Impact of early versus late systemic lupus erythematosus diagnosis on clinical and economic outcomes.

BACKGROUND AND OBJECTIVES: Systemic lupus erythematosus (SLE) is a multisystem complex autoimmune disease that often mimics symptoms of other illnesses, which complicates the ability of healthcare providers to make the diagnosis. The objective of this study was to assess clinical outcomes, resource utilization, and costs between patients with earlier versus later SLE diagnosis. METHODS: Patients aged 18-64 years were identified from a large US commercial claims database between January 2000 and June 2010. Confirmed SLE diagnosis with a claims-based algorithm required either three or more claims for a visit to a rheumatologist on separate dates with an SLE diagnosis (International Classification of Diseases [ICD-9] code 710.0x), two or more claims for visits to a rheumatologist at least 60 days apart with SLE diagnoses, or two or more claims for visits to rheumatologist less than 60 days apart with SLE diagnoses with at least one dispensing for a typical SLE medication. SLE probable onset date was identified during the 12-month baseline period by the second claim for antinuclear antibody tests or prodromal symptoms of SLE. Patients were stratified into early or late diagnosis groups based on time between probable SLE onset and diagnosis (<6 months or ≥6 months, respectively). Each patient observation period began on the date of the first medical claim, with a diagnosis code for SLE that satisfied the inclusion criteria, and ended on the earliest date between health plan disenrollment and 30 June 2010. Patients in each group were propensity-score matched on age, gender, diagnosis year, region, health plan type, and comorbidities. Flare rates and resource utilization were compared post-diagnosis between groups using rate ratios. All-cause and SLE-related costs (adjusted to 2010 US dollars) per patient per month (PPPM) were calculated. RESULTS: There were 4,166 matched patients per group. Post-SLE diagnosis, the early diagnosis group had lower rates of mild (rate ratio [RR] 0.95; 95 % CI 0.93-0.96), moderate (RR 0.96; 95 % CI 0.94-0.99), and severe (RR 0.87; 95 % CI 0.82-0.93) flares compared with the late diagnosis group. The rates of hospitalizations (RR 0.80; 95 % CI 0.75-0.85) were lower for the early diagnosis group than the late diagnosis group. Compared with late diagnosis patients, mean all-cause inpatient costs PPPM were lower for the early diagnosis patients (US$406 vs. US$486; p = 0.016). Corresponding SLE-related hospitalization costs were also lower for early compared with late diagnosis patients (US$71 vs. US$95; p = 0.013). Results were consistent for other resource use and cost categories. CONCLUSIONS: Patients diagnosed with SLE sooner may experience lower flare rates, less healthcare utilization, and lower costs from a commercially insured population perspective. This finding needs to be further explored within the context of background SLE disease activity.

Clinical practice guideline: improving voice outcomes after thyroid surgery.

OBJECTIVE: Thyroidectomy may be performed for clinical indications that include malignancy, benign nodules or cysts, suspicious findings on fine needle aspiration biopsy, dysphagia from cervical esophageal compression, or dyspnea from airway compression. About 1 in 10 patients experience temporary laryngeal nerve injury after surgery, with longer lasting voice problems in up to 1 in 25. Reduced quality of life after thyroid surgery is multifactorial and may include the need for lifelong medication, thyroid suppression, radioactive scanning/treatment, temporary and permanent hypoparathyroidism, temporary or permanent dysphonia postoperatively, and dysphagia. This clinical practice guideline provides evidence-based recommendations for management of the patient's voice when undergoing thyroid surgery during the preoperative, intraoperative, and postoperative period. PURPOSE: The purpose of this guideline is to optimize voice outcomes for adult patients aged 18 years or older after thyroid surgery. The target audience is any clinician involved in managing such patients, which includes but may not be limited to otolaryngologists, general surgeons, endocrinologists, internists, speech-language pathologists, family physicians and other primary care providers, anesthesiologists, nurses, and others who manage patients with thyroid/voice issues. The guideline applies to any setting in which clinicians may interact with patients before, during, or after thyroid surgery. Children under age 18 years are specifically excluded from the target population; however, the panel understands that many of the findings may be applicable to this population. Also excluded are patients undergoing concurrent laryngectomy. Although this guideline is limited to thyroidectomy, some of the recommendations may extrapolate to parathyroidectomy as well. RESULTS: The guideline development group made a strong recommendation that the surgeon should identify the recurrent laryngeal nerve(s) during thyroid surgery. The group made recommendations that the clinician or surgeon should (1) document assessment of the patient's voice once a decision has been made to proceed with thyroid surgery; (2) examine vocal fold mobility, or refer the patient to a clinician who can examine vocal fold mobility, if the patient's voice is impaired and a decision has been made to proceed with thyroid surgery; (3) examine vocal fold mobility, or refer the patient to a clinician who can examine vocal fold mobility, once a decision has been made to proceed with thyroid surgery if the patient's voice is normal and the patient has (a) thyroid cancer with suspected extrathyroidal extension, or (b) prior neck surgery that increases the risk of laryngeal nerve injury (carotid endarterectomy, anterior approach to the cervical spine, cervical esophagectomy, and prior thyroid or parathyroid surgery), or (c) both; (4) educate the patient about the potential impact of thyroid surgery on voice once a decision has been made to proceed with thyroid surgery; (5) inform the anesthesiologist of the results of abnormal preoperative laryngeal assessment in patients who have had laryngoscopy prior to thyroid surgery; (6) take steps to preserve the external branch of the surperior laryngeal nerve(s) when performing thyroid surgery; (7) document whether there has been a change in voice between 2 weeks and 2 months following thyroid surgery; (8) examine vocal fold mobility or refer the patient for examination of vocal fold mobility in patients with a change in voice following thyroid surgery; (9) refer a patient to an otolaryngologist when abnormal vocal fold mobility is identified after thyroid surgery; (10) counsel patients with voice change or abnormal vocal fold mobility after thyroid surgery on options for voice rehabilitation. The group made an option that the surgeon or his or her designee may monitor laryngeal electromyography during thyroid surgery. The group made no recommendation regarding the impact of a single intraoperative dose of intravenous corticosteroid on voice outcomes in patients undergoing thyroid surgery.

Cumulative burden of oral corticosteroid adverse effects and the economic implications of corticosteroid use in patients with systemic lupus erythematosus.

BACKGROUND: Corticosteroids (CSs) are used to treat patients with systemic lupus erythematosus (SLE) and are associated with potential adverse events (AEs). However, few data are currently available on the risk of AEs in CS users in an SLE population. OBJECTIVE: To examine AEs related to CS use and costs of treating CS-related AEs in patients with SLE. METHODS: In a retrospective cohort study using claims data (study period: January 1, 2000-June 30, 2010), patients aged ≥18 years having ≥2 SLE-related (International Classification of Diseases, Ninth Revision, Clinical Modification code 710.0x) outpatient or ≥1 inpatient/emergency department claim were identified with an index diagnosis date deemed as the date of first SLE diagnosis. Receipt of CS therapy was assessed within 6 months of the index diagnosis date. Cox models were used to evaluate risk of AEs in CS users and nonusers. Associated costs were computed for AEs where risk was significantly different among the cohorts. RESULTS: Of 2717 patients with SLE, 989 received CSs and 1728 did not. Users of CSs were ~1.5 times more likely to develop chronic AEs (sleep disturbances, migraines, cataracts, hypertension, and type 2 diabetes mellitus) and ~2 times more likely to develop acute AEs (pneumonia, herpes zoster, fungal infections, and nausea/vomiting) compared with CS nonusers. The mean annual cost for managing AEs was $4607 and was highest for diabetes mellitus ($9764), hypertension ($8773), and sleep disturbances ($5599). Applying differences in 1-year event rates (CS user: 58.1%; CS nonuser: 75.1%) to cost estimates yielded an additional $784 per year per CS user to manage known CS-related AEs compared with CS nonusers. CONCLUSIONS: Although CSs are prescribed to control SLE symptoms, these results highlight potential risks and costs associated with their use, which providers/payers should consider when making treatment decisions.

A case of human T lymphotropic virus type I-associated synovial swelling.

BACKGROUND: Human T lymphotropic virus type 1 (HTLV-I) is associated with T-cell activation, proliferation, and leukemogenesis. HTLV-I is the causative agent of adult T cell leukemia/lymphoma and is associated with myelopathy/tropical spastic paraparesis, uveitis, polymyositis, synovitis, thyroiditis, and bronchoalveolar pneumonia. Since T-cell abnormalities are present in those infected with HTLV-I, the clinical problems might result from abnormal immune function or from direct leukemic or lymphomatous cell infiltration of tissues in the body. Distinguishing between these potential causes might be difficult in patients with joint involvement since the clinical findings can be similar. Consequently, obtaining synovial tissue for analyses is likely to be helpful in determining which process is causing the clinical symptoms. INVESTIGATIONS: Physical examination, comprehensive metabolic panel, complete blood counts, urinalysis, serological testing for rheumatoid factor, antinuclear antibodies, hepatitis, and cytomegalovirus; western blot for HTLV-I/II, lymphocyte phenotyping of peripheral blood, polymerase chain reaction, plain radiographic imaging, CT, MRI skin biopsy with immunohistochemical analysis, lymph node biopsy with immunohistochemical analysis, lymphocyte phenotyping of synovial fluid, synovial tissue biopsy with immunohistochemical analysis of synovial tissue, and synovial tissue culture. DIAGNOSIS: HTLV-I infected synovial cells in conjunction with leukemic/lymphomatous infiltration of synovial tissue. MANAGEMENT: Chemotherapy protocol using alemtuzumab.

Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry.

The origins of autoimmunity in systemic lupus erythematosus (SLE) are thought to involve both genetic and environmental factors. To identify environmental agents that could potentially incite autoimmunity, we have traced the autoantibody response in human SLE back in time, prior to clinical disease onset, and identified the initial autoantigenic epitope for some lupus patients positive for antibodies to 60 kDa Ro. This initial epitope directly cross-reacts with a peptide from the latent viral protein Epstein-Barr virus nuclear antigen-1 (EBNA-1). Animals immunized with either the first epitope of 60 kDa Ro or the cross-reactive EBNA-1 epitope progressively develop autoantibodies binding multiple epitopes of Ro and spliceosomal autoantigens. They eventually acquire clinical symptoms of lupus such as leukopenia, thrombocytopenia and renal dysfunction. These data support the hypothesis that some humoral autoimmunity in human lupus arises through molecular mimicry between EBNA-1 and lupus autoantigens and provide further evidence to suspect an etiologic role for Epstein-Barr virus in SLE.

The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus.

OBJECTIVE: To determine whether antiphospholipid antibodies (aPL) occur before the diagnosis of systemic lupus erythematosus (SLE) and before initial clotting events, and whether their presence early in the disease course influences clinical outcome. METHODS: Serum samples obtained from 130 lupus patients before and after SLE diagnosis were screened for IgG and IgM aPL using an anticardiolipin (aCL) enzyme-linked immunosorbent assay. Medical records of all patients were carefully reviewed for data on the time of onset of SLE features meeting clinical criteria and on disease manifestations. RESULTS: Twenty-four patients (18.5%) were positive for IgG and/or IgM aCL prior to SLE diagnosis. Anticardiolipin antibodies appeared from 7.6 years prior to SLE diagnosis to within the same month as SLE diagnosis, with a mean onset occurring 3.0 years before SLE diagnosis. Additionally, aCL presence early in the disease process seemed to predict a more severe clinical outcome; these patients eventually met an average of 6.1 of the 11 classification criteria for SLE, compared with 4.9 criteria for other patients (P < 0.001). The early aCL-positive population also had more frequent renal disease, central nervous system disease, thrombocytopenia, and clotting events. In this population, aCL preceded initial thrombotic events by a mean of 3.1 years. CONCLUSION: Anticardiolipin antibodies in SLE patients tend to precede initial clotting events by several years. Furthermore, the presence of early, prediagnosis aPL seems to herald a more varied, severe clinical course with earlier onset in patients with SLE.

Development of autoantibodies before the clinical onset of systemic lupus erythematosus.

BACKGROUND: Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of autoantibody development before the clinical diagnosis. METHODS: The Department of Defense Serum Repository contains approximately 30 million specimens prospectively collected from more than 5 million U.S. Armed Forces personnel. We evaluated serum samples obtained from 130 persons before they received a diagnosis of SLE, along with samples from matched controls. RESULTS: In 115 of the 130 patients with SLE (88 percent), at least one SLE autoantibody tested was present before the diagnosis (up to 9.4 years earlier; mean, 3.3 years). Antinuclear antibodies were present in 78 percent (at a dilution of 1:120 or more), anti-double-stranded DNA antibodies in 55 percent, anti-Ro antibodies in 47 percent, anti-La antibodies in 34 percent, anti-Sm antibodies in 32 percent, anti-nuclear ribonucleoprotein antibodies in 26 percent, and antiphospholipid antibodies in 18 percent. Antinuclear, antiphospholipid antibodies, anti-Ro, and anti-La antibodies were present earlier than anti-Sm and anti-nuclear ribonucleoprotein antibodies (a mean of 3.4 years before the diagnosis vs. 1.2 years, P=0.005). Anti-double-stranded DNA antibodies, with a mean onset 2.2 years before the diagnosis, were found later than antinuclear antibodies (P=0.06) and earlier than anti-nuclear ribonucleoprotein antibodies (P=0.005). For many patients, the earliest available serum sample was positive; therefore, these measures of the average time from the first positive antibody test to the diagnosis are underestimates of the time from the development of antibodies to the diagnosis. Of the 130 initial matched controls, 3.8 percent were positive for one or more autoantibodies. CONCLUSIONS: Autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibodies in patients with SLE tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic.