Agranulocytosis in Sjögren's syndrome: two case reports and analysis of 11 additional reported cases.

OBJECTIVES: To report 2 patients who presented with agranulocytosis that was found to be immune-mediated and associated with occult primary Sjögren's syndrome (primary SS) and to identify and study similar cases reported in the literature. METHODS: Two patients encountered in 2 large medical centers over a period of 5 years were studied in detail. All reported cases of agranulocytosis in primary SS identified through a MEDLINE search were reviewed. RESULTS: Two patients presented with marked systemic symptoms alone or associated with recurrent infections. Agranulocytosis with either a pattern of maturation arrest or a hypercellular reactive bone marrow was found and was associated with "acute phase" markers, hypergammaglobulinemia, a small paraprotein peak, and high rheumatoid factor titers. A diagnosis of immune-mediated agranulocytosis associated with an occult primary SS was established and was successfully treated with intravenous immunoglobulins or prednisone. Both patients subsequently developed skin vasculitis. This rare association of agranulocytosis and Sjögren's syndrome was identified in 11 other cases and was the presenting manifestation of primary SS in 10 of 13 (77%) patients. CONCLUSIONS: Agranulocytosis should be recognized as a rare but well-established association of primary SS. Bone marrow neutrophil production may be affected, or neutrophils may be destroyed in the circulation, by both humoral and cellular immune-mediated mechanisms. Agranulocytosis or neutropenia should be added to the varied hematologic manifestations of primary SS and may be its presenting feature and an important clue to diagnosis.

Polymyositis evolving after rhabdomyolysis associated with HMG-CoA reductase inhibitors: a report of two cases.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are commonly used for treatment of hyperlipidemia and its deleterious effects. Myotoxicity has been associated with use of these agents. We report two cases of inflammatory myopathy in patients receiving these agents that did not respond to drug withdrawal and required immunosuppressive treatment. One of these patients developed an antibody to histidyl tRNA synthetase or Jo-1, an autoantibody associated with idiopathic inflammatory myopathies. We suggest that HMG-CoA reductase inhibitor-associated myotoxicity may trigger an immune-mediated inflammatory myopathy. Patients whose muscle abnormalities do not resolve with drug withdrawal should be considered for muscle biopsy.

Visually-guided irrigation in patients with early knee osteoarthritis: a multicenter randomized, controlled trial.

OBJECTIVE: To determine if visually-guided arthroscopic irrigation is an effective therapeutic intervention in patients with early knee osteoarthritis. DESIGN: Ninety patients with knee osteoarthritis were randomized in a double-blind fashion to receive either arthroscopic irrigation with 3000 ml of saline (treatment group) or the minimal amount of irrigation (250 ml) required to perform arthroscopy (placebo group). The primary outcome variable was aggregate WOMAC score. RESULTS: The study did not demonstrate an effect of irrigation on arthritis severity as measured by aggregate WOMAC scores, the primary outcome variable; the mean change in aggregate WOMAC score at 12 months was 15.5 (95% CI 7.7, 23.4) for the full irrigation group compared to 8.9 (95% CI 4.9, 13.0) for the minimal irrigation group (P=0.10). Full irrigation did have a statistically significant effect on patients' self-reported pain as measured by the WOMAC pain subscale and by a visual analog scale (VAS) (the secondary outcome variables). Mean change in WOMAC pain scores decreased by 4.2 (95% CI -0.9, 9.4) for the full irrigation group compared with a mean decrease of 2.3 (95% CI -0.1, 4.7) in the minimal irrigation group (P=0.04). Mean VAS pain scores decreased by 1.47 (95% CI -1.2, 4.1) in the full irrigation group compared to a mean decrease of 0.12 (95% CI 0.0, 0.3) in the minimal irrigation group (P=0.02). A hypothesis-generating post-hoc analysis of the effect of positively birefrigent intraarticular crystals showed that patients with and without intraarticular crystals had statistically significant improvements in pain assessments and aggregate WOMAC scores at 12 months; patients with crystals had statistically greater improvements in pain. CONCLUSIONS: Visually-guided arthroscopic irrigation may be a useful therapeutic option for relief of pain in a subset of patients with knee OA, particularly in those who have occult intraarticular crystals.

Bacterial arthritis.

Reports pertinent to bacterial arthritis in 1997 included two large, multi-year surveys of joint infection in patients from defined European health districts, noting trends including the declining incidence of gonococcal arthritis and an increasing number of prosthetic joint infections. Children with infected joints generally fare better than adults despite having proportionately more infections due to gram-negative organisms, of which Hemophilus influenzae comprises an ever smaller portion as the fastidious Kingella kingea is emerging. Joint infections remain an uncommon complication of immunodeficiency due to HIV, with responsible agents, affected sites, and clinical course also influenced by certain HIV comorbidities such as intravenous drug user and hemophilia. The rare immunodeficient patient with hypogammaglobulinemia retains a nearly unique susceptibility to joint infection with mycoplasmas, which can cause considerable morbidity if not promptly recognized and treated. Polymerase chain reaction can detect remnants of bacteria in the face of negative conventional cultures, but inoculation of synovial fluid into blood cultures bottles may be a more immediate and practical method to increase the yield in suspected septic arthritis.

Inter-observer reliability of the arthroscopic quantification of chondropathy of the knee.

BACKGROUND: Several scoring systems have been proposed in order to quantify the degree of cartilage damage observed by arthroscopy of the knee in patients with osteoarthritis. OBJECTIVE: To evaluate the inter-observer reliability of five different scoring systems of arthroscopic evaluation for chondropathy in osteoarthritis of the knee and to evaluate the utility of a training session between different observations on these scoring systems. METHODS: Videotapes of knee arthroscopies on five patients with osteoarthritis demonstrating different levels of severity of cartilage damage of the medial tibiofemoral compartment were analyzed by nine observers prior to (pre-training evaluation) and 2 months after a 6 h training session (post-training evaluation) by the following scoring systems: (1) cartilage deterioration by a 100 mm visual analogue scale (VAS), (2) overall assessment of degeneration in the entire medial compartment (cartilage, meniscus, osteophyte) using a 100 mm VAS, (3) French Society of Arthroscopy (SFA) Scoring System, (4) SFA Grading System, (5) American College of Rheumatology (ACR) Scoring System. RESULTS: At the pre-training evaluation, the SFA grading system produced the highest coefficient of reliability (r = 0.94), the other systems recording levels of < or = 0.80. At the post-training evaluation, the coefficient of reliability was r > 0.80 for four of the five scoring systems, with lack of improvement in the ACR Scoring System. CONCLUSION: There was an improved and acceptable inter-observer reliability for at least 2 months follow-up in four of five evaluated scoring systems of arthroscopically graded osteoarthritis of the knee following a training session. A scoring system using a 100 mm VAS may produce the best inter-observer reliability. These results show that scoring chondropathy is possible and demonstrate the importance of training in the analysis of articular cartilage breakdown.

Diagnostic arthroscopy.

Arthroscopy has served a diagnostic role for most of this century, but found widespread popularity only when operative interventions were coupled with the procedure. The untapped potential inherent in directly observing the pathoanatomy underlying various rheumatologic disorders is being unlocked by developments on several fronts that have taken arthroscopy away from the operating room environment. Information from arthroscopy can influence diagnosis and treatment in certain non-traumatic knee disorders, particularly when the cause of synovitis is not evident from other clinical features and when knee symptoms are accompanied by bland synovial fluid and X-rays that are normal or show only minimal changes of osteoarthritis. Other joints can now be arthroscoped, which may prove useful for rheumatological diagnosis and evaluation, particularly for the smaller joints of the upper extremity commonly affected in 'early' disease states.

Muscle biopsy.

Muscle biopsy remains a critical component in the evaluation of myopathies. Recent literature demonstrates that percutaneous biopsy instruments can effectively procure muscle tissue for analysis in clinical and research settings. We review issues of muscle biopsy technique and specimen processing in the context of available clinical methods for tissue analysis. A survey of recent literature illustrates contributions made by the histologic, histochemical, and ultrastructural aspects of muscle analysis to our understanding of the pathophysiologic mechanisms and clinical manifestations of selected inflammatory, mitochondrial, and infectious myopathies.

A pilot study of the effect of oral 8-methoxypsoralen and intraarticular ultraviolet light on rheumatoid synovitis.

OBJECTIVE: To determine the feasibility and safety of combining oral 8-methoxypsoralen (8-MOP) and intraarticular ultraviolet A band light (UVA) to treat rheumatoid synovitis, and to demonstrate a favorable biological effect. METHODS: Six patients with rheumatoid arthritis (RA) and clinically evident knee synovitis were given a single oral dose of 8-MOP (0.6 mg/kg) followed by arthroscopy with a UVA laser equipped small arthroscope. Nine tissue samples treated with UVA doses ranging from 4 to 52 J/cm2 were examined by light microscopy and by immunohistochemistry for vascular cell adhesion molecule 1 (VACM-1), intracellular adhesion molecule 1 (ICAM-1), E-selectin and HLA-DR expression. RESULTS: No reduction in inflammation was evident on light microscopy, nor was there any evidence of tissue injury on gross inspection or light microscopy. At 28 and 52 J/cm2, VCAM-1, ICAM-1 and E-selectin staining were reduced in the posttreatment synovial biopsies. No local or systemic complications were observed by Day 30 in any patient. CONCLUSION: This treatment modality appears to be feasible and safe and may potentially be useful in the treatment of the synovitis associated with RA.

Diagnostic arthroscopy in the arthritis patient.

The arthroscope can play an important diagnostic role in the arthritis patient. The major utility of this procedure is in the patient with unexplained knee pain and swelling or in the patient with an established knee arthritis whose symptoms are disproportionate to radiographic findings or refractory to standard-course medical therapy. Technologic advances have led to the production of smaller instruments, making office-based diagnostic arthroscopy a practical, cost-effective alternative in the evaluation of these patients, and supporting the clinical argument for it as a procedure distinct from conventional arthroscopy. Separate clinical scenarios further subdivide the indications for diagnostic arthroscopy and define potential intra-articular abnormalities that, if found, can justify alterations in or additions to therapeutic plans, including arthroscopically directed tissue resection and modification or application of tissue-modifying agents. The research capabilities of needle arthroscopy are only just beginning to be realized; opportunities now exist for design of prospective clinical trials in which patients are randomized based on intra-articular abnormalities, and for the serial assessment of specific treatment effects on gross, microscopic, and molecular features of target tissue as identified by the arthroscope.

Utility of needle muscle biopsy in a university rheumatology practice.

OBJECTIVE: To evaluate the utility of percutaneous needle muscle biopsy (NMB) as an alternative to open biopsy for the evaluation of patients with myopathy encountered in a university hospital based rheumatology setting. METHODS: Chart review of all patients (n = 30) who underwent NMB at our institution over a 4-year period. Patients were grouped according to clinical outcome. Records of 91 patients who underwent open biopsy during the same period were reviewed for comparison. RESULTS: NMB results either confirmed or added to the prebiopsy diagnostic suspicion in 11 patients and excluded a low prebiopsy suspicion in 13, thus yielding useful clinical information in 24 of 30 patients (80%). Biopsy left the suspected diagnosis unresolved more frequently in patients undergoing NMB compared to patients who had open biopsy during the same time period (6/30 vs 1/91). In the 6 cases unresolved by NMB, subsequent open biopsy added additional information in only 2 of 5 patients. Sensitivity of NMB for inflammatory myopathy was 83% in the 23 patients suspected of having this disease. NMB could be arranged twice as fast as open biopsy, and provided adequate tissue for evaluation in all cases. CONCLUSIONS: Our results suggest that NMB is an effective tool for obtaining useful diagnostic information, particularly pertaining to the presence of an inflammatory myopathy. The convenience, low morbidity, and sensitivity of NMB make it a procedure worthy of wider application by rheumatologists.

Tidal irrigation in septic arthritis of the knee: a potential alternative to surgical drainage.

OBJECTIVE: To evaluate the efficacy of tidal irrigation (TI: repeated distention and irrigation of joint with saline under local anesthesia through 14 gauge Vere's needle) as a method to effect drainage in septic arthritis of the knee. METHODS: Eleven episodes of septic arthritis of the knee in 10 patients were approached with TI when drainage of purulent material could no longer be satisfactorily accomplished with repeated arthrocenteses. Clinical and synovial fluid (SF) data were systematically collected and analyzed. RESULTS: Four out of 11 episodes resolved without resorting to further surgical drainage. Cases responding to TI involved significantly older patients with lower volume effusions at presentation. Cases not responding to TI more frequently involved gram negative infection (3/7 cases vs 0/4). Variables of SF obtained preceding and following the first TI predicted outcome, with 3/4 responding cases demonstrating both a drop in white blood cell count of > or = 25% and a decrement of > or = 50% in volume while none of the cases eventually requiring surgery responded in this fashion (p < 0.05). CONCLUSIONS: TI can potentially supplant conventional surgical drainage in some cases of septic knee arthritis that do not respond to medical management.

Detection of intraarticular abnormalities in osteoarthritis of the knee. A pilot study comparing needle arthroscopy with standard arthroscopy.

OBJECTIVE: To determine whether intraarticular abnormalities in osteoarthritis (OA) of the knee can be detected as well by needle arthroscopy as by standard arthroscopy. METHODS: Needle arthroscopy followed by standard arthroscopy was performed on 10 patients with knee OA (diagnosed according to American College of Rheumatology criteria) whose symptoms were not entirely attributable to the OA and were therefore an indication for further evaluation. Each knee was assessed for abnormalities of the menisci, articular cartilage (6 sites), and synovium (6 sites). RESULTS: Evaluation of the 18 menisci visualized with both techniques yielded the same results: 6 abnormal and 12 normal. Among the 54 articular cartilage sites evaluable with both procedures, 16 were judged normal by both needle arthroscopy and standard arthroscopy. Of the 38 cartilage sites judged abnormal by standard arthroscopy, 34 (89%) were abnormal by needle arthroscopy. Both techniques indicated cartilage changes were the same at 42 (78%) of the 54 sites; changes at the other 12 sites were 1 grade higher by standard arthroscopy than by needle arthroscopy. Both needle arthroscopy and standard arthroscopy revealed 51 evaluable sites in the synovium. Of 34 areas judged abnormal by standard arthroscopy, 24 (71%) were also judged abnormal by needle arthroscopy; 17 areas were judged normal by both techniques. The 2 techniques assigned the same macroscopic score in 27 (53%) of 51 areas of the synovium, with a higher grade by standard arthroscopy in all but 1 of the other 16 areas. CONCLUSION: These pilot data suggest that in knee OA, needle arthroscopy can 1) accurately detect meniscal abnormalities, 2) detect cartilage abnormalities, but may underestimate the severity, and 3) detect most synovial abnormalities, but often underestimates the severity. Needle arthroscopy is a potentially valuable rheumatologic tool for the assessment of OA of the knee.

The role of arthroscopy in the differential diagnosis of osteoarthritis of the knee.

The arthroscope, currently used in OA mostly as a tool to deliver surgical therapy, can play an important diagnostic role in patients with knee pain for whom OA is part of the differential diagnosis. Concepts that may seem foreign to clinicians who take care of patients with knee OA (that is, of arthroscopy as a purely diagnostic tool and of knee OA as a clinical situation for which a differential diagnosis might be rendered) are supported by an appreciation for the heterogeneity of conditions of which OA is a part as well as an awareness of the pathoanatomic complexity of symptomatic knee OA as revealed by recent MRI and arthroscopy studies. Inspection of the perplexing OA knee with one of the newly available needle arthroscopes in an ambulatory office setting may be preferable to referral for conventional operating room--based arthroscopy, as this new technique adequately delineates intra-articular anatomical abnormalities (for which surgical therapy is not always indicated) and provides saline lavage to the joint (considered by many as a major factor in the improvement of symptoms reported by many patients with knee OA after arthroscopy). At present arthroscopy can serve to aid differential diagnostic efforts in five clinical situations involving knee OA: painful swollen knee with normal radiographs and noninflammatory fluid, clinical and radiographic OA with pain out of proportion to radiographic findings and refractory to conventional medical therapy, chronic stable (radiographic) OA with profound worsening of symptoms, OA with predominate "mechanical" symptoms, and OA with unexpected synovial fluid characteristics. Future use of needle arthroscopy in knee OA could serve to define the intraarticular correlates of pain in OA, to identify specific subgroups of knee OA upon which prospective randomized testing of arthroscopic surgical interventions could be conducted, and to quantitatively assess the effects of new treatment modalities on articular cartilage and other intraarticular structures.

Tidal irrigation versus conservative medical management in patients with osteoarthritis of the knee: a prospective randomized study. Tidal Irrigation Cooperating Group.

To determine the efficacy of tidal knee irrigation for knee pain due to osteoarthritis (OA), we conducted a randomized, single blind, 14-week prospective trial comparing medical management with tidal knee irrigation in 77 patients with non-end stage OA of the knee and unilateral pain refractory to standard medical treatment. Fifty-seven patients completed the study. Statistically significant differences (p less than 0.05) favoring tidal knee irrigation over medical management were pain after 50' walk, pain after 4-stair climb, most intense pain in previous day, frequency of knee stiffness with inactivity, days of morning knee stiffness in previous week, physician assessment of knee tenderness and overall assessments of therapy effectiveness by both patient and physician. Tidal knee irrigation results in more favorable improvement of pain due to OA than can be accomplished with traditional medical management.