Raphael J. DeHoratius

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.

Systemic lupus erythematosus and acute pancreatitis: a case series

The aim of this study was to evaluate whether corticosteroid use is the etiological agent in acute pancreatitis in patients with systemic lupus erythematosus, or whether it is related to the underlying connective tissue disorder. Hospital admissions at Thomas Jefferson University Hospital between 1982 and 2002 that carried the dual diagnosis of systemic lupus erythematosus and pancreatitis were identified, and demographic data, clinical interventions and parameters of clinical progression of their disease were identified. From 2947 admissions with systemic lupus erythematosus 25 (0.85%) were diagnosed as having acute pancreatitis; 76% of cases had active systemic lupus erythematosus on presentation, with an average of 4.4 organ involvement, and a clustering of renal disease (56%), pleural effusion (48%) and arthritis (44%) in these patients. Fifteen patients with active disease and three whose disease was inactive received increased doses of corticosteroids, and four active cases and one inactive one stayed on the same doses. Two inactive patients received no corticosteroids before or after the diagnosis of pancreatitis. Eighty-two percent of patients had clinical and laboratory improvement on the higher or maintenance dose of corticosteroids. We therefore concluded that acute pancreatitis is a rare manifestation of systemic lupus erythematosus, and corticosteroids do not appear to be the etiological agent.

Musculoskeletal manifestations of endocrine disorders

Purpose of reviewMuch of our education about endocrine disorders focuses on their diagnosis and treatment. Although the musculoskeletal manifestations of endocrine disorders are well documented, they are often overlooked. This review will discuss new developments regarding those rheumatic manifestations. Recent findingsDiabetic research is investigating connective tissue alterations in hand syndromes. A recent review elucidated the natural history of diabetic muscle infarction. Research has identified factors that stimulate osteoblast activity in diffuse idiopathic skeletal hyperostosis and bone loss in diabetics. Accumulating evidence documents thyroid disease coexisting with connective tissue disorders. Reports document cases of vasculitis occurring after propylthiouracil treatment. Finally, data clarifies the effects of thyroid dysfunction, hyperparathyroidism, acromegaly and hypercortisolism on bone. SummaryCurrent research mainly relates to the effects of endocrine disorders on bone. As we advance our understanding of mechanisms that lead to rheumatic disorders in endocrine disease, we will improve our ability to treat them.

Family Distribution of Lymphocytotoxins in Hodgkin's Disease

The prevalence of lymphocytotoxic antibody was studied in 131 relatives of 10 patients with Hodgkins disease. The study group contained nine families, five of which had two subjects with Hodgkins disease. One hundred twenty-eight control family members were studied in parallel. Lymphocytotoxic antibody was present in 35.5% of all family members of patients with Hodgkins disease, and in 8.6% of controls (P less than 0.01). Lymphocytotoxic antibody appeared primarily in consanguineous relatives irrespective of close personal household contact with the probands. The prevalence of the antibody was equal in both first- and second-degree relatives. These findings suggest at least a genetic and possibly an environmental influence in the genesis of lymphocytotoxic antibody among relatives of patients with Hodgkins disease.

Pregnancy Outcomes in Female Renal Recipients: A Comparison of Systemic Lupus Erythematosus With Other Diagnoses

This study compares pregnancy outcomes in systemic lupus erythematosus (SLE) patients post renal transplant with recipients with other primary diagnoses, utilizing data from the National Transplantation Pregnancy Registry, Philadelphia, PA. Recipients were referred from transplant centers nationwide.

Reduced T-lymphocyte subsets in systemic lupus erythematosus: Effects of immune complexes and lymphocytotoxic antibodies

Abstract Patients with active systemic lupus erythematosus (SLE) show significant reductions of T cells with receptors for the Fc portion of IgG, Tγ cells, which have been found to suppress in vitro B-cell responses to pokeweed mitogen. T cells with receptors for the Fc portion of IgM, Tμ cells, which show both helper and suppressor functions, are also reduced in SLE. Levels of both Tγ and Tμ cells in patients with inactive disease are intermediate between those of patients with active SLE and normal individuals. In a majority of individual patients, levels of Tγ cells were found to fluctuate with disease activity. SLE patients with reduced levels of Tγ cells showed high levels of circulating immune complexes, although a uniform inverse correlation was not detected. The pathophysiologic mechanisms in the observed decrease of T-cell subsets in SLE patients were studied by determination of the effect of aggregated IgG (an in vitro model of immune complexes) and lymphocytotoxic antibodies on T-cell subsets from normal individuals. Addition of aggregated IgG led to irreversible reduction of Tγ cells with no effect on Tμ cells. By contrast, both types of T-cell subsets were reversibly decreased by SLE sera with lymphocytotoxic antibody activity. Thus the observed decrease in T-cell subsets appears to be secondary to both immune complexes and lymphocytotoxic antibodies in SLE patients, and is reversible with remission of disease activity. Analysis of T-cell subpopulations in SLE appears to reflect other laboratory parameters associated with disease activity in these patients.

Tuberculous tonsillitis in a patient receiving etanercept treatment

Since the approval by the Food and Drug Administration (FDA) of tumour necrosis factor α antagonists, infections have accounted for 21% of the adverse events reported to the FDA for etanercept and 20% of those reported for infliximab.1,2 As of May 2001, from approximately 147 000 subjects receiving infliximab treatment, 70 patients have been reported to have developed active tuberculosis. Of these, 52% presented with extrapulmonary tuberculosis while 24% presented with disseminated disease.3 As of April 2001, from approximately 102 000 subjects receiving etanercept treatment, nine patients have been reported to have developed active tuberculosis.4 With the …

Infliximab efficacy in rheumatoid arthritis after an inadequate response to etanercept or adalimumab: results of a target-driven active switch study

Abstract Objective: Evaluate efficacy of infliximab with response-driven dosing in patients with active RA. Research design and methods: Patients (n = 203) with active RA despite methotrexate + etanercept/adalimumab, participated in this active-infliximab-switch study. Infliximab 3 mg/kg was infused at Weeks 0, 2, 6, 14, and 22 with escalation to 5 or 7 mg/kg depending on EULAR response at Weeks 14 and 22. The primary endpoint was EULAR response at Week 10. Safety was assessed through Week 30. Infliximab levels and antibodies to infliximab (ATI) were measured at Weeks 0, 6, 14, and 26. Clinical trial registration: NCT 00714493, EudraCT 2007-003288-36. Results: Of 197 evaluable patients, 120/77 previously received etanercept/adalimumab. Baseline mean (SD) swollen and tender joint counts were 17.3 (10.54) and 30.2 (16.89), respectively; mean DAS28-ESR was 6.19 (0.981). At Week 10, 98 (49.7%; 95% CI: 42.6%, 56.9%) patients achieved EULAR response, with a significantly improved DAS28-ESR score (mean [SD] change −1.1 [1.15]; p < 0.001). EULAR response was achieved by 41.7%/62.3% of patients previously receiving etanercept/adalimumab (p = 0.006). At Week 26, 51.8% (95% CI: 44.6%, 58.9%) of patients achieved or maintained EULAR response. Infliximab dose was escalated in 100 patients, 52% of whom achieved EULAR response at Week 26. Median serum concentration levels at Week 26 showed that dose escalation helped EULAR non-responders achieve levels similar to or higher than the levels seen in responders. ATI were associated with lower serum concentrations of infliximab, consistent with lower efficacy rates among ATI-positive patients. Conclusion: Infliximab, in treat-to-target settings with individual dose escalation, demonstrated significant efficacy at Weeks 10 and 26 in patients switched to infliximab after inadequate response to etanercept/adalimumab. The observed efficacy indicated that the switch to infliximab and ability to increase dose in a targeted fashion were beneficial. Key limitations: Given the relatively short duration of study follow-up, these safety findings require confirmation in a longer-term study.

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.

Ethnographic Observational Study of the Biologic Initiation Conversation Between Rheumatologists and Biologic-Naive Rheumatoid Arthritis Patients

This ethnographic market research study investigated the biologic initiation conversation between rheumatologists and biologic‐naive patients with rheumatoid arthritis to assess how therapy options, particularly mode of administration, were discussed.