A 28-year-old man comes to the emergency department due to progressive abdominal pain. Although he has had mild abdominal cramps in the past, he has never before experienced anything this severe. The patient has 8-10 watery stools a day, weight loss, fatigue, and lethargy. Temperature is 38.3 C (100.9 F), blood pressure is 125/82 mm Hg, pulse is 95/min, and respirations are 14/min. The abdomen is tender to palpation without rebound or guarding. Abdominal CT scan reveals inflammatory changes affecting the ascending colon, sigmoid colon, and terminal ileum. Intestinal biopsy reveals the following: Effective treatment of this patient's condition could be achieved by targeting which of the following molecules?

Question

A 28-year-old man comes to the emergency department due to progressive abdominal pain.  Although he has had mild abdominal cramps in the past, he has never before experienced anything this severe.  The patient has 8-10 watery stools a day, weight loss, fatigue, and lethargy.  Temperature is 38.3 C (100.9 F), blood pressure is 125/82 mm Hg, pulse is 95/min, and respirations are 14/min.  The abdomen is tender to palpation without rebound or guarding.  Abdominal CT scan reveals inflammatory changes affecting the ascending colon, sigmoid colon, and terminal ileum.  Intestinal biopsy reveals the following:  Effective treatment of this patient's condition could be achieved by targeting which of the following molecules?

Quizplus · Accepted Answer

11ec160b_3bd1_8187_9249_cfda6b4f4dee_MD0001_00 This patient with recurrent abdominal pain, diarrhea, weight loss, and low-grade fevers has inflammatory changes of the colon and terminal ileum. In association with the characteristic intestinal biopsy findings, this presentation is consistent with Crohn disease (CD). CD is an inflammatory bowel disease that causes patchy inflammation throughout the gastrointestinal (GI) tract but spares the rectum; patients typically have segments of normal bowel interspersed with areas of disease (skip lesions). The presence of noncaseating granulomas on intestinal biopsy is highly suggestive of CD. These lesions are characterized by the accumulation of epithelioid macrophages that fuse to form multinucleated cells surrounded by a band of lymphocytes. Other characteristic histopathologic findings in CD include inflammation involving the entire thickness of the intestinal wall (transmural inflammation), distortion of normal mucosal architecture, and Paneth cell metaplasia. Tumor necrosis factor-alpha (TNF-α), an inflammatory cytokine produced by macrophages, plays a central role in the pathogenesis of CD. It promotes intestinal inflammation by inducing lymphocyte proliferation, enhancing migration of neutrophils into the GI tract, and stimulating macrophage activity. Several TNF-α inhibitors (eg, infliximab, adalimumab) are used as first-line therapy in the treatment of CD. (Choice A) Chronic myeloid leukemia (CML) occurs from a translocation between chromosomes 9 and 22, leading to creation of the BCR-ABL (fusion) protein tyrosine kinase. Imatinib, a direct inhibitor of BCR-ABL, is effective for CML but not for CD. (Choice B) CD20 antigen is specific to B lymphocytes. Rituximab, a monoclonal antibody directed at CD20, results in B cell depletion. It is used in multiple autoimmune disorders (eg, rheumatoid arthritis) but not CD. (Choice C) mTOR (mammalian target of rapamycin) is a stimulator of cell growth and proliferation. Sirolimus, an mTOR inhibitor, is used in patients with solid organ transplants to prevent allograft rejection. (Choice D) Programmed cell death-1 (PD-1) is an immune checkpoint molecule that downregulates the immune response. PD-1 inhibitors (eg, nivolumab, pembrolizumab) are cancer immunotherapy drugs used to stimulate the immune response against malignant cells. Educational objective: Crohn disease is an inflammatory bowel disorder that causes patchy inflammation throughout the gastrointestinal tract. Characteristic histopathologic findings include noncaseating granulomas, transmural inflammation, and Paneth cell metaplasia. Tumor necrosis factor-alpha (TNF-α), a cytokine produced by macrophages, plays a central role in the pathogenesis of CD; anti-TNF-α agents (eg, infliximab, adalimumab) are often used as first-line therapy. __________ References: Role of cytokines in the pathogenesis of inflammatory bowel disease. (http://www.ncbi.nlm.nih.gov/pubmed/10774465)

A 28-Year-Old Man Comes to the Emergency Department Due to Progressive