Angiokeratoma: Decision Making Methodology for the Diagnosis of Fabry Disease

Background 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 alpha-galactosidase deficiency. Glycosphingolipids accumulate in cells throughout the body resulting in progressive multiorgan failure. Difficulties are encountered when trying to interpret the significance of angiokeratomas since they may also occur in other lysosomal storage disorders and rarely in an isolated manner in Fabry disease. Objectives We present an algorithm for the classification of angiokeratomas which might prove useful for the diagnosis and management of Fabry disease. Methods. Assessment of 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, whilst mutation analysis is always needed in females. Results This algorithm can potentially 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 ascertained whether the use of an algorithm may reduce the number of genetic consultations. Conclusion. Since evidences have shown the efficacy of enzyme replacement therapy in halting the progression of 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.