Robert W. Lightfoot

Laboratory Evaluation in the Diagnosis of Lyme Disease

1. Introduction 1.1 Lyme disease is the most common tick-borne disease in North America. From 1982 through 1994, more than 70 000 cases were reported in North America; most of these cases were in the United States [1]. It is important that clinicians diagnose Lyme disease correctly because efficacious therapy is available and delayed or inadequate treatment can lead to many morbid sequelae. Lyme disease is a complex multisystem disease caused by the spirochete Borrelia burgdorferi [2]. It affects persons of all ages and both sexes. Since the disease was recognized in Connecticut in 1975 [3], endemic areas have been identified in several regions in North America. In more restricted areas in some northeastern and upper midwestern U.S. states, the disease has assumed the characteristics of an emerging epidemic [4-9]. The true incidence is almost certainly underestimated because of under-reporting [10, 11]. 1.2 Most patients develop a distinctive rash, erythema migrans, that is accompanied by such flu-like symptoms as fatigue, headache, mild stiff neck, joint and muscle aches, and fever [12]. Some weeks or months after the initial exposure, symptoms and signs of disseminated disease (particularly neurologic, cardiac, or articular disease) may develop in untreated patients [13, 14]. 1.3 Case definitions of Lyme disease have been developed in the United States for national disease surveillance purposes. A positive serologic test result was initially required for patients who had erythema migrans alone and had not been exposed to Lyme disease in endemic areas [15], but the 1990 criteria established in the Centers for Disease Control and Preventions (CDCs) U.S. Lyme disease national surveillance definition reduced this requirement to a recommendation (Table 1) [16]. These criteria were developed for an epidemiologic case definition intended for surveillance purposes only. However, previous national disease surveillance criteria have been used in clinical studies [17, 18], and such definitions do provide standardization. Standardization allows comparisons of clinical studies and permits the performance of meta-analysis to facilitate development of clinically useful guidelines. Table 1. Criteria for Confirmed Lyme Disease 1.4 Requests for laboratory testing for Lyme disease have increased rapidly. In Wisconsin, for example, it was reported that more than 60 000 tests were being done annually [19]; in New Jersey, 5000 tests were done in 1 week in 1989 [20]. According to market projections for the United States, 2.79 million rapid tests were to have been done for Lyme disease in 1995 [21]. Testing is often done in persons who have only nonspecific signs and symptoms of illness, such as headache, fatigue, myalgia, or arthralgia. Even in highly endemic areas, the pretest probability of Lyme disease in such patients is less than 0.20 (usually much lower). Thus, even when highly experienced laboratories are used, the probability of a false-positive test result is higher than that of a true-positive result. This problem is compounded by the lack of standardized serologic tests for Lyme disease. Comparisons of the test results from different laboratories have shown poor reliability and accuracy; up to 21% of standardized positive samples are missed, and up to 7% of samples from persons with no known exposure are incorrectly identified as positive [22]. 1.5 This background paper provides a quantitative and qualitative evaluation of the predictive value of the laboratory diagnosis of Lyme disease. This evaluation forms the basis for guidelines on clinical diagnosis. Practitioners have been confused by the lack of consensus on diagnostic criteria for Lyme disease. The causes of this controversy arise from a combination of factors: the use of different tests in different laboratories, the use of different criteria to set positive and negative cutoff values for the same tests, different degrees of quality control in different laboratories, and differences in the community prevalence of Lyme disease. 1.6 We address each of these factors and make recommendations for the diagnostic workup of patients suspected of having Lyme disease. 2. Methods 2.1 Data Sources Relevant articles from the medical literature were identified by searching the MEDLINE database for English-language articles or articles with English-language abstracts published from 1982 (when the spirochetal cause of Lyme disease was established [23, 24]) to 1996. The keywords used were Lyme disease, Borrelia burgdorferi, diagnosis, ELISA, Western blot, immunofluorescence assay, polymerase chain reaction, urinary antigen detection, and culture. The computerized literature search was complemented by citations from authorities in the field. 2.2 Study Selection All identified articles were reviewed by using a modification of the methodologic criteria for evaluating diagnostic tests developed by Irwig and colleagues [25]. The included studies had to provide the following material: a clear statement on the test of interest, a description of the study characteristics that used a design that permitted the calculation of sensitivity and specificity, reproducible information on the sampling and clinical details of patients with the disease of interest and on controls (that is, data on the presence or absence of the criteria for Lyme disease described in the U.S. Lyme disease national surveillance case definition) (Table 1), and reproducible information on the reference standard (that is, cases diagnosed by experts who were blinded to the results of the diagnostic tests being evaluated). Because there are systematic differences in the strains of B. burgdorferi in different parts of the world, studies were excluded if they described results in patients outside of North America. When the same cohort of patients was described in more than one report, the results for individual patients were included only once. 2.3 Data Extraction Sensitivity, specificity, and likelihood ratios were calculated by using established methods [26]; a random-effects model was used to combine the proportions from the eligible studies [27]. 2.4 Estimates of Prevalence and Incidence Levels of the endemicity of Lyme disease in the United States can be estimated by using the annual incidence of Lyme disease reported to the CDC [1] (Figure 1). Figure 1. Rates of Lyme disease cases in the United States in 1993 as reported by states to the Centers for Disease Control and Prevention. 2.5 Epidemiologic studies of Lyme disease in communities in the eastern United States provide important information on the emergence of the disease in populations newly at risk, as well as some estimates of incidence and prevalence [29]. In two clusters of cases in New Jersey, risk was related to residence in new suburban housing developments and to occupational exposures among outdoor workers at a military reservation [6, 7]. A study on Fire Island, a barrier island off the southern coast of Long Island, New York, reported a seasonal incidence of 1% to 3% and a cumulative prevalence of 7.5% among residents of this summer vacation site [5]. A longitudinal study of a community of about 160 persons on Great Island, Massachusetts, found a slow build-up of incidence to a peak of 3 cases per 100 persons per year and a total cumulative prevalence of 16% over a 20-year period [9]. Two population-based studies in highly endemic suburban communities in Westchester, New York, reported seasonal attack rates of 2.6% and 3% and cumulative prevalences of 8.8% and 17%, respectively [30, 31]. On the basis of these data, we considered four categories of endemicity: low (incidence estimate, 0.01%), moderate (incidence estimate, 0.1%), high (incidence estimate, 1%), and very high (incidence estimate, 3%). 2.6 Likelihood Ratios and Treatment Thresholds of Tests Three of the authors constructed scenarios that describe three hypothetical patients. One had diffuse nonspecific muscle pain (scenario A), one had a rash resembling erythema migrans (scenario B), and one had episodic oligoarticular arthritis (scenario C) (Table 2). These models were used to compute the change in the probability of disease using likelihood ratios (likelihood ratio for positive test result = sensitivity [100 specificity]; likelihood ratio for negative test result = [100 sensitivity] specificity) [26] resulting from the use of enzyme-linked immunosorbent assay (ELISA) and Western blotting. Decision analysis was used to assess the relative cost-effectiveness of the management options in these clinical situations when the clinician must decide whether to perform laboratory testing for Lyme disease [32]. Incremental cost-effectiveness ratios were calculated as costs per quality-adjusted life-year for each scenario. This cost-effectiveness study is described in detail in a forthcoming paper [33]. Table 2. Hypothetical Patient Scenarios 3. Data Synthesis 3.1 Microbial Isolation Cultural isolation of B. burgdorferi is the best diagnostic evidence of Lyme disease. Borrelia burgdorferi grows well in Barbour, Stoenner, Kelly (BSK) medium, but it is difficult to obtain isolates from clinical specimens other than biopsy samples from erythema migrans lesions. 3.2 Thirty-four papers were identified by the literature search. None met the criteria formal analysis, but some case reports were worth noting. In the presence of erythema migrans, material has been collected from cutaneous lesions with various techniques, including direct aspiration of involved skin, aspiration after saline instillation, and skin biopsy. Wormser and colleagues [34] reported success rates of 29% with saline-lavage needle aspiration and 60% with 2-mm punch biopsies of the advancing edge of suspected primary erythema migrans lesions. Berger and colleagues [35] reported a success rate of more than 80% with biopsy specimens obtained from the leading edge of erythema migrans lesions. 3.3 Culture from sites other than the erythem

Empiric parenteral antibiotic treatment of patients with fibromyalgia and fatigue and a positive serologic result for Lyme disease : a cost-effectiveness analysis

Since the original observation of Lyme disease in 1975 in the United States [1], an increase has occurred in the number of articles in the lay and medical press defining its cause, epidemiology, clinical features, and response to therapy, which has resulted in increased awareness of Lyme disease by both physicians and the lay public. Conventionally, the clinical expressions of Lyme disease have been divided into three stages [2]. The first stage begins up to 1 month after a tick bite and is characterized by a pathognomonic skin lesion, erythema chronicum migrans, and associated flu-like symptoms [3]. With dissemination of the infection, prominent systemic symptoms (fever, myalgia, arthralgia, headache, stiff neck) and multiple, secondary skin lesions may occur. In this second stage of Lyme disease, other systemic features may occur, including objective neurologic abnormalities (cranial neuropathies, radiculopathies, meningitis, meningoencephalitis), cardiac manifestations (myocarditis or abnormalities of atrioventricular conduction) [4, 5], and a skin condition known as lymphadenosis benigna cutis. Intermittent oligoarticular and asymmetrical arthritis may also begin during this stage of illness. The third or chronic stage occurs months to years after the initial tick bite and may be expressed by oligoarticular arthritis, particularly affecting the knees. In a small percentage of patients, the arthritis may become chronic, with erosion of cartilage and bone [6]. In addition, this stage can include a chronic skin lesion (acrodermatitis chronica atrophicans, seen predominantly in Europe) [7] and chronic neurologic abnormalities (including subtle encephalopathy and peripheral neuropathies), sometimes called tertiary neuroborreliosis [8-10]. Nonspecific symptoms such as headache, fatigue, and arthralgias can occur during any of the three stages. Approximately 20% of patients with later manifestations of Lyme disease recall no history of tick bite or erythema chronicum migrans [11]. Similarly, patients with Lyme disease arthritis may have no history of earlier symptoms [6]. Although the skin rash and flu-like symptoms of early Lyme disease (stage 1) can be adequately treated in most instances with oral antibiotics [12, 13], later disease symptoms clearly require more aggressive antibiotic therapy [2, 4, 10, 14, 15]. Because the etiologic agent, Borrelia burgdorferi, is difficult to culture, the diagnosis of Lyme disease is based on the occurrence of [1] one or more of the classical features and [2] serum antibodies to the etiologic spirochete after the first 4 to 6 weeks of illness. This has resulted in increased testing for antibodies to B. burgdorferi, the causative agent of Lyme disease, in many patients with nonspecific somatic complaints or fatigue. Increasing numbers of such patients, who completely lack any of the classic clinical features for Lyme disease, are receiving empirical, parenteral antibiotic treatment for suspected late-stage, chronic Lyme disease [16-21]. This treatment consists of 2 to 3 weeks of daily intravenous cephalosporin (ceftriaxone, Rocephin; Roche Laboratories, Nutley, New Jersey) therapy costing between

Test-treatment strategies for patients suspected of having Lyme disease: a cost-effectiveness analysis.

3000 and

Gouty arthritis: A prospective radiographic evaluation of sixty patients

5000. Although little doubt exists that a 2- to 4-week course of intravenous antibiotic therapy can often cure unequivocal, objective symptoms of disseminated (second-stage) and chronic (third-stage) Lyme disease, we found no reports in the peer-reviewed literature suggesting effectiveness of empirical, intravenous antibiotic treatment in patients with nonspecific complaints and a positive antibody titer for Lyme disease. Several reports exist indicating a lack of efficacy of this therapy [16-21]. Nonetheless, many patients with only nonspecific symptoms are given therapy empirically for months. A most striking example is the report of Genese and colleagues [20] of patients given as many as seven courses of intravenous antibiotic therapy. Twenty-five patients who received this therapy for as long as 170 days developed biliary disease, and 14 of these patients needed cholecystectomy. Twenty-two patients in the same cohort developed 29 bloodstream infections associated with intravenous catheter use after a median of 152.5 days of catheterization (range, 16 to 764 days) [20]. Our report examines the risks and benefits of two alternative therapeutic interventions: 1) empirical intravenous antibiotic treatment of the nonspecifically symptomatic patient who has a positive Lyme antibody titer or 2) no antibiotic treatment of such a patient. The analysis indicates that even in a best-case scenario, the risks and dollar costs of empirical therapy are substantially greater than the benefits. Methods To evaluate the relative benefits and costs of the above two alternatives, the following procedures were developed. Data on the epidemiology of Lyme disease, the performance of serologic tests for the disease and the response to parenteral therapy were obtained by computerized search of peer-reviewed literature. Serologic Tests for Lyme Disease No standardized method exists for titering serum antibodies to B. burgdorferi. The two most commonly used methods include enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescent assay using crude homogenates of the etiologic organism [19-26]. Because the ELISA method was developed using standards from the indirect immunofluorescence assay, it behaves similarly to the latter, and it is the method typically used now, we have not considered the latter assay in this analysis. Most investigators have considered a titer by ELISA to be positive if it exceeds by two standard deviations the mean for a group of normal sera [22-26]. Because the serologic test essentially defines the patients affected by this analysis, it is appropriate to examine both the sensitivity and the specificity of this test in different groups of patients. If one assumes a relatively normal distribution of titers in the normal population, then 2.5% of that normal population would be expected to exceed the mean by two standard deviations and thus would have false-positive results. If properly done, the test will detect cross-reactive antibody in patients with other spirochetal diseases. False-positive results have also been reported in varicella infections, infectious mononucleosis, rheumatoid arthritis, and systemic lupus erythematosus. However, after eliminating positive results due to cross-reactivity, published reports indicate a specificity in the ELISA assay of between 97% and 100%. In our baseline analysis, we assumed 100% sensitivity (because it is a positive titer that identifies patients for inclusion in this analysis in the first place) and a specificity of 98% (that is, 2% false positivity). Although investigators anticipate that using purified spirochetal epitopes as antigen in the ELISA in the future will greatly increase specificity, these epitopes are not available. Although Western blot testing is available for a nominal sum, it has not been standardized, and its specificity is only 95%. The specificity of antibody reactivity with any of the several possible epitopes has not been established, and considerable disagreement exists about whether the number of lines, the position of lines, or the intensity of lines in Western blots distinguish true- from false-positive results [27, 28]. In Western blots, many of the antibodies in sera from true-positive patients recognize antigenic epitopes shared by other bacteria. Thus, persons with neither classical Lyme disease nor positive ELISA results have sera that can react with many lines on Western blots, so the specificity of this method and its role in diagnosis is undefined [27, 28]. Therefore, it is the current ELISA technology that is most relevant to our policy statement. Regional Incidences of Lyme Disease and the Fatigue and Myalgia Syndrome A major consideration in attempting to calculate the likelihood of risks and benefits of the parenteral antibiotic intervention is the prior likelihood or incidence of Lyme disease in a given area. Town-specific incidences in the state in which the disease was first defined were 815 per 100 000 (0.8%) in the most endemic area, with a county-specific incidence of 114 per 100 000 (0.1%) and a statewide incidence of 23 per 100 000 (0.02%) [29]. A national surveillance study by Tsai and colleagues [30] from 1987 to 1988 indicated the incidences shown in Table 1. Table 1. Regional Incidence of Lyme Disease It should be noted that the incidence, even within states known to be endemic, can vary greatly. Epidemiologic studies have suggested that the rate of subclinical infection in endemic areas may vary from none to about the same rate as clinically apparent infections [11, 31, 32]. To bias this analysis in favor of antibiotic therapy, we have assumed the latter, that is, for every person contracting Lyme disease in Table 1, one infected asymptomatic seroconverter was at risk for having fatigue and myalgia as the sole symptom of Lyme disease. No data exist on the prevalence of Lyme disease in these areas; however, a period prevalence can be calculated by multiplying the incidence by the duration of the disease. We have assumed that a patient with the fatigue and myalgia syndrome will seek medical attention well within the first 2 years of symptom onset. Thus, in the mid-Atlantic region (where our assumption assumes an incidence rate of 6 nontypical/asymptomatic seroconverters per 100 000 population per year), the prevalence of seroconverters at the end of 2 years will be 12/100 000, which we have used as the baseline assumption for the prevalence of true-positive seroconverters in this analysis. In one report from a small island community in New York State, 9.7% of 176 persons had positive Lyme serologic results. We have examined the implications of this prevalence in our sensitivity analysis. As mentioned earlier, the prevalence of the fatigue and myalgia syndrome, custo

Impaired T-cell activation in patients with systemic lupus erythematosus

Lyme disease, the most common tick-borne disease in North America [1], is often misdiagnosed or treated inappropriately [2]. Most patients referred for assessment of suspected Lyme disease had other major diagnoses [3]. In a community with a low prevalence of disease, 60% of serologic tests for Lyme disease were performed as part of a battery of tests to investigate vague symptoms [4]. Eighty-three percent of surveyed physicians reported that they would treat a patient suspected of having Lyme disease even without positive serologic test results [5]. Patients who have positive results on serologic tests without objective clinical manifestations have received parenteral antibiotic therapy for suspected chronic Lyme disease [5]. Such unnecessary testing and treatment incur substantial costs [6] and adverse effects [7, 8]. The development and use of guidelines for the management of Lyme disease are necessary to decrease health care costs and increase quality of life for patients who may have Lyme disease. We performed a cost-effectiveness analysis to guide selection of test-treatment strategies for patients suspected of having Lyme disease. Incremental cost-effectiveness ratios were calculated for four possible strategies applied to three common patient scenarios. Sensitivity analyses assessed the robustness of the results to changes in the values or assumptions incorporated into the analysis. Methods Test-Treatment Strategies We considered four test-treatment strategies: 1) no testing-no treatment, in which no testing was done and no antibiotic treatment was given for Lyme disease; 2) testing with enzyme-linked immunosorbent assay [ELISA] followed by treatment of patients with positive results; 3) two-step testing with ELISA followed by Western blot of all specimens with equivocal or positive ELISA results and treatment of patients with positive results on either test; and 4) antibiotic treatment for all patients suspected of having Lyme disease. Patient Scenarios Three patient scenarios were considered (Table 1): myalgic symptoms (scenario A), rash resembling erythema migrans (scenario B), and recurrent oligoarticular inflammatory arthritis (scenario C). These scenarios represent common presentations for patients with Lyme disease [9] or clinical syndromes that may be confused with Lyme disease. Table 1. Patient Scenarios Decision Model A simple decision tree was constructed to represent the natural history of patients with possible Lyme disease [10] (Figure 1 , Figure 3). The model considered the incidence of Lyme disease in the community, sensitivity and specificity of laboratory tests, patient adherence to prescribed treatment, effectiveness and adverse effects of therapy, true presence or absence of Lyme disease, and sequelae of Lyme disease. Figure 1. Decision tree. Figure 3. Data and Assumptions Data were obtained by searching the MEDLINE database for English-language articles published from 1992 to 1996. We used the subject headings Borrelia burgdorferi, Borrelia infections, Lyme disease, and tick-borne diseases (Table 2). Most of the identified articles described case series. These articles were supplemented by information from the bibliographies of two recent cost-effectiveness analyses of treatment strategies for Lyme disease [6, 19]. Table 2. Baseline Data* Incidence of Lyme Disease Pretest probability is the probability that a diagnosis will be made before new information is acquired [10]. In our analysis, the pretest probability of Lyme disease before testing or treatment was the annual incidence of new infection within a given area. We used community incidence data rather than prevalence data for two reasons. First, early Lyme disease does not protect against reinfection with B. burgdorferi [31]. In addition, the stage of Lyme disease influences the sensitivity of the tests [32]. A high annual incidence of Lyme disease, 1%, was used for all baseline analyses. Diagnostic Value of Clinical Features Physician-diagnosed erythema migrans is considered pathognomonic for Lyme disease, although not everyone who has Lyme disease develops erythema migrans [33] (Figure 2). A patient with endemic exposure to Lyme disease and characteristic erythema migrans meets the clinical definition of Lyme disease [34] and therefore has a high probability of having Lyme disease. However, fewer than 50% of patients with this rash report a history of tick bite [9, 33, 35-37]. Patients in an endemic area who present during the summer with a large expanding border of erythema at one or more sites are usually considered to have Lyme disease and are treated accordingly, even if they do not recall a tick bite. Therefore, the rash described in scenario B was considered typical of erythema migrans diagnosed by a physician. Figure 2. Erythema migrana. Several dermatologic conditions can be confused with erythema migrans [38]. Although atypical forms of erythema migrans occur, all have expanding borders of erythema. The nature of the rash should therefore be determined clinically. Some patients who present with possible late manifestations of Lyme disease recall a rash resembling erythema migrans or a tick bite [39]. Whether a patient recalls these features helps discriminate between Lyme disease and unrelated diagnoses [40]. If a person recalls having a rash resembling erythema migrans, the probability of Lyme disease increases; lack of such a history decreases the probability of Lyme disease. The ability of this information to discriminate between patients with and without Lyme disease is expressed as a likelihood ratio [41]. A cohort study [40] described the diagnostic value of clinical features associated with Lyme disease. If patients reported a rash resembling erythema migrans, the likelihood ratio for Lyme disease was 21.3 (95% CI, 8.7 to 27.3). If patients did not report such a rash, the likelihood ratio for Lyme disease was 0 (CI, 0 to 0.6). The presence or absence of a history of tick bite had likelihood ratios for Lyme disease of 3.6 (CI, 1.7 to 4.7) and 0.3 (CI, 0.05 to 0.8), respectively. We adjusted the pretest probability of Lyme disease (that is, the community incidence) by using a Bayesian analysis, as follows [10]. The pretest probability was converted to an odds, multiplied by the appropriate likelihood ratio to obtain the post-test odds, and converted to the posterior probability. After we considered other features suggestive of Lyme disease, we used this probability of disease as the pretest probability of disease for the test-treatment strategies. Because no available data describe the likelihood of Lyme disease in a patient who presents with a history of both rash resembling erythema migrans and tick bite, we calculated the likelihood ratio by multiplying the likelihood ratio for tick bite by that for rash resembling erythema migrans [10]. Diagnostic Tests The sensitivity and specificity of tests for Lyme disease were calculated on the basis of pooled estimates from two studies ([11]; Centers for Disease Control and Prevention. Unpublished data). These estimates were calculated with a random-effects model [42]. Treatment Costs For our analysis, we took the perspective of the health care system. Hospital charges were used as a proxy for cost because true costs were unavailable. All cost estimates were expressed in 1993 U.S. dollars; as necessary, these estimates were adjusted for inflation by using the health care component of the consumer price index (Table 2). A discount rate of 5% accounted for future costs and effects. Treatment of early Lyme disease (that is, rash resembling erythema migrans) requires doxycycline, 100 mg twice daily for 30 days [13], with a single follow-up visit to a physician [12]. Treatment of late Lyme disease was assigned the cost of outpatient intravenous ceftriaxone therapy lasting 3 weeks [6]. Treatment of fibromyalgia requires amitryptiline, 25 mg/d [13]. Treatment of osteoarthritis requires naproxen, 500 mg twice daily [13]. In addition, a patient with a chronic illness visits a physician every 3 months [12]. Costs for other health states were derived from the literature. The costs of each chronic state were calculated as follows. Annual costs were discounted over the estimated life expectancy of a person with the relevant condition after the appropriate disutilities were taken into account (see the example in the section on utilities below). Net cost was then calculated by adding the costs of tests, antibiotic therapy, and treatment for the chronic health condition. The costs associated with lost work as a result of illness and death and costs of unrelated future illness were not included in the analysis according to standards proposed by the Panel on Cost-Effectiveness in Health and Medicine, sponsored by the U.S. Public Health Service [43]. Sequelae of Lyme Disease The analysis adjusted for cardiac, late neurologic, and arthritic complications of Lyme disease (Table 2). Cardiac complications almost always occur early in the course of the illness [9, 15-18]; if they are not treated, they last for about 3 months and then resolve [15, 16]. Neurologic manifestations involve the central or peripheral nervous system and result in residual memory difficulty or paresthesias [9, 21, 22, 27]. Refractory or untreated Lyme arthritis is more disabling than osteoarthritis and requires arthroscopic synovectomy [28, 44]. Compared with patients who have early Lyme disease, patients who have late Lyme disease are less likely to develop rheumatologic or neurologic sequelae. Early Lyme disease (for example, erythema migrans) is usually treated with oral antibiotics for at least 2 weeks [9]. Late Lyme disease is usually treated with intravenous antibiotics for 2 to 4 weeks [25, 26, 45]. Oral antibiotics can be used to treat oligoarticular arthritis, but this strategy is associated with a risk for inadequate treatment of unrecognized neurologic involvement [45]. We adjusted the analysis for costs

Interleukin-1-production by monocytes from patients with systemic lupus erythematosus

A prospective analysis of 60 patients with gout was undertaken to evaluate the radiographic spectrum of gouty arthritis in patients treated in the era of hypouricemic therapy. Twenty-two of these patients were clinically tophaceous; 36 were considered to have radiographic findings diagnostic of gouty arthritis by strict radiographic criteria. Up to 24% of the patients denied symptoms in joints with radiographic changes of gout; 42% with no evidence of tophi on clinical examination had radiographic changes characteristic of gout. Radiographic assessment can be extremely helpful in the management of gout by documenting the degree and extent of bony involvement, particularly in patients with limited symptoms or without clinical tophi.

Development of a quality of patient–health care provider communication scale from the perspective of patients with rheumatoid arthritis:

Interleukin-2 (IL-2) production was studied in T lymphocytes from 32 patients with systemic lupus erythematosus (SLE) and 27 healthy volunteers. The IL-2 production by phytohemagglutinin (PHA)-stimulated cells from SLE patients was significantly depressed compared to control values, with a correlation between degree of depression and disease activity. The depressed IL-2 production by SLE T cells are largely reversed by the addition of either phorbol ester (PMA) or partially by a calcium ionophore. SLE T cells had significantly lower peak increases in intracellular free calcium ([Ca2+]i) than controls after stimulation by PHA or by a monoclonal antibody against the CD3 antigen. This abnormality was found even in T cells from patients with mild disease activity or in those whose T cells produced normal amounts of IL-2. Calcium ionophore produced similar increases in [Ca2+]i in SLE patients as in normals. These results suggest that a major component of the defect responsible for decreased IL-2 production by SLE lymphocytes is proximal to protein kinase C activation and may involve impaired signal transduction after activation of the antigen receptor complex.

Foreign Medical Graduates and Board Certification

SummaryProduction of interleukin-1 (IL-1) by glass-adherent monocytes from 18 patients with systemic lupus erythematosus (SLE) was measured. Patients were divided into three groups according to disease activity. A deficient production of IL-1 was found in monocytes of SLE patients both without stimulation and after stimulation with 5 μg of lipopolysaccharide. The decreased production correlated with the degree of disease. Addition of phorbol myristate acetate to monocytes caused only partial normalization of the decreased IL-1 production. The IL-1 deficiency in SLE is postulated to be a part of complex abnormalities of cell-mediated immunity in this disease.

American College of Rheumatology: preliminary definition of improvement in rheumatoid arthritis

Objectives: To devise a patient-perspective driven measure of the quality of patient–health care provider communication and to evaluate the psychometric properties of this scale in a sample of 150 patients with rheumatoid arthritis. Methods: Items were developed from interviews with 15 patients with rheumatoid arthritis. Two rheumatologists, a behavioral scientist, and a nurse researcher provided item feedback. Exploratory factor analysis with Oblimin rotation was used to examine the dimensionality of the newly developed Patient–Health Care Provider Communication Scale (PHCPCS). Cronbach’s alpha was computed to assess internal consistency. Test–retest reliability was determined using the intraclass correlation coefficient. Construct validity was tested by comparing the PHCPCS with the Perceived Involvement in Care Scale (PICS) using correlation analysis. Results: The PHCPCS measured two dimensions of the quality of patient–health care provider communication [Quality Communication (α = 0.94) and Negative Patient–Health Care Provider Communication (α = 0.73)]. The total PHCPCS score and its Quality Communication Subscale were positively correlated with the total score on the PICS and with the doctor facilitation subscale of the PICS. Discussion: This new measure of the quality of patient–health care provider communication has the potential for use in clinical practice, provider education, and further studies to improve health care to patients with rheumatoid arthritis.

The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis

Excerpt To the Editor:The recent report by Ramsey and colleagues (1) on the predictive validity of American Board of Internal Medicine (ABIM) certification represents the culmination of a prodigiou...