Fatal infections in systemic lupus erythematosus: the role of opportunistic organisms.

The causes of death were examined in patients with systemic lupus erythematosus (SLE) who were cared for at the University of California, San Francisco and who died after 1969. Of the 44 deaths analyzed, 33 patients had autopsies. Infections were common and often determined to be the cause of death. Overall, infections were present in 55 percent (22/44), and judged to be a cause of death in 30 percent (13/44) of all deaths. The infections could be divided into 2 groups: those due to common bacterial organisms and those due to opportunistic infections. These two types of infections occurred with similar frequency. When compared to common bacterial infections, however, the opportunistic infections were more likely to be first diagnosed at autopsy (p = .001). In only 3 of the 15 patients with an opportunistic infection was the diagnosis made antemortem. Failure to diagnose an opportunistic infection early occurred when the infection simulated active SLE, and when the possibility of an opportunistic infection was not aggressively investigated. The most common opportunistic infections were Candida albicans and Pneumocystis carinii. The most common site of opportunistic infection was the lung. Seventeen patients had 27 common bacterial infections, chiefly sepsis from Staphylococcus aureus and aerobic gram-negative organisms. Eight patients had both a common bacterial and an opportunistic infection. Stepwise linear regression analysis showed that death from infection correlated most strongly with prednisone and cytotoxic drug use in the 3 months before final admission. No measure of lupus activity was found to correlate with death from infection, except that hypocomplementemia correlated with death from bacterial infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Mononeuritis multiplex: the yield of evaluations for occult rheumatic diseases.

We identified 35 patients who had electrodiagnostic evidence of mononeuritis multiplex and did not have diabetes or multiple nerve compressions. Their charts were reviewed to determine the etiologies of the mononeuritis multiplex and to determine how often the laboratory examination revealed a rheumatic disease in patients whose initial history and physical examination did not suggest that a rheumatic disease was present. In 11/35 (31%; CI = 17-49) a disorder capable of causing mononeuritis multiplex was diagnosed before the symptoms of mononeuritis multiplex began. Ten had a rheumatic disease; 1 had lymphoma. Nine of the other patients were suspected, on the basis of the history and physical examination, of having new onset of a rheumatic disease. Subsequent laboratory evaluation showed that 5/9 (56%; CI = 21-86) had a rheumatic disease, and 4/9 (44%; CI = 14-79) were unknowns. In 15/35 (43%; CI = 26-61) patients with mononeuritis multiplex, no rheumatic disease was suspected on the basis of the initial history and physical examination. The subsequent laboratory examination revealed an underlying rheumatic disease in 0/15 (0%; CI = 0-18). Mean clinical follow-up of 16 +/- 16 months in the patients with mononeuritis multiplex of unknown cause also failed to identify a rheumatic disease. Overall 19/35 (54%; CI = 37-71) did not have a rheumatic disease or any other known cause. Of the 14 patients with mononeuritis multiplex associated with a rheumatic disease, 5/14 (36%; CI = 13-15) had systemic lupus erythematosus; an additional patient had both lupus and the CREST syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of Wegener's granulomatosis.

The two principal aims in the treatment of Wegener's granulomatosis (WG) are to limit the extent and severity of permanent organ damage by controlling the disease promptly and to minimize the short- and long-term morbidity that often results from therapy. Remission is considered to be the absence of disease activity in any organ system. Once the disease has been controlled by the initial treatment regimen, which is dictated by the degree of disease severity, the focus of therapy shifts to maintaining disease remission, often with medications less toxic than those used to induce remission. The description of WG treatments in terms analogous to cancer chemotherapy (i.e., those designed to induce remissions and those intended to maintain them) is useful in the formulation of current disease management strategies and in the investigation of new therapies for WG.

Vasculitis. A collection of pearls and myths.

Important strides have been made in unraveling the pathophysiologic characteristics of some individual forms of vasculitis, but vasculitides continue to pose enormous challenges for clinicians. Over time, numerous myths and an occasional pearl have arisen from the care of patients with these disorders. In this collection of pearls and myths, we have attempted to pool our knowledge about the clinical care of vasculitis patients.

Development and evaluation of a coordinated, ambulatory rheumatology experience for internal medicine residents.

OBJECTIVE: To develop a compulsory ambulatory rotation in rheumatology for internal medicine residents and to evaluate the educational effect of this rotation. METHOD: All year 2 residents in the program participated in the rotation. The perceived quality of the learning experience was assessed by resident self-evaluation using a visual analog scale. Residents used a similar scale to rate their confidence in managing common rheumatologic problems. A validated multiple choice test was used to measure pre- and post-rotation knowledge of rheumatology and skill in interpreting bone radiographs. RESULTS: On a 1 (no learning) to 5 (superior learning) scale, the mean rating of the rheumatology learning experience was 4.7 +/- 0.5. Residents' confidence in clinical skills significantly increased as well. Scores on the post-rotation rheumatology knowledge test increased 15% compared with pre-rotation scores (P < 0.0001). Confidence and skills in interpreting bone radiology films also significantly improved (P < 0.0001 for both items). CONCLUSION: A relatively brief, subspecialty ambulatory rotation can be developed to expose all residents to a rheumatology curriculum. Such a rotation can increase their confidence, knowledge, and skills in important domains of outpatient rheumatology.

Test characteristics of immunofluorescence and ELISA tests in 856 consecutive patients with possible ANCA-associated conditions.

OBJECTIVE: To examine the test characteristics of immunofluorescence (IF) and enzyme-linked immunosorbent assays (ELISA) in a consecutive series of patients under evaluation for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Using stored sera, we performed a cross-sectional study on 856 consecutive patients tested prospectively for ANCA by IF, Based on guidelines from the 1994 Chapel Hill Consensus Conference (CHCC), we determined each patient's underlying diagnosis by a medical records review without regard to their ANCA status (the CHCC guidelines do not require ANCA as a prerequisite for diagnosis). We grouped patients with forms of vasculitis commonly associated with ANCA into one of 4 types of AAV: Wegener's granulomatosis (n = 45), microscopic polyangiitis (n = 12), Churg-Strauss syndrome (n = 4), and pauci-immune glomerulonephritis (n = 8). We also classified patients without clinical evidence of AAV (92% of all patients tested) into 5 predefined categories of disease (including "other") and an additional category for no identifiable disease. In a blinded fashion, we then performed ELISAs on the stored serum for antibodies to proteinase-3 (PR3) and myeloperoxidase (MPO) and calculated the test characteristics for both ANCA assay techniques. RESULTS: Sixty-nine of the 856 patients (8.1%) had clinical diagnoses of AAV based on CHCC guidelines. The positive predictive value (PPV) of ELISA for AAV was superior to that of IF, 83% versus 45%. For patients with both positive IF tests and positive ELISA tests, the PPV increased to 88%. Both IF and ELISA had high negative predictive values (97% and 96%, respectively). Positive ELISA tests were associated with higher likelihood ratios (LR) than IF (54.2 [95% CI = 26.3, 111.5] versus 9.4 [95% CI = 6.9, 12.7]). The LR of both a positive IF and a positive ELISA was 82.1 (95% CI = 33.3, 202.5). CONCLUSIONS: Compared with IF, an ELISA test fo ANCA was associated with a substantially higher PPV and LR for AAV. This fact, combined with the greater sensitivity of IF, suggests that an effective testing strategy is to perform ELISA tests only on samples that are positive for ANCA by IF.

Bilateral ocular ischemic syndrome secondary to giant cell arteritis progressing despite corticosteroid treatment.

PURPOSE: To report the development of a bilateral ocular ischemic syndrome despite corticosteroid treatment in a patient with giant cell arteritis. METHOD: Case report. RESULTS: Despite receiving high-dose intravenous methylprednisolone and oral prednisone for biopsy-proven giant cell arteritis that presented as a severe anterior ischemic optic neuropathy in the right eye, a patient developed progressive ocular ischemia in that eye as well as an ocular ischemic syndrome in the fellow eye. CONCLUSIONS: Some patients with giant cell arteritis, possibly patients with other underlying systemic vasculopathies, are refractory to what should be adequate treatment with systemic corticosteroids and may develop a bilateral ocular ischemic syndrome.

CNS vasculitis in autoimmune disease: MR imaging findings and correlation with angiography.

BACKGROUND AND PURPOSE: MR findings in CNS vasculitis and their correlation with angiography have not been clearly defined. We therefore explored three hypotheses regarding CNS vasculitis associated with autoimmune disease: 1) MR imaging is highly sensitive; 2) a typical MR appearance exists; and, 3) MR and angiographic findings correlate well. METHODS: We studied 18 patients with CNS vasculitis associated with autoimmune disease, characterized the MR lesions by type, size, number, and location, and correlated the MR findings with those of angiography. RESULTS: All patients with CNS vasculitis had abnormalities on MR studies. On average, four +/- two lesions per patient were detected on MR images. The lesions were located in the subcortical white matter (n = 20), cortical gray matter (n = 16), deep gray matter (n = 16), deep white matter (n = 9), and cerebellum (n = 9). Only 65% of MR lesions were evident on angiograms; 44% of the lesions revealed on angiograms were detected by MR. CONCLUSION: MR imaging is sensitive for CNS vasculitis. Lesions attributable to CNS vasculitis in autoimmune disease are distributed nearly equally among cortical, subcortical, and deep gray matter structures. The modest correlation between MR imaging and angiography suggests that the two techniques provide different information about CNS vasculitis and that both types of studies are needed for the complete assessment of damage caused by vascular abnormalities.

Methotrexate in rheumatoid arthritis: when NSAIDs fail.

Methotrexate has become the agent of choice for rheumatoid arthritis that does not respond to nonsteroidal anti-inflammatory drugs. In appropriately selected patients and with diligent monitoring, methotrexate in low weekly doses is effective and has a much better safety profile than was originally perceived.

Immunopathogenesis, diagnosis, and treatment of giant cell arteritis, temporal arteritis, polymyalgia rheumatica, and Takayasu's arteritis.

Although the causes of giant cell arteritis, polymyalgia rheumatica, and Takayasu's arteritis are not known, the immune system participates in the pathogenesis of these disorders. Many reports indicate that cellular immunity is active in giant cell arteritis. The diagnosis of Takayasu's arteritis has been advanced by magnetic resonance imaging and ultrasonography. Neither technique has replaced angiography as the gold standard for diagnosis, but both may help monitor the response of Takayasu's arteritis to therapy. The diagnosis of giant cell arteritis with a low erythrocyte sedimentation rate is unusual but is more frequent in patients with a history of polymyalgia rheumatica or corticosteroid use. One recent retrospective study suggests that 20 mg/d of prednisolone is as effective as higher doses in treating giant cell arteritis. Other preliminary studies indicate that methotrexate may effectively spare corticosteroid use in giant cell arteritis and Takayasu's arteritis. Angioplasty for renal artery stenosis in Takayasu's arteritis initially cures 30% of patients and improves the condition in 70%; however, the long-term success rate is 50%. New studies demonstrate that patients with giant cell arteritis and polymyalgia rheumatica have an increased risk of hypothyroidism.

Medical therapy for SLE.

Today, the major therapeutic challenge in systemic lupus erythematosus is to preserve the gains provided by corticosteroids while reducing their side effects.

Effect of ethyl adenosine on myocardial flow after coronary artery occlusion.

The effect of ethyl adenosine-5'-carboxylate hydrochloride (EA) was determined in 17 dogs by the radioactive microsphere technique. In both experimental and control animals, microspheres were injected 5 min before (preocclusion period), 60 min after (occlusion period), and 75 min after (saline or vasodilation period) ligation of the left anterior descending coronary artery (LAD). Ten seconds prior to the third microsphere injection, saline was administered to five control animals, and saline with 0.5 mg/kg of EA was given to 12 experimental animals. There was no significant change in myocardial blood flow after saline injection. After EA, mean arterial pressure fell 10% (P less than .001); myocardial blood flow increased 275% (P less than .001) in the nonischemic left circumflex artery (CIRC) area and increased 82% (P less than .01) in the occluded LAD area. In addition, those animals with extensive collateral development showed a significantly greater increase in collateral blood flow than those with minimal collateral development (P less than .05). Thus, EA may increase flow to ischemic areas of myocardium dependent upon the extent of preexistent collateral supply.

Takayasu's arteritis associated with crescentic glomerulonephritis.

We describe the initial course and followup of a 16-year-old white female patient who presented in 1983 with aortitis and rapidly progressive renal failure. Renal biopsy revealed crescentic glomerulonephritis. Segmental occlusions of the distal aorta and both common iliac arteries were demonstrated on aortography. Initially, her renal function and arterial occlusions markedly improved with pulse prednisolone therapy, but 34 months later, the glomerulonephritis and aortitis worsened. This case report, the first of its kind, documents both the association of Takayasu's arteritis with crescentic glomerulonephritis and a marked, though incomplete, response to pulse therapy.

Chronic repetitive trauma: a cause of atypical degenerative joint disease.

Six cases of amateur athletes who have severe atypical degenerative joint disease (DJD) are presented; their histories suggest that chronic, repetitive trauma was causative in the development of their arthropathy. Although many examples of this process have been reported in professional athletes, it has not been reported in amateurs. As participation in athletic activities increases we can, perhaps, expect to see more of this type of DJD in the future.

A pilot study of peer review in residency training.

OBJECTIVE: To explore the utility of peer review (review by fellow interns or residents in the firm) as an additional method of evaluation in a university categorical internal medicine residency program. DESIGN/PARTICIPANTS: Senior residents and interns were asked to complete evaluations of interns at the end-of-month ward rotations. MAIN RESULTS: Response rates for senior residents evaluating 16 interns were 70%; for interns evaluating interns, 35%. Analysis of 177 instruments for 16 interns showed high internal consistency in the evaluations. Factor analysis supported a two-dimensional view of clinical competence. Correlations between faculty, senior resident, and intern assessments of interns were good, although varied by domain. CONCLUSIONS: An end-of-year attitude survey found that residents gave high ratings to the value of feedback from peers.