Assessment, classification and treatment of calcinosis as a complication of juvenile dermatomyositis: a survey of pediatric rheumatologists by the childhood arthritis and rheumatology research alliance (CARRA).

BACKGROUND: There is no standardized approach to the management of JDM-associated calcinosis and its phenotypes. Current knowledge of treatment outcomes is confined to small series and case reports. We describe physician perspectives toward diagnostic approach, classification and treatment directly targeting calcinosis, independent of overall JDM therapy. METHODS: An electronic survey of 22 questions was organized into sections regarding individual practices of assessment, classification and treatment of calcinosis, including perceived successes of therapies. Invitations to complete the survey voluntarily and anonymously were sent to CARRA physician members and the Pediatric Rheumatology Bulletin Board, an electronic list-serv. Results were analyzed by descriptive statistics and chi-square analyses. RESULTS: Of 139 survey responses, 118 were included in analysis. Of these, 70% were based in the USA and 88 (75%) were CARRA members. Only 17% of responders have seen more than 20 cases of calcinosis, and only 28% perform screening imaging studies on new JDM diagnoses. Increasing systemic immunosuppression is first-line therapy for 67% of respondents. Targeted therapy against calcinosis is most often instituted for symptomatic patients. IVIG and bisphosphonates are most frequently used and considered most successful, but many other agents are used. Experienced physicians are more likely to use bisphosphonates, calcium channel blockers and topical sodium thiosulfate (p< 0.002 or lower). CONCLUSIONS: Coexisting JDM disease activity influences whether calcinosis is considered active disease or targeted directly. Experience treating JDM-related calcinosis is low, as are rates of formal screening for calcinosis. Experienced physicians are more likely to use non-immunosuppressive treatments.

The ROOT HAIR DEFECTIVE3 gene encodes an evolutionarily conserved protein with GTP-binding motifs and is required for regulated cell enlargement in Arabidopsis.

In plants, morphogenesis is largely determined by the orientation and extent of cell enlargement. To define the molecular mechanisms regulating plant cell enlargement, we have conducted a molecular genetic analysis of the ROOT HAIR DEFECTIVE3 (RHD3) gene of Arabidopsis thaliana. Mutations affecting the RHD3 gene were found to alter cell size, but not cell number, in tissues throughout the plant. Genetic and physiological analyses suggest that the RHD3 gene is not required for proper cell type specification, and it is likely to act downstream of the hormones auxin and ethylene. The RHD3 gene was cloned by a T-DNA tagging method and confirmed by the molecular complementation of the rhd3 mutant phenotype and by the analyses of six rhd3 mutant alleles. Consistent with the global effects of the rhd3 mutations, the RHD3 gene is expressed in all major plant organs. The deduced RHD3 product is a novel 89-kD polypeptide with putative GTP-binding motifs near the amino terminus. RHD3-like genes were identified from a protozoan (Entamoeba histolytica), a fungus (Saccharomyces cerevisiae), and another plant species (Oryza sativa), with the sequence identity including the putative GTP-binding motifs. These results imply that the RHD3 protein is a member of a new class of GTP-binding proteins that is widespread in eukaryotes and required for regulated cell enlargement.