Howard A. Fuchs

Self-Report Questionnaire Scores in Rheumatoid Arthritis Compared with Traditional Physical, Radiographic, and Laboratory Measures

STUDY OBJECTIVE To assess whether scores on a simple self-report questionnaire to depict the clinical status of patients with rheumatoid arthritis are correlated with traditional measures of physical, radiographic, laboratory, functional, and global status. DESIGN The self-report questionnaire was administered at the same time the following variables were assessed: American Rheumatism Association functional class, joint count, hand radiograph, erythrocyte sedimentation rate, rheumatoid factor titer, walking time, grip strength, button test, and global self-assessment. SETTING University rheumatology clinic, the rheumatology clinic of a Veterans Administration hospital, and a private rheumatology practice. PATIENTS The study included 259 patients who met the criteria of the American Rheumatism Association for a diagnosis of definite or classic rheumatoid arthritis. INTERVENTIONS Standard rheumatologic care for patients with rheumatoid arthritis. MEASUREMENTS AND MAIN RESULTS Self-report questionnaire scores were significantly correlated with the joint count, radiographic score, erythrocyte sedimentation rate, grip strength, button test, walking time, American Rheumatism Association functional class, and global self-assessment. Patients were categorized into five questionnaire score categories of 1.00, indicating no dysfunction, and 1.01 to 1.50, 1.51 to 2.00, 2.01 to 3.00, and 3.01 to 4.00, indicating progressive dysfunction. In these five categories, more than ten involved joints were seen in 11%, 37%, 67%, 79%, and 100% of patients, respectively, and erythrocyte sedimentation rates greater than 20 mm/h in 29%, 49%, 64%, 74%, and 85% of patients, respectively. Similar results were seen for other physical and radiographic measures. The questionnaire score was as effective in explaining other measures of clinical status as was any other available measure. CONCLUSIONS A simple self-report questionnaire provides information similar to many traditional measures in rheumatoid arthritis and appears to be an attractive, cost-effective approach to assessing and monitoring quantitatively the status of an individual patient.

Causes and significance of markedly elevated serum ferritin levels in an academic medical center.

Objective A markedly elevated serum ferritin level has been associated with inflammatory conditions such as adult-onset Still’s disease, systemic juvenile idiopathic arthritis, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Hyperferritinemia, however, can also be caused by a wide variety of disparate conditions, often with impressively high serum levels. The objective of this analysis was to investigate the underlying etiology of markedly elevated ferritin levels in a large group of patients treated as outpatients and inpatients in a tertiary-care medical center. Methods Data of all adult patients from 2008 through 2010 with at least 1 serum ferritin level greater than 1000 &mgr;g/L were reviewed. If a patient had multiple qualifying levels, the highest one was used. For each case, the most likely cause of the elevated ferritin was assessed based on the available clinical data using a simple algorithmic approach. Results Six hundred twenty-seven patients were found. The average serum ferritin level was 2647 &mgr;g/L. The most frequent condition was malignancy (153/627), with iron-overload syndromes the second most common (136/627). There were 6 cases of adult-onset Still’s disease, systemic juvenile idiopathic arthritis, or hemophagocytic lymphohistiocytosis/macrophage activation syndrome. The average ferritin level in these syndromes was 14242 &mgr;g/L. Seven patients appeared to have anemia of chronic inflammation, and in 5 patients, there was no clearly definable cause for hyperferritinemia. Conclusions Although extremely elevated ferritin levels may be associated with rheumatologic diseases, more often they are found in patients with other conditions such as malignancy or infection. In addition, extremely high ferritin levels can be found in patients with seemingly indolent disease or levels of chronic inflammation.

Effects of a cognitive–behavioral intervention for women with rheumatoid arthritis

The purpose of this quasi-experimental study was to evaluate the effectiveness of a cognitive-behavioral nursing intervention for women with rheumatoid arthritis (RA). Ninety adult women with RA participated in 1 of 14 nurse-led groups over an 18-month period. Personal coping resources, pain-coping behaviors, psychological well-being, and disease symptomatology were measured at four time periods. There were significant changes on all of the measures of personal coping resources (p < .001) and psychological well-being (p < .05), half of the pain-coping behaviors (p < .05), and one indicator of disease symptomatology (fatigue, p < .05) from pre- to postintervention. Furthermore, the positive changes brought about by the program were maintained over the 3-month follow-up period. The intervention may be adapted to benefit individuals with a variety of stressful medical conditions.

Granulomatous disorders of the nose and paranasal sinuses.

Purpose of reviewTo review granulomatous findings in sinus and nasal tissue as part of a diagnostic indicator of various disease states, focusing on the role of further testing and evaluation to clarify this diagnosis as well as the implications for patient care. Recent findingsInflammatory and infectious diseases as well as neoplasms, cocaine abuse and trauma may have rhinosinus granulomatous findings as part of the disease state. The need for careful histopathologic evaluation as well as the pitfalls and caveats of laboratory testing will be reviewed in this paper. Some infections such as invasive fungal rhinosinusitis and rhinoscleroma may have a chronic granulomatous course, which may require extensive surgical and pharmacologic treatment. Treatment options for Wegeners granulomatosis have shown a lack of effect of etanercept, but hopeful alternatives to prolonged cyclophosphamide use include methotrexate and leflunomide. Cocaine-induced midline destructive lesions unfortunately have a high prevalence of cytoplasmic antineutrophil cytoplasmic antibodies, limiting this tests usefulness in distinguishing this disorder from Wegeners granulomatosis. SummaryThe otorhinolaryngologist must be aware of the differential diagnosis of these chronic inflammatory states to formulate an optimal course of evaluation and longitudinal management for these patients.

Observer variation in quantitative assessment of rheumatoid arthritis part II. A simplified scoring system

A new and more comprehensive simplified scoring system to provide quantitative assessment of radiographic findings in rheumatoid arthritis was studied by six observers with different levels of expertise. Since the observers, film set, and joints scored were the same as in a prior study of a more detailed scoring method, a precise comparison of the results was made. Interobserver variation with the simplified scoring system was small; there were highly significant correlations of the total radiographic scores for all observers (R = .898-.978, P less than .001). There were highly significant correlations between scores obtained with the simplified scoring system and those obtained with the more detailed method (R = .920-.955, P less than .001). When the same joints were evaluated by the two methods, a significantly greater number of possible observations could be scored with the simplified scoring system than with the more detailed method (X2 = 131.07, P less than .001). The simplified scoring system required 2.3 times less time to use in the hands of experienced observers.

Methotrexate increases expression of cell cycle checkpoint genes via JNK activation

OBJECTIVE To assess defects in expression of critical cell cycle checkpoint genes and proteins in patients with rheumatoid arthritis (RA) relative to presence or absence of methotrexate (MTX) treatment, and to investigate the role of JNK in induction of these genes by MTX. METHODS Flow cytometric analysis was used to quantify changes in levels of intracellular proteins, measure reactive oxygen species (ROS), and determine apoptosis in different lymphoid populations. Quantitative reverse transcription-polymerase chain reaction was used to identify changes in cell cycle checkpoint target genes. RESULTS RA patients expressed reduced baseline levels of MAPK9, TP53, CDKN1A, CDKN1B, CHEK2, and RANGAP1 messenger RNA (mRNA) and JNK total protein. The reduction in expression of mRNA for MAPK9, TP53, CDKN1A, and CDKN1B was greater in patients not receiving MTX than in those receiving low-dose MTX, with no difference in expression levels of CHEK2 and RANGAP1 mRNA between MTX-treated and non-MTX-treated patients. Further, JNK levels were inversely correlated with C-reactive protein levels in RA patients. In tissue culture, MTX induced expression of both p53 and p21 by JNK-2- and JNK-1-dependent mechanisms, respectively, while CHEK2 and RANGAP1 were not induced by MTX. MTX also induced ROS production, JNK activation, and sensitivity to apoptosis in activated T cells. Supplementation with tetrahydrobiopterin blocked these MTX-mediated effects. CONCLUSION Our findings support the notion that MTX restores some, but not all, of the proteins contributing to cell cycle checkpoint deficiencies in RA T cells, via a JNK-dependent pathway.

Observer variation in quantitative assessment of rheumatoid arthritis: Part I. Scoring erosions and joint space narrowing

Six observers, including two bone and joint radiologists, two general radiologists, and two senior radiology residents, compared scores to quantitate radiographic findings in the hands and wrists of patients with rheumatoid arthritis. In the scoring system used, erosions and joint-space narrowing are graded separately. This scoring system differs from other methods in that equivocal findings are not scored, while ankylosis, subluxation, and dislocation are scored, and data from postoperative joints are included. Total radiographic scores were highly significantly correlated for all observers (R = .908-.958, P less than .001), as were subtotal scores for erosions (R = .723-.931, P less than .001) and joint-space narrowing (R = 0.843-0.966, P less than .001). Analysis of proximal interphalangeal, metacarpophalangeal, and wrist-joint scores showed highly significant correlations for all observers in each location. Highly significant correlations were found among three separate readings of two bone and joint radiologists (R = .950-.961, P less than .001). This scoring system provides highly consistent and reproducible results, even in the hands of less experienced observers.

Problems with the steinbrocker staging system for radiographic assessment of the rheumatoid hand and wrist

Hand and wrist radiographs of 202 patients with rheumatoid arthritis were graded with the classical Steinbrocker Staging System, and were also assigned quantitative scores for joint space narrowing, erosion, and malalignment according to a detailed scoring method. Steinbrocker Stage scores were correlated significantly with total detailed scores (r = 0.60 to 0.66, P less than 0.001). However, the ranges of detailed total and subtotal scores among the various Steinbrocker Stage scores were broad, with considerable overlap. Practical problems in applying the Steinbrocker staging method were identified in 26.5% of the hands graded with the Steinbrocker method. Additionally, analysis of scoring data showed discrepancies between the scoring methods in 25.2% of the hands examined; one-half of these discrepancies were felt to result from the global or overall approach of the Steinbrocker method in contrast to individual joint analysis. Asymmetry in assigned stages between right and left hands was found in 15.8% of patients. The detailed scoring method, although more time-consuming, appears superior to the Steinbrocker Stage for quantitative assessment of patient radiographic status in rheumatoid arthritis.

Arthritis after Bacillus Calmette-Guerin Therapy

Excerpt To the Editors:A 49-year-old male had transurethral resection and intravesical and intramuscular bacillus Calmette-Guerin (BCG) therapy in 1988 for transitional cell carcinoma of the bladde...

Regulation of Ketogenesis by Epinephrine and Norepinephrine in the Overnight-fasted, Conscious Dog

The effects on ketogenesis and lipolysis of a norepinephrine (0.04 μg/kg-min), epinephrine (0.04 μg/kg-min), or saline infusion were examined in the overnight-fasted, conscious dog. Plasma insulin and glucagon levels were maintained constant by means of a somatostatin infusion (0.8 μg/kg-min) and intraportal replacement infusions of insulin and glucagon. In saline-infused dogs, plasma epinephrine (62 ± 8 pg/ml), norepinephrine (92 ± 29 pg/ml), blood glycerol (87 ± 10μM), and plasma nonesterified fatty acid (NEFA) (0.82 ± 0.17 mM) levels did not change. Total blood ketone body levels tended to rise (62 ± 10 to 83 ± 11 μM) by 3 h as did total ketone body production (1.5 ± 0.4 to 2.2 ± 0.4 (μmol/kg-min) over the same time interval. Norepinephrine infusion to produce plasma levels of 447 ± 86 pg/ml caused a sustained 50% rise in glycerol levels (66 ± 17 to 99 ± 15 μmol/L, P < 0.05) and 53% rise in nonesterified fatty acids (0.53 ± 0.07 to 0.81 ± 0.15 μmol/L, P < 0.05). Total ketone body levels rose by 43% (51 ± 8 to 73 ± 10 μmol/L) and ketone body production rose by a similar proportion (1.5 ± 0.2 to 2.2 ± 0.3 μmol/kg-min), changes that did not differ significantly from control animals. A similar increment in plasma epinephrine levels (75 ± 15 to 475 ± 60 pg/ml) caused glycerol levels to rise by 82% (105 ± 23 to 191 ± 26 (μmol/L) in 30 min, but this rise was not sustained and the level fell to 146 ± 14 (μmol/L by 120 min. Plasma nonesterified fatty acids rose from a basal value of 0.89 ± 0.19 mM to 1.25 ± 0.29 mM during the first 30 min, but fell to 0.60 ± 0.12 mM by 2 h. Ketone body levels remained unchanged (66 ± 10 μmol/L) and ketone body production declined (1.5 ± 0.3 to 1.0 ± 0.2 μmol/kgmin). These data indicate that (1) although the sustained increase in lipolysis caused by norepinephrine was greater than that caused by fasting alone, the ketogenic responses were not different, and (2) epinephrine has a transient lipolytic effect and an antiketogenic effect compared with controls.