A 22-year-old woman comes to the office because of a 6-month history of increasing neck and low back pain that is most severe in the morning. Her pain improves as the day passes. The patient has no history of trauma, rashes, or urinary symptoms. Vital signs are within normal limits. Examination shows tenderness over the lumbosacral area and at the insertion site of the Achilles tendon. Forward flexion is reduced. This patient's symptoms are most likely attributable to upregulation of which of the following cytokines?

Question

A 22-year-old woman comes to the office because of a 6-month history of increasing neck and low back pain that is most severe in the morning.  Her pain improves as the day passes.  The patient has no history of trauma, rashes, or urinary symptoms.  Vital signs are within normal limits.  Examination shows tenderness over the lumbosacral area and at the insertion site of the Achilles tendon.  Forward flexion is reduced.  This patient's symptoms are most likely attributable to upregulation of which of the following cytokines?

Quizplus · Accepted Answer

11ec160b_37e2_e309_9249_250674bdbf71_MD0001_00 This patient with inflammatory back pain (ie, age <40, insidious onset, worse with rest/better with activity) and enthesitis (ie, tenderness at insertion of tendons/ligaments on bone) most likely has ankylosing spondylitis (AS). AS is characterized by bridging syndesmophytes in the vertebral column and ankylosis (bony fusion) of the apophyseal and sacroiliac joints. AS is an inflammatory disorder thought to originate largely in the gut: Defects in the mucosal barrier and an abnormal intestinal microbiome induce an IL-17-mediated inflammatory response via innate lymphoid cells and T helper cells (eg, Th1, Th17). The risk is greater in individuals with human leukocyte antigen B27 (HLA-B27), likely due to altered antigen presentation. IL-17 stimulates production of additional inflammatory factors, primarily tumor necrosis factor-alpha (TNF-alpha) and prostaglandins, which have synergistic effects with IL-17 and induce bony erosions and abnormal bone regrowth. Skeletal manifestations of AS occur primarily at sites of mechanical stress, such as the entheses, likely due to the migration of activated immune cells to these areas. Treatment options include nonsteroidal anti-inflammatory drugs (eg, ibuprofen, naproxen), which inhibit prostaglandin formation, and anti-TNF-alpha (eg, etanercept, infliximab) and anti-IL-17 (eg, secukinumab) agents. (Choice A) IL-2 and interferon gamma have broad immune functions, including activation of the response against viruses and mycobacteria. Both cytokines inhibit Th17 cell differentiation and do not have a significant role in the pathogenesis of AS. (Choice B) IL-4 is important in the differentiation of naïve Th cells into the Th2 subset, alternative macrophage activation (M2 type), and IgE production. It may also have a protective role in AS by limiting IL-17 production by Th1 and Th17 cells. Interferon alpha is involved primarily in antiviral activity and is not a significant factor in the pathogenesis of AS. (Choice C) IL-5 induces B-cell growth, IgA production, and eosinophil activity. IL-5 and IL-4 are important in the etiology of certain allergic disorders (eg, allergic rhinitis, asthma), but do not contribute significantly to AS. (Choice D) IL-10 is an antiinflammatory cytokine. Transforming growth factor-beta has antiinflammatory and profibrotic effects. These cytokines have only a minor effect in AS. Educational objective: The pathogenesis of ankylosing spondylitis likely originates with defects in the intestinal mucosal barrier and exposure to the gut microbiome that lead to an enhanced IL-17-mediated inflammatory response. IL-17 stimulates production of additional inflammatory factors, primarily tumor necrosis factor-alpha and prostaglandins, which have synergistic proinflammatory effects and induce bony erosions and abnormal bone regrowth in the skeleton.

A 22-Year-Old Woman Comes to the Office Because of a 6-Month