Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease for which current therapy is suboptimal. SLE is characterized by autoantibody production, with renal disease and premature atherosclerosis being common and severe manifestations causing appreciable morbidity and mortality. Peroxisome proliferator-activated receptor γ (PPARγ) agonists are widely used in the treatment of diabetes mellitus for their insulin-sensitizing properties, but also have immunomodulatory effects. In this report, we show that the PPARγ agonist rosiglitazone reduces autoantibody production, renal disease, and atherosclerosis in mouse models of SLE. The beneficial effect of rosiglitazone on SLE manifestations depends on the induction of adiponectin, because rosiglitazone has no effect on autoantibody production or renal disease in lupus mice that lack adiponectin. In addition, lupus mice that lack adiponectin develop more severe disease than adiponectin-sufficient lupus mice, indicating that endogenous adiponectin is involved in regulating disease activity. Furthermore, administration of exogenous adiponectin ameliorates disease. These experiments suggest that PPARγ agonists may be useful agents for the treatment of SLE. They also demonstrate that induction of adiponectin is a major mechanism underlying the immunomodulatory effects of PPARγ agonists.

ES-62 is an anti-inflammatory phosphorylcholine-containing glycoprotein secreted by the filarial nematode Acanthocheilonema viteae. Accelerated atherosclerosis frequently occurs in systemic lupus erythematosus (SLE), resulting in substantial cardiovascular morbidity and mortality. We examined the effects of ES-62 in the gld.apoE−/− mouse model of this condition. Treatment with ES-62 did not substantially modulate renal pathology but caused decreased anti-nuclear autoantibody levels. Moreover, a striking 60% reduction in aortic atherosclerotic lesions was observed, with an associated decrease in macrophages and fibrosis. We believe that these latter findings constitute the first example of a defined parasitic worm product with therapeutic potential in atherosclerosis: ES-62-based drugs may represent a novel approach to control accelerated atherosclerosis in SLE.

Lupus nephritis is one of the more serious manifestations of the systemic autoimmune disease, systemic lupus erythematosus, and is associated with considerable morbidity and even mortality. Treatment remains problematic, particularly in terms of controlling the underlying disease process while at the same time preventing unacceptable side effects of therapy. In recent years, clinical trials have started to define optimum regimens of the immunosuppressive agents presently in use. The etiology and pathogenesis of systemic lupus erythematosus and lupus nephritis still are understood incompletely. Nevertheless, insights gained from basic science research in both animals and human beings now are being translated into newer therapies that have the potential to be safer and more specific than those currently available.

A 53-year old man presented to the ED with complaints of fevers and chills for 5 days. Two days prior, he started having generalized arthralgias and a painfully numb left index finger. Similar symptoms had also begun on his left great toe (See Figures D and E, Color Plates page 19). The patient denied recent trauma, although he was unsure if he had sustained an insect bite on the dorsal aspect of his left hand 8 hours prior to the onset of symptoms. Three sets of blood cultures obtained prior to admission were positive for methacillin-sensitive Staphylococcus aureus. The patient was treated with intravenous nafcillin and gentamicin. A transesophageal echocardiography was performed, which showed a friable and perforated left coronary cusp of the aortic valve, resulting in severe aortic insufficiency. The patient was scheduled for emergent aortic valve replacement. It was surmised that the initial site of infection was a badly ulcerated blister located on the patient's right great toe. A Male with Chills and Arthralgias Lo-Ku Chiang MD, PGY-3 Internal Medicine and Ambrish Ojha MD, PGY-5 Infectious Diseases DiscussionThere are numerous peripheral manifestations of bacterial endocarditis. The classic peripheral manifestations are found in up to half of the cases, but the prevalence has decreased in recent years. Janeway lesions are painless erythematous, hemorrhagic, or pustular lesions that are seen on the palms or soles and are often associated with acute bacterial endocarditis. Oslers nodes, which are tender, subcutaneous nodules often located on the pulp of the digits typically seen with subacute bacterial endocarditis. Other vasculitic complications include major arterial emboli, septic pulmonary infarcts, mycotic aneurym, conjunctival petechiae and intracerebral hemorrhages. Immunologic phenomena include glomerulonephritis, a positive rheumatoid factor, Roth spots and superficial retinal hemorrhages. These clinical findings are part of the minor criteria in the Duke classification of diagnosing bacterial endocarditis.Frequently, the presentation of endocarditis is not clear and a high level of clinical suspicion is essential in a patient with fever and systemic symptoms suggestive of infective endocarditis.