Are You Confident of the Diagnosis?

Characteristic findings on physical examination

Lichen amyloidosis is often described as a chronic, pruritic eruption of multiple discrete hyperkeratotic, nontender papules that may coalesce to form plaques with overlying lichenification (Figure 1). Lichen amyloidosis mostly occurs on the pretibial areas with occasional involvement of the arms, thighs, calves, ankles, and dorsa of the feet. Rarely, the face, chest, abdominal wall and anosacral regions are affected. Although itching is a frequent finding, it may be absent.

Figure 1.

Lichen amyloid on the lower leg

Lichen amyloidosis is the most common type of primary localized cutaneous amyloidoses (amyloid deposits are exclusively localized in the skin). The three main forms of primary localized cutaneous amyloidosis are lichen amyloidosis, macular amyloidosis, and nodular amyloidosis. A patient presenting with lichen amyloidosis as well as macular amyloidosis has a condition known as biphasic amyloidosis.

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Expected results of diagnostic studies

On histologic examination of lichen amyloidosis, the epidermis is usually acanthotic, hyperkeratotic, and hyperpigmented. Amyloid deposits are preferentially situated in the papillary dermis surrounded by lymphocytes, fibroblasts, and hyaline bodies. Adnexal structures and blood vessels are characteristically not invaded in lichen amyloidosis but are infiltrated in other types of amyloidoses such as primary localized nodular amyloidosis and primary systemic amyloidosis (Figure 2).

Figure 2.

Characteristic biopsy of lichen or macular amyloid. (Courtesy of Bryan Anderson, MD)

All types of amyloidoses share the following staining patterns: methyl and crystal violet metachromasia, yellow-green birefringence under a fluorescence microscope after thioflavin T staining, and apple-green birefringence under a polarized light after Congo red staining. However, only lichen amyloidosis and macular amyloidosis share the unique ability to stain positive for antikeratin antibodies.

Diagnosis confirmation

The differential diagnosis of lichen amyloidosis includes

–lichen simplex chronicus (lichenification of the skin from chronic scratching)

–lichen planus (violaceous, polygonal papules characteristically on flexural areas with a white lacy appearance on mucosal surfaces)

–prurigo nodularis (pruritic nodules on the extensor surfaces of the arms and legs)

–adult colloid milium (amber to skin-colored papules most commonly on the face, neck, ears and dorsa of the hands resulting from chronic sun exposure)

–keratosis pilaris (keratotic papules within hair follicles typically found on the proximal arms and thighs)

–acral persistent papular mucinosis (skin-colored papules characteristically located on the dorsa of the hands and distal forearms)

–stasis dermatitis (inflammatory skin condition of the lower extremities related to chronic venous insufficiency)

solar (actinic) elastosis (thickened, furrowed skin due to chronic sun exposure)

In differentiating lichen amyloidosis from other skin disorders, it is important to know that small amounts of amyloid may not be detected by methyl violet and Congo red staining. Colloid milium also has the ability to stain with Congo red. Additionally, lichen planus can demonstrate false-positive results with thioflavin T staining.

Who is at Risk for Developing this Disease?

Although most cases of lichen amyloidosis are sporadic, approximately 10% of cases are familial showing an autosomal dominant inheritance. The disease appears to have a higher occurrence in persons of Chinese ancestry. In one study based on patients from Southeast Asia, lichen amyloidosis was more common in women and usually presented between the third to fifth decade of life.

What is the Cause of the Disease?

The precise pathogenesis of lichen amyloidosis has not yet been determined, with chronic friction (associated with rubbing and scratching), genetic factors and viral infection as possible causes. The cutaneous amyloid deposits of lichen amyloidosis are thought to be derived from degenerated keratin peptides of apoptotic keratinocytes transformed by macrophages and fibroblasts.

Systemic Implications and Complications

Lichen amyloidosis has not been reported to progress to systemic disease, with the amyloid deposits exclusively localized to the skin. There is some evidence linking primary localized cutaneous amyloidoses to a variety of immune disorders including systemic sclerosis, CREST syndrome, rheumatoid arthritis, systemic lupus erythematosus, primary biliary cirrhosis, autoimmune cholangitis, Kimura disease, ankylosing spondylitis, autoimmune thyroiditis, IgA nephropathy, and sarcoidosis.

In some families with the hereditary forms of primary localized cutaneous amyloidoses, an association with multiple endocrine neoplasia (MEN) type 2A, also known as Sipple syndrome, has been established. MEN type 2A is an autosomal dominant disorder including the triad of medullary carcinoma of the thyroid, pheochromocytoma, and hyperparathyroidism. It is essential that any individual in such a kindred who presents with either lichen amyloidosis or macular amyloidosis be assessed for the RET protooncogene; if the mutation is present, a prophylactic thyroidectomy should be strongly considered.

Treatment Options

Medical options

1. Topical corticosteroids

2. Topical calcineurin inhibitors

3. Intralesional corticosteroids

4. Topical dimethyl sulfoxide

5. Systemic retinoids

6. Cyclophosphamide

7. Cyclosporine

Physical modalities

1. Broadband and narrowband UVB phototherapy

2. PUVA phototherapy

Surgical options

1. Dermabrasion

2. CO2 laser therapy

3. Pulse dye laser therapy

Optimal Therapeutic Approach for this Disease

There is no uniformly effective therapy for patients with lichen amyloidosis. Patient education is important in breaking the itch-scratch-itch cycle. In mild cases, topical corticosteroids have been beneficial.

In one study, betamethasone 17-valerate ointment (0.1%) was topically applied twice daily for 12 weeks with improvement. Topical calcineurin inhibitors (0.1% tacrolimus) and intralesional corticosteroids (triamcinolone) have been reported as alternative treatments for mild cases, but there are no current recommendations in the literature for dosing regimens. There are a small number of cases involving the daily use of topical dimethyl sulfoxide (concentration ranging from 10% to 100%) for lichen amyloidosis with significant improvement achieved within 1 week.

Systemic therapies such as retinoids, cyclophosphamide, and cyclosporine have been shown to reduce pruritus and promote clearance of lesions but have more associated side effects. In one study, acitretin (0.7mg/kg per day) was given for 4.5 months with significant improvement noted after 6 weeks of treatment. In another study, nine patients were given cyclophosphamide (50mg per day) for at least 6 months with four patients showing at least 50% improvement after 6 months of treatment. In a case of lichen amyloidosis associated with atopic dermatitis, the patient was treated with cyclosporine (initially dosed at 4mg/kg per day) with clinical remission after 12 months of treatment.

Additionally, there is some evidence in the literature promoting the use of phototherapy for lichen amyloidosis. In one study, patients who were initially treated with either BB UVB or PUVA phototherapy (3 times per week) showed noticeable improvement after 8 weeks of treatment. Another report involving a patient who was treated with NB UVB (3 times per week) showed marked improvement after 5 months of treatment. Dermabrasion, CO2 laser, and pulse dye laser provide alternative options for patients unresponsive to other treatments.

Patient Management

Laboratory testing is not recommended for lichen amyloidosis because there are no specific laboratory abnormalities associated with the condition.

The guidelines for monitoring therapy and follow-up for patients with lichen amyloidosis are unclear. More studies are needed to compare different treatments and maintenance regimens. Patients and family members should be informed about the chronicity of the disease and the potential for trying multiple therapies before resolution of symptoms.

Unusual Clinical Scenarios to Consider in Patient Management

There is an unclear link between lichen amyloidosis and a variety of immune disorders such as systemic sclerosis, CREST syndrome, rheumatoid arthritis, systemic lupus erythematosus, primary biliary cirrhosis, autoimmune cholangitis, Kimura disease, ankylosing spondylitis, autoimmune thyroiditis, IgA nephropathy, and sarcoidosis. An association between lichen amyloidosis and multiple endocrine neoplasia (MEN) type 2A has also been established for families presenting with hereditary forms of primary localized cutaneous amyloidosis. Referral to other specialists should be considered if any of these diseases are suspected.

What is the Evidence?

Behr, F, Levine, N, Bagert, J. “Lichen amyloidosis associated with atopic dermatitis”. Arch Dermatol. vol. 137. 2001. pp. 553-5. (This manuscript reports a case of lichen amyloidosis associated with atopic dermatitis successfully treated with cyclosporine after 12 months of continued treatment.)

Borowicz, J, Gillespie, M, Miller, R. “Cutaneous amyloidosis”. Skinmed. vol. 2. 2011. pp. 96-100. (This manuscript provides a brief and current summary of the different cutaneous amyloidoses including primary systemic amyloidosis and primary cutaneous amyloidosis.)

Breathnach, S. “Amyloid and amyloidosis”. J Am Acad Dermatol. vol. 18. 1988. pp. 1-16. (This manuscript provides a decent overview of primary localized cutaneous amyloidosis but most of the text is dedicated to primary systemic amyloidosis.)

Dahdah, M, Kurban, M, Kibbi, A, Ghosen, S. “Primary localized cutaneous amyloidosis: a sign of immune dysregulation?”. Int J Dermatol. vol. 48. 2009. pp. 419-21. (This article discusses the possible pathogenesis and associated immune disorders for primary cutaneous amyloidosis.)

Jin, A, Por, A, Wee, L, Kai, C, Keok, G. “Comparative study of phototherapy (UVB) vs photochemotherapy (PUVA) vs topical steroids in the treatment of primary cutanenous lichen amyloidosis”. Photodermatol Photoimmunol Photomed. vol. 17. 2001. pp. 42-3. (In this small study, patients with lichen amyloidosis received BB UVB, PUVA or topical corticosteroids. Although the results were not statistically significant, both BB UVB and PUVA were determined to be better therapies in comparison to than topical corticosteroids.)

Ratz, J, Bailin, P. “Cutaneous amyloidosis. A case report of the tumefactive variant and a review of the spectrum of clinical presentations”. J Am Acad Dermatol. vol. 4. 1981. pp. 21-6. (This 1981 article provides a good summary of the differences among the amyloidoses with cutaneous manifestations.)

Steciuk, A, Dompmartin, A, Troussard, X, Verneuil, L, Macro, M, Comoz, F. “Cutaneous amyloidosis and possible association with systemic amyloidosis”. Int J Dermatol. vol. 41. 2002. pp. 127-32. (This article provides an overview of the different types of amyloidosis with cutaneous manifestations.)

Tan, T. “Epidemiology of primary cutaneous amyloidosis in southeast Asia”. Clin Dermatol. vol. 8. 1990. pp. 20-4. (In this study based on patients from Southeast Asia, lichen amyloidosis was more common in women and usually presented between the third to fifth decade of life. There are few articles that provide this degree of epidemiologic data for lichen amyloidosis.)

Tanaka, A, Arita, K, Lai-Cheong, J, Palisson, F, Hide, M, McGrath, J. “New insight into mechanisms of pruritus from molecular studies on familial primary localized cutaneous amyloidosis”. Br J Dermatol. vol. 161. 2009. pp. 1217-24. (This article provides general information about macular and lichen amyloidosis with a focus on the possible mechanism underlying familial primary localized cutaneous amyloidosis.)

Touart, D, Sau, P. “Cutaneous deposit diseases. Part I”. J Am Acad Dermatol. vol. 39. 1998. pp. 149-71. (This manuscript provides a good overview for the classification as well as the clinical findings and diagnostic criteria for the different types of amyloidosis involving cutaneous manifestations.)