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Musculoskeletal Manifestations in Inflammatory Bowel Disease: A Revisit in Search of Immunopathophysiological Mechanisms

Sheth, Tejas MD*,†; Pitchumoni, Capecomorin S. MD, FRCP(c), MACP, MACG, MPH, AGAF*,†,‡; Das, Kiron M. MD, PhD, FRCP, FACP, FACG, AGAF§,∥,¶

Journal of Clinical Gastroenterology: April 2014 - Volume 48 - Issue 4 - p 308–317
doi: 10.1097/MCG.0000000000000067
Clinical Review

Inflammatory bowel diseases are chronic inflammatory disorders of multiple organ systems, primarily involving the gut, with chronic relapsing and remitting course. Musculoskeletal involvement is the most common extraintestinal manifestation. Distinct cell-mediated and humoral immunopathophysiological mechanisms have been identified underlying gut and joint inflammation in patients with inflammatory bowel disease and arthritis. Genetic polymorphisms in genes coding for NOD2 and IL12/IL23 complex lead to impaired antigenic handling in the gut and local immune dysregulation. The gut-synovial axis hypothesis implicates both environmental and host factors acting as triggers to initiate inflammation in genetically predisposed individuals, leading to priming of Th1 and Th17 lymphocytes in the gut and subsequent homing to the synovial tissue. Similar to gut, antibody-dependent cell-mediated cytotoxicity and complement-mediated cell lysis may also contribute to the joint damage. Involvement of peripheral joints occurs in 2 distinct manners, one being oligoarticular asymmetric arthritis associated with active disease and the other being polyarticular symmetric involvement of small joints. The axial involvement may include asymptomatic sacroiliitis, inflammatory back pain, and ankylosing spondylitis, running an independent clinical course. Noninflammatory involvement of the musculoskeletal system may present as osteopenia, osteonecrosis, fibromyalgia, or myopathies, leading to significant impact on quality of life.

*Department of Internal Medicine, St Peter's University Hospital, Drexel University College of Medicine

Department of Medicine, New York Medical College, Valhalla, NY

Rutgers-Robert Wood Johnson Medical School and University Hospital

§Department of Medicine, Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School

Division of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School and University Hospital

Crohn's and Colitis Center of NJ, Rutgers-Robert Wood Johnson University Hospital, New Brunswick, NJ

The authors declare that they have nothing to disclose.

Reprints: Kiron M. Das, MD, PhD, FRCP, FACP, FACG, AGAF, Clinical Academic Building, 125 Paterson Street, Suite 5100B, New Brunswick, NJ 08901-1962 (e-mail:

© 2014 by Lippincott Williams & Wilkins