Nodular Localized Cutaneous Amyloidosis

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Nodular Localized Cutaneous Amyloidosis

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Localized cutaneous amyloidosis (LCA) refers to a condition characterized by the deposition of amyloid or amyloid-like proteins in the dermis. Localized cutaneous amyloidosis encompasses several conditions characterized by amyloid deposition, including macular amyloidosis and lichen amyloidosis. Nodular localized cutaneous amyloidosis (NLCA) is the rarest type of localized cutaneous amyloidosis and is distinct from the other two.

Gottron first reported nodular localized cutaneous amyloidosis in 1950. Since then, approximately 60 patients have been reported in the North American, European, and Asian literature. This entity also is termed amyloidosis cutis nodularis atrophicans or tumefactive amyloid. By definition, nodular localized cutaneous amyloidosis describes a primary disease of the skin, although lesions occasionally appear similar to the skin manifestations of systemic amyloidosis.

As a term, “amyloid” was used historically to define proteins that shared similar microscopic characteristics and affinity for certain stains. Research has revealed that “amyloid” proteins are heterogeneous. The various diseases characterized by deposition of “amyloid” proteins are similarly heterogeneous but have in common the deposits of fibrillar proteins characterized as “amyloid” in the dermis. In nodular localized cutaneous amyloidosis, the amyloid is believed to derive from local plasma cells, in contrast to lichenoid or macular amyloidosis, which have keratinocyte-derived amyloid.

In nodular localized cutaneous amyloidosis, plasma cells produce immunoglobulin light chains that are precursors to the amyloid fibril protein(s) termed amyloid L. Reports differ regarding the clonality of this population of plasma cells. In some instances, plasma cells have been monoclonal, suggesting that nodular localized cutaneous amyloidosis is a neoplastic disorder.^[1]On the other hand, cutaneous plasma cell clonality has been observed in the absence of a monoclonal plasma cell population in the bone marrow.^{[1, 2]}In other cases, plasma cells demonstrated polyclonality, which usually is a feature of a more reactive process.

United States

Incidence and prevalence of localized cutaneous amyloidosis in the United States are not known; however, the scarcity of reported patients with localized cutaneous amyloidosis indicates that the condition may be rare.

International

Despite a paucity of reported patients, localized cutaneous amyloidosis, although rare, is represented in the American, Asian, and European literature.

Nodular localized cutaneous amyloidosis typically is benign and limited to the skin. However, lesions are more often persistent. Reported rates of progression to systemic disease are derived from case series with small numbers of patients; these rates vary from 7% to nearly 50%.^{[3, 4]}Progression to fatal systemic amyloidosis has been reported, although this is a rare occurrence.^[5]As many as 25% of reported cases have been associated with Sjögren syndrome. Some speculate that these 2 disorders have may have a shared pathogenesis.^{[6, 7, 8, 9, 10]}

Case reports have also correlated nodular localized cutaneous amyloidosis with other autoimmune disorders such as CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia syndrome), primary biliary cirrhosis, rheumatoid arthritis, and systemic lupus erythematosus.^[11]Other rare associations described in the case report literature include alcoholic cirrhosis^[12]and severe atopic dermatitis.^[13]

Epidemiologic data can be difficult to establish when so few patients are reported. No specific racial, ethnic, or geographic group appears more prone than another to developing nodular localized cutaneous amyloidosis.

Of the first 13 patients described in the Japanese literature, 12 were women; however, this disproportionate ratio has not been seen consistently. In a subsequent series of 12 patients, the male-to-female ratio was equal. Other series have reported equal or nearly equal male-to-female ratios.

Patients reportedly range in age from 33-86 years. The mean age of onset has been reported to be 55 years. Although numbers are small, reports indicate that nodular localized cutaneous amyloidosis is likely to occur during adulthood.

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Nicholas V Nguyen, MD Director of Pediatric Dermatology, Akron Children’s Hospital

Nicholas V Nguyen, MD is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, Society for Pediatric Dermatology