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  • Review Article

    Mechanisms of Disease: IgG4-Related Disease

    IgG4-related disease is a newly recognized fibroinflammatory condition characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and, often but not always, elevated serum IgG4 concentrations. The disease was not recognized as…

    • February 9, 2012
    • Stone J.H., Zen Y., Deshpande V.
    • N Engl J Med 2012; 366:539 - 551

      A number of autoimmune diseases that affect diverse organ systems have recently been noted to be related to IgG4 autoantibodies. The authors review the spectrum of IgG4-related disease and the current status of diagnostic and management approaches.

    • Images in Clinical Medicine

      Hypertrophic Pulmonary Osteoarthropathy and Tripe Palms

      Figure 1.

      • January 26, 2012
      • Saeed H. and Massarweh S.
      • N Engl J Med 2012; 366:360
      • Free Full Text

      A 56-year-old female smoker presented with cough, a weight loss of 27 kg, and diffuse bone pain. There was digital clubbing, and the palms had a raised, velvety texture. There was a fixed, tender lump (4 cm in diameter) on the right lower leg and one over the lower lumbar spine.

    • Original Article

      Bone-Density Testing Interval and Transition to Osteoporosis in Older Women

      Current osteoporosis management guidelines– recommend routine bone mineral density (BMD) screening with the use of dual-energy x-ray absorptiometry (DXA) scans for women 65 years of age or older, but no guidelines specify an osteoporosis screening interval that is based on data from longitudinal…

      • January 19, 2012
      • Gourlay M.L., Fine J.P., Preisser J.S., et al.
      • N Engl J Med 2012; 366:225 - 233
      • CME

      This study analyzed the transition from normal BMD or osteopenia to osteoporosis; in women 67 years of age or older, the time for 10% to develop osteoporosis was approximately 15 years for normal BMD or mild osteopenia at baseline, 5 years for moderate osteopenia, and 1 year for advanced osteopenia.

    • Images in Clinical Medicine

      Tophaceous Gout

      Figure 1.

      • January 19, 2012
      • Samaras N. and Rossi C.
      • N Engl J Med 2012; 366:e6
      • Free Full Text

      A 74-year-old woman with chronic renal failure was admitted for diarrhea and functional impairment. She was noted to have a tender, soft swelling of the medial and distal phalanx of the right index finger (Panel A). She had no history of joint ...

    • Clinical Practice

      Primary Hyperparathyroidism

      Foreword. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. Stage. A 62-year-old…

      • December 22, 2011
      • Marcocci C. and Cetani F.
      • N Engl J Med 2011; 365:2389 - 2397
      • CME
      • Full Text Audio

      This article reviews the differential diagnosis and management of primary hyperparathyroidism. For most patients, parathyroidectomy (usually by a minimally invasive approach) is recommended, but surveillance is an option for asymptomatic patients who meet certain criteria.

    • Review Article

      Mechanisms of Disease: The Pathogenesis of Rheumatoid Arthritis

      Rheumatoid arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications, early death, and socioeconomic costs. The cause of rheumatoid arthritis is unknown, and the prognosis is guarded. However, advances in understanding the pathogenesis of the…

      • December 8, 2011
      • McInnes I.B. and Schett G.
      • N Engl J Med 2011; 365:2205 - 2219

        The increased understanding of the immune mechanisms of rheumatoid arthritis has led to the development of a considerable number of new therapeutic agents that alter the natural history of the disease and reduce mortality.

      • Review Article

        Mechanisms of Disease: Systemic Lupus Erythematosus

        Although the term "lupus erythematosus" was introduced by 19th-century physicians to describe skin lesions, it took almost 100 years to realize that the disease is systemic and spares no organ and that it is caused by an aberrant autoimmune response. The clinical heterogeneity of the disease forced…

        • December 1, 2011
        • Tsokos G.C.
        • N Engl J Med 2011; 365:2110 - 2121

          The author reviews environmental, genetic, epigenetic, and hormonal factors in systemic lupus erythematosus, its diverse organ manifestations, and the myriad immune abnormalities that characterize this autodestructive disease, which mainly affects women of childbearing age.

        • Original Article

          Regulatory T-Cell Responses to Low-Dose Interleukin-2 in HCV-Induced Vasculitis

          Interleukin-2 has been identified for its capacity to stimulate T cells in vitro and has been used to boost effector immune responses in patients with cancers and infectious diseases. It is a registered indication when used as an adjunct for the treatment of renal-cell carcinoma, but there is a…

          • December 1, 2011
          • Saadoun D., Rosenzwajg M., Joly F., et al.
          • N Engl J Med 2011; 365:2067 - 2077

            This phase 1–phase 2a study of the use of low-dose interleukin-2 to treat vasculitis associated with HCV infection suggests the presence of a therapeutic effect that is mediated by an increase in regulatory T cells.

          • Editorial

            The Yin and Yang of Interleukin-2–Mediated Immunotherapy

            In this issue of the Journal, the findings of two case series suggest that in vivo treatment with interleukin-2 can suppress immune-mediated diseases. In one study, Koreth et al. found that low-dose interleukin-2 was associated with reversal of glucocorticoid-refractory chronic graft-versus-host…

            • December 1, 2011
            • Bluestone J.A.
            • N Engl J Med 2011; 365:2129 - 2131

              In this issue of the Journal, the findings of two case series suggest that in vivo treatment with interleukin-2 can suppress immune-mediated diseases. In one study, Koreth et al.1 found that low-dose interleukin-2 was associated with reversal of ...

            • Images in Clinical Medicine

              Metastasis of Renal-Cell Carcinoma

              Figure 1.

              • November 3, 2011
              • Pugliese F. and Pagliuca V.
              • N Engl J Med 2011; 365:e38
              • Free Full Text

              Four years after a right nephrectomy for renal-cell carcinoma, an 89-year-old man was referred for evaluation of a pulsating mass on the fourth digit of the right hand. The mass had increased in size during the preceding 3 months after minor trauma to the finger.

            • Original Article

              Anti-Inhibitor Coagulant Complex Prophylaxis in Hemophilia with Inhibitors

              After exposure to factor VIII, alloantibodies (inhibitors) that neutralize factor VIII clotting function develop in approximately 30% of patients with severe hemophilia A. The development of high-titer factor VIII inhibitors (>5 Bethesda units [BU]) complicates treatment because bleeding no longer…

              • November 3, 2011
              • Leissinger C., Gringeri A., Antmen B., et al.
              • N Engl J Med 2011; 365:1684 - 1692
              • CME

              In patients with hemophilia A in whom inhibitors of factor VIII develop, the prophylactic use of a factor VIII bypassing agent (anti-inhibitor coagulant complex) three times a week significantly reduced the risk of bleeding.

            • Case Records of the Massachusetts General Hospital

              Case 33-2011 — A 56-Year-Old Man with Hypophosphatemia

              Presentation of Case. Dr. Eric Hesse (Harvard School of Dental Medicine): A 56-year-old man was seen in the outpatient endocrinology and oral-surgery clinics of this hospital because of recurrent hypophosphatemia. The patient had been well until 19 years earlier, when rib pain developed and a left…

              • October 27, 2011
              • Bergwitz C., Collins M.T., Kamath R.S., Rosenberg A.E.
              • N Engl J Med 2011; 365:1625 - 1635
              • CME

              A 56-year-old man presented with recurrent bone pain, stress fractures, and hypophosphatemia. A tumor of the jaw had been resected in the past, with resolution of symptoms. Studies of the jaw revealed no recurrent tumor. Diagnostic tests were performed.

            • Original Article

              Brief Report: Inflammatory Skin and Bowel Disease Linked to ADAM17 Deletion

              Inflammatory disorders of the skin and gut, including eczema, psoriasis, and celiac disease, have been linked to changes in barrier function and immune responses, by means of genetic and functional studies. Large case–control studies combined with genomewide association studies have identified…

              • October 20, 2011
              • Blaydon D.C., Biancheri P., Di W.-L., et al.
              • N Engl J Med 2011; 365:1502 - 1508

                A mutation that abrogates the function of ADAM17, an enzyme that cleaves cell-surface proteins such as tumor necrosis factor α, was found to be associated with inflammatory skin and bowel disease in a pair of siblings.

              • Interactive Medical Case

                A Bird's-Eye View of Fever

                A 78-year-old man presented to his primary care physician with a 4-month history of worsening fatigue, generalized weakness, and anorexia, with an unintentional weight loss of 11.4 kg (25 lb). He reported subjective fevers, chills, drenching night sweats, dry mouth, a nonproductive cough, dyspnea…

                • October 13, 2011
                • Ross J.J., Koo S., Lee A.I., Mushlin S.B., Milner D.A.
                • N Engl J Med 2011; 365:e33
                • Free Full Text
                • CME

                A 78-year-old man presented with four months of worsening fatigue, generalized weakness, and anorexia with an unintentional weight loss of 25 pounds (11.4 kg). He reported subjective fevers, chills, drenching night sweats, dry mouth, nonproductive cough, ...

              • Clinical Problem-Solving

                It's Not All in Your Head

                Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors' commentary follows. Stage. A 63-year-old man presented to the…

                • October 6, 2011
                • Towns K., Szmitko P.E., Smith C., Detsky A.S., Mourad O.
                • N Engl J Med 2011; 365:1329 - 1334
                • CME

                A 63-year-old man presented to the emergency department with shaking chills and drenching sweats of 4 days' duration. He reported no weight loss, arthralgias, headache, visual changes, or new skin eruptions, but he had progressively worsening bilateral anterior thigh pain of 10 days' duration.

              • Correspondence

                Atypical Femoral Fractures and Bone Turnover

                To the Editor: Epidemiologic studies and case series and reports suggest that there is a relation between the long-term use of bisphosphonates and the development of atypical femoral fractures. Although the cause of such fractures is unknown, the fact that bisphosphonates decrease bone resorption…

                • September 29, 2011
                • N Engl J Med 2011; 365:1261 - 1262
                • Free Full Text

                A bone biopsy performed in a woman treated with bisphosphonates who had bilateral atypical femoral fractures did not reveal decreased bone turnover, suggesting the possibility that fractures associated with bisphosphonate use are not due to oversuppression of bone turnover.

              • Case Records of the Massachusetts General Hospital

                Case 30-2011 — A 62-Year-Old Woman with Renal Failure

                Presentation of Case. Dr. Kyle Staller (Medicine): A 62-year-old woman was admitted to this hospital because of renal failure. The patient had an autoimmune overlap syndrome with polymyositis, treated with prednisone and mycophenolate mofetil, but had been in her usual health until 6 weeks before…

                • September 29, 2011
                • Cunningham J., Harisinghani M.G., Taheri D.
                • N Engl J Med 2011; 365:1233 - 1243
                • CME

                A 62-year-old woman with autoimmune overlap syndrome and polymyositis presented to this hospital with anemia, thrombocytopenia, and acute renal failure. Four days before admission, she was found on the floor of her home, confused and minimally conversant.

              • Images in Clinical Medicine

                Gout Nodulosis

                Figure 1.

                • September 15, 2011
                • Cheema U.
                • N Engl J Med 2011; 365:e23
                • Free Full Text

                A 70-year-old man presented with tender masses over each elbow that had been gradually enlarging for several years. There was no history of joint pain. Physical examination revealed a large, erythematous, fluctuant, subcutaneous mass covering each olecranon process.

              • Perspective

                Medical Devices — Balancing Regulation and Innovation

                Many Americans benefit from the implantation of medical devices, such as artificial joints and lifesaving defibrillators. Tragically, many also suffer or even die from complications related to medical devices that were never studied in clinical trials before being implanted in patients. As devices…

                • September 15, 2011
                • Curfman G.D. and Redberg R.F.
                • N Engl J Med 2011; 365:975 - 977
                • Free Full Text

                The FDA approval system cannot assure the safety and effectiveness of increasingly complex medical devices. The Institute of Medicine has recommended eliminating a process that permits approval of a device based on its “substantial equivalence” to an existing device.

              • Images in Clinical Medicine

                Scleroderma

                Figure 1.

                • September 1, 2011
                • Fernandes das Neves M. and Oliveira S.
                • N Engl J Med 2011; 365:842
                • Free Full Text

                A 75-year-old woman was evaluated for a history of inflammatory joint pain in both hands. Symptoms of gastroesophageal reflux were present. Examination revealed multiple palpable masses in the soft tissue overlying the extensor surfaces of the elbows, wrists, and hands.

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              Medical Meetings Conferences and Meetings

              American Association for the Study of Liver Diseases

              The following courses will be offered in Atlanta, unless otherwise indicated: "Hepatitis Single Topic Conference: HCV Direct Antiviral Agents (DAA): Concepts, Development and Optimal Use" (March 16 and 17); "The Henry M. and Lillian Stratton Basic Research Single Topic Conference: Mitochondria and Hepatotoxicity" (June 8 and 9); "Clinical Research Single Topic Conference: Acetaminophen Poisoning" (June 9 and 10); and "63rd Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2012" (Boston, Nov. 9-13).

              Contact AASLD, 1001 North Fairfax St., Suite 400, Alexandria, VA 22314; or call (703) 299-9766; or see http://www.aasld.org .

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