title: Cutaneous Manifestations of Familial Transthyretin Amyloid Polyneuropathy.
abstract: Familial amyloid polyneuropathy (FAP) is a rare inherited autosomal dominant form of systemic amyloidosis, which classically presents with severe motor, sensory, and autonomic dysfunction. Cutaneous involvement does not become clinically apparent until late stage symptomatic disease and is rarely reported in modern literature. Here, the authors review the clinical and histologic cutaneous findings of FAP previously described in the literature and report on 3 patients with unique genetic mutations (Thr60Ala and Gly6Ser; Trp41Leu; Glu89Gln) for which cutaneous involvement has not previously been described. Histologically, our patients showed variable amyloid deposition in the subcutaneous adipose tissue, papillary dermis, and dermal blood vessel walls. A review of the literature suggests cutaneous transthyretin deposition is an underrecognized feature of FAP that occurs early on in disease, even before neural involvement and related symptoms as seen in one of our patients. As such, a cutaneous punch biopsy can serve as quick, easy, and relatively noninvasive diagnostic tool in suspected cases.
authors.affiliation: *Medical Student, Icahn School of Medicine at Mount Sinai, New York, NY; †Undergraduate Student, Carnegie Mellon University, Pittsburgh, PA; ‡Professor and Director, Department of Rheumatology, Icahn School of Medicine at Mount Sinai, New York, NY; and §Professor, Division of Dermatopathology, Departments of Dermatology and Pathology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Julien
authors.initials: J
authors.lastname: Lanoue
authors.forename: Nancy
authors.initials: N
authors.lastname: Wei
authors.forename: Peter
authors.initials: P
authors.lastname: Gorevic
authors.forename: Robert G
authors.initials: RG
authors.lastname: Phelps
mesh_terms: D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000473:pathology*; D001706:Biopsy; D004252:DNA Mutational Analysis; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011228:Prealbumin / Q000032:analysis / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D012867:Skin / Q000737:chemistry / Q000473:pathology*
chemical_list: D005819:Genetic Markers; D011228:Prealbumin