eMedicine Specialties > Dermatology > Metabolic Diseases

Amyloidosis, Lichen

Author: Sultan Al-Khenaizan, MBBS, FRCP(C), Consulting Staff, Departments of Dermatology and Internal Medicine, King Fahad National Guard Hospital, Saudi Arabia
Contributor Information and Disclosures

Updated: Mar 7, 2007

Introduction

Background

Amyloidosis is a generic term that signifies the abnormal extracellular tissue deposition of one of a family of biochemically unrelated proteins that share certain characteristic staining properties, including apple-green birefringence of Congo red–stained preparations viewed under polarizing light. Under electron microscopy (EM), amyloid deposits are composed of linear, nonbranching, aggregated fibrils, 7.5-10 nm thick of indefinite length arranged in a loose meshwork.

X-ray diffraction crystallography and infrared spectroscopy revealed that these fibrils have a meridional, antiparallel, beta-pleated sheet configuration with polypeptide chains arranged perpendicular to the long axis of the fibrils.

Amyloid deposits contain (in addition to the fibrillar component) a nonfibrillar protein referred to as amyloid-P (Am-P). This protein is identical to normal plasma globulin, known as serum amyloid-P (SAP). Am-P constitutes 14% of the dry weight of amyloid. This protein is also found in the microfibrillar sheath of elastic fibers. SAP is closely related to the acute phase reactant C-reactive protein (CRP) and has been shown to be an elastase inhibitor.

SAP and the beta-pleated sheet configurations are thought to protect amyloid deposits from degradation and phagocytosis, leading to persistence of the deposits.

Lichen amyloidosis (LA) has been reported in association with few syndromes. The most intriguing is the association with multiple endocrine neoplasia type 2A (MEN 2A), also known as Sipple syndrome. The cardinal triad of this autosomal dominant syndrome is medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. Many cases of familial LA were reported in families with MEN 2A. The LA in this syndrome is usually localized to the interscapular region consisting of lichenoid papules, with hyperpigmentation and fine scaling. The histopathologic and immunohistochemistry findings are similar to those in isolated LA, pointing to keratin-derived amyloidosis.

A single case of LA in Alagille syndrome has been reported. This consists of interlobular biliary duct deficiency and cardiovascular, vertebral, and ocular anomalies.

The disease is associated with marked pruritus secondary to cholestasis. This is believed to be the cause of the amyloid deposition.

Pathophysiology

Amyloid deposits in macular and lichen amyloidosis bind to antikeratin antibodies. These deposits contain sulfhydryl groups, pointing to altered keratin as a source for these deposits. Apaydin et al found no differences in staining characteristics of cytokeratins between macular amyloidosis and LA. Interestingly, in their study, all the cytokeratins detected in amyloid deposits were of basic type (type II). This may be because, in amyloidogenesis, acidic cytokeratins such as cytokeratin 14 are degraded faster than basic types.

Weyers et al presented a convincing argument that the deposition of amyloid in LA is not the cause but the result of itching and scratching. This argument was based on several lines of evidence.

Amyloid deposition per se does not cause itching. Systemic amyloidosis is not associated with pruritus. Nonpruritic LA has also been described. Pruritus usually precedes the development of LA by years. Amyloid cannot be detected in clinically healthy skin of patients with LA.

Striking similarities, both clinically and histopathologically, exist between LA and lichen simplex chronicus (LSC).

Race

LA is believed to be more common in persons of Chinese ancestry than in other people.

Sex

LA is more common in males than in females.

Age

LA occurs most frequently in persons aged 50-60 years.

Clinical

History

Typically, LA is an intensely itchy eruption.

Physical

LA presents as intensely pruritic, red-brown hyperkeratotic papules most commonly seen on the pretibial surfaces, but it can also occur on the feet and the thighs.

Causes

See Pathophysiology.

More on Amyloidosis, Lichen

Overview: Amyloidosis, Lichen
Differential Diagnoses & Workup: Amyloidosis, Lichen
Treatment & Medication: Amyloidosis, Lichen
References
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References

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Further Reading

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Keywords

lichen amyloidosis, LA, amyloid deposits, multiple endocrine neoplasia type 2A, MEN 2A, Sipple syndrome

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Contributor Information and Disclosures

Author

Sultan Al-Khenaizan, MBBS, FRCP(C), Consulting Staff, Departments of Dermatology and Internal Medicine, King Fahad National Guard Hospital, Saudi Arabia
Disclosure: Nothing to disclose.

Medical Editor

C Lisa Kauffman, MD, FACP, Professor, Chief, Division of Dermatology, Departments of Medicine and Pathology, Georgetown University Medical Center
C 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

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

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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