Bobby Kwanghoon Han

The revised fibromyalgia impact questionnaire (FIQR): Validation and psychometric properties

IntroductionThe Fibromyalgia Impact Questionnaire (FIQ) is a commonly used instrument in the evaluation of fibromyalgia (FM) patients. Over the last 18 years, since the publication of the original FIQ, several deficiencies have become apparent and the cumbersome scoring algorithm has been a barrier to widespread clinical use. The aim of this paper is to describe and validate a revised version of the FIQ: the FIQR.MethodsThe FIQR was developed in response to known deficiencies of the FIQ with the help of a patient focus group. The FIQR has the same 3 domains as the FIQ (that is, function, overall impact and symptoms). It differs from the FIQ in having modified function questions and the inclusion of questions on memory, tenderness, balance and environmental sensitivity. All questions are graded on a 0–10 numeric scale. The FIQR was administered online and the results were compared to the same patients online responses to the 36-Item Short Form Health Survey (SF-36) and the original FIQ.ResultsThe FIQR was completed online by 202 FM patients, 51 rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) patients (31 RA and 20 SLE), 11 patients with major depressive disorder (MDD) and 213 healthy controls (HC). The mean total FIQR score was 56.6 ± 19.9 compared to a total FIQ score of 60.6 ± 17.8 (P < 0.03). The total scores of the FIQR and FIQ were closely correlated (r = 0.88, P < 0.001). Each of the 3 domains of the FIQR correlated well with the 3 related FIQ domains (r = 0.69 to 0.88, P < 0.01). The FIQR showed good correlation with comparable domains in the SF-36, with a multiple regression analysis showing that the three FIQR domain scores predicted the 8 SF-36 subscale scores. The FIQR had good discriminant ability between FM and the 3 other groups; total FIQR scores were HC (12.1 ± 11.6), RA/SLE (28.6 ± 21.2) and MDD (17.3 ± 11.8). The patient completion time was 1.3 minutes; scoring took about 1 minute.ConclusionsThe FIQR is an updated version of the FIQ that has good psychometric properties, can be completed in less than 2 minutes and is easy to score. It has scoring characteristics comparable to the original FIQ, making it possible to compare past FIQ results with future FIQR results.

SLE Peripheral Blood B Cell, T Cell and Myeloid Cell Transcriptomes Display Unique Profiles and Each Subset Contributes to the Interferon Signature

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by defective immune tolerance combined with immune cell hyperactivity resulting in the production of pathogenic autoantibodies. Previous gene expression studies employing whole blood or peripheral blood mononuclear cells (PBMC) have demonstrated that a majority of patients with active disease have increased expression of type I interferon (IFN) inducible transcripts known as the IFN signature. The goal of the current study was to assess the gene expression profiles of isolated leukocyte subsets obtained from SLE patients. Subsets including CD19+ B lymphocytes, CD3+CD4+ T lymphocytes and CD33+ myeloid cells were simultaneously sorted from PBMC. The SLE transcriptomes were assessed for differentially expressed genes as compared to healthy controls. SLE CD33+ myeloid cells exhibited the greatest number of differentially expressed genes at 208 transcripts, SLE B cells expressed 174 transcripts and SLE CD3+CD4+ T cells expressed 92 transcripts. Only 4.4% (21) of the 474 total transcripts, many associated with the IFN signature, were shared by all three subsets. Transcriptional profiles translated into increased protein expression for CD38, CD63, CD107a and CD169. Moreover, these studies demonstrated that both SLE lymphoid and myeloid subsets expressed elevated transcripts for cytosolic RNA and DNA sensors and downstream effectors mediating IFN and cytokine production. Prolonged upregulation of nucleic acid sensing pathways could modulate immune effector functions and initiate or contribute to the systemic inflammation observed in SLE.

Criteria for the diagnosis of fibromyalgia: validation of the modified 2010 preliminary American College of Rheumatology criteria and the development of alternative criteria.

To validate the 2011 modification of the 2010 American College of Rheumatology (ACR) preliminary criteria for the diagnosis of fibromyalgia (2011ModCr) and develop alternative criteria in a sample of patients with diverse pain disorders that are commonly seen in everyday practice by pain specialists, rheumatologists, and psychologists.

Increased prevalence of activated CD70+CD4+ T cells in the periphery of patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by loss of immune tolerance. A hallmark of SLE is the presence of autoantibodies resulting from B cell hyperactivity. Previous studies have shown that the presence of abnormal B cell subsets in the periphery, such as CD27highCD20− B cells, correlate with disease activity. We examined the relationship between the expression of CD70, the ligand for CD27 expressed by activated T cells, and indicators of disease activity. A significant increase in median CD70+CD4+ T cell frequencies and memory CD45RA−CD4+ T cell frequencies was observed in SLE samples as compared to healthy controls. The frequencies of CD70+CD4+ T cells correlated with disease duration but not age, treatment, or disease activity. Although a majority of CD70+CD4+ T cells appeared to be effector memory cells, mitogen-stimulated CD70+CD4+ T cells were capable of secreting a full repertoire of effector cytokines. Despite the presence of activated CD4+ T cells, no increase in immunosenescent CD4+ T cells, as defined by the loss of CD28 and/or the acquisition of CD57 was observed in samples from SLE patients. These studies indicate that increased CD70 expression might serve as a useful marker of abnormal T cell activity in SLE.

Clinical presentations and outcomes of systemic lupus erythematosus patients with infection admitted to the intensive care unit.

Objective The objective of this article is to investigate clinical presentations and outcomes of systemic lupus erythematosus (SLE) patients with infection admitted to the intensive care unit (ICU). Methods SLE patients with infection, SLE patients with noninfectious causes, and non-SLE patients with infection were identified from the Cooper University Hospital Project IMPACT database between 2002 and 2010. We examined demographic data, APACHE II scores, physiologic data, laboratory data, length of stay in the ICU and hospital, and mortality of the three groups. Results Twenty-five SLE patients with infection, 45 SLE patients with noninfectious causes, and 1466 non-SLE patients with infection were included in the study. SLE patients with infection had higher APACHE II scores, higher maximum temperature, higher minimum and maximum heart rate (HR), lower minimum and maximum systolic blood pressure (SBP), and longer ICU length of stay in comparison to SLE patients with noninfectious causes. There were no statistical differences in white blood cell (WBC) count. SLE patients with infection had a higher mortality compared to SLE patients with noninfectious causes. There was no difference in mortality between SLE patients with infection and non-SLE patients with infection. Conclusion SLE patients with infection in the ICU had a higher mortality and a higher APACHE II score compared to SLE patients with noninfectious causes in the ICU. Their physiologic signs including temperature, HR, and SBP were more reflective of infection than their WBC count.

Intractable vomiting as an initial presentation of lupus-related neuromyelitis optica.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare neurological condition known to occur in association with systemic autoimmune disorders. We describe here a patient with intractable nausea and vomiting as the first presentation of NMOSD, in which systemic lupus erythematosus was diagnosed subsequently. A previously healthy 41-year-old Chinese woman presented with a 1-week history of severe nausea and vomiting, which was occurring 8 to 10 times daily and was unresponsive to oral antiemetics. She also reported mild paresthesias of the face and extremities. She did not report any other symptoms, such as headaches, visual changes, abdominal pain, or diarrhea. An evaluation by a gastroenterologist included esophagogastroduodenoscopy, gastric emptying scan, and computed tomography of the abdomen; all did not show abnormalities. A magnetic resonance imaging (MRI) of the brain and spine showed a small region of abnormally increased signal intensity within the area postrema and no abnormalities of the cervical spine (Figure). Four days later, the nausea and vomiting resolved spontaneously. She was discharged to home and instructed to schedule a follow-up appointment with neurology. Two months later, the patient presented with increased paresthesias of the left upper and lower extremities and the evolution of weakness in bilateral lower extremities over 1 week. A lumbar puncture revealed 58 white blood cells (reference range, 0Y5) with 97% lymphocytes, normal protein and glucose, no oligoclonal bands, and normal immunoglobulin G (IgG) index. An MRI showed progression of signal abnormalities at the craniocervical junction involving the medulla and upper cervical cord down to the level of C3Y4 with associated mild upper cord expansion with no evidence of optic neuritis (Figure). Complete blood count demonstrated low white blood cell count at 2700/HL (reference, 4000Y11,000/HL) with low absolute lymphocyte count at 550 (reference, 91500) and normal hemoglobin and platelet count. Her serologies were remarkable for a positive antinuclear antibody of 1:640 dilution (reference, G1:80), anti-SSA greater than 8 (reference, G1), anti-SSB greater than 8 (reference, G1), C3 27 mg/dL (reference range, 86Y184 mg/dL), and C4 6 mg/dL (reference range, 20Y59 mg/dL). Anti-Smith, anti-RNP, antiYdouble-stranded DNA antibodies, lupus anticoagulant, anticardiolipin, and anti-A2 glycoprotein I antibodies were negative. Urinalysis was within reference range, and serum creatinine was within reference range. The serum NMO-IgG autoantibody test was positive at 1/1600 U performed by immunofluorescence assay. The patient denied any sicca symptoms, fatigue, joint pain, swelling, or skin rash. Based on her clinical symptoms, positive serology, and MRI findings, coexistence of NMOSD and a systemic autoimmune disorder was highly suspected. The patient received pulse methylprednisolone at a dose of 1000 mg/d for 3 days, which was followed by intravenous cyclophosphamide at a dose of 750 mg/m monthly for 6 cycles. After completion of her cyclophosphamide course, she was switched to maintenance therapy with azathioprine at a dose of 1.5 mg/kg per day. Her prednisone dose was started at 60 mg/d and tapered to 10 mg/d over 6 months. She recovered well in response to treatments and has no residual paresthesias or weakness. A cervical MRI done by the end of her cyclophosphamide course showed near-complete resolution of the previously noted signal abnormalities. After 6 months from her initial presentation, she began to note pain in joints of the hands and feet, which is consistent with a diagnosis of systemic lupus erythematosus. Neuromyelitis optica (also known as Devic disease) is a central nervous system demyelinating autoimmune disease characterized by severe recurrent attacks that target the optic nerves and spinal cord. The prognosis is often unfavorable, with either monocular blindness or loss of ambulatory capacity in more than 50% of patients within 5 years. Its pathophysiology is not entirely understood; however, aquaporin 4, the predominant central nervous system water channel, is believed to be the target antigen for the NMO-IgG autoantibody. According to the first report, NMO-IgG antibody test performed by an indirect immunofluorescence assay had a sensitivity of 73% and a specificity of 91% for NMO. The area postrema, where the vomiting center is located, is an aquaporin 4Yenriched region and is thought to be an important first point of attack in NMO. This finding is compatible with clinical reports of nausea and vomiting preceding episodes of optic neuritis or myelitis in NMO. The initial MRI findings in our case demonstrated isolated involvement of the area postrema during the vomiting episode, supporting the diagnosis of NMO. Intractable nausea and vomiting in association with an abnormal signal in the area postrema on MRI should be regarded as a heralding symptom of NMO. The most widely accepted diagnostic criteria for NMO require the presence of optic neuritis, acute myelitis, and at least 2 out of (i) contiguous spinal cord MRI lesion extending over 3 or more vertebral segments; (ii) brain MRI not meeting diagnostic criteria for multiple sclerosis; and (iii) NMO-IgG seropositive status. Patients with isolated optic neuritis or myelitis and a positive NMO-IgG antibody are described as having NMOSD. It has been recognized that the association of optic neuritis or longitudinally extensive myelitis with systemic autoimmune disorders, as well as with brain MRI lesions such as brainstem lesions, is now considered typical of NMOSD. Our patient fulfills the criteria for NMOSD but not the diagnostic criteria for definite NMO, as she has no evidence of optic neuritis on MRI. CONCISE REPORT

CE-12 Comparison of classification criteria, self-assessments and immunologic profiles in patients with incomplete and systemic lupus erythematosus

Background The syndrome of incomplete lupus erythematosus (ILE) likely includes individuals at risk for development of systemic lupus erythematosus (SLE). Studies of interventions to lower risk or prevent further disease in ILE are of interest. Design of such trials will require methods to classify patients and to assess risk. The goals of the present study were to evaluate performance of updated SLE classification criteria to define ILE and to probe for other features in these patients that might be useful as indicators of disease status. A long term goal is to develop prognostic multifaceted risk profiles that would have clinical applications. Materials and methods Patients with ILE (N = 70) and SLE (N = 32) defined by the 1997 American College of Rheumatology (ACR) criteria were then reclassified using the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. Disease activity, patient self-assessments and levels of autoantibodies, soluble mediators and expressed Type I interferon (IFN) genes also were measured in the ILE and SLE patients and compared to healthy control (HC) individuals. Results The two sets of classification criteria were highly correlated (Figure 1; R2 = 0.87). ILE patients were older (P = 0.0043), with lower SLEDAI scores (P = 0.023) and greater dissatisfaction with their health status (P = 0.034) than SLE patients. Anti-C1q and sCD27 levels were correlated with ACR criteria and SLE Disease Activity Index (SLEDAI) scores (P ≤ 0.0004). Three cytokines, IL-7, IL12p70 and IL-13, were lower in both ILE and SLE than in HCs. Two IFN-related cytokines IP = 10 and MCP-1, were higher in SLE than in ILE. Of three IFN genes measured, IFI27 showed the greatest difference between ILE and SLE. Conclusions The 2012 SLICC SLE classification criteria likely can be used to define ILE in future research trials. Patients with ILE are somewhat dissatisfied with their condition, possibly related to anxiety about the lack of a clear diagnosis. Further patient-reported outcome studies in this population would be of interest. Reliable assessment of lupus risk will likely include demographic, clinical and immunologic features. Some of the latter may suggest novel approaches to early treatment. Abstract CE-12 Figure 1 Correlation between two SLE classification criteria, the 1997 ACR and 2012 SLICC sets, in 102 patients with either ILE or SLE. Values on each axis correspond to numbers of criteria in each of the sets. Significance determined using Pearson’s R. Acknowledgements This project was funded, in part, with a grant from the Pennsylvania Department of Health using Tobacco CURE Funds. The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. It was also?supported in part by the National Institutes of Health, NIAMS U34 AR067392. The data entry assistance of Fan He is appreciated.

Are ocular complications of a high-dose glucocorticoid treatment appropriately monitored in patients with rheumatic diseases?

Glucocorticoid is frequently used in treating various rheumatic conditions. However it is known to cause multiple toxicities including cataract or glaucoma. In this study, we examined whether patients with rheumatic diseases had appropriate ocular monitoring for glucocorticoid toxicities. From rheumatology clinics in South New Jersey of the USA, we retrospectively identified patients with ages between 18 and 60 years old who received a high accumulative dose of glucocorticoid, which was defined as glucocorticoid dose greater than prednisone 7.5mg/day × 6 months = 1,350 mg. We observed rheumatologists recommended eye examinations only in 14/37 (37.8 %) of patients. Family history was present for cataract in 13/37 (35.1 %) patients and for glaucoma in 6/37 (16.2 %) patients. Rheumatologists recommended eye examinations in 4/13 (30.7 %) and 0/6 (0 %) patients in each group. This study suggested that rheumatologists did not appropriately monitor ocular complications of a high dose glucocorticoid, even in patients with a positive family history.

Posterior spondylitis of costovertebral joints in a patient with psoriatic arthritis.

A 41-year-old white man presented with neck and upper back pain of 1-year duration. The pain was excruciating, continuous, and radiating from the upper back to the occipital region. He was diagnosed with psoriasis at 20 years old. He was treated with methotrexate for 1 year and etanercept for 6 months but discontinued these medications because of inefficacy. He developed joint pain, and psoriatic arthritis was diagnosed 5 years ago. On physical examination, there were multiple tender and swollen joints and generalized psoriatic lesions including nail dystrophy. His neck examination showed markedly limited range of motion in all directions. A magnetic resonance imaging (MRI) showed heterogeneous signals at several levels throughout the posterior vertebral endplates of the thoracic spine. These regions of abnormal signal were noted to be of low signal intensity on T1-weighted imaging (Fig. 1A) and increased signal intensity on T2 and Short TI inversion recovery (Fig. 1B). These findings indicated bone marrow edema in costovertebral joints. On a computed tomographyscan, these signals corresponded to regions