Incidence of systemic lupus erythematosus in a population-based cohort using revised 1997 American College of Rheumatology and the 2012 Systemic Lupus International Collaborating Clinics classification criteria.

In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) group published a new set of classification criteria for systemic lupus erythematosus (SLE). Studies applying these criteria to real-life scenarios have found either equal or greater sensitivity and equal or lower specificity to the 1997 ACR classification criteria (ACR 97). Nonetheless, there are no studies that have used the SLICC 12 criteria to investigate the incidence of lupus. We used the resource of the Rochester Epidemiology Project to identify incident SLE patients in Olmsted County, Minnesota, from 1993 to 2005, who fulfilled the ACR 97 or SLICC 12 criteria. A total of 58 patients met criteria by SLICC 12 and 44 patients met criteria by ACR 97. The adjusted incidence of 4.9 per 100,000 person-years by SLICC 12 was higher than that by ACR 97 (3.7 per 100,000 person-years, p = 0.04). The median duration from the appearance of first criterion to fulfillment of the criteria was shorter for the SLICC 12 than for ACR 97 (3.9 months vs 8.1 months). The higher incidence by SLICC 12 criteria came primarily from the ability to classify patients with renal-limited disease, the expansion of the immunologic criteria and the expansion of neurologic criteria.

A contemporary case series of lupus myocarditis.

OBJECTIVES: The purpose of this study was to describe clinical phenotype and treatment outcomes in lupus myocarditis (LM), an uncommon but serious manifestation of systemic lupus erythematosus (SLE). METHODS: The study involved a 10-year retrospective case series of hospitalized patients with LM, with a search of a diagnosis database using systemic lupus erythematosus and either myocarditis, cardiomyopathy, or congestive heart failure, and of a pathology database for biopsy-proved LM. RESULTS: Twenty-four patients met the study criteria, with 79% female and 82% white (age: mean (SD), 47.6 (20.4) years; follow-up: mean (SD), 9.2 (6.1) months). The frequency of antibodies SS-A (69%) and anti-RNP (62%) was greater than in published lupus populations (25%-40%). On echocardiography, the mean initial left ventricular ejection fraction was 33.8%, improving to 49.5% after a mean of 7.2 months. All patients received immunosuppression, most with high-dose corticosteroid treatment and subsequent corticosteroid taper. One patient died of cardiogenic shock during hospitalization; two patients died within one year posthospitalization. CONCLUSIONS: A high index of suspicion is necessary in suspected LM. Higher frequency of elevated SS-A and anti-RNP antibody levels in our series than in the literature is suggestive of an LM association. Echocardiography is a useful initial investigation for LM, but patients should be referred early for cardiac magnetic resonance imaging or endomyocardial biopsy to confirm diagnosis if it is clinically indicated in difficult cases.

Assessment of disease activity in rheumatoid arthritis using a novel folate targeted radiopharmaceutical Folatescan.

OBJECTIVES: Development of a simple and accurate technique for detecting active inflammation in the joints and other tissues of patients with inflammatory disorders is an unmet need in rheumatic diseases. This study is a preliminary assessment of the safety and usage of a radiopharmaceutical, FolateScan (Technetium-99m EC20; 99mTc-EC20), for detecting disease activity in patients with rheumatoid arthritis. METHODS: EC20 is a folate-targeted diagnostic radiopharmaceutical which binds to the folate receptor and is preferentially taken up by activated macrophages. In this open-label, cross-sectional study, a total of 40 patients with RA (26 with one or more swollen joints, 14 with clinically quiescent joint disease; 0/66 joint count) as well as 6 patients with osteoarthritis, 12 patients with other inflammatory conditions and 5 healthy subjects received 0.1 mg of EC20 labeled with 20-25mCi of technetium-99m. Disease activity was scored in each joint and other target tissues by a radiologist blinded to the clinical assessment, and results were compared to the rheumatologist's physical examination, which served as the test standard. RESULTS: The 40 patients (78% female) with RA had a mean age of 56.9 years. Assessment of uptake of 99mTc-EC20 in joints of patients with RA based on image analysis was compared to the clinical examination. FolateScan detected more actively involved joints in 27 patients (68%) than joints recorded as "swollen", and more actively involved joints in 25 patients (63%) than joints recorded as "painful and/or swollen". The number of swollen joints by clinical exam was correlated with ESR (r=0.43; p=0.006) and C-rp (r=0.35; p=0.03). The number of actively involved joints by FolateScan was also correlated with ESR (r=0.47; p=0.002) and C-rp (r=0.36; p=0.02). Joint uptake was also seen in patients with osteoarthritis. CONCLUSION: FolateScan is a potentially useful tool for detection of disease activity in patients with RA and may be more sensitive than the physical examination.

Hematologic malignancies and the use of methotrexate in rheumatoid arthritis: a retrospective study.

PURPOSE: To evaluate the relationship between use of methotrexate in rheumatoid arthritis patients and development of hematologic malignancies. PATIENTS AND METHODS: We retrospectively analyzed all patients registered at the Mayo Clinic from 1976 through 1992 with rheumatoid arthritis (n = 16,263) cross-indexed with patients registered during the same period with a hematologic malignancy (n = 21,270). Adult patients were selected who had rheumatoid arthritis, were treated with a disease-modifying antirheumatic drug, and subsequently developed a hematologic malignancy. RESULTS: Thirty-nine patients met the selection criteria. Twelve of them had been given methotrexate. The characteristics of those who received methotrexate, including the type of hematologic malignancy, did not differ from those of patients who received other disease-modifying antirheumatic drugs. CONCLUSIONS: Hematologic malignancies are uncommon in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, including methotrexate. There does not appear to be a relationship between the peak or cumulative dose or the duration of methotrexate therapy and the subsequent development of hematologic malignancy. The histologic types of hematologic malignancy seen in the methotrexate-treated patients did not differ from those of patients treated with other disease-modifying antirheumatic drugs.

Use and interpretation of rheumatologic tests: a guide for clinicians.

In recent years, several new autoantibody tests have been developed and are being used in the field of rheumatology, including the antineutrophil cytoplasmic antibody (ANCA) and myositis-specific antibodies such as anti-Jo1. Positive test results for ANCAs reveal one of two basic staining patterns: cytoplasmic (c-ANCA) or perinuclear (p-ANCA). The Jo1 antibody test is often helpful at the time of diagnosis of a new case of idiopathic inflammatory myopathy. Herein this article reviews the clinical utility of the new tests in conjunction with the established autoantibody tests including antinuclear antibodies and extractable nuclear antibodies. Both the antinuclear antibody and extractable nuclear antibody tests are helpful in diagnosing connective tissue diseases. Before the results of any of these tests can be interpreted, the physician must consider the sensitivity, specificity, and negative and positive predictive values. Positive results must be analyzed in the clinical context and in relationship to other autoantibody test results.

A coproporphyria-like syndrome induced by glipizide.

A 49-year-old man with a 1-month history of episodic, severe abdominal pain sought medical attention. The patient's history was remarkable for type II diabetes, for which glipizide therapy had been initiated 2 months earlier. No other medications were being taken at the time the paroxysms of pain began. During the episodes of pain, both examination of the abdomen and abdominal roentgenograms revealed normal findings. Initial assessment, including ultrasonography and computed tomographic scanning of the abdomen, upper gastrointestinal and colon roentgenograms, and esophagogastroduodenoscopy, revealed no cause of the pain. Empiric trials of famotidine, sucralfate, and antacids failed to relieve the pain. Both urine and fecal specimens collected after an attack demonstrated substantially increased coproporphyrins. The glipizide regimen was discontinued; 2 months later, the stool coproporphyrins had decreased to normal levels. At follow-up more than 1 year later, the patient had had no recurrence of abdominal pain. Although other orally administered hypoglycemic agents and other sulfa compounds have been reported to precipitate acute attacks of porphyria, to our knowledge this is the first such case associated with glipizide. We suggest that glipizide be added to the list of medications to be avoided in patients with porphyria.

Fatal hypernatremia from exogenous salt intake: report of a case and review of the literature.

Hypernatremia is a common electrolyte disturbance, most often caused by volume depletion. Hypernatremia due to sodium excess occurs less frequently, and fatal hypernatremia solely from ingestion of table salt is rare. We describe a 41-year-old man who had seizures and hypernatremia after ingestion of a supersaturated salt water solution intended for gargling. He had consumed approximately a third cup of table salt (approximately 70 to 90 g of salt or 1,200 to 1,500 meq of sodium). His initial serum sodium concentration was 209 meq/liter. Hypotonic fluid therapy was given to provide free water and to correct the hypernatremia gradually. Our patient, however, failed to recover from the initial insult and died 3 days later. Review of the literature revealed 10 adult and 20 pediatric cases of hypernatremia attributable to exogenous intake of salt. The type of therapy (fluid or peritoneal dialysis), the type of fluid used, and the rate of correction of hypernatremia did not influence survival. The age of the patient and the initial serum sodium concentration were the most important prognostic indicators. Both very young patients and those with lesser degrees of hypernatremia had a better rate of survival than did other patients. In addition, our review illustrates the surprisingly small amount of salt that can cause severe hypernatremia and the danger of using salt or saline as an emetic.

Meningeal involvement in Wegener granulomatosis.

We describe 2 cases and review the literature on the spectrum of clinical manifestations associated with meningeal involvement in patients with Wegener granulomatosis (WG). A 31-year-old man and a 60-year-old woman with WG in complete clinical remission developed severe chronic headaches. No inflammatory activity was detectable at sites of previous disease activity, and nonspecific markers of inflammation were within normal limits. However, both patients had persistently elevated titers of antineutrophil cytoplasmic antibodies (cytoplasmic staining pattern). Cerebrospinal fluid examinations showed no abnormalities that suggested inflammation, infection, or malignancy. Head magnetic resonance imaging with gadolinium contrast revealed enhancement of the dura in both patients, and a meningeal biopsy in 1 patient confirmed active WG. Both patients' symptoms resolved after reinstitution of aggressive immunosuppressive therapy.

A patient with pulseless extremities: an unusual manifestation of cardiac tamponade.

We describe a 51-year-old man who came to our institution with cold cyanotic extremities. He was receiving radiation therapy for adenocarcinoma of the lung and superior vena cava syndrome. Findings on initial physical examination were notable for absent peripheral pulses and increased jugular venous pulsations. Shortly after admission, the patient experienced severe dyspnea and tachypnea. Arterial blood gas studies revealed mild metabolic acidosis. A chest roentgenogram showed an enlarged cardiac silhouette and the known mass in the right upper lobe of the lung. An electrocardiogram demonstrated no evidence of ischemia but low-voltage QRS complexes. An emergency echocardiogram disclosed a large pericardial effusion and evidence of hemodynamic compromise. With use of echocardiographic-guided pericardiocentesis, 600 ml of bloody fluid was removed; the pulses were immediately palpable in the patient's extremities. Although symptoms associated with the extremities are unusual as the initial complaint of patients with cardiac tamponade, we illustrate several key physical findings and abnormal results of laboratory test characteristic of this disorder. In addition, we underscore the importance of considering this diagnosis, especially in patients with a malignant tumor, and we describe the prompt response to therapy.

The shrinking lungs syndrome in systemic lupus erythematosus.

A comprehensive review of the literature on shrinking lungs syndrome (SLS) in systemic lupus erythematosus involved a MEDLINE search (1965-1997) of case reports and clinical series of patients with the diagnosis of SLS. A total of 49 well-documented cases of SLS were reviewed. Shrinking lungs syndrome is characterized by unexplained dyspnea, a restrictive pattern on pulmonary function test results, and an elevated hemidiaphragm. The cause of SLS remains controversial, with several authors attributing the disorder to diaphragmatic weakness and others suggesting that chest wall restriction accounts for the clinical syndrome. No definitive therapy exists. Corticosteroids have been reported to lessen symptoms and improve pulmonary function in some patients with SLS, but other methods of treatment have occasionally been found to be helpful. Clinical presentation, method of diagnosis, pathogenesis, and treatment modalities are summarized in this review. An uncommon complication of systemic lupus erythematosus, SLS causes significant morbidity and, occasionally, mortality.

Cardiac involvement in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a connective tissue disease characterized by the production of autoantibodies, can affect all organ systems. Cardiac involvement in patients with SLE has been described since the early 20th century. The manifestations are numerous and can involve all components of the heart, including the pericardium, conduction system, myocardium, valves, and coronary arteries. In recent years, echocardiography has yielded additional information about the heart in patients who have SLE with and without clinical cardiac involvement. Moreover, antiphospholipid antibodies have been linked to several cardiac manifestations in patients with SLE, including valvular abnormalities and possibly coronary artery disease. This updated, comprehensive review summarizes the new literature on SLE and the heart.

Renal cell carcinoma associated with sarcoidlike tissue reaction.

A 60-year-old man was referred to our institution with the diagnosis of sarcoidosis. Because of several months' complaint of right flank pain and weight loss, the patient had consulted his local physician. After an extensive workup revealed only cholelithiasis, he underwent a cholecystectomy for presumed chronic cholecystitis. At the time of operation, biopsy of several liver nodules and peripancreatic nodes revealed noncaseating granulomas, consistent with sarcoidosis. On initial examination at our institution, the patient had microhematuria. A chest roentgenogram demonstrated multiple pulmonary nodules, an abdominal computed tomographic scan showed an indeterminate left renal mass, and magnetic resonance imaging of the spine revealed abnormal signals in the body of T-12. Open-lung biopsy showed an adenocarcinoma with clear cell features, likely of renal origin. The patient was diagnosed as having a metastatic renal carcinoma associated with a sarcoidlike tissue reaction. Although noncaseating granulomas have been reported in association with other malignant lesions, to our knowledge this is the first report of such an association with renal carcinoma. In addition, this case illustrates several points. First, sarcoidosis is a multisystem disorder with protean extrapulmonary manifestations. In fact, all our patient's findings could have been attributed to sarcoidosis. Second, noncaseating granulomas occur with many types of processes, including infections, chemical exposures, and, as in this case, neoplasms. Thus, noncaseating granulomas are not pathognomonic for sarcoidosis. Third, sarcoidosis is a clinical diagnosis that cannot be based on histologic findings alone.

Prevention of collagen induced arthritis in mice by treatment with an antibody directed against the T cell receptor alpha beta framework.

Collagen induced arthritis (CIA) is an animal model of inflammatory polyarthritis. Type II collagen is the major matrix protein of hyaline cartilage. Susceptibility to CIA is linked to the Major Histocompatibility Complex Class II genes but the presence of T cells expressing specific variable beta (V beta) chain of their T cell receptor (TCR) is also required. Pretreatment with the monoclonal antibody H57-597 directed against the TCR alpha beta framework prevented the onset of arthritis in the majority of animals. The depletion of the T cell population did not lead to any apparent health problems. These experiments demonstrate the important role of the alpha/beta T cell and its receptors in the CIA model. Further, anti-TCR alpha beta antibodies may be of value in the therapy of autoreactive disorders.

Lymphomas in patients with connective tissue disease. Comparison of p53 protein expression and latent EBV infection in patients immunosuppressed and not immunosuppressed with methotrexate.

Cell cycle dysregulation as measured by p53 protein expression and latent Epstein-Barr (EBV) infection are important in the pathogenesis of lymphoma, particularly in immunosuppressed patients. Although latent EBV commonly is detected in lymphomas arising in patients with connective tissue disease who are immunosuppressed with methotrexate, p53 protein expression has not been reported. We compared the immunohistologic expression of p53 protein and the incidence of latent EBV infection in lymphomas arising in patients with connective tissue disease treated and not treated with methotrexate. Increased p53 staining was detected in 10 of 11 lymphomas arising in patients after methotrexate therapy vs 5 of 11 in patients not treated with methotrexate. Latent EBV was detected in 7 of 13 lymphomas arising in patients after methotrexate therapy vs 2 of 11 in patients not treated with methotrexate. Concordant p53 expression and latent EBV were detected in 5 of 7 lymphomas arising after treatment with methotrexate, including 1 that regressed after methotrexate therapy was withdrawn. These findings suggest that cell cycle dysregulation and EBV-related transformation are important in the pathogenesis of lymphomas arising in patients with connective tissue disease who are immunosuppressed with methotrexate.

Mycophenolate mofetil is effective in reducing disease flares in systemic lupus erythematosus patients: a retrospective study.

Mycophenolate mofetil (MMF) is effective in the treatment of patients with active systemic lupus erythematosus (SLE). We sought to evaluate its efficacy in reducing the number of disease flares in adults with SLE. For this retrospective study, all patients seen at our institution over a six year period, 1999-2005, with the diagnosis of SLE treated with MMD were identified. Data regarding lupus flare was obtained for patients at least one and up to two years prior to starting MMF. The number of flares prior to MMF therapy was compared to the number of lupus flares in the one to two year period after starting MMF. Clinical assessment was performed with the SELENA-SLEDAI instrument. Differences between groups were compared using the signed rank test. The rate of flares (flares per person-year), before and after the introduction of MMF were compared assuming the occurrence of flares followed a Poisson distribution. In the evaluable 67 patients, the mean time period of followup prior to starting MMF was 14.1 months (range 0.3-24), mean time period of follow-up after starting MMF was 14.8 months (range 1.5-24); and mean MMF dose was 1328 mg/day (range 250-3000). The mean flare rate was reduced from 8.9 to 5.3 per 10 personyears and the mean prednisone dose was reduced on average 7.3 mg/day after starting MMF therapy. MMF treatment significantly reduced the total number of lupus flares and prednisone requirements. Even with the reduction in mean daily prednisone dose, both the SLEDAI and physican global assessment also improved during MMF therapy.

Maternal and foetal outcomes in pregnant patients with active lupus nephritis.

The objective of this study was to determine the impact of lupus nephritis disease activity on maternal and foetal outcomes in pregnant patients with systemic lupus erythematosus (SLE). Medical records of all pregnant patients with SLE treated at our institution between 1976 and 2007 were reviewed. All patients met American College of Rheumatology classification criteria for SLE. Demographic data, history of lupus nephritis, nephritis disease activity and maternal and foetal outcomes of pregnancy were abstracted. Active lupus nephritis was defined as the presence of proteinuria >0.5 g/day and/or active urinary sediment with or without an elevation in serum creatinine (Cr). Quiescent lupus nephritis was confirmed in the presence of proteinuria <0.5 mg/day and inactive urinary sediment. We identified 58 patients with 90 pregnancies. Compared with pregnancies in SLE patients without renal involvement (n = 47), pregnancies in patients with active lupus nephritis (n = 23) were associated with a higher incidence of maternal complications (57% vs 11%, P < 0.001), whereas those with quiescent lupus nephritis (n = 20) were not (35% vs 11%, P = 0.10). Women with active lupus nephritis were more likely to deliver preterm than women without lupus nephritis, median of 34 weeks vs 40 gestational weeks, respectively (P = 0.002) and were more likely to suffer foetal loss (35% vs 9%, P = 0.031). Active, but not quiescent, lupus nephritis during pregnancy is associated with a higher incidence of maternal and foetal complications compared with pregnancies in SLE patients without renal involvement.

New medications for use in patients with rheumatoid arthritis.

INTRODUCTION: Several new medications have become available to physicians for the treatment of patients with rheumatoid arthritis (RA). LEARNING OBJECTIVES: To familiarize the reader with these new medications, including their benefits and side effects. DATA SOURCES: Data sources include published articles regarding the use of these medications. Study selection includes available information obtained from an online literature search (Mayo Search) regarding these agents, with additional information from the manufactures and our pharmacy. CONCLUSION: The results of this review indicate that leftunomide (Arava) and etanercept (Enbrel) are useful new agents for treatment of patients with rheumatoid arthritis.

Immunologic tests in rheumatology.

LEARNING OBJECTIVES: Reading this article will familiarize the reader with the application and interpretation of different autoantibody tests used in rheumatology. DATA SOURCES: Recent rheumatologic textbooks, relevant review articles, and seminal articles in English regarding specific tests. RESULTS: An understanding of this review should enable the reader to approach diagnostic testing systematically in a patient with a suspected connective tissue disease. CONCLUSIONS: The proper use and interpretation of appropriate immunologic tests are important in the diagnosis and treatment of patients with connective tissue diseases.