Early recognition of aortitis of the aorta ascendens with ¹8F-FDG PET/CT: syphilitic?

We present the case of a 42-year-old woman known with a human leukocyte antigen B27 positive ankylosing spondylitis. Despite treatment with a tumor necrosis factor blocking agent, the patient was not pain free and inflammation markers remained elevated. An (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) was performed in an attempt to exclude possible other inflammatory processes. The (18)F-FDG PET/CT revealed increased metabolic activity in the ascending aortic wall, which appeared unexpectedly related to late syphilis. Based on this case and existing literature on this subject, we come to the conclusion that (18)F-FDG PET/CT can help in an early establishment of syphilitic aortitis before the possible life-threatening sequelae of syphilitic aortitis occur.

Parameters related to a positive test result for FDG PET(/CT) for large vessel vasculitis: a multicenter retrospective study.

The purpose of this study was to identify clinical and laboratory parameters that may improve the effectiveness of the use of fluorodeoxyglucose positron emission tomography ((18)F-FDG PET)(/CT) for diagnosing large vessel vasculitis (LVV), and secondarily to assess the contribution of (18)F-FDG PET/CT in finding other diagnoses for patients without signs of LVV on the scan. A multicenter retrospective study of (18)F-FDG PET(/CT) scans performed between January 2000 and December 2009 for clinical suspicion of LVV was conducted. A total of 304 (18)F-FDG PET(/CT) scans were included, of which 62 (20%) were positive and 242 (80%) were negative for LVV. Univariate analysis showed that patients with a positive scan were older (65.9 ± 13.4 versus 58.6 ± 16.5 years, p = 0.002), were more frequently female (76% versus 55%, p = 0.002), more often had a history of temporal arteritis (10% versus 3%, p = 0.044), less frequently had artralgia (31% versus 67%, p = 0.000), and had higher thrombocyte counts (434 ± 161 versus 373 ± 168 × 10(9)/l, p = 0.049) and a higher erythrocyte sedimentation rate (ESR) (72.6 ± 31.0 versus 51.4 ± 30.5 mm/h, p = 0.001) than patients with a negative scan. In the multivariate analysis, only artralgia (OR 0.091; 95% CI 0.023-0.366) and ESR (OR 1.024; 95% CI 1.002-1.046) remained statistically significant predictors. The presence of artralgia is a statistically significant negative predictor and an elevated ESR a statistically significant positive predictor of LVV showing up on (18)F-FDG PET(/CT). A reliable prediction of the outcome of the scan, based on these two parameters, is not possible however. (18)F-FDG PET(/CT) allows early diagnosis of LVV and may discover occult inflammatory or neoplastic disorders.

The relation between bone mineral density, bone turnover markers, and vitamin D status in ankylosing spondylitis patients with active disease: a cross-sectional analysis.

SUMMARY: Osteoporosis is a well recognized complication of ankylosing spondylitis (AS). This study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis, and that bone turnover markers (BTM) are valuable markers to detect bone loss in AS. INTRODUCTION: The aim of this study was to elucidate the pathophysiology of AS-related osteoporosis by investigating the relation between bone mineral density (BMD), BTM, vitamin D, and clinical assessments of disease activity and physical function, as well as to identify parameters that are related to low BMD (osteopenia or osteoporosis) in AS patients with active disease. METHODS: One hundred twenty-eight consecutive Dutch AS outpatients were included in this cross-sectional study. Bath AS Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), C-reactive protein, ASAS-endorsed disease activity score (ASDAS), Bath AS Functional Index (BASFI), bone formation markers procollagen type 1 N-terminal peptide (PINP) and osteocalcin (OC), bone resorption marker serum C-telopeptides of type I collagen (sCTX), 25-hydroxyvitamin D (25OHvitD), lumbar spine and hip BMD, and vertebral fractures were assessed. Z-scores of BTM were calculated using matched 10-year cohorts of a Dutch reference group to correct for the normal influence that age and gender have on bone turnover. RESULTS: sCTX Z-score, OC Z-score, BASDAI, age, and gender were independently related to low BMD. In addition, PINP Z-score, ESR, 25OHvitD, age, and gender were independently related to sCTX and/or OC Z-score. CONCLUSIONS: This study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis. Furthermore, sCTX and OC Z-scores seem to be valuable markers to detect bone loss in AS patients in daily clinical practice where BMD of the lumbar spine, measured by DXA, may be overestimated due to osteoproliferation in patients with advanced AS.

The formation of autoantibodies and antibodies to TNF-α blocking agents in relation to clinical response in patients with ankylosing spondylitis.

OBJECTIVES: To investigate the influence of antibody formation to TNF-α blocking agents on the clinical response in AS patients treated with infliximab (IFX), etanercept (ETA), or adalimumab (ADA), and to investigate the development of ANA, ANCA, and anti-dsDNA antibodies in association with the formation of antibodies to TNF-α blocking agents. METHODS: Consecutive AS outpatients with active disease who started treatment with IFX (n=20), ETA (n=20), or ADA (n=20) were included in this longitudinal observational study. Clinical data were collected prospectively at baseline and after 3, 6, and 12 months of anti-TNF-α treatment. At the same time points, serum samples were collected. In these samples, antibodies to TNF-α blocking agents, serum TNF-α blocker levels, and ANA, ANCA, and anti-dsDNA antibodies were measured retrospectively. RESULTS: Anti-IFX, anti-ETA, and anti-ADA antibodies were induced in 20%, 0%, and 30% of patients, respectively. Although ANA, ANCA, and anti-dsDNA antibodies were detected during anti-TNF-α treatment, no significant association was found between the presence of these autoantibodies and the formation of antibodies to TNF-α blocking agents. Patients with anti-IFX or anti-ADA antibodies had significantly lower serum TNF-α blocker levels compared to patients without these antibodies. Furthermore, significant negative correlations were found between serum TNF-α blocker levels and assessments of disease activity. CONCLUSIONS: This study indicates that antibody formation to IFX or ADA is related to a decrease in efficacy and early discontinuation of anti-TNF-α treatment in AS patients. Furthermore, autoantibody formation does not seem to be associated with antibody formation to TNF-α blocking agents.

[Clinical reasoning and decision-making in practice. A man with inexplicable joint pain and subsequent poor clinical condition]. / Klinisch denken en beslissen in de praktijk. Een man met onbegrepen gewrichtsklachten en daarna een slechte klinische toestand.

A 52-year-old man presented with polyarthritis and was negative for rheumatoid factor, anti-CCP and ANA. He was treated with low-dose methotrexate, the drug of first choice in rheumatoid arthritis. The arthritis disappeared, but the patient developed fever, progressive dyspnoea, appetite loss and weight loss. Upon hospital admission his medication was stopped and community-acquired pneumonia was diagnosed. The fever persisted despite antibiotic treatment. The tentative diagnosis of rheumatoid arthritis was changed to systemic lupus erythematosus, based on the change in clinical condition that could not be explained by polyarthritis and seroconversion to ANA- and anti-dsDNA-positive. The patient was treated with high-dose steroids and azathioprine and remained in remission for more than 1 year after treatment. The ANA test remained strongly positive, whereas anti-dsDNA was no longer detectable. This case stresses the limited value of classification criteria for the diagnosis of rheumatoid arthritis. To differentiate between rheumatoid arthritis and systemic lupus erythematosus, tests for autoantibodies against citrullinated peptides can be used. To differentiate between systemic lupus erythematosus and infection, tests for anti-dsDNA antibodies, antinuclear antibodies, C-reactive protein and complement can be used.

Tonsillar tuberculosis in a rheumatoid arthritis patient receiving anti-TNFalpha (adalimumab) treatment.

This case report describes a 61-year-old rheumatoid arthritis patient with an atypical clinical presentation of a sore throat. Because of rheumatoid arthritis refractory to conventional disease-modifying antirheumatic drug therapy, anti-TNFalpha was felt to be indicated, and a screening for tuberculosis was carried out. As the screening for tuberculosis (PPD) was positive, isoniazid was prescribed prophylactically for six months. After eight months of anti-TNFalpha (adalimumab) treatment, he developed tonsillar enlargement and nodular pulmonary lesions. Histopathological and microbial investigations established the diagnosis of tonsillar tuberculosis.

Therapeutic drug monitoring of A77 1726, the active metabolite of leflunomide: serum concentrations predict response to treatment in patients with rheumatoid arthritis.

BACKGROUND: Leflunomide is the prodrug of the disease modifying antirheumatic metabolite A77 1726. More than 50% of patients withdraw from leflunomide treatment within one year, mainly because of adverse drug reactions. Therapeutic drug monitoring of A77 1726 may be useful in predicting the efficacy of leflunomide treatment. OBJECTIVE: To study the relation between A77 1726 steady state serum concentrations and disease activity using the 28 joint (DAS28) response. METHODS: Outpatients with rheumatoid arthritis on a stable leflunomide dose for >4 months were included. DAS28 score and adverse drug reactions were recorded. Blood samples were taken for determination of A77 1726 concentrations. The primary end point was the relation of serum A77 1726 concentrations with DAS28 response category. RESULTS: Serum A77 1726 concentrations were determined in 52 patients. A receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.73 (95% confidence interval, 0.54 to 0.93) (p<0.05). The sensitivity exceeded 99% at concentrations below 16 mg/l. DAS28 values at the point of sampling showed no relation with A77 1726 concentrations (AUC of the ROC curve = 0.50 (0.33 to 0.67) (NS)). CONCLUSIONS: A77 1726 steady state serum concentrations show a relation with DAS28 response. Determination of serum A77 1726 concentrations in patients with insufficient response to treatment may help when decisions have to be made about continuation of treatment or dose adjustment.

Leflunomide in active rheumatoid arthritis: a prospective study in daily practice.

AIMS: We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. METHODS: In this prospective case series study, a standard dataset was collected from outpatient medical records, including patient and disease characteristics, data on leflunomide use and adverse drug reactions. RESULTS: During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS(28)) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS(28) response criteria. CONCLUSIONS: In the setting of care-as-usual rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within 1 year of starting leflunomide treatment, mainly because of adverse drug reactions.

Leflunomide in active rheumatoid arthritis: a prospective study in daily practice.

AIMS: We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. METHODS: In this prospective case series study, from outpatient medical records a standard dataset was collected including patient and disease characteristics, data on leflunomide use and adverse drug reactions. RESULTS: During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient-years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS(28)) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS(28) response criteria. CONCLUSIONS: In the setting of care-as-usual, rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within a year after start of leflunomide treatment, mainly because of adverse drug reactions.

[Diagnostic image (176). A man with a black thumb. Necrosis of the thumb as a symptom of rheumatoid vasculitis]. / Diagnose in beeld (176). Een man met een zwarte duim. Necrose van de duimtop als uiting van vasculitis bij reumatoïde artritis.

A 72-year-old man presented with necrosis of the thumb as a symptom of rheumatoid vasculitis.

[Diagnostic image (100). A man with migrating joint complaints. Tophaceous gout]. / Diagnose in beeld (100). Een man met verspringende gewrichtsklachten. Tofi bij arthritis urica.

An 80-year-old man using diuretics for chronic cardiac failure was diagnosed with tophaceous gout.