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Case Records of the Massachusetts General Hospital
Case 4-2012 — A 37-Year-Old Man with Muscle Pain, Weakness, and Weight Loss
Presentation of Case. Dr. Ian J. Barbash (Medicine): A 37-year-old man was admitted to this hospital because of muscle pain and weakness. The patient had been well until the evening before admission, when mild diffuse myalgias developed. He awoke in the morning with diffuse muscle cramps and…
- February 9, 2012
- Rhee E.P., Scott J.A., Dighe A.S.
- N Engl J Med 2012; 366:553 - 560
- CME
A 37-year-old man was admitted to this hospital because of 12 hours of muscle pain and weakness, resulting in the inability to rise from bed. Brief episodes of similar symptoms had occurred during the past month. He reported blurred vision, gynecomastia, and weight loss.
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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.
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Clinical Therapeutics
Fingolimod for Multiple Sclerosis
Foreword. This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are…
- January 26, 2012
- Pelletier D. and Hafler D.A.
- N Engl J Med 2012; 366:339 - 347
- CME
A 37-year-old man with multiple sclerosis has recurrent disease activity despite several previous therapies. Treatment with fingolimod is recommended. Fingolimod blocks the egress of lymphocytes from lymph nodes, preventing them from reaching the central nervous system.
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Original Article
Cold Urticaria, Immunodeficiency, and Autoimmunity Related to PLCG2 Deletions
The genetic dissection of unique inflammatory phenotypes can identify and elucidate immunologic pathways and mechanisms. Such investigations have ultimately led to findings whose significance extends beyond the monogenic diseases harboring the mutations. Examples include the recognition that FOXP3…
- January 26, 2012
- Ombrello M.J., Remmers E.F., Sun G., et al.
- N Engl J Med 2012; 366:330 - 338
Analyses of families affected by cold urticaria, immunodeficiency, and autoimmunity implicate mutations that activate phospholipase Cγ2 (PLCγ2), an enzyme pivotal to the translation of binding events at the cell surface to the intracellular milieu, as a cause of the disease.
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Images in Clinical Medicine
Lung Herniation after Cough-Induced Rupture of Intercostal Muscle
Figure 1.
- January 5, 2012
- O'Shea M. and Cleasby M.
- N Engl J Med 2012; 366:74
- Free Full Text
A 40-year-old woman with asthma presented with pleuritic chest pain of acute onset. She had been coughing markedly for 2 weeks and had been treated with antibiotics for a lower respiratory tract infection. There was no history of trauma.
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Perspective
The Risks and Benefits of Indacaterol — The FDA's Review
In July 2011, the Food and Drug Administration (FDA) approved Arcapta Neohaler (indacaterol maleate powder), a long-acting beta-agonist (LABA), at a dose of 75 μg once daily as a bronchodilator for patients with chronic obstructive pulmonary disease (COPD). Since the European Medicines Agency (EMA)…
- December 15, 2011
- Chowdhury B.A., Seymour S.M., Michele T.M., et al.
- N Engl J Med 2011; 365:2247 - 2249
- Free Full Text
- Audio
In July, the FDA approved Arcapta Neohaler (indacaterol maleate powder), a long-acting beta-agonist, at a daily dose of 75 μg for chronic obstructive pulmonary disease. Why was this dose selected, after the European Medicines Agency approved 150-μg and 300-μg doses?
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Correspondence
Combined C3b and Factor B Autoantibodies and MPGN Type II
To the Editor: Membranoproliferative glomerulonephritis (MPGN) type II (MPGN II), also called dense-deposit disease, is a rare glomerular disease that often progresses to end-stage renal disease. MPGN II is associated with complement because of systemic C3 activation and deposition of C3 cleavage…
- December 15, 2011
- N Engl J Med 2011; 365:2340 - 2342
- Free Full Text
This letter describes two unrelated patients with membranoproliferative glomerulonephritis type 2 and autoantibodies to the two individual components of C3 convertase, factor B and C3. These autoantibodies enhance C3 convertase activity, probably leading to nephritis.
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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.
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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.
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Original Article
Interleukin-2 and Regulatory T Cells in Graft-versus-Host Disease
Allogeneic hematopoietic stem-cell transplantation (HSCT) invokes donor-derived immune responses that can result in therapeutic graft-versus-tumor activity and toxic graft-versus-host disease (GVHD). Chronic GVHD, a systemic inflammatory disorder with pleomorphic autoimmune manifestations that is…
- December 1, 2011
- Koreth J., Matsuoka K.-i., Kim H.T., et al.
- N Engl J Med 2011; 365:2055 - 2066
A low daily dose of subcutaneous interleukin-2 increases the number and function of regulatory T cells and results in substantial improvement in about half of patients with chronic graft-versus-host disease.
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Clinical Implications of Basic Research
Suppressing Immunosuppression after Stroke
Pneumonia is a major cause of death after acute cerebral ischemia. A recent study by Wong and colleagues provides some insight into susceptibility to infection after stroke. Specifically, they found that infections after stroke are promoted by noradrenergic-mediated dysfunction of a small subset of…
- December 1, 2011
- Meisel C. and Meisel A.
- N Engl J Med 2011; 365:2134 - 2136
There is growing evidence that acute injury of the central nervous system, including stroke, impairs the immune system. A recent study implicates the postischemic activation of a particular type of lymphocyte, by noradrenergic signaling, as a mediator of impairment.
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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.
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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 ...
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Original Article
Daily or Intermittent Budesonide in Preschool Children with Recurrent Wheezing
Recurrent wheezing episodes in preschool-age children are usually triggered by respiratory tract infections,, which often progress to severe exacerbations requiring systemic glucocorticoids and frequent use of health care services. In children under the age of 5 years who had at least four wheezing…
- November 24, 2011
- Zeiger R.S., Mauger D., Bacharier L.B., et al.
- N Engl J Med 2011; 365:1990 - 2001
Guidelines suggest daily inhaled glucocorticoids in young children at high risk for asthma exacerbation. These investigators found that such treatment was not superior to the intermittent use of budesonide initiated when signs and symptoms indicated an impending asthma exacerbation.
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Original Article
Mycophenolate versus Azathioprine as Maintenance Therapy for Lupus Nephritis
Systemic lupus erythematosus is an autoimmune disorder often characterized by the development of glomerulonephritis. Renal involvement remains the strongest predictor of morbidity and mortality among patients with lupus, and despite improvements in the management of lupus, the incidence of end…
- November 17, 2011
- Dooley M.A., Jayne D., Ginzler E.M., et al.
- N Engl J Med 2011; 365:1886 - 1895
In this double-blind, randomized trial, mycophenolate mofetil was superior to azathioprine for maintaining a renal response and preventing relapse in patients with lupus nephritis who had had a response to induction therapy.
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Editorial
Toward Better Treatment for Lupus Nephritis
Systemic lupus erythematosus is a prototypical autoimmune disease that can potentially involve every organ. Its clinical spectrum is therefore extremely heterogeneous and varies from relatively mild cases (e.g. involving only the skin or joints) to life-threatening manifestations, with renal…
- November 17, 2011
- Houssiau F.A.
- N Engl J Med 2011; 365:1929 - 1930
Systemic lupus erythematosus is a prototypical autoimmune disease that can potentially involve every organ. Its clinical spectrum is therefore extremely heterogeneous and varies from relatively mild cases (e.g., involving only the skin or joints) to life-...
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Case Records of the Massachusetts General Hospital
Case 34-2011 — A 75-Year-Old Man with Memory Loss and Partial Seizures
Presentation of Case. A 75-year-old physician was seen in an outpatient office at this hospital because of memory loss and episodes of near-syncope. The patient had been generally well, except for mild and gradual memory loss, until 7 months earlier, when episodes of diffuse tingling and a…
- November 10, 2011
- Cash S.S., Larvie M., Dalmau J.
- N Engl J Med 2011; 365:1825 - 1833
A 75-year-old man was seen because of memory loss and episodes of near-syncope, with word-finding difficulty and unilateral twitching. MRI with contrast material revealed hyperintensity and mild expansion of the left hippocampus, without enhancement.
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Perspective
Evidence-Based Medicine in the EMR Era
Many physicians take great pride in the practice of evidence-based medicine. Modern medical education emphasizes the value of the randomized, controlled trial, and we learn early on not to rely on anecdotal evidence. But the application of such superior evidence, however admirable the ambition, can…
- November 10, 2011
- Frankovich J., Longhurst C.A., Sutherland S.M.
- N Engl J Med 2011; 365:1758 - 1759
Pediatricians facing critical clinical decisions often lack data on which to draw. The authors recently put their institution's electronic medical record to unusual use to inform a decision about anticoagulation in a patient with systemic lupus erythematosus.
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Correspondence
Hemophilia A Induced by Ipilimumab
To the Editor: Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte–associated antigen 4, has been reported to improve overall survival in patients with metastatic melanoma. Major side effects include immune-related adverse events. We report a rare and severe case of ipilimumab…
- November 3, 2011
- N Engl J Med 2011; 365:1747 - 1748
- Free Full Text
A case is reported in which ipilimumab therapy for melanoma was followed by the development of an autoantibody to factor VIII.
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Clinical Problem-Solving
A Bird's-Eye View of Fever
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 78-year-old man presented to his…
- November 3, 2011
- Lee A.I., Koo S., Vaidya A., Katz J.T., Loscalzo J.
- N Engl J Med 2011; 365:1727 - 1732
A 78-year-old man presented with a 4-month history of worsening fatigue, weakness, and anorexia, with an unintentional weight loss of 11.4 kg. He reported fevers, chills, night sweats, dry mouth, nonproductive cough, dyspnea with minimal exertion, nausea, and postural light-headedness.
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