Answer: B

Macular amyloidosis (MA) commonly occurs in populations of the Middle East, Asia, and Central and South America. Women, especially those aged 20 to 50 years, are more likely than men to present with MA.11

On physical examination, MA usually presents as symmetric pruritic and hyperpigmented patches or thin plaques of gray-brown macules in a rippled pattern.12 Unusual variants of MA can present as periocular hyperpigmentation, nevoid hyperpigmentation along Blaschko lines, and diffuse MA characterized by an incontinentia pigmenti-like pattern.13 MA lesions usually occur in the interscapular area, shins, and forearms. Lesions also have been reported to appear on the chest, face, neck, thighs, and axilla.11


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Histologically, a hematoxylin and eosin-stained skin biopsy shows eosinophilic faceted amyloid deposits within the papillary dermis, along with frequent foci of pigmentary incontinence. Other findings include basal vacuolar changes, epidermal apoptotic bodies, and the presence of melanophages in dermal deposits.12 Congo red stain shows apple green birefringence under polarized light, revealing amyloid deposits. Direct immunofluorescence shows IgG, IgM, and C3 in the amyloid deposits.14 Electron microscopy reveals the amyloid deposits as linear, non-branching filaments with hollow cores and diameters of 6- to 10-mm.

A histopathologic study of MA patients revealed that 9% have parakeratosis, 27% have acanthosis, and 64% have basal cell vacuolization in the epidermis. Dermal examination of these patients revealed that 82% have melanin incontinence and 91% have perivascular inflammatory infiltration.15

MA patients have a varied clinical presentation, so the condition may be confused with other causes of hyperpigmentation. Ahmed et al reported instances of patients diagnosed with MA presenting with asymptomatic homogenous patches on the legs that gradually grew darker and spread to the arms.16 Skin biopsy and immunohistochemical stains indicated the presence of amyloid deposits consistent with MA. Thus, appearance on initial examination cannot be used as a means of diagnosis in all cases.

Prolonged friction seems to be the most common factor inciting MA, with UV radiation, atopy, and genetics also playing a role in its pathogenesis.13,17 The amyloid deposits in MA are keratinocyte-derived, but the mechanism behind apoptosis of keratinocytes is unclear. Two theories have been proposed to describe generation of the amyloid deposits in MA: fibrillar body and secretory.17 The fibrillar body theory states that necrotic epidermal cells are transformed into amyloid by fibroblasts and macrophages through a process called filamentous degeneration, whereas the secretory theory states that disrupted basal cells secrete amyloid, which then assemble at the dermal-epidermal junction.17

MA is associated with multiple autoimmune diseases including systemic lupus erythematosus, sarcoidosis, IgA nephropathy, ankylosing spondylitis, rheumatoid arthritis, and autoimmune thyroiditis. Genetically linked MA (10% frequency)17 is associated with the autosomal dominant disorder multiple endocrine neoplasia type 2A. Progeny from a family with a history of MA should be tested for the presence of the RET proto-oncogene, and prophylactic thyroidectomy should be considered to prevent malignancy.17

Clinical and histologic analyses are used to diagnose MA. The differential diagnosis includes postinflammatory hyperpigmentation, erythema dischromicum, tinea versicolor, phototoxic dermatitis, notalgia paresthetica, and poikiloderma of Civatte.13 Skin biopsy is effective in differentiating MA from these conditions.

MA results in a characteristic rippling of the skin but is more subtle in appearance than LA. MA also tends to present with less pruritus than LA. The quantity of amyloid deposits is not a distinguishing feature between these 2 conditions. Biphasic amyloidosis, which contains both MA and LA lesions, is present in about 18% to 25% of PCA patients.18

Treatment of MA is aimed at relieving itching, eliminating amyloid deposits, and improving the appearance of the lesions. No uniformly effective treatment is available.11 Some common treatments include sedating antihistamines, topical/intralesional steroids, dimethyl sulfoxide, and phototherapy. Conservative therapies, such as topical corticosteroids, should be attempted before more invasive therapies are considered. Surgical therapy, including excision, laser vaporization, and dermabrasion of lesions, also may be used. Systemic treatments, such as cyclosporine and cyclophosphamide, have some level of effectiveness in reducing pruritus and clearing lesions, but these agents carry a higher risk of systemic adverse effects.13

There are no high-quality randomized clinical trials of MA; thus, management recommendations and timeline of care are based on an individual’s response to treatment. No systemic abnormalities are associated with MA, so laboratory testing is not needed.11  

The patient in this case was encouraged to avoid scratching the affected area. A topical corticosteroid applied twice daily resulted in an improved appearance.

Table. Characteristics of Lichen Amyloidosis and Macular Amyloidosis

Sami Younes, BS, Joanne Jacob, BS, and Emily Burns, BA, are medical students at Baylor College of Medicine, in Houston, Texas, and Christopher Rizk, MD, is a certified dermatologist at Elite Dermatology in Houston.

References

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  17. Nahidi Y, Meibodi NT, Meshkat Z, Nazeri N. Macular amyloidosis and Epstein-Barr virus. Dermatol Res Pract. 2016;2016:6089102.
  18. Vijaya B, Dalal BS, Sunila, Manjunath GV. Primary cutaneous amyloidosis: a clinico-pathological study with emphasis on polarized microscopy. Indian J Pathol Microbiol. 2012;55(2):170-174.