eMedicine Specialties > Dermatology > Metabolic Diseases

Amyloidosis, Nodular Localized Cutaneous

Author: Lauren Biesbroeck, Washington University in St Louis School of Medicine
Coauthor(s): Gregory J Raugi, MD, PhD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle
Contributor Information and Disclosures

Updated: Jan 5, 2010

Introduction

Background

Localized cutaneous amyloidosis (LCA) refers to a condition characterized by the deposition of amyloid or amyloid-like proteins in the dermis. Localized cutaneous amyloidosis encompasses several conditions characterized by amyloid deposition, including macular amyloidosis and lichen amyloidosis. Nodular localized cutaneous amyloidosis (NLCA) is the rarest type of localized cutaneous amyloidosis and is distinct from the other two.

Gottron first reported nodular localized cutaneous amyloidosis in 1950. Since then, approximately 60 patients have been reported in the North American, European, and Asian literature. This entity also is termed amyloidosis cutis nodularis atrophicans or tumefactive amyloid. By definition, nodular localized cutaneous amyloidosis describes a primary disease of the skin, although lesions occasionally appear similar to the skin manifestations of systemic amyloidosis.

Pathophysiology

As a term, "amyloid" was used historically to define proteins that shared similar microscopic characteristics and affinity for certain stains. Research has revealed that "amyloid" proteins are heterogeneous. The various diseases characterized by deposition of "amyloid" proteins are similarly heterogeneous but have in common the deposits of fibrillar proteins characterized as "amyloid" in the dermis. In nodular localized cutaneous amyloidosis, the amyloid is believed to derive from local plasma cells, in contrast to lichenoid or macular amyloidosis, which have keratinocyte-derived amyloid.

In nodular localized cutaneous amyloidosis, plasma cells produce immunoglobulin light chains that are precursors to the amyloid fibril protein(s) termed amyloid L. Reports differ regarding the clonality of this population of plasma cells. In some instances, plasma cells have been monoclonal, suggesting that nodular localized cutaneous amyloidosis is a neoplastic disorder1 ; however, in another instance, plasma cells demonstrated polyclonality, which usually is a feature of a more reactive process.

Frequency

United States

Incidence and prevalence of localized cutaneous amyloidosis in the United States are not known; however, the scarcity of reported patients with localized cutaneous amyloidosis indicates that the condition may be rare.

International

Despite a paucity of reported patients, localized cutaneous amyloidosis, although rare, is represented in the American, Asian, and European literature.

Mortality/Morbidity

Nodular localized cutaneous amyloidosis typically is benign and limited to the skin. However, lesions are more often persistent. Reported rates of progression to systemic disease are derived from case series with small numbers of patients; these rates vary from 7% to nearly 50%.2,3 As many as 25% of reported cases have been associated with Sjögren syndrome. Some speculate that these 2 disorders have may have a shared pathogenesis.4,5,6,7,8  

Case reports have also correlated nodular localized cutaneous amyloidosis with other autoimmune disorders such as CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia syndrome), primary biliary cirrhosis, rheumatoid arthritis, and systemic lupus erythematosus.9

Race

Epidemiologic data can be difficult to establish when so few patients are reported. No specific racial, ethnic, or geographic group appears more prone than another to developing nodular localized cutaneous amyloidosis.

Sex

Of the first 13 patients described in the Japanese literature, 12 were women; however, this disproportionate ratio has not been seen consistently. In a subsequent series of 12 patients, the male-to-female ratio was equal. Other series have reported equal or nearly equal male-to-female ratios.

Age

Patients reportedly range in age from 33-86 years. The mean age of onset has been reported to be 55 years. Although numbers are small, reports indicate that nodular localized cutaneous amyloidosis is likely to occur during adulthood.

Clinical

History

  • Nodular localized cutaneous amyloidosis lesions usually are asymptomatic.
  • Patients can present with single or multiple lesions.
  • In some reports, lesions were present for several years before patients sought medical attention.
  • Troublesome aspects of nodular localized cutaneous amyloidosis primarily result from patient concerns about appearance, although plaques eventually fissured in one patient in whom the plantar aspects of the feet were affected.
  • Up to 25% of reported cases of NLCA have been in patients with Sjögren syndrome.

Physical

  • Firm nodules can present anywhere on the skin, including the face, scalp, extremities, trunk, and genitalia.10,11,12
  • Nodules vary from a few millimeters to a few centimeters.
  • Nodules appear pink to brown or red.
  • Overlying epidermal atrophy has been described.
  • Other terms that describe the various lesions of nodular localized cutaneous amyloidosis include waxy, purpuric, yellowish, or bullous.
  • Lesions tend not to ulcerate.
  • Nodular localized cutaneous amyloidosis lacks extracutaneous findings by definition; however, one patient reported to have nodular localized cutaneous amyloidosis had amyloid deposits in the rectum.
  • Macroglossia, a typical feature of systemic amyloidosis, is not seen in nodular localized cutaneous amyloidosis.

Causes

The cause of nodular localized cutaneous amyloidosis is not known, although the amyloid protein is derived from a localized infiltrate of plasma cells.

More on Amyloidosis, Nodular Localized Cutaneous

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Differential Diagnoses & Workup: Amyloidosis, Nodular Localized Cutaneous
Treatment & Medication: Amyloidosis, Nodular Localized Cutaneous
Follow-up: Amyloidosis, Nodular Localized Cutaneous
Multimedia: Amyloidosis, Nodular Localized Cutaneous
References
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References

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Further Reading

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Keywords

nodular localized cutaneous amyloidosis, localized cutaneous amyloidosis, NLCA, LCA, amyloidosis cutis nodularis atrophicans, tumefactive amyloid, systemic amyloidosis, Sjogren syndrome, Sjögren syndrome

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Contributor Information and Disclosures

Author

Lauren Biesbroeck, Washington University in St Louis School of Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Gregory J Raugi, MD, PhD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle
Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Catharine Lisa Kauffman, MD, FACP, Georgetown Dermatology and Georgetown Dermpath
Catharine Lisa Kauffman, MD, FACP is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Royal Society of Medicine, Society for Investigative Dermatology, and Women's Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey
Warren R Heymann, 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 M Quirk, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania
Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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