title: Angiokeratoma: decision-making aid for the diagnosis of Fabry disease.
abstract: Isolated angiokeratomas are common benign cutaneous lesions, generally deemed unworthy of further investigation. In contrast, diffuse angiokeratomas should alert the physician to a possible diagnosis of Fabry disease, a rare X-linked lysosomal storage disorder, characterized by α-galactosidase deficiency. Glycosphingolipids accumulate in cells throughout the body resulting in progressive multi-organ failure. Difficulties are encountered when trying to interpret the significance of angiokeratomas because they may also occur in other lysosomal storage disorders and rarely in an isolated manner in Fabry disease. We present an algorithm for the classification of angiokeratomas which might prove useful for the diagnosis and management of Fabry disease. Assessment of the clinical features and location of the lesions, personal and family history, skin biopsy, dermoscopy and electron microscopy imaging are sequential steps in the diagnostic process. Assessing the deficiency of α-galactosidase enzyme activity is essential to confirm the diagnosis in males, while mutation analysis is always needed in females. Potentially this algorithm can change the current approach to patients when Fabry disease is suspected, thus improving the diagnostic strategy and management of this disorder. It remains to be decided whether the use of an algorithm might reduce the number of genetic consultations. As evidence has shown the efficacy of enzyme replacement therapy in halting progression of the disease before the onset of irreversible organ damage, it is advisable to aim at an early diagnosis in order to achieve timely initiation of effective treatment with benefits for patients and appropriate use of medical resources.
authors.affiliation: Department of Dermatology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Zampetti
authors.forename: C H
authors.initials: CH
authors.lastname: Orteu
authors.forename: D
authors.initials: D
authors.lastname: Antuzzi
authors.forename: M R
authors.initials: MR
authors.lastname: Bongiorno
authors.forename: S
authors.initials: S
authors.lastname: Manco
authors.forename: M
authors.initials: M
authors.lastname: Gnarra
authors.forename: A
authors.initials: A
authors.lastname: Morrone
authors.forename: G
authors.initials: G
authors.lastname: Cardinali
authors.forename: D
authors.initials: D
authors.lastname: Kovacs
authors.forename: N
authors.initials: N
authors.lastname: Aspite
authors.forename: D
authors.initials: D
authors.lastname: Linder
authors.forename: R
authors.initials: R
authors.lastname: Parini
authors.forename: C
authors.initials: C
authors.lastname: Feliciani
mesh_terms: D000465:Algorithms; D000794:Angiokeratoma / Q000209:etiology*; D001706:Biopsy / Q000379:methods; D003661:Decision Support Techniques; D046169:Dermoscopy; D000795:Fabry Disease / Q000150:complications / Q000473:pathology*; D005260:Female; D006801:Humans; D020140:Lysosomal Storage Diseases, Nervous System / Q000150:complications / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D012867:Skin / Q000473:pathology*