Teaching Topic, Immune Thrombocytopenia CLINICAL PRACTICE Immune Thrombocytopenia N. Cooper and W. Ghanima         Immune thrombocytopenia (ITP) is defined as a platelet count below 100,000 per cubic millimeter in patients in whom other causes of thrombocytopenia have been ruled out. Clinical Pearls   Is ITP a chronic disease? ITP may be a primary condition or it may be caused by other diseases. Although some patients have one episode of ITP followed by an immediate remission, chronic ITP develops in up to 70% of adults with this condition. Both spontaneous and treatment-induced remission can occur many years after diagnosis. Table 1. Differential Diagnosis and Secondary Causes of Immune Thrombocytopenia (ITP).   How common is severe bleeding in patients with ITP? Although only 5% of patients with ITP present with severe bleeding, bleeding leading to hospital admission within 5 years after diagnosis develops in approximately 15%. Irrespective of bleeding problems, patients with ITP often report fatigue and impaired health-related quality of life. The risk of venous thromboembolism is twice as high among patients with ITP as among persons in the general population; the management of venous thromboembolism may be especially problematic given the concomitant risk of bleeding. Morning Report Questions Q. What medical therapies are used to treat ITP? A. Glucocorticoid treatment is the standard initial therapy for patients with ITP. Although 60 to 80% of patients with ITP have an initial response to glucocorticoids, only 30 to 50% of adults have a sustained response after glucocorticoids are discontinued. In some studies, continued use has been associated with a higher incidence of long-term remission, but prolonged exposure to glucocorticoids is not recommended because of adverse effects. Medical therapies for patients with ITP who do not have an initial response to glucocorticoids or who have recurrent decreases in platelet counts after glucocorticoids are discontinued include thrombopoietin-receptor agonists and immunomodulators. In the absence of randomized trials directly comparing these therapies or of biomarkers to guide the choice of medication, treatment decisions are based on other factors, including the availability of medications, adverse effects, the required speed of response, and patient or physician preference. Among the available options, thrombopoietin-receptor agonists, rituximab, and fostamatinib have undergone the most rigorous study. Other immunomodulatory agents such as mycophenolate mofetil, azathioprine, dapsone, and danazol are also used in patients with ITP. Data to support their use are largely limited to retrospective observational studies that suggest that 30 to 60% of patients have a response. Q. What is the role of splenectomy in managing patients with ITP? A. A systematic review showed that splenectomy, which remains the most effective therapy for ITP, induced long-lasting remissions in 60 to 70% of patients. Nevertheless, owing to the emergence of effective medical therapies, the potential complications of splenectomy, and the inability to predict which patients will have a response, consideration of splenectomy is usually limited to patients who do not have a response to or cannot receive standard medical therapies because of side effects and in whom at least a year has passed since diagnosis (to allow for remission to occur). The frequency of splenectomy has decreased substantially during the past two decades.

Teaching Topic A Terminal Event CLINICAL PROBLEM-SOLVING A Terminal Event A.R. Lai and Others    Extraintestinal manifestations of Crohn’s disease include axial or peripheral arthritis, uveitis, psoriasis, erythema nodosum, pyoderma gangrenosum, and, uncommonly, aseptic diskitis and necrobiotic pulmonary nodules. Clinical Pearls   What is axial spondyloarthritis? Spondyloarthritis describes a family of diseases that are characterized by chronic inflammation affecting the axial joints (spine, pelvis, and thoracic cage), peripheral joints (arms and legs), or both. When the axial joints are predominantly involved, the condition is called axial spondyloarthritis; its prototype is ankylosing spondylitis, which is characterized by radiographic evidence of sacroiliitis.   What is peripheral spondyloarthritis? Peripheral spondyloarthritis primarily involves peripheral joints; its prototype is psoriatic arthritis, which is characterized by psoriatic skin lesions, synovitis, enthesitis, and dactylitis. Reactive arthritis, which is triggered by antecedent infection, is another spondyloarthritis that is typically peripheral. Spondyloarthritis in patients with inflammatory bowel disease can be predominantly axial or peripheral. Morning Report Questions Q. What are some of the features of axial spondyloarthritis? A. Inflammatory back pain is the hallmark of axial spondyloarthritis and is characterized by an insidious onset (typically before 40 years of age), morning stiffness lasting longer than 30 minutes, alleviation with exercise but not rest, and nocturnal pain that awakens the patient. The most common extraarticular manifestation of axial spondyloarthritis is anterior uveitis, which is typically associated with HLA-B27. Rarely, aseptic diskitis can accompany inflammatory spondyloarthritis. Aseptic diskitis in axial spondyloarthritis (Andersson’s lesions) can arise through two mechanisms. The first is a fracture of the bridging syndesmophytes with a resultant pseudoarthrosis (false joint) and inflammation of the intervening disk. The second is a primary inflammatory diskitis associated with axial spondyloarthritis (collectively termed spondylodiskitis). Q. What imaging tests are used to identify findings associated with inflammatory back pain? A. In a patient with at least 3 months of inflammatory back pain, plain radiography may show sacroiliitis (with a sensitivity of 48%, as shown in a single-cohort study). If plain radiographs are negative, T1-weighted MRI of the pelvis or symptomatic spinal area can show sacroiliitis or spondylitis, respectively (with a sensitivity of 85%). Fluid-sensitive MRI sequences (e.g., T2-weighted with short-tau inversion recovery [STIR]) are required for detecting spinal inflammation.

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QUOTE OF THE WEEK “In summary, this large, multicenter trial comparing the clinical effectiveness of laser ablation, foam sclerotherapy, and surgery for the treatment of varicose veins showed that in all three groups, quality of life 5 years after treatment was improved from baseline. However, there were clinically important between-group differences in disease-specific quality of life that favored laser ablation and surgery over foam sclerotherapy. Laser ablation was similar to surgery with respect to quality of life and of the three treatments had the highest chance of being cost-effective.” J. Brittenden and Others, Original Article, “Five-Year Outcomes of a Randomized Trial of Treatments for Varicose Veins”