title: Increasing amount of amyloid are associated with the severity of clinical features in hereditary gelsolin (AGel) amyloidosis.
abstract: BACKGROUND
  Patients with hereditary gelsolin (AGel) amyloidosis (HGA) present with hanging skin (cutis laxa) and bilateral cranial neuropathy, and require symptomatic plastic surgery. Our clinical observation of tissue fragility prompted us to design a prospective study.
  
  
  METHODS
  Twenty-nine patients with HGA undergoing surgery were interviewed and clinically examined. The height and thickness of skin folds in standard anatomical localizations were measured. The presence and distribution of amyloid in skin samples were analyzed using Congo red staining and immunohistochemistry using antibodies against gelsolin amyloid (AGel) subunit.
  
  
  RESULTS
  The measured skin folds stretched more in patients with HGA (e.g. skin over olecranon, p < 0.001). The skin folds were thinner in patients with HGA (e.g. forehead skin, p < 0.001). The skin and subcutaneous fat were abnormally fragile during surgery. The total amount of AGel amyloid, and its presence in the deep layers of the skin and subcutaneous fat correlated with the measurements of skin folds, age and extent of cranial neuropathy.
  
  
  CONCLUSIONS
  The AGel amyloid in the skin and subcutis, together with morphologic changes in the dermal stroma and skin adnexa contribute to the atrophied and fragile structure of HGA skin. This is the first study to demonstrate the correlation between AGel amyloid accumulation and clinical disease severity.
authors.affiliation: a Department of Plastic and Reconstructive Surgery , Helsinki University Hospital , Helsinki , Finland.
authors.forename: Tiia
authors.initials: T
authors.lastname: Pihlamaa
authors.affiliation: a Department of Plastic and Reconstructive Surgery , Helsinki University Hospital , Helsinki , Finland.
authors.forename: Sinikka
authors.initials: S
authors.lastname: Suominen
authors.affiliation: b Department of Neurology , Clinical Neurosciences, University of Helsinki , Helsinki , Finland , and.
authors.forename: Sari
authors.initials: S
authors.lastname: Kiuru-Enari
authors.affiliation: c Department of Pathology , University of Helsinki and HUSLAB , Helsinki , Finland.
authors.forename: Maarit
authors.initials: M
authors.lastname: Tanskanen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058227:Amyloidogenic Proteins / Q000235:genetics* / Q000378:metabolism; D028226:Amyloidosis, Familial / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000906:Antibodies / Q000737:chemistry; D003224:Congo Red; D062109:Dermatologic Surgical Procedures; D005260:Female; D018260:Gelsolin / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D050151:Subcutaneous Fat / Q000378:metabolism / Q000473:pathology / Q000601:surgery
chemical_list: D058227:Amyloidogenic Proteins; D000906:Antibodies; D018260:Gelsolin; D003224:Congo Red
keywords: Cutis laxa; fragile skin; loose skin; skin fold measurements