Lawrence H. Brent

Transverse myelopathy in systemic lupus erythematosus: an analysis of 14 cases and review of the literature

OBJECTIVE To give a comprehensive review of transverse myelopathy (TM), a rare but serious condition reported in 1–2% of patients with systemic lupus erythematosus (SLE). METHODS 14 patients with SLE and TM were evaluated and 91 additional cases published in the English and German literature reviewed. RESULTS TM presented either as the initial manifestation or within five years of the diagnosis of SLE. Most patients presented with a detectable sensory deficit at the thoracic level. In our 14 patients, 22% of the patients showed complete neurological recovery, whereas in the total patient population of 105 (our cases plus those reviewed in the literature), complete recovery was observed in 50%, partial recovery in 29% and no improvement or deterioration in 21%. Treatment with intravenous methylprednisolone followed by cyclophosphamide seemed to be most effective. Seventy per cent of the total patient population had abnormal magnetic resonance imaging findings. In our group of 14 patients, those with higher disease activity (measured by the SLAM) at onset of TM were treated more aggressively (for example, with plasmapheresis and intravenous pulse cyclophosphamide). TM in our patients was associated with antiphospholipid antibodies in 43% of the cases as compared with 64% of the total patient population. Optic neuritis occurred in 48% of the total patient population with SLE and TM, suggesting an association. CONCLUSIONS TM in SLE is a poorly understood entity. Outcome might be more favourable than previously suggested. There is an association of TM with antiphospholipid antibodies in SLE patients. Treatment including intravenous cyclophosphamide may improve the final outcome. This report emphasises the need for multicentre trials to establish guidelines for optimal treatment.

Inflammatory arthritis: an overview for primary care physicians.

Abstract Continuing advances in the treatment of inflammatory arthritides such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) have made remission a realistic goal for patients. Despite these advances, early diagnosis of inflammatory arthritis by primary care physicians (PCPs) and subsequent referral to a rheumatologist remain a challenge. Delayed diagnosis and referral, which may extend to several years in some cases, may lead to irreversible joint destruction and compromised function. The aim of this review is to aid PCPs in preventing the potential delay in disease recognition and patient referral by highlighting the currently accepted criteria for disease activity, clinical response, and remission of RA, AS, and PsA. In addition, a discussion of the benefits and risks of the currently approved traditional disease-modifying antirheumatic drugs and biologic treatments, and the importance of comanagement of these conditions across specialties, will be addressed. Because PCPs are often the first point of contact for disease recognition, they can play a critical role in the management of these patients.

Cryoglobulin crystal arthropathy in a patient with multiple myeloma.

Joint involvement is unusual in patients with monoclonal gammopathies. It has been characteristically described as a rheumatoid-like seronegative polyarticular erosive arthropathy, which also has been related to crystal deposition of cryoglobulins in the synovium and several other tissues. This report describes the case of a 57-year-old African American woman with a seronegative polyarthritis associated with deposition of nonbirefringent or weakly positive birefringent rhomboid-shaped crystals in the synovial fluid. The patient, who was subsequently diagnosed with multiple myeloma, showed good clinical response to oral and intra-articular corticosteroids. Type II cryoglobulins were identified in the serum as well as in the synovial fluid. It is important to consider this association as part of the differential diagnosis of a patient with multiple myeloma and arthritis.

Transmembrane potential responses during HL-60 promyelocyte differentiation

Myeloid cells, including granulocytes and monocyte/macrophages, are important in disease‐associated inflammatory reactions. These cells come from a common progenitor, the promyelocyte. The human promyelocytic cell line, HL‐60, can be induced to terminally differentiate into granulocytes or monocyte/macrophages in a controlled fashion providing a model to study various aspects of myelomonocytic differentiation. The expression of several ion channels is controlled in HL‐60 cells in a differentiation specific pattern. The purpose of this study was to determine if lineage‐specific ion channel expression during HL‐60 differentiation resulted in differences in functional responses to external stimuli. This was investigated by examining transmembrane potential responses in HL‐60 promyelocytes, HL‐60‐derived polymorphonuclear cells (PMNs), and monocytes to various stimuli using the transmembrane potential sensitive dye, diSBAC2‐(3). Exposure of HL‐60 promyelocytes to ionomycin or ATP produced a membrane hyperpolarization. Studies using ion substitutions and ion channel blockers indicate that the hyperpolarization was mediated by KCa channels. During HL‐60 promyelocyte differentiation to PMNs, the membrane potential response to ionomycin and ATP shifted from a hyperpolarization to a depolarization over 7 days. Conversely, HL‐60‐derived monocytes exhibited a membrane hyperpolarization in response to ionomycin and ATP. HL‐60‐derived monocytes also exhibit a Cl− conductance specifically induced by ATP. Lineage‐specific expression of ion channels during HL‐60 cell differentiation is important in determining the transmembrane potential response of these cells. This may be translated into functional responses of various myelomonocytic cells during disease‐associated inflammatory reactions.

Mimics of vasculitis: vascular Ehlers-Danlos syndrome masquerading as polyarteritis nodosa.

To the Editor: A 29-year-old African American man presented to the emergency department following a witnessed generalized seizure, his first. He provided a history of 3 days of abdominal discomfort prior to presentation, associated with constipation. History was remarkable for alprazolam abuse that he recently discontinued, and inguinal hernia repair as a child. There was no significant family history. Physical examination, laboratory studies, and computed tomography (CT) scan of the head were normal. A lumbar puncture was not performed. A second witnessed seizure prompted admission. Over the next 2 days he had no further neurological events but complained of persistent abdominal discomfort. On the third hospital day he developed a fever of 38.5°C associated with leukocytosis and decreasing hemoglobin, but normal chemistry results, amylase, and lipase. CT scan of the abdomen/pelvis revealed a ruptured splenic artery aneurysm with intraabdominal hemorrhage, splenic vein thrombosis, celiac artery aneurysm, bilateral external iliac artery aneurysms, renal artery aneurysm, and multiple splenic and renal infarcts. CT angiography further delineated the extent of the vascular abnormalities (Figure 1). Figure 1. Sequence of reconstructed CT … Address correspondence to Dr. R.A. Badawi, Department of Cardiology, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121. E-mail: rbadawi{at}msn.com

A Case of Persistent Parvovirus B19 Infection with Bilateral Cartilaginous and Ligamentous Damage to the Wrists

We describe a case of persistent parvovirus B19 infection in a 48-year-old female physician that was complicated by prolonged fatigue and arthritis associated with cartilaginous and ligamentous damage in both wrists. Nineteen months after presentation, intravenous immunoglobulin therapy resulted in clearance of parvovirus B19 viremia and a significant improvement in the symptoms of fatigue and arthritis.

End-stage renal disease in sarcoidosis of the kidney

We describe two cases of black women with biopsy-proven sarcoidosis of the kidney who developed end-stage renal disease. Treatment with high-dose glucocorticoids resulted in a good initial response, followed by progressive deterioration of renal function requiring hemodialysis.

Clinical response to golimumab in rheumatoid arthritis patients who were receiving etanercept or adalimumab: results of a multicenter active treatment study

Abstract Objective: Evaluate the efficacy and safety of subcutaneous (SC) golimumab + methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite etanercept + MTX or adalimumab + MTX therapy and evaluate whether intravenous (IV) golimumab could rescue patients who were nonresponders to SC golimumab. Methods: In this multicenter, assessor-blinded, active-switch study of patients with RA (n = 433) with inadequate response to etanercept or adalimumab + MTX, patients continued MTX and received open-label SC golimumab 50 mg every 4 weeks through week 12. DAS28-ESR good responders at week 16 continued open-label SC golimumab through week 52 (Group 1); nonresponders were randomized to double-blind golimumab SC 50 mg (Group 2-SC) or IV 2 mg/kg (Group 2-IV). Week 14 ACR20 was the primary endpoint; assessments continued through week 52 and for patients in the voluntary long-term extension through week 76. A major secondary endpoint was the proportions of patients with ACR20 response at week 52 relative to week 16 in Group 2-SC and Group 2-IV. Results: At week 14, 34.9% (p < 0.001) achieved an ACR20. At week 52, patients in Group 1 (n = 75) achieved an ACR20 (62.7%). In Groups 2-SC (n = 91) and 2-IV (n = 184), 13.2% and 9.2% had an ACR20 at week 52 relative to week 16, with no significant difference between the randomized groups; 42.9% and 47.8% achieved DAS28-ESR response relative to week 0. Through week 16, 4.6% of patients had a serious adverse event. No differences in the rates or types of adverse events were observed between SC and IV golimumab from weeks 16 to 52. The trial limitations included a higher than expected discontinuation rate as a result of a programming error. Conclusion: SC golimumab + MTX significantly suppressed disease activity in RA patients with inadequate response to etanercept and/or adalimumab + MTX. Patients randomized to Groups 2-SC and 2-IV had lower response rates than Group 1, with no difference between SC or IV mode of administration. The safety profile with IV golimumab was comparable to that established with SC golimumab. Trial registration: NCT01004432, EudraCT 2009-010582-23.

THU0172 Symptomatic Subcutaneous Anti-Tumor Necrosis Factor-Treated Rheumatoid Arthritis Patients Respond to Golimumab following an Active Switch

Objectives GO-SAVE is a Ph3b, multi-center, switch assessment of SC and IV golimumab (GLM) in RA pts who have inadequate disease control despite treatment with etanercept (ETN) or adalimumab (ADA). Primary objective is to assess the efficacy of GLM at wk14 in pts with active RA and an inadequate response to ETN or ADA. Methods Pts with active RA (DAS28 score ≥3.6 with ≥6 swollen and ≥6 tender joints) who were currently receiving MTX and ETN or ADA were switched to GLM. Pts entered the screening period 6wks prior to receiving GLM (wk -6), remained on their original anti-TNFa, and re-screened again at wk 0. All eligible pts were actively switched to open-label GLM 50mg SC q4w at wk0. At wk16, pts who achieved a good DAS28-ESR response continued to receive open-label GLM 50mg SC q4wks +MTX through wk48 (Grp 1). Those with DAS28-ESR response classified as moderate or nonresponse were randomized (1:2) to double-blind treatment grps: GLM 50mg SC q4wks + MTX (Grp 2a) or GLM 2mg/kg IV q8wks (with a loading dose at wk20) +MTX (Grp 2b). Efficacy and safety evaluations were conducted through wk52. Results 433 pts were enrolled at wk0. All were included in the mITT population analysis. 358 pts (82.7%) were female; mean age was 55.7±11.5 yrs and mean disease duration was 10.7±9.8 yrs. At baseline, mean ± SD number of swollen and tender joints was 18.4±11.8 and 31.3±17.0, resp, and mean DAS28-ESR score was 6.2±0.9. Prior to GLM, 174 (40.2%) pts had received only ETN, and 186 (42.9%) had received only ADA; 73 (16.8%) pts had been previously exposed to both ETN and ADA, but not concomitantly. At wk14, 151 of the 433 pts (34.9%; 95% CI: 30.4%, 39.4%) achieved the primary outcome of an ACR20 response; a moderate or good EULAR response was achieved in 224pts (51.7%; 95% CI: 47.0%, 56.4%) with a mean DAS28-ESR improvement of -1.5 (95% CI: -1.6, -1.3, p<0.001) from baseline. 350 pts were treated from wk16 to wk52; 75 (21.4%) in Grp1 and 275 (78.6%) in Grp2 (91 in 2a and 184 in 2b). 42.8% (71/166) of pts in the SC Grps combined had an ACR20 and 57.2% (95/166) had a moderate or good EULAR response at wk52. Among all pts, a moderate or good EULAR response was maintained to wk52 in 52.3% (183/350), and ACR20 response was maintained to wk52 in 35.7% (125/350). During the blinded treatment interval (wk16 – 52), no significant difference was observed in EULAR responses relative to wk 16 between Grps 2a (SC) and 2b (IV). Through wk48, 246 of the initial 433 enrolled pts completed study injections/infusions. 358 (82.7%) of the 433 pts experienced AEs, and 35 pts (8.1%) experienced SAEs. Injection site reactions were reported in 10 (2.3%) pts. Conclusions GLM significantly improves signs and symptoms in pts with moderate or severe RA responding inadequately to ETN or ADA. Over a third of pts achieved an ACR20 and over half achieved a DAS28-defined EULAR response beyond the results with their previous therapy. No difference was observed between IV and SC GLM. GLM was safe and well-tolerated. Disclosure of Interest : J. Huffstutter Grant/research support: Amgen, Janssen, and Pfizer., Speakers bureau: Janssen and UCB., S. Kafka Grant/research support: same companies, as well as Lilly, Speakers bureau: Pfizer, Abbvie, Janssen, Amgen, BMS, Genentech, UCB, L. Brent Grant/research support: Janssen, Speakers bureau: AbbVie, Genentech, M. Matucci-Cerinic Grant/research support: Janssen, K. Tang Employee of: Janssen Research & Development, LLC., J. Wang Employee of: Janssen Research & Development, LLC., D. Decktor Employee of: Janssen Scientific Affairs, M. Chevrier Employee of: Janssen Scientific Affairs, T. Sprabery Employee of: Janssen Scientific Affairs, R. DeHoratius Employee of: Janssen Scientific Affairs DOI 10.1136/annrheumdis-2014-eular.3766