Eric P. Gall

Arthritis in acute hepatitis and chronic active hepatitis. Pathology of the synovial membrane with evidence for the presence of Australia antigen in synovial membranes.

Abstract Arthritis seen in the prodrome of acute viral hepatitis and as an early manifestation of chronic active hepatitis has been studied in two patients. Both patients had very low levels of serum complement and circulating Australia antigen which suggested the possible mechanism of immune complex deposition in some tissue injury. The synovial effusion in acute hepatitis was inflammatory, but neither synovial membrane showed more than rare inflammatory cells. Evidence for Australia antigen in the synovium was obtained by direct immunofluorescence and by electron microscopic identification of 200 to 250 A and 400 to 600 A particles in vessel endothelium, synovial lining cells and other deep synovial cells. Cell injury in synovial cells containing virus-like particles suggests that direct virus effect on the synovium may be the mechanism for production of arthritis.

Lethal Midline Granuloma With a Novel T-cell Phenotype as Found in Peripheral T-cell Lymphoma

Lethal midline granuloma (LMG), initially a clinical description, includes an uncommon group of disorders characterized by a relentless, destructive process involving the upper respiratory structures. Its etiology and pathogenesis are uncertain, probably varied, and the distinction between inflammatory and malignant processes is difficult despite extensive clinical and histopathologic evaluation. The need for new techniques for rapid diagnosis has important therapeutic implications. Using an extensive panel of T‐ and B‐cell monoclonal antibodies the authors describe a patient with clinically and pathologically typical LMG demonstrating an “activated” T‐cell phenotype with a “novel” patterns characterstic of peripheral T‐cell lymphoma, strongly implying that some cases of LMG are more closely related to neoplastic T‐cell lymphoproliferative disorders than to inflammatory conditions. Further studies using these immunotyping techniques may help clarify the pathogenesis of LMG, and may uncover specific diagnostic and prognostic phenotypic patterns. Cancer 59:936‐939, 1987.

Histological appearance of the synovium in early rheumatoid arthritis

This report reviews and discusses studies on the synovial fluid and biopsy specimens of synovial membrane obtained during the first 6 weeks of synovitis that evolved into rheumatoid arthritis (RA). Five previously unreported cases are described. Early changes in the microvasculature and synovial lining seem to antedate the classical chronic inflammation of established RA. Further characterization in the joint tissues in very early RA offers opportunities for identification of exogenous triggers and may allow more appropriate targeting of early therapy to potentially reversible aspects of pathogenesis.

Ibuprofen Kinetics In Plasma and Synovial Fluid of Arthritic Patients

After administration of a single dose and at steady state, ibuprofen concentrations were measured simultaneously in plasma and synovial fluid obtained from eight patients with rheumatoid arthritis. By seven hours after a dose at steady state, the mean synovial fluid: plasma ibuprofen concentration ratios were constant, and the synovial fluid levels were, on average, greater than those in plasma. The extent to which ibuprofen was bound to protein was somewhat greater in plasma than in synovial fluid. As a result, the mean synovial fluid:plasma free concentration ratio for seven‐hour and later specimens was greater than that based on total concentrations. The degree of accumulation of ibuprofen in each fluid was minimal, consistent with its short half‐life.

Pharmacokinetics of the R(−) and S(+) Enantiomers of Ibuprofen in the Serum and Synovial Fluid of Arthritis Patients

Eight patients with arthritis and knee effusions received 13 doses of a single 800‐mg ibuprofen tablet every 8 hours. Serum and synovial fluid samples were obtained after the first and last doses and assayed for the R(−) and S(+) enantiomers of ibuprofen by a stereospecific assay. Since only S(+)‐ibuprofen inhibits cyclo‐oxygenase, a description of the time course of this isomer in synovial fluid is needed for the development of suitable pharmacodynamic models. The isomers were significantly different with respect to peak concentrations and areas under the concentration—time curves (AUC) in synovial fluid levels. No significant accumulation of either isomer was observed in serum or synovial fluid levels between the first and the last doses. The steady‐state concentration of both isomers fluctuated less in synovial fluid than in plasma, and the synovial fluid concentrations of the S(+) isomer were about twice that of the R(−) isomer. The mean synovial albumin concentration was about 60% of the serum albumin concentration, and the steady‐state isomer AUC values in synovial fluid were significantly correlated with the corresponding serum values after the differences between the two fluids with respect to albumin concentration were corrected. The authors conclude that binding of the isomers to albumin and the serum—synovial fluid albumin ratio controls the steady‐state distribution of the ibuprofen isomers into synovial fluid. The ramifications of these findings in the development of satisfactory concentration—response relationships are discussed.

Aspirin-induced hepatic dysfunction in a patient with adult rheumatoid arthritis.

SummaryA patient with classical rheumatoid arthritis receiving high doses of aspirin developed significant elevation of serum glutamic oxaloacetic transaminase. This patient had recently been on phenylbutazone and an initial liver biopsy, at the time of elevation of the transaminase revealed nonspecific mild fatty infiltration of the liver compatible with the pathology seen with rheumatoid disease. Because of the severity and activity of her rheumatoid arthritis, and thus the need to know whether aspirin was the etiologic factor in liver dysfunction, the patient was challenged with aspirin. SGOT elevation occurred after a 4–6-day lag period, which promptly remitted when salicylates were discontinued. A liver biopsy at this time revealed evidence for degeneration, regeneration, and mild focal mononuclear infiltration. Although previous reports note salicylate-related hepatocellular dysfunction in patients with systemic lupus erythematosus and juvenile rheumatoid arthritis, these data clearly demonstrate the relationship of ASA to liver dysfunction in a patient with adult onset rheumatoid arthritis. The histologic picture as well as the clinical course of this patients hepatic abnormality suggest a toxic rather than hypersensitivity etiology for this syndrome.

Beyond the decade: Strategic priorities to reduce the burden of musculoskeletal disease

In the U.S., direct expenditures involving health-care costs and indirect expenditures involving lost wages of persons with musculoskeletal diseases have been estimated to total

Lumbar Spinal Stenosis in a Patient With Diffuse Idiopathic Skeletal Hypertrophy Syndrome

950 billion, or 7.4% percent of the U.S. gross national product, in 2004-20061. Despite this enormous financial burden, in addition to the personal and societal impact, musculoskeletal research represents less than 2% of the National Institutes of Health (NIH) budget2. This disparity between the burden of these diseases and the investment in research to develop improved preventive and treatment strategies for them is noted in every region of the world and has been a major impetus for the global Bone and Joint Decade movement. After ten years, it is important to undertake a retrospective analysis of what has been accomplished and what remains to be done with this program. The U.S. Bone and Joint Initiative (USBJI, previously called the U.S. Bone and Joint Decade, the National Action Network of the global Bone and Joint Decade) conducted a strategic planning process to determine what the organization is best positioned to accomplish, to assess how it can serve its mission in the future, and to set priorities “beyond the decade.” This was accomplished by six task groups (Arthritis, Bone Health and Osteoporosis, Pediatric Musculoskeletal Conditions, Spinal Disorders and Low Back Pain, Trauma and Injury, and Research). The following is a compilation of the priorities identified by each group. ### Priority Area 1.1: Public Education and Patient Empowerment There needs to be increased public recognition of the benefits of prevention, early diagnosis, and treatment of arthritis, including the importance of positive health behaviors. By the year 2020, the number of persons who attend or participate in arthritis health promotion activities such as public education, patient empowerment, arthritis self-management, exercise, and other programs should increase by 50%. To accomplish this ambitious task, it will be …

Winners of the 2016 American College of Rheumatology Annual Image Competition

Lumbar spinal stenosis is associated with a variety of conditions, including dysplastic narrowing of the spine, lumbar spondylosis, Pagets disease, and achondroplastic dwarfism. No case of lumbar stenosis associated with diffuse idiopathic skeletal hyperostosis (DISH) previously has been described. It would appear that this case could represent either another manifestation of DISH characterized by involvement of the ligamentum flavum or coincidental association with lumbar spondylosis. In either case, physicians treating spinal and skeletal diseases should be aware of potential neurologic complications requiring surgical decompression due to narrowing of the spinal canal in this unusual disorder.

Winners of the 2013 American college of rheumatology annual image competition

The mission of the Image Library Subcommittee is to provide ACR members, as well as the entire medical community, access to a wide variety of clinical images to help educators effectively present the manifestations of the rheumatologic diseases. Additionally, our images have been widely used in peer-reviewed publications and textbooks. Since its inception, the ACR Image Library has become the preeminent collection devoted to the rheumatologic diseases. The collection is a dynamic one, changing yearly because of submissions from the medical community. The Image Library Subcommittee meets annually to review these new images and awards prizes based on the panel’s consensus. Additionally, many nonwinners are introduced into the image library; greatly enhancing the collection. For the 2016 competition, more than 100 entries were received. The subcommittee carefully evaluates each entry. Winners, as well as those images selected for inclusion, are chosen based on image quality and educational value. The 2016 grand prize winner was a series of images showing coronary and other aneurysms in a patient with polyarteritis nodosa (Figure 1). In the stillimage category, the winner was a depiction of pachyderma in a patient with hypertrophic osteoarthropathy (Figure 2). The case study category winner was a series of radiographic and histologic images showing nodal and extranodal involvement in a girl with RosaiDorfman disease (Figure 3). Honorable mention was awarded to images of the following: rheumatoid arthritis: elbow erosions (Sandra Chatrand, MD), cardiac sarcoidosis: ventricular enhancement with noncaseating endomyocardial granulomas (Shakaib Hayat, DO), gout: double contour sign (Jawad Bilal, MD), Sj€ ogren’s syndrome: parotid pseudolymphoma (Santhanam Lakshminarayanan, MD), idiopathic transient osteoporosis: left hip (Aaradhana Kaul,