Amyloidosis is the deposition of extracellular amyloid protein throughout the body with impaired functioning of the affected organs. When isolated to the skin, it is termed primary cutaneous amyloidosis (PCA), with numerous subtypes such as nodular, macular, and lichen (papular).1
Lichen amyloidosis (LA) primarily affects individuals of South East Asian and Central and South American descent. The condition is less common in European or North American populations.1,2 Although studies disagree on the sex prevalence of PCA as a whole, LA seems to occur more frequently in men than women.3
The etiology of LA is not well understood, but it is strongly associated with chronic skin irritation and friction.3 Focal epidermal damage can cause necrosis of keratinocytes and transformation into amyloid within the upper dermis.4 Patients who present with LA often have a history of using scrub products or mechanical exfoliation during bathing. An additional risk factor may be dry skin; cases of LA frequently increase during the winter months.3 LA often presents on areas of the body that are easily scratched, and scratching worsens the pigmentation and accelerates amyloid formation.5
LA can be an autosomal-dominant disorder, with many patients presenting with a family history of LA.6 There is a less common link between LA and multiple endocrine neoplasia type 2A, which should be considered in risk calculations.7
LA often presents clinically as pruritic, painless, dome-shaped yellow-brown papules. The pigmentation in these lesions is not uniform and presents as hyperpigmented dots surrounding a depigmented center.3 The papules often are 1- to -3 mm in size and very closely interspersed.2 The lesions tend to appear on extensor surfaces, such as the pretibial region of the lower limbs but also can present on the face, neck, and axilla.
Spontaneous resolution of LA occurs over 6 to 20 months, but hypertrophic lesions can last longer.3 An uncommon variant of LA can present with bullae in either intraepidermal or subepidermal layers.8 On dermoscopy, LA lesions display white central hubs or a whitish scar-like center, with surrounding brown dots.4
When biopsied and examined histologically, the center scarring corresponds to orthohyperkeratosis and acanthosis.4 This central scarring can be structureless and disorganized or well defined by radial streaking and a rim.4,5 An eosinophilic infiltrate can be noted in the papillary dermis as well.2 Amorphous amyloid deposits can be noted in this layer and often are associated closely with melanin granules. Diagnosis often is supplemented by a Congo red stain and observation of the classic apple green birefringence of amyloid deposits under polarized light.3
The differential diagnosis of LA can include prurigo nodularis, colloid milium, and postinflammatory hyperpigmentation.2,4 The bullous presentation of LA can present similarly to bullous pemphigoid.8 Clinical guidelines suggest that a Congo red stain of a punch biopsy should be used to rule out all nonamyloidosis diagnoses because different types of lesions appear similar on physical examination.1 LA will display a unique immunofluorescence to immunoglobulin (Ig)M, C3, and IgA throughout lesions in either the basement membrane or the papillary dermis. This can aid in diagnosis and help differentiate LA from other conditions.1,3
Chuang et al recommend dermoscopy before invasive skin biopsy because the latter often is not necessary to determine therapeutic management once a diagnosis of LA is made. Thus, they suggest using the unique central scarring and surrounding pigmentation pattern to differentiate LA from other types of lesions to minimize the risk for post-biopsy scarring.4
Both macular amyloidosis (MA) and LA will display apple green birefringence with a Congo red stain and can be difficult to differentiate clinically. LA generally presents with more pruritus and will display central scarring and corresponding orthohyperkeratosis not seen in MA.4 Although the central hub of LA is predominantly white, the central hub of MA can be either white, brown, or a combination of those, and papules usually are organized in a rippled pattern.1,4 Patients may present with overlapping features of LA and MA, called biphasic amyloidosis.
LA is limited to the skin, so the goals of treatment are to decrease pruritus and improve the appearance of the lesion. Treatment recommendations are based on clinical experience and case reports; high-quality data from randomized clinical trials are lacking in the literature. Treatment often includes topical steroids, dimethyl sulfoxide, cyclosporine, or tacrolimus, but these treatments have variable and unpredictable results.3 Other methods of treatment include surgery and laser procedures, but determining if a lesion will respond to such treatment often requires individual case consideration.4
Grimmer et al demonstrated improved resolution of LA pruritus and pigmentation with oral acitretin and bath-water psoralen ultraviolet A therapy (PUVA), a combination often used in the treatment of psoriasis.9 This combination therapy also was associated with reduced recurrence of LA.9 Topical tocoretinate, an ester-bound formulation of retinoic acid and tocopherol, has been shown to have results that are similar to those of oral retinoic acid and can help with symptoms of pruritis.10
The patient in this case was prescribed a topical corticosteroid to be administered twice daily. In addition, she wrapped her calves in occlusive dressings to prevent scratching at night. The appearance of the lesions substantially improved with this regimen.
Click to the next page for Case 2.