Cutaneous light chain amyloidosis with multiple myeloma

Abstract

Objective/Background: Cutaneous immunoglobulin (Ig) amyloid light-chain (AL) amyloidosis associated with overt multiple myeloma (MM) is rare and optimal treatment is not well defined. The recently developed highly efficacious MM therapy has brought on a new set of challenges to this field for consideration. The goal of this paper is to describe the characteristics of cutaneous manifestations of systemic AL amyloidosis associated with MM according to age, sex, race, Ig type, plasma cell percentage, and cytogenetic and fluorescent in situ hybridization studies along with their outcomes. Methods: An electronic search of the PubMed database was performed to obtain key literature in AL amyloidosis and MM, using the following search terms: multiple myeloma, immunoglobulin light chain amyloidosis, and cutaneous amyloidosis. The search results were narrowed by selecting studies in English. Results were confined to the following articles types: case reports, case series, and systematic reviews. Results: We identified 32 cases from the PubMed database search and examined their potential relevance. We found the following: (a) higher prevalence in women (two-thirds) and white population; (b) IgG and IgA were equally distributed with lambda (λ) light chain occurring in 53–66% of cases; (c) majority of cases (56%) presented as hemorrhagic bullous lesions, followed by purpura/ecchymosis in 25% of cases; and (d) majority (64%) died within 6 months since diagnosis. Conclusions: We reviewed the constellation of the cutaneous manifestations of AL amyloidosis with concurrent MM. We found a female predominance, and more than half presented as hemorrhagic bullous lesions. There is a preponderance of λ light chains over kappa (κ) light chains, both as a free light chain (15% vs. 4%) and as an intact Ig (38% vs. 24%; absolute number of 14 vs. 7 patients, respectively). In the subgroup of patients with bullous skin lesions, λ light chain was present in eight cases and κ light chain in seven cases. All κ light chain subtypes presented with bullous lesions and no other cutaneous types of lesions. They carried very poor prognosis with majority of cases surviving only 6 months, much worse than overall patients with AL amyloidosis without myeloma or myeloma without amyloidosis.

Localized immunoglobulin light chain amyloidosis: Novel insights including prognostic factors for local progression

“…Patients with lung locAL are usually older, 12 and skin and ST locAL are more common in women. 16 A cAD and a MC and/or abFLCR are particularly common in these patients. In general, prognosis of locAL is good, however, a worse survival is observed in patients with lung locAL.…”

“…In another patient, amyloid deposits were found in nasopharynx (respiratory involvement) and in a lateral cervical lymph node (lymphatic tissue involvement). 1 141 146 (86) / 1 (16) 2 (29) 100 / 74…”

Nodular amyloidosis of the lips as a presenting feature of systemic amyloidosis associated with multiple myeloma

“…Organs most commonly affected include kidney, heart, liver, nerves, and gastrointestinal tract, but any organ or tissue can be affected, including the skin. The condition, alone or in conjunction with underlying plasma cell dyscrasias, including MM, is commonly diagnosed when patients are in their 60s 5 …”

“…Skin findings secondary to myeloma-associated AL amyloidosis are variable in presentation, with bullae (56%) being the most commonly reported lesion, followed by purpura/ecchymoses (25%) and nodules/papules (16%); a few cases of scleroderma, macroglossia, alopecia, nail dystrophy, and condyloma have also been reported 5 . Nodular and papular lesions, seen in our patient, are caused by direct dermal infiltration of amyloid; they classically appear yellow, shiny, smooth, waxy, and often hemorrhagic and are found on flexor surfaces, face, neck, or buccal mucosa 4 .…”

“…Although there has been progress made in the treatment of patients with MM, management approaches for AL amyloidosis associated with MM are generally not well defined. Prognosis for patients of myeloma-associated AL amyloidosis is poor, with reported median survival as short as 4 months to 5 years 5 . Prognosis of patients with skin involvement is even worse, potentially reflecting extensive systemic involvement 5 …”