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D L Conn

Publications and source records attributed to D L Conn.

At least 19 recordsLinked to original sources
PubMed1992

The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis.

OBJECTIVE: To explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis. DESIGN: Case series of patients with seropositive rheumatoid arthritis. SETTING: The outpatient clinic of the Division of Rheumatology, Mayo Clinic. PATIENTS: One hundred and two patients with seropositive, erosive rheumatoid arthritis and a minimum disease duration of 3 years. MEASUREMENTS: Patients were genotyped for both HLA-DRB1 alleles and were categorized according to the expression of one or two disease-linked HLA-DRB1 alleles. Identification of HLA-DRB1 alleles was done by the polymerase chain reaction and subsequent oligonucleotide hybridization. Homozygosity for allelic variants was confirmed by sequence analysis. Immunogenetically defined patient subgroups were retrospectively evaluated for joint destruction and patterns of disease manifestation, including rheumatoid organ disease. RESULTS: Of 102 patients, 98 (96%) expressed the disease-linked sequence polymorphism. Forty-seven patients (46%) carried a double dose of the relevant sequence stretch: Twenty-eight patients expressed HLA-DRB1*04 variants on both alleles, and 19 combined an HLA-DRB*04 variant with HLA-DRB1*0101 or DRB1*1402. Nodular disease was present in 100% of patients typed as HLA-DRB1*04/04 and in 59% of patients typed as HLA-DRB1*04 and who had inherited only a single dose of the disease-linked sequence polymorphism (P < 0.0001). Major organ systems were involved in 61% and 11% of these two patient groups, respectively (P < 0.0001); and joint surgery was required in 61% and 25% (P < 0.002), respectively. Patients typed as HLA-DR*04/01 had intermediate clinical courses. CONCLUSION: Genotyping patients with rheumatoid arthritis for both HLA-DRB1 alleles identifies clinical subsets with distinct profiles of disease manifestations.

Aged↗
PubMed1992

Vasculitis associated with malignancy.

A large variety of vasculopathic syndromes are uncommonly associated with malignancies. Vasculitis is usually manifested by skin lesions and is generally associated with hematologic malignancies rather than solid tumors. Evidence of autoantibodies, immune complexes, and complement consumption is typically absent. Myelodysplastic syndromes can be confidently linked to vasculitis on the basis of recent literature. The temporal relationship of malignancy to vasculitis development is variable except that vasculitis generally follows the discovery of hairy cell leukemia and splenectomy. Vasculitis may occasionally be a complication of chemotherapy, radiation therapy, and bone marrow transplantation. Occasionally, malignant disorders may mimic vasculitic syndromes. The etiopathogenesis of vasculitis in patients with malignant disorders is unknown. The recent literature on vasculitis and malignancy addresses predominantly case reports and small patient cohorts and identifies clinical characteristics rather than pathogenic mechanisms.

Adult↗
PubMed1991

Rheumatic manifestations in myelodysplastic syndromes.

The myelodysplastic syndromes are characterized by ineffective hematopoiesis with possible transformation to acute nonlymphocytic leukemia. We describe a patient with refractory anemia with excess blasts with unusual rheumatic manifestations of vasculitis, migratory synovitis, arthralgias, and myalgias. A retrospective review over a 6-month period of 162 patients with myelodysplastic syndromes found 16 patients (10%) with several rheumatic manifestations. We divided these manifestations into 4 different categories: cutaneous vasculitis, "lupus-like syndrome," neuropathy, and patients with both a rheumatic disease and a myelodysplastic syndrome. There were 7 with cutaneous vasculitis including leukocytoclastic vasculitis and other individual cases of urticarial vasculitis and panniculitis; 3 with lupus-like manifestations with histological evidence of an inflammatory process; 3 with neuropathic manifestations including peripheral neuropathy, mononeuritis with foot drop, and chronic inflammatory demyelinating polyneuropathy; and 3 patients in which their myelodysplastic syndrome was diagnosed after their rheumatic disease was known, including rheumatoid arthritis. Sjögren's syndrome and mixed connective tissue disease. The class with refractory anemia with excess blasts had 9 patients with rheumatic manifestations but also had the largest number of patients in the study (46/162 or 29%). Three of the 16 patients died, all from the refractory anemia with excess blasts class, reflecting the known mortality in this group of patients. We believe there is a significant association between myelodysplastic syndromes and rheumatic manifestations.

Adult↗
PubMed1990

Polyarteritis.

Polyarteritis is reviewed in detail including a discussion of the cause of arteritis and the effect on blood vessel physiology. The clinical feature of polyarteritis and an approach to the diagnosis are discussed. The controversies in the management of polyarteritis are reviewed, and new approaches to the management are introduced.

Adult↗
PubMed1990

Vasculitis associated with rheumatoid arthritis.

Vasculitis may accompany rheumatoid arthritis. One must distinguish between vascular involvement associated with the pathogenesis of rheumatoid arthritis, isolated digital vasculitis, and the syndrome of clinical rheumatoid vasculitis. The cause of clinical rheumatoid vasculitis is unknown. High titers of rheumatoid factor, cryoglobulins, diminished circulating complement, an increased prevalence of HLA-DR4, and the pathologic findings suggest an immune etiology. However, similar, but perhaps less pronounced, abnormalities occur in uncomplicated rheumatoid arthritis, and these findings are not universal in complicating vasculitis. Classic cutaneous clinical manifestations include ischemic ulcers, digital gangrene, and palpable purpura. Mononeuritis multiplex is another classic presentation of rheumatoid vasculitis. Small digital infarctions may accompany other manifestations in clinical vasculitis or may occur alone as isolated digital arteritis, in which case the prognosis is relatively favorable. Weight loss, pleuritis, pericarditis, ocular inflammation, splenomegaly, hepatomegaly, and Felty's syndrome have also been reported in association with rheumatoid vasculitis. Although renal involvement has been considered unusual in rheumatoid vasculitis, several studies suggest that this may be more common than previously recognized. Ideally, a biopsy or an angiogram confirms the diagnosis of rheumatoid vasculitis, but often the diagnosis rests upon the clinical picture. In general, blind biopsies are not helpful, although one series indicated that a blind rectal biopsy may be an exception to this rule. An elevated erythrocyte sedimentation rate, increased C-reactive protein level, anemia, thrombocytosis, hypoalbuminemia, and a positive rheumatoid factor are common laboratory findings. Leukocytosis, hypergammaglobinemia, leukocytopenia, an elevated creatinine level, and minimal abnormalities of the urinary sediment also occur in patients with rheumatoid vasculitis. However, these abnormalities overlap in patients with uncomplicated rheumatoid arthritis, and their role in distinguishing rheumatoid vasculitis from uncomplicated rheumatoid arthritis is limited. Other immunologic tests have no established clinical role in diagnosing rheumatoid vasculitis. Therapy depends upon the clinical manifestation of rheumatoid vasculitis. Uncomplicated rheumatoid arthritis deserves appropriate therapy, and general attention to nutrition, cessation of tobacco, and control of blood pressure are indicated for all patients. Isolated digital vasculitis generally requires no more than the usual treatment for uncomplicated rheumatoid arthritis. Appropriate dermatologic management is indicated for ischemic ulcers. Most clinical experience in managing more symptomatic rheumatoid vasculitis has focused on glucocorticosteroids, D-penicillamine, and cytotoxic immunosuppressive drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Arthritis, Rheumatoid↗
PubMed1990

Rifampin therapy in rheumatoid arthritis.

Several second-line antirheumatic agents possess both immunosuppressive and antimicrobial properties. Rifampin is an antimicrobial agent recently found to exhibit immunosuppressive activity in both animal and human studies. Intraarticular rifamycin SV, a rifampin derivative, has been reported to cause dramatic improvement in gonarthritis in 15 patients with rheumatoid arthritis (RA). These reports along with the personal observation of spontaneous improvement of arthritic symptoms in 2 patients with RA treated with rifampin at our institution, prompted us to conduct a pilot study using oral rifampin at 600-1200 mg daily in 8 patients with active, adult onset, seropositive RA. Although, no clinically important or statistically significant improvement occurred in any of the outcome variables measured (p greater than 0.12), the power of this study to detect such differences was limited. Alkaline phosphatase increased modestly in 7 patients. One patient developed an acute, drug induced, flu-like syndrome with marked elevation of liver enzymes which resolved promptly with drug withdrawal. We conclude that the potential effectiveness of oral rifampin therapy in RA is doubtful.

Administration, Oral↗
PubMed1989

Update on systemic necrotizing vasculitis.

The systemic necrotizing vasculitides are classified into vasculitic syndromes on the basis of the pattern of clinical and pathologic involvement. The vasculitides have certain common clinical and laboratory abnormalities. Systemic necrotizing vasculitis is diagnosed on the basis of clinical features, and the vascular nature of the disease is determined by biopsy of involved tissue or angiography. The outcome is dependent on the extent of visceral involvement. Vascular inflammation influences the physiologic features of the vessel and may trigger vasoconstriction. Although glucocorticoids combat the inflammation, they may augment vasoconstriction and platelet aggregation. These effects must be considered in designing a management approach and in evaluating the cause and management of ischemic complications.

Arachidonic Acids↗
PubMed1989

Peripheral neuropathy in primary Sjögren's syndrome.

Sjögren's syndrome (dryness of eyes, mouth, and other mucous membranes) may be associated with disease of joints, blood, internal organs, skin, and central and peripheral nervous systems. We reviewed 33 cases of primary Sjögren's syndrome and peripheral neuropathy evaluated by neurologic examinations and EMG at the Mayo Clinic from 1976 to 1988, and studied sural nerve biopsy specimens in 11 of them. Symmetric sensorimotor polyneuropathy occurred most frequently, followed by symmetric sensory neuropathy. Autonomic neuropathy, mononeuropathy, or cranial neuropathy (especially trigeminal neuropathy) was superimposed on generalized neuropathy in approximately one-fourth of patients. The course generally was slowly progressive, except for a few patients who may have improved with prednisone therapy. Although spinal ganglion involvement might have accounted for some of the clinical and neurophysiologic findings, we found evidence that necrotizing vasculitis was involved in fiber degeneration. All nerve biopsies revealed perivascular inflammatory infiltrates and other vessel abnormalities, which were diagnostic in two cases and strongly suggestive of necrotizing vasculitis in six cases. Axonal degeneration predominated over demyelination and sometimes was focal or multifocal. In neuropathy of unknown cause, particularly if it is sensory, autonomic, or involves trigeminal nerve, consider Sjögren's syndrome.

Adult↗
PubMed1989

Characterization of lymph node histology in adult onset Still's disease.

Adult onset Still's disease is an acknowledged cause of fever of unknown origin. Eight patients with adult onset Still's disease each had a lymph node biopsy as part of their initial evaluation. Seven of 8 biopsies exhibited intense, somewhat atypical, paracortical immunoblastic hyperplasia. This nodal histology, while not specific for the disorder, appears distinct from that associated with rheumatoid arthritis, Sjögren's syndrome, and systemic lupus erythematosus. This paracortical cellular proliferation with apparent nodal effacement, along with atypical immunoblasts, can simulate lymphoma. Adult onset Still's disease should be added to the differential consideration of benign lymph node histology simulating lymphoma.

Adult↗
PubMed1987

Nonsystemic vasculitic neuropathy.

Among 65 patients with necrotizing vasculitis, 45 had systemic and 20 had nonsystemic vasculitic neuropathy. In nonsystemic vasculitic neuropathy, clinically only nerves are affected; there are no, or few, constitutional symptoms or serological abnormalities. The clinical and pathological features are those of an ischaemic neuropathy caused by a necrotizing vasculitis of small arterioles. These 20 patients had neuropathic symptoms for a median time of 11.5 yrs (range 1-35 yrs). The clinical pattern of neuropathy was that of multiple mononeuropathy in 13, asymmetric neuropathy in 4, distal polyneuropathy in 3, and sensory polyneuropathy in 1. As compared with their initial evaluation, 8 are now worse, 5 are better, 4 are approximately the same, and 3 are dead from unrelated causes. Prednisone was thought to prevent the development of new lesions in some cases. By contrast, of the 41 patients with systemic necrotizing vasculitis whose outcome is known, 12 are dead (median time, 1.5 yrs, range 3 months-8 yrs) and 29 are alive (median time, 6 yrs, range 6 months-22 yrs).

Adult↗
PubMed1987

Pulmonary disease in polymyositis/dermatomyositis: a clinicopathological analysis of 65 autopsy cases.

The clinical and autopsy records of 65 patients with either polymyositis (24) or dermatomyositis (41) and pulmonary disease were reviewed. Pulmonary symptoms were recorded in 43 of the cases and included dyspnoea in 31, cough in 23, and chest pain in six. Interstitial lung disease was noted at autopsy in 27 patients; almost half of these had arthritis. Bronchopneumonia was found in 35 patients, 31 of these had received prednisone. Dysphagia was present in a similar proportion of patients with and without pneumonia. Pulmonary vasculitis was seen in five patients; pulmonary symptoms, arthritis, and raised erythrocyte sedimentation rate were present in four of these cases and all five had associated interstitial lung disease. Other pulmonary manifestations included pulmonary oedema, primary pulmonary malignancy, diffuse alveolar damage, fibrinous pleuritis, pulmonary emboli, and diaphragmatic atrophy. The mean survival after disease onset was 29 months but was much less for those with interstitial lung disease and pulmonary vasculitis.

Adult↗
PubMed1986

Vasculitis in hairy cell leukemia: review of literature and consideration of possible pathogenic mechanisms.

Systemic vasculitis is an unusual but recently recognized complication of hairy cell leukemia. We studied this relationship further in an attempt to better understand pathogenetic mechanisms of vasculitis. We examined the records of 129 cases of hairy cell leukemia seen at the Mayo Clinic between 1976 and 1983, and identified 2 cases with evidence of systemic vasculitis. The first of these cases is discussed in detail. Immunologic studies were performed but we were unable to demonstrate the presence of shared antigen on hairy cells and endothelial cells. The literature is reviewed and reports of this association are summarized. Possible mechanisms of vascular injury are discussed.

Adult↗
PubMed1986

Interference with total hemolytic complement assay in rheumatoid arthritis: correlation with disease activity.

A subgroup of patients with rheumatoid arthritis (RA) whose sera agglutinated sensitized sheep erythrocytes used for total hemolytic complement determination has been identified. These patients have higher titers of rheumatoid factor (RF) and more severe rheumatoid disease compared to controls. The agglutination of sensitized sheep erythrocytes by sera of some patients with RA may be related to qualitative or quantitative variations in their RF.

Adult↗
PubMed1986

Rheumatoid vasculitis: survival and associated risk factors.

We describe the clinical and laboratory characteristics of 52 patients with rheumatoid vasculitis whose condition was diagnosed at a tertiary care center between 1974 and 1981, and we report their survival and the factors that were associated with decreased survival. The patients with rheumatoid vasculitis had decreased survival in comparison with an age-, sex-, and region-matched general population. Their survival was also decreased in comparison to that of an incidence cohort of community patients with rheumatoid arthritis. In the latter cohort, decreased survival was confined to those patients with classic but not definite rheumatoid arthritis. After partial correction for referral bias, we found no difference in survival between the cohort with rheumatoid vasculitis and the cohort with classic rheumatoid arthritis. We found that the age at diagnosis of rheumatoid vasculitis, the therapeutic decisions before and at diagnosis, and the referral distance were the best predictors of survival. Abnormal urinary sediment and hypergammaglobulinemia also predicted poor survival, but because of a lack of specificity in a small number of clinically abnormal values, we urge a cautious interpretation of their importance.

Adult↗