Annals for Educators - 17 March 2020
Authors: Darren B. Taichman
Journal: Annals of Internal Medicine (2020)

Web Exclusives17 March 2020Annals for Educators - 17 March 2020FREEDarren B. Taichman, MD, PhDDarren B. Taichman, MD, PhDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/AWED202003170 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical Practice PointsAdverse Effects of Low-Dose Methotrexate. A Randomized TrialAlthough low-dose methotrexate is commonly used for the treatment of rheumatic diseases, data regarding potential adverse events are limited. This article reports the results of a rigorous, prospective evaluation of adverse events occurring with the use of low-dose methotrexate in a randomized, placebo-controlled trial.Use this study to:Start a teaching session with a multiple-choice question. We've provided one below!Ask your learners whether any of their patients are taking methotrexate. Who prescribed it? For what indication?How does methotrexate work? Why is folic acid prescribed with it?Ask your learners to list potential side effects of methotrexate. How often do they occur? Are they dose-dependent? How is methotrexate therapy monitored?Review the results of this study. Are they surprising? Reassuring?What are the implications of the study participants having to complete an active “run-in” period? How does this affect our interpretation of the results?Pharmacotherapy for the Treatment of Cannabis Use Disorder. A Systematic ReviewAmong regular users, cannabis may lead to physiologic dependence with withdrawal symptoms, but currently no pharmacotherapies have been approved by the U.S. Food and Drug Administration for treating cannabis use disorder (CUD). This systematic review evaluates available randomized trials of pharmacologic therapies to treat CUD in adults and adolescents.Use this study to:Ask your learners how acute cannabis intoxication may present. Use the information in DynaMed: Cannabis Use, a benefit of your ACP membership. How is CUD defined? What are the potential symptoms? The authors address this in the paper's introduction and discussion.What therapeutic approaches are used for CUD? What did this study find regarding their benefits and risks?What were the limitations of the studies the authors evaluated? How might high rates of attrition bias the results of a clinical trial?Physical Examination PearlsThe Hamman Sign: A Case Report With Audio RecordingThis case report describes the presentation and evaluation of a patient with abnormal sounds in his chest—and includes an audio recording for teaching!Use this report to:Ask your learners if they know what the Hamman sign is.With what entities is it associated?Play the recording of the chest sounds to your learners. Humanism and ProfessionalismOn Being a Doctor: On AgitationDescribing her experiences facing an agitated patient, Dr. McCann reflects, “So many of the emotions that arise when a patient is agitated or upset can feel utterly impermissible, antithetical to what it means to be a good health care provider. Yet, there they are, deep seams coursing through the everyday whether we name and meet them or not.”Use this essay to:Listen to an audio recording, read by Dr. Michael LaCombe. Ask your learners to describe their encounters with acutely agitated patients. Have they felt personally threatened? Have they been scared?What should be done when a patient is a threat to themselves or others? Do your learners know what to do?Are we expected to put ourselves in harm's way?Dr. McCann believes it is better to “meet” our “impermissible” emotions in such situations. What are they? Why is it better to “meet” them?A History LessonAnnals for Hospitalists Inpatient Notes - Hospital WardsDr. Howell's short and engaging essay discusses why hospitals used to have wards, why they disappeared, and how our profession has changed with this evolution.Use this essay to:Ask your learners what is meant by “the wards.” Have any of them seen a large, open hospital ward with multiple patient beds?Do your learners agree with the author that the demise of wards has limited our interaction with nursing colleagues? Can your learners propose changes to current practice to regain some of the prior benefits of practicing on wards?MKSAP 18 Question 1A 67-year-old woman is evaluated for a 3-year history of severe rheumatoid arthritis. She had an inadequate response to methotrexate and low-dose prednisone. She responded well to the addition of infliximab, but eventually the drug lost effect and she required a change in biologic therapy. She has done well with tocilizumab and methotrexate over the past year. She notes several months of prominent fatigue. History is also significant for type 2 diabetes mellitus, hypertension, and hyperlipidemia. Current medications are methotrexate, folic acid, tocilizumab, basal insulin, lisinopril, metoprolol, atorvastatin, ibuprofen, and omeprazole.On physical examination, vital signs are normal. Joint examination reveals no swollen or tender joints. The remainder of the physical examination is normal.Laboratory studies:Hemoglobin9.3 g/dL (93 g/L)Leukocyte count5600/µL (5.6 × 109/L)Mean corpuscular volume111 fLPlatelet count330,000/µL (330 × 109/L)Which of the following is the most likely cause of the anemia?A. InflammationB. Iron deficiencyC. MethotrexateD. TocilizumabCorrect AnswerC. MethotrexateEducational ObjectiveDiagnose methotrexate-induced anemia.CritiqueThe most likely diagnosis is methotrexate-induced anemia. Methotrexate can cause stomatitis, hepatic inflammation and fibrosis, and myelotoxicity, including megaloblastic anemia and pancytopenia. Folic acid supplementation is mandatory in all patients receiving methotrexate and can prevent the development of stomatitis and hepatotoxicity (as measured by elevated aminotransferase levels). Hematologic toxicity, however, can occur even with folic acid supplementation. In this patient, a rise in mean corpuscular volume (MCV) indicates a likely megaloblastic anemia, and methotrexate is the likely cause. Guidelines from the American College of Rheumatology recommend periodic monitoring of the complete blood count every 4 weeks during the first 3 months of therapy, every 8 to 12 weeks from 3 to 6 months, and every 8 to 12 weeks thereafter.Inflammatory anemia (anemia of chronic disease) is a common manifestation of rheumatoid arthritis and is usually a mild, normocytic anemia. Most patients experience symptoms related to their underlying disease rather than the anemia. Inflammatory anemia would not present with this degree of anemia or macrocytosis.Typical features of iron deficiency are identical to those of any symptomatic anemia but may be subtle owing to an insidious onset of the condition. Headache and pica (craving for typically undesirable items such as ice, dirt, clay, paper, and laundry starch) are frequently associated symptoms; other less common symptoms include restless legs syndrome and hair loss. The hallmark of iron deficiency is a microcytic hypochromic anemia. However, this is usually only seen in advanced iron deficiency, and anemia tends to precede morphologic changes in the cells. The presence of macrocytosis makes iron deficiency unlikely.Tocilizumab is not associated with a macrocytic anemia. Through its anti-inflammatory properties, it may decrease the likelihood of inflammatory-induced anemia in patients with rheumatoid arthritis.Key PointMethotrexate use can result in a megaloblastic anemia or pancytopenia; periodic monitoring of the complete blood count is recommended.BibliographyShea B, Swinden MV, Ghogomu ET, Ortiz Z, Katchamart W, Rader T, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. J Rheumatol. 2014;41:1049-60. doi:10.3899/jrheum.130738MKSAP 18 Question 2A 25-year-old woman is hospitalized for a 4-week history of swelling of the legs, weight gain, and shortness of breath on exertion. She was diagnosed with systemic lupus erythematosus 1 year ago when she presented with polyarthritis, rash, and alopecia. She was initially treated with hydroxychloroquine and prednisone with a good response.On physical examination, blood pressure is 142/96 mm Hg; other vital signs are normal. There is pitting edema of the lower extremities extending to the knees. The remainder of the physical examination is normal.Laboratory studies:Erythrocyte sedimentation rate68 mm/hHematocrit38%Complements (C3 and C4)LowCreatinine1.0 mg/dL (88.4 µmol/L)Anti-Smith antibodiesPositiveAnti–double-stranded DNA antibodiesPositiveUrinalysis3+ protein; no erythrocytes; no leukocytes; no castsUrine protein6000 mg/24 hThe patient is started on prednisone, along with diuretics and an ACE inhibitor.Kidney biopsy results show class V (membranous) lupus nephritis with absent chronicity and mild activity.Which of the following is the most appropriate treatment of the kidney disease?A. AdalimumabB. BelimumabC. CyclophosphamideD. MethotrexateE. Mycophenolate mofetilCorrect AnswerE. Mycophenolate mofetilEducational ObjectiveTreat class V (membranous) lupus nephritis.CritiqueMycophenolate mofetil is the most appropriate treatment of this patient's kidney disease. Classification of lupus nephritis is based on findings by light microscopy, electron microscopy, and immunofluorescence. This patient with recently diagnosed systemic lupus erythematosus (SLE) now presents with proteinuria likely due to lupus nephritis (likely class V, membranous). Guidelines recommend aggressive therapy with immunosuppressives for significant kidney involvement. A number of immunosuppressive therapies are beneficial in the treatment of SLE nephritis, including mycophenolate mofetil, cyclophosphamide, azathioprine, and rituximab. In the treatment of isolated class V lupus nephritis, especially without kidney dysfunction, mycophenolate mofetil is the most appropriate initial immunosuppressive therapy based on the guideline recommendations. Importantly, mycophenolate mofetil is teratogenic and has been associated with fetal harm and death; it must be stopped 3 months before a planned pregnancy.Adalimumab has not been shown to be effective in lupus nephritis and may potentially worsen the disease based on animal data.Belimumab may be considered in patients with continued SLE activity after standard therapy has been tried and found to be ineffective. Its role in the treatment of lupus nephritis continues to evolve but is currently not well defined. Its use in this patient should not be considered before having tried standard therapy.Cyclophosphamide may be considered in this patient and used appropriately in patients with lupus nephritis but is not an appropriate first choice due to a higher rate of side effects compared with mycophenolate mofetil, as well as its effect on reducing fertility and premature menopause. Cyclophosphamide is typically reserved for severe active nephritis to induce remission, followed by mycophenolate mofetil or possibly azathioprine as maintenance therapy.Methotrexate is not effective in lupus nephritis and may be associated with toxicity in a patient with kidney disease.Key PointMycophenolate mofetil is the most appropriate initial immunosuppressive therapy in the treatment of isolated class V lupus nephritis, especially without kidney dysfunction.BibliographyHahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al; American College of Rheumatology. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012;64:797-808. doi:10.1002/acr.21664Do you like reading Annals for Educators? Receive it direct to your inbox. Sign up for the Annals for Educators alert today. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From the Editors of Annals of Internal Medicine and Education Guest Editor, Gretchen Diemer, MD, FACP, Associate Dean of Graduate Medical Education and Affiliations, Thomas Jefferson University. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 March 2020Volume 172, Issue 6Page: ED6KeywordsAnemiaCannabis useFolic acidImmunosuppressivesIron deficiencyIron deficiency anemiaKidneysLupus nephritisMethotrexateRheumatoid arthritis ePublished: 17 March 2020 Issue Published: 17 March 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...