TNFα antagonist therapy does not increase the Epstein-Barr virus burden in patients with rheumatoid arthritis or ankylosing spondylitis

ObjectiveThe risk of non-Hodgkin lymphoma is increased in rheumatoid arthritis (RA) but not in ankylosing spondylitis (AS). In RA, the degree of inflammation is closely associated with the lymphoma risk. Whether immunosuppressants such as methotrexate and TNFα antagonists affect the lymphoma risk in RA is unclear. The Epstein-Barr virus (EBV) may contribute to the pathogenesis of RA and may be involved in the development of lymphoma in patients taking methotrexate and/or TNFα antagonists, although these points remain debated. EBV load monitoring during immunosuppressive treatment may predict the occurrence of EBV-related lymphoma. Here, our objective was to prospectively measure the EBV load in patients receiving TNFα antagonists for RA or AS.MethodsWe prospectively studied patients with RA or AS before and after TNFα antagonist therapy initiation. The EBV load was measured in blood samples using the EBV R-gene Quantification Kit. Disease activity at the time of blood sampling was evaluated by determining the Disease Activity Score 28 (DAS28) in RA patients and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS patients.ResultsWe included 46 patients with RA (82.6% women; mean age, 52.7 ± 11.3 years) and 27 with AS (men, 81.5%; mean age, 45.1 ± 12.7 years). In the RA group, the EBV load was measured at baseline and 9.72 ± 5.7 months later. The baseline EBV load was undetectable in 33 (70.2%) patients; mean EBV load in the 13 remaining patients was 9389copies/ml (3.47 log₁₀ ± 0.45). Baseline EBV load did not correlate with disease activity (DAS28). At the follow-up assay, the EBV load became positive in five patients and increased significantly in one patient (four patients on etanercept, one on adalimumab, and one on infliximab); it became negative in six patients (five on adalimumab and one on etanercept) and showed non-significant changes in six patients. Mean EBV load in patients positive at follow-up was 3.63 ± 0.52 log₁₀ copies/ml. Mean DAS28 was 4.78 ± 1.1 at baseline and 2.94 ± 1.24 at follow-up. At follow-up, a good EULAR response was noted in 33 (71.7%) patients and a moderate EULAR response in seven (15.2%) patients. In the AS group, the baseline EBV load measurement occurred after 12.9 ± 10.6 months. Baseline EBV load was undetectable in 25 (92.6%) patients; mean load in the remaining two patients was 4.15 ± 0.46 log₁₀ copies/ml. At follow-up, the EBV load became positive in two patients (one on adalimumab and one on infliximab) and became negative in one patient (on adalimumab). Mean load in positive patients was 3.33 ± 0.24 log₁₀ copies/ml. Mean BASDAI was 55.1 ± 16.2 at baseline and 17.88 ± 18.62 at follow-up. A positive EBV load was significantly more common in the RA group than in the AS group (P = 0.039). EBV load changes did not differ significantly between the RA and AS groups or across TNFα antagonists. No cases of lymphoma were recorded.ConclusionIntroducing TNFα antagonist therapy does not affect the EBV load in patients with RA or AS. EBV load monitoring is probably unnecessary in patients given TNFα antagonists for RA or AS.     

Infection of the sigmoid colon during TNFα antagonist therapy for chronic inflammatory joint disease

We report 7 cases of sigmoid colon infection in patients taking TNFα antagonist therapy to treat chronic inflammatory joint disease. There were 5 women and 2 men with a mean age of 57.5 years (range, 21–77 years). The presenting symptoms were abdominal pain, bowel habit changes, and a fever. These symptoms developed within 6 months after starting TNFα antagonist therapy in 5 of the 7 patients. Empirical antibiotic therapy was used in all 7 patients. Surgical colectomy was performed in 4 patients, including 1 who required a temporary Hartmann's procedure. The risk of infection associated with TNFα antagonist therapy is well documented. However, few cases of colon infection have been reported and little is known about this potentially severe complication. Glucocorticoids or non-steroidal anti-inflammatory drugs may worsen the infection, particularly as they can attenuate the clinical symptoms, thereby delaying the diagnosis. A history of sigmoid colon infection, diverticulosis, and/or diverticulitis must be sought before starting treatment with a biological agent. Prophylactic treatment may be considered if such a history is found. Diagnostic investigations are in order to develop a standardized management strategy in patients with a history of intestinal tract infection.     

Outcome and safety of TNFα antagonist therapy in 475 consecutive outpatients (with rheumatoid arthritis or spondyloarthropathies) treated by a single physician according to their eligibility for clinical trials

ObjectiveTo investigate the effectiveness and safety of TNFα antagonists in patients with rheumatoid arthritis (RA) or spondyloarthropathies (SpA) treated by a single physician, according to the presence of the inclusion and non-inclusion criteria used to select patients for pivotal clinical trials.MethodsEffectiveness was evaluated based on four categories defined by the DAS28-ESR and BASDAI values, from a very good response (mean DAS-28-ESR less than 3.2 and mean BASDAI less than 2.0) to failure (DAS28-ESR unchanged or greater than 5.1 and BASDAI unchanged). Serious adverse events were defined as events that required permanent TNFα antagonist discontinuation or that led to sequelae, hospital admission, or death.ResultsThe study included 475 patients, 230 with RA, 226 with SpA, 10 with juvenile-onset arthritis, and nine with unclassifiable arthritis. Mean number of TNFα antagonists used per patient was 1.3 and mean duration of TNFα antagonist treatment was 28 ± 23 months. Overall, 41% of patients met the inclusion and non-inclusion criteria used in pivotal trials; the proportion was 43% in the RA group and 40% in the SpA group. These patients had a 3-fold higher rate of very good responses (54 versus 19%) and a 5-fold lower rate of failures (5 versus 25%) compared to the other patients. Of the 15 (3%) patients who died, none met pivotal trial criteria. The group that met pivotal trial criteria had a significantly lower rate of serious adverse events (11 versus 16%; Chi², p = 0.0001), although age was similar in the two groups (53 ± 16 years versus 57 ± 14 years).ConclusionPatients meeting the selection criteria used in pivotal trials had a higher response rate and significantly fewer serious adverse events.     

Role for interferon-gamma release assays in latent tuberculosis screening before TNF-α antagonist therapy

TNF-α antagonist therapy is associated with a risk of severe, extrapulmonary, disseminated tuberculosis, which is fatal in 10% of cases. The risk of tuberculosis is increased four-fold in patients on TNF-α antagonist therapy. The main risk factors are a history of untreated or inadequately treated primary tuberculosis, recent contact with a tuberculosis patient, and residence in or travel to a high-endemicity region. Infection surveillance agencies throughout the world have issued recommendations to ensure the detection and treatment of latent tuberculosis before TNF-α antagonist initiation. These recommendations have returned the incidence of tuberculosis to the level seen before the introduction of TNF-α antagonists. Nevertheless, there is still room for improvement. Recommendations about latent tuberculosis screening include the use of tuberculin skin tests. However, these tests are positive in individuals vaccinated with the BCG vaccine, which leads to overuse of tuberculosis chemoprophylaxis and, therefore, to unnecessary patient exposure to hepatotoxic effects. Furthermore, tuberculin skin tests may be falsely negative in immunosuppressed patients, leading to underuse of tuberculosis prophylaxis. These shortcomings of tuberculin skin tests have generated interest in interferon-gamma release assays (IGRAs). In patients with overt tuberculosis, IGRAs are more sensitive and more specific than tuberculin skin tests. However, the accuracy of IGRAs for diagnosing latent tuberculosis remains unknown, because no reference standard is available. In addition, patients taking immunosuppressant agents to treat systemic disease may exhibit anergia, which complicates the interpretation of IGRAs. Until additional data become available, caution requires that IGRAs be used only when a positive or negative result, as assessed on a case-by-case basis, will help to decide whether tuberculosis chemoprophylaxis is in order.     

Creutzfeldt-Jakob disease in a patient treated by etanercept for rheumatoid arthritis (RA): Just a coincidence?

We describe a patient in whom sporadic Creutzfeldt-Jakob disease (sCJD) occured one year after the onset of etanercept therapy for rheumatoid arthritis (RA). This association could be a chance occurrence. However, TNF-α has been implicated in the pathogenesis of neurodegeneration in sCJD and etanercept might worsen the disease. Such an aggravation has been observed in multiple sclerosis, in which TNF-α is the key mediator of demyelination. It may be of interest studying the impact of treatment with TNF-α antagonists on prevalence and incidence of those neurodegenerative diseases involving TNF-α mediation, such as Alzheimer disease.     

General anesthesia in a patient on long-term amphetamine therapy: is there cause for concern?

IMPLICATIONS: Amphetamines are powerful, sympathomimetic amines that, when used chronically, can profoundly effect a patient's cardiovascular stability during anesthesia and surgery. Amphetamines are the third most widely abused class of drugs in the United States. They also have legitimate medical use for attention deficit disorder with hyperactivity, exogenous obesity, and narcolepsy. We report a case of a patient with a 40-yr history of chronic amphetamine use having undergone two general anesthesias without complication.     

Self-resolving spontaneous spinal epidural hæmatoma in a patient on anti-coagulant therapy: a case study

Spinal epidural hæmatoma (SEN) is a rare condition that generally presents as a neurological deficit. It most commonly occurs following a trauma, e.g. whiplash injury, but may also occur spontaneously. The following case reports a chiropractic encounter with one such individual and the fortunate outcome that highlights the need for a thorough examination, which may include special imaging. This report also examines the literature available describing similar cases of spontaneous SEH in an attempt to heighten awareness to SEH and the risk factors associated with this neurosurgical emergency.     

Topical negative pressure therapy for para-ileostomal ulceration in a patient with Behçet's disease

BehCet's disease is a chronic, relapsing, inflammatory disorder. This case report describes how use of an improvised topical negative pressure (TNP) device in a patient with a non-healing para-ileostomal ulcer with Beh?et's disease.     

Lipoprotein(a)- and low-density lipoprotein-derived cholesterol in nephrotic syndrome: Impact on lipid-lowering therapy?

BACKGROUND: Patients with nephrotic syndrome have the highest lipoprotein(a) [Lp(a)] concentrations known. Lp(a) is an low-density lipoprotein (LDL)-like particle consisting of 45% cholesterol. The usual methods to determine LDL cholesterol do not distinguish between cholesterol derived from LDL and Lp(a) and are thus the net result of cholesterol levels from both lipoproteins. High Lp(a) concentrations therefore significantly contribute to the measured or calculated LDL cholesterol levels. Since statins have no influence on Lp(a) levels, it can be expected that the LDL cholesterol-lowering effect of statins may be diminished in patients who have a pronounced elevation of Lp(a) levels accompanied by only moderate elevations of LDL cholesterol. METHODS: We investigated 207 patients with nondiabetic nephrotic syndrome in whom Lp(a) concentrations were strikingly elevated when compared to 274 controls (60.4 +/- 85.4 mg/dL vs. 20.0 +/- 32.8 mg/dL, P < 0.0001). RESULTS: According to National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines for Managing Dyslipidemias, almost 95% of these patients are candidates for a therapeutic intervention to lower LDL cholesterol. LDL cholesterol levels corrected for Lp(a)-derived cholesterol, however, were 27 mg/dL lower than uncorrected concentrations (compared to only 9 mg/dL in controls). If Lp(a)-corrected levels instead of total LDL cholesterol levels were used, 25.7% of patients with low-molecular-weight (LMW) apolipoprotein(a) [apo(a)] isoforms were classified no longer to be in need of LDL cholesterol-lowering therapeutic intervention compared to only 2.3% of patients with high-molecular-weight (HMW) apo(a) phenotypes (P < 0.00001). This ("pseudo") pharmacogenetic effect results in incorrect determination of LDL cholesterol. CONCLUSION: Our observation has an impact on the indication for, and assessment of efficacy of intervention. This potential artifact should be investigated in ongoing large trials in renal patients as well as in nonrenal African American subjects who have on average markedly higher Lp(a) levels. In nonrenal Caucasian subjects with much lower Lp(a) concentrations, this issue will be less relevant.     

The first case of coronary artery by-pass grafting surgery (CABG) in a patient on maintenance dialysis in Iaşi

Coronary artery disease has a significantly higher prevalence in chronic dialysis patients compared to the general population, explained by a cluster of non-specific and specific (uremia-associated) cardiovascular risk factors, typical for these patients. Nephrologists and cardiovascular surgeons worldwide are rather reluctant to offer CABG to dialysis patients, because of concerns about higher risks associated with this procedure in this frail population. However, there is an increasing opinion supporting a more aggressive management of coronary artery disease in uremic individuals. To illustrate this "positive attitude", we report here the first dialysis patient ever treated by CABG in Ia?i; his good outcome was both rewarding and encouraging for us all.     

Anaesthesia for a patient with central alveolar hypoventilation syndrome (Ondine’s curse)

The perioperative anaesthetic management of an adult patient with central alveolar hypoventilation syndrome (CAHS), Ondine's Curse, is described for anterior resection of a carcinoma of the bowel. This rare syndrome results in alveolar hypoventilation, hypercarbia, hypoxaemia with secondary polycythaemia, pulmonary artery hypertension, and cor pulmonale. Epidural morphine was used for postoperative analgesia in an attempt to improve postoperative respiratory function. However, postoperative mechanical ventilation was required until recovery of the respiratory drive, which was ablated by anaesthetic drugs, epidural morphine and high inspired oxygen concentrations. The pathophysiology and treatment of this syndrome are reviewed.