered with the program may prescribe and dispense (program requires mandatory pregnancy testing and limits prescription to 1-mo supply via mail); male patients, including those with vasectomy, must use latex condom during sexual contact with female of childbearing potential; women must not become pregnant 4 wk before starting lenalidomide and 4 wk after discontinuing lenalidomide; may cause anemia, DVT, pulmonary embolism, thrombocytopenia, neutropenia, diarrhea, pruritus, rash, and fatigue; renal excretion substantial, caution in elderly patients or those with renal impairment (may need to decrease dose); not break, chew, or open cap

More on Amyloidosis, Primary Systemic

Overview: Amyloidosis, Primary Systemic
Differential Diagnoses & Workup: Amyloidosis, Primary Systemic
Treatment & Medication: Amyloidosis, Primary Systemic
Follow-up: Amyloidosis, Primary Systemic
References
Further Reading
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References

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Keywords

primary systemic amyloidosis, amyloidosis, PSA, amyloidosis associated with multiple myeloma, secondary systemic amyloidosis

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Contributor Information and Disclosures

Author

Judit Nyirady, MD, MBA, Adjunct Assistant Professor, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School
Judit Nyirady, MD, MBA is a member of the following medical societies: American Academy of Dermatology, European Academy of Dermatology and Venereology, International Society of Dermatology, Society for Investigative Dermatology, and Women's Dermatologic Society
Disclosure: Novartis Pharmaceuticals Corporation Salary Employment

Coauthor(s)

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Takeji Nishikawa, MD, Emeritus Professor, Department of Dermatology, Keio University School of Medicine; Director, Samoncho Dermatology Clinic; Managing Director, The Waksman Foundation of Japan Inc
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

 
 
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