Scott W. Canna, MD

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Assistant Professor of Pediatrics at the Children's Hospital of Philadelphia
Department: Pediatrics
Graduate Group Affiliations

Contact information
University of Pennsylvania School of Medicine
Immune Dysregulation Program, Division of Rheumatology
Children’s Hospital of Philadelphia
Department of Pediatrics
Philadelphia, PA 19104
Office: 267.425.5387
BA (Biology, minor Western Philosophy)
Johns Hopkins University, 2001.
George Washington University School of Medicine, 2006.
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Description of Clinical Expertise

I am a Board Certified Pediatric Rheumatologist with a particular interest in autoinflammatory and immunodysregulatory syndromes, and Macrophage Activation Syndrome/Hemophagocytic Lymphohistiocytosis.

Description of Research Expertise

Inflammation is a core pathogenic mechanism in virtually every disease process. For millenia, we’ve been focused on fighting microbes and viruses as the most important drivers of pathologic inflammation, and sepsis and its accompanying Systemic Inflammatory Response Syndrome (SIRS) remain major problems. But in the 21st century, we recognize that abnormal host responses to inflammatory stimuli can be just as deadly and destructive. In informing our understanding on host susceptibility to immunopathology, understanding how high-penetrance mutations cause inflammatory diseases has been incredibly instructive.

Autoinflammation is defined as systemic or organ-specific inflammation not attributable to infection, malignancy, or antigen-specific autoimmunity.

Hyperinflammation is a state of damaging immune activation that is excessive or disproportionate to what would be expected for a patient’s clinical context.

Our lab is interested in both, but particularly in the ways in which they intersect.

Most “autoinflammatory” patients have chronic organ-specific or systemic inflammation, but only rarely hyperinflammation. The dramatic response of many “autoinflammatory” patients to inhibition of the inflammasome-activated cytokine IL-1 has reinvigorated the quest for anti-inflammatory targets in SIRS and reinforced the therapeutic potential of targeting the inflammasome and related innate immune pathways.

Our group studies the intersections of hyper- and auto-inflammation. In particular, we study two related disorders, Hemophagocytic Lymphohistiocytosis (HLH) and Macrophage Activation Syndrome (MAS), because they typify the concept of hyperinflammation. Whereas the pathogenesis of HLH clearly includes the inflammatory effects of defects in granule-mediated cytotoxicity, the mechanisms at work in MAS are less clear but seem to involve abnormal production and function of the inflammasome-activated cytokine IL-18. We combine clinical insights from rheumatology and innate immunity with basic models of overwhelming systemic inflammation to define new disease subtypes and disease activity biomarkers, to flesh out mechanisms of inflammatory disease, and to test promising therapeutic strategies.

Selected Publications

Tsoukas P, Rapp E, Van Der Kraak L, Weiss E, Dang V, Schneider C, Klein E, Picarsic J, Salcedo R, Stewart CA, Canna SW: Interleukin-18 and cytotoxic impairment are independent and synergistic causes of murine virus-induced hyperinflammation Blood. Online ahead of print (eds.). 136(19): 2162-2174, November 2020 Notes: Featured in: Behrens EM. The Perfect Storm. Blood.

Canna SW, Cron RQ: Highways to hell: mechanism based management of Cytokine Storm Syndromes J Allergy Clin Immunol 146(5): 949-959, November 2020.

Canna S, Marsh R: Pediatric Hemophagocytic Lymphohistiocytosis (HLH). Blood 135(16): 1332-43, April 2020.

Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK, Bassiri H, Behrens EM, Ferris A, Kernan KF, Schulert GS, Seo P, F Son MB, Tremoulet AH, Yeung RSM, Mudano AS, Turner AS, Karp DR, Mehta JJ.: American College of Rheumatology Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19. Arthritis Rheumatol 10(3): 1791-1805, July 2020.

Henderson LA, Canna SW, Schulet GS, Volpi S, Lee PY, Kernan KF, Cariccio R, Mahmud S, Hazen MM, Halyabar O, Hoyt KJ, Han J, Grom AA, Gattorno M, Ravelli A, de Benedetti F, Behrens EM, Cron RQ, Nigrovic PA: On the alert for cytokine storm: Immunopathology in COVID-19. Arthritis & Rheumatology 72(7): 1059-1063, July 2020.

de Jesus AA, Hou Y, Brooks S, Malle L, Biancotto A, Huang Y, Calvo KR, Marrero B, Moir S, Oler AJ, Deng Z, Montealegre GA Sanchez, Ahmed A, Allenspach E, Arabshahi B, Behrens E, Benseler S, Bezrodnik L, Bout-Tabaku S, Brescia AC, Brown D, Burnham JM, Soledad Caldirola M, Carrasco R, Chan AY, Cimaz R, Dancey P, Dare J, DeGuzman M, Dimitriades V, Ferguson I, Ferguson P, Finn L, Gattorno M, Grom AA, Hanson EP, Hashkes PJ, Hedrich CM, Herzog R, Horneff G, Jerath R, Kessler E, Kim H, Kingsbury DJ, Laxer RM, Lee PI, Lee-Kirsch MA, Lewandowski L, Li S, Lilleby V, Mammadova V, Moorthy LN, Nasrullayeva G, O’Neil KM, Onel K, Ozen S, Pan N, Pillet P, Piotto DGP, Punaro MG, Reiff A, Reinhardt A, Rider LG, Rivas-Chacon R, Ronis T, Rösen-Wolff A, Roth J, Mckerran Ruth N, Rygg M, Schmeling H, Schulert G, Scott C, Seminario G, Shulman A, Sivaraman V, Son MB, Stepanovskiy Y, Stringer E, Taber S, Terreri MT, Tifft C, Torgerson T, Tosi L, Van Royen-Kerkhof A, Wampler Muskardin T, Canna SW, Goldbach-Mansky R: Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases. J Clin Invest 130(4): 1669–1682, April 2020.

Saper VE, Chen G, Deutsch GH, Guillerman RP, Birgmeier J, Jagadeesh K, Canna S, Schulert G, Deterding R, Xu J, Leung AN, Bouzoubaa L, Abulaban K, Baszis K, Behrens EM, Birmingham J, Casey A, Cidon M, Cron RQ, De A, De Benedetti F, Ferguson I, Fishman MP, Goodman SI, Graham TB, Grom AA, Haines K, Hazen M, Henderson LA, Ho A, Ibarra M, Inman CJ, Jerath R, Khawaja K, Kingsbury DJ, Klein-Gitelman M, Lai K, Lapidus S, Lin C, Lin J, Liptzin DR, Milojevic D, Mombourquette J, Onel K, Ozen S, Perez M, Phillippi K, Prahalad S, Radhakrishna S, Reinhardt A, Riskalla M, Rosenwasser N, Roth J, Schneider R, Schonenberg-Meinema D, Shenoi S, Smith JA, Sonmez HE, Stoll ML, Towe C, Vargas SO, Vehe RK, Young LR, Yang J, Desai T, Balise R, Lu Y, Tian L, Bejerano G, Davis MM, Khatri P, Mellins ED, Childhood A, Rheumatology Research Alliance Registry I : Emergent high fatality lung disease in systemic juvenile arthritis. Ann Rheum Dis 78(12): 1722–1731, December 2019.

Weiss ES, Girard-Guyonvarc’h C, Holzinger D, de Jesus AA, Tariq Z, Picarsic J, Schiffrin EJ, Foell D, Grom AA, Ammann S, Ehl S, Hoshino T, Goldbach-Mansky R, Gabay C, Canna SW : Dysregulation of Interleukin-18 Diagnostically Distinguishes and Pathogenically Promotes human and murine Macrophage Activation Syndrome. Blood 131(13): 1442-55, March 2018.

Scott W Canna, Adriana A de Jesus, Sushanth Gouni, Stephen R Brooks, Bernadette Marrero, Yin Liu, Michael A DiMattia, Kristien J M Zaal, Gina A Montealegre Sanchez, Hanna Kim, Dawn Chapelle, Nicole Plass, Yan Huang, Alejandro V Villarino, Angelique Biancotto, Thomas A Fleisher, Joseph A Duncan, John J O'Shea, Susanne Benseler, Alexei Grom, Zuoming Deng, Ronald M Laxer, Raphaela Goldbach-Mansky: An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet 46(10): 1140-6, October 2014.

Goldbach-Mansky R, Dailey NJ, Canna SW: Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. The New England Journal of Medicine 355(6): 581-92, August 2006.

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Last updated: 05/29/2023
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