The correct answer is C: This could be a manifestation of multiple myeloma. Serum, urine, and radiologic investigations should be done after confirmatory skin biopsy.
Discussion: The finding of periorbital purpura, especially in the absence of blunt trauma, strongly suggests the diagnosis of primary amyloidosis. This diagnosis was verified by biopsy and special stain (Congo red), followed by positive immunohistochemical staining for light chains. At the time of presentation, no evidence of myeloma was discovered, but periodic re-evaluations are planned.
Amyloid is a complex protein-polysaccharide substance with starch-like characteristics; amyloidosis occurs when this fibril-rich material deposits in various organs and tissues. Amyloidosis may be divided into primary, secondary, familial, and senile forms, each exhibiting a distinct pattern of deposited protein.
Amyloidosis has systemic ramifications, and may be suspected when a patient presents with such otherwise unaccounted for symptoms as: weakness and fatigue; weight loss; cardiac problems such as congestive heart failure and arrhythmia; enlarged liver, spleen, or tongue; carpal tunnel syndrome, paresthesia, or other manifestations of peripheral neuropathy; signs and symptoms consistent with renal failure; and malabsorption. The most recognizable cutaneous manifestation of amyloidosis is purpura, particularly in a periocular distribution. However, a papular or diffuse infiltration of amyloid may occur, leading to a waxy-appearing skin thickening. Hemorrhagic bullae may also be encountered. A screening laboratory investigation most frequently discloses proteinuria, and less often anemia (5% to 10%), thrombocytosis (5% to 10%), and elevated serum alkaline phosphatase (25%).
Primary amyloidosis, also known as AL amyloidosis, is a clonal plasma cell proliferative disorder in which fibrils of monoclonal immunoglobulin light chains (kappa or lambda) are deposited in tissue. The plasma cell proliferation accompanying AL amyloid leads to the presence of a paraprotein in the serum and/or urine in over 90% of cases.[2,3] AL amyloid may be seen in conjunction with a number of different plasma cell disorders, most prominently monoclonal gammopathy of unknown significance, Waldenström macroglobulinemia, and multiple myeloma.
The exact prevalence of amyloid among known myeloma patients and, conversely, how often myeloma ultimately develops in those already diagnosed with amyloid, remains uncertain. Nonetheless, it appears that this bidirectional association is relatively uncommon. In a large series of myeloma cases seen at the Mayo Clinic, only 1.1% developed AL amyloid; conversely, only 0.4% of AL amyloid cases eventually progressed to overt myeloma in a different series from the same institution.[4,5]
However, the most common cutaneous signs of underlying myeloma (excluding those related to therapy) are: ecchymoses with or without associated amyloidosis, normolipemic plane xanthoma, and leukocytoclastic vasculitis.[6,7] The triad of bone pain, cutaneous amyloid verified by biopsy, and proteinuria strongly suggests concurrent myeloma.
The reason for purpura occurring in association with amyloid deposition remains somewhat uncertain. The traditional explanation is a clotting deficiency due to the binding of factor X to the tissue amyloid deposits. However, this has not always been found upon careful examination.
The treatment of amyloidosis is beyond the scope of this presentation, but may include: corticosteroid administration, immunomodulatory drugs, traditional chemotherapy, or stem cell/bone marrow transplantation. Obviously, should myeloma develop, that disorder must also be addressed appropriately.
1. Eder L, Bitterman H. Amyloid purpura. N Engl J Med. 2007;356:2406.
2. Kyle RA, Gertz MA. Primary systemic amyloidosis: Clinical and laboratory features in 474 cases. Semin Hematol. 1995;32:45.
3. Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc. 1983;58:665.
4. Rajkumar SV, Gertz MA, Kyle RA. Primary systemic amyloidosis with progression to multiple myeloma. Cancer. 1998;82:1501.
5. Madan S, Dispenzieri A, Lacy MQ, et al. Clinical features and treatment response of light chain (AL) amyloidosis diagnosed in patients with previous diagnosis of multiple myeloma. Mayo Clin Proc. 2010;85:232.
6. Kois JM, Sexton FM, Lookingbill DP. Cutaneous manifestations of multiple myeloma. Arch Dermatol. 1991;127:69.
7. Bayer-Garner IB, Smoller BR. The spectrum of cutaneous disease in multiple myeloma. J Am Acad Dermatol. 2003;48:497.
8. Gamba G, Montani N, Anesi E, et al. Clotting alterations in primary systemic amyloidosis. Haematologica. 2000;85:289.