Cytokine Storm Syndrome

Members of the UAB Division of Pediatric Rheumatology excel in research of cytokine storm syndromes (CSS) in the pediatric population. Randy Cron, M.D., Ph.D., and co-editor, Dr. Ed Behrens (University of Pennsylvania), recently published the first ever textbook devoted to Cytokine Storm Syndrome (CSS) just months prior to the SARS-CoV-2 worldwide pandemic. Work in the division has focused on the genetics and therapeutics for children and adults with COVID-19 pneumonia and the novel post-infectious entity of multi-systemic inflammatory syndrome in children (MIS-C). Dr. Cron, along with UAB adult rheumatologist, Dr. Winn Chatham, conducted a randomized, double-blinded, placebo controlled trial of the interleukin-1 (IL-1) receptor antagonist, anakinra, in treating adult COVID-19 patients at UAB. As part of this trial, genetic analysis, in collaboration with Dr. Devin Absher (HudsonAlpha Institute for Biotechnology), of trial enrollees revealed mutations in known CSS genes, as well as a novel genetic mutation identified in 40% of those sequenced. Ongoing research efforts are devoted to identifying the molecular mechanism responsible for this gene mutation contributing to COVID-19 CSS. The division, including second-year fellow Dr. Daniel Reiff, has published on clinical (diagnostic and therapeutic) aspects of pediatric SARS-CoV-2 and MIS-C, as the world is learning as we go.

Temporomandibular Joint Arthritis

Dr. Randy Cron and Matthew Stoll, M.D., continue their long-standing clinical research in the arena of temporomandibular joint (TMJ) arthritis in children with juvenile idiopathic arthritis (JIA) from the perspectives of demographics, risk factors and radiologic diagnosis, as well as local and systemic anti-inflammatory therapeutic approaches. This work is in partnership with Children’s of Alabama Radiology Department and UAB Departments of Oral and Maxillofacial Surgery, and Orthodontics. Recent publications include TMJ condyle-fossa relationships in children with JIA, as well as orthodontic and surgical approaches to treatment of dentofacial deformities in children with JIA and TMJ arthritis.

Juvenile Idiopathic Arthritis

Several members of the UAB Division of Pediatric Rheumatology are adept at studying large data sets to explore treatment and outcomes of children with various rheumatic diseases, particularly JIA and pediatric systemic lupus erythematosus (SLE). Based on their publication history and expertise in the field, several members in the division have been recently invited to publish review articles on the topic of treatment for JIA in several academic journals, including Faculty Reviews (Drs. John Bridges & Randy Cron), Paediatric Drugs (Drs. John Bridges & Matthew Stoll), Lancet Rheumatology (Drs. Randy Cron, Daniel Reiff, and Matthew Stoll), and Current Opinions in Pharmacology (Drs. Randy Cron and Melissa Mannion).

Tim Beukelman, M.D., MSCE, serves as the scientific director of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. The CARRA Registry, a multicenter prospective observational registry for children with arthritis, became operational in 2015 and currently has more than 70 clinical sites enrolling patients. The primary aim of the registry is to evaluate the safety of therapeutic agents used to treat pediatric rheumatic diseases, and the secondary aim is to evaluate clinical outcomes and their determinants, including treatment. Dr. Beukelman has worked closely with other members of the registry executive committee to bring the registry to fruition and encourage the performance of Phase IV safety surveillance studies that satisfy FDA requirements. Current work is focused on expanding the capabilities of the registry to allow investigator-initiated observational and interventional sub-studies to be layered on the existing registry infrastructure. In 2021, Dr. Beukelman published no less than eight peer-reviewed manuscripts using the CARRA Registry database.

Dr. Beukelman is also the principal investigator of a pharmacoepidemiology project as part of the Agency for Healthcare Research and Quality (AHRQ) funded UAB Center for Education and Research on Therapeutics (CERTs). This project aims to use administrative claims data, such as Medicaid billing data, to further evaluate the safety of medications used to treat JIA with emphasis on serious infection and malignancy risk. These studies build upon this team’s prior successful publications and will allow for longer-term follow-up of patients, as well as the examination of newer biologic agents. Recently, Dr. Beukelman, in collaboration with Dr. Jeffrey Curtis, UAB Division of Clinical Immunology and Rheumatology, was awarded a grant from PCORI to compare the effectiveness and safety of novel biologic therapies.

Melissa Mannion, M.D., MSPH, conducts research using epidemiologic analysis related to juvenile idiopathic arthritis (JIA) for which she recently received three years of grant funding as an Investigator Award for the Rheumatology Research Foundation. Specifically, she is interested in the use of medications to treat juvenile idiopathic arthritis (JIA), the outcomes of JIA in adulthood and the comparative effectiveness of treatment modalities. Her specific research topics include the risk of malignancy associated with biologic treatments and the transition of pediatric arthritis patients into adult rheumatologic care. Dr. Mannion serves as the UAB site leader for the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) to address related research questions by exploring this large database. She also serves as the site principal investigator for the CARRA Registry.

Spondyloarthritis & The Microbiome

Matthew Stoll, M.D., Ph.D., MSCS, explores the role of the microbiota in children and adults with spondyloarthritis. He has identified various bacterial species in patients with spondyloarthritis that are protective for disease and others which contribute to the pathology. Recently, Dr. Stoll has evaluated the metabolic diversity and functions in the gut microbiomes and shown diminished function in arthritis patients versus controls, as well as alterations in tryptophan metabolism that may alter immune function to allow for autoimmunity. Dr. Stoll also collaborates extensively with Dr. Pamela Weiss (University of Pennsylvania) via various grants to explore pediatric imaging, disease activity measures and treatment of childhood pediatric spondyloarthritis, resulting in three peer-reviewed publications on spondyloarthritis in 2021 alone.

Systemic Lupus Erythematosus

Emily Smitherman, M.D., MSCTR, studies patient-centered outcomes with an emphasis on developing and implementing healthcare system interventions to drive improvement in outcomes. To these ends, Dr. Smitherman was awarded grants in 2019 from the Lupus Foundation of America and two from the Childhood Arthritis and Rheumatology Research Alliance. Recently, Dr. Smitherman was awarded a highly competitive three-year career development grant from the Rheumatology Research Foundation to explore pediatric lupus outcomes, and she has been invited to speak on this topic in several academic settings. Dr. Smitherman also employs the pediatric rheumatology national quality improvement network, PR-COIN, to address related research questions by exploring this large database.

ACR Open Rheumatol. 2021 Aug 25;10.1002/acr2.11331. Performance of Cytokine Storm Syndrome Scoring Systems in Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children. Daniel D Reiff, Randy Q Cron.

Arthritis Care Res (Hoboken). 2021 Jun;73(6):841-848. Variability in Interpretation of Magnetic Resonance Imaging of the Pediatric Sacroiliac Joint. Pamela F Weiss, Timothy G Brandon, John Bohnsack, Merav Heshin-Bekenstein, Michael L Francavilla, Jacob L Jaremko , Lester Liao, Anne McHugh, Edward J Oberle, Dax Rumsey, Hemalatha Srinivasalu, Matthew L Stoll, Nancy A Chauvin.

Arthritis Care Res (Hoboken). 2021 Jun 13;10.1002/acr.24727. Effectiveness and Safety of High-Dose Biologics in Juvenile Idiopathic Arthritis in the Childhood Arthritis and Rheumatology Research Alliance. Colleen K Correll, Peter Shrader, Anne Dennos, Thomas Phillips , Natalie J Shiff, Ruud H J Verstegen, Timothy Beukelman, CARRA Registry Investigators.

Arthritis Care Res (Hoboken). 2021 Aug 7;10.1002/acr.24763 Development and validation of the juvenile spondyloarthritis disease flare (JSpAflare) measure: Ascertaining flare in patients with inactive disease. P F Weiss, T G Brandon, M E Ryan, E B Treemarcki, S Armendariz, T B Wright, C Godiwala , Matthew L Stoll, R Xiao, D Lovell.

J Pediatr. 2021 Aug;235:196-202. Thrombotic Microangiopathy Associated with Macrophage Activation Syndrome: A Multinational Study of 23 Patients. Francesca Minoia, Jessica Tibaldi, Valentina Muratore, Romina Gallizzi, Claudia Bracaglia, Alessia Arduini, Elif Comak, Olga Vougiouka, Ralf Trauzeddel, Giovanni Filocamo, Antonio Mastrangelo, Concetta Micalizzi, Ozgur Kasapcopur, Erbil Unsal, Toshiyuki Kitoh, Elena Tsitsami, Mikhail Kostik, Jana Pachlopnik Schmid, Seraina Prader, Guido Laube, Despoina Maritsi, Marija Jelusic, Susan Shenoi, Sebastiaan Vastert, Gianluigi Ardissino, Randy Q Cron, Angelo Ravelli, MAS/sJIA Working Group of the Pediatric Rheumatology European Society (PReS).

Lupus. 2021 Jul 4;9612033211028658. Principles of pediatric lupus nephritis in a prospective contemporary multi-center cohort. Kathleen M Vazzana, Ankana Daga, Beatrice Goilav, Ekemini A Ogbu, Daryl M Okamura, Catherine Park, Rebecca E Sadun , Emily A Smitherman, Brian R Stotter, Abhijit Dasgupta, Andrea M Knight, Aimee O Hersh, Scott E Wenderfer, Laura B Lewandowski, CARRA Registry investigators.

Orv Hetil. 2021 Apr 10;162(17):652-667. Diagnosis and treatment of paediatric multisystem inflammatory syndrome. Tamás Constantin, Noémi Andrási, Andrea Ponyi, Ádám Goschler, László Ablonczy, Judit Kincs , Monika Csóka, Bálint Egyed, Zsuzsanna Horváth, Krisztina Kalocsai, Rita Káposzta, Kinga Kardics, Viktória Kemény, Bernadett Mosdósi, Tamás Pék, Zsófia Szabó, Attila Tóth , Kálmán Tory, Andrea Tölgyesi, Beáta Ónozó, Hajnalka Vágó, Csaba Vilmányi, Peter Weiser, Zoltán Szekanecz, Gábor Kovács, Attila Szabó.

Pediatr Rheumatol Online J. 2021 Aug 21;19(1):131. Patterns of etanercept use in juvenile idiopathic arthritis in the Childhood Arthritis and Rheumatology Research Alliance Registry. Timothy Beukelman, Aimee Lougee, Roland A Matsouaka, David Collier, Dax G Rumsey, Jennifer Schenfeld, Scott Stryker, Marinka Twilt, Yukiko Kimura, CARRA Registry Investigators.

Pediatr Rheumatol Online J. 2021 Feb 24;19(1):21. Distinguishing active pediatric COVID-19 pneumonia from MIS-C. Daniel D Reiff, Melissa L Mannion, Nichole Samuy, Paul Scalici, Randy Q Cron.

Timothy Beukelman, M.D., MSCE

• Dr. Beukelman is an editorial board member for the journals, Arthritis Care & Research, and Journal of Rheumatology.
• He serves as the scientific director of the North American Childhood Arthritis and Rheumatology Research Alliance (CARRA) disease registry.

Randy Cron, M.D., Ph.D.

• Selected Member, Alpha Omega Alpha (AOA) Honor Medical Society.
• James T. Cassidy Award, Outstanding Achievement in Pediatric Rheumatology, American Academy of Pediatrics.
• Keynote Speaker, AMIGO event, CARRA annual meeting, virtual.
• Becky DeRose Annual Pediatric Rheumatology Lectureship, Medical University of South Carolina, virtual.
• Invited Lecturer, European League Against Rheumatism (EULAR) annual scientific meeting, virtual.
• Keynote Speaker, Congress of Clinical Rheumatology East Immunology Symposium, Destin, Florida.
• Keynote Speaker, Tennessee Rheumatology Society Annual Scientific Meeting, Franklin, Tennessee.
• Invited Debater, 27th European Pediatric Rheumatology Congress (PReS), virtual.
• Keynote Speaker, Thieves’ Market, British Society of Rheumatology (BSR), virtual.
• Keynote Lecturer, 9th Annual James and Nancy Cassidy Endowed Lecture in Pediatric Rheumatology, Symposium on MIS-C, University of Missouri, virtual.
• Keynote Speaker, Hematology Society of Taiwan, virtual.
• In 2021, Dr. Cron was an invited virtual Grand Rounds speaker at the National Institutes of Health (NIH/NIAMS) and at Stanford University (Department of Medicine).
• Dr. Cron served as co-Chair of the Organizing Committee for the Basic Research and Clinical Conference as part of the international American College of Rheumatology (ACR) Annual Convergence, virtual.
• Dr. Cron is the founder and acting chairperson of the Macrophage Activation Syndrome (MAS) Study Group (2009).
• Dr. Cron is the founder and acting chairperson of the Juvenile Arthritis Workgroup (JAW) for TMJ arthritis (2010).
• Dr. Cron is a core/founding member of the Macrophage Activation Syndrome Collaborative (MASC: Harvard University, University of Pennsylvania, University of Pittsburgh, University of Cincinnati, UAB), which is a newly formed quality improvement and research network.
• Dr. Cron also founded the research network, Pediatric Rheumatology of the South (ProS), in 2019.
• Dr. Cron serves on the editorial boards of ACR Open Rheumatology, Frontiers in Immunology, Genes & Immunity, and Pediatric Rheumatology peer-reviewed journals.

Melissa Mannion, M.D., MSPH

• Dr. Mannion serves as the medical director for CampMASH, a weeklong summer camp for children in Alabama with rheumatic diseases held in Mobile, Alabama.
• Dr. Mannion also serves on the Leadership Board for the Arthritis Foundation local chapter.
• She received a three-year development grant from the Rheumatology Research Foundation (RRF) and an RRF Graduate Student Preceptorship Award, in addition to an NIH Loan Repayment grant.

Emily Smitherman, M.D., MSCTR

• Dr. Smitherman was an invited lecturer on the topic of “Optimizing Care Delivery in Pediatric Lupus” for the CARRA Lupus Committee meeting, the PR-COIN Learning Session and CARRA Implementation Science Workgroup meeting.
• Dr. Smitherman received a three-year development grant from the Rheumatology Research Foundation and an NIH Loan Repayment grant.
• Dr. Smitherman serves on the national quality improvement network, Pediatric Rheumatology Care and Outcomes Improvement Network Quality Improvement (PR-COIN).

Matthew Stoll, M.D., Ph.D., MSCS

• In 2021, Dr. Stoll was an invited speaker on topic of “The Microbiota in Juvenile Idiopathic Arthritis: More than Meet the Gut” for the New York University Rheumatology Conference and the annual Pediatric Rheumatology Symposium (PRSYM).
• In 2021, he was also an invited speaker on the topic of “Clinical and Pathologic Features of Psoriatic Juvenile Idiopathic Arthritis” at the Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting.
• Dr. Stoll was an invited lecturer on the topic of “Systemic and Local Treatment of TMJ Arthritis in Children with JIA” for the international TMJaw Symposium.
• Dr. Stoll serves the Spondyloarthritis Research and Treatment Network (SPARTAN) Board of Directors as Treasurer.

Peter Weiser, M.D.

• Dr. Weiser was recognized as one of the 20 Best Rheumatologists in Birmingham by DataGemba.

The Pediatric Rheumatology Fellowship Program at UAB was ACGME-approved in 2009, two years after the Division of Pediatric Rheumatology was created in 2007. The faculty has grown to six board-certified pediatric rheumatologists with four nurse practitioners, making it one of the largest programs in the southeastern United States. The program is designed for extensive clinical experience in the first year, followed by protected time for fellow-directed scholarly activity in the second and third years with the flexibility to address the specific needs of each fellow. Our fellows have opportunities to participate in research training programs sponsored by the UAB Rheumatology Division in addition to the opportunities available to all pediatric fellows through the UAB Department of Pediatrics, as well as a strong collaboration with UAB Adult Rheumatology. Fellows not working in a basic science laboratory are strongly encouraged to get an advanced degree at UAB in public health, clinical epidemiology or a related field of interest. We are excited to be training our first dual medicine-pediatrics trained fellow. Current funding for fellowship slots comes from the Kennedy Endowed Fellowship and grants from the Rheumatology Research Foundation, the Arthritis Foundation and Pfizer. UAB Rheumatology and Immunology T32 training grant slots are also competitively available to our fellows. At graduation, our fellows are well prepared clinically in all aspects of pediatric rheumatology and are set up for success in academic careers.

2021–2022 Fellows

Daniel Reiff, M.D.
Second-Year Fellow
Residency: University of Alabama at Birmingham

John Bridges, M.D., M.S.
Third-Year Fellow
Combined Adult & Pediatric Rheumatology Fellow
Residency: University of Mississippi

Program Director

Randy Cron, M.D., Ph.D.

Program Coordinator

Scott DeFreese