Soft tissue, joint, and bone manifestations of AL amyloidosis: clinical presentation, molecular features, and survival.
OBJECTIVE
To characterize symptoms and signs of AL amyloidosis that may bring patients to the attention of rheumatologists, evaluate Ig V(L) gene usage in this subgroup of patients, and assess the impact of soft tissue and bone involvement and V(L) gene usage on survival.


METHODS
Clinical features of soft tissue and bone involvement were assessed in 191 patients with AL amyloidosis. V(L) gene sequencing was carried out to determine light-chain family, rate of somatic mutation, and evidence of antigen selection. The association of soft tissue and bone involvement with V(L) gene usage was assessed by logistic regression analysis, and survival time was analyzed using log rank tests and Cox regression models.


RESULTS
Soft tissue and bone involvement occurred in 42.9% of the patients, and 9.4% had dominant soft tissue and bone involvement. The most common manifestations were submandibular gland enlargement, macroglossia, and carpal tunnel syndrome. Dominant soft tissue and bone involvement was significantly associated with V(L)kappaI gene usage. Mutation rate and evidence of antigen selection in the V(L) genes were not found to be confounding factors, providing evidence against a contribution of autoimmunity in this type of AL amyloidosis. Survival time was initially longer in patients with dominant soft tissue and bone involvement than in patients with other dominant organ involvement; however, this difference diminished over time.


CONCLUSIONS
Amyloid infiltration into soft tissue, joints, periarticular structures, and bones can bring patients with AL amyloidosis to the attention of rheumatologists. Recognition of the presenting symptoms is essential for accurate diagnosis and appropriate treatment, since the long-term outlook for untreated patients with dominant soft tissue and bone involvement is not better than that for patients with other dominant features of AL amyloidosis.
Prokaeva
Tatiana
T
Boston University School of Medicine, Boston, Massachusetts 02118-2526, USA. prokaeva@bu.edu
Spencer
Brian
B
Kaut
Maurya
M
Ozonoff
Al
A
Doros
Gheorghe
G
Connors
Lawreen H
LH
Skinner
Martha
M
Seldin
David C
DC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D028226:Amyloidosis, Familial / Q000235:genetics / Q000401:mortality / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology; D002349:Carpal Tunnel Syndrome / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015994:Incidence; D007596:Joints / Q000473:pathology; D008260:Macroglossia / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D012307:Risk Factors; D013363:Submandibular Gland / Q000473:pathology; D013364:Submandibular Gland Diseases / Q000235:genetics / Q000401:mortality / Q000473:pathology; D014059:Tongue / Q000473:pathology
D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region