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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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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.
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Case Records of the Massachusetts General Hospital
Case 24-2011 — A 36-Year-Old Man with Headache, Memory Loss, and Confusion
Presentation of Case. Dr. M. Brandon Westover (Neurology): A 36-year-old right-handed man was seen in the neurology clinic of this hospital because of headaches, confusion, and memory loss. The patient had been well until 1 month earlier, when nausea, fevers, chills, diarrhea, malaise, and myalgias…
- August 11, 2011
- Bienfang D.C., McKenna M.J., Papaliodis G.N., Gonzalez R.G., Stemmer-Rachamimov A.
- N Engl J Med 2011; 365:549-559
A 36-year-old man was seen because of headaches, confusion, and memory loss, followed by visual and hearing loss. MRI showed hyperintense lesions in the white matter and corpus callosum. Funduscopic examination showed vascular narrowing and beading.
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Case Records of the Massachusetts General Hospital
Case 22-2011 — A 79-Year-Old Man with a Rash, Arthritis, and Ocular Erythema
Presentation of Case. Dr. Sebastian Unizony (Rheumatology): A 79-year-old man was seen in the rheumatology clinic at this hospital because of a rash, joint swelling and pain in the hands, and ocular erythema. The patient had been in his usual health until approximately 2.5 months earlier, when pain…
- July 21, 2011
- Kroshinsky D., Stone J.H., Nazarian R.M.
- N Engl J Med 2011; 365:252-262
- CME
A 79-year-old man was seen in the clinic because of a rash, painful and swollen hands, and red eyes. There was scleral erythema, urticaria on the torso, palpable purpura on the legs, and swelling and tenderness of the hand joints. A diagnostic procedure was performed.
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Case Records of the Massachusetts General Hospital
Case 14-2011 — A Woman with Asymmetric Sensory Loss and Paresthesias
Presentation of Case. Dr. Sheila L. Arvikar (Medicine): A 52-year-old woman was seen in the neurology clinic at this hospital because of asymmetric sensory loss and paresthesias in both arms and legs as well as impaired dexterity. The patient had been well until 5 months earlier, when her hands and…
- May 12, 2011
- Chad D.A., Stone J.H., Gupta R.
- N Engl J Med 2011; 364:1856-1865
A 52-year-old woman was seen in the Neurology Clinic because of asymmetric sensory loss and paresthesias in both arms and legs, and impaired dexterity, of 5 months' duration, with asymmetric loss of tendon reflexes and no weakness. Diagnostic tests were performed.
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Images in Clinical Medicine
Digital Gangrene
Figure 1.
- April 21, 2011
- Poisson J. and McCudden C.
- N Engl J Med 2011; 364:e34
- Free Full Text
A 71-year-old man presented with palpable purpura and received a diagnosis of type II cryoglobulinemia. He had an elevated cryocrit (13%), evidence of a monoclonal IgM kappa immunoglobulin (0.8 g per deciliter), and a positive result for rheumatoid ...
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Clinical Implications of Basic Research
Sepsis and Endothelial Permeability
Sepsis, derived from the Greek verb sepo (meaning "I rot"), has been recognized for millennia and refers to the disseminated inflammatory response elicited by microbial infections. Despite its ancient etymology, sepsis remains a current challenge: it is increasing in frequency, expensive to treat,…
- August 12, 2010
- Lee W.L. and Slutsky A.S.
- N Engl J Med 2010; 363:689-691
Molecular dissection in three models of sepsis implicates a signaling pathway in maintaining adhesion of endothelial cells to protect against vascular leak.
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Original Article
Rituximab versus Cyclophosphamide in ANCA-Associated Renal Vasculitis
Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, including Wegener's granulomatosis and microscopic polyangiitis, is a multisystem autoimmune syndrome characterized by vasculitis predominantly affecting microscopic vessels and circulating autoantibodies to neutrophil cytoplasmic…
- July 15, 2010
- Jones R.B., Cohen Tervaert J.W., Hauser T., et al.
- N Engl J Med 2010; 363:211-220
- Free Full Text
- CME
A standard glucocorticoid regimen plus rituximab was not superior to standard intravenous cyclophosphamide as induction therapy in patients with newly diagnosed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and renal involvement. Rates of sustained remission were high in both groups.
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Original Article
Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis
Wegener's granulomatosis and microscopic polyangiitis are classified as antineutrophil cytoplasmic antibody (ANCA)−associated vasculitides because most patients with generalized disease have antibodies against proteinase 3 or myeloperoxidase. The ANCA-associated vasculitides affect small-to…
- July 15, 2010
- Stone J.H., Merkel P.A., Spiera R., et al.
- N Engl J Med 2010; 363:221-232
- Free Full Text
This multicenter, randomized, double-blind, double-dummy, noninferiority trial compared rituximab with cyclophosphamide for remission induction in ANCA−associated vasculitis. Rituximab therapy was not inferior to daily cyclophosphamide treatment for remission induction in severe ANCA-associated vasculitis and may be superior in relapsing disease.
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Editorial
Rituximab in ANCA-Associated Disease
Antineutrophil cytoplasmic autoantibodies (ANCAs) are serologic markers of small-vessel vasculitides, including microscopic polyangiitis, granulomatosis with polyangiitis (Wegener's granulomatosis), and the Churg−Strauss syndrome. Since the discovery of ANCAs more than two decades ago,…
- July 15, 2010
- Falk R.J. and Jennette J.C.
- N Engl J Med 2010; 363:285-286
Antineutrophil cytoplasmic autoantibodies (ANCAs) are serologic markers of small-vessel vasculitides, including microscopic polyangiitis, granulomatosis with polyangiitis (Wegener's granulomatosis), and the Churg−Strauss syndrome.¹ Since the discovery of ...
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Images in Clinical Medicine
Peripheral Ulcerative Keratitis in Wegener's Granulomatosis
Figure 1.
- July 8, 2010
- Hood C.T. and Lowder C.Y.
- N Engl J Med 2010; 363:e2
- Free Full Text
This 15-year-old girl reported progressively worsening pain and redness in her left eye. The diagnosis of scleritis with peripheral ulcerative keratitis was made. Testing for antineutrophilic cytoplasmic antibody was positive.
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Correspondence
Mixed Lymphohematopoietic Chimerism and Response in Wegener's Granulomatosis
To the Editor: Animal models have shown that allogeneic hematopoietic stem-cell transplantation can lead to remission of experimental autoimmune disease that is attributed to a "graft-versus-autoimmunity" effect, wherein donor hematopoietic and immune cells apparently tolerize autoreactive…
- June 24, 2010
- N Engl J Med 2010; 362:2431-2432
- Free Full Text
To the Editor: Animal models have shown that allogeneic hematopoietic stem-cell transplantation can lead to remission of experimental autoimmune disease that is attributed to a “graft-versus-autoimmunity” effect,¹ wherein donor hematopoietic and immune ...
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Clinical Problem-Solving
More Than Meets the Ear
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 62-year-old, generally healthy…
- April 1, 2010
- Marinopoulos S.S., Coylewright M., Auwaerter P.G., Flynn J.A.
- N Engl J Med 2010; 362:1228-1233
A 62-year-old, generally healthy man presented with a “clogged” sensation and a 6-week history of diminished hearing in his right ear. He had no tinnitus, ear pain, or dizziness.
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Case Records of the Massachusetts General Hospital
Case 9-2010 — A 37-Year-Old Woman with Paresthesias and Ataxia
Presentation of Case. Dr. Mikael L. Rinne (Neurology): A 37-year-old right-handed woman was admitted to this hospital because of intermittent paresthesias, slurred speech, ataxia, and abnormalities on brain imaging. The patient had been well until 7 months earlier, when numbness and tingling…
- March 25, 2010
- Pless M.L., Chen Y.-B., Copen W.A., Frosch M.P.
- N Engl J Med 2010; 362:1129-1138
A 37-year-old right-handed woman was admitted to this hospital because of a 7-month history of intermittent paresthesias, followed by slurred speech, headaches, ataxia, and cognitive difficulties. Treatment with corticosteroids, verapamil, and azathioprine resulted in little improvement. Imaging studies showed lesions in the cerebral and cerebellar white matter. Gait imbalance, unsteadiness, and visual hallucinations developed. A diagnostic procedure was performed.
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Images in Clinical Medicine
Lupus-Associated Intestinal Vasculitis
Figure 1.
- July 16, 2009
- Huang D.-F. and Chen W.-S.
- N Engl J Med 2009; 361:e3
- Free Full Text
A 28-year-old woman with systemic lupus erythematosus presented with a 2-day history of periumbilical postprandial abdominal pain with nausea and vomiting. She was afebrile and normotensive, with diffuse abdominal distention and mild rebound pain without ...
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Case Records of the Massachusetts General Hospital
Case 17-2009 — A 30-Year-Old Man with Progressive Neurologic Deficits
Presentation of Case. Dr. Katharina Busl (Neurology): A 30-year-old man was admitted to this hospital because of progressive neurologic deficits. Approximately 1 year before this admission, he began to have intermittent headaches and the gradual onset of difficulty with word finding and writing,…
- May 28, 2009
- Greer D.M., Friday R.P., Romero J., Auluck P.K.
- N Engl J Med 2009; 360:2341-2351
A 30-year-old man was admitted to this hospital because of progressive neurologic deficits, which had begun 1 year earlier with headaches and word-finding difficulties, followed by seizures and cognitive and motor deficits. Imaging studies revealed progressive lesions involving predominantly the white matter, basal ganglia, and brain stem. He had a history of painful genital and oral ulcers, associated with arthralgias, for which immunosuppressive medications had been given. A diagnostic procedure was performed.
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Case Records of the Massachusetts General Hospital
Case 12-2009 — A 46-Year-Old Man with Migraine, Aphasia, and Hemiparesis and Similarly Affected Family Members
Presentation of Case. A 46-year-old man was seen in the neurology clinic because of hemiparesis, aphasia, and abnormalities on neuroimaging studies. The patient had been well, except for migraine headaches, until 4 years earlier, when right-sided weakness, clumsiness, and slurred speech developed…
- April 16, 2009
- Brass S.D., Smith E.E., Arboleda-Velasquez J.F., Copen W.A., Frosch M.P.
- N Engl J Med 2009; 360:1656-1665
A 46-year-old man presented to this hospital with migraine headache, a 4-year history of neurologic events resulting in aphasia and hemiparesis, and a family history of two similarly affected brothers. Neuroimaging studies showed white-matter and deep gray-matter abnormalities. A diagnostic test was performed.
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Original Article
Azathioprine or Methotrexate Maintenance for ANCA-Associated Vasculitis
Combined corticosteroid and cyclophosphamide therapy remains the standard care for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides, despite the potential risk of adverse events, particularly with the long-term use of cyclophosphamide. Moreover, even after induction with daily…
- December 25, 2008
- Pagnoux C., Mahr A., Hamidou M.A., et al.
- N Engl J Med 2008; 359:2790-2803
- Free Full Text
Current standard therapy for Wegener's granulomatosis and microscopic polyangiitis combines corticosteroids and cyclophosphamide to induce remission, followed by a less toxic immunosuppressant. This prospective, open-label, multicenter trial indicated that the safety and efficacy of azathioprine and methotrexate are similar for maintenance therapy after initial remission in these two conditions.
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Case Records of the Massachusetts General Hospital
Case 31-2008 — A 39-Year-Old Man with Chest Pain, Arthralgias, and a Mediastinal Mass
Presentation of Case. A 39-year-old man was admitted to this hospital because of chest pain, arthralgias, and a mediastinal mass. Two months before admission, pain in the middle and right chest developed, which radiated intermittently to the right arm, increased in intensity with deep inspiration…
- October 9, 2008
- Merkel P.A., McCarty D., Sharma A., Stone J.R.
- N Engl J Med 2008; 359:1603-1614
- Video
A 39-year-old man was admitted to this hospital because of chest pain, arthralgias, and a mediastinal mass. He had had pericarditis 1 year earlier and optic neuritis 5 years earlier. On examination, the first heart sound was absent, the second was loud with a prominent split, and there was a new systolic ejection murmur at the left upper sternal border. Imaging showed an infiltrative mediastinal mass surrounding the aorta and narrowing the lumen of the main and right pulmonary arteries.
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