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Amyloidosis, Lichen

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

Updated: Nov 6, 2009

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.1

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 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.2,3,4,5,6,7,8,9,10 The cardinal triad of this autosomal dominant syndrome is medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. Many cases of familial lichen amyloidosis were reported in families with MEN 2A. The lichen amyloidosis 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 lichen amyloidosis, pointing to keratin-derived amyloidosis.

A single case of lichen amyloidosis in Alagille syndrome has been reported.11 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.

Maddison et al suggest a possible cause of the severe pruritus associated with lichen amyloidosis in relation to nerve fiber density. They suggest the hypersensitivity of the remaining nerve fibers is a response to an unexplained neurodegeneration of the absent nerve fibers.12

Pathophysiology

Amyloid deposits in macular amyloidosis 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 lichen amyloidosis.13 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 lichen amyloidosis is not the cause but the result of itching and scratching. This argument was based on several lines of evidence.14

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

Striking similarities, both clinically and histopathologically, exist between lichen amyloidosis and lichen simplex chronicus.

Race

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

Sex

Lichen amyloidosis is more common in males than in females.

Age

Lichen amyloidosis occurs most frequently in persons aged 50-60 years.

Clinical

History

Typically, lichen amyloidosis is an intensely itchy eruption.

Physical

Lichen amyloidosis 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.

Differential Diagnoses

Lichen Sclerosus et Atrophicus
Prurigo Nodularis

Other Problems to Be Considered

Hypertrophic lichen planus

Workup

Procedures

A skin biopsy may be performed in lichen amyloidosis.

Histologic Findings

Many stains can demonstrate amyloid deposits in the skin. The best known is the Congo-red stain, which under polarizing light gives apple-green birefringence. Other stains include periodic acid-Schiff (PAS); methyl violet; crystal violet; various cotton dyes (eg, pagoda red, Sirius red); and the fluorescent dyes, thioflavin-T and Phorwhite BBU.

Amyloid deposits in lichen amyloidosis are found in the papillary dermis, usually at the tips of the dermal papillae. Lichen amyloidosis is distinguished from macular amyloidosis by the presence of marked epidermal changes, including hyperkeratosis and acanthosis.

Treatment

Medical Care

Because of the growing appreciation of the importance of pruritus as the primary trigger for the deposition of amyloid, treatment modalities are directed toward the relief of pruritus.

  • Sedating antihistamines have been found to be moderately effective.
  • Menthol, in combination with other agents (eg, antihistamines), has been used successfully to relieve the pruritus associated with lichen amyloidosis.15
  • Topical and intralesional steroids are beneficial if combined with other modalities. Costanedo-Cazares et al reported improvement in lichen amyloidosis using treatment with 0.1% topical tacrolimus ointment.16
  • Topical dimethyl sulfoxide (DMSO), a chemical solvent, was used with moderate success, but failures are also reported.17,18,19 Pandhi et al reported a lack of effect with DMSO treatment for cutaneous amyloidosis.20
  • Anecdotes of both success and failure with etretinate have been reported.21,22,23 Acitretin, a prodrug of etretinate, has been used successfully to relieve pruritus and flatten hyperkeratotic papules in 2 patients with lichen amyloidosis.24
  • Sawamura et al reported satisfying improvement of lichen amyloidosis with pulsed dye laser. Both pruritus and the papular eruption of lichen amyloidosis improved.25
  • In a report emphasizing the localization of lichen amyloidosis in body regions with lower temperatures, narrow-band UVB was used to treat the patient; marked improvement of pruritus and clearing of the amyloid deposits was reported.26
  • In 2009, Aoki and Kawana reported successful treatment of lichen amyloidosis of the auricular concha using electrodesiccation.27

Surgical Care

Aggressive strategies proposed for the removal of amyloid include laser vaporization, dermabrasion, and excision of individual lesions. However, both the lesions and the pruritus usually promptly recur after these treatments.

In a prospective, side-by-side, controlled, clinical trial study, Ostovari et al used the Q-switched Nd:YAG laser (532- and 1064-nm) in 20 subjects with a clinical diagnosis and pathologic confirmation of macular amyloidosis. Using colorimetric score assessment and digital photographs before laser therapy and 8 weeks after treatment, they concluded that the 2 lasers (Q-switched 532- and 1064-nm Nd:YAG) are effective in reducing the degree of pigmentation in macular amyloidosis patches, with the 532-nm laser being more effective than the 1064-nm laser. The pictures shown in this paper were of low quality.28

Medication

The goal of pharmacotherapy for lichen amyloidosis is to reduce morbidity.

Antihistamines

These agents act by competitive inhibition of histamine at the H1 receptor. They may control itching by blocking effects of endogenously released histamine.


Chlorpheniramine (Chlor-Trimeton)

Competes with histamine or H1 receptor sites on effector cells in blood vessels and respiratory tract.

Dosing

Adult

4 mg PO q4-6h; not to exceed 24 mg/d

Pediatric

<6 years: Not recommended
6-12 years: 2 mg PO q4-6h; not to exceed 12 mg/d
>12 years: Administer as in adults

Interactions

CNS toxicity increases with coadministration of other CNS depressants, tricyclic antidepressants, MAOIs, and phenothiazines

Contraindications

Documented hypersensitivity; asthma attacks; narrow-angle glaucoma; symptomatic prostate hypertrophy; bladder neck obstruction; stenosing peptic ulcer

Precautions

Pregnancy

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

Precautions

May cause significant confusional symptoms; not for administration to premature or full-term neonates; drowsiness, dizziness, and dryness of mouth are the most common adverse effects; patients should not operate vehicles or hazardous machinery


Diphenhydramine (Benadryl)

For symptomatic relief of symptoms caused by release of histamine in allergic reactions.

Dosing

Adult

25-50 mg PO tid/qid

Pediatric

<10 kg: Not established
>10 kg: 12.5-25 mg PO tid/qid or 5 mg/kg/d PO divided tid/qid; not to exceed 300 mg/d

Interactions

Potentiates effect of CNS depressants; because of alcohol content, do not give syr dosage form to patient taking medications that can cause disulfiramlike reactions

Contraindications

Documented hypersensitivity; MAOIs

Precautions

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

May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; drowsiness, dizziness, and xerostomia are the most common adverse effects; patients should not operate vehicles or hazardous machinery

Topical anti-inflammatory agents

This agent is an industrial solvent.


Dimethyl sulfoxide (Rimso-50)

May help relieve symptoms. DMSO, an oxidation product of dimethyl sulfide, is an exceptional solvent possessing a number of commercial uses.
Not an FDA-approved indication.

Dosing

Adult

50% solution in water applied topically over affected area

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

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

Garliclike breath odor and taste in the mouth due to excretion of small amount of DMSO as dimethyl sulfide (usually lasts only 24-48 h)

References

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  15. Frolich M, Enk A, Diepgen TL, Weisshaar E. Successful treatment of therapy-resistant pruritus in lichen amyloidosis with menthol. Acta Derm Venereol. 2009;89(5):524-6. [Medline].

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Keywords

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

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

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

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

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.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.

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