eMedicine Specialties > Dermatology > Internal Medicine

Amyloidosis, Primary Systemic: Differential Diagnoses & Workup

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

Differential Diagnoses

Amyloidosis, Lichen
Pseudoxanthoma Elasticum
Amyloidosis, Macular
Scleredema
Amyloidosis, Nodular Localized Cutaneous
Sebaceous Hyperplasia
Cutis Verticis Gyrata
Xanthomas
Mastocytosis

Other Problems to Be Considered

Terrier et al reported on immunoglobulin M – related amyloidosis, which is a rare and little known complication of monoclonal immunoglobulin M – associated disorders.16

Workup

Laboratory Studies

  • In a review of 132 primary systemic amyloidosis cases, Kyle and Bayrd reported that laboratory studies revealed anemia in less than 50% of the cases.8 The white cell count was usually within the reference range, and the erythrocyte sedimentation rate was higher than 50 mm/h in one half of the cases. Hepatic function was abnormal, and the serum creatinine level was increased in 50% of patients. Proteinuria was present in more than 90% of the cases.
  • Conventional urine heat testing and electrophoresis of serum and urine samples may fail to demonstrate small quantities of monoclonal paraprotein or Bence-Jones protein. Immunoelectrophoresis of serum and concentrated urine samples is essential.

Imaging Studies

  • Echocardiography is valuable in the evaluation of amyloid heart disease. It usually reveals a concentrically thickened left ventricle and often a thickened right ventricle, with a normal-to-small cavity.
  • Doppler studies are useful and may show abnormal relaxation early in the course of the disease. Advanced involvement is characterized by restrictive hemodynamics.

Procedures

  • Biopsy of a cutaneous lesion, if present, has the advantage of safety and a high diagnostic yield.
  • Biopsy results in clinically normal skin may be positive in as many as 50% of cases of primary systemic amyloidosis.
  • Findings from abdominal fat aspiration are positive in almost 80% of patients.
  • Rectal biopsy reveals positive findings in about 80% of patients.
  • If specimens from the biopsy sites are negative for amyloid, tissue should be obtained from an organ or area with suspected involvement, such as the kidney, liver, heart, or sural nerve.

Histologic Findings

The best way to identify amyloid is to stain paraffin-embedded sections with alkaline Congo red and to examine them with polarized light to elicit a green fluorescence. Routine hematoxylin-eosin staining may show a homogenous, faintly eosinophilic mass if enough amyloid is present.

Analysis of a skin biopsy specimen of a papule reveals an amorphous or fissured eosinophilic mass in the papillary dermis with associated thinning or obliteration of the rete ridges. Nodules and plaques may demonstrate diffuse amyloid deposition in the reticular dermis or subcutis. Amyloid depositions are usually not associated with an inflammatory infiltrate.

The appearance of amyloid infiltration of the blood vessel walls, pilosebaceous units, arrector pili muscles, and lamina propria of sweat glands and infiltration around individual fat cells in the subcutis (known as amyloid rings) are characteristic findings. Amyloid may be deposited in the nail bed of dystrophic nails.

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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  2. Divry P, Florkin M, Firket J. Sur les proprietes otiques de l'amiloide. C R Soc Biol (Paris). 1927;97:1808-10.

  3. Cohen AS, Calkins E. Electron microscopic observations on a fibrous component in amyloid of diverse origins. Nature. Apr 25 1959;183(4669):1202-3. [Medline].

  4. Murtagh B, Hammill SC, Gertz MA, Kyle RA, Tajik AJ, Grogan M. Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement. Am J Cardiol. Feb 15 2005;95(4):535-7. [Medline].

  5. Wong CK. Mucocutaneous manifestations in systemic amyloidosis. Clin Dermatol. Apr-Jun 1990;8(2):7-12. [Medline].

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  9. Skinner M, Anderson J, Simms R, et al. Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicine versus colchicine only. Am J Med. Mar 1996;100(3):290-8. [Medline].

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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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