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  • Clinical Problem-Solving

    Whistling in the Dark

    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 38-year-old woman living in…

    • May 3, 2012
    • Solomon D.A., Fanta C.H., Levy B.D., Loscalzo J.
    • N Engl J Med 2012; 366:1725-1730
    • CME

    Shortness of breath, fever, and cough productive of yellow sputum developed in a 38-year-old woman soon after the birth of her third child. Although her symptoms initially resolved with antibiotics, an intermittent nonproductive cough, wheezing, and shortness of breath soon followed.

  • Interactive Medical Case

    Whistling in the Dark

    A 38-year-old woman in Florida presented to her primary care physician with shortness of breath, fever, and a cough productive of yellow sputum. She was treated empirically with antibiotics for a presumed respiratory tract infection, and her symptoms resolved. She returned a few weeks later with an…

    • April 12, 2012
    • Vaidya A., Solomon D.A., Fanta C.H.
    • N Engl J Med 2012; 366:e24
    • Free Full Text
    • CME

    A 38-year-old woman had shortness of breath, fever, and cough with yellow sputum soon after childbirth. Her symptoms initially resolved with antibiotics, but she soon had nonproductive cough, wheeze, and shortness of breath. Test your diagnostic and therapeutic skills at NEJM.org.

  • Original Article

    HLA Class II Locus and Susceptibility to Podoconiosis

    Podoconiosis (endemic nonfilarial elephantiasis) is a noninfectious geochemical disease that results in bilateral swelling of the lower legs (Figure 1). It is found among subsistence farmers whose feet are exposed over many years to red-clay soil derived from volcanic rock. Podoconiosis is an…

    • March 29, 2012
    • Tekola Ayele F., Adeyemo A., Finan C., et al.
    • N Engl J Med 2012; 366:1200-1208

      Podoconiosis is a tropical form of noninfectious lymphedema associated with exposure to red-clay soil. It affects over 4 million people and is associated with substantial morbidity. In this genomewide association study in Ethiopia, associations were identified in two HLA class II loci.

    • Editorial

      To Be 17 Again — Anti–Interleukin-17 Treatment for Psoriasis

      Interleukin-17 is a cytokine that belongs to a family of six members (interleukins 17A through 17F), which bind a total of five receptors (interleukins 17RA through 17RE).– Of these six interleukin-17 cytokines, interleukins 17A and 17F are very homologous and bind the same receptor complex…

      • March 29, 2012
      • Waisman A.
      • N Engl J Med 2012; 366:1251-1252

        Interleukin-17 is a cytokine that belongs to a family of six members (interleukins 17A through 17F), which bind a total of five receptors (interleukins 17RA through 17RE).1–3 Of these six interleukin-17 cytokines, interleukins 17A and 17F are very ...

      • Review Article

        Medical Progress: Membranoproliferative Glomerulonephritis — A New Look at an Old Entity

        Membranoproliferative glomerulonephritis (MPGN), also termed mesangiocapillary glomerulonephritis, is diagnosed on the basis of a glomerular-injury pattern that is common to a heterogeneous group of diseases. MPGN accounts for approximately 7 to 10% of all cases of biopsy-confirmed…

        • March 22, 2012
        • Sethi S. and Fervenza F.C.
        • N Engl J Med 2012; 366:1119-1131
        • CME

        This review discusses the causes, pathogenesis, and clinical management of membranoproliferative glomerulonephritis, which accounts for 7 to 10% of biopsy-confirmed glomerulonephritis cases. Current classification reflects advances in the understanding of this condition.

      • Original Article

        Brief Report: Immunologic Correlates of the Abscopal Effect in a Patient with Melanoma

        The abscopal effect refers to a rare phenomenon of tumor regression at a site distant from the primary site of radiotherapy. Localized radiotherapy has been shown to induce abscopal effects in several types of cancer, including melanoma, lymphoma, and renal-cell carcinoma.– The biologic…

        • March 8, 2012
        • Postow M.A., Callahan M.K., Barker C.A., et al.
        • N Engl J Med 2012; 366:925-931

          A patient with metastatic melanoma with slowly progressive disease while receiving ipilimumab underwent radiotherapy for a pleural-based metastasis. Tumor lesions in nonirradiated sites began to disappear, and titers of antibody against a tumor-associated antigen increased.

        • 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.

          • 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 ...

            • 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.

              • 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, ...

              • Images in Clinical Medicine

                Fixed Drug Eruption

                Figure 1.

                • August 11, 2011
                • Valente Duarte de Sousa I.C.
                • N Engl J Med 2011; 365:e12
                • Free Full Text

                A 35-year-old man presented with a 10-day history of a cutaneous lesion on the left anterior chest. Examination revealed an annular, scaly, blistering, violaceous plaque, 5 cm in diameter, with an erythematous periphery. The lesion had appeared 24 hours ...

              • Original Article

                Horse versus Rabbit Antithymocyte Globulin in Acquired Aplastic Anemia

                Acquired aplastic anemia in its severe form is fatal without treatment. The disease is characterized pathologically by an "empty" bone marrow, in which hematopoietic precursor cells are replaced by fat, resulting in pancytopenia. Severe aplastic anemia was first definitively treated with the…

                • August 4, 2011
                • Scheinberg P., Nunez O., Weinstein B., et al.
                • N Engl J Med 2011; 365:430-438
                • Free Full Text

                Despite (or perhaps, because of) its induction of a more profound level of immune suppression, rabbit ATG was significantly less effective than horse ATG in producing hematologic remission in patients with aplastic anemia.

              • Original Article

                Brief Report: Mutual Antagonism of T Cells Causing Psoriasis and Atopic Eczema

                Psoriasis and atopic eczema are prevalent, influence health-related quality of life, are associated with concomitant illness, and pose an economic burden. Whether these diseases are epithelial or immunologic disorders is debated. Both involve complex interactions of hereditary factors and…

                • July 21, 2011
                • Eyerich S., Onken A.T., Weidinger S., et al.
                • N Engl J Med 2011; 365:231-238
                • Free Full Text

                The skin infiltrates of atopic eczema consist predominantly of type 2 helper T cells, whereas those of psoriasis are mainly types 1 and 17. The two diseases are elicited by different types of antigens and are largely mutually exclusive, since one type of infiltrate antagonizes the other.

              • Original Article

                IRF8 Mutations and Human Dendritic-Cell Immunodeficiency

                The discovery of human primary immunodeficiencies that affect the development of granulocytes, B cells, and T cells has been instrumental in defining the contribution of these cell types to protective immunity. Monocytes, macrophages, and dendritic cells — all mononuclear phagocytes — have…

                • July 14, 2011
                • Hambleton S., Salem S., Bustamante J., et al.
                • N Engl J Med 2011; 365:127-138
                • Free Full Text

                Monocytes and dendritic cells regulate adaptive and innate immunity. This study uncovers an association between mutations in the gene encoding interferon regulatory factor 8 and deficiency of dendritic cells and monocytes in the context of disseminated bacille Calmette–Guérin disease.

              • Original Article

                Brief Report: Vaccine-Derived Poliomyelitis 12 Years after Infection in Minnesota

                Poliomyelitis occurs when one of three poliovirus types infects the anterior horn cells of the spinal cord and can result in flaccid paralysis, respiratory failure, and death. Among patients with poliomyelitis, poliovirus can be recovered from the stool, throat, or in rare cases cerebrospinal fluid,…

                • June 16, 2011
                • DeVries A.S., Harper J., Murray A., et al.
                • N Engl J Med 2011; 364:2316-2323
                • Free Full Text

                Wild-type poliovirus type 2 has not been found globally since 1999 and may have been eradicated. However, in 2008, a woman in Minnesota with immunodeficiency died from infection with vaccine-derived poliovirus type 2, probably owing to exposure when her daughter received the oral vaccine.

              • Case Records of the Massachusetts General Hospital

                Case 18-2011 — A 35-Year-Old HIV-Positive Woman with Headache and Altered Mental Status

                Presentation of Case. Dr. Mikael Rinne (Neurology): A 35-year-old right-handed woman with human immunodeficiency virus (HIV) infection was admitted to this hospital because of headache and altered mental status after a motor vehicle accident. Earlier that day, while driving without a seatbelt, the…

                • June 16, 2011
                • Costello D.J., Gonzalez R.G., Frosch M.P.
                • N Engl J Med 2011; 364:2343-2352
                • CME

                A 35-year-old woman with stable HIV infection was admitted to this hospital because of headache and altered mental status. Brain imaging revealed diffuse white-matter abnormalities. A diagnostic test was performed.

              • Editorial

                Milk and Membranous Nephropathy

                Membranous nephropathy is a common cause of the nephrotic syndrome in adults, but it is rare in children, and the prognosis is highly variable.– The diagnosis is based on renal-biopsy findings, including characteristic immune-complex deposits along the glomerular basement membranes and thickened…

                • June 2, 2011
                • Fogo A.B.
                • N Engl J Med 2011; 364:2158-2159

                  Membranous nephropathy is a common cause of the nephrotic syndrome in adults, but it is rare in children, and the prognosis is highly variable.1–3 The diagnosis is based on renal-biopsy findings, including characteristic immune-complex deposits along the ...

                • Editorial

                  Alemtuzumab in Kidney-Transplant Recipients

                  Over the past decade, the use of induction therapy in organ-transplant recipients to intensify immunosuppression during the peritransplantation period has contributed to a reduction in early rejection rates and graft loss in the first year after transplantation. It is now common practice to select…

                  • May 19, 2011
                  • Markmann J.F. and Fishman J.A.
                  • N Engl J Med 2011; 364:1968-1969

                    Over the past decade, the use of induction therapy in organ-transplant recipients to intensify immunosuppression during the peritransplantation period has contributed to a reduction in early rejection rates and graft loss in the first year after ...

                  • Review Article

                    Medical Progress: Acute HIV-1 Infection

                    In 2009, the United Nations estimated that 33.2 million people worldwide were living with human immunodeficiency virus type 1 (HIV-1) infection and that 2.6 million people had been newly infected. The need for effective HIV-1 prevention has never been greater. In this review, we address recent…

                    • May 19, 2011
                    • Cohen M.S., Shaw G.M., McMichael A.J., Haynes B.F.
                    • N Engl J Med 2011; 364:1943-1954
                    • CME

                    More than 33 million people are living with HIV-1, and more than 2.5 million additional cases are detected each year. This review addresses recent advances in our understanding of the transmission of HIV-1 and of acute HIV-1 infection.

                  • Original Article

                    Alemtuzumab Induction in Renal Transplantation

                    In the United States between 1998 and 2007, a total of 78% of renal-transplant recipients received antibody induction therapy. The most frequently used agents have been rabbit antithymocyte globulin (Thymoglobulin, Genzyme), a lymphocyte-depleting polyclonal antibody, and basiliximab (Simulect,…

                    • May 19, 2011
                    • Hanaway M.J., Woodle E.S., Mulgaonkar S., et al.
                    • N Engl J Med 2011; 364:1909-1919
                    • Free Full Text

                    Renal-transplant recipients were given alemtuzumab induction therapy or conventional induction therapy as part of a program of early glucocorticoid withdrawal. Acute rejection was less frequent with alemtuzumab during the first year.

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                  Medical Meetings Pediatrics Conferences and Meetings

                  2012 Certifying Examinations of the American Board of Pediatrics

                  The general pediatrics examination will be held in various cities, Oct. 16-18. Registration for first-time applicants is ongoing through May 3. Registration for re-registrants is ongoing through May 24. The following subspecialty examinations will be held in various cities: "Hospice and Palliative Medicine" (Oct. 4); "Pediatric Transplant Hepatology" (Oct. 11); "Pediatric Cardiology" (Nov. 7); "Pediatric Pulmonology" (Nov. 8); "Medical Toxicology" (Nov. 12); and "Pediatric Critical Care Medicine" (Nov. 14). Registration for first-time applicants is ongoing through April 30. Registration for re-registrants is ongoing through June 15.

                  Contact the American Board of Pediatrics, 111 Silver Cedar Court, Chapel Hill, NC 27514-1513; or call (919) 929-0461; or fax (919) 918-7114 or (919) 929-9255; or see http://www.abp.org .

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