title: Soft tissue, joint, and bone manifestations of AL amyloidosis: clinical presentation, molecular features, and survival.
abstract: 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.
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts 02118-2526, USA. prokaeva@bu.edu
authors.forename: Tatiana
authors.initials: T
authors.lastname: Prokaeva
authors.forename: Brian
authors.initials: B
authors.lastname: Spencer
authors.forename: Maurya
authors.initials: M
authors.lastname: Kaut
authors.forename: Al
authors.initials: A
authors.lastname: Ozonoff
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Doros
authors.forename: Lawreen H
authors.initials: LH
authors.lastname: Connors
authors.forename: Martha
authors.initials: M
authors.lastname: Skinner
authors.forename: David C
authors.initials: DC
authors.lastname: Seldin
mesh_terms: 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
chemical_list: D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region