Current and Investigational Therapeutics for Fabry Disease.

Fabry disease (FD) is an X-linked lysosomal storage disease caused by a deficiency in the lysosomal enzyme α-galactosidase (α-GAL). This in turn leads to the buildup of globotriaosylceramide, resulting classically in progressive kidney disease, peripheral neuropathy, early-onset cerebrovascular disease, gastrointestinal symptoms, hypertrophic cardiomyopathy, arrhythmias, corneal whorls, and angiokeratomas. The diagnosis of FD relies on identification of a low α-GAL enzyme activity, identification of a genetic mutation, or histologic evidence of disease. With more than 900 mutations identified, there is phenotypic variability deriving from both mutational effects as well as the effect of skewed X-inactivation in females. Treatment of this disease has relied on intravenous replacement of the deficient enzyme with agalsidase α or agalsidase ß. However, treatment options for some patients with FD have recently expanded, with the approval of migalastat, an oral molecular chaperone. In addition to chaperone-based therapies, there are several additional therapies under development that could substantially reshape treatment options for patients with FD. Four approaches to gene therapy, through both ex vivo and in vivo methods, are under development. Another approach is through the administration of α-GAL mRNA to help stimulate production of α-GAL, which is another unique form of therapy. Finally, substrate reduction therapies act as inhibitors of glucosylceramide synthase, thus inhibiting the production of GB-3, promise another oral option to treat FD. This article will review the literature around current therapies as well as these newer therapeutics agents in the pipeline for FD.

Remote Patient Management in Home Dialysis: Planning Considerations for the Future.

Remote patient management (RPM) has the potential to improve patient outcomes in home dialysis patients. Achieving this requires an operational plan that addresses data collection, RPM adoption, and plans for therapeutic interventions on abnormal results. The objective of this chapter is to discuss the key factors to be considered when setting up a RPM program, and in particular how a RPM program can be beneficial in the management of home dialysis patients. RPM is already being utilized in many other disease states to a greater extent than the home dialysis population (heart failure, COPD, diabetes) to improve clinical outcomes. The key components needed to set up a RPM program will be discussed in this chapter. Furthermore, literature regarding the potential benefits to the home dialysis population will be reviewed along with barriers to the adoption of technology.

Scleredema diabeticorum.

We present a case of scleredema with a leonine facies in a 56-year-old man with a history of poorly controlled diabetes mellitus. The patient initially presented with erythematous, edematous papules and plaques on the face, neck, and upper back.

Proliferating trichilemmal cyst with focal calcification.

A 64-year-old man presented with a superficial, well-demarcated, skin-colored tumor on the left posterior scalp that measured 4 x 5 x 6 cm. The tumor was nearly hairless, rubbery, non-tender, and mobile over the underlying subcutaneous tissues. The lesion had grown slowly since arising approximately 30 years ago. Treatment options were declined in the past. However, with relatively more rapid growth over the past five years, the nodule began to cause intermittent pain and interfere with the patient's ability to lie on his back. The patient denied a history of similar lesions in himself or his family. A biopsy specimen showed a ruptured proliferating trichilemmal cyst with focal calcification. Complete excision is recommended for all benign proliferating variants owing to their potential for locally aggressive behavior and malignant transformation.