Biomedical subjects
Publications and source records attributed to R S Panush.
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.
Thirty-eight patients with incomplete lupus erythematosus (ILE) (defined as the presence of fewer than four of the criteria of the American College of Rheumatology for systemic lupus erythematosus [SLE]) were identified and compared with 42 patients with SLE. Both groups were comparable with respect to age, sex, and race. Patients with ILE had symptoms for an average of 38 months before seeking rheumatologic care and were followed up for a mean of 19 months; patients with SLE averaged 9 months with symptoms before their diagnosis was made and were followed for a mean of 30 months. Characteristic clinical features of patients with ILE included positive antinuclear antibody titers (83%), polyarticular nonerosive arthritis (47%), and cutaneous findings (61%). These were comparable with findings in the the SLE group. However, patients with ILE had significantly fewer systemic manifestations than did those with SLE. Patients with ILE were treated with nonsteroidal anti-inflammatory drugs more frequently (47%) than were patients with SLE, while the latter group received more topical and oral corticosteroids and immunosuppressives. Only two of the patients with ILE went on to have typical SLE. Thus, ILE may be frequent, mild, and relatively stable or benign, apparently evolving slowly if at all into SLE or other rheumatic disease.
The loss of immune competence that occurs with aging may be responsible for increased morbidity and mortality in elderly individuals. Pharmacologic modulation of the immune response might reverse the immunologic aberrations associated with aging. We, therefore, investigated the effects of isoprinosine, an immunoenhancing drug, on selected in vitro immune responses in elderly subjects. Subjects studied were 65 years of age or older, and all had chronic diseases. We chose this population since they were at greatest risk for morbid events. Isoprinosine significantly enhanced mitogen-stimulated mononuclear cell proliferation, did not affect unstimulated cell growth, and needed to be present for the entire culture period for maximum effect. Isoprinosine is a potent in vitro immunoenhancing agent in aged humans.
Vasculitis is a syndrome which may complicate certain infectious, rheumatic, and allergic diseases. We identified 13 patients, over the past 17 years, who had both vasculitis and lympho- or myeloproliferative disorders and relate their clinical, laboratory, histologic, and immunologic features, course, therapy, and outcome. Nine patients were male, 4 female; ages ranged from 28 to 82 years. Ten of 13 patients presented with cutaneous vasculitis antedating malignancy by an average of 10 months. Three of 13 developed cutaneous vasculitis after malignancy. A statistically significant association between cutaneous vasculitis and lympho- or myeloproliferative malignancies was noted when compared with all other tumors. Dermatologic manifestations included palpable purpura (5 patients), maculopapular eruptions (4), urticarial and petechial lesions (3), and ulcers (1). Hepatitis B surface antigen, Coombs antibodies, rheumatoid factor and antinuclear antibodies were not found. Serum cryoglobulins were detected in 3 patients; serum C3 and C4 were normal in 8 of 9 patients evaluated. Histologic examinations revealed necrotizing leukocytoclastic vasculitis with disruption of endothelial integrity, destruction of endothelium, and neutrophil infiltration. Occasional perivascular mononuclear cell invasion was also noted in 4 patients. Immunofluorescent staining for IgG, IgA, IgM, C3, and C4 was negative in all patients studied. Symptoms were, in general, poorly responsive to therapy, which included nonsteroidal antiinflammatory drugs, antihistamines, antiserotonin agents, and corticosteroids. Chemotherapy directed at the underlying malignancy was also generally ineffective, although the vasculitis appeared to lessen in severity. Vasculitis appeared to lessen in severity as bone marrow function deteriorated. Ten patients died, all as a direct result of their malignancy. We have described a unique clinical syndrome of lympho- and myeloproliferative disease presenting with small-vessel vasculitis. Recognition that rheumatic symptoms may reflect or antedate malignancy may permit early diagnosis, aggressive treatment, and elucidation of pathogenesis.
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Occasionally patients with overlapping features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), termed "rhupus," have been encountered. We wanted to ascertain the frequency of such patients and determine whether they represent a unique overlap syndrome. Of approximately 7000 new patients evaluated over 11 years, we identified six patients who had, on the average, 6.7 American Rheumatism Association criteria for RA and 4.2 criteria for SLE. Criteria for RA included chronic symmetric arthritis with morning stiffness (six patients); subcutaneous nodules (two patients); positive rheumatoid factors test (four patients); and radiologic erosions (four patients). The criteria for SLE included malar rash (three patients); discoid lupus erythematosus (two patients); biopsy-proved nephritis (one patient); photosensitivity (one patient); leukopenia/thrombocytopenia (four patients); positive antinuclear antibodies or lupus erythematosus cell test (six patients); hypocomplementemia (two patients); and abnormal results from skin biopsy (two patients). During observations of up to ten years, the conditions of three patients were stable or improved, one died, and two were unavailable for follow-up. Patients usually did not have conditions that evolved to classic rheumatic disease patterns. Rhupus was not common and did not occur more frequently (0.09% prevalence among our patients) than expected from chance concurrence of SLE and RA (calculated at 1.2%). These observations confirm that rhupus indeed exists as a syndrome manifested by patients sharing features of probable coincidental concurrence of RA and SLE, but not as a unique clinical pathologic or immunologic syndrome. Appreciation of these patients with rhupus is important since their therapy and outcome differ from those having RA or SLE alone.
Early detection of inflammatory arthropathy is notoriously difficult with standard radiographic techniques. We therefore assessed bone turnover with technetium Tc 99m medronate in 16 patients with persistent polyarthralgias who had no clinical synovitis, normal radiographs, and nondiagnostic results from laboratory evaluations. Abnormal scans were found in 11 of 16; five were unremarkable. Scan abnormality corresponded with symptomatic joints (11 of 11 patients). These 11 patients had normal test results for rheumatoid factor, antinuclear antibody, and HLA-B27. Patients with abnormal scans were treated with nonsteroidal antiinflammatory drugs or analgesics (11 of 11), hydroxychloroquine sulfate (four), or gold salts (one), with improvement (nine of 11); patients with normal scans (five of five) were treated successfully with nonsteroidal antiinflammatory drugs or analgesics and reassurance. One patient with a normal scan developed sarcoidosis; one, hypermobility syndrome; and one, a viral syndrome. Two patients had no diagnosis. Abnormal technetium Tc 99m medronate scans in patients with previously undiagnosed polyarthralgias suggested inflammatory arthropathy and influenced management decisions with favorable therapeutic outcomes.
Recurrence of stenosis occurs in 15% to 45% of patients who have undergone successful percutaneous transluminal coronary angioplasty. Restenosis is believed to represent an accelerated form of atherosclerosis. It is recognized that the human coronary artery response to balloon dilatation reflects complex interactions among mediators of tissue injury and inflammation. Prominent among these are monocytes/macrophages, neutrophils, platelets, smooth muscle cells and endothelial cells. Certain changes suggest the potential for immunologically mediated inflammatory responses. It is therefore considered that restenosis, at least in part, reflects perturbations of cellular mediators of tissue injury leading to accelerated atherosclerosis, and that modulation of these processes by glucocorticoids might be therapeutically beneficial.
Silicone generally has been regarded as a biologically inert material. However, recent reports suggest that inflammatory responses to silicone occur. There is some experimental and clinical evidence of a direct inflammatory response to the presence of liquid or particulate silicone. These include granulomatous skin reaction to injected silicone, synovitis around silicone prosthetic joints, and lymphadenopathy proximal to silicone prostheses. There are case reports of systemic rheumatic disease following silicone prostheses, but no definitive proof of a direct relationship between silicone prostheses and systemic disease. The clinical features of the reported cases following breast augmentation include breast tenderness, axillary adenopathy, sclerodermatous skin changes, arthritis, Raynaud's phenomenon, rheumatoid factors, and ANAs. Prior epidemiologic evidence and the number and consistency of our own and others' clinical findings suggest that silicone may indeed be associated with inflammatory processes and rheumatic diseases.
Technetium-99M pyrophosphate (TcPYP) nuclear scans of extremities were performed on 15 patients at 10 minutes and 2 hours after isotope injection. Scans were carried out both to confirm the diagnosis of myositis and to direct subsequent muscle biopsy. Five of six patients with clinical features strongly suggestive of inflammatory muscle disease had positive scans. All muscle biopsies performed at areas of increased isotope uptake showed inflammatory muscle disease. All nine patients not suspected of active inflammatory muscle disease had negative scans. Two of these underwent muscle biopsy with negative results. Our observations suggest that TcPYP muscle scans may be useful both to confirm the clinical suspicion of inflammatory muscle disease and in directing the choice of site for muscle biopsy.
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We identified two siblings with exercise-induced anaphylaxis who share the HLA haplotype A3-B8-DR3 with their atopic father. The index case, a 16-year-old female, noted initial episodes at age 13. Intense pruritus, urticaria, facial edema, choking sensation, nausea, hypothermia, and collapse followed vigorous running but not swimming, cycling, racquetball, solar exposure, or cold exposure. Neither antihistamine, antiserotonin, anticholinergic nor epinephrine therapy was entirely effective or protective; only modification of running prevented episodes. Three similar episodes were noted at age 15 years by a brother who, now age 25, relates a 4-year history of seasonal rhinitis and exercise-related urticaria without anaphylactoid reaction. The remainder of the family (father, 47; mother, 46; brother, 22 years) does not have exercise intolerance. The father has allergic rhinitis; his nephew suffers exercise-induced urticaria without collapse. HLA typing revealed the father to be A1-B8-DR3, A3-B8-DR3; the symptomatic daughter to be A3-B8-DR3, A30-B5-DR8; and the symptomatic son to be A3-B8-DR3, A30-B5-DR8. The asymptomatic mother was A30-B5-DR8, A2-B7-DR5 and the asymptomatic son A1-B8-DR3, A30-B5-DR8. We describe exercise-induced anaphylaxis in a unique familial setting, perhaps linked to the HLA haplotype A3-B8-DR3.
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Little information is available regarding the long-term effects, if any, of running on the musculoskeletal system. We therefore compared the prevalence of degenerative joint disease among 17 male runners (mean age, 56 years; height, 180 cm [5 ft 11 in]; and weight, 73.02 kg [161 lb] with 18 male nonrunners (mean age, 60 years; height, 178 cm [5 ft 10 in]; and weight, 78 kg [171 lb]). Running subjects (53% marathoners) ran a mean of 44.8 km (28 miles)/wk for 12 years. Pain and swelling of hips, knees, ankles, and feet and other musculoskeletal complaints among runners were comparable with those among nonrunners. Radiologic examinations (for osteophytes, cartilage thickness, and grade of degeneration) also were without notable differences among groups. We did not find an increased prevalence of osteoarthritis among the runners. Our observations suggest, within the limits of our study, that long-duration, high-mileage running need not be associated with premature degenerative joint disease in the lower extremities.
Suggestive, but largely unproven, observations have associated arthritis with environmental antigens, including foods. We studied a patient with inflammatory arthritis in a prospective, "blinded," controlled fashion to determine whether her symptoms were associated with food sensitivities. This 52-year-old white woman with 11 years of class I, stage I, active disease, had symptomatic exacerbations allegedly associated with meat, milk, and beans. We observed an increase in symptoms following an unblinded food challenge and then studied her in our clinical research unit. On her normal diet for 6 days, she averaged 30 minutes of morning stiffness, 9 tender joints, 3 swollen joints, 87% subjective assessment (100% = best possible), and 89% examiner assessment. While she was fasting (3 days) or taking Vivonex (2 days), we noted no morning stiffness, tender joint score of 1, swollen joint score of 0, and assessments of 100% (P less than 0.05 versus normal diet). She was then nourished with Vivonex for 33 days without difficulty and challenged in a blinded fashion at mealtimes with lyophilized foods placed into opaque capsules. Four milk challenges (equivalent to greater than or equal to 8 ounces per meal) produced up to 30 minutes of morning stiffness, 14 tender joints, 4 swollen joints, subjective assessment of 85%, and objective assessment of 80% (P less than 0.05 versus fasting-Vivonex), peaking 24-48 hours postchallenge. Placebo and other foods (lettuce and carrots) were without effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Six patients are described whose myeloproliferative disorders were complicated by inflammation in small, predominantly cutaneous blood vessels. The clinical manifestations of the vasculitis included palpable purpura, urticaria, maculopapular lesions, and erythema multiforme. Vascular inflammation was confirmed by skin biopsy. Two patients experienced fleeting, asymmetrical nondestructive arthritis. Transient proteinuria complicated one case and was the only suggestion of visceral vasculitis. The clinical features of cutaneous vasculitis antedated bone marrow deterioration in four patients and diminished as bone marrow function worsened in all patients. Oral corticosteroids or chemotherapy for the underlying disorder inconsistently affected the clinical course of the cutaneous vasculitis. Myeloproliferative disorders should be considered among disorders that are complicated by inflammation in small blood vessels.