Rheumatoid vasculitis: Experience with 13 patients and review of the literature

Rheumatoid vasculitis is an uncommon but potentially catastrophic complication of RA. There are few current extensive experiences and no consensus regarding the clinical, laboratory, histologic features, and management or prognosis of rheumatoid vasculitis. We therefore reviewed selected observations in 13 patients followed over the past decade and compared them with patients reported and with results of a survey of North American Rheumatologists. Our patients were seven men and six women (age, 33 to 70 years) who had had active RA for 4 to 36 years. They exhibited sensory neuropathy, mononeuritis multiplex, Felty syndrome, cutaneous lesions, leg ulcers, gangrene, anemia, leukocytosis, eosinophilia, high titers of RF, hypocomplementemia, and CICs or cryoglobulinemia approximately as frequently as other reported patients with rheumatoid vasculitis, but they displayed constitutional symptoms, subcutaneous nodules, ischemic changes, and proteinuria rather less consistently than in other series. These observations were not necessarily as expected by survey respondents. We, as in other series and suggested by survey respondents, tended to select penicillamine or cytotoxic drugs (or plasmapheresis) for patients with mononeuritis, gangrene, or leg ulcers, and nonsteroidal antiinflammatory drugs, antimalarials, gold, or penicillamine for sensory neuropathy or digital lesions. Four patients died, two deteriorated, and seven were stable or improved, a finding that was also similar to the experiences of others. Rheumatoid vasculitis is an uncommon, potentially catastrophic syndrome with varying clinico-pathologic features that have different prognostic implications and should be managed individually.     

Not for sale,not even for rent: just say no. Thoughts about the American College of Rheumatology adopting a code of ethics

Medicine and industry have a special relationship. In many instances our interests are concordant and our interactions mutually beneficial. There are areas, however, where potential ethical and professional conflicts arise. Such an area is industry gifts and relationships. Gifts and relationships obligate. Acceptance of "gifts" or industry/commercial benefit(s) assumes obligations of grateful conduct, grateful use, reciprocation, and response. Increasing and compelling data document that industry support, gifts, hospitality, generosity, and other contributions clearly influence physicians. Physicians aspiring to the highest standards of professionalism will consider these issues in their personal conduct. Physicians with leadership responsibilities, and the organizations they serve, will eschew gifts and relationships and their inevitable conflicts. While these issues may seem difficult, I suggest they are really rather simple. As this is a time when so much is commercialized, when so much is for sale, when so little public confidence is left in our once noble profession, there is before us an opportunity to not compromise our ethics or our integrity, but rather assert the highest possible standards of professionalism, to remember that we serve our patients, and to champion their welfare. We should certainly not be for sale, not even for rent. We should say an emphatic "no." We should affirm our honor and integrity. The sages wrote "there are three 'crowns' (symbols of earthly accomplishment, stature, dignity, and respect): that of learning, that of priesthood, and that of royalty; but the 'crown' of a good name is the most exalted of all" (Talmud. Avot 4: 17). Let us individually and together, as the ACR, have a good name. Just say no.     

Incidental paranasal sinus abnormalities on MRI of the brain

T2-weighted magnetic resonance imaging (MRI) presents paranasal sinus pathology with remarkable clarity. However, it has yet to be demonstrated that all MRI findings represent true pathology and not minor or incidental findings of no consequence. In an effort to resolve this question, we have analysed retrospectively 263 consecutive T2-weighted MRI examinations of the head performed for indications not associated with possible sinus pathology. We examined these studies for abnormally increased signal in the paranasal sinuses and the sites of involvement. Mucoperiosteal thickening, mucus retention cysts, air-fluid levels or total sinus opacification were recorded. Of the 263 studies examined, 65 (24.7%) demonstrated abnormalities in the paranasal sinuses. We conclude that because of its great sensitivity MRI will often detect abnormalities in the paranasal sinuses which are unrelated to the patients' presenting problems.     

Food induced ("allergic") arthritis: inflammatory synovitis in rabbits

Progress in understanding rheumatoid (RA) and inflammatory arthritis has been limited in part because there has been no widely accepted animal model of naturally occurring human disease and because the clinical syndrome of RA may reflect the expression of multiple etiologies. We have considered that inflammatory joint disease may be induced and/or exacerbated by food related antigens. To facilitate our investigations, we studied inflammatory synovitis in rabbits induced by oral exposure to environmental antigens. In our preliminary experiments, we examined 9 Florida White, 30 New Zealand White, and 9 Old English rabbits. They were nourished with normal rabbit chow supplemented with either water or cow's milk beginning at age 7 to 26 weeks and observed for 81 to 204 days. Animals were then sacrificed. Histological sections of the knees were examined and graded in a blinded fashion for synovial cell hyperplasia, inflammation, and lymphoplasmocytic infiltration. In addition, serum levels of IgG antimilk, IgG antibovine serum albumin, IgG anticasein, and IgG-C3 complexes were quantified. We found no abnormalities among Florida White rabbits but observed histological synovitis in 53% of the milk fed New Zealand White (9/17), 40% of the water fed Old English (2/5), and all of the milk fed Old English rabbits (4/4) (p = 0.05, milk fed vs water fed animals). Milk fed animals had significantly (p less than 0.0005) greater levels of antibodies and complexes than water fed animals. Our data suggest that environmental antigens may be arthritogenic for some rabbit strains. These observations may provide an important model for the study of inflammatory joint disease analogous to oral, environmental antigen exposure in man.     

How to evaluate patients for rheumatic diseases

The rheumatic diseases encompass many common and uncommon disorders. The information derived from a careful history and physical examination can help define the urgency of the problem, classify the disease, provide diagnosis, and permit optimal therapy.     

Magnetic resonance imaging in patients with inflammatory arthritis of the knee

Summary Magnetic resonance imaging (MRI) permits visualization of anatomic structures not appreciated by conventional radiographic imaging and may quantify inflammatory disease and its progression with greater sensitivity than available techniques. We therefore compared MRIwith clinical evaluation and with radiographic examination of 17 patients with inflammatory arthritis of the knee. We sought to determine anatomic integrity of bone, cartilage, menisci, and ligaments, and to quantify joint effusion and synovial proliferation. Patients studied had rheumatoid arthritis (10patients), juvenile rheumatoid arthritis (4patients), ankylosing spondylitis (1 patient), and monoarticular arthritis (2 patients). In all patients MRI revealed clinically important abnormalities not detected by physical or conventional radiographic exams. These included proliferative synovitis (13 patients), cartilage thinning (2 patients), cartilage erosion (8 patients), bone infarction (1 patient), meniscal injury (1 patient), and synovial invagination into bone (1 patient). Also MRI indicated inflammatory disease to be quantitatively greater than had been appreciated on clinical examination or routine X-ray studies-proliferative synovitis (12 patients), erosion (7 patients), effusion (8 patients), cartilage thinning (11 patients), and ligamentous/meniscal damage (1 patient). These findings led to reassessment of anatomic staging and influenced therapeutic decision for these patients. Thus MRI provides clinically important information about joint integrity and inflammatory disease, with a sensitivity and resolution considerably beyond conventional techniques.     

Serum and synovial fluid IgG,IgA and IgM antigammaglobulins in rheumatoid arthritis

Antigammaglobulins of IgG, IgA and IgM classes were measured in normal individuals and in patients with osteoarthritis or rheumatoid arthritis. Serum IgG and IgA and synovial fluid IgG antigammaglobulin levels were significantly higher in patients with rheumatoid arthritis than in other individuals, with highest levels occurring in patients with positive latex fixation tests. IgM antigammaglobulins were elevated only in patients with latex positive rheumatoid arthritis. Increased serum levels of IgG, IgA and IgM antigammaglobulins were each associated with clinical findings of severe rheumatoid arthritis. Increased levels of serum and synovial fluid IgG and IgM antigammaglobulins were each associated with diminished serum and synovial fluid complement levels.     

Modulation of human mononuclear cell responses by neutrophil-derived factors

We previously reported that neutrophil (PMN)-derived factors modulated human mononuclear cell (MNC) responses. These interactions are important in understanding MNC localization, growth, and activation in inflammatory events such as occur in the rheumatoid synovium. We have partially identified and characterized a human neutrophil-derived, lymphocyte-enhancing factor (N-LEF). Highly purified PMN, devoid of MNC or platelets, were obtained by density gradient sedimentation. Supernatants (spt) were prepared from PMN phagocytosis of complement-coated zymosan particles. N-LEF was determined by [3H]TdR uptake or Ig secretion by stimulated MNC of cell lines. Neutral protease activity was quantitated by digestion of 125I-labeled Hb. Sodium dodecylsulfate (SDS) polyacrylamide gel electropheresis (PAGE) was carried out in 15% gels. We found (1) N-LEF biologic activity was cold stable, heat labile, nondialyzable, and diminished at acid pH (less than 4) or alkaline pH (greater than 10); (2) N-LEF biologic activity was abrogated by human plasma; (3) spt contained neutral protease and granule-associated but not cytoplasmic enzyme activities; (4) protease activities (for Hb, fibrin, ATEE, and Ac-Phe-BNa) were recovered from aprotinin-sepharose affinity columns and contained approximately 25,000 and approximately 28,000 molecular weight material on SDS-PAGE; (5) absorbtion of N-LEF spt on aprotinin-sepharose diminished both protease and biologic activities; and (6) N-LEF biologic activity and nonelastase neutral protease activity were found in approximately 13,000 mol wt fractions of Sephadex G100 (where cathepsin G chromatographs). Our observations suggest that phagocytosis of immune complexes by PMN induces release of a mononuclear cell enhancing factor, N-LEF, which may be an important mediator of inflammation, promoting transition from an acute to a chronic inflammatory response. Biologic properties of N-LEF are those of cathepsin G.