Role of bone scan in diagnosis of calciphylaxis: A review
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Bibliographic record
Abstract
To the Editor: Skin biopsy is the gold standard for diagnosing calciphylaxis, but it can worsen lesions and confer poorer disease prognosis.1Dobry A. Shah R. Kroshinsky D. LB1528 The role of skin biopsy in diagnosis and management of calciphylaxis.J Invest Dermatol. 2018; 138: B10https://doi.org/10.1016/j.jid.2018.06.060Abstract Full Text Full Text PDF PubMed Google Scholar Several reports have considered technetium-99m methyl diphosphonate bone scan as a noninvasive diagnostic alternative to skin biopsy in calciphylaxis, but data regarding its sensitivity and specificity are limited. Our goal was to assess the potential diagnostic utility of bone scan in calciphylaxis via a thorough review of the literature. A comprehensive search of PubMed, Scopus, and Cumulative Index to Nursing and Allied Health Literature was conducted on October 3, 2022. Search terms included “calciphylaxis” combined with “bone scan” or “bone scintigraphy.” No time constraints were placed on this search. Articles were included if they used bone scan in the diagnosis and/or assessment of response to treatment in patients with calciphylaxis. The search yielded 11 case reports and 6 case series, with 31 patients in total. Patient characteristics and details of the diagnostic modalities used in calciphylaxis diagnosis are given in Table I2AlBugami M.M. Wilson J.A. Clarke J.R. Soroka S.D. Oral sodium thiosulfate as maintenance therapy for calcific uremic arteriolopathy: a case series.Am J Nephrol. 2013; 37: 104-109https://doi.org/10.1159/000346410Crossref PubMed Scopus (15) Google Scholar, 3Alniemi D.T. Kanner C. Stowman A.M. et al.Diagnosing calciphylaxis: a series of cases with both imaging and tissue biopsy.J Am Acad Dermatol. 2023; 88: 1117-1119https://doi.org/10.1016/j.jaad.2020.05.111Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 4Araya C.E. Fennell R.S. Neiberger R.E. Dharnidharka V.R. Sodium thiosulfate treatment for calcific uremic arteriolopathy in children and young adults.Clin J Am Soc Nephrol. 2006; 1: 1161-1166https://doi.org/10.2215/CJN.01520506Crossref PubMed Scopus (86) Google Scholar, 5Cosmin A. Soudry G. A case of severe calciphylaxis seen on three-phase bone scan.Clin Nucl Med. 2005; 30: 765-766https://doi.org/10.1097/01.rlu.0000182282.66664.64Crossref PubMed Scopus (9) Google Scholar (additional references are present in the Supplementary Material, available via Mendeley at https://data.mendeley.com/datasets/88fkkbwvkt/1). All but 1 patients had renal disease, and most patients had several other comorbidities. Bone scan supported the diagnosis of calciphylaxis in 29 of 31 patients, with 100% sensitivity and specificity, respectively. Among the 15 cases in which both bone scan and biopsy were performed, 3 patients had an equivocal biopsy with positive bone scan, and there were no cases in which biopsy and bone scan results were contradictory. Additionally, the search yielded 3 larger studies from China, United States, and Canada, which reported the sensitivity of bone scan for diagnosing calciphylaxis as 62.5%, 89%, and 94.4%, respectively (Table II and Supplementary Material). One of the studies had a 97% specificity.Table ICharacteristics of patients with calciphylaxis and bone scanPatient No.Patient age (y)Patient sexBone scan resultsBiopsy supports the diagnosis of calciphylaxisOther imaging modalitySource165MalePositiveYesCTItani et al, 2016266FemalePositive (metastatic pulmonary calciphylaxis)EquivocalMagnetic resonance imaging, CTSantos et al, 2021340FemalePositiveYesRaduka et al, 2018432MalePositiveYesDi et al, 2020526FemalePositive (metastatic pulmonary calciphylaxis)NASPECT-CT, low-dose CTMartineau et al, 2017675FemalePositiveNASPECT-CTNorris et al, 2005752FemalePositiveYesX-rayHan et al, 2007819FemalePositiveYes (lung and breast biopsy)CTShen et al, 2017959FemalePositiveNAX-rayWheeler et al, 20151051FemalePositiveNASoni et al, 20081160FemalePositiveNACosmin et al5Cosmin A. Soudry G. A case of severe calciphylaxis seen on three-phase bone scan.Clin Nucl Med. 2005; 30: 765-766https://doi.org/10.1097/01.rlu.0000182282.66664.64Crossref PubMed Scopus (9) Google Scholar, 20051273FemalePositiveYesX-rayFine et al, 19951359FemalePositiveNAFine et al, 19951446FemalePositiveNAFine et al, 19951556FemalePositiveNAX-rayFine et al, 19951641FemalePositiveNAFine et al, 199517NANAPositiveEquivocalAlniemi et al3Alniemi D.T. Kanner C. Stowman A.M. et al.Diagnosing calciphylaxis: a series of cases with both imaging and tissue biopsy.J Am Acad Dermatol. 2023; 88: 1117-1119https://doi.org/10.1016/j.jaad.2020.05.111Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 202018NANAPositiveEquivocalAlniemi et al3Alniemi D.T. Kanner C. Stowman A.M. et al.Diagnosing calciphylaxis: a series of cases with both imaging and tissue biopsy.J Am Acad Dermatol. 2023; 88: 1117-1119https://doi.org/10.1016/j.jaad.2020.05.111Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 202019NANANegativeNoAlniemi et al3Alniemi D.T. Kanner C. Stowman A.M. et al.Diagnosing calciphylaxis: a series of cases with both imaging and tissue biopsy.J Am Acad Dermatol. 2023; 88: 1117-1119https://doi.org/10.1016/j.jaad.2020.05.111Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 202020NANANegativeNoAlniemi et al3Alniemi D.T. Kanner C. Stowman A.M. et al.Diagnosing calciphylaxis: a series of cases with both imaging and tissue biopsy.J Am Acad Dermatol. 2023; 88: 1117-1119https://doi.org/10.1016/j.jaad.2020.05.111Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 20202121MalePositiveNoX-rayAraya et al4Araya C.E. Fennell R.S. Neiberger R.E. Dharnidharka V.R. Sodium thiosulfate treatment for calcific uremic arteriolopathy in children and young adults.Clin J Am Soc Nephrol. 2006; 1: 1161-1166https://doi.org/10.2215/CJN.01520506Crossref PubMed Scopus (86) Google Scholar, 20062212MalePositiveYesAraya et al4Araya C.E. Fennell R.S. Neiberger R.E. Dharnidharka V.R. Sodium thiosulfate treatment for calcific uremic arteriolopathy in children and young adults.Clin J Am Soc Nephrol. 2006; 1: 1161-1166https://doi.org/10.2215/CJN.01520506Crossref PubMed Scopus (86) Google Scholar, 20062321FemalePositiveNAAraya et al4Araya C.E. Fennell R.S. Neiberger R.E. Dharnidharka V.R. Sodium thiosulfate treatment for calcific uremic arteriolopathy in children and young adults.Clin J Am Soc Nephrol. 2006; 1: 1161-1166https://doi.org/10.2215/CJN.01520506Crossref PubMed Scopus (86) Google Scholar, 20062464FemalePositiveYesMaeda et al, 20072521FemalePositiveYesMaeda et al, 20072645FemalePositiveNAAlBugami et al2AlBugami M.M. Wilson J.A. Clarke J.R. Soroka S.D. Oral sodium thiosulfate as maintenance therapy for calcific uremic arteriolopathy: a case series.Am J Nephrol. 2013; 37: 104-109https://doi.org/10.1159/000346410Crossref PubMed Scopus (15) Google Scholar, 20132765MalePositiveNAAlBugami et al2AlBugami M.M. Wilson J.A. Clarke J.R. Soroka S.D. Oral sodium thiosulfate as maintenance therapy for calcific uremic arteriolopathy: a case series.Am J Nephrol. 2013; 37: 104-109https://doi.org/10.1159/000346410Crossref PubMed Scopus (15) Google Scholar, 20132848FemalePositiveNAAlBugami et al2AlBugami M.M. Wilson J.A. Clarke J.R. Soroka S.D. Oral sodium thiosulfate as maintenance therapy for calcific uremic arteriolopathy: a case series.Am J Nephrol. 2013; 37: 104-109https://doi.org/10.1159/000346410Crossref PubMed Scopus (15) Google Scholar, 20132961MalePositiveNAAlBugami et al2AlBugami M.M. Wilson J.A. Clarke J.R. Soroka S.D. Oral sodium thiosulfate as maintenance therapy for calcific uremic arteriolopathy: a case series.Am J Nephrol. 2013; 37: 104-109https://doi.org/10.1159/000346410Crossref PubMed Scopus (15) Google Scholar, 20133044FemalePositiveNAGripp et al, 20153154FemalePositiveNAGripp et al, 2015CT, Computed tomography; NA, not applicable; SPECT, single-photon emission computed tomography. Open table in a new tab Table IISensitivity results from larger studiesStudy typeEpidemiologicalCase controlCase controlStudy locationChinaUSACanadaTotal patients diagnosed with calciphylaxis481836Bone scan sensitivity62.50% (30/48)89% (16/18)94.40% (34/36)Bone scan specificityNA97% (negative in 30/31 controls)NABiopsy sensitivity64.71% (performed in 34/48 cases)NA100% (performed in 4/36 cases)SourceLiu et al, 2022Paul et al, 2017Fine et al, 2002NA, Not applicable. Open table in a new tab CT, Computed tomography; NA, not applicable; SPECT, single-photon emission computed tomography. NA, Not applicable. The individual cases and larger studies presented herein demonstrate that bone scan is a potentially viable noninvasive modality for diagnosing calciphylaxis. The 100% sensitivity of bone scan demonstrated by the individual cases is promising, but there is a limitation that published cases were likely biased toward patients in whom bone scan detected disease. The larger studies reported broader ranges of bone scan sensitivity for calciphylaxis, likely reflecting variability among readers. This is unsurprising considering that there is no grading system for radiologist interpretation of bone scan in calciphylaxis. Standardization of bone scan interpretation guidelines would be useful in future studies, decreasing interreader variability in scan results and determining sensitivity and specificity. Moreover, clinical correlation and collaboration between the dermatologist and the nuclear medicine physician may still be necessary to reach a diagnosis considering the differential diagnosis of dermatologic conditions associated with delayed radiotracer clearance from soft tissues detected on bone scan. Additionally, bone scan has the potential to detect systemic calciphylaxis in cases in which it may not be clinically evident, to monitor response to treatment, and to potentially screen for calciphylaxis in high-risk groups. Given the morbidity and increasing incidence of calciphylaxis and the need for a diagnostic algorithm, the role of bone scan in disease management needs to be defined better. None disclosed.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it