Pathological Calcification in Juvenile Dermatomyositis (JDM): MicroCT and Synchrotron X-Ray Diffraction Reveal Hydroxyapatite with Varied Microstructures

Abstract

The objective of this study was to begin to relate the microstructure of calcinosis samples to clinical and laboratory characteristics of the juvenile dermatomyositis (JDM) patients. Laboratory x-ray microCT (micro-Computed Tomography) noninvasively mapped microstructure for the first time in JDM calcifications. Synchrotron x-ray diffraction (transmission geometry) identified the mineral phase and crystallite size in the deposits. Samples were obtained from four children who had active JDM longer than 80 months and who were typed for TNFα -308 allele polymorphisms. Uniform mineral (giving the appearance of an extruded solid) was observed in one patient, and irregular blocks of differing sizes filled the samples from two other patients. The sample from the fourth patient appeared to combine features of the other two types. These spatial distributions of mineral were quite different from those in a bone reference sample. The only mineral observed in the JDM samples was hydroxyapatite (HAP), and the diffraction peaks of the JDM samples were slightly narrower than those of a trabecular bone reference sample. Diffraction peak widths of the JDM specimens revealed crystallite sizes (∼ 220–240 Åa) that are comparable to values reported in the literature for bone. Three children were positive for TNFα -308 GA polymorphism. The data suggest several possible origins for blocky vs. uniform structure of the JDM calcifications, including differences in duration of untreated inflammation, in TNFα -308 polymorphism, and in mechanical constraint at the calcification site. Information from additional samples is required to determine the relative role of each of these factors. Taken together, non-invasive microCT and x-ray diffraction characterization on the same samples offer an informative window into the dystrophic mineralization process in JDM.

Keywords:

• Calcinosis
• Hydroxyapatite
• Juvenile Dermatomyositis (JDM)
• MicroCT
• X-Ray Diffraction.

Notes

* Calciphylaxis involves selective calcification brought about by sensitization with a systemic calcifying agent followed after a certain time interval by an eliciting agent. Calcergy is produced without sensitization by administration of a direct calcifier [11].