Avis Chan1,2, Hannah Karpel1,2,3, Ellen Spartz1,2,4, Theresa Willett1,2, Bahare Farhadian1,2, Michael Jeng5, Margo Thienemann2,6, Jennifer Frankovich7,8. 1. Division of Allergy, Immunology, & Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA. 2. Stanford PANS Clinic and Research Program at Lucile Packard Children's Hospital, Palo Alto, CA, USA. 3. New York University School of Medicine, New York City, NY, USA. 4. University of Minnesota Medical School, Minneapolis, MN, USA. 5. Division of Hematology & Oncology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA. 6. Division of Child & Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA. 7. Division of Allergy, Immunology, & Rheumatology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA. jfranko@stanford.edu. 8. Stanford PANS Clinic and Research Program at Lucile Packard Children's Hospital, Palo Alto, CA, USA. jfranko@stanford.edu.
Abstract
BACKGROUND: Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt debilitating psychiatric illness. We anecdotally observed hypoferritinemia and iron deficiency in a subset of patients with PANS, prompting this study. METHODS: In this IRB-approved prospective cohort study, we included patients seen at the Stanford PANS Clinic who met study criteria. The prevalence of hypoferritinemia (using cut-offs of 7 ng/ml in children ≤ 15 years and 18 ng/ml in adolescents > 15 years) and iron deficiency was estimated. Differences in patients with and without hypoferritinemia during PANS flare were explored. RESULTS: Seventy-nine subjects (mean age of PANS onset of 8.7 years) met study criteria. Hypoferritinemia was observed in 27% and three quarters occurred during a PANS flare. Compared to patients without hypoferritinemia during PANS flare, patients with hypoferritinemia had worse global impairment, more comorbid inflammatory diseases, and exhibited a chronic course of PANS illness. The estimated prevalence of iron deficiency was 3-8% in the PANS cohort, 1.4-2.0-fold higher than in the age- and sex-matched U.S. POPULATION: More stringent ferritin level cut-offs than the comparison CDC dataset were used. CONCLUSION: Hypoferritinemia and iron deficiency appear to be more common in PANS patients. More research is needed to confirm and understand this association. IMPACT: Our study suggests hypoferritinemia and iron deficiency are more common in patients with pediatric acute-onset neuropsychiatric syndrome (PANS) than in the sex- and age-matched US population. Hypoferritinemia was commonly observed during a disease flare but not associated with dietary or demographic factors. In patients with PANS and iron deficiency, clinicians should consider possibility of inflammation as the cause especially if iron deficiency cannot be explained by diet and blood loss. Future research should include larger cohorts to corroborate our study findings and consider examining the iron dynamics on MRI brain imaging in order to better understand the pathophysiology of PANS.
BACKGROUND: Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt debilitating psychiatric illness. We anecdotally observed hypoferritinemia and iron deficiency in a subset of patients with PANS, prompting this study. METHODS: In this IRB-approved prospective cohort study, we included patients seen at the Stanford PANS Clinic who met study criteria. The prevalence of hypoferritinemia (using cut-offs of 7 ng/ml in children ≤ 15 years and 18 ng/ml in adolescents > 15 years) and iron deficiency was estimated. Differences in patients with and without hypoferritinemia during PANS flare were explored. RESULTS: Seventy-nine subjects (mean age of PANS onset of 8.7 years) met study criteria. Hypoferritinemia was observed in 27% and three quarters occurred during a PANS flare. Compared to patients without hypoferritinemia during PANS flare, patients with hypoferritinemia had worse global impairment, more comorbid inflammatory diseases, and exhibited a chronic course of PANS illness. The estimated prevalence of iron deficiency was 3-8% in the PANS cohort, 1.4-2.0-fold higher than in the age- and sex-matched U.S. POPULATION: More stringent ferritin level cut-offs than the comparison CDC dataset were used. CONCLUSION: Hypoferritinemia and iron deficiency appear to be more common in PANS patients. More research is needed to confirm and understand this association. IMPACT: Our study suggests hypoferritinemia and iron deficiency are more common in patients with pediatric acute-onset neuropsychiatric syndrome (PANS) than in the sex- and age-matched US population. Hypoferritinemia was commonly observed during a disease flare but not associated with dietary or demographic factors. In patients with PANS and iron deficiency, clinicians should consider possibility of inflammation as the cause especially if iron deficiency cannot be explained by diet and blood loss. Future research should include larger cohorts to corroborate our study findings and consider examining the iron dynamics on MRI brain imaging in order to better understand the pathophysiology of PANS.
Authors: Kiki Chang; Jennifer Frankovich; Michael Cooperstock; Madeleine W Cunningham; M Elizabeth Latimer; Tanya K Murphy; Mark Pasternack; Margo Thienemann; Kyle Williams; Jolan Walter; Susan E Swedo Journal: J Child Adolesc Psychopharmacol Date: 2014-10-17 Impact factor: 2.576
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Authors: Jimmy Zheng; Jennifer Frankovich; Emily S McKenna; Nathan C Rowe; Sarah J MacEachern; Nathan N Ng; Lydia T Tam; Peter K Moon; Jaynelle Gao; Margo Thienemann; Nils D Forkert; Kristen W Yeom Journal: JAMA Netw Open Date: 2020-05-01